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Elimination of malaria has become a United Nations member states target: Target 3.3 of the sustainable development goal no. 3 (SDG3). Despite the measures taken, the attainment of this goal is jeopardized by an alarming trend of increasing malaria case incidence. Globally, there were an estimated 241 million malaria cases in 2020 in 85 malaria-endemic countries, increasing from 227 million in 2019. Malaria case incidence was 59, which means effectively no changes in the numbers occurred, compared with the baseline 2015. Jennifer Doudna—co-inventor of CRISPR/Cas9 technology—claims that CRISPR holds the potential to lessen or even eradicate problems lying in the centre of SDGs. On the same note, CRISPR/Cas9-mediated mosquito-targeting gene drives (MGD) are perceived as a potential means to turn this trend back and put momentum into the malaria elimination effort. This paper assessed two of the critical elements of the World Health Organization Genetically modified mosquitoes (WHO GMM) Critical Pathway framework: the community and stakeholders' engagement (inability to employ widely used frameworks, segmentation of the public, 'bystander' status, and guidelines operationalization) and the regulatory landscape (lex generali, 'goldilocks dilemma', and mode of regulation) concerning mosquito-oriented gene drives (MGD) advances. Based on the assessment findings, the author believes that CRISPR/Cas-9-mediated MGD will not contribute to the attainment of SDG3 (Target 3.3), despite the undisputable technology's potential. This research pertains to the state of knowledge, legal frameworks, and legislature, as of November 2022. [ABSTRACT FROM AUTHOR]

Plant genomics plays a pivotal role in enhancing global food security and sustainability by offering innovative solutions for improving crop yield, disease resistance, and stress tolerance. As the number of sequenced genomes grows and the accuracy and contiguity of genome assemblies improve, structural annotation of plant genomes continues to be a significant challenge due to their large size, polyploidy, and rich repeat content. In this paper, we present an overview of the current landscape in crop genomics research, highlighting the diversity of genomic characteristics across various crop species. We also assessed the accuracy of popular gene prediction tools in identifying genes within crop genomes and examined the factors that impact their performance. Our findings highlight the strengths and limitations of BRAKER2 and Helixer as leading structural genome annotation tools and underscore the impact of genome complexity, fragmentation, and repeat content on their performance. Furthermore, we evaluated the suitability of the predicted proteins as a reliable search space in proteomics studies using mass spectrometry data. Our results provide valuable insights for future efforts to refine and advance the field of structural genome annotation. [ABSTRACT FROM AUTHOR]

Background: Canada, Australia, the World Health Organization and other countries have released 24-hour movement guidelines for the early years which integrate physical activity, sedentary behaviour, and sleep, focusing on supporting children to achieve a healthy 24-hour day. The guideline evidence synthesis, however, highlighted the dearth of high-quality evidence, particularly from large-scale studies. The Sleep and Activity Database for the Early Years (SADEY) project aims to assemble a large, pooled database of 24-hour movement behaviours and health indicators in young children (birth to 5.99 years), to advance knowledge in these areas. This paper describes the SADEY design and methods. Methods: Data sets were identified with > 100 children and device-measured (hip-worn ActiGraph accelerometers) physical activity and sedentary behaviour, parent-reported or device-measured sleep, and at least one health outcome: physical (BMI, waist circumference, blood pressure), social-emotional (Strength and Difficulties Questionnaire), cognitive (Early Years Toolbox), or motor development (Test of Gross Motor Development 2). Led by the University of Wollongong co-ordinating centre, the SADEY project collates the datasets to create a pooled database. Findings: To date, 13 studies from 7 countries have been included in the database. Ethics clearance and data sharing agreements have been secured for all studies and the SADEY 1.0 database is being assembled including ~ 8,000 participants. Discussion: SADEY will be used to address questions of global importance to public health policy and practice, for example – Is the mix of movement behaviours across the 24-hour day associated with healthy development?, What is the optimal mix of these behaviours?, and; What factors can be targeted to support young children in achieving the optimal mix of 24-hour movement behaviours? Additionally, SADEY seeks to develop and disseminate protocols, develop capacity on the device-based measurement of movement behaviours, and seeks partnerships with stakeholders that promote knowledge translation on movement behaviours to support healthy development among young children. [ABSTRACT FROM AUTHOR]

Background: Early identification and treatment of chronic disease is associated with better clinical outcomes, lower costs, and reduced hospitalisation. Primary care is ideally placed to identify patients at risk of, or in the early stages of, chronic disease and to implement prevention and early intervention measures. This paper evaluates the implementation of a technological intervention called Future Health Today that integrates with general practice EMRs to (1) identify patients at-risk of, or with undiagnosed or untreated, chronic kidney disease (CKD), and (2) provide guideline concordant recommendations for patient care. The evaluation aimed to identify the barriers and facilitators to successful implementation. Methods: Future Health Today was implemented in 12 general practices in Victoria, Australia. Fifty-two interviews with 30 practice staff were undertaken between July 2020 and April 2021. Practice characteristics were collected directly from practices via survey. Data were analysed using inductive and deductive qualitative analysis strategies, using Clinical Performance - Feedback Intervention Theory (CP-FIT) for theoretical guidance. Results: Future Health Today was acceptable, user friendly and useful to general practice staff, and supported clinical performance improvement in the identification and management of chronic kidney disease. CP-FIT variables supporting use of FHT included the simplicity of design and delivery of actionable feedback via FHT, good fit within existing workflow, strong engagement with practices and positive attitudes toward FHT. Context variables provided the main barriers to use and were largely situated in the external context of practices (including pressures arising from the COVID-19 pandemic) and technical glitches impacting installation and early use. Participants primarily utilised the point of care prompt rather than the patient management dashboard due to its continued presence, and immediacy and relevance of the recommendations on the prompt, suggesting mechanisms of compatibility, complexity, actionability and credibility influenced use. Most practices continued using FHT after the evaluation phase was complete. Conclusions: This study demonstrates that FHT is a useful and acceptable software platform that provides direct support to general practice in identifying and managing patients with CKD. Further research is underway to explore the effectiveness of FHT, and to expand the conditions on the platform. [ABSTRACT FROM AUTHOR]

Background: Recently, the use of inertial measurement units (IMUs) in quantitative gait analysis has been widely developed in clinical practice. Numerous methods have been developed for the automatic detection of gait events (GEs). While many of them have achieved high levels of efficiency in healthy subjects, detecting GEs in highly degraded gait from moderate to severely impaired patients remains a challenge. In this paper, we aim to present a method for improving GE detection from IMU recordings in such cases. Methods: We recorded 10-meter gait IMU signals from 13 healthy subjects, 29 patients with multiple sclerosis, and 21 patients with post-stroke equino varus foot. An instrumented mat was used as the gold standard. Our method detects GEs from filtered acceleration free from gravity and gyration signals. Firstly, we use autocorrelation and pattern detection techniques to identify a reference stride pattern. Next, we apply multiparametric Dynamic Time Warping to annotate this pattern from a model stride, in order to detect all GEs in the signal. Results: We analyzed 16,819 GEs recorded from healthy subjects and achieved an F1-score of 100%, with a median absolute error of 8 ms (IQR [3–13] ms). In multiple sclerosis and equino varus foot cohorts, we analyzed 6067 and 8951 GEs, respectively, with F1-scores of 99.4% and 96.3%, and median absolute errors of 18 ms (IQR [8–39] ms) and 26 ms (IQR [12–50] ms). Conclusions: Our results are consistent with the state of the art for healthy subjects and demonstrate a good accuracy in GEs detection for pathological patients. Therefore, our proposed method provides an efficient way to detect GEs from IMU signals, even in degraded gaits. However, it should be evaluated in each cohort before being used to ensure its reliability. [ABSTRACT FROM AUTHOR]

Background: Technology improves accessibility of psychological interventions for youth. An ecological momentary intervention (EMI) is a digital intervention geared toward intervening in daily life to enhance the generalizability and ecological validity, and to be able to intervene in moments most needed. Identifying working mechanisms of the use of ecological momentary interventions might generate insights to improve interventions. Methods: The present study investigates the working mechanisms of the use and acceptability of an ecological momentary intervention, named SELFIE, targeting self-esteem in youth exposed to childhood trauma, and evaluates under what circumstances these mechanisms of use and acceptability do or do not come into play. A realist evaluation approach was used for developing initial program theories (data: expert interviews and a stakeholders focus group), and subsequently testing (data: 15 interviews with participants, a focus group with therapists, debriefing questionnaire), and refining them. Results: The SELFIE intervention is offered through a smartphone application enabling constant availability of the intervention and thereby increasing accessibility and feasibility. When the intervention was offered on their personal smartphone, this enhanced a sense of privacy and less hesitance in engaging with the app, leading to increased disclosure and active participation. Further, the smartphone application facilitates the practice of skills in daily life, supporting the repeated practice of exercises in different situations leading to the generalizability of the effect. Buffering against technical malfunction seemed important to decrease its possible negative effects. Conclusions: This study enhanced our understanding of possible working mechanisms in EMIs, such as the constant availability supporting increased accessibility and feasibility, for which the use of the personal smartphone was experienced as a facilitating context. Hereby, the current study contributes to relatively limited research in this field. For the field to move forward, mechanisms of use, and acceptability of EMIs need to be understood. It is strongly recommended that alongside efficacy trials of an EMI on specific target mechanisms, a process evaluation is conducted investigating the working mechanisms of use. Trial registration: The current paper reports on a realist evaluation within the SELFIE trial (Netherlands Trial Register NL7129 (NTR7475)). [ABSTRACT FROM AUTHOR]

Background: There is inconclusive evidence for the effects of various leisure activities on attention performance in children. The literature reports inconsistent associations between activities such as physical activities or media use. To date, no study has thoroughly examined the various factors influencing attentional performance in a larger cohort of healthy children. This study aims to close this research gap. Methods: From 2018 to 2019, the Leipzig School Nutrition Study collected data from 1215 children and their families. The children report their dietary behavior (using CoCu- Questionnaire), especially their participation in school lunch and their breakfast habits, through a paper questionnaire. Furthermore, attention performance was assessed using a validated test (FAIR-2) at school. Data on physical activity, media consumption, family eating habits and socio-economic status (SES) were collected from parents using questionnaires. Associations between attention and influencing factors were estimated using hierarchical linear regression. Analyses were adjusted for age, SES, and school type. Results: Attending upper secondary schools (ßadj= 23.6, p < 0.001) and having a higher SES (ß= 1.28, p < 0.001) was associated with higher attention performance. Children doing leisure-time sports (ßadj= 4.18, p = 0.046) or reading books for at least one hour/weekday showed better attention performance (ßadj= 3.8, p = 0.040). Attention performance was also better in children having no electronic devices in the bedroom (ßadj= 13.0, p = 0.005) and in children whose parents limited their children's Internet access (ßadj= 5.2, p = 0.012). We did not find any association between nutritional habits and attention performance. Conclusions: We found that fostering modifiable habits such as reading and physical activity could enhance attention performance. These findings have substantial implications for the development of prevention and intervention programs that aim to improve attention in schoolchildren. It is important to note, however, that social status as a hardly modifiable factor also impacts attention performance. Therefore, interventions should address personal habits in a systemic approach considering the child's social status. Trial registration: The study is retrospectively registered with the German Clinical Trials Register (DRKS00017317, registration: 05-29-2019). [ABSTRACT FROM AUTHOR]

Background: To control resurging infectious diseases like mumps, it is necessary to resort to effective control and preventive measures. These measures include increasing vaccine coverage, providing the community with advice on how to reduce exposure, and closing schools. To justify such intervention, it is important to understand how well each of these measures helps to limit transmission. Methods: In this paper, we propose a simple SEILR (susceptible-exposed-symptomatically infectious-asymptomatically infectious-recovered) model by using a novel transmission rate function to incorporate temperature, humidity, and closing school factors. This new transmission rate function allows us to verify the impact of each factor either separately or combined. Using reported mumps cases from 2004 to 2018 in the mainland of China, we perform data fitting and parameter estimation to evaluate the basic reproduction number R 0 . As a wide range of one-dose measles, mumps, and rubella (MMR) vaccine programs in China started only in 2008, we use different vaccination proportions for the first Stage I period (from 2004 to 2008) and the second Stage II period (from 2009 to 2018). This allows us to verify the importance of higher vaccine coverage with a possible second dose of MMR vaccine. Results: We find that the basic reproduction number R 0 is generally between 1 and 3. We then use the Akaike Information Criteria to assess the extent to which each of the three factors contributed to the spread of mumps. The findings suggest that the impact of all three factors is substantial, with temperature having the most significant impact, followed by school opening and closing, and finally humidity. Conclusion: We conclude that the strategy of increasing vaccine coverage, changing micro-climate (temperature and humidity), and closing schools can greatly reduce mumps transmission. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is a heterogeneous neoplasm characterized by several subtypes. One of the most aggressive with high metastasis rates presents overexpression of the human epidermal growth factor receptor 2 (HER2). A quantitative evaluation of HER2 levels is essential for a correct diagnosis, selection of the most appropriate therapeutic strategy and monitoring the response to therapy. Results: In this paper, we propose the synergistic use of SERS and Raman technologies for the identification of HER2 expressing cells and its accurate assessment. To this end, we selected SKBR3 and MDA-MB-468 breast cancer cell lines, which have the highest and lowest HER2 expression, respectively, and MCF10A, a non-tumorigenic cell line from normal breast epithelium for comparison. The combined approach provides a quantitative estimate of HER2 expression and visualization of its distribution on the membrane at single cell level, clearly identifying cancer cells. Moreover, it provides a more comprehensive picture of the investigated cells disclosing a metabolic signature represented by an elevated content of proteins and aromatic amino acids. We further support these data by silencing the HER2 gene in SKBR3 cells, using the RNA interference technology, generating stable clones further analysed with the same combined methodology. Significant changes in HER2 expression are detected at single cell level before and after HER2 silencing and the HER2 status correlates with variations of fatty acids and downstream signalling molecule contents in the context of the general metabolic rewiring occurring in cancer cells. Specifically, HER2 silencing does reduce the growth ability but not the lipid metabolism that, instead, increases, suggesting that higher fatty acids biosynthesis and metabolism can occur independently of the proliferating potential tied to HER2 overexpression. Conclusions: Our results clearly demonstrate the efficacy of the combined SERS and Raman approach to definitely pose a correct diagnosis, further supported by the data obtained by the HER2 gene silencing. Furthermore, they pave the way to a new approach to monitor the efficacy of pharmacologic treatments with the aim to tailor personalized therapies and optimize patients' outcome. [ABSTRACT FROM AUTHOR]

Background: Individuals facing socioeconomic hardship experience higher than average rates of chronic disease, such as diabetes, with less access to evidence-based treatment. One solution to address these inequities is a team-based care (TBC) model, defined as one in which at least two providers work collaboratively with a patient and their caregiver(s) to make healthcare decisions. This paper seeks to describe the implementation of a TBC model within a safety-net healthcare setting and determine the extent to which it can be an effective, patient-centered approach to treating individuals with diabetes. Methods: Semi-structured interviews were conducted with staff (n = 15) and patients (n = 18). Clinical data were extracted from the electronic medical record of patients (n = 1,599) seen at a safety-net health system in Chicago, Illinois, United States. The mixed methods study was guided by implementation science and participatory research principles. Staff interviews were 60 min and covered patient care activities, work flow, perceived patient experience, and facilitators/barriers to care coordination. Patient interviews were 60 min and covered satisfaction, attitudes about diabetes management, quality of life, and technology. Patient interviews were co-analyzed by research staff and members of a patient advisory committee. Clinical data were collected at an index visit, two years prior and at one-year follow up (n = 1,599). Results: Four themes emerged from the interviews: (1) patients perceived the TBC model to be patient centered and of high quality; (2) technology can be an innovative tool, but barriers exist; (3) diabetes management is a complex process; and (4) staff communication enhances care coordination, but misinterpreting roles reduces care coordination. From pre-enrollment to the follow-up period, we found a statistically significant increase in missed visits, decrease in hemoglobin A1c (HbA1c), decrease in body mass index, and decrease in the percent of patients with high blood pressure. We found that each medical visit during the follow-up period was associated with an HbA1c decrease of 0.26 points. Conclusions: A TBC model is a patient-centered approach to providing care to patients with complex health needs, such as diabetes, patients were satisfied with the care they were receiving, and the model was associated with an improvement in clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Teenage childbearing is a common issue for young people's sexual and reproductive health in the world, particularly in low-income countries, and affects teenagers between the ages of 13 and 19. According to several academics, adolescent pregnancy accounts for the majority of Ethiopia's population increase, and there has been little effort to address this threat. This study aimed to determine the prevalence and associated factors of the time to teenage childbearing in Ethiopia. Method: This paper compares the results of the semi-parametric proportional hazard (PH), parametric PH, and accelerated failure time (AFT) models to find the model that best fits the data. The Akaike Information Criterion (AIC) was used to evaluate the performance of models examined in this investigation. Time to teenage childbearing was the study's outcome variable, while the analysis considered various independent variables. We analyze data from the 2016 National Demographic Health Survey to assess the influence of different risk factors on teenage pregnancy among Ethiopian women. Results: Out of the 10,274 teenagers (aged between 13 and 19) who participated in the 2016 survey, 6,430 (62.59%) were parents. The study findings revealed that these teenage parents were influenced by various time-related factors before becoming parents. The log-normal AFT model has the lowest AIC value and hence it is the best fit for this data. Results from this model indicated that significant factors influencing the time to teenage childbearing include the age of the household head, current age of the respondents, region, religion, educational attainment, wealth status, intention to use contraception, and recent sexual activity. Conclusion: This study reveals that 62.59% of surveyed teenagers aged 13 to 19 were parents. Various factors at both the individual and community levels: including the age of the household head, regional differences, religious affiliation, educational level, economic status, contraceptive intentions, and recent sexual activity, determine the time to teenage childbearing. Targeted interventions addressing these factors are essential for reducing teenage pregnancies and supporting adolescent parents effectively. [ABSTRACT FROM AUTHOR]

Background: The burden of early sexual engagement among youth is enormous. It directly raises the risk of sexually transmitted infections(STIs) and indirectly contributes to unintended pregnancy, unsafe abortion, premature childbirth, and psychosocial issues. The aim of this paper was to estimate the timing of sexual debut and examine the factors influencing the timing of first sexual intercourse following menarche among female youth aged between 15 and 24 in Uganda. Method: Self-reported data were extracted from the 2016 Uganda Demographic and Health Survey (UDHS), with a sub-sample of 7964 female youth from the individual woman file. Kaplan-Meier survival curves, decrement life-table analysis, and the discrete-time logit model were used to examine the timing of sexual debut and associated factors. Results: 67.4% of the female youth had experienced first sexual initiation. Overall, the meantime to sexual debut was 4.4 years and the median time was 4.3 years, and all the female youth had experienced first sexual initiation by the end of the twelfth year following menarche. Significant factors found to influence the timing of sexual initiation include having higher education level (OR = 0.724: 95% CI = 0.59–0.89; p = 0.003), residing in the Northern region (OR = 0.877:95% CI = 0.79–0.97, p = 0.012), being employed (OR = 1.085: 95% CI = 1.01–1.16; p = 0.021), and being literate (OR = 1.155; 95% CI = 1.07–1.25; p < 0.001). Conclusions: These findings are expected to be central in the bid to delay first sexual intercourse. Also they shed light on some of the factors associated with the timing of sexual debut which may be addressed at community level for non-school going youth and in schools, as school based prevention sexual and reproductive health programs. The findings highlight the need for future studies to collect more data to explore further the linkage between time to first debut since menarche and, mass media, religion, type of residence, and wealth index. [ABSTRACT FROM AUTHOR]

Background: Malaria transmission in Tanzania is driven by mosquitoes of the Anopheles gambiae complex and Anopheles funestus group. The latter includes An. funestus s.s., an anthropophilic vector, which is now strongly resistant to public health insecticides, and several sibling species, which remain largely understudied despite their potential as secondary vectors. This paper provides the initial results of a cross-country study of the species composition, distribution and malaria transmission potential of members of the Anopheles funestus group in Tanzania. Methods: Mosquitoes were collected inside homes in 12 regions across Tanzania between 2018 and 2022 using Centres for Disease Control and Prevention (CDC) light traps and Prokopack aspirators. Polymerase chain reaction (PCR) assays targeting the noncoding internal transcribed spacer 2 (ITS2) and 18S ribosomal DNA (18S rDNA) were used to identify sibling species in the An. funestus group and presence of Plasmodium infections, respectively. Where DNA fragments failed to amplify during PCR, we sequenced the ITS2 region to identify any polymorphisms. Results: The following sibling species of the An. funestus group were found across Tanzania: An. funestus s.s. (50.3%), An. parensis (11.4%), An. rivulorum (1.1%), An. leesoni (0.3%). Sequencing of the ITS2 region in the nonamplified samples showed that polymorphisms at the priming sites of standard species-specific primers obstructed PCR amplification, although the ITS2 sequences closely matched those of An. funestus s.s., barring these polymorphisms. Of the 914 samples tested for Plasmodium infections, 11 An. funestus s.s. (1.2%), and 2 An. parensis (0.2%) individuals were confirmed positive for P. falciparum. The highest malaria transmission intensities [entomological inoculation rate (EIR)] contributed by the Funestus group were in the north-western region [108.3 infectious bites/person/year (ib/p/y)] and the south-eastern region (72.2 ib/p/y). Conclusions: Whereas An. funestus s.s. is the dominant malaria vector in the Funestus group in Tanzania, this survey confirms the occurrence of Plasmodium-infected An. parensis, an observation previously made in at least two other occasions in the country. The findings indicate the need to better understand the ecology and vectorial capacity of this and other secondary malaria vectors in the region to improve malaria control. [ABSTRACT FROM AUTHOR]

Background: Effective testing for malaria, including the detection of infections at very low densities, is vital for the successful elimination of the disease. Unfortunately, existing methods are either inexpensive but poorly sensitive or sensitive but costly. Recent studies have shown that mid-infrared spectroscopy coupled with machine learning (MIRs-ML) has potential for rapidly detecting malaria infections but requires further evaluation on diverse samples representative of natural infections in endemic areas. The aim of this study was, therefore, to demonstrate a simple AI-powered, reagent-free, and user-friendly approach that uses mid-infrared spectra from dried blood spots to accurately detect malaria infections across varying parasite densities and anaemic conditions. Methods: Plasmodium falciparum strains NF54 and FCR3 were cultured and mixed with blood from 70 malaria-free individuals to create various malaria parasitaemia and anaemic conditions. Blood dilutions produced three haematocrit ratios (50%, 25%, 12.5%) and five parasitaemia levels (6%, 0.1%, 0.002%, 0.00003%, 0%). Dried blood spots were prepared on Whatman™ filter papers and scanned using attenuated total reflection-Fourier Transform Infrared (ATR-FTIR) for machine-learning analysis. Three classifiers were trained on an 80%/20% split of 4655 spectra: (I) high contrast (6% parasitaemia vs. negative), (II) low contrast (0.00003% vs. negative) and (III) all concentrations (all positive levels vs. negative). The classifiers were validated with unseen datasets to detect malaria at various parasitaemia levels and anaemic conditions. Additionally, these classifiers were tested on samples from a population survey in malaria-endemic villages of southeastern Tanzania. Results: The AI classifiers attained over 90% accuracy in detecting malaria infections as low as one parasite per microlitre of blood, a sensitivity unattainable by conventional RDTs and microscopy. These laboratory-developed classifiers seamlessly transitioned to field applicability, achieving over 80% accuracy in predicting natural P. falciparum infections in blood samples collected during the field survey. Crucially, the performance remained unaffected by various levels of anaemia, a common complication in malaria patients. Conclusion: These findings suggest that the AI-driven mid-infrared spectroscopy approach holds promise as a simplified, sensitive and cost-effective method for malaria screening, consistently performing well despite variations in parasite densities and anaemic conditions. The technique simply involves scanning dried blood spots with a desktop mid-infrared scanner and analysing the spectra using pre-trained AI classifiers, making it readily adaptable to field conditions in low-resource settings. In this study, the approach was successfully adapted to field use, effectively predicting natural malaria infections in blood samples from a population-level survey in Tanzania. With additional field trials and validation, this technique could significantly enhance malaria surveillance and contribute to accelerating malaria elimination efforts. [ABSTRACT FROM AUTHOR]

Background: Fentanyl test strips (FTS) are lateral flow immunoassay strips designed for detection of ng/mL levels of fentanyl in urine. In 2021, the US Centers for Disease Control and the Substance Abuse and Mental Health Administration stated that federal funds could be used for procurement of FTS for harm reduction strategies approved by the government such as drug checking. The market for FTS has expanded rapidly in the US and Canada. However, there is no regulatory oversight by either government to ensure proper function of FTS that are being marketed for drug checking. Main body: Many brands of FTS have rapidly entered the harm reduction market, creating concerns about the reproducibility and accuracy of their performance from brand to brand and lot to lot. Some examples are provided in this Comment. Similar problems with product quality were observed in the mid 2000's when lateral flow immunoassays for malaria were funded in many countries and again in 2020, when COVID-19 tests were in huge demand. The combination of high demand and low levels of regulation and enforcement led some manufacturers to join the goldrush without adequate field testing or quality assurance. We argue that the harm reduction community urgently needs to set a lot checking program in place. A set of simple protocols for conducting the tests and communicating the results have been developed, and are described in the following Perspectives paper in this issue. Conclusion: In the absence of governmental regulation and enforcement, the harm reduction community should implement a FTS lot checking program. Based on previous experience with the malaria diagnostic lot checking program, this inexpensive effort could identify products that are not suitable for harm reduction applications and provide valuable feedback to manufacturers. Dissemination of the results will help harm reduction organizations to ensure that FTS they use for drug checking are fit for the purpose. [ABSTRACT FROM AUTHOR]

Background: In the working population, there are risks of overload due to physical, mental, and emotional demands. No instrument is available in Spanish to measure these three types of work fatigue (WF) separately. This paper adapts the Three-Dimensional Work Fatigue Inventory (3D-WFI) (2015), which is of American origin and measures and differentiates these three different types of WF. It has adequate psychometric properties at its root, as do the subsequent German (2018), Lebanese (2022), and Chinese (2023) adaptations. Methods: A total of 1100 workers (average age = 40 years) from economic sectors such as security and transportation of valuables, secondary and university educational institutions, and healthcare centers participated. They responded to the 3D-WFI, the Health-Related Quality of Life Index, and the Individual Strength Checklist for concurrent validity effects, together with items with sociodemographic and lifestyle variables. Results: A confirmatory factor analysis with the total sample 3D-WFI supports its three-dimensionality; Cronbach's alpha and Omega values are adequate by dimensions: for physical work fatigue (α = 0.92, Ω = 0.92), for mental work fatigue (α = 0.94. Ω = 0.94), and emotional work fatigue (α = 0.95, Ω = 0.95). The 3D-WFI correlates significantly with the Checklist Individual Strength (0.743), and a pattern of significant relationships is found between WF and antecedent variables (e.g., being exposed to heat and noise, emotional labor, concentration, and workwear), as well as some consequences of WF (for example, mental health, absenteeism, work satisfaction, and sleep quality). Conclusions: We contribute here to the cross-cultural validity of the 3D-WFI, which can be used reliably and validly in the Chilean and probably Latin American working population. Some WF predictor variables are confirmed, as well as WF impacts on the absenteeism, health, and quality of life among workers. [ABSTRACT FROM AUTHOR]

Autism is a neurodevelopmental condition, behaviourally identified, which is generally characterised by social communication differences, and restrictive and repetitive patterns of behaviour and interests. It has long been claimed that it is more common in males. This observed preponderance of males in autistic populations has served as a focussing framework in all spheres of autism-related issues, from recognition and diagnosis through to theoretical models and research agendas. One related issue is the near total absence of females in key research areas. For example, this paper reports a review of over 120 brain-imaging studies of social brain processes in autism that reveals that nearly 70% only included male participants or minimal numbers (just one or two) of females. Authors of such studies very rarely report that their cohorts are virtually female-free and discuss their findings as though applicable to all autistic individuals. The absence of females can be linked to exclusionary consequences of autism diagnostic procedures, which have mainly been developed on male-only cohorts. There is clear evidence that disproportionately large numbers of females do not meet diagnostic criteria and are then excluded from ongoing autism research. Another issue is a long-standing assumption that the female autism phenotype is broadly equivalent to that of the male autism phenotype. Thus, models derived from male-based studies could be applicable to females. However, it is now emerging that certain patterns of social behaviour may be very different in females. This includes a specific type of social behaviour called camouflaging or masking, linked to attempts to disguise autistic characteristics. With respect to research in the field of sex/gender cognitive neuroscience, there is emerging evidence of female differences in patterns of connectivity and/or activation in the social brain that are at odds with those reported in previous, male-only studies. Decades of research have excluded or overlooked females on the autistic spectrum, resulting in the construction of inaccurate and misleading cognitive neuroscience models, and missed opportunities to explore the brain bases of this highly complex condition. A note of warning needs to be sounded about inferences drawn from past research, but if future research addresses this problem of male bias, then a deeper understanding of autism as a whole, as well as in previously overlooked females, will start to emerge. Plain Language Summary: Autism is a neurodevelopmental condition, behaviourally identified, which is generally characterised by social communication differences, and restrictive and repetitive patterns of behaviour and interests. It has long been claimed that it is more common in males, with oft-quoted ratios of 4M: 1F. This has been reflected in the development of diagnostic criteria for autism and, consequently, of measures of eligibility for autism research programmes, with females being (as is now emerging) disproportionately excluded. As outlined in this review, this issue has been particularly problematic in brain-based studies of autism. Many studies have only tested male autistic participants, or minimal numbers of autistic females. By default, sex differences were not examined. But the impression given by such research reports has commonly been that the findings would be applicable to all autistic individuals. Recent psychological and clinical research has shown that there are a significant number of autistic females who have been missed by traditional diagnostic practices. Their inclusion has increased their eligibility for autism research studies. With respect to brain research, it has become possible to devise studies with matched numbers of autistic females and males, and to replicate studies that have previously only tested males. Newly emerging findings from such studies are demonstrating that the 'robust' autism-related differences previously observed in autistic male-only cohorts do not fully generalise to autistic females. It will be necessary to exercise caution in drawing inferences from previous male-biased studies of the autistic brain. However, the identification and inclusion of previously excluded female autistic participants hopefully offers more accurate insights into this highly complex and heterogeneous condition. Highlights: Several decades of neuroimaging research into autism has been based almost entirely on males; even big data sets show strong evidence of male bias. There is clear evidence that autistic females are being excluded from the research process by failures in diagnostic practices that have been developed on male-biased cohorts. Models of autism which inform research protocols are based on male autism phenotypes; it appears to have been assumed that the substantially fewer females that are diagnosed will present with equivalent, if milder, patterns of autistic differences. Newly emerging findings from social cognitive neuroscience research studies investigating sex/gender differences in autistic behaviour and associated biological correlates are demonstrating that the 'robust' autism-related differences previously observed in autistic male-only cohorts do not fully generalise to autistic females. Autism research programmes should prioritise the exploration of sex/gender effects. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies have reported the potential impact of immune cells on kidney stone disease (KSD), but definitive causal relationships have yet to be established. The purpose of this paper is to elucidate the potential causal association between immune cells and KSD by Mendelian randomization (MR) analysis. Methods: In our study, a thorough two-sample Mendelian randomization (MR) analysis was performed by us to determine the potential causal relationship between immune cell traits and kidney stone disease. We included a total of four immune traits (median fluorescence intensity (MFI), relative cellular (RC), absolute cellular (AC), and morphological parameters (MP)), which are publicly available data. GWAS summary data related to KSD (9713 cases and 366,693 controls) were obtained from the FinnGen consortium. The primary MR analysis method was Inverse variance weighted. Cochran's Q test, MR Egger, and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) were used to assess the stability of the results. Results: After FDR correction, the CD8 on HLA DR + CD8br (OR = 0.95, 95% CI = 0.93–0.98, p-value = 7.20 × 10− 4, q-value = 0.088) was determined to be distinctly associated with KSD, and we also found other 25 suggestive associations between immune cells and KSD, of which 13 associations were suggested as protective factors and 12 associations were suggested as risk factors. There was no horizontal pleiotropy or significant heterogeneity in our MR analysis, as determined by the p-value results of our Cochrane Q-test, MR Egger's intercept test, and MR-PRESSO, which were all > 0.05. Conclusions: Our study has explored the potential causal connection between immune cells and KSD by Mendelian randomization analysis, thus providing some insights for future clinical studies. [ABSTRACT FROM AUTHOR]

Background: Automated hypothesis generation (HG) focuses on uncovering hidden connections within the extensive information that is publicly available. This domain has become increasingly popular, thanks to modern machine learning algorithms. However, the automated evaluation of HG systems is still an open problem, especially on a larger scale. Results: This paper presents a novel benchmarking framework Dyport for evaluating biomedical hypothesis generation systems. Utilizing curated datasets, our approach tests these systems under realistic conditions, enhancing the relevance of our evaluations. We integrate knowledge from the curated databases into a dynamic graph, accompanied by a method to quantify discovery importance. This not only assesses hypotheses accuracy but also their potential impact in biomedical research which significantly extends traditional link prediction benchmarks. Applicability of our benchmarking process is demonstrated on several link prediction systems applied on biomedical semantic knowledge graphs. Being flexible, our benchmarking system is designed for broad application in hypothesis generation quality verification, aiming to expand the scope of scientific discovery within the biomedical research community. Conclusions: Dyport is an open-source benchmarking framework designed for biomedical hypothesis generation systems evaluation, which takes into account knowledge dynamics, semantics and impact. All code and datasets are available at: https://github.com/IlyaTyagin/Dyport. [ABSTRACT FROM AUTHOR]

Background: In bioinformatics, interactions are modelled as networks, based on graph models. Generally, these support a single-layer structure which incorporates a specific entity (i.e., node) and only one type of link (i.e., edge). However, real-world biological systems consisting of biological objects belonging to heterogeneous entities, and these operate and influence each other in multiple contexts, simultaneously. Usually, node similarities are investigated to assess the relatedness between biological objects in a network of interest, and node embeddings are widely used for studying novel interaction from a topological point of view. About that, the state-of-the-art presents several methods for evaluating the node similarity inside a given network, but methodologies able to evaluate similarities between pairs of nodes belonging to different networks are missing. The latter are crucial for studies that relate different biological networks, e.g., for Network Alignment or to evaluate the possible evolution of the interactions of a little-known network on the basis of a well-known one. Existing methods are ineffective in evaluating nodes outside their structure, even more so in the context of multilayer networks, in which the topic still exploits approaches adapted from static networks. In this paper, we presented pyMulSim, a novel method for computing the pairwise similarities between nodes belonging to different multilayer networks. It uses a Graph Isomorphism Network (GIN) for the representative learning of node features, that uses for processing the embeddings and computing the similarities between the pairs of nodes of different multilayer networks. Results: Our experimentation investigated the performance of our method. Results show that our method effectively evaluates the similarities between the biological objects of a source multilayer network to a target one, based on the analysis of the node embeddings. Results have been also assessed for different noise levels, also through statistical significance analyses properly performed for this purpose. Conclusions: PyMulSim is a novel method for computing the pairwise similarities between nodes belonging to different multilayer networks, by using a GIN for learning node embeddings. It has been evaluated both in terms of performance and validity, reporting a high degree of reliability. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this paper is to conduct a bibliometric analysis to examine the research status and development trend of anterior cruciate ligament injury and reconstruction in children and adolescents over the past 20 years. Design: Descriptive Research. Methods: This study obtained information regarding studies on Anterior Cruciate Ligament Reconstruction in Children and Adolescents from the Web of Science Core Collection database. Visual and bibliometric analysis were conducted using VOSviewer, Origin 2022, Pajek64 5.18and Excel 2019. These analytic tools facilitated the analysis of various aspects, including countries/regions, institutions, authors, journals and keywords related to the research. Results: From 2003 to 2023, a total of 1328 articles were retrieved in WOS, and 637 articles were selected by two authors. The most productive institutions are Childrens Hosp Philadelphia, Kocher, ms. Their articles have the highest number of publications and citations. The American journal of sports medicine is the most frequently cited journal for articles on anterior cruciate ligament reconstruction in children and adolescents. The most common keywords used in these articles were "anterior cruciate ligament reconstruction", "injury, children, adolescent", and "skeletally immature patients". Conclusions: This study provides valuable insights into the research focus of anterior cruciate ligament reconstruction in children and adolescents. In recent years, there has been significant attention paid to areas of "the return to sport, re-repture rate and functional recovery after anterior cruciate ligament reconstruction" in this specific population. These aspects have emerged as key directions for future research in this field. [ABSTRACT FROM AUTHOR]

Background: Cesarean section-induced postpartum hemorrhage (PPH) potentially causes anemia and hypovolemic shock in pregnant women. Hence, it is helpful for obstetricians and anesthesiologists to prepare pre-emptive prevention when predicting PPH occurrence in advance. However, current works on PPH prediction focus on whether PPH occurs rather than assessing PPH amount. To this end, this work studies quantitative PPH prediction with machine learning (ML). Methods: The study cohort in this paper was selected from individuals with PPH who were hospitalized at Shijiazhuang Obstetrics and Gynecology Hospital from 2020 to 2022. In this study cohort, we built a dataset with 6,144 subjects covering clinical parameters, anesthesia operation records, laboratory examination results, and other information in the electronic medical record system. Based on our built dataset, we exploit six different ML models, including logistic regression, linear regression, gradient boosting, XGBoost, multilayer perceptron, and random forest, to automatically predict the amount of bleeding during cesarean section. Eighty percent of the dataset was used as model training, and 20 % was used for verification. Those ML models are constantly verified and improved by root mean squared error(RMSE) and mean absolute error(MAE). Moreover, we also leverage the importance of permutation and partial dependence plot (PDP) to discuss their feasibility. Result: The experiment results show that random forest obtains the highest accuracy for PPH amount prediction compared to other ML methods. Random forest reaches the mean absolute error of 21.7, less than 5.4 % prediction error. It also gains the root mean squared error of 33.75, less than 9.3 % prediction error. On the other hand, the experimental results also disclose indicators that contributed most to PPH prediction, including Ca, hemoglobin, white blood cells, platelets, Na, and K. Conclusion: It effectively predicts the amount of PPH during a cesarean section by ML methods, especially random forest. With the above insight, ML predicting PPH amounts provides early warning for clinicians, thus reducing complications and improving cesarean sections' safety. Furthermore, the importance of ML and permutation, complemented by incorporating PDP, promises to provide clinicians with a transparent indication of individual risk prediction. [ABSTRACT FROM AUTHOR]

Background: Pattern mining techniques are helpful tools when extracting new knowledge in real practice, but the overwhelming number of patterns is still a limiting factor in the health-care domain. Current efforts concerning the definition of measures of interest for patterns are focused on reducing the number of patterns and quantifying their relevance (utility/usefulness). However, although the temporal dimension plays a key role in medical records, few efforts have been made to extract temporal knowledge about the patient's evolution from multivariate sequential patterns. Methods: In this paper, we propose a method to extract a new type of patterns in the clinical domain called Jumping Diagnostic Odds Ratio Sequential Patterns (JDORSP). The aim of this method is to employ the odds ratio to identify a concise set of sequential patterns that represent a patient's state with a statistically significant protection factor (i.e., a pattern associated with patients that survive) and those extensions whose evolution suddenly changes the patient's clinical state, thus making the sequential patterns a statistically significant risk factor (i.e., a pattern associated with patients that do not survive), or vice versa. Results: The results of our experiments highlight that our method reduces the number of sequential patterns obtained with state-of-the-art pattern reduction methods by over 95%. Only by achieving this drastic reduction can medical experts carry out a comprehensive clinical evaluation of the patterns that might be considered medical knowledge regarding the temporal evolution of the patients. We have evaluated the surprisingness and relevance of the sequential patterns with clinicians, and the most interesting fact is the high surprisingness of the extensions of the patterns that become a protection factor, that is, the patients that recover after several days of being at high risk of dying. Conclusions: Our proposed method with which to extract JDORSP generates a set of interpretable multivariate sequential patterns with new knowledge regarding the temporal evolution of the patients. The number of patterns is greatly reduced when compared to those generated by other methods and measures of interest. An additional advantage of this method is that it does not require any parameters or thresholds, and that the reduced number of patterns allows a manual evaluation. [ABSTRACT FROM AUTHOR]

This comprehensive review explores the evolving landscape of sperm selection techniques within the realm of Assisted Reproductive Technology (ART). Our analysis delves into a range of methods from traditional approaches like density gradient centrifugation to advanced techniques such as Magnetic-Activated Cell Sorting (MACS) and Intracytoplasmic Morphologically Selected Sperm Injection (IMSI). We critically assess the efficacy of these methods in terms of sperm motility, morphology, DNA integrity, and other functional attributes, providing a detailed comparison of their clinical outcomes. We highlight the transition from conventional sperm selection methods, which primarily focus on physical characteristics, to more sophisticated techniques that offer a comprehensive evaluation of sperm molecular properties. This shift not only promises enhanced prediction of fertilization success but also has significant implications for improving embryo quality and increasing the chances of live birth. By synthesizing various studies and research papers, we present an in-depth analysis of the predictability of different sperm selection procedures in ART. The review also discusses the clinical applicability of these methods, emphasizing their potential in shaping the future of assisted reproduction. Our findings suggest that the integration of advanced sperm selection strategies in ART could lead to more cost-effective treatments with reduced duration and higher success rates. This review aims to provide clinicians and researchers in reproductive medicine with comprehensive insights into the current state and future prospects of sperm selection technologies in ART. [ABSTRACT FROM AUTHOR]

Background: Two out of three family caregivers are female. However, current trends show that men are more likely to undertake caregiving duties, yet female caregivers report a higher burden. This paper analyzed data from long-term family caregivers to determine whether, under similar circumstances, gender differences in caregiving persist. We examined whether the observed gender gap affects caregivers' satisfaction with their health and quality of life. Methods: We analyze cross-sectional data from family caregivers of persons with spinal cord injury (SCI) in Switzerland. The data provides comprehensive information about the time and type of weekly tasks family caregivers undertake. To determine differences in caregiving related to gender, we balanced the characteristics of the caregiver and the cared-for person using a propensity score kernel matching. With the balanced sample, we estimated how the observed differences in caregiving varied across cohorts using a Poisson regression. Results: Under similar circumstances, male and female caregivers invest similar time in caregiving. This result holds for 21 caregiving tasks, except for household chores, where women spent, on average, four more hours per week than male caregivers. Despite these differences, female caregivers report a quality of life and satisfaction with their health that is similar to that of male caregivers. Conclusion: Gender differences in caregiving narrow over time, except for household chores, where female caregivers continue to spend significantly more hours than male caregivers. Measures designed for family caregivers must consider these gender differences, as the support needs of female caregivers can differ greatly from those of male caregivers. [ABSTRACT FROM AUTHOR]

Background: Changes in demographics with an older population, the illness panorama with increasing prevalence of non-communicable diseases, and the shift from hospital care to home-based care place demand on primary health care, which requires multiprofessional collaboration and team-based organization of work. The COVID-19 pandemic affected health care in various ways, such as heightened infection control measures, changing work practices, and increased workload. Objectives: This study aimed to investigate the association between primary care practices' organization, and quality and safety changes during the COVID-19 pandemic. Design: Data were collected from 38 countries in a large online survey, the PRICOV-19 study. For this paper, the participating practices were categorized as "Only GPs", comprising practices with solely general practitioners (GPs) and/or GP trainees, without any other health care professionals (n = 1,544), and "Multiprofessional," comprising practices with at least one GP or GP trainee and one or more other health professionals (n = 3,936). Results: Both categories of practices improved in infection control routines when compared before and during the COVID-19 pandemic. A larger proportion of the multiprofessional practices changed their routines to protect vulnerable patients. Telephone triage was used in more "Multiprofessional" practices, whereas "Only GPs" were more likely to perform video consultations as an alternative to physical visits. Both types of practices reported that the time to review new guidelines and scientific literature decreased during the pandemic. However, both had more meetings to discuss directives than before the pandemic. Conclusions: Multiprofessional teams were keener to introduce changes to the care organization to protect vulnerable patients. However, practices with only GPs were found to be more aligned with video consultations, perhaps reflecting the close patient-doctor relationship. In contrast, telephone triage was used more in multiprofessional teams. [ABSTRACT FROM AUTHOR]

Gothic literature—a genre brimming with madness, supernaturalism, and psychological terror—offers innumerable case studies potentially representing how psychiatric patients perceive their treatment from healthcare professionals. Charlotte Perkins Gilman's famous 1892 short story "The Yellow Wallpaper" offers a poignant example of this through its fictional narrator, a diarist many interpret to be suffering from postpartum depression. The fiction here does not stray far from reality: Gilman orchestrated her diarist's experience to mirror her own, as both real author and fictional character suffocated from a melancholy only made worse by their physicians' insistence on following the "Rest Cure." While this instruction to cease all work and activity was a prevalent depression treatment at the time, Gilman, through "The Yellow Wallpaper," reveals how the intervention ultimately harmed more than helped because it overlooked her—and, by extension, her fictional diarist's— unique needs and identities. Today, while the ineffective Rest Cure no longer exists, applying observations from "The Yellow Wallpaper" to clinical research calls attention to underrepresentation in treatment development, a costly problem that could be mitigated by mindful incorporation of intersectionality theory into study designs. [ABSTRACT FROM AUTHOR]

Background: This paper reports the first case of basaloid squamous cell carcinoma clinically and radiologically masquerading as a head and neck paraganglioma. Case presentation: A 66-year-old Sinhalese male with unilateral hearing impairment and 7th–12th (excluding 11th) cranial nerve palsies was diagnosed radiologically with a head and neck paraganglioma by magnetic resonance imaging of the brain, which revealed a hypointense and hyperintense punctate mass centered at the jugular fossa with intracranial extension. The ascending pharyngeal artery, recognized as the major feeder, was embolized by percutaneous embolization following digital subtraction angiography. Gross total resection of the tumor was followed by an uneventful postoperative recovery. Combined immunohistochemistry and histopathological morphology revealed a basaloid squamous cell carcinoma, following which the patient completed radiotherapy and is at 3-month follow-up currently. Conclusion: This case report discusses the diagnostic pitfalls and management challenges of this rare entity on the basis of prior evidence, as well as a literature review and clinical and surgical analysis. [ABSTRACT FROM AUTHOR]

Background: Surgical handover is associated with a significant risk of care failures. Existing research displays methodological deficiencies and little consensus on the outcomes that should be used to evaluate interventions in this area. This paper reports a protocol to develop a core outcome set (COS) to support standardisation, comparability, and evidence synthesis in future studies of surgical handover between doctors. Methods: This study adheres to the Core Outcome Measures in Effectiveness Trials (COMET) initiative guidance for COS development, including the COS-Standards for Development (COS-STAD) and Reporting (COS-STAR) recommendations. It has been registered prospectively on the COMET database and will be led by an international steering group that includes surgical healthcare professionals, researchers, and patient and public partners. An initial list of reported outcomes was generated through a systematic review of interventions to improve surgical handover (PROSPERO: CRD42022363198). Findings of a qualitative evidence synthesis of patient and public perspectives on handover will augment this list, followed by a real-time Delphi survey involving all stakeholder groups. Each Delphi participant will then be invited to take part in at least one online consensus meeting to finalise the COS. Ethics and dissemination: This study was approved by the Royal College of Surgeons in Ireland (RCSI) Research Ethics Committee (202309015, 7th November 2023). Results will be presented at surgical scientific meetings and submitted to a peer-reviewed journal. A plain English summary will be disseminated through national websites and social media. The authors aim to integrate the COS into the handover curriculum of the Irish national surgical training body and ensure it is shared internationally with other postgraduate surgical training programmes. Collaborators will be encouraged to share the findings with relevant national health service functions and national bodies. Discussion: This study will represent the first published COS for interventions to improve surgical handover, the first use of a real-time Delphi survey in a surgical context, and will support the generation of better-quality evidence to inform best practice. Trial registration: Core Outcome Measures in Effectiveness Trials (COMET) initiative 2675. http://www.comet-initiative.org/Studies/Details/2675. [ABSTRACT FROM AUTHOR]

Background: Metastasis is one of the main factors leading to the high mortality rate of gastric cancer. The current monitoring methods are not able to accurately monitor gastric cancer metastasis. Methods: In this paper, we constructed a new type of hollow Mn 3 O 4 nanocomposites, Mn 3 O 4 @HMSN-Cy7.5-FA, which had a size distribution of approximately 100 nm and showed good stability in different liquid environments. The in vitro magnetic resonance imaging (MRI) results show that the nanocomposite has good response effects to the acidic microenvironment of tumors. The acidic environment can significantly enhance the contrast of T 1 -weighted MRI. The cellular uptake and endocytosis results show that the nanocomposite has good targeting capabilities and exhibits good biosafety, both in vivo and in vitro. In a gastric cancer nude mouse orthotopic metastatic tumor model, with bioluminescence imaging's tumor location information, we realized in vivo MRI/fluorescence imaging (FLI) guided precise monitoring of the gastric cancer orthotopic and metastatic tumors with this nanocomposite. Results: This report demonstrates that Mn 3 O 4 @HMSN-Cy7.5-FA nanocomposites is a promising nano-diagnostic platform for the precision diagnosis and therapy of gastric cancer metastasis in the future. Conclusions: In vivo MRI/FLI imaging results show that the nanocomposites can achieve accurate monitoring of gastric cancer tumors in situ and metastases. BLI's tumor location information further supports the good accuracy of MRI/FLI dual-modality imaging. The above results show that the MHCF NPs can serve as a good nano-diagnostic platform for precise in vivo monitoring of tumor metastasis. This nanocomposite provides more possibilities for the diagnosis and therapy of gastric cancer metastases. [ABSTRACT FROM AUTHOR]

Background: Geographical environments influence people's active mobility behaviors, contributing to their physical and mental health. The use of Virtual Reality (VR) in experimental research can unveil new insights into the relationship between exposure to geographic environments and active mobility behaviors. This systematic review aims to (1) identify environmental attributes investigated in relation with walking and cycling, using VR, (2) assess their impacts on active mobility behaviors and attitudes, and (3) identify research gaps, strengths and limitations in VR-based experimental research. Methods: Articles published between January 2010 and February 2022 within five databases (PubMed, Scopus, EBSCO, IEEE Xplore, and Cochrane Library) were explored using three keywords and their synonyms: Virtual Reality, Active mobility behavior, and Geographical environments. Studies focusing on indoor environments, driving simulation, disease-specific groups, non-relevant disciplines (e.g. military, emergency evacuation), VR methodology/software optimization, and those with static participants' involvement were excluded. The full protocol is available from PROSPERO (ID = CRD42022308366). Results: Out of 3255 articles, 18 peer-reviewed papers met the selection criteria, mostly focusing on walking (83%). Most studies used head-mounted displays (94%) and relied on convenience sampling (72% below 100 participants). Both static (33%) and dynamic (45%) environmental attributes have been investigated, with only 22% of them simultaneously in the same virtual environment. Greenness and crowd density were the most frequent attributes, rather consistently associated with emotional states and movement behaviors. Few studies have taken into account participant's previous VR experience (33%) and cybersickness (39%) while both are likely to affect an individual's perception and behavior. Conclusions: Future research should explore a broader range of environmental attributes, including static and dynamic ones, as well as a more complex integration of these attributes within a single experiment to mimic the effect of realistic environments on people's active mobility behaviors and attitudes. Larger and more diverse population samples are deemed required to improve result generalizability. Despite methodological challenges, VR emerges as a promising tool to disentangle the effect of complex environments on active mobility behaviors. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Excess glucose alone depress young mesenchymal stromal/stem cell osteogenesis and mitochondria activity within hours/days via NAD+/ SIRT1 axis" published in the Journal of Biomedical Science. The correction addresses two figures in the original paper that still have revision red lettering on some legends. Additionally, the funding section of the article has been updated to reflect the correct year-based numbering of two grants. The original publication has been corrected. [Extracted from the article]

Accelerometers, devices that measure body movements, have become valuable tools for studying the fragmentation of rest-activity patterns, a core circadian rhythm dimension, using metrics such as inter-daily stability (IS), intradaily variability (IV), transition probability (TP), and self-similarity parameter (named α ). However, their use remains mainly empirical. Therefore, we investigated the mathematical properties and interpretability of rest-activity fragmentation metrics by providing mathematical proofs for the ranges of IS and IV, proposing maximum likelihood and Bayesian estimators for TP, introducing the activity balance index (ABI) metric, a transformation of α , and describing distributions of these metrics in real-life setting. Analysis of accelerometer data from 2,859 individuals (age=60-83 years, 21.1% women) from the Whitehall II cohort (UK) shows modest correlations between the metrics, except for ABI and α . Sociodemographic (age, sex, education, employment status) and clinical (body mass index (BMI), and number of morbidities) factors were associated with these metrics, with differences observed according to metrics. For example, a difference of 5 units in BMI was associated with all metrics (differences ranging between -0.261 (95% CI -0.302, -0.220) to 0.228 (0.18, 0.268) for standardised TP rest to activity during the awake period and TP activity to rest during the awake period, respectively). These results reinforce the value of these rest-activity fragmentation metrics in epidemiological and clinical studies to examine their role for health. This paper expands on a set of methods that have previously demonstrated empirical value, improves the theoretical foundation for these methods, and evaluates their empirical use in a large dataset. [ABSTRACT FROM AUTHOR]

Background: Drug design is a challenging and important task that requires the generation of novel and effective molecules that can bind to specific protein targets. Artificial intelligence algorithms have recently showed promising potential to expedite the drug design process. However, existing methods adopt multi-objective approaches which limits the number of objectives. Results: In this paper, we expand this thread of research from the many-objective perspective, by proposing a novel framework that integrates a latent Transformer-based model for molecular generation, with a drug design system that incorporates absorption, distribution, metabolism, excretion, and toxicity prediction, molecular docking, and many-objective metaheuristics. We compared the performance of two latent Transformer models (ReLSO and FragNet) on a molecular generation task and show that ReLSO outperforms FragNet in terms of reconstruction and latent space organization. We then explored six different many-objective metaheuristics based on evolutionary algorithms and particle swarm optimization on a drug design task involving potential drug candidates to human lysophosphatidic acid receptor 1, a cancer-related protein target. Conclusion: We show that multi-objective evolutionary algorithm based on dominance and decomposition performs the best in terms of finding molecules that satisfy many objectives, such as high binding affinity and low toxicity, and high drug-likeness. Our framework demonstrates the potential of combining Transformers and many-objective computational intelligence for drug design. [ABSTRACT FROM AUTHOR]

Background: Electronic nicotine delivery systems (ENDS) offer a substantial harm reduction opportunity for adults who smoke and are unlikely to quit. However, a major concern about ENDS is their use by non-smoking youth, and particularly whether ENDS are acting as a "gateway" that leads youth to later start smoking cigarettes. However, evidence for the gateway hypothesis can be interpreted in alternative ways, e.g. that youth who have certain characteristics were already predisposed to use both ENDS and cigarettes ("common liability" explanation). Aims: This commentary provides an evaluation of the gateway hypothesis that is accessible by a lay audience. This paper first reviews and evaluates the evidence interpreted as supporting the gateway hypothesis. Important alternative explanations (i.e., common liability) are discussed, as are different types of evidence (i.e., population-level trends) that can help differentiate between these competing explanations. Overview: Evidence for the gateway hypothesis is based on the finding that youth who use ENDS are more likely to also smoke cigarettes. However, this evidence suffers from an important flaw: these studies fail to fully account for some youths' pre-existing tendency to use products containing nicotine, and inappropriately interpret the results as ENDS use causing some youth to smoke. Common liability studies suggest that ENDS use does not, in and of itself, directly cause youth to later smoke cigarettes, beyond their pre-existing tendency to use products containing nicotine. Population-level trends show that youth cigarette smoking declined faster after ENDS use became common, which contradicts the central prediction of the gateway hypothesis (i.e. that youth smoking would be more common following ENDS uptake, than otherwise be expected). Conclusion: Evidence offered in support of the gateway hypothesis does not establish that ENDS use causes youth to also smoke cigarettes. Instead, this evidence is better interpreted as resulting from a common liability to use both ENDS and cigarettes. Population-level trends are inconsistent with the gateway hypothesis, and instead are consistent with (but do not prove) ENDS displacing cigarettes. Policies based on misinterpreting a causal gateway effect may be ineffective at best, and risk the negative unintended consequence of increased cigarette smoking. [ABSTRACT FROM AUTHOR]

Background: We sought to determine whether the Good School Toolkit-Primary violence prevention intervention was associated with reduced victimisation and perpetration of peer and intimate partner violence four years later, and if any associations were moderated by sex and early adolescent: family connectedness, socio-economic status, and experience of violence outside of school. Methods: Drawing on schools involved in a randomised controlled trial of the intervention, we used a quasi-experimental design to compare violence outcomes between those who received the intervention during our trial (n = 1388), and those who did not receive the intervention during or after the trial (n = 522). Data were collected in 2014 (mean age 13.4, SD 1.5 years) from participants in 42 schools in Luwero District, Uganda, and 2018/19 from the same participants both in and out of school (mean age 18, SD: 1.77 years). We compared children who received the Good School Toolkit-Primary, a whole school violence prevention intervention, during a randomised controlled trial, to those who did not receive the intervention during or after the trial. Outcomes were measured using items adapted from the International Society for the Prevention of Child Abuse and Neglect Child Abuse Screening Tool-Child Institutional. We used mixed-effect multivariable logistic regression, with school fitted as a random-effect to account for clustering. Results: 1910 adolescents aged about 16–19 years old were included in our analysis. We found no evidence of an average long-term intervention effect on our primary outcome, peer violence victimization at follow-up (aOR = 0.81, 95%CI = 0.59–1.11); or for any secondary outcome. However, exposure to the intervention was associated with: later reductions in peer violence, for adolescents with high family connectedness (aOR = 0.70, 95% CI 0.49 to 0.99), but not for those with low family connectedness (aOR = 1.07, 95% CI 0.69 to 1.6; p-interaction = 0.06); and reduced later intimate partner violence perpetration among males with high socio-economic status (aOR = 0.32, 95%CI 0.11 to 0.90), but not low socio-economic status (aOR = 1.01 95%CI 0.37 to 2.76, p-interaction = 0.05). Conclusions: Young adolescents in connected families and with higher socio-economic status may be better equipped to transfer violence prevention skills from primary school to new relationships as they get older. Trial registration: Clinicaltrials.gov, NCT01678846, registration date 24 August 2012. Protocol for this paper: https://www.researchprotocols.org/2020/12/e20940. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the leading cause of death from cancer in women and is a major public health problem worldwide. Despite the lower incidence rates of breast cancer in resource-limited settings, especially sub-Saharan Africa, there is a higher mortality rate compared to high-resource countries where the disease has a higher incidence. This makes breast cancer the second deadliest cancer in African women. These poor results reflect the weakness in public health policies. The aim of this paper is to contribute to the effective control of breast cancer by designing a framework for a comprehensive and systemic analysis of these policies in Sub-Saharan Africa. Methods: This research is based on a literature review that adopted a systematic approach followed by a modified policy Delphi involving breast cancer experts in Sub-Saharan Africa. We included narrative reviews and systematic reviews/meta-analyses published between 2015 and 2022 as well as official documents in the analysis. We integrated the World Health Organization's health system building blocks with Walt and Gilson's policy analysis triangle to analyse the information collected and develop our analytical framework. Results: A total of 22 reviews and documents were included in the study. Sixteen breast cancer experts from Sub-Saharan Africa participated in the first Delphi round, and nine participated in the second round. The different components identified for a comprehensive and systemic analysis of effective breast cancer policies can be classified into policy content divided according to the health system building blocks and related policy processes; individual, organized national and international policy stakeholders; and policy contexts. Conclusion: This study enabled the design of a framework suitable for the comprehensive and systemic analysis of breast cancer control policies in Sub-Saharan Africa. This framework can be used as a checklist for stakeholders to guide the planning, implementation and evaluation of policies and specific breast cancer control programmes at the national and facility levels. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B is endemic amongst the Australian Aboriginal population in the Northern Territory. A participatory action research project identified the lack of culturally appropriate education tools and led to the development of the "Hep B Story" app in the Aboriginal language Yolŋu Matha. This paper describes a formal evaluation of the app's first version, which informed improvements and translation into a further ten Aboriginal languages. Methods: The evaluation employed Participatory Action Research (PAR) principles to work within Indigenous research methodologies and prioritise Indigenous knowledge to improve the app iteratively. Semi-structured interviews and focus groups were conducted across the Northern Territory with 11 different language groups. Local Community Based Researchers and Aboriginal Research team members coordinated sessions. The recorded, translated conversations were transcribed verbatim and thematically analysed using an inductive and deductive approach. Results: Between November 2018 and September 2020, 94 individuals from 11 language groups participated in 25 semi-structured interviews and 10 focus groups. All participants identified as Aboriginal. Most participants felt the app would be culturally appropriate for Aboriginal communities in the Northern Territory and improve knowledge surrounding hepatitis B. The information gathered from these interviews allowed for identifying five main themes: support for app, relationships, concept versus language, shame, and perceptions of images, along with errors that required modification. Conclusions: A "real-life" evaluation of the app was comprehensively completed using a PAR approach blended with Indigenous research methods. This evaluation allowed us to develop an updated and enhanced version of the app before creating the additional ten language versions. An iterative approach alongside strong community engagement was pivotal in ensuring the app's cultural safety and appropriateness. We recommend avoiding the use of knowledge-based evaluations in an Aboriginal setting to ensure relevant and culturally appropriate feedback is obtained. [ABSTRACT FROM AUTHOR]

Background: There is limited research examining the views of general practice pharmacists (GPPs) on their role and their impact in general practice. The aim of this study was to explore GPPs' views regarding this role and its potential impact within general practice in Northern Ireland (NI). Methods: A paper-based self-administered questionnaire was mailed to 319 general practices in NI in 2022, directed to the GPP who spent most time at the practice. A variety of closed and open questions were included in six sections. Responses to closed questions were analysed descriptively whilst open question responses were analysed using content analysis. To ascertain associations between variables (e.g. GPP prescribing status, working arrangements and aspects of collaboration with GPPs), Fisher's exact test was employed with an a priori significance level of p < 0.05. Results: 155 responses were received equating to a response rate of 48.5%. Most participants (72.3%) were female, independent prescribers (71%), and 64.5% were currently using their independent prescriber qualification. Services that were provided by most GPPs were medication reconciliation (99.4%) and medication reviews (97.4%). The most common method of communication between GPPs and general practitioners (GPs) was face-to-face (89.0%). Telephone was the most common method of communication between GPPs, community pharmacists (97.4%) and patients (98.7%). Most GPPs (> 80%) showed positive attitudes towards collaboration with GPs and those who worked in multiple practices were more likely to agree with the Attitudes Towards Collaboration Instrument for pharmacists (ATCI-P) statements compared to those who worked in a single practice (p < 0.05). Less than 40% (36.8%) of GPPs agreed that patients were aware of the role they provided. The majority of GPPs (80.6%) expressed positive views on their impact on primary care. Analysis of the free-text comments revealed the need for more GPP patient-facing activities, GPP-specific training, and promotion of the GPP role. Conclusion: The findings indicated that GPPs had largely positive views about their role and their impact on primary care. The results may be helpful for practices and service commissioners. Further research is necessary to explore the perspectives of patients regarding the role of the GPP and to enhance patients' awareness of the GPP. [ABSTRACT FROM AUTHOR]

Background: Despite the extensive benefits associated with the provision of comprehensive sexuality education (CSE) within a school context, many initial teacher training programs inadequately prepare pre-service teachers to deliver this content. Programs that do provide such instruction do not routinely share details of their curriculum, syllabi, or evaluation data. Methods: This paper outlines the structure of an Australian undergraduate course for pre-service teachers that focuses on instruction in CSE. This course spans twelve teaching weeks, aligns with evidence-based principles for sexuality education, prioritises experiential learning and requires students to complete authentic, practical assessment tasks. Formative, process, and short-term impact evaluation data, based upon five years of delivery, are described. Results: Students completing this course reported statistically significant improvements in attitudes associated with CSE and comfort in facilitating all domains of learning (knowledge, attitudes, skills). Conclusions: Positive process and short-term impact data provide strong evidence for the provision of CSE to pre-service teachers, regardless of future teaching speciality. Proposed amendments include the creation of a fully online tuition pattern and an expansion of content to incorporate other audiences, such as community-based educators. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) infections can cause cancers of the cervix, vagina, vulva, penis, anus, and oropharynx. The most recently approved HPV vaccine, Gardasil-9, protects against HPV infection and can prevent HPV-associated invasive cancers. However, Gardasil-9 is one of the most underused vaccines in the US today. Young adults are at risk for HPV infection, but many are not vaccinated. This study uses a randomized controlled trial (RCT) to test an innovative multilevel intervention to increase HPV vaccination rates among young adults. In this paper, we describe the research protocol. Methods: The study uses a two by three factorial design. A total of 1200 young adults in Texas, age 18–26 years, who have not been previously fully vaccinated against HPV will be randomly assigned to one of six conditions to receive: (1) standard CDC information about HPV vaccination (control); (2) video narratives about HPV vaccination; (3) written narratives about HPV vaccination; or (4–6) enhanced access to HPV vaccine combined with (4) standard CDC information, (5) video narratives, or (6) written narratives. The two primary outcomes are the rate of HPV vaccination initiation by 3-month follow-up and rate of HPV vaccination completion by 9-month follow-ups. We will determine the impact of the individual level intervention (i.e., persuasive narratives through video or written format), the systemic level intervention (i.e., enhanced access to HPV vaccines), and the combination of both levels, on HPV vaccination initiation and completion. We will also use purposive sampling to select participants to take part in semi-structured interviews/focus groups to better understand the mechanisms of the intervention. Discussion: Recruitment and data collection began in March 2022. We expect to complete data collection by March 2026. We expect that narratives, enhanced access, and the combination of both will improve HPV vaccination initiation and completion rates among young adults. If proven successful, these individual- and system-level interventions can be easily disseminated in regions with low HPV vaccination rates to improve HPV vaccination, and ultimately decrease HPV-related cancer burden. Trial Registration: NCT05057312. [ABSTRACT FROM AUTHOR]

Background: Many children with rheumatic and musculoskeletal diseases are unrecognized. Identifying these children requires health care provider awareness, knowledge, and skills to recognize disease features and how (and when) to refer to specialist care. The aim of this paper is to highlight the need for better access to health care, review the essential role that education and virtual care play to address unmet need in low resource areas and especially to expand workforce capacity. Using collaborative partnerships, virtual platforms, and innovative assessment methods, musculoskeletal care and education can be delivered to reach a greater audience than ever before. Increased awareness through multiple initiatives and readily available resources are imperative to improve global rheumatology care. Conclusion: The needs of children with rheumatic diseases and musculoskeletal conditions are vastly underserved around the world resulting in preventable morbidity and mortality. Expanded implementation of virtual education and e-health care platforms provides an opportunity to increase access to care for children globally. [ABSTRACT FROM AUTHOR]

The increased use of biofuels in place of fossil fuels is one strategy to support the transition to net-zero carbon emissions, particularly in transport applications. However, expansion of the use of 1st generation crops as feedstocks is unsustainable due to the conflict with food use. The use of the lignocellulosic fractions from plants and/or co-products from food production including food wastes could satisfy the demand for biofuels without affecting the use of land and the availability of food, but organisms which can readily ferment all the carbohydrates present in these feedstocks often suffer from more severe bioethanol inhibition effects than yeast. This paper demonstrates the potential of hot gas microbubbles to strip ethanol from a thermophilic fermentation process using Parageobacillus thermoglucosidasius TM333, thereby reducing product inhibition and allowing production to continue beyond the nominal toxic ethanol concentrations of ≤ 2% v/v. Using an experimental rig in which cells were grown in fed-batch cultures on sugars derived from waste bread, and the broth continuously cycled through a purpose-built microbubble stripping unit, it was shown that non/low-inhibitory dissolved ethanol concentrations could be maintained throughout, despite reaching productivities equivalent to 4.7% v/v dissolved ethanol. Ethanol recovered in the condensate was at a concentration appropriate for dewatering to be cost effective and not prohibitively energy intensive. This suggests that hot microbubble stripping could be a valuable technology for the continuous production of bioethanol from fermentation processes which suffer from product inhibition before reaching economically viable titres, which is typical of most thermophilic ethanologenic bacteria. [ABSTRACT FROM AUTHOR]

Background: Drug overdose deaths in the United States increased to historic levels in recent years, with provisional estimates indicating more than 111,000 deaths in the 12 months ending July 2023. In 2019, the Centers for Disease Control and Prevention's Division of Overdose Prevention in collaboration with the National Association of City and County Health Officials, funded local health departments (LHDs) to work on overdose prevention activities. This paper aims to: 1) describe the overdose prevention activities that LHDs implemented during the four eighteen-month funding cycles; 2) identify programmatic successes and areas of opportunity for LHDs to consider when implementing future overdose prevention activities; and to 3) inform policy considerations and future overdose prevention programming at the local level. Methods: We used programmatic data to identify overdose prevention activities implemented by 45 LHDs. Activities were double-coded according to the social-ecological model and the U.S. Department of Health and Human Services Overdose Prevention Strategies and Guiding Principles. We analyzed final codes to identify distribution and overlap of the Strategies and Guiding Principles across the social ecological model co-occurrences. Results: Approximately 55.9% (n=123) of the 220 overdose prevention activities that were coded took place at the community level, 32.3% (n=71) at the individual level, 8.6% (n=19) at the relationship level, and 3.2% (n=7) at the policy level. Most of the activities were coded as coordination, collaboration, and integration (n=52, 23.6%), harm reduction (n=51, 23.1%), data and evidence (n=47, 21.4%) or reducing stigma (n=24, 10.9%). Few activities were related to primary prevention (n=14, 6.4%), equity (n=14, 6.4%), recovery support (n=11, 5.0%), and evidence-based treatment (n=7, 3.2%). Conclusions: Localities have primarily implemented activities focused on the community and individual levels, with most of these centered around coordination, collaboration, and integration; harm reduction; or data and evidence. This study identified gaps in overdose prevention for LHDs related to treatment and health equity and that more interventions should be implemented at the relationship and policy levels. Continuing these efforts is important as LHDs explore opportunities to enhance and expand their work in various strategy areas across the social ecology. Findings from this study may be used to inform localities as they design and implement future overdose prevention activities. [ABSTRACT FROM AUTHOR]

Background: Robotic surgery has gained widespread acceptance in elective interventions, yet its role in emergency procedures remains underexplored. While the 2021 WSES position paper discussed limited studies on the application of robotics in emergency general surgery, it recommended strict patient selection, adequate training, and improved platform accessibility. This prospective study aims to define the role of robotic surgery in emergency settings, evaluating intraoperative and postoperative outcomes and assessing its feasibility and safety. Methods: The ROEM study is an observational, prospective, multicentre, international analysis of clinically stable adult patients undergoing robotic surgery for emergency treatment of acute pathologies including diverticulitis, cholecystitis, and obstructed hernias. Data collection includes patient demographics and intervention details. Furthermore, data relating to the operating theatre team and the surgical instruments used will be collected in order to conduct a cost analysis. The study plans to enrol at least 500 patients from 50 participating centres, with each centre having a local lead and collaborators. All data will be collected and stored online through a secure server running the Research Electronic Data Capture (REDCap) web application. Ethical considerations and data governance will be paramount, requiring local ethical committee approvals from participating centres. Discussion: Current literature and expert consensus suggest the feasibility of robotic surgery in emergencies with proper support. However, challenges include staff training, scheduling conflicts with elective surgeries, and increased costs. The ROEM study seeks to contribute valuable data on the safety, feasibility, and cost-effectiveness of robotic surgery in emergency settings, focusing on specific pathologies. Previous studies on cholecystitis, abdominal hernias, and diverticulitis provide insights into the benefits and challenges of robotic approaches. It is necessary to identify patient populations that benefit most from robotic emergency surgery to optimize outcomes and justify costs. [ABSTRACT FROM AUTHOR]

Background: BERT models have seen widespread use on unstructured text within the clinical domain. However, little to no research has been conducted into classifying unstructured clinical notes on the basis of patient lifestyle indicators, especially in Dutch. This article aims to test the feasibility of deep BERT models on the task of patient lifestyle classification, as well as introducing an experimental framework that is easily reproducible in future research. Methods: This study makes use of unstructured general patient text data from HagaZiekenhuis, a large hospital in The Netherlands. Over 148 000 notes were provided to us, which were each automatically labelled on the basis of the respective patients' smoking, alcohol usage and drug usage statuses. In this paper we test feasibility of automatically assigning labels, and justify it using hand-labelled input. Ultimately, we compare macro F1-scores of string matching, SGD and several BERT models on the task of classifying smoking, alcohol and drug usage. We test Dutch BERT models and English models with translated input. Results: We find that our further pre-trained MedRoBERTa.nl-HAGA model outperformed every other model on smoking (0.93) and drug usage (0.77). Interestingly, our ClinicalBERT model that was merely fine-tuned on translated text performed best on the alcohol task (0.80). In t-SNE visualisations, we show our MedRoBERTa.nl-HAGA model is the best model to differentiate between classes in the embedding space, explaining its superior classification performance. Conclusions: We suggest MedRoBERTa.nl-HAGA to be used as a baseline in future research on Dutch free text patient lifestyle classification. We furthermore strongly suggest further exploring the application of translation to input text in non-English clinical BERT research, as we only translated a subset of the full set and yet achieved very promising results. [ABSTRACT FROM AUTHOR]

Gene therapy aims to modify or manipulate gene expression and change the biological characteristics of living cells to achieve the purpose of treating diseases. The safe, efficient, and stable expression of exogenous genes in cells is crucial for the success of gene therapy, which is closely related to the vectors used in gene therapy. Currently, gene therapy vectors are mainly divided into two categories: viral vectors and non-viral vectors. Viral vectors are widely used due to the advantages of persistent and stable expression, high transfection efficiency, but they also have certain issues such as infectivity, high immunological rejection, randomness of insertion mutation, carcinogenicity, and limited vector capacity. Non-viral vectors have the advantages of non-infectivity, controllable chemical structure, and unlimited vector capacity, but the transfection efficiency is low. With the rapid development of nanotechnology, the unique physicochemical properties of nanomaterials have attracted increasing attention in the field of drug and gene delivery. Among many nanomaterials, iron-based nanomaterials have attracted much attention due to their superior physicochemical properties, such as Fenton reaction, magnetic resonance imaging, magnetothermal therapy, photothermal therapy, gene delivery, magnetically-assisted drug delivery, cell and tissue targeting, and so on. In this paper, the research progress of iron-based nanomaterials in gene delivery and tumor gene therapy is reviewed, and the future application direction of iron-based nanomaterials is further prospected. [ABSTRACT FROM AUTHOR]

Primary graft dysfunction (PGD) is a life-threatening clinical condition with a high mortality rate, presenting as left, right, or biventricular dysfunction within the initial 24 h following heart transplantation, in the absence of a discernible secondary cause. Given its intricate nature, definitive definition and diagnosis of PGD continues to pose a challenge. The pathophysiology of PGD encompasses numerous underlying mechanisms, some of which remain to be elucidated, including factors like myocardial damage, the release of proinflammatory mediators, and the occurrence of ischemia-reperfusion injury. The dynamic characteristics of both donors and recipients, coupled with the inclination towards marginal lists containing more risk factors, together contribute to the increased incidence of PGD. The augmentation of therapeutic strategies involving mechanical circulatory support accelerates myocardial recovery, thereby significantly contributing to survival. Nonetheless, a universally accepted treatment algorithm for the swift management of this clinical condition, which necessitates immediate intervention upon diagnosis, remains absent. This paper aims to review the existing literature and shed light on how diagnosis, pathophysiology, risk factors, treatment, and perioperative management affect the outcome of PGD. [ABSTRACT FROM AUTHOR]

Significant advancements have been made in the application of chimeric antigen receptor (CAR)-T treatment for blood cancers during the previous ten years. However, its effectiveness in treating solid tumors is still lacking, necessitating the exploration of alternative immunotherapies that can overcome the significant challenges faced by current CAR-T cells. CAR-based immunotherapy against solid tumors shows promise with the emergence of macrophages, which possess robust phagocytic abilities, antigen-presenting functions, and the ability to modify the tumor microenvironment and stimulate adaptive responses. This paper presents a thorough examination of the latest progress in CAR-M therapy, covering both basic scientific studies and clinical trials. This study examines the primary obstacles hindering the realization of the complete potential of CAR-M therapy, as well as the potential strategies that can be employed to overcome these hurdles. With the emergence of revolutionary technologies like in situ genetic modification, synthetic biology techniques, and biomaterial-supported gene transfer, which provide a wider array of resources for manipulating tumor-associated macrophages, we suggest that combining these advanced methods will result in the creation of a new era of CAR-M therapy that demonstrates improved efficacy, safety, and availability. [ABSTRACT FROM AUTHOR]

Background: Research demonstrates the importance of documenting adaptations to implementation strategies that support integration of evidence-based interventions into practice. While studies have utilized the FRAME-IS [Framework for Reporting Adaptations and Modifications for Implementation Strategies] to collect structured adaptation data, they are limited by a focus on discrete implementation strategies (e.g., training), which do not reflect the complexity of multifaceted strategies like practice facilitation. In this paper, we apply the FRAME-IS to our trial evaluating the effectiveness of PF on implementation fidelity of an evidence-based technology-facilitated team care model for improved hypertension control within a federally qualified health center (FQHC). Methods: Three data sources are used to document adaptations: (1) implementation committee meeting minutes, (2) narrative reports completed by practice facilitators, and (3) structured notes captured on root cause analysis and Plan-Do-Study-Act worksheets. Text was extracted from the data sources according to the FRAME-IS modules and inputted into a master matrix for content analysis by two authors; a third author conducted member checking and code validation. Results: We modified the FRAME-IS to include part 2 of module 2 (what is modified) to add greater detail of the modified strategy, and a numbering system to track adaptations across the modules. This resulted in identification of 27 adaptations, of which 88.9% focused on supporting practices in identifying eligible patients and referring them to the intervention. About half (52.9%) of the adaptations were made to modify the context of the PF strategy to include a group-based format, add community health workers to the strategy, and to shift the implementation target to nurses. The adaptations were often widespread (83.9%), affecting all practices within the FQHC. While most adaptations were reactive (84.6%), they resulted from a systematic process of reviewing data captured by multiple sources. All adaptations included the FQHC in the decision-making process. Conclusion: With modifications, we demonstrate the ability to document our adaptation data across the FRAME-IS modules, attesting to its applicability and value for a range of implementation strategies. Based on our experiences, we recommend refinement of tracking systems to support more nimble and practical documentation of iterative, ongoing, and multifaceted adaptations. Trial registration: Clinicaltrials.gov NCT03713515, Registration date: October 19, 2018. [ABSTRACT FROM AUTHOR]