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Abstract Synthetic data promise privacy-preserving data sharing for healthcare research and development. Compared with other privacy-enhancing approaches—such as federated learning—analyses performed on synthetic data can be applied downstream without modification, such that synthetic data can act in place of real data for a wide range of use cases. However, the role that synthetic data might play in all aspects of clinical model development remains unknown. In this work, we used state-of-the-art generators explicitly designed for privacy preservation to create a synthetic version of ever-smokers in the UK Biobank before building prognostic models for lung cancer under several data release assumptions. We demonstrate that synthetic data can be effectively used throughout the medical prognostic modeling pipeline even without eventual access to the real data. Furthermore, we show the implications of different data release approaches on how synthetic biobank data could be deployed within the healthcare system.

Abstract Brainstem cerebral cavernous malformations (CCM) are clinically more aggressive compared to superficial CCMs. Due to their location, resection can be challenging, making stereotactic radiosurgery (SRS) an attractive alternative for symptomatic patient. Brainstem CCM patients (n = 170) were treated with Gamma Knife SRS at 11 radiosurgical centers. Hemorrhagic risk reduction, risk factors of post-SRS hemorrhage, and clinical outcomes were retrospectively analyzed. Most patients had a single (165/170 patients) brainstem CCMs treated; the majority of CCMs (165/181) presented with bleeding. Single-session SRS decreased the risk of repeat hemorrhage in patients with hemorrhagic brainstem CCM (HR: 0.17, p 13 Gy (HR = 2.57, p = 0.044). Adverse radiation effect (ARE) occurred in 9 patients (5.3%) and was symptomatic in four (2.4%). At a median follow-up of 3.4 years (Inter-quartile range: 5.4), 13 patients (8.0%) had a worsened clinical status, with the treated CCM being the cause in 5.6% (10) of the patients. Single-session SRS decreased the risk of repeat hemorrhage in patients with hemorrhagic brainstem CCM and conveyed this benefit with a low risk of advrse radiation effects (ARE) and worsening clinical status.

Abstract The integration of next-generation sequencing into clinical diagnostics and surveillance initiatives is impeded by the lack of data analysis pipelines that align with privacy legislation and laboratory certification protocols. To address these challenges, we developed Jovian, an open-source, virus-focused, metagenomic analysis workflow for Illumina data. Jovian generates scaffolds enriched with pertinent annotations, including taxonomic classification, combined with metrics needed for quality assessment (coverage depth, average GC content, localization of open reading frames, minority single nucleotide polymorphisms), and incorporates host and disease metadata. Interactive web-based reports with an audit trail are generated. Jovian was employed on four systems, hosted by three institutes, utilizing grid-computers, a high-performance compute singular server, and a Windows10 laptop. All systems yielded identical results with matching MD5sums. Comparison with a commercial online reference tool using viral gastroenteritis samples confirmed the identification of the same pathogens. Jovian provides comparable results to a commercially available online reference tool and generates identical results at different institutes with different IT architectures, proving it is portable and reproducible. Jovian addresses bottlenecks in the deployment of metagenomics within public health and clinical laboratories and has the potential to enhance the breadth of surveillance and testing programs, thereby fostering more effective public health interventions.

Summary Background Dichotomisation of statistical significance, rather than interpretation of effect sizes supported by confidence intervals, is a long-standing problem. Methods We distributed an online survey to clinical trial statisticians across the UK, Australia and Canada asking about their experiences, perspectives and practices with respect to interpretation of statistical findings from randomised trials. We report a descriptive analysis of the closed-ended questions and a thematic analysis of the open-ended questions. Results We obtained 101 responses across a broad range of career stages (24% professors; 51% senior lecturers; 22% junior statisticians) and areas of work (28% early phase trials; 44% drug trials; 38% health service trials). The majority (93%) believed that statistical findings should be interpreted by considering (minimal) clinical importance of treatment effects, but many (61%) said quantifying clinically important effect sizes was difficult, and fewer (54%) followed this approach in practice. Thematic analysis identified several barriers to forming a consensus on the statistical interpretation of the study findings, including: the dynamics within teams, lack of knowledge or difficulties in communicating that knowledge, as well as external pressures. External pressures included the pressure to publish definitive findings and statistical review which can sometimes be unhelpful but can at times be a saving grace. However, the concept of the minimally important difference was identified as a particularly poorly defined, even nebulous, construct which lies at the heart of much disagreement and confusion in the field. Conclusion The majority of participating statisticians believed that it is important to interpret statistical findings based on the clinically important effect size, but report this is difficult to operationalise. Reaching a consensus on the interpretation of a study is a social process involving disparate members of the research team along with editors and reviewers, as well as patients who likely have a role in the elicitation of minimally important differences.

Abstract Background In view of the conflicting results from previous studies, the benefit of paclitaxel-coated balloons for arteriovenous fistulas is uncertain and equipoise remains. Although an industry-led trial testing the efficacy of sirolimus-coated balloons in AVFs is in progress, the benefit of sirolimus-coated balloons for arteriovenous fistulas is currently unknown. The purpose of this trial is to compare the efficacy of additional paclitaxel-coated or sirolimus-coated balloons on outcomes after a plain balloon fistuloplasty to preserve the patency of arteriovenous fistulae used for haemodialysis. Methods The study design is a multicentre randomised controlled trial. Following a successful plain balloon fistuloplasty, participants will be randomised to further treatment with a paclitaxel-coated balloon, a sirolimus-coated balloon, or an uncoated control balloon. We will recruit 642 patients, each with one or two treatment segments, over a 3-year period. Patients will remain in the trial and be followed up for 1 year. The primary endpoint is time to loss of treatment segment primary patency. Cox-proportional hazards models will be used to estimate hazard ratios for the time to loss of treatment segment primary patency for each treatment group relative to the control group. Analysis of the primary endpoint will be based on treatment segments rather than participants and a shared frailty will be estimated to account for the clustering of treatment segments within patients. Secondary endpoints are time to loss of primary patency at any treatment segment; time to end of access circuit primary patency; time to AVF abandonment; number of radiological or surgical interventions; adverse events; intima-media thickness and degree of stenosis at 3 months on ultrasound; and patient quality of life assessed by EQ-5D-5L and VASQoL. Discussion The three-armed design in this proposal will provide an answer on the efficacy of both paclitaxel- and sirolimus-coated balloons in the same trial. This trial is likely to provide a clear answer regarding the efficacy of drug-coated balloons for arteriovenous fistulas. Trial registration ISRCTN ISRCTN40182296. Registered on 4 August 2023.

Abstract Macaque restricts hepatitis B virus (HBV) infection because its receptor homologue, NTCP (mNTCP), cannot bind preS1 on viral surface. To reveal how mNTCP loses the viral receptor function, we here solve the cryo-electron microscopy structure of mNTCP. Superposing on the human NTCP (hNTCP)-preS1 complex structure shows that Arg158 of mNTCP causes steric clash to prevent preS1 from embedding onto the bile acid tunnel of NTCP. Cell-based mutation analysis confirms that only Gly158 permitted preS1 binding, in contrast to robust bile acid transport among mutations. As the second determinant, Asn86 on the extracellular surface of mNTCP shows less capacity to restrain preS1 from dynamic fluctuation than Lys86 of hNTCP, resulting in unstable preS1 binding. Additionally, presence of long-chain conjugated-bile acids in the tunnel induces steric hindrance with preS1 through their tailed-chain. This study presents structural basis in which multiple sites in mNTCP constitute a molecular barrier to strictly restrict HBV.

Abstract Understanding the genetic basis of routinely-acquired blood tests can provide insights into several aspects of human physiology. We report a genome-wide association study of 42 quantitative blood test traits defined using Electronic Healthcare Records (EHRs) of ~50,000 British Bangladeshi and British Pakistani adults. We demonstrate a causal variant within the PIEZO1 locus which was associated with alterations in red cell traits and glycated haemoglobin. Conditional analysis and within-ancestry fine mapping confirmed that this signal is driven by a missense variant - chr16-88716656-G-TT - which is common in South Asian ancestries (MAF 3.9%) but ultra-rare in other ancestries. Carriers of the T allele had lower mean HbA1c values, lower HbA1c values for a given level of random or fasting glucose, and delayed diagnosis of Type 2 Diabetes Mellitus. Our results shed light on the genetic basis of clinically-relevant traits in an under-represented population, and emphasise the importance of ancestral diversity in genetic studies.

A new era of student-centered learning, fueled by the power of digital tools and advanced teaching methods, means that classrooms are no longer entirely defined by four walls and a teacher at the leadership. At the same time, the educational landscape of African countries is very slowly adapting to these changes: the traditional face-to-face approach to learning dominates, student groups are overcrowded, and there is a significant gap in digital skills between students from urban and rural areas. Today, the development of online education becomes an important prerequisite for addressing the problem of educational disparity, a tool for meeting individual educational needs, increasing students' motivation and responsibility for their learning outcomes. The Self-Determined Learning Approach allows for a personalized learning environment in which students can choose what, how and when they learn, work at their pace, choose or receive learning tasks in an order that makes sense to them, which allows for the individual interests of each student, learning style, cultural identity, life experience and personal challenges. The research is based on the results of in-depth interviews with students aged between 25 and 37 years with work (2‒5 years) and study experience, who fit the profile of self-determined learners, have part-time distance learning experience, are employed in different positions and are currently studying different programs, and are also registered with one of the three Distance Education Institutions. All participants are in their final year of study and have experienced digital transformation in distance education. This qualitative study is based on a constructivist paradigm employing a phenomenological strategy to explain the perceptions of students regarding how self-determined practices are applied at their institutions. The phenomenological approach aimed to capture the lived experiences of these students, focusing on their descriptions and interpretations of encountering self-determination practices in their educational environment. The results of the study confirmed the value of a self-determined approach to learning and its positive impact on enhancing students' workplace adaptability. However, at the same time, the survey revealed that African higher education institutions are not ready for the effective implementation of self-determined learning technologies, the main reasons being the lack of technology and the unpreparedness of teachers.

Abstract Cannabis use disorder (CUD) is associated with adverse mental health effects, as well as social and cognitive impairment. Given prevalence rates of CUD are increasing, there is considerable efforts, and need, to identify prognostic markers which may aid in minimising any harm associated with this condition. Previous neuroimaging studies have revealed changes in white matter (WM) organization in people with CUD, though, the findings are mixed. In this study, we applied MRI-based analysis techniques that offer complimentary mechanistic insights, i.e., a connectome approach and fixel-based analysis (FBA) to investigate properties of individual WM fibre populations and their microstructure across the entire brain, providing a highly sensitive approach to detect subtle changes and overcome limitations of previous diffusion models. We compared 56 individuals with CUD (median age 25 years) to a sample of 38 healthy individuals (median age 31.5 years). Compared to controls, those with CUD had significantly increased structural connectivity strength (FDR corrected) across 9 edges between the right parietal cortex and several cortical and subcortical regions, including left orbitofrontal, left temporal pole, and left hippocampus and putamen. Utilizing FBA, WM density was significantly higher in those with CUD (FWE-corrected) across the splenium of the corpus callosum, and lower in the bilateral cingulum and right cerebellum. We observed significant correlation between cannabis use over the past month and connectivity strength of the frontoparietal edge, and between age of regular use and WM density of the bilateral cingulum and right cerebellum. Our findings enhance the understanding of WM architecture alterations associated with CUD.

Abstract Conventional radiography (CR) is primarily utilized for fracture diagnosis. Artificial intelligence (AI) for CR is a rapidly growing field aimed at enhancing efficiency and increasing diagnostic accuracy. However, the diagnostic performance of commercially available AI fracture detection solutions (CAAI-FDS) for CR in various anatomical regions, their synergy with human assessment, as well as the influence of industry funding on reported accuracy are unknown. Peer-reviewed diagnostic test accuracy (DTA) studies were identified through a systematic review on Pubmed and Embase. Diagnostic performance measures were extracted especially for different subgroups such as product, type of rater (stand-alone AI, human unaided, human aided), funding, and anatomical region. Pooled measures were obtained with a bivariate random effects model. The impact of rater was evaluated with comparative meta-analysis. Seventeen DTA studies of seven CAAI-FDS analyzing 38,978 x-rays with 8,150 fractures were included. Stand-alone AI studies (n = 15) evaluated five CAAI-FDS; four with good sensitivities (> 90%) and moderate specificities (80–90%) and one with very poor sensitivity ( 95%). Pooled sensitivities were good to excellent, and specificities were moderate to good in all anatomical regions (n = 7) apart from ribs (n = 4; poor sensitivity / moderate specificity) and spine (n = 4; excellent sensitivity / poor specificity). Funded studies (n = 4) had higher sensitivity (+ 5%) and lower specificity (-4%) than non-funded studies (n = 11). Sensitivity did not differ significantly between stand-alone AI and human AI aided ratings (p = 0.316) but specificity was significantly higher the latter group (p

Background/purpose: Cognitive flexibility is a personality trait, which can influence how effectively a healthcare professional can manage a challenging clinical situation. This study explored the cognitive flexibility of undergraduate dental hygiene students at two universities in Asia to gather baseline information in order to consider whether there was an educational need for pre-clinical students with regards to this personality factor. Materials and methods: Participants were all undergraduate dental hygiene students in the 2022 academic year at Tokyo Medical and Dental University (TMDU; n = 79) and Taipei Medical University (TMU; n = 88). An anonymous questionnaire was distributed, which included questions on demographic information and the Cognitive Flexibility Inventory (CFI). Results: The response rates were 97.5% (TMDU) and 89.8% (TMU). The CFI total scores were 91.77 for TMDU and 95.87 for TMU, and there was no significant difference between the two schools. The Alternatives scores were significantly higher in TMU than TMDU (P = 0.044), but there were no significant differences in the Control scores between the two schools. There were also no significant differences between school years of both universities. Conclusion: The dental hygiene students from both dental schools exhibit moderate cognitive flexibility. The educators in both dental schools may consider whether they should investigate and develop this personality factor further during the undergraduate training of their dental hygiene students.

Background: /purposeIn cases where oral squamous cell carcinoma (OSCC) invades the jawbone, clinicians frequently observe abnormal attenuation on computed tomography (CT) and pathologic signal intensity (SI) on magnetic resonance (MR) imaging of the affected underlying bone marrow. This study introduced a concept of “underlying bone change” to examine its association with clinicopathological features and prognosis of OSCC, as well as its correlation with medullary invasion. Materials and methods: We enrolled 93 consecutive patients diagnosed with OSCC, who underwent mandibulectomy between 2010 and 2016. CT and MR images, along with electronic medical records, were reviewed to evaluate correlations between underlying bone changes, clinicopathological features, five-year overall survival, and medullary invasion. Results: Of the 93 patients, 69 (74.2%) exhibited underlying bone sclerosis on CT, and 74 (79.6%) displayed pathological SI on MR images. These underlying bone changes correlated with the T stage and recurrence, but not with overall survival.Medullary invasion, observed in 61 (65.6%) patients, was strongly associated with T and TNM stages and was linked to poorer overall survival.The underlying bone changes on CT and MR images were positively associated with medullary invasion; however, no significant differences were found in the occurrence of underlying bone changes between the subtypes based on the extent of medullary invasion. Conclusion: Underlying bone changes on CT and MR images can provide valuable insights into the aggressiveness of bone invasion by OSCC. Accurate interpretation of these imaging findings might be crucial for correctly delineating surgical margins and preventing the overestimation of tumor extent.

The realm of digital property is a new area in the world of technology that must be addressed in different fields, especially law. In our country, the legislator has not yet provided an explicit text regarding the Digital inheritance property. In addition, like intellectual property rights, although digital property is immaterial, they will have a material effect, including patent rights and author's rights, which are recognized in Iranian law; like intellectual property, virtual properties are not physically tangible, but they have the same financial effects and can be classified as property and inheritance. The findings indicate that so far, the Digital inheritance assets have not yet penetrated Iran's laws, and the internal laws in this regard have not been legislated, despite the need and necessity due to the widespread use of these properties, there was no change in the recognition of digital assets. In this case, do digital properties have a place in Iran's law to be recognized as property or not? The Vice President of New Technologies of the Central Bank published a draft of the requirements and regulations in the field of cryptocurrencies in February 2017, and the bill that was recently submitted to the parliament is an attempt to the legal framework and define the rules of digital property in property can be considered with indulgence. According to the general rules governing material property, the digital property can also be considered as part of the property, be inherited, and at the same time be demanded, divided, and traded. The research method in this article is descriptive-analytical.

Abstract Young children receiving outpatient cancer care are vulnerable to undermanaged pain. App‐based solutions that provide pain treatment advice to parents in real‐time and in all environments may improve access to quality pain care. We used a parent co‐design approach involving iterative rounds of user testing and software modification to develop a usable Pain Caregiver Resource (PainCaRe) real‐time pediatric cancer pain management app. Parents of children (2–11 years) with cancer completed three standardized modules using a PainCaRe prototype. App usability and acceptability were evaluated using the validated System Usability Scale and a thematic analysis of app testing sessions and interviews. Iterative testing sessions were conducted until data saturation. Interview themes were synthesized into action items that guided revisions to PainCaRe and additional testing rounds were conducted as necessary. Twenty‐two parents participated in three testing cycles. Overall, parents described PainCaRe as an acceptable and potentially clinically useful pain management tool. Mean system usability scores were in the acceptable scale range during each testing cycle. Usability issues identified and resolved included those related to software malfunction, complicated app navigation logic, lack of clarity on pain assessment questions, and the need for pain management advice specifically tailored to child developmental stage. Using co‐design methods, the PainCaRe cancer pain management app was successfully refined for its acceptability and utility to parents. Next steps will include a PainCaRe pilot study before evaluating the impact of the app on younger children's pain outcomes in a randomized controlled trial.

Background & objectives: Malaria remains a complex challenge in India due to its diverse epidemiology, multi-ethnic population, and multiplicity of malaria vectors. While progress has been made in reducing malaria nationally, persistent pockets hinder elimination efforts. These challenges include hidden reservoirs, inadequate healthcare, suboptimal surveillance, non-compliance, and subclinical infections. Shortage of grassroot level and primary care health staff, transportation issues and general inaccessibility and unavailability of healthcare services are additional challenges. Methods: Mobile healthcare vans have been tried and found useful in enhancing healthcare availability in several health conditions in different settings. Nuh district in Haryana, India is a malaria endemic region; it is indeed one of the districts included by India’s NITI Aayog in the Aspirational Districts Programme, a government initiative that focuses on rapidly transforming and developing the most underdeveloped districts in country. With an aim to improve the healthcare seeking behavior of malaria-endemic community of selected villages of Nuh district, we carried out a study using interventions in two villages of the district, that had mobile malaria clinics and toll-free telephone services in enhancing healthcare access. Results: We found that Sangel village had higher literacy rates (60.6%) as compared to 39.4% in Naushera. Similarly, the unemployment rate was higher for Naushera. It the mobile malaria clinic was deployed from December 2019 to July 2020 and a total of 269 phone calls were received from both the villages. A similar number of rapid tests and microscopy smears were examined and all were negative for malaria. The febrile patients were referred to the nearest healthcare facility. Interpretation & conclusion: The study shows that the community is open to using these healthcare interventions. These initiatives of mobile malaria clinics and toll-free telephone services can bridge healthcare gaps, especially in malaria-endemic regions, aligning with India’s malaria elimination and equitable healthcare access goals.

Abstract Objective Improving care transitions for older adults can reduce emergency department (ED) revisits, and the strain placed upon caregivers. We analyzed whether caregivers felt a change in burden following a care transition, and what may be improved to reduce it. Methods This mixed-methods observational study nested within LEARNING WISDOM included caregivers of older patients who experienced an ED care transition. Burden was collected with the brief Zarit Burden Interview (ZBI-12), and caregivers also commented on the care transition. A qualitative coding scheme of patient care transitions was created to reflect themes important to caregivers. Comments were randomly analyzed until saturation and themes were extracted from the data. We followed both the SRQR and STROBE checklists. Results Comments from 581 caregivers (mean age (SD) 64.5 (12.3), 68% women) caring for patients (mean age (SD) 77.2 (7.54), 48% women) were analyzed. Caregivers overwhelmingly reported dissatisfaction and unmet service expectations, particularly with home care and domestic help. Communication and follow-up from the ED emerged as an area for improvement. Caregivers who reported an increased level of burden following a patient’s care transition had significantly higher ZBI scores than caregivers who self-reported stable burden levels. Conclusion Caregivers with increasing, stable, and improved levels of subjective burden all reported areas for improvement in the care transition process. Themes centering on the capacity to live at home and inadequate communication were most frequently mentioned and may represent serious challenges to caregivers. Addressing these challenges could improve both caregiver burden and ED care transitions.

Abstract Background Sphingosine-1-phosphate lyase insufficiency syndrome (SPLIS) is a recently recognized inborn error of metabolism associated with steroid-resistant nephrotic syndrome as well as adrenal insufficiency and immunological, neurological, and skin manifestations. SPLIS is caused by inactivating mutations in SGPL1, encoding the pyridoxal 5’phosphate-dependent enzyme sphingosine-1-phosphate lyase, which catalyzes the final step of sphingolipid metabolism. Some SPLIS patients have undergone kidney transplantation, and others have been treated with vitamin B6 supplementation. In addition, targeted therapies including gene therapy are in preclinical development. In anticipation of clinical trials, it will be essential to characterize the full spectrum and natural history of SPLIS. We performed a retrospective analysis of 76 patients in whom the diagnosis of SPLIS was established in a proband with at least one suggestive finding and biallelic SGPL1 variants identified by molecular genetic testing. The main objective of the study was to identify factors influencing survival in SPLIS subjects. Results Overall survival at last report was 50%. Major influences on survival included: (1) age and organ involvement at first presentation; (2) receiving a kidney transplant, and (3) SGPL1 genotype. Among 48 SPLIS patients with nephropathy who had not received a kidney transplant, two clinical subgroups were distinguished. Of children diagnosed with SPLIS nephropathy before age one (n = 30), less than 30% were alive 2 years after diagnosis, and 17% were living at last report. Among those diagnosed at or after age one (n = 18), ~ 70% were alive 2 years after diagnosis, and 72% were living at time of last report. SPLIS patients homozygous for the SPL R222Q variant survived longer compared to patients with other genotypes. Kidney transplantation significantly extended survival outcomes. Conclusion Our results demonstrate that SPLIS is a phenotypically heterogeneous condition. We find that patients diagnosed with SPLIS nephropathy in the first year of life and patients presenting with prenatal findings represent two high-risk subgroups, whereas patients harboring the R222Q SGPL1 variant fare better than the rest. Time to progression from onset of proteinuria to end stage kidney disease varies from less than one month to five years, and kidney transplantation may be lifesaving.

l In this article we argue that Ron Athey’s performance Solar Anus is an aberrant adaptation of Shakespeare’s Macbeth in which the parodic world of abundant excess that the witches catalyze is redemptively captured and transformed through the playful, androgynous, and excessive performance of Athey, who fulfills the witches’ prophecy and continues to live on sovereignly as both Macbeth and Lady Macbeth. Athey is a Los Angeles-based performance artist who practices what is sometimes called “extreme performance,” exploring the limits of aesthetics and the capabilities of the human body to express both beauty and pain. His work Solar Anus draws on the works of Georges Bataille, especially his short essay-poem, Solar Anus, as well as Paul Molinier, a queer French painter and visual artist who worked on the fringes of the surrealist movement. We work through the combined sociopolitical theory, performance aesthetics, and research methodology of transversal poetics and engage especially with the theories and explorations of aesthetics and sovereignty by Georges Bataille and Gilles Deleuze and Félix Guattari in order to explore the ways in which Athey is capable of realizing the witches’ prophecy of sovereignty without being destroyed by the parodic world that they create and inhabit. Alongside the concepts of sovereignty, we examine how Bataille’s ideas of parody, sacrifice, and excess offer new ways of understanding the world of Macbeth and how excess and sovereignty both function within its porous borders.

Abstract Background Control of humeral torsion can present a challenge, especially intraoperatively during closed reduction and fixation of humeral shaft fractures or 2-part surgical neck fractures of the proximal humerus. The objective of this study is to develop and validate an indirect method for the assessment of humeral torsion using an index that is linearly correlated with rotational arm position and can be derived from only a single plain radiographic image of the proximal humerus. Methods The Humeral Head Offset Index (HHOI) is calculated as the ratio of the medial and lateral offset of the humeral head measured from the outer cortices of the shaft on a plain radiographic or fluoroscopic image. The relationship of HHOI with humeral torsion was first verified on a sawbone model with radiopaque characteristics under fluoroscopic control. Different degrees of retroversion were simulated through manual rotation of the humerus with a digital protractor in 5° increments until 40° internally rotated and then in 5° increments until 40° externally rotated from the neutral position. The same procedure was subsequently performed digitally on Digitally Reconstructed Radiographs (DRRs) from computed tomography (CT) dataset of the sawbone. Next, the HHOI index was applied to eight randomly selected patients with total humerus CT using the same method. Spearman’s rho was calculated for the bivariate analysis of correlation between the simulated degree of retroversion and the HHOI. Strength of correlation was classified according to Koo and Li. Interrater and intrarater reliability of three blinded observers with repetition of measurement after three months were analyzed by assessing the intraclass correlation coefficient (ICC). Results Both in the sawbone model and in DRRs, we demonstrated a high to very high significant linear correlation between simulated retroversion and the HHOI. ICC values demonstrated excellent interrater reliability and excellent intrarater reliability for measurement of the HHOI. Conclusions The HHOI is a new, simple, reliable index that has a linear relationship to the rotation of the humerus and can therefore allow an indirect control of humeral torsion in comparison to the contralateral side.

Abstract Controlling the succession of chemical processes with high specificity in complex systems is advantageous for widespread applications, from biomedical research to drug manufacturing. Despite synthetic advances in bioorthogonal and photochemical methodologies, there is a need for generic chemical approaches that can universally modulate photodynamic reactivity in organic photosensitizers. Herein we present a strategy to fine-tune the production of singlet oxygen in multiple photosensitive scaffolds under the activation of bioresponsive and bioorthogonal stimuli. We demonstrate that the photocatalytic activity of nitrobenzoselenadiazoles can be fully blocked by site-selective incorporation of electron-withdrawing carbamate moieties and restored on demand upon uncaging with a wide range of molecular triggers, including abiotic transition-metal catalysts. We also prove that this strategy can be expanded to most photosensitizers, including diverse structures and spectral properties. Finally, we show that such advanced control of singlet oxygen generation can be broadly applied to the photodynamic ablation of human cells as well as to regulate the release of singlet oxygen in the semi-synthesis of natural product drugs.

Abstract Resonant inelastic x-ray scattering (RIXS) is a widely used spectroscopic technique, providing access to the electronic structure and dynamics of atoms, molecules, and solids. However, RIXS requires a narrow bandwidth x-ray probe to achieve high spectral resolution. The challenges in delivering an energetic monochromated beam from an x-ray free electron laser (XFEL) thus limit its use in few-shot experiments, including for the study of high energy density systems. Here we demonstrate that by correlating the measurements of the self-amplified spontaneous emission (SASE) spectrum of an XFEL with the RIXS signal, using a dynamic kernel deconvolution with a neural surrogate, we can achieve electronic structure resolutions substantially higher than those normally afforded by the bandwidth of the incoming x-ray beam. We further show how this technique allows us to discriminate between the valence structures of Fe and Fe2O3, and provides access to temperature measurements as well as M-shell binding energies estimates in warm-dense Fe compounds.

Smart ports, utilizing advanced and hybrid technologies, are gaining increasing attention for application in the maritime industry, with driver assistance and autonomous driving being pivotal in container-terminal operations. This study introduces a novel approach for enhancing object detection and distance estimation, focusing principally on decision support for reach stacker container handlers in port terminals by integrating generative and deep learning models. The EfficientDet model, enriched with integrated k-means clustering, is developed to detect and classify objects using a practical dataset of labeled images based on visual features. Moreover, generative models, specifically the diffusion model and generative adversarial network, are utilized to generate depth scenes for estimating object distances. Experimental results indicate that the proposed approach yields superior object detection and distance estimation outcomes in port terminal operations, characterized by high accuracy and reduced computational cost. The proposed method exhibits potential for application across various industries, including transportation, logistics, and security, where precise object detection and distance estimation are vital for efficient and secure operations.

Background: Post-acute sequelae of COVID-19 (PASC) produce significant morbidity, prompting evaluation of interventions that might lower risk. Selective serotonin reuptake inhibitors (SSRIs) potentially could modulate risk of PASC via their central, hypothesized immunomodulatory, and/or antiplatelet properties although clinical trial data are lacking. Materials and Methods: This retrospective study was conducted leveraging real-world clinical data within the National COVID Cohort Collaborative (N3C) to evaluate whether SSRIs with agonist activity at the sigma-1 receptor (S1R) lower the risk of PASC, since agonism at this receptor may serve as a mechanism by which SSRIs attenuate an inflammatory response. Additionally, determine whether the potential benefit could be traced to S1R agonism. Presumed PASC was defined based on a computable PASC phenotype trained on the U09.9 ICD-10 diagnosis code. Results: Of the 17,908 patients identified, 1521 were exposed at baseline to a S1R agonist SSRI, 1803 to a non-S1R agonist SSRI, and 14,584 to neither. Using inverse probability weighting and Poisson regression, relative risk (RR) of PASC was assessed.A 29% reduction in the RR of PASC (0.704 [95% CI, 0.58–0.85]; P = 4 ×10−4) was seen among patients who received an S1R agonist SSRI compared to SSRI unexposed patients and a 21% reduction in the RR of PASC was seen among those receiving an SSRI without S1R agonist activity (0.79 [95% CI, 0.67 - 0.93]; P = 0.005).Thus, SSRIs with and without reported agonist activity at the S1R were associated with a significant decrease in the risk of PASC.

Abstract Background The effects of environmental disturbances on livestock are often observed indirectly through the variability patterns of repeated performance records over time. Sheep are frequently exposed to diverse extensive environments but currently lack appropriate measures of resilience (or sensitivity) towards environmental disturbance. In this study, random regression models were used to analyse repeated records of the fibre diameter of wool taken along the wool staple (bundle of wool fibres) to investigate how the genetic and environmental variance of fibre diameter changes with different growing environments. Results A model containing a fifth, fourth and second-order Legendre polynomial applied to the fixed, additive and permanent environmental effects, respectively, was optimal for modelling fibre diameter along the wool staple. The additive genetic and permanent environmental variance both showed variability across the staple length trajectory. The ranking of sire estimated breeding values (EBV) for fibre diameter was shown to change along the staple and the genetic correlations decreased as the distance between measurements along the staple increased. This result suggests that some genotypes were potentially more resilient towards the changes in the growing environment compared to others. In addition, the eigenfunctions of the random regression model implied the ability to change the fibre diameter trajectory to reduce its variability along the wool staple. Conclusions These results show that genetic variation in fibre diameter measured along the wool staple exists and this could be used to provide greater insight into the ability to select for resilience in extensively raised sheep populations.

This review comprehensively examines the evolution and current state of interbody cage technology for lumbar interbody fusion (LIF). This review highlights the biomechanical and clinical implications of the transition from traditional static cage designs to advanced expandable variants for spinal surgery. The review begins by exploring the early developments in cage materials, highlighting the roles of titanium and polyetheretherketone in the advancement of LIF techniques. This review also discusses the strengths and limitations of these materials, leading to innovations in surface modifications and the introduction of novel materials, such as tantalum, as alternative materials. Advancements in three-dimensional printing and surface modification technologies form a significant part of this review, emphasizing the role of these technologies in enhancing the biomechanical compatibility and osseointegration of interbody cages. In addition, this review explores the increase in biodegradable and composite materials such as polylactic acid and polycaprolactone, addressing their potential to mitigate long-term implant-related complications. A critical evaluation of static and expandable cages is presented, including their respective clinical and radiological outcomes. While static cages have been a mainstay of LIF, expandable cages are noted for their adaptability to the patient’s anatomy, reducing complications such as cage subsidence. However, this review highlights the ongoing debate and the lack of conclusive evidence regarding the superiority of either cage type in terms of clinical outcomes. Finally, this review proposes future directions for cage technology, focusing on the integration of bioactive substances and multifunctional coatings and the development of patient-specific implants. These advancements aim to further enhance the efficacy, safety, and personalized approach of spinal fusion surgeries. Moreover, this review offers a nuanced understanding of the evolving landscape of cage technology in LIF and provides insights into current practices and future possibilities in spinal surgery.

Aims/method This national pre-pandemic survey compared demand and capacity of adult community eating disorder services (ACEDS) with NHS England (NHSE) commissioning guidance. Results Thirteen services in England and Scotland responded (covering 10.7 million population). Between 2016–2017 and 2019–2020 mean referral rates increased by 18.8%, from 378 to 449/million population. Only 3.7% of referrals were from child and adolescent eating disorder services (CEDS-CYP), but 46% of patients were aged 18–25 and 54% were aged >25. Most ACEDS had waiting lists and rationed access. Many could not provide full medical monitoring, adapt treatment for comorbidities, offer assertive outreach or provide seamless transitions. For patient volume, the ACEDS workforce budget was 15%, compared with the NHSE workforce calculator recommendations for CEDS-CYP. Parity required £7 million investment/million population for the ACEDS. Clinical implications This study highlights the severe pressure in ACEDS, which has increased since the COVID-19 pandemic. Substantial investment is required to ensure NHS ACEDS meet national guidance, offer evidence-based treatment, reduce risk and preventable deaths, and achieve parity with CEDS-CYP.

Functional vinegar with high γ-aminobutyric acid (GABA) content was manufactured through a two-stage serial co-fermentation of rice wine lees, a by-product of Korean rice wine, using lactic acid bacteria (LAB) and acetic acid bacteria (AAB). The first LAB fermentation elevated GABA content by utilizing monosodium glutamate (MSG) as a precursor. Lactiplantibacillus plantarum KS2020 converted up to 10% of MSG into GABA and indicated a GABA content of 65.49 mg/g. The concentration of LAB-fermented rice wine lees was then optimized for the second co-fermentation, and Acetobacter aceti was used to produce vinegar. Co-fermentation using 40% first LAB-fermented rice wine lees yielded vinegar with 55.34 mg/g acetic acid and 22.61 mg/g GABA. The temperature-dependent reduction in GABA in GABA-enriched vinegar followed the Arrhenius relationship during storage, with an activation energy of 9.94 kcal/mol (20–35 °C, R2 = 0.99). The GABA present in the vinegar showed evidence of a temperature-/time-dependent decrease, decreasing by 40% over five months. This study first proved the higher GABA-enriched vinegar production from rice wine lees using Lb. plantarum KS2020 and A. aceti.

Abstract Implantable devices interfacing with peripheral nerves exhibit limited longevity and resolution. Poor nerve-electrode interface quality, invasive surgical placement and development of foreign body reaction combine to limit research and clinical application of these devices. Here, we develop cuff implants with a conformable design that achieve high-quality and stable interfacing with nerves in chronic implantation scenarios. When implanted in sensorimotor nerves of the arm in awake rats for 21 days, the devices record nerve action potentials with fascicle-specific resolution and extract from these the conduction velocity and direction of propagation. The cuffs exhibit high biocompatibility, producing lower levels of fibrotic scarring than clinically equivalent PDMS silicone cuffs. In addition to recording nerve activity, the devices are able to modulate nerve activity at sub-nerve resolution to produce a wide range of paw movements. When used in a partial nerve ligation rodent model, the cuffs identify and characterise changes in nerve C fibre activity associated with the development of neuropathic pain in freely-moving animals. The developed implantable devices represent a platform enabling new forms of fine nerve signal sensing and modulation, with applications in physiology research and closed-loop therapeutics.

Background: Some voxels may alter the tractography results due to unintentional alteration of noises and other unwanted factors.Objective: This study aimed to investigate the effect of local phase features on tractography results providing data are mixed by a Gaussian or random distribution noise.Material and Methods: In this simulation study, a mask was firstly designed based on the local phase features to decrease false-negative and -positive tractography results. The local phase features are calculated according to the local structures of images, which can be zero-dimensional, meaning just one point (equivalent to noise in tractography algorithm), a line (equivalent to a simple fiber), or an edge (equivalent to structures more complex than a simple fiber). A digital phantom evaluated the feasibility current model with the maximum complexities of configurations in fibers, including crossing fibers. In this paper, the diffusion images were mixed separately by a Gaussian or random distribution noise in 2 forms: a zero-mean noise and a noise with a mean of data.Results: The local mask eliminates the pixels of unfitted values with the main structures of images, due to noise or other interferer factors. Conclusion: The local phase features of diffusion images are an innovative solution to determine principal diffusion directions.

Abstract Background Studies indicate that the children of mothers who have eating disorders are at an increased risk of developing eating disorders themselves. The aim of this qualitative study was to broaden and extend current understandings of the experiences of mothers with eating disorders. The present report focuses on maternal perspectives, experiences, and support needs in relation to the intergenerational transmission of eating disorders. Method Semi-structured online interviews were conducted with parents living in the UK, USA, and Australia. Participants were eighteen mothers with a self-reported lifetime diagnosis of one or more eating disorders, who had experienced symptoms since becoming a parent, and who had at least one child aged 2 years or older. Data were analysed using reflexive thematic analysis. Results Four major themes relating to the impacts of having an eating disorder on children and intergenerational transmission were identified. These were: impacts (maternal perspectives on the ways having an eating disorder impacted their children, and their reflections around having been impacted by their own parents); breaking the cycle (strategies employed by mothers in efforts to prevent their children developing eating disorders of their own); communicating about the eating disorder (maternal experiences around disclosing or not disclosing having an eating disorder to their children); and support needs (maternal and perceived familial support needs in relation to breaking cycles of intergenerational transmission). Conclusions For mothers with eating disorders, concerns about the potential impacts on their children and fears about intergenerational transmission are salient, and these may vary for children at different ages. The mothers who participated in our study described engaging in a number of conscious strategies in efforts to manage the risks of eating disorder development in their children, but implementing these strategies was not without challenges. Implications for preventative programs to reduce the intergenerational transmission of eating disorders are discussed.

Abstract The phenomenon of BCJ duality implies that gauge theories possess an abstract kinematic algebra, mirroring the non-abelian Lie algebra underlying the colour information. Although the nature of the kinematic algebra is known in certain cases, a full understanding is missing for arbitrary non-abelian gauge theories, such that one typically works outwards from well-known examples. In this paper, we pursue an orthogonal approach, and argue that simpler abelian gauge theories can be used as a testing ground for clarifying our understanding of kinematic algebras. We first describe how classes of abelian gauge fields are associated with well-defined subalgebras of the diffeomorphism algebra. By considering certain special subalgebras, we show that one may construct interacting theories, whose kinematic algebras are inherited from those already appearing in a related abelian theory. Known properties of (anti-)self-dual Yang-Mills theory arise in this way, but so do new generalisations, including self-dual electromagnetism coupled to scalar matter. Furthermore, a recently obtained non-abelian generalisation of the Navier-Stokes equation fits into a similar scheme, as does Chern-Simons theory. Our results provide useful input to further conceptual studies of kinematic algebras.

Abstract Background Male Genital Schistosomiasis (MGS) remains an often-overlooked chronic sequela of urogenital schistosomiasis in endemic areas of sub-Saharan Africa. As part of a 2-year longitudinal study on Hybridization of UroGenital Schistosomiasis (HUGS) in Malawi, a MGS sub-study was conducted to assess whether hybrid schistosomes were incriminated. Methods During recruitment, demographic, health and socio-economic data were collected through individual questionnaire interviews in Mthawira community from Nsanje District along Shire River and Samama community from Mangochi District along Lake Malawi shoreline. Urine and semen samples were collected and analysed to determine the identity of schistosome infection. Urine filtration and microscopy, direct microscopy of semen and its sediments (after centrifugation) were performed. Thereafter, the sediments were examined by molecular DNA analysis with a novel two-tube real-time PCR assay. The participants were also screened for Human papilloma virus (HPV) and other sexually transmitted infections (STIs). Results Twenty-two men were recruited for the sub-study, 8 in Nsanje District and 14 in Mangochi District, with a median age of 22.0 years. By microscopy, ten (45.7%) participants had Schistosoma ova in their urine, 11 (50.0%) in semen while 16 (72.7%) were positive by real-time PCR. One participant had both S. haematobium and S. mattheei ova in his semen, three showed symptoms, and one had a mixed infection of S. mansoni and possible S. haematobium-S. mattheei hybrid. Twelve men had detectable high-risk HPV serotypes 16, 18 and others while six had Trichomonas vaginalis and other STIs. Conclusion Zoonotic and hybrid schistosomes can cause MGS similar to human schistosomes, which can be co-infected with HPV and STIs, thereby posing a new challenge in diagnosis, management and control measures in resource poor settings. Increased awareness of these infections among local communities and primary healthcare workers and improvement of disease management are needed and advocated.

Abstract Background The aim of the study was to test a universal screening strategy on endometrial cancer to evaluate its effectiveness to find Lynch Syndrome (LS) cases to two established clinical criteria: Amsterdam II criteria, and the revised Bethesda criteria to select cases for prescreening with immunohistochemistry (IHC). Cases were subsequently screened for germline disease causing variants regarding the DNA mismatch repair (MMR) genes. Methods IHC was performed on 221 endometrial cancer (EC) cases, using antibodies against the DNA mismatch repair proteins MLH1, PMS2, MSH2, and MSH6. MMR loss was found in 54 cases, and gene mutation screening was undertaken in 52 of those. Results In this set of patients, the use of Amsterdam II criteria detected two (0.9%), the Bethesda criteria two (0.9%), and universal testing five (2.3%) cases of LS. The combination of universal testing and family history criteria resulted in detection of five patients (2.3%) with LS. Conclusions Based on our results and other similar studies to date we propose a screening protocol for LS on EC tumors with prescreening using IHC for the four MMR proteins on all new EC cases diagnosed before 70 years of age, followed by mutation screening of all tumors with loss of MSH2 and/or MSH6 or only PMS2, plus consideration for mutation screening of all LS genes in cases fulfilling the clinical Amsterdam II criteria regardless of MMR status on IHC.

Abstract The eating and feeding disorder section of the Diagnostic and Statistical Manual of Mental Disorders 5 Text Revision (DSM-5-TR) is organized by a diagnostic algorithm that limits the contemporaneous assignment of multiple eating disorder diagnoses. Avoidant/restrictive food intake disorder (ARFID) is a disturbance in food intake typically associated with lack of interest in food, food avoidance based on sensory characteristics, and/or fear of aversive consequences from eating. According to the DSM-5-TR, an ARFID diagnosis cannot be made when weight or shape disturbances are present, and ARFID cannot be co-diagnosed with other eating disorders characterized by these disturbances. However, emerging evidence from both clinical and lived experience contexts suggests that the co-occurrence of ARFID with multiple other types of eating disorders may be problematically invisibilized by this trumping scheme. The diagnostic criteria for ARFID can contribute to inappropriate diagnosis or exclusion from diagnosis due to excessive ambiguity and disqualification based on body image disturbance and other eating disorder pathology, even if unrelated to the food restriction or avoidance. This harmfully limits the ability of diagnostic codes to accurately describe an individual’s eating disorder symptomatology, impacting access to specialized and appropriate eating disorder care. Therefore, revision of the DSM-5-TR criteria for ARFID and removal of limitations on the diagnosis of ARFID concurrent to other full-syndrome eating disorders stands to improve identification, diagnosis, and support of the full spectrum of ARFID presentations.

Abstract Background Outreach clinics were part of efforts to maximise uptake in COVID-19 vaccination. Methods We used controlled interrupted time series, matching on age, sex, deprivation and vaccination eligibility date, to determine the effect of outreach clinics on time to first COVID-19 vaccine, using a population-based electronic health record database of 914,478 people, from December 2020 to December 2021; people living within 1 mile of each outreach clinics were exposed. Results 50% of 288,473 exposed citizens were white British, and 71% were aged 0–49 years. There was no evidence for an overall statistically significant increase in cumulative percentage vaccinated due to the outreach clinic at 6 weeks, with an overall pooled effect estimate of -0.07% (95% CI: -1.15%, 1.02%). The pooled estimate for increased cumulative vaccine uptake varied slightly depending on how the analysis was stratified; by ethnic group it was − 0.12% (95% CI: -0.90%, 0.66%); by age group it was − 0.06% (95% CI: -0.41%, 0.28%); and by deprivation it was 0.03% (95% CI: -0.74%, 0.79%). Conclusions Living within a mile of an outreach clinic was not associated with higher vaccine uptake. Evaluation of future outreach clinics should consider the relative importance of travel amongst other barriers to accessing vaccines.

Abstract The morphology and distribution of airway tree abnormalities enable diagnosis and disease characterisation across a variety of chronic respiratory conditions. In this regard, airway segmentation plays a critical role in the production of the outline of the entire airway tree to enable estimation of disease extent and severity. Furthermore, the segmentation of a complete airway tree is challenging as the intensity, scale/size and shape of airway segments and their walls change across generations. The existing classical techniques either provide an undersegmented or oversegmented airway tree, and manual intervention is required for optimal airway tree segmentation. The recent development of deep learning methods provides a fully automatic way of segmenting airway trees; however, these methods usually require high GPU memory usage and are difficult to implement in low computational resource environments. Therefore, in this study, we propose a data-centric deep learning technique with big interpolated data, Interpolation-Split, to boost the segmentation performance of the airway tree. The proposed technique utilises interpolation and image split to improve data usefulness and quality. Then, an ensemble learning strategy is implemented to aggregate the segmented airway segments at different scales. In terms of average segmentation performance (dice similarity coefficient, DSC), our method (A) achieves 90.55%, 89.52%, and 85.80%; (B) outperforms the baseline models by 2.89%, 3.86%, and 3.87% on average; and (C) produces maximum segmentation performance gain by 14.11%, 9.28%, and 12.70% for individual cases when (1) nnU-Net with instant normalisation and leaky ReLU; (2) nnU-Net with batch normalisation and ReLU; and (3) modified dilated U-Net are used respectively. Our proposed method outperformed the state-of-the-art airway segmentation approaches. Furthermore, our proposed technique has low RAM and GPU memory usage, and it is GPU memory-efficient and highly flexible, enabling it to be deployed on any 2D deep learning model.

Abstract Male sex, early life chemical exposure and the brain aromatase enzyme have been implicated in autism spectrum disorder (ASD). In the Barwon Infant Study birth cohort (n = 1074), higher prenatal maternal bisphenol A (BPA) levels are associated with higher ASD symptoms at age 2 and diagnosis at age 9 only in males with low aromatase genetic pathway activity scores. Higher prenatal BPA levels are predictive of higher cord blood methylation across the CYP19A1 brain promoter I.f region (P = 0.009) and aromatase gene methylation mediates (P = 0.01) the link between higher prenatal BPA and brain-derived neurotrophic factor methylation, with independent cohort replication. BPA suppressed aromatase expression in vitro and in vivo. Male mice exposed to mid-gestation BPA or with aromatase knockout have ASD-like behaviors with structural and functional brain changes. 10-hydroxy-2-decenoic acid (10HDA), an estrogenic fatty acid alleviated these features and reversed detrimental neurodevelopmental gene expression. Here we demonstrate that prenatal BPA exposure is associated with impaired brain aromatase function and ASD-related behaviors and brain abnormalities in males that may be reversible through postnatal 10HDA intervention.

Abstract The cell division cycle 25 phosphatases CDC25A, B and C regulate cell cycle transitions by dephosphorylating residues in the conserved glycine-rich loop of CDKs to activate their activity. Here, we present the cryo-EM structure of CDK2-cyclin A in complex with CDC25A at 2.7 Å resolution, providing a detailed structural analysis of the overall complex architecture and key protein-protein interactions that underpin this 86 kDa complex. We further identify a CDC25A C-terminal helix that is critical for complex formation. Sequence conservation analysis suggests CDK1/2-cyclin A, CDK1-cyclin B and CDK2/3-cyclin E are suitable binding partners for CDC25A, whilst CDK4/6-cyclin D complexes appear unlikely substrates. A comparative structural analysis of CDK-containing complexes also confirms the functional importance of the conserved CDK1/2 GDSEID motif. This structure improves our understanding of the roles of CDC25 phosphatases in CDK regulation and may inform the development of CDC25-targeting anticancer strategies.

The promising future of natural colors in the food industry aligns with the shift in consumer preference toward healthier food options. These naturally derived ingredients gradually replace their artificial counterparts and find applications in a wide range of food categories, and aquatic products have emerged as one of them. In this work, we introduced the characteristics and extraction of several main types of natural pigments and also explored the positive outcomes of integrating the pigments, such as carotenoids, curcumin, anthocyanins, and betalains, in aquatic product processing and preservation. Their outstanding antioxidant and dyeing properties contribute to the production and storage of various aquatic products. This review aims to provide a comprehensive understanding of the current state of natural pigment applications in aquatic products and to provide inspiration for future research and industry practices.

Abstract Sinistral portal hypertension, also known as left-sided portal hypertension, is a rare cause of gastric variceal bleeding which occurs secondary to occlusion of the splenic vein. We present a case of venous occlusion and sinistral portal hypertension secondary to distal pancreatic cancer requiring treatment of gastric variceal bleeding. After failing conservative management, transvenous intervention was attempted, but a venous communication with the gastric varices was unable to be identified on multiple venograms. A percutaneous trans-splenic approach using a 21-G needle and ultrasound guidance was successful in directly accessing an intraparenchymal vein feeding the gastric varices, and glue embolization was performed directly through the access needle with excellent results.

Highlights The capacity fading mechanism of the conventional Na3V2(PO4)3//Na3V2(PO4)3 (NVP//NVP) cell has been investigated. All-solid-state ferroelectric-engineered composite electrolyte could improve the electrolyte–electrode interfacial stability as well as the interfacial ion conduction of the Na-ion battery using the NVP anode. Outstanding cyclic stability has been achieved in the all-solid-state Na-ion battery using the NVP anode, with a capacity fading rate as low as 0.005% per cycle.

Abstract Background Concerns about mental and cognitive health are common among university students. Engaging in regular physical exercise has been shown to enhance both mental health and cognitive performance, yet most students are not participating in the level of exercise required to obtain these benefits. The Behaviour Change Wheel (BCW) provides a framework for developing behavioural interventions that are informed by theory, evidence, and stakeholder perspectives. The current study aimed to apply the BCW to develop the PEAK Mood, Mind, and Marks program (i.e., PEAK), a behaviour change intervention designed to increase university students’ exercise engagement for the benefit of their mental and cognitive health. Methods PEAK was developed across three stages of the BCW: (1) understand the target behaviour, (2) identify intervention options, and (3) identify intervention content and delivery mode. Development was informed by triangulated data from a systematic literature review, co-design consultations with key stakeholders, and knowledge of relevant experts. Consultations with stakeholders involved focus groups with 25 university students and individual interviews with 10 university leaders and staff to identify barriers and facilitators to students’ exercise engagement and the adoption and implementation of PEAK by universities. Template analysis was used to code transcripts to the capability, opportunity, and motivation (COM-B) model of behaviour. The BCW was applied to identify the most appropriate intervention types and behaviour change techniques (BCTs). Results Thirty-one barriers and facilitators were identified and mapped to seven intervention types (Education; Modelling; Persuasion; Environmental Restructuring; Incentivisation; Training; and Enablement) and 26 BCTs, which were delivered across digital channels and in-person. The final intervention consisted of multiple components targeting students’ capability (e.g., increasing knowledge about the mental and cognitive health benefits of exercise), opportunity (e.g., providing a flexible range of accessible exercise options and social support), and motivation (e.g., increasing the perceived importance of exercise) to exercise. Conclusions University students and staff describe a need and appetite for more empowering, scalable solutions to support students’ mental and cognitive health. Exercise-based approaches that are informed by behaviour change frameworks, evidence, and stakeholder perspectives, such as PEAK, have the potential to address this need. Current findings will inform a pilot of PEAK to evaluate its efficacy and implementation.

Abstract We investigate the integrability anomalies arising in the self-dual sectors of gravity and Yang-Mills theory, focusing on their connection to both the chiral anomaly and the trace anomaly. The anomalies in the self-dual sectors generate the one-loop all-plus amplitudes of gravitons and gluons, and have recently been studied via twistor constructions. On the one hand, we show how they can be interpreted as an anomaly of the chiral U(1) electric-magnetic-type duality in the self-dual sectors. We also note the similarity, for the usual fermionic chiral anomaly, between the 4D setting of self-dual Yang-Mills and the 2D setting of the Schwinger model. On the other hand, the anomalies in the self-dual theories also resemble the trace anomaly, sharing the same type of non-local effective action. We highlight the role of a Weyl-covariant fourth-order differential operator familiar from the trace anomaly literature, which (i) explains the conformal properties of the one-loop amplitudes, and (ii) indicates how this story may be extended to non-trivial spacetime backgrounds, e.g. with a cosmological constant. Moving beyond the self-dual sectors, and focusing on the gravity case, we comment on an intriguing connection to the two-loop ultraviolet divergence of pure gravity, whereby cancelling the anomaly at one-loop eliminates the two-loop divergence for the simplest helicity amplitudes.

Abstract Background Recently-updated global guidelines for cervical cancer screening incorporated new technologies—most significantly, the inclusion of HPV DNA detection as a primary screening test—but leave many implementation decisions at countries’ discretion. We sought to develop recommendations for Malawi as a test case since it has the second-highest cervical cancer burden globally and high HIV prevalence. We incorporated updated epidemiologic data, the full range of ablation methods recommended, and a more nuanced representation of how HIV status intersects with cervical cancer risk and exposure to screening to model outcomes of different approaches to screening. Methods Using a Markov model, we estimate the relative health outcomes and costs of different approaches to cervical cancer screening among Malawian women. The model was parameterized using published data, and focused on comparing “triage” approaches—i.e., lesion treatment (cryotherapy or thermocoagulation) at differing frequencies and varying by HIV status. Health outcomes were quality-adjusted life years (QALYs) and deaths averted. The model was built using TreeAge Pro software. Results Thermocoagulation was more cost-effective than cryotherapy at all screening frequencies. Screening women once per decade would avert substantially more deaths than screening only once per lifetime, at relatively little additional cost. Moreover, at this frequency, it would be advisable to ensure that all women who screen positive receive treatment (rather than investing in further increases in screening frequency): for a similar gain in QALYs, it would cost more than four times as much to implement once-per-5 years screening with only 50% of women treated versus once-per-decade screening with 100% of women treated. Stratified screening schedules by HIV status was found to be an optimal approach. Conclusions These results add new evidence about cost-effective approaches to cervical cancer screening in low-income countries. At relatively infrequent screening intervals, if resources are limited, it would be more cost-effective to invest in scaling up thermocoagulation for treatment before increasing the recommended screening frequency. In Malawi or countries in a similar stage of the HIV epidemic, a stratified approach that prioritizes more frequent screening for women living with HIV may be more cost-effective than population-wide recommendations that are HIV status neutral.

Abstract Background Ethnicity is known to be an important correlate of health outcomes, particularly during the COVID-19 pandemic, where some ethnic groups were shown to be at higher risk of infection and adverse outcomes. The recording of patients’ ethnic groups in primary care can support research and efforts to achieve equity in service provision and outcomes; however, the coding of ethnicity is known to present complex challenges. We therefore set out to describe ethnicity coding in detail with a view to supporting the use of this data in a wide range of settings, as part of wider efforts to robustly describe and define methods of using administrative data. Methods We describe the completeness and consistency of primary care ethnicity recording in the OpenSAFELY-TPP database, containing linked primary care and hospital records in > 25 million patients in England. We also compared the ethnic breakdown in OpenSAFELY-TPP with that of the 2021 UK census. Results 78.2% of patients registered in OpenSAFELY-TPP on 1 January 2022 had their ethnicity recorded in primary care records, rising to 92.5% when supplemented with hospital data. The completeness of ethnicity recording was higher for women than for men. The rate of primary care ethnicity recording ranged from 77% in the South East of England to 82.2% in the West Midlands. Ethnicity recording rates were higher in patients with chronic or other serious health conditions. For each of the five broad ethnicity groups, primary care recorded ethnicity was within 2.9 percentage points of the population rate as recorded in the 2021 Census for England as a whole. For patients with multiple ethnicity records, 98.7% of the latest recorded ethnicities matched the most frequently coded ethnicity. Patients whose latest recorded ethnicity was categorised as Other were most likely to have a discordant ethnicity recording (32.2%). Conclusions Primary care ethnicity data in OpenSAFELY is present for over three quarters of all patients, and combined with data from other sources can achieve a high level of completeness. The overall distribution of ethnicities across all English OpenSAFELY-TPP practices was similar to the 2021 Census, with some regional variation. This report identifies the best available codelist for use in OpenSAFELY and similar electronic health record data.

Abstract Background Clinical metagenomics involves the genomic sequencing of all microorganisms in clinical samples ideally after depletion of human DNA to increase sensitivity and reduce turnaround times. Current human DNA depletion methods preferentially preserve either DNA or RNA containing microbes, but not both simultaneously. Here we describe and present data using a practical and rapid mechanical host-depletion method allowing simultaneous detection of RNA and DNA microorganisms linked with nanopore sequencing. Methods The human cells from respiratory samples are lysed mechanically using 1.4 mm zirconium-silicate spheres and the human DNA is depleted using a nonspecific endonuclease. The RNA is converted to dsDNA to allow the simultaneous sequencing of DNA and RNA. Results The method decreases human DNA concentration by a median of eight Ct values while detecting a broad range of RNA & DNA viruses, bacteria, including atypical pathogens (Legionella, Chlamydia, Mycoplasma) and fungi (Candida, Pneumocystis, Aspergillus). The first automated reports are generated after 30 min sequencing from a 7 h end-to-end workflow. Sensitivity and specificity for bacterial detection are 90% and 100%, respectively, and viral detection are 92% and 100% after 2 h of sequencing. Prospective validation on 33 consecutive lower respiratory tract samples from ventilated patients with suspected pneumonia shows 60% concordance with routine testing, detection of additional pathogens in 21% of samples and pathogen genomic assembly achieve for 42% of viruses and 33% of bacteria. Conclusions Although further workflow refinement and validation on samples containing a broader range of pathogens is required, it holds promise as a clinically deployable workflow suitable for evaluation in routine microbiology laboratories.

HR-related risks can disrupt operations and cause significant problems for organizations. Effective HR risk management is essential for mitigating these risks. A strong HR risk management plan ensures adherence to labour laws, prevents costly legal issues, and safeguards public trust. Public sector organisations can proactively address potential HR risks and attract and retain top talent, improve employee morale, and achieve their goals more effectively. The primary purpose of this research was to critically investigate and analyze current HR risk management practices—justification of the choice of the research object. A questionnaire survey was conducted with 30 Erongo Regional Council staff members to explore HR risk management practices in a public sector organization. Justification of the choice of the research and research period: Informational and statistical basis of research. A descriptive research design was used to collect and analyze data. Descriptive statistics, hypothesis testing, and regression analysis were employed. A questionnaire survey was used to collect data from 30 Erongo Regional Council staff members. The main results of the research. The study found that the respondents understand HR risk management practices and the organization manages HR risks. A positive correlation was found between HR risk management and organizational performance. However, the study also revealed challenges in HR risk management implementation. Questionnaires are cost-effective and can reach many respondents within a short time frame. It allows you to gather data from a more comprehensive range of public sector organizations and get a broader perspective. This study recommends increased employee awareness of how HR risks can disrupt operations. By fostering awareness, organizations can minimize the likelihood of overlooking potential risks. These programs can equip them with the knowledge and skills to implement effective risk management strategies.

ABSTRACT: Currently, the dairy industry is facing many challenges that could affect its sustainability, including climate change and public perception of the industry. As a result, interest is increasing in the concept of identifying resilient animals, those with a long productive lifespan, as well as good reproductive performance and milk yield. There is much evidence that events in utero, that is, the developmental origins of health and disease hypothesis, alter the life-course health of offspring and we hypothesized that these could alter resilience in calves, where resilience is identified using lifetime data. The aim of this study was to quantify lifetime resilience scores (LRS) using an existing scoring system, based on longevity with secondary corrections for age at first calving and calving interval, and to quantify the effects of in utero events on the LRS using 2 datasets. The first was a large dataset of cattle on 83 farms in Great Britain born from 2006 to 2015 and the second was a smaller, more granular dataset of cattle born between 2003 and 2015 in the Langhill research herd at Scotland's Rural College. Events during dam's pregnancy included health events (lameness, mastitis, use of an antibiotic or anti-inflammatory medication), the effect of heat stress as measured by temperature-humidity index, and perturbations in milk yield and quality (somatic cell count, percentage fat, percentage protein and fat:protein ratio). Daughters born to dams that experienced higher temperature-humidity indexes while they were in utero during the first and third trimesters of pregnancy had lower LRS. Daughter LRS were also lower where milk yields or median fat percentages in the first trimester were low, and when milk yields were high in the third trimester. Dam LRS was positively associated with LRS of their offspring; however, as parity of the dam increased, LRS of their calves decreased. Similarly, in the Langhill herd, dams of a higher parity produced calves with lower LRS. Additionally, dams that recorded a high maximum locomotion score in the third trimester of pregnancy were negatively associated with lower calf LRS in the Langhill herd. Our results suggest that events that occur during pregnancy have lifelong consequences for the calf's lifetime performance. However, experience of higher temperature-humidity indexes, higher dam LRS, and mothers in higher parities explained a relatively small proportion of variation in offspring LRS, which suggests that other factors play a substantial role in determining calf LRS. Although “big data” can contain a considerable amount of noise, similar findings between the 2 datasets indicate it is likely these findings are real.

Abstract Background Asia’s elderly Baby Boomer demographic (born between 1946 and 1964) faced a huge problem during the COVID-19 pandemic due to increased all-cause mortality. We aimed to provide a unique Taiwan situation regarding the impact of Baby Boomers on excess mortalities from all causes relative to non-Baby Boomers throughout distinct times of SARS-CoV-2 mutations during the COVID-19 pandemic. Methods We used the Poisson time series design with a Bayesian directed acyclic graphic approach to build the background mortality prior to the COVID-19 pandemic between 2015 and 2019. It was then used for predicting the expected all-cause deaths compared to the reported figures during the COVID-19 pandemic period based on Taiwan residents, an Omicron-naïve cohort. Results Baby Boomers experienced a 2% negative excess mortality in 2020 (Wuhan/D614G) and a 4% excess mortality in 2021 (Alpha/Delta) with a rising background mortality trend whereas non-Baby Boomers showed the corresponding figures of 4% negative excess and 1% excess with a stable trend. Baby Boomer and non-Baby Boomer excess mortality soared to 9% (95% CI: 7-10%) and 10% (95% CI: 9-11%), respectively, during the epidemic Omicron period from January to June 2022. Surprisingly, Baby Boomers aged 58–76 experienced the same 9% excess mortality as non-Baby Boomers aged 77 and beyond. Non-COVID-19 deaths were more prevalent among Baby Boomers than non-Baby Boomers (33% vs. 29%). Conclusion Baby Boomers were more likely to die from COVID-19 in early pandemic and had more non-COVID-19 deaths in late pandemic than older non-Baby Boomers demonstrated in Taiwan Omicron-naïve cohort. For this vulnerable population, adequate access to medical care and medical capacity require more consideration.

Study Design This was a retrospective case-control study using 8 years of data from a nationwide database of surgical outcomes in the United States. Purpose This study aimed to improve our understanding of the risk factors associated with a length of stay (LOS) >1 day and aid in reducing postoperative hospitalization and complications. Overview of Literature Despite the proven safety of transforaminal lumbar interbody fusion (TLIF), some patients face prolonged postoperative hospitalization. Methods Data were collected from the American College of Surgeons National Surgical Quality Improvement Program dataset from 2011 to 2018. The cohort was divided into patients with LOS up to 1 day (LOS ≤1 day), defined as same day or next-morning discharge, and patients with LOS >1 day (LOS >1 day). Univariable and multivariable regression analyses were performed to evaluate predictors of LOS >1 day. Propensity-score matching was performed to compare pre- and postdischarge complication rates. Results A total of 12,664 eligible patients with TLIF were identified, of which 14.8% had LOS ≤1 day and 85.2% had LOS >1 day. LOS >1 day was positively associated with female sex, Hispanic ethnicity, diagnosis of spondylolisthesis, American Society of Anesthesiologists classification 3, and operation length of >150 minutes. Patients with LOS >1 day were more likely to undergo intraoperative/postoperative blood transfusion (0.3% vs. 4.5%, p