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Abstract Immunoglobulin G (IgG) is the main isotype of antibody in human blood. IgG consists of four subclasses (IgG1 to IgG4), encoded by separate constant region genes within the Ig heavy chain locus (IGH). Here, we report a genome-wide association study on blood IgG subclass levels. Across 4334 adults and 4571 individuals under 18 years, we discover ten new and identify four known variants at five loci influencing IgG subclass levels. These variants also affect the risk of asthma, autoimmune diseases, and blood traits. Seven variants map to the IGH locus, three to the Fcγ receptor (FCGR) locus, and two to the human leukocyte antigen (HLA) region, affecting the levels of all IgG subclasses. The most significant associations are observed between the G1m (f), G2m(n) and G3m(b*) allotypes, and IgG1, IgG2 and IgG3, respectively. Additionally, we describe selective associations with IgG4 at 16p11.2 (ITGAX) and 17q21.1 (IKZF3, ZPBP2, GSDMB, ORMDL3). Interestingly, the latter coincides with a highly pleiotropic signal where the allele associated with lower IgG4 levels protects against childhood asthma but predisposes to inflammatory bowel disease. Our results provide insight into the regulation of antibody-mediated immunity that can potentially be useful in the development of antibody based therapeutics.

Abstract Background Vulnerable children, including those with neuro-developmental delays and disabilities, often face barriers in accessing early primary education, thus hindering progress toward Sustainable Development Goal 4.2. Evidence-based interventions are essential to enhancing inclusivity and establishing sustainable implementation strategies to address this challenge. This study, Every Newborn—Reach up Early Education Intervention for All Children (EN-REACH), builds on the previous Every Newborn- Simplified Measurement Integrating Longitudinal Neurodevelopmental and Growth (EN-SMILING) observational cohort study. This paper provides the protocol for a cluster randomized controlled trial (cRCT) to evaluate the effectiveness of a parenting group intervention program for enhancing school readiness in Bangladesh, Nepal, and Tanzania, and an embedded process evaluation to inform scalability and feasibility. Methods EN-REACH is a cRCT with at least 150 clusters to evaluate the impact of a parent training program led by trained parent-teacher facilitator pairs, focusing on children aged 4 ~ 6 years preparing for preschool. Approximately 500 participants from the EN-SMILING cohort at each site have been identified. A geographic information system will define ~ 50 clusters in each of the three countries, each with approximately ten parent–child dyads. Half the clusters will be randomly assigned to intervention and control groups. The primary outcome is “school readiness”, assessed using the Measuring Early Learning Quality and Outcomes tool. Secondary outcomes include Intelligence Quotient, child functioning, growth, visual, and hearing assessments. Data will be collected at baseline, and post-intervention data following implementation of the parent group intervention sessions over approximately 5 months. Quantitative data on coverage and quality care, combined with qualitative insights from children, caregivers, facilitators, and stakeholders’ perspectives, will be used to conduct a process evaluation applying the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. Discussion This protocol details a trial focused on enhancing school readiness and cognitive abilities in young children, inclusive of those with disabilities, aiming to bridge gap from home to early primary education. EN-REACH aims to provide insights into the effectiveness and acceptability of a co-designed disability-inclusive school readiness program in three countries, potentially impacting national and global policies for all children, including those with disabilities. Trial registration The trial was retrospectively registered on clinicaltrials.gov on 29 February 2024 (NCT06334627).

Abstract Background Pre-eclampsia is a syndrome that chiefly includes the development of new-onset hypertension and proteinuria after 20 weeks of pregnancy. Pre-eclampsia is one of the major causes of mortality and morbidity in Nepal. Hyperhomocysteinemia may be a cause of the endothelial dysfunction provoked by oxidative stress in pre-eclampsia. This study was designed to evaluate the association of homocysteine with Vitamin B12 and folate in patients with pre-eclampsia. Method An observational cross sectional study was performed in the Gynecology and Obstetrics Department of TUTH involving seventy two subjects with pre-eclampsia. Blood pressure, urinary protein levels, serum homocysteine, Vitamin B12 and folate levels were compared in both mild and severe forms of pre-eclampsia. Concentration of Vitamin B12 and folate were measured using Vitros ECI and homocysteine was measured using CLIA. SPSS 23.0 was used to analyze the data. Tests were performed with Mann Whitney Test and Spearman’s rank correlation test. A p-value

Fever in older adults poses unique challenges due to atypical symptoms, weakened immune responses, and comorbidities. This chapter explores the diverse presentations of fever in the elderly, emphasizing the importance of vigilant monitoring and tailored interventions by healthcare providers and caregivers. Challenges in temperature measurement, communication barriers, and polypharmacy further complicate fever management. The chapter discusses the differences between fever presentations in young and older individuals and addresses the complexities of managing fever in long-term care facilities. In addition, it highlights fever of unknown origin in older persons, stressing the need for timely diagnosis and tailored investigations. Finally, preventive strategies, including vaccination campaigns and infection control measures, are proposed to mitigate fever occurrences in older adults.

Abstract This study on Buddleja polystachya highlights its phytochemical composition, antimicrobial activity, and cytotoxic impacts. The study emphasizes the plant’s potential to treat ocular diseases by identifying important compounds involved in the bioactivity through GC-MS analysis. This study explores the antimicrobial and cytotoxic potential of Buddleja polystachya (stem and leaves) extracts, with a focus on their application in treating bacterial ocular infections and their efficacy against MCF7, HT29, and HepG2 cancer cells. Through comprehensive GC-MS analysis, a diverse array of phytochemicals was identified within Buddleja polystachya stem and leaves extracts, including carbohydrates, phenolic derivatives, fatty acids, and steroidal components. The extracts were then evaluated for their biological activities, revealing significant antimicrobial properties against a range of bacterial strains implicated in ocular infections. The research findings demonstrate that stem extracts derived from Buddleja polystachya demonstrated high to moderate cytotoxic effects on cancer cell lines MCF7, HT29, and HepG2. Notably, these effects were characterized by varying IC50 values, which suggest distinct levels of sensitivity. In contrast, leaf extracts exhibited reduced cytotoxicity when tested against all these cell lines, although they did so with a significantly higher cytotoxicity aganist HepG2 cells. The results of this investigation highlight the potential therapeutic utilization of Buddleja polystachya extracts in the management of ocular infections and cancer. These results support the need for additional research to elucidate the underlying mechanisms of action of these extracts and explore their potential as drugs.

Abstract Background To interrupt residual malaria transmission and achieve successful elimination of Plasmodium falciparum in low-transmission settings, the World Health Organization (WHO) recommends the administration of a single dose of 0.25 mg/kg (or 15 mg/kg for adults) primaquine (PQ) combined with artemisinin-based combination therapy (ACT), without glucose-6-phosphate dehydrogenase (G6PD) testing. However, due to the risk of haemolysis in patients with G6PD deficiency (G6PDd), PQ use is uncommon. Thus, this study aimed to assess the safety of a single low dose of PQ administered to patients with G6PD deficiency. Methods An observational cohort study was conducted with patients treated for uncomplicated P. falciparum malaria with either single-dose PQ (0.25 mg/kg) (SLD PQ) + ACT or ACT alone. Microscopy-confirmed uncomplicated P. falciparum malaria patients visiting public health facilities in Arjo Didessa, Southwest Ethiopia, were enrolled in the study from September 2019 to November 2022. Patients with uncomplicated P. falciparum malaria were followed up for 28 days through clinical and laboratory diagnosis, such as measurements of G6PD levels and haemoglobin (Hb) concentrations. G6PD levels were measured by a quantiative CareSTART™ POCT S1 biosensor machine. Patient interviews were also conducted, and the type and frequency of clinical complaints were recorded. Hb data were taken on days (D) 7, 14, 21, and 28 following treatment with SLD-PQ + ACT or ACT alone. Results A total of 249 patients with uncomplicated P. falciparum malaria were enrolled in this study. Of these, 83 (33.3%) patients received ACT alone, and 166 (66.7%) received ACT combined with SLD-PQ treatment. The median age of the patients was 20 (IQR 28–15) years. G6PD deficiency was found in 17 (6.8%) patients, 14 males and 3 females. There were 6 (7.2%) and 11 (6.6%) phenotypic G6PD-deficient patients in the ACT alone and ACT + SLD-PQ arms, respectively. The mean Hb levels in patients treated with ACT + SLD-PQ were reduced by an average of 0.45 g/dl (95% CI = 0.39 to 0.52) in the posttreatment phase (D7) compared to a reduction of 0.30 g/dl (95% CI = 0.14 to − 0.47) in patients treated with ACT alone (P = 0.157). A greater mean Hb reduction was observed on day 7 in the G6PDd ACT + SLD-PQ group (− 0.60 g/dL) than in the G6PDd ACT alone group (− 0.48 g/dL); however, there was no statistically significant difference (P = 0.465). Overall, D14 losses were 0.10 g/dl (95% CI = − 0.00 to 0.20) and 0.05 g/dl (95% CI = − 0.123 to 0.22) in patients with and without SLD-PQ, respectively (P = 0.412). Conclusions This study’s findings indicate that using SLD-PQ in combination with ACT is safe for uncomplicated P. falciparum malaria regardless of the patient's G6PD status in Ethiopian settings. Caution should be taken in extrapolating this finding in other settings with diverse G6DP phenotypes.

The aim of this study is to see how competence and organizational commitment affect employee productivity. We used the inferential verification technique, which is a strategy employed by researchers to assess the validity of presented hypotheses by gathering actual data from the field of Indonesia's industries. A total of 300 personnel from Indonesia's cable and electrical industries were purposefully chosen as responders. We used Structural Equation Modelling (SEM) analysis, aided by the LISREL 8.80 software, to test the hypotheses. The study's findings are as follows: (1) there is a positive and significant influence of competence (= 0.30) on the work productivity of employees; (2) there is a positive and insignificant influence of organizational commitment (= 0.09) on the work productivity of employees; and (3) there is a positive and significant influence of organizational commitment (= 0.50) on the work productivity of employees Indonesia's industries, (4) Organizational commitment has a mediating function in the effect of competence (t = 4.15) on job productivity of employees in Indonesia's industries. A limitation of this study is that the survey only focused on Indonesia's cable and electricity industry plants and the tactical level management of an organization. The study's findings contribute to boosting organizational commitment and job competence that can boost employee productivity in Indonesia's industries. Due to its relatively rapid economic development, Indonesia is extremely appealing to international investors, particularly in the industrial sector. However, Indonesia must boost its manufacturing sector in order to attract more foreign investors. Also, this study is an empirical investigation, and its results can be generalized to similar industrial establishments.

This study aims to explore the application of an integrated approach in preparing learning plans for Indonesian language subjects at the senior high school level. The research method was qualitative in the form of a case study carried out at some schools in Makassar. The subjects of this research were Indonesian language teachers who were determined purposively. Data collection methods were observation, interviews, and documentation. Data were analyzed using (1) reduction, (2) presentation, and (3) verification techniques. The findings show that empowering the integrated approach always begins, and this was dominated by the speaking aspect rather than the other skills such as reading, writing, and listening skills. On the other hand, linguistic aspects are least programmed by Indonesian language teachers. Linguistic aspects are never combined with literature, even though it is very interesting to teach at the high school level on a multi-ethnic basis. It can be concluded that the Indonesian language is taught by using an integrated approach, which can reshape the students’ speaking competency. This approach is implemented in the lesson plan to enhance the Indonesian learning process.

Cellulase enzymes are widely used in the food, beverage, animal feed, textile, and paper industries. The high cost of producing enzymes and low enzyme activity provides opportunities for using chemicals, and efforts are needed to produce cellulase enzymes economically through media optimization. This research aims to find alternative media that make it possible to produce cellulase enzymes with high activity. This research created a control media (M0) using pro-analysis chemicals and CMC as a carbon source. Three types of cellulolytic bacterial growth media were also created, consisting of technical chemicals, rice straw as a substrate, and different protein sources. M1: alternative media using urea as a protein source; M2: alternative media using powdered milk as a protein source; and M3: alternative media using chicken liver as a protein source. A total of 1% of cellulolytic bacteria (Actinobacillus sp.) was grown in each media and then incubated at 40°C for 33 hours at a speed of 140 rpm, and the production curve and cellulase enzyme activity were measured at every 3-hour interval. The results showed that the highest cellulase enzyme production was achieved at 24 hours using alternative media with powdered milk (M2) as a protein source. The cellulase enzyme activity produced was 2.9612 µ/ml.

The purpose of this research was to determine the correlation between the weight of the ovary, the number of follicles, and the quality of the oocytes from the culling female bovine obtained from the slaughterhouse. The variation may affect the potential of the ovary to produce follicles. Paired ovaries were obtained from female bovines. Follicle numbers were recorded and divided into three size categories (small: 3 mm, medium: < 3 mm-8 mm, and large: > 8 mm). Oocytes were aspirated and the number of oocytes was recorded and graded into four categories (grades A, B, C, and D). There was a positive correlation between the weight of the ovary and the number of follicles, which is 0.560 with the regression equation y = 3.52 + 0.501 x. There was a positive correlation between the number of follicles and the number of oocytes, which is 0.546 with the regression equation y =2.48 + 1.204 x. There was a positive correlation between the number of oocytes and the grade of oocytes, which is 0.520, with the regression equation y = 0.93 + 0.800 x. There was no correlation between the weight of the ovary and oocyte grade A, which is 0.013.

Early cardiopulmonary resuscitation (CPR) intervention is critical for saving individuals experiencing sudden cardiac arrest. Manikins are considered useful for CPR training, but their level of realism is low, given the visible structural differences in the chests of biological men and women. However, to our knowledge, no study has examined whether a patient’s sex has an impact on the performance of chest compression. Therefore, this study aimed to investigate the quality of chest compression in female patients, in relation to the rescuers’ posture. This single-center cross-sectional study was conducted from July to October 2023 on 34 healthcare professional university students. Two postures for chest compression were analyzed: 1) kneeling beside the patient’s chest (conventional compression) and 2) straddling the patient (straddle compression). The mean age of the 34 participants (18 men and 16 women) was 21.2 ± 0.6 years. Significant differences were found in mean compression depth (p = 0.005) and appropriate compression ratio (p = 0.013) between the conventional and straddle compression, but not in other parameters. In conclusion, the rescuers’ posture during chest compression in female patients affects the compression depth and depth ratio. Straddle compression may facilitate the provision of well-balanced compressions of appropriate depth and depth ratio. These findings can be applied to CPR training and provide guidance for administering chest compression to female patients.

Extended-spectrum β-lactamases (ESBLs) are β-lactamase enzymes produced by Gram-negative bacterial pathogens that harbor the ESBL genes. In addition, most ESBL genes are plasmid-mediated and usually encode a broader spectrum of antimicrobial resistance, especially to penicillins, first-generation, second-generation, and third-generation cephalosporins, as well as monobactam, such as aztreonam. Escherichia coli has become an opportunistic pathogen, especially in poultry, and has been implicated in zoonotic diseases that can be transmitted to humans, resulting in public health problems. Poultry can act as carriers of ESBL-producing E. coli (ESBL-EC) bacteria to humans through poultry meat that is contaminated by waste products, feces, and excretions. The ESBL gene CTX-M type was identified as the main cause of infection in humans and was detected in poultry as a cause of infection accompanied by clinical symptoms. Several studies have also shown a link between E. coli and ESBL gene transfer from birds to humans. Controlling the spread of ESBL-EC involves maintaining the cleanliness of poultry products, especially meat, and eliminating contaminant sources from poultry. Likewise, maintaining the environmental cleanliness of poultry slaughterhouses and poultry farms must be taken as a precautionary measure to curtail the increasing spread of ESBL-EC into the environment. This review aimed to explain the spread of ESBL-producing E. coli in poultry.

Abstract Introduction Zinc with oral re-hydration salt supplementation provides much improved outcomes for managing childhood diarrhea. There is scarcity of evidence in the study area regarding zinc supplementation adherence and factors associated with. Thus, the aim of this study was to assess zinc supplementation adherence and associated factors among caregivers of under five children with diarrhea attending health centers in Gondar City. Methods An institutional based cross-sectional study was conducted with 405 caregivers of under-five children with diarrhea who received zinc supplementation in Gondar City health centers. Bivariable and multivariable logistic regression analysis were computed. Results 35% (95% CI: 29.91, 39.21) of caregivers of under five children adhered for zinc supplementation. Adherence was observed among caregivers with good knowledge about zinc supplementation (AOR = 3.01 95%CI = 1.73, 5.24), and who received counseling (AOR = 8.4, 95%CI = 4.66, 15.13), presence of side effects (AOR = 0.35, 95% CI 0.20, 0.65) was negatively associated with zinc supplementation adherence. Conclusion In the study area, more than one third of children with diarrhea were adhered to zinc supplementation. Thus, improving the knowledge of caregivers and enhancing counseling services on benefits, dosage, duration and side effects of zinc supplementation are vital to improve adherence in the area.

Abstract A biometric system is essential in improving security and authentication processes across a variety of fields. Due to multiple criteria and alternatives, selecting the most suitable biometric system is a complex decision. We employ a hybrid approach in this study, combining the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) with the Analytic Hierarchical Process (AHP). Biometric technologies are ranked using the TOPSIS method according to the relative weights that AHP determines. By applying the neutrosophic set theory, this approach effectively handles the ambiguity and vagueness inherent in decision-making. Fingerprint, face, Iris, Voice, Hand Veins, Hand geometry and signature are the seven biometric technologies that are incorporated in the framework. Seven essential characteristics are accuracy, security, acceptability, speed and efficiency, ease of collection, universality, distinctiveness used to evaluate these technologies. The model seeks to determine which biometric technology is best suited for a particular application or situation by taking these factors into account. This technique may be applied in other domains in the future.

Abstract Background Informing individuals about their risk of cancer can sometimes have negative consequences, such as inflicting unnecessary worry and fostering stigma. This study aims to explore how patients diagnosed with breast or colorectal cancer perceive and experience risk communication, particularly concerning the increased focus on lifestyle behaviors as the cause of cancer. Methods Semi-structured interviews were conducted during autumn 2023, with 23 Swedish individuals, aged 34 to 79 years, diagnosed with breast or colorectal cancer. The collected data were analyzed using inductive thematic analysis described by Braun & Clark. The study adopted an experiential orientation grounded in critical realism. Results Five themes with ten sub-themes were identified: Thoughts and feelings about the causes of cancer, Moralizing messages and negative encounters, The need to take action, Balancing uncertain risks and a fulfilling life, and Societal benefits of risk communication. The participants expressed that knowledge of the the cause of cancer is closely related to the possibility of taking preventive action against relapses. Ability to take action was also perceived important for their well-being. Therefore, risk information entails both feelings of self-blame and hope for the future. Participants asked for both information and lifestyle support from healthcare professionals. Lifestyle interventions and patient support groups were solicited and perceived as an important aspect of cancer survivals’ well-being, and may help to reduce the cancer-related stigma. Conclusion Individuals that have or have had breast or colorectal cancer, including those leading healthy lifestyles, found moralistic risk information offensive, leading to feelings of shame when thinking about other peoples thoughts. Balancing information involves providing transparent, evidence-based information while considering individual and social contexts, avoiding stigmatization and blame, and supplementing information with support.

Abstract Background In Ethiopia, there were an estimated 670,906 people living with the Human Immune Virus (HIV). Implementing an HIV test and treat strategy and rapid scale-up of anti-retroviral treatment (ART) provided health facilities increased the number of the number of people living with HIV/AIDS. In the same way, the expansion of viral load monitoring in these health facilities and poor adherence to ART increase the number of high-viral load (HVL) patients. To alleviate this problem, the World Health Organization (WHO) recommended EAC intervention for HVL patients. Therefore, the aim of this research was to determine the level of healthcare providers’ adherence to the EAC intervention protocol and explore barriers and facilitators of the intervention in West Amhara, Northwest Ethiopia. Method Descriptive cross-sectional study design with concurrent mixed-method evaluation was employed. The adherence dimension, with its sub-dimensions of content, coverage, frequency, and duration of the EAC intervention, was used with sixteen indicators. A total of 20 high-case-load public health facilities and 173 HVL patients were included in our study. Quantitative data was entered into Epi Info and exported to SPSS version 25 for analysis. Descriptive statistics are analyzed in terms of frequencies, percentages, variances, and means and presented as narrations, frequency tables, graphs, and charts. Qualitative data were transcribed, translated, coded, and analyzed thematically using Open Code version 4.0 software. The qualitative findings were used to triangulate the quantitative findings. Result The average adherence level of health care providers (HCPs) to the EAC intervention protocol was 55.3%, from which content, coverage, frequency, and duration of the intervention contributed 70.3%, 86.3%, 36.9%, and 27.7%, respectively. Most of the intervention contents were delivered during the session, but none of the providers developed a patient adherence plan at the end of the session. All HVL patients were linked and enrolled in the EAC intervention. But only 6% of them were tested for repeat VL. Conclusion The average adherence level of HCPs to the EAC intervention protocol was very inadequate. The main gap identified was difficulties in completing the EAC intervention sessions based on schedules. Implementing adherence improvement strategies, assigning an adequate number of EAC providers in ART and Prevention of Mother-to-Child Transmission (PMTCT) clinics, and allowing sufficient time during EAC sessions are important.

Abstract Background Japan implemented strict border control measures and all incoming passengers were subject to entry screening with reverse transcription–polymerase chain reaction or antigen testing. From late 2020, exit screening within 72 h of departure to Japan also became mandatory. In this study, we evaluated the effectiveness of the exit screening policy in Japan by analyzing airport screening data from October 2020 to April 2022. Methods In addition to assessing entry screening data over time of passengers from the United Kingdom, we examined the prevalence of coronavirus disease 2019 (COVID-19) in the United Kingdom based on the Office of National Statistics infection survey. We constructed a statistical model that described entry screening positivity over time using Office of National Statistics prevalence data as the explanatory variable. Ideally, the time-dependent patterns of entry screening and Office of National Statistics prevalence data should resemble each other; however, we found that, sometimes, they were different and regarded the difference to statistically partly reflect the effectiveness of exit screening. Results The average proportion positive in one month before mandatory exit screening was implemented among Japanese passengers was 0.67% (95% confidence interval [CI]: 0.45, 0.98), whereas the proportion positive decreased to 0.49% (95% CI: 0.21, 1.15) in the first month of exit screening. Adjusting for time-dependent prevalence at the origin, we concluded that exit screening contributed to reducing passenger positivity by 59.3% (95% CI: 19.6, 81.3). The overall positivity values among passengers during the Delta and Omicron variant periods were 3.46 times and 1.46 times that during the pre-Delta variant period, respectively. Conclusions We used a simplistic statistical model and empirical data from passengers arriving in Japan from the United Kingdom to support that exit screening helped to reduce the proportion positive by 59%. Although the proportion positive later increased considerably and precluded preventing the introduction of imported cases, submitting a certificate for a negative test result contributed to reducing the positivity among travelers.

Abstract The gut microbiota of infants in low- to middle-income countries is underrepresented in microbiome research. This study explored the faecal microbiota composition and faecal cytokine profiles in a cohort of infants in a rural province of Cambodia and investigated the impact of sample storage conditions and infant environment on microbiota composition. Faecal samples collected at three time points from 32 infants were analysed for microbiota composition using 16S rRNA amplicon sequencing and concentrations of faecal cytokines. Faecal bacterial isolates were subjected to whole genome sequencing and genomic analysis. We compared the effects of two sample collection methods due to the challenges of faecal sample collection in a rural location. Storage of faecal samples in a DNA preservation solution preserved Bacteroides abundance. Microbiota analysis of preserved samples showed that Bifidobacterium was the most abundant genus with Bifidobacterium longum the most abundant species, with higher abundance in breast-fed infants. Most infants had detectable pathogenic taxa, with Shigella and Klebsiella more abundant in infants with recent diarrhoeal illness. Neither antibiotics nor infant growth were associated with gut microbiota composition. Genomic analysis of isolates showed gene clusters encoding the ability to digest human milk oligosaccharides in B. longum and B. breve isolates. Antibiotic-resistant genes were present in both potentially pathogenic species and in Bifidobacterium. Faecal concentrations of Interlukin-1alpha and vascular endothelial growth factor were higher in breast-fed infants. This study provides insights into an underrepresented population of rural Cambodian infants, showing pathogen exposure and breastfeeding impact gut microbiota composition and faecal immune profiles.

Abstract Background Ingestion of corrosive substances represents a frequent and consequential medical scenario, significantly impacting both vital and functional prognoses through the emergence of acute complications or stenosis, which pose considerable therapeutic challenges. Currently, endoscopy remains the cornerstone modality for diagnostic assessment and management. Nevertheless, recent research highlights computed tomography (CT) as a promising alternative, avoiding the risks associated with endoscopy and reducing the unnecessary surgical interventions based on its findings. Methods Our retrospective study, spanning three years, encompassed 28 patients who had ingested corrosive substances. Among them, 24 underwent both CT scanning and endoscopic evaluation using CT and endoscopic scores. Results Employing Standardized CT scoring criteria alongside the Zargar’s endoscopic classification, our findings revealed significant concordance between the two modalities, particularly in discerning trans-parietal necrosis within the esophagus and stomach. Notably, radiographic evidence of digestive tract injury was found to be predictive of complications in over 80% of cases, demonstrating high sensitivity and negative predictive value. Furthermore, CT scores indicating moderate to severe injury were significantly associated with stenosis, with slightly inferior performance compared to endoscopy. Of particular note, a CT score indicative of severe injury was found to be a good predictor of mortality, further underscoring the prognostic value of CT in these cases. Conclusion While the utility of CT in this context is undeniable, its integration with endoscopic findings remains imperative. We advocate for a systematic approach incorporating CT scanning, with further prospective research warranted to explore the feasibility of CT as a standalone diagnostic tool, as suggested by some scholars.

Abstract Background Despite calls for regionalizing pancreatic cancer (PC) care to high-volume centers (HVCs), many patients with PC elect to receive therapy closer to their home or at multiple institutions. In the context of cross-institutional PC care, the challenges associated with coordinating care are poorly understood. Methods In this qualitative study we conducted semi-structured interviews with oncology clinicians from a HVC (n = 9) and community-based hospitals (n = 11) to assess their perspectives related to coordinating the care of and treating PC patients across their respective institutions. Interviews were transcribed, coded, and analyzed using deductive and inductive approaches to identify themes related to cross-institutional coordination challenges and to note improvement opportunities. Results Clinicians identified challenges associated with closed-loop communication due, in part, to not having access to a shared electronic health record. Challenges with patient co-management were attributed to patients receiving inconsistent recommendations from different clinicians. To address these challenges, participants suggested several improvement opportunities such as building rapport with clinicians across institutions and updating tumor board processes. The opportunity to update tumor board processes was reportedly multi-dimensional and could involve: (1) designating a tumor board coordinator; (2) documenting and disseminating tumor board recommendations; and (3) using teleconferencing to facilitate community-based clinician engagement during tumor board meetings. Conclusions In light of communication barriers and challenges associated with patient co-management, enabling the development of relationships among PC clinicians and improving the practices of multidisciplinary tumor boards could potentially foster cross-institutional coordination. Research examining how multidisciplinary tumor board coordinators and teleconferencing platforms could enhance cross-institutional communication and thereby improve patient outcomes is warranted.

Abstract Objective The study aims to explore the perceived outcomes of Medical Teaching Institution (MTI) reforms on autonomy and overall performance within tertiary healthcare institutions in Khyber Pakhtunkhwa (KP) province, Pakistan. Methodology A cross-sectional study was carried out from September 2023 to March 2024, involving interviews with frontline staff, administrative personnel, and senior management within MTI-affiliated institutions. The methodology employed, using both qualitative and quantitative data analysis techniques. Results The study showed that institutional staff members’ knowledge and understanding of the MTI changes differed. Some observed very minor adjustments, while others saw advances in hospital operations and service delivery. Administrative complexity, political meddling, and resource allocation problems were noted as challenges. Positive results were also observed, though, and they included improved infrastructure, possibilities for staff training, and decision-making procedures. Conclusion Despite significant improved, there are still challenges, such as inconsistent staff comprehension, mixed impacts on service delivery, resource allocation issues, and political meddling. Addressing these issues necessitates improved communication, continuous evaluation, and coordinated efforts to improve administrative systems and obtain consistent funding.

Abstract Antibacterial resistance requires an advanced strategy to increase the efficacy of current therapeutics in addition to the synthesis of new generations of antibiotics. In this study, copper oxide nanoparticles (CuO-NPs) were green synthesized using Moringa oleifera root extract. CuO-NPs fabricated into a form of aspartic acid-ciprofloxacin-polyethylene glycol coated copper oxide-nanotherapeutics (CIP-PEG-CuO) to improve the antibacterial activity of NPs and the efficacy of the drug with controlled cytotoxicity. These NPs were charachterized by Fourier transform infrared spectroscopy (FTIR), x-rays diffraction spectroscopy (XRD), scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS). Antibacterial screening and bacterial chemotaxis investigations demonstrated that CIP-PEG-CuO NPs show enhanced antibacterial potential against Gram-positive and Gram-negative clinically isolated pathogenic bacterial strains as compared to CuO-NPs. In ex-vivo cytotoxicity CIP-PEG-CuO-nano-formulates revealed 88% viability of Baby Hamster Kidney 21 cell lines and 90% RBCs remained intact with nano-formulations during hemolysis assay. An in-vivo studies on animal models show that Staphylococcus aureus were eradicated by this newly developed formulate from the infected skin and showed wound-healing properties. By using specially designed nanoparticles that are engineered to precisely transport antimicrobial agents, these efficient nano-drug delivery systems can target localized infections, ensure targeted delivery, enhance efficacy through increased drug penetration through physical barriers, and reduce systemic side effects for more effective treatment.

Abstract Chronic inflammation is associated with diabetes and contributes to the development and progression of micro- and macrovascular complications. Transcutaneous vagus nerve stimulation (tVNS) has been proposed to reduce levels of circulating inflammatory cytokines in non-diabetics by activating the cholinergic anti-inflammatory pathway. We investigated the anti-inflammatory potential of tVNS as a secondary endpoint of a randomized controlled trial in people with diabetes (NCT04143269). 131 people with diabetes (type 1: n = 63; type 2: n = 68), gastrointestinal symptoms and various degrees of autonomic neuropathy were included and randomly assigned to self-administer active (n = 63) or sham (n = 68) tVNS over two successive study periods: (1) Seven days with four daily administrations and, (2) 56 days with two daily administrations. Levels of systemic inflammatory cytokines (IL-6, IL-8, IL-10, TNF-α, IFN-γ) were quantified from blood samples by multiplex technology. Information regarding age, sex, diabetes type, and the presence of cardiac autonomic neuropathy (CAN) was included in the analysis as possible confounders. No differences in either cytokine were seen after study period 1 and 2 between active and sham tVNS (all p-values > 0.08). Age, sex, diabetes type, presence of CAN, and baseline levels of inflammatory cytokines were not associated with changes after treatment (all p-values > 0.07). A tendency towards slight reductions in TNF-α levels after active treatment was observed in those with no CAN compared to those with early or manifest CAN (p = 0.052). In conclusion, tVNS did not influence the level of systemic inflammation in people with diabetes.

Abstract In continuous powder handling processes, precise and consistent feeding is crucial for ensuring the quality of the final product. The intermixing effect caused by agitators, which alters the powder’s bulk density, flow rate, and flow patterns, plays a significant role in this process, yet it is often overlooked. This study combines discrete element method (DEM) modeling and experiments using a commercial-scale feeder to propose a Digital Twin (DT) framework. The DEM model accurately captures key flow features, such as bypass trajectories, stagnant zones, and preferential flow patterns, while providing quantitative predictions for the feed factor and zones prone to material accumulation. Scenario analysis is performed to identify the most favorable operating ranges of the screw-agitator ratio and screw speed, considering the cohesive properties of the powder. The study demonstrates that powders with poor flow characteristics require tighter operational constraints, as the screw-agitator ratio is susceptible to variations in mass feed rate. This contribution highlights the importance of selecting an appropriate screw-agitator ratio instead of maintaining a fixed value. Properly choosing this ratio helps determine an optimal operation window, which aims to achieve a minimum agitation level needed to induce unhindered flow and reduce variability in the mass flow rate.

Abstract While data-driven approaches demonstrate great potential in atmospheric modeling and weather forecasting, ocean modeling poses distinct challenges due to complex bathymetry, land, vertical structure, and flow non-linearity. This study introduces OceanNet, a principled neural operator-based digital twin for regional sea-suface height emulation. OceanNet uses a Fourier neural operator and predictor-evaluate-corrector integration scheme to mitigate autoregressive error growth and enhance stability over extended time scales. A spectral regularizer counteracts spectral bias at smaller scales. OceanNet is applied to the northwest Atlantic Ocean western boundary current (the Gulf Stream), focusing on the task of seasonal prediction for Loop Current eddies and the Gulf Stream meander. Trained using historical sea surface height (SSH) data, OceanNet demonstrates competitive forecast skill compared to a state-of-the-art dynamical ocean model forecast, reducing computation by 500,000 times. These accomplishments demonstrate initial steps for physics-inspired deep neural operators as cost-effective alternatives to high-resolution numerical ocean models.

Abstract This study investigates the impact of carbohydrate accumulation in mangrove and halophytic plants on their response to abiotic stress. Using soil analysis and FT-IR spectroscopy, key species (Sueda nudiflora, Aeluropus lagopoides, Avicennia marina) were examined for seasonal changes in sugar content (reducing sugars, total soluble sugars, starch). The elevated carbohydrate levels may serve as an indication of the plant’s ability to adapt to different environmental conditions throughout the year. This accumulation enables plants to adapt to variations in their environment, assuring their survival and functionality during periods of environmental fluctuation. Halophytic plants’ sugar content peaked during the monsoon, suggesting biotic adaptations. The mangrove Avicennia marina had year-round sugar levels. PCA and Hierarchical Cluster Analysis revealed sugar accumulation trends across species and seasons. Partial Least Squares (PLS) analysis revealed correlations between soil characteristics and sugar content, suggesting plant-microbe interactions. K-means clustering and correlation analysis of FT-IR data revealed sugar composition and resource allocation trade-offs. These findings shed light on the role of carbohydrate metabolism in enabling coastal plants to endure stress. Gaining insight into these mechanisms can enhance sustainable agriculture in challenging environments and shed light on plant adaptations to evolving environmental conditions, especially biotic interactions.

Abstract Aortic valve replacement (AVR) leads to reverse cardiac remodeling in patients with aortic stenosis (AS). The aim of this secondary pooled analysis was to assess the degree and determinants of changes in myocardial perfusion post AVR, and its link with exercise capacity, in patients with severe AS. A total of 68 patients underwent same-day echocardiography and cardiac magnetic resonance imaging with adenosine stress pre and 6–12 months post-AVR. Of these, 50 had matched perfusion data available (age 67 ± 8 years, 86% male, aortic valve peak velocity 4.38 ± 0.63 m/s, aortic valve area index 0.45 ± 0.13cm2/m2). A subgroup of 34 patients underwent a symptom-limited cardiopulmonary exercise test (CPET) to assess maximal exercise capacity (peak VO2). Baseline and post-AVR parameters were compared and linear regression was used to determine associations between baseline variables and change in myocardial perfusion and exercise capacity. Following AVR, stress myocardial blood flow (MBF) increased from 1.56 ± 0.52 mL/min/g to 1.80 ± 0.62 mL/min/g (p

Abstract This article presents an investment recommender system based on an Adaptive Neuro-Fuzzy Inference System (ANFIS) and pre-trained weights from a Multimodal Neural Network (MNN). The model is designed to support the investment process for the customers and takes into consideration seven factors to implement the proposed investment system model through the customer or potential investor data set. The system takes input from a web-based questionnaire that collects data on investors' preferences and investment goals. The data is then preprocessed and clustered using ETL tools, JMP, MATLAB, and Python. The ANFIS-based recommender system is designed with three inputs and one output and trained using a hybrid approach over three epochs with 188 data pairs and 18 fuzzy rules. The system's performance is evaluated using metrics such as RMSE, accuracy, precision, recall, and F1-score. The system is also designed to incorporate expert feedback and opinions from investors to customize and improve investment recommendations. The article concludes that the proposed ANFIS-based investment recommender system is effective and accurate in generating investment recommendations that meet investors' preferences and goals. Graphical abstract

Abstract Data has evolved into one of the principal resources for contemporary businesses. Moreover, corporations have undergone digitalization; consequently, their supply chains generate substantial amounts of data. The theoretical framework of this investigation was built on novel concepts like big data analytics—artificial intelligence (BDA-AI) and supply chain ambidexterity’s (SCA) direct impacts on sustainable supply chain management (SSCM) and indirect impacts on sustainable innovation ambidexterity (SIA) and environmental performance (EP). This study selected employees of manufacturing industries as respondents for environmental performance, sustainable supply chain management, big data analytics, artificial intelligence, and supply chain ambidexterity. The results from this study show that BDA-AI and SCA significantly affect SSCM. SSCM has significant associations with SIA and EP. Finally, SIA has a significant impact on EP. According to the results indicating the indirect impacts, BDA-AI has significant indirect relationships with SIA and EP by having SSCM as the mediating variable. Furthermore, SCA has significant indirect associations with SIA and EP, with SSCM as the mediating variable. Additionally, both BDA-AI and SCA have significant indirect associations with EP, while SIA and SSCM are mediating variables. Finally, SSCM has an indirect association with EP while having SIA as a mediating variable. The findings of this paper provide several theoretical contributions to the research in sustainability and big data analytics artificial intelligence field. Furthermore, based on the suggested framework, this study offers a number of practical implications for decision-makers to improve significantly in the supply chain and BDA-AI. For instance, this paper provides significant insight for logistics and supply chain managers, supporting them in implementing BDA-AI solutions to help SSCM and enhance EP.

Abstract The interest in region-specific ethnic fermented foods and their functional microbiota is rising. The demands for functional foods are continuously rising, so research is going on to develop nutritious food with many beneficial attributes and low safety concerns. The present study was designed to isolate and characterize lactobacilli probiotic candidates from locally resourced fermented foods (dahi , lassi, and raabadi) to make ready-to-eat fermented functional products later. Cultures were isolated from 82 fermented food samples collected from different villages. The initial experiments of gram staining, catalase test, and carbohydrate fermentation were assessed for the morphology, purity, and primary characterization on the genus level, which was verified through molecular characterization using PCR. Seven lactobacilli strains (no. MS001-MS007) were then assessed for safety, probiotic candidacy, phytase degradation, and biofilm forming abilities. All seven bacterial cultures showed no hemolytic activity and antibiotic sensitivity against more than 14 antibiotics out of 20. All seven lactobacilli isolates were able to tolerate pH 3.0, 0.3% bile 0.5% pancreatin, lysozyme (100 mg/L to 300 mg/L) and also shown possessed phytase degradation ability. All the cultures showed antioxidative potential and biofilm formation ability. Culture MS007 showed considerably higher bile salt hydrolase activity among all the isolates, whereas MS005 possessed excellent phytate degradation ability among others. Bacterial strains were identified using 16S rRNA gene sequencing. Moreover, the order of preference of isolates was calculated using the multidimensional Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) based on probiotic and other functional properties. The most promising attributes showing cultures were recognised as Limosilactobacillus fermentum MS005 and Lactiplantibacillus plantarum MS007, which could be further used for functional food product development. Graphical Abstract

Abstract Breast cancer is one of the leading causes of death among women globally, making its diagnosis and treatment challenging. The use of nanotechnology for cancer diagnosis and treatment is an emerging area of research. To address this issue, multiwalled carbon nanotubes (MWCNTs) were ligand exchanged with butyric acid (BA) to gain hydrophilic character. The successful functionalization was confirmed by FTIR spectroscopy. Surface morphology changes were observed using SEM, while TEM confirmed the structural integrity of the MWCNTs after functionalization. Particle size, zeta potential, and UV spectroscopy were also performed to further characterize the nanoparticles. The breast cancer aptamer specific to Mucin-1 (MUC-1) was then conjugated with the functionalized MWCNTs. These MWCNTs successfully targeted breast cancer cells (MDA-MB-231) as examined by cellular uptake studies and exhibited a reduction in cancer-induced inflammation, as evidenced by gene transcription (qPCR) and protein expression (immunoblotting) levels. Immunoblot and confocal-based immunofluorescence assay (IFA) indicated the ability of CNTs to induce photothermal cell death of MDA-MB-231 cells. Upon imaging, cancer cells were effectively visualized due to the MWCNTs’ ability to act as magnetic resonance imaging (MRI) contrast agents. Additionally, MWCNTs demonstrated photothermal capabilities to eliminate bound cancer cells. Collectively, our findings pave the way for developing aptamer-labeled MWCNTs as viable “theranostic alternatives” for breast cancer treatment. Graphical abstract

Abstract Background Out-of-hospital cardiac arrest (OHCA) survival in the UK remains overall poor with fewer than 10% of patients surviving to hospital discharge. Extracorporeal cardiopulmonary resuscitation (ECPR) is a developing therapy option that can improve survival in select patients if treatment begins within an hour. Clinicians' perspectives are a pivotal consideration to the development of effective systems for OHCA ECPR, but they have been infrequently explored. This study investigates clinicians' views on the barriers and facilitators to establishing effective systems to facilitate transport of OHCA patients for in-hospital ECPR. Methods In January 2023, Thames Valley Air Ambulance (TVAA) and Harefield Hospital developed an ECPR partnership pathway for conveyance of OHCA patients for in-hospital ECPR. The authors of this study conducted a survey of clinicians across both services looking to identify clear barriers and positive contributors to the effective implementation of the programme. The survey included questions about technical and non-technical barriers and facilitators, with free-text responses analysed thematically. Results Responses were received from 14 pre-hospital TVAA critical care and 9 in-hospital clinicians’ representative of various roles and experiences. Data analysis revealed 10 key themes and 19 subthemes. The interconnected themes, identified by pre-hospital TVAA critical care clinicians as important barriers or facilitators in this ECPR system included educational programmes; collectiveness in effort and culture; teamwork; inter-service communication; concurrent activity; and clarity of procedures. Themes from in-hospital clinicians’ responses were distilled into key considerations focusing on learning and marginal gains, standardising and simplifying protocols, training and simulation; and nurturing effective teams. Conclusion This study identified several clear themes and subthemes from clinical experience that should be considered when developing and modelling an ECPR system for OHCA. These insights may inform future development of ECPR programmes for OHCA in other centres. Key recommendations identified include prioritising education and training (including regular simulations), standardising a ‘pitstop style’ handover process, establishing clear roles during the cannulation process and developing standardised protocols and selection criteria. This study also provides insight into the feasibility of using pre-hospital critical care teams for intra-arrest patient retrieval in the pre-hospital arena.

Abstract Most patients with advanced cancer develop cachexia, a multifactorial syndrome characterized by progressive skeletal muscle wasting. Despite its catastrophic impact on survival, the critical mediators responsible for cancer cachexia development remain poorly defined. Here, we show that a distinct subset of neutrophil-like monocytes, which we term cachexia-inducible monocytes (CiMs), emerges in the advanced cancer milieu and promotes skeletal muscle loss. Unbiased transcriptome analysis reveals that interleukin 36 gamma (IL36G)-producing CD38+ CiMs are induced in chronic monocytic blood cancer characterized by prominent cachexia. Notably, the emergence of CiMs and the activation of CiM-related gene signatures in monocytes are confirmed in various advanced solid cancers. Stimuli of toll-like receptor 4 signaling are responsible for the induction of CiMs. Genetic inhibition of IL36G-mediated signaling attenuates skeletal muscle loss and rescues cachexia phenotypes in advanced cancer models. These findings indicate that the IL36G-producing subset of neutrophil-like monocytes could be a potential therapeutic target in cancer cachexia.

Abstract Gene therapy holds promise for treatment of inherited retinal dystrophies, a group of rare genetic disorders characterized by severe loss of vision. Here, we report up to 3-year pre-specified interim safety and efficacy results of an open-label first-in-human dose-escalation phase 1/2 gene therapy clinical trial in 12 patients with retinal dystrophy caused by biallelic mutations in the retinaldehyde-binding protein 1 (RLBP1) gene of the visual cycle. The primary endpoints were systemic and ocular safety and recovery of dark adaptation. Secondary endpoints included microperimetry, visual field sensitivity, dominant eye test and patient-reported outcomes. Subretinal delivery of an adeno-associated viral vector (AAV8-RLBP1) was well tolerated with dose-dependent intraocular inflammation which responded to corticosteroid treatment, and focal atrophy of the retinal pigment epithelium as the dose limiting toxicity. Dark adaptation kinetics, the primary efficacy endpoint, improved significantly in all dose-cohorts. Treatment with AAV8-RLBP1 resulted in the resolution of disease-related retinal deposits, suggestive of successful restoration of the visual cycle. In conclusion, to date, AAV8-RLBP1 has shown preliminary safety and efficacy in patients with RLBP1-associated retinal dystrophy. Trial number: NCT03374657.

Abstract The genetic factors of stroke in South Asians are largely unexplored. Exome-wide sequencing and association analysis (ExWAS) in 75 K Pakistanis identified NM_000435.3(NOTCH3):c.3691 C > T, encoding the missense amino acid substitution p.Arg1231Cys, enriched in South Asians (alternate allele frequency = 0.58% compared to 0.019% in Western Europeans), and associated with subcortical hemorrhagic stroke [odds ratio (OR) = 3.39, 95% confidence interval (CI) = [2.26, 5.10], p = 3.87 × 10−9), and all strokes (OR [CI] = 2.30 [1.77, 3.01], p = 7.79 × 10−10). NOTCH3 p.Arg231Cys was strongly associated with white matter hyperintensity on MRI in United Kingdom Biobank (UKB) participants (effect [95% CI] in SD units = 1.1 [0.61, 1.5], p = 3.0 × 10−6). The variant is attributable for approximately 2.0% of hemorrhagic strokes and 1.1% of all strokes in South Asians. These findings highlight the value of diversity in genetic studies and have major implications for genomic medicine and therapeutic development in South Asian populations.

Abstract This study aims to assess the effect of familial structures on the still-missing heritability estimate and prediction accuracy of Type 2 Diabetes (T2D) using pedigree estimated risk values (ERV) and genomic ERV. We used 11,818 individuals (T2D cases: 2,210) with genotype (649,932 SNPs) and pedigree information from the ongoing periodic cohort study of the Iranian population project. We considered three different familial structure scenarios, including (i) all families, (ii) all families with ≥ 1 generation, and (iii) families with ≥ 1 generation in which both case and control individuals are presented. Comprehensive simulation strategies were implemented to quantify the difference between estimates of $$\:{\text{h}}^{2}$$ and $$\:{\text{h}}_{\text{S}\text{N}\text{P}}^{2}$$ . A proportion of still-missing heritability in T2D could be explained by overestimation of pedigree-based heritability due to the presence of families with individuals having only one of the two disease statuses. Our research findings underscore the significance of including families with only case/control individuals in cohort studies. The presence of such family structures (as observed in scenarios i and ii) contributes to a more accurate estimation of disease heritability, addressing the underestimation that was previously overlooked in prior research. However, when predicting disease risk, the absence of these families (as seen in scenario iii) can yield the highest prediction accuracy and the strongest correlation with Polygenic Risk Scores. Our findings represent the first evidence of the important contribution of familial structure for heritability estimations and genomic prediction studies in T2D.