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Background: Achieving universal health coverage is one of the prominent targets of the United Nations' sustainable development goals. Reducing out-of-pocket expenditure (OOPE) is essential because high OOPE can deter the use of healthcare services, which can lead to poor health outcomes and medical impoverishment., Objectives: The study sought to determine the effects of various factors such as Domestic General Government Health Expenditure, Gross Domestic Product, Government schemes and compulsory contributory healthcare financing schemes, and Voluntary health insurance schemes on OOPE per Capita in emerging economies., Design: Econometric methods using panel data., Data Sources and Methods: The study analyzed the publicly available panel data from the World Health Organization using fixed, random, and dynamic models., Results: Domestic General Government Health Expenditure and Gross Domestic Product are associated with an increase in OOPE. Government schemes, compulsory contributory healthcare financing schemes, and voluntary health insurance programs are linked to a reduction in OOPE., Conclusion: In conclusion, this study, conducted through econometric methods on panel data, sheds light on the critical importance of reducing OOPE to achieve universal health coverage, aligning with the United Nations' sustainable development goals. Countries shall implement a holistic approach focusing on preventive healthcare and health promotion, providing comprehensive health insurance, strengthening public health systems, and regulating medicine prices., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Many psychiatric conditions have their roots in early development. Individual differences in prenatal brain function (which is influenced by a combination of genetic risk and the prenatal environment) likely interact with individual differences in postnatal experience, resulting in substantial variation in brain functional organization and development in infancy. Neuroimaging has been a powerful tool for understanding typical and atypical brain function and holds promise for uncovering the neurodevelopmental basis of psychiatric illness; however, its clinical utility has been relatively limited thus far. A substantial challenge in this endeavor is the traditional approach of averaging brain data across groups despite individuals varying in their brain organization, which likely obscures important clinically relevant individual variation. Precision functional mapping (PFM) is a neuroimaging technique that allows the capture of individual-specific and highly reliable functional brain properties. Here, we discuss how PFM, through its focus on individuals, has provided novel insights for understanding brain organization across the life span and its promise in elucidating the neural basis of psychiatric disorders. We first summarize the extant literature on PFM in normative populations, followed by its limited utilization in studying psychiatric conditions in adults. We conclude by discussing the potential for infant PFM in advancing developmental precision psychiatry applications, given that many psychiatric disorders start during early infancy and are associated with changes in individual-specific functional neuroanatomy. By exploring the intersection of PFM, development, and psychiatric research, this article underscores the importance of individualized approaches in unraveling the complexities of brain function and improving clinical outcomes across development., (© 2024 The Authors.)

Background: Effective control of hypertension remains challenging in low and middle-income countries. We tested the effectiveness of comprehensive approaches to hypertension management including six home visits by community health workers with regular follow up by a trained healthcare provider on blood pressure levels in Nepal., Methods: We implemented a non-blinded, open-label, parallel-group, two-arm cluster randomised controlled trial, with 1:1 allocation ratio in Budhanilakantha municipality, Kathmandu, Nepal. Ten public health facilities and their catchment area were randomly allocated to receive comprehensive intervention or only usual hypertension care. We recruited 1252 individuals aged 18 years and older with hypertension. The primary outcome was systolic blood pressure. Secondary outcomes were diastolic blood pressure, proportion with controlled blood pressure, waist to hip ratio, body mass index, physical activity, diet quality score, daily salt intake, adherence to antihypertensives, hypertension knowledge and perceived social support. Primary analysis was by intention-to-treat using a linear mixed model., Findings: Participants were, on average 57 years old, 60% females, 84% married, 54% Brahmin/Chettri ethnicity and 33% were illiterate. The decrease in mean systolic blood pressure (1.7 mm Hg, 95% CI -0.1, 3.4) and diastolic blood pressure (1.6 mm Hg, 95% CI 0.5, 2.6) was more in the intervention arm compared to the control. The proportion with blood pressure control (OR 1.5 95% CI 1.0, 2.1) and engaging in adequate physical activity (≥600 Metabolic equivalents of task per week) (OR 2.2, 95% CI 1.6, 3.1) were higher in the intervention arm compared to control. The change in hypertension knowledge score was higher and daily salt intake was lower in the intervention arm compared to control. Waist to hip ratio increased more and global dietary requirement scores decreased more in the intervention group and there was no effect on the body mass index and adherence to antihypertensives., Interpretation: Community health workers facilitated home support and routine follow-up care by healthcare providers was effective in controlling blood pressure in urban Nepal. These findings suggest comprehensive interventions targeting individual, community and health system barriers are feasible in low resource settings, but larger implementation trials are needed to inform future scale-up., Funding: This work was supported by Norwegian University of Science and Technology, Trondheim, Norway (Project number 981023100)., Competing Interests: All authors declare no competing interests., (© 2024 The Author(s).)

Background and objective Midshaft clavicular fractures were managed conservatively in the past, with a significant incidence of nonunion and poor functional outcomes in displaced fractures. Anatomically precontoured clavicle plates, since their introduction, have proved to be a superior method for managing these fractures. While open reduction and internal fixation of displaced clavicular fractures with plates have produced successful functional outcomes, complications like plate prominence, scar, postoperative numbness, wound dehiscence, refracture, and infection continue to discourage surgeons from plating these fractures. This study aimed to evaluate whether the precontoured 3.5-mm locking compression plate (LCP) for the clavicle is effective in the management of displaced clavicular fractures with minimum risk of complications. Methods A prospective observational study was conducted among 26 patients with displaced clavicular fractures that were managed with 3.5-mm precontoured LCP. The functional outcome was assessed by using the Constant-Murley Score (CMS) and healing was assessed radiographically six months postoperatively. Results Twenty-five patients were available for the final follow-up at the end of 24 weeks. All of them achieved excellent functional scores. The mean CMS was 94.9. No complication was observed in 85% of the cases. Implant failure was observed in both fractures of a bilateral clavicle fracture patient within a month of surgery. Implant irritation without prominence was seen in one patient and another had a prominent postoperative scar. The mean time for the radiological union was 13.8 weeks with union time ranging from three to five months. Conclusions Based on our findings, employing 3.5-mm precontoured clavicular LCPs is a useful technique that can provide good functional outcomes in displaced clavicular fractures., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Biomedical Research Ethics Committee, PGIMS issued approval BREC/Th/20/Ortho05. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, M et al.)

Background: Findings from previous studies on maternal 25(OH)D levels during pregnancy and offspring schizophrenia are limited and inconsistent., Methods: We used nationwide population-based register data with a nested case-control design to examine the association between maternal 25(OH)D levels during pregnancy and offspring schizophrenia. The cases of schizophrenia (n = 1145) were born from 1987 to 1997, and received a diagnosis of schizophrenia by 2017, and were matched with equal number of controls. A quantitative immunoassay was used to measure maternal 25(OH)D in archived maternal serum in the national biobank of the Finnish Maternity Cohort, collected during the first and early second trimesters. Conditional logistic regression models examined the association between maternal 25(OH)D levels and offspring schizophrenia., Results: No significant association was found between log-transformed maternal 25(OH)D levels and schizophrenia in unadjusted (OR 0.96, 95 % CI 0.78-1.17, p = 0.69) or adjusted analyses (aOR 0.98, 95 % CI 0.79-1.22, p = 0.89). Analyses by quintiles also revealed no association between the lowest quintile of maternal 25(OH)D levels and schizophrenia (OR 1.09, 95 % CI 0.81-1.45, p = 0.55; aOR 1.06, 95 % CI 0.78-1.45, p = 0.71). Maternal 25(OH)D levels, measured in categories, either in deficient category (OR 1.07 (0.85-1.35), p = 0.52; aOR 1.05 (0.81-1.34), p = 0.88) or insufficient category (OR 1.13, 95 % CI 0.92-1.40, p = 0.23; aOR 1.13, 95 % CI 0.90-1.41, p = 0.27) were also not associated with offspring schizophrenia., Conclusions: Maternal vitamin D levels in early pregnancy were not associated with offspring schizophrenia. Future studies measuring vitamin D during different stages of gestation are needed to draw firm conclusions., Competing Interests: Declaration of competing interest No financial or conflict of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In the intricate landscape of Traumatic Brain Injury (TBI), the management of TBI remains a challenging task due to the extremely complex pathophysiological conditions and excessive release of reactive oxygen species (ROS) at the injury site and the limited regenerative capacities of the central nervous system (CNS). Existing pharmaceutical interventions are limited in their ability to efficiently cross the blood-brain barrier (BBB) and expeditiously target areas of brain inflammation. In response to these challenges herein, we designed novel mussel inspired polydopamine (PDA)-coated mesoporous silica nanoparticles (PDA-AMSNs) with excellent antioxidative ability to deliver a new potential therapeutic GSK-3β inhibitor lead small molecule abbreviated as Neuro Chemical Modulator (NCM) at the TBI site using a neuroprotective peptide hydrogel (PANAP). PDA-AMSNs loaded with NCM (i.e., PDA-AMSN-D) into the matrix of PANAP were injected into the damaged area in an in vivo cryogenic brain injury model (CBI). This approach is specifically built while keeping the logic AND gate circuit as the primary focus. Where NCM and PDA-AMSNs act as two input signals and neurological functional recovery as a single output. Therapeutically, PDA-AMSN-D significantly decreased infarct volume, enhanced neurogenesis, rejuvenated BBB senescence, and accelerated neurological function recovery in a CBI.

Pre-departure orientation training (PDOT) can help equip aspiring migrant workers with skills and knowledge to mitigate vulnerabilities throughout their migration journey, including health. In Nepal, PDOT has been mandatory since 2004 for migrant workers awaiting labour permits. The current PDOT programme includes country-specific information as well as health and well-being advice. However, the views of trainees and trainers on PDOT are largely unknown. This qualitative study aims to explore perceptions of migrant workers and relevant stakeholders on the content and delivery of PDOT. Six focus group discussions and six in-depth interviews were conducted with migrants, and eight interviews with key stakeholders were conducted. Thematic analysis resulted in five themes: (a) PDOT structure, accessibility, and implementation; (b) role of stakeholders in labour migration process; (c) coordination and governance; (d) curriculum development and relevance; and (e) capacity of trainers and effectiveness of training. Our findings emphasise the need for a more tailored curriculum with relevant information, education, and communication resources, possibly with input from former migrant workers. Regular updates of training topics and resources, as well as continued engagement with migrants after their employment, are essential for meeting the dynamic demands of the global employment market.

The study explored Simarouba glauca DC. for mosquito larvicidal potential by performing bioactivity-guided chemical investigation of its root extract resulting in isolation of the known bioactive metabolite glaucarubinone ( 1 ). Mosquito larvicidal activity of glaucarubinone ( 1 ) against the three vector species viz. Anopheles stephensi, Aedes aegypti, and Culex quinquefasciatus was determined using a modified WHO 2005 protocol. It was observed that Culex quinquefasciatus larvae were the most susceptible species with LC 50 13.88 ppm and LC 90 70.01 ppm followed by Aedes aegypti and Anopheles stephensi at 24 h of exposure. The mode of action as observed microscopically is the lysis of midgut and thorax cells of the third instar larvae. The crystal structure of the glaucarubinone ( 1 ) is reported for the first time using X-ray crystallography. This phytochemical product has the potential to act as a green alternative to existing chemical-based insecticides for integrated vector management.

The coordination chemistry of an amine-rich Cp N3 ligand has been explored with cobalt. We demonstrate that in the presence of NaCo(CO) 4 , the cationic precursor [CpN3]+ yields the complex CpN3CoI(CO)2. While 2e - oxidation generates new Co III complexes such as [CpN3Co(NCMe)3]2+ and CpN3CoI2(CO), subsequent ligand loss is facile, generating free [CpN3]+ or the protonated dication [CpN3H]2+. We have structurally characterized both these ligand release products via single crystal X-ray diffraction and obtained thermochemical C-H bond strengths via experiment and density functional theory (DFT). Upon reversible 1e - reduction, the radical cation [CpN3H]˙+ has a weak C-H BDFE of 52 kcal mol -1 in acetonitrile. Mechanistic analysis shows that [CpN3H]˙+ undergoes radical-radical disproportionation in the absence of exogenous H-atom acceptors, which is supported by deuterium isotope labelling experiments. Structural comparison of these organic molecules shows a high degree of iminium-like electron delocalization over the C-N bonds connected to the central five-membered ring.

Background: Abortion was legalized by the 2002 Muluki Ain to combat the surging rates of maternal mortality and morbidity. By 2021, the Maternal Mortality Rate plummeted to 151 from 539 in 1996. The decline in the abortion-related maternal mortality attributes to the implication of progressive abortion policies that includes expanded safe abortion services introduction of medical abortion, constitutional recognition of abortion, the mandates by Safe Motherhood and Reproductive Health Rights Act, and free-of-cost abortion services in government health facilities. This review study delves into exploring the contemporary abortion policies and its implications on women's access to safe abortion services as well as the factors that affect the access., Methods: This study incorporates findings from extensive desk review of abortion services in Nepal., Results: The 2021 safe abortion services Program Implementation Guideline aims to expand safe abortion sites; however, the Nepal's challenging geography ensues its inequitable distribution, especially in mountainous area. Policy provisions on information and financial accessibility to abortion are well navigated by the Safe Motherhood and Reproductive Health Rights Act and regulation but consistent to sporadic gaps in its implementation were comprehended in this study. This paper further discussed the Safe Motherhood and Reproductive Health Rights Act's regressive mandate of 28-week gestational limit at any condition and the role of gender in abortion decision-making under the pretext of factors influencing safe abortion services., Conclusions: The review study recommends strategies: improving capacity for abortion services under federalism, combating stigma, improving the private sector's readiness, and building a resilient health system.

Background: Despite policy advances and public health initiatives in Nepal to improve access to reproductive healthcare, disparities persist in utilization of abortion services. Grounded in longitudinal data from the Nepal Demographic and Health Survey from 1996 to 2022, this study aims to shed light on evolving patterns in pregnancy outcomes and inequities in use of abortion services across ecological zones and wealth quintiles., Methods: Utilizing six rounds of Nepal Demographic and Health Survey data, pregnancy outcomes were categorized as abortion, delivery, miscarriage, or stillbirth. Income-related inequality in the utilization of abortion services was assessed through the concentration index, ranging from -1 to 1. Trends over time were evaluated using the annual rate of change., Results: The ARC indicated a substantial rise in induced abortion rates, surging from 0.4% in 1996 to 8.8% in 2022. In contrast, live births witnessed a decline from 92.8% to 81.2%. Significant variations were observed across ecological zones and wealth quintiles, with the Mountain zone and the Poorest group experiencing the most pronounced increases in induced abortion rates. By 2022, the concentration index reached a near-zero value, signifying a near-elimination of income-related disparities in the use of induced abortion services., Discussion: The findings suggest that while there has been significant progress in access to and use of abortion services in Nepal, particularly post-2002 policy shifts, challenges remain. Women from lower socio-economic backgrounds continue to face barriers, indicating the need for a multi-pronged approach to address residual challenges., Conclusions: Nepal has made remarkable strides in enhancing equitable access to and use of induced abortion services, but more needs to be done to guarantee equitable access for all women. Future efforts should focus on policy reforms, infrastructural improvements, and societal change to eliminate existing barriers to reproductive healthcare.

Spontaneous aggregation of amyloid beta (Aβ) leads to the formation of neurotoxic senile plaque considered as the most crucial event in Alzheimer's disease (AD) progression. Inhibition or disruption of this deadly aggregate formation is one of the most efficient strategies for the development of potential therapeutics, and extensive research is in progress by various research groups. In this direction, the development of a peptide analogous to that of the native Aβ peptide is an attractive strategy. Based on this rationale, β-sheet breakers were developed from the Aβ central hydrophobic core. These peptide derivatives will bind to the full length of the parent Aβ and interfere in self-recognition, thereby preventing the folding of the Aβ peptide into cross β-sheet neurotoxic aggregates. However, this approach is effective in the inhibition of fibrillar aggregation, but this strategy is ineffective in the Aβ neurotoxic oligomer formation. Therefore, an alternative and efficient approach is to use the Aβ peptide analogous to the C-terminal region, which arbitrates fibrillation and oligomerization. Herein, we developed the Aβ C-terminal fragment (ACT-1 to ACT-7) for inhibition of oligomerization as well as fibrillar aggregation. Screening of these seven peptides resulted in an efficient anti-Aβ peptide aggregative agent (ACT-7), which was evaluated by the ThT assay peptide. The ThT assay reveals complete inhibition and showed significant neuroprotection of PC-12-derived neurons from Aβ-induced toxicity and reduced cell apoptosis. Further, analysis using CD and FTIR spectroscopy reveals that the ACT-7 peptide efficiently inhibits the formation of the β-sheet secondary structure content. HR-TEM microscopic analysis confirmed the inhibition of formation. Therefore, the inhibition of β-sheet Aβ fibrillary aggregation by the protease-stable ACT-7 peptide may provide a beneficial effect on AD treatment to control the Aβ aggregates. Finally, we anticipate that our newly designed ACT peptides may also assist as a template molecular scaffold for designing potential anti-AD therapeutics.

The tumor microenvironment (TME) is a complex ecosystem of diverse cell types whose interactions govern tumor growth and clinical outcome. While the TME's impact on immunotherapy has been extensively studied, its role in chemotherapy response remains less explored. To address this, we developed DECODEM (DEcoupling Cell-type-specific Outcomes using DEconvolution and Machine learning), a generic computational framework leveraging cellular deconvolution of bulk transcriptomics to associate the gene expression of individual cell types in the TME with clinical response. Employing DECODEM to analyze the gene expression of breast cancer (BC) patients treated with neoadjuvant chemotherapy, we find that the gene expression of specific immune cells ( myeloid , plasmablasts , B-cells ) and stromal cells ( endothelial , normal epithelial , CAFs ) are highly predictive of chemotherapy response, going beyond that of the malignant cells. These findings are further tested and validated in a single-cell cohort of triple negative breast cancer. To investigate the possible role of immune cell-cell interactions (CCIs) in mediating chemotherapy response, we extended DECODEM to DECODEMi to identify such CCIs, validated in single-cell data. Our findings highlight the importance of active pre-treatment immune infiltration for chemotherapy success. The tools developed here are made publicly available and are applicable for studying the role of the TME in mediating response from readily available bulk tumor expression in a wide range of cancer treatments and indications., Competing Interests: COMPETING INTERESTS E.R. is a co-founder of Medaware Ltd. (https://www.medaware.com/), Metabomed (https://www.metabomed.com/), and Pangea Biomed (https://pangeamedicine.com/). He has divested and serves as an unpaid scientific consultant to the latter company. The rest of the authors declare no conflicts of interest.

Finger millet, an important 'Nutri-Cereal' and climate-resilient crop, is cultivated as a marginal crop in calcareous soils. Calcareous soils have low organic carbon content, high pH levels, and poor structure. Such a situation leads to poor productivity of the crop. Site-specific nutrient management (SSNM), which focuses on supplying optimum nutrients when a crop is needed, can ensure optimum production and improve the nutrient and energy use efficiency of crops. Moreover, developing an appropriate SSNM technique for this crop could offer new insights into nutrient management practices, particularly for calcareous soils. A field experiment was conducted during the rainy seasons of 2020 and 2021 in calcareous soil at Dr. Rajendra Prasad Central Agricultural University, Pusa, India. The experiment consisted of 8 treatments, viz . control, nitrogen (N)/phosphorus (P)/potassium (K)-omission, 75 %, 100 %, and 125 % recommended fertilizer dose (RFD), and 100 % recommended P and K + 30 kg ha -1 N as basal + rest N as per GreenSeeker readings. From this study, it was observed that the GreenSeeker-based SSNM resulted in the maximum grain yield (2873 kg ha -1 ), net output energy (96.3 GJ ha -1 ), and agronomic efficiency of N (30.6 kg kg -1 ), P (68.9 kg kg -1 ), and K (68.9 kg kg -1 ). The application of 125 % RFD resulted in ∼7 % lower yield than that under GreenSeeker-based nutrient management. Approximately 12 % greater energy use efficiency and 21-36 % greater nutrient use efficiency were recorded under GreenSeeker-based nutrient management than under 125 % RDF. The indigenous supplies of N, P, and K were found to be 14.31, 3.00, and 18.51 kg ha -1 , respectively. Thus, 100 % of the recommended P and K + 30 kg ha -1 N as basal + rest N according to GreenSeeker readings can improve the yield, nutrient use efficiency, and energy balance of finger millet in calcareous soils., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Saleh H. Salmen reports financial support was provided by 10.13039/501100002383King Saud University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Recording and modulation of neuronal activity enables the study of brain function in health and disease. While translational neuroscience relies on electrical recording and modulation techniques, mechanistic studies in rodent models leverage genetic precision of optical methods, such as optogenetics and imaging of fluorescent indicators. In addition to electrical signal transduction, neurons produce and receive diverse chemical signals which motivate tools to probe and modulate neurochemistry. Although the past decade has delivered a wealth of technologies for electrophysiology, optogenetics, chemical sensing, and optical recording, combining these modalities within a single platform remains challenging. This work leverages materials selection and convergence fiber drawing to permit neural recording, electrical stimulation, optogenetics, fiber photometry, drug and gene delivery, and voltammetric recording of neurotransmitters within individual fibers. Composed of polymers and non-magnetic carbon-based conductors, these fibers are compatible with magnetic resonance imaging, enabling concurrent stimulation and whole-brain monitoring. Their utility is demonstrated in studies of the mesolimbic reward pathway by simultaneously interfacing with the ventral tegmental area and nucleus accumbens in mice and characterizing the neurophysiological effects of a stimulant drug. This study highlights the potential of these fibers to probe electrical, optical, and chemical signaling across multiple brain regions in both mechanistic and translational studies., Competing Interests: Conflict of Interest N.D., M.-J. A. and P.A. are co-founders and have a financial interest in NeuroBionics Inc.

The leaves of Araucaria cunninghamii are known to be nonedible and toxic. Previous studies have identified biflavones in various Araucaria species. This study aimed to investigate the in vitro cytotoxicity of the isolated compounds from Araucaria cunninghamii after metabolomics and network pharmacological analysis. Methanol extract of Araucaria cunninghamii leaves was subjected to bioassay-guided fractionation. The active fraction was analyzed using LC-HRMS, through strategic database mining, by comparing the data to the Dictionary of Natural Products to identify 12 biflavones, along with abietic acid, beta-sitosterol, and phthalate. Eight compounds were screened for network pharmacology study, where in silico ADME analysis, prediction of gene targets, compound-gene-pathway network and hierarchical network analysis, protein-protein interaction, KEGG pathway, and Gene Ontology analyses were done, that showed PI3KR1, EGFR, GSK3B, and ABCB1 as the common targets for all the compounds that may act in the gastric cancer pathway. Simultaneously, four biflavones were isolated via chromatography and identified through NMR as dimeric apigenin with varying methoxy substitutions. Cytotoxicity study against the AGS cell line for gastric cancer showed that AC1 biflavone (IC 50 90.58 μM) exhibits the highest cytotoxicity and monomeric apigenin (IC 50 174.5 μM) the lowest. Besides, the biflavones were docked to the previously identified targets to analyze their binding affinities, and all the ligands were found to bind with energy ≤-7 Kcal/mol., (© 2024 John Wiley & Sons Ltd.)

Tailoring optimal treatment for individual cancer patients remains a significant challenge. To address this issue, we developed PERCEPTION (PERsonalized Single-Cell Expression-Based Planning for Treatments In ONcology), a precision oncology computational pipeline. Our approach uses publicly available matched bulk and single-cell (sc) expression profiles from large-scale cell-line drug screens. These profiles help build treatment response models based on patients' sc-tumor transcriptomics. PERCEPTION demonstrates success in predicting responses to targeted therapies in cultured and patient-tumor-derived primary cells, as well as in two clinical trials for multiple myeloma and breast cancer. It also captures the resistance development in patients with lung cancer treated with tyrosine kinase inhibitors. PERCEPTION outperforms published state-of-the-art sc-based and bulk-based predictors in all clinical cohorts. PERCEPTION is accessible at https://github.com/ruppinlab/PERCEPTION . Our work, showcasing patient stratification using sc-expression profiles of their tumors, will encourage the adoption of sc-omics profiling in clinical settings, enhancing precision oncology tools based on sc-omics., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The release of organic pollutants and dyes into the environment by industries has had profound and harmful effects on both humans and ecosystems. Graphene oxide (GO) and its reduced form have been investigated for their effectiveness in removing pollutant dyes. GO nano-powder was synthesized using an improved version of Hummer's method and subsequently thermally reduced at various temperatures, including 125, 150, 175, and 200 °C, under vacuum conditions. In the X-ray diffraction spectra, an intense (001) diffraction peak was initially observed at 9.136° (2θ) for pristine GO. This peak gradually shifted towards higher angles as the reduction process took place and eventually disappeared when the GO was reduced at 200 °C. The intensity ratio of the D and G bands (ID/IG ratio) for GO nano-powder in the Raman spectra decreased from 0.94 to 0.76 due to the reduction process. The FTIR spectra of GO and reduced graphene oxide (rGO) also illustrated the reduction process. The bandgap of pristine GO significantly decreased from 2.31 to 0.73 eV, as determined by ultraviolet-visible (UV-Vis) diffuse reflectance spectrophotometry during the reduction process. The surface area and pore volume of both pristine GO and rGO-150 were determined using the BET (Brunauer-Emmett-Teller) and BJH (Barrett-Joyner-Halenda) methods. The results indicated an increase in the BET surface area from 6.61 to 7.86 m 2 /g and a corresponding enhancement in pore volume from 0.118 to 0.128 cc/g after reduction. The adsorption and photocatalytic degradation behavior of pristine GO and reduced graphene oxides (rGOs) were examined using methylene blue dye. The pristine GO demonstrated impressive adsorption capability, effectively removing the dye by 85.78 % within just 15 min and achieving nearly 97 % removal after 4 h. In contrast, the highest photocatalytic degradation of methylene blue, about 47.58 %, was attained for the rGO sample reduced at 150 °C under the illumination of visible light., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Meningioma, the most common brain tumor, traditionally considered benign, has a relatively high risk of recurrence over a patient's lifespan. In addition, with the emergence of several clinical, radiological, and molecular variables, it is becoming evident that existing grading criteria, including Simpson's and World Health Organization classification, may not be sufficient or accurate. As web-based tools for widespread accessibility and usage become commonplace, such as those for gene identification or other cancers, it is timely for meningioma care to take advantage of evolving new markers to help advance patient care., Methods: A scoping review of the meningioma literature was undertaken using the MEDLINE and Embase databases. We reviewed original studies and review articles from September 2022 to December 2023 that provided the most updated information on the demographic, clinical, radiographic, histopathological, molecular genetics, and management of meningiomas in the adult population., Results: Our scoping review reveals a large body of meningioma literature that has evaluated the determinants for recurrence and aggressive tumor biology, including older age, female sex, genetic abnormalities such as telomerase reverse transcriptase promoter mutation, CDKN2A deletion, subtotal resection, and higher grade. Despite a large body of evidence on meningiomas, however, we noted a lack of tools to aid the clinician in decision-making. We identified the need for an online, self-updating, and machine-learning-based dynamic model that can incorporate demographic, clinical, radiographic, histopathological, and genetic variables to predict the recurrence risk of meningiomas., Conclusion: Although a challenging endeavor, a recurrence prediction tool for meningioma would provide critical information for the meningioma patient and the clinician making decisions on long-term surveillance and management of meningiomas., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Surgical Neurology International.)

Typhoid fever is caused by Salmonella species. The most common hematological complications described are anemia and disseminated intravascular coagulation. Splenic infarction is an unusual complication of typhoid fever, and this presentation is rarely described. We report the case of a young female who presented with complaints of severe left upper quadrant pain after being diagnosed with typhoid fever. Computed tomography (CT) revealed multiple wedge-shaped splenic infarcts. She was treated with antibiotics and was also started on antiplatelets. She had a complete recovery with this management, and antiplatelets were tapered off on subsequent visits., (© Journal of the Association of Physicians of India 2024.)

Growers have depended on the specificity and efficacy of streptomycin and oxytetracycline as a part of their plant disease arsenal since the middle of the 20th century. With climate change intensifying plant bacterial epidemics, the established success of these antibiotics remains threatened. Our strong reliance on certain antibiotics for devastating diseases eventually gave way to resistance development. Although antibiotics in plant agriculture equal to less than 0.5% of overall antibiotic use in the United States, it is still imperative for humans to continue to monitor usage, environmental residues, and resistance in bacterial populations. This review provides an overview of the history and use, resistance and mitigation, regulation, environmental impact, and economics of antibiotics in plant agriculture. Bacterial issues, such as the ongoing Huanglongbing (citrus greening) epidemic in Florida citrus production, may need antibiotics for adequate control. Therefore, preserving the efficacy of our current antibiotics by utilizing more targeted application methods, such as trunk injection, should be a major focus. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license., Competing Interests: The author(s) declare no conflict of interest.

Although the general location of functional neural networks is similar across individuals, there is vast person-to-person topographic variability. To capture this, we implemented precision brain mapping functional magnetic resonance imaging methods to establish an open-source, method-flexible set of precision functional network atlases-the Masonic Institute for the Developing Brain (MIDB) Precision Brain Atlas. This atlas is an evolving resource comprising 53,273 individual-specific network maps, from more than 9,900 individuals, across ages and cohorts, including the Adolescent Brain Cognitive Development study, the Developmental Human Connectome Project and others. We also generated probabilistic network maps across multiple ages and integration zones (using a new overlapping mapping technique, Overlapping MultiNetwork Imaging). Using regions of high network invariance improved the reproducibility of executive function statistical maps in brain-wide associations compared to group average-based parcellations. Finally, we provide a potential use case for probabilistic maps for targeted neuromodulation. The atlas is expandable to alternative datasets with an online interface encouraging the scientific community to explore and contribute to understanding the human brain function more precisely., (© 2024. The Author(s).)

The Genus Dysoxylum (Meliaceae) consists of approximately 80 species that are abundant in structurally diverse triterpenoids. The present study focused on isolating new triterpenoids from the bark of Dysoxylum malabaricum, one of the predominant species of Dysoxylum present in India. The methanol-dichloromethane bark extract was subjected to LCMS profiling followed by silica gel column chromatography and HPLC analysis to target new compounds. Two new ring A-modified cycloartane-type triterpenoids (1 and 2) were isolated from the bark extract. Spectroscopic methods like NMR, HRESIMS data, and electronic circular dichroism calculations elucidated the structuresandabsolute configurations of the isolated compounds. These compounds were evaluated for their cytotoxic potential against breast cancer cells and displayed notable cytotoxicity. Compound 1 exhibited the highest cytotoxicity against the MDA-MB-231 cells and induced apoptotic cell death. Also, it was able to inhibit glucose uptake and increase nitric oxide production in breast cancer cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The financial implications of central nervous system (CNS) cancers are substantial, not only for the healthcare service and payers, but also for the patients who bear the brunt of direct, indirect, and intangible costs. This study sought to investigate the impact of healthcare spending on CNS cancer survival using recent US data., Methods: This study used public data from the Disease Expenditure Project 2016 and the Global Burden of Disease Study 2019. The primary outcome was the annual healthcare spending trend from 1996 and 2016 on CNS tumors adjusted for disease prevalence, alongside morbidity and mortality. Secondary outcomes included drivers of change in healthcare expenditures for CNS cancers. Subgroup analysis was performed stratified by age group, expenditure type, and care type provided., Results: There was a significant increase in total healthcare spending on CNS cancers from $2.72 billion (95% CI: $2.47B to $2.97B) in 1996 to $6.85 billion (95% CI: $5.98B to $7.57B) in 2016. Despite the spending increase, the mortality rate per 100 000 people increased, with 5.30 ± 0.47 in 1996 and 7.02 ± 0.47 in 2016, with an average of 5.78 ± 0.47 deaths per 100 000 over the period. The subgroups with the highest expenditure included patients aged 45 to 64, those with private insurance, and those receiving inpatient care., Conclusions: This study highlights a significant rise in healthcare costs for CNS cancers without corresponding improvements in mortality rate, indicating a mismatch of healthcare spending, contemporary advances, and patient outcomes as it relates to mortality., Competing Interests: The authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Agriculture plays a critical role in ensuring food and nutrition security, livelihood, and rural employment in Nepal. Despite substantial investments and institutional reforms, irrigation projects have faced consistently low performance. While existing studies have shed light on technical aspects of irrigation performance, they often focus on specific themes rather than holistic evaluations of sustainability. This research systematically assesses barriers and challenges to effective irrigation water management in Nepal by assessing and ranking the challenges faced by three irrigation systems in western Nepal: Mahakali, Rani Jamara Kulariya, and Babai. To investigate these challenges, we collected data from 449 households, which provided insights into 33 indicators representing key barriers to effective irrigation and agricultural management. The identified challenges were categorized into four broad thematic areas: physical and structural, agricultural and water, socioeconomic and market, and gender and governance. A comprehensive evaluation was conducted to compare these challenges among the three irrigation schemes, different thematic areas, and various locations within each scheme (namely, the head, mid, and tail sections of the system). The findings revealed that timely access and availability of fertilizers, spring water availability and fair market prices of agricultural products are the most significant challenges. The Babai irrigation system faced the most substantial challenges among the three systems, particularly in the mid section. These findings emphasize the interconnectedness of these challenges, highlighting the need for a holistic approach to planning, implementation, and management. Integrated strategies are essential to address socioeconomic, market, and endogenous farming issues, ensuring reliable irrigation water availability for sustainable agricultural production., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Objective: War profoundly impacts people's lives, causing death, displacement, and psychological trauma, but research investigating suicidality of adolescents in this context has been limited. We compared suicidality or self-harm behavior among adolescents in regions that were, and were not, affected by Russia's initial invasion of Ukraine in 2014., Method: This cross-sectional study comprised 2,752 school students aged 11 to 17 years from the war-affected Donetsk region and non-war Kirovograd region. Data collection occurred in 2016 and 2017 using self-report tools to assess suicidality or self-harm behavior; psychopathology including posttraumatic stress disorder (PTSD), depression, and anxiety; and war trauma exposure., Results: Adolescent girls in the war-affected region reported more suicide attempts (9.5% vs 5.1%; adjusted odds ratio [aOR] 1.8, 95% CI 1.2-2.8), suicidal ideation (39.3% vs 19.6%; aOR 2.6, 95% CI 2.01-3.3), or self-harm behavior (19.6% vs 13.1%; aOR 1.6, 95% CI 1.2-2.1), and boys reported more suicidal ideation (17.0% vs 9.8%; aOR 1.7, 95% CI 1.2-2.4). Boys and girls with PTSD, depression, or anxiety showed increased risks for any suicidality or self-harm. A dose-effect relation was observed between war trauma exposure and suicidality or self-harm. The association was strongest for adolescents who had experienced 5 or more different war trauma exposures (aOR 3.2, 95% CI 2.2-4.8)., Conclusion: War trauma exposure and psychopathology were strongly associated with suicidality or self-harm behavior, with a greater impact in girls than boys. The high prevalence of suicidality found in this study emphasizes the need for intervention on a large scale for adolescents living in war situations., (Copyright © 2024 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Introduction: Social support is considered vital for effective management of chronic conditions, but its role in improving adherence to antihypertensive medication and control of hypertension in urban Nepal is unknown. We examined the role of social support in adherence to antihypertensives and controlled blood pressure to inform future interventions for hypertension management., Methods: We analyzed cross-sectional data collected at baseline of a cluster randomized trial of hypertension patients (n=1252) in the community between May and November 2022. Multidimensional scale of perceived social support was used to measure social support, adherence to antihypertensives was measured using the Morisky medication adherence scale -8, and individuals with systolic- and diastolic- blood pressure less than 140 and 90 mmHg respectively were considered to have controlled hypertension. Modified Poisson regression models were used to estimate the prevalence ratios and corresponding 95% confidence intervals., Results: We found that 914 (73%) individuals received moderate to high social support. Participants receiving high social support had a numerically lower proportion of controlled hypertension (51%) however not statistically significant. The proportion of good adherence to antihypertensives did not differ between the social support categories. There was no association in overall, family, friends, and significant other sub-scales of social support with controlled hypertension and adherence to antihypertensives., Discussion: Further studies to understand the quality and mechanisms through which social support contributes to blood pressure control are needed for the health system to include social support in designing and implementing community-based interventions for hypertension management., Competing Interests: The authors declare that they have no competing interests in this work., (© 2024 Bhattarai et al.)

This study is a comprehensive assessment of the waste management system in Besisahar municipality. Information and some data have been collected from the municipality of Besisahar, followed by interviews with municipal officials responsible for waste management, stakeholders, waste workers, and residents. A total of 230 households, 20 schools, 10 government and private offices, 10 financial institutions, 60 commercial hotels, restaurants, and shops, and 20 medical shops and healthcare institutions, were selected in this study by random sampling. An extensive field study was conducted within all municipal wards and at dump sites. The results indicated that 42.14% of solid waste was collected through door-to-door collection services, 5.87% was mismanaged in open public places, 11.21% was used as compost manure, and the rest was discarded on riverbanks, dug up, and burned. A large component of the characterization of household waste consisted of organic waste (68.03%), followed by paper/paper products (8.13%), agricultural waste (5.5%), plastic (5.21%), construction (3.81%), textile (2.72%), metals (0.54%), glass (1.01%), rubber (0.10%), electronic (0.05%), pharmaceutical (0.1%) and others (4.78%) in the Besishahar municipality. Solid waste generation was found to be at 197.604 g/capita/day, as revealed by cluster sampling in 230 households. Around 4.285 tons-solid waste/day were generated in urban areas, while 16.13 tons-solid waste/day was estimated for the whole municipality. An important correlation between the parameters of solid waste was found by statistical analysis. Currently, solid waste is dumped on riverbanks, open fields, and springs, creating environmental and health hazards. The findings of this study will be useful to Besisahar municipality and its stakeholders in forming policies that facilitate waste management practices in this region and promote sustainable waste management systems., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Aryal, Adhikary. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Carotid occlusion often leads to the formation of a collateral network. On rare occasions, due to hemodynamic influence, aneurysms can occur. Here, the authors describe a 69-year-old male presenting with intracerebral hemorrhage secondary to a ruptured aneurysm within such a network., Observations: The patient presented to the emergency department with an altered level of consciousness. Imaging showed a left temporal lobe hemorrhage extending into the ventricle, subdural hematoma, and evidence of contrast extravasation. Digital subtraction angiography revealed an occluded left internal carotid artery with the left middle cerebral artery territory reconstituted by flow through an external carotid artery-internal carotid artery anastomosis. The latter was formed by the superficial temporal artery-superior orbital artery, as well as pial-pial collaterals from the posterior temporal artery. Notably, a 4-mm aneurysm arising from the pial-pial collateral network was identified. Surgical intervention involved a left temporal craniectomy and aneurysm excision, with special attention paid to preserving the anastomotic flow through the superficial temporal artery., Lessons: This case underscores the importance of recognizing and preserving collateral vascular pathways in cases of carotid occlusion with an associated aneurysm. It emphasizes the necessary balance between managing aneurysm risk and maintaining cerebral perfusion, highlighting the need for careful preoperative planning and intraoperative caution.

A bio-nanocomposite "Co-doped-g-C 3 N 4 @ biomolecule assisted electrochemically reduced graphene nanosheets (Co-g-C 3 N 4 @GN bme )" was prepared by electrochemical exfoliation of GO from graphite anode in the presence of amino acid 'l-cysteine' followed by its association with Co-g-C 3 N 4. The preparation of material has been confirmed by characterizations with FTIR, XRD, XPS and Raman spectroscopy. The morphology was investigated with TEM and SEM. Further, Co-g-C 3 N 4 @GN bme modified GC electrode was utilized for detecting and quantifying the 'Quinol' (a skin lightning agent) in cosmetic samples electrochemically. Quinol is a fundamental constituent utilized in various industries such as pharmaceuticals, oil refineries, textiles, and dyes. In the realm of cosmetics, it is utilized as a skin-lightning agent to inhibit the production of melanin in the skin. However, prolonged use of this component often results in allergic reactions among individuals. Furthermore, the effluents discharged from its manufacturing units pose a significant threat to the environment and human health due to its slow degradation. The detection limit was calculated to be 2.4 nM (S/N = 3)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The discovery of new natural products has become more challenging because of the re-isolation of compounds and the lack of new sources. Microbes dwelling in extreme conditions of high salinity and temperature are huge prospects for interesting natural metabolites. In this study, the endophytic bacteria Bacillus velezensis 7NPB-3B isolated from the halophyte Salicornia brachiata was screened for its biofilm inhibition against methicillin-resistant Staphylococcus aureus (MRSA). The fractionation of the crude extract was guided by bioassay and LC-HRMS-based metabolomics using multivariate analysis. The 37 fractions obtained by high-throughput chromatography were dereplicated using an in-house MS-Excel macro coupled with the Dictionary of Natural Products database. Successive bioactivity-guided separation yielded one novel compound ( 1 ), a diketopiperazine ( m / z 469.258 [M - H] - ) with an attached saturated decanoic acid chain, and four known compounds ( 2 - 5 ). The compounds were identified based on 1D- and 2D-NMR and mass spectrometry. Compounds 1 and 5 exhibited excellent biofilm inhibition properties of >90% against the MRSA pathogen at minimum inhibition concentrations of 25 and 35 µg/mL, respectively. The investigation resulted in the isolation of a novel diketopiperazine from a bacterial endophyte of an untapped plant using an omics approach.

Parkinson's disease (PD) is a common neurological illness that causes several motor and non-motor symptoms, most characteristically limb tremors and bradykinesia. PD is a slowly worsening disease that arises due to progressive neurodegeneration of specific areas of the brain, especially the substantia nigra of the midbrain. Even though PD has continuously been linked to a higher mortality risk in numerous epidemiologic studies, there have been significant discoveries regarding the connection between PD and stroke. The incidence of strokes such as cerebral infarction and hemorrhage is substantially associated with the development of PD. Moreover, cognitive impairments, primarily dementia, have been associated with stroke and PD. However, the underlying molecular mechanism of this phenomenon is still obscure. This concise review focuses on the relationship between stroke and PD, emphasizing the molecular mechanism of cognition deficit and memory loss evident in PD and stroke. Furthermore, we are also highlighting some potential drug molecules that can target both PD and stroke., Competing Interests: Declaration of competing interest The authors declare no potential competing interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) is a leading cause of mortality in sub-Saharan Africa (SSA). This systematic review aimed to appraise all population-based studies describing the management and outcomes of HCC in SSA., Methods: A systematic review based on a search in PubMed, PubMed Central, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), AfricaWide and Cochrane up to June 2023 was performed. PRISMA guidelines for systematic reviews were followed. The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (registration no: CRD42022363955)., Results: Thirty-nine publications from 15 of 48 SSA countries were identified; 3989 patients were studied. The majority (74%) were male, with median ages ranging from 28 to 54 years. Chronic Hepatitis B infection was a leading aetiology and non-cirrhotic HCC was frequently reported. Curative treatment (liver resection, transplantation and ablation) was offered to 6% of the cohort. Most patients (84%) received only best supportive care (BSC), with few survivors at one year., Conclusion: The majority of SSA countries do not have data reporting outcomes for HCC. Most patients receive only BSC, and curative treatment is seldom available in the region. Outcomes are poor compared to high-income countries., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Data on antimicrobial resistance (AMR) from sites not participating in the National AMR surveillance network, conducted by National Public Health Laboratory (NPHL), remain largely unknown in Nepal. The "Capturing Data on Antimicrobial Resistance Patterns and Trends in Use in Regions of Asia" (CAPTURA) assessed AMR data from previously untapped data sources in Nepal. A retrospective cross-sectional data review was carried out for the AMR data recorded between January 2017 and December 2019 to analyze AMR data from 26 hospital-based laboratories and 2 diagnostic laboratories in Nepal. Of the 56 health facilities initially contacted to participate in this project activity, 50.0% (28/56) signed a data-sharing agreement with CAPTURA. Eleven of the 28 hospitals were AMR surveillance sites, whereas the other 17, although not part of the National AMR surveillance network, recorded AMR-related data. Data for 663 602 isolates obtained from 580 038 patients were analyzed. A complete record of the 11 CAPTURA priority variables was obtained from 45.5% (5/11) of government hospitals, 63.6% (7/11) of private hospitals, and 54.6% (6/11) of public-private hospitals networked with NPHL for AMR surveillance. Similarly, 80% (8/10) of clinics and 54.6% (6/11) of laboratories outside the NPHL network recorded complete data for the 10 Global Antimicrobial Resistance and Use Surveillance System (GLASS) priority variables and 11/14 CAPTURA priority variables. Retrospective review of the data identified areas requiring additional resources and interventions to improve the quality of data on AMR in Nepal. Furthermore, we observed no difference in the priority variables reported by sites within or outside the NPHL network, thus suggesting that policies could be made to expand the surveillance system to include these sites without substantially affecting the government's budget., Competing Interests: Potential conflicts of interest. S. M. reports payments made to their institution from the International Vaccine Institute; grants and contracts from the International Vaccine Institute; payment made to their institution from Anweshan Private Limited; support for attending meetings as part of the project implementation plan, multiple meetings with stakeholders and hospital authority were required that needed distant travelling. P. G. reports receiving compensation from the International Vaccine Institute. M. G. reports payments made to their institution from the International Vaccine Institute; payments made to their institution from Anweshan Private limited; and received travel support as part of the project implementation plan, multiple meetings with stakeholders and hospital authority were required that needed distant travelling. M. J. S. reports working as a CAPTURA Country Coordinator for Bangladesh from 2020 to 2022; worked as a full-time staff member of the International Vaccine Institute in Seoul and supported the CAPTURA implementation; received consultancy fees from the International Vaccine Institute. A. T. A. reports working as an employee of Brigham and Women's Hospital since April 2021; received consultancy fees for work with CAPTURA project as a consultant between September 2021 and March 2022. S. G. reports receiving consultancy payments for manuscript preparation; and salary support from the International Vaccine Institute. J. S. reports salary support through a subcontract. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Although the Government of Nepal has achieved high and sustained childhood vaccination coverage, reaching under-immunized and zero-dose children requires different approaches. Behavioral science offers promise in better understanding the drivers of vaccination and development of more effective programs; however, the application of behavioral science to immunization programs in Nepal is nascent. Through the Behavioral Science Immunization Network, JSI, UNICEF Nepal, and Dhulikhel Hospital-Kathmandu University School of Medical Sciences established a Behavioral Science Center to engage a diverse group of stakeholders in increasing the capacity of practitioners to use behavioral science in immunization programming. As a result of the engagement during formative research, government stakeholders requested and applied tools from behavioral science to solve different immunization challenges. Of particular value was the use of the Journey to Health and Immunization framework, which helped stakeholders identify behavioral and social drivers of zero-dose communities in Kathmandu. Our experience in Nepal demonstrates that there is strong demand for approaches and tools from behavioral science to use in relation to immunization and that this type of engagement model is effective for generating demand for and strengthening capacity to use behavioral science approaches.

The liver plays a significant role in regulating a wide range of metabolic, homeostatic, and host-defense functions. However, the impact of liver injury on the host's ability to control bacteremia and morbidity in sepsis is not well understood. Leukocyte recruitment and activation lead to cytokine and chemokine release, which, in turn, trigger hepatocellular injury and elevate nucleotide levels in the extracellular milieu. P2Y2 purinergic receptors, G protein-coupled and activated by extracellular ATP/UTP, are expressed at the cell surface of hepatocytes and nonparenchymal cells. We sought to determine whether P2Y2 purinergic receptor function is necessary for the maladaptive host response to bacterial infection and endotoxin-mediated inflammatory liver injury and mortality in mice. We report that P2Y2 purinergic receptor knockout mice (P2Y2 -/- ) had attenuated inflammation and liver injury, with improved survival in response to LPS/galactosamine (LPS/GalN; inflammatory liver injury) and cecal ligation and puncture (CLP; polymicrobial sepsis). P2Y2 -/- livers had attenuated c-Jun NH2-terminal kinase activation, matrix metallopeptidase-9 expression, and hepatocyte apoptosis in response to LPS/GalN and attenuated inducible nitric oxide synthase and nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 protein expression in response to CLP. Implicating liver injury in the disruption of amino acid homeostasis, CLP led to lower serum arginine and higher bacterial load and morbidity in the WT mice, whereas serum arginine levels were comparable to sham-operated controls in P2Y2 -/- mice, which had attenuated bacteremia and improved survival. Collectively, our studies highlight the pathophysiological relevance of P2Y2 purinergic receptor function in inflammatory liver injury and dysregulation of systemic amino acid homeostasis with implications for sepsis-associated immune dysfunction and morbidity in mice. NEW & NOTEWORTHY Our studies provide experimental evidence for P2Y2 purinergic receptor-mediated potentiation of inflammatory liver injury, morbidity, and mortality, in two well-established animal models of inflammatory liver injury. Our findings highlight the potential to target P2Y2 purinergic signaling to attenuate the induction of "cytokine storm" and prevent its deleterious consequences on liver function, systemic amino acid homeostasis, host response to bacterial infection, and sepsis-associated morbidity and mortality.

Introduction: The burden of chronic viral hepatitis (CVH) in the UK Nepali population is unknown. We aimed to determine knowledge of liver disease (LD) and prevalence of CVH in this community., Methods: This was a mixed method (qualitative and quantitative) study guided by a multidisciplinary stakeholder group. Focus groups (FG) led by Nepali community leaders explored LD knowledge. Thereafter, a prospective community-based cohort study utilising dried-blood spot testing was conducted. Thematic analysis explored FG data with categorical data analysed with Excel and R Studio., Results: FG data showed a lack of LD knowledge, with conflict between the roles of traditional and modern practices; 1,005 participants (525 male, 480 female) were tested for CVH, with a mean age of 63 years (range:19-86). Rates of CVH infection were low: 0.3% had current hepatitis B, with no active hepatitis C., Discussion: Key drivers for enthusiastic participation were development of peer support networks and advisory groups to disseminate information, including hepatitis B vaccine recommendations., (© Royal College of Physicians 2023. All rights reserved.)

An electron donor-acceptor (EDA)-triggered hydrogen atom transfer (HAT) process is developed for the efficient generation of an α-alkoxy radical from cyclic ethers to synthesize exocyclic alkenylated ethers with exclusive E -selectivity. A judiciously chosen donor-acceptor pair (DABCO and maleimide) serves as the desired HAT reagent under visible light irradiation without using any photocatalyst or peroxide. A wide variety of substrates were explored to demonstrate the diverse applicability and practical viability of this cross-dehydrogenative transformation. Detailed mechanistic studies revealed a radical reaction pathway under the oxidative environment.

Background: The purpose of this study was to conduct a randomized controlled clinical trial to compare and evaluate the effect of provisional restorations fabricated by two techniques, namely, conventional and three-dimensional (3D) printing processes on the peri-implant hard and soft tissues over early nonfunctional loaded implants in the mandibular posterior region., Materials and Methods: A randomized controlled clinical trial was conducted across 24 subjects broadly divided into two groups with 12 dental implants each, i.e., GpIC with conventionally fabricated provisional restoration and GpIID with 3D printed fabricated provisional restoration. The prosthetic phase was carried out at 2 weeks, and subjects were evaluated at baseline (at the time of prosthesis placement), 2 months, and 4 months for peri-implant marginal bone level, mucosal suppuration, sulcular probing depth, and modified sulcular bleeding index. Patient satisfaction was assessed using 5-item questionnaires at 4 months. The intragroup comparison for all the data was done using Wilcoxon signed-rank test. The intergroup comparison for all the data was done using Mann-Whitney U -test. The comparison of frequency of responses between GpIC and GpIID was done using Chi-square test. P < 0.05 was considered to be statistically significant., Results: Nonsignificant difference was observed in all the hard and soft tissue parameters between the groups at baseline, 2 months, and 4 months ( P > 0.05). Improvement in bleeding on probing was found to be greater around dental implants restored with 3D printed provisional restoration than dental implants restored with conventionally fabricated provisional restoration from baseline to 4 months of follow-up, and the difference in finding was statistically significant ( P < 0.05). There was a statistically nonsignificant difference seen for the frequencies between the groups ( P > 0.05) for all questions related to patient satisfaction., Conclusion: The effect of conventionally fabricated and 3D printed provisional restorations on peri-implant hard and soft tissues was comparable to each other on an early nonfunctionally loaded implant in the mandibular posterior region., Competing Interests: The authors of this manuscript declare that they have no conflicts of interest, real or perceived, financial or nonfinancial in this article., (Copyright: © 2023 Dental Research Journal.)

Objectives: The aim of this study is to provide an updated overview of the oral health status and associated risk factors in maritime settings., Methods: We systematically searched PubMed, Ovid Embase, Web of Science, CINAHL and SCOPUS from January 2010 to April 2023. Two independent reviewers extracted the data. The quality of included studies was assessed using relevant assessment tools., Results: A total of 260 records were found in the initial search; 24 articles met the inclusion criteria. Most studies had descriptive design, and only two randomized controlled trials were found. The main oral health issues noted are oral cancer, dental caries, periodontal diseases, oral mucosal lesions, and dental emergency. Male seafarers have higher risk of oral cancers in the tongue, lips, and oral cavity while oral mucosal lesions are more prevalent among fishermen., Conclusions: Dental caries and periodontal diseases are prevalent in both seafarers and fishermen. The consumption of tobacco, alcohol, fermentable carbohydrate, and poor oral hygiene are risk factors that affect the oral health status at sea. The occurrence of oral diseases in maritime setting requires more attention of researchers and authorities to develop strategies to tackle these issues., Trial Registration: Systematic review registration number in PROSPERO: CRD42020168692., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Nguyen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Chimeric antigen receptor (CAR) T cell therapies have yielded transformative clinical successes for patients with blood tumors, but their full potential remains to be unleashed against solid tumors. One challenge is finding selective targets, which we define intuitively to be cell surface proteins that are expressed widely by cancer cells but minimally by healthy cells in the tumor microenvironment and other normal tissues. Analyzing patient tumor single-cell transcriptomics data, we first defined and quantified selectivity and safety scores of existing CAR targets for indications in which they are in clinical trials or approved. We then sought new candidate cell surface CAR targets that have better selectivity and safety scores than those currently being tested. Remarkably, in almost all cancer types, we could not find such better targets, testifying to the near optimality of the current target space. However, in human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSC), for which there is currently a dearth of existing CAR targets, we identified a total of twenty candidate novel CAR targets, five of which have both superior selectivity and safety scores. These newly identified cell surface targets lay a basis for future investigations that may lead to better CAR treatments in HNSC.

Objective: The objective was to assess the performance of a context-enriched large language model (LLM) compared with international neurosurgical experts on questions related to the management of vestibular schwannoma. Furthermore, another objective was to develop a chat-based platform incorporating in-text citations, references, and memory to enable accurate, relevant, and reliable information in real time., Methods: The analysis involved 1) creating a data set through web scraping, 2) developing a chat-based platform called neuroGPT-X, 3) enlisting 8 expert neurosurgeons across international centers to independently create questions (n = 1) and to answer (n = 4) and evaluate responses (n = 3) while blinded, and 4) analyzing the evaluation results on the management of vestibular schwannoma. In the blinded phase, all answers were assessed for accuracy, coherence, relevance, thoroughness, speed, and overall rating. All experts were unblinded and provided their thoughts on the utility and limitations of the tool. In the unblinded phase, all neurosurgeons provided answers to a Likert scale survey and long-answer questions regarding the clinical utility, likelihood of use, and limitations of the tool. The tool was then evaluated on the basis of a set of 103 consensus statements on vestibular schwannoma care from the 8th Quadrennial International Conference on Vestibular Schwannoma., Results: Responses from the naive and context-enriched Generative Pretrained Transformer (GPT) models were consistently rated not significantly different in terms of accuracy, coherence, relevance, thoroughness, and overall performance, and they were often rated significantly higher than expert responses. Both the naive and content-enriched GPT models provided faster responses to the standardized question set than expert neurosurgeon respondents (p < 0.01). The context-enriched GPT model agreed with 98 of the 103 (95%) consensus statements. Of interest, all expert surgeons expressed concerns about the reliability of GPT in accurately addressing the nuances and controversies surrounding the management of vestibular schwannoma. Furthermore, the authors developed neuroGPT-X, a chat-based platform designed to provide point-of-care clinical support and mitigate the limitations of human memory. neuroGPT-X incorporates features such as in-text citations and references to enable accurate, relevant, and reliable information in real time., Conclusions: The present study, with its subspecialist-level performance in generating written responses to complex neurosurgical problems for which evidence-based consensus for management is lacking, suggests that context-enriched LLMs show promise as a point-of-care medical resource. The authors anticipate that this work will be a springboard for expansion into more medical specialties, incorporating evidence-based clinical information and developing expert-level dialogue surrounding LLMs in healthcare.

Introduction: Examination of the tongue and knowledge of its variation can aid clinicians in correctly assessing the cause of a patient's complaint. Despite World Health Organization recommendations to encourage more epidemiological assessment of oral mucosal variations and lesions, the volume of literature in this area is limited. This study aimed to find out the prevalence of fissured tongues among patients visiting the Department of Oral Medicine and Radiology in a tertiary care centre., Methods: A descriptive cross-sectional study was conducted among patients visiting the Department of Oral Medicine and Radiology in a tertiary care centre. Data was collected from 12 March 2023 to 10 May 2023 after obtaining ethical approval from the same institute. A convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval., Results: Out of 540 patients, the prevalence of fissured tongue was 73 (13.51%) (10.63-16.40, 95% Confidence Interval). A total of 34 (46.57%) were males and 39 (53.42%) were females., Conclusions: The prevalence of fissured tongue among patients visiting the Department of Oral Medicine and Radiology was higher than other studies done in similar settings., Keywords: anatomic variation; fissured tongue; Nepal; oral mucosa; prevalence.

Introduction: In Nepal, one-fourth of the adult population has hypertension. Despite provision of comprehensive hypertension services through the primary healthcare system, huge gaps in treatment and control of hypertension exist. Our study explored the individual, interpersonal, health system and community-level barriers and facilitators affecting hypertension management in urban Nepal., Methods: We used a qualitative methodology informed by Kaufman's socioecological model, conducting focus group discussions with hypertension patients and their family members. In-depth interviews with hypertension patients, healthcare providers and municipal officials were also conducted., Results: We found that inadequate knowledge about hypertension and harmful cultural beliefs hindered effective treatment of hypertension. Interrupted medical supply and distrust in primary healthcare providers affected the poor's access to hypertension services. Poor communication between family members and gender norms affected adaptation of treatment measures. This study emphasised the role of family members in supporting patients in adhering to treatment measures and rebuilding community trust in primary healthcare providers for better access to hypertension services. The findings guided the development of a manual to be used by community health workers during home visits to support patients to control high blood pressure., Conclusion: The study highlights the importance of integrating various aspects of care to overcome the multiple barriers to hypertension management in urban settings in low-resource countries. Participatory home visits have the potential to empower individuals and families to develop and implement feasible and acceptable actions for home management of hypertension through improved adherence to antihypertensive medication, and behaviour change., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: Gentle tissue handling to avoid excessive motion of affected fragile vessels during surgical dissection is essential for both surgeon proficiency and patient safety during carotid endarterectomy (CEA). However, a void remains in the quantification of these aspects during surgery. The video-based measurement of tissue acceleration is presented as a novel metric for the objective assessment of surgical performance. This study aimed to evaluate whether such metrics correlate with both surgeons' skill proficiency and adverse events during CEA., Methods: In a retrospective study including 117 patients who underwent CEA, acceleration of the carotid artery was measured during exposure through a video-based analysis. Tissue acceleration values and threshold violation error frequencies were analyzed and compared among the surgeon groups with different surgical experience (3 groups: novice , intermediate , and expert ). Multiple patient-related variables, surgeon groups, and video-based surgical performance parameters were compared between the patients with and without adverse events during CEA., Results: Eleven patients (9.4%) experienced adverse events after CEA, and the rate of adverse events significantly correlated with the surgeon group. The mean maximum tissue acceleration and number of errors during surgical tasks significantly decreased from novice, to intermediate, to expert surgeons, and stepwise discriminant analysis showed that the combined use of surgical performance factors could accurately discriminate between surgeon groups. The multivariate logistic regression analysis revealed that the number of errors and vulnerable carotid plaques were associated with adverse events., Conclusion: Tissue acceleration profiles can be a novel metric for the objective assessment of surgical performance and the prediction of adverse events during surgery. Thus, this concept can be introduced into futuristic computer-aided surgeries for both surgical education and patient safety., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)