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Typhoid fever is a significant public health concern with most of the sufferers between 15 and 25 y of age in Nepal. We undertook this study to demonstrate Vi polysaccharide conjugated with diphtheria toxoid (Vi-DT) conjugate vaccine which is non-inferior to Typbar typhoid conjugate vaccine, a Vi polysaccharide vaccine conjugated with tetanus toxoid (Vi-TT) with a focus on the adult population from Dhulikhel Hospital which was one of the total four sites in Nepal. In this study, we assigned the eligible participants in 1:1:1:1 ratio by block randomization, and stratified into three age groups (6 months to less than 2 y, 2 y to less than 18 y, and 18 y to 45 y), allotted to Group A, B, C, and D. Group A, B, and C received 25 μg (0.5 mL) of Vi-DT study vaccine and participants in Group D received 25 μg (0.5 mL) Vi-TT vaccine. We descriptively analyzed safety in all the participants receiving one dose of the investigational vaccine. The anti-Vi-IgG seroconversion rate in Vi-DT recipients was 99.71% (97.5% CI 98.04-99.96; 344 of 345 participants) and 99.13% (94.27-99.87; 114 of 115) in Vi-TT recipients which indicates that Vi-DT vaccine is non-inferior to Vi-TT vaccine. In safety aspect, 16.81% of total subject had at least one solicited adverse reaction and 22.61% of the Vi-TT participants experienced at least one solicited adverse reaction with most of them being local adverse reactions. None of the enrolled participants reported serious adverse events. Our study shows that a single dose of the Vi-DT vaccine is immunogenic, safe to administer and non-inferior to the Vi-TT vaccine four weeks after vaccination.

Competing Interests: Competing interests: None declared.

Bone homeostasis within the skeletal system is predominantly maintained by bone formation and resorption. Where formation of new bone involves maturation of stromal cells to mineral and matrix secreting mature osteoblasts, which requires cellular energy or adenosine triphosphate (ATP). Alterations in systemic metabolism can influence osteoblast functioning. In line with this, type 2 diabetes mellitus (T2DM), a common metabolic disorder is also associated with reduced bone formation and increased risk of fracture. Impairment in lipid metabolism is one of the key features associated with T2DM-related pathologies in multiple tissues. Therefore, we tested the hypothesis that the reduced bone formation reported in obese murine models of impaired glucose tolerance is a function of disrupted lipid metabolism in osteoblasts. We first confirmed that mice fed a high fat diet have reduced bone microarchitecture along with lower bone formation rates. Interestingly, osteoblasts from obese mice harbor higher numbers of cytosolic lipid droplets along with decreased bioenergetic profiles compared to control cells. Further supporting this observation, bone tibia cortex demonstrated higher total lipid content in high fat diet fed mice compared to control-fed mice. As a further proof of principle, we generated a novel murine model to conditionally delete Plin2 in osteoblast-progenitor cells using Prrx1-Cre, to enhance lipid droplet breakdown. Our data demonstrate that knocking down Plin2 in an osteoprogenitor specific manner protects from high-fat diet induced osteoblast dysfunction. Furthermore, the mechanism of action involves enhanced osteoblast fatty acid oxidation. In conclusion, the current studies establish that high fat diet induced glucose intolerance leads to perturbations in osteoblast lipid metabolism, thus causing lower bone formation, which can be protected against by increasing fatty acid oxidation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Angina Bullosa Hemorrhagica is characterized with rapid appearance of soft, blood-filled blisters on the mucosa of oral cavity and oropharynx. It is a benign condition, and is not associated with any systemic hematological disorder. No etiological factors have been identified and there are no established guidelines for its management. The current case report describes the sudden appearance of large, bluish, soft lesion on the soft palate which was managed with incision and drainage, and healed completely over the next three weeks., (© Association of Otolaryngologists of India 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objective: Examine the association between military blast exposure and functional status among veterans with a focus on functional disability as a proxy for quality of life and explore the potential modifying effect of hearing loss on this association., Study Design: Prospective cohort., Setting: Multi-institutional tertiary referral centers., Patients: 540 veterans., Exposure: Self-reported military blast exposure with and without tinnitus; high-frequency hearing loss (yes/no)., Main Outcome Measure: WHO Disability Assessment Schedule 2.0 questionnaires at baseline and annually over 5 years. The odds of membership into three functional disability trajectory groups: low functional disability, moderate functional disability, and high functional disability., Results: Of 540 veterans, 197 (36.5%) self-reported a blast exposure history, and 106 of 197 (53.8%) reported tinnitus as a direct result of the blast. Blast exposure without tinnitus increased the odds of moderate functional disability compared with low functional disability (odds ratio [OR] = 1.5; 95% confidence interval [CI], 0.92-2.51), which strengthened among those with blast with tinnitus (OR, 3.6; 95% CI, 2.1-6.1). Blast exposure without tinnitus also increased the odds of membership to high functional disability versus low functional disability (OR, 2.2; 95% CI, 1.1-4.8). Hearing loss further increased the odds of reporting functional disability. The probability of low functional disability was approximately 60% if there was no history of blast or hearing loss, dropping to 20% if there was blast, tinnitus, and hearing loss history., Conclusions: Blast exposure negatively affects the quality of life of veterans, especially when compounded with tinnitus and hearing loss., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2024, Otology & Neurotology, Inc.)

Tick-borne pathogens (TBPs) in dogs are a major global health concern, with their zoonotic importance often being neglected in developing countries due to a lack of surveillance. This study aimed to highlight the incidence of six important TBPs belonging to the genera Babesia, Theileria, Hepatozoon, Anaplasma, Ehrlichia, and Rickettsia in a total of 230 community dogs from two sites: Lumbini and the Kathmandu Valley, of Nepal. A total of 75 (32.6 %) dogs were found to be infected with at least one TBP, with 11 (4.7 %) being co-infected with more than one TBP. The detection rates of TBPs were 13.9 % (n = 32) for Ehrlichia canis, 9.1 % (n = 21) for Anaplasma platys, 8.6 % (n = 20) for Babesia vogeli, and 6.5 % (n = 15) for Babesia gibsoni. None of the samples were positive for Theileria, Hepatozoon, or Rickettsia. There was a significant association between A. platys and E. canis infections, respectively, with the locations from which the samples were collected. Infections of TBPs in community dogs might be the source of infection for pet dogs or even humans in shared habitats. Further studies are needed to determine the prevalence and diversity of TBPs in dogs in other regions of Nepal. As some of these parasites are zoonotic, concerted efforts are required to raise awareness of, and control efforts for, these tick-borne pathogens., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Inspite of high prevalence of mental illness in developing countries, access to health care for addressing mental health issues has several existing barriers at different levels leading to disproportionate adverse health outcomes, summarised as the three Ds of death, disability, and health-economic deficit. This study aims at examining the perspectives of patients with mental illness on barriers to access mental care., Methods: In this study, we searched EMBASE, PubMed, Scopus and PsycNet databases. Database search examined qualitative articles on barriers to access mental health care published from January, 2013 to January, 2023. Papers appropriate for inclusion were selected in the South Asian Association for Regional Cooperation (SAARC) nations, employed qualitative methodologies, and focused on patients, caregiver, or healthcare practitioners' perspective on challenges to access care. The Mixed Methods Appraisal Tool (MMAT) - Version 2018 was used to assess quality., Results: Out of 351 papers, only 24 met the inclusion requirements. A multilevel conceptual framework guided the reporting of emergent themes. Patient with mental disorder experienced four levels of barriers while receiving mental health services: 1. sociocultural (family support, community support networks, and cultural attitudes), 2. organizational (organizational characteristics, service access, and inadequacy of resources), 3. structural (poor implementation of existing policy) and 4. individual levels (knowledge, attitudes, and individual characteristics)., Conclusions: Complex, interlinked, multilevel barriers existed while accessing MHS for patient in SAARC nations. To improve access to MHS, multilevel solutions ought to tackle individual, organizational, societal, and structural barriers at various phases of the care pathway is imperative., Competing Interests: Declaration of Competing Interest The authors have declared that no competing interest exist., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Narcissistic personality disorder (NPD) is associated with a complex interplay of genetic, neurobiological, and environmental factors. In this case report, we discuss the association between adverse childhood experiences (ACEs) and the development of NPD in adulthood., Case Presentation: Here, we report a clinical case of NPD to illustrate how ACEs, particularly physical and emotional neglect, combined with early life parental overvaluation, can impair emotional regulation and self-worth, contributing to the development of narcissistic traits. We analyse, in light of existing literature, how ACEs are associated with a wide spectrum of personality disorders, how parental overvaluation is linked to grandiose narcissism, and how childhood neglect and abuse are associated with vulnerable narcissism., Conclusion: ACEs are the primary risk factor for the development of NPD in adulthood. Dysfunctional household environments and parenting practices compound the association between ACEs and pathological narcissism. It is important to address childhood trauma for the prevention and treatment of NPD. Further research is necessary to clarify how individual factors influence the relationship between ACEs and pathological narcissism., Competing Interests: Declarations. Ethical approval and consent to participate: Not applicable. Consent for publication: Written informed consent was obtained from the patient for the publication of his personal or clinical details, along with any identifying images, in this study. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: To investigate the sociodemographic, anthropometric, biochemical, lifestyle and cardiometabolic risk factors associated with type 2 diabetes (T2D) among First Nations Australians., Methods: A systematic review of prospective cohorts and cross-sectional studies was conducted. Electronic data sources (MEDLINE/PubMed, Embase, CINHAL, and PsycINFO) were searched for peer-reviewed articles until August 2023. We reviewed observational and interventional studies on T2D that reported sociodemographic, anthropometric, lifestyle, and biochemical risk factors for Australian First Nations people. Narrative synthesis was applied without meta-analysis. We highlighted the major risk factors for T2D by reporting the most significant findings from individual studies in the results. The review followed PRISMA guidelines., Results: The review included 20 eligible studies: 12 cross-sectional studies and 8 prospective cohort studies. The findings from these studies showed that First Nations people who resided in very remote areas (Modified Monash Category 7; MM7) (OR = 1.61; 95% CI: 1.03, 2.52), living adjacent to food store stocking "Western" food items (OR = 2.92; 95% CI: 1.51, 5.63), rented their home (OR = 2.07; 95% CI: 1.30, 3.30) and part-time employment (OR = 2.47; 95% CI: 1.54, 3.95) were associated with a statistically higher risk of developing T2D. First Nations people who had obesity class 1 (BMI > 30 kg/m 2 ), central obesity (WC > 88 cm in women; >102 cm in men), and higher waist-to-hip ratio (WHR) (≥ 1.0 in men and 0.85 in women) were more likely to have T2D. First Nations people with elevated triglycerides (≥ 1.7 mmol/L) (OR = 4.9; 95% CI: 2.7, 8.8), one standard deviation (SD) increase in C-reactive protein (CRP) value (AHR = 1.23; 95% CI: 1.05, 1.45) and lower levels of vitamin D (< 53 nmol/L) (AOR = 2.15; 95% CI: 1.10, 2.18) were significantly associated with a higher risk of T2D. However, no significant association was found with either daily smoking or daily alcohol., Conclusion: To address the First Nations Health Gap attributed to T2D in Australia, interventions should prioritise remote areas, socioeconomic disadvantage, central obesity, elevated triglycerides, and vitamin D deficiency. This was the first comprehensive systematic review examining sociodemographic, anthropometric, biochemical, lifestyle, and cardiometabolic risk factors associated with T2D among First Nations Australians., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The biodiversity and distribution of epiphytic orchids are strongly influenced by their relationship with host plants, and environmental variables like elevation, slope, and local climate are key factors in determining the abundance and diversity of these orchids. The aim of this study was to examine the richness of orchid species at different elevations within the research area of Nepal. Sampling was conducted at elevations ranging from 1300 m to 2800 m above sea level, using a systematic sampling technique known as belt transects. Six circular plots with a diameter of 5.6 m were established in a horizontal transect at each site, spaced at least 50 m apart, with 100 elevation interval. The analysis revealed a hump-shaped relationship between orchid species richness and elevation, with the highest species richness observed at altitude of 2100-2200 m. The abundance of orchids was significantly correlated with host characteristics, including habit (shrub/tree), bark texture, nature (deciduous/evergreen), and physical factors. This study underscores the significant contribution of host characteristics and environmental factors in explaining the diversity of epiphytic orchid species along the elevation of the Himalayas.

Subdural empyema is rare but serious intracranial infection characterized by accumulation of pus between dura mater and arachnoid layer. The spread of infection is typically originating from sinusitis, otitis media, or osteomyelitis. Early diagnosis by radiological imaging and prompt treatment, either by surgical intervention or by broad spectrum antibiotics are crucial to prevent life threatening complications. Here, we present a case of subdural empyema in a 13-year-old male managed by surgical drainage and intravenous antibiotics., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Objectives: Metabolic changes are crucially involved in osteoclast development and may contribute to bone degradation in rheumatoid arthritis (RA). The enzyme aconitate decarboxylase 1 (Acod1) is known to link the cellular function of monocyte-derived macrophages to their metabolic status. As osteoclasts derive from the monocyte lineage, we hypothesised a role for Acod1 and its metabolite itaconate in osteoclast differentiation and arthritis-associated bone loss., Methods: Itaconate levels were measured in human peripheral blood mononuclear cells (PBMCs) of patients with RA and healthy controls by mass spectrometry. Human and murine osteoclasts were treated with the itaconate derivative 4-octyl-itaconate (4-OI) in vitro. We examined the impact of Acod1-deficiency and 4-OI treatment on bone erosion in mice using K/BxN serum-induced arthritis and human TNF transgenic (hTNFtg) mice. SCENITH and extracellular flux analyses were used to evaluate the metabolic activity of osteoclasts and osteoclast progenitors. Acod1-dependent and itaconate-dependent changes in the osteoclast transcriptome were identified by RNA sequencing. CRISPR/Cas9 gene editing was used to investigate the role of hypoxia-inducible factor (Hif)-1α in Acod1-mediated regulation of osteoclast development., Results: Itaconate levels in PBMCs from patients with RA were inversely correlated with disease activity. Acod1-deficient mice exhibited increased osteoclast numbers and bone erosion in experimental arthritis while 4-OI treatment alleviated inflammatory bone loss in vivo and inhibited human and murine osteoclast differentiation in vitro. Mechanistically, Acod1 suppressed osteoclast differentiation by inhibiting succinate dehydrogenase-dependent production of reactive oxygen species and Hif1α-mediated induction of aerobic glycolysis., Conclusion: Acod1 and itaconate are crucial regulators of osteoclast differentiation and bone loss in inflammatory arthritis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Understanding the contribution of intimate partner violence (IPV) to childhood health outcomes (eg, morbidity and mortality) is crucial for improving child survival in sub-Saharan Africa. This comprehensive study aimed to explore the associations between maternal exposure to physical, sexual, or emotional violence and adverse childhood health outcomes in sub-Saharan Africa., Methods: We analysed Demographic Health Survey datasets from 37 sub-Saharan African countries from 2011 to 2022. A generalised linear mixed model was used to examine the associations between maternal physical violence, sexual violence, or emotional violence, and early childhood health outcomes (eg, acute respiratory infection, diarrhoea, undernutrition, and child mortality). A random effects meta-analysis was used to calculate pooled odds ratios (ORs) for adverse childhood health outcomes. The odds of undernutrition and mortality were 55% and 58% higher among children younger than 5 years born to mothers who were exposed to physical and sexual violence, respectively., Findings: 238 060 children younger than 5 years were included. Children whose mothers experienced physical violence (adjusted OR 1·33, 95% CI 1·29-1·42), sexual violence (1·47, 1·34-1·62), emotional violence (1·39, 1·32-1·47), or a combination of emotional and sexual violence (1·64, 1·20-2·22), or a combination of all the three forms of violence (1·88, 1·62-2·18) were associated with an increased odds of developing diarrhoeal disease. Similarly, children whose mothers experienced physical violence (1·43, 1·28-1·59), sexual violence (1·47, 1·34-1·62), emotional violence (1·39, 1·32-1·47), or a combination of emotional and sexual violence (1·48, 1·16-1·89), or a combination of all three forms of violence (1·66, 1·47-1·88) were positively associated with symptoms of acute respiratory infection., Interpretation: We found a strong link between maternal exposure to IPV and health outcomes for children younger than 5 years in sub-Saharan Africa, with minor variations across countries. To address childhood morbidity and mortality attributed to IPV, interventions need to be tailored for specific countries. Burkina Faso, Burundi, Chad, Comoros, Gabon, Liberia, Nigeria, Sierra Leone, South Africa, and Uganda should be priority nations., Funding: None., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Prior research has indicated an association between epilepsy and psychosis. This review aimed to estimate the global prevalence rate of psychosis and schizophrenia in epilepsy and assess the odds of psychosis and schizophrenia among patients with epilepsy (PWE)., Method: A comprehensive literature search was carried out utilizing relevant keywords in PubMed/MEDLINE and Scopus, covering from January 1, 1990, to November 18, 2023. The meta-analysis was performed using R software employing a random-effect model to establish the overall prevalence and odds ratio (OR), with 95 % confidence intervals (95 % CI), of psychosis and schizophrenia in epilepsy., Result: Eighty-one studies encompassing 970,497 PWE met the inclusion criteria. The meta-analysis revealed that the overall prevalence of psychosis and schizophrenia among PWE was 7.8 % (95 % CI: 6.3-9.2 %, I 2 = 100 %) and 3 % (95 % CI: 1.7-4.3 %, I 2 = 95 %), respectively. Moreover, epilepsy was associated with a threefold rise in the odds of psychosis (OR = 3.41, 95 % CI: 2.3-5.08, p-value < 0.01, I 2 = 99 %, p-heterogeneity < 0.01). Furthermore, epilepsy was found to be significantly correlated with a fivefold increased odds of schizophrenia (OR = 5.22, 95 % CI: 2.99-9.11, p-value < 0.01, I 2 = 94 %, p-heterogeneity < 0.01) CONCLUSION: Epilepsy can increase the risk of developing psychosis and schizophrenia. Additional longitudinal research is warranted to elucidate the influence of epilepsy and its treatments on the risk of psychosis and schizophrenia, and also a comprehensive suite of confounding adjustments will be requisite., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of preterm infants that is associated with life-long morbidities. Inflammatory insults contribute to BPD pathogenesis. Although the proinflammatory cytokine, IL-17a, plays a role in various neonatal inflammatory disorders, its role in BPD pathogenesis is unclear. To test the hypothesis that blocking IL-17a signaling decreases lipopolysaccharide (LPS)-mediated experimental BPD in neonatal mice, wild-type mice were injected intraperitoneally with phosphate-buffered saline or LPS during the saccular lung developmental phase. Pulmonary IL-17a expression was determined by enzyme-linked immunosorbent assay and by flow cytometry. LPS-injected mice had higher pulmonary IL-17a protein levels and IL-17a + and IL-22 + cells. γδ T cells, followed by non-T lymphoid cells, were the primary producers of IL-17a. Wild-type mice were then injected intraperitoneally with isotype antibody (Ab) or IL-17a Ab, while they were treated with phosphate-buffered saline or LPS, followed by quantification of lung inflammatory markers, alveolarization, vascularization, cell proliferation, and apoptosis. LPS-mediated alveolar simplification, apoptosis, and cell proliferation inhibition were significantly greater in mice treated with isotype Ab than in those treated with IL-17a Ab. Furthermore, STAT1 activation and IL-6 levels were significantly greater in LPS-exposed mice treated with isotype Ab than in those treated with IL-17a Ab. The study results indicate that blocking IL-17a signaling decreases LPS-mediated experimental BPD., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Men exhibit higher prevalence of modifiable risk factors, such as smoking and alcohol consumption, leading to greater cancer incidence and lower survival rates. Comprehensive evidence on global cancer burden among men, including disparities by age group and country, is sparse. To address this, the authors analyzed 30 cancer types among men in 2022, with projections estimated for 2050., Methods: The 2022 GLOBOCAN estimates were used to describe cancer statistics for men in 185 countries/territories worldwide. Mortality-to-incidence ratios (MIRs) were calculated by dividing age-standardized mortality rates by incidence rates., Results: In 2022, a high MIR (indicating poor survival) was observed among older men (aged 65 years and older; 61%) for rare cancer types (pancreatic cancer, 91%) and in countries with low a Human Development Index (HDI; 74%). Between 2022 and 2050, cancer cases are projected to increase from 10.3 million to 19 million (≥84%). Deaths are projected to increase from 5.4 million to 10.5 million (≥93%), with a greater than two-fold increase among men aged 65 years and older (≥117%) and for low-HDI and medium-HDI countries/territories (≥160%). Cancer cases and deaths are projected to increase among working-age groups (≥39%) and very-high-HDI countries/territories (≥50%)., Conclusions: Substantial disparities in cancer cases and deaths were observed among men in 2022, and these are projected to widen by 2050. Strengthening health infrastructure, enhancing workforce quality and access, fostering national and international collaborations, and promoting universal health coverage are crucial to reducing cancer disparities and ensuring cancer equity among men globally., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Objective: Examine associations between military blast exposures on hearing loss and self-reported hearing difficulties among Active-Duty Service Members (ADSM) and Veterans from the Noise Outcomes in Servicemembers Epidemiology (NOISE) study., Study Design: Cross-sectional., Setting: Multi-institutional tertiary referral centers., Methods: Blast exposure was assessed with a comprehensive blast questionnaire. Outcome measures included pure-tone hearing thresholds; Speech Recognition in Noise Test; Hearing Handicap Inventory for Adults (HHIA); and Speech, Spatial and Qualities of Hearing Scale (SSQ)-12., Results: Twenty-one percent (102/494) of ADSM and 36.8% (196/533) of Veterans self-reported blast exposure. Compared to ADSM without blast exposure, blast-exposed ADSM had increased odds of high frequency (3-8 kHz) and extended-high frequency (9-16 kHz) hearing loss (odds ratio [OR] = 2.5, CI: 1.3, 4.7; OR = 3.7, CI: 1.9, 7.0, respectively). ADSM and Veterans with blast exposure were more likely than their nonblast exposed counterparts to report hearing difficulty on the HHIA (OR = 1.9, CI: 1.1, 3.3; OR = 2.1, CI: 1.4, 3.2, respectively). Those with self-reported blast exposure also had lower SSQ-12 scores (ADSM mean difference = -0.6, CI: -1.0, -0.1; Veteran mean difference: -0.9, CI: -1.3, -0.5)., Conclusion: Results suggest that blast exposure is a prevalent source of hearing injury in the military. We found that among ADSM, blast exposure was associated with hearing loss, predominately in the higher frequencies. Blast exposure was associated with poorer self-perceived hearing ability in ADSM and Veterans. IRB: #FWH20180143H Joint Base San Antonio (JBSA) Military Healthcare System; #3159/9495 Joint VA Portland Health Care System (VAPORHCS) Oregon Health and Science University (OHSU)., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)

The diagnosis of pulmonary hypertension in non-Hodgkin's lymphoma confers a relatively poor prognosis, emphasizing the critical need for early recognition and tailored management strategies. Standard pulmonary hypertension treatments may yield suboptimal responses due to the underlying neoplastic origin, highlighting the importance of prompt initiation of chemotherapy. We present a unique case of pulmonary hypertension in marginal zone lymphoma along with a comprehensive review of reported non-Hodgkin's lymphoma cases associated with pulmonary hypertension, shedding light on the diagnostic and therapeutic challenges encountered in clinical practice., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

A novel photoinduced Fe(OTf) 2 /2,4,6-collidine-catalyzed alkylation of Morita-Baylis-Hillman (MBH) acetates using carboxylic acids in a regio- and stereoselective manner is reported. This method demonstrates a broad scope, encompassing various carboxylic acids and MBH acetates, including drugs and bioactive molecules, to synthesize densely functionalized cinnamates and acrylates. The reactions are performed in the green solvent dimethyl carbonate under oxidant-free conditions. Based on control experiments, a plausible mechanism involving an Fe(II)-Fe(III)-Fe(II) cycle is proposed.

The Herlyn-Werner-Wunderlich syndrome is a rare congenital disorder with uterus didelphys, unilateral obstructed hemivagina and ipsilateral renal agenesis, more common on right side. HWW syndrome usually presents at puberty with symptoms like pelvic pain, dysmenorrhea and palpable mass due to the associated hematocolpos or hematometra. Delayed presentation in adulthood as infertility can occur in case of incomplete vaginal septum. Short term complications like pyohematocolpos, pyosalpinx, or pelviperitonitis, and long-term complications, such as endometriosis, increased risk of abortion and infertility can occur. Ultrasound is the initial investigation which demonstrates uterine anomaly, renal agenesis and hematocolpos.Magnetic resonance imaging (MRI) is the imaging modality of choice which helps in confirmation of diagnosis, delineation of vaginal septum, communication between 2 cavities and associated pathologies like adenomyosis better.Vaginal septum resection is the treatment of choice for obstructed hemivagina with hematocolpos. We present you a case of 43 years female with cyclical dysmenorrhea starting few years after menarche with uterine didelphys, left sided vaginal septum with hematocolpos and left renal agenesis. Along with this, diffuse bilateral adenomyosis was present which is uncommonly associated with this anomaly as obstruction is at the level of vagina. Patient was diagnosed late due to misdiagnosis and later treated with septal resection for hematocolpos and with hormonal medications for adenomyosis., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Background: The usual surgical technique for heart surgery has been median sternotomy, which provides excellent exposure of all cardiac structures and facilitates the establishment of cardiopulmonary bypass with central cannulation. A number of alternative surgical techniques, including the right anterolateral thoracotomy, posterolateral thoracotomy, and partial sternotomy, have been suggested. We want to share our experience with right anterior mini-thoracotomy versus right axillary mini-thoracotomy for closing an atrial septal defect., Methods: The study was a retrospective cross-sectional study conducted in a hospital. The study comprised patients with atrial septal defect admitted to Green City Hospital in Kathmandu, Nepal. From May 2016 until September 2021. Data was extracted to MS excel sheet, and then transported to the STATA version 17 for analysis. First, we computed descriptive analysis which included calculation of frequency, percentage, mean and median for presentation of socio-demographic variables. Continuous data were tested for normality using Shapiro-Wilk test., Results: A total of 25 patient were included in the study with median age 26 years (20-32). The median aortic cross clamp time was 25 minutes ranging 20-35 min. The median duration of cardiopulmonary bypass time ranging from 31to 161 minutes. The median time of Ax was 25 minutes and 26 minutes for right anterior mini-thoracotomy and right axillary mini-thoracotomy respectively. The median duration of hospital stay was 4 days ranging from 3-4 days. Nearly 36% study participants were associated with abnormal body mass index. (Either under nutrition or over nutritional status)., Conclusions: There were no significant differences between the duration of intensive care unit and hospital stays, aortic cross clamp time, and complications between the two groups. However, the possibility of less blood loss during surgery and of cosmetic appearance in axillary incision is of special importance.

A lack of consumption of a diversified diet is associated with poor physical and cognitive development in children. Evidence on the relationship between minimum dietary diversity (MDD) and childhood malnutrition remains inconclusive in India. We hypothesized that children aged 6 to 23 months on a diversified diet (five out of eight defined foods and beverages) are less likely to be malnourished (stunting, wasting, and underweight) compared to their counterparts who are not on a diversified diet. This cross-sectional study was based on the 2019-2021 National Family Health Survey of India, comprising a weighted sample of 57,714 children aged 6 to 23 months. Multilevel logistic regression was conducted for data analysis. The results showed a significant protective effect of dietary diversity on underweight (odds ratios [OR] = 0.91; 95% confidence intervals [CI]: 0.86-0.96). In addition, children who did not consume eggs (OR = 1.09; 95% CI; 1.03-1.15), dairy products (OR = 1.22; 95% CI: 1.17-1.27), or fruits and vegetables (OR = 1.11; 95% CI: 1.06-1.17) were more likely to be underweight than children who did. Children who did not consume dairy products, fruits, and vegetables were also more likely to be stunted and wasted. However, we did not find significant associations of MDD with wasting and stunting. Nutritional interventions promoting daily consumption of dairy products, eggs, fruit, and vegetables are recommended to address the growing problem of childhood malnutrition in India. Regions with higher rates of malnutrition and those lacking MDD, such as Uttar Pradesh and Rajasthan, should be prioritized., Competing Interests: Author declarations None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: The Syrian refugee crisis has led to significant population displacement, with many seeking refuge and asylum in Nordic countries. While these countries offer safety and stability, the resettlement process combined with the refugees' own traumatic experiences can exacerbate existing or precipitate new mental health issues., Aim: This systematic review aims to comprehensively analyse the literature on mental health problems among Syrian refugees resettled in Nordic countries, exploring their prevalence and associated factors., Methods: A comprehensive literature search was conducted following PRISMA guidelines, utilizing databases including Web of Science, PubMed, MEDLINE, and Cochrane. The included studies focused on adult Syrian refugees or asylum seekers aged 18 and above, residing within Nordic countries, and investigated various mental health problems between March 2011 and January 2024, conducted in various Nordic countries., Results: Studies revealed high prevalence rates of PTSD (26%-45%), depression (40%-45%), and anxiety (30%-32%). Factors contributing to mental health problems included pre- and post-migration trauma, perceived discrimination, and socio-demographic variables. Pre-migration trauma exposure, such as witnessing violent events, was linked to trauma centrality and emotional suppression. Post-migration stressors like discrimination and financial strain, along with socio-demographic factors like gender and age, were associated with mental health issues. Specifically, female and older refugees reported higher levels of anxiety, depression, and low future expectations., Conclusion: The findings underscore the urgent need for comprehensive mental health assessment and services for Syrian refugees in Nordic countries. Addressing trauma, discrimination, and socio-economic challenges is crucial for improving their well-being and facilitating successful integration into host countries.

Competing Interests: Conflicts of interest The authors declare that they have no conflict of interest.

How do ordinary people evaluate robots that make morally significant decisions? Previous work has found both equal and different evaluations, and different ones in either direction. In 13 studies (N = 7670), we asked people to evaluate humans and robots that make decisions in norm conflicts (variants of the classic trolley dilemma). We examined several conditions that may influence whether moral evaluations of human and robot agents are the same or different: the type of moral judgment (norms vs. blame); the structure of the dilemma (side effect vs. means-end); salience of particular information (victim, outcome); culture (Japan vs. US); and encouraged empathy. Norms for humans and robots are broadly similar, but blame judgments show a robust asymmetry under one condition: Humans are blamed less than robots specifically for inaction decisions-here, refraining from sacrificing one person for the good of many. This asymmetry may emerge because people appreciate that the human faces an impossible decision and deserves mitigated blame for inaction; when evaluating a robot, such appreciation appears to be lacking. However, our evidence for this explanation is mixed. We discuss alternative explanations and offer methodological guidance for future work into people's moral judgment of robots and humans., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To assess the efficacy of intralesional steroid treatment in preventing vocal fold scarring following vocal fold surgery using a rabbit model., Methods: The research involved 42 male New Zealand white rabbits. Fourteen rabbits underwent vocal fold scar surgery using a 532nm laser and served as controls (control group). The remaining rabbits were divided into two groups of 14: one group received vocal fold scar surgery followed by dexamethasone injection (Dexa group) and the other received the same surgery followed by triamcinolone injection (Triam group). Four weeks after surgery, histological examinations and high-speed video analyses of vocal fold vibration were conducted. The maximum amplitude of vibration was the primary measure for assessing vocal fold function. In addition, real-time polymerase chain reaction (PCR) studies were undertaken to analyze scar regeneration and remodeling., Results: The maximum amplitude differences were notably higher in the Dexa and Triam groups than in controls. Histologically, the collagen density (CD) ratios in both the Dexa and Triam groups were significantly reduced compared with controls. Real-time PCR analysis indicated marked elevations of Has-2 and Mmp-9 in the Dexa and Triam groups relative to controls., Conclusions: Intralesional steroid injections after vocal fold surgery are effective for reducing vocal fold scarring in a rabbit model., Level of Evidence: NA Laryngoscope, 135:176-182, 2025., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Around half of preterm births lack identifiable causes, indicating the need for further investigation to understand preterm birth risk factors. Existing studies on the intergenerational association of preterm birth showed inconsistency in effect size and direction., Objective: This systematic review and meta-analysis aimed to review existing studies and provide comprehensive evidence on the intergenerational association of preterm births., Search Strategy: We searched MEDLINE, Embase and Maternity and Infant Care databases, from the inception of each database to 04 April 2024., Selection Criteria: Eligibility criteria included studies that reported on women who had given birth and had recorded information about a family history of preterm birth in one or both of the child's biological parents., Data Collection and Analysis: Data were extracted by two independent reviewers. A random-effects model was used to compute pooled estimates using odds ratios., Main Results: Sixteen eligible studies with a total of 2 271 612 mothers were included. The findings indicated a 1.44 (OR = 1.44, 95% CI: 1.34, 1.54) fold increase in odds of giving preterm births among women who were born preterm. Additionally, having a sibling born preterm (OR = 1.53, 95% CI: 1.24, 1.87) and having a partner born preterm (OR = 1.12, 95% CI: 1.01, 1.25) were associated with increased likelihood of giving preterm births among women., Conclusion: The study revealed that women with a family history of preterm birth face an increased risk of giving preterm births. Screening pregnant women for a family history of preterm birth is essential, with those having a positive family history requiring closer follow-up., (© 2024 The Author(s). BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

The rapid epidemiological transition in Asian countries, resulting from the rising trend of urbanisation and lifestyle changes, is associated with an increasing risk of obesity in women of reproductive age. This is the first study to investigate the trends and population-attributable fraction (PAF) of obesity, and the interaction effects of education and wealth on obesity among reproductive-age women aged 15-49 years in ten Asian countries. This cross-sectional study examined the most recent (2000 to 2022) Demographic and Health Surveys (DHS) data from ten Central and Southeast Asian countries. Multilevel multinomial logistic regression models were used to compute odds ratios (ORs). PAFs adjusted for communality were calculated using adjusted ORs and prevalence estimates for each risk factor. This study included a weighted sample of 743,494 reproductive-age women. All the countries showed an increasing trend for obesity and a decreasing trend for underweight, except for the Maldives. The highest PAFs of obesity were associated with women who were married (PAF = 22.2%; 95% CI 22.1, 22.4), aged 35-49 years (PAF = 16.4%; 95% CI 15.5, 17.1), resided in wealthy households (PAF = 14.5%; 95% CI 14.4, 14.5), watched television regularly (PAF = 12.5%; 95% CI 12.1, 12.8), and lived in urban areas (PAF = 7.8%; 95% CI 7.7, 8.0). The combined PAF showed that these five risk factors were associated with 73.3% (95% CI 71.8, 74.9) of obesity among reproductive-age women. Interaction analysis between women's education and household wealth revealed that having a secondary or higher level of education and residing in a wealthier household was associated with a lower risk of obesity (OR = 0.71, 95% CI 0.66, 0.76). The findings of this study suggest that, in order to address the rising rate of obesity among women in Asian countries, education and lifestyle modifications in urban areas should be a priority. Pakistan and the Maldives need to be a priority given the rapidly increasing trends in obesity and underweight subpopulations in their respective countries., (© 2024. The Author(s).)

Introduction: Sleep is a fundamental human requirement, considered one of the major contributing factors to physical and mental health, especially among adolescents. Poor quality sleep has many potential consequences including non-suicidal self-injury (NSSI), suicidal thoughts or behaviour and complete suicide. The NSSI and suicidal behaviour are increasing in Nepal. Thus, this study aimed to assess the role of sleep problem on suicidal behaviour and non-suicidal self-injury among adolescents in Pokhara metropolitan, Nepal., Methods: A cross-sectional analytical study was conducted among 673 adolescents using a multistage cluster sampling technique from private and public schools in Pokhara Metropolitan. Self-administered questionnaire was used for data collection. Collected data was entered and managed in EpiData (version 3.1) and analysed in IBM SPSS (version 23). Binary logistic regression was used to identify the association of sleep problem with NSSI and suicidal behaviour., Results: The study found that sleep problem (65.2%, 439), suicidal behaviour (18.6%, 125) and NSSI (57.9%, 390) were prevalent among adolescents in study setting. The presence of sleep problem significantly influenced the suicidal behavior (AOR = 3.88, 95% CI = 2.27-6.63) alongside the sex of student (AOR = 1.96, 95% CI = 1.28-3.00), adolescents from family having monthly income less than NPR 40,000 (AOR = 1.97 95% CI = 1.16-3.35) and private schools students (AOR = 2.99, 95% CI = 1.84-4.86). Likewise, sleep problem was also associated with non-suicidal self-injury (AOR = 3.24, 95% CI = 2.26-4.65), in addition to attending private school (AOR = 2.52, 95% CI = 1.71-3.72)., Conclusion: This study concludes that sleep problem is prevalent among the adolescents and increase the risk of NSSI and suicidal behaviour. Therefore, parents and teachers need to assess their conditions and help them maintain sound sleep. Additionally, suicide prevention strategies need to be adopted to mitigate further risk., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Thapa, Yadav. 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 and Objectives: There is no disease-modifying treatment of corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP), 2 disorders characterized by their striking phenotypic, and, in CBS, pathologic heterogeneity. Seed amplification assays (SAAs) could enable the detection of neuropathologic processes, such as α-synuclein (αSyn) copathology, that affect the success of future disease-modifying treatment strategies. The primary objective was to assess possible αSyn copathology in CBS and PSP, as detected in CSF using an αSyn SAA (αSyn-SAA). Secondary objectives were to evaluate the association of αSyn-SAA positivity with other biomarkers including of Alzheimer disease (AD), and with clinical presentation. We hypothesized that αSyn-SAA positivity would be detectable in CBS and PSP and that it would be associated with AD biomarker positivity and β-amyloid (Aβ) 42 levels, neurodegeneration as assessed by neurofilament light chain (NfL) levels, and symptoms associated with synucleinopathies., Methods: This cross-sectional observational study included patients clinically diagnosed with CBS and PSP who underwent a lumbar puncture between 2012 and 2021 (Toronto Western Hospital, Canada). CSF was tested for αSyn-SAA positivity, AD biomarkers, and NfL levels. Clinical data were derived from medical records., Results: We tested the CSF of 40 patients with CBS (19 female patients, 65.9 ± 8.6 years) and 28 with PSP (13 female patients, 72.5 ± 8.7 years old), mostly White (n = 50) or Asian (n = 14). αSyn-SAA positivity was observed in 35.9% patients with CBS and 28.6% with PSP. In young-onset, but not late-onset patients, αSyn-SAA positivity and AD positivity were associated (odds ratio [OR] 8.8, 95% CI 1.2-82.6, p < 0.05). A multivariable linear regression analysis showed a significant interaction of αSyn-SAA status by age at onset on CSF Aβ42 levels (β = 0.3 ± 0.1, p < 0.05). Indeed, age at onset was positively related to Aβ42 levels only in αSyn-SAA-positive patients, as shown by slope comparison. A logistic regression analysis also suggested that REM sleep behavior disorder was associated with αSyn-SAA positivity (OR 60.2, 95% CI 5.2-1,965.8; p < 0.01)., Discussion: We detected a frequency of αSyn-SAA positivity in CBS and PSP in line with pathologic studies, highlighting the usefulness of SAAs for in vivo detection of otherwise undetectable neuropathologic processes. Our results also suggest that AD status (specifically low Aβ42) and older age at onset may contribute to αSyn-SAA positivity. This opens new perspectives for the stratification of patients in clinical trials.

Background: Aboriginal and Torres Strait Islander peoples face an increased risk of common mental disorders, which may be associated with underlying socio-economic challenges, racism, and discrimination. This is the first study to calculate the population attributable fractions (PAFs) for depression and anxiety attributed to potentially modifiable risk factors such as health behaviour, social and cultural characteristics, and past adverse events among Aboriginal and Torres Strait Islander peoples aged ≥15 years., Methods: This cross-sectional study examined the 2018-19 National Aboriginal and Torres Strait Islander Health Survey conducted by the Australian Bureau of Statistics. Logistic regression models were used to compute odds ratios (ORs). PAFs adjusted for communality were calculated using adjusted ORs and prevalence estimates for each risk factor., Findings: This study included a weighted sample of 5362 individuals, with a mean age of 40.8 years (SD = ±17.2). Personal income below the national average (PAF = 13.4%; 95% CI: 12.4, 14.5), severed access to Indigenous cultural affiliations (PAF = 12.8%; 95% CI: 11.8, 13.8), central obesity (PAF = 7.2%; 95% CI: 6.4, 8.0), daily smoking (PAF = 5.9%; 95% CI: 5.2, 6.7) and severed access to Indigenous knowledge (PAF = 5.2%; 95% CI: 4.5, 5.8) were associated with 45% of depression cases. Personal income below the national average (PAF = 10.7%; 95% CI: 9.8, 11.7), limited access to Aboriginal Community Controlled Health Services (PAF = 10.6%; 95% CI: 9.7, 11.6), central obesity (PAF = 7.1%; 95% CI: 6.3, 7.9), severed access to Indigenous knowledge (PAF = 5.7%; 95% CI: 4.9, 6.4) and the experience of discrimination in the last 12 months (PAF = 4.7%; 95% CI: 4.0, 5.3) were associated with 39% of anxiety cases., Interpretation: To reduce the burden of depression and anxiety disorder among Aboriginal and Torres Strait Islander peoples, addressing socio-economic and cultural harms that constrain healthy connections to people/kin, their rights, languages, land, and healthy food sources should be a priority., Funding: This work was funded by a grant from the Commonwealth of Australia, represented by the Department of Health and Aged Care (Grant Activity 4-DGEJZ1O/4-CW7UT14)., Competing Interests: The authors declare no conflict of interests., (© 2024 The Author(s).)

Leea asiatica (L.) Ridsdale has been used by different ethnic communities to manage diseased conditions that can be traced to oxidative stress and cellular inflammations but scientific evidences to support the claim are scanty. The objective of this study was to isolate and identify the antioxidants present in the aerial parts of Leea asiatica, perform their molecular docking against proteins to inspect whether the traditional uses of the plant can be validated by an in-silico approach. Quercetin ( 1 ), gallic acid ( 2 ), kaempferol ( 3 ), methyl gallate ( 4 ), myricetin 3- O - α -L-rhamnopyranoside ( 5 ), (-)-epicatechin-3- O -gallate ( 6 ) and (-)-epigallocatechin-3- O -gallate ( 7 ) were isolated from the 70 % methanolic extract of the aerial parts. Compounds 2 , 4 , 6 , and 7 are reported for the first time from Leea asiatica . Quercetin ( 1 ), gallic acid ( 2 ), (-)-epicatechin-3- O -gallate ( 6 ) and (-)-epigallocatechin-3- O -gallate ( 7) showed potent antioxidant activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. Molecular docking with NADPH oxidase and TNF- α revealed that epicatechin-3- O- gallate, epigallocatechin-3- O -gallate and quercetin bound with the least binding energy amongst the isolated compounds as well as standard (Trolox and Prednisolone). By molecular dynamics analysis, epicatechin-3- O- gallate maintained stable conformation with NADPH oxidase and TNF- α and was found to possess good ADMET profile thereby validating the ethnic use of the plant as a medicine in the management of inflammatory conditions by an in vitro and in silico approach., 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.)

Introduction and Importance: Swyer syndrome or complete/pure gonadal dysgenesis, a rare genetic disorder, presents with a female phenotype despite a 46, XY karyotype. The case highlights the importance of early diagnosis and management in XY females to prevent gonadal malignancy and facilitate proper growth of secondary sexual characteristics of the patient by initiating hormone replacement therapy (HRT)., Case Presentation: A 15-year-old female presented with lower abdominal pain, seeking an investigation, ultrasonography revealed the non-visualization of the uterus. Further examination with MRI revealed a hypoplastic uterus and non-visualization of ovaries. Clinical examination and diagnostic laparoscopy along with karyotype analysis confirmed the diagnosis of Swyer syndrome, prompting bilateral Salpingo-oophorectomy and initiation of HRT after the surgery. Follow-up showed improvement in the growth of the uterus and secondary sexual characteristics., Clinical Discussion: Case discussion explores into the unique clinical findings of Swyer syndrome, emphasizing the importance of differentiating it from other disorders of sex development (DSD) like Mayer-Rokitansky-Küster-Hauser syndrome and androgen insensitivity syndrome. Genetic and hormonal aspects of the condition are also explored in relation to the patient's presentation and management., Conclusion: The case highlights the significance of early diagnosis and comprehensive management of Swyer syndrome. It emphasizes the need for multidisciplinary care, including fertility counseling and psychological support, in addressing the complexities of rare genetic disorders like Swyer syndrome. The key message includes the importance of considering Swyer syndrome in cases of primary amenorrhea, the benefits of early surgical intervention, and the necessity of psychological support for patients., Competing Interests: The authors report no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Pure tone audiometry (PTA) is considered the standard method of hearing assessment. However, technical and logistical challenges preclude its usage for hearing screening at primary healthcare facilities. Free field hearing (FFH) tests such as conversation voice (CV) and whispered voice (WV) tests have been used for hearing assessment. However, their correlation to PTA and accuracy in detection of hearing loss are doubtful. This study aims to determine if FFH tests can be used for estimation of hearing thresholds., Methods: A retrospective analytical study was conducted at the otorhinolaryngology department. Spearman's correlation coefficient ( ρ ) was determined between FFH recognition distance and average air conduction PTA thresholds. A statistical regression model was developed to estimate hearing thresholds from the FFH recognition distance. The FFH tests were studied for their accuracy in detection of hearing loss., Results: The audiometric records of 437 persons (874 ears) were analysed. The CV and WV tests were found to have a high correlation ( ρ  = -0.757 and -0.758, respectively) with average PTA thresholds in persons with hearing loss. The WV test was found to have a 94.7% sensitivity, 90.8% specificity, 97.6% positive predictive value, 80.9% negative predictive value, and 93.9% accuracy in detection of hearing loss., Conclusion: FFH tests such as WV test can be used to estimate the hearing thresholds and screen for hearing loss when audiometric tests are not logistically feasible, such as at primary-level healthcare facilities, remote locations, and in schools. However, such tests should not be regarded as a substitute to PTA., Competing Interests: All authors have none to declare., (© 2023 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. Ltd.)

Fusarium head blight (FHB) remains one of the most destructive diseases of wheat (Triticum aestivum L.), causing considerable losses in yield and end-use quality. Phenotyping of FHB resistance traits, Fusarium-damaged kernels (FDK), and deoxynivalenol (DON), is either prone to human biases or resource expensive, hindering the progress in breeding for FHB-resistant cultivars. Though genomic selection (GS) can be an effective way to select these traits, inaccurate phenotyping remains a hurdle in exploiting this approach. Here, we used an artificial intelligence (AI)-based precise FDK estimation that exhibits high heritability and correlation with DON. Further, GS using AI-based FDK (FDK&#95;QVIS/FDK&#95;QNIR) showed a two-fold increase in predictive ability (PA) compared to GS for traditionally estimated FDK (FDK&#95;V). Next, the AI-based FDK was evaluated along with other traits in multi-trait (MT) GS models to predict DON. The inclusion of FDK&#95;QNIR and FDK&#95;QVIS with days to heading as covariates improved the PA for DON by 58% over the baseline single-trait GS model. We next used hyperspectral imaging of FHB-infected wheat kernels as a novel avenue to improve the MT GS for DON. The PA for DON using selected wavebands derived from hyperspectral imaging in MT GS models surpassed the single-trait GS model by around 40%. Finally, we evaluated phenomic prediction for DON by integrating hyperspectral imaging with deep learning to directly predict DON in FHB-infected wheat kernels and observed an accuracy (R 2  = 0.45) comparable to best-performing MT GS models. This study demonstrates the potential application of AI and vision-based platforms to improve PA for FHB-related traits using genomic and phenomic selection., (© 2024 The Authors. The Plant Genome published by Wiley Periodicals LLC on behalf of Crop Science Society of America.)

Background: The long-term consequences of concussions may include pathological neurodegeneration as seen in Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE). Tau-PET showed promise as a method to detect tau pathology of CTE, but more studies are needed OBJECTIVE: This study aimed (1) to assess the association of imaging evidence of tau pathology with brain volumes in retired athletes and (2) to examine the relationship between tau-PET and neuropsychological functioning., Methods: Former contact sport athletes were recruited through the Canadian Football League Alumni Association or the Canadian Concussion Centre clinic. Athletes completed MRI, [ 18 F]flortaucipir tau-PET, and a neuropsychological battery. Memory composite was created by averaging the Rey Auditory Verbal Learning Test and Rey Visual Design Learning Test z-scores. Grey matter (GM) volumes were age/intracranial volume corrected using normal control MRIs. Tau-PET % positivity in GM was calculated as the number of positive voxels (≥ 1.3 standardized uptake value ratio (SUVR)/total voxels)., Results: 47 retired contact sport athletes negative for AD (age:51 ± 14; concussions/athlete:15 ± 2) and 54 normal controls (age:50 ± 13) were included. Tau-PET positive voxels had significantly lower GM volumes, compared to tau-PET negative voxels (- 0.37 ± 0.41 vs. - 0.31 ± 0.37, paired p = .006). There was a significant relationship between GM tau-PET % positivity and memory composite score (r =  - .366, p = .02), controlled for age, PET scanner, and PET scan duration. There was no relationship between tau-PET measures and concussion number, or years of sport played., Conclusion: A higher tau-PET signal was associated with reduced GM volumes and lower memory scores. Tau-PET may be useful for identifying those at risk for neurodegeneration., (© 2024. The Author(s).)

Objective: Diabetic individuals have a higher probability of suffering from illness and death due to small blood vessel-related problems such as retinopathy, neuropathy, nephropathy, and stroke than other complications. There are many synthetic anti-diabetic agents available, but these can be expensive and have undesirable pathological effects. The enzyme α-amylase (hydrolase), catalyzes the hydrolysis of starch to maltose and glucose via the cleavage of α-1,4-glucosidic linkages. Diabetes mellitus patients may benefit from a therapeutic strategy that involves slowing the hydrolysis of starch by inhibiting the activity of α-amylase. Thus, looking for cost-effective, natural, and safe antidiabetic agents is essential. This study aims to screen phytoconstituents and evaluate the in-vitro and in-silico α-amylase inhibitory activity of the ethanolic extract of Adhatoda vasica leaves., Methods: The extraction of Adhatoda vasica leaves was performed using ethanol via the Soxhlet extraction process. Different concentrations (100 μg/mL to 1000 μg/mL) of ethanolic extract, Acarbose, and Sitagliptin, were prepared and evaluated for α-amylase inhibitory activity using the spectrophotometric method. Molecular docking (AutodockVina 1.2.0) and toxicity profiling (SToPToX web server) studies were performed., Results: The ethanolic extract of Adhatoda vasica leaves showed the highest percentage inhibition against α-amylase (56.763 ± 0.0035) at a concentration of 1000 μg/mL. The in-silico study supported this inhibitory activity. Vasicoline ( C5 ) and Quercetin ( C9 ), the active constitute of Adhatoda vasica , showed the best binding energies of -8.3 and -8.0 Kcal/mol, respectively against α-amylase enzyme (PDBID: 4W93). A toxicity study revealed the safety profile of the plant extract., Conclusion: It was concluded that Adhatoda vasica leaves possess some bioactive compounds that are responsible for controlling blood glucose levels, and their identification, purification, and isolation may lead to the development of new therapeutic agents with fewer side effects than the available drugs., (© The Author(s) 2024.)

In order to monitor public health trends and identify disease outbreaks early, efficient and reliable notification and surveillance systems are essential. Nepal uses a 1-3-7 malaria surveillance approach. The Short Message System (SMS) -based system for timely notification has been established. However, knowledge gaps exist regarding the timeliness of notification, treatment initiation, and case-based investigations. Hence, this study identifies the timeliness of notification and factors associated with delayed notification. This study used a cross-sectional approach and used secondary malaria surveillance data from Nepal's national malaria elimination program for the period of 2018 to 2022. The study revealed that the majority (79.9%) of malaria cases were male, with a male-to-female ratio of 3.96:1. Occupation was found to be significantly associated with delayed notification. Repatriate workers had 0.60 times lower odds of experiencing delayed notification compared to the reference occupation. Similarly, individuals diagnosed in the Sudurpaschim and Lumbini provinces had significantly lower odds (0.48 and 0.38, respectively) of encountering delayed notification compared to the reference province. Furthermore, relying on a single laboratory tool for malaria diagnosis (either RDT or microscopy only) was significantly associated with delayed notification. Individuals diagnosed solely with RDT or microscopy had 2.04 and 1.79 times higher odds of experiencing delayed notification, respectively, compared to those diagnosed using both laboratory tools. This study provides insight into the timeliness of surveillance system approach by assessing delayed notification and the factors associated with it. No delays are identified in median notification, treatment time and in case investigation. Improvement in the timeliness of malaria reporting over the years was observed. Provinces with high burden of malaria and repatriate workers showed lower delayed notification and conversely, cases diagnosed with single laboratory tool showed delayed notification time., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kandel 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.)

The metastasis of poorly differentiated epithelioid carcinoma to the axillary node is uncommon. This tumor has heterogeneous expression and is challenging to diagnose with certainty. Often, it necessitates immunoperoxidase staining to ascertain the tumor lineage, and diagnosis is prolonged due to low suspicion. Herein, we present a case involving a 75-year-old male war veteran with a prior history of a gunshot wound complicated by colostomy that presented with an axillary mass, fecal and urinary incontinence, leg weakness, fevers, night sweats, and substantial weight loss. On admission, he had heightened leukocytosis (43K), anemia (hemoglobin 6.6), and thrombophilia (1000). This patient constantly picked at his back to remove recurrent "gun shrapnel" eruptions. An excisional biopsy of the axillary mass was performed for diagnosis and lymph node removal. Notably, after excision, there was marked improvement in the presenting symptoms. Diagnostic challenges arose due to the tumor cells' inconsistent immunohistochemical marker expression. The staining patterns alluded to metastatic melanoma. Yet, the tumor displayed epithelial characteristics, supported by an immunophenotypic marker pattern indicative of poorly differentiated carcinoma. This case underscores the morphological and immunoperoxidase staining similarities between poorly differentiated carcinoma and dedifferentiated tumors of varying origins. It illustrates the intricate nature of these malignant metastatic tumors and their overlapping manifestations, which requires provider awareness. The timely diagnosis of poorly differentiated epithelial carcinoma remains paramount to early treatment and improved prognosis. Therefore, in patients manifesting with an axillary mass, fecal and urinary incontinence, and B-symptoms, poorly differentiated epithelial carcinoma should be included in the differential diagnosis.

Background: Increasing melanoma incidence with less increasing mortality is observed in several countries. This discrepancy is not well understood., Objectives: In this study, our aim was to discuss factors [ultraviolet radiation (UVR) exposure, melanoma treatment, diagnostic activity, overdiagnosis, pathologists' diagnostic threshold and clinicians' propensity to remove suspect skin lesions] that might influence melanoma incidence and mortality in Denmark., Methods: This was a register study with the number of melanocyte-related lesions and melanoma mortality based on comprehensive national pathology and mortality databases for the period 1999-2019. We investigated melanocyte-related diagnoses and mortality in a population of 5.5 million with a national healthcare system. Age-adjusted melanoma mortality and age-adjusted incidence of benign naevi, atypical lesion, or melanoma in situ and of invasive melanoma were computed for data analysis., Results: In total, 1 434 798 biopsies were taken from 704 682 individuals (65% female). The mean age at biopsy was 39.8 years in males and 37.6 in females. In males and females, the incidence of invasive melanoma increased by 87% during the period 1999-2011. During the subsequent period it increased by 9% in males but remained unchanged in females. The incidence of melanoma in situ increased by 476% in males and 357% in females during the study period, while the increases for atypical melanocytic lesions were 1928% and 1686%, respectively. Biopsy rates increased by 153% in males and 118% in females from 1999 through 2011 but fell by 20% in males and 22% in females during the subsequent period. Mortality varied slightly from year to year without any significant time trend for males or females. We identified no evidence of increased UVR exposure over the latest 30 years in Denmark. Immunotherapy of advanced melanoma was introduced in Denmark in 2010 and came into general use in 2014., Conclusions: Comprehensive national data demonstrate increasing melanoma incidence correlated with increasing biopsy rates, but with no change in mortality. Previously suggested explanations for such a trend are a lowered threshold of melanoma diagnosis among pathologists, increased diagnostic activity in the presence of overdiagnosis and improved melanoma treatment. Because the study is observational and we have more explanatory factors than outcomes, the findings do not warrant conclusions about causal relationships., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

HIV-1 transcript function is controlled in part by twinned transcriptional start site usage, where 5' capped RNAs beginning with a single guanosine (1G) are preferentially packaged into progeny virions as genomic RNA (gRNA) whereas those beginning with three sequential guanosines (3G) are retained in cells as mRNAs. In 3G transcripts, one of the additional guanosines base pairs with a cytosine located within a conserved 5' polyA element, resulting in formation of an extended 5' polyA structure as opposed to the hairpin structure formed in 1G RNAs. To understand how this remodeling influences overall transcript function, we applied in vitro biophysical studies with in-cell genome packaging and competitive translation assays to native and 5' polyA mutant transcripts generated with promoters that differentially produce 1G or 3G RNAs. We identified mutations that stabilize the 5' polyA hairpin structure in 3G RNAs, which promote RNA dimerization and Gag binding without sequestering the 5' cap. None of these 3G transcripts were competitively packaged, confirming that cap exposure is a dominant negative determinant of viral genome packaging. For all RNAs examined, conformations that favored 5' cap exposure were both poorly packaged and more efficiently translated than those that favored 5' cap sequestration. We propose that structural plasticity of 5' polyA and other conserved RNA elements place the 5' leader on a thermodynamic tipping point for low-energetic (~3 kcal/mol) control of global transcript structure and function., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Medical image analysis, particularly in the context of visual question answering (VQA) and image captioning, is crucial for accurate diagnosis and educational purposes., Objective: Our study aims to introduce BioMedBLIP models, fine-tuned for VQA tasks using specialized medical data sets such as Radiology Objects in Context and Medical Information Mart for Intensive Care-Chest X-ray, and evaluate their performance in comparison to the state of the art (SOTA) original Bootstrapping Language-Image Pretraining (BLIP) model., Methods: We present 9 versions of BioMedBLIP across 3 downstream tasks in various data sets. The models are trained on a varying number of epochs. The findings indicate the strong overall performance of our models. We proposed BioMedBLIP for the VQA generation model, VQA classification model, and BioMedBLIP image caption model. We conducted pretraining in BLIP using medical data sets, producing an adapted BLIP model tailored for medical applications., Results: In VQA generation tasks, BioMedBLIP models outperformed the SOTA on the Semantically-Labeled Knowledge-Enhanced (SLAKE) data set, VQA in Radiology (VQA-RAD), and Image Cross-Language Evaluation Forum data sets. In VQA classification, our models consistently surpassed the SOTA on the SLAKE data set. Our models also showed competitive performance on the VQA-RAD and PathVQA data sets. Similarly, in image captioning tasks, our model beat the SOTA, suggesting the importance of pretraining with medical data sets. Overall, in 20 different data sets and task combinations, our BioMedBLIP excelled in 15 (75%) out of 20 tasks. BioMedBLIP represents a new SOTA in 15 (75%) out of 20 tasks, and our responses were rated higher in all 20 tasks (P<.005) in comparison to SOTA models., Conclusions: Our BioMedBLIP models show promising performance and suggest that incorporating medical knowledge through pretraining with domain-specific medical data sets helps models achieve higher performance. Our models thus demonstrate their potential to advance medical image analysis, impacting diagnosis, medical education, and research. However, data quality, task-specific variability, computational resources, and ethical considerations should be carefully addressed. In conclusion, our models represent a contribution toward the synergy of artificial intelligence and medicine. We have made BioMedBLIP freely available, which will help in further advancing research in multimodal medical tasks., (©Usman Naseem, Surendrabikram Thapa, Anum Masood. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 05.08.2024.)

Introduction: IgA nephropathy is the leading cause of primary glomerulonephritis worldwide. The Oxford classification can predict IgA nephropathy prognosis through renal biopsy however its applicability to the Nepalese population remains unexplored. This study aimed to evaluate the MEST-C score and treatment response in patients with IgA nephropathy., Methods: This descriptive cross-sectional study was conducted at a tertiary care center from November 2021 to November 2022 after obtaining ethical approval [IRC-193(6-11)t2078/079]. Total population sampling was done. Fifty-two consenting patients aged 16 or older with confirmed IgA nephropathy were included, excluding those with liver disease or expected survival of less than six months. The study assessed the MEST-C score, demographic factors, and clinical parameters. Data analysis was done using Statistical Package of Social Sciences., Results: Among 52 patients with segmental glomerulosclerosis (S1), 11 (24.44%) achieved complete remission, 30 (66.67%) partial remission, and 5 (11.11%) progressed to end-stage renal disease. In those with tubular atrophy/interstitial fibrosis (T1), 1 (5.88%) achieved complete remission, 13 (76.47%) partial remission, and 4 (23.53%) progressed to end-stage renal disease. For glomerular crescents (C1), 9 (47.37%) achieved complete remission, 9 (47.37%) partial remission, and 1 (5.26%) progressed to end-stage renal disease. IFTA% of 0-25% had complete remission in 15 (46.88%). Among the two patients with IFTA% ≥50%, one (50%) developed end-stage renal disease and the other achieved partial remission., Conclusions: The S1 and T1/2 components of the MEST-C score had higher rates of partial remission and progression to end-stage renal disease, while other indices showed mixed results. The risk of failing to achieve complete increased with an IFTA of more than 25%.

Working equids play a central role in mountainous communities, but their work often goes unnoticed by the wider world, with sparse documentation of their role, value, or welfare - a state which often extends to their human counterparts. Communities living in the remote Manaslu Valley, Nepal, face a number of uncertainties, including extreme weather events due to the seasonal monsoon and, more recently, the construction of a new road network. Using semi-structured interviews, questionnaires, and Equine Assessment Research and Scoping (EARS) welfare assessments, we outline the specific role of pack mules in supporting the lives of local people, explain the nuanced links between human experience and mule welfare, and gain insight into how people living in this volatile environment manage uncertainty and risk. Mule work was felt to be the 'only option' for a sustainable livelihood for most mule owners although, in some cases, mules had enabled respondents to diversify their income. Mule owners with more husbandry experience did not own mules in more positive behavioural states, which may suggest a lack of generational knowledge and support networks. Short-term ongoing risks, such as the monsoon or unstable tracks, had a larger impact both financially and emotionally than the long-term but distant implications of the road construction. Mule owners must constantly balance the risk of working during the monsoon season, when conditions are treacherous but pay was higher, with losing valuable income but keeping themselves and their mules safe; they do, however, have a more mobile option for employment than non-owners. Mules enable a level of resilience and agility for communities living with constant uncertainty and change, which is only beginning to be recognised formally within the sustainable development sphere. Integration of animal welfare into the SDGs would allow humanitarian aid initiatives to strengthen support networks around working equids, which would greatly benefit the mules and humans alike., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kubasiewicz, Watson, Thapa, Nye and Chamberlain.)

Gynecological disorders such as endometriosis, polycystic ovary syndrome, and gynecological cancers are increasingly recognized as potential risk factors for cardiovascular disease (CVD). Endometriosis, a chronic inflammatory condition, exhibits shared pathogenic mechanisms with CVD, including endothelial dysfunction and an atherogenic lipid profile. Emerging evidence suggests a link between endometriosis and an elevated risk of cardiovascular events such as myocardial infarction, ischemic heart disease, and hypertension. Polycystic ovary syndrome, characterized by hormonal imbalances and metabolic derangements, is associated with an increased risk of hypertension, myocardial infarction, and structural cardiac abnormalities, even after controlling for obesity. Gynecological cancers, such as ovarian, endometrial, and cervical cancers, are also associated with an increased burden of cardiovascular comorbidities and mortality. Cancer treatments, including chemotherapy and radiation therapy, can further contribute to cardiovascular toxicity. Understanding the interplay between gynecological disorders and CVD is crucial for identifying high-risk individuals, implementing preventive strategies, and providing comprehensive care. A multidisciplinary approach involving gynecologists, cardiologists, and other specialists is essential for optimizing the management of these complex conditions and improving overall patient outcomes., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Genus Swertia under the family Gentianaceae is morphologically and taxonomically distinct with about 14 species from Sikkim Himalayan region. A Chrono-spatial floral phenology study was conducted on Swertia bimaculata from 1580 to 2400 m altitude in West Sikkim Himalayan region. The floral phenology was studied in a field nursery at 1200 m altitude and spatial floral phenology was studied over a 1580-2400 m altitudinal range in the West Sikkim Himalayan region. Detailed study on flowering pattern and seed formation in S. bimaculata revealed late flowering at 1200 m compared to 2400 m. Plants at the lower altitude showed prolonged and variable flowering from September to November and seed formation from November to December. During September to mid-October, pentamerous and bisexual flowers were observed, followed by 9-16 % tetramerous until November; and up to 24 % trimerous and 10 % bimerous until the end of flowering season in December. By the end of December, 43 % of flowers become stamen-less (monoclinous). Less than 2 % seed formation was observed in stamen-less flowers. The temporal phenological behavior reveals a successful reproductive adaptive strategy, depicting pentamerous flowers during favorable conditions, reducing to tetramerous, followed by tri- & bimerous with female (monoclinous) flowers until the end of flowering with stressful conditions, suggesting its suitability as a stress indicator to the changing climatic conditions. Along the altitudinal range floral anomalies from the usually observed pentamerous (and very rare hexamerous) flowers in favorable conditions change to tetramerous and/or trimerous, as the environmental conditions become more stressful, suggesting that the changes in this species could be used as an indicator of stress in changing climatic conditions., Competing Interests: The authors declare that there is no conflict of interest., (© 2024 The Authors.)

Background: Current therapeutic strategies for multiple sclerosis (MS) aim to suppress the immune response and reduce relapse rates. As alternative treatments, mesenchymal stem cells (MSCs) are being explored. MSCs show promise in repairing nerve tissue and reducing autoimmune responses in people with MS (pwMS)., Objective: This review delves into the literature on the efficacy and safety of MSC therapy for pwMS., Methods: A comprehensive search strategy was employed to identify relevant articles from five databases until January 2024. The inclusion criteria encompassed interventional studies. Efficacy and safety data concerning MSC therapy in relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS) groups were extracted and analyzed., Results: A comprehensive analysis encompassing 30 studies revealed that individuals who underwent intrathecal (IT) protocol-based transplantation of MSCs experienced a noteworthy improvement in their expanded disability status scale (EDSS) compared to the placebo group. Weighted mean difference (WMD) was -0.28; 95 % CI -0.53 to -0.03, I 2 = 0 %, p-value = 0.028); however, the intravenous (IV) group did not show significant changes in EDSS scores. The annualized relapse rate (ARR) did not significantly decrease among pwMS (WMD = -0.34; 95 % CI -1.05 to 0.38, I 2 = 98 %, p-value = 0.357). Favorable results were observed in magnetic resonance imaging (MRI), with only 19.11 % of pwMS showing contrast-enhanced lesions (CEL) in the short term and no long-term MRI activity. The most common complications in both short-term and long-term follow-ups were infection, back pain, and gastrointestinal symptoms., Conclusions: The study highlights the safety potential of MSC therapy for pwMS. While MRI-based neural regeneration shows significant treatment potential, the effectiveness of MSC therapy remains uncertain due to study limitations and ineffective outcome measures. Further research is needed to establish efficacy and optimize evaluation methods for MSC therapy on pwMS., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)