Search

Meta-analyses consistently have found that antenatal multiple micronutrient supplementation (MMS) compared with iron and folic acid (IFA) alone reduce adverse birth outcomes. In 2020, the World Health Organization (WHO) placed a conditional recommendation for MMS and requested additional trials using ultrasounds to establish gestational age, because the evidence on low birthweight (LBW), preterm birth and small for gestational age (SGA) was considered inconsistent. We conducted meta-analyses to determine if the effects of MMS on LBW, preterm birth and SGA differed by gestational age assessment method. Using data from the 16 trials in the WHO analyses, we calculated the effect estimates of MMS versus IFA on birth outcomes (generic inverse variance method and random effects model) stratified by method of gestational age assessment: ultrasound, prospective collection of the date of last menstrual period (LMP) and confirmation of pregnancy by urine test and recall of LMP. The effects of MMS versus IFA on birthweight, preterm birth and SGA appeared consistent across subgroups with no evidence of subgroup differences (p > 0.05). When limited to the seven trials that used ultrasound, the beneficial effects of MMS were demonstrated: risk ratios of 0.87 (95% confidence interval [CI] 0.78-0.97) for LBW, 0.90 (95% CI, 0.79-1.03) for preterm birth and 0.9 (95% CI, 0.83-0.99) for SGA. Sensitivity analyses indicated consistency in the results. These results, together with recent analyses demonstrating comparable effects of MMS (vs. IFA) on maternal anaemia outcomes, strengthen the evidence to support a transition from IFA to MMS programmes in low- and middle-income countries.

III‐V semiconductors are favoured photo absorber materials for solar energy conversion due to their ideal bandgap, yet their high‐cost hinders widespread adoption. Utilizing thin films of these semiconductors presents a viable way to address the cost‐related challenges. Here, a novel mechanical exfoliation technique is demonstrated, also known as controlled spalling, as a cost‐effective and facile way to obtain thin films of III‐V semiconductors. As a proof of concept, 15 μm thick InP films are successfully exfoliated from their original wafers. Thorough characterization using cathodoluminescence and photoluminescence spectroscopy confirms that the opto‐electronic properties of the exfoliated InP films remain unaffected. Utilizing these InP thin films, InP thin‐film heterojunction solar cells with efficiencies exceeding 13% are demonstrated. Additionally, InP photoanodes are fabricated by integrating NiFeOOH catalyst onto these InP thin‐film solar cells, achieving an impressive photocurrent density of 19.3 mA cm−2 at 1.23 V versus reversible hydrogen electrode, along with an applied bias photon‐to‐current efficiency of ≈4%. Overall, this study showcases the efficacy of controlled spalling in advancing economically viable and efficient III‐V semiconductor‐based solar energy conversion devices.

Abiotic stress, which includes salinity, drought, heat, and cold, as well as their many combinations, severely reduces crop productivity across the globe each year. Considering the intensified worldwide climatic changes, the effects of these conditions on plant productivity become increasingly more concerning. Sulfur is essential for several metabolic processes, including the organization and control of electron transport. Reductive assimilation and integration into cysteine and methionine, sulfate absorption, and reductive assimilation and integration are the key methods that oxidized and reduced forms of organically bound sulfur get to their different roles. Protective compounds with sulfur, such as glutathione, phytochelatins, S-rich proteins, and several secondary metabolites, are essential for plants to survive abiotic stress, such as dihydroasparagusic acid, hydrogen sulfide, etc. This thorough review covered the regulation of sulfur at the protein and gene transcription levels in response to abiotic stress.

Advancing understanding of the diverse properties of essential oils has spurred a significant increase in both their production and application. The current research aimed to study the chemical, physical, and antifungal characteristics of Vinca rosea leaves’ essential oil compared to its extract. The leaf’s essential oil and extract composition were examined using GC-MS and further tested for antifungal activity against Fusarium graminearum and Bipolaris sorokiniana by poisoned food technique. 34 compounds were identified in leaves essential oil predominantly composed of butylated hydroxytoluene (32.74%). The methanolic extract showed the presence of alkaloids, mainly vindoline, and the non-polar extract showed the presence of cholesterol as the primary compound. The methanolic extract demonstrated stronger antifungal activity against F. graminearum, with ED50 and ED90 of 80 and 240 µg/mL, compared to the essential oil, which had higher ED50 and ED90 of 98 and 865 µg/mL, respectively. In the case of B. sorokiniana, ED50 values of methanol extract, essential oil, and hexane extract were 76, 100, and >1000 µg/ml, respectively, and ED90 were observed to be 290, 875, and >1000 µg/ml. Vinca rosea essential oil can potentially be used to develop natural antifungal agents. For the first time, the chemical composition of the essential oil of V. rosea cultivated in the Northern Indian region is being reported.

Objective: We developed and evaluated a training program for Accredited Social Health Activists (ASHAs), female community health workers (CHWs) in India, on non-communicable diseases (NCDs). Methods: A 5-day training program, developed using government-approved manuals, was tested in a randomised controlled trial in the Tehri-Garhwal district. Quantitative comparisons were undertaken using Student's t-test and two-way ANOVA. ASHAs in the intervention group were asked questions about new skills learnt. Results: Thirty-six ASHAs (20 intervention, 16 controls) participated (response rate 75.0%). Mean pre-test knowledge score was 43.3/100 points (95% CI 36.7–49.9) for the intervention group and 44.4 (38.9–49.9) for controls. The mean post-test knowledge score increased more in the intervention group (48.5-point increase; P

ABSTRACT Whole-cell pertussis (wP) vaccines introduced in the 1940s led to a dramatic reduction of pertussis incidence and are still widely used in low- and middle-income countries (LMICs) worldwide. The reactogenicity of wP vaccines resulted in reduced public acceptance, which drove the development and introduction of acellular pertussis (aP) vaccines in high-income countries in the 1990s. Increased incidence of pertussis disease has been observed in high-income countries following the introduction of aP vaccines despite near universal rates of pediatric vaccination. These increases are attributed to the reduced protection against colonization, carriage, and transmission as well as reduced duration of immunity conferred by aP vaccines relative to the wP vaccines they replaced. A reduced reactogenicity whole-cell pertussis (RRwP) vaccine was recently developed with the goal of achieving the same protection as conferred by wP vaccination but with an improved safety profile, which may benefit countries in which wP vaccines are still in routine use. In this study, we tested the RRwP vaccine in a baboon model of pertussis infection. We found that the RRwP vaccine induced comparable cellular and humoral immune responses and comparable protection following challenge relative to the wP vaccine, while significantly reducing injection-site reactogenicity.IMPORTANCEThe World Health Organization (WHO) recommended in 2015 that countries administering wP vaccines in their national vaccine programs should continue to do so, and that switching to aP vaccines for primary infant immunization should only be considered if periodic booster vaccinations and/or maternal immunization could be assured and sustained in their national immunization schedules (WHO, Vaccine 34:1423–1425, 2016, https://doi.org/10.1016/j.vaccine.2015.10.136). Due to the considerably higher cost of aP vaccines and the larger number of doses required, most LMICs continue to use wP vaccines. The development and introduction of a wP vaccine that induces fewer adverse events without sacrificing protection would significantly benefit countries in which wP vaccines are still in routine use. The results of this study indicate this desirable goal may be achievable.

Transplant Renal Artery Stenosis (TRAS) is the leading vascular complication following kidney transplantation (KT), causing premature allograft loss and increased post-KT mortality. While risk factors for TRAS, such as prolonged cold ischemia time and delayed graft function, are well-documented in deceased donor-KT, the risk factors remain less clearly defined in living donor-KT. This matched case-control study, conducted at a leading national transplant center predominantly performing living donor-KT, evaluated risk factors and long-term outcomes of clinical TRAS (cTRAS). cTRAS cases diagnosed from January 2009 to December 2022 were matched with four control kidney transplant recipients (KTRs) in a study powered to assess whether ex-vivo arterial vascular reconstruction of multiple renal arteries (VR-MRA) increases the risk of cTRAS. Among 2,454 KTs, 28 KTRs (1.14%) were diagnosed with cTRAS around 3.62 ± 1.04 months post-KT, with renal allograft dysfunction (92.86%) as the most common presenting feature. Notably, 27 cTRAS cases were successfully treated with endovascular intervention, yielding favorable outcomes over a 6–180 months follow-up period. The study identified ex-vivo VR-MRA as an independent risk factor for cTRAS (P < 0.001). cTRAS cases receiving timely treatment exhibited long-term outcomes in graft and patient survival similar to control KTRs. Early screening and timely intervention for cTRAS post-KT may improve graft and patient outcomes.

The rapid integration of generative AI (GenAI) into industries and society has prompted a re-evaluation of copyright and intellectual property rights (IPR) frameworks. GenAI's ability to produce original content using data from human-created sources raises critical ethical and legal concerns. Current copyright and IPR frameworks, designed around human authorship, are insufficient to address these challenges. This study, using a multi-perspective approach, explores GenAI's disruptive potential in replicating or transforming copyrighted materials, challenging established IPR norms. Findings highlight gaps in legislation and the opacity of GenAI platforms. To address these issues, this study presents a Dynamic Ethical Framework linked to a future global fair use policy, aiming to guide responsible GenAI development and use. By incorporating insights from domain experts, this study contextualizes emerging challenges and potential solutions within broader societal and technological trends. That said, this study calls for international collaboration and further research to reform IPR related laws and frameworks, ensuring they remain relevant and equitable in a GenAI-driven era.

Background:. The No Surprises Act (NSA) went into effect on January 1, 2022. This federal law is designed to minimize surprise bills for emergency care, out of network (OON) care, and care for uninsured or self-pay individuals. To achieve these goals, the NSA relies heavily on physicians providing cost estimates to patients prior to administering care. Because healthcare is often price-opaque, this study was conducted to assess physician and patient attitudes toward price transparency in plastic surgery and aesthetic/self-pay medicine. Methods:. Two cohorts of providers received a survey asking whether and how their practice offers pricing information prior to a consultation and their views regarding the NSA. Patients who had previously used an online price estimator tool also received a survey regarding their experience and accuracy of estimates received online. Results:. Most surveyed providers do not share the costs of their services online, whereas patients had a positive experience when receiving estimates of medical services before consultation. Although many providers cited the inaccuracy of price estimator tools as a reason not to incorporate them into their website, most patients reported that their final cost of service was close to (or even less than) the estimate received online prior to the consultation. Conclusions:. This study suggests that price transparency is a patient satisfier. Therefore, plastic surgeons should exercise price transparency to be compliant with federal law and to gain a competitive advantage in the market, as the decision to implement price transparency can be mutually beneficial to patients and providers.

Neurological complications, including encephalopathy and stroke, occur in a significant proportion of COVID-19 cases but viral protein is seldom detected in the brain parenchyma. To model this situation, we developed a novel low-inoculum K18-hACE2 mouse model of SARS-CoV-2 infection during which active viral replication was consistently seen in mouse lungs but not in the brain. We found that several mediators previously associated with encephalopathy in clinical samples were upregulated in the lung, including CCL2, and IL-6. In addition, several inflammatory mediations, including CCL4, IFNγ, IL-17A, were upregulated in the brain, associated with microglial reactivity. Parallel in vitro experiments demonstrated that the filtered supernatant from SARS-CoV-2 virion exposed brain endothelial cells induced activation of uninfected microglia. This model successfully recreates SARS-CoV-2 virus-associated para-infectious brain inflammation which can be used to study the pathophysiology of the neurological complications and the identification of potential immune targets for treatment.

BackgroundRheumatoid arthritis (RA) is a common condition treated with biological disease-modifying anti-rheumatic medicines (bDMARDs). However, many patients exhibit resistance, necessitating the use of machine learning models to predict remissions in patients treated with bDMARDs, thereby reducing healthcare costs and minimizing negative effects.ObjectiveThe study aims to develop machine learning models using data from the Kuwait Registry for Rheumatic Diseases (KRRD) to identify clinical characteristics predictive of remission in RA patients treated with biologics.MethodsThe study collected follow-up data from 1,968 patients treated with bDMARDs from four public hospitals in Kuwait from 2013 to 2022. Machine learning techniques like lasso, ridge, support vector machine, random forest, XGBoost, and Shapley additive explanation were used to predict remission at a 1-year follow-up.ResultsThe study used the Shapley plot in explainable Artificial Intelligence (XAI) to analyze the effects of predictors on remission prognosis across different types of bDMARDs. Top clinical features were identified for patients treated with bDMARDs, each associated with specific mean SHAP values. The findings highlight the importance of clinical assessments and specific treatments in shaping treatment outcomes.ConclusionThe proposed machine learning model system effectively identifies clinical features predicting remission in bDMARDs, potentially improving treatment efficacy in rheumatoid arthritis patients.

Abstract Balanced energy protein (BEP) supplementation in pregnancy is recommended in the context of undernutrition for the reduction of small‐for‐gestational age neonates and stillbirths. To inform an effectiveness trial, we evaluated the acceptability of a packaged, ready‐to‐eat fortified BEP product among women of reproductive age and their health care providers (HCPs) in rural Bangladesh and explored the feasibility of adhering to daily supplementation. We implemented a formative study using focus groups discussions with women (n = 29) and HCPs (n = 17) to introduce the product and investigate components of acceptability. A “trials of improved practice” activity was conducted in subset of women (n = 16) to evaluate adherence to BEP over a 2‐week period, followed by focus group discussions to identify challenges with adherence and strategies employed. Contributors to BEP acceptability included the product's sensory attributes, such as taste, smell and texture; the attractive packaging and informative labelling; and the perceived benefits of use. Participants also identified household and community level factors influencing the adoption of BEP, such as trust in the provider, cultural beliefs on supplement use in pregnancy, and family member tasting and approval. Over the 2‐week period, women consumed over 80% of the supplements provided to them and identified strategies for adherence, including visual aids and reminders from family members or providers. HCPs recommended targeted communication messages for mothers‐in‐law to foster a supportive home environment. Findings informed changes to the BEP product to improve acceptability and shaped the content of communication messages to optimise adherence in a forthcoming effectiveness trial.

Abstract Balanced energy protein (BEP) supplementation is an efficacious intervention in pregnancy for improving birthweight and is recommended by World Health Organization (WHO) in countries with high maternal undernutrition. Few countries have implemented BEP programmes due in part to high cost, lack of data on acceptability and feasibility, and complexity of delivery. We sought to address implementation gaps in BEP interventions through a formative study designed to understand implementation outcomes. We conducted 52 in‐depth interviews and 8 focus‐group discussions with married women of reproductive age, family members, health care providers and pharmacists in three unions of the Gaibandha district in rural Bangladesh. Interviews were translated and transcribed in English and analysed using an analytic framework for implementation science in nutrition. BEP was viewed as an acceptable and appropriate intervention to combat undernutrition in this setting. There was a lack of clarity on who should or could be responsible for providing/distributing BEP in a way convenient to mothers. Many participants preferred door‐to‐door delivery and thought this approach could address social and gender inequities, but providers mentioned already being overworked and worried about adding new tasks. Participants were concerned about the affordability of BEP and opportunity costs associated with travel to proposed distribution sites such as ANC or pharmacies. Women in these communities do not always have the agency to travel without supervision or make purchasing decisions. BEP supplementation is a complex intervention; future trials seek to assess ways to overcome these implementation challenges and inform a long‐term systems‐owned BEP intervention.

Abstract Balanced energy protein supplementation (BEP) is recommended for contexts of high maternal undernutrition by the World Health Organization. Despite recent improvements in undernutrition, Bangladesh remains a context where BEP could help accelerate progress towards nutrition goals. In preparation for an effective trial testing a fortified BEP, a qualitative study was undertaken to better understand sociocultural factors influencing dietary behaviours in pregnancy. Married women of reproductive age (n = 23), their husbands (n = 6) and mothers‐in‐law (n = 6) were interviewed, and focus group discussions were conducted with women (n = 4). Women had a clear understanding of which nutritious foods are important to consume during pregnancy, including green leafy vegetables, dairy and other animal‐source foods. Many explained affordability as a barrier to consuming those foods with the desired frequency. Women acquired information about diet and nutrition in pregnancy from community health workers as well as other women in the community. Most preferred to seek information from their own networks before formal health care providers. Women and husbands generally had positive views about micronutrient supplements, although some mothers‐in‐law were more hesitant. Some food taboos relating to the consumption of certain foods like duck and pigeon meat persist, mainly stemming from concerns for the unborn child. Opportunities exist to build on existing perceptions of healthy diets, potentially framing food or nutrient supplements as a beneficial ‘add‐on’ to promote a healthy pregnancy. There is a scope to strengthen nutrition counselling, especially for the family members, to dispel myths and misconceptions and promote dietary and other support for pregnant women.

Infections due to Non Typhoidal Salmonella (NTS) are emerging as a major health problem for both humans and animals worldwide including in India. In humans, NTS infections routinely remain restricted to the intestinal tract and may or may not manifest as a clinical illness but in immunocompromised patients systemic involvement may result in frank bacteraemia or focal involvement depending on the site of localisation. A 70-year-old, male presented to the Emergency Department with complaints of pain for about five days, on the right side of the scrotum. A drained pus sample was received at the Department of Microbiology for culture and sensitivity. Salmonella kentucky was identified by standard microbiological techniques. Here the authors present a case of scrotal abscess caused by Salmonella kentucky in an old immunocompromised patient and this possibly appears to be the first case report of scrotal involvement from India. No single diagnostic approach may be able to identify the NTS up to the species level. To determine the identity of organisms in cases where individual labs may not have the necessary capacity to produce the results, it would be extremely sensible from a scientific standpoint to create a network of cooperating labs with varying diagnostic capacities.

The Gene Ontology (GO) knowledgebase (http://geneontology.org) is a comprehensive resource concerning the functions of genes and gene products (proteins and noncoding RNAs). GO annotations cover genes from organisms across the tree of life as well as viruses, though most gene function knowledge currently derives from experiments carried out in a relatively small number of model organisms. Here, we provide an updated overview of the GO knowledgebase, as well as the efforts of the broad, international consortium of scientists that develops, maintains, and updates the GO knowledgebase. The GO knowledgebase consists of three components: (1) the GO-a computational knowledge structure describing the functional characteristics of genes; (2) GO annotations-evidence-supported statements asserting that a specific gene product has a particular functional characteristic; and (3) GO Causal Activity Models (GO-CAMs)-mechanistic models of molecular "pathways" (GO biological processes) created by linking multiple GO annotations using defined relations. Each of these components is continually expanded, revised, and updated in response to newly published discoveries and receives extensive QA checks, reviews, and user feedback. For each of these components, we provide a description of the current contents, recent developments to keep the knowledgebase up to date with new discoveries, and guidance on how users can best make use of the data that we provide. We conclude with future directions for the project.

The lack of multi-omics cancer datasets with extensive follow-up information hinders the identification of accurate biomarkers of clinical outcome. In this cohort study, we performed comprehensive genomic analyses on fresh-frozen samples from 348 patients affected by primary colon cancer, encompassing RNA, whole-exome, deep T cell receptor and 16S bacterial rRNA gene sequencing on tumor and matched healthy colon tissue, complemented with tumor whole-genome sequencing for further microbiome characterization. A type 1 helper T cell, cytotoxic, gene expression signature, called Immunologic Constant of Rejection, captured the presence of clonally expanded, tumor-enriched T cell clones and outperformed conventional prognostic molecular biomarkers, such as the consensus molecular subtype and the microsatellite instability classifications. Quantification of genetic immunoediting, defined as a lower number of neoantigens than expected, further refined its prognostic value. We identified a microbiome signature, driven by Ruminococcus bromii, associated with a favorable outcome. By combining microbiome signature and Immunologic Constant of Rejection, we developed and validated a composite score (mICRoScore), which identifies a group of patients with excellent survival probability. The publicly available multi-omics dataset provides a resource for better understanding colon cancer biology that could facilitate the discovery of personalized therapeutic approaches.

PURPOSE: Adults with high-grade glioma (HGG), WHO grade III or IV, have substantial palliative care needs. Our aim was to determine occurrence, timing, and factors associated with palliative care consultation (PCC) in HGG at one large academic institution. METHODS: HGG patients receiving care between 08/1/2011 and 01/23/2020 were identified retrospectively from a multi-center healthcare system cancer registry. Patients were stratified by any PCC (yes/no), and timing of initial PCC by disease phase: diagnosis (before radiation), during initial treatment (first-line chemotherapy/radiation), second-line treatment(s), or end-of-life (after last chemotherapy). RESULTS: Of 621 HGG patients, 134 (21.58%) received PCC with the vast majority occurring during hospital admission [111 (82.84%)]. Of the 134, 14 (10.45%) were referred during the diagnostic phase; 35 (26.12%) during initial treatment; 20 (14.93%) during second-line treatment; and 65 (48.51%) during end of life. In multivariable logistic regression, only higher Charlson Comorbidity Index was associated with greater odds of PCC [OR 1.3 (95% CI 1.2-1.4), p

With the increasing prevalence of Alzheimer's disease (AD) among aging populations and the limited therapeutic options available to slow or reverse its progression, the need has never been greater for improved diagnostic tools for identifying patients in the preclinical and prodomal phases of AD. Biophysics models of the connectome-based spread of amyloid-beta (Aβ) and microtubule-associated protein tau (τ) have enjoyed recent success as tools for predicting the time course of AD-related pathological changes. However, given the complex etiology of AD, which involves not only connectome-based spread of protein pathology but also the interactions of many molecular and cellular players over multiple spatiotemporal scales, more robust, complete biophysics models are needed to better understand AD pathophysiology and ultimately provide accurate patient-specific diagnoses and prognoses. Here we discuss several areas of active research in AD whose insights can be used to enhance the mathematical modeling of AD pathology as well as recent attempts at developing improved connectome-based biophysics models. These efforts toward a comprehensive yet parsimonious mathematical description of AD hold great promise for improving both the diagnosis of patients at risk for AD and our mechanistic understanding of how AD progresses.

Human milk is the ideal source of nutrition for most infants, but significant gaps remain in our understanding of human milk biology. As part of addressing these gaps, the Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN) Project Working Groups 1-4 interrogated the state of knowledge regarding the infant-human milk-lactating parent triad. However, to optimize the impact of newly generated knowledge across all stages of human milk research, the need remained for a translational research framework specific to the field. Thus, with inspiration from the simplified environmental sciences framework of Kaufman and Curl, Working Group 5 of the BEGIN Project developed a translational framework for science in human lactation and infant feeding, which includes 5 nonlinear, interconnected translational stages, T1: Discovery; T2: Human health implications; T3: Clinical and public health implications; T4: Implementation; and T5: Impact. The framework is accompanied by 6 overarching principles: 1) Research spans the translational continuum in a nonlinear, nonhierarchical manner; 2) Projects engage interdisciplinary teams in continuous collaboration and cross talk; 3) Priorities and study designs incorporate a diverse range of contextual factors; 4) Research teams include community stakeholders from the outset through purposeful, ethical, and equitable engagement; 5) Research designs and conceptual models incorporate respectful care for the birthing parent and address implications for the lactating parent; 6) Research implications for real-world settings account for contextual factors surrounding the feeding of human milk, including exclusivity and mode of feeding. To demonstrate application of the presented translational research framework and its overarching principles, 6 case studies are included, each illustrating research gaps across all stages of the framework. Applying a translational framework approach to addressing gaps in the science of human milk feeding is an important step toward the aligned goals of optimizing infant feeding across diverse contexts as well as optimizing health for all.

Associations between human genetic variation and clinical phenotypes have become a foundation of biomedical research. Most repositories of these data seek to be disease-agnostic and therefore lack disease-focused views. The Type 2 Diabetes Knowledge Portal (T2DKP) is a public resource of genetic datasets and genomic annotations dedicated to type 2 diabetes (T2D) and related traits. Here, we seek to make the T2DKP more accessible to prospective users and more useful to existing users. First, we evaluate the T2DKP's comprehensiveness by comparing its datasets with those of other repositories. Second, we describe how researchers unfamiliar with human genetic data can begin using and correctly interpreting them via the T2DKP. Third, we describe how existing users can extend their current workflows to use the full suite of tools offered by the T2DKP. We finally discuss the lessons offered by the T2DKP toward the goal of democratizing access to complex disease genetic results.