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ABSTRACT: Most genotypes in the National Cooperator Database now originate from cows, but most previous studies validating genomic predictions have primarily focused on bulls. This study paired official within-breed genomic PTA (GPTA) and parent average (PA) for genotyped heifer calves born between 2019 and 2021 using the August 2021 database with their corresponding performance deviations (PDEV) for 17 different traits. The PDEV data became available when the heifers completed their first lactation and were extracted from the August 2023 database in which at least one PDEV value for those 17 traits existed for each genotyped heifer record. The separate breed analyses included records for 219 Ayrshires (AY), 2,715 Brown Swiss (BS), 1,055 Guernseys (GU), 949,904 Holsteins (HO), and 125,275 Jerseys (JE). These validation cows were heifer calves born between 2019 and 2021. However, due to timing or recording patterns, each trait had missing or incomplete PDEV data, leading to unbalanced distributions of records across traits. The squared accuracy of genomic prediction, or genomic reliability (r2), was divided by the corresponding heritability for each trait, as only the heritable portion of cow records could be predicted, and this reliability varied across different traits and breeds. For HO and JE, the predictive ability of GPTA outperformed PA in predicting cow PDEV for yield, productive life, SCS, fertility, and health traits. The improvement ranged from 33% to 142% compared with the predictive ability of the PA. However, the results for AY, BS, and GU breeds were less consistent due to the smaller number of genotyped heifers. The r2 gains in those breeds were smaller and aligned with the published reliabilities of GPTA. Weighted and unweighted regressions of PDEV on GPTA and PA traits mostly exceeded the expected value of 2.00 when predicting the future trait PDEV using GPTA or PA. The larger number of observations and lower SE of the weighted regression coefficient prediction in HO and JE breeds contributed to more stable and consistent regression coefficients for all traits except milk fever and heifer livability. Our study suggests that herd owners may experience greater benefits from genomics than originally forecast.

Background Cyclin D1 is a protein that can enhance the proliferation of cancer cells and has been detected in various malignancies, including lung cancer. However, routine examinations for Cyclin D1 in lung cancer cases have not been conducted in Kerala. Aim This study sought to evaluate the links between cyclin D1 expression, clinicopathological characteristics, and 2-year survival rates in lung cancer. Methods This retrospective cohort study used medical records and paraffin blocks of lung cancer patients at the Regional Cancer Centre in Kerala, India, between 2015 and 2018. The data were collected from 61 subjects, comprising of lung adenocarcinoma (18%), lung squamous cell carcinoma (27.9%), non–small-cell lung carcinoma (18%), poorly differentiated carcinoma (19.7%), and negative for malignant cells (16.4%). Data analysis was conducted using SPSS. Results The study revealed that 31.10% of the lung cancer patients exhibited overexpression of cyclin D1. A significant correlation was observed between cyclin D1 expression and histopathological results (P = 0.002), indicating that the level of cyclin D1 might be linked to specific histopathological subtypes of lung cancer. Despite this significant finding, cyclin D1 expression did not show any association with the clinical stage of the cancer or other clinical characteristics of the patients. Furthermore, when examining the 2-year survival rates of the patients, the study found no significant difference between those who had overexpression of cyclin D1 and those who did not (P = 0.145). Conclusion Cyclin D1 expression was associated with histology type of lung cancer with no significant association to prognosis.

Cyclic peptides have emerged as versatile scaffolds in drug discovery due to their stability and specificity. Here, we present the cPEPmatch webserver (accessible at https://t38webservices.nat.tum.de/cpepmatch/), an easy-to-use interface for the rational design of cyclic peptides targeting protein-protein interactions combined with a semi-quantitative evaluation of binding stability. This platform also offers access to a comprehensive database of cyclic peptide crystal structures. We demonstrate the webserver's utility through a series of case studies involving medically relevant protein systems, highlighting its potential to significantly advance drug discovery efforts.

In this article, we employ the Laplace transform (LT) method to study fractional differential equations with the problem of displacement of motion of mass for free oscillations, damped oscillations, damped forced oscillations, and forced oscillations (without damping). These problems are solved by using the Caputo and Atangana-Baleanu (AB) fractional derivatives, which are useful fractional derivative operators consist of a non-singular kernel and are efficient in solving non-local problems. The mathematical modelling for the displacement of motion of mass is presented in fractional form. Moreover, some examples are solved.

Abstract Non-alcoholic fatty liver disease and neurodegenerative disorders represent significant health challenges worldwide, with shared pathophysiological mechanisms. Evolving data indicates a bidirectional relationship between NAFLD and neurodegenerative disorders, with common risk factors, such as metabolic syndrome, inflammation, oxidative stress, and genetic predisposition, contributing to both conditions. Mechanistic links connecting NAFLD and neurodegeneration include systemic inflammation, dysregulation of the gut-liver-brain axis, and vascular dysfunction. This comprehensive review explores the intricate relationship between NAFLD and neurodegenerative disorders, focusing on shared pathophysiological mechanisms, common risk factors, and emerging therapeutic strategies. Furthermore, it presents evidence of the association between NAFLD and neurodegenerative disorders from clinical studies, underscoring the importance of understanding and addressing these interconnected conditions. A broad understanding of the complex linking between NAFLD and neurodegenerative disorders is essential for the advancement of future therapeutic strategies that can effectively lessen the load of these devastating conditions. By unveiling the shared pathophysiological mechanisms, common risk factors, and interconnected pathways linking NAFLD and neurodegeneration, researchers can identify novel therapeutic targets and interventions aimed at halting disease progression and preserving patient health.

Background Definite history is not always present in children with foreign body aspiration (FBA), hence necessitating a high index of suspicion. Objective To assess the predictive value of clinico-radiological variables among children presenting with features of suspected FBA and to document their course in a tertiary care teaching hospital. Materials and Methods In this retrospective observational study, we included children aged below 15 years presenting with clinical features of suspected FBA. Data was obtained from case records. Multivariable binary logistic regression analysis (MVA) was performed to determine statistically significant predictors of FBA, and Weighted Risk Scores (WRS) were calculated to determine the significance of the model. Results Of the 296 children included in the study and having undergone bronchoscopy, 84.5% were toddlers; 269 (90.87%) had a foreign body (FB) removed. Organic material was commonly found with 64.3% being peanut and right main bronchus, the commonest lodging site (50.6%). Of the 54 (18%) children with symptomatic but unwitnessed FBA, 45 (83.3%) had a FB retrieved. Choking with sudden onset cough, stridor, unilateral decreased breath sounds, abnormal chest radiograph, unilateral hyperinflation and mediastinal shift correlated with FBA (P < 0.05). MVA confirmed statistical significance with choking with sudden onset cough to predict FBA (P = 0.024) with overall sensitivity and specificity of 60.9% and 77.8%, respectively. Total WRS with cut-off >2 showed good power of discrimination with sensitivity, specificity and AUC of 60.2%, 77.8% and 0.704%, respectively. Conclusions The proposed predictive value-based scoring system enhances accuracy in decision-making regarding bronchoscopy in children with suspected FBA.

The experiment was undertaken to study the effect of indoxacarb on various biochemical parameters in White Leghorn layer birds for a period of 14 days following a single oral administration. The study follows OECD guideline no. 223. White Leghorn layer birds (n=30) weighing between 1.2 to 1.6 kg were used for the study. Six birds were kept as the control group and approximately 2 ml of blood was collected in EDTA tubes on days 7 and 14 of the experiment. Biochemical parameters such as alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine and blood urea nitrogen (BUN) were estimated. The mean values of ALP, AST, ALT and BUN were found significantly higher on days 7 and 14 of the acute toxicity study of indoxacarb in layers as compared to that of the control group. Keywords: Biochemical, layers, indoxacarb

The increasing incidence of tick-borne diseases and the growing resistance to conventional acaricides underscore the urgent need for innovative and sustainable tick management strategies. This study investigates the potential of assembly and sex pheromones for the control of larval stages of Rhipicephalus sanguineus, the brown dog tick, which poses significant health risks to dogs. The ticks were collected from various canine hosts in Thrissur, Kerala and subjected to Petri-dish bioassays using vapour patches impregnated with synthetic assembly pheromone (AP) and sex pheromone (SP), both individually and in combination. The efficacy of these semiochemicals was assessed based on the attraction and clustering behaviour of unfed larvae and partially fed adult ticks over a 24-hour period. Results demonstrated a significantly higher attraction to AP-impregnated patches, with notable efficacy observed in causing tick aggregation, particularly beyond 30 min of exposure. While SP also showed potential in attracting ticks, the combination of SP and AP did not result in a synergistic effect. The study highlights the potential of using semiochemicals as an environmentally sustainable alternative to traditional acaricides, highlighting their role in integrated pest management strategies Keywords: Rhipicephalus sanguineus, adenine, guanine, xanthine, 2,6-DCP, Petri-dish bioassay

Schistosomosis is a prevalent zoonotic parasitic disease affecting both humans and animals on a global scale, with an estimated 165 million cattle and 200 million people impacted worldwide. Eventhough, serological methodologies designed for the identification of specific antibodies targeting parasitic antigens are esteemed for their high sensitivity, there are criticisms due to their incapacity to reliably indicate active infection, inability to correlate with the intensity of infection and lack of specificity. Enhancing the specificity of serological assays presents a significant challenge, primarily attributable to the identification and synthesis of specific antigens. In addressing these limitations, recombinant technology with specific immunogenic proteins as candidate antigens emerges as a viable alternative. In this study, induction of 22.6 kDa recombinant tegument protein of Schistosoma spindale was achieved using 0.6 mM concentration of IPTG at 37°C for four hours. Nickel chelating affinity chromatography was employed for protein purification, yielding maximum protein concentration at 75mM elution. Subsequently, the dialysis technique was employed to remove contaminants, while lyophilisation method was employed for protein concentration. The protein concentration post dialysis was measured at 0.220 mg/mL, while lyophilisation resulted in a concentration of 2mg/m Keywords: 22.6 kDa tegumental protein, Schistosoma spindale, dialysis, lyophilisation

Abstract Primary cultures of proximal tubule cells are widely used to model the behavior of kidney epithelial cells in vitro. However, de-differentiation of primary cells upon culture has been observed and appreciated for decades, yet the mechanisms driving this phenomenon remain poorly understood. This confounds the interpretation of experiments using primary kidney epithelial cells and prevents their use to engineer functional kidney tissue ex vivo. In this report, we measure the dynamics of cell-state transformations in early primary culture of mouse proximal tubules to identify key pathways and processes that correlate with and may drive de-differentiation. Our data show that the loss of proximal-tubule-specific genes is rapid, uniform, and sustained even after confluent, polarized epithelial monolayers develop. This de-differentiation occurs uniformly across many common culture condition variations. Changes in early culture were strongly associated with the loss of HNF4A. Exogenous re-expression of HNF4A can promote expression of a subset of proximal tubule genes in a de-differentiated proximal tubule cell line. Using genetically labeled proximal tubule cells, we show that selective pressures very early in culture influence which cells grow to confluence. Together, these data indicate that the loss of in vivo function in proximal tubule cultures occurs very early and suggest that the sustained loss of HNF4A is a key regulatory event mediating this change.

Background: The study aimed to determine whether there was a difference or an association between auditory memory and visual memory in typically developing children. Methods: Eighteen children, aged 8 to 12 years, with normal hearing and visual acuity, were evaluated using the Children’s Memory Scale (CMS) to determine their auditory and visual memory performance. Using the core subtest battery of the CMS, auditory/verbal (immediate and delayed), visual/nonverbal (immediate and delayed), and general memory index scores were assessed. Results: No significant difference was found between auditory/verbal memory and visual/nonverbal memory scores for both immediate and delayed recall. Likewise, no correlation between auditory/verbal memory and visual/nonverbal memory scores was found. However, there was a significant correlation between immediate and delayed recall scores within each modality. Conclusions: The non-significant difference between the two modalities for both immediate and delayed recall gives the impression that memory is modality independent. However, the lack of any correlation between the two suggests there was no association between them. The absence of a significant difference between modalities can be attributed to the auditory and visual test material used in CMS not being analogous. It can thus be inferred that the auditory and visual modalities are independent. While the visual material evaluates simultaneous/concurrent perception, the auditory material assesses sequential perception.

Introduction: Any significant changes in the growth and development of any aspect of life will ultimately affect the health-related quality of life (HRQOL) of children with nephrotic syndrome. Various factors can influence treatment adherence, which can promote or decline the child’s quality of life (QOL). Objective: To assess the quality of life and adherence to treatment regimen and to identify the predictors of QOL and adherence to treatment regimen among children with nephrotic syndrome. Method: A cross-sectional study was conducted among 59 children with nephrotic syndrome who attended the Paediatric Department of AIIMS, Bhubaneswar, using the PedsQL 4.0 generic core scale to assess the quality of life and adherence response scale. Both descriptive and inferential statistics were performed using the SPSS 20 version. Results: The overall QOL median score was 93.48, with an IQR of 18.48, which indicated good QOL. A median score of treatment adherence was 16 with IQR 5, which indicated that the overall treatment adherence was good. Type of nephrotic syndrome (P = 0.014), developmental stage (P = 0.018), education of mother (P = 0.026), and occupation of mother (P = 0.026) were the variables predicted QOL. Duration of disease (P = 0.006) and duration of therapy (P = 0.005) significantly predicted treatment adherence. Conclusion: Children need continuous reinforcement on treatment adherence strategies to attain and maintain good QOL so that it can help to reduce the disease severity. Controlling the predictors that influence the QOL and treatment adherence has to be counseled among the parents so that their adherence can be sustained throughout the disease process to maintain good QOL.

Introduction: Subarachnoid Block (SAB) is a commonly used technique for lower abdominal surgery. Dexamethasone has been proven effective as an additive when used with bupivacaine. However, there has been no study comparing the analgesic efficacy of dexamethasone with levobupivacaine under SAB. Aim: To compare the analgesic efficacy of levobupivacaine with or without dexamethasone in patients scheduled for lower abdominal surgeries. Materials and Methods: A pilot randomised double-blind controlled trial was undertaken in the Department of Anaesthesiology, University College of Medical Sciences Guru Tagh Bahudur (UCMS-GTB) Hospital, New Delhi, India on 60 patients with Americian Soceity of Anaesthesiolgy (ASA) grade I or II, aged 18-65 years, undergoing lower abdominal surgeries under SAB from January 2021 to August 2022. In Group LS, 12.5 mg of 0.5% isobaric levobupivacaine (2.5 mL) with normal saline (1 mL) was administered, and in Group LD, 12.5 mg of 0.5% isobaric levobupivacaine (2.5 mL) with 4 mg dexamethasone (1 mL) was given. Patients were assessed for sensory and motor block, haemodynamic parameters, pain score, and side-effects. Unpaired t-tests/Mann-Whitney U tests were used to determine significance. A p-value of less than 0.05 was considered significant. Results: The two groups were comparable in terms of demographic profile. The age in the LS group was 37.80±9.98 years, and in the LD group, it was 38.63±12.37 years. The male-to-female ratio in the LS and LD groups was 17:13 and 21:9, respectively. The weight range in both groups was between 50 to 67 kg. The Basal Metabolic Index (BMI) was 22.40±2.43 kg/m2 and 21.70±2.21 kg/m2 in the LD and LS groups, respectively. All these parameters, including height, had a p-value of more than 0.005, except for the duration of analgesia. The duration of effective analgesia was also longer in the LD group (247.00±36.69 min) than in the LS group (138.50±22.52 min) with a p-value of

Abstract Background Bioinspired nanomaterials have widely been employed as suitable alternatives for controlling biofilm and pathogens due to their distinctive physico-chemical properties. Methodology This study explored the antibiofilm as well as photocatalytic potential of silver (Ag) nanoparticles (NPs) synthesized using the cell-free supernatant of Lactobacillus acidophilus for the disinfection of multi-drug-resistant (MDR) strains of enteroaggregative E. coli (EAEC), Salmonella Typhimurium, S. Enteritidis and methicillin-resistant Staphylococcus aureus (MRSA) on exposure to LED light. In addition, the removal of toxic cationic dyes i.e., methylene blue (MB), rhodamine B (RhB) and crystal violet (CV) was explored on exposure to sunlight, LED and UV lights. Results Initially, the synthesis of AgNPs was verified using UV- Vis spectroscopy, X-ray diffraction and transmission electron microscopy. The synthesized AgNPs exhibited MIC and MBC values of 7.80 and 15.625 µg/mL, respectively. The AgNPs exhibited significant inhibition (P

The developments of nano-roughness surface textures are important to implement enhanced osseointegration, cell adhesion, and proliferation in polymers for biomedical applications such as tissue engineering scaffolds and orthopaedic implants. The hydrophilicity of the polymeric implants is a crucial factor for cell adhesion, which can be improved via adapting the roughness of the surface. This study explores the surface modification of poly (lactic acid) (PLA) polymer through an alkaline wet etching process, varying alkaline concentration and etching time under both room temperature and elevated conditions. The main objective is to refine the PLA surface through wet etching, altering its properties for potential use in biomedical contexts. The assessment of surface roughness is conducted through scanning electron microscopy (SEM), atomic force microscopy (AFM), and fourier-transform infrared spectroscopy (FTIR). These techniques offer a comprehensive analysis of surface topography, nanoscale roughness, and potential chemical changes resulting from the wet etching process. The nano-roughness of treated 3D printed PLA was increased by 1.4 times compared to the control 3D printed PLA. The research contributes to the broader field of biomaterial engineering, laying the groundwork for subsequent investigations that will focus on applying the derived conclusions to enhance PLA’s biocompatibility and functionality in tissue engineering and orthopaedic applications.

Background: Pancytopenia is a common hematological entity and a striking feature of many life-threatening illnesses. Aims and Objectives: The study was conducted to identify the etiology of pancytopenia. (i) To find out primary bone marrow (BM) causes of pancytopenia. (ii) To evaluate the spectrum of BM morphology in pancytopenia cases. Materials and Methods: This hospital-based observational study was conducted between June 2021 and May 2022 in a tertiary care hospital in Dibrugarh in all pancytopenia cases of age above 12 years and meeting the inclusion criteria. After taking written consent, detailed history, clinical examination, and baseline investigations were done followed by BM examination. Results: Mean age was 45.39±15.49 years. Majority were males 41 (56.9%) and 31 (43.1%) were females. The most common cause of pancytopenia was Megaloblastic anemia (30.5%) cases, followed by aplastic anemia (18%) and myelodysplastic syndromes (16.7%). About 72 (100%) had pallor followed by weakness (86.1%), bleeding tendencies (70.8%), and fever (52.8%). Conclusion: The study underscores the critical role of BM biopsy in the diagnostic workup of pancytopenia. It confirms that BM biopsy is indispensable for identifying the diverse etiologies of pancytopenia and in implementing the appropriate therapy.

The urbanization development in India over the last few decades has been fast, very unequal, and not sustainable. The UN projects that by 2050, it will be one of the top three nations in terms of urbanization. India's urban population is expected to grow from 481 million to 814 million by 2050 an added 333 million. There will be significant effects on energy consumption patterns and GHG emissions when India's urban population increases from 34.93% now to 57.7% in 2050. Conventional construction materials have a high embodied energy, and buildings account for most of the world's energy usage. The production of today's standard materials accounts for 20% of global CO2 emissions and 25% of global energy usage. Rapid building is required to satisfy the need for housing, but if it is done wrongly, it will only meet the demand for housing temporarily and at the expense of livability, sustainability, pollution, resilience, and ultimately economic competitiveness. The Compressed Stabilized Earth Blocks (CSEB) have the potential to revolutionize environmentally friendly construction in India. CSEBs provides the perspective of energy-efficient, cost-reduction, and environmentally-friendly building materials, overall contributing to sustainable development, at a time when there is a growing concern of awareness regarding environmental issue. Since CSEBs are unburned materials, no coal or other burning fuel is required in their manufacturing. The paper delves into the history of CSEB, passive architecture, and circular economy in Indian residences, incorporating many strategies into one plan, the potential to reduce a building's overall energy consumption while simultaneously improving its cost-effectiveness, usability, and social cohesion. The goal of this study is to demonstrate that stabilized earth walls may be utilized in low and medium-rise structures when paired with a frame constructed of today's standard materials, lowering total use while achieving density requirements.

Background and Aims: Vasopressor usage can affect the rostral spread of intrathecal drug and, hence, its requirement during cesarean delivery. Although a decreased spread is evidenced with phenylephrine, there is no data for norepinephrine usage. The present study aimed to evaluate the minimum effective dose of intrathecal hyperbaric bupivacaine for cesarean section with and without prophylactic norepinephrine infusion. Material and Methods: Patients scheduled for elective cesarean section under combined spinal–epidural block were randomized to receive intravenous infusion of norepinephrine (0.05 μg/kg/min) or normal saline (placebo), initiated immediately after intrathecal injection. Postspinal hypotension in either group (systolic arterial pressure ≤0.8 baseline) was treated with norepinephrine 4 μg rescue. Dose of intrathecal hyperbaric bupivacaine (0.5%) was decided for individual patients using up-and-down sequential allocation method. Primary outcome measure was the minimum effective dose of intrathecal hyperbaric bupivacaine (0.5%) defined as ED50, while secondary observations included spinal block characteristics and neonatal outcomes. Results: Demographic parameters were statistically similar between both groups (P > 0.05). ED50 of intrathecal hyperbaric bupivacaine was 7.8 mg (95% confidence interval [CI]: 6.7–8.8) and 7.4 mg (95% CI: 6.1–8.7) for normal saline and norepinephrine group respectively (P = 0.810). Block characteristics were similar between both groups as was neonatal APGAR score, but umbilical artery base excess was greater for norepinephrine versus normal saline group (−4.4 ± 3.6 vs. −6.5 ± 2.4, P = 0.038). Conclusion: Use of prophylactic norepinephrine (0.05 μg/kg/min) during cesarean delivery does not require adjustment of intrathecal hyperbaric bupivacaine.

Prostate cancer (PC) depicts a major health challenge all over the globe due to its complexities in the treatment and diverse clinical trajectories. Even in the advances in the modern treatment strategies, the spectrum of resistance to the therapies continues to be a significant challenge. This review comprehensively examines the underlying mechanisms of the therapy resistance occurred in PC, focusing on both the tumor microenvironment and the signaling pathways implicated in the resistance. Tumor microenvironment comprises of stromal and epithelial cells, which influences tumor growth, response to therapy and progression. Mechanisms such as microenvironmental epithelial-mesenchymal transition (EMT), anoikis suppression and stimulation of angiogenesis results in therapy resistance. Moreover, dysregulation of signaling pathways including androgen receptor (AR), mammalian target of rapamycin/phosphoinositide 3 kinase/AKT (mTOR/PI3K/AKT), DNA damage repair and Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways drive therapy resistance by promoting tumor survival and proliferation. Understanding these molecular pathways is important for developing targeted therapeutic interventions which overcomes resistance. In conclusion, a complete grasp of mechanisms and pathways underlying medication resistance in PC is important for the development of individualized treatment plans and enhancements of clinical outcomes. By studying and understanding the complex mechanisms of signaling pathways and microenvironmental factors contributing to therapy resistance, this study focuses and aims to guide the development of innovative therapeutic approaches to effectively overcome the PC progression and improve the survival rate of patients.

Abstract Background Anti-HER2 therapies, including the HER2 antibody–drug conjugates (ADCs) trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd), have led to improved survival outcomes in patients with HER2-overexpressing (HER2+) metastatic breast cancer. However, intrinsic or acquired resistance to anti-HER2–based therapies remains a clinical challenge in these patients, as there is no standard of care following disease progression. The purpose of this study was to elucidate the mechanisms of resistance to T-DM1 and T-DXd in HER2+ BC patients and preclinical models and identify targets whose inhibition enhances the antitumor activity of T-DXd in HER2-directed ADC-resistant HER2+ breast cancer in vitro and in vivo. Methods Targeted DNA and whole transcriptome sequencing were performed in breast cancer patient tissue samples to investigate genetic aberrations that arose after anti-HER2 therapy. We generated T-DM1 and T-DXd–resistant HER2+ breast cancer cell lines. To elucidate their resistance mechanisms and to identify potential synergistic kinase targets for enhancing the efficacy of T-DXd, we used fluorescence in situ hybridization, droplet digital PCR, Western blotting, whole-genome sequencing, cDNA microarray, and synthetic lethal kinome RNA interference screening. In addition, cell viability, colony formation, and xenograft assays were used to determine the synergistic antitumor effect of T-DXd combinations. Results We found reduced HER2 expression in patients and amplified DNA repair–related genes in patients after anti-HER2 therapy. Reduced ERBB2 gene amplification in HER2-directed ADC–resistant HER2+ breast cancer cell lines was through DNA damage and epigenetic mechanisms. In HER2-directed ADC–resistant HER2+ breast cancer cell lines, our non-biased RNA interference screening identified the DNA repair pathway as a potential target within the canonical pathways to enhance the efficacy of T-DXd. We validated that the combination of T-DXd with ataxia telangiectasia and Rad3-related inhibitor, elimusertib, led to significant breast cancer cell death in vitro (P

Background and Aims: Data focussing on acute kidney injury (AKI) in obstetric patients admitted to the intensive care unit (ICU) are scarce and even more so regarding the role of neutrophil gelatinase-associated lipocalcin (NGAL) in detecting AKI or predicting outcomes in these patients. Hence, we aim to evaluate the incidence of AKI in obstetric ICU patients and validate the role of urinary and serum NGAL in predicting the onset of AKI and mortality. Methods: This prospective observational cohort included 45 obstetric patients admitted in ICU, excluding those with prior renal dysfunction. Serum creatinine and urine output were monitored for the occurrence of AKI during the ICU stay. The outcome of the patient (survival or death) in the ICU and hospital was recorded, and serum and urinary NGAL were determined at the time of ICU admission. Results: AKI occurred in 32 [71.1%; 95% confidence interval (CI): 55.4%, 86.8%] patients during their ICU stay. Serum NGAL showed an area under receiver operating characteristic curve (AUROCC) of 0.630 (95% CI: 0.417, 0.842) (P = 0.231) for AKI and 0.486 (95% CI: 0.295, 0.676) (P = 0.883) for ICU mortality. Urinary NGAL showed AUROC = 0.472 (95% CI: 0.285, 0.660) (P = 0.772) to predict AKI and 0.430 (95% CI: 0.268, 0.652) (P = 0.684) for ICU mortality. Conclusions: AKI is common amongst critically ill obstetric ICU patients. However, serum and urinary NGAL cannot be advocated to discriminate between patients with or without AKI or between survivors and non-survivors in critically ill obstetric patients.

Abstract Light-matter superposition states obtained via strong coupling play a decisive role in quantum information processing, but the deleterious effects of material dissipation and environment-induced decoherence inevitably destroy coherent light-matter polaritons over time. Here, we propose the use of coherent perfect absorption under near-field driving to prepare and protect the polaritonic states of a single quantum emitter interacting with a plasmonic nanocavity at room temperature. Our scheme of quantum nanoplasmonic coherent perfect absorption leverages an inherent frequency specificity to selectively initialize the coupled system in a chosen plasmon-emitter dressed state, while the coherent, unidirectional and non-perturbing near-field energy transfer from a proximal plasmonic waveguide can in principle render the dressed state robust against dynamic dissipation under ambient conditions. Our study establishes a previously unexplored paradigm for quantum state preparation and coherence preservation in plasmonic cavity quantum electrodynamics, offering compelling prospects for elevating quantum nanophotonic technologies to ambient temperatures.

Abstract Rice brown spot is an important disease of rice worldwide that inflicts substantial yield losses. The antimicrobial potential of methanol, acetone and dimethyl sulfoxide (DMSO) extracts of different medicinal plants, viz., Syzygium aromaticum, Saussurea costus, Acorus calamus, Bergenia ciliate, Geranium pratense, Mentha longifolia, Inula racemosa, Podophyllum hexandrum, Heracleum candicans and Picrorhiza kurroa, against the brown spot pathogen Bipolaris oryzae in vitro was evaluated via mycelial growth inhibition and spore germination inhibition assays. Among the plant extracts tested, 100% mycelial inhibition was observed for the methanol extract of Syzygium aromaticum at all three concentrations (2000 ppm, 3000 ppm and 4000 ppm), followed by the methanol extract of Inula racemosa (90.33%) at 4000 ppm. A maximum conidial germination inhibition of 83.54% was exhibited by the Heracleum candicans leaf extract. Phytochemical profiling of Syzygium aromaticum and Inula racemosa through liquid chromatography and mass spectrometry (HR-LCMS) revealed the presence of several compounds, such as eugenol, ursolic acid, quercetin, chlorogenic acid, and noscapine. A molecular docking approach was used to identify key inhibitory molecules against B. oryzae. Among the compounds detected in S. aromaticum and Inula racemosa, ursolic acid and noscapine were found to have the greatest binding affinity for the Big Mitogen Activated Protein Kinase (BMK-1) enzyme present in B. oryzae. In conclusion, S. aromaticum and Inula racemosa are potent compounds that could serve as lead compounds for drug discovery in the future.

PurposeThe primary objective of this study was to measure and quantify the current level of physical activity among persons with disability in Qatar. The secondary objective was to assess and analyze the duration of sedentary behavior among individuals with disability in Qatar.MethodsThis was a cross-sectional epidemiological study of persons with disability living in Qatar. The study period was from October 2020 to December 2021Results96 persons with disabilities participated in this study. They included individuals with amputations, spinal cord injuries, cerebral palsy, and other developmental impairments. Of the respondents, 56% were male and 64% were Qataris. Of the respondents, 61.5%said that they felt psychologically and emotionally better when engaging in physical activity, and this difference was statistically significant. 71% of all those who reported feeling physically good after sport, 65% said that they enjoyed the social aspects of sports. This corroborates the beneficial effects of exercise, sports, and physical activity in persons with all types of disabilities.ConclusionThere was a definite impact on the emotional and physical well-being of those who participated in the physical activities. There was less participation in team activities and two-thirds preferred to exercise alone. However, their numbers were not statistically significant because of low enrollment in the study.

A novel self-propelled smart herbicide applicator (1600 mm × 500 mm × 1100 mm) was developed using machine vision to target weeds and apply herbicides variably in wide row-spaced crops. The applicator integrates a weed detection system, smart sprayer, mechanical components, and power transmission system. The weed detection system utilizes a webcam based image sensor, with images processing performed through MATLAB's image processing toolbox. The system processed images using an RGB-based algorithm (R > G + 5, & R > B + 5) to separate weeds from soil. Weed density, calculated as the green area percentage (ratio of green pixels to total pixels), was sent to a microcontroller-operated smart sprayer via a serial port. The microcontroller regulates herbicide flow by controlling the flow control valve with a servo motor, following an algorithm based on green area percentage. Field tests demonstrated a 40 % reduction in herbicide use, 91.26 % weeding efficiency, and 63.4 % field efficiency. The smart herbicide applicator's unique features include real-time measurement, portability, and precise herbicide application for wide-row crops, even at night. It also reduced environmental hazards and drudgery among farmers.

This study presents the synthesis and optimization of Methylene polyethyl glycol −Polystyrene (mPEG-PS) Diblock (DIP) copolymer-based solid lipid nanoparticles (SLNs) using ultrasonication for advanced drug delivery systems targeting the human immunodeficiency virus (HIV-1). The mPEG-PS block copolymer was synthesized by ring opening polymerization mechanism under nitrogen atmosphere for 24hrs and characterized using Fourier Transform Infrared Spectroscopy (FTIR) spectroscopy and NMR, confirming the formation of DIP polymers. Optimization of SLNs formulation was achieved through a systematic approach, utilizing response surface methodology, optimal conditions for SLNs synthesis were determined, resulting in nanoparticles with a particle size of 198 nm and an entrapment efficiency of 67.42 %. Cell viability assays, quantitative PCR for viral DNA analysis, caspase-3 enzyme assays, and quantitative uptake studies using High Performance Liquid Chromatography (HPLC) provided quantitative insights into the efficacy and biocompatibility of the synthesized nanoparticles. The experimental data demonstrate that nanoparticle treatments significantly influence cellular responses, providing valuable insights into their therapeutic potential and underlying mechanisms. By employing precise experimental methods alongside rigorous analytical techniques, this study enhances our understanding of nanoparticle-based drug delivery systems, particularly in the context of HIV treatment. These findings pave the way for optimizing therapeutic strategies to improve patient outcomes.

Background: Long non-coding RNAs (lncRNAs) can perform tasks of key relevance in fat cells, contributing, when defective, to the burden of obesity and its sequelae. Here, scrutiny of adipose tissue transcriptomes before and after bariatric surgery (GSE53378) granted identification of 496 lncRNAs linked to the obese phenotype. Only expression of linc-GALNTL6-4 displayed an average recovery over 2-fold and FDR-adjusted p-value

Background Community health is key for improving Reproductive, Maternal, Newborn, Child, and Adolescent Health and Nutrition (RMNCAH-N). However, how community health supports integrated RMNCAH-N service delivery in francophone West Africa is under-researched. Objective We examined how six francophone West African countries (Burkina Faso, Côte d’Ivoire, Guinea, Mali, Niger, and Senegal) support community health through the Global Financing Facility for Women, Children and Adolescents (GFF). Methods We conducted a content analysis on Investment Cases and Project Appraisal Documents from selected countries, and set out the scope of the analysis and the key search terms. We applied an iterative hybrid inductive-deductive approach to identify themes for data coding and extraction. The extracted data were compared within and across countries and further grouped into meaningful categories. Results In country documents, there is a commitment to community health, with significant attention paid to various cadres of community health workers (CHWs) who undertake a range of preventive, promotive and curative roles across RMNCAH-N spectrum. While CHWs renumeration is mentioned, it varies considerably. Most community health indicators focus on CHWs’ deliverables, with few related to governance and civil registration. Challenges in implementing community health include poor leadership and governance and resource shortages resulting in low CHWs performance and service utilization. While some countries invest significantly in training CHWs, structural reforms and broader community engagement are lacking. Conclusions There is an opportunity to better prioritize and streamline community health interventions, including integrating them into health system planning and budgeting, to fully harness their potential to improve RMNCAH-N.

Background: Craniopharyngiomas are rare benign tumors located in the sellar and suprasellar region, with an incidence of 0.5–2 cases per million as reported in Western studies. Post-treatment, including surgery and/or radiotherapy, many patients develop significant obesity, primarily due to hypothalamic damage and associated complications such as hypopituitarism. In the South Asian population, genetic predisposition to obesity at lower BMIs, coupled with a carbohydrate-rich diet, may exacerbate obesity in craniopharyngioma patients, presenting a unique challenge. Methods: This submission is a commentary based on a comprehensive literature review. The authors conducted the review using PubMed to focus on English-language articles covering hypothalamic obesity, craniopharyngioma and obesity in the South Asian population from 1939 to the present. Results: The literature review revealed that 50–60 % of patients treated for craniopharyngioma develop obesity, predominantly linked to hypothalamic damage, although these data are mainly derived from Western studies. Hypopituitarism was frequently observed, further contributing to the obesity. Despite a caloric intake appropriate for the age and gender, these patients exhibited reduced physical activity as measured by wrist accelerometers. Patients with hypothalamic obesity due to craniopharyngioma are at risk for metabolic syndrome and cardiovascular morbidity. Additionally, visual impairment was common, leading to a decreased quality of life. The South Asian population, genetically predisposed to visceral obesity and a carbohydrate-rich diet, may display a distinct phenotype. Although multiple treatment modalities have been tried, there is no definite treatment modality available to counteract this condition at present. Conclusion: South Asian phenotype of craniopharyngioma-related obesity is characterized by significant metabolic and hormonal dysregulation, influenced by both dietary and genetic factors. Nevertheless, there may be a lot to be still understood about this devastating, rapid, relentless hypothalamic obesity syndrome. Also, a higher morbidity rate within this population, underscores the need for further research to develop targeted interventions.

Heavy metal (HM) toxicity of agricultural soils poses a major risk to plant health, human life, and global food chain. Crop output and health are negatively impacted when HM levels in agricultural soils reach hazardous points. The nano-biochar (nano-BC) mediated stress tolerance has attracted growing scientific interest because biochar has the potential to be a novel and sustainable solution that may be actively included into the development of sustainable agriculture and food production. At present, biochar is extensively employed as a powerful tool to enhance sustainable agriculture with minimal impact on ecosystems and the environment. Nano-BC offers improved surface area, adsorption and mobility properties in soil compared to traditional fertilizers. Furthermore, nano-BC may prove to be the most practical substitute for traditional waste management techniques because of its affordability, sustainability, and environmental friendliness. In this review, we examine the application of nano-BC in the regulation of HM stress tolerance for improving plant growth and development. We focus on the impact of HMs impact on crop productivity, nano-BC amendments, their application, and production. The article also explores the nano-BC risk and toxicity. Through the perspective of multidisciplinary research, this work highlights the significance of nano-BC as cutting-edge tools in the field of agriculture, igniting a paradigm shift toward sustainable and stress-resilient farming systems.

Faced with heightened state anxiety, today’s youth are turning to lo-fi music for relief – but does it truly work, how and why? This study represents a pioneering initial exploration of lo-fi music and state anxiety through the lens of critical realism. It employs a mixed-methods intervention design to assess the preliminary effectiveness of lo-fi music in alleviating state anxiety and explores its possible underlying mechanisms. A pre-post experiment (n = 76) followed by interviews (n = 27) was conducted on young adults pursuing post-graduate education in Karnataka, India. Results demonstrate a significant reduction in state anxiety after lo-fi exposure. Participants reported that lo-fi disrupts intrusive thoughts and promotes relaxation, sleep, and positive mental states, construing it as an antidote to anxiety. This research unearths the unique characteristics of lo-fi music that may drive this effect. Future investigation is warranted to test the efficacy of this music in youth-focused mental health interventions.

Introduction Patients with chronic kidney disease (CKD) are at increased risk of developing tuberculosis (TB). These patients may also be at higher risk of developing antitubercular treatment (ATT)-associated adverse drug reactions (ADRs). Although dose modification has been recommended, data regarding the impact of impaired kidney function on ATT-associated ADRs is sparse. We studied the incidence and profile of ATT-associated ADRs in patients with CKD and compared them with those with normal kidney function.Methodology This retrospective study analyzed all patients initiated on ATT from January 2016 to August 2019. Patients were grouped into CKD and normal kidney function based on their eGFR. Data on ATT-associated ADRs were collected from medical records. Predictors of ADRs were assessed using univariable and multivariable logistic regression. Additionally, Propensity score matching and analysis were done for CKD and normal kidney function in 1:3 ratio.Results Of 1815 patients on ATT, 75 (4.1%) had CKD. ADRs were more frequent [36/75 (48.0%) vs. 239/1740 (13.7%), p ≤ 0.0001] and more severe [15/46 (32.6%) vs. 43/283 (15.1%), p = 0.010] in CKD than those with normal kidney function. The most common ADRs were hepatobiliary [23/75 (30.6%) vs. 156/1740 (8.9%), p ≤ 0.0001], neuropsychiatric [8/75(10.6%) vs. 21/1740(1.2%), p ≤ 0.0001], renal [4/75(5.3%) vs. 8/1740(0.4%), p = 0.001], and gastrointestinal [5/75(6.6%) vs. 34/1740 (1.9%), p = 0.020]. CKD was an independent predictor for ADRs (OR −4.96, 95% CI: 2.79–8.82; p ≤ 0.0001). The matched cohort showed similar results.Conclusion ATT-associated ADRs were more common and severe in patients with CKD, despite drug dose modifications. Optimal dosing of ATT in CKD needs to be further evaluated.

Financial Inclusion (FI) is one of the most important indicators of inclusive growth of an economy. This paper examines the status of FI in India by constructing a comprehensive financial inclusion index (FII). The data analysis indicates that states such as Goa, Kerala, Tamil Nadu, Maharashtra, and Telangana performed well in FI. Further, a panel data regression model is estimated to know the determinants of financial inclusion in 27 Indian States for the period 2005 to 2020. The composite index can be used to monitor and assess financial inclusion over time and at the grass root level also. The estimated results show that per capita NSDP, literacy rate, urban population share, road length, and number of factories are perhaps the most important financial inclusion determinants. The novelty of this study is to provide a comprehensive understanding of financial inclusion levels across different states in India for two-decade period along with rural and urban financial inclusion levels.

Interfacial solar steam generation is considered as economical and more effective implementation of Solar steam generation (SSG) where solar energy is concentrated at the liquid surface via the utilization of heat localization materials (HLM). Herein we report the fabrication of an HLM constituted of a nanocomposite absorber of graphitic carbon nitride (g-C3N4) and covellite copper sulfide (CuS) supported on a mixed cellulose ester membrane, with a substrate of air laid paper-wrapped polystyrene foam. This structure allowed for strong broad-spectrum absorbance, increased hydrophilic character and minimal thermal losses. The HLM system absorbed 98% of the material and had an evaporation rate of 2.58 kgs per square meter per hour. This is twice the evaporation rate of water tested under the same conditions. Moreover, as fabricated HLM was also incorporated in a solar still in order to assess its practical performance in solar distillation. Initial studies proved that HLM modified solar still was more effective than conventional solar stills.

Background In 2015, Uganda joined the Global Financing Facility (GFF), a Global Health Initiative for Reproductive, Maternal, Newborn, Child, and Adolescent Health (RMNCAH). Similar initiatives have been found to be powerful entities influencing national policy and priorities in Uganda, but few independent studies have assessed the GFF. Objective To understand the policy process and contextual factors in Uganda that influenced the content of the GFF policy documents (Investment Case and Project Appraisal). Methods We conducted a qualitative policy analysis. The data collection included a document review of national RMNCAH policy documents and key informant interviews with national stakeholders involved in the development process of GFF policy documents (N = 16). Data were analyzed thematically using the health policy triangle. Results The process of developing the GFF documents unfolded rapidly with a strong country-led approach by the government. Work commenced in late 2015; the Investment Case was published in April 2016 and the Project Appraisal Document was completed and presented two months later. The process was steered by technocrats from government agencies, donor agencies, academics and selected civil society organisations, along with the involvement of political figures. The Ministry of Health was at the center of coordinating the process and navigating the contestations between technical priorities and political motivations. Although civil society organisations took part in the process, there were concerns that some were excluded. Conclusion The learnings from this study provide insights into the translation of globally conceived health initiatives at country level, highlighting enablers and challenges. The study shows the challenges of trying to have a ‘country-led’ initiative, as such initiatives can still be heavily influenced by ‘elites’. Given the diversity of actors with varying interests, achieving representation of key actors, particularly those from underserved groups, can be difficult and may necessitate investing further time and resources in their engagement.

Background Burkina Faso joined the Global Financing Facility for Women, Children and Adolescents (GFF) in 2017 to address persistent gaps in funding for reproductive, maternal, newborn, child, and adolescent health and nutrition (RMNCAH-N). Few empirical papers deal with how global funding mechanisms, and specifically GFF, support resource mobilisation for health nationally. Objective This study describes the policy processes of developing the GFF planning documents (the Investment Case and Project Appraisal Document) in Burkina Faso. Methods We conducted an exploratory qualitative policy analysis. Data collection included document review (N = 74) and in-depth semi-structured interviews (N = 23). Data were analysed based on the components of the health policy triangle. Results There was strong national political support to RMNCAH-N interventions, and the process of drawing up the investment case (IC) and the project appraisal document was inclusive and multi-sectoral. Despite high-level policy commitments, subsequent implementation of the World Bank project, including the GFF contribution, was perceived by respondents as challenging, even after the project restructuring process occurred. These challenges were due to ongoing policy fragmentation for RMNCAH-N, navigation of differing procedures and perspectives between stakeholders in the setting up of the work, overcoming misunderstandings about the nature of the GFF, and weak institutional anchoring of the IC. Insecurity and political instability also contributed to observed delays and difficulties in implementing the commitments agreed upon. To tackle these issues, transformational and distributive leaderships should be promoted and made effective. Conclusions Few studies have examined national policy processes linked to the GFF or other global health initiatives. This kind of research is needed to better understand the range of challenges in aligning donor and national priorities encountered across diverse health systems contexts. This study may stimulate others to ensure that the GFF and other global health initiatives respond to local needs and policy environments for better implementation.

Background The Global Financing Facility (GFF) supports national reproductive, maternal, newborn, child, adolescent health, and nutrition needs. Previous analysis examined how adolescent sexual and reproductive health was represented in GFF national planning documents for 11 GFF partner countries. Objectives This paper furthers that analysis for 16 GFF partner countries as part of a Special Series. Methods Content analysis was conducted on publicly available GFF planning documents for Afghanistan, Burkina Faso, Cambodia, CAR, Côte d’Ivoire, Guinea, Haiti, Indonesia, Madagascar, Malawi, Mali, Rwanda, Senegal, Sierra Leone, Tajikistan, Vietnam. Analysis considered adolescent health content (mindset), indicators (measure) and funding (money) relative to adolescent sexual and reproductive health needs, using a tracer indicator. Results Countries with higher rates of adolescent pregnancy had more content relating to adolescent reproductive health, with exceptions in fragile contexts. Investment cases had more adolescent content than project appraisal documents. Content gradually weakened from mindset to measures to money. Related conditions, such as fistula, abortion, and mental health, were insufficiently addressed. Documents from Burkina Faso and Malawi demonstrated it is possible to include adolescent programming even within a context of shifting or selective priorities. Conclusion Tracing prioritisation and translation of commitments into plans provides a foundation for discussing global funding for adolescents. We highlight positive aspects of programming and areas for strengthening and suggest broadening the perspective of adolescent health beyond the reproductive health to encompass issues, such as mental health. This paper forms part of a growing body of accountability literature, supporting advocacy work for adolescent programming and funding.

Alcohol harms threaten global population health, with youth particularly vulnerable. Low – and middle-income countries (LMIC) are increasingly targeted by the alcohol industry. Intersectoral and whole-of-community actions are recommended to combat alcohol harms, but there is insufficient global evidence synthesis and research examining interventions in LMIC. This paper maps existing literature on whole-of – community and intersectoral alcohol harms reduction interventions in high-income countries (HIC) and LMIC. Systematic searching and screening produced 61 articles from an initial set of 1325: HIC (n = 53), LMIC (n = 8). Data were extracted on geographic location, intersectoral action, reported outcomes, barriers, and enablers. HIC interventions most often targeted adolescents and combined community action with other components. LMIC interventions did not target adolescents or use policy, schools, alcohol outlets, or enforcement components. Programme enablers were a clear intervention focus with high political support and local level leadership, locally appropriate plans, high community motivation, community action and specific strategies for parents. Challenges were sustainability, complexity of interventions, managing participant expectations and difficulty engaging multiple sectors. A learning agenda to pilot, scale and sustain whole-of-community approaches to address alcohol harms in settings is crucial, with consideration of local contexts and capacities, more standardised methods, and a focus on community-driven action.

ABSTRACTType I interferons (IFN-Is) have key roles in immune defense and treatments for various diseases, including chronic hepatitis B virus (HBV) infection. All IFN-Is signal through a shared IFN-I heterodimeric receptor complex comprising IFN-α receptor 1 (IFNAR1) and IFNAR2 subunits, but differences in antiviral and immunomodulatory responses among IFN-I subtypes remain largely unknown. Because the IFN-IFNAR interactions are species-specific, mice exhibit weak responses to human IFN-I. To more fully characterize the actions of human IFN-α and its subtypes in vivo, a gene targeting strategy was employed to generate gene knock-in mice with extracellular-humanized IFNAR1/2 (IFNAR-hEC) in the C57BL/6N strain. IFNAR-hEC mice actively responded to human IFN-I, and endogenous mouse IFN-I signalling remained active in heterozygous mice (IfnarhEC/+). Analyses of IFNAR-hEC mice and isolated cells showed that human IFN-α2 and α14 subtypes exerted differential effect on the activation of JAK-STAT signalling and immune responses. Compared with IFN-α2, IFN-α14 induced greater activation of STAT1/2 and IFN-stimulated genes, synergistically elicited IFN-α and -γ signalling, and induced higher numbers of antigen-specific CD8+ T cells. Moreover, IFNAR-hEC mice with HBV replication displayed long-term viral suppression upon treatment with the clinically-used PEGylated hIFN-α2. These results indicate that IFNAR-hEC mice may be useful for elucidating antiviral and immunomodulatory functions of human IFN-Is and for conducting preclinical studies. A better understanding of the distinct activities of IFN-α subtypes can provide insights concerning the development of improved IFN-based therapy.

This research delves into the global understanding of smart education from various perspectives, including expert viewpoints, policy dimensions, public datasets, and visions of equity and inclusion. Multiple webinars have revealed that the concept of smart education with a shared vision of quality education in the age of AI is being understood by different countries through diverse cultural, technological, and pedagogical lenses. We collected 48 topical digital education policies from Africa, the Americas, Asia-Pacific, and Europe and conducted coding analysis on inspective digital education policies for smart education to find that creating a high-quality, inclusive, and sustainable digital education ecosystem is the main concern in digital education policy vision and plan. Infrastructure development and human capacity building are also integral to digital education policies. Analysis of public datasets identified a global framework for tracking smart education encompassing 10 indicators and 30 sub-indicators was identified which coincide well with the GSE datasets covering 58 observing data points. Additionally, we organized a series of webinars with participants from 13 countries and explored specific cases to find pathways to achieve Sustainable Development Goal 4.

IntroductionSocial determinants of health (SDOH) are the conditions in which individuals are born, grow, work, live, and age.MethodsWe examined the literature on the association between SDOH and survival of patients with gastrointestinal (GI) cancer [esophageal, duodenal and gastric cancer (GC)] in the United States from 2001 to 2022.ResultsFrom 38,654 studies across COCHRANE, EMBASE, SCOPUS, WEB OF SCIENCE, and PubMed, we identified 14 relevant studies focusing on GI cancer using the PRISMA flowchart. Eight of the 12 GC studies specifically focused on gastric adenocarcinoma (GAC), the most common histologic subtype. Uninsured patients had a significantly worse overall survival probability. For patients with GI cancer, the highest income level (i.e., in the highest quartile) was associated with improved survival. Being unmarried had a negative impact on overall survival. Overall, people with insurance, higher incomes, and who were married had better overall survival rates.DiscussionOur findings suggest a clear association between SDOH and survival for patients with GI cancers. However, there is great variability in the factors studied and how these are measured and reported. A better understanding of SDOH is needed to design strategies with an aim to improve patient outcomes.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, PROSPERO (CRD42022346854).

IntroductionRecent interest in the diverse ecosystem of bacteria, fungi and viruses that make up the skin microbiome has led to numerous studies investigating the skin microbiome in healthy skin and in dermatological conditions. However, skin microbiome analysis is challenging due to relatively low numbers of skin microorganisms compared to mucosal sites, such as the respiratory or gastrointestinal tracts. Microbiome results are heavily influenced by sampling methods. Previous sampling methods include that of cotton swabs, tape stripping, patch sampling and punch biopsies. It is essential to have a standardised sampling method for microbiome studies to have comparable results between studies. Two non-invasive methods of sampling the skin microbiome; a skin scraping versus a flocked swab were chosen as methodologies likely to be efficient, effective, and easy to access for future skin microbiome studies in children. Here we compare the two sampling methods to describe the composition of the skin microbiome in healthy children.MethodSamples were collected from six healthy children aged three to nine years from the skin overlying the cubital fossa, cheek and axilla using (i) flocked swabs and (ii) skin scrapings with a glass slide. Samples were collected from the left and right sides of the body at two separate time points, one week apart. Quantitative PCR of the gene encoding 16S ribosomal ribonucleic acid (rRNA) was performed to compare the bacterial load collected by each sampling method. Full-length 16S rRNA gene amplicon sequencing was performed to compare the relationship of sampling method and time with the diversity and ecology of bacteria between different body sites.ResultsFrom six children, 78 flocked swabs and 78 skin scraping samples were collected, along with details of their overall health and skin care practices. qPCR results indicated higher total bacterial load from flocked swabs compared with skin scrapings. Flocked swabs and skin scraping methods had very similar bacterial compositional profiles. The skin microbiome was diverse between individuals and remained relatively stable within individuals over time.DiscussionOverall, results were similar between sample types, however bacterial DNA yield was higher for flocked swab samples (compared to skin scraping methods) and with a simpler protocol is the preferred sampling method for future studies.

ABSTRACT Controlled human infection (CHI) models can provide insights into transmission of pathogens such as Streptococcus pyogenes (Strep A). As part of the Controlled Human Infection with Penicillin for Streptococcus pyogenes (CHIPS) trial, we explored the potential for transmission among participants deliberately infected with the Strep A emm75 strain. Three approaches to understanding transmission were employed: the use of agar settle plates to capture possible droplet or airborne spread of Strep A; measurement of distance droplets could spread during conversation; and environmental swabbing of high-touch items to detect Strep A on surfaces. Of the 60 (27%) CHIPS trial participants across five cohorts, 16 were enrolled in this sub-study; availability of study staff was the primary reason for selection. In total, 189 plates and 260 swabs were collected. Strep A was grown on one settle plate from a participant on the second day, using plates placed 30 cm away. This participant received the placebo dose of penicillin and had met the primary endpoint of pharyngitis. Whole-genome sequencing identified this to be the challenge strain. Strep A was not detected on any swabs. In this small sample of CHI participants, we did not find evidence of Strep A transmission by the airborne route or fomites, and just one instance of droplet spread while acutely symptomatic with streptococcal pharyngitis. Although these experiments provide evidence of minimal transmission within controlled clinical settings, greater efforts are required to explore Strep A transmission in naturalistic settings.IMPORTANCEStreptococcus pyogenes remains a significant driver of morbidity and mortality, particularly in under-resourced settings. Understanding the transmission modalities of this pathogen is essential to ensuring the success of prevention methods. This proposed paper presents a nascent attempt to determine the transmission potential of Streptococcus pyogenes nested within a larger controlled human infection model.

Introduction In children, obstructive sleep apnea (OSA) is a sleep-related breathing disorder that is caused by adenotonsillar hypertrophy and is characterized by upper airway obstruction disturbing sleep.

Background Mental health (MH) conditions are prevalent in adolescents with childhood-onset SLE (cSLE). Early identification is crucial in preventing poor patient outcomes; however, MH screening rates remain low.Local problem From July 2021–January 2022, only 15% of adolescents in a paediatric tertiary care cSLE clinic were being screened for depression and anxiety. By November 2023, we aimed to increase the percentage of patients with cSLE (≥12–18 years) screened for depression (Patient Health Questionnaire: PHQ-9) and anxiety (Generalised Anxiety Disorder-7: GAD-7) from 15% to 80%.Methods This quality improvement project employed the Model for Improvement framework. Stakeholders included the clinic team, patients and families, and MH providers. Statistical process control charts were used to analyse the outcome measure for percentage of screened patients with cSLE. Patient and caregiver satisfaction surveys were conducted at baseline and after screening as a balancing measure.Interventions MH screening workflow with a referral algorithm was developed with stakeholders. Additional interventions included two MH training workshops for healthcare providers and a preclinic reminder of eligible patients for screening.Results Over 21 months, 146 patients with cSLE completed 270 MH screens, increasing the screening rate from 15%, peaking at 100%, to a median of 56%. Sixty-six individuals (45%) reported symptoms of depression and/or anxiety on their initial screen. Of 270 screens, 44 individuals (17%) reported moderate to severe symptoms meeting the screening workflow criteria for referral to a MH service; 10% of patients screened were referred and seen by the MH service within 2–12 weeks. Patients and caregivers reported satisfaction with the MH screening process and quality of MH follow-up.Conclusion Despite not sustainably meeting the target, MH screening rates increased in the cSLE clinic by nearly fourfold, demonstrating feasibility and acceptability. Patients expressed satisfaction with their mental health follow-up, emphasising its importance in their care.

BackgroundPoint of care hemoglobin meters play key roles in increasing access to anemia screening in antenatal care especially in settings with limited access to laboratories. We aimed to determine the diagnostic accuracy of a non-invasive spot-check hemoglobin (SpHb) meter, Masimo Rad-67® Pulse CO-Oximeter®, in the diagnosis of anemia in pregnant women attending antenatal care clinics in Kilifi, Kenya.MethodsThis was a diagnostic accuracy study that retrospectively evaluated SpHb against a validated reference standard of laboratory assessed hemoglobin (Lab Hb) by a SYSMEX XN-330 automated hematology analyzer. The study was nested within a prospective pregnancy cohort study that recruited unselected pregnant women from antenatal care clinics in two public hospitals in Kilifi County, coastal Kenya. Records with both SpHb and Lab Hb were selected from pregnancy visits between May 2021 and December 2022. Linear regression and Bland-Altman analysis were performed to compare the two tests and diagnostic accuracy parameters obtained for the diagnosis of anemia.ResultsA total of 2,975 records (from 2,203 unique participants), with paired SpHb and Lab Hb were analyzed. Linear regression showed a significant but weak positive correlation, a proportional bias of 0.44 (95% CI 0.41–0.47) and a constant of 7.59 (95% CI 7.30–7.87, p

ObjectivesThe objective of this study was to evaluate global longitudinal publication trends in oncology in the Cochrane Database of Systematic Reviews (CDSR) from 2001-2020.DesignRetrospective bibliometric analysis.Primary and secondary outcome measuresThe primary outcome measures were the numbers and percentages of women as first, last, and corresponding author across all CDSR oncology publications. Additional outcomes included authorship differences between countries and percentages of women authors over time compared using the Cochran-Armitage trend test.ResultsIn total, 548 articles were analyzed. Women were first authors in 52.26% (n=277) and corresponding authors in 50.75% (n=272), respectively. Women represented only 39.4% (n=210) of last authors, significantly less frequent than male counterparts (p < 0.001). The percentage of women last and corresponding authors has increased significantly in the past 20 years (p < 0.05). Countries such as the Netherlands and Australia consistently showed equitable representation in first, corresponding, and last authorship, while other countries such as Italy and China had uniformly low rates of female authorship.CoclusionsOur results highlight patterns of gender inequity in oncology publication authorship in the CDSR from 2001-2020 at a global level. Notably, women were less likely to serve in the last author position which, independent of assigned corresponding authorship, is generally assumed in academic oncology to designate the leader of a published study. Substantive efforts to correct this disparity are needed to achieve gender parity in publicly perceived leadership in oncology publications.