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Ultrahigh energy-storage dielectric ceramics via synergistic polymorphic nanodomain and defect design

Feed management practices used for dairy cows in confined dairies in Brazil

Despite the critical role that feeding and feed bunk management practices play in dairy herd performance, limited information is available on how these practices are implemented across different production levels in Brazilian confined dairy systems. We aimed to gather information on the producers ‘reported feeding practices used on confined dairy operations and identify their relationship with average herd milk production. An electronic survey of 38 questions was emailed to 500 Brazilian dairy producers. Out of the 135 responses received, answers from 82 producers were included, and herds were ranked according to their 305-d milk production (kg) as low (LP; < 7,000; n = 27), medium (MP; 7,000–10,000; n = 35), and high production (HP; > 10,000; n = 20). The HP and MP herds had greater odds of evaluating particle size distribution, forage DM, TMR physically effective fiber NDF (peNDF), corn kernel processing, and having a water trough wash protocol and cooling system than LP herds. The HP herds had greater odds of grouping primiparous separated than LP herds. The feed refusals and frequencies of feed efficiency, feed bunk clean-up, and TMR peNDF were similar among herds. The HP producers reported a greater feeding frequency, feed push-up, and cleaning water troughs than MP and LP, respectively. Producers reported evaluating forage DM monthly and when a new silo was opened, regardless of milk production level. In conclusion, this survey demonstrates that producers of HP and MP herds showed a greater frequency of use of feeding management practices than those of LP herds. Furthermore, survey results can be used to develop and disseminate target information on feeding practices and feed bunk management in dairy operations.

Confined-hydrogel fluidic memristor crossbar array for neuromorphic computing

A computational method to estimate the relative biological effectiveness and tumor control probability for low-LET proton irradiations

A constant relative biological effectiveness (RBE) value of 1.1 is used for proton therapy (PT) in many clinical treatment plans. However, several studies show that RBE varies with proton energy, linear energy transfer (LET), and oxygen concentration. This study presents a computational method based on the linear quadratic (LQ) and repair-misrepair-fixation (RMF) models to calculate tumor control probability (TCP) under varying oxygen conditions. We analyze the impact of hypoxia on the parameters of the LQ model, focusing on the ratio and RBE. The proposed method allows for TCP calculations across different oxygen concentrations and for various ion therapies, such as proton and carbon ion therapy. Our results show that increasing the LET from 1 to 12 keV/μm enhances TCP from 61% to 98% under aerobic conditions (21% O 2 ), 45% to 98% under moderately hypoxic conditions (2% O 2 ), and from 1% to 48% under severely hypoxic conditions (0.1% O 2 ). These findings are compared with clinical trial data, demonstrating that hypoxia significantly affects TCP for low-LET radiations.

Structural mechanism of substrate binding and inhibition of human taurine transporter

Comparison of CD34+ cell enumeration between flow cytometric analysis and ADAMII-CD34 image-based fluorescence cell counter

Background Accurate CD34 + cell enumeration is essential in stem cell transplantation. Flow cytometry (FC) is the standard method to determine optimal collection time of CD34 + stem cells harvesting for peripheral blood stem cell (PBSC) transplantation but is costly and requires skilled personnel. The ADAMII-CD34 cell counter may be a feasible alternative for PBSC apheresis samples and for cryopreserved stem cell products which are assessed by manual cell viability counting using the trypan blue exclusion method. Methods Fifty samples were analyzed (PBSC apheresis samples n = 25, cryopreserved stem cell products n = 25) from patients undergoing autologous PBSC transplantation or healthy donors. We assessed the quantitative agreement between methods. Results In the 25 PBSC apheresis samples, FC-based median viable CD34 + absolute count was 764.7 cells/µL (IQR 453.7–1532.5; range 60.5–3233.8). ADAMII-CD34 cell counter and FC showed almost perfect agreement [Lin’s concordance correlation coefficient (CCC) 0.99 (95% CI: 0.98 to 1.00), bias –0.46% (95% CI: –5.45 to 4.53), upper limit of agreement (LoA) 22.2% (95% CI: 13.5 to 30.8), and lower LoA –23.1% (95% CI: –31.7 to –14.4)]. For cryopreserved stem cell products, viable CD34 + cell dose (×10 6 cells/kg) measured by the ADAMII-CD34 cell counter and the estimated viable CD34 + cell dose (×10 6 cells/kg) determined by the trypan blue exclusion method showed poor agreement [Lin’s CCC 0.58 (95% CI: 0.31 to 0.76)]. Weighted Deming regression showed proportional bias [95% CI: slope 0.02 to 0.61]. Conclusions Quantitative agreement between the ADAMII-CD34 cell counter and FC for CD34 + enumeration in PBSC apheresis samples was acceptable within the analyzed range. It is user-friendly and more affordable than FC. However, ADAMII-CD34 and the trypan blue exclusion method of cryopreserved stem cell products showed a proportional bias. Further considerations are needed to optimize the process for cryopreserved stem cell products.

Dalpiciclib plus chidamide in HR + /HER2−advanced breast cancer after CDK4/6 inhibitor failure: a phase Ib trial

Abstract The optimal therapy after cyclin‑dependent kinase 4/6 inhibitor (CDK4/6i) failure in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR + /HER2 − ) advanced breast cancer (BC) remains undefined. In this study, we demonstrate that dalpiciclib combined with chidamide exerted synergistic antitumor effects in estrogen receptor-positive (ER + )/HER2 − BC cell lines and patient-derived organoids, providing a rationale for subsequent clinical evaluation. We conducte a single‑arm, phase Ib, Bayesian optimal interval dose‑escalation study (NCT05586841) evaluating dalpiciclib plus chidamide across four groups [A, 125 mg dalpiciclib mg/d and chidamide 25 mg twice a week (BIW); B, dalpiciclib 125 mg/d, chidamide 20 mg BIW; C, dalpiciclib 100 mg/d, 25 mg chidamide BIW; D, dalpiciclib 100 mg/d, chidamide 20 mg BIW]. The primary endpoint is maximum tolerated dose (MTD), and the secondary endpoints are objective response rate (ORR), progression‑free survival (PFS), disease control rate and safety. Among 22 enrolled patients, dose‑limiting toxicities occur in 3 patients, and the MTD is identified as group C. Grade 3–4 adverse events include neutropenia (100%), leukopenia (64%), and thrombocytopenia (36%). The ORR is 9.1% overall and 16.7% at the MTD, with median PFS of 5.8 months overall and 12.3 months at the MTD. Patients with PIK3CA mutations have shorter mPFS [5.04 months; 95% CI: 2.0−not estimable (NE)] compared to those with wild type (9.25 months; 95% CI: 1.97–NE). Here we show that dalpiciclib plus chidamide has manageable safety and preliminary antitumor activity in HR + /HER2− advanced BC following CDK4/6i failure.

Development of a survey and worry score to evaluate physician burnout and wellness interventions during COVID-19 in the Rio Grande Valley: A pilot study

Background Current research on physician burnout is limited in rural communities and physicians caring for the medically underserved. This study aimed to create an instrument to quantify the rate of physician burnout during the COVID-19 pandemic and identify effective coping interventions in an underserved mixed rural-urban region along the Texas–Mexico border. Methods We conducted a regional study in a sample of US physicians using a structured questionnaire developed by a multidisciplinary group. Thirty-one participants were contacted over a five-week period between December 2022 to January 2023. Participants self-selected based on their experiences of burnout during various phases of the COVID-19 pandemic (e.g., Initial Surge, Lock Down, Adjustment Period, Vaccine Distribution, Delta Variant, Booster Available). A 5-point Likert scale was used to assess and rank the perceived effectiveness of services employed to cope with burnout and its negative implications. Results We found that 43% of participants experienced burnout during the COVID-19 pandemic, with flexible schedules and personal wellness being the top alleviators of burnout. The survey showed good internal consistency and reliability (Cronbach’s alpha coefficient = 0.7680), McDonald’s omega was 0.80, and identified three “worry types” through latent factor analysis. Worry types included: (1) physicians with a desire to self-preserve but showed negative coping, (2) physicians with a desire for occupational harmony but with concerns about patient safety, and (3) physicians with concerns about personal safety and their mortality potential. Additionally, latent factor analysis showed that 9 questions from the survey could be used to create a Worry Score to classify burnout and coping strategies related to the COVID-19 pandemic. Conclusion These findings suggest that healthcare administrators and policymakers should prioritize implementing and promoting flexible work schedules and opportunities for personal time as part of comprehensive strategies to improve physician wellness and mitigate burnout. Additional research is needed to determine the effectiveness of the interventions in addressing physician burnout.

Ultrathin crown ether-based polyamide membrane for ion-ion separations

Abstract Membrane-based liquid separations that selectively extract valuable ionic species from water can enhance resource circularity across industries. However, commercial membranes lack the selectivity required to target specific ions. Here we design crown-ether-based polymeric membranes for ion–ion separations using principles inspired by biological ion channels. Ultrathin membranes (~6 nm) are fabricated via interfacial polymerization of crosslinked 18-crown-6 units. The membranes preferentially sorb and transport potassium, which forms the most stable complexes with the crown ether motifs. Sorption experiments show strong potassium preference in mixed-salt environments, where competitive interactions increase selectivity. Transport measurements demonstrate selective permeation of potassium over competing monovalent and divalent cations, with selectivities of ~4 over cesium and lithium. The combination of ultrathin architecture, high crosslinking degree, and high binding-site density enables this behavior. This work establishes interfacial polymerization as a strategy to incorporate macrocycles into membranes for precise ion separation.

Assessment of compliance with quality laboratory standards in medical laboratories within the Kumasi Metropolis, Ghana

Background In Ghana, medical laboratories are a vital component of the health system, but there has been limited evidence on how well they meet international quality standards. This study assessed compliance with laboratory standards by medical laboratories in the Kumasi Metropolis of Ghana. Methods A descriptive cross-sectional survey was conducted among forty-three (43) laboratory facilities, including those operating within healthcare facilities and private standalone laboratories, in the Kumasi metropolis from 8th March to 26th November, 2021. The healthcare facilities assessed include seven (7) government, four (4) Christian Health Association of Ghana (GHAG), twenty-one (21) private hospitals, and eleven (11) standalone laboratories. The World Health Organisation Stepwise Laboratory Quality Improvement Process Towards Accreditation (WHO SLIPTA) checklist was used to assess compliance with laboratory standards. The checklist comprises 12 main sections, containing 117 questions, resulting in a total of 275 scores. Each item is awarded a point value of 2, 3, or 5 points based on relative importance and complexity. Scores and percentages of compliance are categorized as follows: 0–150 (<55%), 151–177 (55–64%), 178–205 (65–74%), 206–232 (75–84%), 233–260 (85–94%), and 261–275 (≥95%). These categories ultimately translate to a rating of 0–5 stars. Descriptive analysis and the Kruskal-Wallis test were conducted to examine the differences in overall compliance scores across the types of health facilities. Results The overall median compliance score was 61(interquartile range 53–66), the minimum score was 49, and the maximum score was 104. CHAG facilities had significantly higher scores than private facilities (Z = 2.53, p = 0.03) and standalone facilities (Z = 3.60, p < 0.001). Similarly, scores for government facilities were significantly higher than standalone facilities (Z = 3.30, p < 0.001). Conclusion All facilities had a zero (0) star rating and failed to meet the minimum compliance level of 55%.

Transcriptional competence defines the heterochromatin nucleating potential of isolated MSR units

Abstract In mouse cells, constitutive heterochromatin is associated with underlying arrays of A/T-rich DNA repeat elements, called the major satellite repeats (MaSat or MSR). We examine >18,000 MSR copies in mouse ES cells and identify that heterochromatin forms only at transcriptionally competent MSR units. To directly dissect the function of MSR DNA, we insert isolated MSR units into an inert genomic region that is repeat- and gene-free. Insertion of three or more intact MSR units induces heterochromatic histone marks, recruitment of HP1 and incorporation of histone H1. Only transcriptionally competent MSR units, but not permutated MSR variants or LINE1 5’UTR elements, nucleate de novo heterochromatin. MSR-derived transcription is bi-directional and MSR-originating transcripts are attenuated by the RNAPII-associated Integrator complex. Instructively, multi-copy intact MSR units impart an unwound DNA template that facilitates RNAPII engagement. Together, this study uncovers a DNA/RNA-based logic and transcription-coupled mechanism for the nucleation of heterochromatin.

Pooled prevalence and co-occurrence of diarrhea and wasting and its associated factors among children aged 6–24 months in East Africa: Insight from recent demographic health survey: A multilevel analysis

Background Young children experiencing both diarrhea and wasting (DW) are at increased risk of severe malnutrition, impaired immune function, and greater susceptibility to infections. This dual burden of illness significantly impacts their health, survival, and development. Diarrhea and wasting are often interlinked, with one exacerbating the other, leading to various cycle of malnutrition and frequent infections.in the long term, these conditions contribute to stunted growth delayed cognitive development and decreased survival rates. Given the vulnerability of children aged 6–24 months, addressing the dual burden of diarrhea and wasting is crucial for improving child health outcomes. This study aims to investigate the pooled prevalence and associated factors of diarrhea and wasting multimorbidity (DW) among children aged 6–24 months in East Africa. Methods A pooled prevalence analysis was conducted using data from the Demographic and Health Surveys (DHS) across 11 East African countries, including a total weighted sample of 78,982 children aged 6–24 months. Given hierarchical structure of the DHS data, a multilevel binary logistics regression model was employed to identify significant factors associated with DWM. The Intra-class correlation (ICC), Median odds ratio (MOR), and LogliklihoodRatio (LLR), AIC and Deviance test were used to compare model fit and assess the contribution of different levels of variability. In bivariate analysis factors with p-value<0.2 were selected for inclusion in the multivariable multilevel logistics regression model. The final model provided the Adjusted Odds Ratios (AOR) with Corresponding 95% Confidence Intervals (CIs) to indicate the strength and directions of significance associations. Result The pooled prevalence of diarrhea and wasting co-occurrence (DW) among children aged 6−24 months in East Africa was 11% (95% CI: 10.8%−11.2%), with country-specific prevalence ranging from 3% in Zimbabwe to 17% in Malawi. Several factors were significantly associated with increased odds of DWM. Male children had an 84% higher risk of DWM (AOR 1.84; 95% CI: 1.69–2.02). Children born to mothers with no formal education (AOR 3.33; 95% CI: 2.30–4.81) or with primary (AOR 2.12; 95% CI: 1.59–2.74) or secondary education (AOR 1.47; 95% CI: 1.16–3.03) also had increased odds of DWM. Inadequate sanitation facilities, such as unimproved latrine facilities (AOR 1.47; 95% CI: 1.31–1.65) and unimproved water sources (AOR 1.47; 95% CI: 1.31–1.64), were similarly associated with higher odds of DWM. Additionally, not initiating breastfeeding in a timely manner was linked to increased odds of DWM (AOR 1.25; 95% CI: 1.10–1.41). Conversely, certain factors were associated with a reduced risk of DWM. Children living in rural areas had lower odds of DWM (AOR 0.85; 95% CI: 0.68–0.94). Additionally, children residing in Mozambique (AOR 0.59; 95% CI: 0.45–0.75) and Rwanda (AOR 0.57; 95% CI: 0.42–0.77) were less likely to experience DWM. Conclusion The study highlighted that the co-occurrence of diarrhea and wasting among children aged 6–24 months represents a significant public health issue in East African countries. To address this challenge, public health interventions focusing on improving maternal education, enhancing sanitation facilities, and promoting timely breastfeeding practices are essential for reducing the burden of diarrhea and wasting multimorbidity.

A disease-agnostic approach to ensemble learning for infectious disease forecasting

Abstract Accurate forecasting of infectious diseases drives modern public health interventions that reduce morbidity and mortality. However, accurate forecasting in real-time remains a challenge for the modeling community. Ensembling has emerged as a critical tool for accurate forecasting by leveraging multiple component (individual) models into a single weighted average. Traditional ensembling strategies have relied on bespoke component models that weight the contributions of individual models according to extensive historical data for specific diseases. This is impractical for an emerging disease, since there would be very little – if any – data. We propose an ensembling strategy, called epiFFORMA , that determines component weights for an ensemble model without historical data and is therefore disease-agnostic. The epiFFORMA model builds upon the FFORMA model from the M4 forecasting competition to harness epidemiological dynamics through synthetic data. We demonstrate that epiFFORMA performs better than a naive, equal-weighting ensembling strategy when forecasting outbreaks of COVID-19, diphtheria, influenza-like illness, dengue, measles, mumps, polio, rubella, smallpox, and chikungunya. We further show that epiFFORMA, on average, performs better than the individual component models in the ensemble.

Sex differences in physical fitness among 10,000 adolescents aged 13–15 years

Physical fitness during adolescence is critical for health and sports participation, with sex-specific developmental trajectories influencing performance. The aim of this cross-sectional study was to examine sex differences in physical fitness among non-athletic adolescents aged 13–15 years and to provide reference values for fitness parameters across age and sex. We assessed 9,669 non-athletic adolescents (64% females) aged 13–15 years. Fitness tests included Sargent jump, standing long jump, 30m sprint, medicine ball chest throw, and 6-minute shuttle run. Interactions between sex and age were analyzed using two-way ANOVA, with effect sizes (Cohen’s d ) and mean differences calculated between 13–15 years of age. Pearson correlation coefficients were used to examine relevant relationships, and were compared between sexes using Fisher’s r-to-z transformation. Significant sex-by-age interactions were observed for all fitness parameters (p < 0.001). Boys showed greater differences than girls from 13 to 15 years, with mean differences for Sargent jump (7.0 vs. 1.6 cm), standing long jump (28 vs. 7 cm), 30m sprint (−0.54 vs. −0.01 s), medicine ball throw (1.6 m vs. 0.4 m), and 6-minute shuttle run (2.0 vs. −0.3 laps). Height correlated moderately with the power-based tests in both sexes (p < 0.001), particularly in boys (R = 0.21 to 0.56 depending on age and test), but not with endurance. Correlations between tests were stronger (p < 0.01) in boys for all comparisons except medicine ball throw vs. shuttle run. We conclude that boys show larger fitness differences from 13 to 15 years of age than girls, likely due to pubertal changes that increase stature and improve muscle mass and body composition. These reference values serve as a basis for sex-specific interventions to improve adolescent health, performance, and sports participation.

High-resolution phage-host assignment through key proteins using large language models

What is the appropriate timing for advance care planning according to patients and their relatives? A scoping review

Background Advance care planning (ACP) is often initiated in the last phase of life. However, patients and relatives may need earlier conversations about their care preferences in the disease trajectory. Objective To synthesize empirical research on the appropriate timing of ACP from the perspective of patients and relatives. Additionally, we investigated facilitators, challenges, and triggers related to that timing. Design and method A scoping review was conducted using PubMed and CINAHL databases (up to April 2023; updated June 2025). Eligible studies focused on ACP timing from the perspectives of patients with cancer, heart or lung disease, and relatives. Two researchers independently screened papers and extracted data. Extracted data were clustered using thematic analysis. Results: In total, 29 papers were included. Both patients’ and relatives’ perspectives regarding the appropriate timing of initiating ACP varied widely and encompassed the entire continuum from healthy state, through illness, until the end of life. Timing related facilitating factors for initiating ACP were: clear information about prognosis, readiness, ACP as part of standard care, and clarity about who initiates ACP. Timing challenges were categorized as patient- (individual needs, coping, mutual protection), illness- (prognosis or illness related uncertainty) and professional-related (reluctance, time constraints). Additionally, patient-related (age, experiences in life) and trigger points in illness were identified. Conclusion The wide range of perspectives regarding appropriate timing of ACP requires a personalized approach. Clinical triggers may provide guidance, though they are not universally applicable. Professionals should timely and regularly explore patients’ preferences and readiness for initiating ACP conversations.

AP-1 mediates cellular adaptation and memory formation

Abstract Cellular responses to environmental stimuli are typically thought to be governed by genetically encoded programs. We demonstrate that cancer cells can form and maintain cellular memories when becoming drug resistant, exhibiting characteristics of cellular learning that are dependent on the transcription factor AP-1. We show that cells exposed to a low dose of therapy adapt to become resistant to a high dose, demonstrating that cells can adapt during this time of stress. The application of therapy itself results in the encoding of transient gene expression into cellular memory and that this encoding occurs for both transiently induced and probabilistically arising expression. Chromatin accessibility shows concomitant persistence. A two-color AP-1 reporter system shows that these memories are encoded in cis , constituting an example of activating cis epigenetics. Our findings establish the formation and maintenance of cellular memories as a critical aspect of gene regulation during the development of therapy resistance.

Patient satisfaction among national health insurance enrollees in an accredited hospital of Kathmandu Valley: A cross-sectional, mixed methods study

Background The national health insurance program was piloted in 2016 in Nepal with a political commitment of reducing out-of-pocket expenditure and improving access to quality healthcare services. However, it has been facing challenges of declining renewal rates and high drop-outs over the years. The study sought to assess patient satisfaction and factors influencing satisfaction among national health insurance enrollees. Method A sequential explanatory mixed methods study was conducted in a provincial government hospital of Nepal. Patient satisfaction was first assessed among 391 insured patients, followed by in-depth interviews with seven healthcare providers to explore barriers to healthcare provision underlying the observed levels of patient satisfaction in quantitative survey. Both insured patients and providers were purposively selected. Quantitative data was analyzed using descriptive and bivariate analysis, as well as ordinal logistic regression, while qualitative data were analyzed thematically. Lastly, an integrative analysis was undertaken to synthesize and draw inferences from both the quantitative and qualitative findings. Findings The satisfaction was recorded as highest in the domain of interpersonal manner (79.54%) and lowest in the domain of accessibility and convenience (32.33%). Medicine availability stood as a strong predictor of patient satisfaction across multiple satisfaction domains which was validated by the qualitative findings. Qualitative findings revealed barriers to provision of healthcare including explanations to the observed levels of satisfaction: limited resources, medicine stock-outs, delays in reimbursement, and ex-post moral hazard among service users. Interpretation The study gives insights into both patient-based and provider-based determinants of patient satisfaction. The findings provide recommendations for maintaining an uninterrupted medicine supply chain under the insurance benefit package and necessitate the allocation of enrollees according to the human resource capacity of health institutions which can influence the perceived quality of health services for the long-term sustainability of the insurance program.

Distinct roles of cortical layer 5 subtypes in associative learning

Abstract Adaptive behavior relies on associating sensory cues with rewarding or aversive outcomes. In mammals, the primary sensory cortex processes stimuli and distributes information to cortical and subcortical targets. Layer 5 (L5) contains two major projection neuron classes, intratelencephalic (IT) and extratelencephalic (ET); however, their roles in associative learning remain unclear. Using transgenic mice, we identified IT and ET neurons in primary somatosensory cortex and tracked their activity with longitudinal two-photon imaging during Pavlovian conditioning with whisker stimulation. IT neurons stably encoded stimulus identity across training, whereas ET neurons showed dynamic changes that paralleled the emergence of anticipatory licking. Chemogenetic silencing of each subtype impaired learning in distinct, phase-specific ways. A reinforcement-learning model reproduced these dynamics, suggesting that IT neurons provide stable sensory representations needed to form cue-reward associations, while ET neurons encode reward expectation to refine behavior. These findings reveal complementary, cell-type-specific contributions of L5 neurons to associative learning.

Machine learning of factors for improving oyster hatchery production

Oyster aquaculture and restoration in the Chesapeake Bay are vital, yet hatcheries frequently struggle with inconsistent larval growth and sudden mass mortality events. Unpredictable disruptions in larval production cause large economic losses, represent a perceived risk to growers, and impede industry expansion. To better understand associations between production yield and its potential predictors, we applied machine learning (random forest, and neural network) and statistical (generalized additive model) models to a comprehensive dataset of environmental, water quality, and operational parameters from a Maryland oyster hatchery, aiming to identify key yield predictors and develop a robust forecasting tool. We used recursive Boruta algorithm for variable selection, pinpointing critical predictors, and employed cross-validation to fine-tune model settings. Shapley value analysis offered crucial insights into model interpretations, highlighting week number, Normalized Difference Vegetation Index, salinity, turbidity, and fecundity as primary drivers of yield variability. For low-yield cases, salinity-related variables were particularly important. Our findings provide an early warning system for potential production downturns, empowering hatchery operators to make data-driven decisions for optimizing water conditions, feeding schedules, and broodstock management. By boosting predictability and efficiency, this research directly supports economic stability of the oyster industry and ecological health of the Chesapeake Bay.