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The structural diversity of psychedelic drug actions revealed

Person-centered occupational therapy intervention for the prevention of delirium and improvement in occupational performance in elderly patients admitted to an intensive care unit: A randomized controlled single-blinded trial protocol

Among the deleterious effects caused by hospitalization of elderly patients in intensive care unit (ICU), delirium and impaired performance in occupations are frequent and have long-term negative outcomes. Delirium protocols described in the literature vary in frequency, intensity, and content regarding pertinent interventions. Occupational Therapy (OT) practices are heterogeneous and generally consist of non-personalized interventions. For this reason, the primary outcome of this research is to evaluate the effect of a person-centered OT protocol on the prevention of delirium and the occupational performance of elderly patients admitted to the ICU. This is a randomized clinical trial with blinded assessment of the primary outcome (delirium). A total of 114 patients will be recruited and randomized to the intervention group, where care goals will be defined according to meaningful occupations and personalized cognitive stimulation will be based on patient´s topics of interest, in addition to the institutional standard protocol (ISP); or to the control group, which will receive only the ISP. To our knowledge, this will be the first randomized controlled trial with personalized occupational therapy interventions, as well as care goals, based on patients´ meaningful occupations for the prevention of delirium and improvement of occupational performance in critically ill elderly patients. This clinical trial is duly registered on the ClinicalTrials.gov platform (NCT06479031).

Orally delivered toxin–binding protein protects against diarrhoea in a murine cholera model

Abstract The ongoing seventh cholera pandemic, which began in 1961, poses an escalating threat to public health. There is a need for new cholera control measures, particularly ones that can be produced at low cost, for the one billion people living in cholera-endemic regions. Orally delivered VHHs, functioning as target-binding proteins, have been proposed as a potential approach to control gastrointestinal pathogens. Here, we describe the development of an orally deliverable bivalent VHH construct that binds to the B-pentamer of cholera toxin, showing that it inhibits toxin activity in a murine challenge model. Infant mice given the bivalent VHH prior to V. cholerae infection exhibit a significant reduction in cholera toxin–associated intestinal fluid secretion and diarrhoea. In addition, the bivalent VHH reduces V. cholerae colonization levels in the small intestine by a factor of 10. This cholera toxin–binding protein holds promise for protecting against severe diarrhoea associated with cholera.

Low morphology does not lower success after intrauterine insemination unless inseminating motile sperm count is low

The objective of this study was to determine the relationship between strict morphology as assessed on the initial semen analysis during fertility workup and pregnancy rates after intrauterine insemination. This is a retrospective study of couples undergoing intrauterine insemination from 2007 to 2012. Couple characteristics and semen analysis parameters were recorded and evaluated. Risk ratios (RR) and 95% confidence intervals (95% CI) were calculated, accounting for within-couple (cluster) correlation among repeated intrauterine insemination cycles. Four hundred thirty-five women (average ±  standard deviation age 31.7 ±  4.8) undergoing 1,287 intrauterine insemination cycles were analyzed. Fecundability was not statistically different when low strict morphology (≤1% and 2-4%) was compared to the reference range of morphology > 14% [RR 0.99 (0.41-2.40) and 0.90 (0.48-1.70)]. Results were unchanged when adjusted for female characteristics, medication, and inseminating total motile sperm count [aRR 1.22 (0.51-2.93) and 1.00 (0.53-1.91)]. Evaluating combined effects of morphology with inseminating total motile sperm count, pregnancy rates among cycles with total motile count <  5 million and strict morphology ≤  4% normal were reduced when compared to cycles with total motile count > 20 million and morphology > 4% normal (RR 0.37, 95% CI 0.17-0.82). These relationships remained when evaluating live birth/ongoing pregnancy per cycle. In intrauterine insemination cycles, initial strict morphology was associated with subsequent fecundability only when inseminating total motile count was below 5 million. For cycles with total motile count above this threshold, no impact of low morphology on success rates with intrauterine insemination was observed.

Real-time observation of the spin Hall effect of light using metasurface-enabled single-shot weak measurements

Modelling the potential impact of climate change on the productivity of soybean in the Nigeria Savannas

A well-calibrated and evaluated GROPGRO module of the Decision Support System for Agro-technological Transfer (DSSAT) was used to simulate productivity of soybean in northern Nigeria under climate change. Both historical (1990–2019) and projected climate scenarios from 5 general circulation models (GCMs) under two representative concentration pathways (RCP 4.5 and RCP 8.5) in the mid-century (2040–2069) and end of the century (2070–2099) periods were used. Depending on climate scenario, the minimum temperature is expected to rise by 1.7–4.4oC at Kano in the Sudan savanna (SS) agroecological zone (AEZ) and 1.4–4.0oC at Zaria in the northern Guinea savanna (NGS) AEZ, while maximum temperatures are projected to increase by 1.7–4.1oC in the SS and 1.3–3.6oC in the NGS. Seasonal average rainfall will increase by 4.8–14.5% in the SS and decrease by 2.6–3.8% in the NGS, relative to the baseline climate. The model predicted delaying trends for days to flowering and maturity for both varieties in all climate scenarios in the two AEZs. Despite the delay in flowering and increase in crop cycle length, climate change will result in grain yield reduction in most of the future scenarios. Across location, variety and time slice, the grain yield will decline by between 8.4 and 23.6% under RCP4.5 scenario, with much higher decline by between 28.7 and 51.4% under RCP 8.5 scenario. However, using the early maturing variety can reduce the adverse effects of climate change on grain yield. On average, the yield of the early-maturing TGX1835-10E is predicted to be 15.2% higher under RCP4.5 scenario and up to 21.7% under RCP8.5 than that of the medium-maturing TGX1951-3F for both centuries in the SS AEZ. In the NGS, the average yield of TGX1835-10E is predicted to be 9.0% and 7.5% higher than that of TGX1951-3F under RCP4.5 and RCP8.5 scenarios, respectively. Using early-maturing soybean varieties is a key management strategy to boost the resilience of soybean production in Nigeria’s savannas under climate change conditions.

Multiphasic condensates formed with mono-component of tetrapeptides via phase separation

Liver transplantation for NASH-related hepatocellular carcinoma versus non-NASH etiologies of hepatocellular carcinoma: A systematic review and meta-analysis

Background Non-alcoholic steatohepatitis (NASH)-associated hepatocellular carcinoma (HCC) has been emerging a predominant reason for liver transplantation (LT). The complexity of comorbidities in this population increases the possibility of poor transplant outcomes. The purpose of this study was to evaluate the differences in survival after transplantation among patients with NASH HCC and those with non-NASH HCC. Method We conducted systematic searches of the PubMed, Embase, Web of Science, and Cochrane Library databases. To analyze the data, both fixed and random-effects models were employed to aggregate hazard ratios (HRs) along with 95% confidence intervals (CIs) for recurrence-free survival (RFS) and overall survival (OS) outcomes. This study is registered with PROSPERO as CRD42024578441. Results A total of seven studies were included in this study. This study revealed that there was no significant difference in OS between liver transplant recipients with NASH HCC and those with non-NASH HCC. The RFS of NASH HCC patients were significantly longer. The HRs were 0.70 (95% CI: 0.51-0.97, P = 0.03) for RFS and 0.88 (95% CI: 0.72-1.07, P = 0.21) for OS, respectively. Conclusion This study indicates that patients with NASH HCC who undergo LT have comparable OS as those with non-NASH HCC, while NASH HCC was associated with increased RFS. However, further research in randomized trials is necessary to verify these results and address potential selection biases.

A wearable repetitive transcranial magnetic stimulation device

A framework to identify opportunities to address socioscientific issues in the elementary school curricula: A case study from England, Italy, and Portugal

Scientific literacy is crucial to address important and complex societal problems, both current and future. Teaching using a socioscientific issues (SSI) approach is a potential strategy to develop students’ scientific literacy, although teachers have reported concerns about its implementation, such as the inability to add additional distinct requirements to already demanding curricula. To facilitate this task, we describe the development of a valid and reliable instrument for curricula analysis, called “Framework for Identifying Opportunities to implement an SSI approach in science school curricula” (FIOSSI), and use it to identify opportunities to implement the SSI approach in the elementary school science curriculum of three European countries (England, Italy and Portugal). The framework categorizes SSI opportunities into three areas: 1) awareness of the issue; 2) socioscientific reasoning; and 3) socioscientific identity. Our analyses of the three countries’ elementary curricula reveal that the current versions have significant opportunities to explore awareness of SSI (especially relating to environmental and human health issues), promote the development of socioscientific reasoning, and foster socioscientific identity. FIOSSI can be a useful tool for education research and practice, and our results can help inform future research and guide educational policies.

Deciphering the folding code of collagens

Epidemiological dynamics of dengue in Peru: Temporal and spatial drivers between 2000 and 2022

Dengue, a vector-borne disease driven by climate change, urbanization, and the adaptation of its vector, Aedes aegypti, poses a significant public health challenge. This study analyzed 23 years (2000–2022) of epidemiological data from Peru to examine the temporal and spatial drivers influencing dengue reported cases. Using secondary data from the Peruvian Ministry of Health, 501,027 cases were stratified by clinical severity, gender, geographic distribution, and temporal trends. The Amazonian and coastal regions, particularly Loreto, Ucayali, and Piura, bore the highest burden, collectively accounting for more than 60% of cases during epidemic years. Seasonal spikes in transmission consistently aligned with the rainy season, underscoring the dependence of Aedes aegypti proliferation on climatic conditions. The analysis revealed progressive geographic expansion of dengue into previously low-risk areas, including Andean highlands and peri-urban zones, driven by climatic shifts and unregulated urbanization. Gender-based comparisons indicated a higher overall case burden among females, though severe forms of dengue were unequally observed in males, particularly in rural areas. Clinical classifications highlighted that 78% of cases presented without warning signs, 18% with warning signs, and 4% as severe dengue. Socioeconomic factors, such as inadequate sanitation, urban slums, and water storage practices, contributed significantly to vector breeding in high-burden areas. Moreover, the role of extreme climatic events, including El Niño, exacerbated outbreak intensity and duration. The findings emphasize the urgent need for innovative approaches and provides actionable insights into regional dynamics and highlights critical areas for research, including predictive climate-disease modeling and the integration of molecular surveillance. These strategies are essential to mitigating the growing dengue burden and strengthening public health systems in Peru and similar endemic regions.

In-depth insight into structure-reactivity/regioselectivity relationship of Lewis acid catalyzed cascade 4πe-cyclization/dicycloexpansion reaction

Vibrational exercise for Crohn’s to observe response (VECTOR): Protocol for a randomized controlled trial

Crohn’s disease (CD) is a long-term inflammatory gastrointestinal disorder, often adversely affecting physical, emotional, and psychological well-being. Pharmaceutical management is habitually adopted; although medicinal therapies require continuous administration, and are often associated with significant side effects and low adherence rates. Whole body vibration (WBV) represents a non-invasive technique, that provides vibration stimulation to the entire body. As WBV appears to target the physiological pathways and symptoms pertinent to CD epidemiology, it may have significant potential as a novel non-pharmaceutical intervention therapy in CD. This paper presents the study protocol for a randomised controlled trial investigating the impact of WBV on health outcomes in individuals with CD. This 6-week, parallel randomised controlled trial will recruit 168 individuals, assigned to receive WBV and lifestyle education 3 times per week compared to control, receiving lifestyle education only. The primary outcome of the trial will be the difference from baseline to post-intervention in health-related quality of life between the groups, assessed with the Inflammatory Bowel Disease Quality of Life Questionnaire. Secondary outcomes will include between-group differences in other questionnaires assessing fatigue, anxiety and pain, measures of physical fitness, and biological markers for disease activity and inflammation. Statistical analyses will follow an intention-to-treat approach, using linear mixed-effects models to compare changes between time points and both trial groups. Ethical approval was granted by the Nottingham Research Ethics Committee (REC: 24/EM/0106) and the study has been registered prospectively as a clinical trial (NTC06211400).

Recapitulating hypoxic metabolism in cartilaginous organoids via adaptive cell-matrix interactions enhances histone lactylation and cartilage regeneration

Evaluating and implementing machine learning models for personalised mobile health app recommendations

This paper focuses on the evaluation and recommendation of healthcare applications in the mHealth field. The increase in the use of health applications, supported by an expanding mHealth market, highlights the importance of this research. In this study, a data set including app descriptions, ratings, reviews, and other relevant attributes from various health app platforms was selected. The main goal was to design a recommendation system that leverages app attributes, especially descriptions, to provide users with relevant contextual suggestions. A comprehensive pre-processing regime was carried out, including one-hot encoding, standardisation, and feature engineering. The feature, “Rating_Reviews”, was introduced to capture the cumulative influence of ratings and reviews. The variable ‘Category’ was chosen as a target to discern different health contexts such as ‘Weight loss’ and ‘Medical’. Various machine learning and deep learning models were evaluated, from the baseline Random Forest Classifier to the sophisticated BERT model. The results highlighted the efficiency of transfer learning, especially BERT, which achieved an accuracy of approximately 90% after hyperparameter tuning. A final recommendation system was designed, which uses cosine similarity to rank apps based on their relevance to user queries.

Author Correction: Chimeric antigen receptor macrophages (CAR-M) sensitize HER2+ solid tumors to PD1 blockade in pre-clinical models

Enhanced prediction of thrombotic events in hospitalized COVID-19 patients with soluble thrombomodulin

We aimed to determine the predictive accuracy of elevated soluble thrombomodulin (sTM) and angiopoietin-2 (Ang2) for thrombotic events (TE) in hospitalized COVID-19 patients. We conducted a nested case-control study within a cohort of people admitted to hospital with COVID-19 from March 2020 to August 2022. The cases (people with TE within 28 days after hospital admission) were matched by propensity score to comparable patients without TE. We determined plasma levels of sTM and Ang2 in all available frozen samples, prioritizing the earliest post-admission samples, using an automated immunoassay technique. Among 2,524 hospitalized COVID-19 patients (43% females; median age 67 years), 73 had TE (incidence 1.15 events per 1000 patient-days of follow-up). Frozen plasma samples were available for 43 cases and 176 controls. Elevated plasma concentration of sTM was significantly associated with TE (2.8 [1.8, 4] vs. 1.52 [1.1, 2.65] ng/mL; p =  0.001) and mortality (median [Q1, Q3], 3.32 [2.16, 4.65] vs. 1.58 [1.11, 2.73] ng/mL; p =  0.001), while D-dimer showed a specific association with TE (2.3 [0.8, 7.4] vs. 0.75 [0.4, 1.6] mcg/mL; p =  0.001). In contrast, Ang2 was not associated with any of these events. The association with thrombotic events remained in adjusted models (HR [95%CI] per unit increase, 1.24 [1.04-1.47] for sTM; 1.07 [1.03-1.10] for D-dimer). The adjusted regression model that included both biomarkers, sTM and D-dimer, improved (AUC 73%, sensitivity 77% and specificity 65% for TE diagnosis; p =  0.007) the predictive capacity of the same model without sTM. In conclusion, determination of soluble thrombomodulin along with D-dimer enhances thrombotic risk assessment in hospitalized COVID-19 patients.

Within-species floral evolution reveals convergence in adaptive walks during incipient pollinator shift

Abstract Understanding how evolution proceeds from molecules to organisms to interactions requires integrative studies spanning biological levels. Linking phenotypes with associated genes and fitness illuminates how adaptive walks move organisms between fitness peaks. Floral evolution can confer rapid reproductive isolation, often converging in association with pollinator guilds. Within the monkeyflowers ( Mimulus sect. Erythranthe ), yellow flowers within red hummingbird-pollinated species have arisen at least twice, suggesting possible pollinator shifts. We compare two yellow-flowered forms of M. cardinalis and M. verbenaceus to their red counterparts in floral phenotypes, biochemistry, transcriptomic and genomic variation, and pollinator interactions. We find convergence in ongoing adaptive walks of both yellow morphs, with consistent changes in traits of large effect (floral pigments, associated gene expression), resulting in strong preference for yellow flowers by bumblebees. Shifts in scent emission and floral opening size also favor bee adaptation, suggesting smaller-effect steps from hummingbird to bee pollination. By examining intraspecific, incipient pollinator shifts in two related species, we elucidate adaptive walks at early stages, revealing how convergent large effect mutations (floral color) may drive pollinator attraction, followed by smaller effect changes for mechanical fit and reward access. Thus, ongoing adaptive walks may impact reproductive isolation and incipient speciation via convergent evolution.

Pilot implementation outcomes of a community-based tele- practice model for identification and rehabilitation of children with hearing loss within a public-health system of a Rural District in Southern India

Background The current study is an effort to evaluate pilot outcomes of a comprehensive tele-practice model for identification and rehabilitation of hearing loss among children below six years of age, which can then inform suitable adaptations prior to the implementation. The outcomes of tele-facilitator training, limited-efficacy measures, and caregiver acceptability and satisfaction with tele-practice were analyzed. Method Two special educators were trained as tele-facilitators for tele-diagnostic testing. Screening was done using the validated SRESHT screener in the Perambalur district by trained nurses in the Upgraded Primary Healthcare Centers at all four blocks until at least five children with ‘refer’ results were obtained. For tele-rehabilitation, we enrolled five children with hearing loss who used amplification devices and attended the District Early Intervention Centre. To measure the limited- efficacy, the outcomes of pre-pilot and post-pilot were compared. The caregiver acceptability and satisfaction with tele-practice were also assessed. Results In all 12 children (age range of 5 months to 6 years; 6 male and 6 female) with ‘refer’ results in hearing screening underwent tele- diagnostic testing. Tele-rehabilitation outcomes were studied on 5 children with hearing loss (age range of 4 years to 6 years; 3 male and 2 female) who had already used amplification devices. When comparing the outcomes of limited-efficacy with the existing data, it was found that the model identified older children with hearing loss. The time lapse between screening/hearing loss suspicion and diagnosis reduced from a median of 216 days to eight days. For tele-rehabilitation, the number of sessions attended in a span of three months increased from a median of zero to three sessions. Based on the satisfaction questionnaire, most people had a positive experience and found the travel time to the testing site convenient and affordable. Few parents reported encountering difficulties as a result of inadequate ventilation and internet connectivity within the mobile van where tele-diagnostic testing was conducted. Conclusion The pilot outcomes suggest that a block-level service enabled using tele-practice to overcome professional shortages was beneficial in reducing time gap between screening/suspicion and diagnosis and also enhanced attendance for rehabilitation. The pilot outcomes provided insights on adaptations related to screening sites, test infrastructure, and internet optimization that may be required before implementation.