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Abstract Free-electron-lasers fill a critical gap in the space of THz-sources as they can reach high average and peak powers with spectral tunability. Using a waveguide in a THz FEL significantly increases the coupling between the relativistic electrons and electromagnetic field enabling large amounts of radiation to be generated in a single passage of electrons through the undulator. In addition to transversely confining the radiation, the dispersive properties of the waveguide critically affect the velocity and slippage of the radiation pulse which determine the central frequency and bandwidth of the generated radiation. In this paper, we characterize the spectral properties of a compact waveguide THz FEL including simultaneous lasing at two different frequencies and demonstrating tuning of the radiation wavelength in the high frequency branch by varying the beam energy and ensuring that the electrons injected into the undulator are prebunched on the scale of the resonant radiation wavelength.

Abstract Background Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease characterized by the accumulation of aggregated tau proteins in astrocytes, neurons, and oligodendrocytes. Previous genome-wide association studies for PSP were based on genotype array, therefore, were inadequate for the analysis of rare variants as well as larger mutations, such as small insertions/deletions (indels) and structural variants (SVs). Method In this study, we performed whole genome sequencing (WGS) and conducted association analysis for single nucleotide variants (SNVs), indels, and SVs, in a cohort of 1,718 cases and 2,944 controls of European ancestry. Of the 1,718 PSP individuals, 1,441 were autopsy-confirmed and 277 were clinically diagnosed. Results Our analysis of common SNVs and indels confirmed known genetic loci at MAPT, MOBP, STX6, SLCO1A2, DUSP10, and SP1, and further uncovered novel signals in APOE, FCHO1/MAP1S, KIF13A, TRIM24, TNXB, and ELOVL1. Notably, in contrast to Alzheimer’s disease (AD), we observed the APOE ε2 allele to be the risk allele in PSP. Analysis of rare SNVs and indels identified significant association in ZNF592 and further gene network analysis identified a module of neuronal genes dysregulated in PSP. Moreover, seven common SVs associated with PSP were observed in the H1/H2 haplotype region (17q21.31) and other loci, including IGH, PCMT1, CYP2A13, and SMCP. In the H1/H2 haplotype region, there is a burden of rare deletions and duplications (P = 6.73 × 10–3) in PSP. Conclusions Through WGS, we significantly enhanced our understanding of the genetic basis of PSP, providing new targets for exploring disease mechanisms and therapeutic interventions.

Abstract Background Acute pulmonary embolism (APE) is a potentially life‐threatening disorder, emphasizing the importance of accurate risk stratification and survival prognosis. The exploration of imaging biomarkers that can reflect patient survival holds the potential to further enhance the stratification of APE patients, enabling personalized treatment and early intervention. Therefore, in this study, we develop computed tomography pulmonary angiography (CTPA) radiomic signatures for the prognosis of 7‐ and 30‐day all‐cause mortality in patients with APE. Methods Diagnostic CTPA images from 829 patients with APE were collected. Two hundred thirty‐four features from each skeletal muscle (SM), intramuscular adipose tissue (IMAT) and both tissues combined (SM + IMAT) were calculated at the level of thoracic vertebra 12. Radiomic signatures were derived using 10 times repeated three‐fold cross‐validation on the training data for SM, IMAT and SM + IMAT for predicting 7‐ and 30‐day mortality independently. The performance of the radiomic signatures was then evaluated on held‐out test data and compared with the simplified pulmonary embolism severity index (sPESI) score, a well‐established biomarker for risk stratification in APE. Predictive accuracy was assessed by the area under the receiver operating characteristic curve (AUC) with a 95% confidence interval (CI), sensitivity and specificity. Results The radiomic signatures based on IMAT and a combination of SM and IMAT (SM + IMAT) achieved moderate performance for the prediction of 30‐day mortality on test data (IMAT: AUC = 0.68, 95% CI [0.57–0.78], sensitivity = 0.57, specificity = 0.73; SM + IMAT: AUC = 0.70, 95% CI [0.60–0.79], sensitivity = 0.74, specificity = 0.54). Radiomic signatures developed for predicting 7‐day all‐cause mortality showed overall low performance. The clinical signature, that is, sPESI, achieved slightly better performance in terms of AUC on test data compared with the radiomic signatures for the prediction of both 7‐ and 30‐day mortality on the test data (7 days: AUC = 0.73, 95% CI [0.67–0.79], sensitivity = 0.92, specificity = 0.16; 30 days: AUC = 0.74, 95% CI [0.66–0.82], sensitivity = 0.97, specificity = 0.16). Conclusions We developed and tested radiomic signatures for predicting 7‐ and 30‐day all‐cause mortality in APE using a multicentric retrospective dataset. The present multicentre work shows that radiomics parameters extracted from SM and IMAT can predict 30‐day all‐cause mortality in patients with APE.

Abstract To help with preparedness efforts of Canadian public health and safety systems for adaptation to climate change, the humidity index (humidex) and three threshold‐based humidex indices (annual number of days with humidex greater than 30, 35 and 40) were computed for a multi‐model ensemble of climate change projections, over Canada. The ensemble consists of one run from each 19 Coupled Model Intercomparison Project Phase 6 (CMIP6) global climate models and offers historical simulations starting in 1950 and future projections out to 2100 following Shared Socioeconomic Pathways (SSPs): SSP1‐2.6, SSP2‐4.5 and SSP5‐8.5. Each ensemble member was bias‐adjusted and statistically downscaled using the Multivariate bias correction—N‐dimensional probability density function transform (MBCn) with hourly data from ERA5‐Land as the target dataset and following a method proposed by Diaconescu et al. (2023; International Journal of Climatology, 43, 837) to calculate humidex from daily climate model outputs. This paper details the steps for data production including evaluation of the target historical gridded data and selection of downscaling method and presents some of the resulting humidex projections at the end of the century.

Abstract There has been limited research on the health impacts of extreme bushfire exposure among emergency responders (ER) involved in suppressing extreme bushfires. This study aimed to evaluate the associations between extreme bushfires and ER’s compensated injury and illness in Victoria, Australia. State-wide ER compensation claims from January 2005 to April 2023 were analysed. Logistic regression modelling was used to identify factors associated with compensation claims during the extreme bushfire periods in 2009 and 2019/20, compared to all other claims, adjusting for seasonality (summer). Of the 44,164 included claims, 1105 (2.5%) had recorded injury/disease onset dates within extreme bushfire periods, and 11,642 (26.4%) occurred in summer months. Over half of claims were made by police (52.4%), followed by ambulance officers/paramedics (27.2%) and firefighters (20.5%). Extreme bushfire period claims were associated with older workers (odds ratio/OR = 1.58,95%CI = 1.30–1.92, ages ≥ 55 vs. 35–44 years). Mental disorders (OR = 1.61,95%CI = 1.25–2.07), intracranial injuries (OR = 3.04,95%CI = 1.69–5.48) and infections/parasites (OR = 3.11,95%CI = 1.61–5.98) vs. wounds were associated with extreme bushfire period claims. Given the expected increase in extreme bushfire events and the ageing workforce, study findings underscore the importance of primary and secondary prevention in ER. This can include periodic health surveillance for older workers, access to early treatment, and ongoing support for mental health conditions.

Abstract As part of the advancement in therapeutic decision-making for brain tumor patients at St. Jude Children’s Research Hospital (SJCRH), we developed three robust classifiers, a deep learning neural network (NN), k-nearest neighbor (kNN), and random forest (RF), trained on a reference series DNA-methylation profiles to classify central nervous system (CNS) tumor types. The models’ performance was rigorously validated against 2054 samples from two independent cohorts. In addition to classic metrics of model performance, we compared the robustness of the three models to reduced tumor purity, a critical consideration in the clinical utility of such classifiers. Our findings revealed that the NN model exhibited the highest accuracy and maintained a balance between precision and recall. The NN model was the most resistant to drops in performance associated with a reduction in tumor purity, showing good performance until the purity fell below 50%. Through rigorous validation, our study emphasizes the potential of DNA-methylation-based deep learning methods to improve precision medicine for brain tumor classification in the clinical setting.

Abstract Charon, Pluto’s largest moon, has been extensively studied, with research focusing on its primitive composition and changes due to radiation and photolysis. However, spectral data have so far been limited to wavelengths below 2.5 μm, leaving key aspects unresolved. Here we present the detection of carbon dioxide (CO2) and hydrogen peroxide (H2O2) on the surface of Charon’s northern hemisphere, using JWST data. These detections add to the known chemical inventory that includes crystalline water ice, ammonia-bearing species, and tholin-like darkening constituents previously revealed by ground- and space-based observations. The H2O2 presence indicates active radiolytic/photolytic processing of the water ice-rich surface by solar ultraviolet and interplanetary medium Lyman-α photons, solar wind, and galactic cosmic rays. Through spectral modeling of the surface, we show that the CO2 is present in pure crystalline form and, possibly, in intimately mixed states on the surface. Endogenically sourced subsurface CO2 exposed on the surface is likely the primary source of this component, with possible contributions from irradiation of hydrocarbons mixed with water ice, interfacial radiolysis between carbon deposits and water ice, and the implantation of energetic carbon ions from the solar wind and solar energetic particles.

Abstract Disruption of SYNGAP1 directly causes a genetically identifiable neurodevelopmental disorder (NDD) called SYNGAP1-related intellectual disability (SRID). Without functional SynGAP1 protein, individuals are developmentally delayed and have prominent features of intellectual disability (ID), motor impairments, and epilepsy. Over the past two decades, there have been numerous discoveries indicating the critical role of Syngap1. Several rodent models with a loss of Syngap1 have been engineered, identifying precise roles in neuronal structure and function, as well as key biochemical pathways key for synapse integrity. Homozygous loss of SYNGAP1/Syngap1 is lethal. Heterozygous mutations of Syngap1 result in a broad range of behavioral phenotypes. Our in vivo functional data, using the original mouse model from the Huganir laboratory, corroborated behaviors including robust hyperactivity and deficits in learning and memory in young adults. Furthermore, we described impairments in the domain of sleep, characterized using neurophysiological data that was collected with wireless, telemetric electroencephalography (EEG). Syngap1 +/− mice exhibited elevated spiking events and spike trains, in addition to elevated power, most notably in the delta power frequency. For the first time, we illustrated that primary neurons from Syngap1 +/− mice displayed: 1) increased network firing activity, 2) greater bursts, 3) and shorter inter-burst intervals between peaks, by utilizing high density microelectrode arrays (HD-MEA). Our work bridges in vitro electrophysiological neuronal activity and function with in vivo neurophysiological brain activity and function. These data elucidate quantitative, translational biomarkers in vivo and in vitro that can be utilized for the development and efficacy assessment of targeted treatments for SRID.

Abstract Consumer devices are increasingly used to monitor peripheral body temperature (PBT) for menstrual cycle tracking, but the link between PBT and hormone variations remains underexplored. This study examines the relationship between these variables with a focus on nightly wrist skin temperature (WST). Fifty participants provided physiological and self-reported data, including WST, daily step counts, glucose levels, hormone levels (E3G, LH), and diary entries. Results show a negative correlation between WST and hormone levels when E3G and LH are below average, and this trend was robust to demographics and self-reported stress. Increased variance between mid-cycle hormonal peaks and WST fluctuations may stem from differences between basal body temperature (BBT) and WST. This research suggests that algorithms reliant on body temperature for tracking hormonal changes or other aspects of the menstrual cycle may need to account for increased variance in WST trends if they are meant to be deployed on wearable devices.

Abstract Vitamin B12 is an essential nutritional co-factor for the folate and methionine cycles, which together constitute one-carbon metabolism. Here, we show that dietary uptake of vitamin B12 modulates cell fate decisions controlled by the conserved RAS/MAPK signaling pathway in C. elegans. A bacterial diet rich in vitamin B12 increases vulval induction, germ cell apoptosis and oocyte differentiation. These effects are mediated by different one-carbon metabolites in a tissue-specific manner. Vitamin B12 enhances via the choline/phosphatidylcholine metabolism vulval induction by down-regulating fat biosynthesis genes and increasing H3K4 tri-methylation, which results in increased expression of RAS/MAPK target genes. Furthermore, the nucleoside metabolism and H3K4 tri-methylation positively regulate germ cell apoptosis and oocyte production. Using mammalian cells carrying different activated KRAS and BRAF alleles, we show that the effects of methionine on RAS/MAPK-regulated phenotype are conserved in mammals. Our findings suggest that the vitamin B12-dependent one-carbon metabolism is a limiting factor for diverse RAS/MAPK-induced cellular responses.

Abstract Background CrossFit® combines different types of activities (weightlifting, gymnastics, and cardiovascular training) that challenge aerobic and anaerobic pathways. Over the last few years, the scientific interest in CrossFit® has increased considerably. However, there have been no published reviews characterizing the physical demands and physiological responses to CrossFit®. The present study synthesizes current evidence on the physical demands and physiological responses to CrossFit®. Methods The search was performed in three electronic databases (PubMed, Scopus, and Web of Science). Manuscripts related to the physical and physiological performance of adult CrossFit® participants written in English, Portuguese, and Spanish were retrieved for the analysis. Results In addition, a meta-correlation was conducted to examine the predictors of CrossFit® performance. A total of 68 papers were included in the review. Physical and physiological markers differed between the different workouts analyzed. In addition, 48 to 72 h are needed to recover from a CrossFit® challenge. Specific tests that involve CrossFit® movements were more related to CrossFit® performance than non-specific. Conclusion Although the characterization of CrossFit® is dependent on the workout examined, the benefits of muscle hypertrophy are aligned with the recent findings of concurrent training. The characterization of CrossFit® entire sessions and appropriate recovery strategies should be considered in future studies to help coaches manipulate and adjust the training load.

Abstract Background Working during the night interferes with the timing of normal daily activities and is associated with an increased risk of chronic diseases. Under controlled experimental conditions, interventions focusing on sleep and nutrition can mitigate the short-term adverse effects of shift work. However, it is unclear how these results translate to real-life, how they can be targeted to individual conditions, and how they relate to long-term health. Therefore, the current study aims to implement a personalized sleep and nutritional intervention among night shift workers in the field. Methods A non-blinded controlled intervention study is used, consisting of a run-in period, an intervention of 3 months, post-intervention measurements, and a follow-up after 12 months. Three study arms are included: sleep intervention, nutritional intervention, and control group (n = 25 each). Participants are healthy 18–60-year male night shift workers, with at least one year of experience in night shift work. Information from the run-in period will be used to personalize the interventions. The main outcomes are sleep measurements and continuous interstitial glucose levels. Furthermore, general health biomarkers and parameters will be determined to further evaluate effects on long-term health. Discussion This study aims to mitigate negative health consequences associated with night shift work by introducing two personalized preventive interventions. If proven effective, the personalized interventions may serve as practical solutions that can have a meaningful impact on the sustainable health and employability of night shift workers. This study will thereby contribute to the current need for high–quality data on preventative strategies for night shift work in a real-life context. Trial registration This trial has been registered under ClinicalTrials.gov Identifier NCT06147089. Registered 27 November 2023.

Abstract Background The COVID-19 pandemic has had an unparalleled impact, precipitating not only direct threats to physical health but also widespread economic and psychological challenges. This study aims to explore the dynamics of coping behaviour and psychological distress (PD) across different phases of the pandemic within an adult general population sample, spanning Austria and Italy. Methods An online questionnaire-based panel study was conducted between 2020 and 2023 including three measurements. We collected data on sociodemographic variables, coping responses (Brief COPE), and PD (Brief-Symptom-Checklist). Statistical analyses were conducted within a linear-mixed-model framework. Multiple imputation and sensitivity analysis were applied to validate the results obtained by complete case analysis. Results The study follows 824 participants and reveals a marginal decrease in overall PD from the first to the second follow-up, particularly in clinically relevant phobic anxiety (35.6% and 34.5% to 25.4%). Most coping behaviours exhibited stable mean-levels with intra-individual variability across the study period. Maladaptive coping strategies were consistently linked to increased PD, whereas adaptive strategies were associated with decreased PD. Conclusion Our findings underscore the complex nature of coping behaviours and PD during and after the pandemic, suggesting that while mean-levels of PD and coping responses remained relatively stable, most coping strategies were subject to intra-individual change. Maladaptive strategies were associated with increased PD, pinpointing to the need for interventions that establish the foundation for adaptive coping mechanisms and promote their application. Further research should explore the reciprocal influences of mental health on coping behaviour, incorporating interventional designs to unravel the nuances of these relationships.

Background & objectives: Anopheles stephensi is responsible for the transmission of malaria in urban areas. Vector competence of An. stephensi from a non-malarious (Coimbatore) and highly malarious (Chennai) urban area were investigated to find out the reason for the non-transmission of malaria in Coimbatore. Methods: Vector competence (Susceptibility/refractoriness) of An. stephensi mosquitoes from Chennai (Malarious) and Coimbatore (Non-malarious), Tamil Nadu, India to Plasmodium vivax (Chennai) were investigated. Bioassays were carried out concurrently in both these strains by artificial membrane feeding technique using the same malaria infected blood. An. stephensi were dissected to observe infection in the midgut and salivary glands. The parasite infection, oocyst and sporozoite positivity rate, the oocyst load, correlation between male-female gametocyte ratio and infection, and Survival Analysis of parasitic stages during sporogony were analyzed and compared. Results: The overall infection rate was 45.8 and 41.2 per cent in Chennai and Coimbatore. Oocyst count ranged from 1-80 and 1-208 respectively and not statistically significant. Oocyst positivity was high from Day 8-21in both strains. The Mean Survival Day (MSD) for oocyst was Day 14 in both strains. Sporozoite was observed in four experiments in each of the strains and the MSD for sporozoites was Day 20 and Day 17 in Chennai and Coimbatore. Interpretation & conclusion: An. stephensi of Chennai and Coimbatore are equally susceptible to P. vivax infection and the non-transmission of malaria in Coimbatore can be attributed to external factors such as the presence of preferential breeding habitat, vector density, vector survival, and weather. The only difference observed was the comparatively shortened oocyst maturation time in the Coimbatore strain which requires further investigation.

For the first time, the species Sicarius rugosus is recorded from Guatemala, based on a male and two immatures collected in the department of Zacapa and a female from the department of El Progreso. The specimens of S. rugosus they were found living in construction zones, in gardens of human dwellings, in dry forest fragments and xeric environments.

Trametes hirsuta GMA-01 was cultivated in a culture medium supplemented with orange waste, starch, wheat bran, yeast extract, and salts. The fungus produced several holoenzymes, but the laccase levels were surprisingly high. Given the highlighted applicability of laccases in various biotechnological areas with minimal environmental impact, we provided a strategy to increase its production using response surface methodology. The immobilization of laccase into ionic supports (CM-cellulose, DEAE-agarose, DEAE-cellulose, DEAE-Sephacel, MANAE-agarose, MANAE-cellulose, and PEI-agarose) was found to be efficient and recuperative, showcasing the technical prowess of research. The crude extract laccase (CE) and CM-cellulose-immobilized crude extract (ICE) showed optimum activity in acidic conditions (pH 3.0) and at 70 °C for the CE and 60 °C for the ICE. The ICE significantly increased thermostability at 60 °C for the crude extract, which retained 21.6% residual activity after 240 min. The CE and ICE were successfully applied to sugarcane bagasse hydrolysis, showing 13.83 ± 0.02 µmol mL−1 reducing sugars after 48 h. Furthermore, the CE was tested for dye decolorization, achieving 96.6%, 71.9%, and 70.8% decolorization for bromocresol green, bromophenol blue, and orcein, respectively (0.05% (w/v) concentration). The properties and versatility of T. hirsuta GMA-01 laccase in different biotechnological purposes are interesting and notable, opening several potential applications and providing valuable insights into the future of biotechnological development.

Abstract Background In February 2022, the Ministry of Health received reports of more than 100 child deaths from a ‘strange disease’ in Namutumba District over a period of 6 months from politicians through the media. Preliminary investigations by the district rapid response team confirmed the strange disease to be severe malaria. The scope of severe malaria deaths was investigated, associated factors identified, and recommendations made for control measures to inform early malaria treatment strategies in Namutumba District. Methods A retrospective study was conducted in March 2022 in the most affected subcounty (Ivukula Subcounty) involving cases and controls. A case was defined as a death with a positive malaria test, fever and any of the following: convulsions, difficulty breathing, yellowing of eyes or palms, tea-coloured urine, anaemia (evidenced by pale eyes or palms, or clinically-identified in medical records), loss of consciousness, or reduced urine output (very little or no urine in a day) in a child ≤ 12 years from September 2021 to February 2022 in Ivukula Subcounty, Namutumba District. Controls were survivors with the same signs and symptoms, recruited in a 2:1 ratio with cases. Cases and controls were actively searched using a door-to-door approach with the help of community health workers. Caretakers were interviewed to obtain data on signs and symptoms, socio-demographic information, health-seeking behaviours and health system risk factors. Drugs and bloodstock status information was obtained from health workers using an interview guide. Factors associated with death were identified using multivariate logistic regression and thematic analysis for qualitative data. Results Among 46 cases, 29 (63%) were

Abstract Transition metal oxides are state-of-the-art materials for catalysing the oxygen evolution reaction (OER), whose slow kinetics currently limit the efficiency of water electrolysis. However, microscale physicochemical heterogeneity between particles, dynamic reactions both in the bulk and at the surface, and an interplay between particle reactivity and electrolyte makes probing the OER challenging. Here, we overcome these limitations by applying state-of-the-art compressive Raman imaging to uncover concurrent bias-dependent pathways for the OER in a dense, crystalline electrocatalyst, α-Li2IrO3. By spatially and temporally tracking changes in stretching modes we follow catalytic activation and charge accumulation following ion exchange under various electrolytes and cycling conditions, comparing our observations with other crystalline catalysts (IrO2, LiCoO2). We demonstrate that at low overpotentials the reaction between water and the oxidized catalyst surface is compensated by bulk ion exchange, as usually only found for amorphous, electrolyte permeable, catalysts. At high overpotentials the charge is compensated by surface redox active sites, as in other crystalline catalysts such as IrO2. Hence, our work reveals charge compensation can extend beyond the surface in crystalline catalysts. More generally, the results highlight the power of compressive Raman imaging for chemically specific tracking of microscale reaction dynamics in catalysts, battery materials, or memristors.

Abstract Background Continuous monitoring of antimicrobial resistance (AMR) in Uganda involves testing bacterial isolates from clinical samples at national and regional hospitals. Although the National Microbiology Reference Laboratory (NMRL) analyzes these isolates for official AMR surveillance data, there's limited integration into public health planning. To enhance the utilization of NMRL data to better inform drug selection and public health strategies in combating antibiotic resistance, we evaluated the trends and spatial distribution of AMR to common antibiotics used in Uganda. Methods We analyzed data from pathogenic bacterial isolates from blood, cerebrospinal, peritoneal, and pleural fluid from AMR surveillance data for 2018–2021. We calculated the proportions of isolates that were resistant to common antimicrobial classes. We used the chi-square test for trends to evaluate changes in AMR resistance over the study period. Results Out of 537 isolates with 15 pathogenic bacteria, 478 (89%) were from blood, 34 (6.3%) were from pleural fluid, 21 (4%) were from cerebrospinal fluid, and 4 (0.7%) were from peritoneal fluid. The most common pathogen was Staphylococcus aureus (20.1%), followed by Salmonella species (18.8%). The overall change in resistance over the four years was 63–84% for sulfonamides, fluoroquinolones macrolides (46–76%), phenicols (48–71%), penicillins (42–97%), β-lactamase inhibitors (20–92%), aminoglycosides (17–53%), cephalosporins (8.3–90%), carbapenems (5.3–26%), and glycopeptides (0–20%). There was a fluctuation in resistance of Staphylococcus aureus to methicillin (60%-45%) (using cefoxitin resistance as a surrogate for oxacillin resistance) Among gram-negative organisms, there were increases in resistance to tetracycline (29–78% p

Abstract COVID-19 remains a severe condition for many including immunocompromised individuals. There remains a need for effective measures against this and other respiratory infections, which transmit via virus-laden droplets that reach the nasal or oral mucosae. Nasal sprays offer potential protection against viruses. Such formulations should preserve normal nasal mucociliary function. The antiviral barrier efficacy and effects on mucociliary function of astodrimer sodium nasal spray (AS-NS) were evaluated and compared with other available nasal sprays—low pH hydroxypropyl methylcellulose (HPMC-NS), iota-carrageenan (Carr-NS), nitric oxide (NO-NS), and povidone iodine (PI-NS). Assays simulated clinical conditions. Antiviral barrier function and cell viability were assessed in airway cell monolayers, while a model of fully differentiated human nasal epithelium (MucilAir™) was utilized to evaluate tissue integrity, cytotoxicity, cilia beating frequency, and mucociliary clearance. AS-NS reduced infectious virus in cell monolayers and demonstrated a benign cytotoxicity profile. In human nasal epithelium ex vivo, AS-NS had no impact on mucociliary function (cilia beating nor mucociliary clearance). Carr-NS, HPMC-NS, NO-NS and PI-NS demonstrated limited antiviral effects, while HPMC-NS caused inhibition of mucociliary function. Astodrimer sodium nasal spray demonstrates an acceptable nonclinical efficacy and safety profile as a barrier nasal spray against respiratory viral infection in the nasal cavity.

Abstract Background Few studies have quantified multimorbidity and frailty trends within hospital settings, with even fewer reporting how much is attributable to the ageing population and individual patient factors. Studies to date have tended to focus on people over 65, rarely capturing older people or stratifying findings by planned and unplanned activity. As the UK’s national health service (NHS) backlog worsens, and debates about productivity dominate, it is essential to understand these hospital trends so health services can meet them. Methods Hospital Episode Statistics inpatient admission records were extracted for adults between 2006 and 2021. Multimorbidity and frailty was measured using Elixhauser Comorbidity Index and Soong Frailty Scores. Yearly proportions of people with Elixhauser conditions (0, 1, 2, 3 +) or frailty syndromes (0, 1, 2 +) were reported, and the prevalence between 2006 and 2021 compared. Logistic regression models measured how much patient factors impacted the likelihood of having three or more Elixhauser conditions or two or more frailty syndromes. Results were stratified by age groups (18–44, 45–64 and 65 +) and admission type (emergency or elective). Results The study included 107 million adult inpatient hospital episodes. Overall, the proportion of admissions with one or more Elixhauser conditions rose for acute and elective admissions, with the trend becoming more prominent as age increased. This was most striking among acute admissions for people aged 65 and over, who saw a 35.2% absolute increase in the proportion of admissions who had three or more Elixhauser conditions. This means there were 915,221 extra hospital episodes in the last 12 months of the study, by people who had at least three Elixhauser conditions compared with 15 years ago. The findings were similar for people who had one or more frailty syndromes. Overall, year, age and socioeconomic deprivation were found to be strongly and positively associated with having three or more Elixhauser conditions or two or more frailty syndromes, with socioeconomic deprivation showing a strong dose–response relationship. Conclusions Overall, the proportion of hospital admissions with multiple conditions or frailty syndromes has risen over the last 15 years. This matches smaller-scale and anecdotal reports from hospitals and can inform how hospitals are reimbursed.

Abstract Background Medical students gain essential skills through hospital training and internships, which complement their theoretical education. However, virtual patient platforms have been shown to effectively promote clinical reasoning and enhance learning outcomes. This study evaluates a web-based platform designed for learning clinical reasoning in cardiovascular diseases, detailing its functionalities and user satisfaction. Methods The Virtual Patient platform presents medical students with clinically valid scenarios, encompassing stages such as patient description, anamnesis, objective examination, presumptive diagnosis, health investigations, treatment planning, complications, differential and final diagnoses, and prognosis. Scenarios are generated either automatically or manually by professors, based on labeled and annotated clinical data. The Virtual Patient contains two types of medical cases: simple scenarios describing patients with one pathology, and complex scenarios describing patients with several related pathologies. The platform was evaluated by a total of 210 users: 178 medical students, 7 professors, and 25 engineering students, using questionnaires adjusted for each evaluation round to assess satisfaction and gather feedback. The evaluation by medical students was performed in four rounds, each round corresponding to successive enhancements of the platform functionalities and addition of new cases, with a total number of 1,098 evaluation sessions. Results The platform was evaluated at different implementation stages, involving simple and complex scenarios for various heart diseases. The majority of students found the platform very useful (82.58%), with significant appreciation for its features and functionalities, for example the dialogue module supporting natural language interactions in Romanian and English or the feed-back obtained during interaction. Professors highly valued the platform’s flexibility in scenario generation, real-time feedback provision, and data management capabilities. They appreciated the possibility to provide feedback and score student performance in real-time or after the session, though some professors suggested improving the explainability of the scores. Conclusions The Virtual Patient platform enables medical students to virtually replicate hospital interactions, diagnose patients, and plan treatments in clinically valid scenarios for cardiovascular diseases. User evaluations demonstrated high satisfaction and appreciation for the platform’s features. Future work will focus on expanding medical cases, enhancing the dialogue module, improving scenario generation for complex cases, and extending the synthetic data generation component to produce additional types of medical investigations.

Abstract Background Out-of-hospital cardiac arrest (OHCA) survival in the UK remains overall poor with fewer than 10% of patients surviving to hospital discharge. Extracorporeal cardiopulmonary resuscitation (ECPR) is a developing therapy option that can improve survival in select patients if treatment begins within an hour. Clinicians' perspectives are a pivotal consideration to the development of effective systems for OHCA ECPR, but they have been infrequently explored. This study investigates clinicians' views on the barriers and facilitators to establishing effective systems to facilitate transport of OHCA patients for in-hospital ECPR. Methods In January 2023, Thames Valley Air Ambulance (TVAA) and Harefield Hospital developed an ECPR partnership pathway for conveyance of OHCA patients for in-hospital ECPR. The authors of this study conducted a survey of clinicians across both services looking to identify clear barriers and positive contributors to the effective implementation of the programme. The survey included questions about technical and non-technical barriers and facilitators, with free-text responses analysed thematically. Results Responses were received from 14 pre-hospital TVAA critical care and 9 in-hospital clinicians’ representative of various roles and experiences. Data analysis revealed 10 key themes and 19 subthemes. The interconnected themes, identified by pre-hospital TVAA critical care clinicians as important barriers or facilitators in this ECPR system included educational programmes; collectiveness in effort and culture; teamwork; inter-service communication; concurrent activity; and clarity of procedures. Themes from in-hospital clinicians’ responses were distilled into key considerations focusing on learning and marginal gains, standardising and simplifying protocols, training and simulation; and nurturing effective teams. Conclusion This study identified several clear themes and subthemes from clinical experience that should be considered when developing and modelling an ECPR system for OHCA. These insights may inform future development of ECPR programmes for OHCA in other centres. Key recommendations identified include prioritising education and training (including regular simulations), standardising a ‘pitstop style’ handover process, establishing clear roles during the cannulation process and developing standardised protocols and selection criteria. This study also provides insight into the feasibility of using pre-hospital critical care teams for intra-arrest patient retrieval in the pre-hospital arena.

Abstract Transition metal d-electron oxides with an odd number of electrons per unit cell are expected to form metals with partially occupied energy bands, but exhibit in fact a range of behaviors, being either insulators, or metals, or having insulator-metal transitions. Traditional explanations involved predominantly electron-electron interactions in fixed structural symmetry. The present work focuses instead on the role of symmetry breaking local structural motifs. Viewing the previously observed V-V dimerization in VO2 as a continuous knob, reveals in density functional calculations the splitting of an isolated flat band from the broad conduction band. This leads past a critical percent dimerization to the formation of the insulating phase while lowering the total energy. In VO2 this transition is found to have a rather low energy barrier approaching the thermal energy at room temperature, suggesting energy-efficient switching in neuromorphic computing. Interestingly, sufficient V-V dimerization suppresses magnetism, leading to the nonmagnetic insulating state, whereas magnetism appears when dimerization is reduced, forming a metallic state. This study opens the way to design novel functional quantum materials with symmetry breaking-induced flat bands.

Abstract Graphene placed on hexagonal boron nitride (hBN) has received significant interest due to its excellent electrical performance and physics phenomena, such as superlattice Dirac points. Direct molecular beam epitaxy growth of graphene on hBN offers an alternative fabrication route for hBN/graphene devices. Here, we investigate the electronic transport of moiré field effect transistors (FETs) in which the conducting channel is monolayer graphene grown on hexagonal boron nitride by high temperature molecular beam epitaxy (HT-MBE). Alignment between hBN and HT-MBE graphene crystal lattices gives rise to a moiré-fringed hexagonal superlattice pattern. Its electronic band structure takes the form of a “Hofstadter butterfly”. When a strong magnetic field B is applied perpendicular to the graphene layer, the electrical conductance displays magneto-oscillations, periodic in B −1, over a wide range of gate voltages and temperatures up to 350 K. We attribute this behaviour to the quantisation of electronic charge and magnetic flux within each unit cell of the superlattice, which gives rise to so-called Brown-Zak oscillations, previously reported only in high-mobility exfoliated graphene. Thus, this HT-MBE graphene/hBN heterostructure provides a platform for observation of room temperature quantum effects and device applications.

Abstract Culturing and genomic sequencing of Mycobacterium tuberculosis (MTB) from tuberculosis (TB) cases is the basis for many research and clinical applications. The alternative, culture-free sequencing from diagnostic samples, is promising but poses challenges to obtain and analyse the MTB genome. Paradoxically, culture is assumed to impose a diversity bottleneck, which, if true, would entail unexplored consequences. To unravel this paradox we generate high-quality genomes of sputum-culture pairs from two different settings after developing a workflow for sequencing from sputum and a tailored bioinformatics analysis. Careful downstream comparisons reveal sources of sputum-culture incongruences due to false positive/negative variation associated with factors like low input MTB DNA or variable genomic depths. After accounting for these factors, contrary to the bottleneck dogma, we identify a 97% variant agreement within sputum-culture pairs, with a high correlation also in the variants’ frequency (0.98). The combined analysis from five different settings and more than 100 available samples shows that our results can be extrapolated to different TB epidemic scenarios, demonstrating that for the cases tested culture accurately mirrors clinical samples.

Abstract Autophagy is a finely orchestrated process required for the lysosomal degradation of cytosolic components. The final degradation step is essential for clearing autophagic cargo and recycling macromolecules. Using a CRISPR/Cas9-based screen, we identify RNAseK, a highly conserved transmembrane protein, as a regulator of autophagosome degradation. Analyses of RNAseK knockout cells reveal that, while autophagosome maturation is intact, cargo degradation is severely disrupted. Importantly, lysosomal protease activity and acidification remain intact in the absence of RNAseK suggesting a specificity to autolysosome degradation. Analyses of lysosome fractions show reduced levels of a subset of hydrolases in the absence of RNAseK. Of these, the knockdown of PLD3 leads to a defect in autophagosome clearance. Furthermore, the lysosomal fraction of RNAseK-depleted cells exhibits an accumulation of the ESCRT-III complex component, VPS4a, which is required for the lysosomal targeting of PLD3. Altogether, here we identify a lysosomal hydrolase delivery pathway required for efficient autolysosome degradation.

Abstract Neuroepithelial tumors with fusion of PLAGL1 or amplification of PLAGL1/PLAGL2 have recently been described often with ependymoma-like or embryonal histology respectively. To further evaluate emerging entities with PLAG-family genetic alterations, the histologic, molecular, clinical, and imaging features are described for 8 clinical cases encountered at St. Jude (EWSR1-PLAGL1 fusion n = 6; PLAGL1 amplification n = 1; PLAGL2 amplification n = 1). A histologic feature observed on initial resection in a subset (4/6) of supratentorial neuroepithelial tumors with EWSR1-PLAGL1 rearrangement was the presence of concurrent ependymal and ganglionic differentiation. This ranged from prominent clusters of ganglion cells within ependymoma/subependymoma-like areas, to interspersed ganglion cells of low to moderate frequency among otherwise ependymal-like histology, or focal areas with a ganglion cell component. When present, the combination of ependymal-like and ganglionic features within a supratentorial neuroepithelial tumor may raise consideration for an EWSR1-PLAGL1 fusion, and prompt initiation of appropriate molecular testing such as RNA sequencing and methylation profiling. One of the EWSR1-PLAGL1 fusion cases showed subclonal INI1 loss in a region containing small clusters of rhabdoid/embryonal cells, and developed a prominent ganglion cell component on recurrence. As such, EWSR1-PLAGL1 neuroepithelial tumors are a tumor type in which acquired inactivation of SMARCB1 and development of AT/RT features may occur and lead to clinical progression. In contrast, the PLAGL2 and PLAGL1 amplified cases showed either embryonal histology or contained an embryonal component with a significant degree of desmin staining, which could also serve to raise consideration for a PLAG entity when present. Continued compilation of associated clinical data and histopathologic findings will be critical for understanding emerging entities with PLAG-family genetic alterations.

Transphobic and homophobic violence and discrimination within homes and housing programs lead many 2-Spirit, lesbian, gay, bisexual, transgender, and queer (2SLGBTQ+) youth to find alternative, temporary, and insecure housing. These types of living situations are considered “hidden homelessness”. This study interviewed 2SLGBTQ+ youth (n = 6) and key informants (n = 12) who have experienced and/or who support hidden homelessness across three sites in Ontario (Toronto, York Region, and London). The results suggest experiences of hidden homelessness for 2SLGBTQ+ youth are nonlinear, with pathways driven by family conflict combined with the high cost of living and lack of employment, making independent living unaffordable. Additionally, youth avoid services where they experience discrimination and often experience social isolation. In rural and suburban areas, youth have fewer options for safe and inclusive services. When services are accessible, wrap-around supports that address the complexity of their situations help youth exit hidden homelessness. Prevention strategies should focus on addressing family conflict and supporting reunification when it is safe to do so. For those who are unable to return home, there is a need for increased financial support and more affordable housing. Building comprehensive population-based support services is recommended to address the overrepresentation of 2SLGBTQ+ youth experiencing homelessness.

Background: As patients interact with a healthcare service system, patterns of service utilization (PSUs) emerge. These PSUs are embedded in the sparse high-dimensional space of longitudinal cross-continuum health service encounter data. Once extracted, PSUs can provide quality assurance/quality improvement (QA/QI) efforts with the information required to optimize service system structures and functions. This may improve outcomes for complex patients with chronic diseases. Method: Working with longitudinal cross-continuum encounter data from a regional health service system, various pattern detection analyses were conducted, employing (1) graph community detection algorithms, (2) natural language processing (NLP) clustering, and (3) a hybrid NLP–graph method. Result: These approaches produced similar PSUs, as determined from a clinical perspective by clinical subject matter experts and service system operations experts. Conclusions: The similarity in the results provides validation for the methodologies. Moreover, the results stress the need to engage with clinical or service system operations experts, both in providing the taxonomies and ontologies of the service system, the cohort definitions, and determining the level of granularity that produces the most clinically meaningful results. Finally, the uniqueness of each approach provides an opportunity to take advantage of the various analytical capabilities that each approach brings, which will be further explored in our future research.

The examination of fungal secretomes has garnered attention for its potential to unveil the repertoire of secreted proteins, notably CAZymes (Carbohydrate-Active enzymes), across various microorganisms. This study presents findings on categorizing the secretome profile of CAZymes by their function and family, derived from the filamentous fungus Trichoderma longibrachiatum LMBC 172. The cultivation was performed through submerged fermentation with three distinct carbon sources: sugarcane bagasse, tamarind seeds, and a control simulating hemicellulose containing 0.5% beechwood xylan plus 0.5% oat spelt xylan. The secretome analysis revealed 206 distinct CAZymes. Each carbon source showed particularities and differences. Of these, 89 proteins were produced simultaneously with all the carbon sources; specifically, 41 proteins using only the hemicellulose simulation, 29 proteins when sugarcane bagasse was used as a carbon source, and only 3 when tamarind seeds were used. However, in this last condition, there was a high intensity of xyloglucanase GH74 production, thus reaffirming the richness of xyloglucan in the constitution of these seeds. When evaluating the proteins found in two conditions, 18 proteins were shown between the simulation of hemicellulose and sugarcane bagasse, 11 proteins between the simulation of hemicellulose and tamarind seeds, and 15 proteins between sugarcane bagasse and tamarind seeds. Among the proteins found, there are representatives of different families such as glycosyl hydrolases (GHs) that cleave cellulose, hemicellulose, pectin, or other components; carbohydrate esterases (CEs); polysaccharide lyases (PLs); carbohydrate-binding modules (CBMs); and auxiliary activity enzymes (AAs). These results demonstrate the importance of analyzing CAZymes secreted by microorganisms under different culture conditions.

Individuals from a variety of backgrounds are affected by the opioid crisis. To provide optimal care for individuals at risk of opioid overdose and prevent subsequent overdoses, a more targeted response that goes beyond the traditional taxonomical diagnosis approach to care management needs to be adopted. In previous works, Graph Machine Learning and Natural Language Processing methods were used to model the products for planning and evaluating the treatment of patients with complex issues. This study proposes a methodology of partitioning patients in the opioid overdose cohort into various communities based on their patterns of service utilization (PSUs) across the continuum of care using graph community detection and applying survival analysis to predict time-to-second overdose for each of the communities. The results demonstrated that the overdose cohort is not homogeneous with respect to the determinants of risk. Moreover, the risk for subsequent overdose was quantified: there is a 51% higher chance of experiencing a second overdose for a high-risk community compared to a low-risk community. The proposed method can inform a more efficient treatment heterogeneity approach for a cohort made of diverse individuals, such as the opioid overdose cohort. It can also guide targeted support for patients at risk of subsequent overdoses.

Resumen. Se registra por primera vez la depredación del escorpión Centruroides bicolor (Pocock, 1898) (Buthidae) por el geco de cola de nabo Thecadactylus rapicauda (Houttuyn, 1782) (Phyllodactylidae), y del geco Hemidactylus frenatus Dumeril y Bibron, 1836 (Gekkonidae), por Centruroides edwardsii (Gervais, 1843). El primer caso fue observado en Costa Rica y el segundo, en Nicaragua. También se registra el primer evento de necrofagia en escorpiones, ocurrido en condiciones naturales. Se incluye una lista de los casos de depredación entre escorpiones y reptiles (Squamata) registrados en Centroamérica.

Abstract Orange II, an azo dye used in textile and leather industries, is toxic and contributes to reducing dissolved oxygen in water. In this sense, agri-food waste adsorbents offer efficient, cost-effective dye removal. In this study, potato surpluses were evaluated as adsorbents for the removal of Orange II at 22 °C and pH values between 4 and 9. The adsorbents were characterized by their morphology, elemental composition, infrared spectra, and point of zero charge. Adsorption isotherms were analysed using Langmuir and Freundlich models, revealing that the Langmuir equation (0.933 0.882) better described the adsorption process compared to the Freundlich model (0.909 0.852). The maximum adsorption capacity at pH 4 was 1.1 and 2.3 times higher than at pH 7 and 9, respectively. This increased capacity at pH 4 was due to favourable electrostatic interactions between the cationic adsorbent surface and the anionic dye. A kinetic model was developed to understand the adsorption dynamics of Orange II, demonstrating high accuracy with coefficients of determination (r2) exceeding 0.99 across various pH values. The predictions of the kinetic model aligned well with the Langmuir isotherm results, indicating a strong theoretical foundation. The critical contact time required to achieve the minimum adsorbent concentration necessary for meeting a discharge limit of 14.7 mg L−1 was determined using both the Langmuir and kinetic models. Simulation profiles showed that when the adsorbent concentration was increased from 12 to 40 g L−1, the contact time necessary to achieve the discharge limit decreased from 26 to 3.35 h, highlighting the trade-off between contact time and cost. This study offers a cost-effective solution for wastewater treatment and presents a robust model for optimizing batch adsorption processes, marking a significant advancement in using potato surpluses for dye removal.

Abstract Background Although HIV vertical transmission has declined significantly in sub-Saharan Africa, incident HIV infection in pregnant and postpartum women is estimated to account for over one-third of HIV vertical transmission. Oral pre-exposure prophylaxis (PrEP) for pregnant and breastfeeding women (PBFW) is included in South African PrEP guidelines since 2021; however, integration of PrEP services within ante- and postnatal care remains limited. Methods Between March 2022 and September 2023, we evaluated the integration of PrEP for PBFW in eight antenatal clinics in Cape Town, South Africa, following training and mentorship of providers. We applied an adapted Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework to evaluate the integration of PrEP services for pregnant and breastfeeding women. Before the study, PrEP was not routinely offered. We implemented a staff didactic/practice-based training and mentorship on PrEP provision targeting PBFW. We evaluated the following: (1) Reach as the proportion of women initiating PrEP among women counselled and tested for HIV, (2) effectiveness as PrEP continuation up to 3 months by pregnant vs. breastfeeding women, (3) adoption of PrEP integration via pre- and post-training assessments and ongoing mentorship assessments, (4) implementation through clinic trends of PrEP offer over time, and (5) maintenance: continued PrEP offer 3 months following the intervention. Results In 8 facilities providing ante- and postnatal care, we trained 224 healthcare providers (127 nurses and 37 counsellors). Of those, we mentored 60 nurses, midwives, and HIV counsellors working with pregnant and breastfeeding women, with 80% of nurse/midwives and 65% of counsellors scoring ≥ 80% on the final mentoring assessment. Overall, 12% of HIV-negative pregnant women started PrEP, and 41% of those continued PrEP up to 3 months. Among HIV-negative breastfeeding women, 14% initiated PrEP, and 25% continued PrEP up to 3 months. All eight facilities continued providing PrEP 3 months post intervention. Conclusions In these high HIV prevalence clinics, the proportion of pregnant and breastfeeding women initiating and continuing PrEP rapidly increased but was limited among breastfeeding women. Staff training, mentorship, and PrEP integration were well-adopted by nurses and counsellors, and services continued following the intervention. Barriers included limited HIV testing of breastfeeding mothers and need for additional PrEP-trained nurses.

The article addresses the challenges faced in conducting network research, considering the constraints imposed by the pandemic condition and the predominant individualistic and meritocratic context in Brazilian universities. The focus is on the research Education and Rural Schools in times of the Covid-19 pandemic" conducted from May 2020 to December 2023 by five groups of the Latin American Network of Marxist Studies and Research in Rural Education/Educação do Campo. Over the three years of research, 91 activities were carried out, involving participating groups and covering all stages of the process, from conception to methodological analysis, collectively and interinstitutionally. The text highlights the influence of virtual tools in research due to social isolation, pointing out limitations. On the other hand, it emphasizes collective and cooperative work as a positive response, reaffirming the principles and materiality of Rural Education Educação do Campo.

The text addresses part of the results of the research Education and Rural Schooling in the time of the Covid-19 pandemic conducted by groups of the Latin American Network of Studies and Research in Rural Education. Our objective is to analyze the diversity and inequalities in continuing education in the context of the Covid-19 pandemic in rural schools, including those in water and forest areas, in dialectical relation to the totality. To achieve this, we utilized data from 645 respondents from a virtual questionnaire conducted by the research, as well as excerpts from interviews with 19 educators who worked in schools in the years 2020 and/or 2021. We discuss the diversity of human experience, encompassing elements of culture, lifestyle, and the political and social organization of communities. We reflect on the challenges posed by the pandemic in the context of a society organized under the aegis of financial and neoliberal capital, impacting the ongoing training of teachers. Finally, we highlight the diversity of territories, how life is organized, the understanding of education and schools, and, at the same time, the unity imposed by the social form of capital, with neoliberal policies and the commodification of education.

Abstract The presence of defects at the interface between the perovskite film and the carrier transport layer poses significant challenges to the performance and stability of perovskite solar cells (PSCs). Addressing this issue, we introduce a dual host-guest (DHG) complexation strategy to modulate both the bulk and interfacial properties of FAPbI3-rich PSCs. Through NMR spectroscopy, a synergistic effect of the dual treatment is observed. Additionally, electro-optical characterizations demonstrate that the DHG strategy not only passivates defects but also enhances carrier extraction and transport. Remarkably, employing the DHG strategy yields PSCs with power conversion efficiencies (PCE) of 25.89% (certified at 25.53%). Furthermore, these DHG-modified PSCs exhibit enhanced operational stability, retaining over 96.6% of their initial PCE of 25.55% after 1050 hours of continuous operation under one-sun illumination, which was the highest initial value in the recently reported articles. This work establishes a promising pathway for stabilizing high-efficiency perovskite photovoltaics through supramolecular engineering, marking a significant advancement in the field.

Abstract More than half of the world’s rivers dry up periodically, but our understanding of the biological communities in dry riverbeds remains limited. Specifically, the roles of dispersal, environmental filtering and biotic interactions in driving biodiversity in dry rivers are poorly understood. Here, we conduct a large-scale coordinated survey of patterns and drivers of biodiversity in dry riverbeds. We focus on eight major taxa, including microorganisms, invertebrates and plants: Algae, Archaea, Bacteria, Fungi, Protozoa, Arthropods, Nematodes and Streptophyta. We use environmental DNA metabarcoding to assess biodiversity in dry sediments collected over a 1-year period from 84 non-perennial rivers across 19 countries on four continents. Both direct factors, such as nutrient and carbon availability, and indirect factors such as climate influence the local biodiversity of most taxa. Limited resource availability and prolonged dry phases favor oligotrophic microbial taxa. Co-variation among taxa, particularly Bacteria, Fungi, Algae and Protozoa, explain more spatial variation in community composition than dispersal or environmental gradients. This finding suggests that biotic interactions or unmeasured ecological and evolutionary factors may strongly influence communities during dry phases, altering biodiversity responses to global changes.

Abstract Background In phenylketonuria (PKU), attending multidisciplinary clinic reviews is an important aspect of life-long care. Since the COVID-19 pandemic, video and telephone clinics are used as alternative methods for people with PKU to have contact with their care team. There is limited research concerning patient preference, experience and perceptions of alternative types of clinic review. Individuals from the UK with PKU and their caregivers were invited to complete an online questionnaire, hosted on the National Society for PKU (NSPKU) website and social media platform. Results Data was available from 203 respondents. Forty one per cent of respondents (n = 49/119) preferred in-person clinics; 41% (n = 49) a hybrid of in-person, video and telephone clinics; 9% (n = 11) video clinics only, 6% (n = 7) telephone only and 3% (n = 3) were unsure. The main respondent obstacles to in-person clinics were costs, travel and time, but this was balanced by the benefits of a physical examination and better patient engagement/motivation. Twenty one per cent (n = 36/169) of respondents were uncomfortable with the number of healthcare professionals (HCPs) in a clinic room. Patients were less likely to consult with a doctor on video (64%, n = 91/143) or phone (50%, n = 59/119) reviews compared to in-person (80%, n = 146/183). Issues with video and telephone reviews included the shorter time length of review, distractions, technical issues and poor patient engagement. Conclusions Online video and telephone clinic platforms were effective in overcoming the challenging circumstances in management, monitoring and treatment of patients with PKU during the COVID-19 pandemic. However, in-person clinics remain the preferred respondent option. It is important that HCPs are flexible, enabling people with PKU a choice of clinic options according to their individual clinical need and circumstances.

Abstract Background The elevated blood pressure (BP) and lower cardiac autonomic modulation (CAM) are associated with higher morbidity mortality risk among older adults. Although exercise is an important intervention for cardiovascular promotion, it is unclear whether combat sports training could benefit cardiovascular outcomes as much as autonomic in this population. This study compared the effects of 12 weeks of Muay Thai (MT) training against functional training (FT) on CAM and hemodynamic parameters in older adults. Methods The sample consisted of 50 older adults (41 women; 66.0 ± 5.3 years old), who were equaly randomized into FT (n = 25) and MT (n = 25) intervention groups. CAM was measured by 30-min rest heart rate variability. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and resting heart rate (RHR) were measured using an automatic oscillometric device. Pulse pressure (PP) and the double product (DP) were also calculated. The interventions were carried out three times a week, with 60-min length per session, during 12 consecutive weeks. The intensity of the interventions was measured using the subjective perception of exertion scale and by accelerometer. Two-factor repeated measures analysis of covariance was used for groups comparison, considering intervention group and body mass as factors. The 95% confidence interval of the difference (95%CIdif) was also calculated and the effect size was measured using partial eta squared (η2 p). Results CAM indices did not show significant changes across moments and intervention groups. In hemodynamic parameters, only in DBP was there an effect of the moment (F1,39 = 8.206; P = 0.007; η2 p = 0.174, large) and interaction effect between group*moment (F1,39 = 7.950; P = 0.008; η2 p = 0.169, large). Specifically, the MT group at the post-training moment showed lower DBP (P = 0.010; 95%CIdif = -13.3; -1.89) in relation to the FT group. Furthermore, the MT group showed a decrease in DBP during training (P = 0.002; 95%CIdif = -10.3; -2.6). Also, an increase in training intensity was also found over the 12 weeks in FT, with no difference between the groups. Conclusion After 12 weeks of MT practice there was a reduction in DBP compared to FT in older adults. Trial registration NCT03919968 Registration date: 01/02/2019.

Abstract The Asia–Pacific region has had decades of progress in reducing malaria cases and deaths. The region is now accelerating its efforts towards malaria elimination by 2030 using a science-based approach by applying evidence-based best practices alongside existing tools. However, there are concerns of knowledge gaps and external factors challenging this goal. The COVID-19 pandemic served as reminder of the need for a holistic approach. This report summarizes the outcomes of the discussions from the “Asia Pacific Conference on Mosquito and Vector Control” held in Chiang Mai, Thailand from 27 to 30 November, 2023. The conference aims to provide insights into recent research, cutting-edge tools, and the strength of the Asia–Pacific regional mosquito and vector control capacity post-COVID-19 pandemic era. The conference featured discussions on mosquito surveillance, monitoring and control; enabling the resolution of local problems with local expertise and forging new partnerships; and exploring recent research advancements in vector control strategies. More than 500 experts from 55 countries attended.

Abstract Background Malaria is a serious, fatal disease, and a high-risk determinant for human health globally. Children, pregnant women, and migrants are vulnerable groups for malaria infection in African regions. Recently, malaria is an endemic disease in Ethiopia. Objectives This study aimed to determine the pooled prevalence of malaria and its determinant factors among the most vulnerable populations in Ethiopia. Methods Electronic databases, including PubMed, Google Scholar, Web of Science, Semantic Scholar, and Scopus were used for searching articles published since the 2020 Gregorian calendar and onwards. All peer-reviewed Ethiopian journals, health institutions, and Universities were considered for article searching. A PRISMA flow chart and Endnote software were used for article screening, and to remove duplications, respectively. The modified version of the Newcastle–Ottawa Scale was used for potential risk of bias assessments. The heterogeneity among the included studies was evaluated using the indicator of heterogeneity (I2). Egger’s test and funnel plot were used to examine the possible publication bias. A random-effects analysis was used to assess the pooled prevalence of malaria, and its determinant factors with a 95% CI. The screening process, data extraction, and quality assessment were done independently, and any disagreements were resolved through discussions. Results A total of twelve studies were included in this study. The pooled malaria prevalence was 11.10% (95% CI: 6.10, 16.11). Stagnant water (AOR: 4.19, 95% CI: 2.47, 7.11), no insecticide-treated net utilization (AOR: 3.15, 95% CI: 1.73, 5.73), and staying outdoors at night (AOR: 5.19, 95% CI: 2.08, 12.94) were the pooled estimated statistically risk factors for malaria prevalence. Whereas, insecticide-treated bed net utilization (AOR: 1.59, 95% CI: 0.23, 10.95) reduces the risk of malaria infection. Conclusions The pooled prevalence of malaria is high among vulnerable populations. Creating awareness regarding utilization of insecticide-treated bed nets, and draining stagnant water from the environment are possible interventions to reduce the prevalence of malaria.

Abstract The ongoing efforts to optimize rechargeable Li-ion batteries led to the interest in intercalation of nanoscale layered compounds, including bilayer graphene. Its lithium intercalation has been demonstrated recently but the mechanisms underpinning the storage capacity remain poorly understood. Here, using magnetotransport measurements, we report in-operando intercalation dynamics of bilayer graphene. Unexpectedly, we find four distinct intercalation stages that correspond to well-defined Li-ion densities. Transitions between the stages occur rapidly (within 1 sec) over the entire device area. We refer to these stages as ‘in-plane’, with no in-plane analogues in bulk graphite. The fully intercalated bilayers represent a stoichiometric compound C14LiC14 with a Li density of ∼2.7·1014 cm−2, notably lower than fully intercalated graphite. Combining the experimental findings and DFT calculations, we show that the critical step in bilayer intercalation is a transition from AB to AA stacking which occurs at a density of ∼0.9·1014 cm−2. Our findings reveal the mechanism and limits for electrochemical intercalation of bilayer graphene and suggest possible avenues for increasing the Li storage capacity.

Abstract C4ʹ-modified nucleoside analogues continue to attract global attention for their use in antiviral drug development and oligonucleotide-based therapeutics. However, current approaches to C4ʹ-modified nucleoside analogues still involve lengthy (9–16 steps), non-modular routes that are unamenable to library synthesis. Towards addressing the challenges associated with their syntheses, we report a modular 5-step process to a diverse collection of C4ʹ-modified nucleoside analogues through a sequence of intramolecular trans-acetalizations of readily assembled polyhydroxylated frameworks. Overall, the 2–3 fold reduction in step-count compares favorably to even recently reported biocatalytic approaches and should ultimately enable new opportunities in drug design around this popular chemotype.

Abstract Background It is vital that health service delivery and health interventions address patients’ needs or preferences, are relevant for practice and can be implemented. Involving those who will use or deliver healthcare in priority-setting can lead to health service delivery and research that is more meaningful and impactful. This is particularly crucial in rural communities, where limited resources and disparities in healthcare and health outcomes are often more pronounced. The aim of this study was to determine the health and healthcare priorities in rural communities using a region-wide community engagement approach. Methods This multi-methods study was conducted in five rural communities in the Grampians region, Western Victoria, Australia. It involved six concept mapping steps: (1) preparation, (2) generation (brainstorming statements and identifying rating criteria), (3) structuring statements (sorting and rating statements), (4) representation of statements, (5) interpretation of the concept map and (6) utilization. Community forums, surveys and stakeholder consultations with community members and health professionals were used in Step 2. An innovative online group concept mapping platform, involving consumers, health professionals and researchers was used in Step 3. Results Overall, 117 community members and 70 health professionals identified 400 health and healthcare issues. Six stakeholder consultation sessions (with 16 community members and 16 health professionals) identified three key values for prioritizing health issues: equal access for equal need, effectiveness and impact (number of people affected). Actionable priorities for healthcare delivery were largely related to access issues, such as the challenges navigating the healthcare system, particularly for people with mental health issues; the lack of sufficient general practitioners and other health providers; the high travel costs; and poor internet coverage often impacting technology-based interventions for people in rural areas. Conclusions This study identified actionable health and healthcare priorities from the perspective of healthcare service users and providers in rural communities in Western Victoria. Issues related to access, such as the inequities in healthcare costs, the perceived lack of quality and availability of services, particularly in mental health and disability, were identified as priorities. These insights can guide future research, policy-making and resource allocation efforts to improve healthcare access, quality and equity in rural communities.

Abstract Since 2021, the emergence of variants of concern (VOC) has led Brazil to experience record numbers of in COVID-19 cases and deaths. The expanded spread of the SARS-CoV-2 combined with a low vaccination rate has contributed to the emergence of new mutations that may enhance viral fitness, leading to the persistence of the disease. Due to limitations in the real-time genomic monitoring of new variants in some Brazilian states, we aimed to investigate whether genomic surveillance, coupled with epidemiological data and SARS-CoV-2 variants spatiotemporal spread in a smaller region, can reflect the pandemic progression at a national level. Our findings revealed three SARS-CoV-2 variant replacements from 2021 to early 2022, corresponding to the introduction and increase in the frequency of Gamma, Delta, and Omicron variants, as indicated by peaks of the Effective Reproductive Number (Reff). These distinct clade replacements triggered two waves of COVID-19 cases, influenced by the increasing vaccine uptake over time. Our results indicated that the effectiveness of vaccination in preventing new cases during the Delta and Omicron circulations was six and eleven times higher, respectively, than during the period when Gamma was predominant, and it was highly efficient in reducing the number of deaths. Furthermore, we demonstrated that genomic monitoring at a local level can reflect the national trends in the spread and evolution of SARS-CoV-2.

Abstract Production of hard X-ray via inverse Compton scattering at photon energies below 100 keV range aimed at potential applications in medicine and material research is reported. Experiments have been performed at the Brookhaven National Laboratory, Accelerator Test Facility, employing the counter collision of a 70 MeV, 0.3 nC electron beam with a near infra-red Nd: YAG laser (1064 nm wavelength) pulse containing ~ 100 mJ in a single shot basis. The radiation distribution of the scattered photon beam is assessed to be sufficiently quasi monochromatic to produce clear contrast from the Au K- edge at 80.7 keV.

Abstract Background Prostate cancer (PCa) shows a rewired metabolism featuring increased fatty acid uptake and synthesis via de novo lipogenesis, both sharply related to mitochondrial physiology. The docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (PUFA) that exerts its antitumoral properties via different mechanisms, but its specific action on mitochondria in PCa is not clear. Therefore, we investigated whether the DHA modulates mitochondrial function in PCa cell lines. Methods Here, we evaluated mitochondrial function of non-malignant PNT1A and the castration-resistant (CRPC) prostate 22Rv1 and PC3 cell lines in response to DHA incubation. For this purpose, we used Seahorse extracellular flux assay to assess mitochondria function, [14C]-glucose to evaluate its oxidation as well as its contribution to fatty acid synthesis, 1H-NMR for metabolite profile determination, MitoSOX for superoxide anion production, JC-1 for mitochondrial membrane polarization, mass spectrometry for determination of phosphatidylglycerol levels and composition, staining with MitoTracker dye to assess mitochondrial morphology under super-resolution in addition to Transmission Electron Microscopy, In-Cell ELISA for COX-I and SDH-A protein expression and flow cytometry (Annexin V and 7-AAD) for cell death estimation. Results In all cell lines DHA decreased basal respiratory activity, ATP production, and the spare capacity in mitochondria. Also, the omega-3 induced mitochondrial hyperpolarization, ROS overproduction and changes in membrane phosphatidylglycerol composition. In PNT1A, DHA led to mitochondrial fragmentation and it increased glycolysis while in cancer cells it stimulated glucose oxidation, but decreased de novo lipogenesis specifically in 22Rv1, indicating a metabolic shift. In all cell lines, DHA modulated several metabolites related to energy metabolism and it was incorporated in phosphatidylglycerol, a precursor of cardiolipin, increasing the unsaturation index in the mitochondrial membrane. Accordingly, DHA triggered cell death mainly in PNT1A and 22Rv1. Conclusion In conclusion, mitochondrial metabolism is significantly affected by the PUFA supplementation to the point that cells are not able to proliferate or survive under DHA-enriched condition. Moreover, combination of DHA supplementation with inhibition of metabolism-related pathways, such as de novo lipogenesis, may be synergistic in castration-resistant prostate cancer.