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Psoriasis, an immune-mediated inflammatory skin disorder characterized by a chronically relapsing-remitting course, continues to be primarily managed through topical therapy. While oral administration of tyrosine kinase 2 inhibitors (TYK2i) stands as an effective approach for psoriasis treatment, the potential efficacy of topical application of TYK2i remains unexplored. Herein, the carbomer/alginic acid hydrogel is embedded with borneol (BO) as a new topical carrier of TYK2i for achieving enhanced transdermal permeation and anti-psoriasis efficacy. The hydrogel system, i.e., TYK2i-BO-gel, exhibits significantly improved preventative and therapeutic effects in mice models of psoriasiform dermatitis, as evidenced by phenotypical images, psoriasis severity score index (PSI), histology, immunohistochemical staining, and PCR analysis. Remarkably, TYK2i-BO-gel outperforms conventional topical corticosteroid therapy by significantly preventing psoriatic lesion recurrence as measured by a nearly 50 % reduction in ear thickness changes (p

Abstract Regular counts of walruses (Odobenus rosmarus) across their pan‐Arctic range are necessary to determine accurate population trends and in turn understand how current rapid changes in their habitat, such as sea ice loss, are impacting them. However, surveying a region as vast and remote as the Arctic with vessels or aircraft is a formidable logistical challenge, limiting the frequency and spatial coverage of field surveys. An alternative methodology involving very high‐resolution (VHR) satellite imagery has proven to be a useful tool to detect walruses, but the feasibility of accurately counting individuals has not been addressed. Here, we compare walrus counts obtained from a VHR WorldView‐3 satellite image, with a simultaneous ground count obtained using a remotely piloted aircraft system (RPAS). We estimated the accuracy of the walrus counts depending on (1) the spatial resolution of the VHR satellite imagery, providing the same WorldView‐3 image to assessors at three different spatial resolutions (i.e., 50, 30 and 15 cm per pixel) and (2) the level of expertise of the assessors (experts vs. a mixed level of experience – representative of citizen scientists). This latter aspect of the study is important to the efficiency and outcomes of the global assessment programme because there are citizen science campaigns inviting the public to count walruses in VHR satellite imagery. There were 73 walruses in our RPAS ‘control’ image. Our results show that walruses were under‐counted in VHR satellite imagery at all spatial resolutions and across all levels of assessor expertise. Counts from the VHR satellite imagery with 30 cm spatial resolution were the most accurate and least variable across levels of expertise. This was a successful first attempt at validating VHR counts with near‐simultaneous, in situ, data but further assessments are required for walrus aggregations with different densities and configurations, on different substrates.

Abstract Background Vitamin D deficiency has been linked to poor muscle function, cartilage degeneration, and the development of knee osteoarthritis. However, the impact of serum 25-hydroxyvitamin D [25(OH)D] level on quadriceps muscle strength remains inconclusive, largely due to variations in study designs, differences in study populations, and the influence of confounding factors such as co-supplementation with other vitamins. The existing literature presents mixed findings, highlighting the need for a comprehensive evaluation of the available evidence. Purpose This systematic review and meta-analysis aim to summarise. Study design Systematic review; Level of evidence, 4. Methods Searches were conducted using Medline (Ovid), Embase (Ovid), CINAHL (EBSCOhost), and SPORTDiscus (EBSCOhost), which aimed to summarise recent (published after 2000 and before March 1st, 2024) studies reporting the effects of serum 25(OH)D levels on quadriceps strength. Appraisal tool for Cross-Sectional Studies (AXIS) for cross-sectional studies and Quality in Prognosis Studies (QUIPS) for longitudinal studies. Results from the AXIS and QUIPS tools were used for GRADE quality assessment. The review was carried out using PRIMSA guidelines and registered in PROSPERO (ID: CRD42022313240). Results Four hundred studies were screened and 28 studies with 5752 participants were included. 28 published studies (24 cross-sectional and 4 longitudinal) were identified. Key results supported the significant positive correlation between serum 25(OH)D levels and isokinetic quadriceps strength at 180°/s in elderly and athletic populations with a correlation coefficient of 0.245 (95%CI: 0.078–0.398, p = 0.004). However, no significant correlation was found with isometric quadriceps strength or isokinetic strength at 60°/s (r = 0.190, p = 0.085). There was only a weak negative correlation with MVC. Conclusion This review found a statistically significant positive correlation between serum 25(OH)D levels and isokinetic quadriceps strength. This has important clinical implications, especially in the elderly cohort, with higher 25(OH)D levels being associated with a reduced incidence of falls and fragility fractures.

Abstract Background Through advocacy initiatives such as roadshows during “National ACP Week”, the Agency for Integrated Care (AIC) had increased advance care planning (ACP) engagement since 2011. Project Happy Apples (PHA), a community initiative project led by medical students from the National University of Singapore, also conducted a public exhibition to raise ACP awareness during this period. This study aimed to investigate and identify predictors of attitudes towards ACP documentation among ‘ACP Week’ respondents which may be used to formulate strategies to increase ACP documentation in Singapore. Methods A cross-sectional study on ACP documentation attitudes of 262 respondents during local roadshows were conducted. Multiple logistic regression models were built to investigate the associations between demographic variables and attitudes toward ACP documentation. Results The mean age was 43.5 years (SD = 17.4), 79 (30.15%) were males and 49 (18.7%) were healthcare professionals (HCP). 117 (44.66%) respondents had prior experience with serious illness and 116 (44.27%) had heard of ACP. Age was a significant predictor of readiness to sign official papers naming nominated healthcare spokesperson (NHS) (OR = 1.04, 95%CI: 1.02–1.07). Experience with serious illness was a significant predictor of readiness to discuss end-of-life (EOL) care with healthcare professionals (HCP) (OR = 3.65, 95%CI: 1.36–11.61). Being female was a significant predictor for readiness to speak to their nominated healthcare spokesperson about EOL care (OR = 7.33, 95%CI: 2.06–46.73). Subgroup analyses revealed that those aged 20–39 were less likely to speak to their healthcare professional about or sign official papers regarding EOL care. We also found that being a healthcare professional does not necessitate better or worse attitudes. Conclusion Advocacy programs tailored to targeting respondents of different age groups and prior experience with serious illness may improve the efficacy of advocacy efforts.

Abstract Purpose The purpose of this study is to investigate the impact of Mayo Adhesive Probability (MAP) score and body mass index (BMI) on renal function decline after robotic assisted partial nephrectomy (RAPN). Methods We queried our prospective database for patients who underwent RAPN between January 2018 and December 2023. Outcomes were development of de novo CKD‐S3 (estimated glomerular filtration rate [eGFR]

Abstract The interaction of condensed phase systems with external electric fields is of major importance in a myriad of processes in nature and technology, ranging from the field-directed motion of cells (galvanotaxis), to geochemistry and the formation of ice phases on planets, to field-directed chemical catalysis and energy storage and conversion systems including supercapacitors, batteries and solar cells. Molecular simulation in the presence of electric fields would give important atomistic insight into these processes but applications of the most accurate methods such as ab-initio molecular dynamics (AIMD) are limited in scope by their computational expense. Here we introduce Perturbed Neural Network Potential Molecular Dynamics (PNNP MD) to push back the accessible time and length scales of such simulations. We demonstrate that important dielectric properties of liquid water including the field-induced relaxation dynamics, the dielectric constant and the field-dependent IR spectrum can be machine learned up to surprisingly high field strengths of about 0.2 V Å−1 without loss in accuracy when compared to ab-initio molecular dynamics. This is remarkable because, in contrast to most previous approaches, the two neural networks on which PNNP MD is based are exclusively trained on molecular configurations sampled from zero-field MD simulations, demonstrating that the networks not only interpolate but also reliably extrapolate the field response. PNNP MD is based on rigorous theory yet it is simple, general, modular, and systematically improvable allowing us to obtain atomistic insight into the interaction of a wide range of condensed phase systems with external electric fields.

In anticipation of potential future pandemics, we examined the challenges and opportunities presented by the COVID-19 outbreak. This analysis highlights how artificial intelligence (AI) and predictive models can support both patients and clinicians in managing subsequent infectious diseases, and how legislators and policymakers could support these efforts, to bring learning healthcare system (LHS) from guidelines to real-world implementation. This report chronicles the trajectory of the COVID-19 pandemic, emphasizing the diverse data sets generated throughout its course. We propose strategies for harnessing this data via AI and predictive modelling to enhance the functioning of LHS. The challenges faced by patients and healthcare systems around the world during this unprecedented crisis could have been mitigated with an informed and timely adoption of the three pillars of the LHS: Knowledge, Data and Practice. By harnessing AI and predictive analytics, we can develop tools that not only detect potential pandemic-prone diseases early on but also assist in patient management, provide decision support, offer treatment recommendations, deliver patient outcome triage, predict post-recovery long-term disease impacts, monitor viral mutations and variant emergence, and assess vaccine and treatment efficacy in real-time. A patient-centric approach remains paramount, ensuring patients are both informed and actively involved in disease mitigation strategies.

Mycobacteria are causative agents of tuberculosis (TB), which is a global health concern. Drug-resistant TB strains are rapidly emerging, thereby necessitating the urgent development of new drugs. Two-component signal transduction systems (TCSs) are signaling pathways involved in the regulation of various bacterial behaviors and responses to environmental stimuli. Applying specific inhibitors of TCSs can disrupt bacterial signaling, growth, and virulence, and can help combat drug-resistant TB. We conducted a comprehensive pharmacophore-based inhibitor screening and biochemical and biophysical examinations to identify, characterize, and validate potential inhibitors targeting the response regulators PhoP and MtrA of mycobacteria. The constructed pharmacophore model Phar-PR-n4 identified effective inhibitors of formation of the PhoP–DNA complex: ST132 (IC50 = 29 ± 1.6 µM) and ST166 (IC50 = 18 ± 1.3 µM). ST166 (KD = 18.4 ± 4.3 μM) and ST132 (KD = 14.5 ± 0.1 μM) strongly targeted PhoP in a slow-on, slow-off manner. The inhibitory potency and binding affinity of ST166 and ST132 for MtrAC were comparable to those of PhoP. Structural analyses and molecular dynamics simulations revealed that ST166 and ST132 mainly interact with the α8-helix and C-terminal β-hairpin of PhoP, with functionally essential residue hotspots for structure-based inhibitor optimization. Moreover, ST166 has in vitro antibacterial activity against Macrobacterium marinum. Thus, ST166, with its characteristic 1,2,5,6-tetrathiocane and terminal sulphonic groups, has excellent potential as a candidate for the development of novel antimicrobial agents to combat pathogenic mycobacteria.

Formulating interventions when working with children from a wide age range who have experienced familial adversity with diverse developmental needs present significant challenges that warrant investigation. The MAP framework, which was established by a support service in Hong Kong, encompasses guidelines for both therapeutic goals and strategies to facilitate focus and clarity in the therapeutic work based on literature review, critical reflection, and feedback from participants. As therapeutic goals, M stands for mindful awareness and management of emotions, A denotes attachment building, and P refers to positive self-worth. In working toward intervention strategies, M represents mindfulness practice, and A and P refer to art and play mediums, respectively. Case examples are included to illustrate the application of the model.

Abstract Derivatives of the potassium-sparing diuretic amiloride are preferentially cytotoxic toward tumor cells relative to normal cells, and have the capacity to target tumor cell populations resistant to currently employed therapeutic agents. However, a major barrier to clinical translation of the amilorides is their modest cytotoxic potency, with estimated IC50 values in the high micromolar range. Here we report the synthesis of ten novel amiloride derivatives and the characterization of their cytotoxic potency toward MCF7 (ER/PR-positive), SKBR3 (HER2-positive) and MDA-MB-231 (triple negative) cell line models of breast cancer. Comparisons of derivative structure with cytotoxic potency toward these cell lines underscore the importance of an intact guanidine group, and uncover a strong link between drug-induced cytotoxicity and drug lipophilicity. We demonstrate that our most potent derivative called LLC1 is preferentially cytotoxic toward mouse mammary tumor over normal epithelial organoids, acts in the single digit micromolar range on breast cancer cell line models representing all major subtypes, acts on cell lines that exhibit both transient and sustained resistance to chemotherapeutic agents, but exhibits limited anti-tumor effects in a mouse model of metastatic breast cancer. Nonetheless, our observations offer a roadmap for the future optimization of amiloride-based compounds with preferential cytotoxicity toward breast tumor cells.

Abstract Halide solid electrolytes do not currently display ionic conductivities suitable for high-power all-solid-state batteries. We explore the model system A2ZrCl6 (A = Li, Na, Cu, Ag) to understand the fundamental role that A-site chemistry plays on fast ion transport. Having synthesised the previously unknown Ag2ZrCl6 we reveal high room temperature ionic conductivities in Cu2ZrCl6 and Ag2ZrCl6 of 1 × 10−2 and 4 × 10−3 S cm−1, respectively. We introduce the concept that there are inherent limits to ionic conductivity in solids, where the energy and number of transition states play pivotal roles. Transport that involves multiple coordination changes along the pathway suffer from an intrinsic minimum activation energy. At certain lattice sizes, the energies of different coordinations can become equivalent, leading to lower barriers when a pathway involves a single coordination change. Our models provide a deeper understanding into the optimisation and design criteria for halide superionic conductors.

Abstract The Arctic is experiencing rapid reductions in sea ice, affecting all ice-dependant species. In the present study we examine interannual seasonal movements and habitat use in relation to sea ice coverage for one of the Arctic endemic marine mammals. We tagged 40 male walruses (Odobenus rosmarus) in the Svalbard Archipelago with custom-designed tusk-mounted GPS loggers. Twelve of these animals provided tracks that lasted 1–6 years. Eleven of the walruses displayed clear seasonal migratory behaviour between summer foraging areas and winter breeding areas. Individuals showed high inter-individual variation, but clear site fidelity, using the same areas in consecutive years despite variable sea ice conditions. The walruses swam 5225–10,406 km per year and travelled remarkably similar distances between years on an individual basis. The phenology of migration was not impacted by sea ice concentrations or daylight length but was consistent at the individual level, suggesting endogenous drivers. Sea ice concentrations influenced movement behaviour with animals showing more tortuous paths when in areas with heavy sea ice, possibly searching for polynyas where females reside. Ongoing climate change is expected to drastically change walrus habitat, and it remains to be seen if walruses will be able to shift from their fixed seasonal migratory routines.

Abstract Determining one’s confidence in a decision is a vital part of decision-making. Traditionally, psychological experiments have assessed a person’s confidence by eliciting confidence judgments. The notion that such judgments can be elicited without impacting the accuracy of the decision has recently been challenged by several studies which have shown reactivity effects—either an increase or decrease in decision accuracy when confidence judgments are elicited. Evidence for the direction of reactivity effects has, however, been decidedly mixed. Here, we report three studies designed to specifically make reactivity effects more prominent by eliciting confidence judgment contemporaneously with perceptual decisions. We show that confidence judgments elicited contemporaneously produce an impairment in decision accuracy, this suggests that confidence judgments may rely on a partially distinct set of cues/evidence than the primary perceptual decision and, additionally, challenges the continued use of confidence ratings as an unobtrusive measure of metacognition.

Highlights Inspired by transport system in trees, a two-way water and salt transport mechanism is realized in a structurally graded aerogel, enabling simultaneous fast water uptake and salt rejection. The horizontally aligned pore channels near the surface achieve excellent heat localization by maximizing solar absorption and minimizing heat loss. The integrated water, salt, and thermal transports impart an impressive evaporation rate of 1.94 kg m−2 h−1 in a 20 wt% NaCl solution for 8 h without salt accumulation.

ABSTRACT Aims/Introduction To determine the population health burden attributable to the development of diabetes among women with a history of gestational diabetes mellitus (GDM). Materials and Methods We conducted a retrospective analysis of women with a history of GDM attending the Hong Kong Hospital Authority between 2000 and 2019. The time‐varying population attributable fraction was calculated. Results A total of 76,181 women with a history of gestational diabetes mellitus were included, 6,606 of them developed diabetes during a median follow‐up of 8.6 years. The respective hazard ratios (95% confidence interval) among women with GDM who developed diabetes vs those with GDM only were 2.8 (2.2, 3.7) for cardiovascular disease (CVD), 4.8 (3.0, 7.7) for end‐stage kidney disease (ESKD), 2.2 (1.9, 2.6) for infection‐related hospitalization, and 1.8 (1.3, 2.4) for all‐cause mortality. The development of diabetes was associated with 1.3 (0.8, 1.7), 0.6 (0.3, 0.8), 3.2 (2.4, 4.0), and 0.5 (0.2, 0.9) additional incident cases per 1,000 person‐years, accounting for 24.0% (13.2%, 35.9%), 42.0% (22.5%, 58.8%), 10.8% (7.1%, 14.9%), and 6.0% (−3.1%, 16.1%) of absolute number of CVD, ESKD, infection‐related hospitalization, and all‐cause mortality over 20 years after GDM, respectively. Conclusions Diabetes is a significant contributor to the population health burden of some clinical outcomes in women with a history of gestational diabetes mellitus, but other risk factors need to be considered.

This study analysed the composition and leaching results for 12 IFA samples from a local incineration plant by XRF and leaching tests based on BS EN12457-1:2002. XRF results show that the main elements are Ca, Cl and S in all IFA samples. Leaching test results shows a high leachability of Na, Cl, Br, Pb, Zn and Cu. The accelerated carbonation with (NH4)2CO3 was attempted to inhibit heavy metals leaching and remove soluble salts. The effect of (NH4)2CO3 concentration on carbonation efficiency and inhibition of heavy metal leaching was systematically investigated. TGA and ICP-MS were used to determine carbonation capacity and heavy metal leaching, respectively. TGA results show the maximum carbonation capacity is achieved in one hour with 10 wt% (NH4)2CO3 and 76% carbonation occurs -in the first 10 min. Leaching test results reveal that Cu and Pb are efficiently immobilised when the concentration of (NH4)2CO3 is as low as 2 wt% with a s/l ratio of 1:5 within 1 hr. Increasing the concentration of (NH4)2CO3 to 4 wt%, the leaching rate of Zn is also below NEA RVs (National Environment Agency of Singapore). Carbonation is also effective to immobilise Cd and Ni, but not for Cr since it exists as CrO42- and cannot be carbonated. XRF results from a larger scale reaction confirm the significant removal of soluble salts, and lower leachability (except SO42-) is substantiated by leaching tests. By integrating the processes of CO2 capture with ammonia and accelerated carbonation, our work contributes to CO2 sequestration and IFA detoxification.

Abstract Throughout the Arctic, ice‐affiliated marine mammals constitute local subsistence resources but detrimental effects of declines in their sea ice habitats create a need for harvest sustainability assessments in light of climate change. At the same time, empirical data required for thorough population analysis of these species are often sparse at best, as illustrated by the focal species in this study, ringed seals in Svalbard: the last population survey took place two decades ago (2002–2003), demographic data are limited to age, sex, and reproductive status of a small subset of shot individuals, and harvest reporting is patchy and incomplete. Data sparsity is one of the main reasons why potential biological removal (PBR) became a commonly used tool for assessing sustainability of marine mammal harvests. Herein, we calculated PBR for Svalbard ringed seals using both recommended default parameters and population‐specific parameters obtained from an integrated population model (IPM). PBR estimates were highly uncertain, suggesting the number of sustainably harvestable individuals could lie anywhere between 0 and 91, with a substantial chance of any harvest being unsustainable under current environmental conditions and trends. Subsequent population viability analyses (PVAs) further confirmed that the current harvest was likely unsustainable, even in a scenario in which sea ice conditions would not deteriorate (and therefore lower pup survival) further. However, uncertainty in population projections was high, and forecasts thus not ideal for formulating management advice. Better forecasts will require more frequent population surveys and obtaining more knowledge regarding the links between vital rates and environmental conditions, both of which may be facilitated by the adoption of novel technology (e.g., drone monitoring, genetic studies). The modeling framework created in this study can be readily updated with new data as they become available, and can serve as a tool for adaptive management of this and other marine mammal populations.

Climate change is impacting marine ecosystems throughout the circumpolar Arctic, altering seasonal habitats and the food bases for fishes, seabirds, and marine mammals. Arctic and Subarctic regions provide resources for resident species and for species that migrate to the north from more southerly regions. Changes in northerly latitudes thus impact endemic as well as non-endemic animals. Herein, we review what is known about climate-driven changes in the migration patterns of Arctic and Subarctic marine vertebrates, including: 1) Arctic residents with seasonal movements – those fishes, seabirds, and marine mammals that complete their entire life cycle within the Arctic but exhibit seasonal movements; 2) Breeding migrants – many seabirds enter the Arctic to breed and subsequently migrate south in the fall; and 3) Summer visitors for feeding – certain species of boreal fishes, seabirds and marine mammals arrive during the northern summer to feed on abundant prey though they breed elsewhere. Migratory movements are often driven by the timing and extent of sea ice, which defines suitable habitat for some animals and limits access to open water and prey for others. Longer open-water seasons, warmer ocean temperatures, and stronger winds have resulted in earlier production blooms in spring and often, extended open-ocean plankton blooms into late summer, resulting in altered prey types and distributions. A common thread among taxa is that shifts in distribution and timing of migrating animals indicate they are traveling farther north, or shifting longitudinally, and migrations are occurring over longer seasonal time frames. Species performing multiple lifetime migrations or long-distance migrants may need to adjust migration timing or routing iteratively to match changes in marine productivity. Altered animal distributions or phenology, and reduced sea ice, affects access to animals that are critical nutritional, economical, and cultural components of Indigenous people’s lives in the Arctic. Ongoing changes challenge the resilience and adaptability of Arctic people and ecosystems, and will require adaptive research and management approaches.

Introduction Extirpative bladder surgery for bladder cancer requires urinary diversion which causes cosmetic and functional changes that affect a patient’s body image and quality of life. Current health-related quality of life (HRQOL) surveys validated for use in bladder cancer patients have no dedicated domain evaluating body image. We sought to validate the ten-item Body Image Scale (BIS) for use in bladder cancer patients. The BIS is scored on a 4-point Likert scale with a maximum score of 30. Higher scores represent increasing distress. Methods With Institutional Review Board approval, native English or Spanish speaking patients who had undergone radical cystectomy and urinary diversion with either ileal conduit formation or orthotopic neobladder creation within the past 5 years for muscle-invasive bladder cancer were identified. The survey was conducted via telephone or e-mail. Surveys were scored and analyzed for reliability and validity. Results 32 patients were identified (22 men, 10 women). 25 patients had ileal conduits and 7 had orthotopic neobladders. Cronbach’s alpha reliability coefficient measuring internal consistency for the BIS instrument in this group was 0.926. All ten items met the response criteria (score of >0 by >30% respondents) in our study population. Though the ileal conduit group mean (17.4) and median (16) scores were lower than the neobladder (mean=19.1 and median=22), there was no statistically significant difference in BIS scores between the two cohorts (p=0.755). Conclusions We present a validation study for use of BIS in bladder cancer patients to be utilized in future clinical trials or psycho-oncology research.

Nutrient recovery is crucial for sustainability as it helps to recycle valuable resources, reduce environmental pollution, and promote the efficient use of natural materials in various agricultural and industrial processes. The present study investigated the impact of using brine and struvite as sustainable nutrient sources on the growth and c-phycocyanin (C-PC) production by the cyanobacterium Arthrospira platensis. Three modified growth media were compared to the standard SAG-spirul medium under yellow-white light [YLT], and blue-white light [BLT]. In the modified medium BSI, a struvite solution was utilized to replace dipotassium phosphate, while diluted brine was used to replace NaCl and de-ionized H2O. For BSII, struvite and brine were used as in BSI, with elimination of the micronutrient from the solution. In BSIII, no other nutrient sources than bicarbonate-buffer were used in addition to struvite and brine. For each medium, A. platensis was cultivated and incubated under YLT or BLT till the stationary phase. The results showed that the combinations of brine and struvite did not have any significant negative impact on the growth rates in BSIII. However, adding struvite as a phosphorus source boosted C-PC production just as effectively as YLT, with boosting biomass yield, unlike when only BLT was used. In conclusion, the brine/struvite-based media resulted in high biomass productivity with higher C-PC yields, making it an ideal growth medium for commercial sustainable C-PC production.

Microplastics have become major pollutants in the marine environment and can accumulate in high concentrations, especially in the gut of marine organisms. Unlike other seafood, bivalves are consumed whole, along with their digestive systems, resulting in the transfer of microplastics to humans. Therefore, there is an urgent need to review the status of microplastic pollution in marine bivalves. In this context, this article provides a comprehensive review of the status of microplastic pollution in marine bivalves and the impact of microplastics on the physiology and immunology of marine bivalves. In general, marine bivalves can accumulate high levels of microplastics in a tissue-specific manner. Although microplastic pollution does not cause mortality in bivalves, it can adversely affects bivalves' immunity, byssus production, and reproduction, potentially affecting bivalve populations. This article provides important information that will aid establishing management measures and determining the direction of future research.

In the dynamic interaction between the runner and the ground, the running shoe is the only medium that bears the impact force of body weight and plays a crucial role in athletic performance. Traditional designs do not adequately consider the different shapes of the foot, which often leads to discomfort and aggravation of foot disorders. This study presents an innovative approach to running shoe midsole design using 3D-printed chiral negative poisson’s ratio (NPR) structures to enhance shock absorption and support, thereby optimizing biomechanical performance and comfort. Using computer-aided design (CAD) and computer-aided engineering (CAE), the biomechanical effects of different midsole structures has been explored through finite element analysis (FEA). The study focuses on optimizing the cushioning, propulsion and stability of the midsole to mitigate the impact on the ankle and knee. Static compression and dynamic impact simulations were utilized to comprehensively select optimized design of midsole structure and the selected structures was 3D printed to validate the biomechanical benefits in a wear trial. The results of the study highlight the superior performance of chiral NPR structures in reducing forefoot stress during standing and movement and advance the design and functionality of 3D printed materials in running shoes.

Summary: Abdominal and thoracic aortic aneurysms (AAAs, TAAs) remain a major cause of deaths worldwide, in part due to the lack of reliable prognostic markers or early warning signs. Sox6 has been found to regulate renin controlling blood pressure. We hypothesized that Sox6 may serve as an important regulator of the mechanisms contributing to hypertension-induced aortic aneurysms. Phenotype and laboratory-wide association scans in a clinical cohort found that SOX6 gene expression is associated with aortic aneurysm in subjects of European ancestry. Sox6 and tumor necrosis factor alpha (TNF-α) expression were upregulated in aortic tissues from patients affected by either AAA or TAA. In Sox6 knockout mice with angiotensin-II-induced AAA, we found that Sox6 plays critical role in the development and progression of AAA. Our data support a regulatory role of SOX6 in the development of hypertension-induced AAA, suggesting that Sox6 may be a therapeutic target for the treatment of aortic aneurysms.

Abstract Optimal treatment of infants with many renally cleared drugs must account for maturational differences in renal transporter (RT) activity. Pediatric physiologically‐based pharmacokinetic (PBPK) models may incorporate RT activity, but this requires ontogeny profiles for RT activity in children, especially neonates, to predict drug disposition. Therefore, RT expression measurements from human kidney postmortem cortical tissue samples were normalized to represent a fraction of mature RT activity. Using these data, maximum likelihood estimated the distributions of RT activity across the pediatric age spectrum, including preterm and term neonates. PBPK models of four RT substrates (acyclovir, ciprofloxacin, furosemide, and meropenem) were evaluated with and without ontogeny profiles using average fold error (AFE), absolute average fold error (AAFE), and proportion of observations within the 5–95% prediction interval. Novel maximum likelihood profiles estimated ontogeny distributions for the following RT: OAT1, OAT3, OCT2, P‐gp, URAT1, BCRP, MATE1, MRP2, MRP4, and MATE‐2 K. Profiles for OAT3, P‐gp, and MATE1 improved infant furosemide and neonate meropenem PBPK model AFE from 0.08 to 0.70 and 0.53 to 1.34 and model AAFE from 12.08 to 1.44 and 2.09 to 1.36, respectively, and improved the percent of data within the 5–95% prediction interval from 48% to 98% for neonatal ciprofloxacin simulations, respectively. Even after accounting for other critical population‐specific maturational differences, novel RT ontogeny profiles substantially improved neonatal PBPK model performance, providing validated estimates of maturational differences in RT activity for optimal dosing in children.

Introduction: Telehealth utilization surged during the COVID-19 pandemic, offering expanded health care access. Audio-only visits emerged as a crucial tool for patients facing technology or connectivity barriers to still use telehealth. This qualitative study aims to better understand patient perceptions of audio-only versus video telehealth visits during the COVID-19 pandemic, and how patients perceive the role of each in their overall health care. Methods: Semi-structured interviews were conducted with 14 adult patients seeking care at an academic medical center located in the Southeast region of the United States. Patients had experienced both an audio-only and video telehealth visit within the past 6 months. Topics covered in the interview included comfort, preference, quality, and communication during each type of visit. Interviews were transcribed verbatim, coded, and analyzed using a general inductive approach. Results: Participants valued having both modalities available largely due to convenience and saw these visits as supplemental or supporting their in-person care. Preferences for visit types were varied among participants and were context-specific, influenced by visit purpose and provider rapport. Patients viewed audio-only visits favorably for informational follow-ups and highlighted their convenience, particularly for multitasking and caregiving duties. In contrast, video visits were seen as more effective for communication due to visual cues and better suited for demonstrating health conditions. Audio-only visits were also seen as less technology-dependent and served as a vital back-up to failed video encounters. Discussion: Despite varied preferences, patients perceived both modalities as complementary to in-person care. Concerns around the quality of care were mitigated by patients' and providers' judicious use of visit types based on clinical appropriateness and existing rapport. The results emphasize the necessity and flexibility of audio-only visits in ensuring equitable access to telehealth, especially for those with technology limitations or demanding responsibilities. To maintain the access and convenience afforded by telehealth and ensure these benefits are offered equitably, policy makers and health care organizations must continue to provide flexible telehealth options, including audio-only visits.

Abstract Aims and objectives To analyze anti-MMP mode of action of Quaternary Ammonium Silane (QAS, codenamed as k21) by binding onto specific MMP site using computational molecular simulation and Anti-Sortase A (SrtA) mode of action by binding onto specific site using computational molecular simulation. Materials and methods In silico Molecular Dynamics (MD) was used to determine the interactions of K21 inside the pocket of the targeted protein (crystal structure of fibroblast collagenase-1 complexed to a diphenyl-ether sulphone based hydroxamic acid; PDB ID: 966C; Crystal structure of MMP-2 active site mutant in complex with APP-derived decapeptide inhibitor. MD simulations were accomplished with the Desmond package in Schrödinger Drug Discovery Suite. Blood samples (~ 0.5 mL) collected into K2EDTA were immediately transferred for further processing using the Litron MicroFlow® PLUS micronucleus analysis kit for mouse blood according to the manufacturer’s instructions. Bacterial Reverse Mutation Test of K21 Molecule was performed to evaluate K21 and any possible metabolites for their potential to induce point mutations in amino acid-requiring strains of Escherichia coli (E. coli) (WP2 uvrA (tryptophan-deficient)). Results Molecular Simulation depicted that K21 has a specific pocket binding on various MMPs and SrtA surfaces producing a classical clouting effect. K21 did not induce micronuclei, which are the result of chromosomal damage or damage to the mitotic apparatus, in the peripheral blood reticulocytes of male and female CD-1 mice when administered by oral gavage up to the maximum recommended dose of 2000 mg/kg. The test item, K21, was not mutagenic to Salmonella typhimurium (S. typhimurium) strains TA98, TA100, TA1535 and TA1537 and E. coli strain WP2 uvrA in the absence and presence of metabolic activation when tested up to the limit of cytotoxicity or solubility under the conditions of the test. Conclusion K21 could serve as a potent protease inhibitor maintaining the physical and biochemical properties of dental structures.

Abstract Despite the well-documented, broad global distribution of sperm whales (Physeter macrocephalus), their distributional patterns remain poorly known in Arctic regions, where year-round monitoring is challenging. Adult male sperm whales are known to migrate seasonally between nutrient-rich high latitude waters and low latitude breeding grounds. However, knowledge is limited regarding fine-scale distribution and seasonal presence at high latitudes. To investigate the acoustic occurrence of this vocally active species in the High Arctic of the Northeast Atlantic, this study combined automated and manual click detection methods to analyze passive acoustic data collected at eight locations around the Svalbard Archipelago, Norway, between 2012 and 2021. The results revealed the presence of sperm whales at six recording sites and demonstrated sperm whale “hotspots” in ice-free areas in eastern Fram Strait along the shelf break and close to the west coast of Spitsbergen from May–January, with some variation between years and locations. Although acoustic presence decreased with increasing latitude, even the northern-most location (81° N) recorded sperm whale vocal activity between August and January. This study provides a baseline for sperm whale acoustic presence in the High Arctic, which will be essential in the context of detecting future changes and also for predicting future distribution patterns in the rapidly changing Arctic marine environment.

Abstract Objective The prevalence of atrial fibrillation (AF) in type 2 diabetes mellitus (DM) patients under primary care in Hong Kong was yet to be explored. We aimed to evaluate the prevalence of AF in patients with DM so as to provide evidence-based recommendations to incorporate AF screening as a component in regular diabetic risk and complication assessment. The performance of automated BP machine Microlife WatchBP Office AFIB as a screening tool for the detection of AF was also evaluated. Method This was a cross-sectional study. Patients with type 2 DM who attended the regular diabetic risk and complication assessment in the participating clinics from 24 August 2021 to 27 January 2022 were recruited. Blood pressure measurement by Microlife WatchBP Office AFIB and 12-lead ECGs were performed for AF screening. Results Among 2015 DM patients in primary care, the prevalence of AF was found to be 1.9% (95% confidence interval [CI] 1.3–2.6). The prevalence of AF increased with age, from 0.5% in patients aged

Spatial neglect in stroke survivors is associated with a decrease in quality of life. This disorder occurs in 20–80% of stroke survivors and up to 1/3 of stroke survivors will continue to experience chronic impairment. Occupational therapists are uniquely qualified to treat stroke survivors with spatial neglect due to their holistic approach but access to therapy is limited. Diagnostic coding is used to help determine appropriate reimbursement and continuation of care including rehabilitation services. The objectives of this study were to 1) identify the prevalence of diagnostic coding for spatial neglect in stroke survivors, and 2) identify the prevalence and types of rehabilitation for patients with diagnostic coding for spatial neglect. We completed a retrospective cohort analysis using 2018 and 2019 5% Medicare Limited Data Sets from the Centers for Medicare and Medicaid Services. We extracted all ischemic stroke survivors and stratified them by the presence of a secondary diagnostic code indicating spatial neglect. Rehabilitation Current Procedural Terminology codes were used to identify stroke survivors who received rehabilitation. Despite recommendations from clinical practice, only 4.9% had a diagnostic code for spatial neglect. Of those formally diagnosed, only 2.3% received outpatient occupational therapy after being discharged from acute care.

Background: Human Normal Immunoglobulin (HNIg) is a complex plasma-derived blood product used to treat a variety of medical conditions. Global supply problems have increased focus on HNIg stewardship, including mandatory recording of HNIg usage on the National Immunoglobulin Database (NIgD). Local departmental audits identified significant inconsistencies in data uploaded to NIgD. Inventory management issues caused a number of stock losses in the last financial year. A paper-based HNIg batch number recording system was replaced with the use of Automated Dispensing Cabinets (ADCs), which generated an electronic batch number report, with matching fields required for electronic upload to NIgD. Aim: To measure the impact of ADC implementation on the accuracy of data uploaded to NIgD, HNIg stock control and staff time associated with processes of HNIg data and inventory management. Method: Three months of pre- and post-implementation HNIg dispensing data was compared to the data uploaded to the NIgD for discrepancies. Inventory reports were used to identify unexplained stock adjustments. Time and motion methods were used to quantify staff time associated with HNIg activities. Results: Pre-implementation: 20.7 % (3762.5 g/18,217 g) of HNIg by volume (23.7 % of dispensing episodes; 66/279) were inaccurately uploaded or absent on the NIgD and three stock adjustments were made (loss of >£15 k). Post-implementation: 12 % (2325 g/19,347 g) of HNIg by volume (10.8 % of dispensing episodes; 31/286) were inaccurately uploaded or absent on the NIgD and zero stock adjustments were observed; Mean time for dispensing per HNIg prescription reduced from 17 min to 8 min; Time spent uploading data to NIgD per month reduced from 5 h to 1.75 h. Discussion/Conclusion: The use of ADCs improved accuracy of NIgD data upload. Following implementation direct observations have cited unregistered or finished patient episodes, dispensing procedural compliance, and user familiarity with the system as common reasons for incomplete data uploads to NIgD. The new ADC process had consequences of forcing dispensing procedure compliance to improve uploads, whilst reducing dispensing times. It led to improved stock control and removed upload burden from dispensers. ADC stock discrepancy alerts allowed staff to proactively resolve discrepancies in real time. Time taken for additional processes to support management of stocks in ADCs, including monthly stock cycle counts, were important considerations for implementation. The key advantage of using ADC batch number reports is the ability to upload as a single monthly batch without having to manually access individual patient records on the NIgD. It facilitates early identification of failed upload attempts and supports resolution of stock discrepancies.

Background: Parents of children with hematological cancers such as leukemia and lymphoma need to cope with stress related to their child’s diagnosis. The Coping Self-Efficacy Scale is a widely used and validated tool to measure an individual’s confidence in dealing with stressful situations. Appropriate translation and validation are needed to produce a localized language version suitable for Malaysian contexts. Objective: The study aimed to examine the linguistic and construct validity of the Malay version of the Coping Self-Efficacy Scale (CSES-My) among parents of children with hematological cancer. Methods: The CSES-My was created through a sequential series of steps, starting with the translation of the original English version, followed by cultural adaptation, and then cognitive interviewing. The 26-item CSES-My was self-administered in a sample of parents of children with leukemia and lymphoma from October 2021 until February 2022. They were recruited via online or face-to-face methods. Exploratory factor analysis was performed to examine the construct validity of the CSES-My. Results: A total of 165 complete responses were analyzed. The scale has two factors, including Personal Coping and Social Coping, accounting for 58.3% of the variance. Personal Coping (19 items, Cronbach’s alpha = 0.958) represented the respondents’ self-efficacy for independently executing coping strategies, whether through solving problems or changing the way they think about the situation. Social Coping (6 items, Cronbach’s alpha = 0.867) represented their confidence in executing coping strategies, which involved using social resources such as seeking external support, distraction, and avoiding loneliness. Conclusions: The CSES-My had reliable and valid psychometric properties, providing evidence for its utility in evaluating coping self-efficacy among parents of children with leukemia or lymphoma in Malaysia. The CSES-My is a valuable tool for nurses and other healthcare professionals investigating coping self-efficacy in Malay-speaking populations, and it may also aid in the development of future coping interventions.

Sinus tarsi syndrome (STS) is a clinical entity characterized by pain of the lateral hindfoot and a sense of instability especially on uneven surfaces due to chronic inflammation characterized by fibrotic tissue remnants and synovitis of the sinus tarsi, associated with both traumatic and nontraumatic causes. Arthroscopic debridement of the subtalar joint is an effective and safe alternative in the treatment of STS refractory to conservative treatment. The purpose of this Technical Note is to report the details of arthroscopic management of STS.

Industrial waste, including wastewater and solid waste, often contains toxic heavy metals that necessitate extraction and separation prior to safe disposal or reusing them. Sewage sludge incineration ash (SSIA), a non-incinerable waste, holds significant amounts of heavy metals such as iron, zinc, copper, nickel, chromium, and lead. Recovery and reuse of heavy metals from SSIA and further application of treated SSIA sludge remain challenging. Ethylenediaminetetraacetic acid (EDTA) is widely used for heavy metals chelation in different applications. While its chelation with heavy metals is rapid and easy to achieve, the de-chelation of the metal complexes is otherwise slow (∼3 days) and challenging due to their high stability constants. In this study, we investigate the recovery of heavy metals from SSIA through chelation using EDTA, and develop, for the first time, a method to rapidly de-chelate the EDTA-metal complexes through the facile chilling process (1 – 3 h) that accelerates the separation of EDTA and metal ions. A sequential precipitation of high-purity heavy metals from the EDTA-metal complexes was demonstrated with and without de-chelation. This novel and versatile method allows the separation of many valuable compounds from the treated SSIA, including regenerated EDTA, potassium hexafluorosilicate, iron phosphate, iron(III) hydroxide, iron silicate, titanium phosphate, calcium phosphate, copper(I) thiocyanate, nickel bis(dimethylglyoximate), lead(II) sulfate, and zinc sulfide. This approach opens doors for more sustainable waste management and the recovery of valuable resources from industrial waste.

Brown seaweed polysaccharides (BSPs) are potential alternative sources of bioactive compounds. The food and pharmaceutical industries have a great interest in BSPs because of their various bioactivities, such as anticancer, antioxidant, and immunomodulatory activities. Studies have demonstrated that the bioactivities of BSPs are significantly influenced by their structural characteristics and chemical constitution; but, their specific conformational relationships are complex and required further study. However, systematic reviews of the biological activities and mechanisms of action of BSPs are currently inadequate. Thus, this paper summarizes recent studies on the physicochemical and structural features, characterization methods, biological activities, and related action mechanisms of BSPs from different sources. Based on these findings, future prospects include the following three aspects. More advanced research techniques need to be developed to identify the exact main and branch structure of BSPs; in-depth studies of the detailed structure of BSPs are needed to elucidate the conformational relationships between polysaccharides and their activities, and clinical trials should be conducted to verify the effectiveness of BSPs in the prevention and treatment of various diseases. The information provided here aims to offer a theoretical foundation for further research on the structural properties, mechanism of action, and potential applications of BSPs in food and pharmaceutical industries as well as, to increase the economic value of BSPs and extend their application range.

The heightened transmissibility and capacity of African swine fever virus (ASFV) induce fatal diseases in domestic pigs and wild boars, posing significant economic repercussions and global threats. Despite extensive research efforts, the development of potent vaccines or treatments for ASFV remains a persistent challenge. Recently, inhibiting the AsfvPolX, a key DNA repair enzyme, emerges as a feasible strategy to disrupt viral replication and control ASFV infections. In this study, a comprehensive approach involving pharmacophore-based inhibitor screening, coupled with biochemical and biophysical analyses, were implemented to identify, characterize, and validate potential inhibitors targeting AsfvPolX. The constructed pharmacophore model, Phar-PolX-S, demonstrated efficacy in identifying a potent inhibitor, D-132 (IC50 = 2.8 ± 0.2 µM), disrupting the formation of the AsfvPolX-DNA complex. Notably, D-132 exhibited strong binding to AsfvPolX (KD = 6.9 ± 2.2 µM) through a slow-on-fast-off binding mechanism. Employing molecular modeling, it was elucidated that D-132 predominantly binds in-between the palm and finger domains of AsfvPolX, with crucial residues (R42, N48, Q98, E100, F102, and F116) identified as hotspots for structure-based inhibitor optimization. Distinctively characterized by a 1,2,5,6-tetrathiocane with modifications at the 3 and 8 positions involving ethanesulfonates, D-132 holds considerable promise as a lead compound for the development of innovative agents to combat ASFV infections.

NIR sensors, in conjunction with advanced chemometric algorithms, have proven to be a powerful and efficient tool for intelligent quality evaluation of sweetpotato roots throughout the entire supply chain. By leveraging NIR data in different wavelength ranges, the physicochemical, nutritional and antioxidant compositions, as well as variety classification of sweetpotato roots during the different stages were adequately evaluated, and all findings involving quantitative and qualitative investigations from the beginning to the present were summarized and analyzed comprehensively. All chemometric algorithms including both linear and nonlinear employed in NIR analysis of sweetpotato roots were introduced in detail and their calibration performances in terms of regression and classification were assessed and discussed. The challenges and limitations of current NIR application in quality evaluation of sweetpotato roots are emphasized. The prospects and trends covering the ongoing advancements in software and hardware are suggested to support the sustainable and efficient sweetpotato processing and utilization.

Summary: It is well-understood that the science, technology, engineering, and mathematics (STEM) fields have unique challenges that discourage recruiting and retaining underrepresented minorities. Research programs aimed at undergraduates have arisen as a critical mechanism for fostering innovation and addressing the challenges faced by underrepresented minorities. Here, we review various undergraduate research programs designed to provide exposure to undergraduates, with a focus on underrepresented minorities in STEM disciplines. We provide insight into selected programs' objectives, key features, potential limitations, and outcomes. We also offer recommendations for future improvements of each research program, particularly in the context of mentorship. These programs range from broad-reaching initiatives (e.g., Leadership Alliance) to more specific programs targeting underrepresented students. By offering a nuanced understanding of each program’s structure, we seek to provide a brief overview of the landscape of diversity-focused STEM initiatives and a guide on how to run a research program effectively.

Use of automated dispensing cabinets (ADCs) is increasing in hospital settings. ADCs bring various potential benefits, among which are improvements to patient safety and reduction of medication errors. A core function of ADCs is to prevent medication stock outs by triggering an order when stock is reaching low levels. A quantifiable patient safety measure is the occurrence of omitted or delayed doses, which can range in severity from being negligible, to potentially fatal. The purpose of this review is to identify and synthesise the existing evidence regarding the impact of ADCs situated in secondary and tertiary care inpatient settings, on the rate of omitted and delayed doses as a specific subsection of medication errors. In April 2024 searches were conducted in Embase, PubMed and CINAHL, with additional articles discovered through citation searching and from colleagues. A total of 375 articles were returned from the search. Nine articles met the inclusion criteria. The most common reason for exclusion was due to lack of relevance. The included papers were focused on centres which had implemented six or fewer ADCs. The studies mostly presented findings which suggest ADCs have a positive impact on the rate of omitted or delayed doses, although crucially only two papers correlated missed doses due to unavailability of medications The studies highlighted other factors which should be considered prior to the implementation of ADCs. Factors included staffing requirement, type of stock held in the cabinets, and interoperability with other systems. Studies only reported omitted or missed doses, none reported results on delayed doses. It is widely accepted that ADCs can prevent medication unavailability but there is a paucity of evidence linking the improved availability of medications through the utilisation of ADCs with the perceived impact on missed or delayed doses. Further multi-centre studies are needed to determine this causality.

Porphyra haitanensis, a red seaweed species, represents a bountiful and sustainable marine resource. P. haitanensis polysaccharide (PHP), has garnered considerable attention for its numerous health benefits. However, the comprehensive utilization of PHP on an industrial scale has been limited by the lack of comprehensive information. In this review, we endeavor to discuss and summarize recent advancements in PHP extraction, purification, and characterization. We emphasize the multifaceted mechanisms through which PHP promotes gastrointestinal health. Furthermore, we present a summary of compelling evidence supporting PHP's protective role against oxidative stress. This includes its demonstrated potent antioxidant properties, its ability to neutralize free radicals, and its capacity to enhance the activity of antioxidant enzymes. The information presented here also lays the theoretical groundwork for future research into the structural and functional aspects of PHP, as well as its potential applications in functional foods.

To accurately, efficiently, and environmentally prepare carrageenan oligosaccharides, we have developed a method that uses H2O2 and TiO2 as catalysts for the photodegradation of κ-carrageenan (KC). The photodegradation of KC was monitored using various amounts of TiO2 and H2O2 and different concentrations of KC via HPLC and it could decrease the average molecular weight of KC into 1.6 kDa within 2 h. Further research under optimal conditions. As a control, the effects of UV, UV/H2O2, UV/TiO2, and H2O2/TiO2 treatments were studied. In contrast, UV/H2O2/TiO2 treatments showed a coordinated effect. The effect of degradation on the structure of KC was investigated by FT-IR, XRD, and there was no obvious remotion of sulfate groups. Furthermore, oral administration of KCO prolonged the healthy lifespan of nematodes induced by ultraviolet stress and significantly regulated oxidative stress. This study suggests that the precise preparation and application of KCO may be beneficial.

Southeast Asia is vulnerable to climate change with over half of its population already being impacted by drought, flooding, and rise in sea levels recently. This work reviews the current water resource challenges in Indonesia, prone to the rising impacts of climate change. A baseline assessment of Indonesia's water and drinking water resources related to its original sources is presented. In response to a growing concern over chronic challenges that undermine water supply nationwide, this study analyses drinking water safety supervision. To accomplish this, a literature survey (100 studies published during the 2000–2023 period) was performed to identify regional groundwater resources sustainability and water security issues. Among the main findings of this study, only 10% of rainfall infiltrates to the groundwater, while 70% of its rivers are heavily polluted by domestic waste. During the study period, water availability decreased to 1,200 m3/year in 2020, with only 35% of the resources being economically feasible for reuse. The water supply deficit in Indonesia was estimated to be 5.5 hm3/year with roughly 67% of the population's water demand satisfied in 2021. Although this deficit might be fulfilled with private vendors, water supply/demand forecasts in 2030 suggest that the gap could not be closed by increasing water supply. HIGHLIGHTS About 70% of rivers in Indonesia were heavily polluted by domestic waste.; Water availability decreased to 1,200 m3/year in 2020.; Only 35% of the water is economically feasible to be reused.; Only 67% of the water demand was supplied in 2021.; Only 10% of rainfall infiltrates the underlying groundwater.;

Abstract Invariant natural killer T (iNKT) cells, a unique T cell population, lend themselves for use as adoptive therapy due to diverse roles in orchestrating immune responses. Originally developed for use in cancer, agenT-797 is a donor-unrestricted allogeneic ex vivo expanded iNKT cell therapy. We conducted an open-label study in virally induced acute respiratory distress syndrome (ARDS) caused by the severe acute respiratory syndrome-2 virus (trial registration NCT04582201). Here we show that agenT-797 rescues exhausted T cells and rapidly activates both innate and adaptive immunity. In 21 ventilated patients including 5 individuals receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO), there are no dose-limiting toxicities. We observe an anti-inflammatory systemic cytokine response and infused iNKT cells are persistent during follow-up, inducing only transient donor-specific antibodies. Clinical signals of associated survival and prevention of secondary infections are evident. Cellular therapy using off-the-shelf iNKT cells is safe, can be rapidly scaled and is associated with an anti-inflammatory response. The safety and therapeutic potential of iNKT cells across diseases including infections and cancer, warrants randomized-controlled trials.

Abstract Background Recent technological advances have led to a surge in the use of wearable devices for personal health and fitness monitoring; however, clinical uptake of wearable devices for remote or ‘free-living’ measurement of daily health-related behavior has lagged. To advance the field, there is need for valid and reliable outcomes across multiple health domains specific to the cohorts or patients of interest and centralized tools to build capacity for use of these data. The NiMBaLWear pipeline provides a flexible and integrated approach to wearables analytics applied to raw sensor data that considers multiple, inter-related physiological and behavioral signals to provide a holistic view of health status. Results & discussion NiMBaLWear is a modular, open-source, wearable sensor analytic pipeline that quantifies physical activity, mobility, and sleep from raw single- or multi-sensor free-living data collected over multiple days. Data captured from any device, in different possible formats, are standardized prior to processing. Data preparation includes accelerometer autocalibration, cross-device synchronization, and non-wear detection. Validated, domain-specific algorithms detect events, generate outcome measures, and output standardized tabular data and user-friendly summary collection reports. NiMBaLWear was developed in Python using an iterative and incremental software development process, which included a combination of semi-automated inspection and expert review of data collected from 286 participants across two remote-measurement studies. A comparative analysis revealed a paucity of open-source packages capable of deriving and sharing health-related behavioral outcomes across multiple domains from multi-sensor wearables data. Forthcoming improvements to the pipeline will leverage sensor fusion techniques to add new, and refine existing, domain- and disease-specific analytics, and optimize pipeline accessibility and reporting. Conclusion The NiMBaLWear pipeline transforms raw multi-sensor wearables data into accurate and relevant outcomes across multiple health domains to objectively characterize and measure an individual’s daily health-related behavior. NiMBaLWear’s focus on high-quality, clinically relevant outcomes, as well as end-user optimization, provides a foundation for innovation to improve the utility of wearables for clinical care and self-management of health.

Assessing plantar pressure is crucial for fabricating diabetic insoles and preventing diabetic foot ulcers (DFUs), which are caused by increased plantar pressure. However, the commonly used methods for assessing plantar pressure distribution involve professional sensor-based equipment and expertise, which are costly and time-consuming. Given the qualitative association between ink footprint images and plantar pressure, this study proposes using the footprint images to predict the quantitative values of dynamic plantar pressure in barefoot and 4 different insole conditions (including Nora Lunalastik EVA, Nora Lunalight A fresh, Pe-Lite, and PORON® Medical 4708) based on a multilayer perceptron (MLP) neural network model. To provide more precise insole material recommendations for specific foot regions for better plantar pressure distribution, the plantar of the foot is divided into 5 regions: the toes, metatarsal heads, medial midfoot, lateral midfoot, and heel. Patch-based MLP with localization embedding is introduced to learn the correspondence between ink density and plantar pressure information. Ground-truth data collected from 52 diabetes patients is constructed as a dataset named diabetes-footprint-to-pressure and used to train and validate the model. The mean absolute error (MAE) of the models for the barefoot and 4 insole conditions is 5.51% (33.06 kPa), 3.99% (23.94 kPa), 4.85% (29.10 kPa), 4.25% (25.50 kPa), and 3.57% (21.42 kPa) of the sensing range, respectively. Compared to traditional methods for plantar pressure assessment, this approach streamlines the process of acquiring the overall and regional dynamic plantar pressure with barefoot and 4 different insole materials. Clinicians can quickly provide recommendations on the type of insole material for individual patients.

Abstract Prior research has established that people use reappraisal to regulate others’ emotions in higher-emotional intensities but use distraction in lower-emotional intensities. However, research has not compared different reappraisal subtypes, such as reconstrual versus minimizing. In three pre-registered studies, participants completed a novel advice-giving task where they selected regulation strategies (distraction, reconstrual, or minimizing) to help a ‘partner’ who was ostensibly experiencing stimuli of differing emotional intensities and types (the partner was, in fact, non-existent). In Experiment 1, participants selected reconstrual over distraction significantly more for low versus high intensity stimuli. In Experiment 2, participants showed no significant preference for minimizing over distraction on low versus high intensity stimuli. In Experiment 3, participants selected reconstrual over minimizing significantly more on low versus high intensity stimuli. Results indicate that previous findings regarding the effect of emotional intensity on ‘reappraisal’ preference are limited to reconstrual and may not generalize to other reappraisal subtypes (i.e., minimizing) which require lower cognitive costs and emotional engagement with the stimuli.

Reliable operation of oil-immersed power transformers is crucial for electrical transmission and distribution networks. However, the aging of high voltage assets including power transformers along with the increasing of load demand have heightened the importance of adopting cost-effective asset management strategies. Dissolved gas analysis (DGA) has been recognized as a valuable diagnostic tool for detecting potential faults and monitoring the condition of oil-immersed power transformers. Traditional offline DGA method involves periodic sampling and laboratory analysis, which often results in delayed detection and response to emerging faults. To address these limitations, online DGA approach has been emerged to provide real-time monitoring and continuous data acquisition. This paper presents a new asset management approach for mineral oil-immersed power transformers by analysing the online DGA data using convolutional neural networks. The proposed approach provides real time solutions to classify emerging fault type and predict transformer health deterioration level with high accuracy. Results show that the accuracy of fault diagnostics of the proposed approach is approximately 87%.

Abstract Background Neural tube defects (NTDs) are caused by genetic and environmental factors. ARMC5 is part of a novel ubiquitin ligase specific for POLR2A, the largest subunit of RNA polymerase II (Pol II). Results We find that ARMC5 knockout mice have increased incidence of NTDs, such as spina bifida and exencephaly. Surprisingly, the absence of ARMC5 causes the accumulation of not only POLR2A but also most of the other 11 Pol II subunits, indicating that the degradation of the whole Pol II complex is compromised. The enlarged Pol II pool does not lead to generalized Pol II stalling or a generalized decrease in mRNA transcription. In neural progenitor cells, ARMC5 knockout only dysregulates 106 genes, some of which are known to be involved in neural tube development. FOLH1, critical in folate uptake and hence neural tube development, is downregulated in the knockout intestine. We also identify nine deleterious mutations in the ARMC5 gene in 511 patients with myelomeningocele, a severe form of spina bifida. These mutations impair the interaction between ARMC5 and Pol II and reduce Pol II ubiquitination. Conclusions Mutations in ARMC5 increase the risk of NTDs in mice and humans. ARMC5 is part of an E3 controlling the degradation of all 12 subunits of Pol II under physiological conditions. The Pol II pool size might have effects on NTD pathogenesis, and some of the effects might be via the downregulation of FOLH1. Additional mechanistic work is needed to establish the causal effect of the findings on NTD pathogenesis.

Abstract Background Uptake of COVID-19 vaccines remains problematically low in the USA, especially in rural areas. COVID-19 vaccine hesitancy is associated with lower uptake, which translates to higher susceptibility to SARS-CoV-2 variants in communities where vaccination coverage is low. Because community pharmacists are among the most accessible and trusted health professionals in rural areas, this randomized clinical trial will examine implementation strategies to support rural pharmacists in delivering an adapted evidence-based intervention to reduce COVID-19 vaccine hesitancy. Methods We will use an incomplete stepped wedge trial design in which we will randomize 30 rural pharmacies (unit of analysis) to determine the effectiveness and incremental cost-effectiveness of a standard implementation approach (consisting of online training that describes the vaccine hesitancy intervention, live webinar, and resource website) compared to adding on a virtual facilitation approach (provided by a trained facilitator in support of the delivery of the vaccine hesitancy counseling intervention by pharmacists). The intervention (ASORT) has been adapted from an evidence-based vaccine communication intervention for HPV vaccines through a partnership with rural pharmacies in a practice-based research network in seven southern US states. ASORT teaches pharmacists how to identify persons eligible for COVID-19 vaccination (including a booster), solicit and address vaccine concerns in a non-confrontational way, recommend the vaccine, and repeat the steps later if needed. The primary trial outcome is fidelity to the ASORT intervention, which will be determined through ratings of recordings of pharmacists delivering the intervention. The secondary outcome is the effectiveness of the intervention, determined by rates of patients who agree to be vaccinated after receiving the intervention. Other secondary outcomes include feasibility, acceptability, adoption, reach, and cost. Cost-effectiveness and budget impact analyses will be conducted to maximize the potential for future dissemination and sustainability. Mixed methods will provide triangulation, expansion, and explanation of quantitative findings. Discussion This trial contributes to a growing evidence base on vaccine hesitancy interventions and virtual-only facilitation of evidenced-based practices in community health settings. The trial will provide the first estimate of the relative value of different implementation strategies in pharmacy settings. Trial registration NCT05926544 (clinicaltrials.gov); 07/03/2023.