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Abstract Background Chronic pain often clusters in families, where parents and their offspring both experience chronic pain conditions. Young children of parents with irritable bowel syndrome (IBS) represent an at-risk group for the development of abdominal pain, disability, and excess health care visits in later childhood. Parental solicitous responses to children’s expressions of discomfort and maternal modeling of their own illness behavior contribute to a greater focus on somatic sensations, leading to illness behaviors in children. This randomized controlled trial will test the effectiveness of an early preventive web-based psychosocial intervention (REACH)[TM] vs. an educational web-based safety comparison condition delivered to parents with IBS to alter parental responses and lead to improved child health and decreased health care costs. Methods Parents with IBS who have children ages 4–7 years are recruited via community-based approaches (e.g., social media advertisements, school electronic distribution, research networks) and health care providers. The target sample is 460 parents randomized to REACH, a web-based social learning and cognitive behavior therapy (SLCBT) intervention or an educational web-based safety comparison condition (EC). Participants will be assessed at baseline, 6-week (immediate post-intervention), 6-month, 12-month, and 18-month follow-up periods (months post-completion of intervention). The primary outcome is change in parental solicitous/protective behaviors. Secondary outcomes include parent risk and protective factors, child health and symptom outcomes, and health care utilization and cost savings. Discussion This study adapts a validated, parent-delivered intervention to treat chronic pain in children to a web-based application designed to prevent the development of chronic pain in very young, high-risk children. If successful, this strategy can both prevent adverse sequelae of this condition from developing as well as be widely accessible. Furthermore, the availability of a prevention model for parent training could result in significant short- and long-term health benefits across a broad spectrum of conditions. Trial registration ClinicalTrials.gov NCT05730491. Registered on February 15, 2023.

Current assessment standards for peripheral arterial disease (PAD), such as the ankle brachial index, are limited in their utility and portability. Near-infrared spectroscopy (NIRS) has shown some promise in diagnosing PAD when used in conjunction with a provocative maneuver. The purpose of this study was to assess the viability of NIRS in conjunction with a transient leg elevation provocative maneuver for detecting severe PAD. This retrospective observational cross-sectional study assessed 57 limbs in 34 patients receiving routine vascular screening for PAD at Madigan Army Medical Center. The patient limbs were stratified into normal (n = 17), mild (n = 9), moderate (n = 16), and severe (n = 15) PAD groups based on the clinician assessments. Additionally, the patients were assessed with NIRS measurements taken with the patient in the supine position at rest and using a provocative leg raise maneuver of transient leg elevation of 45° for 60 seconds. The resting tissue oxygen saturation (StO2) and the change in StO2 (ΔStO2) from rest to elevation were recorded and compared between the PAD severity groups via independent measures analysis of variance with the Tukey honest significant difference post hoc test. The supine resting StO2 was not different between the normal (77.5% ± 7.7%), mild (72.5% ± 7.4%), moderate (72.0% ± 10.3%), and severe (74.2% ± 5.4%) PAD groups (P = .23). However, the ΔStO2 with transient leg elevation was significantly greater in the severe PAD group (−17.2% ± 6.0%) compared with the normal (−3.9% ± 4.8%), mild (−6.9% ± 4.7%), and moderate (−9.7% ± 5.2%) PAD groups (P < .002 for all). Similar results were observed in the changes in oxyhemoglobin and deoxyhemoglobin. The leg elevation protocol was also used for two patients before and after lower limb revascularization, which demonstrated that the ΔStO2 corresponded with the clinical assessment of PAD severity. Resting supine NIRS images were unable to detect any differences among normal and limbs with different PAD severity. However, NIRS imaging with 45° leg elevation for 60 seconds showed a significant difference between severe PAD compared healthy patients and those with mild to moderate PAD in a fast, precise, and accurate manner. These preliminary data support the use of NIRS and transient leg elevation as a tool to diagnose severe PAD but do not support the use of NIRS alone as a screening test for PAD. NIRS measurements with leg elevation might be a viable noninvasive, noncontact, and portable method of assessing severe PAD for home monitoring, in rural communities, and/or in standard clinical practice.

As Southeast Asia grapples with extreme heat occurrences in recent years, mapping which areas are clustered with elevated temperatures is crucial for monitoring the at-risk population. Identifying the contributing factors to the warming trends in these areas is also vital in formulating adaptation and mitigation strategies. This dataset comprises land surface temperature (LST) in three metropolises in the region – Metropolitan Manila, Bangkok Metropolitan Area, and Greater Jakarta – downloaded and processed from the Moderate Resolution Imaging Spectroradiometer (MODIS) instrument. We used MODIS’ inherent grid system to map LST values at the satellite image's most granular level. We combined them with selected environmental and socioeconomic variables, including building and built-up areas, areas of greeneries, industrial zones, and water bodies, nighttime light (to approximate areas of economic activities), gridded population, distance from water bodies, and indicators on which urban infrastructures, i.e. roads and airports, are present in each grid. Available in shapefile and comma-separate variable file format, this dataset is useful for urban studies in these three cities. The dataset can be easily updated as additional data on LST and other variables becomes available.

Introduction Home-based, virtually-supported care models may represent the most efficient and scalable approach to delivering prehabilitation services. However, virtual approaches to prehabilitation are understudied. This manuscript describes the protocol for an internal pilot randomised controlled trial of a virtually-delivered, multimodal prehabilitation intervention.Methods and analysis We will conduct a pragmatic, individual patient, internal pilot randomised controlled trial of home-based, virtually supported, multimodal prehabilitation compared with standard perioperative care in adults undergoing elective, inpatient thoracic, abdominal, pelvic and vascular surgery at five Canadian hospitals. Participants will be partially blinded; clinicians and outcome assessors will be fully blinded. The intervention consists of 3–12 weeks of a home-based, multimodal (exercise, nutrition and psychosocial support) prehabilitation programme supported through an online platform. The primary feasibility outcomes and their progression targets are (1) monthly recruitment of>6 participants at each centre, (2) intervention adherence of>75%, (3) retention of>90% of participants at the patient-reported primary outcome point of 30-days after surgery and (4) elicitation of patient, clinician and researcher-identified barriers to our pragmatic trial. A sample size of 144 participants will be adequate to estimate recruitment, adherence and retention rates with acceptable precision. All participants will be followed to either death or up to 1 year. As an internal pilot, if no substantive changes to the trial or intervention design are required, pilot participant outcome data will migrate, unanalysed by allocation, to the future full-scale trial.Ethics and dissemination Ethical approval has been granted by Clinical Trials Ontario (Project ID: 4479) and our ethics review board (Protocol Approval #20230399–01T). Results will be disseminated through presentations at scientific conferences, peer-reviewed publications, partner organisations and engagement of social and traditional media.Trial registration number ClinicalTrials.gov identifier NCT06042491. Protocol, V.1.2, dated 6 June 2024.

Abstract The ongoing evolution of SARS-CoV-2 to evade vaccines and therapeutics underlines the need for innovative therapies with high genetic barriers to resistance. Therefore, there is pronounced interest in identifying new pharmacological targets in the SARS-CoV-2 viral life cycle. The small molecule PAV-104, identified through a cell-free protein synthesis and assembly screen, was recently shown to target host protein assembly machinery in a manner specific to viral assembly. In this study, we investigate the capacity of PAV-104 to inhibit SARS-CoV-2 replication in human airway epithelial cells (AECs). We show that PAV-104 inhibits >99% of infection with diverse SARS-CoV-2 variants in immortalized AECs, and in primary human AECs cultured at the air-liquid interface (ALI) to represent the lung microenvironment in vivo. Our data demonstrate that PAV-104 inhibits SARS-CoV-2 production without affecting viral entry, mRNA transcription, or protein synthesis. PAV-104 interacts with SARS-CoV-2 nucleocapsid (N) and interferes with its oligomerization, blocking particle assembly. Transcriptomic analysis reveals that PAV-104 reverses SARS-CoV-2 induction of the type-I interferon response and the maturation of nucleoprotein signaling pathway known to support coronavirus replication. Our findings suggest that PAV-104 is a promising therapeutic candidate for COVID-19 with a mechanism of action that is distinct from existing clinical management approaches.

Frankincense is produced by Boswellia trees, which can be found throughout the Middle East and parts of Africa and Asia. Boswellia serrata extract has been shown to have anti-cancer, anti-inflammatory, and antimicrobial effects. Periodontitis is an oral chronic inflammatory disease that affects nearly half of the US population. We investigated the antimicrobial effects of B. serrata extract on two oral pathogens associated with periodontitis. Using the minimum inhibitory concentration and crystal violet staining methods, we demonstrated that Porphyromonas gingivalis growth and biofilm formation were impaired by treatment with B. serrata extracts. However, the effects on Fusobacterium nucleatum growth and biofilm formation were not significant. Using quantification of colony-forming units and microscopy techniques, we also showed that concentrations of B. serrata that were not toxic for host cells decreased intracellular P. gingivalis infection in human gingival epithelial cells. Our results show antimicrobial activity of a natural product extracted from Boswellia trees (B. serrata) against periodontopathogens. Thus, B. serrata has the potential for preventing and/or treating periodontal diseases. Future studies will identify the molecular components of B. serrata extracts responsible for the beneficial effects.

Type 2 diabetes mellitus (T2DM) accounts for one-sixth of deaths globally, whereas cancer is the second leading cause of death in the U.S. T2DM is a known risk factor for many cancers. Reactive oxygen species (ROS)-altered metabolic and signaling pathways link T2DM to cancer. These reprogrammed metabolic and signaling pathways contribute to diabetic complications, impact the redox balance (oxidative stress), and have differential roles in the early and late stages of cancer. A respiratory chain that is highly reduced (as under hyperglycemic conditions) or if reduced cofactors accumulate, ROS are greatly elevated. ROS may cause mutations in mitochondrial DNA (mtDNA) that result in further ROS elevations. The amplification of ROS results in the activation of PKC, an overarching signaling pathway that activates MAPK with a subsequent regulation in several factors that result in pathophysiological manifestations of T2DM and cancer. An upregulation in PKC leads to a deregulation in NF-kß, which regulates the PKB/P13/Akt pathway and orchestrates the cell survival, growth, proliferation, and glucose metabolism manifested in cancer. It also affects Insulin Receptor Substrate (IRS-1), decreasing insulin-stimulated glucose transport and glucose uptake, disrupting subsequent cell signaling pathways contributing to the development of T2DM. Dyslipidemia is a hallmark of T2DM and cancer. ROS-induced lipid peroxidation leads to systemic inflammation, producing inflammatory prostaglandins, cytokines, and chemokines that result in tumor proliferation, rapid tumor growth, and modulation of immunity. The dual role of ROS in the early and late stages of cancer makes antioxidant therapy precarious and may be responsible for controversial results. A system that delivers an antioxidant directly to mitochondria may be useful in inhibiting the formation of ROS early during the pre-diabetic stage, whereas antioxidant therapy must be halted in later stages to retard metastasis.

BackgroundAdolescents and young adults (AYAs) with cancer are at risk of poor psychosocial outcomes. AYAs grew up with the internet and digital technology, and mobile Health (mHealth) psychosocial interventions have the potential to overcome care access barriers. ObjectiveThis pilot randomized controlled trial (RCT) aimed to establish the feasibility, acceptability, and preliminary efficacy of a fully automated mobile app version of the Promoting Resilience in Stress Management intervention (mPRISM). Promoting Resilience in Stress Management is an evidence-based intervention developed in collaboration with AYAs, based on stress and coping theory, resilience theory, and evidence-based coping strategies. We hypothesized that mPRISM would be feasible, acceptable, and appropriate. MethodsThis is a parallel, 2-arm, single-site pilot RCT with a waitlist control design. The study will recruit 80 AYAs with cancer from a clinic. Eligible AYAs are aged 12 to 25 years, within 12 months of a new cancer diagnosis, receiving chemotherapy or radiation therapy, speak, read, or write in English, and are cognitively able to participate in study procedures. Recruitment by clinical research coordinators will occur remotely by phone, video, or text. Participants will be randomized to psychosocial usual care (UC) alone or UC plus mPRISM for an 8-week intervention period, and will remain unblinded to study condition. Enrolled participants will complete surveys at baseline before randomization, 8 weeks, and 3-month follow-up. Using a waitlist design, the UC arm will receive mPRISM upon completion of 3-month follow-up surveys. Those in the UC arm will complete 2 additional measurement points at immediate posttreatment and 3 months later. The primary outcomes of interest are feasibility, defined as ≥60% enrollment and ≥70% retention (ie, percentage of participants who completed the study), and “feasibility, acceptability, and appropriateness” as defined by cut-off scores ≥4/5 on 3 brief validated implementation outcome measures (feasibility of implementation measure, acceptability of intervention measure [AIM], intervention appropriateness measure [IAM]). We will apply top-box scoring for the implementation measures. Exploratory outcomes of interest include patient-reported health-related quality of life, resilience, distress, anxiety, depression, pain, and sleep. We will conduct an intention-to-treat analysis to compare the outcomes of the mPRISM arm versus the control arm with covariate-adjusted regression models. We will summarize individual digital usage metrics using descriptive statistics. ResultsSince September 2023, we have enrolled 20 participants and recruitment is ongoing. ConclusionsAlthough our previous work suggests AYAs with cancer are interested in mHealth psychosocial interventions, such interventions have not yet been sufficiently evaluated or implemented among AYA oncology patients. mPRISM may serve as a potential mHealth intervention to fill this gap. In this study, we will test the feasibility, acceptability, and preliminary efficacy of mPRISM. This work will inform future larger-scale RCTs powered for efficacy outcomes. Trial RegistrationClinicalTrials.gov NCT05842902; https://clinicaltrials.gov/study/NCT05842902 International Registered Report Identifier (IRRID)DERR1-10.2196/57950

We present a novel small molecule antiviral chemotype that was identified by an unconventional cell-free protein synthesis and assembly-based phenotypic screen for modulation of viral capsid assembly. Activity of PAV-431, a representative compound from the series, has been validated against infectious viruses in multiple cell culture models for all six families of viruses causing most respiratory diseases in humans. In animals, this chemotype has been demonstrated efficacious for porcine epidemic diarrhoea virus (a coronavirus) and respiratory syncytial virus (a paramyxovirus). PAV-431 is shown to bind to the protein 14-3-3, a known allosteric modulator. However, it only appears to target the small subset of 14-3-3 which is present in a dynamic multi-protein complex whose components include proteins implicated in viral life cycles and in innate immunity. The composition of this target multi-protein complex appears to be modified upon viral infection and largely restored by PAV-431 treatment. An advanced analog, PAV-104, is shown to be selective for the virally modified target, thereby avoiding host toxicity. Our findings suggest a new paradigm for understanding, and drugging, the host–virus interface, which leads to a new clinical therapeutic strategy for treatment of respiratory viral disease.

H5 subtype high-pathogenicity avian influenza (HPAI) viruses continue to devastate the poultry industry and threaten food security and public health. The first outbreak of H5 HPAI in the Philippines was reported in 2017. Since then, H5 HPAI outbreaks have been reported in 2020, 2022, and 2023. Here, we report the first publicly available complete whole-genome sequence of an H5N1 high-pathogenicity avian influenza virus from a case in Central Luzon. Samples were collected from a flock of layer chickens exhibiting signs of lethargy, droopy wings, and ecchymotic hemorrhages in trachea with excessive mucus exudates. A high mortality rate of 96–100% was observed within the week. Days prior to the high mortality event, migratory birds were observed around the chicken farm. Lungs, spleen, cloacal swabs, and oropharyngeal–tracheal swabs were taken from two chickens from this flock. These samples were positive in quantitative RT-PCR assays for influenza matrix and H5 hemagglutinin (HA) genes. To further characterize the virus, the same samples were subjected to whole-virus-genome amplification and sequencing using the Oxford Nanopore method with mean coverages of 19,190 and 2984, respectively. A phylogenetic analysis of the HA genes revealed that the H5N1 HPAI virus from Central Luzon belongs to the Goose/Guangdong lineage clade 2.3.4.4b viruses. Other segments also have high sequence identity and the same genetic lineages as other clade 2.3.4.4b viruses from Asia. Collectively, these data indicate that wild migratory birds are the likely source of H5N1 viruses from the 2022 outbreaks in the Philippines. Thus, biosecurity practices and surveillance for HPAI viruses in both domestic and wild birds should be increased to prevent and mitigate HPAI outbreaks.

Selective RET inhibitors, such as selpercatinib and pralsetinib, have revolutionized the treatment of cancers with RET gene alterations. These inhibitors have shown remarkable clinical efficacy, particularly in RET-driven lung cancer, medullary thyroid cancer, and other solid tumors driven by RET gene fusions. The assessment of treatment response in oncology has been greatly enhanced by Fluorodeoxyglucose Positron Emission Tomography (FDG-PET), a valuable tool that measures tumor metabolism and provides early indicators of treatment effectiveness. This work explores the effectiveness of selective RET inhibitors in targeting RET-positive cancers and investigates the utility of FDG-PET in assessing treatment response. The paper includes insightful case studies that highlight the successful application of RET inhibitors in the treatment of RET-positive cancers. The findings suggest that FDG-PET has the potential to serve as a non-invasive biomarker for monitoring treatment response in patients with RET-positive cancers. However, further research is required to establish standardized criteria for interpreting FDG-PET scans in the context of selective RET inhibitors and to uncover the broader applications of FDG-PET in precision oncology.

Abstract Severe COVID-associated lung injury is a major confounding factor of hospitalizations and death with no effective treatments. Here, we describe a non-classical fibrin clotting mechanism mediated by SARS-CoV-2 infected primary lung but not other susceptible epithelial cells. This infection-induced fibrin formation is observed in all variants of SARS-CoV-2 infections, and requires thrombin but is independent of tissue factor and other classical plasma coagulation factors. While prothrombin and fibrinogen levels are elevated in acute COVID BALF samples, fibrin clotting occurs only with the presence of viral infected but not uninfected lung epithelial cells. We suggest a viral-induced coagulation mechanism, in which prothrombin is activated by infection-induced transmembrane serine proteases, such as ST14 and TMPRSS11D, on NHBE cells. Our finding reveals the inefficiency of current plasma targeted anticoagulation therapy and suggests the need to develop a viral-induced ARDS animal model for treating respiratory airways with thrombin inhibitors.

Developmental tasks theory suggests that the wellbeing of adolescents can be better understood by considering their developmental tasks, rather than just viewing it as a specific age. This concept has significantly influenced contemporary studies on the transition to adulthood. Study explains that psychosocial developmental tasks involve shifts in an individual's psychological state and social relationships, potentially disrupting their previous equilibrium. Authors stress the importance of forming personal identity and fostering a healthy sense of independence, especially concerning identity and autonomy tasks, as crucial elements for adolescent wellbeing analysis. In line with this, the study focuses on the concurrent and predictive relationship between identity process of commitment, emotional autonomy, and psychological wellbeing among adolescents. Four hundred fifty-four (454) participants with an age ranged from 15 to 19 years (m = 17.96) completed surveys measuring emotional autonomy, identity commitment, and psychological wellbeing. The findings revealed that both emotional autonomy and identity commitment predicted psychological wellbeing, but in different ways. The study revealed that emotional autonomy is inversely associated with psychological wellbeing in middle and late adolescents, indicating that their ability to establish independence from their parents or relinquish unrealistic parental expectations may be linked to a decline in their mental health. The results also indicated that identity commitment is moderately and positively related to psychological wellbeing, suggesting that when adolescents have a clear sense of their identity, they may experience greater wellbeing. This finding underscores the importance of encouraging adolescents to explore their values, interests, and goals, as well as providing them with support and guidance throughout the process. Additionally, the findings of the study revealed that emotional autonomy has a negative influence on psychological wellbeing when identity commitment is low or average. Specifically, when individuals have a low level of identity commitment, emotional autonomy significantly predicts lower psychological wellbeing. Similarly, when identity commitment is at an average level, emotional autonomy also has a detrimental effect on psychological wellbeing. Lastly, the study revealed that when individuals have a high level of identity commitment, emotional autonomy does not have a significant impact on psychological wellbeing. In simpler terms, when individuals possess a strong sense of commitment to their identity, their level of emotional autonomy does not play a significant role in influencing their psychological wellbeing.

Machines operate under increasingly harsher contact conditions, causing significant wear and contact fatigue. Sub-surface stresses are responsible for the premature contact fatigue of rolling element bearings, meshing gears, and cam–follower pairs. Surface protection measures include hard, wear-resistant coatings. Traditionally, contact integrity has been predicted using classical Hertzian contact mechanics. However, the theory is only applicable when the contact between a pair of ellipsoidal solids of revolution may be considered as a rigid indenter penetrating a semi-infinite elastic half-space. Many coatings act as thin bonded elastic layers that undergo considerably higher pressures than those predicted by the classical theory. Furthermore, inelastic deformation of bonded solids can cause plastic flow, work-hardening, and elastoplastic behaviour. This paper presents a comprehensive, integrated contact mechanics analysis that includes induced sub-surface stresses in concentrated counterformal finite line contacts for all the aforementioned cases. Generated pressures and deformation are predicted for hard coated surfaces, for which there is a dearth of relevant analysis. The contact characteristics, which are of particular practical significance, of many hard, wear-resistant advanced coatings are also studied. The paper clearly demonstrates the importance of using efficient semi-analytical, detailed holistic contact mechanics rather than the classical idealised methods or empirical numerical ones such as FEA. The novel approach presented for the finite line contact of thin-layered bonded solids has not hitherto been reported in the open literature.

Abstract Spaceflight presents a multifaceted environment for plants, combining the effects on growth of many stressors and factors including altered gravity, the influence of experiment hardware, and increased radiation exposure. To help understand the plant response to this complex suite of factors this study compared transcriptomic analysis of 15 Arabidopsis thaliana spaceflight experiments deposited in the National Aeronautics and Space Administration’s GeneLab data repository. These data were reanalyzed for genes showing significant differential expression in spaceflight versus ground controls using a single common computational pipeline for either the microarray or the RNA-seq datasets. Such a standardized approach to analysis should greatly increase the robustness of comparisons made between datasets. This analysis was coupled with extensive cross-referencing to a curated matrix of metadata associated with these experiments. Our study reveals that factors such as analysis type (i.e., microarray versus RNA-seq) or environmental and hardware conditions have important confounding effects on comparisons seeking to define plant reactions to spaceflight. The metadata matrix allows selection of studies with high similarity scores, i.e., that share multiple elements of experimental design, such as plant age or flight hardware. Comparisons between these studies then helps reduce the complexity in drawing conclusions arising from comparisons made between experiments with very different designs.

This paper presents an investigation of the frictional behaviour of three-piece piston oil control rings. A bespoke tribometer replicates the kinematics of the contact between a full oil control ring and the cylinder liner. The three-piece oil control ring is composed of two segments, separated by a waveform-type expander. The experimental results indicate the dominance of a mixed regime of lubrication throughout the stroke. This is particularly the case when the experiments are conducted at 80 °C, a typical engine sump temperature, when compared with those at 20 °C (a typical engine start-up temperature in the UK in the summer). A mixed hydrodynamic analytical model of the oil control ring–cylinder liner tribological interface is employed to apportion frictional contributions with their physical underlying mechanisms. Therefore, combined numerical and experimental investigations are extended to lubricant contamination/dilution by ethanol-based fuels. This study shows that the transition from E10 to E85 would have an insignificant effect on the friction generated in the oil control ring conjunction. This holistic approach, using a detailed predictive l mixed regime of lubrication model and a representative bespoke tribometry, has not hitherto been reported in the open literature.

Abstract The objective of this study is to evaluate the potential for History Matching (HM) to tune a climate system with multi‐scale dynamics. By considering a toy climate model, namely, the two‐scale Lorenz96 model and producing experiments in perfect‐model setting, we explore in detail how several built‐in choices need to be carefully tested. We also demonstrate the importance of introducing physical expertise in the range of parameters, a priori to running HM. Finally we revisit a classical procedure in climate model tuning, that consists of tuning the slow and fast components separately. By doing so in the Lorenz96 model, we illustrate the non‐uniqueness of plausible parameters and highlight the specificity of metrics emerging from the coupling. This paper contributes also to bridging the communities of uncertainty quantification, machine learning and climate modeling, by making connections between the terms used by each community for the same concept and presenting promising collaboration avenues that would benefit climate modeling research.

In time of pandemic, synchronous and asynchronous learning occurred as a form of distance learning implemented by the Commission on Higher Education and the Department of Education. This research entitled “Academic Dishonesty Cheating in Synchronous and Asynchronous Classes: A Proctored Examination Intervention” was conducted to identify the self-report and types of assessment stated by the respondents. It also determined the effectiveness of proctored synchronous and asynchronous examination in preventing the cheating practices of students. The researchers used a quantitative research design and three adapted questionnaires with 40 participants. The results generated from the questionnaires were analyzed using frequency, percentage, and Mann-Whitney U test. The results obtained the following: most students cheated on assignments, exams, or quizzes; the primary reasons for student dishonesty were stress and worry essentially, and homework was the kind of evaluation that enabled pupils to cheat. Proctored exams provide similar results regardless of whether the exams were conducted asynchronously or synchronously. The following findings on the impact of proctored synchronous and asynchronous exams on students revealed that: most students will be less likely to cheat in a proctored examination. Most of the students believed that these proctored examinations would be a good solution in monitoring remote learning. Therefore, proctored synchronous and asynchronous examinations prevent the academic dishonesty or cheating practices of students.

ABSTRACT Osteoblast Wnt/β‐catenin signaling conditions skeletal development and health. Bone formation is stimulated when on the osteoblast surface a Wnt binds to low‐density lipoprotein receptor‐related protein 5 (LRP5) or 6 (LRP6), in turn coupled to a frizzled receptor. Sclerostin and dickkopf1 inhibit osteogenesis if either links selectively to the first β‐propeller of LRP5 or LRP6, thereby disassociating these cognate co‐receptors from the frizzled receptor. Sixteen heterozygous mutations identified since 2002 within LRP5 and three heterozygous mutations identified since 2019 within LRP6 prevent this binding of sclerostin or dickkopf1 and account for the exceptionally rare, but highly instructive, autosomal dominant disorders called LRP5 and LRP6 high bone mass (HBM). Herein, we characterize LRP6 HBM in the first large affected family. Their novel heterozygous LRP6 missense mutation (c.719C>T, p.Thr240Ile) was present in two middle‐aged sisters and three of their sons. They considered themselves healthy. Their broad jaw and torus palatinus developed during childhood and, contrary to the two previous reports of LRP6 HBM, the appearance of their adult dentition was unremarkable. Skeletal modeling, defined radiographically, supported classification as an endosteal hyperostosis. Areal bone mineral density (g/cm2) of the lumbar spine and total hip featured accelerated increases reaching Z‐scores of ~ +8 and +6, respectively, although biochemical markers of bone formation were normal. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

This work demonstrates a novel, state-of-the-art method to reconstruct colored images via the dynamic vision sensor (DVS). The DVS is an image sensor that indicates only a binary change in brightness, with no information about the captured wavelength (color) or intensity level. However, the reconstruction of the scene’s color could be essential for many tasks in computer vision and DVS. We present a novel method for reconstructing a full spatial resolution, colored image utilizing the DVS and an active colored light source. We analyze the DVS response and present two reconstruction algorithms: linear-based and convolutional-neural-network-based. Our two presented methods reconstruct the colored image with high quality, and they do not suffer from any spatial resolution degradation as other methods. In addition, we demonstrate the robustness of our algorithm to changes in environmental conditions, such as illumination and distance. Finally, compared with previous works, we show how we reach the state-of-the-art results. We share our code on GitHub.

The paper provides a commentary on the theme of “Current and Future Trends in Tribological Research: Fundamentals and Applications”, which is a special feature issue commemorating the 10th anniversary of the journal, Lubricants. A historical discourse is provided regarding various aspects of tribology as a multi-disciplinary subject that interacts in an inter-disciplinary manner with many other subjects: multi-body dynamics, thermofluids and heat transfer, contact mechanics, surface science, chemistry, rheology, data science, and biology, to name but a few. Such interactions lead to many important topics including propulsion with different sources of energy, mitigating emissions, palliation of friction, enhancing durability and sustainability, optimization through detailed analysis, and the use of artificial intelligence. Additionally, issues concerning kinetics at various physical scales (from macroscale to microscale onto mesoscale and nanoscale) affecting the kinematics of contacts are discussed. The broad range of considered applications includes vehicular powertrains, rotor bearings, electrical machines, mammalian endo-articular joints, nanobiological attachment/detachment, and locomotion. Current state-of-the-art tribological research is highlighted within a multi-physics, multi-scale framework, an approach not hitherto reported in the open literature.

Abstract Background Spinal fusion surgery is associated with severe acute postsurgical pain and high rates of chronic postsurgical pain in adolescents. Psychological distress, sleep disturbance, and low pain self-efficacy predict higher acute pain and likelihood of developing chronic postsurgical pain. Interventions targeting baseline psychosocial risk factors have potential to interrupt a negative trajectory of continued pain and poor health-related quality of life (HRQL) over time but have not yet been developed and evaluated. This randomized controlled trial will test effectiveness of a digital peri-operative cognitive-behavioral intervention (SurgeryPalTM) vs. education-control delivered to adolescents and their parents to improve acute and chronic pain and health outcomes in adolescents undergoing spine surgery. Methods Adolescents 12–18 years of age undergoing spinal fusion for idiopathic conditions, and their parent, will be recruited from pediatric centers across the USA, for a target complete sample of 400 dyads. Adolescents will be randomized into 4 study arms using a factorial design to SurgeryPalTM or education control during 2 phases of treatment: (1) pre-operative phase (one-month before surgery) and (2) post-operative phase (1 month after surgery). Acute pain severity and interference (primary acute outcomes) and opioid use will be assessed daily for 14 days following hospital discharge. Chronic pain severity and interference (primary acute outcomes), as well as HRQL, parent and adolescent distress, sleep quality, and opioid use/misuse (secondary outcomes), will be assessed at 3 months and 6 months post-surgery. Discussion Demonstration of effectiveness and understanding optimal timing of perioperative intervention will enable implementation of this scalable psychosocial intervention into perioperative care. Ultimately, the goal is to improve pain outcomes and reduce reliance on opioids in adolescents after spine surgery. Trial registration NCT04637802 ClinicalTrials.gov. Registered on November 20, 2020

With the growing adoption of wide bandgap devices in power electronic applications, current sensor design for switching current measurement has become more important. The demands for high accuracy, high bandwidth, low cost, compact size, and galvanic isolation pose significant design challenges. The conventional modeling approach for bandwidth analysis of current transformer sensors assumes that the magnetizing inductance remains constant, which does not always hold true in high-frequency operations. This can result in inaccurate bandwidth estimation and affect the overall performance of the current sensor. To address this limitation, this paper provides a comprehensive analysis of nonlinear modeling and bandwidth, considering the varying magnetizing inductance in a wide frequency range. A precise and straightforward arctangent-based fitting algorithm was proposed to accurately emulate the nonlinear feature, and the fitting results were compared with the magnetic core’s datasheet to confirm its accuracy. This approach contributes to more accurate bandwidth prediction in field applications. In addition, the droop phenomenon of the current transformer and saturation effects are analyzed in detail. For high-voltage applications, different insulation methods are compared and an optimized insulation process is proposed. Finally, the design process is experimentally validated. The bandwidth of the proposed current transformer is around 100 MHz and the cost is around $20, making it a low-cost and high-bandwidth solution for switching current measurements in power electronic applications.

As SARS-CoV-2, the virus responsible for COVID-19, spread globally, the most severely affected sub-populations were the elderly and those with multi-morbidity largely related to non-communicable diseases (NCDs), e.g., heart disease, hypertension, type 2 diabetes, obesity. NCDs are largely preventable with healthy nutrition, regular activity, and not smoking. This perspective outlines the rationale for health professionals' including physical therapists' role in reducing COVID-19 susceptibility. Evidence is synthesized supporting the pro-inflammatory effects of the western diet, increasingly consumed globally, inactivity, and smoking; and the immune-boosting, anti-inflammatory effects of a whole food plant-based diet, regular physical activity, and not smoking. An increased background of chronic low-grade systemic inflammation associated with unhealthy lifestyle practices appears implicated in an individual's susceptibility to SARS-CoV-2. It is timely to re-double efforts across healthcare sectors to reduce the global prevalence of NCDs on two fronts: one, to reduce SARS-CoV-2 susceptibility; and two, to reduce the impact of subsequent waves given high blood pressure and blood sugar, common in people with multi-morbidity, can be improved within days/weeks with anti-inflammatory healthy lifestyle practices, and weight loss and atherosclerosis reduction/reversal, within months/years. With re-doubled efforts to control NCD risk factors, subsequent waves could be less severe. Health professionals including physical therapists have a primary role in actively leading this initiative.

A crisis of mass immigration detention exists in the United States, which is home to the world’s largest immigration detention system. The immigration detention system is legally classified as civil, rather than criminal, and therefore non-punitive. Yet it mimics the criminal incarceration system and holds detained individuals in punitive, prison-like conditions. Within immigration detention centers, there are increasing reports and recognition of civil and human rights abuses, including preventable in-custody deaths. In this paper, we propose understanding the health impacts of detention as an accumulation of mental and physical trauma that take place during the entirety of a detained immigrant’s experience, from migration to potential deportation and removal. Further, we explore the social-structural determinants of health as they relate to immigration detention, contextualize these determinants within a human rights framework, and draw parallels to the larger context of US mass incarceration. Realizing the right to health requires addressing these social-structural determinants of health. For the care of immigrant patients to be effective, clinicians and public health professionals must incorporate an awareness of the health risks of the immigration detention system into trauma- and human rights-informed models of care during and after detention.

Cricothyrotomy is an emergency procedure that is utilized in situations that require immediate access to a breathing pathway. This procedure may be performed by professionals in a variety of healthcare fields depending upon the specific emergency scenario, so the development of an interprofessional workshop is imperative for procedural confidence and skill development. Our team developed a training workshop with a specific focus on procedural skills, risks, benefits, and psychological ramifications associated with a cricothyrotomy procedure. Pre-workshop and post-workshop surveys were obtained for comparison of participant confidence. Overall, the organization and delivery of a cricothyrotomy training workshop significantly increased the overall participant confidence surrounding this procedure.

Objectives The Tactical Combat Casualty Care (TCCC) guidelines detail resuscitation practices in prehospital and austere environments. We sought to review the content and quality of the current TCCC and civilian prehospital literature and characterize knowledge gaps to offer recommendations for future research.Methods MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials were searched for studies assessing intervention techniques and devices used in civilian and military prehospital settings that could be applied to TCCC guidelines. Screening and data extraction were performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Quality appraisal was conducted using appropriate tools.Results Ninety-two percent (n=57) of studies were observational. Most randomized trials had low risk of bias, whereas observational studies had higher risk of bias. Interventions of massive hemorrhage control (n=17) were wound dressings and tourniquets, suggesting effective hemodynamic control. Airway management interventions (n=7) had high success rates with improved outcomes. Interventions of respiratory management (n=12) reported low success with needle decompression. Studies assessing circulation (n=18) had higher quality of evidence and suggested improved outcomes with component hemostatic therapy. Hypothermia prevention interventions (n=2) were generally effective. Other studies identified assessed the use of extended focused assessment with sonography in trauma (n=3) and mixed interventions (n=2).Conclusions The evidence was largely non-randomized with heterogeneous populations, interventions, and outcomes, precluding robust conclusions in most subjects addressed in the review. Knowledge gaps identified included the use of blood products and concentrate of clotting factors in the prehospital setting.Level of evidence Systematic review, level III.

The positive education movement has called attention to the importance of student well-being and the role of positive constructs, such as hope, in the educational process. The external locus-of-hope dimensions, or positive cognitions about the role of external actors in the pursuit of important goals, positively predict student well-being, learning approaches, and achievement. However, external locus-of-hope dimensions were found to be associated with maladaptive coping styles among Asian students. In this study, we revisit this relationship between external locus-of-hope dimensions and coping among students, by focusing on collectivist coping strategies that are assumed to be more relevant to Asian students. A total of 780 university students from three Asian cities (Hong Kong, n = 295; Macau, n = 225; Manila, n = 260) were asked to complete a questionnaire on collectivist coping styles, internal and external locus-of-hope dimensions. Separate multiple regression analyses indicated that the coping style of acceptance/reframing/striving was mainly predicted by internal locus-of-hope in the three groups, but the coping styles of family support and religious coping were consistently predicted by external locus-of-hope dimensions in all three groups of students. The two other coping styles of avoidance/detachment and personal emotional outlets were also predicted by specific external locus-of-hope dimensions, but only in particular groups. The results are discussed in terms of how external locus-of-hope dimensions might evoke both adaptive and maladaptive coping among Asian students, which may be associated with primary and secondary control dimensions of the collectivist coping styles.

Bone is the most common metastatic site in prostate cancer (PCa). 68Ga-PSMA-11 (or gozetotide) and sodium fluoride-18 (Na18F) are rather new radiopharmaceuticals for assessing PCa-associated bone metastases. Gozetotide uptake reflects cell membrane enzyme activity and the sodium fluoride uptake measures bone mineralization in advanced PCa. Here, we aim to characterize this difference and possibly provide a new method for patient selection in targeted therapies. Methods: The study consisted of 14 patients with advanced PCa (M group > 5 lesions), who had had routine PET/CT both with PSMA and NaF over consecutive days, and 12 PCa patients with no skeletal metastases (N). The bone regions in CT were used to coregister the two PET/CT scans. The whole skeleton volume(s) of interest (VOIs) were defined using the CT component of PET (HU > 150); similarly, the sclerotic/dense bone was defined as HU > 600. Additional VOIs were defined for PET, with pathological threshold values for PSMA (SUV > 3.0) and NaF (SUV > 10). Besides the pathological bone volumes measured with each technique (CT, NaF, and PSMA-PET) and their contemporaneous combinations, overlapping VOIs with the CT-based skeletal and sclerotic volumes were also recorded. Additionally, thresholds of 4.0, 6.0, and 10.0 were tested for SUVPSMA. Results: In group M, the skeletal VOI volumes were 8.77 ± 1.80 L, and the sclerotic bone volumes were 1.32 ± 0.50 L; in contrast, in group N, they were 8.73 ± 1.43 L (skeletal) and 1.23 ± 0.28 L (sclerosis). The total enzyme activity for PSMA was 2.21 ± 5.15 in the M group and 0.078 ± 0.053 in the N group (p < 0.0002). The total bone demineralization activity for NaF varied from 4.31 ± 6.17 in the M group and 0.24 ± 0.56 in group N (p < 0.0002). The pathological PSMA volume represented 0.44–132% of the sclerotic bone volume in group M and 0.55–2.3% in group N. The pathological NaF volume in those patients with multiple metastases represented 0.27–68% of the sclerotic bone volume, and in the control group, only 0.00–6.5% of the sclerotic bone volume (p < 0.0003). Conclusions: These results confirm our earlier findings that CT alone does not suit the evaluation of the extent of active skeletal metastases in PCa. PSMA and NaF images give complementary information about the extent of the active skeletal disease, which has a clinical impact and may change its management. The PSMA and NaF absolute volumes could be used for planning targeted therapies. A cut-off value 3.0 for SUVPSMA given here is the best correlation in the presentation of active metastatic skeletal disease.

Introduction Acute traumatic coagulopathy (ATC) in bleeding trauma patients increase in-hospital mortality. Fibrinogen concentrate (FC) and prothrombin complex concentrate (PCC) are two purified concentrates of clotting factors that have been used to treat ATC. However, there is a knowledge gap on their use compared with the standard of care, the transfusion of plasma.Methods and analysis The factors in the initial resuscitation of severe trauma 2 trial is a multicentre, randomised, parallel-control, single-blinded, phase IV superiority trial. The study aims to address efficacy and safety of the early use of FC and PCC compared with a plasma-based resuscitation. Adult trauma patients requiring massive haemorrhage protocol activation on hospital arrival will receive FC 4 g and PCC 2000 IU or plasma 4 U, based on random allocation. The primary outcome is a composite of the cumulative number of all units of red cells, plasma and platelets transfused within 24 hours following admission. Secondary outcomes include measures of efficacy and safety of the intervention. Enrolment of 350 patients will provide an initial power >80% to demonstrate superiority for the primary outcome. After enrolment of 120 patients, a preplanned adaptive interim analysis will be conducted to reassess assumptions, check for early superiority demonstration or reassess the sample size for remainder of the study.Ethics and dissemination The study has been approved by local and provincial research ethics boards and will be conducted according to the Declaration of Helsinki, Good Clinical Practice guidelines and regulatory requirements. As per the Tri-Council Policy Statement, patient consent will be deferred due to the emergency nature of the interventions. If superiority is established, results will have a major impact on clinical practice by reducing exposure to non-virally inactivated blood products, shortening the time for administration of clotting factors, correct coagulopathy more efficaciously and reduce the reliance on AB plasma.Trial registration number NCT04534751, pre results.

High-temperature superconducting (HTS) cables are expected to be installed in cable tunnels that are already constructed in urban districts. Therefore, the installation of normal joint boxes is inevitable, and it is necessary to develop a diagnostic methodology that considers both the existence of the joints and the electrical characteristics of HTS cables. In this work, temporal sliding long short-term memory (TS-LSTM) is proposed to estimate the locations of the joints that can be hidden by multiple reflections. TS-LSTM includes short-term TS-LSTM and long-term TS-LSTM for analyzing various time dependencies. The reflected signals of the actual joints, which are distinguished from multiple reflections, are analyzed via the chirplet transform (CT) which is one of the time-frequency (TF) analysis methods. The proposed condition monitoring method is applied to an AC 154 kV 600 MVA HTS cable system (1 km) connected to a real power grid network in Jeju, South Korea. For the validation of the proposed methodology, the dielectric and electrical characteristics of the 154 kV HTS cable system are monitored during the cooling process.

How the airway microbiome influences asthma pathophysiology remains unclear. Here, the authors analyse nasal samples of cohort of school-age children with persistent asthma and find that the microbiota’s patterns and composition at time of early loss of asthma control associate with severe asthma exacerbations.