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Abstract Background People with mobility limitations have a disproportionately higher rate of acquiring secondary conditions such as obesity, cardiovascular comorbidity, pain, fatigue, depression, deconditioning, and type 2 diabetes. These conditions often result from poor access to home and community-based health promotion/wellness programs. The aim of this project was to determine the feasibility of delivering an online community membership-based fitness program for individuals with mobility impairments. Methods For this prospective single-arm study, participants were recruited from members of a community fitness facility that serves people with physical disabilities and chronic health conditions. While all members had access to the online platform, individuals had to opt-in to participate in the research component. Activity options included 16 pre-recorded videos and 9 live exercise classes. During the 8-week program, participants had an opportunity to earn three exercise incentives for reaching certain activity milestones. Enrollment percentage, attendance, and attrition were tracked to assess program feasibility and acceptability. Changes in participant-reported outcomes including self-reported physical activity, psychosocial outcomes, and health-related quality of life (HRQOL) were examined using non-parametric analyses. Results A total of 146 eligible individuals were screened of which 33 enrolled (22.6%). Two participants withdrew from the study, so a total of 31 were used for analyses. Participants included 29 women and 12 Black people with an average age of 60 (± 15.9) years. Health conditions included stroke, post-polio, arthritis, neuropathy, cerebral palsy, and obesity. Ten participants used an assistive device to get around inside the home. Twenty-six participants (78.8%) completed the online program, and 5 participants earned all 3 participation incentives. The mean number of live Zoom exercise classes attended by the participants was 12.8 (range = 0–43) over 8 weeks; 3 of 31 participants did not attend any classes. On average, participants watched 128 min (range = 0–704 min) of pre-recorded videos; 6 of 31 participants did not view any pre-recorded videos. Self-reported physical activity showed the largest improvement (11.15 units; 95% CI, 3.08, 19.56) with an effect size of 0.51 (Cohen’s d). Conclusions This pilot study of an online membership-based fitness program for people with mobility impairments demonstrated preliminary effectiveness in increasing physical activity and was found to be feasible and acceptable. Feasibility endpoints do indicate potential to improve retention. These results suggest that online delivery of exercise programs can broaden the reach of specialized community fitness programs and is a promising direction for future work and fully powered trials are warranted to assess intervention efficacy. Trial registration ClinicalTrials.gov, NCT05138809. Registered September 2, 2021, ClinicalTrials.gov PRS: Record Summary NCT05138809.

Objectives. Knee injuries are prevalent among professional tennis players and have a significant impact on their athletic performance and longevity. This study aimed to evaluate the dynamic and postural balance differences between injured and healthy professional tennis players, reflecting the broader implications of knee injuries on player stability and performance. Materials and methods. A total of 80 professional tennis players, comprising 40 individuals in the knee injury group (IG) and 40 individuals in the non-injury group (NIG), were selected to participate in this cross-sectional study. Participants’ postural sway was assessed under various conditions, including standing on different surfaces with open and closed eyes using a Wii Balance Board. The Y-Balance Test was performed to evaluate the player’s dynamic balance. An Independent t-test was used to examine the difference in postural sway and dynamic balance between the two groups. Results. The results of this study indicated that players with knee injuries showed significantly worse performance in both dynamic balance (p

Abstract In Māori and Pacific adults, the CREBRF rs373863828 minor (A) allele is associated with increased body mass index (BMI) but reduced incidence of type-2 and gestational diabetes mellitus. In this prospective cohort study of Māori and Pacific infants, nested within a nutritional intervention trial for pregnant women with obesity and without pregestational diabetes, we investigated whether the rs373863828 A allele is associated with differences in growth and body composition from birth to 12–18 months’ corrected age. Infants with and without the variant allele were compared using generalised linear models adjusted for potential confounding by gestation length, sex, ethnicity and parity, and in a secondary analysis, additionally adjusted for gestational diabetes. Carriage of the rs373863828 A allele was not associated with altered growth and body composition from birth to 6 months. At 12–18 months, infants with the rs373863828 A allele had lower whole-body fat mass [FM 1.4 (0.7) vs. 1.7 (0.7) kg, aMD −0.4, 95% CI −0.7, 0.0, P = 0.05; FM index 2.2 (1.1) vs. 2.6 (1.0) kg/m2 aMD −0.6, 95% CI −1.2,0.0, P = 0.04]. However, this association was not significant after adjustment for gestational diabetes, suggesting that it may be mediated, at least in part, by the beneficial effect of CREBRF rs373863828 A allele on maternal glycemic status.

Background: Intrinsic capacity, the combination of physical and mental abilities, is vital for healthy aging. As the elderly population is projected to double by 2050, preserving the well-being of older adults necessitates a comprehensive understanding of and intervention in intrinsic capacity decline. This study aims to assess the pooled prevalence of intrinsic capacity impairment using WHO's ICOPE screening tool. Methods: The systematic review used PRISMA guidelines, conducting an extensive search across multiple databases such as PUBMED, SCOPUS, CINHAL and Google Scholar. The articles that have assessed the intrinsic capacity with various domains like locomotion, cognition, psychology, vitality, vision, and hearing using WHO ICOPE tool were included in this review. We evaluated the risk of bias in cross-sectional studies using the modified Joanna Briggs Institute criteria. Results: A total of nine studies were included for this review, involving participants from various regions all over the world. The pooled prevalence of intrinsic capacity impairment was 55.0 % in the Random Effects Model. While assessing for various domains, the pooled prevalence of locomotion, cognition, psychology, vitality, vision, and hearing was found to be 17.5 %, 18.2 %, 12.1 %, 8.5 %, 17.9 % and 14.4 % respectively. Conclusion: This meta-analysis contributes a comprehensive overview of intrinsic capacity decline prevalence, offering valuable evidence for policymakers and healthcare stakeholders. The findings underscore the urgency of implementing targeted interventions to promote healthy aging and intrinsic capacity preservation worldwide.

Carbon dots (CDs) have been utilized as a fluorescence probe to detect heavy metal ions. They have good optical qualities and are easily produced from inexpensive materials. They offer excellent photoluminescence characteristics. The optical characteristics of the produced CDs can also be impacted by the synthesis procedure. The special optical emission allows the detection of heavy metals, biological heavy metals and hypochlorite anions. When used as fluorescent probes, CDs provide for a wide concentration range and a low detection limit. They can be used to assemble actual examples of electronic devices that have intriguing qualities. Since, CDs have distinct excitation-based emissions and photoluminescence, quenching and reversing the quenching process can be utilized as an analytical technique to detect specific analytes. CDs have been extensively utilized as metal ion sensors for the detection of Fe3+, Fe2+, Cu2+, Hg2+, Ag+, Au3+, Cd2+, Pb2+, Cr6+, Zn2+, As3+, V5+, Mo6+ and Al3+ as this review explains. The comparison based on quantum yield, sensitivity, selectivity, particle size, detection limit and sensing mechanisms are also described.

Decaying DC offset frequently emerges as a major issue in power systems, especially under fault conditions. This leads to a distortion in the current waveform associated with the fault, which could significantly challenge protective and control mechanisms, possibly leading to their malfunction or breakdown. These decaying DC components (DDCs) complicate the extraction of critical parameters such as the current magnitude and phase angle of the fundamental frequency component from fault signals, which is crucial for the accurate operation of protective relays. Discrete Fourier Transform (DFT)-based algorithms are frequently used for phasor estimation, but their accuracy suffers when confronted with decaying DC components (DDCs) in power system fault currents. The low sampling rate further exacerbates the inaccuracy of DFT-based estimations, leading to inaccurate fault detection by protective relays. This paper comprehensively reviews three innovative methods that leverage the Multiple Delayed Signal Cancellation (MDSC) filter to overcome these limitations. The MDSC-based phasor estimation effectively attenuates the DDC component, enabling precise and rapid phasor estimation, benefiting from its higher sampling rate, and enhancing accuracy in relaying applications. The theoretical foundations of each method are analyzed, with an emphasis on their unique advantages and potential applications in digital relaying and power system protection. This review provides valuable insights into the latest advancements in DDC elimination, offering a pathway to more reliable and efficient fault analysis in power systems. Numerical and simulation tests unequivocally demonstrated the effectiveness of the proposed approach by showcasing its superior performance compared to four other phasor estimation methods. The proposed methods demonstrated exceptional performance in conditions plagued by multiple DDCs, harmonics, noise, and off-nominal frequencies, achieving fast and precise phasor estimation.

Background/Objectives: The hepatitis A virus (HAV) cellular receptor 1 (HAVCR1) is a type I integral membrane glycoprotein discovered in monkeys and humans as a HAV receptor. HAVCR1 contains an N-terminal immunoglobulin-like variable domain (IgV) followed by a mucin-like domain (Muc), a transmembrane domain, and a cytoplasmic tail with a canonical tyrosine kinase phosphorylation site. The IgV binds phosphatidylserine on apoptotic cells, extracellular vesicles, and enveloped viruses. Insertions/deletions at position 156 (156ins/del) of the Muc were associated in humans with susceptibility to atopic, autoimmune, and infectious diseases. However, the molecular basis for the differential function of the HAVCR1 variants is not understood. Methods: We used mutagenesis, apoptotic cell binding, and signal transduction analyses to study the role of the 156ins/del in the function of HAVCR1. Results: We found that the HAVCR1 variant without insertions at position 156 (156delPMTTTV, or short-HAVCR1) bound more apoptotic cells than that containing a six amino acid insertion (156insPMTTTV, or long-HAVCR1). Furthermore, short-HAVCR1 induced stronger cell signaling and phagocytosis than long-HAVCR1. Conclusions: Our data indicated that the 156ins/del determine how the IgV is presented at the cell surface and modulate HAVCR1 binding, signaling, and phagocytosis, suggesting that variant-specific targeting could be used as therapeutic interventions to treat immune and infectious diseases.

Caregiving for children with neurodevelopment disorders (NDDs) can be a lifelong process that takes hold of an individual’s time, energy, and resources. This raises a question about the caregivers’ needs and concerns and the extent to which they receive medical or psychological attention during caregiving. This scoping review examines the psychosocial interventions conducted in India for caregivers of children with NDDs. The search strategy involved analyzing published literature on interventions for caregivers of children with NDDs in India from online databases from 2013 to March 2023. Sixteen intervention studies were identified and categorized into child-centric, caregiver-centric, and family-based approaches. Most studies were limited to thesis publications and lacked peer-reviewed publications. However, there has been a gradual increase in caregiver-centric intervention studies since 2019, focusing on alleviating distress and promoting caregiver well-being. Approximately 87.5% (14 out of 16 studies) adopted intervention components focusing on the caregiver’s outcomes and well-being. It can be concluded from the review that more applied research on caregiver-centric interventions is needed in India, focusing on the caregivers’ concerns in depth. The study will provide insights into the importance of practicing caregiver-centric interventions and recommend healthcare providers and policymakers initiate policies, provisions, and programs that benefit the caregiver community.

Endocrine society has evidence that plastics can disrupt the endocrine system to cause severe diseases in humans and animals. However, plastics are still used in a variety of models for their applications. The overproduction of plastics simultaneously increases health hazards in human and animal living society. The pancreas is an endocrine system to produces insulin to maintain the glucose level in the blood when that insulin level resists or does not synthesize causing diabetes mellitus. It is one of the highest prevalence diseases occurred in worldwide. Sirtuin-1 is a protein involved in glucose homeostasis and it regulates insulin action. In the human body, hampered the level of insulin, sirtuin-1, and glucose cause diabetes and its vascular complications. Furthermore, many researchers evidenced that the endocrine disruptor of bisphenol A (BPA) causes diabetes mellitus and its vascular complications. Nevertheless, the biological pathway is unclear. This review discusses the linkage between the endocrine disruptor of BPA and diabetes and explores Sirtuin-1 mediated BPA-induced diabetic vascular complications.

This comprehensive review delves into the intricate world of assisted reproductive technologies (ART) and hormonal treatments, exploring their profound psychological effects on women undergoing IVF treatment. The psychological distress of infertility, combined with the demanding nature of ART, has been widely acknowledged, yet a comprehensive examination of the psychological impacts has remained elusive. This study examined the psychological repercussions of hormonal medications used in IVF, addressing the complex interplay of hormones and their effects in each stage of the IVF process. This review followed PRISMA guidelines and included studies from PubMed, Google Scholar, and ScienceDirect. A total of nine papers were collected. The findings of this study identified that depression, anxiety, mood swings, irritability, sleep disturbances, and cognitive changes were the most commonly seen medically induced psychological effects among the IVF patients. This review offers a holistic understanding of the psychological intricacies of IVF treatment, highlighting the imperative need for a more comprehensive approach to address the emotional wellbeing of individuals undergoing fertility procedures.

BackgroundThe lack of regular physical activity (PA) in individuals with spinal cord injury (SCI) in the United States is an ongoing health crisis. Regular PA and exercise-based interventions have been linked with improved outcomes and healthier lifestyles among those with SCI. Providing people with an accurate estimate of their everyday PA level can promote PA. Furthermore, PA tracking can be combined with mobile health technology such as smartphones and smartwatches to provide a just-in-time adaptive intervention (JITAI) for individuals with SCI as they go about everyday life. A JITAI can prompt an individual to set a PA goal or provide feedback about their PA levels. ObjectiveThe primary aim of this study is to investigate whether minutes of moderate-intensity PA among individuals with SCI can be increased by integrating a JITAI with a web-based PA intervention (WI) program. The WI program is a 14-week web-based PA program widely recommended for individuals with disabilities. A secondary aim is to investigate the benefit of a JITAI on proximal PA, defined as minutes of moderate-intensity PA within 120 minutes of a PA feedback prompt. MethodsIndividuals with SCI (N=196) will be randomized to a WI arm or a WI+JITAI arm. Within the WI+JITAI arm, a microrandomized trial will be used to randomize participants several times a day to different tailored feedback and PA recommendations. Participants will take part in the 24-week study from their home environment in the community. The study has three phases: (1) baseline, (2) WI program with or without JITAI, and (3) PA sustainability. Participants will provide survey-based information at the initial meeting and at the end of weeks 2, 8, 16, and 24. Participants will be asked to wear a smartwatch every day for ≥12 hours for the duration of the study. ResultsRecruitment and enrollment began in May 2023. Data analysis is expected to be completed within 6 months of finishing participant data collection. ConclusionsThe JITAI has the potential to achieve long-term PA performance by delivering tailored, just-in-time feedback based on the person’s actual PA behavior rather than a generic PA recommendation. New insights from this study may guide intervention designers to develop engaging PA interventions for individuals with disability. Trial RegistrationClinicalTrials.gov NCT05317832; https://clinicaltrials.gov/study/NCT05317832 International Registered Report Identifier (IRRID)DERR1-10.2196/57699

Summary: Background: Ebola virus disease (EVD) survivors experience ocular sequelae including retinal lesions, cataracts, and vision loss. While monoclonal antibodies targeting the Ebola virus glycoprotein (EBOV-GP) have shown promise in improving prognosis, their effectiveness in mitigating ocular sequelae remains uncertain. Methods: We developed and characterized a BSL-2-compatible immunocompetent mouse model to evaluate therapeutics targeting EBOV-GP by inoculating neonatal mice with vesicular stomatitis virus expressing EBOV-GP (VSV-EBOV). To examine the impact of anti-EBOV-GP antibody treatment on acute retinitis and ocular sequelae, VSV-EBOV-infected mice were treated with polyclonal antibodies or monoclonal antibody preparations with antibody-dependent cellular cytotoxicity (ADCC-mAb) or neutralizing activity (NEUT-mAb). Findings: Treatment with all anti-EBOV-GP antibodies tested dramatically reduced viremia and improved survival. Further, all treatments reduced the incidence of cataracts. However, NEUT-mAb alone or in combination with ADCC-mAb reduced viral load in the eyes, downregulated the ocular immune and inflammatory responses, and minimized retinal damage more effectively. Interpretation: Anti-EBOV-GP antibodies can improve survival among EVD patients, but improved therapeutics are needed to reduce life altering sequelae. This animal model offers a new platform to examine the acute and long-term effect of the virus in the eye and the relative impact of therapeutic candidates targeting EBOV-GP. Results indicate that even antibodies that improve systemic viral clearance and survival can differ in their capacity to reduce acute ocular inflammation, and long-term retinal pathology and corneal degeneration. Funding: This study was partly supported by Postgraduate Research Fellowship Awards from ORISE through an interagency agreement between the US DOE and the US FDA.

The safrole and isosafrole are constitutional isomers that have been theoretically characterized utilizing Density Functional Theory (DFT) employed with the B3LYP/6-311++G(d,p) basis set to simulate geometrical parameters, vibrational aspects, electronic properties, and chemical shifts and explored the solvent effect on electronic spectra of safrole and isosafrole in different solvents, including polar solvents such as acetone, Dimethyl sulfoxide (DMSO), and methanol, nonpolar solvents such as chloroform, cyclohexane, and toluene, and the gas phase using Time Dependent-Density Functional Theory (TD-DFT) methods. In addition, Natural Orbital (NBO), Mulliken population analysis, and Molecular Electrostatic Potential (MEP) surface have been simulated to understand better the reactive sites in the molecular structures of safrole and isosafrole. The frontier molecular orbitals (FMO) energy gaps of safrole and isosafrole were simulated in polar and nonpolar solvents, confirming the safrole and isosafrole kinetic stability and chemical reactivity. The in-silico ADMET indices were utilized to ascertain the probable pharmacokinetic and biological features of safrole and isosafrole. A molecular docking investigation was also conducted to investigate the potential biological activity of safrole and isosafrole against the SARS-CoV-2 spike protein, providing more support for its antiviral efficacy.

Pharmaceutical effluents (PEs) have emerged as a global threat to mankind owing to their adverse health effects on humans. Generally, PEs are acquainted with the environment via direct emissions from drug manufacturing plants, unplanned disposal of unused or expired medicines, unprocessed patient/animal excretion, aquafarming, etc. Unlike other pollutions, PE-based contaminations can lead to catastrophic consequences via genotoxic, ecotoxicological, mutagenic effects, etc., causing behavioural changes, reproductive damage, and chronic damage. Therefore, a susceptible detection platform for PE traces in different sources like water bodies, human biofluids, etc., is in high demand. Owing to their high surface area, chemical stability, and electrocatalytic activity, the 2D graphitic carbon nitride (gCN) has gathered significant research interest. It has been examined for the electrochemical detection of PE traces in different ecological and biological samples. In this mini-review, we discuss the exciting advancements in the design and fabrication of gCN and its nanocomposite-based electrochemical sensors for other trace-level detection of different PEs in ecological and biological systems. The table in this review provides a clear insight into the reported gCN-based electrochemical sensors and their performance analysis towards sensing of EFs. The anticipated developments are discussed with current limitations in gCN-based electrochemical sensors for PE detection.

The emergence of COVID-19 had an unprecedented impact on society, leading to the widespread usage and disposal of surgical face masks (FMs). This work contributes to repurposing FMs into carbon materials through simplified solvothermal-assisted pyrolysis processes for supercapacitor applications. XRD and FESEM were employed to investigate the materials' microstructural and micrographic characteristics. The FM 700 has a specific capacitance value of 182.61 Fg−1, more significant than the other produced sample in the 1 M KOH electrolyte. The symmetric solid-state supercapacitor with a maximum capacitance of 92.67 Fg−1 is constructed under perfect circumstances. After 10,000 cycles, FM 700-SSSD maintained 89 % of its value. Turning FMs into carbon materials for energy storage applications is made more accessible by this method and also prevents the environment from pollution.

Background and Study Aim. Foot posture is an important determinant of a basketball player's performance. It influences their ability to generate power, maintain balance, and absorb shock. The aim of the current study was therefore to examine the association between foot posture and landing error score in recreational basketball players. Material and Methods. A cross-sectional study design was adopted. Fifty recreational basketball players from selected basketball clubs were chosen for the study. Their Foot Posture Index (FPI) and Landing Error Scores (LESS) were assessed. Nonparametric statistics, such as chi-square tests and the Mann-Whitney U test, were employed to examine the relationship between selected demographic variables and FPI and LESS scores. Additionally, assessed the difference in foot posture between the dominant and non-dominant legs. p-value less than 0.05 was considered significant. Results. Most participants exhibited normal foot posture, with no significant differences between the dominant and non-dominant legs, as assessed by FPI (p < 0.05). Additionally, an association was found between FPI and LESS scores, with 44% of participants showing a propensity for landing errors. The analysis revealed that a notable number of participants were categorized as 'poor' in LESS even with normal foot posture. This implies that landing errors are not only influenced by foot posture. Conclusions. There is an association between foot posture and the occurrence of landing errors in basketball players. This study emphasizes the need to thoroughly examine basketball players' FPI. It also underscores the importance of developing strategies aimed at helping them maintain optimal foot posture. These strategies can assist in avoiding landing errors, reducing the risk of injury, and promoting good health and well-being.

Tool condition monitoring (TCM) systems have evolved into an essential requirement for contemporary manufacturing sectors of Industry 4.0. These systems employ sensors and diverse monitoring techniques to swiftly identify and diagnose tool wear, defects, and malfunctions of computer numerical control (CNC) machines. Their pivotal role lies in augmenting tool lifespan, minimizing machine downtime, and elevating productivity, thereby contributing to industry growth. However, the efficacy of CNC machine TCM hinges upon multiple factors, encompassing system type, data precision, reliability, and adeptness in data analysis. Globally, extensive research is underway to enhance real-time TCM system efficiency. This review focuses on the significance and attributes of proficient real-time TCM systems of CNC turning centers. It underscores TCM’s paramount role in manufacturing and outlines the challenges linked to TCM data processing and analysis. Moreover, the review elucidates various TCM system variants, including cutting force, acoustic emission, vibration, and temperature monitoring systems. Furthermore, the integration of industrial Internet of things (IIoT) and machine learning (ML) into CNC machine TCM systems are also explored. This article concludes by underscoring the ongoing necessity for research and development in TCM technology to empower modern intelligent industries to operate at peak efficiency.

Background: India is facing triple epidemic of Non communicable diseases (NCDs) including high body mass index (BMI), high blood pressure and high blood glucose, contributing to more than half of deaths of all mortality, however, information in different demographics is limited, especially, in India. The aim of the study is to compare the prevalence of overweight, obesity, hypertension, and diabetes, along with the occurrence of multi-morbidity, across gender-specific populations in rural, suburban, and urban regions of India. Methods: This was a cross-sectional, population-based study including adults aged 20 and above in rural, suburban, and urban areas near Coimbatore, India. All participants were interviewed using a detailed questionnaire and had their anthropometric measurements, including height, weight, blood pressure, and blood samples collected. Gender specific and location specific prevalence of overweight, obesity, hypertension, diabetes, and multimorbidity were assessed. Results: This study included 2976 individuals, of which 865 were from rural areas, 1030 from sub-urban areas, and 1081 from metropolitan areas. The mean systolic and diastolic blood pressure were higher in rural participants than in sub-urban and urban participants, despite the fact that the prevalence of hypertension was higher in sub-urban (47.1%) than in rural (36.4%) and urban (39.7%, p < 0.001). In sub-group analysis, sub-urban areas had a greater prevalence of hypertension in both men and women (53.5% and 41.7%, p < 0.001) than rural areas (41.9% and 31.3%, p = 0.001) or urban areas (45.9% and 35.5%, p < 0.001). Compared to rural (16.1%) and urban (23%), sub-urban areas had a greater prevalence of diabetes (25.8%, p < 0.001). Urban residents (47.5%) had higher rates of overweight and obesity than rural (31.4%) and sub-urban (34.1%, p < 0.001) residents. The association between diabetes and hypertension was present in the unadjusted model and persisted even after age and BMI adjustments. Though not in men, higher levels of education were associated to a higher prevalence of diabetes in women. Diabetes was associated to being overweight or obese in women, however this association was significantly reduced once BMI was taken into account. The overall multimorbidity was 3.8%, however, women had a higher overlapping prevalence (2.8%) compared to men (1%, p < 0.001). Conclusions: Diabetes and hypertension were prevalent comorbidities across all demographics, with higher rates in suburban and urban areas. Women exhibited higher rates of multimorbidity than men, regardless of the demographic area.

Tool condition monitoring (TCM) is crucial in the machining process to confirm product quality as well as process efficiency and minimize downtime. Traditional methods for TCM, while effective to a degree, often fall short in real-time adaptability and predictive accuracy. This research work aims to advance the state-of-the-art methods in predictive maintenance for TCM and improve tool performance and reliability during the milling process. The present work investigates the application of Deep Learning (DL) and Reinforcement Learning (RL) techniques to monitor tool conditions in milling operations. DL models, including Long Short-Term Memory (LSTM) networks, Feed Forward Neural Networks (FFNN), and RL models, including Q-learning and SARSA, are employed to classify tool conditions from the vibration sensor. The performance of the selected DL and RL algorithms is evaluated through performance metrics like confusion matrix, recall, precision, F1 score, and Receiver Operating Characteristics (ROC) curves. The results revealed that RL based on SARSA outperformed other algorithms. The overall classification accuracies for LSTM, FFNN, Q-learning, and SARSA were 94.85%, 98.16%, 98.50%, and 98.66%, respectively. In regard to predicting tool conditions accurately and thereby enhancing overall process efficiency, SARSA showed the best performance, followed by Q-learning, FFNN, and LSTM. This work contributes to the advancement of TCM systems, highlighting the potential of DL and RL techniques to revolutionize manufacturing processes in the era of Industry 5.0.

The colorimetric detection of metal ions has witnessed a surge in advancements, with nanostructured fibers emerging as a powerful platform for environmental monitoring and remediation applications. These fibers offer several advantages, including a high surface area, enhanced sensitivity and selectivity, non-intrusive analysis, rapid response times, robustness under harsh conditions, and user-friendly handling. This unique combination makes them particularly suitable for visible eye detection of metal ions in remote or challenging environments. This review provides a concise overview of recent developments in nanostructured fibers, and their cutting-edge fabrication methods, for the colorimetric-based detection of various heavy metal ions in real-time samples. By exploiting the unique properties of these fibers, colorimetric detection offers a promising and cost-effective approach for heavy metal ion determination. This review delves into the design principles, functionalization strategies, and detection mechanisms employed in these innovative sensors. We highlight the potential of nanostructured fibers as a well-established and efficient platform for the colorimetric detection of heavy metals, paving the way for more sustainable and accessible environmental monitoring solutions.

Biological therapeutic agents are highly targeted and potent but limited in their ability to reach intracellular targets. These limitations often necessitate high therapeutic doses and can be associated with less-than-optimal therapeutic activity. One promising solution for therapeutic agent delivery is use of cell-penetrating peptides. Canonical cell-penetrating peptides, however, are limited by low efficiencies of cellular uptake and endosomal escape, minimal proteolytic stability, and toxicity. To overcome these limitations, we designed a family of proprietary cyclic cell-penetrating peptides that form the core of our endosomal escape vehicle technology capable of delivering therapeutic agent-conjugated cargo intracellularly. We demonstrated the therapeutic potential of this endosomal escape vehicle platform in preclinical models of muscular dystrophy with distinct disease etiology. An endosomal escape vehicle-conjugated, splice-modulating oligonucleotide restored dystrophin protein expression in striated muscles in the mdx mouse, a model for Duchenne muscular dystrophy. Furthermore, another endosomal escape vehicle-conjugated, sterically blocking oligonucleotide led to knockdown of aberrant transcript expression levels in facioscapulohumeral muscular dystrophy patient-derived skeletal muscle cells. These findings suggest a significant therapeutic potential of our endosomal escape vehicle conjugated oligonucleotides for targeted upregulation and downregulation of gene expression in neuromuscular diseases, with possible broader application of this platform for delivery of intracellular biological agents.

Abstract Chimeric antigen receptor (CAR)-T cell therapy is rapidly advancing as cancer treatment, however, designing an optimal CAR remains challenging. A single-chain variable fragment (scFv) is generally used as CAR targeting moiety, wherein the complementarity-determining regions (CDRs) define its specificity. We report here that the CDR loops can cause CAR clustering, leading to antigen-independent tonic signalling and subsequent CAR-T cell dysfunction. We show via CARs incorporating scFvs with identical framework and varying CDR sequences that CARs may cluster on the T cell surface, which leads to antigen-independent CAR-T cell activation, characterized by increased cell size and interferon (IFN)-γ secretion. This results in CAR-T cell exhaustion, activation-induced cell death and reduced responsiveness to target-antigen-expressing tumour cells. CDR mutagenesis confirms that the CAR-clustering is mediated by CDR-loops. In summary, antigen-independent tonic signalling can be induced by CDR-mediated CAR clustering, which could not be predicted from the scFv sequences, but could be tested for by evaluating the activity of unstimulated CAR-T cells.

BackgroundIndividuals with physical disabilities experience higher rates of chronic health conditions than individuals without physical disabilities. Self-management programs that use health coaching are effective at eliciting health behavior change in health outcomes such as goal setting, adherence, and health care use. Additionally, web-based resources such as telehealth-based technologies, including SMSS text messaging, web-based applications, and educational multimedia content, can complement health coaching to improve health-related behaviors and the use of health services. The complexity of studies using these resources requires a fidelity protocol to ensure that health behavior studies are administered properly. ObjectiveThe My Health, My Life, My Way fidelity protocol provides methods, strategies, and procedures of a multifaceted telehealth program for individuals with permanent physical disabilities and chronic health conditions. This health behavior study is a randomized controlled trial with four study arms: (1) scheduled coaching calls with gamified rewards, (2) no scheduled coaching calls with gamified rewards, (3) scheduled coaching calls with fixed rewards, and (4) no scheduled coaching calls with fixed rewards. To guide the fidelity protocol developed, we used the National Institutes of Health Behavior Change Consortium framework (NIH BCC). MethodsThe fidelity intervention protocol was developed by using the 5 primary domains provided by the NIH BCC: study design, provider training, treatment delivery, treatment receipt, and enactment of treatment skills. Following the NIH BCC guidelines and implementing social cognitive theory, this study is designed to ensure that all study arms receive equal treatment across conditions and groups. Health coaches and providers will be trained to deliver consistent health coaching, and thus participants will receive appropriate attention. Educational content will be developed to account for health literacy and comprehension of the material. Multiple fidelity intervention steps such as coaching call logs, regular content review, and participant progress monitoring will translate to participants using the skills learned in their daily lives. Different monitoring steps will be implemented to minimize differences among the 4 treatment groups. ResultsMy Health, My Life, My Way has been approved by the institutional review board and will begin enrollment in January 2024 and end in December 2024, with results reported in early 2025. ConclusionsIntervention fidelity protocols are necessary to ensure that health behavior change studies can be implemented in larger real-world settings. The My Health, My Life, My Way fidelity protocol has used the guidelines by the NIH BCC to administer a telehealth intervention combined with health coaching for individuals with physical disabilities and chronic health conditions. This fidelity protocol can be used as a complementary resource for other researchers who conduct similar research using telehealth technologies and health coaching in real-world settings. Trial RegistrationClinicalTrials NCT05481593; https://clinicaltrials.gov/study/NCT05481593 International Registered Report Identifier (IRRID)PRR1-10.2196/53410

BackgroundPeople with disabilities experience numerous barriers to being physically active, such as transportation issues, a lack of trained exercise professionals who understand disabilities, and facility access. The use of a virtual exercise platform (VEP) may provide an alternative and limit certain barriers. ObjectiveThe aim of this mixed method study was to evaluate user interaction (effectiveness, efficiency, and satisfaction), the strengths and weaknesses of the user interface, and the user experience with a VEP. MethodsParticipants were recruited from a community fitness facility that offers programs for people with disabilities. Inclusion criteria were being older than 18 years, fluent in English, and availability of internet access. Features of the VEP included articles, prerecorded videos, live Zoom classes, web-based class registration, weekly progress tracking, incentives, and surveys. A one-on-one Zoom session was scheduled with each participant, during which they completed certain tasks: (1) create an account or login, (2) register for class, (3) join class, (4) add to calendar, and (5) complete surveys. As participants completed tasks, quantitative observations (time on task, task success, rate of task completion, and number of errors by users, which determined task difficulty), qualitative observations were made and interviews were conducted at the end of the session. The “concurrent think-aloud” method was encouraged by the moderator to gauge participants’ thoughts as they worked through testing. Participants also completed the System Usability Scale (SUS) and Questionnaire for User Interface Satisfaction (QUIS). ResultsA total of 5 people with disabilities (3 male, 2 female), aged 36-78 (mean 54) years, with education levels from high school to PhD, were recruited. Devices used for testing included a laptop (n=3), a Chromebook (n=1), and a desktop (n=1). All participants completed tasks #1 and #2 without errors but could not complete task #4. One participant completed task #5 with difficulty and another completed task #3 with difficulty. The average time to complete each task was: (1) 82 seconds (55-110), (2) 11 seconds (4-21), (3) 9 seconds (5-27), and (4) 921.5 seconds (840-958). The mean SUS score was 86.5/100, and the mean user QUIS score was 8.08 out of 10. Qualitative observations indicated that the system was simple, user-friendly, and accessible. ConclusionsPeople with disabilities reported high usability and user satisfaction with the web-based exercise platform, and the system appears to be an efficient and effective physical activity option.

An attempt was made to identify the chromosomes from different species genomes in BC₂ progenies of Erianthus procerus x Saccharum officinarum through multi-color GISH (MCGISH). The BC₂ population was derived from the cross between a BC1 hybrid (GU 12-14) and a commercial variety, Co 16018. The BC2 progenies were studied for their somatic chromosome number and two cytotypes were observed, i.e., 2n=92 (2) and 2n=96 (5). GISH revealed that the majority of progenies were having nine Erianthus chromosomes, except 2 clones (25-5 and 25-10) were having nine Erianthus chromosomes with one chromosome fragment. The methodology for multi-color GISH was standardized and it distinguished the chromosomes from different genomes. Interspecific recombination was also detected in somatic cells of one BC₂ clone, 25-10. The hybridity of the introgressed lines has been confirmed with amplification of Erianthus specific tandem repeat sequences.

BackgroundWhile self-management programs have had significant improvements for individuals with chronic conditions, less is known about the impact of self-management programs for individuals with physical disabilities who experience chronic conditions, as no holistic self-management programs exist for this population. Similarly, there is limited knowledge of how other stakeholders, such as caregivers, health experts, and researchers, view self-management programs in the context of disability, chronic health conditions, and assistive technologies. ObjectiveThis study aimed to obtain insight into how stakeholders perceive self-management relating to physical disability, chronic conditions, and assistive technologies. MethodsNine focus groups were conducted by 2 trained facilitators using semistructured interview guides. Each guide contained questions relating to stakeholders’ experiences, challenges with self-management programs, and perceptions of assistive technologies. Focus groups were audio recorded and transcribed. Thematic analysis was conducted on the focus group data. ResultsA total of 47 individuals participated in the focus groups. By using a constructivist grounded approach and inductive data collection, three main themes emerged from the focus groups: (1) perspectives, (2) needs, and (3) barriers of stakeholders. Stakeholders emphasized the importance of physical activity, mental health, symptom management, medication management, participant centeredness, and chronic disease and disability education. Participants viewed technology as a beneficial aide to their daily self-management and expressed their desire to have peer-to-peer support in web-based self-management programs. Additional views of technology included the ability to access individualized, educational content and connect with other individuals who experience similar health conditions or struggle with caregiving duties. ConclusionsThe findings suggest that the development of any web-based self-management program should include mental health education and resources in addition to physical activity content and symptom management and be cost-effective. Beyond the inclusion of educational resources, stakeholders desired customization or patient centeredness in the program to meet the overall needs of individuals with physical disabilities and caregivers. The development of web-based self-management programs should be holistic in meeting the needs of all stakeholders. Trial RegistrationClinicalTrials.gov NCT05481593; https://clinicaltrials.gov/study/NCT05481593

Tertiary lymphoid structures (TLS) are lymph node-like aggregates that can form in association with chronic inflammation or cancer. Mature TLS are organized into B and T cell zones, and are not encapsulated but include all cell types necessary for eliciting an adaptive immune response. TLS have been observed in various cancer types and are generally associated with a positive prognosis as well as increased sensitivity to cancer immunotherapy. However, a comprehensive understanding of the roles of TLS in eliciting anti-tumor immunity as well as the mechanisms involved in their formation and function is still lacking. Further studies in orthotopic, immunocompetent cancer models are necessary to evaluate the influence of TLS on cancer therapies, and to develop new treatments that promote their formation in cancer. Here, we review key insights obtained from functional murine studies, discuss appropriate models that can be used to study cancer-associated TLS, and suggest guidelines on how to identify TLS and distinguish them from other antigen-presenting niches.

Increased global energy consumption demands the use of more energy resources, aggravating environmental issues. This study focused on analyzing biogas production from a mixture of cow dung, water hyacinth, and food waste and checking the efficiency of the biogas. The efficiency of biogas production was tested using two alternative settings in the study. The first setup employs Eichhornia crassipes that have been NaOH-treated and mixed with co-digestion substrates such as cow manure and food waste which have been stored at room temperature for 32 days. The second setup contains five different types of substrates such as L1-cow dung, L2- cow dung: water hyacinth, L3-cow dung: food waste, L4-cow dung: water hyacinth: food waste, and L5-water hyacinth. The properties of the Eichhornia crassipes were studied on several biogas substrates, such as pH, temperature, COD, TOC, and NPK tests, as well as total biogas output and methane percentage. The results of the comparison analysis show that the substrate L4 has a high level of NPK (4.7 %) and a higher amount of COD (137600 mg/l). These characteristics enhance the gas yield and methane percentage (85 %). Overall, the water hyacinth mixed with cow dung and food waste exceeded the other four substrates. The total yield of biogas from the first setup was 8.5 litres, the flammability was tested on the 28th day, and the blue flame was obtained. Water hyacinth was removed from aquatic areas and used as an alternative energy source, hence being environmentally friendly.

The development of complete natural composite with natural fiber and natural resin is one of the challenges in the material era. To address the issue, this research article is aimed to study the possibility of utilizing the natural resin Vajram with natural banana fiber to develop a natural composite. In addition to that alkali treatment of banana fiber with 5%, 10% and 15% sodium hydroxide (NaOH) solution to improve the properties also analyzed. All the composites were prepared using a hand layup technique followed by compression molding. All the mechanical testings were conducted as per corresponding ASTM standards. The experimental results showed that 5% NaOH treated fibers recorded higher tensile strength 170.12 MPa than other fibers. Banana fiber reinforced phenolic resin composite (BFRPC) with 5% NaOH treated fibers with a 30% fiber weight ratio recorded the highest mechanical properties such as 22.62 MPa, 33.84 MPa, and 5.87 kJ/m2 in tensile, flexural, and impact strength respectively. 21.53%, 38.39%, and 44.63% reduction in tensile, flexural, and impact strength respectively were noted due to the 80% Vajram mixed banana fiber-reinforced composite. This kind of low strength natural Vajram resin mixed banana fiber composites is well suitable for automobile applications as non-structural components.

Although many isolation techniques for algaeaxenic cultures of algae are known, successful isolation approaches are species and contaminant-specific. The commercially important alga Haematococcus lacustris has been intensively studied due to its natural production of the high-value carotenoid astaxanthin, yet there are no reports of axenic H. lacustris cultures. In this article, we describe the successful isolation of axenic H. lacustris, originally isolated in non-axenic form from its natural habitat and adopted to be used daily in vitro, in our laboratory. We verify the absence of bacteria and identify the bacterial communities in the non-axenic algal culture. using PCR amplification with selected universal primers for 16S rRNA gene amplification in the gDNA. Amplification of the 16S rRNA gene of the non-axenic culture showed the presence of bacteria with high identity to Massilia, Blastococcus and Deinococcus species. The bacteria which were identified in our strain further expand our knowledge of bacterial communities on algae, and because we established axenic H. lacustris culture, testing their effect on growth or astaxanthin accumulation in controlled co-cultures is now available. The isolation technique described herein can be applied to other green algal species to eliminate bacteria, and the selected primers can be used to verify the axenic nature of other green algal cultures. The resulting axenic culture is required for molecular genetics research and will be very valuable for establishing heterotrophic growth in laboratory or industrial bioreactors.

In India, research on the development of new composite materials is extensively increased. In the present study, composites are developed with the renewable materials of plant and animal-based natural fibers. The present study will lead to the experimental and statistical investigation of the composite produced with a combination of plant-based natural fibers, i.e., jute and coco peat powder with the animal-based natural fibers, i.e., silk. In the present study, jute and silk were utilized as reinforcement material, cocopeat powder as a filler material (5%), and epoxy resin as matrix material (35%). The composites were prepared with the varying composition of reinforcement material, and also the filler and matrix material were kept constant. Furthermore, mechanical properties such as tensile, flexural, and impact tests were performed on the developed composites. Further, a comparative study was drawn on the mechanical test results of tensile and flexural strength of the composite using power and polynomial regression model. The regression coefficient (R2) was used to study the correlation between the experimental and predicted values. The results showed that the polynomial regression is the best suitable mathematical model than the power regression model for predicting the composites’ tensile and flexural test performance.

Communicable diseases are one of the challenges to people’s health and fitness. Consuming contaminated water or food and inhaling contaminated water droplets are the main causes of water-borne pathogens spread. This paper studies the spreading dynamics of water-borne diseases with vaccination and preventive measures over a multilayer network. SVIR-process for disease spread over humans and SIS-process for disease spread over water supply mediums and UAU-process for awareness diffusion over humans via social media are taken to study the spreading dynamics. The Discrete-time Markov chain approach is used to frame and analyse the model. The optimal value corresponding to the vaccination parameter is found to control the disease spread. The impact of awareness and vaccination over disease spread and the characteristics of basic reproduction number are found via numerical simulation.

Identification of promising genotypes in sugarcane (Saccharum spp. hybrids) breeding is achieved by multi-stage evaluation initiated by evaluation of thousands of seedlings derived from true seed and then vegetatively propagated. Family selection for cane yield in ground nursery is done through weighing cane yield / plot, which is laborious and expensive. In recent times, various statistical tools have been applied for overcoming the constraints in family selection at single stool stage. A population of 1,800 seedlings derived from fifteen bi-parental crosses involving Indian Co canes and Erianthus introgressed hybrids were evaluated in seedling stage. A subset comprised of 450 clones selected from the single stool stage was evaluated in the first clonal trial. Random Coefficient Model (RCM)was employed to predict the promising families contributing a greater number of high yielding clones using the cane yield data recorded in the early stages of selection viz., single stool and first clonal crop stages. The hybrids of the five elite parental combinations viz., Co 86011 x CoT 8201, Co 8371 x Co 86011, Co 86002 x CoC 671, Co 62198 x Co 8353 and GU04(28) E02 self x Co 0314 identified through RCM analysis showed an improvement of 41.86 % higher cane yield than the clones in the average families (Co 85002 x Co 8209, CoM 0265 x Co 0314, Co 8371 x Co 94008, Co 11015 x Co 775 andGU04 (50) RE6 x Co 94008). The positive slope values estimated by the RCM method for the superior crosses highly correlated with the proportion of elite cane yielding clones in the plant crop trial.

Commercial sugarcane hybrids are derivatives from Saccharum officinarum and Saccharum spontaneum hybrids containing the full complement of S. officinarum and a few S. spontaneum chromosomes and recombinants with favorable agronomic characters from both the species. The combination of the two sub-genomes in varying proportions in addition to the recombinants presents a challenge in the study of gene expression and regulation in the hybrid. We now report the transcriptome analysis of the two progenitor species and a modern commercial sugarcane hybrid through long read sequencing technology. Transcripts were profiled in the two progenitor species S. officinarum (Black Cheribon), and S. spontaneum (Coimbatore accession) and a recent high yielding, high sugar variety Co 11015. The composition and contribution of the progenitors to a hybrid with respect to sugar, biomass, and disease resistance were established. Sugar related transcripts originated from S. officinarum while several stress and senescence related transcripts were from S. spontaneum in the hybrid. The hybrid had a higher number of transcripts related to sugar transporters, invertases, transcription factors, trehalose, UDP sugars, and cellulose than the two progenitor species. Both S. officinarum and the hybrid had an abundance of novel genes like sugar phosphate translocator, while S. spontaneum had just one. In general, the hybrid shared a larger number of transcripts with S. officinarum than with S. spontaneum, reflecting the genomic contribution, while the progenitors shared very few transcripts between them. The common isoforms among the three genotypes and unique isoforms specific to each genotype indicate that there is a high scope for improvement of the modern hybrids by utilizing novel gene isoforms from the progenitor species.

BackgroundParticipating in an adequate amount of physical activity to acquire health benefits is challenging for people with spinal cord injury (SCI) due to personal and logistic barriers. Barriers in the built and social environments may include lack of transportation, lack of accessible facilities or programs, and lack of training among fitness personnel. Low self-efficacy, lack of self-regulation skills, and improper outcome expectations are examples of personal barriers. Current approaches to investigating physical activity programs in people with SCI have been limited to traditional “one-size-fits-all” design, which has yielded low adherence rates, high dropout rates, and participants not maintaining physical activity levels at follow-up. ObjectiveThe primary aim of this study is to test the feasibility of a tele-exercise program that applies an adaptive intervention design for 30 adults with SCI, targeting increases in adherence to the exercise program and physical activity participation. MethodsThe Sequential Multiple Assignment Randomized Trial for Home-based Exercise and Lifestyle Tele-Health (SMART-HEALTH) is a 12-week, home-based, movement-to-music (M2M) program. The goal of a SMART-designed study is to develop an adaptive intervention that modifies support provisions based on response levels. In SMART-HEALTH, 2 groups of participants will undergo 3-week and 6-week asynchronous M2M interventions in the first phase. Participants who did not achieve the desired adherence rate (≥95% of video watch minutes) will be rerandomized into M2M Live (switch) or individualized behavioral coaching (augmented with the asynchronous M2M program). The study will primarily assess rates of recruitment or enrollment, adherence and retention, timing to identify nonresponders, and scientific outcomes (eg, physical activity and exercise self-efficacy). The study will qualitatively evaluate the acceptability of the study using semistructured interviews among participants who complete the 12-week intervention. ResultsRecruitment procedures started in June 2022. All data are expected to be collected by September 2023. Full trial results are expected to be published by March 2024. Secondary analyses of data will be subsequently published. Results will include exercise adherence rates; changes in self-reported physical activity levels and blood pressure; and changes in secondary conditions including pain, sleep, and fatigue. Thematic analysis of semistructured interviews will include results on participant enjoyment and acceptability of SMART-HEALTH and inform modifications for future delivery of the program. ConclusionsThis study will strengthen our understanding of the potential benefits of the tele-exercise intervention for people with SCI and build upon adaptive intervention design and its delivery strategies that aim to increase adoption and sustainable exercise behavior. This pilot trial will inform future SMART-designed studies and provide new and innovative strategies for investigating intervention effects on physical activity behavior in the SCI population. Trial RegistrationClinicalTrials.gov NCT04726891; https://classic.clinicaltrials.gov/ct2/show/NCT04726891 International Registered Report Identifier (IRRID)DERR1-10.2196/47665

The current study is rooted in the theory of conservation of resources, exploring the associations between mental health factors namely stress, anxiety and depression with organizational citizenship behavior and counterproductive wok behavior. Data gathered from an Indian automobile sector revealed interconnections between the variables. It was found that stress, anxiety and depression have a positive relationship with OCB and stress and anxiety have negative relationship with CWB. The manuscript further evaluates the results drawing upon conservation of resources theory as we find striking differences between our hypotheses and results, and that opens up new avenues for future research.

Perineuronal nets (PNNs) form a specialized extracellular matrix that predominantly surrounds parvalbumin (PV)-expressing GABAergic inhibitory interneurons and help regulate neuronal activity. Their formation early in the postnatal period is regulated by neuronal signaling and glial activation raising concerns that part of the long-term effects ascribed to perinatal viral infections could be mediated by altered PNN formation. Previously, we developed a model of neonatal Zika virus (ZIKV) infection where mice have lifelong neurological sequelae that includes motor disfunction and reduced anxiety coupled with a persistent low-grade expression in proinflammatory markers despite resolving the acute infection. Here, we demonstrate that ZIKV infection to P1 neonatal mice results in a reduction of PNN formation during the acute disease with significant reduction in Wisteria floribunda agglutinin (WFA) staining at the peak of infection [15 days post infection (dpi)] that persisted after the symptoms resolved (30 dpi). At 60 dpi, when there is residual inflammation in the CNS, the number of WFA+ cells and the level of WFA staining as well as levels of aggrecan and brevican in the brains of convalescent mice were not different from those in uninfected controls, however, there was increased frequency of PNNs with an immature phenotype. Over time the impact of the perinatal infection became less evident and there were no clear differences in PNN morphology between the groups at 1 year post infection. Of note, the reduction in PNNs during acute ZIKV infection was not associated with decreased mRNA levels of aggrecan or brevican, but increased levels of degraded aggrecan and brevican indicating increased PNN degradation. These changes were associated with increased expression of matrix metalloproteinase 12 (MMP12) and MMP19, but not MMP9, a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) or ADAMTS5. Together our findings indicate that infection at the time of PNN development interferes with PNN formation, but the nets can reform once the infection and inflammation subside.

Summary: Identifying population-specific genetic variants associated with disease and disease-predisposing traits is important to provide insights into the genetic determinants of health and disease between populations, as well as furthering genomic justice. Various common pan-population polymorphisms at CETP associate with serum lipid profiles and cardiovascular disease. Here, sequencing of CETP identified a missense variant rs1597000001 (p.Pro177Leu) specific to Māori and Pacific people that associates with higher HDL-C and lower LDL-C levels. Each copy of the minor allele associated with higher HDL-C by 0.236 mmol/L and lower LDL-C by 0.133 mmol/L. The rs1597000001 effect on HDL-C is comparable with CETP Mendelian loss-of-function mutations that result in CETP deficiency, consistent with our data, which shows that rs1597000001 lowers CETP activity by 27.9%. This study highlights the potential of population-specific genetic analyses for improving equity in genomics and health outcomes for population groups underrepresented in genomic studies.

Background and Objectives: MicroRNAs are short noncoding RNAs that play an essential role in controlling gene expression at the posttranscriptional level. They can serve as biomarkers in the management of obesity. Circulating miRNAs levels change with exercise, impacting various physiological and biological systems, including structural and functional changes. Aim: The purpose of this study is to evaluate the levels of miRNAs 423-5p and 128-1 in young adolescents with obesity before and after an aerobic exercise programme. We also analyse the relationship between those microRNAs and obesity-related parameters in response to aerobic exercise training. Materials and Methods: A total of 64 adolescent individuals (32 individuals with obesity and 32 healthy individuals) were enrolled in the study to participate in a 6-month aerobic exercise programme. Anthropometric measurements, biochemical parameters and blood samples were collected from all the participants prior to exercise training and after the 6-month programme. Gene expression analysis of the study participants was performed using quantitative real-time PCR. Results: Expression levels of circulating microRNAs 423-5p (p < 0.01) and 128-1 (p < 0.01) differed significantly before and after exercise in the study population. Circulating miRNA 423-5p increased and correlated significantly with BMI while circulating miRNA 128-1 decreased and also significantly correlated with BMI after the 6-month aerobic exercise programme. Logistic regression analysis shows that the elevation in miRNAs expression levels has a strong significant association with the increased levels of the cytokines IL-6 and TNF-α (p < 0.05). Conclusions: Obesity leads to alterations in the expressions of miRNA 423-5p and miRNA 128-1. The significant changes observed after an aerobic exercise programme demonstrate the potential of these miRNAs as diagnostic and prognostic biomarkers for obesity.

Plastic consumption is increasing on a daily basis, despite efforts to minimize it. On the other hand, the management of waste plastic was a significant issue in several countries around the world. A healthy and sustainable reuse of plastics has numerous benefits. The acceptability and benefits of recycled plastics as Coarse aggregate in concrete are explored here. Plastic aggregate parameters such as density and specific gravity were determined through tests. Because complete replacement of natural Coarse aggregate with plastic Coarse aggregate is impractical, partial replacement at various percentages was investigated. In addition to that silica fume is added as a binding material at a constant of 10%. The substitution of 15 Percent Plastic aggregate resulted in high compressive, splitting tensile, and flexural strength.

Abstract Acute myeloid leukemia (AML) is a malignant disease of immature myeloid cells and the most prevalent acute leukemia among adults. The oncogenic homo-tetrameric fusion protein RUNX1/ETO results from the chromosomal translocation t(8;21) and is found in AML patients. The nervy homology region 2 (NHR2) domain of ETO mediates tetramerization; this oligomerization is essential for oncogenic activity. Previously, we identified the first-in-class small-molecule inhibitor of NHR2 tetramer formation, 7.44, which was shown to specifically interfere with NHR2, restore gene expression down-regulated by RUNX1/ETO, inhibit the proliferation of RUNX1/ETO-depending SKNO-1 cells, and reduce the RUNX1/ETO-related tumor growth in a mouse model. However, no biophysical and structural characterization of 7.44 binding to the NHR2 domain has been reported. Likewise, the compound has not been characterized as to physicochemical, pharmacokinetic, and toxicological properties. Here, we characterize the interaction between the NHR2 domain of RUNX1/ETO and 7.44 by biophysical assays and show that 7.44 interferes with NHR2 tetramer stability and leads to an increase in the dimer population of NHR2. The affinity of 7.44 with respect to binding to NHR2 is K lig = 3.75 ± 1.22 µM. By NMR spectroscopy combined with molecular dynamics simulations, we show that 7.44 binds with both heteroaromatic moieties to NHR2 and interacts with or leads to conformational changes in the N-termini of the NHR2 tetramer. Finally, we demonstrate that 7.44 has favorable physicochemical, pharmacokinetic, and toxicological properties. Together with biochemical, cellular, and in vivo assessments, the results reveal 7.44 as a lead for further optimization towards targeted therapy of t(8;21) AML.

The current study intended to determine recreational runners' knowledge, attitude, and practices toward CSE to prevent LBP. Materials and Methods: A cross-sectional study design was adopted. Two hundred fifty-seven recreational runners were chosen using a simple random sampling approach and administered with a semi-structured questionnaire to evaluate their KAP toward CSE. Data analysis was carried out using SPSS 28.0. Results: The correct response to the knowledge-related items in the questionnaire was from 65% to 91%. Precisely, 91.4% of study participants understood CSE. Furthermore, most participants showed a positive attitude toward CSE, considering that it is essential for running (79%), improving fitness (76%), reducing the risk of injuries (71%), and boosting their appearance (54%). Most participants (>85%) performed CSE for recommended frequency and duration to strengthen their core muscles and prevent LBP. The recreational runners had good practice toward CSE. Conclusion: Recreational runners possess adequate knowledge, a positive attitude, and good practice toward CSE. This study suggested that motivational strategies and awareness programs can be conducted to improve recreational runners' KAP toward CSE preventing LBP.

AimsMonogenic diabetes accounts for 1-2% of diabetes cases yet is often misdiagnosed as type 2 diabetes. The aim of this study was to examine in Māori and Pacific adults clinically diagnosed with type 2 diabetes within 40 years of age, (a) the prevalence of monogenic diabetes in this population (b) the prevalence of beta-cell autoantibodies and (c) the pre-test probability of monogenic diabetes.MethodsTargeted sequencing data of 38 known monogenic diabetes genes was analyzed in 199 Māori and Pacific peoples with BMI of 37.9 ± 8.6 kg/m2 who had been diagnosed with type 2 diabetes between 3 and 40 years of age. A triple-screen combined autoantibody assay was used to test for GAD, IA-2, and ZnT8. MODY probability calculator score was generated in those with sufficient clinical information (55/199).ResultsNo genetic variants curated as likely pathogenic or pathogenic were found. One individual (1/199) tested positive for GAD/IA-2/ZnT8 antibodies. The pre-test probability of monogenic diabetes was calculated in 55 individuals with 17/55 (31%) scoring above the 20% threshold considered for diagnostic testing referral.DiscussionOur findings suggest that monogenic diabetes is rare in Māori and Pacific people with clinical age, and the MODY probability calculator likely overestimates the likelihood of a monogenic cause for diabetes in this population.

BackgroundIndividuals with disabilities living with chronic health conditions require self-management programs that are accessible, sustainable, inclusive, and adaptable. Health coaching is an effective approach to promoting behavior change in self-management. Health coaching combined with telehealth technology has the potential to improve the overall quality of, and access to, health services. ObjectiveThis protocol outlines the study design for implementing the My Health, My Life, My Way intervention. The study will assess the feasibility, acceptability, and preliminary efficacy of the intervention for people with disabilities and optimize it. MethodsThe My Health, My Life, My Way study is a 4-arm randomized controlled trial evaluating the delivery of a 6-month intervention involving telecoaching, inclusive educational content, and technology access for 200 individuals with chronic conditions and physical disabilities. This study uses the engineering-inspired multiphase optimization strategy (MOST) framework to evaluate intervention components and assess whether a combination or lack of individual elements influences behavior. Participants will be randomized to 1 of 4 study arms: scheduled coaching calls and gamified rewards, no scheduled coaching calls and gamified rewards, scheduled coaching calls and flat rewards, and no scheduled coaching calls and flat rewards. ResultsThe My Health, My Life, My Way study was approved by the institutional review board of the University of Alabama at Birmingham, and recruitment and enrollment will begin in May 2023. Data analysis is expected to be completed within 6 months of ending data collection. This clinical trial protocol was developed based on the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 statement. ConclusionsThe My Health, My Life, My Way study will help to optimize and improve our understanding of the feasibility and efficacy of a web-based self-management program for people with physical disabilities and chronic conditions. More specifically, My Health, My Life, My Way will determine which combination of interventions (coaching calls and gamification) will result in increased participation in self-management programming. The My Health, My Life, My Way intervention has the potential to become a scalable and novel method to successfully manage chronic conditions in people with disabilities. Trial RegistrationClinicalTrials.gov NCT05481593; https://clinicaltrials.gov/ct2/show/NCT05481593 International Registered Report Identifier (IRRID)PRR1-10.2196/31694

BackgroundReplacing sedentary behaviors during leisure time with active video gaming has been shown to be an enjoyable option for increasing physical activity. However, most off-the-shelf active video gaming controllers are not accessible or usable for individuals with mobility impairments. To address this requirement, a universal video game controller (called the GAIMplank) was designed and developed. ObjectiveThis study aimed to assess the usability of the GAIMplank video game controller for playing PC video games among individuals with mobility impairments. Measures of enjoyment, perceived exertion, and qualitative data on the user experience were also examined. MethodsAdults (aged 18-75 years) with a mobility impairment were recruited to participate in a single testing session in the laboratory. Before testing began, basic demographic information, along with minutes of weekday and weekend physical activity, minutes of weekday and weekend video game play, and video game play experience were collected. The GAIMplank was mapped to operate as a typical joystick controller. Depending on their comfort and functional ability, participants chose to play seated in a chair, standing, or in their own manual wheelchair. Leaning movements of the trunk created corresponding action in the game (ie, lean right to move right). The participants played a total of 5 preselected video games for approximately 5 minutes each. Data were collected to assess the usability of the GAIMplank, along with self-efficacy regarding execution of game play actions, rating of perceived exertion and enjoyment for each game, and overall qualitative feedback. ResultsA total of 21 adults (n=15, 71% men; n=6, 29% women) completed the usability testing, with a mean age of 48.8 (SD 13.8; range 21-73) years. Overall, 38% (8/21) of adults played while standing, 33% (7/21) of adults played while seated in a chair, and 29% (6/21) played in their own manual wheelchair. Scores from the System Usability Scale indicated above average (74.8, SD 14.5) usability, with scores best for those who played seated in a chair, followed by those standing, and then individuals who played seated in their own wheelchairs. Inconsistencies in the responsiveness of the controller and general feedback for minor improvements were documented. Rating of perceived exertion scores ranged from light to moderate intensity, with the highest scores for those who played seated in a chair. Participants rated their experience with playing each game from above average to very enjoyable. ConclusionsThe GAIMplank video game controller was found to be usable and accessible, providing an enjoyable option for light-to-moderate intensity exercise among adults with mobility impairments. Minor issues with inconsistencies in controller responsiveness were also recorded. Following further development and refinement, the next phase will include a pilot exercise intervention using the GAIMplank system.