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The ProteinPaint Hi-C tool (ppHiC) facilitates web-based visualization and collaborative exploration of Hi-C data, a vital resource for understanding three-dimensional genomic structures. ppHiC allows researchers to easily analyze large Hi-C datasets on a web browser without requiring the computational expertise that has heretofore limited access to this complex genomic data. The platform is compatible with multiple Hi-C data versions and boasts a highly customizable interface, including a configuration panel for the precise adjustment of key visualization parameters. The tool’s interactive features offer a broad range of views, from whole-genome landscapes to detailed interactions between pairs of loci, that are accessible within a single, integrated environment. Here, we demonstrate how using ppHiC to visualize an altered chromatin conformational landscape in neuroblastoma can inform understanding of the genomic rearrangements in this cancer.

Craig Hilburn, Vicki A Nejtek, Wendy A Underwood, Meharvan Singh, Gauravkumar Patel, Pooja Gangwani, Michael J ForsterUniversity of North Texas Health Science Center at Fort Worth, TX, USABackground: Data suggests that brain-derived neurotropic factor (BDNF) plays a neuroadaptive role in addiction. Whether serum BDNF levels are different in alcohol or psychostimulants as a function of craving is unknown. Here, we examined craving and serum BDNF levels in persons with alcohol versus psychostimulant dependence. Our goals were to explore BDNF as an objective biomarker for 1) craving 2) abstinence, and 3) years of chronic substance use.Methods: An exploratory, cross-sectional study was designed. Men and women between 20–65 years old with alcohol, cocaine, or methamphetamine dependence were eligible. A craving questionnaire was used to measure alcohol, cocaine and methamphetamine cravings. Serum levels of BDNF were measured using enzyme linked immunoassay. Analysis of variance, chi-square, and correlations were performed using a 95% confidence interval and a significance level of P < 0.05.Results: We found a significant difference in the mean craving score among alcohol, cocaine and methamphetamine dependent subjects. There were no significant influences of race, gender, psychiatric disorder or psychotropic medication on serum BDNF levels. We found that among psychostimulant users BDNF levels were significantly higher in men than in women when the number of abstinent days was statistically controlled. Further, a significant correlation between serum BDNF levels and the number of abstinent days since last psychostimulant use was found.Conclusion: These data suggest that BDNF may be a biomarker of abstinence in psychostimulant dependent subjects and inform clinicians about treatment initiatives. The results are interpreted with caution due to small sample size and lack of a control group.Keywords: BDNF, alcohol, cocaine, methamphetamine, craving

BackgroundThe optimal timing of esophagogastroduodenoscopy (EGD) and the impact of clinico-demographic factors on hospitalization outcomes in non-variceal upper gastrointestinal bleeding (NVUGIB) remains an area of active research.AimTo identify independent predictors of outcomes in patients with NVUGIB, with a particular focus on EGD timing, anticoagulation (AC) status, and demographic features.MethodsA retrospective analysis of adult patients with NVUGIB from 2009 to 2014 was performed using validated ICD-9 codes from the National Inpatient Sample database. Patients were stratified by EGD timing relative to hospital admission (≤ 24 h, 24-48 h, 48-72 h, and > 72 h) and then by AC status (yes/no). The primary outcome was all-cause inpatient mortality. Secondary outcomes included healthcare usage.ResultsOf the 1082516 patients admitted for NVUGIB, 553186 (51.1%) underwent EGD. The mean time to EGD was 52.8 h. Early (< 24 h from admission) EGD was associated with significantly decreased mortality, less frequent intensive care unit admission, shorter length of hospital stays, lower hospital costs, and an increased likelihood of discharge to home (all with P < 0.001). AC status was not associated with mortality among patients who underwent early EGD (aOR 0.88, P = 0.193). Male sex (OR 1.30) and Hispanic (OR 1.10) or Asian (aOR 1.38) race were also independent predictors of adverse hospitalization outcomes in NVUGIB.ConclusionBased on this large, nationwide study, early EGD in NVUGIB is associated with lower mortality and decreased healthcare usage, irrespective of AC status. These findings may help guide clinical management and would benefit from prospective validation.

Background: Yoga is an ancient wisdom that originated in India and encompasses eight limbs, including yama, niyama, asanas, pranayama, pratyahara, dharana, dhyana, and samadhi. Despite its holistic nature, many studies on yoga tend to focus solely on its physical aspects, breathing practices, and meditation, neglecting other essential components. To address this gap, a study was conducted to determine the perception and practice of all eight limbs of yoga among yoga teachers. Method: A self-designed questionnaire containing 28 items was used for assessing the knowledge, perception, and practice of the eight limbs of yoga among yoga teachers. A total of 37 yoga teachers participated in the study. Cross-tabulation was performed to analyze the data. Results: The majority of participants (>80%) in this study on the practice of astanga yoga reported that all limbs of yoga were essential in their practice. However, there were varying degrees of emphasis placed on each limb. Pranayama (91.9%) and asana (89.2%) were given the most emphasis, while niyama (75.7%), yama (73%), pratyahara (70.3%), dhyana (70.3%), and dharana (64.9%) were given slightly less emphasis. Interestingly, those with more experience placed greater emphasis on various aspects of yoga. Conclusion: Practitioners should embrace all eight limbs of yoga when introducing it to new populations to increase access to yoga. This will help promote the benefits of yoga and make it more accessible to those who may benefit from it. Health professionals should have a comprehensive understanding of the holistic practice of yoga, including its ethics, postures, breath, mindfulness, and meditation, to promote its maximum benefits and avoid potentially harmful practices.

Huntington's disease (HD) is caused by expanded CAG repeats in the huntingtin gene (HTT) resulting in expression of mutant HTT proteins (mHTT) with extended polyglutamine tracts, including in striatal neurons and astrocytes. It is unknown whether pathophysiology in vivo can be attenuated by lowering mHTT in either cell type throughout the brain, and the relative contributions of neurons and astrocytes to HD remain undefined. We use zinc finger protein (ZFP) transcriptional repressors to cell-selectively lower mHTT in vivo. Astrocytes display loss of essential functions such as cholesterol metabolism that are partly driven by greater neuronal dysfunctions, which encompass neuromodulation, synaptic, and intracellular signaling pathways. Using transcriptomics, proteomics, electrophysiology, and behavior, we dissect neuronal and astrocytic contributions to HD pathophysiology. Remarkably, brain-wide delivery of neuronal ZFPs results in strong mHTT lowering, rescue of HD-associated behavioral and molecular phenotypes, and significant extension of lifespan, findings that support translational development.

Gamma-aminobutyric acid (GABA)ergic neurons, the most abundant inhibitory neurons in the human brain, have been found to be reduced in many neurological disorders, including Alzheimer’s disease and Alzheimer’s disease-related dementia. Our previous study identified the upregulation of microRNA-502-3p (miR-502-3p) and downregulation of GABA type A receptor subunit α-1 in Alzheimer’s disease synapses. This study investigated a new molecular relationship between miR-502-3p and GABAergic synapse function. In vitro studies were performed using the mouse hippocampal neuronal cell line HT22 and miR-502-3p agomiRs and antagomiRs. In silico analysis identified multiple binding sites of miR-502-3p at GABA type A receptor subunit α-1 mRNA. Luciferase assay confirmed that miR-502-3p targets the GABA type A receptor subunit α-1 gene and suppresses the luciferase activity. Furthermore, quantitative reverse transcription-polymerase chain reaction, miRNA in situ hybridization, immunoblotting, and immunostaining analysis confirmed that overexpression of miR-502-3p reduced the GABA type A receptor subunit α-1 level, while suppression of miR-502-3p increased the level of GABA type A receptor subunit α-1 protein. Notably, as a result of the overexpression of miR-502-3p, cell viability was found to be reduced, and the population of necrotic cells was found to be increased. The whole cell patch-clamp analysis of human-GABA receptor A-α1/β3/γ2L human embryonic kidney (HEK) recombinant cell line also showed that overexpression of miR-502-3p reduced the GABA current and overall GABA function, suggesting a negative correlation between miR-502-3p levels and GABAergic synapse function. Additionally, the levels of proteins associated with Alzheimer’s disease were high with miR-502-3p overexpression and reduced with miR-502-3p suppression. The present study provides insight into the molecular mechanism of regulation of GABAergic synapses by miR-502-3p. We propose that micro-RNA, in particular miR-502-3p, could be a potential therapeutic target to modulate GABAergic synapse function in neurological disorders, including Alzheimer’s disease and Alzheimer’s disease-related dementia.

Professionalism and communication were formally introduced in India's Competency-Based Curriculum (CBC) as part of the five roles of an Indian medical graduate and 10 core competencies in the Bachelor of Science Nursing program. It may be challenging to teach the complexity of clinical medical ethics to undergraduate students at a young age in the absence of direct patient interaction. Trigger films (TFs) are brief (3-10 min) clips that have been used in the West to provoke debate, promote reflection, and assist trainees in dealing with ethical dilemmas. The aim of this study was to determine whether TFs can be used to teach professionalism and ethics to undergraduate medical and nursing students as an innovative and interesting tool and to see whether this results in any changes in knowledge. A 2-h module supported by an introductory PowerPoint presentation and using four TFs on the four pillars of ethics (beneficence, nonmaleficence, autonomy, and justice) was developed and piloted in the foundation course for the new cohort of medical and nursing students. Quantitative, open-ended feedback was taken from learners after module delivery, and knowledge was assessed with a retrospective pre-post questionnaire. The majority of students found TFs an innovative and interesting tool to teach medical ethics. There was a gain in knowledge of autonomy (52%), beneficence (48%), nonmaleficence (46%), and justice (38%). TFs can be effective tools to impart core competencies in ethics and professionalism to both nursing and medical students in the new CBC.

Enhanced myometrial vascularity (EMV) is a rare disorder associated with various obstetrical and gynecological pathologies. We describe a unique case of interstitial ectopic pregnancy associated with EMV successfully managed with bilateral uterine artery embolization.

The current study examined the impact of religious beliefs and practices implemented by Muslims in Saudi Arabia on their ability to cope with stress, social isolation, uncertainty, and providing social support during the COVID-19 pandemic. The study included a questionnaire with a sample of 1,511 respondents. The relationship of demographic variables and religious beliefs and practices of respondents was analyzed using a correlation table. It was found that gender and civil status positively correlated with religious beliefs and practices. Whereas nationality, location, employment status, and monthly income had no significant impact on religious beliefs and practices. The study revealed a positive association of religious beliefs and practices on an individual's ability to cope with stress, social isolation, and uncertainty during the COVID-19 pandemic. Some interventions, such as using social media, helped them cope as well.

ObjectiveTo document the recovery of vascular services in Europe following the first COVID-19 pandemic peak.MethodsAn online structured vascular service survey with repeated data entry between 23 March and 9 August 2020 was carried out. Unit level data were collected using repeated questionnaires addressing modifications to vascular services during the first peak (March - May 2020, "period 1"), and then again between May and June ("period 2") and June and July 2020 ("period 3"). The duration of each period was similar. From 2 June, as reductions in cases began to be reported, centres were first asked if they were in a region still affected by rising cases, or if they had passed the peak of the first wave. These centres were asked additional questions about adaptations made to their standard pathways to permit elective surgery to resume.ResultsThe impact of the pandemic continued to be felt well after countries' first peak was thought to have passed in 2020. Aneurysm screening had not returned to normal in 21.7% of centres. Carotid surgery was still offered on a case by case basis in 33.8% of centres, and only 52.9% of centres had returned to their normal aneurysm threshold for surgery. Half of centres (49.4%) believed their management of lower limb ischaemia continued to be negatively affected by the pandemic. Reduced operating theatre capacity continued in 45.5% of centres. Twenty per cent of responding centres documented a backlog of at least 20 aortic repairs. At least one negative swab and 14 days of isolation were the most common strategies used for permitting safe elective surgery to recommence.ConclusionCentres reported a broad return of services approaching pre-pandemic "normal" by July 2020. Many introduced protocols to manage peri-operative COVID-19 risk. Backlogs in cases were reported for all major vascular surgeries.

Abstract Introduction The current study, focusing on a significant US (United States) colorectal cancer (CRC) burden, employs machine learning for predicting future rates among young population. Methods CDC WONDER data from 1999 to 2022 was analyzed for CRC‐related mortality in patients younger than 56 years. Temporal trends in age‐adjusted mortality rates (AAMRs) were assessed via Joinpoint software. Future mortality rates were forecasted using an optimal Autoregressive Integrated Moving Average (ARIMA) model. Results From 1999 to 2022, we observed 150,908 deaths with CRC listed as the underlying cause, predominantly in males, with an upward trend in AAMR. The ARIMA model projects an increase in CRC mortality by 2035, estimating an average annual percent change (AAPC) of 1.3% overall, 1% for females, and 1.5% for males. Conclusion Our study findings emphasize the need for more robust preventive measures to reduce future CRC mortality among younger population. These results have significant implications for public health policies, particularly for males under 56, and underscore the importance of early screening and lifestyle modifications.

Astrocytes respond to neurotransmitters and neuromodulators using G-protein-coupled receptors (GPCRs) to mediate physiological responses. Despite their importance, there has been no method to genetically, specifically, and effectively attenuate astrocyte Gq GPCR pathways to explore consequences of this prevalent signaling mechanism in vivo. We report a 122-residue inhibitory peptide from β-adrenergic receptor kinase 1 (iβARK; and inactive D110A control) to attenuate astrocyte Gq GPCR signaling. iβARK significantly attenuated Gq GPCR Ca2+ signaling in brain slices and, in vivo, altered behavioral responses, spared other GPCR responses, and did not alter astrocyte spontaneous Ca2+ signals, morphology, electrophysiological properties, or gene expression in the striatum. Furthermore, brain-wide attenuation of astrocyte Gq GPCR signaling with iβARK using PHP.eB adeno-associated viruses (AAVs), when combined with c-Fos mapping, suggested nuclei-specific contributions to behavioral adaptation and spatial memory. iβARK extends the toolkit needed to explore functions of astrocyte Gq GPCR signaling within neural circuits in vivo.

Abstract The success of the business directly contributes towards the growth of the nation. Hence it is important to evaluate and predict whether the business will be successful or not. In this study, we use the company’s dataset which contains information from startups to Fortune 1000 companies to create a machine learning model for predicting business success. The main challenge of business success prediction is twofold: (1) Identifying variables for defining business success; (2) Feature selection and feature engineering based on Investor-Business-Market interrelation to provide a successful outcome of the predictive modeling. Many studies have been carried out using only the available features to predict business success, however, there is still a challenge to identify the most important features in different business angles and their interrelation with business success. Motivated by the above challenge, we propose a new approach by defining a new business target based on the definition of business success used in this study and develop additional features by carrying out statistical analysis on the training data which highlights the importance of investments, business, and market features in forecasting business success instead of using only the available features for modeling. Ensemble machine learning methods as well as existing supervised learning methods were applied to predict business success. The results demonstrated a significant improvement in the overall accuracy and AUC score using ensemble methods. By adding new features related to the Investor-Business-Market entity demonstrated good performance in predicting business success and proved how important it is to identify significant relationships between these features to cover different business angles when predicting business success. Graphical Abstract

Wireless Sensor Networks (WSNs) are crucial in various fields including Health Care Monitoring, Battlefield Surveillance, and Smart Agriculture. However, WSNs are susceptible to malicious attacks due to the massive quantity of sensors within them. Hence, there is a demand for a trust evaluation framework within WSNs to function as a secure system, to identify and isolate malicious or faulty sensor nodes. This information can be leveraged by neighboring nodes, to prevent collaboration in tasks like data aggregation and forwarding. While numerous trust frameworks have been suggested in the literature to assess trust scores and examine the reliability of sensors through direct and indirect communications, implementing these trust evaluation criteria is challenging due to the intricate nature of the trust evaluation process and the limited availability of datasets. This research conducts a novel comparative analysis of three trust management models: “Lightweight Trust Management based on Bayesian and Entropy (LTMBE)”, “Beta-based Trust and Reputation Evaluation System (BTRES)”, and “Lightweight and Dependable Trust System (LDTS)”. To assess the practicality of these trust management models, we compare and examine their performance in multiple scenarios. Additionally, we assess and compare how well the trust management approaches perform in response to two significant cyber-attacks. Based on the experimental comparative analysis, it can be inferred that the LTMBE model is optimal for WSN applications emphasizing high energy efficiency, while the BTRES model is most suitable for WSN applications prioritizing critical security measures. The conducted empirical comparative analysis can act as a benchmark for upcoming research on trust evaluation frameworks for WSNs.

BackgroundPerturbation-based training has shown to be effective in reducing fall-risk in people with chronic stroke (PwCS). However, most evidence comes from treadmill-based stance studies, with a lack of research focusing on training overground perturbed walking and exploring the relative contributions of the paretic and non-paretic limbs. This study thus examined whether PwCS could acquire motor adaptation and demonstrate immediate retention of fall-resisting skills following bilateral overground gait-slip perturbation training.Methods65 PwCS were randomly assigned to either (i) a training group, that received blocks of eight non-paretic (NP-S1 to NP-S8) and paretic (P-S1 to P-S8) overground slips during walking followed by a mixed block (seven non-paretic and paretic slips each interspersed with unperturbed walking trials) (NP-S9/P-S9 to NP-S15/P-S15) or (ii) a control group, that received a single non-paretic and paretic slip in random order. The assessor and training personnel were not blinded. Immediate retention was tested for the training group after a 30-minute rest break. Primary outcomes included laboratory-induced slip outcomes (falls and balance loss) and center of mass (CoM) state stability. Secondary outcomes to understand kinematic contributors to stability included recovery strategies, limb kinematics, slipping kinematics, and recovery stride length.ResultsPwCS within the training group showed reduced falls (p 0.01). On comparing the first and last training trial (S1 vs. S15), post-slip stability improved on both non-paretic and paretic slips, however, pre-slip stability improved only on the non-paretic slip (p

In this paper, we present the design, implementation, and evaluation of a secure sensing data processing and logging system. The system is inspired and enabled by the blockchain technology. In this system, a public blockchain is used as immutable datastore to log the most critical data needed to secure the system. Furthermore, several innovative blockchain-inspired mechanisms have been incorporated into the system to provide additional security for the system’s operations. The first priority in securing sensing data processing and logging is admission control, i.e., only legitimate sensing data are accepted for processing and logging. This is achieved via a sensor identification and authentication mechanism. The second priority is to ensure that the logged data remain intact overtime. This is achieved by storing a small amount of data condensed from the raw sensing data on a public blockchain. A Merkel-tree based mechanism is devised to link the raw sensing data stored off-chain to the condensed data placed on public blockchain. This mechanism passes the data immutability property of a public blockchain to the raw sensing data stored off-chain. Third, the raw sensing data stored off-chain are secured with a self-protection mechanism where the raw sensing data are grouped into chained blocks with a moderate amount of proof-of-work. This scheme prevents an adversary from making arbitrary changes to the logged data within a short period of time. Fourth, mechanisms are developed to facilitate the search of the condensed data placed on the public blockchain and the verification of the raw sensing data using the condensed data placed on the public blockchain. The system is implemented in Python except the graphical user interface, which is developed using C#. The functionality and feasibility of the system have been evaluated locally and with two public blockchain systems, one is the IOTA Shimmer test network, and the other is Ethereum.

We have evaluated the effectiveness of compatibilizers in blends and composites produced using a solvent manufacturing process. The compatibilizers were two different types of polyethylene (linear low-density and high-density) grafted with maleic anhydride (MAH) and a highly functionalized, epoxy-based compatibilizer with the tradename Joncryl. The selected material combinations were an ultra-high-molecular-weight polyethylene (UHMWPE) with MAH-based materials as compatibilizers and a polyphenylene sulfide plus polytetrafluoroethylene (PPS-PTFE) polymer blend with an epoxy-based compatibilizer. The findings revealed that while the compatibilizers consistently enhanced the properties, such as the impact strength and hardness of PPS-based compositions, their utility is constrained to less complex compositions, such as fibrous-reinforced PPS or PPS-PTFE polymer blends. For fibrous-reinforced PPS-PTFE composites, the improvement in performance does not justify the presence of compatibilizers. In contrast, for UHMWPE compositions, compatibilizers demonstrated negligible or even detrimental effects, particularly in reinforced UHMWPE. Overall, the epoxy-based compatibilizer Joncryl stands out as the only effective option for enhancing mechanical performance. Thermal and chemical characterization indicated that the compatibilizers function as chain extenders and enhance the fiber–matrix interface in PPS-based compositions, while they remain inactive in UHMWPE-based compositions. Ultimately, the incompatibility of the compatibilizers with certain aspects of the manufacturing method and the inconsistent integration with the polymer are the main reasons for their ineffectiveness in UHMWPE compositions.

Hyperactivity and disturbances of attention are common behavioral disorders whose underlying cellular and neural circuit causes are not understood. We report the discovery that striatal astrocytes drive such phenotypes through a hitherto unknown synaptic mechanism. We found that striatal medium spiny neurons (MSNs) triggered astrocyte signaling via γ-aminobutyric acid B (GABAB) receptors. Selective chemogenetic activation of this pathway in striatal astrocytes in vivo resulted in acute behavioral hyperactivity and disrupted attention. Such responses also resulted in upregulation of the synaptogenic cue thrombospondin-1 (TSP1) in astrocytes, increased excitatory synapses, enhanced corticostriatal synaptic transmission, and increased MSN action potential firing in vivo. All of these changes were reversed by blocking TSP1 effects. Our data identify a form of bidirectional neuron-astrocyte communication and demonstrate that acute reactivation of a single latent astrocyte synaptogenic cue alters striatal circuits controlling behavior, revealing astrocytes and the TSP1 pathway as therapeutic targets in hyperactivity, attention deficit, and related psychiatric disorders.

Channelrhodopsin2 (ChR2) optogenetic excitation is widely used to study neurons, astrocytes, and circuits. Using complementary approaches in situ and in vivo, we found that ChR2 stimulation leads to significant transient elevation of extracellular potassium ions by ∼5 mM. Such elevations were detected in ChR2-expressing mice, following local in vivo expression of ChR2(H134R) with adeno-associated viruses (AAVs), in different brain areas and when ChR2 was expressed in neurons or astrocytes. In particular, ChR2-mediated excitation of striatal astrocytes was sufficient to increase medium spiny neuron (MSN) excitability and immediate early gene expression. The effects on MSN excitability were recapitulated in silico with a computational MSN model and detected in vivo as increased action potential firing in awake, behaving mice. We show that transient, physiologically consequential increases in extracellular potassium ions accompany ChR2 optogenetic excitation. This coincidental effect may be important to consider during astrocyte studies employing ChR2 to interrogate neural circuits and animal behavior.

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