Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploring Ligand Binding to Calcitonin Gene-Related Peptide Receptors

Class B1 G protein-coupled receptors (GPCRs) are important targets for many diseases, including cancer, diabetes, and heart disease. All the approved drugs for this receptor family are peptides that mimic the endogenous activating hormones. An understanding of how agonists bind and activate class B1 GPCRs is fundamental for the development of therapeutic small molecules. We combined supervised molecular dynamics (SuMD) and classic molecular dynamics (cMD) simulations to study the binding of the calcitonin gene-related peptide (CGRP) to the CGRP receptor (CGRPR). We also evaluated the association and dissociation of the antagonist telcagepant from the extracellular domain (ECD) of CGRPR and the water network perturbation upon binding. This study, which represents the first example of dynamic docking of a class B1 GPCR peptide, delivers insights on several aspects of ligand binding to CGRPR, expanding understanding of the role of the ECD and the receptor-activity modifying protein 1 (RAMP1) on agonist selectivity.
Efficiency Assessment of BLDC type Solar Water Pumping System fed by Photovoltaic and Grid

This paper optimizes the operation of Brushless DC motor (BLDC) operated solar water pumping system. The proposed system is assisted with single phase supply to ensure the system operation in the high efficiency zone which is governed by the pump. In conventional systems consisting of either AC supply or PV leads to low reliable and inconsistent operation of the motor for water pumping applications. The proposed system consists of Power Factor Correction (PFC) converter for grid input, DC-DC converter as MPPT channel for PV, and three phase inverter to control BLDC type motor-pump set. The entire system is equipped with the control strategy which has multiple modes of operation based on availability of sources. The modelling of all the power converters and their compensator design are provided in this paper. Performance of the system is investigated using developed test-bed with water-pump, tank, power conditioning unit, solar PV simulator, and grid supply. The control strategy and overall system efficiency is verified by simulation and experimental results.
Comparative effects of dietary functional nutrients on growth performance, meat quality, immune responses, and stress biomarkers in broiler chickens raised under heat stress conditions

Objective The objective of the present study was to investigate the comparative effects of dietary functional nutrients including glutamine (Gln), chromium picolinate (Cr picolinate), vitamin C (Vit C), betaine (Bet), and taurine (Tau) on growth performance, meat quality, immune responses, and stress biomarkers in broiler chickens raised under heat stress conditions. Methods A total of 420 21-d-old Ross 308 male broiler chickens (initial body weight = 866±61.9 g) were randomly allotted to 1 of 7 treatment groups with 6 replicates. One group was kept under thermoneutral conditions and was fed a basal diet (PC, positive control). Other 6 groups were exposed to a cyclic heat stress condition. One of the 6 groups was fed the basal diet (NC, negative control), whereas 5 other groups were fed the basal diet supplemented with 0.5% Gln, 500 ppb Cr picolinate, 250 mg/kg Vit C, 0.2% Bet, or 1.0% Tau. The diets and water were provided ad libitum for 21 d. Results Broiler chickens in NC group had decreased (p<0.05) growth performance and immune responses measured based on cutaneous basophil hypersensitivity (CBH), but increased (p<0.05) stress responses measured based on feather corticosterone concentrations and blood heterophil:lymphocyte than those in PC group. However, none of dietary functional nutrients had a positive effect on growth performance of broiler chickens. Dietary supplementation of 250 mg/kg Vit C improved (p<0.05) CBH responses of broiler chickens, but other functional nutrients had no such an improvement in CBH responses. All functional nutrients decreased (p<0.05) stress responses of broiler chickens. Conclusion Functional nutrients including Gln, Cr picolinate, Vit C, Bet, and Tau at the supplemental levels used in this study decrease stress responses of broiler chickens to a relatively similar extent. However, this reduction in stress responses could not fully ameliorate decreased productive performance of broiler chickens raised under the current heat stress conditions.
A Multicenter Analysis of the Outcome of Cancer Patients with Neutropenia and COVID-19 Optionally Treated with Granulocyte-Colony Stimulating Factor (G-CSF): A Comparative Analysis

Simple Summary Infections with COVID-19 in neutropenic cancer patients are related to poor outcomes. A G-CSF treatment used in neutropenic cancer with SARS-CoV-2 infections is related to a higher rate of respiratory failure according to progressive and growing evidence. In this small retrospective non-randomized study, we found an association between G-CSF treatment and the parameters predisposing for worse infections with COVID-19 and neutropenia compared with patients not treated with G-CSF. We also found that the number of days on G-CSF treatment was related to a higher risk of mortality in a multivariable analysis among patients treated with G-CSF. Abstract Background: Approximately 15% of patients infected by SARS-CoV-2 develop a distress syndrome secondary to a host hyperinflammatory response induced by a cytokine storm. Myelosuppression is associated with a higher risk of infections and mortality. There are data to support methods of management for neutropenia and COVID-19. We present a multicenter experience during the first COVID-19 outbreak in neutropenic cancer patients infected by SARS-CoV-2. Methods: Clinical retrospective data were collected from neutropenic cancer patients with COVID-19. Comorbidities, tumor type, stage, treatment, neutropenia severity, G-CSF, COVID-19 parameters, and mortality were analyzed. A bivariate analysis of the impact on mortality was carried out. Additionally, we performed a multivariable logistic regression to predict respiratory failure and death. Results: Among the 943 cancer patients screened, 83 patients (11.3%) simultaneously had neutropenia and an infection with COVID-19. The lungs (26%) and breasts (22%) were the primary locations affected, and most patients had advanced disease (67%). In the logistic model, as adjusted covariates, sex, age, treatment (palliative vs. curative), tumor type, and the lowest level of neutrophils were used. A significant effect was obtained for the number of days of G-CSF treatment (OR = 1.4, 95% CI [1,1,03,92], p-value = 0.01). Conclusions: Our findings suggest that a prolonged G-CSF treatment could be disadvantageous for these cancer patients with infections by COVID-19, with a higher probability of worse outcome.
A Review of Shannon and Differential Entropy Rate Estimation

In this paper, we present a review of Shannon and differential entropy rate estimation techniques. Entropy rate, which measures the average information gain from a stochastic process, is a measure of uncertainty and complexity of a stochastic process. We discuss the estimation of entropy rate from empirical data, and review both parametric and non-parametric techniques. We look at many different assumptions on properties of the processes for parametric processes, in particular focussing on Markov and Gaussian assumptions. Non-parametric estimation relies on limit theorems which involve the entropy rate from observations, and to discuss these, we introduce some theory and the practical implementations of estimators of this type.
Drug Targeting of Inflammatory Bowel Diseases by Biomolecules

Inflammatory bowel disease (IBD) is a group of disabling, destructive and incurable immune-mediated inflammatory diseases comprising Crohn’s disease (CD) and ulcerative colitis (UC), disorders that are highly prevalent worldwide and demand a large investment in healthcare. A persistent inflammatory state enables the dysfunction and destruction of healthy tissue, hindering the initiation and endurance of wound healing. Current treatments are ineffective at counteracting disease progression. Further, increased risk of serious side effects, other comorbidities and/or opportunistic infections highlight the need for effective treatment options. Gut microbiota, the key to preserving a healthy state, may, alternatively, increase a patient’s susceptibility to IBD onset and development given a relevant bacterial dysbiosis. Hence, the main goal of this review is to showcase the main conventional and emerging therapies for IBD, including microbiota-inspired untargeted and targeted approaches (such as phage therapy) to infection control. Special recognition is given to existing targeted strategies with biologics (via monoclonal antibodies, small molecules and nucleic acids) and stimuli-responsive (pH-, enzyme- and reactive oxygen species-triggered release), polymer-based nanomedicine that is specifically directed towards the regulation of inflammation overload (with some nanosystems additionally functionalized with carbohydrates or peptides directed towards M1-macrophages). The overall goal is to restore gut balance and decrease IBD’s societal impact.
The Effects of City-County Mergers on Urban Energy Intensity: Empirical Evidence from Chinese Cities

The adjustment of administrative division is one of the powerful tools used to promote urbanization by the Chinese government in recent decades, and there is little literature to discuss whether the government-led expansion of urban space through city-county mergers can bring about a decline in urban energy intensity. With the multi-period difference-in-differences (DID) method and comprehensive urban datasets, this research investigates the urban energy intensity results of the city-county mergers policy experiment in China from 2000 to 2017. We present evidence that city-county mergers are indeed beneficial in reducing urban energy intensity, and that the energy-saving effect of the policy only starts to become significant in the third year after implementation. We also further adopt a series of robustness tests, such as the counterfactual test, placebo tests and PSM-DID tests to find if this effect still exists. The mechanism test with mediating effects indicates they are potential contributors to the positive effects of mergers with moderate fiscal centralization, population agglomeration and regional integration. We further explore positive effects of mergers, relying on the scientifically design official appraisal system and improve government efficiency.
COVID-19 Vaccine Literacy of Family Carers for Their Older Parents in Japan

In super-ageing Japan, COVID-19 vaccinations were starting to reach older people as of June 2021, which raises the issue of vaccine literacy. This study focuses on family members who work and also care for their older parents, as they are at risk of COVID-19 and also risk transmitting COVID-19 to the parents they care for and potentially influencing their parents’ vaccine uptake. Such family carers are central to the approach in Japan to achieving a sustainable and resilient society in response to ageing. Contrasting family carers’ COVID-19 vaccine literacy with their overall health literacy provides insights into their preparedness for COVID-19 vaccinations. The purpose of this study is to understand how vaccine literacy, compared to health literacy, varies across family carers and the sources of information they use. Through a cross-sectional online survey, family carers’ vaccine literacy, health literacy and their sources of information, including mass media, social media, health and care professionals, family, colleagues, friends, and others, were assessed. The participants’ (n = 292) mean age was 53, with 44% women, and an average of 8.3 h per week caring for their parents. Notwithstanding the increased risks from COVID-19 with age, COVID-19 vaccine literacy relative to health literacy for older family carers is lower on average, higher with increased provision of care, and more variable, resulting in a substantial proportion of older family carers with relatively low vaccine literacy. At this stage of vaccine rollout in Japan, family carers’ sources of information to inform COVID-19 vaccine literacy is distinct, including more national and local mass media versus less health and care professionals and informal networks, which indicates the importance of tailored health communication strategies to enhance vaccine literacy
Expanding the analysis of mechanisms of action in behavioral interventions: cognitive change versus cognitive activation

Abstract Objective To understand the mechanisms of action underlying behavioral interventions, researchers typically examine whether the treatment changes cognitions and whether changes in cognition predict behavior (cognitive change). This current research explores an alternative mechanism whereby the intervention increases the impact of pre-existing cognitions on behavior (cognitive activation). We tested whether cognitive change or cognitive activation explains the impact of cigarette pack messages on smoking restraint. Design The research comprised a validation experiment (N = 135) and a 4-week RCT (N = 719) with smokers. Main Outcome Measures At both baseline and follow-up of the RCT, smokers self-reported threat appraisals, coping appraisals, and smoking restraint. Results Intervention messages heightened the accessibility of threat appraisals compared to control messages (validation experiment). In the RCT, smoking restraint increased among intervention participants but not controls. Trial arm showed no corresponding change in threat or coping appraisals. However, trial arm interacted with baseline health cognitions such that synergies between threat appraisal components, and between threat appraisals and coping appraisals, predicted smoking restraint for intervention participants but not for controls. Conclusion Our findings support a cognitive activation process whereby health messages on cigarette packs increase the impact of pre-existing threat appraisals on smoking restraint.
Secondary Analysis of a Study on Exercise Therapy in Hip Osteoarthritis: Follow-Up Data on Pain and Physical Functioning

We evaluated the short- and longer-term effects of exercise therapy in hip osteoarthritis patients (OA) at baseline, three, six, and 12 months in a randomized setting, followed by a non-randomized setting. The primary randomized intervention (E = exercise, P = placebo–ultrasound, C = control) was followed by a voluntary three-month exercise therapy for P and C (renamed P-E, C-E). Participants randomized to E were not offered treatment again (E-C). Effect sizes (ES; 95% CI) were calculated for within-group effects across time for bodily pain (SF-36) and WOMAC pain, function, and stiffness. ANCOVAs of post-treatment scores were used for group comparison after the group-specific exercise intervention phase. Exercise adherence was assessed and related to post-treatment scores of clinical outcomes. Data of 115 participants of the RCT eligible for follow-up and completing exercise therapy were included into our analyses. Small to medium beneficial long-term effects of cumulative interventional effects, including exercise training, persisted in all groups. Group E-C (n = 49) showed significant 12 months vs. baseline within-group ES in all outcomes (ES 0.39–0.59) except stiffness. Findings were less prominent for exercise therapy in a non-randomized setting (C-E, P-E, both n = 33). Differences are partially explained by adherence rates, highlighting the relevance of therapy compliance strategies. Short-term between-group differences (ANCOVAs) only showed statistically significant differences for WOMAC function between P-E and E-C in favor of E-C (6.4 (95% CI 1.6–11.2; score range 0–100)).
MicroRNAs and Stem-like Properties: The Complex Regulation Underlying Stemness Maintenance and Cancer Development

Embryonic stem cells (ESCs) have the extraordinary properties to indefinitely proliferate and self-renew in culture to produce different cell progeny through differentiation. This latter process recapitulates embryonic development and requires rounds of the epithelial–mesenchymal transition (EMT). EMT is characterized by the loss of the epithelial features and the acquisition of the typical phenotype of the mesenchymal cells. In pathological conditions, EMT can confer stemness or stem-like phenotypes, playing a role in the tumorigenic process. Cancer stem cells (CSCs) represent a subpopulation, found in the tumor tissues, with stem-like properties such as uncontrolled proliferation, self-renewal, and ability to differentiate into different cell types. ESCs and CSCs share numerous features (pluripotency, self-renewal, expression of stemness genes, and acquisition of epithelial–mesenchymal features), and most of them are under the control of microRNAs (miRNAs). These small molecules have relevant roles during both embryogenesis and cancer development. The aim of this review was to recapitulate molecular mechanisms shared by ESCs and CSCs, with a special focus on the recently identified classes of microRNAs (noncanonical miRNAs, mirtrons, isomiRs, and competitive endogenous miRNAs) and their complex functions during embryogenesis and cancer development.
Tele-Neuropsychological Assessment of Alzheimer’s Disease

Background: Because of the new pandemic caused by the novel coronavirus disease (COVID-19), the demand for telemedicine and telemonitoring solutions has been exponentially raised. Because of its special advantage to treat patients in an emergency without physical presence at a hospital via video conferencing, telemedicine has been used to overcome distance barriers and to improve access to special domains like neurology. In these pandemic times, telemedicine has been also employed as a support for the diagnosis and treatment of adult-onset dementia disorders including Alzheimer’s disease. Objective: In this study, we carried out a systematic literature analysis to clarify if the neuropsychological tests traditionally employed in face-to-face (FTF) contexts are reliable via telemedicine. Methods: A systematic literature search for the past 20 years (2001–2020) was carried out through the medical databases PubMed (Medline) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). The quality assessment was conducted by adopting the Newcastle Ottawa Scale (NOS) and only studies with a NOS ≥ 7 were included in this review. Results: The Mini-Mental State Examination (MMSE) results do not differ when tests are administered in the traditional FTF modality or by videoconference, and only negligible minor changes in the scoring system were noticeable. Other neuropsychological tests used to support the diagnosis of AD and dementia such as the Token Test, the Comprehension of Words and Phrases (ACWP), the Controlled Oral Word Association Test showed high reliability between the two modalities considered. No differences in the reliability concerning the living setting or education of the subjects were reported. Conclusions: The MMSE, which is the main screening test for dementia, can be administered via telemedicine with minor adaptation in the scoring system. Telemedicine use for other neuropsychological tests also resulted in general reliability and enough accuracy. Cognitive assessment by videoconference is accepted and appreciated and therefore can be used for dementia diagnosis in case of difficulties to performing FTF assessments. This approach can be useful given a personalized medicine approach for the treatment of adult-onset dementia disorders.
Role of Lung Ultrasound in Predicting Clinical Severity and Fatality in COVID-19 Pneumonia

Background: Lung ultrasound (LUS) is a useful imaging method for identifying COVID-19 pneumonia. The aim of this study was to explore the role of LUS in predicting the severity of the disease and fatality in patients with COVID-19. Methods: This was a single-center, follow-up study, conducted from 1 November 2020, to 22 March 2021. The LUS protocol was based on the assessment of 14 lung zones with a total score up to 42, which was compared to the disease severity and fatality. Results: A total of 133 patients with COVID-19 pneumonia confirmed by RT-PCR were enrolled, with a median time from hospital admission to lung ultrasound of one day. The LUS score was correlated with clinical severity at hospital admission (Spearman’s rho 0.40, 95% CI 0.24 to 0.53, p < 0.001). Patients with higher LUS scores were experiencing greater disease severity; a high flow nasal cannula had an odds ratio of 1.43 (5% CI 1.17–1.74) in patients with LUS score > 29; the same score also predicted the need for mechanical ventilation (1.25, [1.07–1.48]). An LUS score > 30 (1.41 [1.18–1.68]) and age over 68 (1.26 [1.11–1.43]) were significant predictors of fatality. Conclusions: LUS at hospital admission is shown to have a high predictive power of the severity and fatality of COVID-19 pneumonia.
Associations between Perceptions and Measures of Weather and Walking, United States—2015

Introduction: Weather can be a barrier to walking. Understanding how perceptions of weather as a barrier and measured temperature are associated with walking can inform monitoring and promotion strategies. The objective of this study is to examine the association between perceptions of weather as a barrier to walking and measured weather with the volume of leisure and transportation walking. Methods: The 2015 National Health Interview Survey (NHIS) assessed participation in and volume of walking (transportation, leisure) in the past week and frequency of reporting weather as a barrier to walking. Data were collected over the entire year. In 2019, we merged month-specific temperature data from the PRISM climate group with individual NHIS records. We examined associations using logistic (participation) and linear regression models (volume). Results: Participation in walking increased as frequency of reporting weather as a barrier to walking decreased, from ‘almost always’ (transportation: 23%, leisure: 42%) to ‘a little of the time’ (transportation: 40%, leisure: 67%). Among adults reporting walking, walking volume increased as frequency of reporting weather as a barrier decreased from ‘almost always’ (transportation: 51 min/week, leisure: 64 min/week) to ‘never’ (transportation: 69 min/week, leisure: 98 min/week). Month-specific temperature was significantly associated with leisure walking with lower participation at the lowest and highest temperature quintiles, although the strength of the association differed by frequency of reporting weather as a barrier. Conclusions: In general, prevalence and volume of leisure and transportation walking decreased as the perception of weather as a barrier increased. Low and high temperature conditions were also associated with leisure walking participation, particularly among adults with increased perceptions of weather as a barrier. Our findings highlight the importance of including strategies to help adults overcome perceived and actual weather-related barriers in walking promotion efforts.