Miracle-dz/UniFAR-FTUs huggingface dataset:
Situating Meditation Apps Within the Ecosystem of Meditation Practice: Population-Based Survey Study

Background Meditation apps have the potential to increase access to evidence-based strategies to promote mental health. However, it is currently unclear how meditation apps are situated within the broader landscape of meditation practice and what factors may influence engagement with them. Objective This study aimed to clarify the prevalence and correlates of meditation app use in a population-based sample of individuals with lifetime exposure to meditation in the United States. In addition, we sought to identify the concerns and desired features of meditation apps among those with lifetime exposure to meditation. Methods A total of 953 participants completed an initial screening survey. Of these 953 participants, 434 (45.5%) reported lifetime exposure to meditation and completed a follow-up survey (434/470, 92.3% response rate) assessing their meditation app use, anxiety, depression, loneliness, initial motivation for meditation, and concerns about and desired features of meditation apps. Results Almost half (434/953, 45.5%) of the participants who completed the screening survey reported lifetime exposure to meditation. Among those with lifetime exposure to meditation (ie, meditators), more than half (255/434, 58.8%) had used meditation apps at least once in their lives, and 21.7% (94/434) used meditation apps weekly or daily (ie, active users). Younger age, higher anxiety, and a mental health motivation for practicing meditation were associated with lifetime exposure to meditation apps. Among meditators, those with lifetime exposure to meditation apps were more likely to report concerns about apps, including concerns regarding the cost and effectiveness of apps, time required for use, technical issues with apps, and app user-friendliness. Meditators who used meditation apps weekly or daily (ie, active users) were younger, less likely to be men and non-Latinx White individuals and have lower income, and more likely to have an initial spiritual motivation for meditation. Active users reported more concerns regarding usability and technical problems and were less likely to report disinterest in apps. Headspace and Calm were the most frequently used apps. Tips and reminders for practice, encouragement of “mini” practices, and mental health content were the most desired features. Participants were less interested in social features (eg, the ability to communicate with other users or teachers). Conclusions Meditation apps are commonly used by meditators in the United States, with a higher use among certain demographic groups. Future studies may increase user engagement in meditation apps by addressing concerns (eg, cost and effectiveness) and incorporating desired features (eg, tips and reminders for practice).
Phenotypic screening using waveform analysis of synchronized calcium oscillations in primary cortical cultures

At present, in vitro phenotypic screening methods are widely used for drug discovery. In the field of epilepsy research, measurements of neuronal activities have been utilized for predicting efficacy of anti-epileptic drugs. Fluorescence measurements of calcium oscillations in neurons are commonly used for measurement of neuronal activities, and some anti-epileptic drugs have been evaluated using this assay technique. However, changes in waveforms were not quantified in previous reports. Here, we have developed a high-throughput screening system containing a new analysis method for quantifying waveforms, and our method has successfully enabled simultaneous measurement of calcium oscillations in a 96-well plate. Features of waveforms were extracted automatically and allowed the characterization of some anti-epileptic drugs using principal component analysis. Moreover, we have shown that trajectories in accordance with the concentrations of compounds in principal component analysis plots were unique to the mechanism of anti-epileptic drugs. We believe that an approach that focuses on the features of calcium oscillations will lead to better understanding of the characteristics of existing anti-epileptic drugs and allow to predict the mechanism of action of novel drug candidates.
Renal proximal tubule cells: power and finesse

The proximal tubule is the high-capacity reabsorptive powerhouse of the kidney. Two papers in recent issues of the JCI highlight mechanisms of more delicate effects of the proximal tubule. Yoon et al. demonstrated the intracellular mechanism by which parathyroid hormone (PTH) increases production of 1,25-vitamin D. Activation of PTH receptor 1/cAMP/PKA signaling inhibited salt-inducible kinase 2 (SIK2) and SIK3, which increased CYB27B1 transcription and 1,25-vitamin D production. Replication of these effects with small-molecule SIK inhibitors suggests possible therapeutic applications for patients with disorders characterized by 1,25-vitamin D deficiency. Zhou et al. discovered that proximal tubule glycolysis acts as a phosphate sensor that regulates fibroblast growth factor 23 production in bone. They described several kidney-specific metabolic modifications that enabled glycolysis to be deployed as a phosphate sensor. The provocative results raise intriguing questions with implications for patients with disorders of phosphate homeostasis, including chronic kidney disease.
Country of birth is associated with antiretroviral therapy choice in treatment-naive persons with HIV in France

Objectives: We aimed to describe factors associated with the choice of first antiretroviral therapy (ART) in persons with HIV (PWH) in France, included the country of birth, as well as the time to undetectable viral load and treatment discontinuation. Design: Observational study conducted from the national Dat’AIDS prospectively collected database. Methods: We included all adults who started their first ART between 01 January 2014 and 31 December 2020, with a pretherapeutic plasma viral load (pVL) at least 400 copies/ml. Univariable and multivariable logistic regressions were used to analyze PWH characteristics driving to an integrase strand transfer inhibitors (INSTI)-based first prescribed regimen. We also analyzed time to first line discontinuation, and to a first undetectable pVL, using Kaplan–Meier model. Results: We analyzed data from 9094 PWH: 45% MSM, 27% women and 27% heterosexual men; 48% born abroad; 4.7 and 2.8% with concomitant hepatitis B and tuberculosis, respectively. INSTIs were prescribed as first-line therapy in 50% of PWH, which increased over time. Native French PWH were more likely to receive an INSTI-based regimen than PWH born abroad [adjusted prevalence ratio 1.47, 95% confidence interval (CI) 1.33–1.60], as were high pVL at diagnosis, hepatitis B or concomitant tuberculosis. Time before discontinuation of the first ART and reaching a first undetectable pVL was not different according to the place of birth. Conclusion: Despite unrestricted access to INSTIs in France, independently from HIV disease parameters, PWH born abroad received INSTIs less frequently as a first regimen than those born in France. Qualitative data are needed to better understand physicians’ prescribing practices.
Reconstructed human intestinal comet assay, a possible alternative in vitro model for genotoxicity assessment

Abstract The aim of the present study was to evaluate the compatibility of reconstructed 3D human small intestinal microtissues to perform the in vitro comet assay. The comet assay is a common follow-up genotoxicity test to confirm or supplement other genotoxicity data. Technically, it can be performed utilizing a range of in vitro and in vivo assay systems. Here, we have developed a new reconstructed human intestinal comet (RICom) assay protocol for the assessment of orally ingested materials. The human intestine is a major site of food digestion and adsorption, first-pass metabolism as well as an early site of toxicant first contact and thus is a key site for evaluation. Reconstructed intestinal tissues were dosed with eight test chemicals: ethyl methanesulfonate (EMS), ethyl nitrosourea (ENU), phenformin hydrochloride (Phen HCl), benzo[a]pyrene (BaP), 1,2-dimethylhydrazine hydrochloride (DMH), potassium bromate (KBr), glycidamide (GA), and etoposide (Etop) over a span of 48 h. The RICom assay correctly identified the genotoxicity of EMS, ENU, KBr, and GA. Phen HCl, a known non-genotoxin, did not induce DNA damage in the 3D reconstructed intestinal tissues whilst showing high cytotoxicity as assessed by the assay. The 3D reconstructed intestinal tissues possess sufficient metabolic competency for the successful detection of genotoxicity elicited by BaP, without the use of an exogenous metabolic system. In contrast, DMH, a chemical that requires liver metabolism to exert genotoxicity, did not induce detectable DNA damage in the 3D reconstructed intestinal tissue system. The genotoxicity of Etop, which is dependent on cellular proliferation, was also undetectable. These results suggest the RICom assay protocol is a promising tool for further investigation and safety assessment of novel ingested materials. We recommend that further work will broaden the scope of the 3D reconstructed intestinal tissue comet assay and facilitate broader analyses of genotoxic compounds having more varied modes of actions.
Propensity score-matched analysis of physician-controlled wire-guided cannulation as an effective technique against difficult cannulation in endoscopic retrograde cholangiopancreatography: A retrospective study

Background Advanced endoscopic retrograde cholangiopancreatography (ERCP) cannulation strategies for difficult cases could replace conventional techniques, in which assistants control guidewires. We aimed to compare the safety and efficacy of a new salvage cannulation strategy, physician-controlled wire-guided cannulation (PCWGC), with those of a conventional strategy. Methods This retrospective study included patients with naïve papillae who underwent ERCP between January 2018 and December 2020. Patients, divided into two groups, received initial cannulation using a conventional catheter. After failed cannulation, the second attempt used PCWGC and double-guidewire technique (DGT) in the new and conventional strategy groups, respectively. Propensity score-matching (PSM) analysis compared outcomes between groups. Primary outcome included overall success rate, while secondary outcomes included cannulation time, adverse events, and cannulation difficulty subgroup analysis. Results The new strategy group comprised 255 (47.6%) of 536 patients who underwent ERCP. The total cannulation success rate was 98.4% (vs. 97.2%, p = 0.318), with similar post-ERCP pancreatitis (PEP) (1.8% vs. 2.4%, p = 0.64) rates. Following 1:1 PSM, 219/438 patients were allocated to both the conventional and new strategy groups, and 46 patients from the difficult cannulation subgroup were distributed evenly among groups. No difference in overall cannulation success rate existed between the groups before (97.2% vs. 98.4%) and after PSM (96.8% vs. 98.2%). The primary cannulation success rate was higher in the conventional strategy group, while the secondary cannulation success rate was higher in the new strategy group. However, the difficult cannulation subgroup PSM results showed that only the salvage cannulation success rate was significant (9/23, 39.1% vs. 18/23, 78.3%, p = 0.007). In the difficult cannulation subgroup, the salvage cannulation success rate for PCWGC was four times higher than DGT (95% confidence interval; 1.129–14.175), with no significant difference in PEP rate (p = 0.571). Conclusions PCWGC demonstrated greater efficacy than the conventional salvage technique. PCWGC could be a safe and useful technique, especially for difficult biliary cannulation.
Genomic analysis unveils genome degradation events and gene flux in the emergence and persistence of S. Paratyphi A lineages

Paratyphoid fever caused by S. Paratyphi A is endemic in parts of South Asia and Southeast Asia. The proportion of enteric fever cases caused by S. Paratyphi A has substantially increased, yet only limited data is available on the population structure and genetic diversity of this serovar. We examined the phylogenetic distribution and evolutionary trajectory of S. Paratyphi A isolates collected as part of the Indian enteric fever surveillance study “Surveillance of Enteric Fever in India (SEFI). ” In the study period (2017–2020), S. Paratyphi A comprised 17.6% (441/2503) of total enteric fever cases in India, with the isolates highly susceptible to all the major antibiotics used for treatment except fluoroquinolones. Phylogenetic analysis clustered the global S. Paratyphi A collection into seven lineages (A-G), and the present study isolates were distributed in lineages A, C and F. Our analysis highlights that the genome degradation events and gene acquisitions or losses are key molecular events in the evolution of new S. Paratyphi A lineages/sub-lineages. A total of 10 hypothetically disrupted coding sequences (HDCS) or pseudogenes-forming mutations possibly associated with the emergence of lineages were identified. The pan-genome analysis identified the insertion of P2/PSP3 phage and acquisition of IncX1 plasmid during the selection in 2.3. 2/2.3. 3 and 1.2. 2 genotypes, respectively. We have identified six characteristic missense mutations associated with lipopolysaccharide (LPS) biosynthesis genes of S. Paratyphi A, however, these mutations confer only a low structural impact and possibly have minimal impact on vaccine effectiveness. Since S. Paratyphi A is human-restricted, high levels of genetic drift are not expected unless these bacteria transmit to naive hosts. However, public-health investigation and monitoring by means of genomic surveillance would be constantly needed to avoid S. Paratyphi A serovar becoming a public health threat similar to the S. Typhi of today.
Effectiveness and health benefits of a nutritional, chronobiological and physical exercise primary care intervention in fibromyalgia and chronic fatigue syndrome: SYNCHRONIZE + mixed-methods study protocol

Introduction: Chronic pain, fatigue and insomnia are classic symptoms of fibromyalgia (FM) and chronic fatigue syndrome (CFS) and seriously affect quality of life. Nutrition and chronobiology are often overlooked in multicomponent approach despite their potential. This study aims to evaluate the effectiveness of a multidisciplinary group intervention based on nutrition, chronobiology, and physical exercise in the improvement of lifestyle and quality of life in FM and CFS. Methods: Mixed-methods study based on a randomized clinical trial and qualitative analysis with a descriptive phenomenological approach. The study will be conducted in primary care in Catalonia. The control group will follow the usual clinical practice and the intervention group the usual practice plus the studied intervention (12 hours over 4 days). The intervention based on nutrition, chronobiology and physical exercise will be designed considering participants’ opinions as collected in 4 focus groups. To evaluate effectiveness, EuroQol-5D, multidimensional fatigue inventory, VAS pain, Pittsburgh Sleep Quality Index, erMEDAS-17, biological rhythms interview of assessment in neuropsychiatry, REGICOR-Short, FIQR and Hospital Anxiety and Depression Scale questionnaires will be collected at baseline, and at 1, 3, 6, and 12 months post-intervention. Food intake, body composition, resistance and, strength will also be evaluated. The effect size will be calculated using Cohen d and logistic regression models will be used to quantify the impact of the intervention by adjusting for different variables. Discussion: It expected that the intervention will improve the patients’ quality of life, fatigue, pain and insomnia, as well as food and physical exercise habits, providing effectiveness evidence of a new therapy in addressing these syndromes in Primary Heath Care. Improvements in the quality of life will have a positive socioeconomic impact by reducing health expenditure on recurrent medical consultation, medication, complementary medical tests, etc and favor the maintenance of an active working life and productivity.
Paradoxical effect of Aβ on protein levels of ABCA1 in astrocytes, microglia, and neurons isolated from C57BL/6 mice: an in vitro and in silico study to elucidate the effect of Aβ on ABCA1 in the brain cells

Abstract Impaired cholesterol metabolism has been reported in Alzheimer’s disease. Since ABCA1 is one of the main players in the brain’s cholesterol homeostasis, here we used the in-vitro and in-silico experiments to investigate the effect of Aβ on ABCA1 protein levels in microglia, astrocytes, and neurons in mice. Microglia, astrocytes, and neurons were cultured and exposed to beta amyloid. ABCA1 in cell lysates was determined by Western blotting, and cholesterol efflux was measured in the conditioned media. Molecular docking, molecular dynamics simulations, and MM-GBSA analysis were conducted to gain a better understanding of the effects of Aβ on ABCA1. In response to Aβ, the protein levels of ABCA1 increase significantly in microglia, astrocytes, and neurons; however, its ability to enhance cholesterol efflux is diminished. Aβ inhibited the function of ABCA1 by obstructing the extracellular tunnel that transports lipids outside the cell, as determined by molecular docking. MD simulation analysis validated these findings. Our results demonstrated that Aβ could increase ABCA1 protein levels in various brain cells, regardless of cell type. Molecular docking, molecular dynamics simulation, and MM-GBSA studies indicate that Aβ has a significant effect on the structural conformation of ABCA1, possibly interfering with its function. We believe that the conformational changes of ABCA1 will inhibit its ability to subsequently release cellular cholesterol. Aβ may obstruct the extracellular tunnel of ABCA1, rendering it less accessible to proteases such as the calpain family, which may explain the increase in ABCA1 levels but decrease in its function. Communicated by Ramaswamy H. Sarma
Mutations in SARS-CoV-2 variant nsp6 enhance type-I interferon antagonism

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve after its emergence. Given its importance in viral infection and vaccine development, mutations in the viral Spike gene have been studied extensively; however, the impact of mutations outside the Spike gene are poorly understood. Here, we report that a triple deletion (ΔSGF or ΔLSG) in nonstructural protein 6 (nsp6) independently acquired in Alpha and Omicron sublineages of SARS-CoV-2 augments nsp6-mediated antagonism of type-I interferon (IFN-I) signaling. Specifically, these triple deletions enhance the ability of mutant nsp6 to suppress phosphorylation of STAT1 and STAT2. A parental SARS-CoV-2 USA-WA1/2020 strain containing the nsp6 ΔSGF deletion (ΔSGF-WA1) shows reduced susceptibility to IFN-I treatment in vitro, outcompetes the parental strain in human primary airway cultures, and increases virulence in mice; however, the ΔSGF-WA1 virus is less virulent than the Alpha variant (which has the nsp6 ΔSGF deletion and additional mutations in other genes). Analyses of host responses from ΔSGF-WA1-infected mice and primary airway cultures reveal activation of pathways indicative of a cytokine storm. These results provide evidence that mutations outside the Spike protein affect virus-host interactions and may alter pathogenesis of SARS-CoV-2 variants in humans.
First results of flowing liquid lithium limiter in HT-7

Two different types of flowing liquid lithium limiters were firstly installed and successfully tested in HT-7 tokamaks in 2012 and some encouraging results were obtained. Two limiters of the first type, called FLiLi limiters, used a thin lithium layer flowing under gravity. The other type had lithium-metal infused trenches (LIMIT) for thermoelectric magnetohydrodynamic drive of the liquid metal flow. The surface of one of the FLiLi limiters was coated by evaporated lithium before liquid lithium was injected by Ar pressure into a special distributor of the limiter. Then the liquid lithium could slowly move along the plasma facing guide surface of the limiter due to gravity. For LIMIT, it was found that liquid lithium could flow along the trenches as expected with a velocity of about 3.7 ± 0.5 cm s−1 driven by the electromagnetic force, which came from the interaction between the thermoelectric current and magnetic field. Use of flowing liquid lithium limiters in HT-7 resulted in reduction of particle recycling, suppression of impurity emission and improvement of the confinement.
Organic waste recycling by vermicomposting amended with rock phosphate impacts the stability and maturity indices of vermicompost

ABSTRACT Recycling organic waste can help the land be nourished, properly disposed of, and protected from the negative impacts of chemical fertilizers. Organic additions like vermicompost can help restore and preserve the quality of the soil, however, producing vermicompost of a high enough standard is difficult. This study was planned to prepare vermicompost by utilizing two different organic wastes viz. household waste and organic residue amended with rock phosphate and further evaluate their stability and maturity indices during vermicomposting for quality of produce. For this study, the organic wastes were collected and vermicompost was prepared by using earthworm (Eisenia fetida) and with or without enriching with rock phosphate. Results showed that pH, bulk density, and biodegradability index were decreased and water holding capacity and cation exchange capacity was increased with the gradual progress of composting starting from 30 to 120 days of sampling/composting (DAS). Initially (upto 30 DAS) water-soluble carbon and water-soluble carbohydrate increased with rock phosphate enrichment. The population of the earthworms and enzymatic activities (CO2 evolution, dehydrogenase, and alkaline phosphatase) were also increased on enriching with rock phosphate and with the progression of the composting period. Rock phosphate addition (enrichment) also reflected the higher content of phosphorus (106% and 120% for household waste and organic residue, respectively) in the final product of vermicompost. The vermicompost prepared from household waste and enriched with rock phosphate showed greater maturity and stability indices. Overall, this can be concluded that the maturity and stability of vermicompost depend on the substrate used and improves on enriching with rock phosphate. Implications: Our study concludes that the quality of vermicompost depends on different substrates, composting period, and enrichment with rock phosphate. The qualities of vermicompost were best found under household waste-based vermicompost enriched with rock phosphate. The efficiency of vermicomposting process using earthworms was found maximum for enriched and without enriched household-based vermicompost. The study also indicated that several stability and maturity indices are influenced by different parameters and hence cannot be determined by a single parameter. The addition of rock phosphate increased the cation exchange capacity, phosphorus content, and alkaline phosphatase. Nitrogen, zinc, manganese, dehydrogenase, and alkaline phosphatase were found higher under household waste-based vermicompost relative to organic residue-based vermicompost. All four substrates promoted earthworm growth and reproduction in vermicompost.