Miracle-dz/UniFAR-FTUs huggingface dataset:
Switch to second-line versus continued first-line antiretroviral therapy for patients with low-level HIV-1 viremia: An open-label randomized controlled trial in Lesotho

Background Current World Health Organization (WHO) antiretroviral therapy (ART) guidelines define virologic failure as two consecutive viral load (VL) measurements ≥1,000 copies/mL, triggering empiric switch to next-line ART. This trial assessed if patients with sustained low-level HIV-1 viremia on first-line ART benefit from a switch to second-line treatment. Methods and findings This multicenter, parallel-group, open-label, superiority, randomized controlled trial enrolled patients on first-line ART containing non-nucleoside reverse transcriptase inhibitors (NNRTI) with two consecutive VLs ≥100 copies/mL, with the second VL between 100–999 copies/mL, from eight clinics in Lesotho. Consenting participants were randomly assigned (1:1), stratified by facility, demographic group, and baseline VL, to either switch to second-line ART (switch group) or continued first-line ART (control group; WHO guidelines). The primary endpoint was viral suppression (<50 copies/mL) at 36 weeks. Analyses were by intention to treat, using logistic regression models, adjusted for demographic group and baseline VL. Between August 1, 2017, and August 7, 2019, 137 individuals were screened, of whom 80 were eligible and randomly assigned to switch (n = 40) or control group (n = 40). The majority of participants were female (54 [68%]) with a median age of 42 y (interquartile range [IQR] 35–51), taking tenofovir disoproxil fumarate/lamivudine/efavirenz (49 [61%]) and on ART for a median of 5.9 y (IQR 3.3–8.6). At 36 weeks, 22/40 (55%) participants in the switch versus 10/40 (25%) in the control group achieved viral suppression (adjusted difference 29%, 95% CI 8%–50%, p = 0.009). The switch group had significantly higher probability of viral suppression across different VL thresholds (<20, <100, <200, <400, and <600 copies/mL) but not for <1,000 copies/mL. Thirty-four (85%) participants in switch group and 21 (53%) in control group experienced at least one adverse event (AE) (p = 0.002). No hospitalization or death or other serious adverse events were observed. Study limitations include a follow-up period too short to observe differences in clinical outcomes, missing values in CD4 cell counts due to national stockout of reagents during the study, and limited generalizability of findings to other than NNRTI-based first-line ART regimens. Conclusions In this study, switching to second-line ART among patients with sustained low-level HIV-1 viremia resulted in a higher proportion of participants with viral suppression. These results endorse lowering the threshold for virologic failure in future WHO guidelines. Trial registration The trial is registered at ClinicalTrials.gov, NCT03088241.
A DNA Methylation Reader–Chaperone Regulator–Transcription Factor Complex Activates OsHKT1;5 Expression during Salinity Stress

OsSUVH7, OsBAG4, and OsMYB106 form a DNA methylation reader–chaperone regulator–transcription factor complex on the promoter region of OsHKT1;5 to activate its expression during salinity stress. Irrigated lands are increasingly salinized, which adversely affects agricultural productivity. To respond to high sodium (Na+) concentrations, plants harbor multiple Na+ transport systems. Rice (Oryza sativa) HIGH-AFFINITY POTASSIUM (K+) TRANSPORTER1;5 (OsHKT1;5), a Na+-selective transporter, maintains K+/Na+ homeostasis under salt stress. However, the mechanism regulating OsHKT1;5 expression remains unknown. Here, we present evidence that a protein complex consisting of rice BCL-2-ASSOCIATED ATHANOGENE4 (OsBAG4), OsMYB106, and OsSUVH7 regulates OsHKT1;5 expression in response to salt stress. We isolated a salt stress–sensitive mutant, osbag4-1, that showed significantly reduced OsHKT1;5 expression and reduced K+ and elevated Na+ levels in shoots. Using comparative interactomics, we isolated two OsBAG4-interacting proteins, OsMYB106 (a MYB transcription factor) and OsSUVH7 (a DNA methylation reader), that were crucial for OsHKT1;5 expression. OsMYB106 and OsSUVH7 bound to the MYB binding cis-element (MYBE) and the miniature inverted-repeat transposable element (MITE) upstream of the MYBE, respectively, in the OsHKT1;5 promoter. OsBAG4 functioned as a bridge between OsSUVH7 and OsMYB106 to facilitate OsMYB106 binding to the consensus MYBE in the OsHKT1;5 promoter, thereby activating the OsHKT1;5 expression. Elimination of the MITE or knockout of OsMYB106 or OsSUVH7 decreased OsHKT1;5 expression and increased salt sensitivity. Our findings reveal a transcriptional complex, consisting of a DNA methylation reader, a chaperone regulator, and a transcription factor, that collaboratively regulate OsHKT1;5 expression during salinity stress.
Colchicine to Weather the Cytokine Storm in Hospitalized Patients with COVID-19

The repurposing of colchicine for the treatment of COVID-19 was suggested based in its immunomodulatory, anti-inflammatory, and anti-viral properties. We performed a single-center propensity score matched cohort study, including all consecutive COVID-19 patients admitted to a community hospital between 1 March 2020 and 30 May 2020. Patients were stratified according to the receipt of colchicine. The primary endpoint was defined as in-hospital death within 28-days follow-up. Secondary endpoints included favorable change in the Ordinal Scale for Clinical Improvement on days 14 and 28 versus baseline, proportion of patients not requiring supplemental oxygen on days 14 and 28, and proportion of patients discharged by day 28. In total data for 303 PCR positive COVID-19 patients were extracted and 66 patients were included in the 1:1 matched cohort study. At the end of the 28 day follow-up, patients receiving colchicine were approximately five times more likely to be discharged (odds ratio, 5.0; 95% confidence interval, 1.25–20.1; p = 0.023) and when comparing mortality, there were 3 deaths (9.1%) in patients receiving colchicine versus 11 deaths (33.3%) in the groups receiving standard of care (odds ratio, 0.20; 95% confidence interval, 0.05–0.80; p = 0.023). These observations warrant further investigation in large controlled clinical trials.
Higher Energy and Zinc Intakes from Complementary Feeding Are Associated with Decreased Risk of Undernutrition in Children from South America, Africa, and Asia

ABSTRACT Background Few studies have focused on quantitatively analyzing nutrients from infant diets, compromising complementary feeding evaluation and health promotion worldwide. Objectives This study aimed to describe dietary intake in infants from 9 to 24 mo of age, determining nutrient intakes associated with the risk of underweight, wasting, and stunting. Methods Usual nutrient intakes from complementary feeding were determined by 24-h recalls collected when infants were 9–24 mo of age in communities from 7 low- and middle-income countries: Brazil (n = 169), Peru (n = 199), South Africa (n = 221), Tanzania (n = 210), Bangladesh (n = 208), India (n = 227), and Nepal (n = 229), totaling 1463 children and 22,282 food recalls. Intakes were corrected for within- and between-person variance and energy intake. Multivariable regression models were constructed to determine nutrient intakes associated with the development of underweight, wasting, and stunting at 12, 18, and 24 mo of age. Results Children with malnutrition presented significantly lower intakes of energy and zinc at 12, 18, and 24 mo of age, ranging from −16.4% to −25.9% for energy and −2.3% to −48.8% for zinc. Higher energy intakes decreased the risk of underweight at 12 [adjusted odds ratio (AOR): 0.90; 95% CI: 0.84, 0.96] and 24 mo (AOR: 0.91; 95% CI: 0.86, 0.96), and wasting at 18 (AOR: 0.91; 95% CI: 0.83, 0.99) and 24 mo (AOR: 0.83; 95% CI: 0.74, 0.92). Higher zinc intakes decreased the risk of underweight (AOR: 0.12; 95% CI: 0.03, 0.55) and wasting (AOR: 0.19; 95% CI: 0.04, 0.92) at 12 mo, and wasting (AOR: 0.05; 95% CI: 0.00, 0.76) at 24 mo. Conclusions Higher intakes of energy and zinc in complementary feeding were associated with decreased risk of undernutrition in the studied children. Data suggest these are characteristics to be improved in children's complementary feeding across countries.
Effect of Bornel on Cytoplasmic Free Calcium Level in Rat Platelets

Objective To investigate the effect of bornel on cytoplasmic free calcium level in rat platelets and its possible mechanism of anti-platelet aggregation.Methods Plateleti was determined by double beam fluorescence spectrophotometric method.Results With or without the presence of extracellular Ca2+,bornel inhibited the increased i induced by 5-HT.Conclusion Bornel markedly inhibits the platelet aggregation,and its mechanism may be related to its depression on the rise of platelet i.
Modeling Network Public Opinion Propagation with the Consideration of Individual Emotions

The occurrence of popular social events causes fluctuations and changes of public emotions, while the rapid development of online social platforms and networks has made individual interactions more intense and further escalated public emotions into public opinion. However, there is a lack of consideration of individual emotions in the current research on online public opinion. Based on this, this paper firstly expounds the quantitative representation of attitude and emotion, analyzes the formation and propagation process of online public opinion by combining individual’s expression willingness, individual’s expression ability, attitude perception value, attitude change probability and other factors, and constructs a network public opinion propagation model that takes individual emotion into consideration. Finally, the main factors affecting the formation and propagation of network public opinion are discussed through simulation experiments. The results demonstrate that: (1) fear is conducive to the formation of online public opinion, but the speed is relatively slow; sadness is not conducive to the formation, but once enough people participate in the exchange of views, the formation of online public opinion will be faster; (2) the influence of online public opinion on individual emotions expands with the increase of the number of individual interactions; (3) different network structures impact differently on the propagation of public opinion. Among them, BA (BA network is a scale-free network model proposed by Barabasi and Albert in order to explain the generation mechanism of power law, BA model has two characteristics: growth and priority connection mechanism) and ER (ER network is a network with random connectivity proposed by Erdös-Renyi) random networks can promote the propagation of online public opinion, which is prone to “one-sided” online public opinion. WS small-world networks (proposed by Watts and Strogatz. It is a kind of network with short average path length and high clustering coefficient) and fully-connected networks have an inhibitory effect on the spread of online public opinion, easily maintaining the multi-dimensional nature of online public opinion.
Single-cell RNA sequencing reveals profibrotic roles of distinct epithelial and mesenchymal lineages in pulmonary fibrosis.

Pulmonary fibrosis (PF) is a form of chronic lung disease characterized by pathologic epithelial remodeling and accumulation of extracellular matrix (ECM). To comprehensively define the cell types, mechanisms, and mediators driving fibrotic remodeling in lungs with PF, we performed single-cell RNA sequencing of single-cell suspensions from 10 nonfibrotic control and 20 PF lungs. Analysis of 114,396 cells identified 31 distinct cell subsets/states. We report that a remarkable shift in epithelial cell phenotypes occurs in the peripheral lung in PF and identify several previously unrecognized epithelial cell phenotypes, including a KRT5- /KRT17 + pathologic, ECM-producing epithelial cell population that was highly enriched in PF lungs. Multiple fibroblast subtypes were observed to contribute to ECM expansion in a spatially discrete manner. Together, these data provide high-resolution insights into the complexity and plasticity of the distal lung epithelium in human disease and indicate a diversity of epithelial and mesenchymal cells contribute to pathologic lung fibrosis.
Cardiac electrophysiological effects of ibuprofen in dog and rabbit ventricular preparations: Possible implication to enhanced proarrhythmic risk.

Ibuprofen is a widely used non-steroidal anti-inflammatory drug, which has recently been associated with increased cardiovascular risk, but its electrophysiological effects have not yet been properly studied in isolated cardiac preparations. We studied the effects of ibuprofen on action potential characteristics and several transmembrane ionic currents using the conventional microelectrode technique and the whole-cell configuration of the patch-clamp technique on cardiac preparations and enzymatically isolated ventricular myocytes. In dog (200 µM; n=6) and rabbit (100 µM; n=7) papillary muscles, ibuprofen moderately but significantly prolonged repolarization at 1 Hz stimulation frequency. In dog Purkinje fibers, repolarization was abbreviated, and maximal rate of depolarization was depressed in a frequency-dependent manner. Levofloxacin (40 µM) alone did not alter repolarization, but augmented the ibuprofen-evoked repolarization lengthening in rabbit preparations (n=7). In dog myocytes, ibuprofen (250 µM) did not significantly influence IK1, but decreased the amplitude of Ito and IKr potassium currents by 28.2% (60 mV) and 15.2% (20 mV) respectively. Ibuprofen also depressed INaL and ICa currents by 19.9% and 16.4%. We conclude that ibuprofen seems to be free from effects on AP parameters at lower concentrations. However, at higher concentrations it may alter repolarization reserve, contributing to the observed proarrhythmic risk in patients.
Willingness to Discuss Clinical Trials Among Black vs White Men With Prostate Cancer.

Importance Black individuals are underrepresented in cancer clinical trials. Objective To examine whether Black and White men with prostate cancer differ in their willingness to discuss clinical trials with their physicians and, if so, whether patient-level barriers statistically mediate racial differences. Design, Setting, and Participants This cross-sectional survey study used baseline data from Partnering Around Cancer Clinical Trials, a randomized clinical trial to increase Black individuals' enrollment in prostate cancer clinical trials. Data were collected from 2016 through 2019 at 2 National Cancer Institute-designated comprehensive cancer centers; participants were Black and White men with intermediate-risk to high-risk prostate cancer. In mediation analysis, path models regressed willingness onto race and each potential mediator, simultaneously including direct paths from race to each mediator. Significant indirect effect sizes served as evidence for mediation. Exposures Race was the primary exposure. Potential mediators included age, education, household income, perceived economic burden, pain/physical limitation, health literacy, general trust in physicians, and group-based medical suspicion. Main Outcomes and Measures The primary outcome was the answer to a single question: "If you were offered a cancer clinical trial, would you be willing to hear more information about it? " Results A total of 205 participants were included (92 Black men and 113 White men), with a mean (range) age of 65.7 (45-89) years; 32% had a high school education or lower, and 27.5% had a household income of less than $40 000. Most (88.3%) reported being definitely or probably willing to discuss trials, but White participants were more likely to endorse this highest category of willingness than Black participants (82% vs 64%; χ22 = 8.81; P = .01). Compared with White participants, Black participants were younger (F1,182 = 8.67; P < .001), less educated (F1,182 = 22.79; P < .001), with lower income (F1,182 = 79.59; P < .001), greater perceived economic burden (F1,182 = 42.46; P < .001), lower health literacy (F1,184 = 9.84; P = .002), and greater group-based medical suspicion (F1,184 = 21.48; P < .001). Only group-based medical suspicion significantly mediated the association between race and willingness to discuss trials (indirect effect, -0.22; P = .002). Conclusions and Relevance In this study of men with prostate cancer, most participants were willing to discuss trials, but Black men were significantly less willing than White men. Black men were more likely to believe that members of their racial group should be suspicious of the health care system, and this belief was associated with lower willingness to discuss trials. Addressing medical mistrust may improve equity in clinical research.
Dietary Patterns, Ceramide Ratios, and Risk of All-Cause and Cause-Specific Mortality: The Framingham Offspring Study.

BACKGROUND Prior evidence suggests that diet modifies the association of blood ceramides with the risk of incident cardiovascular disease (CVD). It remains unknown if diet quality modifies the association of very long-chain-to-long-chain ceramide ratios with mortality in the community. OBJECTIVES Our objectives were to determine how healthy dietary patterns associate with blood ceramide concentrations and to examine if healthy dietary patterns modify associations of ceramide ratios (C22:0/C16:0 and C24:0/C16:0) with all-cause and cause-specific mortality. METHODS We examined 2157 participants of the Framingham Offspring Study (mean age = 66 y, 55% women). Blood ceramides were quantified using a validated assay. We evaluated prospective associations of the Dietary Guidelines Adherence Index (DGAI) and Mediterranean-style Diet Score (MDS) with incidence of all-cause and cause-specific mortality using Cox proportional hazards models. Cross-sectional associations of the DGAI and MDS with ceramides were evaluated using multivariable linear regression models. RESULTS The C22:0/C16:0 and C24:0/C16:0 ceramide ratios were inversely associated with all-cause, CVD, and cancer mortality; multivariable-adjusted HRs (95% CIs) were 0.73 (0.67, 0.80) and 0.70 (0.63, 0.77) for all-cause mortality, 0.74 (0.60, 0.90) and 0.69 (0.55, 0.86) for CVD mortality, and 0.75 (0.65, 0.87) and 0.75 (0.64, 0.88) for cancer mortality, respectively. Inverse associations of the C22:0/C16:0 and C24:0/C16:0 ceramide ratios with cancer mortality were attenuated among individuals with a higher diet quality (DGAI or MDS above the median, all P-interaction ≤0.1). The DGAI and MDS had distinct associations with ceramide ratios (DGAI: lower C22:0/C16:0 across quartiles; MDS: higher C24:0/C16:0 across quartiles; all P-trend ≤0.01). CONCLUSION In our community-based sample, ceramide ratios (C22:0/C16:0 and C24:0/C16:0) were associated with a lower risk of all-cause and cause-specific mortality. Further, we observed that a higher overall diet quality attenuates the association between blood ceramide ratios and cancer mortality and that dietary patterns have distinct relations with ceramide ratios.
Comparison of Clinical Outcomes in Patients with ST Elevation Myocardial Infarction with Percutaneous Coronary Intervention and the Use of a Telemedicine App Before and After the COVID-19 Pandemic at a Center in Beijing, China, from August 2019 to March 2020

Background The efficacy of telemedicine in reducing delay times and short-term adverse clinical outcomes in patients with ST segment elevation myocardial infarction (STEMI) during the coronavirus disease 2019 (COVID-19) pandemic is unclear. This study compared outcomes in patients with STEMI who had percutaneous coronary intervention (PCI) and the use of a telemedicine app from August 2019 to March 2020 at a single center in Beijing, China. Material/Methods A total of 243 patients with STEMI who underwent PCI were consecutively enrolled and divided into 2 groups according to the date, before or after the pandemic. The 2 groups were further divided into patients who used the app for consulting and those who did not. Results The time from symptom onset to calling an ambulance (SCT), door to balloon time (DTB), and total ischemia time (TIT) were significantly prolonged in patients after the pandemic. Patients who used the app had shorter SCT, DTB, and TIT before and after the pandemic compared to those who did not. Adverse clinical outcomes were significantly higher after compared with before the pandemic, despite the incidence rate of stroke, any revascularization, and stent thrombosis. However, there was no significant difference in short-term adverse clinical outcomes between patients who used the app and those who did not before and after the pandemic. Conclusions Telemedicine reduced the delay time of STEMI patients during the COVID-19 pandemic. The difference in short-term adverse clinical outcomes was not statistically significant between patients who used the app and those who did not.
Females and males do not differ for fatigability, muscle damage and magnitude of the repeated bout effect following maximal eccentric contractions.

Unaccustomed eccentric (ECC) exercise induces muscle fatigue as well as damage and initiates a protective response to minimize impairments from a subsequent bout (i.e., repeated bout effect; RBE). It is uncertain if the sexes differ for neuromuscular responses to ECC exercise and the ensuing RBE. Twenty-six young adults (13 females) performed two bouts (four weeks apart) of 200 ECC maximal voluntary contractions (MVCs) of the dorsiflexors. Isometric (ISO) MVC torque and the ratio of ISO torque in response to low- vs. high-frequency stimulation (10:100Hz) were compared before and after (2-10min and 2, 4, and 7d) exercise. The decline in ECC and ISO MVC torque, and the 10:100Hz ratio following bout one did not differ between sexes (P > 0.05), with reductions from baseline of 31.5 ± 12.3, 24.1 ± 15.4, and 51.3 ± 12.2%, respectively. After bout two, the 10:100Hz ratio declined less (45.0 ± 12.4% from baseline) and ISO MVC torque recovered sooner compared to bout one but no differences between sexes were evident for the magnitude of the RBE (P > 0.05). These data suggest that fatigability with ECC exercise does not differ for the sexes and adaptations that mitigate impairments to calcium handling are independent of sex. NOVELTY BULLETS: • One bout of 200 maximal eccentric dorsiflexor contractions caused equivalent muscle fatigue and damage for females and males • The repeated bout effect observed after a second bout four weeks later also had no sex-related differences • Prolonged low-frequency force depression is promoted as an indirect measure of muscle damage in humans.