Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-Term Outcomes Following Drug-Eluting Balloons Versus Thin-Strut Drug-Eluting Stents for Treatment of In-Stent Restenosis (DEB-Dragon-Registry)

Supplemental Digital Content is available in the text. Background: Data regarding the use of percutaneous coronary intervention with drug-eluting balloons (DEB) versus thin-strut drug-eluting stents (thin-DES) for treating DES in-stent restenosis in everyday clinical practice is scarce. Our goal was to evaluate the efficacy and safety profile of DEB versus thin-DES in DES in-stent restenosis. Methods: Consecutive patients with DES in-stent restenosis who underwent percutaneous coronary intervention between 2008 and 2019 entered the multicenter DEB-DRAGON Registry with a follow-up of 3 years. Patients who received DEB at the index procedure (n=557, 49.9%) were compared with those who received thin-DES (n=560, 50.1%). Results: Analysis of the unmatched cohort revealed lower rates of target lesion revascularization (9.1% versus 13.6%; hazard ratio [HR], 0.58 [95% CI, 0.41–0.83], P=0.003), target vessel revascularization (11.8% versus 16.7%; HR, 0.62 [95% CI, 0.45–0.84], P=0.003) and device-oriented composite end point, defined as a composite of cardiac death, target lesion revascularization, and target vessel myocardial infarction (12.7% versus 16.0%; HR, 0.69 [95% CI, 0.50–0.94], P=0.018) in the thin-DES group compared with the DEB group. The incidence of cardiac death, target vessel-myocardial infarction, and myocardial infarction were similar in both groups. However, after propensity score matching, there were no significant differences in target lesion revascularization (11.2% versus 11.2%; HR, 0.91 [95% CI, 0.55–1.51], P=0.707), target vessel revascularization (13.4% versus 14.2%; HR, 0.86 [95% CI, 0.55–1.36], P=0.523), and device-oriented composite end point (14.2% versus 14.2%; HR, 0.91 [95% CI, 0.58–1.42], P=0.667) between the thin-DES and DEB group, respectively. Conclusions: This analysis of a real-life registry revealed similar long-term outcomes of thin-DES and DEB in DES in-stent restenosis regarding target lesion revascularization, myocardial infarction, cardiac death, and device-oriented composite end point. Registration: URL: https://www.clinicaltrials. gov; Unique identifier: NCT04415216.
Cimicifuga racemosa isopropanolic extract for menopausal symptoms: an observational prospective case–control study

Abstract Objective We aimed to investigate the effectiveness of isopropanolic extract of Cimicifuga Racemosa (iCR) on reducing menopausal symptoms. Materials and Methods A single-center observational prospective case–control study was performed to assess the improvement of menopausal symptoms in menopausal women undergone iCR administration (cases) or no treatment (controls). Menopausal symptoms were assessed through a modified version of the Menopause Rating Scale questionnaire (mMRS) at T0 (baseline), T1 (1-month follow-up), and T2 (3 months follow-up). Univariate comparisons between cases and controls were performed by using the unpaired T test for two-tailed P value with α = 0.05 significance level. Results A total of 163 women (83 cases and 80 controls) were enrolled in the study. The difference in menopausal symptoms between cases and controls from T0 to T2, and from T0 to T1, was found significant for all analyses. In particular, the difference in all menopausal symptoms was 20.56 ± 0.90 points (95%CI: 18.77–22.33, p < .001) from T0 to T2, and 10.69 ± 0.6 (95%CI: 9.49–11.88, p < .001) from T0 to T1. Conclusion iCR may be effective in reducing menopausal symptoms, both after 1 month and after 3 months of treatment. The improvement was higher in vasomotor symptoms, sleep problems, and irritability.
Passive immunization of the human vagina

ABSTRACT The vagina is an excellent site for topical passive immunization, as access is relatively easy, and it is an enclosed space that has been shown to retain bioactive antibodies for several hours. A number of sexually transmitted infections could potentially be prevented by delivery of specific monoclonal antibodies to the vagina. Furthermore, our group is developing antisperm antibodies for vaginally delivered on-demand topical contraception. In this article, we describe physical features of the vagina that could play a role in antibody deployment, and antibody modifications that could affect mAb retention and function in the female reproductive tract. We also review results of recent Phase 1 clinical trials of vaginal passive immunization with antibodies against sexually transmitted pathogens, and describe our current studies on the use of anti-sperm mAbs for contraception.
Stability investigations of cytochrome P450 (CYP) enzymes immediately after death in a pig model support the applicability of postmortem hepatic CYP quantification

Quantification of drug‐metabolizing cytochrome P450 (CYP) isoforms using LC–MS/MS has been proposed as a potential way of estimating antemortem CYP levels using postmortem tissue, but the postmortem stability of CYP proteins is incompletely investigated. If one can use data obtained from the analysis of postmortem specimens to inform physiologically based pharmacokinetic (PBPK) models this greatly increases the access to rare specimens among special subpopulations. In this study, we developed and validated an LC–MS/MS method for targeted CYP protein quantification in a porcine animal model to study postmortem stability. We measured 19.9–28.3 pmol CYP1A2, 50.3–66.2 pmol CYP2D25, 132.9–142.7 pmol CYP2E1, and 16.8–48 pmol CYP3A29 protein per mg PLM in nondegraded tissue. In tissue stored at 4°C, we found that the CYP protein levels were unaffected by degradation after 72 h. At 21°C CYP1A2, CYP2D25, and CYP2E1 protein levels were nearly unaffected by degradation after 24 h, whereas a loss of approximately 50% was seen after 48 h. At 21°C CYP3A29 had a loss of 50% at 24 h and 70% at 48 h exhibiting less postmortem stability. In vitro enzyme activity measurements in the same tissue stored at 21°C showed a 50% decrease after 24 h and a complete loss of enzyme activity after 48 h. When stored at 4°C, the in vitro enzyme activity decreased to 50% activity after 96 h. In conclusion, measuring CYP levels by an LC–MS/MS approach was clearly less affected by postmortem changes than an activity‐based approach. The found postmortem stability for 24 h at 21°C for 3 out of 4 CYP isoforms supports the use of properly stored postmortem tissue to inform PBPK models.
Re-envisioning health promotion: Thinking and acting salutogenically towards equity for historically resilient communities

This paper explores how the salutogenic theory can enable us to re-envision health promotion work with marginalized communities, towards an approach that acknowledges and honours their resilience. We use the three core concepts in Antonovsky’s salutogenic model of health – sense of coherence, generalized resistance resources and specific resistance resources – to explore the theory’s relevance to health equity, thus presenting new opportunities for how we might radically re-evaluate current health promotion approaches. We conclude that a more equitable health promotion requires increased participation of marginalized communities in shaping their futures and suggest a new model for historically grounded salutogenic health promotion.
Association Between COVID-19 and Myocarditis Using Hospital-Based Administrative Data — United States, March 2020–January 2021

Viral infections are a common cause of myocarditis, an inflammation of the heart muscle (myocardium) that can result in hospitalization, heart failure, and sudden death (1). Emerging data suggest an association between COVID-19 and myocarditis (2-5). CDC assessed this association using a large, U.S. hospital-based administrative database of health care encounters from >900 hospitals. Myocarditis inpatient encounters were 42.3% higher in 2020 than in 2019. During March 2020-January 2021, the period that coincided with the COVID-19 pandemic, the risk for myocarditis was 0.146% among patients diagnosed with COVID-19 during an inpatient or hospital-based outpatient encounter and 0.009% among patients who were not diagnosed with COVID-19. After adjusting for patient and hospital characteristics, patients with COVID-19 during March 2020-January 2021 had, on average, 15.7 times the risk for myocarditis compared with those without COVID-19 (95% confidence interval [CI] = 14.1-17.2); by age, risk ratios ranged from approximately 7.0 for patients aged 16-39 years to >30.0 for patients aged <16 years or ≥75 years. Overall, myocarditis was uncommon among persons with and without COVID-19; however, COVID-19 was significantly associated with an increased risk for myocarditis, with risk varying by age group. These findings underscore the importance of implementing evidence-based COVID-19 prevention strategies, including vaccination, to reduce the public health impact of COVID-19 and its associated complications.
Wetting of phase-separated droplets on plant vacuole membranes leads to a competition between tonoplast budding and nanotube formation

Seeds of dicotyledonous plants store proteins in dedicated membrane-bounded organelles called protein storage vacuoles (PSVs). Formed during seed development through morphological and functional reconfiguration of lytic vacuoles in embryos [M. Feeney et al., Plant Physiol. 177, 241–254 (2018)], PSVs undergo division during the later stages of seed maturation. Here, we study the biophysical mechanism of PSV morphogenesis in vivo, discovering that micrometer-sized liquid droplets containing storage proteins form within the vacuolar lumen through phase separation and wet the tonoplast (vacuolar membrane). We identify distinct tonoplast shapes that arise in response to membrane wetting by droplets and derive a simple theoretical model that conceptualizes these geometries. Conditions of low membrane spontaneous curvature and moderate contact angle (i.e., wettability) favor droplet-induced membrane budding, thereby likely serving to generate multiple, physically separated PSVs in seeds. In contrast, high membrane spontaneous curvature and strong wettability promote an intricate and previously unreported membrane nanotube network that forms at the droplet interface, allowing molecule exchange between droplets and the vacuolar interior. Furthermore, our model predicts that with decreasing wettability, this nanotube structure transitions to a regime with bud and nanotube coexistence, which we confirmed in vitro. As such, we identify intracellular wetting [J. Agudo-Canalejo et al., Nature 591, 142–146 (2021)] as the mechanism underlying PSV morphogenesis and provide evidence suggesting that interconvertible membrane wetting morphologies play a role in the organization of liquid phases in cells.
Behavior change factors and retention in dietary interventions for older adults: scoping review.

BACKGROUND AND OBJECTIVES Although poor diet is a major driver of morbidity and mortality in people 60 and older, few dietary interventions are widely implemented for this population. We mapped behavior change theories, agents, and techniques in dietary interventions for adults 60+ and explored relationships between these factors and ability to retain at least 80% of the study participants. RESEARCH DESIGN AND METHODS We conducted a scoping review using MEDLINE, CINAHL, and Web of Science through April 2021 for dietary interventions in adults 60 and older. We collated, summarized, and calculated frequency distributions of behavior change theories, behavior change agents, and behavior change techniques (BCTs) using BCTv1 taxonomy with regard to participant retention across 43 studies. RESULTS Only 49% and 30% of the studies reported behavior theory and change agents respectively. Of the studies reporting on theory and agents, the most common were social cognitive theory and the related mechanism of self-efficacy. The most common BCTv1 were "shaping knowledge" and "goals and planning. " Several BCTv1 such as "antecedents" and "reward and threat" and evidence for concordance between BCTs and change agents were more common in interventions with higher retention rates. DISCUSSION AND IMPLICATIONS Mechanistically concordant studies with BCTs that involve resource allocation and positive reinforcement through rewards may be advantageous for retention in dietary intervention for older adults. Future studies should continue developing theory and mechanism-oriented research. Furthermore, future studies should consider diversifying the portfolio of currently deployed BCTs and strengthening a concordance between BCTs and mechanisms of change.
Exploiting Electrostatic Interaction for Highly Sensitive Detection of Tumor-Derived Extracellular Vesicles by an Electrokinetic Sensor

We present an approach to improve the detection sensitivity of a streaming current-based biosensor for membrane protein profiling of small extracellular vesicles (sEVs). The experimental approach, supported by theoretical investigation, exploits electrostatic charge contrast between the sensor surface and target analytes to enhance the detection sensitivity. We first demonstrate the feasibility of the approach using different chemical functionalization schemes to modulate the zeta potential of the sensor surface in a range −16.0 to −32.8 mV. Thereafter, we examine the sensitivity of the sensor surface across this range of zeta potential to determine the optimal functionalization scheme. The limit of detection (LOD) varied by 2 orders of magnitude across this range, reaching a value of 4.9 × 106 particles/mL for the best performing surface for CD9. We then used the optimized surface to profile CD9, EGFR, and PD-L1 surface proteins of sEVs derived from non-small cell lung cancer (NSCLC) cell-line H1975, before and after treatment with EGFR tyrosine kinase inhibitors, as well as sEVs derived from pleural effusion fluid of NSCLC adenocarcinoma patients. Our results show the feasibility to monitor CD9, EGFR, and PD-L1 expression on the sEV surface, illustrating a good prospect of the method for clinical application.
Glycolytic preconditioning in astrocytes mitigates trauma-induced neurodegeneration

Concussion is associated with a myriad of deleterious immediate and long-term consequences. Yet the molecular mechanisms and genetic targets promoting the selective vulnerability of different neural subtypes to dysfunction and degeneration remain unclear. Translating experimental models of blunt force trauma in C. elegans to concussion in mice, we identify a conserved neuroprotective mechanism in which reduction of mitochondrial electron flux through complex IV suppresses trauma-induced degeneration of the highly vulnerable dopaminergic neurons. Reducing cytochrome C oxidase function elevates mitochondrial-derived reactive oxygen species, which signal through the cytosolic hypoxia inducing transcription factor, Hif1a, to promote hyperphosphorylation and inactivation of the pyruvate dehydrogenase, PDHE1α. This critical enzyme initiates the Warburg shunt, which drives energetic reallocation from mitochondrial respiration to astrocyte-mediated glycolysis in a neuroprotective manner. These studies demonstrate a conserved process in which glycolytic preconditioning suppresses Parkinson-like hypersensitivity of dopaminergic neurons to trauma-induced degeneration via redox signaling and the Warburg effect.
Thrombosis of the palmar digital vein after Oxford‐AstraZeneca COVID‐19 vaccination

14.7% of patients had skin lesions as their first symptom. Interestingly, our patient’s cutaneous findings were the only manifestation of this viral illness. He had no history of allergy or any similar hands or feet manifestations in the past, and his RT-PCR became negative concomitantly with the resolution of the dermatological manifestations. All in all, these findings are in favor of a viral-induced skin eruption associated with COVID-19. While recognition of COVID-19 in asymptomatic or minimally symptomatic patients is challenging, it is mandatory to public health. Therefore, dermatologists should be conscious of their role during this pandemic as skin findings can be the first and sometimes only manifestation of COVID-19.
Evaluation of Changes in Depression, Anxiety, and Social Anxiety Using Smartphone Sensor Features: Longitudinal Cohort Study

Background The assessment of behaviors related to mental health typically relies on self-report data. Networked sensors embedded in smartphones can measure some behaviors objectively and continuously, with no ongoing effort. Objective This study aims to evaluate whether changes in phone sensor–derived behavioral features were associated with subsequent changes in mental health symptoms. Methods This longitudinal cohort study examined continuously collected phone sensor data and symptom severity data, collected every 3 weeks, over 16 weeks. The participants were recruited through national research registries. Primary outcomes included depression (8-item Patient Health Questionnaire), generalized anxiety (Generalized Anxiety Disorder 7-item scale), and social anxiety (Social Phobia Inventory) severity. Participants were adults who owned Android smartphones. Participants clustered into 4 groups: multiple comorbidities, depression and generalized anxiety, depression and social anxiety, and minimal symptoms. Results A total of 282 participants were aged 19-69 years (mean 38.9, SD 11.9 years), and the majority were female (223/282, 79.1%) and White participants (226/282, 80.1%). Among the multiple comorbidities group, depression changes were preceded by changes in GPS features (Time: r=−0.23, P=.02; Locations: r=−0.36, P<.001), exercise duration (r=0.39; P=.03) and use of active apps (r=−0.31; P<.001). Among the depression and anxiety groups, changes in depression were preceded by changes in GPS features for Locations (r=−0.20; P=.03) and Transitions (r=−0.21; P=.03). Depression changes were not related to subsequent sensor-derived features. The minimal symptoms group showed no significant relationships. There were no associations between sensor-based features and anxiety and minimal associations between sensor-based features and social anxiety. Conclusions Changes in sensor-derived behavioral features are associated with subsequent depression changes, but not vice versa, suggesting a directional relationship in which changes in sensed behaviors are associated with subsequent changes in symptoms.
Preliminary Validation of the Learning Ratio for the HVLT–R and BVMT–R in Older Adults

Background: The learning slope is typically represented as the raw difference between the final score and the score of the first learning trial. A new method for calculating the learning slope, the learning ratio (LR), was recently developed; it is typically represented as the number of items that are learned after the first trial divided by the number of items that are yet to be learned. Objective: To evaluate the convergent and criterion validity of the LR in order to understand its sensitivity to Alzheimer disease (AD) pathology. Method: Fifty-six patients from a memory clinic underwent standard neuropsychological assessment and quantitative brain imaging. LR scores were calculated from the Hopkins Verbal Learning Test—Revised and the Brief Visuospatial Memory Test—Revised and were compared with both standard memory measures and total hippocampal volumes, as well as between individuals with AD and those with mild cognitive impairment. Results: Lower LR scores were consistently associated with poorer performances on standard memory measures and smaller total hippocampal volumes, generally more so than traditional learning slope scores. The LR scores of the AD group were smaller than those of the group with mild cognitive impairment. Furthermore, the aggregation of LR scores into a single metric was partially supported. Conclusion: The LR is sensitive to AD pathology along the AD continuum. This result supports previous claims that the LR score can reflect learning capacity better than traditional learning calculations can by considering the amount of information that is learned at trial 1.
Ruminal pH pattern, fermentation characteristics and related bacteria in response to dietary live yeast (Saccharomyces cerevisiae) supplementation in beef cattle

Objective In this study we aimed to evaluate the effect of dietary live yeast supplementation on ruminal pH pattern, fermentation characteristics and associated bacteria in beef cattle. Methods This work comprised of in vitro and in vivo experiments. In vitro fermentation was conducted by incubating 0%, 0.05%, 0.075%, 0.1%, 0.125%, and 0.15% active dried yeast (Saccharomyces cerevisiae, ADY) with total mixed ration substrate to determine its dose effect. According to in vitro results, 0.1% ADY inclusion level was assigned in in vivo study for continuously monitoring ruminal fermentation characteristics and microbes. Six ruminally cannulated steers were randomly assigned to 2 treatments (Control and ADY supplementation) as two-period crossover design (30-day). Blood samples were harvested before-feeding and rumen fluid was sampled at 0, 3, 6, 9, and 12 h post-feeding on 30 d. Results After 24 h in vitro fermentation, pH and gas production were increased at 0.1% ADY where ammonia nitrogen and microbial crude protein also displayed lowest and peak values, respectively. Acetate, butyrate and total volatile fatty acids concentrations heightened with increasing ADY doses and plateaued at high levels, while acetate to propionate ratio was decreased accordingly. In in vivo study, ruminal pH was increased with ADY supplementation that also elevated acetate and propionate. Conversely, ADY reduced lactate level by dampening Streptococcus bovis and inducing greater Selenomonas ruminantium and Megasphaera elsdenii populations involved in lactate utilization. The serum urea nitrogen decreased, whereas glucose, albumin and total protein concentrations were increased with ADY supplementation. Conclusion The results demonstrated dietary ADY improved ruminal fermentation dose-dependently. The ruminal lactate reduction through modification of lactate metabolic bacteria could be an important reason for rumen pH stabilization induced by ADY. ADY supplementation offered a complementary probiotics strategy in improving gluconeogenesis and nitrogen metabolism of beef cattle, potentially resulted from optimized rumen pH and fermentation.