Miracle-dz/UniFAR-FTUs huggingface dataset:
CHA2DS2‐VASc Score and the Risk of Ventricular Tachyarrhythmic Events and Mortality in MADIT‐CRT

Background We hypothesized that multiple cardiovascular comorbidities, incorporated in the CHA 2 DS 2‐VASc score, may be useful in the assessment of ventricular tachyarrhythmias (VTAs) and mortality risk in heart failure (HF) patients. Methods and Results We evaluated the association between the CHA 2 DS 2‐VASc score (dichotomized as high at the upper quartile [≥5] and further assessed as a continuous measure) and the risk of VTA and death among 1804 patients enrolled in MADIT‐CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy). A high CHA 2 DS 2‐VASc score (n=464; 26%) was inversely associated with the risk of any VTA (hazard ratio [HR]: 0.64; P=0.001), fast VTA >200 beats/min (HR; 0.51; P<0.001), and appropriate implantable cardioverter‐defibrillator shocks (HR: 0.60; P<0.001). In contrast, a high score was directly correlated with mortality risk (HR: 1.92; P<0.001) and the risk of HF or death (HR: 1.60; P<0.001). Consistently, each 1‐U increment in CHA 2 DS 2‐VASc was associated with a significant 13% (P=0.003) reduction in VTA risk but a corresponding 33% (P<0.001) increase in mortality risk. Patients with a high CHA 2 DS 2‐VASc score and left bundle‐branch block derived a pronounced 53% (P<0.001) reduction in the risk of HF or death with cardiac resynchronization therapy with defibrillator versus implantable cardioverter‐defibrillator–only therapy. Conclusions Our findings suggest that a high CHA 2 DS 2‐VASc score can be used to identify patients with mild HF who have low VTA risk and high morbidity or mortality risk and may derive a pronounced clinical benefit from cardiac resynchronization therapy without a defibrillator. These data suggest a possible role for the CHA 2 DS 2‐VASc score in device selection among candidates for biventricular pacing.
Effects of experimentally induced fatigue on healthy older adults’ gait: A systematic review

Introduction While fatigue is ubiquitous in old age and visibly interferes with mobility, studies have not yet examined the effects of self-reported fatigue on healthy older adults’ gait. As a model that simulates this daily phenomenon, we systematically reviewed eleven studies that compared the effects of experimentally induced muscle and mental performance fatigability on gait kinematics, variability, kinetics, and muscle activity in healthy older adults. Methods We searched for studies in databases (PubMed and Web of Science) using Fatigue, Gait, and Clinical conditions as the main terms and extracted the data only from studies that experimentally induced fatigue by sustained muscle or mental activities in healthy older adults. Results Eleven studies were included. After muscle performance fatigability, six of nine studies observed increases in stride length, width, gait velocity (Effect Size [ES] range: 0.30 to 1.22), inter-stride trunk acceleration variability (ES: 2.06), and ankle muscle coactivation during gait (ES: 0.59, n = 1 study). After sustained mental activity, the coefficient of variation of stride outcomes increased (ES: 0.59 to 0.67, n = 1 study) during dual-task but not single-task walking. Conclusion Muscle performance fatigability affects spatial and temporal features of gait and, mainly, inter-stride trunk acceleration variability. In contrast, sustained mental activity tends only to affect step variability during dual tasking. A critical and immediate step for future studies is to determine the effects of self-reported fatigue on gait biomechanics and variability in healthy older adults to verify the viability of experimentally induced fatigue as a model for the study of gait adaptability in old age.
IL-23 supports host defense against systemic Candida albicans infection by ensuring myeloid cell survival

The opportunistic fungal pathogen Candida albicans can cause invasive infections in susceptible hosts and the innate immune system, in particular myeloid cell-mediated immunity, is critical for rapid immune protection and host survival during systemic candidiasis. Using a mouse model of the human disease, we identified a novel role of IL-23 in antifungal defense. IL-23-deficient mice are highly susceptible to systemic infection with C. albicans. We found that this results from a drastic reduction in all subsets of myeloid cells in the infected kidney, which in turn leads to rapid fungal overgrowth and renal tissue injury. The loss in myeloid cells is not due to a defect in emergency myelopoiesis or the recruitment of newly generated cells to the site of infection but, rather, is a consequence of impaired survival of myeloid cells at the site of infection. In fact, the absence of a functional IL-23 pathway causes massive myeloid cell apoptosis upon C. albicans infection. Importantly, IL-23 protects myeloid cells from apoptosis independently of the IL-23-IL-17 immune axis and independently of lymphocytes and innate lymphoid cells. Instead, our results suggest that IL-23 acts in a partially autocrine but not cell-intrinsic manner within the myeloid compartment to promote host protection from systemic candidiasis. Collectively, our data highlight an unprecedented and non-canonical role of IL-23 in securing survival of myeloid cells, which is key for maintaining sufficient numbers of cells at the site of infection to ensure efficient host protection.
Introduction of NGS in Environmental Surveillance for Healthcare-Associated Infection Control

The hospital environment significantly contributes to the onset of healthcare associated infections (HAIs), representing the most frequent and severe complications related to health care. The monitoring of hospital surfaces is generally addressed by microbial cultural isolation, with some performance limitations. Hence there is need to implement environmental surveillance systems using more effective methods. This study aimed to evaluate next-generation sequencing (NGS) technologies for hospital environment microbiome characterization, in comparison with conventional and molecular methods, in an Italian pediatric hospital. Environmental samples included critical surfaces of randomized rooms, surgical rooms, intensive care units and delivery rooms. The resistome of the contaminating population was also evaluated. NGS, compared to other methods, detected with higher sensitivity the environmental bacteria, and was the only method able to detect even unsearched bacteria. By contrast, however, it did not detect mycetes, nor it could distinguish viable from dead bacteria. Microbiological and PCR methods could identify and quantify mycetes, in addition to bacteria, and PCR could define the population resistome. These data suggest that NGS could be an effective method for hospital environment monitoring, especially if flanked by PCR for species identification and resistome characterization, providing a potential tool for the control of HAI transmission.
Pathways Linking Exposure to Community Violence, Self-serving Cognitive Distortions and School Bullying Perpetration: A Three-Wave Study

School bullying is a social phenomenon stemming from a complex interrelationship between the individuals and their environments. Underpinned by the social-ecological models, this study investigated the mediation of self-serving cognitive distortions (CDs) in the relationship between community violence exposure, as a victim and as a witness, and bullying perpetration. Bidirectional associations between violence exposure and bullying perpetration, and between CDs and bullying perpetration over time were also hypothesized. The study used a three-waves cross-lagged panel modeling in a sample of 829 Italian high school adolescents (46% males; Mage [Time 1; T1] = 12.71; Standard deviation [SD] = 1.68). The results showed that being exposed to community violence as a witness at T1 increased the development of CDs at Time 2 (T2), which in turn promoted the bullying perpetration at Time 3 (T3). Being exposed to community violence as a victim was not a significant predictor of CDs and bullying perpetration over time. Bidirectional associations were found between witnessing violence and bullying perpetration, and between CDs and bullying perpetration. The association between community violence exposure and individual moral cognitions over time plays a crucial role in predicting bullying perpetration. These findings highlight the need to consider both contextual and individual factors in understanding and preventing bullying perpetration.
Highlights of the 2019 Japanese Society of Hypertension Guidelines and perspectives on the management of Asian hypertensive patients

Unlike other international guidelines but in accord with the earlier Japanese Society of Hypertension (JSH) guidelines, the 2019 JSH guidelines (“JSH 2019”) continue to emphasize the importance of out‐of‐office blood pressure (BP) measurements obtained with a home BP device. Another unique characteristic of JSH 2019 is that it sets clinical questions about the management of hypertension that are based on systematic reviews of updated evidence. JSH 2019 states that individuals with office BP < 140/90 mm Hg do not have normal BP. The final decisions regarding the diagnosis and treatment of hypertension should be performed based on out‐of‐office BP values together with office BP measurements. For hypertensive adults with comorbidities, the office BP goal is usually <130/80 mm Hg and the home BP goal is <125/75 mm Hg. Recommendations of JSH 2019 would be valuable for not only Japanese hypertensive patients but also Asian hypertensive patients, who share the same features including higher incidence of stroke compared with that of myocardial infarction and a steeper blood pressure‐vascular event relationship.
Irradiance, Photofrin® Dose and Initial Tumor Volume are Key Predictors of Response to Interstitial Photodynamic Therapy of Locally Advanced Cancers in Translational Models

The objective of the present study was to develop a predictive model for Photofrin®‐mediated interstitial photodynamic therapy (I‐PDT) of locally advanced tumors. Our finite element method was used to simulate 630‐nm intratumoral irradiance and fluence for C3H mice and New Zealand White rabbits bearing large squamous cell carcinomas. Animals were treated with light only or I‐PDT using the same light settings. I‐PDT was administered with Photofrin® at 5.0 or 6.6 mg kg−1, 24 h drug‐light interval. The simulated threshold fluence was fixed at 45 J cm−2 while the simulated threshold irradiance varied, intratumorally. No cures were obtained in the mice treated with a threshold irradiance of 5.4 mW cm−2. However, 20–90% of the mice were cured when the threshold irradiances were ≥8.6 mW cm−2. In the rabbits treated with I‐PDT, 13 of the 14 VX2 tumors showed either local control or were cured when threshold irradiances were ≥15.3 mW cm−2 and fluence was 45 J cm−2. No tumor growth delay was observed in VX2 treated with light only (n = 3). In the mouse studies, there was a high probability (92.7%) of predicting cure when the initial tumor volume was below the median (493.9 mm3) and I‐PDT was administered with a threshold intratumoral irradiance ≥8.6 mW cm−2.
Metabolomic Profile of Oviductal Extracellular Vesicles across the Estrous Cycle in Cattle

Oviductal extracellular vesicles (oEVs) have been proposed as key modulators of gamete/embryo maternal interactions. The aim of this study was to examine the metabolite content of oEVs and its regulation across the estrous cycle in cattle. Oviductal EVs were isolated from bovine oviducts ipsilateral and contralateral to ovulation at four stages of the estrous cycle (post-ovulatory stage, early and late luteal phases, and pre-ovulatory stage). The metabolomic profiling of EVs was performed by proton nuclear magnetic resonance spectroscopy (NMR). NMR identified 22 metabolites in oEVs, among which 15 were quantified. Lactate, myoinositol, and glycine were the most abundant metabolites throughout the estrous cycle. The side relative to ovulation had no effect on the oEVs’ metabolite concentrations. However, levels of glucose-1-phosphate and maltose were greatly affected by the cycle stage, showing up to 100-fold higher levels at the luteal phase than at the peri-ovulatory phases. In contrast, levels of methionine were significantly higher at peri-ovulatory phases than at the late-luteal phase. Quantitative enrichment analyses of oEV-metabolites across the cycle evidenced several significantly regulated metabolic pathways related to sucrose, glucose, and lactose metabolism. This study provides the first metabolomic characterization of oEVs, increasing our understanding of the potential role of oEVs in promoting fertilization and early embryo development.
Yarrow Supercritical Extract Ameliorates the Metabolic Stress in a Model of Obesity Induced by High-Fat Diet

Nowadays, obesity and its associated metabolic disorders, including diabetes, metabolic syndrome, cardiovascular disease, or cancer, continue to be a health epidemic in westernized societies, and there is an increased necessity to explore anti-obesity therapies including pharmaceutical and nutraceutical compounds. Considerable attention has been placed on the identification of bioactive compounds from natural sources to manage the metabolic stress associated with obesity. In a previous work, we have demonstrated that a CO2 supercritical fluid extract from yarrow (Yarrow SFE), downregulates the expression of the lipogenic master regulator SREBF1 and its downstream molecular targets FASN and SCD in a tumoral context. Since obesity and diabetes are strongly considered high-risk factors for cancer development, herein, we aimed to investigate the potential therapeutic role of Yarrow SFE in the metabolic stress induced after a high-fat diet in mice. For this purpose, 32 C57BL/6 mice were distributed in four groups according to their diets: standard diet (SD); SD supplemented with Yarrow SFE (SD + Yarrow); high-fat diet (HFD); and HFD supplemented with Yarrow SFE (HFD + Yarrow). Fasting glycemia, insulin levels, homeostasis model assessment for insulin resistance (HOMA-IR), lipid profile, gene expression, and lipid content of liver and adipose tissues were analyzed after three months of treatment. Results indicate improved fasting glucose levels in plasma, enhanced insulin sensitivity, and diminished hypercholesterolemia in the HFD + Yarrow group compared to the HFD group. Mechanistically, Yarrow SFE protects liver from steatosis after the HFD challenge by augmenting the adipose tissue buffering capacity of the circulating plasma glucose.
Cross-talk between microglia and neurons regulates HIV latency

Despite effective antiretroviral therapy (ART), HIV-associated neurocognitive disorders (HAND) are found in nearly one-third of patients. Using a cellular co-culture system including neurons and human microglia infected with HIV (hμglia/HIV), we investigated the hypothesis that HIV-dependent neurological degeneration results from the periodic emergence of HIV from latency within microglial cells in response to neuronal damage or inflammatory signals. When a clonal hμglia/HIV population (HC69) expressing HIV, or HIV infected human primary and iPSC-derived microglial cells, were cultured for a short-term (24 h) with healthy neurons, HIV was silenced. The neuron-dependent induction of latency in HC69 cells was recapitulated using induced pluripotent stem cell (iPSC)-derived GABAergic cortical (iCort) and dopaminergic (iDopaNer), but not motor (iMotorNer), neurons. By contrast, damaged neurons induce HIV expression in latently infected microglial cells. After 48–72 h co-culture, low levels of HIV expression appear to damage neurons, which further enhances HIV expression. There was a marked reduction in intact dendrites staining for microtubule associated protein 2 (MAP2) in the neurons exposed to HIV-expressing microglial cells, indicating extensive dendritic pruning. To model neurotoxicity induced by methamphetamine (METH), we treated cells with nM levels of METH and suboptimal levels of poly (I:C), a TLR3 agonist that mimics the effects of the circulating bacterial rRNA found in HIV infected patients. This combination of agents potently induced HIV expression, with the METH effect mediated by the σ1 receptor (σ1R). In co-cultures of HC69 cells with iCort neurons, the combination of METH and poly(I:C) induced HIV expression and dendritic damage beyond levels seen using either agent alone, Thus, our results demonstrate that the cross-talk between healthy neurons and microglia modulates HIV expression, while HIV expression impairs this intrinsic molecular mechanism resulting in the excessive and uncontrolled stimulation of microglia-mediated neurotoxicity.
Whole-Genome Signatures of Selection in Sport Horses Revealed Selection Footprints Related to Musculoskeletal System Development Processes

Selective breeding has led to gradual changes at the genome level of horses. Deciphering selective pressure patterns is progressive to understand how breeding strategies have shaped the sport horse genome; although, little is known about the genomic regions under selective pressures in sport horse breeds. The major goal of this study was to shed light on genomic regions and biological pathways under selective pressures in sport horses. In this study, whole-genome sequences of 16 modern sport and 35 non-sport horses were used to investigate the genomic selective signals of sport performance, by employing fixation index, nucleotide diversity, and Tajima's D approaches. A total number of 49 shared genes were identified using these approaches. The functional enrichment analysis for candidate genes revealed novel significant biological processes related to musculoskeletal system development, such as limb development and morphogenesis, having been targeted by selection in sport breeds.
Compression-Responsive Photonic Crystals Based on Fluorine-Containing Polymers

Fluoropolymers represent a unique class of functional polymers due to their various interesting and important properties such as thermal stability, resistance toward chemicals, repellent behaviors, and their low refractive indices in comparison to other polymeric materials. Based on the latter optical property, fluoropolymers are particularly of interest for the preparation of photonic crystals for optical sensing application. Within the present study, photonic crystals were prepared based on core-interlayer-shell particles focusing on fluoropolymers. For particle assembly, the melt-shear organization technique was applied. The high order and refractive index contrast of the individual components of the colloidal crystal structure lead to remarkable reflection colors according to Bragg’s law of diffraction. Due to the special architecture of the particles, consisting of a soft core, a comparably hard interlayer, and again a soft shell, the resulting opal films were capable of changing their shape and domain sizes upon applied pressure, which was accompanied with a (reversible) change of the observed reflection colors as well. By the incorporation of adjustable amounts of UV cross-linking agents into the opal film and subsequent treatment with different UV irradiation times, stable and pressure-sensitive opal films were obtained. It is shown that the present strategy led to (i) pressure-sensitive opal films featuring reversibly switchable reflection colors and (ii) that opal films can be prepared, for which the written pattern—resulting from the compressed particles—could be fixed upon subsequent irradiation with UV light. The herein described novel fluoropolymer-containing photonic crystals, with their pressure-tunable reflection color, are promising candidates in the field of sensing devices and as potential candidates for anti-counterfeiting materials.
Mechanisms of Calorie Restriction: A Review of Genes Required for the Life-Extending and Tumor-Inhibiting Effects of Calorie Restriction

This review focuses on mechanisms of calorie restriction (CR), particularly the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis as an evolutionary conserved signal that regulates aging and lifespan, underlying the effects of CR in mammals. Topics include (1) the relation of the GH-IGF-1 signal with chronic low-level inflammation as one of the possible causative factors of aging, that is, inflammaging, (2) the isoform specificity of the forkhead box protein O (FoxO) transcription factors in CR-mediated regulation of cancer and lifespan, (3) the role for FoxO1 in the tumor-inhibiting effect of CR, (4) pleiotropic roles for FoxO1 in the regulation of disorders, and (5) sirtuin (Sirt) as a molecule upstream of FoxO. From the evolutionary view, the necessity of neuropeptide Y (Npy) for the effects of CR and the pleiotropic roles for Npy in life stages are also emphasized. Genes for mediating the effects of CR and regulating aging are context-dependent, particularly depending on nutritional states.
The Diagnosis and Treatment of Snoring in Adults.

BACKGROUND Snoring in adults is a common cause of distress for patients and their bedpartners and calls for appropriate counseling, diagnostic evaluation, and treatment. METHODS A systematic literature search in the PubMed, Cochrane Library, Web of Science Core Collection, and ClinicalTrials.gov databases was carried out in February 2018 and yielded pertinent publications from 2000 onward. The guideline was created according to the methodological requirements of the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der wissenschaft- lichen medizinischen Fachgesellschaften, AWMF). RESULTS The diagnostic evaluation of snoring is based on the history and phyical examination. In certain situations, a specialized sleep study should be performed to obtain objec- tive findings. The recommended methods of conservative treatment include, in particular, positioning therapy and weight loss. Mandibular protrusion splints can lessen snoring in suitable cases. If breathing through the nose is impaired, rhinological or rhinosurgical treatment is recommended; for certain anatomical abnormalities of the soft palate, a suitable minimally invasive surgical procedure can be considered. The level of the available evidence is low, as most of the under- lying clinical studies involved small patient groups and short follow-up. CONCLUSION In the treatment of snoring, evidence-based recommendations derived from the findings of randomized trials can be given for selected situations, yet the overall state of the evidence on many diagnostic and therapeutic tech- niques remains limited.
Relationship between scapular initial position and scapular movement during dynamic motions

Optimal scapular position and movement are necessary for normal function of the shoulder joint and it is essential to focus on scapula in the rehabilitation for shoulder disorders. The aim of this study was to discover the relationship between the scapular initial position and scapular movement during dynamic motions in healthy young men. Thirty-four men participated in this study. The scapular angles at initial position and in elevation and lowering during flexion and abduction were measured using an electromagnetic tracking device. The scapular movements from 30° to 120° during flexion and abduction were calculated. Spearman’s rank correlation coefficients were used to analyze the relationship between the scapular initial position and scapular movements. For upward rotation and posterior tilt of the scapula, there were significant positive correlations between the scapular initial position and scapular movement during flexion and abduction. For internal rotation, there were significant positive correlations, except 90° in lowering phase and 120° in both phases. While the humeral elevation increased, the correlation coefficients tended to decrease. Except for the internal rotation our results clarified the interactions between the scapular initial position and scapular movement during dynamic motions in healthy young men. The tendency of the decrease in correlation coefficient with elevation angle was shown.