Miracle-dz/UniFAR-FTUs huggingface dataset:
Limits to Submaximal and Maximal Exercise in Patients with Hypertrophic Cardiomyopathy.

BACKGROUND Patients with hypertrophic cardiomyopathy (HCM) often have reduced exercise capacity, and it is unclear whether cardiovascular regulation during exercise is intact in these patients. We aimed to determine the relationship between cardiac output (Q̇c) and oxygen uptake (V̇O2), and stroke volume (SV) reserve in HCMcompared to healthy participants and participants with left ventricular hypertrophy (LVH) but not HCM. METHODS Sixteen patients with HCM (48±7 years, 44% female), 16 participants with LVH (49±5 years, 44% female), and 61 healthy controls (CON: 52±5 years, 52% female) completed submaximal steady-state treadmill exercise followed by a maximal exercise test. V̇O2, Q̇c,SV and arterio-venous oxygen difference were measured during rest and exercise, and Q̇c/V̇O2 slopes were constructed. RESULTS The Q̇c/V̇O2 slopewas blunted in HCM compared to CON and LVH (HCM 4.9±0.7 vs. CON 5.5± 1.0 [P = 0.027], vs LVH 6.0±1.0AU [P = 0.002]) and participants with HCM had a lower SV reserve (HCM 53±33%, controls 83±33%, LVH 82±22%; HCM vs. controls P = 0.002; HCM vs. LVH P = 0.015). Despite a blunted Q̇c/V̇O2 slope, 75% of patients with HCM achieved ≥80% predicted V̇O2max by augmenting a-vO2 difference at maximal exercise (16.0±0.8 mL/100mL vs 13.8±2.7 mL/100mL, P = 0.021). CONCLUSIONS Patients with HCM do not appropriately match Q̇c to metabolic demand, primarily due to inadequate stroke volume augmentation. Despite this central limitation, many patients achieve normal exercise capacities by significantly increasing peripheral oxygen extraction.
Body Mass Index Trajectories, Weight Gain, and Risks of Liver and Biliary Tract Cancers

Abstract Background Little is known about the role of early obesity or weight change during adulthood in the development of liver cancer and biliary tract cancer (BTC). Methods We investigated the associations of body mass index (BMI) and weight trajectories with the risk of liver cancer and BTC in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. BMI was self-reported at ages 20 years and 50 years and at enrollment. BMI trajectories were determined using latent class growth models. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results During a median follow-up of 15.9 years among 138 922 participants, 170 liver cancer and 143 BTC cases were identified. Compared with those whose BMI did not exceed 25 kg/m2, participants with BMI exceeding 25 kg/m2 at age 20 years had increased risks of liver cancer (HR = 2.03, 95% CI = 1.26 to 3.28) and BTC (HR = 1.99, 95% CI = 1.16 to 3.39). Compared with participants maintaining normal BMI until enrollment, trajectory of normal weight at age 20 years to obesity at enrollment was associated with increased risk for liver cancer (HR = 2.50, 95% CI = 1.55 to 4.04) and BTC (HR = 1.83, 95% CI = 1.03 to 3.22). Compared with adults with stable weight (±5 kg) between age 20 years and 50 years, weight gain of 20 kg and greater between ages 20 years and 50 years had higher hazard ratios of 2.24 (95% CI = 1.40 to 3.58) for liver cancer and 1.86 (95% CI = 1.12 to 3.09) for BTC. Conclusions Being overweight and/or obese at age 20 years and BMI trajectories that result in being overweight and/or obese may increase risk for both liver cancer and BTC.
What Are Gamma-Ray Bursts?

Gamma-ray bursts are the brightest--and, until recently, among the least understood--cosmic events in the universe. Discovered by chance during the cold war, these evanescent high-energy explosions confounded astronomers for decades. But a rapid series of startling breakthroughs beginning in 1997 revealed that the majority of gamma-ray bursts are caused by the explosions of young and massive stars in the vast star-forming cauldrons of distant galaxies. New findings also point to very different origins for some events, serving to complicate but enrich our understanding of the exotic and violent universe. What Are Gamma-Ray Bursts? is a succinct introduction to this fast-growing subject, written by an astrophysicist who is at the forefront of today's research into these incredible cosmic phenomena. Joshua Bloom gives readers a concise and accessible overview of gamma-ray bursts and the theoretical framework that physicists have developed to make sense of complex observations across the electromagnetic spectrum. He traces the history of remarkable discoveries that led to our current understanding of gamma-ray bursts, and reveals the decisive role these phenomena could play in the grand pursuits of twenty-first century astrophysics, from studying gravity waves and unveiling the growth of stars and galaxies after the big bang to surmising the ultimate fate of the universe itself. What Are Gamma-Ray Bursts? is an essential primer to this exciting frontier of scientific inquiry, and a must-read for anyone seeking to keep pace with cutting-edge developments in physics today.
Phenomenology of supersymmetric models with anomalous symmetries $U(1)_{H}$

We adopt in this thesis a new approach by assuming a set of $H$-charges that give rise to a self-consistent model of $R$-parity breaking and baryon-number violation. As a consequence of our $H$-charge assignments, it is not possible to generate a Majorana mass term for left-handed neutrinos. However, a neutrino Dirac matrix can be built after the introduction of right-handed neutrinos with proper $H$-charges. We also show that by adding a second flavon field with fractional charge, it is possible to build a Majorana neutrino mass matrix. In both cases an anarchical matrix. The consequences for collider physics are mentioned. We will generalize the mechanism of obtain $R$--parity from an horizontal symmetry to the context of $SU(5)$ SUSY $+ \widehat{N}$, and computable group theoretical coefficients that, at leading order, determine the structure of the neutrino mass matrix in a parameter independent way.
Sodium Pyruvate Nasal Spray Reduces the Severity of Nasal Inflammation and Congestion in Patients with Allergic Rhinitis

Background: As an anti-inflammatory and antioxidant, sodium pyruvate significantly reduces inflammatory cytokines and oxygen radicals such as interleukin (IL) IL-6, IL-8, Monocyte Chemoattractant Protein-1, and hydrogen peroxide. Thus, sodium pyruvate holds promise as a treatment for many respiratory diseases, including allergic rhinitis (AR). Novel treatments for AR are needed as current medications, including steroids, often fail to treat severe symptoms. Methods: The data from five human clinical studies were analyzed to determine the effect of 20 mM sodium pyruvate nasal spray (N115) in patients with AR. Nasal inflammation scores were compared to a placebo control or a no-treatment baseline control. Three studies were open-labeled and two were appropriately blinded to both patients and clinicians using computer randomization of subjects. Results: The intranasal administration of sodium pyruvate significantly improved nasal inflammation scores in all five clinical trials of patients with AR (p < 0.0001 in all trials). Conclusions: These results give credence to the overall ability of sodium pyruvate, administered by nasal spray, to treat inflammation of the nasal airways.
Biological activities and safety data of kojic acid and its derivatives: A review

Kojic acid presents a variety of applications for human use, especially as a depigmenting agent. Its derivatives are also proposed in order to prevent chemical degradation, prevent adverse effects and improve efficacy. The aim of this study was to peer review the current scientific literature concerning the biological activities and safety data of kojic acid or its derivatives, aiming at human use and trying to elucidate the action mechanisms. Three different databases were assessed, and the word “kojic” was crossed with “toxicity,” “adverse effect,” “efficacy,” “effect,” “activity” and “safety. ” Articles were selected according to pre‐defined criteria. Besides the depigmenting activity, kojic acid and derivatives can act as antioxidant, antimicrobial, anti‐inflammatory, radioprotector, anticonvulsant and obesity management agents, and present potential as antitumor substances. Depigmenting activity is due to the molecules, after penetrating the cell, binding to tyrosinase active site, regulating melanogenesis factors, leucocytes modulation and free radical scavenging activity. Hence, polarity, size and ligands are also important factors for activity. Kojic acid and derivatives present cytotoxicity to some cancerous cell lines, including melanoma, hepatocellular carcinoma, ovarian cancer, breast cancer and colon cancer. Regarding safety, kojic acid or its derivatives are safe molecules for human use in the concentrations tested. Kojic acid and its derivatives have great potential for cosmetic, pharmaceutical and medical applications.
miR-15b-5p REGULATES THE NLRP3 INFLAMMASOME SIGNAL THROUGH TARGETING SIRT3 TO REGULATE HYPOXIA/REOXYGENATION-INDUCED CARDIOMYOCYTE PYROPTOSIS PROCESS

ABSTRACT Hypoxia/reoxygenation (H/R) induces pyroptosis in the setting of acute myocardial infarction (AMI). Previous studies have shown that the expression of the miR-15 family is stimulated in myocardial ischemia–reperfusion injury or H/R-induced cardiomyocyte injury, and miR-15 is a promoter of cardiac ischemia–reperfusion or H/R injury. However, whether miR-15b-5p regulates H/R injury and cardiomyocyte pyroptosis and its mechanism still need to be further clarified. Bioinformatics analysis elicited that SIRT3 was the downstream regulatory target gene of miR-15b-5p. SIRT3 has been shown to participate in the regulation of pyroptosis by negatively regulating the NLRP3 inflammasome pathway. Therefore, we hypothesized that miR-15b-5p targets SIRT3 and activated the NLRP3 inflammasome pathway to promote H/R-induced cardiomyocyte pyroptosis. We first show that H/R increases miR-15b-5p in rat cardiomyocytes H9C2. Next, we tested the effects of inhibition of miR-15b-5p or overexpression of SIRT3. We found that miR-15b-5p downregulation or SIRT3 overexpression could reverse the H/R-induced pyroptosis. Furthermore, silencing SIRT3 antagonized the protective effect of miR-15b-5p downregulation on H9C2 cells. NLRP3 inhibitor MCC950 annulled the previously mentioned antagonistic effect of silencing SIRT3 on the protection of miR-15b-5p downregulation against pyroptosis. We then used a rat AMI model to analyze myocardial infarction area by triphenyl tetrazolium chloride staining and assess serum cardiac troponin T level by ELISA and found that miR-15b-5p silencing reduced AMI injury in rats. Collectively, these results suggest that miR-15b-5p increase H/R-induced pyroptosis in cardiomyocytes by targeting SIRT3 and activating the NLRP3 inflammasome.
The evolutionary network of whiptail lizards reveals predictable outcomes of hybridization

Hybridization between diverging lineages is associated with the generation and loss of species diversity, introgression, adaptation, and changes in reproductive mode, but it is unknown when and why it results in these divergent outcomes. We estimate a comprehensive evolutionary network for the largest group of unisexual vertebrates and use it to understand the evolutionary outcomes of hybridization. Our results show that rates of introgression between species decrease with time since divergence and suggest that species must attain a threshold of evolutionary divergence before hybridization results in transitions to unisexuality. Rates of hybridization also predict genome-wide patterns of genetic diversity in whiptail lizards. These results distinguish among models for hybridization that have not previously been tested and suggest that the evolutionary outcomes can be predictable. Description Divergent species create distinct hybrids Hybridization between species is common in many taxa and can lead to a variety of outcomes. Hybrids can backcross with parent lineages, increasing genetic diversity, or they can develop into new species. In squamate lizards, hybridization can create polyploid species with unisexual reproduction (parthenogenesis). Barley et al. used North American whiptail lizards, which include 15 recognized unisexual species, as a model system to examine the possible outcomes of hybridization. Phylogenetic analyses showed that divergence time between parents predicts the effects of their hybridization. Hybrid speciation and unisexuality were more common with more time since the parent species diverged from a common ancestor. —BEL Evolutionary time since divergence predicts outcomes of hybridization in a diverse lizard clade.
The role of internal fixation in the treatment of femoral head necrosis with ipsilateral hip fracture

Whether internal fixation or hip arthroplasty is the most appropriate initial treatment for patients with ipsilateral hip fracture and osteonecrosis of the femoral head remains unknown. In this study, the prognoses of patients who underwent internal fixation or hip arthroplasty were analyzed and compared to explore the role of internal fixation in treating such patients. We retrospectively reviewed 69 patients diagnosed with osteonecrosis of the femoral head and ipsilateral hip fracture from 1999 to 2018. They were divided into the hip arthroplasty or internal fixation group. The visual analog scale and Harris score were used. The incidence of complications and the conversion to arthroplasty were also investigated to further explore the role of internal fixation. Male patients (male/female: 25/31 vs 20/38, P = .015), younger patients (average age: 46.80 ± 13.14 vs 61.07 ± 15.61, P < .001), and patients with femoral neck fractures (fracture type, femoral neck/trochanter: 21/31 vs 12/38, P = .003) were more likely to receive 1-stage hip arthroplasty. Of 38 patients undergoing internal fixation, fracture nonunion was identified in 9, and progression of osteonecrosis was identified in 16. Meanwhile, conversion to secondary hip arthroplasty occurred in 13 patients. Four independent risk factors for conversion to secondary hip arthroplasty were identified: age of ≤60 years (odds ratio [OR] = 9.786, 95% confidence interval [CI] = 2.735–35.015), male sex (OR = 6.790, 95% CI = 1.718–26.831), collapse of the femoral head before injury (OR = 7.170, 95% CI = 2.004–25.651), and femoral neck fracture (OR = 8.072, 95% CI = 2.153–30.261). A new scoring system was constructed for predicting conversion to hip arthroplasty in patients undergoing internal fixation treatment. A cutoff of ≤2 points indicated low risk for conversion, 3 to 4 points indicated moderate risk, and ≥5 points indicated high risk. Patients who underwent internal fixation had worse prognoses than those who underwent 1-stage hip arthroplasty. However, in this study, hip arthroplasty conversion did not occur in most patients who received internal fixation. Using the new scoring system to identify patients who may require conversion to replacement may help make appropriate patient management and clinical decisions.
Comparative effectiveness of group v. individual trauma-focused treatment for posttraumatic stress disorder in veterans

Abstract Background Cognitive processing therapy (CPT) and prolonged exposure (PE) delivered in an individual setting are efficacious and effective treatments for veterans with posttraumatic stress disorder (PTSD). Group CPT has been shown to be less efficacious than individual CPT, however, evidence regarding real-world effectiveness is limited. Methods We conducted a retrospective, observational, comparative effectiveness study including veterans that received at least eight sessions of group CPT, individual CPT, or individual PE, and were discharged from PTSD residential treatment at the Department of Veterans Affairs between 1 October 2015, and 30 September 2020. PTSD symptom severity was assessed with the PTSD Checklist for DSM-5 (PCL-5) and treatments delivered in a group (CPT) or individual (CPT or PE) setting were compared at discharge and 4-month post-discharge follow-up. Results Of 6735 veterans, 3888 [653 women (17%), median (IQR) age 45 (35–55) years] received individual and 2847 [206 women (7.2%), median (IQR) age 42 (34–54)] received group therapy. At discharge, improvement in PTSD severity was statistically greater among those treated individually (mean difference on the PCL-5, 2.55 (95% CI 1.61–3.49); p = <0.001]. However, the difference was smaller than the minimal clinically important difference of 7.9 points. The groups did not differ significantly at 4-month follow-up [mean difference on the PCL-5, 0.37 (95% CI −0.86 to 1.60); p = 0.551]. Conclusion Group CPT was associated with a slightly smaller reduction of PTSD symptom severity than individual CPT or PE in veterans at the end of residential treatment. There were no differences at 4-month follow-up.
Modelling the microelimination of chronic hepatitis C in the canton of Bern, Switzerland: Reaching the Swiss Hepatitis Strategy goals despite the impact of the COVID 19 pandemic

Aims of the study Since 2014, the Swiss Hepatitis Strategy (SHS) has targeted the elimination of Hepatitis C Virus (HCV) in Switzerland. The epidemiology of HCV is diverse across Swiss cantons, therefore cantonal-level screening and treatment strategies should be developed. This study aimed to identify scenarios to achieve HCV elimination in the canton of Bern by 2030. Methods A preexisting Markov disease burden model was populated with data for Bern, and used to forecast the current and future prevalence of HCV, annual liver-related deaths (LRDs), and incidence of hepatocellular carcinoma and decompensated cirrhosis until 2030. Scenarios were developed to assess the current standard of care and potential long-term impact of the COVID-19 crisis on the HCV infected population. Additionally, potential scenarios for achieving the WHO 2030 targets and the SHS 2025 and 2030 targets (reduction of new cases of HCV, HCV-related mortality and viremic HCV cases) were identified. Results In 2019, there were an estimated 4,600 (95% UI: 3,330–4,940) viremic infections in the canton of Bern and 57% (n = 2,600) of viremic cases were diagnosed. This modelling forecasted a 10% increase in LRDs (28 in 2020 to 31 in 2030) with the current standard of care and a 50% increase in LRDs in a scenario assuming long-term delays. To achieve the WHO and SHS targets, the canton of Bern needs to increase the annual number of patients diagnosed (from 90 in 2019 to 250 per year in 2022–2024 [WHO], or 500 per year in 2022–2025 [SHS]) and treated (from 130 in 2019 to 340 per year in 2022–2024 [WHO] or 670 per year in 2022–2025 [SHS]). Conclusions The SHS goals and the WHO targets for HCV elimination can be achieved in the Swiss canton of Bern by 2030; however, not at the current pace of screening, linkage to care and treatment.
Preterm Infants on Early Solid Foods and Vitamin D Status in the First Year of Life—A Secondary Outcome Analysis of a Randomized Controlled Trial

Preterm birth places infants at high risk for mineral and micronutrient deficiencies important for bone health. The aim of this study was to examine whether two timepoints for the introduction of solid foods in preterm infants have an impact on vitamin D status in the first year of life. This is a secondary outcome analysis of a prospective, randomized trial on very low birth weight (VLBW) infants, randomized to an early (10–12th week corrected age) or a late (16–18th week corrected age) complementary-feeding group. Vitamin D status was assessed by blood samples taken at 6 weeks, 6, and 12 months corrected age. In total, 177 infants were randomized (early group: n = 89, late group: n = 88). There was a tendency toward lower levels of serum 25-OH-vitamin D in the early group throughout the first year of life (p = not significant (n.s.)); no differences were detected in the other parameters. At 6 months corrected age, infants of the early group had a significantly higher incidence of vitamin D deficiency. The timepoint of the introduction of solid foods had no impact on the serum 25-OH-vitamin D levels and other parameters important for bone health but showed a tendency toward lower levels in the early-feeding group.
Opioid Use Increases the Rate of Pseudarthrosis and Revision Surgery in Patients Undergoing Anterior Cervical Discectomy and Fusion

Study Design Retrospective Cohort Objectives To (1) quantify the risk opioids impart on pseudarthrosis development, (2) analyze the effect of pseudarthrosis on clinical outcomes, and (3) identify if the amount of opioids prescribed are predictive of pseudarthrosis revision. Methods Patients who underwent ACDF at a single institution between 2017-2019 were retrospectively identified. Postoperative dynamic cervical spine radiographs were reviewed to assess fusion status. Logistic regression models measured the effect of morphine milligram equivalents (MME) prescribed on the likelihood of pseudarthrosis development. Receiver operating characteristic (ROC) curves were generated to predict the probability of surgical revision based on MME prescribed. Results Of 298 included patients, an average of 2.01 ± 0.82 levels were included in the construct and 121 (40.9%) patients were diagnosed with a pseudarthrosis. However, only 14 (4.7%) required a pseudarthrosis revision. Patients requiring pseudarthrosis revision had worse one-year postoperative Δ PCS-12 (−1.70 vs. 7.58, P = 0.004), Δ NDI (3.33 vs. −15.26, P = 0.002), and Δ VAS Arm (2.33 vs. −2.48, P = .047). Multivariate logistic regression analyses found the three-month postoperative (OR=1.00, P = .010), one-year postoperative (OR=1.001, P = 0.025), and combined pre- and postoperative MME (OR=1.000, P = .035) increased the risk of pseudarthrosis. ROC analysis identified cutoff values to predict pseudarthrosis revision at 90.00 (area under the curve (AUC): 0.693, confidence interval (CI): 0.554-0.832), 132.86 (0.710, CI: 0.589-0.840), 224.76 (0.687, CI: 0.558-0.817) and 285.00 (0.711, CI: 0.585-0.837) MME in the preoperative, three-month postoperative, one-year postoperative, and combined pre-and postoperative period. Conclusion Increased prescription of opioid medications following ACDF procedures may increase the risk of pseudarthrosis development and revision surgery. Level of Evidence Therapeutic Level III
Théorie générale des jeux à $n$ personnes

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Two-pore channels: going with the flows

In recent years, our understanding of the structure, mechanisms and functions of the endo-lysosomal TPC (two-pore channel) family have grown apace. Gated by the second messengers, NAADP and PI(3,5)P2, TPCs are an integral part of fundamental signal-transduction pathways, but their array and plasticity of cation conductances (Na+, Ca2+, H+) allow them to variously signal electrically, osmotically or chemically. Their relative tissue- and organelle-selective distribution, together with agonist-selective ion permeabilities provides a rich palette from which extracellular stimuli can choose. TPCs are emerging as mediators of immunity, cancer, metabolism, viral infectivity and neurodegeneration as this short review attests.
Ten year age‐ and sex‐specific temporal trends in incidence and prevalence of heart failure in Västra Götaland, Sweden

Heart failure (HF) is predominantly a disorder of the elderly. During the last decades, cardiovascular primary and secondary prevention and life expectancy have improved. Accordingly, trends in incidence and prevalence of HF are dynamic and may differ over time by age and gender. We aim to investigate the overall and age‐specific and sex‐specific trends, in incidence, prevalence, and the proportion with co‐morbidities of HF over a 10 year period in Region Västra Götaland, Sweden.