Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of interval training with non-invasive ventilation in severe chronic obstructive pulmonary disease-a prospective cohort study with matched control group.

BACKGROUND In severe chronic obstructive pulmonary disease (COPD), interval training (IT) can be performed with oxygen support, which provides beneficial effect on metabolic processes, tissue perfusion, and peripheral muscle function. METHODS A prospective cohort study with matched controls was performed on patients in Budapest at the Department of Pulmonary Rehabilitation of the National Koranyi Institute of Pulmonology between January 1, 2020 and March 1, 2020. After a complex condition assessment, both case and control patients participated in a 3-week long complex pulmonary rehabilitation (PR) program that included individual training, education, nutrition, and psychological counseling. Anthropometric and functional data of patients were recorded at both the beginning and end of the PR program. Our research aimed to assess the effect of non-invasive ventilation (NIV) in patients with severe COPD who underwent IT. RESULTS A total of 18 [male/female: 10 (55.6%)/8 (44.4%)] patients were enrolled in our study. IT with NIV significantly improved the patients' 6-minute walking distance (6MWD) (m) [216.0 (211.5-233.7) vs. 274.0 (247.5-313.5); P<0.001] and quality of life [COPD Assessment Test (CAT): 29.0 (26.9-32.0) vs. 15.0 (13.5-17.5); P<0.001], [modified Medical Research Council (mMRC): 2.0 (1.5-2.0) vs. 1.0 (1.0-2.0); P=0.009]; in addition, there was a significant increase in inspiratory vital capacity (IVC) (ref%) [65.0 (63.0- 69.0) vs. 74.7 (70.5-75.0); P=0.015], in chest kinematics (cm) [3.0 (2.5-4.0) vs. 5.5 (4.0-6.5); P<0.001], work rate (Watt) [25.0 (24.0-27.0) vs. 36.0 (35.0-38.0); P<0.001], volume of oxygen consumption [VO2/kg (mL/ kg/min): 8.8 (8.5-9.2) vs. 10.3 (10.2-10.7); P<0.001], and Body-mass index, airflow Obstruction, Dyspnea, and Exercise (BODE) index [5.0 (5.0-6.7) vs. 4.0 (3.0-5.0); P=0.006], while the results of the control group were non-significant [6MWD, maximal inspiratory pressure (MIP), CAT, mMRC, BODE index]. CONCLUSIONS In severe COPD, IT with NIV is well tolerated during PR, it has a significant beneficial effect on the quality of life, improves exercise capacity and respiratory functions, decreases dynamic hyperinflation and dyspnea.
New roles for dopamine in motor skill acquisition: Lessons from primates, rodents, and songbirds.

Motor learning is a core aspect of human life, and appears to be ubiquitous throughout the animal kingdom. Dopamine, a neuromodulator with a multifaceted role in synaptic plasticity, may be a key signaling molecule for motor skill learning. Though typically studied in the context of reward-based associative learning, dopamine appears to be necessary for some types of motor learning. Mesencephalic dopamine structures are highly conserved among vertebrates, as are some of their primary targets within the basal ganglia, a subcortical circuit important for motor learning and motor control. With a focus on the benefits of cross-species comparisons, this review examines how "model-free" and "model-based" computational frameworks for understanding dopamine's role in associative learning may be applied to motor learning. The hypotheses that dopamine could drive motor learning either by functioning as a reward prediction error, through passive facilitating of normal basal ganglia activity, or through other mechanisms are examined in light of new studies using humans, rodents, and songbirds. Additionally, new paradigms that could enhance our understanding of dopamine's role in motor learning by bridging the gap between the theoretical literature on motor learning in humans and other species are discussed.
Novel Mycoviruses Discovered in the Mycovirome of a Necrotrophic Fungus

The results obtained here have expanded our knowledge of mycoviral diversity, horizontal transfers, and putative cross-kingdom events. To date, this study presents the most extensive and wide diversity collection of mycoviruses infecting the necrotrophic fungus B. cinerea. ABSTRACT Botrytis cinerea is one of the most important plant-pathogenic fungus. Products based on microorganisms can be used in biocontrol strategies alternative to chemical control, and mycoviruses have been explored as putative biological agents in such approaches. Here, we have explored the mycovirome of B. cinerea isolates from grapevine of Italy and Spain to increase the knowledge about mycoviral diversity and evolution, and to search for new widely distributed mycoviruses that could be active ingredients in biological products to control this hazardous fungus. A total of 248 B. cinerea field isolates were used for our metatranscriptomic study. Ninety-two mycoviruses were identified: 62 new mycoviral species constituting putative novel viral genera and families. Of these mycoviruses, 57 had a positive-sense single-stranded RNA (ssRNA) genome, 19 contained a double-stranded RNA (dsRNA) genome, 15 had a negative-sense ssRNA genome, and 1 contained a single-stranded DNA (ssDNA) genome. In general, ssRNA mycoviruses were widely distributed in all sampled regions, the ssDNA mycovirus was more frequently found in Spain, and dsRNA mycoviruses were scattered in some pools of both countries. Some of the identified mycoviruses belong to clades that have never been found associated with Botrytis species: Botrytis-infecting narnaviruses; alpha-like, umbra-like, and tymo-like ssRNA+ mycoviruses; trisegmented ssRNA− mycovirus; bisegmented and tetrasegmented dsRNA mycoviruses; and finally, an ssDNA mycovirus. Among the results obtained in this massive mycovirus screening, the discovery of novel bisegmented viruses, phylogenetically related to narnaviruses, is remarkable. IMPORTANCE The results obtained here have expanded our knowledge of mycoviral diversity, horizontal transfers, and putative cross-kingdom events. To date, this study presents the most extensive and wide diversity collection of mycoviruses infecting the necrotrophic fungus B. cinerea. The collection included all types of mycoviruses, with dsRNA, ssRNA+, ssRNA–, and ssDNA genomes, most of which were discovered here, and some of which were previously reported as infecting B. cinerea or other plant-pathogenic fungi. Some of these mycoviruses are reported for the first time here associated with B. cinerea, as a trisegmented ssRNA– mycovirus and as an ssDNA mycovirus, but even more remarkablly, we also describe here four novel bisegmented viruses (binarnaviruses) not previously described in nature. The present findings significantly contribute to general knowledge in virology and more particularly in the field of mycovirology.
Spectroscopic and Potentiometric Study of 2,3-Dihydroxybenzoic Acid and its Complexation with La(III) Ion

The equilibrium reactions between 2,3-dihydroxybenzoic acid (2,3-DHBA) and Lanthanum(III) ion was investigated in an aqueous medium of 0.1M ionic strength and 25±1 °C by potentiometric and spectrophotometric methods. Formation of complexes of the types ML and ML2H were observed and their stability constants were reported. The ligand showed competitive coordination mode in solution: in acidic medium, 2,3-DHBA showed preference to salicyclate type whereas catecholate type in basic media.
Inherited Variants in SCARB1 Cause Severe Early-Onset Coronary Artery Disease

Supplemental Digital Content is available in the text. Rationale: Coronary artery disease (CAD) is a pervasive and critical health care problem. Elevated high-density lipoprotein-associated cholesterol (HDL-C) is associated with improved atherosclerotic cardiovascular disease outcomes on a population level, but clinical trials aimed at HDL-C elevation have not succeeded in improving atherosclerotic cardiovascular disease event risk. Nevertheless, human variants in the HDL receptor, encoded by SCARB1, are associated with dyslipidemia, suggesting that HDL metabolism, not HDL-C, is a suitable target for therapy. However, variants in SCARB1 have never been directly attributed to CAD by Mendelian inheritance. Objective: To determine if compound heterozygous variants in SCARB1 cause disease in 2 brothers with severe, early-onset CAD. Methods and Results: Using whole exome sequencing, we have identified rare, compound heterozygous variants in SCARB1 that segregate with severe, premature CAD, following patterns of Mendelian inheritance. Using induced pluripotent stem cell–derived hepatocyte-like cells from the proband, we discovered the maternal variant (c.754_755delinsC) to be the first identified SCARB1 null allele, characterized by the absence of RNA and protein expression. Further, we demonstrate that the variant on the paternal allele (c.956G>T [p.G319V]) results in decreased cholesterol uptake, decreased SR-BI:HDL binding, and increased affinity for SR-BI dimerization. Finally, we generated a p.G319V knock-in mouse model that displays nearly 100% homozygous lethality and elevated plasma cholesterol in heterozygous animals, confirming pathogenicity of this variant. Conclusions: In summary, our data provide the first molecular mechanism to show the Mendelian inheritance of CAD as a result of human SCARB1 variants. The rarity of these variants supports pathogenicity in this family. Furthermore, SR-BI p.G319V, which has previously been reported benign in the context of heterozygosity, was uniquely presented alongside a null allele, demonstrating the disease-contributing capability of loss-of-function SCARB1 variants within the population.
Improving Medication Adherence Through Adaptive Digital Interventions (iMedA) in Patients With Hypertension: Protocol for an Interrupted Time Series Study

Background There is a strong need to improve medication adherence (MA) for individuals with hypertension in order to reduce long-term hospitalization costs. We believe this can be achieved through an artificial intelligence agent that helps the patient in understanding key individual adherence risk factors and designing an appropriate intervention plan. The incidence of hypertension in Sweden is estimated at approximately 27%. Although blood pressure control has increased in Sweden, barely half of the treated patients achieved adequate blood pressure levels. It is a major risk factor for coronary heart disease and stroke as well as heart failure. MA is a key factor for good clinical outcomes in persons with hypertension. Objective The overall aim of this study is to design, develop, test, and evaluate an adaptive digital intervention called iMedA, delivered via a mobile app to improve MA, self-care management, and blood pressure control for persons with hypertension. Methods The study design is an interrupted time series. We will collect data on a daily basis, 14 days before, during 6 months of delivering digital interventions through the mobile app, and 14 days after. The effect will be analyzed using segmented regression analysis. The participants will be recruited in Region Halland, Sweden. The design of the digital interventions follows the just-in-time adaptive intervention framework. The primary (distal) outcome is MA, and the secondary outcome is blood pressure. The design of the digital intervention is developed based on a needs assessment process including a systematic review, focus group interviews, and a pilot study, before conducting the longitudinal interrupted time series study. Results The focus groups of persons with hypertension have been conducted to perform the needs assessment in a Swedish context. The design and development of digital interventions are in progress, and the interventions are planned to be ready in November 2020. Then, the 2-week pilot study for usability evaluation will start, and the interrupted time series study, which we plan to start in February 2021, will follow it. Conclusions We hypothesize that iMedA will improve medication adherence and self-care management. This study could illustrate how self-care management tools can be an additional (digital) treatment support to a clinical one without increasing burden on health care staff. Trial Registration ClinicalTrials.gov NCT04413500; https://clinicaltrials.gov/ct2/show/NCT04413500 International Registered Report Identifier (IRRID) DERR1-10.2196/24494
One-year outcome using cyanoacrylate glue to ablate truncal vein incompetence: A Singapore VenaSeal™ real-world post-market evaluation study (ASVS)

Objective We present 12 months efficacy data from A Singapore VenaSeal™ real-world post-market evaluation Study (ASVS), a prospective single-arm Asian population registry aimed to evaluate cyanoacrylate glue (CAG) closure of refluxing truncal veins. Methods Duplex ultrasound was used to assess truncal vein closure. The revised Venous Clinical Severity Score (rVCSS) and three quality of life (QoL) questionnaires were completed to assess improvement in venous disease symptoms. Results 90/100 (90%) patients (136 legs; 140 truncal veins) completed evaluation at 6- and 12 months. The truncal closure rates at 6 and 12 months were 139/140 (99.3%) and 137/140 (97.9%), respectively. rVCSS and QoL questionnaires scores were sustained from the 3 to 12 months visits, although there were no futher significant improvement. No serious adverse events were reported between 3 and 12 months. Conclusions CAG remains a safe and efficacious venous ablative technology at 12 months and is associated with a high rate of target vein occlusion and sustained QoL improvement.
Three-Dimensional Morphology of Natural Snow Crystals

We reveal that the external form of a snow crystal consists of the combination of one basal plane and an intricate 3D rounded surface. Snow crystals have various morphologies including needles, plates, sectors, and dendrites. Many of these snow-crystal shapes are planar, and thus are often treated as a two-dimensional or a faceted crystal consisting of only basal and prism planes despite their complex three-dimensional (3D) features. In this study, we directly measure the 3D morphology of natural snow crystals using a Michelson interferometer combined with a reflecting microscope. The 3D morphologies of both stellar with sectors and dendrite are analyzed from the distribution of interference fringes observed on their surfaces. Additionally, dendrite crystal has a thickness of only several micrometers at the middle of the branch and no prism face. On the nonbasal surfaces, there are ridges and sub-ridges, similar to those in mountain topography.
Scalp Melanoma Treated with Ipilimumab in Elderly Patient: A Complete Response to Treatment—Case Report

Melanoma is a malignant neoplasm that affects the melanocytes. Its treatment is based on cancer staging. In immunotherapy, it can be pointed out the ipilimumab, used in the systemic therapy for unresectable and/or metastatic melanoma in the first or the second line treatment with increased survival. However, limiting toxicity and the low complete response discourage its use in the elderly patients. The aim of this study is to report the case of an 83-year-old man, white, with scalp melanoma measuring 3.5 cm in its major axis. After two resections was verified that the deep margin was involved, making the lesions unresectable. The evaluation of distant metastasis, by skull, chest and abdomen CT-scan (computed tomography-scan), was performed and did not detect the presence of any metastatic foci. The patient underwent the first cycle of chemotherapy with DTIC (dacarbazine) protocol. After the first cycle, the medication was discontinued due to significant myelotoxicity and Grade 3 thrombocytopenia. Underwent second line treatment with ipilimumab by four cycles. After this, the patient follow with complete local response, asymptomatic, with no signs of local recurrence or distant metastasis site, and no limiting toxicity during and after a year of treatment with ipilimumab. Thus, it is possible to suggest that the use of ipilimumab isolatedly as a second line treatment may have a good response even in elderly patients.
A qualitative study to assess perceptions, barriers, and motivators supporting smokeless tobacco cessation in the US fire service

While firefighters currently have low smoking rates, rates of smokeless tobacco (SLT) use among this population are remarkably high and substantially greater than similar occupational groups, and the general population. This study explored determinants associated with SLT use, barriers to cessation, and motivators for SLT cessation in the fire service. Key informant interviews were conducted in 23 career firefighters who were current (n = 14) and former (n = 9) SLT users from across the U.S. Discussions were recorded and independently coded according to questions and themes. Major themes that developed among firefighters regarding SLT use determinants included positive perceptions of SLT products, social influences from their peers and family members, acceptability of SLT use in the fire service, and a coping resource for job stress. Firefighters discussed several barriers to SLT cessation, including intrapersonal barriers such as SLT use habits and its dependency, concerns about withdrawal symptoms; and social-environmental barriers including lack of support from health and other services providers, and lack of enforcement of existing tobacco policies regarding SLT use. Firefighters also mentioned both internal and external motivators for cessation. Internal motivators included self-motivation and their health concerns while external motivators included friends and family support, incentives or rewards, and price of SLT products. Findings provide unique perspectives from firefighters on factors that influence SLT use and barriers and motivators to SLT cessation. These are insufficiently assessed and considered by the fire service organizations and their health care providers. Thus, the organizations must understand these issues in order to mitigate barriers and motivate the personnel to quit using SLT. Information gained from firefighters who were current and former SLT users can be used to develop an effective, culturally-tailored intervention that is acceptable to fire service personnel.
WDNE: an integrative graphical model for inferring differential networks from multi-platform gene expression data with missing values

The mechanisms controlling biological process, such as the development of disease or cell differentiation, can be investigated by examining changes in the networks of gene dependencies between states in the process. High-throughput experimental methods, like microarray and RNA sequencing, have been widely used to gather gene expression data, which paves the way to infer gene dependencies based on computational methods. However, most differential network analysis methods are designed to deal with fully observed data, but missing values, such as the dropout events in single-cell RNA-sequencing data, are frequent. New methods are needed to take account of these missing values. Moreover, since the changes of gene dependencies may be driven by certain perturbed genes, considering the changes in gene expression levels may promote the identification of gene network rewiring. In this study, a novel weighted differential network estimation (WDNE) model is proposed to handle multi-platform gene expression data with missing values and take account of changes in gene expression levels. Simulation studies demonstrate that WDNE outperforms state-of-the-art differential network estimation methods. When applied WDNE to infer differential gene networks associated with drug resistance in ovarian tumors, cell differentiation and breast tumor heterogeneity, the hub genes in the estimated differential gene networks can provide important insights into the underlying mechanisms. Furthermore, a Matlab toolbox, differential network analysis toolbox, was developed to implement the WDNE model and visualize the estimated differential networks.
Continuous Analysis of Marathon Running Using Inertial Sensors: Hitting Two Walls?

Abstract Marathon running involves complex mechanisms that cannot be measured with objective metrics or laboratory equipment. The emergence of wearable sensors introduced new opportunities, allowing the continuous recording of relevant parameters. The present study aimed to assess the evolution of stride-by-stride spatio-temporal parameters, stiffness, and foot strike angle during a marathon and determine possible abrupt changes in running patterns. Twelve recreational runners were equipped with a Global Navigation Satellite System watch, and two inertial measurement units clamped on each foot during a marathon race. Data were split into eight 5-km sections and only level parts were analyzed. We observed gradual increases in contact time and duty factor as well as decreases in flight time, swing time, stride length, speed, maximal vertical force and stiffness during the race. Surprisingly, the average foot strike angle decreased during the race, but each participant maintained a rearfoot strike until the end. Two abrupt changes were also detected around km 25 and km 35. These two breaks are possibly due to the alteration of the stretch-shortening cycle combined with physiological limits. This study highlights new measurable phenomena that can only be analyzed through continuous monitoring of runners over a long period of time.
Elevated temperatures accelerate the formation of toxic amyloid fibrils of hen egg‐white lysozyme

Abstract The formation of amyloid fibrils is critical for neurodegenerative diseases. Some physiochemical conditions can promote the conversion of proteins from soluble globular shapes into insoluble well‐organized amyloid fibrils. The aim of this study was to investigate the effect of temperatures on amyloid fibrils formation in vitro using the protein model of hen egg‐white lysozyme (HEWL). The HEWL fibrils were prepared at temperatures of 37, 45, 50 and 57°C in glycine solution of pH 2.2. Under transmission electron microscopy, we found the well‐organized HEWL amyloid fibrils at temperatures of 45, 50 and 57°C after 10 days of incubation. Thioflavin T and Congo red florescence assays confirmed that the formation and growth of HEWL fibrils displayed a temperature‐dependent increase, and 57°C produced the most amounts. Meanwhile, the surface hydrophobicity of aggregates was greatly increased by ANS binding assay, and β‐sheet contents by circular dichroism analysis were increased by 17.8%, 22.0% and 34.9%, respectively. Furthermore, the HEWL fibrils formed at 57°C caused significant cytotoxicity in SH‐SY5Y cells after 48 hr exposure, and the cell viability determined by MTT assay was decreased, with 81.35 ± 0.29% for 1 μM, 61.45 ± 2.62% for 2 μM, and 11.58 ± 0.39% (p < .01) for 3 μM. Nuclear staining results also confirmed the apoptosis features. These results suggest that the elevated temperatures could accelerate protein unfolding of the native structure and formation of toxic amyloid fibrils, which can improve understanding the mechanisms of the unfolding and misfolding process of prion protein.