Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical Characteristics of an Internet-Based Cohort of Patient-Reported Diagnosis of Granulomatosis With Polyangiitis and Microscopic Polyangiitis: Observational Study

Background Utilizing the traditional centers of excellence approach to conduct clinical trials involving rare diseases remains challenging. Patient-based registries have been shown to be both feasible and valid in several other diseases. Objective This report outlines the clinical characteristics of a large internet registry cohort of participants with a self-reported diagnosis of granulomatosis with polyangiitis or microscopic polyangiitis. Methods Patients with a self-reported diagnosis of granulomatosis with polyangiitis or microscopic polyangiitis in an internet-based prospective longitudinal cohort (from the Vasculitis Patient-Powered Research Network) were included. Data on symptoms, diagnostic testing, and treatment were collected using standardized questionnaires. Results The study compared patients with granulomatosis with polyangiitis (n=762) and patients with microscopic polyangiitis (n=164). Of the cohort, 97.7% (904/925) reported the diagnosis had been confirmed by a physician. Compared to microscopic polyangiitis, patients with granulomatosis with polyangiitis reported significantly more ear, nose, and throat manifestations (granulomatosis with polyangiitis: 641/723, 88.7%; microscopic polyangiitis: 89/164, 54.3%; z=10.42, P<.001), fevers (granulomatosis with polyangiitis: 325/588, 55.3%; microscopic polyangiitis: 64/139, 46.0%; z=1.96, P=.05), joint involvement (granulomatosis with polyangiitis: 549/688, 79.8%; microscopic polyangiitis: 106/154, 68.8%; z=2.96, P=.003), and pulmonary involvement (granulomatosis with polyangiitis: 523/734, 71.3%; microscopic polyangiitis: 90/154, 58.4%; z=3.13, P=.002). Compared to microscopic polyangiitis, patients with granulomatosis with polyangiitis reported significantly less renal involvement (granulomatosis with polyangiitis: 457/743, 61.5%; microscopic polyangiitis: 135/163, 82.8%; z=–5.18, P<.001) and renal transplantation (granulomatosis with polyangiitis: 10/721, 1.4%; microscopic polyangiitis: 7/164, 4.3%; z=–2.43, P=.02). Antineutrophil cytoplasmic antibody positivity was reported in 94.2% (652/692) of patients with granulomatosis with polyangiitis and 96.1% (147/153) of patients with microscopic polyangiitis. A biopsy showing vasculitis was reported in 77.0% (562/730) of patients with granulomatosis with polyangiitis and 81.9% (131/160) of patients with microscopic polyangiitis. Conclusions In this large, internet-based cohort of patients with a self-reported diagnosis of granulomatosis with polyangiitis or microscopic polyangiitis, disease manifestations were consistent with expectations for each type of vasculitis. Given the rarity of these and other vasculitides, conducting some types of research through internet-based registries may provide an efficient alternative to inperson, center-of-excellence clinical trials.
Effects of cobalt and chromium ions on glycolytic flux and the stabilization of hypoxia‐inducible factor‐1α in macrophages in vitro

Implant wear and corrosion have been associated with adverse tissue reactions that can lead to implant failure. Wear and corrosion products are therefore of great clinical concern. For example, Co2+ and Cr3+ originating from CoCrMo‐based implants have been shown to induce a proinflammatory response in macrophages in vitro. Previous studies have also shown that the polarization of macrophages by some proinflammatory stimuli is associated with a hypoxia‐inducible factor‐1α (HIF‐1α)‐dependent metabolic shift from oxidative phosphorylation (OXPHOS) towards glycolysis. However, the potential of Co2+ and Cr3+ to induce this metabolic shift, which plays a determining role in the proinflammatory response of macrophages, remains largely unexplored. We recently demonstrated that Co2+, but not Cr3+, increased oxidative stress and decreased OXPHOS in RAW 264.7 murine macrophages. In the present study, we analyzed the effects of Co2+ and Cr3+ on glycolytic flux and HIF‐1α stabilization in the same experimental model. Cells were exposed to 6 to 24 ppm Co2+ or 50 to 250 ppm Cr3+. Glycolytic flux was determined by analyzing extracellular flux and lactate production, while HIF‐1α stabilization was analyzed by immunoblotting. Results showed that Co2+, and to a lesser extent Cr3+, increased glycolytic flux; however, only Co2+ acted through HIF‐1α stabilization. Overall, these results, together with our previous results showing that Co2+ increases oxidative stress and decreases OXPHOS, suggest that Co2+ (but not Cr3+) can induce a HIF‐1α‐dependent metabolic shift from OXPHOS towards glycolysis in macrophages. This metabolic shift may play an early and pivotal role in the inflammatory response induced by Co2+ in the periprosthetic environment.
Nutrition and nutraceuticals in the changing management of osteoarthritis for dogs and cats.

1335 Osteoarthritis is a progressively painful disease characterized by articular cartilage degradation with loss of proteoglycan and collagen, subchondral bone sclerosis, periarticular proliferation of new bone, and chronic inflammation of synovial membranes.1 Osteoarthritis is estimated to affect approximately 20% of dogs ≥ 1 year of age and 90% of dogs > 5 years of age.2–5 Cats are similarly affected by osteoarthritis, with prevalences ranging from 16.5% to 91% and increasing with age.6–9 Given the high prevalences reported, it is possible that companion animals may have undiagnosed osteoarthritis and the associated pain that goes unnoticed. Cats in particular may not show clinical signs typically associated with osteoarthritis, and even subtle changes in a cat’s behavior at home may be caused by osteoarthritis-associated pain. Veterinarians should closely evaluate patients’ joints at every annual examination and discuss signs of osteoarthritis and pain with clients. To prevent disease progression as early as possible, discussions about osteoarthritis should take place for patients as young as 1 year of age. Careful evaluation and client education are essential to identifying osteoarthritis in its earliest stages. Clinical signs of osteoarthritis include evidence of pain or tenderness, decreased range of motion, swelling, stiffness, muscle atrophy, crepitus, and effusion. The presence of pain can cause an animal’s behavior to change, leading to aggression or decreased activity, in addition to signs such as limping and difficulty rising, climbing stairs, or getting onto furniture.10 Painful disease makes it difficult for pets to interact with people, which strains the human-animal bond and can damage the relationship with the owner. Because of osteoarthritis-related pain, pets may have trouble walking around the home. They Nutrition and nutraceuticals in the changing management of osteoarthritis for dogs and cats
Long-Range Exciton Diffusion in Two-Dimensional Assemblies of Cesium Lead Bromide Perovskite Nanocrystals.

Förster Resonant Energy Transfer (FRET)-mediated exciton diffusion through artificial nanoscale building block assemblies could be used as an optoelectronic design element to transport energy. However, so far nanocrystal (NC) systems supported only diffusion lengths of 30 nm, which are too small to be useful in devices. Here, we demonstrate a FRET-mediated exciton diffusion length of 200 nm with 0.5 cm2/s diffusivity through an ordered, two-dimensional assembly of cesium lead bromide perovskite nanocrystals (CsPbBr3 PNCs). Exciton diffusion was directly measured via steady-state and time-resolved photoluminescence (PL) microscopy, with physical modeling providing deeper insight into the transport process. This exceptionally efficient exciton transport is facilitated by PNCs' high PL quantum yield, large absorption cross-section, and high polarizability, together with minimal energetic and geometric disorder of the assembly. This FRET-mediated exciton diffusion length matches perovskites' optical absorption depth, thus enabling the design of device architectures with improved performances, and providing insight into the high conversion efficiencies of PNC-based optoelectronic devices.
Influence of the SARS-CoV-2 Outbreak on the Uptake of a Popular Smoking Cessation App in UK Smokers: Interrupted Time Series Analysis

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak may motivate smokers to attempt to stop in greater numbers. However, given the temporary closure of UK stop smoking services and vape shops, smokers attempting to quit may instead seek out mobile health support, such as smartphone apps. Objective We examined, using an interrupted time series approach, whether the SARS-CoV-2 outbreak has been associated with a step change or increasing trend in UK downloads of an otherwise popular smoking cessation app, Smoke Free. Methods Data were from daily and nondaily adult smokers in the United Kingdom who had downloaded the Smoke Free app between January 1, 2020, and March 31, 2020 (primary analysis), and January 1, 2019, and March 31, 2020 (secondary analysis). The outcome variable was the number of downloads aggregated at the 12-hourly (primary analysis) or daily level (secondary analysis). The explanatory variable was the start of the SARS-CoV-2 outbreak, operationalized as March 1, 2020 (primary analysis), and January 15, 2020 (secondary analysis). Generalized additive mixed models adjusted for relevant covariates were fitted. Results Data were collected on 45,105 (primary analysis) and 119,881 (secondary analysis) users. In both analyses, there was no evidence for a step change or increasing trend in downloads attributable to the start of the SARS-CoV-2 outbreak. Calculation of Bayes factors (BFs) indicated that the data for the primary analysis favored the null hypothesis compared with large associations (for level, BF=0.25; for slope, BF=0.26) but were insensitive to the detection of small associations (for level, BF=0.78; for slope, BF=1.35). Conclusions In the United Kingdom, between January 1, 2020, and March 31, 2020, and between January 1, 2019, and March 31, 2020, there was no evidence that the SARS-CoV-2 outbreak has been associated with a large step change or increasing trend in downloads of a popular smoking cessation app. Findings on the association of the SARS-CoV-2 outbreak with a small step change or increasing trend were inconclusive.
Removal of hydrogen sulfide from biogas using activated carbon synthesized from different locally available biomass wastes - a case study from Palestine

ABSTRACT The main aim of this study was to remove hydrogen sulfide (H2S) from biogas by adsorption using synthesized activated carbon prepared using locally available biomass. The effect of the type of precursors, impregnation reagent and bed height was studied in continuous reactors. Three types of biomass wastes (almond shells, eucalyptus and coffee grains) were collected, grinded, sieved, pyrolyzed at 500°C and impregnated with chemical reagents such as potassium hydroxide or zinc chloride. Adsorption tests were performed using a fixed bed filter filled with the produced activated carbon. The highest biochar yield of 36% was obtained eucalyptus followed by almond shells (28.5%) and coffee grains (24%), respectively. The highest adsorption capacity and removal efficiency were obtained with eucalyptus followed by almond shells and coffee grains, respectively. For instance, eucalyptus showed an adsorption capacity of ~690 (mg hydrogen sulfide/g adsorbent) followed by almond (230 mg hydrogen sulfide/g adsorbent) and coffee grains (22 mg hydrogen sulfide/g adsorbent). As an impregnation reagent, potassium hydroxide gave the highest adsorption efficiency and capacity than zinc chloride. Furthermore, the breakthrough time with KOH (180 min) was higher than ZnCl2 (70 min). Increasing the bed height during continuous breakthrough tests increased the adsorption capacity and hydrogen sulfide removal efficiency. The results of this study showed that the adsorption efficiency of the synthesized activated carbon and consequently the hydrogen sulfide removal efficiency could be fine-tuned by selecting an appropriate biomass precursor and proper impregnation reagent. Graphical abstract
The diet of a coastal population of European bee‐eaters (Merops apiaster) compared to prey availability (Tuscany, central Italy)

Abstract We studied the diet of a coastal population of European bee‐eaters during the 1986 breeding season by pellet analysis and estimates of prey availability. The results showed that the population fed preferentially on Hymenoptera, which were more preyed upon than their availability in both May and July. Beetles were the second prey category, Odonata and Hemiptera being included in the diet mainly in July, when food needs of the chicks forced the adults to include larger prey items in their diet. Diptera were always rejected by bee‐eaters despite their great availability in both months.
The role of socioeconomic and sociocultural predictors of Spanish and English proficiencies of young Latino children of immigrants

Abstract Young Latino children of immigrants typically speak primarily Spanish at home and are exposed to varying amounts of English. As a result, they often enter school with a wide range of proficiencies in each language. The current study investigated family background, language use at home and early childhood settings as predictors of Spanish and English language proficiencies among Latino dual language children (N = 228). Findings demonstrated divergent sets of predictors were associated with either Spanish or English proficiencies at kindergarten and second grade. Sociocultural variables (parent origin, gender, home language use, home literacy practices, and language use in early childhood settings) predicted children's Spanish proficiency, while socioeconomic variables (poverty, and maternal and paternal education) predicted children's English proficiency, with little to no overlap in these predictions. These results suggest that different supports are required for proficiency in Spanish and in English, highlighting the importance of sociocultural and socioeconomic factors.
Acyltransferase-mediated selection of the length of the fatty acyl chain and of the acylation site governs activation of bacterial RTX toxins

In a wide range of organisms, from bacteria to humans, numerous proteins have to be posttranslationally acylated to become biologically active. Bacterial repeats in toxin (RTX) cytolysins form a prominent group of proteins that are synthesized as inactive protoxins and undergo posttranslational acylation on ε-amino groups of two internal conserved lysine residues by co-expressed toxin-activating acyltransferases. Here, we investigated how the chemical nature, position, and number of bound acyl chains govern the activities of Bordetella pertussis adenylate cyclase toxin (CyaA), Escherichia coli α-hemolysin (HlyA), and Kingella kingae cytotoxin (RtxA). We found that the three protoxins are acylated in the same E. coli cell background by each of the CyaC, HlyC, and RtxC acyltransferases. We also noted that the acyltransferase selects from the bacterial pool of acyl–acyl carrier proteins (ACPs) an acyl chain of a specific length for covalent linkage to the protoxin. The acyltransferase also selects whether both or only one of two conserved lysine residues of the protoxin will be posttranslationally acylated. Functional assays revealed that RtxA has to be modified by 14-carbon fatty acyl chains to be biologically active, that HlyA remains active also when modified by 16-carbon acyl chains, and that CyaA is activated exclusively by 16-carbon acyl chains. These results suggest that the RTX toxin molecules are structurally adapted to the length of the acyl chains used for modification of their acylated lysine residue in the second, more conserved acylation site.
The role of the gut microbiota in the pathophysiology of mental and neurological disorders

In recent decades, the concept of the gut microbiota as a potential novel therapeutic strategy for mental health has emerged. The tiny microbes inhabiting our gut communicate through a bidirectional communication signaling with the brain that influences gut physiology, brain function and behavior. Accumulating evidence suggests that perturbation of the gut microbiota contributes to the pathophysiology of mental illnesses including autism, depression and anxiety as well as neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. This review will highlight recent findings in both human and animal studies indicating how changes in the gut microbiota can impact the pathophysiology of such diseases. The current work will also provide an understanding of the efficacy of microbiota-targeted therapies on psychiatric disorders.
CD36‐fibrin interaction propagates FXI‐dependent thrombin generation of human platelets

Thrombin converts fibrinogen to fibrin and activates blood and vascular cells in thrombo‐inflammatory diseases. Platelets are amplifiers of thrombin formation when activated by leukocyte‐ and vascular cell‐derived thrombin. CD36 on platelets acts as sensitizer for molecules with damage‐associated molecular patterns, thereby increasing platelet reactivity. Here, we investigated the role of CD36 in thrombin‐generation on human platelets, including selected patients with advanced chronic kidney disease (CKD). Platelets deficient in CD36 or blocked by anti‐CD36 antibody FA6.152 showed impaired thrombin generation triggered by thrombin in calibrated automated thrombography. Using platelets with congenital function defects, blocking antibodies, pharmacological inhibitors, and factor‐depleted plasma, CD36‐sensitive thrombin generation was dependent on FXI, fibrin, and platelet signaling via GPIbα and SFKs. CD36‐deficiency or blocking suppressed thrombin‐induced platelet αIIbβ3 activation, granule exocytosis, binding of adhesion proteins and FV, FVIII, FIX, FX, but not anionic phospholipid exposure determined by flow cytometry. CD36 ligated specifically soluble fibrin, which recruited distinct coagulation factors via thiols. Selected patients with CKD showed elevated soluble fibrin plasma levels and enhanced thrombin‐induced thrombin generation, which was normalized by CD36 blocking. Thus, CD36 is an important amplifier of platelet‐dependent thrombin generation when exposure of anionic phospholipids is limited. This pathway might contribute to hypercoagulability in CKD.
Proposed Changes to the 2021 Residency Application Process in the Wake of COVID-19

The COVID-19 pandemic has brought unique challenges to the delivery of undergraduate medical education, particularly for current third-year medical students who are preparing to apply to residency. In mid-March, medical schools suspended all clinical rotations for the remainder of the 2019–2020 academic year. As such, third-year medical students may not be able to complete sufficient clinical experiences to make important career choices before they have to submit their residency applications. While the decision to suspend clinical rotations was necessary to protect students, specialty organizations and residency programs must mitigate the deficits in students’ clinical education caused by the COVID-19 pandemic. In this Perspective, the authors identify potential challenges for third-year medical students and advocate for solutions to improve the residency application process for students and programs. First, they propose delaying the date that programs can access applicant data through the Electronic Residency Application Service, thereby affording students more time to complete clinical experiences, solidify their specialty decision, and strengthen their residency application. Second, the authors recommend a restriction on the number of visiting rotations that students are expected to complete to allow for a more equitable distribution of these important experiences. Third, they suggest that program directors from each specialty agree on a maximum number of applications per applicant (based on historical data) to curb an upsurge in applications that may stem from the unique circumstances created by COVID-19 without causing applicants undue stress. Lastly, the authors advocate that residency programs develop infrastructure to conduct video-based interviews and engage students through virtual networking events. Amidst the unique environment created by COVID-19, the authors urge governing bodies, specialty organizations, and residency programs to consider these recommendations to improve the efficiency and reduce the stress surrounding the 2021 Match.
Clinical features, isolation, and complete genome sequence of severe acute respiratory syndrome coronavirus 2 from the first two patients in Vietnam

In January 2020, we identified two severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐infected patients in a familial cluster with one person coming from Wuhan, China. The complete genome sequences of two SARS‐CoV‐2 strains isolated from these patients were identical and 99.98% similar to strains isolated in Wuhan. This is genetically suggestive of human‐to‐human transmission of SARS‐CoV‐2 and indicates Wuhan as the most plausible origin of the early outbreak in Vietnam. The younger patient had a mild upper respiratory illness and a brief viral shedding, whereas the elderly with multi‐morbidity had pneumonia, prolonged viral shedding, and residual lung damage. The evidence of nonsynonymous substitutions in the ORF1ab region of the viral sequence warrants further studies.
Thigh loaded wearable resistance increases sagittal plane rotational work of the thigh resulting in slower 50-m sprint times

ABSTRACT This study determined the acute changes in rotational work with thigh attached wearable resistance (WR) of 2% body mass during 50-m sprint-running. Fourteen athletes completed sprints with, and without, WR in a randomised order. Sprint times were measured via timing gates at 10-m and 50-m. Rotational kinematics were obtained over three phases (steps 1–2, 3–6 and 7–10) via inertial measurement unit attached to the left thigh. Quantification of thigh angular displacement and peak thigh angular velocity was subsequently derived to measure rotational work. The WR condition was found to increase sprint times at 10-m (1.4%, effect size [ES] 0.38, p 0.06) and 50-m (1.9%, ES 0.55, p 0.04). The WR condition resulted in trivial to small increases in angular displacement of the thigh during all phases (0.6–3.4%, ES 0.04–0.26, p 0.09–0.91). A significant decrease in angular velocity of the thigh was found in all step phases (−2.5% to −8.0%, ES 0.17–0.51, p < 0.001–0.04), except extension in step phase 1 with the WR. Rotational work was increased (9.8–18.8%, ES 0.35–0.53, p < 0.001) with WR in all phases of the sprint. Thigh attached WR provides a means to significantly increase rotational work specific to sprinting.