Miracle-dz/UniFAR-FTUs huggingface dataset:
The Pleural Effusion And Symptom Evaluation (PLEASE) study of breathlessness in patients with a symptomatic pleural effusion

Introduction Pathophysiology changes associated with pleural effusion, its drainage and factors governing symptom response are poorly understood. Our objective was to determine: 1) the effect of pleural effusion (and its drainage) on cardiorespiratory, functional and diaphragmatic parameters; and 2) the proportion as well as characteristics of patients with breathlessness relief post-drainage. Methods Prospectively enrolled patients with symptomatic pleural effusions were assessed at both pre-therapeutic drainage and at 24–36 h post-therapeutic drainage. Results 145 participants completed pre-drainage and post-drainage tests; 93% had effusions ≥25% of hemithorax. The median volume drained was 1.68 L. Breathlessness scores improved post-drainage (mean visual analogue scale (VAS) score by 28.0±24 mm; dyspnoea-12 (D12) score by 10.5±8.8; resting Borg score before 6-min walk test (6-MWT) by 0.6±1.7; all p<0.0001). The 6-min walk distance (6-MWD) increased by 29.7±73.5 m, p<0.0001. Improvements in vital signs and spirometry were modest (forced expiratory volume in 1 s (FEV1) by 0.22 L, 95% CI 0.18–0.27; forced vital capacity (FVC) by 0.30 L, 95% CI 0.24–0.37). The ipsilateral hemi-diaphragm was flattened/everted in 50% of participants pre-drainage and 48% of participants exhibited paradoxical or no diaphragmatic movement. Post-drainage, hemi-diaphragm shape and movement were normal in 94% and 73% of participants, respectively. Drainage provided meaningful breathlessness relief (VAS score improved ≥14 mm) in 73% of participants irrespective of whether the lung expanded (mean difference 0.14, 95% CI 10.02–0.29; p=0.13). Multivariate analyses found that breathlessness relief was associated with significant breathlessness pre-drainage (odds ratio (OR) 5.83 per standard deviation (sd) decrease), baseline abnormal/paralyzed/paradoxical diaphragm movement (OR 4.37), benign aetiology (OR 3.39), higher pleural pH (OR per sd increase 1.92) and higher serum albumin level (OR per sd increase 1.73). Conclusions Breathlessness and exercise tolerance improved in most patients with only a small mean improvement in spirometry and no change in oxygenation. Breathlessness improvement was similar in participants with and without trapped lung. Abnormal hemi-diaphragm shape and movement were independently associated with relief of breathlessness post-drainage. The majority of patients improve after pleural fluid drainage. Abnormal diaphragmatic function may be an important contributor to breathlessness in patients with pleural effusion. http://bit.ly/2SyF8RW
Processing of the SARS-CoV pp1a/ab nsp7–10 region

Severe acute respiratory syndrome coronavirus (SARS-CoV) is the causative agent of a respiratory disease with a high case fatality rate. During the formation of the coronaviral replication/transcription complex (RTC), essential steps include processing of the conserved polyprotein nsp7-10 region by the main protease Mpro and subsequent complex formation of the released nsp’s. Here, we analyzed processing of the coronavirus nsp7-10 region using native mass spectrometry showing consumption of substrate, rise and fall of intermediate products and complexation. Importantly, there is a clear order of cleavage efficiencies, which is influenced by the polyprotein tertiary structure. Furthermore, the predominant product is an nsp7+8(2:2) hetero-tetramer with nsp8 scaffold. In conclusion, native MS, opposed to other methods, can expose the processing dynamics of viral polyproteins and the landscape of protein interactions in one set of experiments. Thereby, new insights into protein interactions, essential for generation of viral progeny, were provided, with relevance for development of antivirals.
Redefining Hematoma Expansion With the Inclusion of Intraventricular Hemorrhage Growth

Supplemental Digital Content is available in the text. Background and Purpose— Definitions of significant hematoma expansion traditionally focus on changes in intraparenchymal volume. The presence of intraventricular hemorrhage (IVH) is a predictor of poor outcome, but current definitions of hematoma expansion do not include IVH expansion. We evaluated whether including IVH expansion to current definitions of hematoma expansion improves the ability to predict 90-day outcome. Methods— Using data from the PREDICT-ICH study (Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT), we compared a standard definition of hematoma expansion (≥6 mL or ≥33%) to revised definitions that includes new IVH development or expansion (≥6 mL or ≥33% or any IVH; ≥6 mL or ≥33% or IVH expansion ≥1 mL). The primary outcome was poor clinical outcome (modified Rankin Scale score, 4–6) at 90 days. Diagnostic accuracy measures were calculated for each definition, and C statistics for each definition were compared using nonparametric methods. Results— Of the 256 patients eligible for primary analysis, 127 (49.6%) had a modified Rankin Scale score of 4 to 6. Sensitivity and specificity for the standard definition (n=80) were 45.7% (95% CI, 36.8–54.7) and 82.9% (95% CI, 75.3–88.9), respectively. The revised definition, ≥6 mL or ≥33% or any IVH (n=113), possessed a sensitivity of 63.8% (95% CI, 54.8–72.1) and specificity of 75.2% (95% CI, 66.8–82.4). Overall accuracy was significantly improved with the revised definition (P=0.013) and after adjusting for relevant covariates, was associated with a 2.55-fold increased odds (95% CI, 1.31–4.94) of poor outcome at 90 days. A second revised definition, ≥6 mL or ≥33% or IVH expansion ≥1 mL, performed similarly (sensitivity, 56.7% [95% CI, 47.6–65.5]; specificity, 78.3% [95% CI, 40.2–85.1]; aOR, 2.40 [95% CI, 1.23–4.69]). Conclusions— In patients with mild-to-moderate ICH, including IVH expansion to the definition of hematoma expansion improves sensitivity with only minimal decreases to specificity and improves overall prediction of 90-day outcome.
The Anticancer Efficacy of Immune Checkpoint Inhibitors According to Patients’ Age: A Systematic Review and Meta-Analysis

Supplemental Digital Content is available in the text. Limited prospective data about the activity of immune checkpoint inhibitors (ICIs) are available for elderly patients. The aim of our analysis was to determine the relative efficacy of ICIs versus available standard therapies [standard of care (SOC)] in subgroups defined by patients’ age. Searching the MEDLINE/PubMed, Cochrane Library, and American Society of Clinical Oncology (ASCO) Meeting abstracts randomized clinical trials were identified. Data extraction was conduced according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The measured outcome was overall survival (OS). Twenty-nine randomized clinical trials (18,839 patients) were selected. As for the distribution of patients by age, all but 3 of the selected studies considered young the patients younger than 65 years (n=10,832) and elderly those with 65 years and older (n=7723); 7 studies identified a third subgroup of very elderly patients aged 75 years and above (n=421). In elderly and very elderly patients ICIs significantly reduced the risk of death by 23% compared with SOC [hazard ratio (HR), 0.77; P<0.00001)]. On the contrary, a lack of a survival advantage of immunotherapy was observed in the subgroup of very elderly patients (HR, 0.85; P=0.39). When comparing the efficacy of ICIs between the 2 subpopulations (elderly vs. young), no significant difference in OS was observed (HR, 0.76; P=0.66). ICIs prolonged OS compared with SOC in both elderly and young patients affected by lung cancer, melanoma, and renal carcinoma, regardless of the age. In conclusion, ICIs (as monotherapy or combinations) significantly improved OS compared with SOC in both young and elderly patients with advanced cancers, regardless of the tumor type. The magnitude of this benefit is debated in patients aged 75 years and above.
Flaxseed Cake as a Tool for the Improvement of Nutraceutical and Sensorial Features of Sourdough Bread

Flaxseed has been recently studied for the formulation of healthy functional foods that are also useful for the prevention of chronic diseases. In this context, the production of sourdough bread fortified with different percentages of flaxseed cake was performed and the interactions among the bioactive compounds derived from both sourdough and flaxseed cake were investigated. The organoleptic properties as well as nutraceutical and chemical characteristics regarding pH, ethanol, lactic and acetic acid content, fatty acids profile, the concentration of total polyphenols, antioxidant capacity, and aroma volatile organic compounds were determined to evaluate the efficacy of leavening in the different matrices in comparison with the traditional bread. The results obtained demonstrated that flaxseed cake-enriched sourdough bread can represent a potential vehicle for bioactive compounds with the possibility of obtaining high-quality products with improved nutritional profiles and desired health attributes. Furthermore, the bread obtained with the addition of 7.5% of flaxseed cake was individuated as the best formulation to produce sourdough bread fortified with flaxseed cake by the overlap between three series of information coming from physical-chemical, nutritional, and sensorial analyses. In conclusion, in the operating conditions adopted, the use of flaxseed cake could represent a viable alternative for the production of fortified bread based on sourdough technology.
The Multifaceted Dimensions of Food Choice and Nutrition

The Special Issue "Food Choice and Nutrition" deals with the relationship between the food choices of different population groups or consumer segments and its impact on the nutritional status, improvement of dietary quality, food and nutrition-related behaviour, food preferences, taste education, sensory characteristics of foods and their role in consumer choice, etc [. ].
Comparison of putative BH3 mimetics AT-101, HA14-1, sabutoclax and TW-37 with ABT-737 in platelets

Abstract Platelet lifespan is regulated by intrinsic apoptosis. Platelet apoptosis can be triggered by BH3 mimetics that inhibit the pro-survival Bcl-2 family protein, Bcl-xL. Here, we investigated several small molecules that are reported to act as BH3 mimetics and compared their effects to the well-established BH3 mimetic, ABT-737. Platelet phosphatidylserine (PS) exposure was determined by flow cytometry. Changes in cytosolic Ca2+ signaling were detected using Cal-520. Plasma membrane integrity was determined by calcein leakage. The roles of caspases and calpain in these processes were determined using Q-VD-OPh and calpeptin, respectively. As previously reported, ABT-737 triggered PS exposure in a caspase-dependent manner and calcein loss in a caspase and calpain-dependent manner. In contrast, AT-101 and sabutoclax triggered PS exposure independently of caspases. HA14-1 also triggered PS exposure in a caspase-independent but calpain-dependent manner. There were also significant differences in the pattern and protease-dependency of cytosolic Ca2+ signaling in response to these drugs compared to ABT-737. Since there are clear differences between the action of ABT-737 and the other putative BH3 mimetics investigated here, AT-101, HA14-1 and sabutoclax cannot be considered as acting as BH3 mimetics in platelets. Furthermore, the platelet death caused by these drugs is likely to be distinct from apoptosis.
Characterization of gut microbiomes of household pets in the United States using a direct-to-consumer approach

The role of gut microbiomes as important regulators of mammalian health is increasingly recognized, although feline and canine gut microbiomes remain poorly characterized. In this proof-of-concept study, we assessed the utility of a direct-to-consumer approach to executing pet microbiome studies. We characterized the gut microbiomes of 238 pets (46 cats and 192 dogs) by generating ~11 million merged reads that were mapped to the V4 region of 16S ribosomal RNA gene at a sequencing depth of 45,806 (±22,325) reads per sample. Analyses of these reads revealed that both feline and canine gut microbiomes are dominated by three major phyla, namely Firmicutes, Proteobacteria, and Bacteroides and that alpha diversity is higher in the feline gut. In addition to interspecies differences between the feline and canine gut, we also detected appreciable intraspecies bacterial variation within the canine population. While the dogs in this dataset could be assigned to three distinct clusters based on their gut microbiome, no clustering was observed within the feline population. Integration of additional data obtained from survey questionnaires revealed that geography and body weight may be associated with canine gut microbiome composition. Furthermore, we found that both the inter and intraspecies differences are more pronounced at finer taxonomic levels, indicating that strain-level investigations may be necessary in the future. This study demonstrates that the direct-to-consumer approach overcomes existing limitations in pet microbiome research, for example, it allows collection of large numbers of pet samples. The direct-to-consumer approach has proven successful in human genomics as well as human microbiomics and this study demonstrates that by building partnerships with an engaged general public this approach can also propel the field of pet microbiomics forward.
Active Commuting to School and Physical Activity Levels among 11 to 16 Year-Old Adolescents from 63 Low- and Middle-Income Countries

Background: Global physical activity levels are low. Active commuting to school is a low-cost and sustainable behaviour that promotes adolescents’ physical activity levels. Despite its importance, data on low- and middle-income countries is scarce. This study aimed to assess the relationship between active commuting to school and physical activity (PA) levels among 11–16 years-old adolescents from 63 low- and middle-income countries and six world regions. Methods: Data were from the GSHS database. Participants were 187,934 adolescents (89,550 boys), aged 11–16 years-old, from 63 low- and middle-income countries. Active commuting to school and PA were self-reported as the number of days adolescents walked or cycled to school and engaged in physical activity for at least 60 min in the past 7 days. Results: Boys and girls who actively commuted to school presented higher prevalence of attaining the PA recommendations, but only for the 13–14 (boys: 16.6% versus 22.0%; girls: 9.8% versus 14.6%) and 15–16 (boys: 16.3% versus 21.6%; girls: 8.0% versus 14.0%) year-old age groups. Only for Oceania, Central Asian, Middle Eastern, and North African girls and Sub-Saharan African boys no difference was found in the prevalence of attaining the PA recommendations between those who actively commuted to school and those who did not. Boys who actively commuted to school were 42% (95% CI: 1.37, 1.46) more likely to achieve the PA recommendations, while girls were 66% (95% CI: 1.59, 1.73) more likely to achieve the PA recommendations. Conclusions: Active commuting to school is associated with the adolescents’ physical activity levels. However, it may have a lesser influence in helping younger adolescents attaining physical activity recommendations. Public health authorities should promote active commuting to school among adolescents in order to improve the PA levels and promote health.
Increases in Secondhand Smoke After Going Smoke Free: An Assessment of the Impact of a Mandated Smoke-Free Housing Policy.

OBJECTIVE The 12-month impact of federally-mandated smoke free housing (SFH) policy adoption (July 2018) was assessed using two markers of ambient secondhand smoke (SHS): airborne nicotine and particulate matter at the 2.5 micrometer threshold (PM2.5). METHODS We measured markers of SHS in Norfolk, VA from December 2017 to December 2018 in six federally-subsidized multi-unit public housing buildings. Multi-level regression was used to model the following comparisons: (1) the month immediately before SFH implementation vs. the month immediately after, and (2) December, 2017 vs. December, 2018. RESULTS There was a 27% reduction in indoor PM2.5 and a 32% reduction in airborne nicotine in the first month after SFH adoption, compared to the month prior to adoption. However, there was a 33% increase in PM2.5 and a 25% increase in airborne nicotine after 12 months. CONCLUSIONS HUD-mandated SFH can reduce SHS in multi-unit housing. However, SFH could also plausibly increase indoor smoking. Policy approaches adopted by individual properties or housing authorities-for example, property-wide bans vs. allowing designated smoking areas-could be driving this potential unintended consequence.
Bicuspid Aortic Valve in 2 Model Species and Review of the Literature

Bicuspid aortic valve (BAV) is the most common human congenital cardiac malformation. Although the etiology is unknown for most patients, formation of the 2 main BAV anatomic types (A and B) has been shown to rely on distinct morphogenetic mechanisms. Animal models of BAV include 2 spontaneous hamster strains and 27 genetically modified mouse strains. To assess the value of these models for extrapolation to humans, we examined the aortic valve anatomy of 4340 hamsters and 1823 mice from 8 and 7 unmodified strains, respectively. In addition, we reviewed the literature describing BAV in nonhuman mammals. The incidences of BAV types A and B were 2.3% and 0.03% in control hamsters and 0% and 0.3% in control mice, respectively. Hamsters from the spontaneous model had BAV type A only, whereas mice from 2 of 27 genetically modified strains had BAV type A, 23 of 27 had BAV type B, and 2 of 27 had both BAV types. In both species, BAV incidence was dependent on genetic background. Unlike mice, hamsters had a wide spectrum of aortic valve morphologies. We showed interspecific differences in the occurrence of BAV between humans, hamsters, and mice that should be considered when studying aortic valve disease using animal models. Our results suggest that genetic modifiers play a significant role in both the morphology and incidence of BAV. We propose that mutations causing anomalies in specific cardiac morphogenetic processes or cell lineages may lead to BAV types A, B, or both, depending on additional genetic, environmental, and epigenetic factors.
Nutrient-Induced Metabolic Stress, Adaptation, Detoxification, and Toxicity in the Pancreatic β-Cell

Paraphrasing the Swiss physician and father of toxicology Paracelsus (1493–1541) on chemical agents used as therapeutics, “the dose makes the poison,” it is now realized that this aptly applies to the calorigenic nutrients. The case here is the pancreatic islet β-cell presented with excessive levels of nutrients such as glucose, lipids, and amino acids. The short-term effects these nutrients exert on the β-cell are enhanced insulin biosynthesis and secretion and changes in glucose sensitivity. However, chronic fuel surfeit triggers additional compensatory and adaptive mechanisms by β-cells to cope with the increased insulin demand or to protect itself. When these mechanisms fail, toxicity due to the nutrient surplus ensues, leading to β-cell dysfunction, dedifferentiation, and apoptosis. The terms glucotoxicity, lipotoxicity, and glucolipotoxicity have been widely used, but there is some confusion as to what they mean precisely and which is most appropriate for a given situation. Here we address the gluco-, lipo-, and glucolipo-toxicities in β-cells by assessing the evidence both for and against each of them. We also discuss potential mechanisms and defend the view that many of the identified “toxic” effects of nutrient excess, which may also include amino acids, are in fact beneficial adaptive processes. In addition, candidate fuel-excess detoxification pathways are evaluated. Finally, we propose that a more general term should be used for the in vivo situation of overweight-associated type 2 diabetes reflecting both the adaptive and toxic processes to mixed calorigenic nutrients excess: “nutrient-induced metabolic stress” or, in brief, “nutri-stress. ”
Circulating SHBG (Sex Hormone-Binding Globulin) and Risk of Ischemic Stroke

Supplemental Digital Content is available in the text. Background and Purpose— Circulating levels of SHBG (sex hormone-binding globulin) have been inversely linked to obesity, diabetes mellitus, and other cardiometabolic disorders. It remains uncertain whether low SHBG is prospectively predictive of stroke risk, particularly in women. We investigated whether SHBG is associated with risk of incident ischemic stroke (IS) among women in the WHI (Women’s Health Initiative). Methods— From an observational cohort of 161 808 postmenopausal women enrolled in the WHI at 40 sites across the United States from 1993 to 1998, we identified 13 192 participants free of prevalent stroke at baseline who were included in an ancillary study that measured serum SHBG. We used Cox proportional hazards regression, stratified by SHBG measurement assay, to assess IS risk across quintiles of SHBG (Q1–Q5), adjusting first for demographic variables (model 1), additionally for body mass index, hypertension, alcohol use, and smoking status (model 2), and for physical activity and reproductive risk factors (model 3). In sensitivity analyses, potential mediators (diabetes mellitus status, levels of estradiol, testosterone, and CRP [C-reactive protein]) were included. Results— Of 13 192 participants (mean age, 62.5 years; 67.4% non-Hispanic white, 18.5% black, 7.6% Hispanic, and 5.0% Asian), after following for an average of 11.6 years, 768 IS events were adjudicated. Compared with the highest quintile of SHBG levels (referent), women in the lowest SHBG quintile had a higher risk of IS in all 3 multivariable models (model 1: hazard ratio, 1.88 [95% CI, 1.47–2.41]; model 2: hazard ratio, 1.69 [95% CI, 1.30–2.20]; model 3: hazard ratio, 1.61 [95% CI, 1.19–2.19]; trend tests P<0.05 for all models). Including potential mediators such as diabetes mellitus, estradiol, and testosterone in the models attenuated but did not eliminate significant inverse associations between SHBG and IS. Conclusions— In this prospective cohort of postmenopausal women, there was a statistically significant inverse association between serum SHBG levels and IS risk, which supports the notion that SHBG could be used as a risk stratification tool for predicting IS in women.
Free Vibration Analysis of Closed Moderately Thick Cross-Ply Composite Laminated Cylindrical Shell with Arbitrary Boundary Conditions

A semi-analytic method is adopted to analyze the free vibration characteristics of the moderately thick composite laminated cylindrical shell with arbitrary classical and elastic boundary conditions. By Hamilton’s principle and first-order shear deformation theory, the governing equation of the composite shell can be established. The displacement variables are transformed into the wave function forms to ensure the correctness of the governing equation. Based on the kinetic relationship between the displacement variables and force resultants, the final equation associated with arbitrary boundary conditions is established. The dichotomy method is conducted to calculate the natural frequencies of the composite shell. For verifying the correctness of the present method, the results by the present method are compared with those in the pieces of literatures with various boundary conditions. Furthermore, some numerical examples are calculated to investigate the effect of several parameters on the composite shell, such as length to radius ratios, thickness to radius ratios and elastic restrained constants.