Miracle-dz/UniFAR-FTUs huggingface dataset:
An Estimation Model for Cardiorespiratory Fitness in Adults with Rheumatoid Arthritis.

PURPOSE Cardiopulmonary exercise testing of peak oxygen uptake (VO2peak) is the gold standard to measure cardiorespiratory fitness (CRF). For resource-intensive evaluation, equations estimating CRF (eCRF) may be used. The purpose was to investigate if an eCRF equation from a healthy population is useful in persons with rheumatoid arthritis (RA), and if necessary, develop new equations for eCRF in this group. METHODS VO2peak results from 93 persons with RA were compared to eCRF calculated by an established equation for healthy individuals including age, sex, physical activity (PA index), resting heart rate (RHR) and waist circumference. Because of deviation from the observed VO2peak, new equations for eCRF in persons with RA were developed from regression analysis of variables associated with observed VO2peak. RESULTS The established equation over-estimated CRF (R=0.48, RMSE=7.07). The new RA equation more accurately estimated CRF (R=0.81, RMSE=4.44) (female=0, male=1; never smoked=0, ever smoked=1): eCRF = 77.961 + (sex × 28.791) - (age × 0.358) - (age × sex interaction × 0.326) - (body mass index (BMI) × 0.700) - (RHR ×0.125) - (smoking × 1.854) + (PA index × 0.211) - (patient global RA assessment × 0.071). Alternative new RA equation (R=0.79, RMSE=4.63): eCRF = 77.851 + (sex × 25.460) - (age × 0.381) - (age × sex interaction × 0.254) - (BMI × 0.743) - (RHR × 0.115) - (smoking × 2.154) + (PA index × 0.209). CONCLUSIONS The new RA equations better predicted CRF in individuals with RA, preventing overestimation in low-fit persons. The new equation should be preferred when estimating CRF in individuals with RA. The alternative equation, without patient global assessment, is useful for individuals with RA in population-based studies.
Compressive Strength Prediction of PVA Fiber-Reinforced Cementitious Composites Containing Nano-SiO2 Using BP Neural Network

In this study, a method to optimize the mixing proportion of polyvinyl alcohol (PVA) fiber-reinforced cementitious composites and improve its compressive strength based on the Levenberg-Marquardt backpropagation (BP) neural network algorithm and genetic algorithm is proposed by adopting a three-layer neural network (TLNN) as a model and the genetic algorithm as an optimization tool. A TLNN was established to implement the complicated nonlinear relationship between the input (factors affecting the compressive strength of cementitious composite) and output (compressive strength). An orthogonal experiment was conducted to optimize the parameters of the BP neural network. Subsequently, the optimal BP neural network model was obtained. The genetic algorithm was used to obtain the optimum mix proportion of the cementitious composite. The optimization results were predicted by the trained neural network and verified. Mathematical calculations indicated that the BP neural network can precisely and practically demonstrate the nonlinear relationship between the cementitious composite and its mixture proportion and predict the compressive strength. The optimal mixing proportion of the PVA fiber-reinforced cementitious composites containing nano-SiO2 was obtained. The results indicate that the method used in this study can effectively predict and optimize the compressive strength of PVA fiber-reinforced cementitious composites containing nano-SiO2.
Disruption of the Unique ABCG-Family NBD:NBD Interface Impacts Both Drug Transport and ATP Hydrolysis

ABCG2 is one of a triumvirate of human multidrug ATP binding cassette (ABC) transporters that are implicated in the defense of cells and tissues against cytotoxic chemicals, but these transporters can also confer chemotherapy resistance states in oncology. Understanding the mechanism of ABCG2 is thus imperative if we are to be able to counter its deleterious activity. The structure of ABCG2 and its related family members (ABCG5/G8) demonstrated that there were two interfaces between the nucleotide binding domains (NBD). In addition to the canonical ATP “sandwich-dimer” interface, there was a second contact region between residues at the C-terminus of the NBD. We investigated this second interface by making mutations to a series of residues that are in close interaction with the opposite NBD. Mutated ABCG2 isoforms were expressed in human embryonic kidney (HEK) 293T cells and analysed for targeting to the membrane, drug transport, and ATPase activity. Mutations to this second interface had a number of effects on ABCG2, including altered drug specificity, altered drug transport, and, in two mutants, a loss of ATPase activity. The results demonstrate that this region is particularly sensitive to mutation and can impact not only direct, local NBD events (i.e., ATP hydrolysis) but also the allosteric communication to the transmembrane domains and drug transport.
MPL Mutations in Essential Thrombocythemia Uncover A Common Path of Activation with Eltrombopag Dependent on W491.

Mutations in the gene (MPL) encoding the human thrombopoietin receptor (TpoR) drive sporadic and familial essential thrombocythemia (ET). We identified two ET patients that harbor double mutations in cis in MPL, namely L498W-H499C and H499Y-S505N. Using biochemical and signaling assays along with partial saturation mutagenesis we show that L498W is an activating mutation potentiated by H499C, and that H499C/Y enhance the activity of the canonical S505N mutation. L498W and H499C can activate a truncated TpoR mutant, which lacks the extracellular domain, indicating these mutations act on the transmembrane (TM)-cytosolic domain. Using a protein complementation assay we show that L498W and H499C strongly drive dimerization of TpoR. Activation by tryptophan substitution is exquisitely specific for position 498. Using structure-guided mutagenesis we identify upstream amino acid W491 as a key residue required for activation by L498W or canonical activating mutations such as S505N and W515K, as well as by eltrombopag. Structural data point to a common dimerization and activation path for TpoR via its TM domain that is shared between the small molecule agonist eltrombopag and canonical and novel activating TpoR mutations that all depend on W491, a potentially accessible extracellular residue that could become a target for therapeutic intervention.
The potential impact of the Affordable Care Act and Medicaid expansion on reducing colorectal cancer screening disparities in African American males

Few investigations have explored the potential impact of the Affordable Care Act on health disparity outcomes in states that chose to forgo Medicaid expansion. Filling this evidence gap is pressing as Congress grapples with controversial healthcare legislation that could phase out Medicaid expansion. Colorectal cancer (CRC) is a commonly diagnosed, preventable cancer in the US that disproportionately burdens African American men and has substantial potential to be impacted by improved healthcare insurance coverage. Our objective was to estimate the impact of the Affordable Care Act (increasing insurance through health exchanges alone or with Medicaid expansion) on colorectal cancer outcomes and economic costs among African American and White males in North Carolina (NC), a state that did not expand Medicaid. We used an individual-based simulation model to estimate the impact of ACA (increasing insurance through health exchanges alone or with Medicaid expansion) on three CRC outcomes (screening, stage-specific incidence, and deaths) and economic costs among African American and White males in NC who were age-eligible for screening (between ages 50 and 75) during the study period, years of 2013–2023. Health exchanges and Medicaid expansion improved simulated CRC outcomes overall, though the impact was more substantial among AAs. Relative to health exchanges alone, Medicaid expansion would prevent between 7.1 to 25.5 CRC cases and 4.1 to 16.4 per 100,000 CRC cases among AA and White males, respectively. Our findings suggest policies that expanding affordable, quality healthcare coverage could have a demonstrable, cost-saving impact while reducing cancer disparities.
Morphine consumption during pregnancy exacerbates neonatal hypoxia‐ischemia injury in rats

Hypoxia‐Ischemia (HI) is the most common cause of death and disability in human infants. The use of opiate in pregnant women affects their children. The aim of this study was to evaluate the effect of morphine consumption during pregnancy and lactation on vulnerability to neonatal HI in rats.
Dissipation of Emamectin Benzoate Residues in Rice and Rice-Growing Environments

The experiment developed the ultra-high-performance liquid chromatography–tandem mass spectrometry (UPLC/MS/MS) method for testing emamectin benzoate, and studied the metabolism of emamectin benzoate in rice plants and rice-growing environments via application of this testing method. The dissipation curve of emamectin benzoate standard substance was good at 0.5–200 μg L−1, and its correlation coefficient was greater than 0.99. In the concentration range of 0.1–50 μg kg−1, the average recovery rate of plants, soil, and field water was 82 %–102 %, and relative standard deviation (RSD) was between 0.3 % and 15.9 %. Half-lives in rice plants and soil were 0.8–2.8 days and 1.9–3.8 days, respectively, and emamectin benzoate was not detected in rice or rice hull. The experiment showed that emamectin benzoate is harmless to human health at the concentration recommended by the manufacturer.
Adult Migraine Hospital Admission Trends in Finland: A Nationwide Registry Study

Population-level data on migraine hospital admission trends are unavailable. Changes in stroke care may have influenced these, since migraine is one of the most common stroke mimics. In this study, all hospital admissions on neurological, internal medicine, and pediatric wards in Finland with migraine as the primary diagnosis for persons at least 16 years of age in 2004–2014 were studied, resulting in an analysis of 6195 individuals with 7764 migraine discharges. The number of discharges increased by 4.2% annually (p = 0.000084), with no change in age of the admitted patients. Comorbidity burden was low but increased during the study period (p < 0.0001). The frequency of common vascular risk factors as comorbidities increased by 11–19% annually. Admission duration shortened by 2% annually (p < 0.0001). An intravenous thrombolysis was given in four admissions. It seems that migraine hospital admissions have become more frequent and the patients more often have cardiovascular risk factors, suggesting increased awareness and more aggressive acute evaluation of suspected stroke as the cause.
De Novo ARID1B mutations cause growth delay associated with aberrant Wnt/β–catenin signaling

Haploinsufficiency of ARID1B (AT‐rich interaction domain 1B) has been involved in autism spectrum disorder, nonsyndromic and syndromic intellectual disability, and corpus callosum agenesis. Growth impairment is a major clinical feature caused by ARID1B mutations; however, the mechanistic link has not been elucidated. Here, we confirm that growth delay is a common characteristic of patients with ARID1B mutations, which may be associated with dysregulation of the Wnt/β–catenin signaling pathway. An analysis of patients harboring pathogenic variants of ARID1B revealed that nearly half had short stature and nearly all had below‐average height. Moreover, the percentage of patients with short stature increased with age. Knockdown of arid1b in zebrafish embryos markedly reduced body length and perturbed the expression of both chondrogenic and osteogenic genes including sox9a, col2a1a, runx2b, and col10a1. Knockout of Arid1b in chondrogenic ATDC5 cells inhibited chondrocyte proliferation and differentiation. Finally, Wnt/β–catenin signaling was perturbed in Arid1b‐depleted zebrafish embryos and Arid1b knockout ATDC5 cells. These data indicate that ARID1B modulates bone growth possibly via regulation of the Wnt/β–catenin pathway, and may be an appropriate target for gene therapy in disorders of growth and development.
Gastric Cancer in History: A Perspective Interdisciplinary Study

Background: Gastric adenocarcinoma is the fourth most common type of cancer and the second leading cause of cancer death in the world. Despite abundant traces of an ancient history, the comprehension of its pathogenic mechanisms is rather recent and continuously updated. Methods: We investigated about how the ancient civilizations tried to understand the exactly physiopathology of gastric cancer, from the time when they could not examine deeply the histological and pathophysiologic aspects of the disease, but they just based their knowledge on a visual analysis of the signs and consequences of such disease. We examined the historical evolving knowledge of the disease along the centuries on the gastroenterological, pharmacological, and surgical fields, defining how gastric cancer became an increasingly curable disease. Results: Cancer was known in the ancient world. Ancient people did not know exactly the causes but the climatic, hygienic, and food conditions were the first to be considered over time, also taking into consideration supernatural negative influences. During the Renaissance, a tumultuous time of scientific discoveries started, thanks to an increasing number of autopsies made on cadavers and to the progressions in visual analysis of the stomach mucosa throughout endoscopy. From the first gastric surgery in 1879, many steps forward have been made and, today, gastric cancer is regarded as a more curable disease; one important discovery in this field has been the revelation of the role of Helicobacter pylori in the peptic ulcer disease (PUD) and in some forms of gastric lymphoma. Conclusions: Gastric cancer has the fourth highest incidence of various cancers worldwide and is ranked second as a cause of cancer-related death. It exists from the antiquity and a lot of hypotheses have been developed about its etiology during the centuries, influencing its therapy. During the 20th century, thanks to the scientific and technological progresses the causes of the cancer have been discovered and the role of the bacterium Helicobacter pylori has been demonstrated, and new perspective research are currently trying to investigate the role of other microorganisms in gastric physiopathology, as well as its possible modulation by probiotics.
Efficacy of salbutamol in the treatment of infants with bronchiolitis

Abstract Background: To systematically evaluate the clinical efficacy of salbutamol treatment in infants with bronchiolitis. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) investigating the use of salbutamol in infants with bronchiolitis was performed. The Cochrane Risk of Bias Assessment Tool was used to evaluate the quality of RCTs. Data were extracted and meta-analyzed using STATA version 12.0 (StataCorp, College Station, TX). Results: Thirteen RCTs, including a total of 977 participants, were assessed in the present meta-analysis. Results indicated that salbutamol therapy for bronchiolitis in infants led to an increase in respiratory rate (weighted mean difference [WMD] 2.26 [95% confidence interval {CI} 0.36–4.16]) and higher heart rate (WMD 12.15 [95% CI 9.24–15.07]). However, as a selective β2-agonist, salbutamol did not improve the clinical severity score of infants with bronchiolitis (WMD –0.11 [95% CI –0.26 to 0.03]), length of hospital stay (WMD 0.12 [95% CI –0.32 to 0.56]), or oxygen saturation (WMD 0.20 [95% CI –0.35 to 0.75]). Conclusion: Based on the results of this systematic review, the use of salbutamol had no effect on bronchiolitis in children <24 months of age. Moreover, the treatment can also lead to side effects, such as high heart rate. As such, salbutamol should not be recommended for treatment of bronchiolitis in infants.
Reducing the structure bias of RNA-Seq reveals a large number of non-annotated non-coding RNA

Abstract The study of RNA expression is the fastest growing area of genomic research. However, despite the dramatic increase in the number of sequenced transcriptomes, we still do not have accurate estimates of the number and expression levels of non-coding RNA genes. Non-coding transcripts are often overlooked due to incomplete genome annotation. In this study, we use annotation-independent detection of RNA reads generated using a reverse transcriptase with low structure bias to identify non-coding RNA. Transcripts between 20 and 500 nucleotides were filtered and crosschecked with non-coding RNA annotations revealing 111 non-annotated non-coding RNAs expressed in different cell lines and tissues. Inspecting the sequence and structural features of these transcripts indicated that 60% of these transcripts correspond to new snoRNA and tRNA-like genes. The identified genes exhibited features of their respective families in terms of structure, expression, conservation and response to depletion of interacting proteins. Together, our data reveal a new group of RNA that are difficult to detect using standard gene prediction and RNA sequencing techniques, suggesting that reliance on actual gene annotation and sequencing techniques distorts the perceived architecture of the human transcriptome.
Intra-individual variation of particles in exhaled air and of the contents of Surfactant protein A and albumin

Introduction Particles in exhaled air (PEx) provide samples of respiratory tract lining fluid from small airways containing, for example, Surfactant protein A (SP-A) and albumin, potential biomarkers of small airway disease. We hypothesized that there are differences between morning, noon, and afternoon measurements and that the variability of repeated measurements is larger between days than within days. Methods PEx was obtained in sixteen healthy non-smoking adults on 11 occasions, within one day and between days. SP-A and albumin were quantified by ELISA. The coefficient of repeatability (CR), intraclass correlation coefficient (ICC), and coefficient of variation (CV) were used to assess the variation of repeated measurements. Results SP-A and albumin increased significantly from morning towards the noon and afternoon by 13% and 25% on average, respectively, whereas PEx number concentration and particle mean mass did not differ significantly between the morning, noon and afternoon. Between-day CRs were not larger than within-day CRs. Conclusions Time of the day influences the contents of SP-A and albumin in exhaled particles. The variation of repeated measurements was rather high but was not influenced by the time intervals between measurements.
Light microscopy of Pakistani Berberis leaf cuticles and its taxonomic implications

Taxonomy of the genus Berberis is quite complex, due to overlapping morphological characters, making it very difficult to differentiate the species within the genus. In order to resolve this taxonomic complexity, the foliar anatomy of 10 Berberis L. species was carried out, for the first time from Pakistan, using light microscopy (LM). Significant variation in terms of epidermal cells shape, size, cell wall pattern, and stomata type was observed. B. baluchistanica has the largest epidermal cells, Adaxial: length = 45–(53.9 ± 3.6)–62.5 μm; and width = 22.5–(26.3 ± 1.3)–30 μm; Abaxial: length = 37.5–(43.25 ± 2.5)–50 μm; and width = 20–(22.6 ± 0.8)–25. The highest number of stomata was observed in B. glaucocarpa as 62 on the abaxial surface while the lowest number of stomata was recorded in B. baluchistanica as 8 on the adaxial surface. Of 10 investigated species, 6 possess anomocytic type stomata, while 2 species that is, B. aitchisonii and B. parkeriana have both anomocytic and anisocytic stomata while B. baluchistanica and B. calliobotrys have only paracytic type stomata. The highest number of cells per unit area was present on the adaxial surface of B. calliobotrys ranging from 245–(252.4)–260 followed by B. parkeriana with 209–(227.8)–250 on the abaxial surface. Stomatal index (SI) also varied considerably and was the lowest (2.6) percentage in B. baluchistanica and highest (31.9) percentage in B. kunawurensis. A taxonomic key based on micro‐morphological characters is provided for species identification.
Simple Syntheses of New Pegylated Trehalose Derivatives as a Chemical Tool for Potential Evaluation of Cryoprotectant Effects on Cell Membrane

In our work, we developed the synthesis of new polyfunctional pegylated trehalose derivatives and evaluated their cryoprotective effect using flow cytometry. We showed that new compounds (modified trehaloses) bound to appropriate extracellular polymeric cryoprotectants could be helpful as a chemical tool for the evaluation of their potential toxic cell membrane influences. Our aim was to form a chemical tool for the evaluation of cryoprotectant cell membrane influences, which are still not easily predicted during the freezing/thawing process. We combined two basic cryoprotectants: polyethyleneglycols (PEGs) and trehalose in the new chemical compounds—pegylated trehalose hybrids. If PEG and trehalose are chemically bound and trehalose is adsorbed on the cell surface PEGs molecules which are, due to the chemical bonding with trehalose, close to the cell surface, can remove the cell surface hydration layer which destabilizes the cell membrane. This was confirmed by the comparison of new material, PEG, trehalose, and their mixture cryoprotective capabilities.
Laboratory strains of Bacillus anthracis lose their ability to rapidly grow and sporulate compared to wildlife outbreak strains

Bacillus anthracis is the causative agent of anthrax in animals and humans. The organism lies in a dormant state in the soil until introduced into an animal via, ingestion, cutaneous inoculation or inhalation. Once in the host, spores germinate into rapidly growing vegetative cells elaborating toxins. When animals die of anthrax, vegetative bacteria sporulate upon nutrient limitation in the carcass or soil while in the presence of air. After release into the soil environment, spores form a localized infectious zone (LIZ) at and around the carcass. Laboratory strains of B. anthracis produce fewer proteins associated with growth and sporulation compared to wild strains isolated from recent zoonotic disease events. We verified wild strains grow more rapidly than lab strains demonstrating a greater responsiveness to nutrient availability. Sporulation was significantly more rapid in these wild strains compared to lab strains, indicating wild strains are able to sporulate faster due to nutrient limitation while laboratory strains have a decrease in the speed at which they utilize nutrients and an increase in time to sporulation. These findings have implications for disease control at the LIZ as well as on the infectious cycle of this dangerous zoonotic pathogen.