Miracle-dz/UniFAR-FTUs huggingface dataset:
Change in Myocardial Contractility in Response to Treatment with Norepinephrine in Septic Shock.

1. Leitao Filho FS,Mattman A, Schellenberg R, Criner GJ,Woodruff P, Lazarus SC, et al. Serum IgG levels and risk of COPD hospitalization: a pooled meta-analysis. Chest 2020;158:1420–1430. 2. Suissa S, Dell’Aniello S, Ernst P. Long-term natural history of chronic obstructive pulmonary disease: severe exacerbations and mortality. Thorax 2012;67:957–963. 3. Alotaibi NM, Chen V, Hollander Z, Leipsic JA, Hague CJ, Murphy DT, et al. Phenotyping and outcomes of hospitalized COPD patients using rapid molecular diagnostics on sputum samples. Int J Chron Obstruct Pulmon Dis 2019;14:311–319. 4. Perez EE, Orange JS, Bonilla F, Chinen J, Chinn IK, DorseyM, et al.Update on the use of immunoglobulin in human disease: a review of evidence. J Allergy Clin Immunol 2017;139:S1–S46. 5. Mattman A, Hollander Z, Chen VY, Ng R, Fitzgerald JM, Leung JM, et al. Hypogammaglobulinemia is associated with increased 1-year mortality in chronic obstructive pulmonary disease [abstract]. Am J Respir Crit Care Med 2020;201:A4483. 6. van der Gugten G, DeMarco ML, Chen LYC, Chin A, Carruthers M, Holmes DT, et al. Resolution of spurious immunonephelometric IgG subclass measurement discrepancies by LC-MS/MS.Clin Chem 2018;64:735–742. 7. Dati F, Schumann G, Thomas L, Aguzzi F, Baudner S, Bienvenu J, et al.; International Federation of Clinical Chemistry. Community Bureau of Reference of the Commission of the European Communities. College of American Pathologists. Consensus of a group of professional societies and diagnostic companies on guidelines for interim reference ranges for 14 proteins in serum based on the standardization against the IFCC/BCR/ CAP ReferenceMaterial (CRM 470). Eur J Clin ChemClin Biochem 1996; 34:517–520. 8. Leitao Filho FS,WonRaS,MattmanA, SchellenbergRS, FishbaneN,Criner GJ, et al. Serum IgG and risk of exacerbations and hospitalizations in chronic obstructive pulmonary disease. J Allergy Clin Immunol 2017;140: 1164–1167.e6. 9. Cowan J, Gaudet L, Mulpuru S, Corrales-Medina V, Hawken S, Cameron C, et al. A retrospective longitudinal within-subject risk interval analysis of immunoglobulin treatment for recurrent acute exacerbation of chronic obstructive pulmonary disease. PLoS One 2015;10:e0142205. 10. McCullagh BN, Comellas AP, Ballas ZK, Newell JD Jr, Zimmerman MB, Azar AE. Antibody deficiency in patients with frequent exacerbations of chronic obstructive pulmonary disease (COPD). PLoS One 2017;12: e0172437. 11. Upton J. Immunodeficiencies with hypergammaglobulinemia: a review. LymphoSign Journal 2014;2:57–73. 12. Agust ı A, Edwards LD, Rennard SI, MacNee W, Tal-Singer R, Miller BE, et al.; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Persistent systemic inflammation is associated with poor clinical outcomes in COPD: a novel phenotype. PLoS One 2012;7:e37483. 13. L opez-Campos JL, Fern andez-Villar A, Ruano-Ravina A. Triple-therapy trials for chronic obstructive pulmonary disease: Methodological considerations in the mortality effect. Am J Respir Crit Care Med 2021; 203:925-926.
Shift of Dominant Species in Plant Community and Soil Chemical Properties Shape Soil Bacterial Community Characteristics and Putative Functions: A Case Study on Topographic Variation in a Mountain Pasture

Reducing management intensity according to the topography of pastures can change the dominant plant species from sown forages to weeds. It is unclear how changes in species dominance in plant community drive spatial variation in soil bacterial community characteristics and functions in association with edaphic condition. Analysing separately the effects of both plant communities and soil chemical properties on bacterial community is crucial for understanding the biogeographic process at a small scale. In this paper, we investigated soil bacterial responses in five plant communities (two forage and three weed), where >65% of the coverage was by one or two species. The structure and composition of the bacterial communities in the different microbiome were analysed using sequencing and their characteristics were assessed using the Functional Annotation of Prokaryotic Taxa (FAPROTAX) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Firmicutes and Planctomycetes responded only to one specific plant community, and each plant community harboured unique operational taxonomic units (OTUs) at the species level. There were a large percentage of uniquely absent OTUs for specific plant communities, suggesting that a negative effect is critical in the relationship between plants and bacteria. Bacterial diversity indices were influenced more by soil chemical properties than by plant communities. Some putative functions related to C and N recycling including nitrogen fixation were correlated with pH, electrical conductivity (EC) and nutrient levels, and this also implied that some biological functions, such as ureolysis and carbon metabolism, may decline when fertilisation intensity is reduced. Taken together, these results suggest that a shift of dominant species in plant community exerts individual effects on the bacterial community composition, which is different from the effect of soil chemical properties.
Advances in Genomic Discovery and Implications for Personalized Prevention and Medicine: Estonia as Example

The current paradigm of personalized medicine envisages the use of genomic data to provide predictive information on the health course of an individual with the aim of prevention and individualized care. However, substantial efforts are required to realize the concept: enhanced genetic discoveries, translation into intervention strategies, and a systematic implementation in healthcare. Here we review how further genetic discoveries are improving personalized prediction and advance functional insights into the link between genetics and disease. In the second part we give our perspective on the way these advances in genomic research will transform the future of personalized prevention and medicine using Estonia as a primer.
Prevalence of sarcopenic obesity and association with metabolic syndrome in an adult Iranian cohort: The Fasa PERSIAN cohort study

Sarcopenic obesity (SO) is characterised by a concomitant high fat mass (FM) and low fat free mass (FFM) leading to an increased cardio‐metabolic risk. This analysis aims to estimate the SO prevalence in Iranian adults and evaluate the association of SO with metabolic syndrome (MetS) risk. This cross‐sectional analysis included 4296 subjects (age 35‐70 years, 55.2% females). Body composition parameters, measured by bioelectrical impedance included: FM, FFM, appendicular lean mass (ALM) and skeletal mass index. SO was classified according to five criteria: (1) FM%‐SMI; (2) FM%‐ALM/% weight (wt%); (3) FM%‐ALM/body mass index (BMI); (4) Residuals of ALM and FM and (5) FM/FFM Ratio. Multivariate logistic regression was applied to explore the association between SO models with MetS risk stratified by gender. Receiving operating characteristic (ROC) curves were used to identify the best FM/FFM ratio cut‐off value for detecting MetS cases in males and females. The prevalence of SO varied between 4% and 26% depending upon the classification method. The prevalence of MetS was 12.8% and 31.6% in males and females, respectively. SO models based on ALM/wt% and FM/FFM ratio showed the strongest association with MetS risk in males (OR: 11.5, 95%CI: 7.5‐17.7, p < 0.001 and OR: 10.1, 95%CI: 6.9‐14.7, p < 0.001, respectively) and females (OR: 4.1, 95%CI: 3.0‐5.6, p < 0.001 and OR: 4.6, 95%CI: 3.5‐5.9, p < 0.001, respectively). SO is a prevalent condition in an adult Iranian population and the ALM/wt% and the FM/FFM ratio models of SO appeared to be associated with higher MetS risk.
Effects of TGF-β1 Receptor Inhibitor GW788388 on the Epithelial to Mesenchymal Transition of Peritoneal Mesothelial Cells

We investigated the effectiveness of the transforming growth factor beta-1 (TGF-β) receptor inhibitor GW788388 on the epithelial to mesenchymal transition (EMT) using human peritoneal mesothelial cells (HPMCs) and examined the effectiveness of GW788388 on the peritoneal membrane using a peritoneal fibrosis mouse model. HPMCs were treated with TGF-β with or without GW788388. Animal experiments were conducted on male C57/BL6 mice. Peritoneal fibrosis was induced by intraperitoneal injection of chlorhexidine gluconate. GW788388 was administered by once-daily oral gavage. The morphological change, cell migration, and invasion resulted from TGF-β treatment, but these changes were attenuated by cotreatment with GW788388. TGF-β-treated HPMCs decreased the level of the epithelial cell marker and increased the levels of the mesenchymal cell markers. Cotreatment with GW788388 reversed these changes. Phosphorylated Smad2 and Smad3 protein levels were stimulated with TGF-β and the change was attenuated by cotreatment with GW788388. For the peritoneal fibrosis mice, thickness and collagen deposition of parietal peritoneum was increased, but this change was attenuated by cotreatment with GW788388. GW788388, an orally available potent TGF-β receptor type 1 inhibitor, effectively attenuated TGF-β-induced EMT in HPMCs. Cotreatment with GW788388 improved peritoneal thickness and fibrosis, and recovered peritoneal membrane function in a peritoneal fibrosis mouse model.
Solubility and Stability of Some Pharmaceuticals in Natural Deep Eutectic Solvents-Based Formulations

Some medicines are poorly soluble in water. For tube feeding and parenteral administration, liquid formulations are required. The discovery of natural deep eutectic solvents (NADES) opened the way to potential applications for liquid drug formulations. NADES consists of a mixture of two or more simple natural products such as sugars, amino acids, organic acids, choline/betaine, and poly-alcohols in certain molar ratios. A series of NADES with a water content of 0–30% (w/w) was screened for the ability to solubilize (in a stable way) some poorly water-soluble pharmaceuticals at a concentration of 5 mg/mL. The results showed that NADES selectively dissolved the tested drugs. Some mixtures of choline-based NADES, acid-neutral or sugars-based NADES could dissolve chloral hydrate (dissociated in water), ranitidine·HCl (polymorphism), and methylphenidate (water insoluble), at a concentration of up to 250 mg/mL, the highest concentration tested. Whereas a mixture of lactic-acid–propyleneglycol could dissolve spironolacton and trimethoprim at a concentration up to 50 and 100 mg/mL, respectively. The results showed that NADES are promising solvents for formulation of poorly water-soluble medicines for the development of parenteral and tube feeding administration of non-water-soluble medicines. The chemical stability and bioavailability of these drug in NADES needs further studies.
Resolving Entangled JH-H-Coupling Patterns for Steroidal Structure Determinations by NMR Spectroscopy

For decades, high-resolution 1H NMR spectroscopy has been routinely utilized to analyze both naturally occurring steroid hormones and synthetic steroids, which play important roles in regulating physiological functions in humans. Because the 1H signals are inevitably superimposed and entangled with various JH–H splitting patterns, such that the individual 1H chemical shift and associated JH–H coupling identities are hardly resolved. Given this, applications of thess information for elucidating steroidal molecular structures and steroid/ligand interactions at the atomic level were largely restricted. To overcome, we devoted to unraveling the entangled JH–H splitting patterns of two similar steroidal compounds having fully unsaturated protons, i.e., androstanolone and epiandrosterone (denoted as 1 and 2, respectively), in which only hydroxyl and ketone substituents attached to C3 and C17 were interchanged. Here we demonstrated that the JH–H values deduced from 1 and 2 are universal and applicable to other steroids, such as testosterone, 3β, 21-dihydroxygregna-5-en-20-one, prednisolone, and estradiol. On the other hand, the 1H chemical shifts may deviate substantially from sample to sample. In this communication, we propose a simple but novel scheme for resolving the complicate JH–H splitting patterns and 1H chemical shifts, aiming for steroidal structure determinations.
The Roles of Calcium and ATP in the Physiology and Pathology of the Exocrine Pancreas.

This review deals with the roles of calcium and ATP in the control of the normal functions of the different cell types in the exocrine pancreas as well as the roles of these molecules in the pathophysiology of Acute Pancreatitis. Repetitive rises in the local cytosolic calcium ion concentration in the apical part of the acinar cells do not only activate exocytosis but also, via an increase in the intra-mitochondrial calcium ion concentration, stimulate the ATP formation that is needed to fuel the energy-requiring secretion process. However, intracellular calcium overload, resulting in a global sustained elevation of the cytosolic calcium ion concentration, has the opposite effect of decreasing mitochondrial ATP production and this initiates processes that lead to the necrotic destruction of the cells. In the last few years it has become possible to image calcium signalling events simultaneously in acinar, stellate and immune cells in intact lobules of the exocrine pancreas. This has disclosed processes by which these cells interact with each other, particularly in relation to the initiation and development of Acute Pancreatitis. By unravelling the molecular mechanisms underlying this disease, several promising therapeutic intervention sites have been identified. This provides hope that we may soon be able to effectively treat this often fatal disease.
Haematotoxic effects of methanolic extract of Boswellia sacra oleo gum resin (frankinccense) in rats

In several parts of the world, Boswellia sacra Fluck. is one of the most commonly used herbs for the treatment of arthritis. Its usage should be validated in light of recent findings of haematotoxicity. This study was aimed to determine the effect of chronic administration of standardized methanolic extract of frankincense on blood cell count in experimental animals. Using high-performance liquid chromatography, the active constituents of B. sacra extract; boswellic acids were analyzed. The effect of three different doses of the extract (250, 500, and 1000 mg/kg) on different blood cells and associated parameters was investigated. The behavior, food, and water consumption of the rats were recorded. Boswellic acids were present in varying amounts with α-boswellic acid and β-boswellic acid present in more amounts compared to other boswellic acids in the extract. All three doses tested had no effect on the animals’ behavior, food consumption, or weight gain. The administration of a low (500 mg/kg) and high (1000 mg/kg) dose of the extract resulted in a non-dose dependent reduction in MCH (p < 0.01 and p < 0.05, respectively), but no other blood parameters were significantly affected. The B. sacra extract produces hypochromic normocytic anemia in rats at higher doses of 500 and 1000 mg/kg and this effect was not dose-dependent.
Reaching underserved South Africans with integrated chronic disease screening and mobile HIV counselling and testing: A retrospective, longitudinal study conducted in Cape Town

Background Community-based, mobile HIV counselling and testing (HCT) and screening for non-communicable diseases (NCDs) may improve early diagnosis and referral for care in underserved populations. We evaluated HCT/NCD data and described population characteristics of those visiting a mobile clinic in high HIV disease burden settings in Cape Town, South Africa, between 2008 and 2016. Methods Trained counsellors registered patients ≥12 years old at a mobile clinic, which offered HCT and blood pressure, diabetes (glucose testing) and obesity (body mass index) screening. A nurse referred patients who required HIV treatment or NCD care. Using multivariable logistic regression, we estimated correlates of new HIV diagnoses adjusting for gender, age and year. Results Overall, 43,938 individuals (50% male; 29% <25 years; median age = 31 years) tested for HIV at the mobile clinic, where 27% of patients (66% of males, 34% of females) reported being debut HIV testers. Males not previously tested for HIV had higher rates of HIV positivity (11%) than females (7%). Over half (55%, n = 1,343) of those previously diagnosed HIV-positive had not initiated ART. More than one-quarter (26%) of patients screened positive for hypertension (males 28%, females 24%, p<0.001). Females were more likely overweight (25% vs 20%) or obese (43% vs 9%) and presented with more diabetes symptoms than males (8% vs 4%). Females (3%) reported more symptoms of STIs than males (1%). Reporting symptoms of sexually transmitted infections (aOR = 3.45, 95% CI = 2.84, 4.20), diabetes symptoms (aOR = 1.61, 95% 1.35, 1.92), and TB symptoms (aOR = 4.40, 95% CI = 3.85, 5.01) were associated with higher odds of a new HIV diagnosis after adjusting for covariates. Conclusion Findings demonstrate that mobile clinics providing integrated HCT and NCD screening may offer the opportunity of early diagnosis and referral for care for those who delay screening, including men living with HIV not previously tested.
Virulence Factors and Antifungal Susceptibility Profile of C. tropicalis Isolated from Various Clinical Specimens in Alexandria, Egypt

Background: The incidence of candidiasis caused by non-albicans Candida (NAC) species is increasing. Candida tropicalis has emerged as one of the most important NAC species. This study aims to examine the antifungal susceptibility profile and some virulence factors of C. tropicalis isolated from various clinical specimens. Methods: A total of 71 C. tropicalis isolates from various clinical specimens (69.01%, 18.31%, 9.86%, and 2.82% of isolates were collected from urine, respiratory samples, blood, and skin and soft tissue infections, respectively) from ICU patients in Alexandria, Egypt. The isolates were identified at species level by CHROMagar Candida and VITEK 2 compact system. Furthermore, the antifungal susceptibility was determined using the VITEK 2 system AST-YS07 card containing different antifungals. Hemolysin, phospholipase, and proteinase activity and biofilm formation were also tested as virulence factors. Results: Only 30 isolates (42.25%) were non-susceptible (MIC ≥ 4 µg/mL) to fluconazole, of which 28 isolates showed non-susceptibility (MIC ≥ 0.25 µg/mL) to voriconazole. All isolates showed both hemolysin and proteinase activities, while only 9 isolates (12.68%) showed phospholipase production and 70 isolates (98.59%) demonstrated biofilm formation. Strong biofilm production was observed among the blood culture isolates (85.71%), followed by the respiratory and urinary isolates (61.54% and 46.94%, respectively). Conclusions: This study sought to provide useful data on the antifungal susceptibility of C. tropicalis isolates from ICU patients suffering from invasive infections with an increased trend towards elevated MICs levels of both fluconazole and voriconazole. Due to the high incidence of systemic candidiasis and antifungal resistance, C. tropicalis is emerging as a serious root of infections. Therefore, early and accurate identification of Candida species along with susceptibility testing is of utmost importance.
Preoperative risk factors influencing inter-stage mortality after the Norwood procedure.

OBJECTIVES With improvements in early survival after the stage I palliation (S1P) Norwood procedure for hypoplastic left heart syndrome (HLHS) and its variants, inter-stage death accounts for an increasing proportion of mortality. Our aim was to identify the risk factors for inter-stage mortality. METHODS The records of 322 neonates with HLHS or a variant who underwent the Norwood procedure at our centre between 2001 and 2019 were retrospectively analysed. RESULTS The diagnoses included 271 neonates with HLHS (84%) and 51 with variants (16%). Aortic atresia was observed in 138 (43%) patients, mitral atresia in 91 (28%), extracardiac anomalies in 42 (13%) and genetic disorder in 14 (4%). The median age and weight of the patients at the S1P Norwood procedure were 9 (interquartile range: 7-12) days and 3.2 (2.9-3.5) kg, respectively. The median cardiopulmonary bypass time was 137 (107-163) min. Modified Blalock-Taussig shunts were used in 159 (49%) and unvalved right ventricle-to-pulmonary artery shunts in 163 (51%) patients. The number of inter-stage deaths was as follows: between S1P and stage II palliation (S2P), 61 including 38 early (<30 days) and 23 late (>30 days) deaths, and between S2P and stage III palliation, 32 deaths. Low birth weight (<2.5 kg) (odds ratio 4.37, P = 0.020) and restrictive atrial septum (odds ratio 2.97, P = 0.013) were identified as risks for early mortality. Low birth weight [hazard ratio (HR) 0.99/g, P = 0.002] was a risk for inter-stage mortality between S1P and S2P. Extracardiac anomalies (HR 4.75, P = 0.049) and significant pre-S1P atrioventricular valve regurgitation (HR: 7.72, P = 0.016) were risks for inter-stage mortality between S2P and stage III palliation. Other anatomical variables including aortic atresia, anatomical subtypes and the diameter of the ascending aorta nor shunt type were not identified as risk factors for mortality during any inter-stage period. CONCLUSIONS The risk factors for inter-stage attrition after the Norwood procedure were different between each stage. Preoperative factors, including birth weight, restrictive atrial septum and extracardiac anomalies, adversely affected the inter-stage mortality.
Extending approximate Bayesian computation with supervised machine learning to infer demographic history from genetic polymorphisms using DIYABC Random Forest

Simulation‐based methods such as approximate Bayesian computation (ABC) are well‐adapted to the analysis of complex scenarios of populations and species genetic history. In this context, supervised machine learning (SML) methods provide attractive statistical solutions to conduct efficient inferences about scenario choice and parameter estimation. The Random Forest methodology (RF) is a powerful ensemble of SML algorithms used for classification or regression problems. Random Forest allows conducting inferences at a low computational cost, without preliminary selection of the relevant components of the ABC summary statistics, and bypassing the derivation of ABC tolerance levels. We have implemented a set of RF algorithms to process inferences using simulated data sets generated from an extended version of the population genetic simulator implemented in DIYABC v2.1. 0. The resulting computer package, named DIYABC Random Forest v1.0, integrates two functionalities into a user‐friendly interface: the simulation under custom evolutionary scenarios of different types of molecular data (microsatellites, DNA sequences or SNPs) and RF treatments including statistical tools to evaluate the power and accuracy of inferences. We illustrate the functionalities of DIYABC Random Forest v1.0 for both scenario choice and parameter estimation through the analysis of pseudo‐observed and real data sets corresponding to pool‐sequencing and individual‐sequencing SNP data sets. Because of the properties inherent to the implemented RF methods and the large feature vector (including various summary statistics and their linear combinations) available for SNP data, DIYABC Random Forest v1.0 can efficiently contribute to the analysis of large SNP data sets to make inferences about complex population genetic histories.