Miracle-dz/UniFAR-FTUs huggingface dataset:
Organic contamination detection for isotopic analysis of water by laser spectroscopy.

RATIONALE Hydrogen and oxygen stable isotope ratios (δ2 H, δ17 O, and δ18 O values) are commonly used tracers of water. These ratios can be measured by isotope ratio infrared spectroscopy (IRIS). However, IRIS approaches are prone to errors induced by organic compounds present in plant, soil, and natural water samples. A novel approach using 17 O-excess values has shown promise for flagging spectrally-contaminated plant samples during IRIS analysis. A systematic assessment of this flagging system is needed to prove it useful. METHODS Errors induced by methanol and ethanol water mixtures on measured IRIS and IRMS results were evaluated. For IRIS analyses both liquid and vapour-mode (via direct vapour equilibration) methods are used. The δ2 H, δ17 O, and δ18 O values were measured and compared with known reference values to determine the errors induced by methanol and ethanol contamination. In addition, the 17 O-excess contamination detection approach was tested. This is a post processing detection tool for both liquid and vapour IRIS triple-isotope analyses, utilizing calculated 17 O-excess values to flag contaminated samples. RESULTS Organic contamination induced significant errors in IRIS results which were not seen in IRMS results. Methanol caused larger errors than ethanol. Results from vapour-IRIS analyses had larger errors than those from liquid-IRIS analyses. The 17 O-excess approach identified methanol driven error in liquid and vapour-mode IRIS samples at levels where isotope results became unacceptably erroneous. For ethanol contaminated samples a mix of erroneous and correct flagging occurred with the 17 O-excess method. Our results indicate that methanol is the more problematic contaminant for data corruption. The 17 O-excess method was therefore useful for data quality control. CONCLUSION Organic contamination caused significant errors in IRIS stable isotope results. These errors were larger during vapour analysis than during liquid IRIS analyses, and larger for methanol than ethanol contamination. The 17 O-excess method is highly sensitive for detecting narrowband (methanol) contamination error in vapour and liquid analysis modes on IRIS.
Lead and Cadmium as Cardiovascular Risk Factors: The Burden of Proof Has Been Met

Globally, cardiovascular disease (CVD) is the leading cause of mortality, taking an estimated 17.9 million lives annually. Myocardial infarction and stroke account for 80% of these deaths.1 Over decades, through epidemiologic, basic, and clinical studies, physicianscientists have recognized that increasing age, male sex, heredity, tobacco smoke, high blood cholesterol, high blood pressure, physical inactivity, obesity, diabetes mellitus, stress, excessive alcohol use, and diet/nutrition promote the development of atherosclerotic heart disease. We contend that 2 environmental metal contaminants, lead and cadmium, have met the burden of proof to be considered coronary risk factors. To support our viewpoint, we follow a framework that bases causality assessments on the integration of clinical, toxicological, and experimental evidence.2
Keeping up with the Bacillus cereus group: taxonomy through the genomics era and beyond

Abstract The Bacillus cereus group, also known as B. cereus sensu lato (s.l.), is a species complex that contains numerous closely related lineages, which vary in their ability to cause illness in humans and animals. The classification of B. cereus s.l. isolates into species-level taxonomic units is thus essential for informing public health and food safety efforts. However, taxonomic classification of these organisms is challenging. Numerous—often conflicting—taxonomic changes to the group have been proposed over the past two decades, making it difficult to remain up to date. In this review, we discuss the major nomenclatural changes that have accumulated in the B. cereus s.l. taxonomic space prior to 2020, particularly in the genomic sequencing era, and outline the resulting problems. We discuss several contemporary taxonomic frameworks as applied to B. cereus s.l. , including (i) phenotypic, (ii) genomic, and (iii) hybrid nomenclatural frameworks, and we discuss the advantages and disadvantages of each. We offer suggestions as to how readers can avoid B. cereus s.l. taxonomic ambiguities, regardless of the nomenclatural framework(s) they choose to employ. Finally, we discuss future directions and open problems in the B. cereus s.l. taxonomic realm, including those that cannot be solved by genomic approaches alone.
Bioanalysis in the Age of New Drug Modalities

In the absence of regulatory guidelines for the bioanalysis of new drug modalities, many of which contain multiple functional domains, bioanalytical strategies have been carefully designed to characterize the intact drug and each functional domain in terms of quantity, functionality, biotransformation, and immunogenicity. The present review focuses on the bioanalytical challenges and considerations for RNA-based drugs, bispecific antibodies and multi-domain protein therapeutics, prodrugs, gene and cell therapies, and fusion proteins. Methods ranging from the conventional ligand binding assays and liquid chromatography-mass spectrometry assays to quantitative polymerase chain reaction or flow cytometry often used for oligonucleotides and cell and gene therapies are discussed. Best practices for method selection and validation are proposed as well as a future perspective to address the bioanalytical needs of complex modalities.
Etiology, Clinical Course, and Outcomes of Pneumonia in the Elderly: A Retrospective and Prospective Cohort Study in Thailand

Abstract. Pneumonia is a leading cause of hospitalization and death among elderly adults. We performed a retrospective and prospective observational study to describe the etiology, clinical course, and outcomes of pneumonia for patients 60 years and older in Thailand. We enrolled 490 patients; 440 patients were included in the retrospective study and 50 patients were included in the prospective study. The CURB-65 score and a modified SMART-COP score (SMART-CO score) were used to assess disease severity. The median patient age was 80 years (interquartile range, 70–87 years); 51.2% were men. Klebsiella pneumoniae (20.4%) and Pseudomonas aeruginosa (15.5%) were the most common causative agents of pneumonia. A significant minority (23%) of patients were admitted to the intensive care unit (ICU), and mortality among this subset of patients was 45%. Most patients (80.8%) survived and were discharged from the hospital. The median duration of hospitalization was 8 days (interquartile range, 4–16 days). In contrast, 17.6% of patients died while undergoing care and 30-day mortality was 14%. Factors significantly associated with mortality were advanced age (P = 0.004), male sex (P = 0.005), multiple bacterial infections (P = 0.007; relative risk [RR], 1.88; 95% confidence interval [CI], 1.19–2.79), infection with multi-drug-resistant/extended-spectrum B-lactamase-producing organisms (P < 0.001; RR, 2.82; 95% CI, 1.83–4.85), ICU admission (P < 0.001; RR, 1.8; 95% CI, 1.4–2.3), and complications of pneumonia (P < 0.001; RR, 2.5; 95% CI, 1.8–3.4). Patients with higher SMART-CO and CURB-65 scores had higher rates of ICU admission and higher 30-day mortality rates (P < 0.001). These results emphasize the importance of Gram-negative bacteria, particularly K. pneumoniae and P. aeruginosa, as major causes of pneumonia among the elderly in contrast to other reports, Streptococcus pneumoniae is a common cause of pneumonia among elderly individuals worldwide. The SMART-COP and CURB-65 scores were developed to assess pneumonia severity and predict mortality of young adults with pneumonia. Few studies have examined the appropriateness of these scores for elderly patients with multiple comorbidities. A limited number of studies have used modified versions of these scores among elderly individuals. We found that Gram-negative bacteria has a major role in the etiology of pneumonia among elderly individuals in Southeast Asia. A significant proportion of elderly individuals with low CURB-65 scores were admitted to the hospital, indicating that hospital admission may reflect fragility among elderly individuals with low CURB-65 scores. The modified SMART-COP score (SMART-CO score) sufficiently predicted intensive care unit admission and the need for intensive vasopressor or respiratory support. A SMART-CO score ≥ 7 accurately predicted 30-day mortality.
Antioxidant Activity and Trace Elements Profile of Extracts of Cymbopogon jwarancusa (Jones.) leaves

This research paper report the antioxidant activity and trace element analysis of Cymbopogon jwarancusa (Jones.). The ethanol extract showed highest antioxidant activity in DPPH (32.08 ± 0.53 % inhibition) and FRAP (39.01±0.64 Fe (II) micromole per litre) assay while water extract showed highest antioxidant activity in βCL (54.26±1.09 %) at 1mg/10ml concentration. BHT and ascorbic acid were used as standards. Trace elements analysis showed sodium (Na+) 0.08%, potassium (K+) 0.05%, lithium (Li+) below detection limit, , nickel (Ni++) 0.03%, lead (Pb++) 0.04%, cadmium (Cd++) 0.08%, zinc (Zn++) 0.08%, copper (Cu++) 0.05%, manganese (Mn++) 0.18%, iron (Fe++) 0.22%, and Cobalt (Co++)0.08%, Calcium (Ca++) 0.50%, Magnesium (Mg++)0.02%, Silicon (Si+4) 0.24%, Phosphorus (P-3) 0.08% and Sulphur (S--)0.01%. were determined.
Factors influencing sustainability of online platforms for professionals: a mixed-method study in OECD countries

Summary Online platforms can support health and educational professionals in their daily work; however, it is challenging to keep online platforms sustainable. This paper aims to indicate the most important factors of platform sustainability from the perspective of professionals involved in online platforms. Further, it aims to understand how these factors operate. A mixed methods study was carried out among professionals from Europe, Australia, the USA and Canada. In the first phase, the importance of 54 factors from the literature was assessed with a questionnaire among 17 professionals. The relative importance of the factors and the consensus regarding this importance were calculated using median scores and interquartile deviations. In total, 19 factors were selected representing general characteristics, characteristics related to the platform, communication, visitor and context. In the second phase, insight was gained regarding the experiences with those factors through 12 individual Skype interviews. The most frequently mentioned important factors of platform sustainability were (i) having sufficient time, resources and expertise, (ii) user friendliness and (iii) creating a sense of belonging. Platforms should use a planned approach to address a combination of factors directly from platform development. Gaining long-term resources is challenging and should be considered from the start of a project by building partnerships. To promote user friendliness, platforms should be simple, have a clear set-up and provide high-quality tools. Finally, establishing a sense of belonging could be supported by branding and face-to-face networking activities. For all aspects, involving visitors and stakeholders is essential.
Transcatheter mitral valve repair in a high‐surgical risk patient with severe degenerative mitral regurgitation using the novel DragonFly™ Transcatheter Repair device—First in man implantation in China

Transcatheter repair of mitral regurgitation (MR) by edge‐to‐edge therapy has become increasingly accepted for patients with severe MR at high or prohibitive surgical risk in primary or degenerative mitral regurgitation (DMR). The technological approach has evolved from the initial transcatheter edge‐to‐edge device to improve on its acute reduction in MR and durability of results, particularly in complex primary pathology. In this study, we reported the first case of DragonFly™ Transcatheter Valve Repair device in a patient with severe DMR.
Has beverage composition of alcohol consumption in Sweden changed over time? An age-period-cohort analysis.

INTRODUCTION In recent years, beverage composition of total alcohol consumption has changed substantially in Sweden. As beverage choice is strongly associated with drinking practices, our paper aims to analyse trends in beverage composition of alcohol consumption by age, period and cohort. METHODS Age-period-cohort (APC) analysis was conducted using monthly data from the Swedish Alcohol Monitoring Survey (2003-2018). The sample consisted of n = 260 633 respondents aged 16-80 years. APC analysis was conducted on drinkers only (n = 193 954; 96 211 males, 97 743 females). Beverage composition was defined as the beverage-specific proportion of total intake in litre ethanol. Fractional multinomial logit regression was applied to estimate the independent effects of age, period and cohort on trends in beverage composition. RESULTS Regression models revealed statistically significant effects of age on all beverages except for medium-strength beer and spirits in males. Controlling for age and cohort, decreasing trends were found over time for medium-strength beer and spirits. The proportion of regular beer increased statistically significantly in males and the proportion of wine in females, whereas the trends for the opposite sex remained stable in each case. Predictions for cohorts showed statistically significant decreasing trends for medium-strength beer in males, lower proportions for regular beer and higher proportions for spirits in the youngest cohorts. DISCUSSION AND CONCLUSIONS The increasing proportion of wine drinking, which is associated with less risky drinking practices, may decrease alcohol-related morbidity and mortality. Increasing proportions of spirits in the youngest cohorts raises concerns of a possible revival in spirits consumption among the youngest.
FOB-SH: Fragment orbital-based surface hopping for charge carrier transport in organic and biological molecules and materials

We introduce a fragment orbital-based fewest switches surface hopping method, FOB-SH, designed to efficiently simulate charge carrier transport in strongly fluctuating condensed phase systems such as organic semiconductors and biomolecules. The charge carrier wavefunction is expanded and the electronic Hamiltonian constructed in a set of singly occupied molecular orbitals of the molecular sites that mediate the charge transfer. Diagonal elements of the electronic Hamiltonian (site energies) are obtained from a force field, whereas the off-diagonal or electronic coupling matrix elements are obtained using our recently developed analytic overlap method. We derive a general expression for the exact forces on the adiabatic ground and excited electronic state surfaces from the nuclear gradients of the charge localized electronic states. Applications to electron hole transfer in a model ethylene dimer and through a chain of ten model ethylenes validate our implementation and demonstrate its computational efficiency. On the larger system, we calculate the qualitative behaviour of charge mobility with change in temperature T for different regimes of the intermolecular electronic coupling. For small couplings, FOB-SH predicts a crossover from a thermally activated regime at low temperatures to a band-like transport regime at higher temperatures. For higher electronic couplings, the thermally activated regime disappears and the mobility decreases according to a power law. This is interpreted by a gradual loss in probability for resonance between the sites as the temperature increases. The polaron hopping model solved for the same system gives a qualitatively different result and underestimates the mobility decay at higher temperatures. Taken together, the FOB-SH methodology introduced here shows promise for a realistic investigation of charge carrier transport in complex organic, aqueous, and biological systems.
A Validated Grading Scale for Downturned Oral Commisure in Asian Faces

Supplemental Digital Content is Available in the Text. BACKGROUND Downturned oral commissures develop gradually with aging. Tools have been developed to evaluate the marionette line or the lower face. However, there is no validated and reproducible tool to evaluate the progress after oral commissure treatment in clinical practice. OBJECTIVE The authors aimed to develop a scoring system to evaluate therapeutic interventions for downturned oral commissures and to verify its reliability, reproducibility, and clinical significance. METHODS AND MATERIALS In the Scale Development Group, the Delphi method was used to establish a 5-graded scoring system to evaluate oral commissure position. The scoring system was applied to 50 participants. The authors recorded and compared the intrarater agreement, interrater agreement, and significance of the grade-dependent scale. RESULTS Delphi analysis of the scoring system verified the grade description adequacy. Intrarater agreement showed almost perfect agreement, and the intraclass correlation coefficient of the interrater agreement had a significantly higher agreement rate. The differences between the clinical grades were significant. CONCLUSION The Hugel Downturned Oral Commissure Scale is precise, reproducible, and reflective of the clinical differences for downturned oral commissure. Its novelty lies in the use of specific angles and ratio. This scale has clinical trial potential owing to its standardized and quantitative assessment.
Characteristics and outcomes of in-hospital cardiac arrest in COVID-19. A systematic review and meta-analysis

Background The purpose herein, was to perform a systematic review of interventional outcome studies in patients with in-hospital cardiac arrest before and during the coronavirus disease 2019 (COVID-19) pandemic period. Methods A meta-analysis was performed of publications meeting the following PICOS criteria: (1) participants, patients > 18 years of age with cardiac arrest due to any causes; (2) intervention, cardiac arrest in COVID-19 period; (3) comparison, cardiac arrest in pre-COVID-19 period; (4) outcomes, detailed information for survival; (5) study design, randomized controlled trials, quasi-randomized or observational studies comparing cardiac arrest in COVID-19 and pre-COVID-19 period for their effects in patients with cardiac arrest. Results Survival to hospital discharge for the pre-pandemic and pandemic period was reported in 3 studies (n =1432 patients) and was similar in the pre-pandemic vs. the pandemic period, 35.6% vs. 32.1%, respectively (odds ratio [OR] 1.72; 95% confidence interval [CI] 0.81–3.65; p = 0.16; I2 = 72%). Return of spontaneous circulation was reported by all 4 studies and were also similar in the pre and during COVID-19 periods, 51.9% vs. 48.7% (OR 1.27; 95% CI 0.78–2.07; p = 0.33; I2 = 71%), respectively. Pooled analysis of cardiac arrest recurrence was also similar, 24.9% and 17.9% (OR 1.60; 95% CI 0.99–2.57; p = 0.06; I2 = 32%) in the pre and during COVID-19 cohorts. Survival with Cerebral Performance Category 1 or 2 was higher in pre vs. during pandemic groups (27.3 vs. 9.1%; OR 3.75; 95% CI 1.26–11.20; p = 0.02). Finally, overall mortality was similar in the pre vs. pandemic groups, 65.9% and 67.2%, respectively (OR 0.67; 95% CI 0.33–1.34; p = 0.25; I2 = 76%). Conclusions Compared to the pre-pandemic period, in hospital cardiac arrest in COVID-19 patients was numerically higher but had statistically similar outcomes.
Host Chromatin Regulators Required for Aggregatibacter actinomycetemcomitans Cytolethal Distending Toxin Activity in Saccharomyces cerevisiae Model

Cytolethal distending toxin (CDT) is a bacterial genotoxin that causes host cell cycle arrest and death. We previously employed a Saccharomyces cerevisiae model with inducible expression of the CDT catalytic subunit from Aggregatibacter actinomycetemcomitans, AaCdtB, and showed that a wide variety of host factors play a role in facilitating the activity of CdtB. ABSTRACT Cytolethal distending toxin (CDT) is a bacterial genotoxin that causes host cell cycle arrest and death. We previously employed a Saccharomyces cerevisiae model with inducible expression of the CDT catalytic subunit from Aggregatibacter actinomycetemcomitans, AaCdtB, and showed that a wide variety of host factors play a role in facilitating the activity of CdtB. Our observation that a yeast H2B mutant defective in chromatin condensation was partially resistant to CdtB implies that chromatin structure may affect CDT function. In this study, we identified host chromatin regulatory genes required for CdtB cytotoxicity. We found that the deletion of HTZ1 or certain subunits of SWR, INO80, and SIR complexes increased cellular resistance to CdtB. We hypothesized that CdtB may interact with Htz1 or the chromatin, but immunoprecipitation experiments failed to detect physical interaction between CdtB and Htz1 or the chromatin. However, we observed reduced nuclear localization of CdtB in several mutants, suggesting that impaired nuclear translocation may, at least partly, explain the mechanisms of CdtB resistance. In addition, mutations in chromatin regulatory genes induce changes in the global gene expression profile, and these may indirectly affect CdtB toxicity. Our results suggest that decreased expression of endoplasmic reticulum (ER)-Golgi transport-related genes that may be involved in CdtB transport and/or increased expression of DNA repair genes may contribute to CdtB resistance. These results suggest that the functions of chromatin regulators may contribute to the activity of CDT in host cells.
Targeting the EMT transcription factor Snail overcomes resistance to osimertinib in EGFR‐mutant non‐small cell lung cancer

The resistance mechanism of the third generation of epidermal growth factor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib is complex. Epithelial mesenchymal transition (EMT) is a common mechanism of EGFR‐TKI acquired resistance. Snail is an important transcription factor related to EMT. Whether targeting Snail can reverse the resistance of osimertinib by downregulating Snail is unknown.