Miracle-dz/UniFAR-FTUs huggingface dataset:
Racial/Ethnic Disparities in All-Cause Mortality among Patients Diagnosed with Triple-Negative Breast Cancer

These findings highlight the need for equal healthcare to mitigate the black–white disparity and for investigations of contributors beyond healthcare for lower mortality among Asians and Hispanics. It is unclear whether racial/ethnic disparities in triple-negative breast cancer (TNBC) mortality remain after accounting for clinical characteristics, treatment, and access-to-care–related factors. In this study, women with a primary diagnosis of TNBC during 2010–2014 were identified from the National Cancer Database. Hazard ratios (HR) and 95% confidence intervals (CI) for 3- and 5-year all-cause mortality associated with race/ethnicity were estimated using Cox proportional hazards models with stepwise adjustments for age, clinical characteristics, treatment, and access-to-care–related factors. Of 78,708 patients, non-Hispanic (NH) black women had the lowest 3-year overall survival rates (79.4%), followed by NH-whites (83.1%), Hispanics (86.0%), and Asians (87.1%). After adjustment for clinical characteristics, NH-blacks had a 12% higher risk of dying 3 years post-diagnosis (HR, 1.12; 95% CI, 1.07–1.17), whereas Hispanics and Asians had a 24% (HR, 0.76; 95% CI, 0.70–0.83) and 17% (HR, 0.83; 95% CI, 0.73–0.94) lower risk than their NH-white counterparts. The black–white disparity became non-significant after combined adjustment for treatment and access-to-care–related factors (HR, 1.04; 95% CI, 0.99–1.09), whereas the white-Hispanic and white-Asian differences remained. Stratified analyses revealed that among women aged less than or equal to 50 with stage III cancer, the elevated risk among NH-blacks persisted (HR, 1.20; 95% CI, 1.04–1.39) after full adjustments. Similar results were seen for 5-year mortality. Overall, clinical characteristics, treatment, and access-to-care–related factors accounted for most of the white–black differences in all-cause mortality of TNBC but explained little about Hispanic- and Asian-white differences. Significance: These findings highlight the need for equal healthcare to mitigate the black–white disparity and for investigations of contributors beyond healthcare for lower mortality among Asians and Hispanics.
Protein Carbonylation and Lipid Peroxidation in Hematological Malignancies

Among the different mechanisms involved in oxidative stress, protein carbonylation and lipid peroxidation are both important modifications associated with the pathogenesis of several diseases, including cancer. Hematopoietic cells are particularly vulnerable to oxidative damage, as the excessive production of reactive oxygen species and associated lipid peroxidation suppress self-renewal and induce DNA damage and genomic instability, which can trigger malignancy. A richer understanding of the clinical effects of oxidative stress might improve the prognosis of these diseases and inform therapeutic strategies. The most common protein carbonylation and lipid peroxidation compounds, including hydroxynonenal, malondialdehyde, and advanced oxidation protein products, have been investigated for their potential effect on hematopoietic cells in several studies. In this review, we focus on the most important protein carbonylation and lipid peroxidation biomarkers in hematological malignancies, their role in disease development, and potential treatment implications.
Increased risk of second primary tumours in patients with oesophageal squamous cell carcinoma: a nationwide study in a Western population

Abstract Background Patients with primary oesophageal squamous cell carcinoma are at risk of developing multiple primary tumours in the upper aero digestive tract. To date, most studies are performed in the Asian population. We aimed to evaluate the risk of multiple primary tumours in the upper aero digestive tract and stomach in patients with oesophageal squamous cell carcinoma in a Western population. Methods We performed a nationwide, retrospective cohort study in collaboration with the Netherlands Cancer Registry. Patients with primary oesophageal squamous cell carcinoma, diagnosed between 2000 and 2016, were included. Primary endpoints were synchronous and metachronous multiple primary tumour risk. Results The cohort consisted of 9058 patients, diagnosed with oesophageal squamous cell carcinoma (male: 57.3%, median age 67 years). In 476 patients (5.3%), 545 multiple primary tumours have been diagnosed. Most of them were located in the head and neck region (49.5%). Among all multiple primary tumours, 329 (60.4%) were diagnosed synchronously (<6 months after oesophageal squamous cell carcinoma diagnosis) and 216 (39.6%) metachronously (6 months). Patients with oesophageal squamous cell carcinoma had a significantly increased risk of both synchronous (standardised incidence ratio 10.95, 99% confidence interval 9.40–12.53) and metachronous multiple primary tumours (standardised incidence ratio 4.36, 99% confidence interval 3.56–5.10), compared to the general population. The median interval to metachronous second primary tumour diagnosis was 3.0 years (interquartile range 1.8–5.9). Conclusion Approximately one in 20 patients with primary oesophageal squamous cell carcinoma have a second primary tumour in the upper aero digestive tract or stomach, either at the time of oesophageal squamous cell carcinoma diagnosis or at a later stage. As second primary tumours occur at an increased risk compared to the general population, prospective studies are necessary to investigate the yield and survival benefit of screening for second primary tumours in patients with oesophageal squamous cell carcinoma.
Antimicrobial activity of various fractions of ethanol extract of Bacopa monnieri Linn. aerial parts

The ethyl acetate and n-butanol fractions of ethanol extract of Bacopa monnieri Linn. aerial parts were screened for antibacterial and antifungal activities by both zone of inhibition study and determination of minimum inhibitory concentration (MIC). The ethyl acetate fraction was found to be more potent than the n-butanol fraction, though both of them were endowed with antimicrobial activity. The present study reveals the potential usefulness of B. monnieri aerial parts in the treatment of various pathogenic diseases as mentioned in the Ayurvedic literature.
Intake of Various Food Groups and Risk of Breast Cancer: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies.

Despite increasing evidence for the association of food-based dietary patterns with breast cancer risk, knowledge about the shape of the relationship and the quality of meta-evidence are insufficient. We aimed to summarize the associations between food groups and risks of breast cancer. We performed a systematic literature search of the PubMed and Embase databases up to March 2020. We included cohort, case-cohort, nested case-control studies, and follow-up studies of randomized controlled trials that investigated the relationship between breast cancer risk and at least 1 of the following food groups: red meat, processed meat, fish, poultry, egg, vegetables, fruit, dairy product (overall, milk, yogurt, and cheese), grains/cereals, nuts, legumes, soy, and sugar-sweetened beverages. Summary risk ratios (RRs) and 95% CIs were estimated using a random-effects model for linear and nonlinear relationships. Inverse linear associations were observed for vegetables (RR per 100 g/d, 0.97; 95% CI, 0.95-0.99), fruit (RR per 100 g/d, 0.97; 95% CI, 0.95-0.99), cheese (RR per 30 g/d, 0.95; 95% CI, 0.91-1.00), and soy (RR per 30 g/d, 0.96; 95% CI, 0.94-0.99), while positive associations were observed for red (RR per 100 g/d, 1.10; 95% CI, 1.03-1.18) and processed meat (RR per 50 g/d, 1.18; 95% CI, 1.04-1.33). None of the other food groups were significantly associated with breast cancer risk. A nonlinear association was observed only for milk, such that the intake of >450 g/d increased the risk, while no association was observed for lower intake amounts. High intakes of vegetables, fruit, cheese, and soy products and low intakes of red and processed meat were associated with lower risks of breast cancer. However, causality cannot be inferred from these statistical correlations.
High-Density Lipoprotein (HDL) in Allergy and Skin Diseases: Focus on Immunomodulating Functions

From an evolutionary perspective, lipoproteins are not only lipid transporters, but they also have important functions in many aspects of immunity. High-density lipoprotein (HDL) particles are the most abundant lipoproteins and the most heterogeneous in terms of their composition, structure, and biological functions. Despite strong evidence that HDL potently influences the activity of several immune cells, the role of HDL in allergies and skin diseases is poorly understood. Alterations in HDL-cholesterol levels have been observed in allergic asthma, allergic rhinitis, atopic dermatitis (eczema), psoriasis, urticaria, and angioedema. HDL-associated apolipoprotein (apo) A-I, apoA-IV, and apoC-III, and lyso-phosphatidylcholines potently suppress immune cell effector responses. Interestingly, recent studies provided evidence that allergies and skin diseases significantly affect HDL composition, metabolism, and function, which, in turn, could have a significant impact on disease progression, but may also affect the risk of cardiovascular disease and infections. Interestingly, not only a loss in function, but also, sometimes, a gain in function of certain HDL properties is observed. The objective of this review article is to summarize the newly identified changes in the metabolism, composition, and function of HDL in allergies and skin diseases. We aim to highlight the possible pathophysiological consequences with a focus on HDL-mediated immunomodulatory activities.
Degradation Products of Amyloid Protein: Are They The Culprits?

OBJECTIVES Beta-amyloid (Aβ) peptides are most toxic to cells in oligomeric form. It is commonly accepted that oligomers can form ion channels in cell membranes and allow calcium and other ions to enter cells. The activation of other mechanisms, such as apoptosis or lipid peroxidation, aggravates the toxicity, but it itself can result from the same initial point, that is, ion disturbance due to an increased permeability of membranes. However, experimental studies of membrane channels created by Aβ are surprisingly limited. METHODS Here, we report a novel flow cytometry technique which can be used to detect increased permeability of membranes to calcium induced by the exposure to amyloid peptides. Calcium entry into the liposome is monitored using calcium-sensitive fluorescent probe. Undamaged lipid membranes are not permeable to calcium. Liposomes that are prepared in a calcium-free medium become able to accumulate calcium in a calcium-containing medium only after the formation of channels. Using this technique, we demonstrated that the addition of short amyloid fragment Aβ, which is known for its extreme toxicity on cultured neurons, readily increased membrane permeability to calcium. However, neither similarly sized peptide Ab22-35 nor full-length peptide Ab1-42 were producing channels. The formation of channels was observed in the membranes made of phosphatidylserine, a negatively charged lipid, but not in membranes made of the neutral phosphatidylcholine. RESULTS In the Discussion section, we have analyzed several issues which could be critical for understanding the pathogenesis of Alzheimer's disease, specifically 1) the need for a negatively charged membrane to produce the ion channel; 2) the potential role of the aggregated form in cellular toxicity of Ab peptides; 3) channel-forming ability of multiple degradation products of amyloid; 4) non-specificity of ion channels formed by amyloid peptides. Potential targets of channel-forming oligomers appear to be intracellular and are organelles well-known for dysfunction in Alzheimer's disease (mitochondria and lysosomes). In fact, lysosomes can also be the producers of degraded amyloid. Provided speculations support the hypothesis that neuronal toxicity can be caused by the degradation products of beta-amyloid.
Supplementation of Kaempferia parviflora Extract Enhances Physical Fitness and Modulates Parameters of Heart Rate Variability in Adolescent Student-Athletes: A Randomized, Double-Blind, Placebo-Controlled Clinical Study

Abstract This randomized double-blind controlled study aimed to investigate the effects of a standardized Kaempferia parviflora (KP) extract on the physical fitness and heart rate variability (HRV) parameters in adolescent sport school students. 194 male students were recruited and randomized into two groups (n = 97), matched by age and sports. The KP-treated group received KP extract capsules at a dose of 360 mg/day and the control group received placebo capsules, continuously for 12 weeks. Physical fitness performance and HRV parameters were monitored with blood biochemical analysis for product safety. KP extract significantly increased the right-hand grip strength, the back-leg strength and maximal oxygen consumption (VO2 max) and decreased the time used for 50-meter sprint test without changing the sit-and-reach test and the 40 yard technical test. For HRV parameters, KP extract significantly increased standard deviation of normal to normal intervals (SDNN), square root of the mean of square of successive normal to normal interval differences (RMSSD) and high frequency (HF) norm, without changing low frequency (LF) norm and LF/HF ratio. The increase in stress resistance and decrease in stress index were found in the KP-treated group, without changing the autonomic nervous system (ANS) activity and balance. Blood biochemical analysis showed normal values of all participants. This data indicates the safety and positive effects of KP on muscle strength, endurance and speed, but not on the flexibility and agility. The modulatory effects of KP extract on HRV parameters suggest its anti-stress effects and would encourage the application in a sport training and exercise.
Resting Energy Expenditure of Physically Active Boys in Southeastern Poland—The Accuracy and Validity of Predictive Equations

Optimization of energy intake in the diet of young athletes is of primary importance. In addition to the energy expenditure associated with their body development, the demand resulting from intensive physical activity also increases. The aim of this study was to compare the accuracy of formulas commonly used for resting energy expenditure (REE) calculations with values obtained from measurements using indirect calorimetry among male children and adolescents practicing football. The study was conducted among 184 boys aged 9 to 17 using a calorimeter and a device for assessing body composition by means of electrical bioimpedance using a segment analyzer. The mean error ranged from −477 kcal/d by the Maffeis formula to −182 kcal/d for the Institute of Medicine of the National Academies (IMNA) formula. A statistically significant difference was found for all formulas in the calculated value in relation to the measured REE value (p < 0.0001). Most “ready-to-use” formulas underestimate REE, which can be a risk in determining the total energy demand in a group that requires more calories, especially when due to intensive growth and development and the expenditure associated with regular training and increased physical activity.
Depressed Older Patients with Death Wishes: Experimental Evidence for Psychotherapists’ Age and Health Bias

ABSTRACT Objectives: When psychotherapists encounter an older patient with depression and death wishes, especially when burdened by physical illness, they may be subject to judgmental biases. This study investigates how this group of patients with highest suicide risk may experience discrimination both on age and health status. Methods: Using a 2 × 2 [chronological age x physical health status] vignette design, psychotherapists (N = 147) were randomly presented with one of the four variants of a case describing a patient with depression and death wishes (i.e., 78 years old + poor physical health; 78 years old + normal physical health; 48 years old + poor physical health; 48 years old + normal physical health). Afterward, participants’ attitudes toward the case were assessed. Results: In case of the hypothetical patient’s old age and poor health status, participants did not underestimate the pathological significance of his death wishes, but nevertheless showed less optimistic treatment attitudes and less confidence in psychotherapeutic treatment. Conclusions: Psychotherapists’ age bias and health bias may serve as two potentially fatal factors influencing the provision of mental health services. Clinical Implications: Psychotherapists may contribute to better mental health-care provision of older adults with depression and the prevention of late-life suicide by increasing awareness of their age and health bias.
Effect of heat flux and density variation on electron temperature profiles in JET ELMy H-modes

Forschungszentrum J¨ulich, EURATOM Association, J¨ulich, GermanyIntroductionA class of transport-relevant instabilities, including Ion Temperature Gradient (ITG), TrappedElectron (TEM) and Electron Temperature Gradient (ETG) driven modes induce a heat ﬂuxwhich increases strongly with temperature gradient above a certain threshold of the inversetemperature gradient length 1 L
External Validity of the Multicenter Randomized PREOPANC Trial on Neoadjuvant Chemoradiotherapy in Pancreatic Cancer

Objectives: To investigate the accrual proportion and patients’ reasons for not participating in the PREOPANC trial on neoadjuvant chemoradiotherapy versus immediate surgery in resectable and borderline resectable pancreatic cancer, and to compare these patients’ outcomes with those of patients who had been randomized in the trial. Summary of Background Data: The external validity of multicenter randomized trials in cancer treatment has been criticized for suboptimal non-representative inclusion. In trials, it is unclear how outcomes compare between randomized and nonrandomized patients. Methods: At 8 of 16 participant centers, this multicenter observational study identified validation patients, who had been eligible but not randomized during recruitment for the PREOPANC trial. We assessed the accrual proportion, investigated their most common reasons for not participating in the trial, and compared resection rates, radical (R0) resection rates, and overall survival between the validation patients and PREOPANC patients, who had been randomized in the trial to immediate surgery. Results: In total, 455 patients had been eligible during the recruitment period, 151 of whom (33%) had been randomized. Fifty-five percent of the 304 validation patients had refused to participate. Median overall survival in the validation group was 15.2 months, against 15.5 months in the PREOPANC group (P = 1.00). The respective resection rates (76% vs 73%) and R0 resection rates (51% vs 46%) did not differ between the groups. Conclusions: The PREOPANC trial included a reasonable percentage of 33% of eligible patients. In terms of the outcomes survival, resection rate, and R0 resection rate, this appeared to be a representative group.
Bacterial tRNA 2′-O-methylation is dynamically regulated under stress conditions and modulates innate immune response

Abstract RNA modifications are a well-recognized way of gene expression regulation at the post-transcriptional level. Despite the importance of this level of regulation, current knowledge on modulation of tRNA modification status in response to stress conditions is far from being complete. While it is widely accepted that tRNA modifications are rather dynamic, such variations are mostly assessed in terms of total tRNA, with only a few instances where changes could be traced to single isoacceptor species. Using Escherichia coli as a model system, we explored stress-induced modulation of 2′-O-methylations in tRNAs by RiboMethSeq. This analysis and orthogonal analytical measurements by LC-MS show substantial, but not uniform, increase of the Gm18 level in selected tRNAs under mild bacteriostatic antibiotic stress, while other Nm modifications remain relatively constant. The absence of Gm18 modification in tRNAs leads to moderate alterations in E. coli mRNA transcriptome, but does not affect polysomal association of mRNAs. Interestingly, the subset of motility/chemiotaxis genes is significantly overexpressed in ΔTrmH mutant, this corroborates with increased swarming motility of the mutant strain. The stress-induced increase of tRNA Gm18 level, in turn, reduced immunostimulation properties of bacterial tRNAs, which is concordant with the previous observation that Gm18 is a suppressor of Toll-like receptor 7 (TLR7)-mediated interferon release. This documents an effect of stress induced modulation of tRNA modification that acts outside protein translation.
Plasma symmetric dimethylarginine and creatinine concentrations and glomerular filtration rate in cats with normal and decreased renal function

Abstract Background Glomerular filtration rate (GFR) is the gold standard in assessing renal function but is impractical. Serum creatinine (sCr) has limited sensitivity in identifying early chronic kidney disease (CKD), whereas symmetric dimethylarginine (SDMA) has been commercialized as more accurate biomarker. Studies comparing SDMA and sCr with GFR in cats are limited. Objectives To further investigate the diagnostic performance of SDMA in nonazotemic and azotemic cats. Animals Forty‐nine client‐owned cats: 17 cats with CKD, 15 cats with diabetes mellitus (DM), and 17 healthy cats. Methods Retrospective study using spare blood samples from cats with documented sCr and GFR results for SDMA analysis. Diagnostic performances of SDMA and sCr were evaluated using correlation coefficients, sensitivities, specificities, and receiver operator characteristic curves. Results Compared to healthy cats and cats with DM, CKD cats had significantly higher SDMAplasma (26.7 ± 9.9 μg/dL) and sCr (249.7 ± 71.6 μmol/L [2.8 ± 0.8 mg/dL]; both P < .001) values. SDMAplasma (τ B = −0.57; P < .001) and sCr (τ B = −0.56; P < .001) were significantly correlated with GFR. SDMAplasma (τ B = 0.52; P < .001) had a significant relationship with sCr. SDMAplasma and sCr had similar sensitivity (76%‐94% and 71%‐88%, respectively) in detecting reduced renal function. Creatinine had higher specificity (94%‐96%) than SDMAplasma (75%‐76%) (P < .05). Conclusion and Clinical Importance In this study of azotemic and nonazotemic cats, SDMA was a reliable marker to identify decreased GFR. However, superiority of SDMA over sCr could not be confirmed.
Rapid Colorimetric Detection of Genome Evolution in SCRaMbLEd Synthetic Saccharomyces cerevisiae Strains

Genome-scale engineering and custom synthetic genomes are reshaping the next generation of industrial yeast strains. The Cre-recombinase-mediated chromosomal rearrangement mechanism of designer synthetic Saccharomyces cerevisiae chromosomes, known as SCRaMbLE, is a powerful tool which allows rapid genome evolution upon command. This system is able to generate millions of novel genomes with potential valuable phenotypes, but the excessive loss of essential genes often results in poor growth or even the death of cells with useful phenotypes. In this study we expanded the versatility of SCRaMbLE to industrial strains, and evaluated different control measures to optimize genomic rearrangement, whilst limiting cell death. To achieve this, we have developed RED (rapid evolution detection), a simple colorimetric plate-assay procedure to rapidly quantify the degree of genomic rearrangements within a post-SCRaMbLE yeast population. RED-enabled semi-synthetic strains were mated with the haploid progeny of industrial yeast strains to produce stress-tolerant heterozygous diploid strains. Analysis of these heterozygous strains with the RED-assay, genome sequencing and custom bioinformatics scripts demonstrated a correlation between RED-assay frequencies and physical genomic rearrangements. Here we show that RED is a fast and effective method to evaluate the optimal SCRaMbLE induction times of different Cre-recombinase expression systems for the development of industrial strains.