Miracle-dz/UniFAR-FTUs huggingface dataset:
Low‐dose fludarabine and cyclophosphamide combined with rituximab in the first‐line treatment of elderly/comorbid patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL): long‐term results of project Q‐lite by the Czech CLL Study Group

Therapeutic options used to be very limited for treatment‐naïve elderly/comorbid patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) before the introduction of chemo‐immunotherapy. Because dose‐reduced fludarabine‐based regimens yielded promising results, the Czech CLL Study Group initiated a prospective observational study to assess safety and efficacy of low‐dose fludarabine and cyclophosphamide combined with rituximab (FCR) in elderly/comorbid patients. Between March 2009 and July 2012, we enrolled 107 patients considered ineligible for full‐dose FCR (median age, 70 years; median Cumulative Illness Rating Scale score, 5; median creatinine clearance, 69 ml/min). Notably, 77% patients had unfavourable biological prognosis [unmutated immunoglobulin heavy‐chain variable‐region gene (IGHV), 74%; deletion 17p, 9%). Fludarabine was reduced to 12 mg/m2 intravenously (iv) or 20 mg/m2 orally on days 1–3 and cyclophosphamide to 150 mg/m2 iv/orally on days 1–3. Grade 3–4 neutropenia occurred in 56% of the patients, but there were serious infections in only 15%. The median progression‐free survival was 29 months, but was markedly longer in patients with mutated IGHV (median 53 months), especially in absence of del 11q or 17p (median 74 months). Low‐dose FCR is a well‐tolerated and effective first‐line regimen for selected elderly/comorbid patients with CLL/SLL with favourable biology. The study was registered at clinicaltrials.gov (NCT02156726).
Association Between Previous Concussion Education and Concussion Care-Seeking Outcomes Among National Collegiate Athletic Association Division I Student-Athletes.

CONTEXT Limited data exist concerning differences in concussion-education exposure and how education exposures relate to care seeking and symptom disclosure, specifically by National Collegiate Athletic Association Division I student-athletes. OBJECTIVE To investigate demographic characteristics associated with concussion-education exposure and examine whether overall education exposure (yes versus no) and education-source exposure number (multiple sources versus a single source) affect concussion care-seeking and disclosure factors in Division I student-athletes. DESIGN Cross-sectional study. SETTING Classroom or online survey. PATIENTS OR OTHER PARTICIPANTS Division I student-athletes (n = 341). MAIN OUTCOME MEASURE(S) Frequencies and proportions were computed for sex, race, school year, sport, and concussion history across concussion-education groups. Prevalence ratios (PRs) and 95% CIs were calculated to quantify the associations between student-athlete characteristics and (1) overall concussion-education exposure and (2) source-exposure number. Separate multivariable linear regression models estimated adjusted mean differences (MDs) and 95% CIs, which allowed us to assess differences in concussion knowledge, attitudes, and perceived social norms relative to concussion-education exposure and exposure to multiple sources. Separate multivariable binomial regression models were performed to estimate adjusted PRs and 95% CIs in order to evaluate associations of intention, perceived control, and care-seeking or disclosure behaviors and overall concussion-education exposure and exposure to multiple sources. All models controlled for sex, sport, and concussion history. RESULTS Overall, 276 (80.9%) participants reported previous concussion education, with 179 (64.9%) being exposed to multiple sources. Student-athletes who participated in a contact sport (adjusted PR = 1.24; 95% CI = 1.06, 1.44) and those who had a concussion history (adjusted PR = 1.19; 95% CI = 1.09, 1.31) had higher prevalences of concussion-education exposure. Females had a lower prevalence of reporting multiple sources (adjusted PR = 0.82; 95% CI = 0.68, 0.99). Overall concussion-education exposure was significantly associated with more favorable perceived social norms surrounding concussion care seeking (adjusted MD = 1.37; 95% CI = 0.13, 2.61). CONCLUSIONS These findings highlighted the potential differences in overall concussion-education exposure and provide clinicians with information on groups who may benefit from additional targeted education.
Evaluating the Quality of Tuberculosis Contact Investigation in Cali, Colombia: A Retrospective Cohort Study.

Tuberculosis (TB) contact investigation facilitates earlier TB diagnosis and initiation of preventive therapy, but little data exist about the quality of its implementation. We conducted a retrospective cohort study to evaluate processes of TB contact investigation for index TB patients diagnosed in Cali, Colombia, in 2017, including dropout at each stage and overall yield. We constructed multivariable models to identify predictors of completing 1) the baseline household visit and 2) a follow-up clinic visit for TB evaluation among referred contacts. Sixty-eight percent (759/1,120) of registered TB patients were eligible for contact investigation; 77% (582/759) received a household visit. Odds of completing a household visit were significantly lower among men (adjusted odds ratio [aOR]: 0.6; 95% CI: 0.4-0.9; P = 0.009) and patients living in Cali's western zone (aOR: 0.5; 95% CI: 0.3-0.8; P = 0.008). Among 1880 screened contacts, 31% (n = 582) met the criteria for clinic referral, 47% (n = 271) completed a clinic visit, and 85% (231/271) completed testing. After adjusting for clustering by index patient, odds of completing referral were higher among contacts with cough (aOR: 22; 95% CI: 7.1-66; P < 0.001) and contacts living in the western zone (aOR: 4.1; 95% CI: 1.2-15; P = 0.03). The cumulative probability of a symptomatic contact from an eligible household completing TB evaluation was only 28%. The yield of active TB patients among contacts was only 0.3% (5/1880). Only 16% (17/103) of children aged < 5 years were included, and none of the eight persons were living with HIV-initiated preventive therapy. Routine monitoring of process indicators may facilitate quality improvement to close gaps in contact tracing and increase yield.
Dietary saturated fatty acid palmitate promotes cartilage lesions and activates the unfolded protein response pathway in mouse knee joints

Increased intake of dietary saturated fatty acids has been linked to obesity and the development of Osteoarthritis (OA). However, the mechanism by which these fats promote cartilage degradation and the development of OA is not clearly understood. Here, we report the effects of consumption of common dietary saturated and unsaturated fatty acids, palmitate and oleate, respectively, on body weight, metabolic factors, and knee articular cartilage in a mouse model of diet-induced obesity. Mice fed on a diet rich in saturated or unsaturated fatty acid gained an equal amount of weight; however, mice fed a palmitate diet, but not a control or oleate diet, exhibited more cartilage lesions and increased expression of 1) unfolded protein response (UPR)/endoplasmic reticulum (ER) stress markers including BIP, P-IRE1α, XBP1, ATF4, and CHOP; 2) apoptosis markers CC3 and C-PARP; and 3) negative cell survival regulators Nupr1 and TRB3, in knee articular cartilage. Palmitate-induced apoptosis was confirmed by TUNEL staining. Likewise, dietary palmitate was also increased the circulatory levels of classic proinflammatory cytokines, including IL-6 and TNF-α. Taken together, our results demonstrate that increased weight gain is not sufficient for the development of obesity-linked OA and suggest that dietary palmitate promotes UPR/ER stress and cartilage lesions in mouse knee joints. This study validates our previous in vitro findings and suggests that ER stress could be the critical metabolic factor contributing to the development of diet/obesity induced OA.
Differential Associations of SLCO Transporters with Prostate Cancer Aggressiveness between African Americans and European Americans

Background: Androgen receptor signaling is crucial to prostate cancer aggressiveness. Members of the solute carrier family of the organic anion transporting peptides (SLCO) are potential regulators of androgen availability in prostate tissue. It remains unknown whether genetic variations in SLCOs contribute to the differences in prostate cancer aggressiveness in African Americans (AA) and European Americans (EA). Methods: SNPs in 11 SLCO members were selected, with addition of 139 potentially functional SNPs and 128 ancestry informative markers. A total of 1,045 SNPs were genotyped and analyzed in 993 AAs and 1,057 EAs from the North Carolina–Louisiana Prostate Cancer Project. Expression and cellular localization of SLCOs were examined using qRT-PCR, IHC, and in situ RNA hybridization in independent sets of prostate cancer cases. Results: Significant associations with prostate cancer characteristics were found for SNPs in SLCO2A1 and SLCO5A1. The associations differed by race (Pinteraction < 0.05). SNPs in SLCO2A1 were associated with reduced tumor aggressiveness and low Gleason score in AAs; whereas, SNPs in SLCO5A1 were associated with high clinical stage in EAs. In prostate tissue, SLCO2A1 and SLCO5A1 were the most expressed SLCOs at the mRNA level and were expressed predominantly in prostate endothelial and epithelial cells at the protein level, respectively. Conclusions: SLCO2A1 and SLCO5A1 play important but different roles in prostate cancer aggressiveness in AAs versus EAs. Impact: The finding calls for consideration of racial differences in biomarker studies of prostate cancer and for investigations on functions of SLCO2A1 and SLCO5A1 in prostate cancer.
Validation of a commercial enzyme immunoassay to assess urinary oxytocin in humans

Within the last decade, oxytocin (OT) has attracted a lot of attention in the context of various human social behaviors. Besides its importance in regulating physiological processes in females related to giving birth and lactation, OT is involved in the establishment and maintenance of social relationships, trust and emotion recognition. However, results are not always consistent across studies, which may partly be due to the incomplete validation of methods used to assess OT levels. Carefully validating a method before its use is of crucial importance to ensure that it can be used to accurately, reliably and repeatedly assess OT levels. With this study we evaluated a commercially available Enzyme Immunoassay to assess OT in human urine samples by conducting a careful analytical validation. Results indicate that, with regard to parallelism and immunoreactivity, human urinary OT can be assessed reliably. However, extraction methods need further improvement to optimize measures of accuracy and extraction efficiency, especially in the lower range of the assay system. Tests on OT stability indicate that OT is affected by degradation when stored at 4°C or room temperature. Storing urine samples over longer periods revealed that OT levels are most stable when stored as ethanol extracts at −20°C compared to being stored as samples at −20°C or −80°C. Although some of the validated parameters did not reach the intended quality criteria, this study highlights the importance of such in depth validation procedures and reporting results to make them available to researchers embarking on projects utilizing such methods.
Educational inequality in the Dietary Approach to Stop Hypertension diet in the UK: evaluating the mediating role of income

Abstract Apparent differences in the adoption of the Dietary Approach to Stop Hypertension (DASH) diet have been reported between less and more educated individuals. However, the mediating role of income has not been clarified. In this study, we aimed at quantifying the mediating effect of income on the relationship between education and the DASH score in the UK population. We analysed data on 4864 subjects aged 18 years and older collected in three waves of the National Diet and Nutrition Survey (2008–2016). The DASH score was calculated using sex-specific quintiles of DASH items. We carried out a counterfactual-based mediation analysis to decompose the total effect of education on DASH score into average direct effect and average causal mediation effect mediated by income. We found that the overall mediating effect of income on the relationship between education and the DASH score was only partial, with an estimated proportion mediated ranging between 6 and 9 %. The mediating effect was higher among females (11·6 %) and younger people (17·9 %). Further research is needed to investigate which other factors may explain the socio-economic inequality in the adoption of the DASH diet in the UK.
Bias in two-sample Mendelian randomization when using heritable covariable-adjusted summary associations

Abstract Background Two-sample Mendelian randomization (MR) allows the use of freely accessible summary association results from genome-wide association studies (GWAS) to estimate causal effects of modifiable exposures on outcomes. Some GWAS adjust for heritable covariables in an attempt to estimate direct effects of genetic variants on the trait of interest. One, both or neither of the exposure GWAS and outcome GWAS may have been adjusted for covariables. Methods We performed a simulation study comprising different scenarios that could motivate covariable adjustment in a GWAS and analysed real data to assess the influence of using covariable-adjusted summary association results in two-sample MR. Results In the absence of residual confounding between exposure and covariable, between exposure and outcome, and between covariable and outcome, using covariable-adjusted summary associations for two-sample MR eliminated bias due to horizontal pleiotropy. However, covariable adjustment led to bias in the presence of residual confounding (especially between the covariable and the outcome), even in the absence of horizontal pleiotropy (when the genetic variants would be valid instruments without covariable adjustment). In an analysis using real data from the Genetic Investigation of ANthropometric Traits (GIANT) consortium and UK Biobank, the causal effect estimate of waist circumference on blood pressure changed direction upon adjustment of waist circumference for body mass index. Conclusions Our findings indicate that using covariable-adjusted summary associations in MR should generally be avoided. When that is not possible, careful consideration of the causal relationships underlying the data (including potentially unmeasured confounders) is required to direct sensitivity analyses and interpret results with appropriate caution.
Leader–Follower Congruence in MD Propensity and UPB: A Polynomial Regression Analysis

Abstract Drawing on previous work on moral disengagement and balance theory, the (in)congruence effect of leader and follower moral disengagement (MD) propensity on followers’ unethical pro-organizational behavior (UPB) was examined in this study. Dyad data were gathered from 185 CEOs and 555 followers from 185 firms located in China. The polynomial regression analysis results suggest that followers in the presence of leader–follower congruence in MD propensity conduct more UPBs. Moreover, followers conduct more UPBs with MD propensity in the presence of congruence. We also found asymmetrical incongruence effects. Followers engage more in UPBs when their MD propensity exceeds their leaders’ MD propensity than when their leaders’ MD propensity exceeds their own. Overall, the findings emphasize the value of considering followers’ and leaders’ traits for shedding light on the occurrence of UPBs.
Antioxidant Activities of Aminophenols against Oxidation of Methyl Linoleate in Solution.

The antioxidant activities of 48 kinds of aminophenols, chromanols, indoles, carbazoles, aromatic amines, and related compounds were assessed in the oxidations of methyl linoleate in acetonitrile solution induced by azo radical initiator. Chromanols, aminochroman and p-phenylenediamines exhibited strong antioxidant activity. Indole and carbazole did not act as antioxidant per se, but those having either amino or hydroxy group as substituent at the para position acted as potent antioxidant. Amino-substituted compounds were in general more potent than hydroxy-substituted ones. These results were interpreted by both polar and resonance effect.
Safety and Efficacy of Endovascular Treatment of Portal Vein Stenosis in Liver Transplant Recipients: A Systematic Review

Purpose: To evaluate the efficacy of Angioplasty and Stent Placement for the treatment of Portal Vein Stenosis in Liver Transplant Recipients by performing a systematic review. Materials and Methods: The PubMed Database was extensively searched for articles describing Portal Vein Stenosis (PVS) as a complication in Liver Transplant (LT) patients. The initial database search yielded 488 unique records published in the PubMed Database, 19 of which were deemed to meet the inclusion criteria. Outcomes were separated into 2 groups (Group A included patients with primary angioplasty, Group B included patients with primary stent placement), and further subdivided into Adult and Pediatric populations. Results: Group A included a total of 282 LT patients with portal vein stenosis. The population was predominantly pediatric (n = 243). Group B included a total of 111 LT patients with portal vein stenosis. This population was predominantly adult (n = 66). Technical success was significantly higher in both Group B pediatric (100%) and adults (97%) compared to Group A (69.5%) and (66.7%) respectively. Re-stenosis rates were significantly lower in Group B pediatric group compared to Group A (2.3% vs 29.7%, χ2 = 13.9; p < 0.001). Overall major (3.1%) and minor complications rates (1.5%) were low. Conclusion: Primary stent placement appears to have higher technical success in both populations and lower re-stenosis rates for treatment of PVS in pediatric populations.
Reprograming of sRNA target specificity by the leader peptide peTrpL in response to antibiotic exposure

Abstract Trans-acting regulatory RNAs have the capacity to base pair with more mRNAs than generally detected under defined conditions, raising the possibility that sRNA target specificities vary depending on the specific metabolic or environmental conditions. In Sinorhizobium meliloti, the sRNA rnTrpL is derived from a tryptophan (Trp) transcription attenuator located upstream of the Trp biosynthesis gene trpE(G). The sRNA rnTrpL contains a small ORF, trpL, encoding the 14-aa leader peptide peTrpL. If Trp is available, efficient trpL translation causes transcription termination and liberation of rnTrpL, which subsequently acts to downregulate the trpDC operon, while peTrpL is known to have a Trp-independent role in posttranscriptional regulation of antibiotic resistance mechanisms. Here, we show that tetracycline (Tc) causes rnTrpL accumulation independently of Trp availability. In the presence of Tc, rnTrpL and peTrpL act collectively to destabilize rplUrpmA mRNA encoding ribosomal proteins L21 and L27. The three molecules, rnTrpL, peTrpL, and rplUrpmA mRNA, form an antibiotic-dependent ribonucleoprotein complex (ARNP). In vitro reconstitution of this ARNP in the presence of competing trpD and rplU transcripts revealed that peTrpL and Tc cause a shift of rnTrpL specificity towards rplU, suggesting that sRNA target prioritization may be readjusted in response to changing environmental conditions.
Fluorination Reaction of Uranium Dioxide by Fluorine

Kinetics of the fluorination reaction of uranium dioxide is studied using un-reacted core model with shrinking particles. The model includes the film mass transfer of fluorine gas and its diffusion in the particle. The rate constants of the model are determined by fitting the experimental data for 370–450°C. The model successfully represents the fluorination in this temperature range. The rate control step is identified by examining the rate constants of the model for 300–1,800°C. For temperature range up to 900°C, the fluorination reaction is rate controlling. For over 900°C, both mechanisms of the mass transfer of fluorine and the fluorination reaction control the rate of the fluorination. With further increase of the temperature, however, the fluorination reaction becomes so fast that the mass transfer of fluorine eventually controls the rate of the fluorination.
Leaching and reclamation of calcareous saline-sodic soil by moderately saline and moderate-SAR water using gypsum and calcium chloride

Lysimeter experiments were conducted with sandy-clay-loam soil to study the efficiency of two amendments in reclaiming saline-sodic soil using moderately saline and SAR (sodium-adsorption ratio) irrigation water. Gypsum obtained from industrial phosphate by-products and reagent grade Ca chloride were applied to packed soil columns and irrigated with moderately saline (ECe = 2.16 dS m–1), moderate-SAR water (SAR = 4.8). Gypsum was mixed with soil prior to irrigation at application rates of 5, 10, 15, 20, 25, and 32 Mg ha–1, and Ca chloride was dissolved directly in leaching water at application rates of 4.25, 8.5, 12.75, 17.0, and 21.25 Mg ha–1, respectively. The highest application rate in both amendments resulted in 96% reduction of total Na in soil. The hydraulic conductivity (HC) of soils receiving gypsum increased in all treatments. The highest HC value of 6.8 mm h–1 was obtained in the highest application rate (32 Mg ha–1), whereas the lowest value of 5.2 mm h–1 was observed with the control treatment. Both amendments were efficient in reducing soil salinity and sodicity (exchangeable-sodium percentage, ESP); however, Ca chloride was more effective than gypsum as a reclaiming material. Exchangeable Na and soluble salts were reduced with gypsum application by 82% and 96%, and by 86% and 93% with Ca chloride application, respectively. Exchangeable Ca increased with increasing amendment rate. Results of this study revealed that sodium was removed during cation-exchange reactions mostly when the SAR of effluent water was at maximum with subsequent passage of 3 to 4 pore volumes. Gypsum efficiently reduced soil ESP, soil EC, leaching water, and costs, therefore, an application rate of 20 Mg ha–1 of gypsum with 3 to 4 pore volumes of leaching water is recommended for reclaiming the studied soil.
Microbial signatures in the lower airways of mechanically ventilated COVID19 patients associated with poor clinical outcome

Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal (Mycoplasma salivarium), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized.