Miracle-dz/UniFAR-FTUs huggingface dataset:
Axial Muscle Size as a Strong Predictor of Death in Subjects With and Without Heart Failure

Background The impact of skeletal muscle size, quantified using simple noninvasive images routinely obtained during cardiac magnetic resonance imaging studies on mortality in the heart failure (HF) population is currently unknown. Methods and Results We prospectively enrolled 567 subjects without HF (n=364), with HF with reduced ejection fraction (n=111), or with HF with preserved ejection fraction (n=92), who underwent a cardiac magnetic resonance imaging. Skeletal muscle cross‐sectional area was assessed with manual tracing of major thoracic muscle groups on axial chest magnetic resonance images. Factor analysis was used to identify a latent factor underlying the shared variability in thoracic muscle cross‐sectional area. Cox regression was used to assess the relationship between these measurements and all‐cause mortality (median follow up, 36.4 months). A higher overall thoracic muscle area factor assessed with principal component analysis was independently associated with lower mortality (standardized hazard ratio, 0.51; P<0.0001). The thoracic muscle area factor was predictive of death in subjects with HF with preserved ejection fraction, HF with reduced ejection fraction, and those without HF. Among all muscle groups, the pectoralis major cross‐sectional area was the most representative of overall muscle area and was also the most robust predictor of death. A higher pectoralis major cross‐sectional area predicted a lower mortality (standardized hazard ratio, 0.49; P<0.0001), which persisted after adjustment for various confounders (standardized hazard ratio, 0.55; P=0.0017). Conclusions Axial muscle size, and in particular smaller size of the pectoralis major, is independently associated with higher risk of mortality in patients with and without HF. Further work should clarify the role of muscle wasting as a therapeutic target in patients with HF.
Simultaneous Detection and Differentiation between Wild-Type and Vaccine Measles Viruses by a Multiplex Real-Time Reverse Transcription-PCR Assay

Measles is one of the most contagious viral respiratory infections and was declared to be eliminated from Canada in 1998; however, measles cases and outbreaks still occur every year through reintroduction from other parts of the world. Laboratory confirmation of measles virus (MV) RNA by real-time PCR provides a definitive diagnosis, and molecular analysis to determine the genotype is the only way to distinguish between wild-type and vaccine strains. ABSTRACT Measles is one of the most contagious viral respiratory infections and was declared to be eliminated from Canada in 1998; however, measles cases and outbreaks still occur every year through reintroduction from other parts of the world. Laboratory confirmation of measles virus (MV) RNA by real-time PCR provides a definitive diagnosis, and molecular analysis to determine the genotype is the only way to distinguish between wild-type and vaccine strains. This distinction is important since live attenuated vaccine strains are able to replicate in the patient and can be associated with rash and fever but are poorly transmissible, if at all. Prompt reporting of measles cases to local authorities, including differentiation between wild-type and vaccine strains, allows for optimal management and contact tracing. The development and validation of a multiplex real-time reverse transcription-PCR (rtRT-PCR) assay for the simultaneous detection and differentiation of the Moraten and Schwarz vaccine strains from presumptive wild-type MV in a format that can be easily implemented for high-throughput testing of patient samples are reported here. This assay is sensitive, specific, reproducible, and 100% accurate in comparison with the gold standard comparator assay.
β‐Blockers and 1‐Year Postdischarge Mortality for Heart Failure and Reduced Ejection Fraction and Slow Discharge Heart Rate

Background Many hospitalized patients with heart failure and reduced ejection fraction (HFrEF) have a slow heart rate at discharge, and the effect of β‐blockers may be reduced in those patients. We sought to examine the variable effect of β‐blockers on clinical outcomes according to the discharge heart rate of hospitalized HFrEF patients. Methods and Results The KorAHF (Korean Acute Heart Failure) registry consecutively enrolled 5625 patients hospitalized for acute heart failure. In this analysis, we included patients with HFrEF (left ventricular ejection fraction ≤40%). Slow heart rate was defined as <70 beats per minute regardless of the use of β‐blockers. The primary outcome was 1‐year all‐cause postdischarge death according to heart rate. Among 2932 patients with HFrEF, 840 (29%) had a slow heart rate and 56% received β‐blockers at discharge. Patients with slow heart rates were older and had lower 1‐year mortality than those with high heart rates (P<0.001). A significant interaction between discharge heart rate and β‐blocker use was observed (P<0.001 for interaction). When stratified, only patients without a β‐blocker prescription and with a high heart rate showed higher 1‐year mortality. In a Cox‐proportional hazards regression analysis, β‐blocker prescription at discharge was associated with 24% reduced risk for 1‐year mortality in patients with high heart rates (hazard ratio: 0.76; 95% CI, 0.61–0.95) but not in those with slow heart rates (hazard ratio: 1.02; 95% CI, 0.68–1.55). Conclusions Many patients with acute heart failure have slow discharge heart rates, and β‐blockers may have a limited effect on HFrEF and slow discharge heart rate. Clinical Trial Registration URL: http://www.clinicaltrial. gov. Unique identifier: NCT01389843.
Trends in Treatment, Outcomes, and Incidence of Orthopedic Surgery in Patients with Rheumatoid Arthritis: An Observational Cohort Study Using the Japanese National Database of Rheumatic Diseases

Objective. In this study, we investigated the changes in clinical outcome, treatment, and incidence of orthopedic surgery in patients with rheumatoid arthritis (RA) from 2004 to 2014. Methods. Data were studied from the Japanese nationwide cohort database, NinJa (National Database of Rheumatic Diseases by iR-net in Japan), from 2004 to 2014. The time trends in the incidence of orthopedic procedures were analyzed using linear regression analysis. The cross-sectional annual data were compared between 2004 and 2014 to analyze the changes in clinical outcome and treatment. Results. The incidence of orthopedic surgeries in patients with RA consistently decreased from 72.2 procedures per 1000 patients in 2004 to 51.5 procedures per 1000 patients in 2014 (regression coefficient = −0.0028, 95% CI −0.0038 to −0.0019, p < 0.001). The greatest reduction was found in total knee arthroplasty and total hip arthroplasty. Disease activity and functional disability improved significantly over this decade. The proportions of patients receiving methotrexate and biologic disease-modifying antirheumatic drugs significantly increased from 39.6% and 1.7% in 2004 to 63.8% and 27.4% in 2014, respectively. Conclusion. The overall incidence of orthopedic surgeries in patients with RA significantly decreased, accompanied by improved clinical outcomes because of the expanded use of effective drugs; however, the declining trend differed between procedures or locations. The results from the present study suggest that there might be a change in supply and demand for orthopedic surgeries.
Troponin Testing for Assessing Sepsis-Induced Myocardial Dysfunction in Patients with Septic Shock

(1) Background: Myocardial dysfunction in patients with sepsis is not an uncommon phenomenon, yet reported results are conflicting and there is no objective definition. Measurement of troponin may reflect the state of the heart and may correlate with echocardiographically derived data. This study aimed to evaluate the role of admission and peak troponin-I testing for the identification of sepsis-induced myocardial dysfunction (SIMD) by transthoracic echocardiography (TTE). (2) Methods: This was a retrospective cohort study using a prospective registry of septic shock at an Emergency Department from January 2011 and April 2017. All 1,776 consecutive adult septic shock patients treated with protocol-driven resuscitation bundle therapy and tested troponin-I were enrolled. SIMD was defined as left ventricular (LV) systolic/diastolic dysfunction, right ventricular (RV) diastolic dysfunction, or global/regional wall motion abnormalities (WMA). (3) Results: Of 660 (38.4%) septic shock patients with an elevated hs-TnI (≥0.04 ng/mL) at admission, 397 patients underwent TTE and 258 cases (65%) showed SIMD (LV systolic dysfunction (n = 163, 63.2%), LV diastolic dysfunction (n = 104, 40.3%), RV dysfunction (n = 97, 37.6%), and WMA (n = 186, 72.1%)). In multivariate analysis, peak hs-TnI (odds ratio 1.03, 95% confidence interval 1.01–1.06, p = 0.008) and ST-T wave changes in the electrocardiogram (odds ratio 1.82, 95% confidence interval 1.04–2.39, p = 0.013) were associated with SIMD, in contrast to hs-TnI level at admission. The area under the curve of peak hs-TnI was 0.668. When the peak hs-TnI cutoff value was 0.634 ng/mL, the sensitivity and specificity for SIMD were 58.6% and 59.1%, respectively. 4) Conclusions: About two-thirds of patients with an elevated hs-TnI level have various cardiac dysfunctions in terms of TTE. Rather than the initial level, the peak hs-TnI and ST-T change may be considered as a risk factor of SIMD.
Variation within 3′-UTRs of Base Excision Repair Genes and Response to Therapy in Colorectal Cancer Patients: A Potential Modulation of microRNAs Binding

Purpose: Colorectal cancer is routinely treated with a 5-fluorouracil (5-FU)–based chemotherapy. 5-FU incorporates into DNA, and the base excision repair (BER) pathway specifically recognizes such damage. We investigated the association of single-nucleotide polymorphisms (SNP) in the 3′-untranslated regions (UTR) of BER genes, and potentially affecting the microRNA (miRNA) binding, on the risk of colorectal cancer, its progression, and prognosis. SNPs in miRNA-binding sites may modulate the posttranscriptional regulation of gene expression operated by miRNAs and explain interindividual variability in BER capacity and response to 5-FU. Experimental Design: We tested 12 SNPs in the 3′-UTRs of five BER genes for colorectal cancer susceptibility in a case–control study (1,098 cases and 1,459 healthy controls). Subsequently, we analyzed the role of these SNPs on clinical outcomes of patients (866 in the Training set and 232 in the Replication set). Results: SNPs in the SMUG1 and NEIL2 genes were associated with overall survival. In particular, SMUG1 rs2233921 TT carriers showed increased survival compared with those with GT/GG genotypes [HR, 0.54; 95% confidence interval (CI), 0.36–0.81; P = 0.003] in the Training set and after pooling results from the Replication set. The association was more significant following stratification for 5-FU–based chemotherapy (P = 5.6 × 10−5). A reduced expression of the reporter gene for the T allele of rs2233921 was observed when compared with the common G allele by in vitro assay. None of the genotyped BER polymorphisms were associated with colorectal cancer risk. Conclusions: We provide the first evidence that variations in miRNA-binding sites in BER genes 3′-UTR may modulate colorectal cancer prognosis and therapy response. Clin Cancer Res; 19(21); 6044–56. ©2013 AACR.
Oral Treatment with BT-11 Ameliorates Inflammatory Bowel Disease by Enhancing Regulatory T Cell Responses in the Gut

Inflammatory bowel disease (IBD) is an expanding autoimmune disease afflicting millions that remains difficult to treat due to the accumulation of multiple immunological changes. BT-11 is an investigational new drug for IBD that is orally active, gut restricted, and targets the lanthionine synthetase C-like 2 immunometabolic pathway. CD25+ FOXP3+ CD4+ T cells are increased locally within the colon of BT-11–treated mice in Citrobacter rodentium and IL-10−/− mouse models of colitis. The maintained efficacy of BT-11 in the absence of IL-10 combined with the loss of efficacy when direct cell–cell interactions are prevented suggest that the regulatory T cell (Treg)–related elements of suppression are cell contact–mediated. When PD-1 is inhibited, both in vitro and in vivo, the efficacy of BT-11 is reduced, validating this assertion. The depletion of CD25+ cells in vivo abrogated the retention of therapeutic efficacy postdiscontinuation of treatment, indicating that Tregs are implicated in the maintenance of tolerance mediated by BT-11. Furthermore, the involvement of CD25 suggested a role of BT-11 in IL-2 signaling. Cotreatment with BT-11 and IL-2 greatly enhances the differentiation of CD25+ FOXP3+ cells from naive CD4+ T cells relative to either alone. BT-11 enhances phosphorylation of STAT5, providing a direct linkage to the regulation of FOXP3 transcription. Notably, when STAT5 is inhibited, the effects of BT-11 on the differentiation of Tregs are blocked. BT-11 effectively enhances the IL-2/STAT5 signaling axis to induce the differentiation and stability of CD25+ FOXP3+ cells in the gastrointestinal mucosa to support immunoregulation and immunological tolerance in IBD.
Expression of interleukin (IL)‐10 family cytokines in aqueous humour of patients with specific endogenous uveitic entities: elevated levels of IL‐19 in human leucocyte antigen‐B27‐associated uveitis

Evidence exists that the interleukin (IL)‐10 family of cytokines is involved in autoimmune diseases. The aim of this study was to analyse the levels of the IL‐10 family cytokines IL‐10, IL‐19, IL‐20, IL‐22, IL‐26, IL‐28A and IL‐29 in aqueous humour (AH) samples from patients with specific uveitic entities. In addition, we correlated their levels with the levels of the proinflammatory cytokines tumour necrosis factor‐α (TNF‐α) and IL‐1β.
The impact of cricothyroid involvement on adductor recovery in unilateral vocal fold paralysis

Wide variation in postinjury functional recovery is a hallmark of unilateral vocal fold paralysis (UVFP), ranging from zero to full recovery. The present study examined the impact of cricothyroid (CT) muscle involvement on recovery using quantitative laryngeal electromyography (LEMG) of the thyroarytenoid–lateral cricoarytenoid (TA‐LCA) muscle complex at multiple times postinjury.
Secreted frizzled‐related protein 5 serum levels in human periodontitis—A nested case–control study

AIM Recombinant secreted frizzled-related protein 5 (sFRP5) improved periodontal status in mice. Thus, this study aimed to investigate this finding in human periodontitis using an epidemiological approach. MATERIALS AND METHODS sFRP5 and wnt5a concentrations were determined in human serum from the Food Chain Plus cohort using ELISAs. A total of 128 patients with periodontitis and tooth loss and 245 patients with periodontitis without tooth loss were compared to 373 sex-, smoker-, age- and BMI-matched individuals in a nested case-control design. RESULTS Systemic sFRP5 serum levels were significantly lower in patients with periodontitis and tooth loss (2.5 [0.0-10.4] ng/ml, median [IQR]) compared to patients with periodontitis without tooth loss (6.0 [2.5-15.8] ng/ml, median [IQR], p = 0.04] and matched controls (7.0 [2.5-18.3] ng/ml, median [IQR], p = 0.02). No significant differences in sFRP5 serum levels were found among patients with periodontitis without tooth loss (6.0 [2.5-15.8] ng/ml, median [IQR]) and controls (3.1 [0.0-10.6] ng/ml, median [IQR], p = 0.06). CONCLUSIONS sFRP5 might serve as a novel biomarker for periodontitis severity. Modulating the inflammatory background of severe forms of periodontitis, in the time of precision medicine, needs to be revealed in further studies.
Evaluation of ForenSeq™ Signature Prep Kit B on predicting eye and hair coloration as well as biogeographical ancestry by using Universal Analysis Software (UAS) and available web‐tools

This study examined 266 individuals from various populations including African American, East Asian, South Asian, European, and mixed populations to evaluate the ForenSeq™ Signature Prep Kit Primer Mix B. Focus was placed on phenotypic and biogeographical ancestry predictions by Illumina's Universal Analysis Software (UAS). These outcomes were compared to those obtained through web‐tools developed at the Erasmus Medical Center (EMC) and available from the Forensic Resource/Reference on Genetics‐knowledge base (FROG‐kb), as well as to eye color predictions by the 8‐plex system. Due to drop‐outs, predictions for eye and hair color by UAS failed for various samples in each run. By including reads below thresholds, predictions could be obtained for all samples through the web‐tools. Eye and hair color predictions for African Americans, East Asians, and South Asians showed no errors. Difficulties however, were noted in intermediate (neither blue nor brown) eye color predictions. These were mitigated by the 8‐plex system through exclusion of one eye color (e.g. “not brown”). Additionally, notable discrepancies were observed in hair color predictions, where some black/dark‐brown haired individuals were predicted to have blond hair. Overall, ancestry predictions were more accurate by FROG‐kb compared to UAS, which did not predict South Asian ancestry, particularly Indian individuals.
Imaging for Prediction of Functional Outcome and Assessment of Recovery in Ischemic Stroke

Stroke is a leading cause of long-term adult disability worldwide. Only a small proportion of stroke survivors (≈14%) achieve full recovery of activities of daily living, whereas 25% to 50% require some assistance and approximately half experience long-term dependency.1 Prediction of outcome after ischemic stroke, therefore, is important for setting realistic and attainable treatment goals, informing patients and their relatives properly, facilitating discharge planning, and anticipating possible consequences for home adjustments and community support.2 Moreover, knowledge of the expected recovery pattern is necessary to assess the effectiveness of new therapeutic interventions and their contribution to recovery and should be applied to select comparable patients populations for treatment trials.3 Several standardized measures assess various aspects of stroke outcome and recovery, including quantification of neurological deficits, functional outcome measures, and quality of life measures. Activities of daily living, including dressing, mobility, and bathing, are assessed most frequently by the Barthel Index4 and by the modified Rankin Scale (mRS)5 but also by the Glasgow Outcome Scale,6 the Functional Independence Measure,7 or other activities of daily living assessment tools.8 Frequently used measures of quality of life include the Stroke Impact Scale and European Quality of Life Scale (EQ-5D). 9,10 A considerable number of prognostic stroke studies used the Barthel Index and the mRS as the primary outcome measure reached after 3 to 6 months and found that scores on scales assessing severity of neurological deficits such as the National Institutes of Healt Stroke Scale (NIHSS)11–13 and Canadian Neurological Scale14 in acute stroke (ie, within 72 hours) are strongly associated with outcome beyond 3 months.2,15 A systemic review of prognostic studies8 indicated that age and motor weakness were important predictive variables of outcome in addition to stroke …
Acoustic Voice Quality Index - AVQI for brazilian portuguese speakers: analysis of different speech material.

PURPOSE This study aimed to verify the best speech material for the AVQI for Brazilian Portuguese language and identify the best validity results between the auditory perceptual judgment (APJ) and the AVQI score on different speech materials. METHODS We recorded voice samples of 50 individuals (dysphonic and vocally healthy) of several continuous speech (cs) variants (i.e., months of the year, numbers 1 to 20, and CAPE-V sentences) and attached the vowel /a/ in each case. The recorded samples were edited to three different durations of cs variants plus vowel: D1-total speech material; D2-customized speech material without voiceless parts; D3-pre-defined cut-off point speech material. These samples were submitted to three voice experts who judged the overall voice quality; and the AVQI analysis. AVQI's precision and concurrent validity were evaluated considering a Gmean threshold of G<0.5 and G<0.68. RESULTS The concurrent validity of AVQI and APJ ranged from r = 0.482 to r = 0.634. Numbers presented higher values for all durations. For G<0.5, the best sensitivity and area under the ROC curve was for CAPE-V sentences at D3 (57.8%; 72%). For G<0.68, numbers 1 to 10 had the best diagnostic accuracy and numbers 1 to 20 had the best sensitivity. CONCLUSION Numbers from 1 to 10 had the best correlation results between APJ and AVQI. For G<0.5, sentences had the best diagnostic accuracy; while for G<0.68, numbers had the best diagnostic accuracy. Numbers are commonly used in the Brazilian clinic routine. According to the validity results and daily clinical practice in Brazil, we suggest the use of numbers as cs for concatenated voice samples of voice quality assessments.
Small RNAs in Rat Sperm Are a Predictive and Sensitive Biomarker of Exposure to the Testicular Toxicant Ethylene Glycol Monomethyl Ether.

Testicular histology and semen parameters are considered the gold standards when determining male reproductive toxicity. Ethylene glycol monomethyl ether (EGME) is a testicular toxicant with well-described effects on histopathology and sperm parameters. To compare the predictivity and sensitivity of molecular biomarkers of testicular toxicity to the traditional endpoints, small RNAs in the sperm were analyzed by next generation RNA-sequencing (RNA-seq). Adult rats were exposed to 0, 50, 60, or 75 mg/kg EGME by oral gavage for 5 consecutive days. Testis histology, epididymal sperm motility, and sperm small RNAs, including microRNAs (miRNAs), mRNA fragments, piwi-interacting RNAs (piRNAs), and tRNA fragments (tRFs), were analyzed 5 weeks after cessation of exposure. Testicular histology showed a significant dose-dependent increase in retained spermatid heads (RSH), while sperm motility declined with increasing dose. RNA-sequencing of sperm small RNAs was used to identify significant dose-dependent changes in percent mRNA fragments (of total reads), percent miRNAs (of total reads), average tRF length, average piRNA length, and piRNA and tRF length-distributions. Discriminant analysis showed relatively low predictivity of exposure based on RSH or motility compared to the average read length of all assigned RNAs. Benchmark dose (BMD) modeling resulted in a BMD of 62 mg/kg using RSH, whereas average read length of all assigned RNAs resulted in a BMD of 47 mg/kg. These results showed that sperm small RNAs are sensitive and predictive biomarkers of EGME-induced male reproductive toxicity.