Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effects of Indirect- and Direct-Acting Anticoagulants on Lupus Anticoagulant Assays: A Large, Retrospective Study at a Coagulation Reference Laboratory

Objectives To investigate the effects of indirect- and direct-acting anticoagulants on the interpretation of lupus anticoagulant (LAC) assays. Methods A retrospective database review was performed to identify all LAC panels from November 2012 to November 2015. The positivity rates for three LAC tests were compared among various anticoagulant medications. Results This analysis included 7,721 LAC panels. Direct oral anticoagulants, warfarin, and unfractionated heparin (UFH) were associated with higher LAC positivity rates compared with patients not receiving documented anticoagulation (83% for argatroban, 58% for dabigatran, 72% for rivaroxaban, 53% for apixaban, 56% for warfarin, and 36% for UFH vs 29% for no anticoagulation, P < .025). Direct thrombin inhibitors mainly affected the activated partial thromboplastin time-based assays and the tissue thromboplastin inhibition index (TTI), while direct factor Xa inhibitors mainly affected the TTI and the dilute Russell viper venom ratio. Conclusions Results of LAC testing performed while patients are receiving anticoagulant therapies should be interpreted with caution to avoid misdiagnosing patients with the antiphospholipid syndrome and potentially committing them to long-term anticoagulation therapy.
Safety, long-term outcomes and predictors of recurrence after first-line combined endoepicardial ventricular tachycardia substrate ablation in arrhythmogenic cardiomyopathy. Impact of arrhythmic substrate distribution pattern. A prospective multicentre study

Background First-line endoepicardial ventricular tachycardia (VT) ablation has been proposed for patients with arrhythmogenic cardiomyopathy (AC). This study reports procedural safety, outcomes, and predictors of recurrence. Methods and Results Forty-one consecutive patients [12 with left ventricle (LV) involvement, 7 left-dominant] underwent first-line endoepicardial VT substrate ablation. Standard bipolar and unipolar thresholds were used to define low-voltage areas (LVA). Arrhythmogenic substrate area (ASA) was defined as the area containing electrograms with delayed components. Implantable cardioverter defibrillator interrogations were evaluated for VT recurrence. Epicardial LVA was larger in all cases (102.5 ± 78.6 vs. 19.3 ± 24.4 cm2; P< 0.001). Consistent with an epicardium-to-endocardium arrhythmogenic substrate progression pattern, epicardial ASA (epi-ASA) was negatively correlated with bipolar endocardial LVA (r = -0.368; P= 0.035) and with endocardial bipolar/unipolar-LVA (Bi/Uni-LVA) ratio (r= -0.38; P= 0.037). A Bi/Uni-LVA ratio >0.23 predicted an epi-ASA ≤10 cm2 (100% sensitivity, 84% specificity). Patients showing an epi-ASA < 10 cm2 required less epicardial (8.4 ± 5.8 vs. 25.3 ± 16; P= 0.045) and more endocardial (16.5 ± 8.6 vs. 7.5 ± 8.2; P= 0.047) radiofrequency applications. One patient with epi-ASA < 10 cm2 died of cardiac tamponade after epicardial puncture. Acute success (no VT inducibility after procedure) was achieved in 36 patients (90%). After 32.2 ± 21.8 months, 11 (26.8%) patients had VT recurrences. Left-dominant AC was associated with an increased risk of recurrence (HR = 3.41 [1.1-11.2], P= 0.044; log-rank P= 0.021). Conclusion First-line endoepicardial VT substrate ablation achieves good long-term results in AC. Left-dominant AC is associated with an increased risk of recurrence. The Bi/Uni-LVA ratio identifies patients with limited epicardial arrhythmogenic substrate in whom the indication of epicardial approach should be more cautiously assessed.
eConsultations to Infectious Disease Specialists: Questions Asked and Impact on Primary Care Providers’ Behavior

Abstract Background Since 2010, the Champlain BASE (Building Access to Specialist Advice through eConsultation) has allowed primary care providers (PCPs) to submit clinical questions to specialists through a secure web service. The study objectives are to describe questions asked to Infectious Diseases specialists through eConsultation and assess impact on physician behaviors. Methods eConsults completed through the Champlain BASE service from April 15, 2013 to January 29, 2015 were characterized by the type of question asked and infectious disease content. Usage data and PCP responses to a closeout survey were analyzed to determine eConsult response time, change in referral plans, and change in planned course of action. Results Of the 224 infectious diseases eConsults, the most common question types were as follows: interpretation of a clinical test 18.0% (41), general management 16.5 % (37), and indications/goals of treating a particular condition 16.5% (37). The most frequently consulted infectious diseases were as follows: tuberculosis 14.3% (32), Lyme disease 14.3% (32), and parasitology 12.9% (29). Within 24 hours, 63% of cases responded to the questions, and 82% of cases took under 15 minutes to complete. In 32% of cases, a face-to-face referral was originally planned by the PCP but was no longer needed. In 8% of cases, the PCP referred the patient despite originally not planning to make a referral. In 55% of cases, the PCP either received new information or changed their course of action. Conclusions An eConsult service provides PCPs with timely access to infectious disease specialists’ advice that often results in a change in plans for a face-to-face referral.
Ethnic and socioeconomic variation in incidence of congenital heart defects

Introduction Ethnic differences in the birth prevalence of congenital heart defects (CHDs) have been reported; however, studies of the contemporary UK population are lacking. We investigated ethnic variations in incidence of serious CHDs requiring cardiac intervention before 1 year of age. Methods All infants who had a cardiac intervention in England and Wales between 1 January 2005 and 31 December 2010 were identified in the national congenital heart disease surgical audit and matched with paediatric intensive care admission records to create linked individual child records. Agreement in reporting of ethnic group by each audit was evaluated. For infants born 1 January 2006 to 31 December 2009, we calculated incidence rate ratios (IRRs) for CHDs by ethnicity and investigated age at intervention, antenatal diagnosis and area deprivation. Results We identified 5350 infants (2940 (55.0%) boys). Overall CHD incidence was significantly higher in Asian and Black ethnic groups compared with the White reference population (incidence rate ratios (IRR) (95% CIs): Asian 1.5 (1.4 to 1.7); Black 1.4 (1.3 to 1.6)); incidence of specific CHDs varied by ethnicity. No significant differences in age at intervention or antenatal diagnosis rates were identified but affected children from non-White ethnic groups were more likely to be living in deprived areas than White children. Conclusions Significant ethnic variations exist in the incidence of CHDs, including for specific defects with high infant mortality. It is essential that healthcare provision mitigates ethnic disparity, including through timely identification of CHDs at screening, supporting parental choice and effective interventions. Future research should explore the factors underlying ethnic variation and impact on longer-term outcomes.
Psychophysical Evaluation of Subdermal Electrical Stimulation in Relation to Prosthesis Sensory Feedback

This paper evaluated the psychophysical properties of subdermal electrical stimulation to investigate its feasibility in providing sensory feedback for limb prostheses. The detection threshold (DT), pain threshold (PT), just noticeable difference (JND), as well as the elicited sensation quality, comfort, intensity, and location were assessed in 16 healthy volunteers during stimulation of the ventral and dorsal forearm with subdermal electrodes. Moreover, the results were compared with those obtained from transcutaneous electrical stimulation. Despite a lower DT and PT, subdermal stimulation attained a greater relative dynamic range (i.e., PT/DT) and significantly smaller JNDs for stimulation amplitude. Muscle twitches and movements were more commonly elicited by surface stimulation, especially at the higher stimulation frequencies, whereas the pinprick sensation was more often reported with subdermal stimulation. Less comfort was perceived in subdermal stimulation of the ventral forearm at the highest tested stimulation frequency of 100 Hz. In summary, subdermal electrical stimulation was demonstrated to be able to produce similar sensation quality as transcutaneous stimulation and outperformed the latter in terms of energy efficiency and sensitivity. These results suggest that stimulation through implantable subdermal electrodes may lead to an efficient and compact sensory feedback system for substituting the lost sense in amputees.
Assessing Energy Requirements in Women With Polycystic Ovary Syndrome: A Comparison Against Doubly Labeled Water

Context Weight loss is prescribed to offset the deleterious consequences of polycystic ovary syndrome (PCOS), but a successful intervention requires an accurate assessment of energy requirements. Objective Describe energy requirements in women with PCOS and evaluate common prediction equations compared with doubly labeled water (DLW). Design Cross-sectional study. Setting Academic research center. Participants Twenty-eight weight-stable women with PCOS completed a 14-day DLW study along with measures of body composition and resting metabolic rate and assessment of physical activity by accelerometry. Main Outcome Total daily energy expenditure (TDEE) determined by DLW. Results TDEE was 2661 ± 373 kcal/d. TDEE estimated from four commonly used equations was within 4% to 6% of the TDEE measured by DLW. Hyperinsulinemia (fasting insulin and homeostatic model assessment of insulin resistance) was associated with TDEE estimates from all prediction equations (both r = 0.45; P = 0.02) but was not a significant covariate in a model that predicts TDEE. Similarly, hyperandrogenemia (total testosterone, free androgen index, and dehydroepiandrosterone sulfate) was not associated with TDEE. In weight-stable women with PCOS, the following equation derived from DLW can be used to determine energy requirements: TDEE (kcal/d) = 438 - [1.6 * Fat Mass (kg)] + [35.1 * Fat-Free Mass (kg)] + [16.2 * Age (y)]; R2 = 0.41; P = 0.005. Conclusions Established equations using weight, height, and age performed well for predicting energy requirements in weight-stable women with PCOS, but more precise estimates require an accurate assessment of physical activity. Our equation derived from DLW data, which incorporates habitual physical activity, can also be used in women with PCOS; however, additional studies are needed for model validation.
Comparison of Methods for Estimating Unbound Intracellular-to-Medium Concentration Ratios in Rat and Human Hepatocytes Using Statins

It is essential to estimate concentrations of unbound drugs inside the hepatocytes to predict hepatic clearance, efficacy, and toxicity of the drugs. The present study was undertaken to compare predictability of the unbound hepatocyte-to-medium concentration ratios (Kp,uu) by two methods based on the steady-state cell-to-medium total concentration ratios at 37°C and on ice (Kp,uu,ss) and based on their initial uptake rates (Kp,uu,V0). Poorly metabolized statins were used as test drugs because of their concentrative uptake via organic anion-transporting polypeptides. Kp,uu,ss values of these statins provided less interexperimental variation than the Kp,uu,V0 values, because only data at longer time are required for Kp,uu,ss. Kp,uu,V0 values for pitavastatin, rosuvastatin, and pravastatin were 1.2- to 5.1-fold Kp,uu,ss in rat hepatocytes; Kp,uu,V0 values in human hepatocytes also tended to be larger than corresponding Kp,uu,ss. To explain these discrepancies, theoretical values of Kp,uu,ss and Kp,uu,V0 were compared with true Kp,uu (Kp,uu,true), considering the inside-negative membrane potential and ionization of the drugs in hepatocytes and medium. Membrane potentials were approximately −30 mV in human hepatocytes at 37°C and almost abolished on ice. Theoretical equations considering the membrane potentials indicate that Kp,uu,ss values for the statins are 0.85- to 1.2-fold Kp,uu,true, whereas Kp,uu,V0 values are 2.2- to 3.1-fold Kp,uu,true, depending on the ratio of the passive permeability of the ionized to nonionized forms. In conclusion, Kp,uu,ss values of anions are similar to Kp,uu,true when the inside-negative membrane potential is considered. This suggests that Kp,uu,ss is preferable for estimating the concentration of unbound drugs inside the hepatocytes.
Targeted sequencing of tonsillar and base of tongue cancer and human papillomavirus positive unknown primary of the head and neck reveals prognostic effects of mutated FGFR3

BACKGROUND Human papillomavirus positive (HPV+) tonsillar cancer (TSCC), base of tongue cancer (BOTSCC) and unknown primary cancer of the head and neck (HNCUP) have better outcome than corresponding HPV− cancers. To find predictive markers for response to treatment, and correlations and differences in mutated oncogenes and suppressor genes between HPV+ TSCC/BOTSSCC and HPV+ HNCUP and HPV− TSCC/BOTSCC targeted next-generation sequencing was performed of frequently mutated regions in 50 cancer related genes. PATIENTS AND METHODS DNA from 348 TSCC/BOTSCC and 20 HNCUP from patients diagnosed 2000-2011, was sequenced by the Ion Proton sequencing platform using the Ion AmpliSeq Cancer Hotspot Panel v2 to identify frequently mutated regions in 50 cancer related genes. Ion Torrent Variant Caller software was used to call variants. RESULTS 279 HPV+ TSCC/BOTSCC, 46 HPV− TSCC/BOTSCC and 19 HPV+ HNCUP samples qualified for further analysis. Mutations/tumor were fewer in HPV+ TSCC/BOTSCC and HNCUP, compared to HPV− tumors (0.92 vs. 1.32 vs. 1.68). Differences in mutation frequency of TP53 and PIK3CA were found between HPV+ TSCC/BOTSCC and HNCUP and HPV− TSCC/BOTSCC. In HPV+ TSCC/BOTSCC presence of FGFR3 mutations correlated to worse prognosis. Other correlations to survival within the groups were not disclosed. CONCLUSIONS In HPV+ TSCC/BOTSCC mutation of PIK3CA was most frequently observed, while TP53 mutations dominated in HPV− TSCC/BOTSCC. In HPV+ TSCC/BOTSCC and HNCUP, mutations/tumor were similar in frequency and fewer compared to that in HPV− TSCC/BOTSCC. Notably, FGFR3 mutations in HPV+ TSCC/BOTSCC indicated worse prognosis.
Experimental analysis of anisotropic damage in dual-phase steel by resonance measurement

The ductile damage in deformed dual-phase steel sheets (DP600) was investigated based on measurements of the degradation of the direction-dependent Young’s modulus. The study focuses on the material-induced damage anisotropy in such advanced high-strength steel. The elastic properties in the direction of applied loading of the deformed sheets were determined by measuring the resonance frequency of rectangular samples. The material was investigated in the as-delivered condition and after annealing at 220℃ for 48 h. Tensile strains of up to 10% were applied after annealing. Tensile tests were performed in different directions with respect to the rolling direction to determine the evolution of damage in different directions. The comparison of the obtained results with the electron micrographs shows that the damage in the steel sheets occurs in the form of nano and micro damages near the grain boundary and interfaces of phases. The maximum decrease of the Young’s modulus in the transverse direction was observed for the largest applied deformation of 10% tensile strain in the transverse direction. An efficient calculation method to obtain information on the distribution of anisotropy in the plane of the sheet was applied. This calculation method relies on an efficient representation of the material’s texture. In order to assess the influence of texture, the texture was determined experimentally.
Virulence Traits of Environmental and Clinical Legionella pneumophila Multilocus Variable-Number Tandem-Repeat Analysis (MLVA) Genotypes

ABSTRACT Legionella pneumophila causes water-based infections resulting in severe pneumonia. Recently, we showed that different MLVA-8 (multilocus variable-number tandem-repeat analysis using 8 loci) genotypes dominated different sites of a drinking-water distribution system. Each genotype displayed a unique temperature-dependent growth behavior. Here we compared the pathogenicity potentials of different MLVA-8 genotypes of environmental and clinical strains. The virulence traits studied were hemolytic activity and cytotoxicity toward amoebae and macrophages. Clinical strains were significantly more hemolytic than environmental strains, while their cytotoxicity toward amoebae was significantly lower at 30°C. No significant differences were detected between clinical and environmental strains in cytotoxicity toward macrophages. Significant differences in virulence were observed between the environmental genotypes (Gt). Gt15 strains showed a significantly higher hemolytic activity. In contrast, Gt4 and Gt6 strains were more infective toward Acanthamoeba castellanii. Moreover, Gt4 strains exhibited increased cytotoxicity toward macrophages and demonstrated a broader temperature range of amoebal lysis than Gt6 and Gt15 strains. Understanding the virulence traits of Legionella genotypes may improve the assessment of public health risks of Legionella in drinking water. IMPORTANCE Legionella pneumophila is the causative agent of a severe form of pneumonia. Here we demonstrated that clinical strains were significantly more cytotoxic toward red blood cells than environmental strains, while their cytotoxicity toward macrophages was similar. Genotype 4 (Gt4) strains were highly cytotoxic toward amoebae and macrophages and lysed amoebae in a broader temperature range than to the other studied genotypes. The results can explain the relatively high success of Gt4 in the environment and in clinical samples; thus, Gt4 strains should be considered a main factor for the assessment of public health risks of Legionella in drinking water. Our findings shed light on the ecology, virulence, and pathogenicity potential of different L. pneumophila genotypes, which can be a valuable parameter for future modeling and quantitative microbial risk assessment of Legionella in drinking-water systems.
The Distribution of Cicadellinae Leafhoppers and Other Auchenorrhyncha on Coffee and Citrus in Puerto Rico

Abstract Cicadellinae leafhoppers and other Auchenorrhyncha in coffee and citrus farms in Puerto Rico were surveyed five times over 18 mo. We frequently collected four of the seven species of Cicadellinae previously found in Puerto Rico, yet only one species (Caribovia coffeacola Dozier) fed directly on coffee; no species was observed to feed directly on citrus. Populations of C. coffeacola were higher during the rainy season and were more common at higher elevations. Feeding preference and performance experiments established that C. coffeacola preferentially fed, and could survive exclusively, on coffee and the common shade host Inga vera. Within-farm distribution of C. coffeacola was examined at a site with high populations, and abundances were higher with proximity to I. vera. Lastly, sets of novel sites were selected in four municipalities to test hypotheses concerning effects of season, elevation, and host plant assemblages on Cicadellinae populations. These tests confirmed that C. coffeacola was the only species that frequently fed on coffee and no species fed on citrus. Populations of C. coffeacola were higher in the rainy season and at higher elevations. Abundances were also higher when Inga vera was interspersed in coffee plantings compared to when other shade species were present or when coffee was grown as a monoculture (sun coffee). Cicadellinae were our focus, as within this study this subfamily is the predominant potential vector of the bacterium Xylella fastidiosa (Wells). Xylella fastidiosa has yet to be confirmed in Puerto Rico, but both citrus and coffee are susceptible to X. fastidiosa diseases.
Long-term exposure to transportation noise and air pollution in relation to incident diabetes in the SAPALDIA study

Abstract Background Epidemiological studies have inconsistently linked transportation noise and air pollution (AP) with diabetes risk. Most studies have considered single noise sources and/or AP, but none has investigated their mutually independent contributions to diabetes risk. Methods We investigated 2631 participants of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA), without diabetes in 2002 and without change of residence between 2002 and 2011. Using questionnaire and biomarker data, incident diabetes cases were identified in 2011. Noise and AP exposures in 2001 were assigned to participants’ residences (annual average road, railway or aircraft noise level during day-evening-night (Lden), total night number of noise events, intermittency ratio (temporal variation as proportion of event-based noise level over total noise level) and nitrogen dioxide (NO2) levels. We applied mixed Poisson regression to estimate the relative risk (RR) of diabetes and their 95% confidence intervals (CI) in mutually-adjusted models. Results Diabetes incidence was 4.2%. Median [interquartile range (IQR)] road, railway, aircraft noise and NO2 were 54 (10) dB, 32 (11) dB, 30 (12) dB and 21 (15) μg/m3, respectively. Lden road and aircraft were associated with incident diabetes (respective RR: 1.35; 95% CI: 1.02–1.78 and 1.86; 95% CI: 0.96–3.59 per IQR) independently of Lden railway and NO2 (which were not associated with diabetes risk) in mutually adjusted models. We observed stronger effects of Lden road among participants reporting poor sleep quality or sleeping with open windows. Conclusions Transportation noise may be more relevant than AP in the development of diabetes, potentially acting through noise-induced sleep disturbances.
Complete mitochondrial genome of the Pseudopleuronectes yokohamae (Pleuronectiforll: Pleuronectidae)

Abstract In this study, the complete mitochondrial genome of the Pseudopleuronectes yokohamae was sequenced. The mitochondrial genome is 17 383 bp in length, consisting of 13 protein-coding genes, 2 ribosomal RNA genes (rRNAs), 22 transfer RNA genes (tRNAs) and a control region (D-loop). The gene order and composition of P. yokohamae mitochondrial genome was similar to that of most other vertebrates. Two rRNA genes for 12S rRNA (949 bases) and 16S rRNA (1716 bases) are located between tRNA-Phe (GAA) and tRNA-Leu (TAA) and separated by the tRNA-Val. The control region of P. yokohamae, is located after tRNA-Pro and found to be 1679 bp. The overall nucleotides base composition of the heavy strand is A (27.55%), T (26.45%), G (28.75%), C (17.26%). With the exception of the NADH dehydrogenase subunit 6 (ND6) and eight tRNA genes, all other mitochondrial genes are encoded on the heavy strand. The 22 tRNA genes could be folded into a typical clover-leaf secondary structure. The phylogenetic trees consistently show that P. yokohama, Kareius bicoloratus and Platichthys stellatus from the same genus clustered into one branch. The complete mitogenome sequence information of P. yokohamae would provide useful data for further studies on population genetics and molecular systematics.