Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Specific MicroRNA Biomarkers in Early Stages of Hepatocellular Injury, Cholestasis, and Steatosis in Rats

Recently, studies on circulating microRNAs (miRNAs) as potential biomarkers of drug-induced liver injury (DILI) have received increasing attention. It has been demonstrated that miR-122 and miR-192, which are liver enriched, could be potential biomarkers of DILI; however, these miRNAs cannot discern types of injuries. In the present study, we comprehensively analyzed time-dependent plasma miRNA profiles in rats with drug- or chemical-induced hepatocellular injury, cholestasis, and steatosis with high-throughput miRNA sequencing. To enable the comparison of miRNA expression levels between DILI models with different severity and peak time of injuries, the stages of injury were defined as early, middle, and late, according to cluster patterns of miRNA expression profiles. Through differential analysis, we characterized miRNAs that were specifically up- or down-regulated in each DILI model. Several miRNAs were dramatically changed earlier than traditional biomarkers such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST). For example, in an acetaminophen (APAP)-induced hepatocellular injury model, plasma let-7b-5p was up-regulated as early as 3 h after dosing, whereas a significant change in ALT level was observed at 12 h. We then focused on the DILI type-specific miRNAs in plasma that were up-regulated at the early stage of injury. RT-qPCR analysis validated that let-7b-5p and miR-1-3p for hepatocellular injury, miR-143-3p and miR-218a-5p for cholestasis, and miR-320-3p for steatosis models showed significant increases in the early stage of the injuries. The present study suggests the utility of miRNAs as specific biomarkers for the early detection of DILI.
Kernelized Hashcode Representations for Biomedical Relation Extraction

Kernel methods have produced state-of-the-art results for a number of NLP tasks such as relation extraction, but suffer from poor scalability due to the high cost of computing kernel similarities between discrete natural language structures. A recently proposed technique, kernelized locality-sensitive hashing (KLSH), can significantly reduce the computational cost, but is only applicable to classifiers operating on kNN graphs. Here we propose to use random subspaces of KLSH codes for efficiently constructing an explicit representation of NLP structures suitable for general classification methods. Further, we propose an approach for optimizing the KLSH model for classification problems by maximizing a variational lower bound on mutual information between the KLSH codes (feature vectors) and the class labels. We evaluate the proposed approach on biomedical relation extraction datasets, and observe significant and robust improvements in accuracy w.r. t. state-of-the-art classifiers, along with drastic (orders-of-magnitude) speedup compared to conventional kernel methods.
Does perturbation-based balance training prevent falls among individuals with chronic stroke? A randomised controlled trial

Objectives No intervention has been shown to prevent falls poststroke. We aimed to determine if perturbation-based balance training (PBT) can reduce falls in daily life among individuals with chronic stroke. Design Assessor-blinded randomised controlled trial. Setting Two academic hospitals in an urban area. Interventions Participants were allocated using stratified blocked randomisation to either ‘traditional’ balance training (control) or PBT. PBT focused on improving responses to instability, whereas traditional balance training focused on maintaining stability during functional tasks. Training sessions were 1 hour twice/week for 6 weeks. Participants were also invited to complete 2 ‘booster’ training sessions during the follow-up. Participants Eighty-eight participants with chronic stroke (>6 months poststroke) were recruited and randomly allocated one of the two interventions. Five participants withdrew; 42 (control) and 41 (PBT group) were included in the analysis. Primary and secondary outcome measures The primary outcome was rate of falls in the 12 months post-training. Negative binomial regression was used to compare fall rates between groups. Secondary outcomes were measures of balance, mobility, balance confidence, physical activity and social integration. Results PBT participants reported 53 falls (1.45 falls/person-year) and control participants reported 64 falls (1.72 falls/person-year; rate ratio: 0.85(0.42 to 1.69); p=0.63). Per-protocol analysis included 32 PBT and 34 control participants who completed at least 10/12 initial training sessions and 1 booster session. Within this subset, PBT participants reported 32 falls (1.07 falls/person-year) and control participants reported 57 falls (1.75 falls/person-year; rate ratio: 0.62(0.29 to 1.30); p=0.20). PBT participants had greater improvement in reactive balance control than the control group, and these improvements were sustained 12 months post-training. There were no intervention-related serious adverse effects. Conclusions The results are inconclusive. PBT may help to prevent falls in daily life poststroke, but ongoing training may be required to maintain the benefits. Trial registration number ISRCTN05434601; Results.
Distinguishing IgG4-Related Ophthalmic Disease From Graves Orbitopathy.

PURPOSE The authors aimed to determine key features of IgG4-related ophthalmic disease (IgG4-ROD) and Graves orbitopathy (GO) to aid in diagnosis. METHODS The authors retrospectively identified ophthalmology patients seen between June 2009 and November 2013 with clinical overlap of GO and IgG4-ROD. Patient findings were reviewed to characterize the 2 conditions. RESULTS Among 8 patients (7 male and 1 female), the mean age was 45.8 years. Time between diagnoses of GO and IgG4-ROD ranged from 1 month to 8 years. Imaging showed enlarged extraocular muscles in all patients. Enlarged infraorbital nerves were seen in 4 patients. Tissue biopsy showed CD20+ lymphocytes with a large proportion of IgG4 plasma cells in 7 of 8 orbital specimens. Six patients had a ratio of IgG4:IgG cells >40%. DISCUSSION No pathognomonic clinical findings for GO or IgG4-ROD have been reported, but some key features can help distinguish the conditions. GO is likely if findings include increased thyrotropin receptor antibodies, lid retraction/lid lag, and enlarged extraocular muscles with typical tendon-sparing morphology. Findings suggestive of IgG4-ROD include history of asthma and progressive orbital disease in patients with previous diagnosis of GO, disproportionately large lateral rectus muscle, and enlarged infraorbital nerves. Increased serum IgG4 level and biopsy showing >10 IgG4+ plasma cells/high-power field and IgG4:IgG ratio >40% will support the diagnosis of IgG4-ROD. CONCLUSIONS GO and IgG4-ROD are complicated inflammatory processes affecting the orbit and present diagnostic challenges. The authors recommend biopsy for patients who do not follow the usual clinical course of GO or have clinical characteristics of IgG4-ROD.
Review of Smart Services for Tinnitus Self-Help, Diagnostics and Treatments

In the recent years, there has been an increasing interest in the potential of internet- and smartphone-based technologies for the support of tinnitus patients. A broad spectrum of relevant approaches, some in the form of studies, others in the form of market products, have been mentioned in literature. They include auditory treatments, internet-based Cognitive Behavioral Therapy (iCBT), serious games, and questionnaires for tinnitus monitoring. The goal of this study is to highlight the role of existing internet-based and smart technologies for the advancement of tinnitus clinical practice: we consider contributions that refer to treatments and diagnostics, and we include contributions refering to self-help measures. We elaborate on the potential and challenges of such solutions and identify constraints associated to their deployment, such as the demand for familiarity with internet-based services and the need to re-design interactive services so that they fit on the small surface of a smartwatch.
Effect of a single dose of mannitol on hydration status and electrolyte concentrations in patients with tick-borne encephalitis

Objective This study was performed to assess the effect of a single dose of 15% mannitol on the hydration status and electrolyte balance in patients with tick-borne encephalitis (TBE). Methods Forty-one patients with TBE were treated with 0.25 g/kg of 15% mannitol. The electrolyte concentrations (Na, K, and Cl), creatinine concentration, and hydration status were measured before and after mannitol infusion. Results After mannitol administration, 7 patients had hyponatremia, 3 had hypokalemia, 1 had hyperkalemia, and 17 had hypochloremia. The total body water volume (TBW) changed by 0.44% ± 0.55%, the external body water volume (EBW) changed by 0.12% ± 0.15%, and the internal body water volume (IBW) changed by 0.19% ± 0.40%. The mean ECW/ICW ratio was 0.7694 ± 0.07 before treatment and 0.7699 ± 0.07 after treatment. Age was correlated with the TBW change in men (R = 0.42, p < 0.05) and with the potassium change in women (R = 0.66, p < 0.05). Conclusions Patients with TBE should receive mannitol two to four times daily depending on the clinical manifestation. Administration of a single dose of mannitol (0.25 g/kg) requires at least 300 mL of fluid supplementation. Bioimpedance might be useful for individual evaluation of dehydration. Additionally, patients require monitoring for potential hyponatremia. Older men may be more prone to dehydration after receiving mannitol.
The impact of attention deficit hyperactivity disorder (ADHD) in adulthood: a qualitative study

Objectives There is limited evidence of the unmet needs and experiences of adults with attention deficit hyperactivity disorder (ADHD). Previous research in this area is predominantly quantitative by nature, few studies employing qualitative approaches. This study seeks to provide a deeper insight into the lived experiences of adults with ADHD within Western Ireland. Methods A qualitative design, consisting of semi-structured face-to-face interviews with a clinical sample in the Sligo/Leitrim area. Participants were eligible for this study if they screened positive for symptoms of ADHD, and diagnosed with ADHD with the Conners’ Adult ADHD Diagnostic Interview for DSM-IV. In total, 11 participants completed this research. The interviews were open ended and exploratory, adopting a phenomenological approach. Results Thematic analysis was used to explore three main themes; The Burden of symptoms of ADHD, Perceived Positive and Negative Effects of ADHD and Challenge of Accessing Services, each with several subthemes. Conclusion This research highlights the experiences of adults with ADHD. It is important for practitioners to be aware of the perceived positive and negative effects of the disorder, and how it can impact on their patient’s lives. In addition, becoming aware of the stigma associated with ADHD can help clinicians improve upon individual treatment plans to meet their patient’s needs. It is important to note that this sample experienced co-morbid diagnoses and so this may limit the interpretation of the findings. Further research in this area could explore patient’s attitudes towards receiving a formal diagnosis of ADHD.
Human Ovarian Theca-Derived Multipotent Stem Cells Have The Potential to Differentiate into Oocyte-Like Cells In Vitro

Objective In this study, we have examined human theca stem cells (hTSCs) in vitro differentiation capacity into human oocyte like cells (hOLCs). Materials and Methods In this interventional experiment study, hTSCs were isolated from the theca layer of small antral follicles (3-5 mm in size). Isolated hTSCs were expanded and cultured in differentiation medium, containing 5% human follicular fluid, for 50 days. Gene expressions of PRDM1, PRDM14, VASA, DAZL, OCT4, ZP1, 2, 3 GDF9, SCP3 and DMC1 were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) on days 0, 18, and 25 after monoculture as well as one week after co-culture with human granulosa cells (hGCs). In addition, GDF9, OCT4, DAZL, VASA, and ZP3 proteins were immune-localized in oocyte-like structures. Results After 16-18 days, the color of the medium became acidic. After 25 days, the cells started to differentiate into round-shaped cells (20-25 µm diameter). One week after co-culturing with hGCs, the size of the round cells increased 60 to70 µm and convert to hOLCs. However, these growing cells expressed some primordial germ cell (PGC)- and germ cell genes (PRDM1, PRDM14, VASA, DAZL, and OCT4) as well as oocyte specific genes (ZP1, 2, 3 and GDF9), and meiotic-specific markers (SCP3 and DMC1). In addition, GDF9, OCT4, DAZL, VASA, and ZP3 proteins were present in hOLCs. Conclusion To sum up, hTSCs have the ability to differentiate into hOLCs. This introduced model paved the way for further in vitro studies of the exact mechanisms behind germ cell formation and differentiation. However, the functionality of hOLCs needs further investigation.
Comparison of sodium nitroprusside and adenosine for fractional flow reserve assessment: a systematic review and meta-analysis

ABSTRACT Background: Fractional flow reserve (FFR) has become a useful tool in the assessment of physiological significance of coronary artery stenosis (CAS), and Adenosine (ADE) is associated with a high incidence of transient side effects. Sodium nitroprusside (NPS) has been proposed as an alternative vasodilator agent. A meta-analysis of studies comparing ADE and NPS for FFR assessment in the same coronary lesions was performed. Methods: Authors searched for articles comparing NPS and ADE for FFR assessment in intermediate coronary lesions published through January 2018. The following keywords were used: ‘fractional flow reserve’ AND ‘nitroprusside’. Data were summarized using weighted mean differences for paired data. Results: Seven studies were identified comprising 342 patients and 401 lesions. Four studies evaluated intravenous ADE and 3 studies intracoronary ADE administration. Weighted means FFR values obtained with ADE and NPS were 0.8411 and 0.8445, respectively (weighted mean difference: 0.00, 95% confidence interval (CI) −0.01 to 0.01, p = 0,548). Adverse events were significantly reduced with IC NPS (RR = 0.08, 95%CI 0.02–0.30, P < 0.0001). Conclusions: NPS produces similar FFR measurements compared to ADE with a significant reduction in adverse effects. These results may support its use as a suitable alternative to ADE for FFR assessment.
A loss of heterozygosity, a loss in competition? The effects of inbreeding, pre‐ and postnatal conditions on nestling development

Abstract The early developmental trajectory is affected by genetic and environmental factors that co‐depend and interact often in a complex way. In order to distinguish their respective roles, we used canaries (Serinus canaria) of different genetic backgrounds (inbred and outbred birds). An artificial size hierarchy was created to provoke within‐nest competition, manipulating postnatal conditions. To this end, inbred birds were weight‐matched with outbred birds into duos, and each nest contained one duo of size‐advantaged, and one duo of size‐disadvantaged inbred and outbred nestlings. Prenatal (maternal) effects were taken into account also, enabling us to study the separate as well as the interactive effects of inbreeding, pre‐ and postnatal conditions on nestling development. We find that postnatal conditions were the most important determinant of early growth, with size‐advantaged nestlings growing faster and obtaining larger size/body mass at fledging in comparison with size‐disadvantaged nestlings. Prenatal conditions were important too, with birds that hatched from eggs that were laid late in the laying order obtaining a larger size at fledging than those hatched from early laid eggs. Inbreeding inhibited growth, but surprisingly this did not depend on (dis)advantageous pre‐ or postnatal conditions. Our findings imply that inbred individuals lose when they are in direct competition with same‐sized outbred individuals regardless of the rearing conditions, and we thus propose that reduced competitiveness is one of the driving forces of inbreeding depression.
Canonical Causal Diagrams to Guide the Treatment of Missing Data in Epidemiologic Studies

Abstract With incomplete data, the “missing at random” (MAR) assumption is widely understood to enable unbiased estimation with appropriate methods. While the need to assess the plausibility of MAR and to perform sensitivity analyses considering “missing not at random” (MNAR) scenarios has been emphasized, the practical difficulty of these tasks is rarely acknowledged. With multivariable missingness, what MAR means is difficult to grasp, and in many MNAR scenarios unbiased estimation is possible using methods commonly associated with MAR. Directed acyclic graphs (DAGs) have been proposed as an alternative framework for specifying practically accessible assumptions beyond the MAR-MNAR dichotomy. However, there is currently no general algorithm for deciding how to handle the missing data given a specific DAG. Here we construct “canonical” DAGs capturing typical missingness mechanisms in epidemiologic studies with incomplete data on exposure, outcome, and confounding factors. For each DAG, we determine whether common target parameters are “recoverable,” meaning that they can be expressed as functions of the available data distribution and thus estimated consistently, or whether sensitivity analyses are necessary. We investigate the performance of available-case and multiple-imputation procedures. Using data from waves 1–3 of the Longitudinal Study of Australian Children (2004–2008), we illustrate how our findings can guide the treatment of missing data in point-exposure studies.
Is time to progression associated with post-progression survival in previously treated metastatic non-small cell lung cancer with BRAF V600E mutation? A secondary analysis of phase II clinical trial data

Objective Longer time to progression (TTP) is associated with prolonged post-progression survival (PPS) in anaplastic lymphoma kinase+non-small cell lung cancer (NSCLC). This study evaluated whether TTP is associated with PPS among previously treated patients with metastatic v-Raf murine sarcoma viral oncogene homolog B V600E NSCLC receiving dabrafenib as monotherapy or in combination with trametinib. Design Secondary analysis of phase II clinical trial data. Setting Patients who experienced disease progression treated with dabrafenib monotherapy or in combination with trametinib as second line or later in an open-label, non-randomised, phase II study. Primary outcome measures The primary outcome was the TTP–PPS association. PPS was assessed with Kaplan-Meier analysis among patients with shorter versus longer TTP (< or ≥6 months). The TTP–PPS association was quantified in the Cox models adjusting for clinical covariates. Results Of the 84 included patients who progressed on dabrafenib monotherapy (n=57) or combination therapy (n=27), 60 (71%) died during post-progression follow-up. Patients with TTP ≥6 months experienced significantly longer PPS compared with those with TTP <6 months (median PPS: 9.5 vs 2.7 months, log-rank p<0.001). Each 3 months of longer TTP was associated with a 32% lower hazard of death following progression (HR 0.68, 95% CI 0.52 to 0.88) in the multivariable Cox model. Similar associations were seen in each treatment arm. Conclusion A longer TTP duration after treatment with dabrafenib monotherapy or combination therapy was associated with significantly longer PPS duration. Trial registration number NCT01336634; Post-results.
Examining the Role of Task Requirements in the Magnitude of the Vigilance Decrement

The vigilance decrement in sustained attention tasks is a prevalent example of cognitive fatigue in the literature. A critical challenge for current theories is to account for differences in the magnitude of the vigilance decrement across tasks that involve memory (successive tasks) and those that do not (simultaneous tasks). The empirical results described in this paper examine this issue by comparing performance, including eye movement data, between successive and simultaneous tasks that require multiple fixations to encode the stimulus for each trial. The findings show that differences in the magnitude of the vigilance decrement between successive and simultaneous tasks were observed only when a response deadline was imposed in the analysis of reaction times. This suggests that memory requirements did not exacerbate the deleterious impacts of time on task on the ability to accurately identify the critical stimuli. At the same time, eye tracking data collected during the study provided evidence for disruptions in cognitive processing that manifested as increased delays between fixations on stimulus elements and between encoding the second stimulus element and responding. These delays were particularly pronounced in later stages of encoding and responding. The similarity of the findings for both tasks suggests that the vigilance decrement may arise from common mechanisms in both cases. Differences in the magnitude of the decrement arise as a function of how degraded cognitive processing interacts with differences in the information processing requirements and other task characteristics. The findings are consistent with recent accounts of the vigilance decrement, which integrate features of prior theoretical perspectives.
Estimators for QST and coalescence times

Abstract Comparisons of QST to FST can provide insights into the evolutionary processes that lead to differentiation, or lack thereof, among the phenotypes of different groups (e.g., populations, species), and these comparisons have been performed on a variety of taxa, including humans. Here, I show that for neutrally evolving (i.e., by genetic drift, mutation, and gene flow alone) quantitative characters, the two commonly used QST estimators have somewhat different interpretations in terms of coalescence times, particularly when the number of groups that have been sampled is small. A similar situation occurs for FST estimators. Consequently, when observations come from only a small number of groups, which is not an unusual situation, it is important to match estimators appropriately when comparing QST to FST.