Miracle-dz/UniFAR-FTUs huggingface dataset:
ChIPulate: A comprehensive ChIP-seq simulation pipeline

ChIP-seq (Chromatin Immunoprecipitation followed by sequencing) is a high-throughput technique to identify genomic regions that are bound in vivo by a particular protein, e.g., a transcription factor (TF). Biological factors, such as chromatin state, indirect and cooperative binding, as well as experimental factors, such as antibody quality, cross-linking, and PCR biases, are known to affect the outcome of ChIP-seq experiments. However, the relative impact of these factors on inferences made from ChIP-seq data is not entirely clear. Here, via a detailed ChIP-seq simulation pipeline, ChIPulate, we assess the impact of various biological and experimental sources of variation on several outcomes of a ChIP-seq experiment, viz., the recoverability of the TF binding motif, accuracy of TF-DNA binding detection, the sensitivity of inferred TF-DNA binding strength, and number of replicates needed to confidently infer binding strength. We find that the TF motif can be recovered despite poor and non-uniform extraction and PCR amplification efficiencies. The recovery of the motif is however affected to a larger extent by the fraction of sites that are either cooperatively or indirectly bound. Importantly, our simulations reveal that the number of ChIP-seq replicates needed to accurately measure in vivo occupancy at high-affinity sites is larger than the recommended community standards. Our results establish statistical limits on the accuracy of inferences of protein-DNA binding from ChIP-seq and suggest that increasing the mean extraction efficiency, rather than amplification efficiency, would better improve sensitivity. The source code and instructions for running ChIPulate can be found at https://github.com/vishakad/chipulate.
Emerging Roles for Serotonin in Regulating Metabolism: New Implications for an Ancient Molecule.

Serotonin is a phylogenetically ancient biogenic amine that has played an integral role in maintaining energy homeostasis for billions of years. In mammals, serotonin produced within the central nervous system regulates behavior, suppresses appetite and promotes energy expenditure by increasing sympathetic drive to brown adipose tissue. In addition to these central circuits, emerging evidence also suggests an important role for peripheral serotonin as a factor that enhances nutrient absorption and storage. Specifically, glucose and fatty acids stimulate the release of serotonin from the duodenum promoting gut peristalsis and nutrient absorption. Serotonin also enters the blood stream and interacts with multiple organs, priming the body for energy storage by promoting insulin secretion, de novo lipogenesis in the liver and white adipose tissue, while reducing lipolysis and the metabolic activity of brown and beige adipose tissue. Collectively, peripheral serotonin acts as an endocrine factor to promote the efficient storage of energy by upregulating lipid anabolism. Pharmacological inhibition of serotonin synthesis or signaling in key metabolic tissues are potential drug targets for obesity and non-alcoholic fatty liver disease.
Effects of periodic carbohydrate ingestion on endurance and cognitive performances during a 40-km cycling time-trial under normobaric hypoxia in well-trained triathletes

ABSTRACT The purpose of this study was to examine CHO ingestion on a cognitive task using a field-simulated time-trial (TT) under hypoxia in well-trained triathletes. Ten male triathletes (age: 22.1 ± 1.1 years; VO2max: 59.4 ± 1.4 ml/kg/min) participated in this double-blind/crossover/counter-balanced design study. Participants completed 3 TT trials: 1) normoxic placebo (NPLA; FiO2 = 20.9%), 2) hypoxic placebo (HPLA; FiO2 = 16.3%), and 3) hypoxic CHO (HCHO; 6% CHO provided as 2 ml/kg/15 min; FiO2 = 16.3%). During the TT, physiological responses (SpO2, HR, RPE, and blood glucose/lactate), cognitive performance, and cerebral haemodynamics were measured. Hypoxia reduced TT performance by ~3.5–4% (p < 0.05), but CHO did not affect TT performance under hypoxia. For the cognitive task, CHO slightly preserved exercise-induced cognitive reaction speed but did not affect response accuracy during hypoxic exercise. However, CHO did not preserve the decreased Hb-Diff (cerebral blood flow, CBF) and increased HHb in the prefrontal lobe (p < 0.05) during hypoxic exercise, and CHO failed to preserve hypoxia-suppressed prefrontal CBF and tissue oxygen saturation. In conclusion, the present study demonstrates that CHO is effective in sustaining reaction speed for a cognitive task but not promoting TT performance during hypoxic exercise, which would be important for strategy-/decision-making when athletes compete at moderate high-altitude.
A novel strip meniscometry method for measuring aqueous tear volume in dogs: Clinical correlations with the Schirmer tear and phenol red thread tests.

OBJECTIVES The strip meniscometry test (SMT) is a novel method for quantitative measurement of tear volume with only five seconds. We aimed to evaluate clinical correlations of SMT with the gold standard Schirmer tear test (STT) and phenol red thread test (PRT) in dogs, including normal and tear-deficient eyes. ANIMALS STUDIED Left eyes from 621 outpatient dogs with and without ocular disorders were evaluated. PROCEDURES Each subject underwent SMT, PRT, and STT without topical anesthesia in the described order with five-minute intervals. The total population was divided into four groups by classifying tear deficiency severity based on STT results: "severe" (0-5 mm/min), "moderate" (6-10 mm/min), "subclinical" (11-14 mm/min), and "normal" (15 or more mm/min). RESULTS The strongest correlation coefficient was found between SMT-STT (0.676), followed by PRT-STT (0.637) and SMT-PRT (0.600) pairs. Mean(SD) scores of SMT, PRT, and STT in total population were 9.47 (4.08) mm/5 s, 33.30 (8.52) mm/15 s, and 16.47 (7.01) mm/min. Significant differences were found among STT-classified groups, both using SMT and PRT results. Receiver operating characteristic (ROC) curves revealed that SMT better agreed with STT than PRT; agreement increased with increasing STT severity. A cutoff for SMT was identified at 10 mm/5 s to discriminate normal eyes from tear-deficient eyes, yielding high sensitivities and acceptable specificities. CONCLUSIONS SMT could be superior to PRT for discriminating tear-deficient eyes. The high sensitivity of SMT could be useful as an initial diagnostic tool to rule out normal eyes with the short testing time.
The effect of automated landmark identification on morphometric analyses

Morphometric analysis of anatomical landmarks allows researchers to identify specific morphological differences between natural populations or experimental groups, but manually identifying landmarks is time‐consuming. We compare manually and automatically generated adult mouse skull landmarks and subsequent morphometric analyses to elucidate how switching from manual to automated landmarking will impact morphometric analysis results for large mouse (Mus musculus) samples (n = 1205) that represent a wide range of ‘normal’ phenotypic variation (62 genotypes). Other studies have suggested that the use of automated landmarking methods is feasible, but this study is the first to compare the utility of current automated approaches to manual landmarking for a large dataset that allows the quantification of intra‐ and inter‐strain variation. With this unique sample, we investigated how switching to a non‐linear image registration‐based automated landmarking method impacts estimated differences in genotype mean shape and shape variance‐covariance structure. In addition, we tested whether an initial registration of specimen images to genotype‐specific averages improves automatic landmark identification accuracy. Our results indicated that automated landmark placement was significantly different than manual landmark placement but that estimated skull shape covariation was correlated across methods. The addition of a preliminary genotype‐specific registration step as part of a two‐level procedure did not substantially improve on the accuracy of one‐level automatic landmark placement. The landmarks with the lowest automatic landmark accuracy are found in locations with poor image registration alignment. The most serious outliers within morphometric analysis of automated landmarks displayed instances of stochastic image registration error that are likely representative of errors common when applying image registration methods to micro‐computed tomography datasets that were initially collected with manual landmarking in mind. Additional efforts during specimen preparation and image acquisition can help reduce the number of registration errors and improve registration results. A reduction in skull shape variance estimates were noted for automated landmarking methods compared with manual landmarking. This partially reflects an underestimation of more extreme genotype shapes and loss of biological signal, but largely represents the fact that automated methods do not suffer from intra‐observer landmarking error. For appropriate samples and research questions, our image registration‐based automated landmarking method can eliminate the time required for manual landmarking and have a similar power to identify shape differences between inbred mouse genotypes.
Essentials when studying child-father attachment: A fundamental view on safe haven and secure base phenomena

ABSTRACT The most relevant functions of an attachment figure for a child from evolutionary, cultural, and individual perspectives are being a safe haven and secure base for the child. The concepts of behavioral systems and emotional security are delineated. Central to a child’s emotional security is her smooth transition between seeking a safe haven when distressed and a secure base when at ease with her attachment figures. The special quality of the child-father attachment relationship is marked by an emphasis on supporting the child’s exploration and her emotional intensity during agitated play. Systematic analysis of child-father attachment requires careful, realistic, and lengthy natural, ethological observations of behaviors that indicate the child’s attachment to father. Such observations would result in a fuller understanding of the infants’ or children’s contribution to their development of psychological security.
Severe Hypoxia Does Not Offset the Benefits of Exercise on Cognitive Function in Sedentary Young Women

Purpose: To examine the effect of acute moderate-intensity continuous exercise performed under normobaric severe hypoxia on cognition, compared to sea-level normoxia. Methods: Thirty healthy inactive women randomly performed two experimental trials separated by at least three days but at approximately the same time of day. Executive functions were measured during the follicular stage via an interference control task before (rest) and during exercise with 45% peak power output under normobaric normoxia (PIO2 = 150 mmHg, FIO2 = 0.21), and (2) hypoxia (PIO2 = 87 mmHg, FIO2 = 0.12, simulated at an altitude of 4000 m). Reaction time (RT), accuracy rate (AC), heart rate, ratings of perceived exertion, and peripheral oxygen saturation (SpO2) were collected before and during exercise. Results: RT (p < 0.05, η2p = 0.203) decreased during moderate exercise when compared at rest, while a short bout of severe hypoxia improved RT (p < 0.05, η2p = 0.134). Exercise and hypoxia had no effects on AC (p > 0.05). No significant associations were found between the changes of RT and SpO2 under the conditions of normoxia and hypoxia (p > 0.05). Conclusions: At the same phase of the menstrual cycle, a short bout of severe hypoxia simulated at 4000 m altitude caused no impairment at rest. RT during moderate exercise ameliorated in normoxia and severe hypoxia, suggesting that both exercise and short-term severe hypoxia have benefits on cognitive function in sedentary young women.
Optimizing neuromuscular electrical stimulation for hand opening

Abstract Aim: To investigate the effect of introducing an interphase interval to a biphasic pulse on force production and muscle fatigue, during stimulation of the wrist and finger extensors and to determine whether the IPI effect on force is dependent on electrode position. Methods: Electrically-induced contraction forces of the wrist and finger extensors were measured in 15 healthy subjects undergoing stimulation. These forces were assessed with interphase interval settings at 0, 100, and 200μs, with both electrodes located just distal to common extensor origin (proximal placement) or with the distal electrode placed over the extensor and abductor policies longus muscles (distal placement). The degree of discomfort related to stimulation sensation was evaluated using a numeric rating scale. Muscle fatigue was measured during proximal placement. Results: Under both electrode locations, introduction of 100 or 200 μs interphase interval enhanced force production; yet, only the 100μs interphase interval increased force without increasing discomfort. Additionally, stimulation sensation was more comfortable with proximal placement. Introducing interphase interval significantly increased the muscle force output during a repetitive stimulation fatigue protocol. Conclusions: When using neuromuscular electrical stimulation to activate the wrist and finger extensors, clinicians should consider locating both stimulating electrodes proximally over the extensor surface of the forearm and apply a 100 µs interphase interval to a biphasic pulse. Future research that should establish these findings in individuals with various pathologies, especially in patients with residual hand spasticity.
Determination of Neurocognitive Changes Using Electroencephalography and the Mini-Mental Test in Coronary Bypass Patients Who Underwent Operation with Pulsatile and Non-Pulsatile Cardiopulmonary Bypass

Introduction: The aim of this study was to compare the neurocognitive effects of pulsatile and non-pulsatile perfusion using electroencephalography and the Mini-Mental State Examination (MMSE) in patients undergoing coronary bypass surgery. Patients and Methods: We created two groups, each containing 11 consecutive randomized patients, who were candidates for coronary bypass surgery. Pulsatile cardiopulmonary bypass (CPB) was conducted in Group I, and non-pulsatile CPB was conducted in Group II. An electroencephalogram (EEG) was performed preoperatively, intraoperatively, 15 minutes after placement of the cross-clamp, and seven days postoperatively. The MMSE was performed preoperatively and on postoperative day seven. Results: In both groups, pathological EEG waves were detected intraoperatively. However, no statistically significant difference was found between the groups (p> 0.05). Urine output was significantly higher at postoperative day1 in Group I. Overall urine drainage was higher in Group I, but the difference was not statistically significant. Diabetes mellitus, hypercholesterolemia, hypertension, cross-clamp, and perfusion time did not have a significant impact on the formation of pathological EEG waves. The difference between preand postoperative MMSE scores was not statistically significant (p> 0.05). Conclusion: No remarkable superiority was shown between CPB pulsatile and non-pulsatile perfusion in our study. Improving physiology of perfusion techniques during CPB and performing further studies on patients at high risk for organ perfusion would suggest more comprehensive perfusion flow strategies.
Diastolic Reverse Dipping Pattern Is the Predictor for the Echocardiographic Changes in the Untreated Masked Hypertensive Patients

BACKGROUND The prognostic value of the dipping categories of diastolic blood pressure (DBP) is unknown. This study aimed to investigate the association between DBP dipping categories of diastolic blood pressure and echocardiographic changes in untreated masked hypertension (MH) patients. METHODS This retrospective study included 721 untreated MH patients between June 2006 and June 2016. Nocturnal dipping categories were defined according to the percentage decrease in nocturnal blood pressure (BP) compared to daytime BP as follows: non-dipping: decrease 0% to <10%, dipping: decrease 10% to 20%, reverse dipping: decrease <0%, and extreme dipping: decrease >20%. The echocardiographic findings were analyzed. RESULTS The 4 echocardiographic parameters (left atrium [LA] dimension, interventricular septum [IVS] thickness, linear left ventricular end-diastolic dimension [LVEDD], and left ventricular [LV] mass) were significantly different among the 4 DBP dipping categories. Multivariate linear regression analysis showed that DBP reverse dipping pattern was associated with higher IVS thickness (B: 0.53, 95% CI: 0.24 to 0.82; P < 0.001) and LV mass (B: 12.36, 95% CI: 2.38 to 22.35; P = 0.015), whereas DBP extreme dipping was associated with lower LVEDD (B: -7.05, 95% CI: -11.30 to -2.80; P = 0.001). The nocturnal systolic hypertension was associated with higher IVS thickness (B: 0.42, 95% CI: 0.14 to 0.71; P = 0.003) and LV mass (B:14.21, 95% CI: 4.54 to 23.88; P = 0.004). The nocturnal systolic blood pressure was associated with LA dimension, IVS thickness, left ventricular posterior wall thickness, and LV mass (all Ps < 0.05). CONCLUSIONS These results suggest that specific DBP dipping categories and nocturnal systolic hypertension were the predictive factors for the echocardiographic changes in untreated MH patients.
Employment Status and Work Ability in Long-Term Young Adult Cancer Survivors.

Purpose: In young adult cancer survivors (YACSs) to explore the rate of being nonemployed and having low work ability, and to identify factors associated with these two outcomes. Methods: All Norwegian YACSs (N = 3558) diagnosed at ages 19-39 years and treated between 1985 and 2009 for breast or colorectal cancer, leukemia, non-Hodgkin lymphoma, or melanoma, and alive in 2015, were mailed a questionnaire. The response rate was 42%. For treatment, a minimal surgery-only group (N = 198) was defined as reference group, and 1000 YACSs represented the local, systemic, and systemic plus other treatment groups. Work status was compared with normative data. Results: The sample included 63% females. Median age at survey was 49 years (range 27-65), and median time since first cancer diagnosis was 16 years (range 6-31). At survey, 25% (95% confidence interval [CI]: 22-27) of YACSs were nonemployed, and 38% (95% CI: 35-41) reported low work ability. The rate of being nonemployed was similar to normative data. More female YACSs held disability pension compared with normative data. In multivariable analyses, an increasing number of adverse effects (AEs), cardiovascular diseases, lower basic education, reduced level of self-rated health, and increased level of depression were significantly associated with both being nonemployed and having low work ability. Conclusions: In YACSs surveyed at median 49 years of age, 25% were nonemployed and 38% had low current work ability. An increased mean number of long-term AEs and several other health-related factors were significantly associated with both these outcomes. Health care providers responsible for YACSs should be attentive to such factors and work ability.
Genomic epidemiology of erythromycin-resistant Bordetella pertussis in China

ABSTRACT Macrolides such as erythromycin are the empirical treatment of Bordetella pertussis infections. China has experienced an increase in erythromycin-resistant B. pertussis isolates since they were first reported in 2013. Here, we undertook a genomic study on Chinese B. pertussis isolates from 2012 to 2015 to elucidate the origins and phylogenetic relationships of erythromycin-resistant B. pertussis isolates in China. A total of 167 Chinese B. pertussis isolates were used for antibiotic sensitivity testing and multiple locus variable-number tandem repeat (VNTR) analysis (MLVA). All except four isolates were erythromycin-resistant and of the four erythromycin-sensitive isolates, three were non-ptxP1. MLVA types (MT), MT55, MT104 and MT195 were the predominant types. Fifty of those isolates were used for whole genome sequencing and phylogenetic analysis. Genome sequencing and phylogenetic analysis revealed three independent erythromycin-resistant lineages and all resistant isolates carried a mutation in the 23S rRNA gene. A novel fhaB3 allele was found uniquely in Chinese ptxP1 isolates and these Chinese ptxP1-ptxA1-fhaB3 had a 5-fold higher mutation rate than the global ptxP1-ptxA1 B. pertussis population. Our results suggest that the evolution of Chinese B. pertussis is likely to be driven by selection pressure from both vaccination and antibiotics. The emergence of the new non-vaccine fhaB3 allele in Chinese B. pertussis population may be a result of selection from vaccination, whereas the expansion of ptxP1-fhaB3 lineages was most likely to be the result of selection pressure from antibiotics. Further monitoring of B. pertussis in China is required to better understand the evolution of the pathogen.
Detection of Financial Reporting Fraud: The Case of Socially Responsible Firms

This study aims to analyze the implementation of fraud pentagon theory, covering pressure, opportunity, rationalization, competence, and arrogance variables on financial statement fraud using the Beneish M-score method for socially responsible companies listed in the SRI-KEHATI index of the Indonesia Stock Exchange in the period 2013-2018. The secondary data were taken from the annual reports and audited financial statements of companies. The sample was selected using a purposive sampling in which 13 SRI-KEHATI index companies as the sample with a four-year research period in 2013-2018, a totally of 78 samples. The data were analyzed using descriptive statistical analysis and logistic regression analysis using IBM SPSS statistical software 25. The results showed financial targets, ineffective monitoring, and the nature of the industry, changes in directors, and the frequency of the appearance of CEO photos simultaneously influencing financial statement fraud. Partially, ineffective monitoring, changes in directors and the frequency of CEO photos on fraudulent financial statements have a negative effect, and the nature of the industry has a positive effect, while financial targets do not affect financial statement fraud. This research can be used as a reference for stakeholders in the company to consider the proportion of independent directors and the ratio of receivables in detecting fraud in a company.