Miracle-dz/UniFAR-FTUs huggingface dataset:
Interaction Effects between the Cumulative Genetic Score and Psychosocial Stressor on Self-Reported Drinking Urge and Implicit Attentional Bias for Alcohol: A Human Laboratory Study

Aims The current candidate gene and environment interaction (cGxE) study examined whether the effects of an experimentally manipulated psychosocial stressor on self-reported drinking urge and implicit attentional bias for alcohol cues differ as a function of a cumulative genetic score of 5-HTTLPR, MAO-A, DRD4, DAT1 and DRD2 genotypes. The current study also examined whether salivary alpha-amylase level or self-reported anxiety state mediate these cGxE effects. Short Summary Individuals with high cumulative genetic risk score of the five monoamergic genotypes showed greater attentional bias toward alcohol cues when exposed to a psychosocial stressor than when not exposed. Methods Frequent binge-drinking Caucasian young adults (N = 105; mean age = 19; 61% male) completed both the control condition and stress condition (using the Trier Social Stress Test) in order. Results Regarding attentional bias, individuals with high and medium cumulative genetic risk scores showed greater attentional bias toward alcohol stimuli in the stress condition than in the control condition, whereas, those with low genetic risk scores showed greater attentional bias toward alcohol stimuli in the control condition than in the stress condition. No mediating roles of salivary alpha-amylase and anxiety state in the cGxE effect were found. Regarding self-reported drinking urge, individuals with high cumulative genetic score reported greater drinking urge than those with low genetic score regardless of experimental conditions. Conclusions Although replication is necessary, the findings suggest that the association of a psychosocial stressor on implicit (but not explicit, self-reported) alcohol outcomes may differ as a function of the collective effects of five monoamine genes.
Conventional Microscopical versus Digital Whole-Slide Imaging-Based Diagnosis of Thin-Layer Cervical Specimens: A Validation Study

Background: Whole-slide imaging (WSI) has been implemented in many areas of pathology, but primary diagnostics of cytological specimens are lagging behind. One of the objectives of viewing scanned whole-slide images from histological or cytological specimens is remote exchange of knowledge and expertise of professionals to increase diagnostic accuracy. We compared the scoring results of our team obtained in double readings of two different data sets: conventional light microscopy (CLM) versus CLM and CLM versus WSI. We hypothesized that WSI is noninferior to CLM for primary diagnostics of thin-layer cervical slides. Materials and Methods: First, we determined the concordance rate at different thresholds of the participating cytotechnicians by double reading with CLM of 500 thin-layer cervical slides (Cohort 1). Next, CLM was compared with WSI examination of another 505 thin-layer cervical slides (Cohort 2) scanned at ×20 in single focus plane. Finally, all major discordant cases of Cohort 1 were evaluated by an external expert in the field of gynecological cytology and of Cohort 2 in the weekly case meetings. Results: The overall concordance rate of Cohort 1 (CLM vs. CLM) was 97.8% (95% confidence interval [CI]: 96.0%–98.7%) and of Cohort 2 was 95.3% (95% CI: 93.0%–96.9%). Conclusion: Concordance rates of WSI versus CLM were comparable with those of CLM versus CLM. We have made a step forward paving the road to implementation of WSI also in routine diagnostic cytology.
Macular Pigment and Visual Function in Patients With Glaucoma: The San Diego Macular Pigment Study

Purpose Although recent studies have shown that macular pigment (MP) is significantly lower in glaucoma patients, this relationship merits further investigation. Methods This cross-sectional study included 85 glaucoma patients and 22 controls. All subjects had standard automated perimetry (SAP) and retinal nerve fiber layer (RNFL) thickness measurements. Intake of lutein (L) and zeaxanthin (Z) was estimated using a novel dietary screener. The Heidelberg Spectralis dual-wavelength autofluorescence (AF) technology was employed to study the relationship between MP and glaucoma. The association between MP volume and glaucoma was investigated using linear regression models accounting for potential confounding factors. Results Glaucoma patients had significantly worse SAP mean deviation (MD) and lower RNFL thickness in the study eye compared to control subjects (P < 0.001 for both). MP (volume) was comparable between groups (P = 0.436). In the univariable model, diagnosis of glaucoma was not associated with MP volume (R2 = 1.22%; P = 0.257). Dietary intake of L and Z was positively and significantly related to MP in the univariable (P = 0.022) and multivariable (P = 0.020) models. Conclusions These results challenge previous studies that reported that glaucoma is associated with low MP. Dietary habits were found to be the main predictor of MP in this sample. Further research is merited to better understand the relationship between glaucoma, MP, and visual performance in these patients.
Behavioral Analysis at Scale: Learning Course Prerequisite Structures from Learner Clickstreams

Knowledge of prerequisite dependencies is crucial to several aspects of learning, from the organization of learning content to the selection of personalized remediation or enrichment for each learner. As the amount of content is scaled up, however, it becomes increasingly difﬁcult to manually specify all of the prerequisites among the different content parts, necessitating automation. Since existing approaches to automatically inferring prerequisite dependencies rely on analysis of content ( e.g., topic modeling of text) or performance ( e.g., quiz results tied to content) data, they are not feasible in cases where courses have no assessments or only short content pieces ( e.g., short video segments). In this paper, we propose an algo-rithm that extracts prerequisite information using learner behavioral data instead of content and performance data, and apply it to an online short course. By modeling learner interaction with course content through a recurrent neural network-based architecture, our algorithm characterizes the prerequisite structure as latent variables, and estimates them from learner behavior. Through evaluation on a dataset of roughly 12,000 learners in a course we hosted on our platform, we show that our algorithm excels at both predicting behavior and revealing ﬁne-granular insights into prerequisite dependencies between content segments, with validation provided by a course administrator. Our approach of content analytics using large-scale behavioral data complements existing approaches that focus on course content and/or performance data.
Sertraline-Induced Rhabdomyolysis, Trismus, and Cardiac Arrest in a Child

Revealing a potentially fatal complication of a commonly used medication, we illustrate with this case the complex pharmaco-physiologic and interindividual differences in medication efficacy and side effects. Selective serotonin reuptake inhibitors are a commonly used and often effective class of medications in the treatment of mood disorders such as anxiety and depression. Sertraline (1S,4S-N-methyl-4-[3,4-dichlorophenyl]-1,2,3,4-tetrahydro-1-naphthylamine [Zoloft; Pfizer, New York City, NY]) is a frequently used selective serotonin reuptake inhibitor that has shown efficacy in children, adolescents, and adults. We report the case of a 13-year-old boy with sertraline-induced rhabdomyolysis and renal failure, trismus, and cardiopulmonary arrest. Pharmacogenetic testing later revealed our patient had serotonin transporter polymorphisms and enzymatic alterations that put him at risk for increased levels of sertraline and greater likelihood for untoward side effects.
Intensity-modulated radiotherapy for synchronous cancer of the anal canal and cervix

Due to recent advancements in diagnostic techniques, the incidence of multiple primary cancer has increased; however, synchronous cancer of the anal canal and cervix (SCACC) is rare, and no previous studies have investigated the treatment of this disease. The present study reports a case in which intensity-modulated radiotherapy (IMRT) was used to treat a 64-year-old female with SCACC, inguinal lymphadenopathy and anal pain. The patient was diagnosed with cT3N3M0 stage IIIb anal canal squamous cell carcinoma and cT1b1N0M0 stage Ib1 cervical squamous cell carcinoma, based on biopsy and imaging study data. According to the definitive treatment for advanced-stage anal canal cancer, outpatient treatment with chemoradiotherapy (CRT) using S-1 for SCACC was recommended, as the patient did not want to undergo resection of the anus. Considering the lymph node regions involved in SCACC and the necessary doses, the treatment plan was as follows: Whole pelvis and inguinal lymph node region radiation (36 Gy/20 fractions); a first booster radiation dose (9 Gy/5 fractions) for the whole pelvis; and a second booster radiation dose (14.4 Gy/8 fractions) for the primary lesions. The patient was prescribed S-1 at a dose of 60 mg/m2/day twice daily on days 1–14 and 29–42. The patient experienced grade 2 diarrhea and anal mucositis, but CRT was completed without discontinuation and hospitalization. The patient exhibited a complete response and remained disease-free without any treatment-associated complications at the 6-month follow-up. In conclusion, SCACC was successfully treated with IMRT in the present case. It is important to determine the treatment strategy for synchronous cancer types, taking into consideration the tumor stage, tumor location and patient situation.
A perspective on nonadherence to drug therapy: psychological barriers and strategies to overcome nonadherence

Medication adherence represents an inefficiency and ongoing challenge within medical care. The problem has been long-recognized – indeed, the research literature contains thousands of articles on the topic. Nonetheless, because of the complex nature of the problem, it still cannot be considered to be solved. Reasons for nonadherence are myriad but psychological barriers to adherence are most difficult to mitigate and, thus, are the focus of this paper. The present narrative review sketches a summary of theoretical models commonly utilized to understand and help address medication nonadherence; uses a patient-centered care approach to contextualize the problem of nonadherence to drug therapies; and then outlines a set of best-practice recommendations based on the extant data and framed from the perspective of the Information-Motivation-Strategy model.
Exposure to non‐ionizing electromagnetic radiation of public risk prevention instruments threatens the quality of spermatozoids

The use of artificial insemination in cattle breeding has evolved to global extent, and insemination doses are often shipped via air transport which requires strict radiation-based examinations. For the determination of effect of non-ionizing radiation (NIR), to which are beings frequently exposed due to protection of airport or cultural event security, freshly ejaculated and cryopreserved bovine spermatozoa were used as experimental model. Following radiation with hand-held metal detector in various exposition times (0, 10 s, 15, 30 and 60 min-groups FR, FR10, FR15, FR30 and FR60) the spermatozoa underwent motility and DNA fragmentation analyses. Study on cryoconserved semen treated with NIR was performed in time intervals 0, 10 s, 1 and 5 min (insemination doses radiated before cryoconservation-CB, CB10, CB1, CB5; samples radiated after freezing-CA, CA10, CA1 and CA5). Fresh semen and insemination doses radiated after cryoconservation showed significantly lower total and progressive motility. No effect on motility parameters was detected in semen extended with cryopreservative medium and radiated prior to freezing. Surprisingly, NIR showed a potential to stimulate spermatozoa velocity; however, the effect was modulated throughout the post-thawing incubation. Based on the DNA fragmentation assay, sperm DNA stayed intact. Present study underlines the potential harm of NIR, which is frequently used in everyday life, with overall adverse impact on human and animal reproduction. Current study also points out on interesting short-term spermatozoa stimulation induced by NIR.
The Prevalence of Autism Spectrum Disorders in Adult Psychiatric Inpatients: A Systematic Review

Background: Whilst the prevalence of autism spectrum disorders in adults within the community setting is well-established, less is known about the prevalence among adults based within a psychiatric inpatient setting. Objective: To conduct a systematic literature review pertaining to the prevalence of autism spectrum disorders among the adult psychiatric inpatient population. Method: Eligibility criteria included: (a) investigation of the prevalence of autism spectrum disorders (b) adult psychiatric inpatient study population (c) published in English language. Electronic databases accessed included PubMed, Medline, CINAHL, PsycINFO and EMBASE. Additionally, the ancestry method was utilised for the references of eligible papers, as well as grey literature searches and consultation with experts in the field. Results: From the search, 4 studies were identified which satisfied the inclusion criteria, conducted in a variety of inpatient psychiatric settings, including secure forensic and intellectual disability units and a state psychiatric hospital. There were significant differences in methodological approaches, including the screening tests, diagnostic instruments and diagnostic criteria utilised. Autism spectrum disorder prevalence estimates varied considerably, from 2.4-9.9%. Conclusion: From the limited research data currently available, it appears that the prevalence of autism spectrum disorders is increased in inpatient psychiatric settings relative to the general population. There is a need for further high quality research in this patient group, to add to this limited evidence base, as well as in developing effective strategies to identify patients with a high likelihood of autism spectrum disorders within this setting.
Unveiling the transcriptional control of pleiotropic drug resistance in Saccharomyces cerevisiae: Contributions of André Goffeau and his group

Studies in the yeast Saccharomyces cerevisiae have provided much of the basic detail underlying the organization and regulation of multiple or pleiotropic drug resistance gene network in eukaryotic microbes. As with many aspects of yeast biology, the initial observations that drove the eventual molecular characterization of multidrug resistance gene were provided by genetics. This review focuses on contributions from the laboratory of Dr. André Goffeau that uncovered key aspects of the transcriptional regulation of these multidrug resistance genes. André's group made many seminal discoveries that helped lead to the current picture we have of how eukaryotic microbes respond to and deal with a variety of antifungal agents. The importance of the transcriptional contribution to antifungal drugs is illustrated by the large number of drug resistant mutants found in several yeast species that lead to increased activity of transcriptional regulators. The characterization of the Saccharomyces cerevisiae PDR1 gene by the Goffeau group provided the first molecular basis explaining the link between this hyperactive transcription factor and drug resistance.
An Academic Definitions Test.

L2 vocabulary is commonly conceptualized in terms of a size or depth of one’s total lexical knowledge and tested discretely with selection-type items. Concerns exist, however, regarding L2 users’ ability to cope with unknown vocabulary, especially in the context of academic reading. This motivated the creation of a test which measures the ability to identify definitions for unknown terms in an academic text. The test comprised a 768word introductory biology textbook excerpt with non-words replacing ten technical terms, and test takers were asked to write definitions for each term. The test was piloted with 158 prospective university students of varying L2 English proficiency. Support for test score interpretations was sought by investigating the test’s reliability, correlation with reading comprehension, and the qualities of test-taker responses. Internal consistency was adequately high, and a moderate correlation with reading comprehension was found. Test-taker responses aligned with expectations, demonstrating utilization of the in-text definitions. The test shows promise for those interested in academic reading abilities and vocabulary learning.
Review article: drug‐induced liver injury in the context of nonalcoholic fatty liver disease – a physiopathological and clinical integrated view

Nonalcoholic fatty disease (NAFLD) is the most common liver disease, since it is strongly associated with obesity and metabolic syndrome pandemics. NAFLD may affect drug disposal and has common pathophysiological mechanisms with drug‐induced liver injury (DILI); this may predispose to hepatoxicity induced by certain drugs that share these pathophysiological mechanisms. In addition, drugs may trigger fatty liver and inflammation per se by mimicking NAFLD pathophysiological mechanisms.
Hyperprogressive Disease in Patients With Advanced Non–Small Cell Lung Cancer Treated With PD-1/PD-L1 Inhibitors or With Single-Agent Chemotherapy

Importance Hyperprogressive disease (HPD) is a new pattern of progression recently described in patients with cancer treated with programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors. The rate and outcome of HPD in advanced non–small cell lung cancer (NSCLC) are unknown. Objectives To investigate whether HPD is observed in patients with advanced NSCLC treated with PD-1/PD-L1 inhibitors compared with single-agent chemotherapy and whether there is an association between treatment and HPD. Design, Setting, and Participants In this multicenter retrospective study that included patients treated between August 4, 2011, and April 5, 2017, the setting was pretreated patients with advanced NSCLC who received PD-1/PD-L1 inhibitors (8 institutions) or single-agent chemotherapy (4 institutions) in France. Measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) on at least 2 computed tomographic scans before treatment and 1 computed tomographic scan during treatment was required. Interventions The tumor growth rate (TGR) before and during treatment and variation per month (&Dgr;TGR) were calculated. Hyperprogressive disease was defined as disease progression at the first evaluation with &Dgr;TGR exceeding 50%. Main Outcomes and Measures The primary end point was assessment of the HPD rate in patients treated with IO or chemotherapy. Results Among 406 eligible patients treated with PD-1/PD-L1 inhibitors (63.8% male), 46.3% (n = 188) were 65 years or older, 72.4% (n = 294) had nonsquamous histology, and 92.9% (n = 377) received a PD-1 inhibitor as monotherapy in second-line therapy or later. The median follow-up was 12.1 months (95% CI, 10.1-13.8 months), and the median overall survival (OS) was 13.4 months (95% CI, 10.2-17.0 months). Fifty-six patients (13.8%) were classified as having HPD. Pseudoprogression was observed in 4.7% (n = 19) of the population. Hyperprogressive disease was significantly associated with more than 2 metastatic sites before PD-1/PD-L1 inhibitors compared with non-HPD (62.5% [35 of 56] vs 42.6% [149 of 350]; P = .006). Patients experiencing HPD within the first 6 weeks of PD-1/PD-L1 inhibitor treatment had significantly lower OS compared with patients with progressive disease (median OS, 3.4 months [95% CI, 2.8-7.5 months] vs 6.2 months [95% CI, 5.3-7.9 months]; hazard ratio, 2.18 [95% CI, 1.29-3.69]; P = .003). Among 59 eligible patients treated with chemotherapy, 3 (5.1%) were classified as having HPD. Conclusions and Relevance Our study suggests that HPD is more common with PD-1/PD-L1 inhibitors compared with chemotherapy in pretreated patients with NSCLC and is also associated with high metastatic burden and poor prognosis in patients treated with PD-1/PD-L1 inhibitors. Additional studies are needed to determine the molecular mechanisms involved in HPD.
Co-evolution networks of HIV/HCV are modular with direct association to structure and function

Mutational correlation patterns found in population-level sequence data for the Human Immunodeficiency Virus (HIV) and the Hepatitis C Virus (HCV) have been demonstrated to be informative of viral fitness. Such patterns can be seen as footprints of the intrinsic functional constraints placed on viral evolution under diverse selective pressures. Here, considering multiple HIV and HCV proteins, we demonstrate that these mutational correlations encode a modular co-evolutionary structure that is tightly linked to the structural and functional properties of the respective proteins. Specifically, by introducing a robust statistical method based on sparse principal component analysis, we identify near-disjoint sets of collectively-correlated residues (sectors) having mostly a one-to-one association to largely distinct structural or functional domains. This suggests that the distinct phenotypic properties of HIV/HCV proteins often give rise to quasi-independent modes of evolution, with each mode involving a sparse and localized network of mutational interactions. Moreover, individual inferred sectors of HIV are shown to carry immunological significance, providing insight for guiding targeted vaccine strategies. Author summary HIV and HCV cause devastating infectious diseases for which no functional vaccine exists. A key problem is that while immune cells may induce individual mutations that compromise viral fitness, this is typically restored through other “compensatory” mutations, leading to immune escape. These compensatory pathways are complicated and remain poorly understood. They do, however, leave co-evolutionary markers which may be inferred from measured sequence data. Here, by introducing a new robust statistical method, we demonstrated that the compensatory networks employed by both viruses exhibit a remarkably simple decomposition involving small and near-distinct groups of protein residues, with most groups having a clear association to biological function or structure. This provides insights that can be harnessed for the purpose of vaccine design.
Finding Topics in Enrollment Data

Analyses of student data in post-secondary education should be sensitive to the fact that there are many different topics of study. These different areas will interest different kinds of students, and entail different experiences and learning activities. However, it can be challenging to identify the distinct academic themes that students might pursue in higher education, where students commonly have the freedom to sample from thousands of courses in dozens of degree programs. In this paper, we describe the use of topic modeling to identify distinct themes of study and classify students according their observed course enrollments, and present possible applications of this technique for the broader field of educational data mining.