Miracle-dz/UniFAR-FTUs huggingface dataset:
Three Weeks of Binge Alcohol Drinking Generates Increased Alcohol Front-loading and Robust Compulsive-Like Alcohol Drinking in Male and Female C57BL/6J Mice.

BACKGROUND Current models of compulsive-like quinine-adulterated alcohol (QuA) drinking in mice warrant improvements to be more useful for uncovering neural mechanisms of compulsive-like alcohol drinking. The purpose of these experiments was to further characterize & improve the validity of a model of compulsive-like QuA drinking in C57BL/6J mice. We sought to determine if compulsive-like alcohol drinking can be achieved following two or three weeks of Drinking-in-the-Dark (DID), provide evidence for a robust model of compulsive-like alcohol drinking by inclusion of a water control group and use of a highly concentrated QuA solution, determine if repeated QuA exposures alter compulsive-like drinking, and to identify sex differences in compulsive-like alcohol drinking. METHODS Male and Female C57BL/6J mice were allowed free access to either 20% alcohol or tap water for two hours each for approximately three weeks. After two or three weeks the mice were given QuA (500 μM) and the effect of repeated QuA drinking sessions were assessed for compulsive-like alcohol drinking. 30 minute front-loading, 2 hour binge-drinking, and blood alcohol concentrations were determined. RESULTS Compulsive-like QuA drinking was achieved after 3weeks, but not 2weeks, of daily alcohol access as determined by alcohol history mice consuming significantly more QuA than water history mice and drinking statistically nondifferent amounts of QuA than non-adulterated alcohol at baseline. 30 minute front-loading of QuA revealed that alcohol history mice front-loaded significantly more QuA compared to water history mice, but still find the QuA solution aversive. Repeated QuA exposures did not alter these patterns, compulsive-like drinking did not differ by sex, and BACs for QuA drinking were at the level of a binge. CONCLUSIONS These data suggest that compulsive-like QuA drinking can be robustly achieved following three weeks DID and male and female C57BL/6J mice do not differ in compulsive-like alcohol drinking.
Crystal structure of methyl 5-acetyl-2-hydroxybenzoate, at 200 K, C10H10O4

C10H10O4, monoclinic, P21/c (no. 14), a = 8.7782(4) Å, b = 7.4533(3) Å, c = 14.7842(8) Å, $ = 103.364(2)°, V = 941.1 Å, Z = 4, Rgt(F) = 0.0410, wRref(F ) = 0.1198, T = 200 K.
Inhibition of Biofilm Formation by the Synergistic Action of EGCG-S and Antibiotics

Biofilm, a stress-induced physiological state, is an established means of antimicrobial tolerance. A perpetual increase in multidrug resistant (MDR) infections associated with high mortality and morbidity have been observed in healthcare settings. Multiple studies have indicated that the use of natural products can prevent bacterial growth. Recent studies in the field have identified that epigallocatechin gallate (EGCG), a green tea polyphenol, could disrupt bacterial biofilms. A modified lipid-soluble EGCG, epigallocatechin-3-gallate-stearate (EGCG-S), has enhanced the beneficial properties of green tea. This study focuses on utilizing EGCG-S as a novel synergistic agent with antibiotics to prevent or control biofilm. Different formulations of EGCG-S and selected antibiotics were used to study their combinatorial effects on biofilms produced by five potential pathogenic bacteria, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, and Mycobacterium smegmatis. The crystal violet (CV) assay and the sensitive fluorescence-based resazurin biofilm viability assay were used to assess the biofilm production. Our results identified optimal formulation for each bacterium, effectively inhibiting biofilm formation to an extent of 95–99%. Colony-forming unit (CFU) and cell viability analyses showed a decrease of viable bacteria. These results depict the potential of EGCG-S as a synergistic agent with antibiotics and as an anti-biofilm agent.
How society modulates our behavior: Effects on error processing of masked emotional cues contextualized in social status

ABSTRACT In the present study, we investigate whether subliminal complex social cues have an impact on error-monitoring processes. For this purpose, we presented two social status ranks (high and low) with three possible emotional expressions (happy, neutral, angry), using a backward masking paradigm. Participants were instructed to perform a flanker task while recording Event-Related brain Potentials. Results showed larger amplitudes for the Error-Related Negativity index after the presentation of high relative to low social ranks, only for neutral expressions. Neither the angry nor the happy faces induced significant differences in social rank processing. This indicates that subliminal high social ranks, specifically with neutral expressions, increase error processing by boosting attentional control to perform the ongoing task. Our findings extend current knowledge on the automaticity of social and emotional processing and its influence on performance monitoring mechanisms.
Incidence and Predictors of Mental Health Outcomes Among Survivors of Adolescent and Young Adult Cancer: A Population-Based Study Using the IMPACT Cohort.

PURPOSE Risk and predictors of long-term mental health outcomes in survivors of adolescent and young adult (AYA) cancers are poorly characterized. Mental health is consequently neglected in long-term follow-up. METHODS We identified all AYA in Ontario, Canada age 15-21 years when diagnosed with one of six common cancers between 1992-2012 using a population-based database, and compared them with matched controls. Linkage to provincial healthcare data allowed analysis of rates of outpatient (family physician and psychiatrist) visits for psychiatric indications and time to severe psychiatric events (emergency room visit, hospitalization, and suicide). Demographic-, disease-, and treatment-related predictors of adverse outcomes, including treatment setting (adult v pediatric), were examined. RESULTS Among 2,208 survivors and 10,457 matched controls, 5-year survivors experienced higher rates of outpatient mental health visits than controls (671 visits per 1,000 person-years v 506; adjusted rate ratio [RR] 1.3; 95% CI, 1.1 to 1.5; P = .006). Risk of a severe psychiatric episode was also increased among survivors (adjusted hazard ratio [HR], 1.2; 95% CI, 1.1 to 1.4, P = .008). Risk of a psychotic disorder-associated severe event was doubled in survivors (HR, 2.0, 95% CI, 1.3 to 2.4; P = .007) although absolute risk remained low (15-year cumulative incidence 1.7%; 95% CI, 1.0 to 2.7). In multivariable analysis, survivors treated in adult centers experienced substantially higher outpatient visit rates compared with those treated in pediatric settings (RR 1.8; 95% CI, 1.0 to 3.1; P = .04). CONCLUSION Survivors of AYA cancer are at substantially increased risk of adverse mental health outcomes, with those treated in adult centers at particular risk. Although absolute incidence was low, survivors were at increased risk of psychotic disorder-associated severe events. Long-term mental health surveillance is warranted, as is research into effective interventions during or after cancer treatment.
Do Adolescents Who Meet Physical Activity Recommendations on Weekdays Also Meet Them on Weekends? A Cross-Sectional Study in Colombia

The purpose of this study was to examine whether Colombian adolescents fulfill physical activity (PA) recommendations by type of day depending on several variables. A cross-sectional study was carried out on a sample of 2624 adolescents from Neiva (Colombia) using the Seven Day PA Recall and the Family Affluence Scale II self-reported questionnaires. Statistical analyses were performed to find any differences by gender, socioeconomic status, PA recommendations accomplishment, participation in organized and non-organized PA, parents’ involvement in sport, and adolescents’ academic achievement, and to determine the probability of complying with the PA guidelines. Only 12.3% of the participants met the PA recommendations on weekdays and weekends. Girls maintained their (in)active patterns during the week more than boys (84.4% vs. 70.7%, respectively), while more boys than girls changed them according to the type of day (25.3% vs. 19.6%). Participation in organized sports was the predictor variable with the highest probability of both boys and girls complying with the PA recommendations on weekdays. Non-organized activities were more likely to make girls more active on weekends. In conclusion, a wider offer of organized and non-competitive PA over the weekend and broader sports schedules should be provided to youth in Neiva.
Murine Typhus in Canary Islands, Spain, 1999–2015

To document the epidemiology, clinical features, and outcomes of murine typhus patients in the Canary Islands (Spain), we analyzed data that were retrospectively collected for 16 years for 221 patients. Murine typhus in the Canary Islands is characterized by a high rate of complications (31.6%), mainly liver, lung, kidney or central nervous system involvement.
Cannabinoid and Cannabinoid-Related Receptors in the Myenteric Plexus of the Porcine Ileum

Simple Summary The endocannabinoid system (ECS) has opened the door to novel therapeutical approaches targeting cancer, pain, anxiety, stress, and inflammatory diseases. The ECS is ubiquitously expressed in almost all members of Animalia, but its precise localization outside the central nervous system is still under investigation. In this study, the localization of the main and related cannabinoid receptors in the myenteric plexus of the porcine ileum was immunohistochemically analyzed. The myenteric plexus neurons were found to be positive for cannabinoid receptor 1 (CB1R) and the cannabinoid-related receptors transient potential vanilloid receptor 1 (TRPV1), transient potential ankyrin receptor 1 (TRPA1), and serotonin receptor 5-HT1a (5-HT1aR). In addition, the ECS receptors were also located on nerve fibers, the tunica muscularis, and the endothelium. The wide distribution of cannabinoid and cannabinoid-related receptors in the myenteric plexus provides the anatomical basis for additional investigation, suggesting the possible role of the ECS in treating pathological conditions in livestock. Abstract An important piece of evidence has shown that molecules acting on cannabinoid receptors influence gastrointestinal motility and induce beneficial effects on gastrointestinal inflammation and visceral pain. The aim of this investigation was to immunohistochemically localize the distribution of canonical cannabinoid receptor type 1 (CB1R) and type 2 (CB2R) and the cannabinoid-related receptors transient potential vanilloid receptor 1 (TRPV1), transient potential ankyrin receptor 1 (TRPA1), and serotonin receptor 5-HT1a (5-HT1aR) in the myenteric plexus (MP) of pig ileum. CB1R, TRPV1, TRPA1, and 5-HT1aR were expressed, with different intensities in the cytoplasm of MP neurons. For each receptor, the proportions of the immunoreactive neurons were evaluated using the anti-HuC/HuD antibody. These receptors were also localized on nerve fibers (CB1R, TRPA1), smooth muscle cells of tunica muscularis (CB1R, 5-HT1aR), and endothelial cells of blood vessels (TRPV1, TRPA1, 5-HT1aR). The nerve varicosities were also found to be immunoreactive for both TRPV1 and 5-HT1aR. No immunoreactivity was documented for CB2R. Cannabinoid and cannabinoid-related receptors herein investigated showed a wide distribution in the enteric neurons and nerve fibers of the pig MP. These results could provide an anatomical basis for additional research, supporting the therapeutic use of cannabinoid receptor agonists in relieving motility disorders in porcine enteropathies.
The Efficacy of Hybrid Telesimulation with Standardized Patients in Teaching Medical Students Clinical Lactation Skills: A Pilot Study.

Introduction: Medical students lack competencies in clinical lactation. We determined the effect of hybrid telesimulation with a standardized patient (SP) on medical students' clinical performance in lactation support. We assessed students' engagement and satisfaction with the experience. Materials and Methods: Undergraduate medical students (n = 13) completed (1) preparatory case scenarios with multiple-choice questions and (2) three telesimulations with SPs wearing a high-fidelity breast model. Students had the option to complete the Encounter Documentation. SPs used the Formative Assessment Rubric (FAR) to evaluate students' interpersonal skills and clinical lactation experts used the Summative Assessment Rubric to evaluate documentation skills. Investigators collected satisfaction data from a focus group and written evaluation. Dunn's multiple comparison and Freidman tests were used to measure differences in FAR scores between cases and telesimulations. Qualitative data were analyzed using thematic analysis. Results: Most students (70%) attempted case questions multiple times and scores improved (p < 0.0001) between attempts. FAR scores suggest students were prepared for telesimulations (5.5/6-pt Likert) and interpersonal skills were appropriate (5.4/6), with no differences by case (p = 0.11). FAR scores increased between telesimulation 1-2 (+24.5/114, p = 0.002) and 2-3 (+17.5/114, p = 0.014). Students were satisfied with the experience and would recommend it to classmates (both 4.6/6). Thematic analysis revealed feedback regarding interpersonal skills was helpful. Conclusions: Medical students must develop skills to support breastfeeding in virtual settings. Telesimulation can be incorporated into existing curricula to support clinical lactation competencies.
Therapeutic Sequencing in ALK+ NSCLC

Anaplastic lymphoma kinase-rearranged non-small-cell lung cancer (ALK+ NSCLC) is a model disease for the use of targeted pharmaceuticals in thoracic oncology. Due to higher systemic and intracranial efficacy, the second-generation ALK tyrosine kinase inhibitors (TKI) alectinib and brigatinib have irrevocably displaced crizotinib as standard first-line treatment, based on the results of the ALEX and ALTA-1L trials. Besides, lorlatinib and brigatinib are the preferred second-line therapies for progression under second-generation TKI and crizotinib, respectively, based on the results of several phase II studies. Tissue or liquid rebiopsies at the time of disease progression, even though not mandated by the approval status of any ALK inhibitor, are gaining importance for individualization and optimization of patient management. Of particular interest are cases with off-target resistance, for example MET, HER2 or KRAS alterations, which require special therapeutic maneuvers, e.g., inclusion in early clinical trials or off-label administration of respectively targeted drugs. On the other hand, up to approximately half of the patients failing TKI, develop anatomically restricted progression, which can be initially tackled with local ablative measures without switch of systemic therapy. Among the overall biologically favorable ALK+ tumors, with a mean tumor mutational burden uniquely below 3 mutations per Mb and the longest survival among NSCLC currently, presence of the EML4-ALK fusion variant 3 and/or TP53 mutations identify high-risk cases with earlier treatment failure and a need for more aggressive surveillance and treatment strategies. The potential clinical utility of longitudinal ctDNA assays for earlier detection of disease progression and improved guidance of therapy in these patients is a currently a matter of intense investigation. Major pharmaceutical challenges for the field are the development of more potent, fourth-generation TKI and effective immuno-oncological interventions, especially ALK-directed cell therapies, which will be essential for further improving survival and achieving cure of ALK+ tumors.
Long-Term Outcomes and Sequelae Analysis of Intracranial Germinoma: Need to Reduce the Extended-Field Radiotherapy Volume and Dose to Minimize Late Sequelae

Purpose We aimed to refine the radiotherapy (RT) volume and dose for intracranial germinoma considering recurrences and long-term toxicities. Materials and Methods Total 189 patients with intracranial germinoma were treated with RT alone (n=50) and RT with upfront chemotherapy (CRT) (n=139). All cases were confirmed histologically. RT fields comprised the extended-field and involved-field only for primary site. The extended-field, including craniospinal, whole brain (WB), and whole ventricle (WV) for cranial field, is followed by involved-field boost. The median follow-up duration was 115 months. Results The relapses developed in 13 patients (6.9%). For the extended-field, cranial RT dose down to 18 Gy exhibited no cranial recurrence in 34 patients. In CRT, 74 patients (56.5%) showed complete response to chemotherapy and no involved-field recurrence with low-dose RT of 30 Gy. WV RT with chemotherapy for the basal ganglia or thalamus germinoma showed no recurrence. Secondary malignancy developed in 10 patients (5.3%) with a latency of 20 years (range, 4 to 26 years) and caused mortalities in six. WB or craniospinal field rather than WV or involved-field significantly increased the rate of hormone deficiencies, and secondary malignancy. RT dose for extended-field correlated significantly with the rate of hormone deficiencies, secondary malignancy, and neurocognitive dysfunction. Conclusion De-intensifying extended-field rather than involved-field or total scheme of RT will be critical to decrease the late toxicities. Upfront chemotherapy could be beneficial for the patients with complete response to minimize the RT dose down to 30 Gy. Prospective trials focused on de-intensification of the extended-field RT are warranted.
Deleting Mecp2 from the cerebellum rather than its neuronal subtypes causes a delay in motor learning in mice

Rett syndrome is a devastating childhood neurological disorder caused by mutations in MECP2. Of the many symptoms, motor deterioration is a significant problem for patients. In mice, deleting Mecp2 from the cortex or basal ganglia causes motor dysfunction, hypoactivity, and tremor, which are abnormalities observed in patients. Little is known about the function of Mecp2 in the cerebellum, a brain region critical for motor function. Here we show that deleting Mecp2 from the cerebellum, but not from its neuronal subtypes, causes a delay in motor learning that is overcome by additional training. We observed irregular firing rates of Purkinje cells and altered heterochromatin architecture within the cerebellum of knockout mice. These findings demonstrate that the motor deficits present in Rett syndrome arise, in part, from cerebellar dysfunction. For Rett syndrome and other neurodevelopmental disorders, our results highlight the importance of understanding which brain regions contribute to disease phenotypes.
Simulation code for estimating external gamma-ray doses from a radioactive plume and contaminated ground using a local-scale atmospheric dispersion model

In this study, we developed a simulation code powered by lattice dose-response functions (hereinafter SIBYL), which helps in the quick and accurate estimation of external gamma-ray doses emitted from a radioactive plume and contaminated ground. SIBYL couples with atmospheric dispersion models and calculates gamma-ray dose distributions inside a target area based on a map of activity concentrations using pre-evaluated dose-response functions. Moreover, SIBYL considers radiation shielding due to obstructions such as buildings. To examine the reliability of SIBYL, we investigated five typical cases for steady-state and unsteady-state plume dispersions by coupling the Gaussian plume model and the local-scale high-resolution atmospheric dispersion model using large eddy simulation. The results of this coupled model were compared with those of full Monte Carlo simulations using the particle and heavy-ion transport code system (PHITS). The dose-distribution maps calculated using SIBYL differed by up to 10% from those calculated using PHITS in most target locations. The exceptions were locations far from the radioactive contamination and those behind the intricate structures of building arrays. In addition, SIBYL’s computation time using 96 parallel processing elements was several tens of minutes even for the most computationally expensive tasks of this study. The computation using SIBYL was approximately 100 times faster than the same calculation using PHITS under the same computation conditions. From the results of the case studies, we concluded that SIBYL can estimate a ground-level dose-distribution map within one hour with accuracy that is comparable to that of the full Monte Carlo simulation.
Quantified growth of the human embryonic heart

ABSTRACT The size and growth patterns of the components of the human embryonic heart have remained largely undefined. To provide these data, three-dimensional heart models were generated from immunohistochemically stained sections of ten human embryonic hearts ranging from Carnegie stage 10 to 23. Fifty-eight key structures were annotated and volumetrically assessed. Sizes of the septal foramina and atrioventricular canal opening were also measured. The heart grows exponentially throughout embryonic development. There was consistently less left than right atrial myocardium, and less right than left ventricular myocardium. We observed a later onset of trabeculation in the left atrium compared to the right. Morphometry showed that the rightward expansion of the atrioventricular canal starts in week 5. The septal foramina are less than 0.1 mm2 and are, therefore, much smaller than postnatal septal defects. This chronological, graphical atlas of the growth patterns of cardiac components in the human embryo provides quantified references for normal heart development. Thereby, this atlas may support early detection of cardiac malformations in the foetus. This article has an associated First Person interview with the first author of the paper. Summary: This paper provides quantitative data on the growth of 58 structures of the human embryonic heart between weeks 4 and 8 of development.
Dynamic assessment of interleukin‐6 during hemodialysis and mortality in coronavirus disease‐19

The impact of the newly discovered severe acute respiratory syndrome coronavirus 2 causing coronavirus disease‐19 (COVID‐19) in hemodialysis patients remains poorly characterized. Some hemodialysis techniques reduce systemic inflammation but their impact on COVID‐19 has not been addressed. The aim of this prospective study was to evaluate factors associated with mortality in COVID‐19 hemodialysis patients, including the impact of reducing interleukin‐6 using a cytokine adsorbent filter. This is a prospective single‐center study including 16 hemodialysis patients with COVID‐19. All were dialyzed using a polymethyl methacrylate (PMMA) filter. Interleukin‐6 levels were obtained before and after the first admission hemodialysis session and at 1 week. Baseline comorbidities, laboratory values, chest X‐ray, and treatments were recorded and compared between survivors and non‐survivors. Out of 16 patients (13 males, mean age 72 ± 15 years), 4 (25%) died. Factors associated with mortality were dialysis vintage (P = 0.01), chest X‐ray infiltrates (P = 0.032), serum C‐reactive protein (P = 0.05), and lactate dehydrogenase (P = 0.02) at 1 week, oxygen therapy requirement (P = 0.02) and anticoagulation (P < 0.01). At admission, non‐survivors had higher predialysis and postdialysis interleukin‐6 levels (P = 0.02 for both) and did not present the reduction of interleukin‐6 levels during the dialysis session with PMMA filter that was observed in survivors (survivors vs. non‐survivors: 25.0 [17.5–53.2]% vs. −2.8 [−109.4–12.8]% reduction, P = 0.04). A positive balance of interleukin‐6 during the admission dialysis was associated with mortality (P = 0.008). In conclusion, in hemodialysis COVID‐19 patients, a positive interleukin‐6 balance during the admission hemodialysis session was associated with higher mortality.