Miracle-dz/UniFAR-FTUs huggingface dataset:
A Psychiatric Intensive Care Unit in a General Hospital Setting

A twelve month period of the functioning of a psychiatric intensive care unit in a general hospital is reviewed. The unit has actually been functioning for about three and a half years. Although there were growing pains initially, the unit has become an integral part of the psychiatric inpatient service. It serves to provide intensive care to acutely inpatients and provides a safe, secure environment. It also reduces the number of disturbed patients on the two general units. Very disturbed patients are expertly managed by the staff and a surprisingly low percentage of patients have to be transferred to the local mental hospital under certification. The experience demonstrates that a psychiatric intensive care unit based on a general medical intensive care unit model can function well with benefit both to patients and staff.
Prion Protein Aggregation Reverted by Low Temperature in Transfected Cells Carrying a Prion Protein Gene Mutation*

Prion diseases are characterized by the conversion of the normal cellular prion protein (PrPC), a glycoprotein that is anchored to the cell membrane by a glycosylphosphatidylinositol moiety, into an isoform that is protease-resistant (PrPres) and pathogenic. In inherited prion diseases, mutations in the prion protein (PrPM) engender the conversion of PrPM into PrPres. We developed a cell model of Gerstmann-Sträussler-Scheinker disease, a neurodegenerative condition characterized by PrPM-containing amyloid deposits and neuronal loss, by expressing the Gerstmann-Sträussler-Scheinker haplotype Q217R-129V in human neuroblastoma cells. By comparison to PrPC, this genotype results in the following alterations of PrPM: 1) expression of an aberrant form lacking the glycosylphosphatidylinositol anchor, 2) increased aggregation and protease resistance, and 3) impaired transport to the cell surface. Most of these alterations are temperature-sensitive, indicating that they are due to misfolding of PrPM.
Multiflora and Gram-Negative Microorganisms Predominate in Infections Affecting Pelvic Endoprostheses Following Tumor Resection

Background: Periprosthetic infections after pelvic reconstruction are common, with reported rates ranging from 11% to 53%. Management of these infections is troublesome, as they commonly necessitate multiple surgical interventions and implant removal. The epidemiology and outcomes of these infections are largely unknown. The aim of this study was to analyze the causative microorganisms and the clinical outcome of treatment in a series of patients with pelvic endoprostheses affected by infection following tumor resection. Methods: In this retrospective, multicenter cohort study, we identified all patients who developed an infection after endoprosthetic reconstruction in periacetabular tumor resection, between 2003 and 2017. The microorganisms that were isolated during the first debridement were recorded, as were the number of reoperations for ongoing infection, the antimicrobial treatment strategy, and the outcome of treatment. Results: In a series of 70 patients who underwent pelvic endoprosthetic reconstruction, 18 (26%) developed an infection. The type of pelvic resection according to the Enneking-Dunham classification was type P2-3 in 14 (78%) of these patients and type P2 in 4 (22%). Median follow-up was 66 months. Fourteen (78%) of the 18 patients with infection had a polymicrobial infection. Enterobacteriaceae were identified on culture for 12 (67%). Of a total 42 times that a microorganism was isolated, the identified pathogen was gram-negative in 26 instances (62%). Microorganisms associated with intestinal flora were identified 32 times (76%). At the time of latest follow-up, 9 (50%) of the patients had the original implant in situ. Of these, 2 had a fistula and another 2 were receiving suppressive antibiotic therapy. In the remaining 9 (50%) of the patients, the original implant had been removed. At the time of final follow-up, 3 of these had a second implant in situ. The remaining 6 patients had undergone no secondary reconstruction. Conclusions: Infections that affect pelvic endoprostheses are predominantly polymicrobial and caused by gram-negative microorganisms, and may be associated with intestinal flora. This differs fundamentally from mono-bacterial gram-positive causes of conventional periprosthetic joint infections and may indicate a different pathogenesis. Our results suggest that prophylaxis and empiric treatment may need to be re-evaluated. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Augmentor α and β (FAM150) are ligands of the receptor tyrosine kinases ALK and LTK: Hierarchy and specificity of ligand–receptor interactions

Significance Many cancers (e.g., subpopulations of lung cancer, anaplastic lymphoma, and neuroblastoma) are driven by mutations in the receptor tyrosine kinase ALK (for anaplastic lymphoma kinase). However, the extracellular protein signals that regulate ALK’s activity and its ligand-induced mechanism of activation remain elusive. Here we describe a cytokine designated augmentor-α that binds with high affinity and specificity to ALK’s extracellular glycine-rich region, resulting in robust receptor activation. Augmentor-α also potently activates the related leukocyte tyrosine kinase (LTK) receptor, whereas a previously identified LTK ligand (augmentor-β) only weakly activates ALK. These experiments reveal an important missing link necessary for the regulation of a known oncogenic RTK, providing important insights into its biology and offering new opportunities for therapeutic intervention. Receptor tyrosine kinases (RTKs) are a class of cell surface receptors that, upon ligand binding, stimulate a variety of critical cellular functions. The orphan receptor anaplastic lymphoma kinase (ALK) is one of very few RTKs that remain without a firmly established protein ligand. Here we present a novel cytokine, FAM150B, which we propose naming augmentor-α (AUG-α), as a ligand for ALK. AUG-α binds ALK with high affinity and activates ALK in cells with subnanomolar potency. Detailed binding experiments using cells expressing ALK or the related receptor leukocyte tyrosine kinase (LTK) demonstrate that AUG-α binds and robustly activates both ALK and LTK. We show that the previously established LTK ligand FAM150A (AUG-β) is specific for LTK and only weakly binds to ALK. Furthermore, expression of AUG-α stimulates transformation of NIH/3T3 cells expressing ALK, induces IL-3 independent growth of Ba/F3 cells expressing ALK, and is expressed in neuroblastoma, a cancer partly driven by ALK. These experiments reveal the hierarchy and specificity of two cytokines as ligands for ALK and LTK and set the stage for elucidating their roles in development and disease states.
Strength and Conditioning for Soccer Players

ABSTRACT SOCCER IS CHARACTERIZED AS A HIGH-INTENSITY, INTERMITTENT, CONTACT TEAM SPORT THAT REQUIRES A NUMBER OF PROFICIENT PHYSICAL AND PHYSIOLOGICAL CAPABILITIES TO PERFORM SUCCESSFULLY. APART FROM THE NECESSARY TECHNICAL AND TACTICAL SKILLS REQUIRED, SOCCER PLAYERS MUST ALSO DEVELOP AND RETAIN A HIGH LEVEL OF AEROBIC AND ANAEROBIC CONDITIONING, SPEED, AGILITY, STRENGTH, AND POWER. THESE ARE BEST DEVELOPED THROUGH HIGH-INTENSITY INTERVAL TRAINING, SMALL-SIDED GAMES, REPEATED SPRINTS, COACHED SPEED AND AGILITY SESSIONS AND STRENGTH AND POWER-BASED GYM SESSIONS. SOCCER COACHES AND STRENGTH AND CONDITIONING COACHES MUST WORK COHESIVELY TO ENSURE A STRUCTURED AND EFFECTIVE PROGRAM IS ADHERED TO.
Mortality for emergency laparotomy is not affected by the weekend effect: a multicentre study

INTRODUCTION The ‘weekend effect’ describes variation in outcomes of patients treated over the weekend compared with those treated during weekdays. This study examines whether a weekend effect exists for patients who undergo emergency laparotomy. MATERIALS AND METHODS Data entered into the National Emergency Laparotomy Audit between 2014 and 2017 at four NHS trusts in England and Wales were analysed. Patients were grouped into those admitted on weekdays and those on weekends (Friday 5pm to Monday 8am). Patient factors, markers of quality of care and patient outcomes were compared. Secondary analysis was performed according to the day of surgery. RESULTS After exclusion of patients who underwent laparotomy more than one week after admission to hospital, a total of 1717 patients (1138 patients admitted on weekdays and 579 admitted on weekends) were analysed. Age, preoperative lactate and P‐POSSUM scores were not significantly different between the two groups. Time from admission to consultant review, decision to operate, commencement of antibiotics and theatre were not significantly different. Grades of operating surgeon were also similar in both groups. Inpatient 60‐day mortality was 12.5% on weekdays and 12.8% on weekends (P = 0.878). Median length of postoperative stay was 12 days in both groups. When analysed according to day of surgery, only number of hours from admission to antibiotics (12.8 weekday vs 9.4 weekend, P = 0.046) and number of hours to theatre (26.5 weekday vs 24.1 hours weekend, P = 0.020) were significantly different. DISCUSSION Quality of care and clinical outcomes for patients undergoing emergency laparotomy during the weekend are not significantly different to those carried out during weekdays.
Multimorbidity prevalence in Canada: a comparison of Northern Territories with Provinces, 2013/14

ABSTRACT Rapid social, economic, and environmental changes in the northern territories of Canada have raised concerns about potentially increasing levels of chronic disease. This concern prompted us to compare multimorbidity prevalence in Canada between the territories and provinces. We analyzed Canadian Community Health Survey data for 2013/14. We defined multimorbidity, the outcome, as having 3 or more chronic conditions and used survey-weighted multivariable logistic regression for comparisons between territories and provinces. We found a prevalence of multimorbidity in Canada of 14.0% (95% CI: 13.6, 14.3). We could not find significant difference in multimorbidity prevalence between the territories and provinces of Canada overall; however, the territories tended to have lower prevalence estimates than provinces for multimorbidity (adj-OR = 0.88; 95% CI: 0.74–1.04). Sensitivity analyses from propensity score analyses had similar conclusions. Effect modification analyses identified lower multimorbidity in territories versus provinces among households without a post-secondary graduate (adj-OR = 0.46; 95% CI: 0.34–0.61 for northern residence), males (adj-OR = 0.71; 95% CI: 0.54–0.93), and ages 12–29 years (adj-OR = 0.63; 95% CI: 0.39–0.99). Caution is needed in interpreting the results in light of representativeness of CCHS in northern populations of Canada.
Perinatal High Fat Diet Alters Development of GABAA Receptor Subunits in the Dorsal Motor Nucleus of the Vagus.

Perinatal high fat diet (pHFD) exposure increases the inhibition of dorsal motor nucleus of the vagus (DMV) neurons, potentially contributing to the dysregulation of gastric functions. The aim of this study was to test the hypothesis that pHFD increases the inhibition of DMV neurons by disrupting GABAA receptor subunit development. In vivo gastric recordings were made from adult anesthetized Sprague-Dawley rats fed a control or pHFD (14 or 60% kcal from fat, respectively) from embryonic day 13 (E13) to A a subunits, while mRNA and protein expression were measured via qPCR and western blotting, respectively. pHFD decreased basal antrum and corpus motility, while brainstem microinjection of L838,417 (positive allosteric modulator of a2/3 subunit-containing GABAA receptors) produced a larger decrease in gastric tone and motility. GABAergic miniature inhibitory postsynaptic currents in pHFD DMV neurons were responsive to L838,417 throughout development, unlike control DMV neurons, which were responsive only at early postnatal timepoints. Brainstem mRNA and protein expression of the GABAA a1,2, and 3 subunits, however, did not differ between control and pHFD rats. This study suggests that pHFD exposure arrests the development of synaptic GABAA a2/3 receptor subunits on DMV neurons, and that functional synaptic expression is maintained into adulthood, although cellular localization may differ. The tonic activation of slower GABAA a2/3 subunit-containing receptors implies such developmental changes may contribute to the observed decreased gastric motility.
Characterizing the Implementation of Software Reuse Processes in Brazilian Organizations

Software reuse has come a long way in terms of academic research and industrial practice, and is present in day-today software development activities. However, although it is known that many software organizations still do not perform reuse in a controlled, pre-planned, strategic, or systematic way, the problems faced by many of them have not yet been properly characterized, particularly in Brazil. In this sense, this work contributes with a characterization of the Brazilian scenario, by presenting a study conducted with implementers and assessors of MR-MPS-SW, a Brazilian maturity model that comprises software reuse processes, regarding the outcomes related to reuse activities. The main goal of this study is to get an overview of how reuse practices have been implemented and performed in software development organizations in Brazil so far. The research findings show that most problems are recurring, especially in terms of the lack of adequate tool support and the need for more engagement in reuse initiatives. The results also indicate the need for actions from both academia and industry in terms of an effective understanding of software reuse practices and their benefits, as well as bridging the (still large) gap between research and practice.
Transcriptomic analysis of human IL‐7 receptor alpha low and high effector memory CD8+ T cells reveals an age‐associated signature linked to influenza vaccine response in older adults

Here, we investigated the relationship of the age‐associated expansion of IL‐7 receptor alpha low (IL‐7Rαlow) effector memory (EM) CD8+ T cells with the global transcriptomic profile of peripheral blood cells in humans. We found 231 aging signature genes of IL‐7Rαlow EM CD8+ T cells that corresponded to 15% of the age‐associated genes (231/1,497) reported by a meta‐analysis study on human peripheral whole blood from approximately 15,000 individuals, having high correlation with chronological age. These aging signature genes were the target genes of several transcription factors including MYC, SATB1, and BATF, which also belonged to the 231 genes, supporting the upstream regulatory role of these transcription factors in altering the gene expression profile of peripheral blood cells with aging. We validated the differential expression of these transcription factors between IL‐7Rαlow and high EM CD8+ T cells as well as in peripheral blood mononuclear cells (PBMCs) of young and older adults. Finally, we found a significant association with influenza vaccine responses in older adults, suggesting the possible biological significance of the aging signature genes of IL‐7Rαlow EM CD8+ T cells. The results of our study support the relationship of the expansion of IL‐7Rαlow EM CD8+ T cells with the age‐associated changes in the gene expression profile of peripheral blood cells and its possible biological implications.
Attention-over-Attention Neural Networks for Reading Comprehension

Cloze-style reading comprehension is a representative problem in mining relationship between document and query. In this paper, we present a simple but novel model called attention-over-attention reader for better solving cloze-style reading comprehension task. The proposed model aims to place another attention mechanism over the document-level attention and induces “attended attention” for final answer predictions. One advantage of our model is that it is simpler than related works while giving excellent performance. In addition to the primary model, we also propose an N-best re-ranking strategy to double check the validity of the candidates and further improve the performance. Experimental results show that the proposed methods significantly outperform various state-of-the-art systems by a large margin in public datasets, such as CNN and Children’s Book Test.
Immuno-PET Imaging of the Programmed Cell Death-1 Ligand (PD-L1) Using a Zirconium-89 Labeled Therapeutic Antibody, Avelumab

Objective: The goal is to evaluate avelumab, an anti-PD-L1 monoclonal immunoglobulin G antibody labeled with zirconium-89 in human PD-L1-expressing cancer cells and mouse xenografts for clinical translation. Methods: [89Zr]Zr-DFO-PD-L1 monoclonal antibody (mAb) was synthesized using avelumab conjugated to desferrioxamine. In vitro binding studies and biodistribution studies were performed with PD-L1+MDA-MB231 cells and MDA-MB231 xenograft mouse models, respectively. Biodistributions were determined at 1, 2, 3, 5, and 7 days post coinjection of [89Zr]Zr-DFO-PD-L1 mAb without or with unlabeled avelumab (10, 20, 40, and 400 µg). Results: [89Zr]Zr-DFO-PD-L1 mAb exhibited high affinity (Kd ∼ 0.3 nM) and detected moderate PD-L1 expression levels in MDA-MB231 cells. The spleen and lymph nodes exhibited the highest [89Zr]Zr-DFO-PD-L1 mAb uptakes in all time points, while MDA-MB231 tumor uptakes were lower but highly retained. In the unlabeled avelumab dose escalation studies, spleen tissue–muscle ratios decreased in a dose-dependent manner indicating specific [89Zr]Zr-DFO-PD-L1 mAb binding to PD-L1. In contrast, lymph node and tumor tissue–muscle ratios increased 4- to 5-fold at 20 and 40 µg avelumab doses. Conclusions: [89Zr]Zr-DFO-PD-L1 mAb exhibited specific and high affinity for PD-L1 in vitro and had target tissue uptakes correlating with PD-L1 expression levels in vivo. [89Zr]Zr-DFO-PD-L1 mAb uptake in PD-L1+tumors increased with escalating doses of avelumab.
Associations between folate and choline intake, homocysteine metabolism, and genetic polymorphism of MTHFR, BHMT and PEMT in healthy pregnant Polish women.

AIM Physiological homocysteine (Hcy) concentrations depend on several factors, both dietary (including folate and choline intake) and biological (such as polymorphism of the genes involved in Hcy metabolism). This study aimed to thus test the associations between genes functionally linked with Hcy metabolism (MTHFR, BHMT and PEMT), folate and choline intakes, and total Hcy (tHcy) concentrations of healthy pregnant women. METHODS One hundred and three healthy Polish women aged 18-44 years, in the third trimester of pregnancy, were enrolled. RESULTS Mean blood tHcy and glutathione (GSH) concentrations were 8.08 ± 3.25 μM and 4.84 ± 1.21 μM, respectively. Concentrations of tHcy were found to be lower in the women who were taking folic acid supplements than in those who did not take these supplements (7.42 ± 1.78 μM vs 9.28 ± 4.42 μM, P < 0.05). There were no associations found between the examined parameters and BHMT (rs7356530), MTHFR (rs1801133) and PEMT (rs12325817) alone. However, blood tHcy concentrations differed in the PEMT genotype subgroups when choline and folate intakes were considered: respectively, 25% and 20% lower levels were observed in the C allele carriers who met their needs of choline or folate than in those who did not take enough these nutrients (P < 0.05 for both associations). CONCLUSIONS This study suggests that choline and folate intakes might interact with MTHFR, BHMT and PEMT polymorphisms to determine tHcy and GSH blood concentrations in healthy pregnant women.
Quantitative sensory testing and predicting outcomes for musculoskeletal pain, disability, and negative affect: a systematic review and meta-analysis.

Hypersensitivity due to central pain mechanisms can influence recovery and lead to worse clinical outcomes, but the ability of quantitative sensory testing (QST), an index of sensitisation, to predict outcomes in chronic musculoskeletal disorders remains unclear. We systematically reviewed the evidence for ability of QST to predict pain, disability, and negative affect using searches of CENTRAL, MEDLINE, EMBASE, AMED, CINAHL, and PubMed databases up to April 2018. Title screening, data extraction, and methodological quality assessments were performed independently by 2 reviewers. Associations were reported between baseline QST and outcomes using adjusted (β) and unadjusted (r) correlations. Of the 37 eligible studies (n = 3860 participants), 32 were prospective cohort studies and 5 randomised controlled trials. Pain was an outcome in 30 studies, disability in 11, and negative affect in 3. Meta-analysis revealed that baseline QST predicted musculoskeletal pain (mean r = 0.31, 95% confidence interval [CI]: 0.23-0.38, n = 1057 participants) and disability (mean r = 0.30, 95% CI: 0.19-0.40, n = 290 participants). Baseline modalities quantifying central mechanisms such as temporal summation and conditioned pain modulation were associated with follow-up pain (temporal summation: mean r = 0.37, 95% CI: 0.17-0.54; conditioned pain modulation: mean r = 0.36, 95% CI: 0.20-0.50), whereas baseline mechanical threshold modalities were predictive of follow-up disability (mean r = 0.25, 95% CI: 0.03-0.45). Quantitative sensory testing indices of pain hypersensitivity might help develop targeted interventions aiming to improve outcomes across a range of musculoskeletal conditions.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.
A case report and review of literature

Rationale:Rosai-Dorfman disease (RDD) is a rare non-Langerhans cell histiocytosis. Petroclival RDD is extremely rare. To the best of our knowledge, only 7 cases of petroclival RDD have been reported so far. Herein, we present the 8th case of intracranial RDDwith the petroclival and parasellar involvement mimicking multiple meningiomas. Patient concerns:A57-year-oldwomanpresentedwith a 1-year history of vision diminution and 1-month hearing loss in her right ear. Diagnoses:Contrast-enhanced Magnetic resonance imaging (MRI) of the brain demonstrated multiple well-defined, homogenous mass which closely related to the dura mater in the bilateral parasellar and petroclival regions range from the basement of anterior to posterior cranial fossa. The lesions were T1 isointense, T2 hypointense, and homogeneously enhanced. Initial diagnosis of multiple meningiomas was made according to MRI findings. Final diagnosis of RDD was confirmed by histopathological and immunohistochemical examinations after subtotal surgical resection. Interventions: The patient received subtotal resection because multiple lesions were extensive. Outcomes: The vision diminution recovered well after the surgery but the hearing loss in her right ear was still persisted. Lessons:Although rare, a standard RDD typically are dural-based, extra-axial, well-circumscribedmassesmimicking meningioma, and presenting with characterized hypo to isointense on T1-weighted images, hypo to isointense on T2-weighted images, and obvious enhancement. Resection of the intracranial lesion is the most effective treatment. In case of subtotal resection, the application of adjunctive radiotherapy and/or steroid agents should be advised. Final diagnosis of RDD should be confirmed by histopathological and immunohistochemical examinations. Abbreviations: CNS= central nervous system, CT= computed tomography, GFAP= glial fibrillary acidic protein, MRI=magnetic resonance imaging, RDD = Rosai-Dorfman disease.