Takshan/R1 huggingface dataset:
Responding to chemical weapons violations in Syria: legal, health, and humanitarian recommendations.

Background: The repeated use of prohibited chemical weapons in the Syrian conflict poses serious health, humanitarian, and security threats to civilians, healthcare personnel, and first responders. Moreover, the use of chemical weapons constitutes a clear and egregious violation of international law-likely amounting to a war crime-for which continued impunity is setting a dangerous precedent in relation to current and future conflicts. This debate article calls upon concerned states, organizations, and individuals to respond urgently and unequivocally to this serious breach of international legal and humanitarian norms. Main Body: Based on health, humanitarian, and legal findings, this article calls for concrete action to: 1) reduce the risk of chemical weapons being used in current and future conflicts; 2) review and support the preparedness equipment and antidote supplies of first responders, humanitarian organizations, and military forces operating in Syria; 3) support international mechanisms for monitoring and enforcing the prohibition on chemical weapons, including through criminal accountability; 4) support civilian victims of chemical weapons attacks, including refugees; and 5) re-commit to the complete elimination of chemical weapons in compliance with the Chemical Weapons Convention (1993), a comprehensive treaty that bans chemical weapons and requires their complete destruction. Conclusion: All involved states and organizations should take urgent steps to ensure the protection of the most vulnerable victims of conflict, including victims of chemical weapons attacks in Syria, and to reinforce international law in the face of such serious violations.
Sleep-related vehicle crashes on low speed roads.

BACKGROUND: Very little is known about the characteristics of sleep related (SR) crashes occurring on low speed roads compared with current understanding of the role of sleep in crashes occurring on high speed roads e.g. motorways. To address this gap, analyses were undertaken to identify the differences and similarities between (1) SR crashes occurring on roads with low (≤60km/h) and high (≥100km/h) speed limits, and (2) SR crashes and not-SR crashes occurring on roads with low speed limits. METHOD: Police reports of all crashes occurring on low and high speed roads over a ten year period between 2000 and 2009 were examined for Queensland, Australia. Attending police officers identified all crash attributes, including 'fatigue/fell asleep', which indicates that the police believe the crash to have a causal factor relating to falling asleep, sleepiness due to sleep loss, time of day, or fatigue. Driver or rider involvement in crashes was classified as SR or not-SR. All crash-associated variables were compared using Chi-square tests (Cramer's V=effect size). A series of logistic regression was performed, with driver and crash characteristics as predictors of crash category. A conservative alpha level of 0.001 determined statistical significance. RESULTS: There were 440,855 drivers or riders involved in a crash during this time; 6923 (1.6%) were attributed as SR. SR crashes on low speed roads have similar characteristics to those on high speed roads with young (16-24y) males consistently over represented. SR crashes on low speed roads are noticeably different to not-SR crashes in the same speed zone in that male and young novice drivers are over represented and outcomes are more severe. Of all the SR crashes identified, 41% occurred on low speed roads. CONCLUSION: SR crashes are not confined to high speed roads. Low speed SR crashes warrant specific investigation because they occur in densely populated areas, exposing a greater number of people to risk and have more severe outcomes than not-SR crashes on the same low speed roads.
Associations Between Neuropsychological, Neurobehavioral and Emotional Functioning and Either Narcolepsy or Idiopathic Hypersomnia in Children and Adolescents.

STUDY OBJECTIVES: Narcolepsy and idiopathic hypersomnia are chronic neurological sleep disorders characterized by hypersomnolence or excessive daytime sleepiness. This review aims to systematically examine the scientific literature on the associations between narcolepsy and idiopathic hypersomnia and their effect on intellectual functioning, academic achievement, behavior, and emotion. METHODS: Published studies that examined those associations in children and adolescents were included. Studies in which children or adolescents received a clinical diagnosis, and in which the associated function was measured with at least one objective instrument were included. Twenty studies published between 1968 and 2017 were eligible for inclusion in this review. RESULTS: There does not appear to be a clear association between intellectual functioning and narcolepsy or idiopathic hypersomnia; however, limited research is an obstacle to obtaining generalizability. The variability in results from studies investigating associations between academic achievement and these two hypersomnolence disorders suggests that further research using standardized and validated assessment instruments is required to determine if there is an association. Behavior and emotion appear to be significantly affected by narcolepsy. Only two studies included populations of children and adolescents with idiopathic hypersomnia. CONCLUSIONS: Further research using larger populations of children and adolescents with narcolepsy or idiopathic hypersomnia while utilizing standardized and validated instruments is required, because the effect of these conditions of hypersomnolence varies and is significant for each individual.
Role of Prophylactic Antibiotics in Laparoscopic Cholecystectomy.

BACKGROUND: Antibiotic prophylaxis is routinely administered in laparoscopic cholecystetomy but its role is debatable. METHODS: From January 2004 to August 2008, 417 patients were randomized into 208 in antibiotic group (AG) and 209 in non antibiotic group (NAG). AG received one dose each of injection ciprofloxacin (200 mg) and metronidazole (500mg) preoperatively. NAG was given only intravenous fluids. Besides routine care, all underwent abdominal sonography and liver function tests at least once during the 30 postoperative days. RESULT: Age, sex and co-morbidity distribution were similar in both the groups. One patient who was on weekly 5mg methotraxate (NAG) had erythema around umbilical port. Other three having umbilical discharge recovered without antibiotics. Nine patients had subhepatic collection (5 AG and 4 NAG). One from NAG underwent re-laparoscopy and drainage. Ten patients had fever. Two from AG had basal lung collapse and were given antibiotics. CONCLUSION: Antibiotic prophylaxis is not needed for laparoscopic cholecystectomy.
Stromal TRIM28-associated signaling pathway modulation within the colorectal cancer microenvironment.

BACKGROUND: Stromal gene expression patterns predict patient outcomes in colorectal cancer. TRIM28 is a transcriptional co-repressor that regulates an abundance of genes through the KRAB domain family of transcription factors. We have previously shown that stromal expression of TRIM28 is a marker of disease relapse and poor survival in colorectal cancer. Here, we perform differential epithelium-stroma proteomic network analyses to characterize signaling pathways associated with TRIM28 within the tumor microenvironment. METHODS: Reverse phase protein arrays were generated from laser capture micro-dissected carcinoma and stromal cells from fresh frozen colorectal cancer tissues. Phosphorylation and total protein levels were measured for 30 cancer-related signaling pathway endpoints. Strength and direction of associations between signaling endpoints were identified using Spearman's rank-order correlation analysis and compared to TRIM28 levels. Expression status of TRIM28 in tumor epithelium and stromal fibroblasts was assessed using IHC in formalin fixed tissue and the epithelium to stroma protein expression ratio method. RESULTS: We found distinct proteomic networks in the epithelial and stromal compartments which were linked to expression levels of TRIM28. Low levels of TRIM28 in tumor stroma (high epithelium: stroma ratio) were found in 10 out of 19 cases. Upon proteomic network analyses, these stromal high ratio cases revealed moderate signaling pathway similarity exemplified by 76 significant Spearman correlations (ρ ≥ 0.75, p ≤ 0.01). Furthermore, low levels of stromal TRIM28 correlated with elevated MDM2 levels in tumor epithelium (p = 0.01) and COX-2 levels in tumor stroma (p = 0.002). Low TRIM28 epithelium to stroma ratios were associated with elevated levels of caspases 3 and 7 in stroma (p = 0.041 and p = 0.036) and an increased signaling pathway similarity in stromal cells with 81 significant Spearman correlations (ρ ≥ 0.75, p ≤ 0.01). CONCLUSIONS: By dissecting TRIM28-associated pathways in stromal fibroblasts and epithelial tumor cells, we performed comprehensive proteomic analyses of molecular networks within the tumor microenvironment. We found modulation of several signaling pathways associated with TRIM28, which may be attributed to the pleiotropic properties of TRIM28 through its translational suppression of the family of KRAB domain transcription factors in tumor stromal compartments.
Pitfalls in the ankle-brachial index and brachial-ankle pulse wave velocity.

Background: The ankle-brachial index (ABI) and pulse wave velocity (PWV) are indices of atherosclerosis and arterial stiffness. The Japan-made measuring devices of those indices have spread widely because of their convenience and the significance of the parameters. However, studies that comprehensively discuss the various pitfalls in using these indices are not available. Methods: This study presents several representative pitfalls in using the ABI and brachial-ankle PWV (baPWV) by showing the result sheets of the device, "the Vascular Profiler". Furthermore, some considerations when utilizing these indices in the future are also discussed. Results: Several diseases such as arteriosclerosis obliterans (ASO), arterial calcification in the lower limb, arterial stenosis in the right upper-limb, aortic valve diseases, arterial stenosis in the upper-limb of the contralateral side of the hemodialysis access, are the representative pitfalls when evaluating ABI and baPWV. Moreover, a measurement error is found to actually exist. Furthermore, same phenomena are considered most likely to occur when using other similar indices and devices. Conclusion: The ABI and baPWV are the useful and significant biomarkers. Nevertheless, caution is sometimes necessary when interpreting them. Moreover, rigorous patient exclusion criteria should be considered when using those indices in the severely conditioned patient population. And the results of this study can be applied to enhance the literacy using other indices, such as the cardio-ankle vascular index and other similar devices.
Resting-state EEG power and coherence vary between migraine phases.

BACKGROUND: Migraine is characterized by a series of phases (inter-ictal, pre-ictal, ictal, and post-ictal). It is of great interest whether resting-state electroencephalography (EEG) is differentiable between these phases. METHODS: We compared resting-state EEG energy intensity and effective connectivity in different migraine phases using EEG power and coherence analyses in patients with migraine without aura as compared with healthy controls (HCs). EEG power and isolated effective coherence of delta (1-3.5 Hz), theta (4-7.5 Hz), alpha (8-12.5 Hz), and beta (13-30 Hz) bands were calculated in the frontal, central, temporal, parietal, and occipital regions. RESULTS: Fifty patients with episodic migraine (1-5 headache days/month) and 20 HCs completed the study. Patients were classified into inter-ictal, pre-ictal, ictal, and post-ictal phases (n = 22, 12, 8, 8, respectively), using 36-h criteria. Compared to HCs, inter-ictal and ictal patients, but not pre- or post-ictal patients, had lower EEG power and coherence, except for a higher effective connectivity in fronto-occipital network in inter-ictal patients (p < .05). Compared to data obtained from the inter-ictal group, EEG power and coherence were increased in the pre-ictal group, with the exception of a lower effective connectivity in fronto-occipital network (p < .05). Inter-ictal and ictal patients had decreased EEG power and coherence relative to HCs, which were "normalized" in the pre-ictal or post-ictal groups. CONCLUSION: Resting-state EEG power density and effective connectivity differ between migraine phases and provide an insight into the complex neurophysiology of migraine.
Predicting excess cost for older inpatients with clinical complexity: A retrospective cohort study examining cognition, comorbidities and complications.

BACKGROUND: Hospital-acquired complications increase length of stay and contribute to poorer patient outcomes. Older adults are known to be at risk for four key hospital-acquired complications (pressure injuries, pneumonia, urinary tract infections and delirium). These complications have been identified as sensitive to nursing characteristics such as staffing levels and level of education. The cost of these complications compared to the cost of admission severity, dementia, other comorbidities or age has not been established. METHOD: To investigate costs associated with nurse-sensitive hospital-acquired complications in an older patient population 157,178 overnight public hospital episodes for all patients over age 50 from one Australian state, 2006/07 were examined. A retrospective cohort study design with linear regression analysis provided modelling of length-of-stay costs. Explanatory variables included patient age, sex, comorbidities, admission severity, dementia status, surgical status and four complications. Extra costs were based on above-average length-of-stay for each patient's Diagnosis Related Group from hospital discharge data. RESULTS: For adults over 50 who have length of stay longer than average for their diagnostic condition, comorbid dementia predicts an extra cost of A$874, (US$1,247); any one of four key complications predicts A$812 (US$1,159); each increase in admission severity score predicts A$295 ($US421); each additional comorbidity predicts A$259 (US$370), and for each year of age above 50 predicts A$20 (US$29) (all estimates significant at p<0.0001). DISCUSSION: Hospital-acquired complications and dementia cost more than other kinds of inpatient complexity, but admission severity is a better predictor of excess cost. Because complications are potentially preventable and dementia care in hospitals can be improved, risk-reduction strategies for common complications, particularly for patients with dementia could be cost effective. CONCLUSIONS: Complications and dementia were found to cost more than other kinds of inpatient complexity.
Central blockade of NLRP3 reduces blood pressure via regulating inflammation microenvironment and neurohormonal excitation in salt-induced prehypertensive rats.

BACKGROUND: Inflammation has been implicated in the development of cardiovascular disease. We determined whether nod-like receptor with pyrin domain containing 3 (NLRP3) involved in the process of prehypertension, central blockade of NLRP3 decreased inflammation reaction, regulated neurohormonal excitation, and delayed the progression of prehypertension. METHODS: Prehypertensive rats were induced by 8% salt diet. The rats on high-salt diet for 1 month were administered a specific NLRP3 blocker in the hypothalamic paraventricular nucleus (PVN) for 4 weeks. ELISA, western blotting, immunohistochemistry, and flow cytometry were used to measure NLRP3 cascade proteins, pro-inflammation cytokines (PICs), chemokine ligand 2 (CCL2), C-X-C chemokine receptor type 3 (CXCR3), vascular cell adhesion molecule 1 (VCAM-1), neurotransmitters, and leukocytes count detection, respectively. RESULTS: NLRP3 expression in PVN was increased significantly in prehypertensive rats, accompanied by increased number of microglia, CD4+, CD8+ T cell, and CD8+ microglia. Expressions of PICs, CCL2, CXCR3, and VCAM-1 significantly increased. The balance between 67-kDa isoform of glutamate decarboxylase (GAD67) and tyrosine hydroxylase (TH) was damaged. Plasma norepinephrine (NE) in prehypertensive rats was increased and gamma-aminobutyric acid (GABA) was reduced. NLRP3 blockade significantly decreased blood pressure, reduced PICs, CCL2, VCAM-1 expression in PVN, and restored neurotransmitters. Blood pressure and inflammatory markers were upregulated after termination of central blockage NLRP3. CONCLUSIONS: Salt-induced prehypertension is partly due to the role of NLRP3 in PVN. Blockade of brain NLRP3 attenuates prehypertensive response, possibly via downregulating the cascade reaction triggered by inflammation and restoring the balance of neurotransmitters.
The use of whole exome sequencing and murine patient derived xenografts as a method of chemosensitivity testing in sarcoma.

Background: Soft tissue and bone sarcoma represent a broad spectrum of different pathology and genetic variance. Current chemotherapy regimens are derived from randomised trials and represent empirical treatment. Chemosensitivity testing and whole exome sequencing (WES) may offer personalized chemotherapy treatment based on genetic mutations. Methods: A pilot, prospective, non-randomised control experimental study was conducted. Twelve patients with metastatic bone or soft tissue sarcoma that had failed first line chemotherapy treatment were enrolled for this study. Human tissue taken at surgical biopsy under general anaesthetic was divided between two arms of the trial. Subsections of the tumour were used for WES and the remainder was implanted subcutaneously in immunodeficient mice (PDX). Results of WES were analysed using a bioinformatics pipeline to identify mutations conferring susceptibility to kinase inhibitors and common chemotherapeutic agents. PDX models exhibiting successful growth underwent WES of the tumour and subsequent chemosensitivity testing. Results: WES was successful in all 12 patients, with successful establishment PDX tumours models in seven patients. WES identified potential actionable therapeutics in all patients. Significant variation in predicted therapeutics was demonstrated between three PDX samples and their matched tumour samples. Conclusion: Analysis of WES of fresh tumour specimens via a bioinformatics pipeline may identify potential actionable chemotherapy agents. Further research into this field may lead to the development of personalized cancer therapy for sarcoma.
Muscle mass, BMI, and mortality among adults in the United States: A population-based cohort study.

BACKGROUND: The level of body-mass index (BMI) associated with the lowest risk of death remains unclear. Although differences in muscle mass limit the utility of BMI as a measure of adiposity, no study has directly examined the effect of muscle mass on the BMI-mortality relationship. METHODS: Body composition was measured by dual-energy x-ray absorptiometry in 11,687 participants of the National Health and Nutrition Examination Survey 1999-2004. Low muscle mass was defined using sex-specific thresholds of the appendicular skeletal muscle mass index (ASMI). Proportional hazards models were created to model associations with all-cause mortality. RESULTS: At any level of BMI ≥22, participants with low muscle mass had higher body fat percentage (%TBF), an increased likelihood of diabetes, and higher adjusted mortality than other participants. Increases in %TBF manifested as 30-40% smaller changes in BMI than were observed in participants with preserved muscle mass. Excluding participants with low muscle mass or adjustment for ASMI attenuated the risk associated with low BMI, magnified the risk associated with high BMI, and shifted downward the level of BMI associated with the lowest risk of death. Higher ASMI was independently associated with lower mortality. Effects were similar in never-smokers and ever-smokers. Additional adjustment for waist circumference eliminated the risk associated with higher BMI. Results were unchanged after excluding unintentional weight loss, chronic illness, early mortality, and participants performing muscle-strengthening exercises or recommended levels of physical activity. CONCLUSIONS: Muscle mass mediates associations of BMI with adiposity and mortality and is inversely associated with the risk of death. After accounting for muscle mass, the BMI associated with the greatest survival shifts downward toward the normal range. These results provide a concrete explanation for the obesity paradox.
Serum cortisol level and survival rate of juvenile Epinephelus fuscoguttatus following exposure to different salinities.

Background and Aim: Brown-marbled grouper Epinephelus fuscoguttatus is a premium marine food fish with high demand in Asia. In fish, stress due to environmental changes such as fluctuations in the salinity can result in increased cortisol level. Stress in fish increases susceptibility to diseases ultimately resulting in death. Therefore, the aim of this study was to investigate the salinity tolerance of E. fuscoguttatus and their survival in lower salinities. Materials and Methods: In this study, grouper juveniles (92.43±standard error of the mean 0.51 mm) maintained in 31 ppt seawater were transferred into five tanks with seawater diluted to 25, 20, 15, 10, and 5 ppt. The salinity of the control group was not changed and was maintained at 31 ppt. Serum cortisol was measured using ELISA at 0, 30, 60, and 120 min after the fish were transferred to the different concentrations of salinity. Results: The survival percentage was recorded for 14 days following the transfer and the results revealed that serum cortisol of fish in a high change in salinity (15, 10, and 5 ppt) was significantly higher than the control group immediately after exposure. At the high salinity change, the cortisol levels gradually decrease at 30 min and 60 min, until no difference in cortisol concentration was observed at 120 min. No mortality was observed in fish exposed to low salinity change (25 and 20 ppt) while in higher salinity change (5 ppt), the survival percentage was 50%. Conclusion: The study revealed that the serum cortisol concentration was high initially and continues to decrease to resting cortisol level at 120 min indicating that cortisol hormone is released following acute stress as a primary response in grouper juveniles.
Sleeping Beauty transposon integrates into non-TA dinucleotides.

Background: Sleeping Beauty transposon (SB) has become an increasingly important genetic tool for generating mutations in vertebrate cells. It is widely thought that SB exclusively integrates into TA dinucleotides. However, this strict TA-preference has not been rigorously tested in large numbers of insertion sites that now can be detected with next generation sequencing. Li et al. found 71 SB insertions in non-TA dinucleotides in 2013, suggesting that TA dinucleotides are not the only sites of SB integration, yet further studies on this topic have not been carried out. Results: In this study, we re-analyzed 600 million pairs of Illumina sequence reads from a high-throughput SB mutagenesis screen and identified 28 thousand SB insertions in non-TA sites. We recovered some of these non-TA sites using PCR and confirmed that at least a subset of the insertions at non-TA sites are real integrations. The consensus sequence of these non-TA sites shows an asymmetric pattern distinct from the symmetric pattern of the canonical TA sites. Perfect similarity between the downstream flanking sequence and SB transposon ends indicates there may be interaction between the transposon DNA binding domain of transposase and the target DNA. Conclusion: The TA-preference of SB transposon is not as strict as what people had thought. And the SB integrations at non-TA sites might be guided by the interaction between the transposon DNA binding domain of SB transposase and the target DNA.