Miracle-dz/UniFAR-FTUs huggingface dataset:
Illicit drugs are now more common than alcohol among South Australian crash-involved drivers and riders

Abstract Objectives: For a jurisdiction to apply appropriate countermeasures for impaired driving, it is necessary to track drug and alcohol involvement in road crashes. In South Australia, it is mandated that all injured road users aged over 10 who attend a hospital for treatment must have a blood sample taken, which is tested for alcohol and drugs. The drug testing covers the three drugs included in South Australia’s roadside drug testing program: delta-9-tetrahydrocannabinol (THC or cannabis), methamphetamine (‘ice’) and 3,4-methylenedioxymethamphetamine (MDMA or ‘ecstasy’). Methods: The present study involved analysis of the results of drug tests from 2014 to 2017 for road users over the age of 16 at the major trauma hospital in Adelaide, the capital city of South Australia. Comparisons were made to the results of blood tests from an earlier study using data from 2008 to 2010. Results: It was found in the most recent dataset that just over 11 per cent of drivers and just under 5 per cent of motorcyclists had a blood alcohol concentration (BAC) above the legal limit of 0.05 g/100 ml. In regard to the three proscribed drugs, the rates for both drivers and motorcyclists were over 15 per cent. Among drivers, methamphetamine was most common (9.7%), followed by THC (6.3%). Among motorcyclists, THC was most common (9.4%), followed by methamphetamine (6.2%). Inspection of data from 2008 to 2010 reveals that rates of having an illegal BAC when involved in a crash have declined over the past decade (from 20.2% down to 9.3%), while rates of drug use among crash involved drivers and riders have increased (from 10.5% to 15.2%). Conclusions: Although the apparent decline in alcohol involvement in road crashes in recent years in South Australia is to be welcomed, the increasing proportion of road crashes involving drug impaired drivers, particularly those affected by methamphetamine, is cause for concern. A National Drug Driving Working Group has been set up by Austroads to examine improvements in drug driving enforcement practices. The recommendations arising from their work need to be considered for implementation to prevent rising drug driving crashes from replacing the reduction in road crashes attributable to drink driving.
Amphetamine promotes cortical Up state: Role of adrenergic receptors

Cortical neurons oscillate synchronously between the Up and Down state during slow‐wave sleep and general anesthesia. Using local‐field‐potential recording in the rat prefrontal cortex (PFC), we have shown that systemic administration of methylphenidate promotes PFC Up states and reduces PFC slow oscillation, suggesting a depolarizing effect of the drug on PFC neurons. Here, we report that systemic injection of d‐amphetamine produced similar effects. Our evidence further suggests that norepinephrine (NE) plays a major role in the effects of d‐amphetamine since they were mimicked by the NE reuptake inhibitors tomoxetine and nisoxetine and completely blocked by the α1 receptor antagonist prazosin. The effects of d‐amphetamine persisted, however, in the presence of α2 or β receptor blockade. Experiments with α1 subtype‐selective antagonists further suggest that d‐amphetamine's effects depend on activation of central, but not peripheral, α1A receptors. Unexpectedly, the putative α1 receptor agonist cirazoline failed to mimic the effects of d‐amphetamine. Previous studies suggest that cirazoline is also an antagonist at α2 receptors. Furthermore, it is a partial, not full, agonist at α1B and α1D receptors. Whether or not these properties of cirazoline contribute to its failure to mimic d‐amphetamine's effects remains to be determined. Methylphenidate and d‐amphetamine are two most common medications for attention‐deficit/hyperactivity disorder (ADHD). Both, however, are associated with adverse effects including abuse potential and psychotomimetic effects. Further understanding of their mechanisms of action will help develop safer treatments for ADHD and offer new insights into drug addiction and psychosis.
Predator coexistence through emergent fitness equalization.

The competitive exclusion principle is one of the oldest ideas in ecology, and states that without additional self-limitation two predators cannot coexist on a single prey. The search for mechanisms allowing coexistence despite this has identified niche differentiation between predators as crucial: without this, coexistence requires the predators to have exactly the same R* values, which is considered impossible. However, this reasoning misses a critical point: predators' R* values are not static properties, but affected by defensive traits of their prey, which in turn can adapt in response to changes in predator densities. Here I show that this feedback between defense and predator dynamics enables stable predator coexistence without ecological niche differentiation. Instead, the mechanism driving coexistence is that prey adaptation causes defense to converge to the value where both predators have equal R* values ("fitness equalization"). This result is highly general, independent of specific model details, and applies to both rapid defense evolution and inducible defenses. It demonstrates the importance of considering long-standing ecological questions from an eco-evolutionary viewpoint, and showcases how the effects of adaptation can cascade through communities, driving diversity on higher trophic levels. These insights offer an important new perspective on coexistence theory.
Bta‐miR‐149‐5p inhibits proliferation and differentiation of bovine adipocytes through targeting CRTCs at both transcriptional and posttranscriptional levels

MicroRNAs are small, single stranded, and noncoding RNAs that have been proven to be potent regulators of adipogenesis. However, the role of bta‐miR‐149‐5p in regulating bovine adipogenesis is still unclear. Expression profiling in different stages of adipogenesis revealed that bta‐miR‐149‐5p was enriched in the proliferation stage, and also on Day 9 of differentiation in bovine adipocytes. Our gain of function study showed that bta‐miR‐149‐5p can negatively regulate both bovine adipocyte proliferation and differentiation. Overexpression of bta‐miR‐149‐5p suppressed the expression of proliferation marker genes at both the messenger RNA (mRNA) and protein levels, markedly decreased the percentage of S‐phase cells, decreased the number of EdU‐stained cells, and substantially reduced adipocyte proliferation vitality in the cell count assay. Collectively, these findings elucidated that bta‐miR‐149‐5p inhibits adipocyte proliferation. Furthermore, overexpression of bta‐miR‐149‐5p also suppressed the expression of adipogenic genes at both the mRNA and protein levels, inhibited lipid accumulation, and reduced the secretion of adiponectin in bovine adipocytes. Furthermore, a luciferase activity assay explored how bta‐miR‐149‐5p targeted CRTCs (CRTC1 and CRTC2) directly. This targeting was further validated by the mRNA and protein level expression of CRTC1 and CRTC2, which were down regulated by bta‐miR‐149‐5p overexpression. Moreover, bta‐miR‐149‐5p indirectly targeted CRTC1 and CRTC2 through regulating their key transcription factors. Overexpression of bta‐miR‐149‐5p suppressed the expression of SMAD3, while enriched the expression of NRF1, which are the key transcription factors and proven regulators of CRTC1. Overexpression of bta‐miR‐149‐5p also repressed the expression of C/EBPγ, XBP1, INSM1, and ZNF263, which are the key regulators of CRTCs, at both the mRNA and protein levels. These findings suggest that bta‐miR‐149‐5p is a negative regulator of CRTC1 and CRTC2 both at transcriptional and posttranscriptional level. Taken together, these findings suggest that bta‐miR‐149‐5p can regulate adipogenesis, which implies that bta‐miR‐149‐5p could be a target for increasing intramuscular fat in beef cattle.
Lung Cancer Staging and Associated Genetic and Epigenetic Events

The first step in treating lung cancer is to establish the stage of the disease, which in turn determines the treatment options and prognosis of the patient. Many factors are involved in lung cancer staging, but all involve anatomical information. However, new approaches, mainly those based on the molecular biology of cancer, have recently changed the paradigm for lung cancer treatment and have not yet been incorporated into staging. In a group of patients of the same stage who receive the same treatment, some may experience unexpected recurrence or metastasis, largely because current staging methods do not reflect the findings of molecular biological studies. In this review, we provide a brief summary of the latest research on lung cancer staging and the molecular events associated with carcinogenesis. We hope that this paper will serve as a bridge between clinicians and basic researchers and aid in our understanding of lung cancer.
CT Imaging of the 2019 Novel Coronavirus (2019-nCoV) Pneumonia

References 1. Zhu N, Zhang D, Wang W, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med 2020 Jan 24. doi: 10.1056/ NEJMoa2001017. [Epub ahead of print] 2. Munster VJ, Koopmans M, van Doremalen N, van Riel D, de Wit E. A Novel Coronavirus Emerging in China Key Questions for Impact Assessment. N Engl J Med 2020 Jan 24. doi: 10.1056/NEJMp2000929. [Epub ahead of print] A 33-year-old woman presented to the hospital with a 5-day history of fever and cough of unknown cause. She indicated that she worked in Wuhan, China (the center of novel coronavirus outbreak) but had traveled to Lanzhou, China, 6 days before presentation to the hospital. At admission, her body temperature was elevated to 39.0°C (102.2°F) and coarse breath sounds of both lungs were heard at auscultation. Laboratory studies showed leucopenia (white blood cell count: 2.91 3 109/L). The white blood cell differential count showed 70.0% neutrophils and 0.1% eosinophils. There were elevated blood levels for C-reactive protein (16.16 mg/L; normal range, 0–10 mg/L), erythrocyte sedimentation rate (29 mm/h; normal range, ,20 mm/h), and D-dimer (580 ng/mL; normal range, 500 ng/mL). Unenhanced chest CT showed multiple peripheral ground-glass opacities in both lungs (Figure, A) that did not spare the subpleural regions. Real-time fluorescence polymerase chain reaction of the patient’s sputum was positive for the 2019 novel coronavirus (2019-nCoV) nucleic acid. Unenhanced CT images in a 33-year-old woman. A, Image shows multiple ground-glass opacities in bilateral lungs. Ground-glass opacities are seen in the posterior segment of right upper lobe and apical posterior segment of left superior lobe. B, Image obtained 3 days after follow-up shows progressive ground-glass opacities in the posterior segment of right upper lobe and apical posterior segment of left superior lobe. The bilateralism of the peripheral lung opacities, without subpleural sparing, are common CT findings of the 2019 novel coronavirus pneumonia.
The effects of vaping electronic cigarettes on periodontitis.

BACKGROUND Electronic cigarettes (E-cigs) have been gaining popularity, increasingly used to help reduce or cease smoking traditional cigarettes (T-cigs). Although E-cigs are considered a far less harmful alternative to T-cigs, there is not enough information regarding the effects of vaping E-cigs on periodontal health. AIM The aim of this study is to investigate the effects of vaping E-cigs, smoking T-cigs and smoking cessation on oxidative stress markers, proinflammatory cytokines levels and periodontal clinical parameters in patients with periodontitis. METHODS The study included a total of 57 individuals who were divided into three groups: T-cig smokers (Group I, n = 19), E-cig vapers (Group II, n = 19) and former smokers (Group III, n = 19). Full-mouth clinical periodontal parameters were recorded and gingival crevicular fluid (GCF) samples were collected. RESULTS The mean interleukin-8 (IL-8) level of Group I (70.47 ± 2.76) was significantly lower than in Groups II and III. The mean tumour necrosis factor-α (TNF-α) level of Group I (4.20 ± 0.14) was significantly higher than in Groups II and III. CONCLUSIONS T-cigs and vaping E-cigs had the same unfavourable effects on the markers of oxidative stress and inflammatory cytokines.
Understanding, Experience and Response to Sexual Harassment among the Female Students: A Mixed Method Study.

BACKGROUND Sexual harassment has received global attention and has been recognized as a public health problem with increased physical and mental health risks among the victims. This study attempted to assess understanding, experience, response and effect of sexual harassment among the secondary school female students in Kathmandu, Nepal. METHODS It was a mixed method study conducted among 441 secondary level female students. In quantitative component, a structured questionnaire was used to collect information relating to socio-demographic characteristics, and understanding, experience, response and effect of sexual harassment from 441 participants from three clusters (schools) of Tokha Municipality, Kathmandu. For qualitative method, two focused group discussions were conducted to assess the understanding of and response to sexual harassment. Quantitative and qualitative data were analyzed using Chi square test and thematic analysis method respectively. RESULTS Around 76% of the participants had experienced some forms of sexual harassment in their life. Sexual harassment was significantly associated with religion and parental occupation. Majority of participants who faced sexual harassment reported that the perpetrators were strangers and they either ignored it or did nothing at the time of events. School, roads and public places were the most common settings where participants encountered sexual harassment. CONCLUSIONS Sexual harassment is prevalent among female secondary students in Kathmandu. However, they lacked a clear understating of and ways to respond to sexual harassment. Raising awareness to recognize and respond to different forms of harassment and to change the victim-blaming attitudes can be a potential strategy for tackling the problem in Nepalese society.
Treatment of spontaneous osteonecrosis of the knee by daily teriparatide

Abstract Rationale: Although the treatment of femoral head necrosis has already been established with the adoption of daily teriparatide, a clear consensus on the treatment of spontaneous osteonecrosis of the knee (SONK) has yet to be reached. Therefore, we focused on the treatment of SONK with daily teriparatide administration (20 μg, subcutaneous) and confirmed its effects to determine whether it is a valid option. Patients’ concerns: Three osteoporotic patients who were diagnosed with SONK complained of knee pain. Diagnosis: SONK was diagnosed on magnetic resonance imaging in all cases. Interventions: All patients took daily teriparatide as a treatment for SONK. Outcomes: There was a significant and dramatic reduction in the visual analog scale score 1 month after treatment. After 6 months of treatment, the sizes of the affected SONK lesions were smaller than in the initial phase, and plain X-rays showed no further signs of progression. Lessons: Daily teriparatide might be an effective treatment for SONK.
Invasive Pulmonary Aspergillosis

Abstract Invasive pulmonary aspergillosis (IPA) remains difficult to diagnose and to treat. Most common risk factors are prolonged neutropenia, hematopoietic stem cell or solid organ transplantation, inherited or acquired immunodeficiency, administration of steroids or other immunosuppressive agents including monoclonal antibodies and new small molecules used for cancer therapy. Critically ill patients are also at high risk of IPA. Clinical signs are unspecific. Early computed tomography (CT)-scan identifies the two main aspects, angioinvasive and airway invasive aspergillosis. Although CT-scan findings are not fully specific they usually allow early initiation of therapy before mycological confirmation of the diagnosis. Role of 18F-fludeoxyglucose positron emission tomography with computed tomography (18F-FDG PET/CT) is discussed. Confirmation is based on microscopy and culture of respiratory samples, histopathology in case of biopsy, and importantly by detection of Aspergillus galactomannan using an immunoassay in serum and bronchoalveolar lavage fluid. Deoxyribonucleic acid detection by polymerase chain reaction is now standardized and increases the diagnosis yield. Two point of care tests detecting an Aspergillus glycoprotein using a lateral flow assay are also available. Mycological results allow classification into proven (irrespective of underlying condition), probable or possible (for cancer and severely immunosuppressed patients) or putative (for critically ill patients) IPA. New antifungal agents have been developed over the last 2 decades: new azoles (voriconazole, posaconazole, isavuconazole), lipid formulations of amphotericin B (liposomal amphotericin B, amphotericin B lipid complex), echinocandins (caspofungin, micafungin, anidulafungin). Results of main trials assessing these agents in monotherapy or in combination are presented as well as the recommendations for their use according to international guidelines. New agents are under development.
Wnt signaling associated small molecules improve the viability of pPSCs in a PI3K/Akt pathway dependent way

Although we have obtained porcine pluripotent stem cell lines (pPSCs) from blastocysts, the cells exhibit flat clonal morphology and do not support single‐cell passage. There is massive cell death after cell dissociation, and the efficiency of single‐cell colony is generally ≤10%. In a recent study, we got a new pPSCs using two Wnt signaling pathway regulators CHIR99021 and XAV939. This cell had strong biological viability, small‐domed morphology, and its cloning efficiency after dissociation was 80–90%. The CH/XAV‐treated cells expressed elevated levels of pluripotent genes, and possessed differentiation abilities both in vitro and in vivo, proven by the formation of embryonic bodies and teratomas with three germ layers. Furthermore, we found that the combinative use of CHIR99021 and XAV939 resulted in β‐catenin‐maintained expression in the cytoplasm but not translocation to the nuclei for WNT/TCF activation. In the meanwhile, E‐cadherin located on the cell membrane, thereby activated the PI3K/Akt signaling pathway to enhance the pluripotency of the cells. Our study obtained new pPSCs, which were even closer to the naïve state with only two small molecule inhibitors, and the improved pluripotency of pPSCs could facilitate transgenic manipulation and regenerative medicine research. Besides, our study casted a light on the understanding of pPSCs and the derivation of authentic porcine embryonic stem cells.
Dysregulated FXR-FGF19 Signaling and Choline Metabolism is Associated with Gut Dysbiosis and Hyperplasia in a Novel Pig Model of Pediatric NASH.

To investigate the role of bile acids (BA) in the pathogenesis of diet-induced non-alcoholic steatohepatitis (NASH), we fed a "Western-style diet" (HFF) enriched with fructose, cholesterol and saturated fat for 10 weeks to juvenile Iberian pigs. We also supplemented probiotics with in vitro BA deconjugating activity to evaluate their potential therapeutic effect in NASH. Liver lipid and function, cytokines and hormones were analyzed using commercially available kits. Metabolites, BAs, and fatty acids were measured by liquid chromatography-mass spectrometry. Histology and gene and protein expression analyses were performed using standard protocols. HFF-fed pigs developed NASH, cholestasis and impaired enterohepatic Farnesoid-X receptor (FXR)-Fibroblast growth factor 19 (FGF19) signaling, in the absence of obesity and insulin resistance. Choline depletion in HFF livers was associated with decreased lipoprotein and cholesterol in serum, and an increase of choline-containing phospholipids in colon contents and trimethylamine-N-oxide in the liver. Additionally, gut dysbiosis and hyperplasia increased with the severity of NASH, and were correlated with increased colonic levels of choline metabolites and secondary BAs. Supplementation of probiotics in the HFF diet enhanced NASH, inhibited hepatic autophagy, increased excretion of taurine and choline, and decreased gut microbial diversity. In conclusion, dysregulation of BA homeostasis was associated with injury and choline depletion in the liver, as well as increased biliary secretion, gut metabolism and excretion of choline-based phospholipids. Choline depletion limited lipoprotein synthesis resulting in hepatic steatosis, while secondary BAs and choline-containing phospholipids in colon may have promoted dysbiosis, hyperplasia and trimethylamine synthesis, causing further damage to the liver.
The role of infectious agents in cancer of the ocular region

The purpose of the study was to investigate the association between infectious agents and the development of cancer in the ocular adnexa. A comprehensive literary study was carried out, reviewing and summarizing previous reports on the topic. A broad range of malignancies of the ocular adnexa are associated with infectious agents. A strong association and possible causal relationship between the infectious agent and the development of ocular adnexal cancer are seen in Merkel cell carcinoma (Merkel cell polyomavirus), Burkitt lymphoma (Epstein–Barr virus) and Kaposi sarcoma (human herpesvirus 8). Infection with Chlamydia psittaci has been associated with the development of extranodal marginal zone B‐cell lymphoma in Italy. Human papillomavirus infection has been associated with the development of squamous cell carcinomas of the ocular adnexa, although with a highly variable reported prevalence. By exploring the role of infectious agents in the ocular adnexa and the mechanism by which they contribute to oncogenesis, the diagnostics, management and prevention of these malignancies may also improve. Antibiotic treatment and vaccines against infectious agents may be valuable in future treatment. Additionally, the presence of infectious agents within the tumours may have a prognostic or predictive value.
Simultaneous measurement method of erythrocyte sedimentation rate and erythrocyte deformability in resource-limited settings

Objective: The individual effects of plasma and red blood cells (RBCs) on the biophysical properties of blood can be monitored by measuring the erythrocyte sedimentation rate (ESR) and RBC deformability simultaneously. However, the previous methods require bulky and expensive facilities (i.e. microscope, high-speed camera, and syringe pump) to deliver blood or capture blood flows. Approach: To resolve these issues, a simple method for sequential measurement of the ESR and RBC deformability is demonstrated by quantifying the cell-free volume (VCF), cell-rich volume (VCR), and blood volume (VB) inside an air-compressed syringe (ACS). A microfluidic device consists of multiple micropillar channels, an inlet, and outlet. After the ACS is filled with air (Vair = 0.4 ml) and a blood sample (VB = 0.6 ml, hematocrit = 30%) sequentially, the ACS is fitted into the inlet. The cavity inside the ACS is compressed to Vcomp = 0.4 ml after closing the outlet with a stopper. A smartphone camera is employed to capture variations in the VCF, VCR, and VB inside the ACS. The ESR index suggested in this study (ESRPM) is obtained by dividing the VCF (t = t1) with an elapse of t1. By removing the stopper, ΔVB (ΔVB = VB [t = t1] − VB) is obtained and fitted as a two-term exponential model (. As a performance demonstration, the proposed method is employed to detect an ESR-enhanced blood sample, homogeneous hardened blood sample, and heterogeneous blood sample. Main results: From the experimental results, it is found that the proposed method has the ability to detect various bloods by quantifying the ESRPM and two coefficients (a, b) simultaneously. Significance: In conclusion, the present method can be effectively used to measure the ESR and RBC deformability in resource-limited settings.