Miracle-dz/UniFAR-FTUs huggingface dataset:
Automated Quantitative Measures of Terminal Duct Lobular Unit Involution and Breast Cancer Risk

Background: Manual qualitative and quantitative measures of terminal duct lobular unit (TDLU) involution were previously reported to be inversely associated with breast cancer risk. We developed and applied a deep learning method to yield quantitative measures of TDLU involution in normal breast tissue. We assessed the associations of these automated measures with breast cancer risk factors and risk. Methods: We obtained eight quantitative measures from whole slide images from a benign breast disease (BBD) nested case–control study within the Nurses' Health Studies (287 breast cancer cases and 1,083 controls). Qualitative assessments of TDLU involution were available for 177 cases and 857 controls. The associations between risk factors and quantitative measures among controls were assessed using analysis of covariance adjusting for age. The relationship between each measure and risk was evaluated using unconditional logistic regression, adjusting for the matching factors, BBD subtypes, parity, and menopausal status. Qualitative measures and breast cancer risk were evaluated accounting for matching factors and BBD subtypes. Results: Menopausal status and parity were significantly associated with all eight measures; select TDLU measures were associated with BBD histologic subtype, body mass index, and birth index (P < 0.05). No measure was correlated with body size at ages 5–10 years, age at menarche, age at first birth, or breastfeeding history (P > 0.05). Neither quantitative nor qualitative measures were associated with breast cancer risk. Conclusions: Among Nurses' Health Studies women diagnosed with BBD, TDLU involution is not a biomarker of subsequent breast cancer. Impact: TDLU involution may not impact breast cancer risk as previously thought.
Volatile versus total intravenous anesthesia for 30-day mortality following non-cardiac surgery in patients with preoperative myocardial injury

We evaluated whether volatile anesthetics can improve the postoperative outcomes of non-cardiac surgery in patients with preoperative myocardial injury defined by the cardiac troponin elevation. From January 2010 to June 2018, 1254 adult patients with preoperative myocardial injury underwent non-cardiac surgery under general anesthesia and were enrolled in this study. Patients were stratified into following two groups according to anesthetic agents; 115 (9.2%) patients whose anesthesia was induced and maintained with continuous infusion of propofol and remifentanil (TIVA group) and 1139 (90.8%) patients whose anesthesia was maintainted with volatile anesthetics (VOLATILE group). The primary outcome was 30-day mortality. To diminish the remifentanil effect, a further analysis was conducted after excluding the patients who received only volatile anesthetics without remifentanil infusion. In a propensity-score matched analysis, 30-day mortality was higher in the TIVA group than the VOLATILE group (17.0% vs. 9.1%; hazard ratio [HR] 2.60; 95% confidence interval [CI], 1.14–5.93; p = 0.02). In addition, the TIVA group showed higher 30-day mortality than the VOLATILE group, even after eliminating the effect of remifentanil infusion (15.8% vs. 8.3%; HR 4.62; 95% CI, 1.82–11.74; p = 0.001). In our study, the use of volatile anesthetics showed the significant survival improvement after non-cardiac surgery in patients with preoperative myocardial injury, which appears to be irrelevant to the remifentanil use. Further studies are needed to confirm this beneficial effect of volatile anesthetics. Clinical trial number and registry URL: KCT0004349 (www.cris.nih.go.kr)
Implementation of a High-Flow Nasal Cannula Management Protocol in the Pediatric ICU

BACKGROUND: High-flow nasal cannula (HFNC) therapy is a respiratory modality that has been adopted to support pediatric patients with bronchiolitis. There is no standardized protocol for initiation, escalation, or weaning of HFNC in the pediatric ICU. The aim of this respiratory therapist (RT)-driven quality improvement management protocol was to decrease duration of HFNC. METHODS: An RT-driven HFNC management protocol based on an objective respiratory score was implemented in 2017 at a quaternary care children’s hospital. Subjects included children less than 2 y old admitted to the pediatric ICU with bronchiolitis. All subjects needing HFNC were scored and placed within the protocol as appropriate for age, then weaned or escalated per the scoring tool. Comparison to a pre-intervention control group was performed. Average HFNC duration per subject was used as the primary outcome measure. Protocol compliance was used as a process measure. Noninvasive ventilation use, intubation rate, and 30-d pediatric ICU readmission rate were used as balancing measures. RT satisfaction with HFNC management before and after protocol implementation were measured. RESULTS: Protocol compliance was sustainable and above the goal of 80% after 4 months of protocol implementation. HFNC duration decreased from 2.5 d to 2 days for each subject during planning and then to 1.8 d after protocol implementation. Length of stay (LOS) in the pediatric ICU and hospital LOS decreased from 2.6 d to 2.1 d and from 5.7 d to 4.7 d after protocol implementation, respectively. The use of noninvasive ventilation and the rate of intubation did not change significantly. RTs reported increased involvement in HFNC management decisions and appropriateness on how quickly the team weaned HFNC. CONCLUSIONS: An RT-driven HFNC management protocol was safely implemented in a pediatric ICU and decreased HFNC duration, pediatric ICU LOS, and hospital LOS. It allows the RT to work independently to the highest extent of their scope of practice, leading to improvement in RT job satisfaction.
STIM1 Deficiency Leads to Specific Down-Regulation of ITPR3 in SH-SY5Y Cells

STIM1 is an endoplasmic reticulum (ER) protein that modulates the activity of a number of Ca2+ transport systems. By direct physical interaction with ORAI1, a plasma membrane Ca2+ channel, STIM1 activates the ICRAC current, whereas the binding with the voltage-operated Ca2+ channel CaV1.2 inhibits the current through this latter channel. In this way, STIM1 is a key regulator of Ca2+ signaling in excitable and non-excitable cells, and altered STIM1 levels have been reported to underlie several pathologies, including immunodeficiency, neurodegenerative diseases, and cancer. In both sporadic and familial Alzheimer’s disease, a decrease of STIM1 protein levels accounts for the alteration of Ca2+ handling that compromises neuronal cell viability. Using SH-SY5Y cells edited by CRISPR/Cas9 to knockout STIM1 gene expression, this work evaluated the molecular mechanisms underlying the cell death triggered by the deficiency of STIM1, demonstrating that STIM1 is a positive regulator of ITPR3 gene expression. ITPR3 (or IP3R3) is a Ca2+ channel enriched at ER-mitochondria contact sites where it provides Ca2+ for transport into the mitochondria. Thus, STIM1 deficiency leads to a strong reduction of ITPR3 transcript and ITPR3 protein levels, a consequent decrease of the mitochondria free Ca2+ concentration ([Ca2+]mit), reduction of mitochondrial oxygen consumption rate, and decrease in ATP synthesis rate. All these values were normalized by ectopic expression of ITPR3 in STIM1-KO cells, providing strong evidence for a new mode of regulation of [Ca2+]mit mediated by the STIM1-ITPR3 axis.
Disorders of synaptic vesicle fusion machinery

The revolution in genetic technology has ushered in a new age for our understanding of the underlying causes of neurodevelopmental, neuromuscular and neurodegenerative disorders, revealing that the presynaptic machinery governing synaptic vesicle fusion is compromised in many of these neurological disorders. This builds upon decades of research showing that disturbance to neurotransmitter release via toxins can cause acute neurological dysfunction. In this review, we focus on disorders of synaptic vesicle fusion caused either by toxic insult to the presynapse or alterations to genes encoding the key proteins that control and regulate fusion: the SNARE proteins (synaptobrevin, syntaxin‐1 and SNAP‐25), Munc18, Munc13, synaptotagmin, complexin, CSPα, α‐synuclein, PRRT2 and tomosyn. We discuss the roles of these proteins and the cellular and molecular mechanisms underpinning neurological deficits in these disorders.
Adverse electrocardiographic effects of rituximab infusion in pemphigus patients

Pemphigus encompasses a group of chronic autoimmune blistering diseases of the skin and/or mucosa. Rituximab (RTX) has shown promising efficacy for the treatment of pemphigus in the past decade. Considering potential cardiac side effects, this study was conducted to assess the effects of RTX on electrocardiogram (ECG) parameters in pemphigus patients. This observational cross‐sectional study was conducted in 80 consecutive patients with pemphigus who were eligible for RTX infusion. The patients' heart rhythm was monitored before, during and after RTX infusion and ECG parameters were compared before and after the infusion. Eighty patients were included in the study. The median age of the patients was 42 years. The mean and maximum heart rate (HR) increased significantly after RTX infusion compared with pre‐infusion mean and maximum HR. The mean corrected QT (QTc) interval, premature atrial contraction (PAC), and premature ventricular contraction (PVC) counts increased significantly after RTX infusion (P value: 0.009, 0.004 and 0.007 respectively). According to the results of this study, RTX has potential arrhythmogenic side effects including increased mean and maximum HR, QTc interval, PAC and PVC count. However, these findings are minor and should not prevent eligible patients from receiving RTX infusion.
Culture density contributes to hepatic functions of fresh human hepatocytes isolated from chimeric mice with humanized livers: Novel, long-term, functional two-dimensional in vitro tool for developing new drugs

Chimeric mice with humanized livers are considered a useful animal model for predicting human (h-) drug metabolism and toxicity. In this study, the characteristics of fresh h-hepatocytes (cFHHs, PXB-cells®) isolated from chimeric mice (PXB-mice®) were evaluated in vitro to confirm their utility for drug development. cFHHs cultured at high density (2.13 × 105 cells/cm2) displayed stable production of h-albumin and cytochrome P450 (CYP) 3A activities for at least 21 days. The mRNA expression levels of 10 of 13 CYP, UDP-glucuronosyltransferase (UGT), and transporters were maintained at >10% of the levels of freshly isolated cFHHs after 21 days. From 1 week, many bile canaliculi were observed between cFHHs, and the accumulation of the multidrug resistance-associated protein and bile salt export pump substrates in these bile canaliculi was clearly inhibited by cyclosporin A. Microarray analysis of cFHHs cultured at high density and at low density (0.53 × 105 cells/cm2) revealed that high density culture maintained high expressions of some transcription factors (HNF4α, PXR, and FXR) perhaps involved in the high CYP, UGT and transporter gene expressions of cFHHs. These results strongly suggest that cFHHs could be a novel in vitro tool for drug development studies.
Knowledge, attitude, and practice among staff associated with Human Papillomavirus Vaccine of young children in Iran.

INTRODUCTION This study aimed to evaluate knowledge, attitudes, practice associated with Human Papillomavirus (HPV) Vaccine for Young Children among lecturers and health staffs of Shahid Beheshti University of Medical Sciences (SBMU). METHOD This was a cross-sectional study with 220 adults from five different specialties, randomly selected. Data was collected using 45-item questionnaire on knowledge (12- item), attitude (18-item) and practice (15-item) (KAP) about HPV. The demographic questionnaire included information on age, gender, level of education, occupation, and marital status. Content validity was calculated by content validity ratio (CVR) and content validity index (CVI). Reliability was evaluated using test-retest and by Cronbach's Alpha coefficient, internal consistency was calculated values >0.81 which considered as satisfactory. RESULTS The mean age of the studied population was 37.70± 8.07 (23-67) years. Of the 220 participants, 80 (36.4%) were males and 140 (63.6%) were females. In evaluating KAP in the men and women, the mean and standard deviation of knowledge were estimated at good level and one-way ANOVA analysis showed significant differences between women and men (p=0.019). There was no significant difference in men and women related to attitude (p=0.92) and practice (p=0.38). CONCLUSION The KAP about HPV among participants was significantly higher at good levels compared to average levels. Women's knowledge was significantly higher than men. Attitude and practice could have been higher because there was consensus to the usage of vaccine among the specialists to prevent HPV.
Explaining the travelling behaviour of migrants using Facebook audience estimates

The paper explores the travelling behaviour of migrant groups using Facebook audience estimates. Reduced geographical mobility is associated with increased risk of social exclusion and reduced socio-economic and psychological well-being. Facebook audience estimates are timely, openly available and cover most of the countries in the world. Facebook classifies its users based on multiple attributes such as the country of their previous residence, and whether they are frequent travellers. Using these data, we modelled the travelling behaviour of Facebook users grouped by countries of previous and current residence, gender and age. We found strong indications that the frequency of travelling is lower for Facebook users migrating from low-income countries and for women migrating from or living in countries with high gender inequality. Such mobility inequalities impede the smooth integration of migrants from low-income countries to new destinations and their well-being. Moreover, the reduced mobility of women who have lived or currently live in countries with conservative gender norms capture another aspect of the integration which is referring to socio-cultural norms and gender inequality. However, to provide more solid evidence on whether our findings are also valid for the general population, collaboration with Facebook is required to better understand how the data is being produced and pre-processed.
RGB-D Object SLAM Using Quadrics for Indoor Environments

Indoor service robots need to build an object-centric semantic map to understand and execute human instructions. Conventional visual simultaneous localization and mapping (SLAM) systems build a map using geometric features such as points, lines, and planes as landmarks. However, they lack a semantic understanding of the environment. This paper proposes an object-level semantic SLAM algorithm based on RGB-D data, which uses a quadric surface as an object model to compactly represent the object’s position, orientation, and shape. This paper proposes and derives two types of RGB-D camera-quadric observation models: a complete model and a partial model. The complete model combines object detection and point cloud data to estimate a complete ellipsoid in a single RGB-D frame. The partial model is activated when the depth data is severely missing because of illuminations or occlusions, which uses bounding boxes from object detection to constrain objects. Compared with the state-of-the-art quadric SLAM algorithms that use a monocular observation model, the RGB-D observation model reduces the requirements of the observation number and viewing angle changes, which helps improve the accuracy and robustness. This paper introduces a nonparametric pose graph to solve data associations in the back end, and innovatively applies it to the quadric surface model. We thoroughly evaluated the algorithm on two public datasets and an author-collected mobile robot dataset in a home-like environment. We obtained obvious improvements on the localization accuracy and mapping effects compared with two state-of-the-art object SLAM algorithms.
Transcranial Doppler Evaluation of the Cerebral Vasculature in Women Patients who Have Migraine with Aura.

BACKGROUND Previous studies suggest that increased cerebrovascular reactivity might be a feature of patients who have migraine with aura (MwA). The correlation between the clinical presentation of migraine with aura and transcranial Doppler parameters remains unclear. OBJECTIVE The main aim of this study was to explore cerebral blood flow, vascular resistance, and cerebrovascular reactivity in women MwA. Also, the relationships between hemodynamic conditions and aura characteristics are examined. DESIGN Cross-sectional study. SETTING Headache Center, Neurology Clinic, Clinical Center of Serbia. SUBJECTS Fifty-four women MwA and 49 healthy controls (HCs). METHODS Transcranial Doppler sonography examination was used to determine blood flow mean velocity (MV) and pulsatility index (PI), as well as breath-holding index (BHI), in 15 arterial segments comprising the circle of Willis. RESULTS A total of 54 women MwA and 49 HCs were studied. The PIs of all segments of the left and right middle cerebral arteries and the left and right anterior cerebral arteries were significantly higher in MwA with regards to HCs. Also, both the left and right BHIs were significantly higher in MwA than HCs. In addition, MVs of the right vertebral artery and the first segment of the basilar artery were significantly lower in MwA than HCs. Longer duration of migraine aura showed a weak negative correlation with the PI of the left posterior cerebral artery. CONCLUSIONS Our findings suggest increased vessel pulsatility, abnormal cerebrovascular reactivity, and decreased cerebral blood flow velocity in several arterial segments of the Willis circle in women MwA.
Urinary markers of oxidative stress respond to infection and late-life in wild chimpanzees

Oxidative stress (OS) plays a marked role in aging and results from a variety of stressors, making it a powerful measure of health and a way to examine costs associated with life history investments within and across species. However, few urinary OS markers have been examined under field conditions, particularly in primates, and their utility to non-invasively monitor the costs of acute stressors versus the long-term damage associated with aging is poorly understood. In this study, we examined variation in 5 urinary markers of oxidative damage and protection under 5 validation paradigms for 37 wild, chimpanzees living in the Kibale National Park, Uganda. We used 924 urine samples to examine responses to acute immune challenge (respiratory illness or severe wounding), as well as mixed-longitudinal and intra-individual variation with age. DNA damage (8-OHdG) correlated positively with all other markers of damage (F-isoprostanes, MDA-TBARS, and neopterin) but did not correlate with protection (total antioxidant capacity). Within individuals, all markers of damage responded to at least one if not both types of acute infection. While OS is expected to increase with age, this was not generally true in chimpanzees. However, significant changes in oxidative damage were detected within past-prime individuals and those close to death. Our results indicate that OS can be measured using field-collected urine and integrates short- and long-term aspects of health. They further suggest that more data are needed from long-lived, wild animals to illuminate if common age-related increases in inflammation and OS damage are typical or recently aberrant in humans.
A new advanced in silico drug discovery method for novel coronavirus (SARS-CoV-2) with tensor decomposition-based unsupervised feature extraction

Background: COVID-19 is a critical pandemic that has affected human communities worldwide, and there is an urgent need to develop effective drugs. Although there are a large number of candidate drug compounds that may be useful for treating COVID-19, the evaluation of these drugs is time-consuming and costly. Thus, screening to identify potentially effective drugs prior to experimental validation is necessary. Method: In this study, we applied the recently proposed method tensor decomposition (TD)-based unsupervised feature extraction (FE) to gene expression profiles of multiple lung cancer cell lines infected with severe acute respiratory syndrome coronavirus 2. We identified drug candidate compounds that significantly altered the expression of the 163 genes selected by TD-based unsupervised FE. Results: Numerous drugs were successfully screened, including many known antiviral drug compounds such as C646, chelerythrine chloride, canertinib, BX-795, sorafenib, sorafenib, QL-X-138, radicicol, A-443654, CGP-60474, alvocidib, mitoxantrone, QL-XII-47, geldanamycin, fluticasone, atorvastatin, quercetin, motexafin gadolinium, trovafloxacin, doxycycline, meloxicam, gentamicin, and dibromochloromethane. The screen also identified ivermectin, which was first identified as an anti-parasite drug and recently the drug was included in clinical trials for SARS-CoV-2. Conclusions: The drugs screened using our strategy may be effective candidates for treating patients with COVID-19.
Draft Genome Assembly of the Freshwater Apex Predator Wels Catfish (Silurus glanis) Using Linked-Read Sequencing

The wels catfish (Silurus glanis) is one of the largest freshwater fish species in the world. This top predator plays a key role in ecosystem stability, and represents an iconic trophy-fish for recreational fishermen. S. glanis is also a highly valued species for its high-quality boneless flesh, and has been cultivated for over 100 years in Eastern and Central Europe. The interest in rearing S. glanis continues to grow; the aquaculture production of this species has almost doubled during the last decade. However, despite its high ecological, cultural and economic importance, the available genomic resources for S. glanis are very limited. To fulfill this gap we report a de novo assembly and annotation of the whole genome sequence of a female S. glanis. The linked-read based technology with 10X Genomics Chromium chemistry and Supernova assembler produced a highly continuous draft genome of S. glanis: ∼0.8Gb assembly (scaffold N50 = 3.2 Mb; longest individual scaffold = 13.9 Mb; BUSCO completeness = 84.2%), which included 313.3 Mb of putative repeated sequences. In total, 21,316 protein-coding genes were predicted, of which 96% were annotated functionally from either sequence homology or protein signature searches. The highly continuous genome assembly will be an invaluable resource for aquaculture genomics, genetics, conservation, and breeding research of S. glanis.