Miracle-dz/UniFAR-FTUs huggingface dataset:
Healthcare provider perspectives on the uptake of the human papillomavirus vaccine among newcomers to Canada: a qualitative study

ABSTRACT Human papillomavirus is among the most common sexually transmitted infections in the world. Newcomers, defined in Canada as foreign-born individuals who are either immigrants or refugees, but may also include students and undocumented migrants, face numerous barriers to HPV vaccination. This study sought to understand, from the perspective of healthcare providers, barriers and facilitators to HPV vaccination, and recommendations to improve HPV vaccine uptake among newcomers. Semi-structured interviews were conducted with 10 healthcare providers between March and April 2018. Data were analyzed at the manifest level using a Qualitative Content Analysis approach. Categories of barriers to vaccination included: access, communication, knowledge, culture, and provider-related factors. Facilitators included targeted health promotion; understanding the relevance of HPV vaccination; trusting the healthcare system; and cultural sensitivity. Two overarching recommendations were to publicly fund the HPV vaccine, and enhance language- and culturally-appropriate health promotion activities. Further research should explore informational desires and needs from the perspective of newcomers to inform strategies to promote equitable HPV vaccine coverage.
Identification of two principal amyloid-driving segments in variable domains of Ig light chains in systemic light-chain amyloidosis

Systemic light-chain amyloidosis (AL) is a human disease caused by overexpression of monoclonal immunoglobulin light chains that form pathogenic amyloid fibrils. These amyloid fibrils deposit in tissues and cause organ failure. Proteins form amyloid fibrils when they partly or fully unfold and expose segments capable of stacking into β-sheets that pair and thereby form a tight, dehydrated interface. These structures, termed steric zippers, constitute the spines of amyloid fibrils. Here, using a combination of computational (with ZipperDB and Boston University ALBase), mutational, biochemical, and protein structural analyses, we identified segments within the variable domains of Ig light chains that drive the assembly of amyloid fibrils in AL. We demonstrate that there are at least two such segments and that each one can drive amyloid fibril assembly independently of the other. Our analysis revealed that peptides derived from these segments form steric zippers featuring a typical dry interface with high-surface complementarity and occupy the same spatial location of the Greek-key immunoglobulin fold in both λ and κ variable domains. Of note, some predicted steric-zipper segments did not form amyloid fibrils or assembled into fibrils only when removed from the whole protein. We conclude that steric-zipper propensity must be experimentally validated and that the two segments identified here may represent therapeutic targets. In addition to elucidating the molecular pathogenesis of AL, these findings also provide an experimental approach for identifying segments that drive fibril formation in other amyloid diseases.
Assessment of oxygen-uptake efficiency slope in healthy children and children with heart disease: Generation of appropriate reference values for the OUES variable

Background Oxygen-uptake efficiency slope (OUES) is an objective measure of functional capacity that does not require a maximal effort but is considerably dependent on anthropometric variables and requires the generation of an appropriate reference value in children. This study aimed to establish normal reference values for OUES/kg in children with and without congenital heart diseases. Besides that, reference values are presented secondarily for OUES per body surface area (OUES/BSA). Design Cross-sectional. Methods Six hundred and seventy-six children and adolescents performed a maximal cardiopulmonary exercise test (305 healthy controls and 371 individuals with congenital heart defect), between four and 21 years old (481 males and 195 females, with a mean age of 12 years). Results The OUES reference value for the classification of children and adolescents with normal functional capacity (>80% of predicted maximum oxygen uptake) was 34.63 (sensitivity 77% and specificity 83%, p < 0.05). Regarding the body surface area, considering healthy patients and those with heart disease, the cutoff value of the OUES/BSA was 1151 with sensitivity of 79% and specificity of 79%. Conclusions OUES/kg may be an important marker tool in the differentiation between preserved or abnormal functional capacity in children and adolescents with and without congenital heart disease, even at the submaximal level of exercise.
Single-cell stabilization method identifies gonadotrope transcriptional dynamics and pituitary cell type heterogeneity

Abstract Immediate-early response genes (IEGs) are rapidly and transiently induced following an extracellular signal. Elucidating the IEG response patterns in single cells (SCs) requires assaying large numbers of timed samples at high accuracy while minimizing handling effects. To achieve this, we developed and validated RNA stabilization Buffer for Examination of Single-cell Transcriptomes (RNA-Best), a versatile single-step cell and tissue preservation protocol that stabilizes RNA in intact SCs without perturbing transcription patterns. We characterize for the first time SC heterogeneity in IEG responses to pulsatile gonadotropin-releasing hormone (GnRH) stimuli in pituitary gonadotrope cells. Our study identifies a gene-specific hierarchical pattern of all-or-none transcript induction elicited by increasing concentrations of GnRH. This quantal pattern of gene activation raises the possibility that IEG activation, when accurately resolved at the SC level, may be mediated by gene bits that behave as pure binary switches.
Estimating reaction time in Adaptive Cruise Control System

Vehicle automation and cooperation is progressively being introduced in traffic networks. As a consequence research to assess its impacts is currently on-going. Adaptive Cruise Control (ACC) is one of the first automated functionalities available for privately owned vehicles. An experimental study has been conducted to investigate the key features of the ACC controller using Global Navigation Satellite System data. The first remarks based on the data focus on the controller’s reaction time and desired time gap. Both parameters are essential in order to assess the influence of these technologies to safety and traffic flow. It is a common assumption that autonomous vehicles will have negligible reaction time and desired time gap comparable to that of a human driver. This paper presents an experimental study of an ACC-enabled vehicle on car following mode and a methodology for the estimation of the controller’s reaction time that can be used as benchmark in other scenarios. The results show the reaction time to be around l.ls and the time gap to be distinctly larger than that of a human driver. This poses concern on the impact of ACC on traffic flow when a significant number of vehicles will have such systems operating on-board.
Clinical significance of isolated tumor cells and micrometastasis in low‐grade, stage I endometrial cancer

Ultrastaging in endometrial cancer (EC) led to increased detection of isolated tumor cells (ITC, ≤0.2 mm) and micrometastases (MM, 0.2‐2 mm), with unclear effect on prognosis. Our aim was to characterize the impact of ITC and MM on the outcome of these patients.
What’s special about orthographic processing? Further evidence from transposition effects in same-different matching

We sought evidence for letter-specific processing in the same-different matching task by comparing performance to random consonant strings and either strings of symbols (Experiment 1) or strings of digits (Experiment 2). The strings could be aligned horizontally or vertically, and on “different” response trials the to-be-matched strings could differ by the transposition of two adjacent characters or by the substitution of two adjacent characters. Making a “different” response was harder when the difference involved a transposition compared with a substitution—the transposition effect. Crucially, the transposition effect was significantly greater for letters than for symbols or digits when stimuli were aligned horizontally, but did not differ significantly across stimulus type with vertically aligned strings. These results suggest that it is processing specific to horizontally aligned letter strings, a reading-specific mechanism, that causes the greater transposition effects for letter stimuli in the same-different matching task when stimuli are arranged horizontally.
Antiplatelet Therapy in Primary Spontaneous and Oral Anticoagulation–Associated Intracerebral Hemorrhage

Background and Purpose— This study determined the influence of concomitant antiplatelet therapy (APT) on hematoma characteristics and outcome in primary spontaneous intracerebral hemorrhage (ICH), vitamin K antagonist (VKA)- and non–VKA oral anticoagulant-associated ICH. Methods— Data of retrospective cohort studies and a prospective single-center study were pooled. Functional outcome, mortality, and radiological characteristics were defined as primary and secondary outcomes. Propensity score matching and logistic regression analyses were performed to determine the association between single or dual APT and hematoma volume. Results— A total of 3580 patients with ICH were screened, of whom 3545 with information on APT were analyzed. Three hundred forty-six (32.4%) patients in primary spontaneous ICH, 260 (11.4%) in VKA-ICH, and 30 (16.0%) in non–VKA oral anticoagulant-associated ICH were on APT, and these patients had more severe comorbidities. After propensity score matching VKA-ICH patients on APT presented with less favorable functional outcome (modified Rankin Scale score, 0–3; APT, 48/202 [23.8%] versus no APT, 187/587 [31.9%]; P=0.030) and higher mortality (APT, 103/202 [51.0%] versus no APT, 237/587 [40.4%]; P=0.009), whereas no significant differences were present in primary spontaneous ICH and non–VKA oral anticoagulant-associated ICH. In VKA-ICH, hematoma volume was significantly larger in patients with APT (21.9 [7.4–61.4] versus 15.7 [5.7–44.5] mL; P=0.005). Multivariable regression analysis revealed an association of APT and larger ICH volumes (odds ratio, 1.80 [1.20–2.70]; P=0.005), which was more pronounced in dual APT and supratherapeutically anticoagulated patients. Conclusions— APT does not affect ICH characteristics and outcome in primary spontaneous ICH patients; however, it is associated with larger ICH volume and worse functional outcome in VKA-ICH, presumably by additive antihemostatic effects. Combination of anticoagulation and APT should, therefore, be diligently evaluated and restricted to the shortest possible time frame.
Identification of eight key miRNAs associated with renal cell carcinoma: A meta-analysis

Renal cell carcinoma (RCC) is the most common renal carcinoma in the human kidney. To date, to the best of our knowledge, there are no biomarkers for the early monitoring and diagnosis of RCC patients. The present study aimed to develop deeper insight into the molecular mechanisms of microRNAs (miRNAs/miRs) in the regulation of RCC development and to reveal candidate miRNA biomarkers in human RCC. A meta-analysis was used to integrate the published and independent RCC miRNA expression profiling investigations that compared the miRNA expression profiles in RCC samples with control samples. The meta-signature miRNA target genes were then predicted in TargetScan. The predicted targets were further analyzed using Gene Ontology and pathway enrichment analysis with the Database for Annotation, Visualization and Integrated Discovery online tool, and then the transcription factors of meta-signature miRNA target genes were identified in Tfacts. A total of 7 publicly available and independent RCC miRNA expression profiling datasets were collected, and 2 upregulated (hsa-miR-155-5p and hsa-miR-210-5p) and 6 downregulated (hsa-miR-138-5p, hsa-miR-141-5p, hsa-miR-200c-5p, hsa-miR-362-5p, hsa-miR-363-5p and hsa-miR-429) meta-signature miRNAs in renal carcinoma were identified. The targeted gene enrichment analysis indicated that the meta-signature miRNAs may influence several pathways that participate in cancerogenesis, including the ‘rap1 signaling pathway’, ‘renal cell carcinoma’ and ‘microRNAs in cancer’. Overall, the present meta-analysis identified 2 upregulated and 6 downregulated meta-signature miRNAs from 7 renal carcinoma datasets, the dysregulated miRNAs that may contribute to kidney carcinoma development. This research may reveal candidate miRNA biomarkers in human RCC.
The assessment of different risk classification systems for gastrointestinal stromal tumors (GISTs): the analytic results from the SEER database

Abstract Background: Although various risk classification systems for GISTs have been proposed, the optimum one remains uncertain. In the present study, we compared the prognostic stratification of different risk classification systems for GIST patients. Methods: We reviewed those patients who were pathologically diagnosed with GISTs in the SEER database between 2009 and 2014. All patients were classified into different risk groups according to the NIH criteria, AFIP criteria and AJCC staging system, respectively. The prognostic differences between different risk groups were compared and clinicopathologic features were analyzed. Results: The prognosis of small intestinal GISTs was not significantly different from that of gastric GISTs. For gastric GIST patients, there was no significant prognostic difference between very low risk and low risk group according to the NIH and AFIP criteria. However, the prognostic stratification for two groups could be improved by the AJCC staging system. For small intestinal GIST patients, the prognostic difference between low risk and intermediate risk group was not stratified properly by the NIH and AFIP criteria. However, the prognostic difference between two groups could reach statistical significance according to the AJCC staging system. Unlike gastric GISTs, tumor size was not identified as an independent factor influencing the prognosis of small intestinal GISTs. Conclusions: The AJCC staging system could provide a better prognostic stratification for GIST patients compared with the NIH and AFIP criteria, regardless of gastric or small intestinal tumor. However, primary tumor location and tumor size may be reconsidered and revised in the risk classification system.
Interventions to increase hand hygiene compliance in a tertiary university hospital over a period of 5 years: An iterative process of information, training and feedback.

AIMS AND OBJECTIVE To explore whether an iterative process of information and training paired with a feedback system to observed healthcare professionals and the respective management improves hand hygiene (HH) compliance. BACKGROUND Healthcare-associated infections are a major risk for patient safety, and adherence to the "My five moments" (M5M) for HH varies significantly within organisations as well as within healthcare professional groups. Identified barriers in a baseline survey revealed the need of more information, training, repetitive compliance measurements and feedback to all healthcare professionals. DESIGN A quality improvement project using the method of direct observation of healthcare professionals in nonsurgical and surgical wards. METHODS Between 2013 and 2017, 6,009 healthcare professionals were informed and trained, and HH compliance measurements were performed by hygiene experts. Compliance measurement results were documented in an online tool to give an immediate feedback to observed healthcare professionals. Additionally, a report was forwarded to the management of the respective department to raise awareness. Compliance rates per year were descriptively summarised. The research and reporting methodology followed SQUIRE 2.0. RESULTS In total, 84 compliance measurements with 19,295 "M5M for HH" were observed in 49 wards. Overall, mean HH compliance increased from 81.9 ± 5.2% in 2013 to 94.0 ± 3.6% in 2017. Physicians' HH compliance rate improved from 69.0 ± 16.6% to 89.3 ± 6.6%, that of nurses from 86.0 ± 6.9% to 96.4 ± 3.1%, and that of others from 60.5 ± 27.9% to 83.8 ± 20.2%. All M5M for HH (#1-#5) increased over the study period (#1: +16.9%; #2: +20.5%; #3: +7.6%; #4: +5.9%; #5: +12.7%). CONCLUSIONS Results demonstrated that an iterative process of information, training, observation and feedback over a period of 5 years can be successful in increasing HH compliance. Positive trends were observed for HH compliance rates across all healthcare professional groups as well as for all M5M for HH.
Potential Antinociceptive Effects of Chinese Propolis and Identification on Its Active Compounds

Propolis is an important bee product which has been applied to the treatment of several diseases. The aim of this study was to understand the material basis of Chinese propolis on pain relief; different Chinese propolis fractions (40W, 40E, 70E, and 95E raw propolis extracted followed by 40%, 70%, or 95% ethanol) were prepared, and their antinociceptive effects were evaluated. By analyzing using UPLC-Q-TOF-MS, we showed that 40W was rich in phenolic acids, like caffeic acid, while 40E, 70E, and 95E have relatively high levels in flavonoids, like galangin, pinocembrin, and chrysin. Notably, chrysin amounts in 70E and 95E are much higher than those in 40E fraction. Antinociceptive effects by these propolis fractions were evaluated in mice using acetic acid-induced writhing test, hot plate test, and tail immersion test, respectively. We noticed that only 40E fraction showed a significant reduction on acetic acid-induced writhing test. Importantly, in the hot plate test, all groups showed their effectiveness, except for the 70E group. We also noticed that 40W, 40E, and 95E administration caused an increase in the tail withdrawal latency of the mice. These data suggested that the different antinociceptive effects of different fractions from Chinese propolis extracts are directly link to their flavonoid composition.
Minimum sample size for developing a multivariable prediction model: PART II ‐ binary and time‐to‐event outcomes

When designing a study to develop a new prediction model with binary or time‐to‐event outcomes, researchers should ensure their sample size is adequate in terms of the number of participants (n) and outcome events (E) relative to the number of predictor parameters (p) considered for inclusion. We propose that the minimum values of n and E (and subsequently the minimum number of events per predictor parameter, EPP) should be calculated to meet the following three criteria: (i) small optimism in predictor effect estimates as defined by a global shrinkage factor of ≥0.9, (ii) small absolute difference of ≤ 0.05 in the model's apparent and adjusted Nagelkerke's R2, and (iii) precise estimation of the overall risk in the population. Criteria (i) and (ii) aim to reduce overfitting conditional on a chosen p, and require prespecification of the model's anticipated Cox‐Snell R2, which we show can be obtained from previous studies. The values of n and E that meet all three criteria provides the minimum sample size required for model development. Upon application of our approach, a new diagnostic model for Chagas disease requires an EPP of at least 4.8 and a new prognostic model for recurrent venous thromboembolism requires an EPP of at least 23. This reinforces why rules of thumb (eg, 10 EPP) should be avoided. Researchers might additionally ensure the sample size gives precise estimates of key predictor effects; this is especially important when key categorical predictors have few events in some categories, as this may substantially increase the numbers required.
Tackling Sequence to Sequence Mapping Problems with Neural Networks

In Natural Language Processing (NLP), it is important to detect the relationship between two sequences or to generate a sequence of tokens given another observed sequence. We call the type of problems on modelling sequence pairs as sequence to sequence (seq2seq) mapping problems. A lot of research has been devoted to finding ways of tackling these problems, with traditional approaches relying on a combination of hand-crafted features, alignment models, segmentation heuristics, and external linguistic resources. Although great progress has been made, these traditional approaches suffer from various drawbacks, such as complicated pipeline, laborious feature engineering, and the difficulty for domain adaptation. Recently, neural networks emerged as a promising solution to many problems in NLP, speech recognition, and computer vision. Neural models are powerful because they can be trained end to end, generalise well to unseen examples, and the same framework can be easily adapted to a new domain. The aim of this thesis is to advance the state-of-the-art in seq2seq mapping problems with neural networks. We explore solutions from three major aspects: investigating neural models for representing sequences, modelling interactions between sequences, and using unpaired data to boost the performance of neural models. For each aspect, we propose novel models and evaluate their efficacy on various tasks of seq2seq mapping.
Peroxiredoxin 1/2 protects brain against H2O2‐induced apoptosis after subarachnoid hemorrhage

Recent studies suggest that peroxiredoxin1/2 (Prx1/2) may be involved in the pathophysiology of post‐ischemic inflammatory responses in the brain. In this study, we assessed the distribution and function of Prx1/2 in mice after experimental subarachnoid hemorrhage (SAH). We investigated the distribution of Prx1/2 in the brains of mice both in vivo and in vitro using immunofluorescence staining. The expression of Prx1/2 after SAH was determined by Western blot. Adenanthin was used to inhibit Prx1/2 function, and Prx1/2 overexpression was achieved by injecting adeno‐associated virus. Oxidative stress and neuronal apoptosis were assessed both in vivo and in vitro. The neurologic function, inflammatory response, and related cellular signals were analyzed. The results showed that Prx1 was mainly expressed in astrocytes, and Prx2 was abundant in neurons. The expression of Prx1/2 was elevated after SAH, and their expression levels peaked before proinflammatory cytokines. Inhibiting Prx1/2 promoted neuronal apoptosis by increasing the hydrogen peroxide (H2O2) levels via the apoptosis signal‐regulating kinase 1/p38 pathway. By contrast, overexpression of Prx1/2 attenuated oxidative stress and neuronal apoptosis after SAH. Thus, early expression of Prx1/2 may protect the brain from oxidative damage after SAH and may provide a novel target for treating SAH. —Lu, Y. , Zhang, X. ‐S. , Zhou, X. ‐M. , Gao, Y. ‐Y. , Chen, C. ‐L. , Liu, J.‐P., Ye, Z. ‐N. , Zhang, Z. ‐H. , Wu, L. ‐Y. , Li, W. , Hang, C. ‐H. Peroxiredoxin 1/2 protects brain against H2O2‐induced apoptosis after subarachnoid hemorrhage. FASEB J. 33, 3051–3062 (2019). www.fasebj. org