Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk Factors and Prognostic Factors of Hearing Impairment in Neonatal Intensive Care Unit-Treated Infants

Background: Infants admitted to the neonatal intensive care unit (NICU) have a higher incidence of congenital hearing loss compared with the healthy newborn population. Objectives: To clarify the relationship between risk factors for hearing impairment in NICU-treated infants and deterioration of the auditory brainstem response (ABR) threshold during childhood. Method: We screened 1,071 high-risk infants admitted to the NICU for hearing impairment. One-hundred forty-eight infants exhibited an abnormal ABR threshold of ≥40 dB nHL. We analyzed the correlation of change in ABR threshold with risk factors for future hearing impairment. Results: Among infants treated in the NICU, 148 (13.8%) exhibited an ABR threshold of ≥40 dB nHL; 107 of these 148 (72.3%) showed hearing change in the process (102 showed improvement to normal hearing level, whereas 5 showed further deterioration). Our analysis showed that the factors contributing to the elevation of ABR threshold were oxygen administration and chromosomal aberrations. Conclusions: Factors related to the elevation of ABR threshold were oxygen administration and the presence of chromosomal aberrations. Awareness of risk factors that are more likely to cause hearing loss in infants may aid in follow-up treatment of these children.
Polymorphisms of Ionotropic Glutamate Receptor-Related Genes and the Risk of Autism Spectrum Disorder in a Chinese Population

Objective To evaluate the association of GRIK2 and NLGN1 with autism spectrum disorder in a Chinese population. Methods We performed spatio-temporal expression analysis of GRIK2 and NLGN1 in the developing prefrontal cortex, and examined the expression of the genes in ASD cases and healthy controls using the GSE38322 data set. Following, we performed a case-control study in a Chinese population. Results The analysis using the publicly available expression data showed that GRIK2 and NLGN1 may have a role in the development of human brain and contribute to the risk of ASD. Later genetic analysis in the Chinese population showed that the GRIK2 rs6922753 for the T allele, TC genotype and dominant model played a significant protective role in ASD susceptibility (respectively: OR=0.840, p=0.023; OR=0.802, p=0.038; OR=0.791, p=0.020). The NLGN1 rs9855544 for the G allele and GG genotype played a significant protective role in ASD susceptibility (respectively: OR=0.844, p=0.019; OR=0.717, p=0.022). After adjusting p values, the statistical significance was lost (p>0.05). Conclusion Our results suggested that GRIK2 rs6922753 and NLGN1 rs9855544 might not confer susceptibility to ASD in the Chinese population.
Somatic mutations and promotor methylation of the ryanodine receptor 2 is a common event in the pathogenesis of head and neck cancer

Genomic sequencing projects unraveled the mutational landscape of head and neck squamous cell carcinoma (HNSCC) and provided a comprehensive catalog of somatic mutations. However, the limited number of significant cancer‐related genes obtained so far only partially explains the biological complexity of HNSCC and hampers the development of novel diagnostic biomarkers and therapeutic targets. We pursued a multiscale omics approach based on whole‐exome sequencing, global DNA methylation and gene expression profiling data derived from tumor samples of the HIPO‐HNC cohort (n = 87), and confirmed new findings with datasets from The Cancer Genome Atlas (TCGA). Promoter methylation was confirmed by MassARRAY analysis and protein expression was assessed by immunohistochemistry and immunofluorescence staining. We discovered a set of cancer‐related genes with frequent somatic mutations and high frequency of promoter methylation. This included the ryanodine receptor 2 (RYR2), which showed variable promoter methylation and expression in both tumor samples and cell lines. Immunohistochemical staining of tissue sections unraveled a gradual loss of RYR2 expression from normal mucosa via dysplastic lesion to invasive cancer and indicated that reduced RYR2 expression in adjacent tissue and precancerous lesions might serve as risk factor for unfavorable prognosis and upcoming malignant conversion. In summary, our data indicate that impaired RYR2 function by either somatic mutation or epigenetic silencing is a common event in HNSCC pathogenesis. Detection of RYR2 expression and/or promoter methylation might enable risk assessment for malignant conversion of dysplastic lesions.
Epidemiology of genital human papillomavirus infection.

Recent clinical research has suggested a link between specific human papillomavirus types and the development of cancers of the genital tract and anus; however, supportive epidemiologic data are not well developed. In both the US and the UK, condylomata acuminata is the most commonly diagnosed viral sexually transmitted disease. The highest incidence is among females 20-24 years of age. The results of 6 studies to examine the prevalence of human papillomavirus suggest a rate of 1-13%, with a positive association to the prevalence of cervical intraepithelial neoplasia in that population. It is estimated that genital human papillomavirus infection has a 10% prevalence among men and women in the US 15-49 years of age: 1% have condylomata, 2% have lesions visible only by magnification with the colposcope or hand lens, and 7% have clinically inapparent infections. Human papillomavirus types 6 and 11 tend to cause condylomata and low-grade epithelial cell atypia, while types 16, 18, and 31 have been found in higher-grade intraepithelial neoplasia and invasive cervical cancers. Current evidence suggests a long latency between acquisition of genital papillomavirus infection and the development of cervical malignancy, with cervical cancer generally not developing until the 5th decade and beyond. From an epidemiologic point of view, the current research literature lacks evidence of careful selection and definition of study populations, consistent quality control of clinical and laboratory methods, and thorough statistical analyses. To make it more possible to compare the results of different studies, more attention to epidemiologic factors is needed.
Reduplication in child phonology

In recent issues of this journal, two articles-Schwartz, Leonard, Wilcox & Folger (1980) and Fee & Ingram (1982) — have provided valuable data and new insights on the phenomenon of reduplication in phonological development. The best general treatment of the phenomenon is probably still the lengthy section in Leopold (1947: 213-26), but the new studies sharpen the focus and add the sophistication of statistical and functional analysis. In this note I would like to restate four of the principal issues and comment on the different positions taken on them. These issues are: reduplication as a general (universal) strategy vs. an individual strategy, the relation of the use of reduplication to the child's age or stage of language development, the apparent functions of reduplication in development, and the place of reduplication in a general theory of phonological development.
ASSESSMENT OF CFD CODES USED IN NUCLEAR REACTOR SAFETY SIMULATIONS

* , to produce state-of-the-art reports on different aspects of the subject. The work of the second group, WG2, was to document the existing assessment databases for CFD simulation in the context of Nuclear Reactor Safety (NRS) analysis, to gain a measure of the degree of quality and trust in CFD as a numerical analysis tool, and to take initiatives to extend the existing databases. The group worked over the period of 2003-2007 and produced a final state-of- the-art report. The present paper summarises the material gathered during the study, illustrating the points with a few highlights. A total of 22 safety issues were identified for which the application of CFD was considered to potentially bring real benefits in terms of better understanding and increased safety. A list of the existing databases was drawn up and synthesised, both from the nuclear area and from other parallel, non-nuclear, industrial activities. The gaps in the technology base were also identified and discussed. In order to initiate new ways of bringing experimentalists and numerical analysts together, an international workshop -- CFD4NRS (the first in a series) -- was organised, a new blind benchmark activity was set up based on turbulent mixing in T- junctions, and a Wiki-type web portal was created to offer online access to the material put together by the group giving the reader the opportunity to update and extend the contents to keep the information source topical and dynamic.
Raman imaging highlights biochemical heterogeneity of human eosinophils versus human eosinophilic leukaemia cell line

Eosinophils are acidophilic granulocytes that develop in the bone marrow. Although their population contributes only to approximately 1–6% of all leucocytes present in the human blood, they possess a wide range of specific functions. They play a key role in inflammation‐regulating processes, when their numbers can increased to above 5 × 109/l of peripheral blood. Their characteristic feature is the presence of granules containing eosinophil peroxidase (EPO), the release of which can trigger a cascade of events promoting oxidative stress, apoptosis or necrosis, leading finally to cell death. Raman spectroscopy is a powerful technique to detect EPO, which comprises a chromophore protoporphyrin IX. Another cell structure associated with inflammation processes are lipid bodies (lipid‐rich organelles), also well recognized and imaged using high resolution confocal Raman spectroscopy. In this work, eosinophils isolated from the blood of a human donor were analysed versus their model, EoL‐1 human eosinophilic leukaemia cell line, by Raman spectroscopic imaging. We showed that EPO was present only in primary cells and not found in the cell line. Eosinophils were activated using phorbol 12‐myristate 13‐acetate, which resulted in lipid bodies formation. An effect of cells stimulation was studied and compared for eosinophils and EoL‐1.
Clinician Perception of a Machine Learning-Based Early Warning System Designed to Predict Severe Sepsis and Septic Shock.

OBJECTIVE To assess clinician perceptions of a machine learning-based early warning system to predict severe sepsis and septic shock (Early Warning System 2.0). DESIGN Prospective observational study. SETTING Tertiary teaching hospital in Philadelphia, PA. PATIENTS Non-ICU admissions November-December 2016. INTERVENTIONS During a 6-week study period conducted 5 months after Early Warning System 2.0 alert implementation, nurses and providers were surveyed twice about their perceptions of the alert's helpfulness and impact on care, first within 6 hours of the alert, and again 48 hours after the alert. MEASUREMENTS AND MAIN RESULTS For the 362 alerts triggered, 180 nurses (50% response rate) and 107 providers (30% response rate) completed the first survey. Of these, 43 nurses (24% response rate) and 44 providers (41% response rate) completed the second survey. Few (24% nurses, 13% providers) identified new clinical findings after responding to the alert. Perceptions of the presence of sepsis at the time of alert were discrepant between nurses (13%) and providers (40%). The majority of clinicians reported no change in perception of the patient's risk for sepsis (55% nurses, 62% providers). A third of nurses (30%) but few providers (9%) reported the alert changed management. Almost half of nurses (42%) but less than a fifth of providers (16%) found the alert helpful at 6 hours. CONCLUSIONS In general, clinical perceptions of Early Warning System 2.0 were poor. Nurses and providers differed in their perceptions of sepsis and alert benefits. These findings highlight the challenges of achieving acceptance of predictive and machine learning-based sepsis alerts.
Modeling and Predicting Developmental Trajectories of Neuropsychiatric Dimensions Associated With Copy Number Variations

Abstract Copy number variants, such as duplications and hemizygous deletions at chromosomal loci of up to a few million base pairs, are highly associated with psychiatric disorders. Hemizygous deletions at human chromosome 22q11.2 were found to be associated with elevated instances of schizophrenia and autism spectrum disorder in 1992 and 2002, respectively. Following these discoveries, many mouse models have been developed and tested to analyze the effects of gene dose alterations in small chromosomal segments and single genes of 22q11.2. Despite several limitations to modeling mental illness in mice, mouse models have identified several genes on 22q11.2—Tbx1, Dgcr8, Comt, Sept5, and Prodh—that contribute to dimensions of autism spectrum disorder and schizophrenia, including working memory, social communication and interaction, and sensorimotor gating. Mouse studies have identified that heterozygous deletion of Tbx1 results in defective social communication during the neonatal period and social interaction deficits during adolescence/adulthood. Overexpression of Tbx1 or Comt in adult neural progenitor cells in the hippocampus delays the developmental maturation of working memory capacity. Collectively, mouse models of variants of these 4 genes have revealed several potential neuronal mechanisms underlying various aspects of psychiatric disorders, including adult neurogenesis, microRNA processing, catecholamine metabolism, and synaptic transmission. The validity of the mouse data would be ultimately tested when therapies or drugs based on such potential mechanisms are applied to humans.
Dexketoprofen Versus IV Paracetamol in Patients Presenting With Dysmenorrhea to the Emergency Department : A Randomized Controlled Trial

Address for Correspondence: Dr. Mustafa Serinken, Department of Emergency Medicine, Pamukkale University School of Medicine, Denizli, Turkey e-mail: aserinken@hotmail.com Received: 4 July 2017 Accepted: 30 January 2018 • DOI: 10.4274/balkanmedj.2016. 0536 Available at www.balkanmedicaljournal. org Cite this article as: Serinken M, Eken C. Karcıoğlu Ö. IV Dexketoprofen vs. IV Paracetamol in Patients Presented with Dysmenorrhea to Emergency Department: A Randomized Controlled Trial. Balkan Med J ©Copyright 2018 by Trakya University Faculty of Medicine / The Balkan Medical Journal published by Galenos Publishing House. Mustafa Serinken1, Cenker Eken2, Özgür Karcıoğlu3
Prediction Accuracy With Electronic Medical Records Versus Administrative Claims

Supplemental Digital Content is available in the text. Objective: The objective of this study was to evaluate the incremental predictive power of electronic medical record (EMR) data, relative to the information available in more easily accessible and standardized insurance claims data. Data and Methods: Using both EMR and Claims data, we predicted outcomes for 118,510 patients with 144,966 hospitalizations in 8 hospitals, using widely used prediction models. We use cross-validation to prevent overfitting and tested predictive performance on separate data that were not used for model training. Main Outcomes: We predict 4 binary outcomes: length of stay (≥7 d), death during the index admission, 30-day readmission, and 1-year mortality. Results: We achieve nearly the same prediction accuracy using both EMR and claims data relative to using claims data alone in predicting 30-day readmissions [area under the receiver operating characteristic curve (AUC): 0.698 vs. 0.711; positive predictive value (PPV) at top 10% of predicted risk: 37.2% vs. 35.7%], and 1-year mortality (AUC: 0.902 vs. 0.912; PPV: 64.6% vs. 57.6%). EMR data, especially from the first 2 days of the index admission, substantially improved prediction of length of stay (AUC: 0.786 vs. 0.837; PPV: 58.9% vs. 55.5%) and inpatient mortality (AUC: 0.897 vs. 0.950; PPV: 24.3% vs. 14.0%). Results were similar for sensitivity, specificity, and negative predictive value across alternative cutoffs and for using alternative types of predictive models. Conclusion: EMR data are useful in predicting short-term outcomes. However, their incremental value for predicting longer-term outcomes is smaller. Therefore, for interventions that are based on long-term predictions, using more broadly available claims data is equally effective.
A Power Adaptive, 1.22-pW/Hz, 10-MHz Read-Out Front-End for Bio-Impedance Measurement

This paper presents a read-out front-end application-specific integrated circuit (ASIC) for the measurement of tissue impedances. The 10 mm2 2-channel front-end ASIC is fabricated in a 0.18 μm CMOS technology. The measurement results show that the proposed ASIC operates over a frequency range of 100 Hz up to 10 MHz. The ASIC has 1.22 pW/Hz power performance, with an SNR over 72 dB for frequencies $\leq$1 MHz, and over 65 dB SNR for frequencies $\geq$1 MHz. The total measured power consumption of the read-out front-end is shown to range from 2.1 to 21.7 mW depending on the input frequency. To achieve a wide dynamic range, the instrumentation amplifier has an adaptive gain control feature, and it employs programmable bias currents and reconfigurable structure to save power while processing low-frequency signals. A dual digital-to-analog converter (DAC) hybrid SAR analog-to-digital converter (ADC) is presented that reduces the power consumption of the ADC driver by sevenfold for frequencies between 4 kHz and 1 MHz.
The effect of emergency department delays on 30-days mortality in Central Norway.

OBJECTIVE To assess whether prolonged length of stay in the emergency department was associated with risk of death. METHODS We analysed data from 165,183 arrivals at St. Olav's University Hospital's emergency department from 2011 to 2018, using an instrumental variable method. As instruments for prolonged length of emergency department stay, we used indicators measured before arrival of the patient. These indicators were used to study the association between prolonged length of emergency department stay and risk of death, being discharged from the emergency department and length of hospitalisation for those who were hospitalised. RESULTS Mean length of stay in the emergency department was 2.9 hours, and 30-day risk of death was 3.4%. Per hour prolonged length of stay in the emergency department, the overall change in risk of death was close to zero, with a narrow 95% confidence interval of -0.5 to 0.7 percentage points. Prolonged emergency department stay was associated with a higher probability of being discharged from the emergency department without admission to the hospital. We found no substantial differences in length of hospitalisation for patients who were admitted. CONCLUSION In this study, prolonged emergency department stay was not associated with increased risk of death.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Considerations of heterogeneity in clinical trials for hepatocellular carcinoma

ABSTRACT Introduction: Clinical trials in hepatocellular carcinoma (HCC) exhibit a high degree of heterogeneity. These heterogeneities may lead to unexpected results among clinical trials. Area covered: In this review, we address the heterogeneity noted in early phase HCC trials, trials involving transarterial chemoembolization, and advanced HCC trials. Furthermore, we discuss possible methods to attenuate the detrimental effects of heterogeneity when conducting clinical trials. Expert opinion: Clinical trials in HCC exhibit an inherently high degree of heterogeneity because of various reasons: tumor heterogeneity, different cirrhotic backgrounds, various etiologies of cirrhosis, and geographical differences in practice and expertise. Such heterogeneity may cause imbalance among the enrolled patient population, premature withdrawal from the clinical trial, and variable response to the treatment. In addition, methodological heterogeneity also exists in designing trial protocol and response evaluation. All these factors may eventually lead to conflicting results among clinical trials. Accounting for these heterogeneities is important to foster the success of future trials. In recent years, significant progress with molecular targeted agents and immune checkpoint inhibitors was made in advanced HCC. These new agents are also being tested in clinical trials involving earlier stage HCC and will also face the challenge of these issues.
Mechanisms of Toxicity and Cardiotoxicity of Alcohol Extract from Root, Stem and Leaf of Chloranthus Serratus.

Abstract Objective To compare the differences of cardiotoxicity of alcohol extract from root, stem and leaf of Chloranthus serratus in the rats, and discuss preliminarily its mechanism of toxicity. Methods Rats were randomly divided into four groups: blank, root alcohol, stem alcohol and leaf alcohol, with 8 in each group. After 14 days of continuous intragastric administration, the body mass change curves were drawn. The cardiac coefficient was calculated. The contents of creatine kinase （CK）, creatine kinase isoenzyme （CK-MB）, lactate dehydrogenase （LDH） and α-hydroxybutyrate dehydrogenase （α-HBDH） as well as the content changes of oxidative stress indexes - total superoxide dismutase （T-SOD） and malondialdehyde （MDA） in the serum of rats were detected. The cardiac pathomorphology changes in the rats were observed. The expression of intercellular adhesion molecule （ICAM-1） and heme oxygenase （HO-1） in myocardial tissue was detected. Results Body mass growth rate： stem alcohol group was the smallest, followed by leaf alcohol group. The difference of cardiac coefficient of every group had no statistical significance （P>0.05）. The myocardial tissues of stem alcohol group suffered the most serious damage, followed by the leaf alcohol group. The contents of CK, CK-MB, LDH and α-HBDH in stem alcohol group increased （P<0.05）. The increase of MDA content and decrease of T-SOD content in stem alcohol group had statistical significance compared with the blank group and root alcohol group, while the leaf alcohol group only had statistical significance in the decrease of T-SOD content compared with the blank group （P<0.05）. The positive expression of ICAM-1 enhanced and the expression of HO-1 protein decreased in every group after the intervention of different extracts. The change trend was stem alcohol > leaf alcohol > root alcohol group. Conclusion The alcohol extract from the stem has the highest cardiotoxicity, followed by the leaf extract, and its mechanism of toxicity may be related to oxidative stress.