Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuropsychological Norms for the U.S.-Mexico Border Region in Spanish (NP-NUMBRS) Project: Methodology and sample characteristics

Abstract Objective The present paper describes the methodology and sample characteristics of the Neuropsychological Norms for the U.S.-Mexico Border Region in Spanish (NP-NUMBRS) Project, which aimed to generate demographically-adjusted norms for a battery of neuropsychological tests in this population. Methods The sample consisted of 254 healthy Spanish-speakers, ages 19-60 years, recruited from the U.S.-Mexico border regions of Arizona (n = 102) and California (n = 152). Participants completed a comprehensive neuropsychological test battery assessing multiple domains (verbal fluency, speed of information processing, attention/working memory, executive function, learning and memory, visual-spatial skills and fine motor skills). Fluency in both Spanish and English was assessed with performance-based measures. Other culturally-relevant data on educational, social, and language background were obtained via self-report. Demographic influences on test performances were modeled using fractional polynomial equations that allow consideration of linear and non-linear effects. Results There were no significant demographic differences between participants tested in Arizona and California. Age and gender were similar across education ranges. Two thirds of the sample were Spanish dominant and the remainder were considered bilingual. Individual articles in this Special Issue detail the generation of demographically adjusted T-scores for the various tests in the battery as well as an exploration of bilingualism effects. Discussion Norms developed through the NP-NUMBRS project stand to improve the diagnostic accuracy of neuropsychological assessment in Spanish-speaking young-to-middle-aged adults living in the U.S.-Mexico border region. Application of the present norms to other groups should be done with caution.
Phase I/II Study of Erlotinib to Determine the Optimal Dose in Patients With Non‐Small Cell Lung Cancer Harboring Only EGFR Mutations

The recommended daily dose of erlotinib was determined for patients with all types of non‐small cell lung cancer (NSCLC). We determined the optimal dose (OD) in patients with NSCLC harboring only epidermal growth factor receptor (EGFR) sensitizing mutations. EGFR‐tyrosine kinase inhibitor‐naïve patients with sensitizing mutations were eligible. Clinical OD was determined in a phase I/II study based on the continual re‐assessment method (CRM) of both disease control and dose‐limiting toxicity, defined as any toxicity of grade 2 (G2) or higher within 8 weeks. We also determined the pharmacologic OD via a pharmacokinetic (PK) study. Thirty‐eight patients were enrolled. Clinical OD was 25 mg/day by the CRM. Median progression‐free survival (mPFS) was 9.3 months. In receiver operating characteristic (ROC) analysis of mPFS, the trough concentration ( Cminss ) was ≥ 0.30 μg/mL. The area under the curve (AUC) and Cminss were predicted via population PK (PopPK) or a bootstrap of 100 iterations (PopPK100). TOX20 was defined as < 20% duration of any toxicity ≥ G2 during the PFS period. In ROC analysis of mPFS and TOX20 in the PopPK100 study, Cminss was ≥ 0.17 and < 0.32 μg/mL, respectively. In ROC analysis of mPFS and TOX20 in the PopPK100 study, Cminss was ≥ 0.15 and < 0.31 μg/mL, AUC was ≥ 14.4 and < 14.5 μg/mL•hour, and the dosage was ≥ 58.4 and < 58.8 mg/day, respectively. Clinical and pharmacologic ODs were 25 by CRM and 50–60 mg/day by PK, respectively. The proposed starting OD is 50–60 mg/day, with personalized adjustment of 0.15–0.31 μg/mL based on Cminss as determined by PopPK monitoring.
Optimization of seat allocation with fixed prices: An application of railway revenue management in China

China Railway Corporation (CRC) has been paid more attention to passenger transportation revenue, with its increase proportion in transportation revenue. Due to the price regulation, the only way CRC can improve ticket sale profit is to find a best seat allocation scheme. This study focuses on the optimization of railway revenue management problem in China with consideration of i) customer behaviors including their arrival and purchase preferences, ii) a specific ticket booking mechanism called “seat-based control”. To evaluate the performance of seat-based control, we build a Discrete-Time Markov Chain model to describe the ticket reservation process and then design a genetic algorithm to find approximate solutions. The performance of proposed method is tested in two experiments with two other benchmarks. Finally, we apply it to practical data of the Nanning-Guangzhou high-speed railway line.
Outcome after Tibial Plateau Levelling Osteotomy and Modified Maquet Procedure in Dogs with Cranial Cruciate Ligament Rupture

Abstract Objective The aim of this study was to compare outcomes after tibial plateau levelling osteotomy (TPLO) and modified Maquet procedure (MMP) for the treatment of cranial cruciate ligament rupture (CCLR) in dogs using clinical and radiographic evaluation and treadmill-based force plate gait analysis. Study Design This study was a prospective, randomized, controlled study. Materials and Methods Sixty-one dogs (76 joints) with CCLR were treated with TPLO (n = 30 dogs, 41 joints) or MMP (n = 31 dogs, 35 joints) and compared with a control group of 16 healthy Labrador Retrievers. Outcomes after surgery were compared by clinical orthopaedic assessment, radiographic evaluation and force plate gait analysis performed preoperatively, and then at 6 weeks, 3 and 6 months postoperatively. For objective comparison of ground reaction forces, the data were compared with the control group. Major complications were reported. Results A significant improvement in ground reaction forces was reached in all surgically treated dogs. No significant difference was found between the surgical methods at any postoperative re-examination. With regard to peak vertical force (PVF), there were significantly more patients with TPLO within the reference range of healthy dogs at the 3 months re-examination than dogs with MMP. There was no significant difference in mean value comparisons between TPLO and control groups 6 months postoperatively. Compared with the control group, mean values of 93.9% (PVF) and 85.9% (vertical impulse [VI]) were reached by the TPLO group and 89.4% (PVF) and 79.9% (VI) by the MMP group, 6 months postoperatively. No significant differences were found regarding major complications or progression of osteoarthritis. Conclusions Although no significant differences were found between the surgical methods, TPLO patients showed superiority with regard to clinical outcome.
Transcriptional and Metabolic Changes Associated with Phytoglobin Expression during Germination of Barley Seeds

To understand how the class 1 phytoglobin is involved in germination process via the modulation of the nitric oxide (NO) metabolism, we performed the analysis of physiological and molecular parameters in the embryos of transgenic barley (Hordeum vulgare L. cv Golden Promise) plants differing in expression levels of the phytoglobin (Pgb1) gene during the first 48 h of germination. Overexpression of Pgb1 resulted in a higher rate of germination, higher protein content and higher ATP/ADP ratios. This was accompanied by a lower rate of NO emission after radicle protrusion, as compared to the wild type and downregulating line, and a lower rate of S-nitrosylation of proteins in the first hours postimbibition. The rate of fermentation estimated by the expression and activity of alcohol dehydrogenase was significantly higher in the Pgb1 downregulating line, the same tendency was observed for nitrate reductase expression. The genes encoding succinate dehydrogenase and pyruvate dehydrogenase complex subunits were more actively expressed in embryos of the seeds overexpressing Pgb1. It is concluded that Pgb1 expression in embryo is essential for the maintenance of redox and energy balance before radicle protrusion, when seeds experience low internal oxygen concentration and exerts the effect on metabolism during the initial development of seedlings.
Endophthalmitis prophylaxis study. Report 1: Intracameral cefuroxime and moxifloxacin prophylaxis for the prevention of postcataract endophthalmitis in rural India

Purpose: Intracameral antibiotics are known to reduce the incidence of acute endophthalmitis. Various drugs are available for intracameral use. This prospective study was carried out to compare the efficacies of intracameral cefuroxime and moxifloxacin prophylaxis in reducing the incidence of acute endophthalmitis after cataract surgery in rural India. Methods: This was a prospective, nonrandomized, comparative, interventional study. Between October 2016 and March 2018, 15 eye care facilities spread over four Indian states were preselected to use either of the intracameral antibiotics, cefuroxime or moxifloxacin, following cataract surgery (phacoemulsification or manual small incision cataract surgery, SICS). The main outcome measure was the occurrence of acute clinical endophthalmitis within six weeks of the surgery. This was compared with the earlier rate of endophthalmitis in the same locations. Results: The study was done in 42,466 eyes. Of the total, 42.2% received intracameral cefuroxime and 57.8% received intracameral moxifloxacin. SICS was performed more often. Clinical acute endophthalmitis occurred in 15 eyes. This accounted to a 72.22% reduction, from the earlier 0.126% to 0.035%, of postcataract surgery acute endophthalmitis. The reduction in the incidence of endophthalmitis after intracameral cefuroxime was 0.017% and that after intracameral moxifloxacin was 0.049%. With either intracameral antibiotics, the reduction in incidence was statistically significant (P < 0.001), but not between the molecules. Intracameral cefuroxime showed 66.67% reduction and intracameral moxifloxacin showed 74.74% reduction. Conclusion: A 3.6-fold decrease in postcataract surgery endophthalmitis was observed upon the use of intracameral antibiotics in rural India. Both intracameral cefuroxime and moxifloxacin proved efficacious.
Systematic review of prediction models for gestational hypertension and preeclampsia

Introduction Prediction models for gestational hypertension and preeclampsia have been developed with data and assumptions from developed countries. Their suitability and application for low resource settings have not been tested. This review aimed to identify and assess the methodological quality of prediction models for gestational hypertension and pre-eclampsia with reference to their application in low resource settings. Methods Using combinations of keywords for gestational hypertension, preeclampsia and prediction models seven databases were searched to identify prediction models developed with maternal data obtained before 20 weeks of pregnancy and including at least three predictors (Prospero registration CRD 42017078786). Prediction model characteristics and performance measures were extracted using the CHARMS, STROBE and TRIPOD checklists. The National Institute of Health quality assessment tools for observational cohort and cross-sectional studies were used for study quality appraisal. Results We retrieved 8,309 articles out of which 40 articles were eligible for review. Seventy-seven percent of all the prediction models combined biomarkers with maternal clinical characteristics. Biomarkers used as predictors in most models were pregnancy associated plasma protein-A (PAPP-A) and placental growth factor (PlGF). Only five studies were conducted in a low-and middle income country. Conclusions Most of the studies evaluated did not completely follow the CHARMS, TRIPOD and STROBE guidelines in prediction model development and reporting. Adherence to these guidelines will improve prediction modelling studies and subsequent application of prediction models in clinical practice. Prediction models using maternal characteristics, with good discrimination and calibration, should be externally validated for use in low and middle income countries where biomarker assays are not routinely available.
Tyrosine Hydroxylase Neurons Regulate Growth Hormone Secretion via Short-Loop Negative Feedback

Classical studies suggest that growth hormone (GH) secretion is controlled by negative-feedback loops mediated by GH-releasing hormone (GHRH)- or somatostatin-expressing neurons. Catecholamines are known to alter GH secretion and neurons expressing TH are located in several brain areas containing GH-responsive cells. However, whether TH-expressing neurons are required to regulate GH secretion via negative-feedback mechanisms is unknown. In the present study, we showed that between 50% and 90% of TH-expressing neurons in the periventricular, paraventricular, and arcuate hypothalamic nuclei and locus ceruleus of mice exhibited STAT5 phosphorylation (pSTAT5) after an acute GH injection. Ablation of GH receptor (GHR) from TH cells or in the entire brain markedly increased GH pulse secretion and body growth in both male and female mice. In contrast, GHR ablation in cells that express the dopamine transporter (DAT) or dopamine β-hydroxylase (DBH; marker of noradrenergic/adrenergic cells) did not affect body growth. Nevertheless, less than 50% of TH-expressing neurons in the hypothalamus were found to express DAT. Ablation of GHR in TH cells increased the hypothalamic expression of Ghrh mRNA, although very few GHRH neurons were found to coexpress TH- and GH-induced pSTAT5. In summary, TH neurons that do not express DAT or DBH are required for the autoregulation of GH secretion via a negative-feedback loop. Our findings revealed a critical and previously unidentified group of catecholaminergic interneurons that are apt to sense changes in GH levels and regulate the somatotropic axis in mice. SIGNIFICANCE STATEMENT Textbooks indicate until now that the pulsatile pattern of growth hormone (GH) secretion is primarily controlled by GH-releasing hormone and somatostatin neurons. The regulation of GH secretion relies on the ability of these cells to sense changes in circulating GH levels to adjust pituitary GH secretion within a narrow physiological range. However, our study identifies a specific population of tyrosine hydroxylase-expressing neurons that is critical to autoregulate GH secretion via a negative-feedback loop. The lack of this mechanism in transgenic mice results in aberrant GH secretion and body growth. Since GH plays a key role in cell proliferation, body growth, and metabolism, our findings provide a major advance to understand how the brain regulates the somatotropic axis.
The understanding of research ethics at health sciences schools in Jordan: a cross-sectional study

Background Research ethics is required for high-quality research that positively influences society. There is limited understanding of research ethics in Middle Eastern countries including Jordan. Here, we aim to investigate the level of understanding of research ethics principles among health sciences faculty members in Jordan. Methods This is a cross sectional study where faculty members from the University of Jordan were surveyed for their knowledge and, attitude of research ethics principles. The study was conducted in the period between July 2016 to July 2017 using a customized-design questionnaire involving demographic data and participants’ contributions toward research, and assessment of participants’ knowledge, belief and attitude towards research ethics. Different question-formats have been used including multiple-choice, yes or no, and a four point Likert-type questions. Obtained responses were tabulated according to gender, academic-rank, and knowledge about research ethics principles. Results The study had a response rate of 51%. Among the 137 participants of this study, most (96%) were involved in human and animal research, yet, only 2/3 had prior training in research ethics. Moreover, 91% believed that investigators should have training in research ethics and 87% believed that there should be a mandatory postgraduate course on that. The average correct scores for correct understanding of researchers towards research ethics was 62%. Yet, there were some misconceptions about the major ethical principles as only 43% identified them correctly. Additionally, the role of research ethics committees was not well understood by most of the respondents. Conclusions Although there is acceptable knowledge about research ethics, discrepancies in understanding in research ethics principles seems to exist. There is a large support for further training in responsible conduct of research by faculty in health sciences in Jordan. Thus, such training should be required by universities to address this knowledge gap in order to improve research quality and its impact on society.
Identification of Candidate Genes Associated with Susceptibility to Ovarian Clear Cell Adenocarcinoma Using cis-eQTL Analysis

Ovarian clear cell adenocarcinoma (Ov-CCA) has a higher prevalence in the Japanese ancestry than other populations. The ancestral disparities in Ov-CCA prevalence suggests the presence of Ov-CCA-specific genetic alterations and may provide an opportunity to identify the novel genes associated with Ov-CCA tumorigenesis. Using 94 previously reported genes as the phenotypic trait, we conducted multistep expression quantitative trait loci (eQTL) analysis with the HapMap3 project datasets. Four single-nucleotide polymorphisms (SNPs) (rs4873815, rs12976454, rs11136002, and rs13259097) that had different allele frequencies in the Japanese ancestry and seven genes associated in cis (APBA3, C8orf58, KIAA1967, NAPRT1, RHOBTB2, TNFRSF10B, and ZNF707) were identified. In silico functional annotation analysis and in vitro promoter assay validated the regulatory effect of rs4873815-TT on ZNF707 and rs11136002-TT on TNFRSF10B. Furthermore, ZNF707 was highly expressed in Ov-CCA and had a negative prognostic value in disease recurrence in our sample cohort. This prognostic power was consistently observed in The Cancer Genome Atlas (TCGA) clear cell renal cell carcinoma dataset, suggesting that ZNF707 may have prognostic value in clear cell histology regardless of tissue origin. In conclusion, rs4873815-TT/ZNF707 may have clinical significance in the prognosis and tumorigenesis of Ov-CCA, which may be more relevant to clear cell histology. Besides, this study may underpin the evidence that cis-eQTL analysis based on ancestral disparities can facilitate the discovery of causal genetic alterations in complex diseases, such as cancer.
Local properties and rupture characteristics of thoracic aortic aneurysm tissue

Ascending thoracic aortic aneurysms (ATAAs) are focal dilatations in the aorta that are prone to rupture or dissect. Currently, the clinically used indicator of the rupture risk is the diameter. However, it has been demonstrated that the diameter alone may not properly predict the risk. To evaluate the rupture risk, one must look into the local mechanical conditions at the rupture site and understand how rupture is triggered in the tissue which is a layered fibrous media. A challenge facing experimental studies of ATAA rupture is that the ATAA tissue is highly heterogeneous; experimental protocols that operate under the premise of tissue homogeneity will have difficulty delineating the heterogeneous properties. In general, rupture initiates at the location where the micro-structure starts to break down and consequently, it is more meaningful to investigate the local conditions at the rupture site. In this work, a combined experimental and computational method was developed and employed to characterize wall stress, strain, and property distributions in harvested ATAA samples to a sub-millimeter resolution. The results show that all tested samples exhibit a significant degree of heterogeneous in their mechanical properties. Large inter-subject variability is also observed. A heterogeneous anisotropic finite strain hyperelastic model was introduced to describe the tissue; the distributions of the material parameters were identified. The elastic energy stored in the tissue was computed. It was found that the tissue fractures preferentially in the direction of the highest stiffness, generating orifices that are locally transverse to the
Frequency and clinical significance of red cell antibodies in pregnancy – A prospective study from India

Background: For appropriate management of hemolytic disease of the fetus and newborn (HDFN), it is important to detect irregular red cell antibody in the antenatal period. Though it is a simple one-step method, it is not part of routine antenatal screening in many developing countries. To reiterate the importance of antenatal antibody screening, we have assessed the frequency and clinical significance of irregular red cell antibodies in our patient population. Materials and Methods: A prospective study was carried out from October 2013 to May 2015 at a tertiary care center from south India. All antenatal samples received by the laboratory for red cell antibody screening were screened using a commercial three-cell screening panel. Antibody identification along with further Immunohematological techniques as required were performed for cases with positive screening results. Neonates of the alloimmunized cases were followed up to determine the clinical significance of the antibody. Results: A total of 2336 antenatal mothers were screened for red cell antibodies. The overall rate of alloimmunization in the study group was 2.27%. Alloimmunization rate among RhD-negative pregnancies was 6.9%. Other than anti-D (49%), we identified anti-D + anti-C (5%), anti-G (5%), anti-c (5%), anti-E (2%), anti-e (2%), anti-H (Bombay phenotype) (7%), anti-M (2%), anti-Lea (2%), anti-Leb (12%), and autoantibodies (9%) in the maternal serum. Anti-D, anti-D + anti-C, anti-G, anti-c, and anti-H were found to be clinically significant in this study. Conclusion: This study showed that 1 in 125 RhD-positive pregnancies can develop red cell alloantibodies. Hence, implementing routine antenatal antibody screening irrespective of RhD status is essential.
Ebola virus glycoprotein stimulates IL-18–dependent natural killer cell responses

BACKGROUND NK cells are activated by innate cytokines and viral ligands to kill virus-infected cells. These functions are enhanced during secondary immune responses and after vaccination by synergy with effector T cells and virus-specific antibodies. In human Ebola virus infection, clinical outcome is strongly associated with the initial innate cytokine response, but the role of NK cells has not been thoroughly examined. METHODS The novel 2-dose heterologous Adenovirus type 26.ZEBOV (Ad26.ZEBOV) and modified vaccinia Ankara-BN-Filo (MVA-BN-Filo) vaccine regimen is safe and provides specific immunity against Ebola glycoprotein, and is currently in phase 2 and 3 studies. Here, we analyzed NK cell phenotype and function in response to Ad26.ZEBOV, MVA-BN-Filo vaccination regimen and in response to in vitro Ebola glycoprotein stimulation of PBMCs isolated before and after vaccination. RESULTS We show enhanced NK cell proliferation and activation after vaccination compared with baseline. Ebola glycoprotein–induced activation of NK cells was dependent on accessory cells and TLR-4–dependent innate cytokine secretion (predominantly from CD14+ monocytes) and enriched within less differentiated NK cell subsets. Optimal NK cell responses were dependent on IL-18 and IL-12, whereas IFN-γ secretion was restricted by high concentrations of IL-10. CONCLUSION This study demonstrates the induction of NK cell effector functions early after Ad26.ZEBOV, MVA-BN-Filo vaccination and provides a mechanism for the activation and regulation of NK cells by Ebola glycoprotein. TRIAL REGISTRATION ClinicalTrials.gov NCT02313077. FUNDING United Kingdom Medical Research Council Studentship in Vaccine Research, Innovative Medicines Initiative 2 Joint Undertaking, EBOVAC (grant 115861) and Crucell Holland (now Janssen Vaccines and Prevention B.V.), European Union’s Horizon 2020 research and innovation programme and European Federation of Pharmaceutical Industries and Associations (EFPIA).