bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interferon β-1a (IFNβ-1a) in COVID-19 patients (INTERCOP): study protocol for a randomized controlled trial.
Authors: Bosi Emanuele , Bosi Carlo , Querini Patrizia Rovere , Mancini Nicasio , Calori Giliola , Ruggeri Annalisa , Canzonieri Cecilia , Callegaro Luciano , Clementi Massimo , De Cobelli Francesco , Filippi Massimo , Bregni Marco 
Published: August 2020

Abstract
Background: Pharmacological therapies of proven efficacy in coronavirus disease 2019 (COVID-19) are still lacking. We have identified IFNβ-1a as the most promising drug to be repurposed for COVID-19. The rationale relies on the evidence of IFNβ anti-viral activity in vitro against SARS-CoV-2 and animal models resembling SARS-CoV-2 infection and on a recent clinical trial where IFNβ was indicated as the key component of a successful therapeutic combination. Methods: This is a randomized, controlled, open-label, monocentric, phase II trial (INTERCOP trial). 126 patients with positive swab detection of SARS-CoV-2, radiological signs of pneumonia, and mild-to-moderate disease will be randomized 2:1 to IFNβ-1a in addition to standard of care vs standard of care alone. No other anti-viral drugs will be used as part of the regimens, both in the control and the intervention arms. IFNβ-1a will be administered subcutaneously at the dose of 44 mcg (equivalent to 12 million international units) three times per week, at least 48 hours apart, for a total of two weeks. The primary outcome is the time to negative conversion of SARS-CoV-2 nasopharyngeal swabs. Secondary outcomes include improvement or worsening in a clinical severity score measured on a 7-point ordinal scale (including transfer to intensive care unit and death), oxygen- and ventilator-free days, mortality, changes in pulmonary computed tomography severity score, hospital stay duration, reduction of viral load measured on nasopharyngeal swabs, number of serious adverse events, changes in biochemical markers of organ dysfunction. Exploratory outcomes include blood cell counts, cytokine and inflammatory profile, peripheral mRNA expression profiles of interferon-stimulated genes, antibodies to SARS-CoV-2 and to IFNβ-1a. INTERCOP is the first study to specifically investigate the clinical benefits of IFNβ-1a in COVID-19 patients.Discussion: Potential implications of this trial are multifaceted: should the primary outcome be fulfilled and the treatment be safe, one may envisage that IFNβ-1a be used to reduce the infectivity of patients with mild-to moderate disease. In case IFNβ-1a reduced the duration of hospital stay and/or ameliorated the clinical status, it may become a cornerstone of COVID-19 treatment.Trial registration: EudraCT 2020-002458-25. Registered on May 11, 2020ClinicalTrials.gov Identifier: NCT04449380
Evaluation of Immunophenotypic Markers and Clinico-Hematological Profile in Chronic Lymphocytic Leukemia: Implications for Prognosis
Authors: bagheri Marziye , Vosoughi Tina , Hosseinzadeh Mehran , saki najmaldin 
Published: August 2020

Abstract
Objective: Chronic lymphocytic leukemia (CLL) is an adult leukemia presented with clonal accumulation of lymphocytes. Immunophenotypic changes can be effective in predicting clinical course, the survival of patients, and determining first-line treatment. This is a study of the association between immunophenotypic markers with complete blood cell count (CBC) values and clinical parameters.Results: Peripheral blood samples were collected from 35 newly diagnosed CLL patients. The expression of immunophenotypic markers and CBC were evaluated. Platelet counts and hemoglobin concentration had a significant, inverse association with Rai staging, modified Rai staging, Binet staging systems (all p< 0.001 in both parameters), and splenomegaly (p = 0.001 and 0.007, respectively). The platelet/lymphocyte ratio (PLR) had a significant, inverse ‎association with Rai staging (p = 0.014), modified Rai staging (p = 0.024), Binet staging systems (p = 0.027), and splenomegaly (p = 0.033). However, CD38, CD25, and double-positive CD56/CD117 expression, group3 of innate lymphocyte cells (ILC3s), had no significant association with clinical parameters. In regression analysis, that ILC3s has an inverse correlation with neutrophil/lymphocyte ratio (r = -0.340, p = 0.046). Given that there is an inverse ‎association between PLR and advanced clinical stages, it seems that PLR may have prognostic value in CLL.
Triboelectric touch sensor for position mapping during total hip arthroplasty
Authors: Jeong Jae Bum , Kim Hyeok , YOO JUN-IL 
Published: August 2020

Abstract
Objective: In this research, a triboelectric nanogenerator (TENG) was utilized to determine if a pressure-based sensor could detect bearing friction in a total hip arthroplasty (THA) and detect the contact of specific areas during ROM checks. Results : The pressure-based sensor shows capability to sense bearing friction. In more detail, the TENG embedded in four different sides of the trial exhibits up to 1 V from peak-to-peak. Moreover, these flexible touch sensors with TENG describes a peak signal in output voltage which should lead to extremely sensitive detection of bearing friction induced by the THA.
Comparative Proteomic Analysis of Nicotiana Benthamiana Seedings Under Chinese Wheat Mosaic Virus Infection
Authors: He Long , Jin Peng , Chen Xuan , Zhang Tian-Ye , Zhong Kai-Li , Liu Peng , Chen Jian-Ping , Yang Jian 
Published: August 2020

Abstract
Background: Chinese wheat mosaic virus (CWMV) is a severe threat to winter wheat, and it is transmitted by Polymyxa graminis. However, the mechanisms of interactions between CWMV and plants are poorly understood. In this study, a comparative proteomics analysis based on nanoliquid chromatography (LC)- mass spectrometry (MS)/MS technique was conducted to characterize the proteomic changes of plants in response to CWMV infection. Results: A total of 2,751 host proteins were identified, 1,496 of which were quantified. 146 up-regulated and 248 down-regulated proteins were identified as differentially expressed proteins (DEPs). KEGG enrichment analysis showed that the DEPs were most strongly associated with Photosynthesis - antenna proteins, MAPK signaling – plant and Glyoxylate and dicarboxylate metabolism pathways. Subcellular localization analysis showed that more than half of DEPs were predicted to be localized in the chloroplast, an organelle indispensable for abscisic acid (ABA) synthesis. Our results suggested that CWMV infection interrupts normal chloroplast functions and decreased the contents of ABA in Nicotiana benthamiana. Further analysis showed that the ABA pathway was suppressed under CWMV infection and ABA treatment did induce plant hosts defense against CWMV. Conclusions: In summary, our results identified several candidate proteins under CWMV infection, and the ABA pathway was deeply involved in the responses to CWMV infection in N. benthamiana.
Personalised health education against the health damage of COVID-19 epidemic in Hungary (PROACTIVE-19): protocol of an adaptive randomised controlled clinical trial.
Authors: Erőss Bálint , Molnár Zsolt , Szakács Zsolt , Zádori Noémi , Szakó Lajos , Váncsa Szilárd , Juhász Félix , Ocskay Klementina , Vörhendi Nóra , Márta Katalin , Szentesi Andrea , Párniczky Andrea , Hegyi Péter J. , Kiss Szabolcs , Földi Mária , Dembrovszky Fanni , Kanjo Anna , Pázmány Piroska , Varró András , Csathó Árpád , Helyes Zsuzsanna , Péterfi Zoltán , Czopf László , Kiss István , Zemplényi Antal , Czapári Dóra , Hegyi Eszter , Dobszai Dalma , Miklós Emőke , Márta Attila , Tóth Dominika , Farkas Richard , Farkas Nelli , Birkás Béla , Pintér Erika , Pethő Gábor , Zsigmond Borbála , Sárközi Andrea , Nagy Anikó , Hegyi Péter 
Published: August 2020

Abstract
Background: Early reports indicate that COVID-19 may require intensive care unit (ICU) admission in 5-26% and overall mortality can rise to 11% of the recognized cases, particularly affecting the elderly. There is a lack of evidence-based targeted pharmacological therapy for prevention and treatment alike. We aim to compare the effects of a World Health Organisation (WHO) recommendations’ based education and a personalised complex preventive lifestyle intervention package (based on the same WHO recommendation) on the outcomes of the COVID-19.Methods: PROACTIVE-19 is a pragmatic, randomized controlled clinical trial with adaptive “sample size re-estimation” design. Hungarian population over the age of 60 years without confirmed COVID-19 will be approached to participate in a telephone health assessment and lifestyle counselling voluntarily. Volunteers will be randomized into two groups: (A) general health education; (B) personalized health education. Participants will go through questioning and recommendation in 5 fields: (1) mental health, (2) smoking habits, (3) physical activity, (4) dietary habits, (5) alcohol consumption. Both groups A and B will receive the same line of questioning to assess habits concerning these topics. Assessment will be done weekly during the first month, every second week in the second month, then monthly. The composite primary endpoint will include the rate of ICU admission, hospital admission (longer han 48 hours) and mortality in COVID-19 positive cases. The estimated sample size is 3788 subjects per study arm. The planned duration of the follow-up is a minimum of one year.Discussion: These interventions may boost the body’s cardiovascular and pulmonary reserve capacities, leading to improved resistance against the damage caused by COVID-19. Consequently, lifestyle changes can reduce the incidence of life-threatening conditions and attenuate the detrimental effects of the pandemic seriously affecting the older population. Trial registration: The study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (IV/2428- 2 /2020/EKU) and has been registered at clinicaltrials.gov (NCT04321928) on 25 March, 2020.
Mother's support in NICU: A Focused Ethnographic Study
Authors: Negarandeh Reza , Hassankhani Hadi , Jabraeili Mahnaz , Abbaszadeh Mohammaf , Best Amy 
Published: August 2020

Abstract
Background: Mothers of premature infants in the neonatal intensive care unit (NICU) have complex needs and require a significant amount of support during the NICU admission. However, little is known about Iranian mothers support needs in the NICU. To explore Iranian mother’s experience of support in the NICU as well as explore nursing perceptions of mothers needs and practices that support mothers in the NICU.Methods: A focused ethnographic approach was adopted. Observation and interviews with 21 mothers, 18 nurses and 5 doctors were undertaken over a seven month period. Qualitative data analysis was conducted using the Roper and Shapira (2000) five-step framework. Result: The specific support needs of mothers of neonates in the NICU did not appear to be adequately identified by the treating healthcare team. There was also poor communication and inadequate sharing of information regarding the neonate’s clinical condition, diagnosis and treatment between both medical/nursing staff and the mother. This appeared to be a source of maternal distress. Conclusion: Cultural perspective Iranian nurses perceive providing support to mothers as an act of human kindness, a new paradigm is required where supporting mothers becomes a fundamental component of care provision.
Reducing the use of physical restraints in home care - Development and evaluation of a multicomponent program to support the implementation of a guideline
Authors: Vandervelde Sara , Scheepmans Kristien , Milisen Koen , Achterberg Theo van , Vlaeyen Ellen , Flamaing Johan , de Casterlé Bernadette Dierckx 
Published: August 2020

Abstract
Background: A validated evidence-based guideline was developed to reduce physical restraint use in home care. However, the implementation of guidelines in home care is challenging. Therefore, this study aims to systematically develop and evaluate a multicomponent program for the implementation of the guideline for reducing the use of physical restraints in home care.Methods: Intervention Mapping was used to develop a multicomponent program. This method contains six steps. Each step comprises several tasks towards the design, implementation and evaluation of an intervention; which is theory and evidence informed, as well as practical. To ensure that the multicomponent program would support the implementation of the guideline in home care, a feasibility study of eight months was organized in one primary care district in Flanders, Belgium. A concurrent mixed methods design was used to evaluate the multicomponent program consisting of a knowledge test, focus groups and an online survey.Results: The Social Cognitive Theory and the Theory of Planned Behavior are the foundations of the multicomponent program. Based on modeling, active learning, guided practice, belief selection and resistance to social pressure, eight practical applications were developed to operationalize these methods. The key components of the program are: the ambassadors for restraint-free home care (n =15), the tutorials, the physical restraint checklist and the flyer. The results of the feasibility study show the necessity to select uniform terminology and definition for physical restraints, to involve all stakeholders from the beginning of the process, to take time for the implementation process, to select competent ambassadors and to collaborate with other home care providers.Conclusions: The multicomponent program shows promising results. Prior to future use, further research needs to focus on the last two steps of Intervention Mapping (program implementation plan and developing an evaluation plan), to guide implementation on a larger scale and to formally evaluate the effectiveness of the multicomponent program.
A review of clinical profile, complications and antibiotic susceptibility pattern of extensively drug resistant (XDR) Salmonella Typhi isolates in children in Karachi.
Authors: Shahid Saba , Mahesar Marvi , Ghouri Nida , Noreen Saba 
Published: August 2020

Abstract
Background: Enteric fever is a systemic infection, which can be caused by Salmonella enterica; Typhi and Paratyphi A. Over a period of time Salmonella Typhi has developed resistance to many antibiotics which has resulted in emergence of extensively drug resistant (XDR) enteric fever. WHO estimated 5274 cases of XDR Enteric fever in Karachi from November 2016 to December 2019.This study aims to determine clinical course, complications and outcomes of XDR enteric fever among the pediatric population coming to Indus HospitalMethods: A retrospective chart review of pediatric patients (aged 1 month–15 years) seen in Indus Hospital between July 2017 to December 2018 was conducted. A pre-designed data abstraction form was used to record detailed information about seasonality and distribution of cases, demographic details, signs and symptoms, clinical course, treatment, complications and final outcomes of the cases treated for XDR Enteric feverResults: Six hundred and eighty children were included in the study. The median (IQR) age of the patients was 5 (2-8) years. More than half (n=391, 57.5%) of the patients were males. Most common clinical manifestations included fever vomiting and diarrhea which were noted in 680 (100%), 242 (35%) and 174 patients (25%) Final outcomes of 270 (39.7%) patients have been recorded; 351 (51.6%) were lost to follow up, 52 (7.6%) were referred out and 7 (1%) left without medical advice. 266 (39.1%) patients were cured and 4 children (0.6%) expired. Seventy eight patients (82%) and 15 patients (16.3%) got cured on Azithromycin and Meropenum alone while 157 patients got cured on combination of drugs.Conclusion: Our review indicated that children under 5 years of age were affected more with XDR Enteric fever. Meropenum and Azithromycin, either alone or in combination were the most effective antibiotics for treating XDR Enteric fever in children coming to Indus hospital
Quad test for fetal aneuploidy screening as a predictor of fetal growth restriction: A population-based study
Authors: Boonpiam Rakchanok , Wanapirak Chanane , Sirichotiyakul Supatra , Sekararithi Ratanaporn , Traisrisilp Kuntharee , Tongsong Theera 
Published: August 2020

Abstract
Background: To identify the relationship between quadruple test for aneuploidy screening (alpha-fetoprotein: AFP; free beta-human chorionic gonadotropin: b-hCG; unconjugated estriol: uE3 and inhibin-A: IHA) and fetal growth restriction and to construct predictive models for fetal growth restriction (FGR).Methods: Women who underwent quadruple test for aneuploidy were followed-up for final outcomes. The multiple of median (MoMs) of the four biochemical markers for the FGR group and those of normal fetuses were compared. The models for predicting FGR by the individual biomarkers and their combination were constructed using binary logistic regression analysis, and their diagnostic performances in predicting FGR were determined.Results: Of 10,155 eligible pregnant women, 578 (5.7%) and 9577 (94.3%) had FGR and normal growth, respectively. High levels of AFP, b-hCG and IHA but low levels of uE3 significantly increased the risk of FGR. The constructed predictive equations had predictive performance for FGR, with areas under the receiver-operated characteristic curve of 0.724, 0.655, 0.597, 0.664 and 0.754 for AFP, b-hCG, uE3, IHA, and the combination, respectively.Conclusion: The quad test for aneuploidy screening could also be used as a predictor of FGR, without extra-effort and extra-cost.
A prospective study of the muscle strength and reaction time of the quadriceps, hamstring, and gastrocnemius muscles in patients with plantar fasciitis
Authors: Lee Jin Hyuck , Jang Woo Young 
Published: August 2020

Abstract
Background: Muscle weakness has been reported to be an important etiological factor in plantar fasciitis (PF), but the data available in the quadriceps, hamstring, gastrocnemius (GCM) muscles is limited . The aim of the study was to compare the strength and reaction time of the quadriceps, hamstring, and gastrocnemius (GCM) muscles and foot pressure between patients with PF and normal controls. Methods: 21 PF patients and 21 normal controls were registered. Muscle strength was measured by the peak torque per body weight (Nm kg−1 × 100). Muscle reaction time was evaluated by the acceleration time (AT, milliseconds). Foot pressure and posture were assessed by pedobarography [valgus/varus index (VV index), %].Results: The strength of the quadriceps was significantly decreased in the affected ankles of the PF group than in the control group (p=0.005). The AT of the quadriceps and hamstring muscles was significantly increased in the affected ankles of the PF group than in the control group (quadriceps: p=0.012, hamstring: p=0.001), while the AT of the GCM muscle was significantly decreased (p=0.009) and was significantly negatively correlated with quadriceps muscle strength (r=-.598, p = .004) and AT (r=-.472, p=.031). Forefoot (p=0.001) and hindfoot (p=0.000) pressure were significantly greater, with the VV index showing hindfoot valgus, in the affected ankles of the PF group when compared to those of the control group (p=0.039).Conclusion: This study demonstrated weakness and delayed reaction time of the quadriceps and hamstring muscles, with a rapid reaction time of the GCM muscle, in PF patients. Clinical Relevance: Clinicians and therapists should assess the function of the quadriceps and hamstring muscles when planning the management of PF patients without muscle tightness.
Hypoxia-sensitive Long Noncoding RNA CASC15 Promotes Lung Tumorigenesis by Regulating the SOX4/β-catenin Axis
Authors: Sun Jianyong , Xiong Yanlu , Jiang Kuo , Xin Bo , Jiang Tongtong , Wei Renji , Zou Yuankang , Tan Hong , Jiang Tao , Yang Angang , Jia Lintao , Wang Lei 
Published: August 2020

Abstract
Background: Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) are involved in the hypoxia-related cancer process and play pivotal roles in enabling malignant cells to survive under hypoxic stress. However, the molecular crosstalk between lncRNAs and hypoxia signaling cascades in non-small cell lung cancer (NSCLC) remains largely elusive. Methods: Firstly, we identified differentially expressed lncRNA cancer susceptibility candidate 15 (CASC15) as associated with NSCLC based on bioinformatic data. The clinical significance of CASC15 in lung cancer was investigated by Kaplan-Meier survival analysis. Then, we modulated CASC15 expression in NSCLC cell lines by RNAi. CCK-8 and transwell assays were carried out to examine the effects of CASC15 on proliferation and migration of NSCLC cells. Upstream activator and downstream targets of CASC15 were validated by luciferase reporter assay, qRT-PCR, Western blotting, and chromatin immunoprecipitation (ChIP). Lastly, RNA in situ hybridization (RNA-ISH) and immunohistochemistry (IHC) were performed to confirm the genetic relationships between CASC15 and related genes in clinical samples. Results: CASC15 was highly expressed in NSCLC tissues and closely associated with poor prognosis. Loss-of-function analysis demonstrated that CASC15 was essential for NSCLC cell migration and growth. Mechanistic study revealed that CASC15 was transcriptionally activated by hypoxia signaling in NSCLC cells. Further analysis showed that hypoxia-induced CASC15 transactivation was mainly dependent on hypoxia-inducible factor 1α (HIF-1α) and hypoxia response elements (HREs) located in CASC15 promoter. CASC15 promotes the expression of its chromosomally nearby gene, SOX4. Then SOX4 functions to stabilize β-catenin protein, thereby enhancing the proliferation and migration of NSCLC cells. HIF-1α/CASC15/SOX4/β-catenin pathway was activated in a substantial subset of NSCLC patients. Conclusions: HIF-1α/CASC15/SOX4/β-catenin axis plays an essential role in the development and progression of NSCLC. The present work provides new evidence that lncRNA CASC15 holds great promise to be used as novel biomarkers for NSCLC. Blocking the HIF-1α/CASC15/SOX4/β-catenin axis can serve as a potential therapeutic strategy for treating NSCLC.
Long Non-Coding RNA SNHG12 Promotes Prostate Tumor Occurrence and Progression via AKT Regulation
Authors: Chen Zheng , Qi Tao , Qin Xiaoping , Wang Jue , Huang Zhangsen , Hu Xiaoyong , Chen Guo , Ju Lijun , Zhuo Yu-min 
Published: August 2020

Abstract
The authors have withdrawn this preprint due to author disagreement.
Non-synonymous to Synonymous Substitutions Suggest That Orthologs Tend to Keep Their Functions, While Paralogs Are a Source of Functional Novelty
Authors: Escorcia-Rodriguez Juan Miguel , Esposito Mario , Freyre-Gonzalez Julio Augusto , Moreno-Hagelsieb Gabriel 
Published: August 2020

Abstract
Background: Orthologs diverge after speciation events and paralogs after gene duplication. It is thus expected that orthologs would tend to keep their functions, while paralogs could be a source of new functions. Because protein functional divergence follows from non-synonymous substitutions, we performed an analysis based on the ratio of non-synonymous to synonymous substitutions (dN/dS) as proxy for functional divergence. We used four working definitions of orthology, including reciprocal best hits (RBH), among other definitions based on network analyses and clustering.Results: The results showed that orthologs, by all definitions tested, had values of dN/dS noticeably lower than those of paralogs, not only suggesting that orthologs keep their functions better, but also that paralogs are a readily source of functional novelty. The differences in dN/dS ratios remained favouring the functional stability of orthologs after eliminating gene comparisons with potential problems, such as genes having a high codon usage bias, low coverage of either of the aligned sequences, or sequences with very high similarities. The dN/dS ratios kept suggesting better functional stability of orthologs regardless of overall sequence divergence.Availability: A couple of programs for obtaining orthologs and dN/dS values as tested in this manuscript are available at github: https://github.com/Computational-conSequences/SequenceTools.