bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular epidemiology of Chinese Han deaf patients with bi-allelic and mono-allelic GJB2 mutations
Authors: Yu Xiaoyu , Lin Yun , Xu Jun , Che Tuanjie , Li Lin , Yang Tao , Wu Hao 
Published: January 2020

Abstract
Background
Recessive mutations in GJB2 is the most common cause of genetic hearing loss worldwide. The aim of this study is to determine the spectrum and frequency of GJB2 variants in Chinese Han deaf patients and to investigate the underlying causative genes in patients with mono-allelic GJB2 mutations.

Methods
We analyzed the mutation screening results of GJB2 in 1852 Chinese Han probands with apparently autosomal-recessive hearing loss in our laboratory. Targeted next-generation sequencing of 139 known deafness-related genes were performed in 44 probands with mono-allelic GJB2 mutations.

Results
Bi-allelic GJB2 mutations was identified in 25.65% of patients, in which the c.235delC (p.L79Cfs*3) mutation is the most frequent cause for both severe-to-profound (84.93%) and mild-to-moderate hearing loss (54.05%), while the c.109G > A (p.V37I) mutation is another frequent cause for mild-to-moderate hearing loss (40.54%). In 3.89% of patients only one mutant allele can be identified in GJB2. Targeted next generation sequencing in 44 such probands revealed digenic heterozygous mutations in GJB2/GJB6 and GJB2/GJB3 as the likely pathogenic mechanism in three probands. In 13 probands, on the other hand, pathogenic mutations in other deafness-associated genes (STRC, EYA1, MITF, PCDH15, USH2A, MYO15A, CDH23, OTOF, SLC26A4, SMPX, and TIMM8A) can be identified as the independent genetic cause, suggesting that the mono-allelic GJB2 mutations in those probands is likely co-incidental.

Conclusions
Our results demonstrated that GJB2 should be a primary target for mutation screening in Chinese Han deaf patients, and those with mono-allelic GJB2 mutations should be further screened by next generation sequencing.
Multicentre, double-blind, randomised, sham-controlled trial of 10 khz high-frequency spinal cord stimulation for chronic neuropathic low back pain (MODULATE-LBP): a trial protocol
Authors: Al-Kaisy Adnan , Royds Jonathan , Palmisani Stefano , Pang David , Wesley Samuel , Taylor Rod S. , Cook Andrew , Eldabe Sam , McCracken Lance , Duarte Rui , Fairbank Jeremy 
Published: January 2020

Abstract
Introduction
Chronic neuropathic low back pain (CNLBP) is a debilitating condition in which established medical treatments seldom alleviate symptoms. Evidence demonstrates that high-frequency 10 kHz spinal cord stimulation (SCS) reduces pain and improves health-related quality of life in patients with failed back surgery syndrome (FBSS), but evidence of this effect is limited in individuals with CNLBP who have not had surgery. The aim of this multicentre randomised trial is to assess the clinical and cost-effectiveness of 10 kHz SCS for this population.

Methods
This is a multicentre, double-blind, randomised, sham-controlled trial with a parallel economic evaluation. A total of 96 patients with CNLBP who have not had spinal surgery will be implanted with an epidural lead and a sham lead outside the epidural space without a screening trial. Patients will be randomised 1:1 to 10 kHz SCS plus usual care (intervention group) or to sham 10 kHz SCS plus usual care (control group) after receiving the full implant. The SCS devices will be programmed identically using a cathodal cascade. Participants will use their handheld programmer to alter the intensity of the stimulation as per routine practice. The primary outcome will be a 7-day daily pain diary. Secondary outcomes include the Oswestry Disability Index, complications, EQ-5D-5 L, and health and social care costs. Outcomes will be assessed at baseline (pre-randomisation) and at 1 month, 3 months and 6 months after device activation. The primary analyses will compare primary and secondary outcomes between groups at 6 months, while adjusting for baseline outcome scores. Incremental cost per quality-adjusted life year (QALY) will be calculated at 6 months and over the lifetime of the patient.

Discussion
The outcomes of this trial will inform clinical practice and healthcare policy on the role of high-frequency 10 kHz SCS for use in patients with CNLBP who have not had surgery.

Trial registration
Clinicaltrials.gov, NCT03470766. Registered on 20 March 2018.

Disclaimer
The views expressed here are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The NIHR had no role in the study design, writing of the manuscript or the decision to submit for publication.

Roles and Responsibilities
AK, SP, DP, SW, RST, AC, SE, LM, RD and JF all contributed to the trial design and to securing trial funding. AK, JR, SP, DP, and SE are involved in the recruitment, the intervention and the follow-up. SW will perform data collection and analysis. RST will be responsible for the statistical analysis, and RD will be responsible for the health economic analysis. All authors read and approved the final manuscript.
Efficacy of acupuncture at three nasal acupoints plus acupoint application for perennial allergic rhinitis: A multicenter, randomized controlled trial protocol
Authors: Shou Yin , Hu Li , Zhang Cuihong , Xu Shifen , Jin Qi , Huang Li , Li Bingrong , Yuan Long , Xu Siwei , Zhang Kaiyong , Jiang Huiru , Zhang Bimeng 
Published: January 2020

Abstract
Background
Many studies have shown the potential therapeutic effect of acupuncture on allergic rhinitis. Most of these studies were limited by low-quality evidence. Preliminary experiments showed that the use of acupuncture at three nasal acupoints plus acupoint application (AAP) achieves a more persistent effect in the treatment of perennial allergic rhinitis than acupuncture alone. In this study, a multicenter, single-blind, randomized controlled trial will be performed, in which acupuncture at nonmeridian acupoints and sham AAP will be used as the control group to evaluate the effect of AAP through long-term observation.

Methods
The trial is designed on the basis of the Consolidated Standards of Reporting Trials 2010 guidelines and Standards for Reporting Interventions in Controlled Trials of Acupuncture. A total of 120 participants with perennial allergic rhinitis will be randomly assigned to a treatment or control group. A specially appointed investigator will be in charge of randomization. The participants in the treatment group will be treated with acupuncture at EX-HN3, LI20, and EX-HN8 thrice per week for a total of 12 sessions. In addition, they will undergo AAP at DU14, BL13, EX-BI, and RN22. The participants in the control group will be treated with sham AAP. The primary outcome will be the change in the Total Nasal Symptom Score from baseline to the completion of 4-week treatment. Secondary outcomes include changes in visual analog scale and total non-nasal symptom scores from baseline to the second and fourth weeks of treatment, as well as 1, 3, and 6 months after the completion of treatment. Peripheral blood IL-4, IL-5, IL-6, IL-8, and IL-10 levels will be measured, and any side effects related to treatment will be observed and recorded.

Discussion
It is expected that this randomized clinical trial will provide evidence to determine the effects of AAP compared with acupuncture at nonmeridian acupoints and sham AAP, particularly the long-term effect. These findings will help improve the clinical application of this technique.

Trial registration
Acupuncture-Moxibustion Clinical Trial Registry AMCTR-ICR-18000179. Registered on 12 April 2018.
Craig plot 2.0: an interactive navigation in the substituent bioisosteric space
Authors: Ertl Peter 
Published: January 2020

AbstractBioisosteric replacement is a standard technique that is used in medicinal chemistry to design analogs of bioactive molecules with similar biological activity and with additional improved characteristics. Successful application of this technique relies on a good knowledge of physicochemical properties of common organic substituents and an efficient way to navigate their space. In this study the properties of the most common substituents present in bioactive molecules are analysed and a freely-available web tool https://bit.ly/craigplot that allows visualization, analysis and selection of bioisosteric substituents is presented.
Socio-economic status, self-rated health and mental health: the mediation effect of social participation on early-late midlife and older adults
Authors: Achdut Netta , Sarid Orly 
Published: January 2020

Abstract
Background
Socioeconomic status (SES) is a major determinant of diverse health outcomes, among these are self-rated-health and mental health. Yet the mechanisms underlying the SES—health relation are not fully explored. Socioeconomic inequalities in health and mental health may form along several pathways. One is social participation which is linked to better self-rated-health and mental health. We examined (1) whether various social participation practices, including the usage of information and communication technology, relate to a unidimensional or multidimensional phenomenon (2) the relationship among SES, social participation, self-rated-health and mental health; (3) whether social participation and mental health mediates the association between SES and self-rated-health; (4) whether social participation and self-rated-health mediates the links between SES and mental health.

Method
Cross-sectional data for individuals aged 35 and older were taken from the Israeli Social Survey for 2016 (N = 4848). Social participation practices included connection with family and friends, self-perceived-support, self-perceived trust, volunteering, civic and political involvement, and information and communication technology usage. An exploratory factor analysis was conducted for all social participation practices. We then constructed structural Equation Modeling (SEM) to explore paths of relations among SES, social participation, self-rated-health and mental health.

Results
We found disparities in self-rated health and mental health across SES. Social participation practice, ‘frequency of meeting with friends’, mediated the links between SES-self-rated health and SES-mental health. Formal social participation practices along with internet usage mediated the SES- self-rated health link. Informal social participation practices and self-perceived trust mediated the SES-mental health link. Mental health mediated the SES- self-rated health link and self-rated health mediated the SES-mental health link.

Conclusion
The links between SES and the two health constructs were enhanced by common and distinct social participation practices. Enhancement of social participation practices among low SES individuals is recommended. Social participation should be a prominent aspect of preventive medicine practice and health promotion interventions. Policy makers are called to support such programs as an important way to promote public health.
Application of artificial neural networks for the prediction of interface mechanics: a study on grain boundary constitutive behavior
Authors: Fernández Mauricio , Rezaei Shahed , Rezaei Mianroodi Jaber , Fritzen Felix , Reese Stefanie 
Published: January 2020

AbstractThe present work aims at the identification of the effective constitutive behavior of $$\Sigma 5$$Σ5 aluminum grain boundaries (GB) for proportional loading by using machine learning (ML) techniques. The input for the ML approach is high accuracy data gathered in challenging molecular dynamics (MD) simulations at the atomic scale for varying temperatures and loading conditions. The effective traction-separation relation is recorded during the MD simulations. The raw MD data then serves for the training of an artificial neural network (ANN) as a surrogate model of the constitutive behavior at the grain boundary. Despite the extremely fluctuating nature of the MD data and its inhomogeneous distribution in the traction-separation space, the ANN surrogate trained on the raw MD data shows a very good agreement in the average behavior without any data-smoothing or pre-processing. Further, it is shown that the trained traction-separation ANN captures important physical properties and is able to predict traction values for given separations not contained in the training data. For example, MD simulations show a transition in traction-separation behaviour from pure sliding mode under shear load to combined GB sliding and decohesion with intermediate hardening regime at mixed load directions. These changes in GB behaviour are fully captured in the ANN predictions. Furthermore, by construction, the ANN surrogate is differentiable for arbitrary separation and also temperature, such that a thermo-mechanical tangent stiffness operator can always be evaluated. The trained ANN can then serve for large-scale FE simulation as an alternative to direct MD-FE coupling which is often infeasible in practical applications.
A machine learning approach for differentiating malignant from benign enhancing foci on breast MRI
Authors: D’Amico Natascha C. , Grossi Enzo , Valbusa Giovanni , Rigiroli Francesca , Colombo Bernardo , Buscema Massimo , Fazzini Deborah , Ali Marco , Malasevschi Ala , Cornalba Gianpaolo , Papa Sergio 
Published: January 2020

Abstract
Background
Differentiate malignant from benign enhancing foci on breast magnetic resonance imaging (MRI) through radiomic signature.

Methods
Forty-five enhancing foci in 45 patients were included in this retrospective study, with needle biopsy or imaging follow-up serving as a reference standard. There were 12 malignant and 33 benign lesions. Eight benign lesions confirmed by over 5-year negative follow-up and 15 malignant histopathologically confirmed lesions were added to the dataset to provide reference cases to the machine learning analysis. All MRI examinations were performed with a 1.5-T scanner. One three-dimensional T1-weighted unenhanced sequence was acquired, followed by four dynamic sequences after intravenous injection of 0.1 mmol/kg of gadobenate dimeglumine. Enhancing foci were segmented by an expert breast radiologist, over 200 radiomic features were extracted, and an evolutionary machine learning method (“training with input selection and testing”) was applied. For each classifier, sensitivity, specificity and accuracy were calculated as point estimates and 95% confidence intervals (CIs).

Results
A k-nearest neighbour classifier based on 35 selected features was identified as the best performing machine learning approach. Considering both the 45 enhancing foci and the 23 additional cases, this classifier showed a sensitivity of 27/27 (100%, 95% CI 87–100%), a specificity of 37/41 (90%, 95% CI 77–97%), and an accuracy of 64/68 (94%, 95% CI 86–98%).

Conclusion
This preliminary study showed the feasibility of a radiomic approach for the characterisation of enhancing foci on breast MRI.
Determination of diagnostic value (validity) leukocyte esterase (urine dipstick strip) in differentiating inflammatory arthritis from bacterial arthritis
Authors: Hassas Yeganeh Mehrnoush , Talaei Maryam , Bazzaz Alireza Ebrahimi , Rahmani Khosro , Sinaei Reza , Fathi Mohamadreza , Shiari Reza , Hosseinzadeh Hamid 
Published: January 2020

Abstract
Background
The current diagnostic cornerstone for septic arthritis contains gram stains, bacterial culture, and cell count with a differential of aspirated synovial fluid. Recently, a synovial leukocyte esterase (LE) test has been used for diagnosing septic arthritis. Since this test measures the esterase activity of leukocytes, there is always a dilemma for using this test in patients with inflammatory arthritis.

Methods
We collected the synovial fluid specimens as part of the general diagnostic protocol for patients suspected of Juvenile Idiopathic Arthritis (JIA) or Septic Arthritis (SA). Each group included 34 patients. We compared the result of the synovial LE test with the result of the culture of each patient.

Results
The mean ages of patients were 64.14 ± 31.27 and 50.88 ± 23.19 months in the JIA group and septic arthritis group, respectively. The LE test results were positive in 30 specimens, trace in 3 and negative in one in the first-time test and were positive in 31 specimens and trace in 3 in the second-time test, while it was negative in all patients with JIA. Hence, the sensitivity of the synovial LE test was 80.8%, the specificity, PPV, and NPV were 78.6, 70.0, 86.8% respectively based on a positive culture.

Conclusion
The leukocyte esterase strip test can be used as a rapid, bedside method for diagnosing or excluding bacterial infections in different body fluids. The synovial LE test can be used as an accurate test to rapidly rule in or out an acute articular bacterial infection, even in patients with concurrent inflammatory arthritis.
Evaluation of an Educational Whiteboard Video to Introduce Fertility Preservation to Female Adolescents and Young Adults With Cancer
Authors: Greenspoon Talia , Charow Rebecca , Papadakos Janet , Samadi Mahsa , Maloney Anne Marie , Paulo Chelsea , Forcina Victoria , Chen Li , Thavaratnam Adrian , Mitchell Laura , Lorenzo Armando , Gupta Abha A. 
Published: January 2020

PURPOSE: Fertility is an important issue for adolescents and young adults with cancer facing potential infertility. Egg cryopreservation options exist, but information is sometimes overwhelming. We evaluated a fertility preservation educational video and assessed patient and family knowledge and impressions at pre- and post-video timepoints. METHODS: We developed a whiteboard video to explain egg cryopreservation to patients and families. The video was evaluated on the basis of patient education best practices (readability, understandability, actionability). Participants were recruited using convenience sampling in oncology clinics. They completed questionnaires before and after watching to assess knowledge and interest. Inclusion criteria were patients age 13-39 years and minimum 1 month from diagnosis. Descriptive statistics, correlation analyses, and mean comparisons were conducted. RESULTS: The video script read at a grade 8 reading level. Average understandability and actionability scores were below the acceptable standard. We recruited 108 patients (mean age, 27 years) and 39 caregivers/partners. Patients’ knowledge about fertility preservation increased after viewing the video. Interest was high before and after, and satisfaction was high for both patients and caregivers. Participants appreciated information on process, procedure, and delivery but desired more information on logistics, including cost. CONCLUSION: A targeted patient education video about fertility preservation options can build knowledge and encourage discussions about infertility. The video can be used as a model for videos on related topics to provide accurate information in a youth-friendly medium; however, following patient education best practices for readability, understandability, and actionability may increase video effectiveness. Future research should assess how audiovisual patient education material affects patient behavior.
NPR2 Variants Are Frequent among Children with Familiar Short Stature and Respond Well to Growth Hormone Therapy
Authors: Plachy Lukas , Dusatkova Petra , Maratova Klara , Petruzelkova Lenka , Zemkova Dana , Elblova Lenka , Kucerova Petra , Toni Ledjona , Kolouskova Stanislava , Snajderova Marta , Sumnik Zdenek , Lebl Jan , Pruhova Stepanka 
Published: January 2020

Abstract

Context
The C-type natriuretic peptide receptor encoded by the NPR2 gene is a paracrine regulator of the growth plate; heterozygous NPR2 variants cause short stature with possible presence of different signs of bone dysplasia. To date, the effect of growth hormone (GH) treatment has been described in a few individuals with NPR2 gene variants with inconsistent results.

Objectives
To identify NPR2 gene variants among children with familial short stature (FSS) and to describe their phenotype, including GH treatment response.

Design, Settings and Patients
Out of 747 patients with short stature treated with GH in a single center, 87 with FSS met the inclusion criteria (pretreatment height ≤ –2 standard deviation in both the patient and the shorter parent, unknown genetic etiology). Next-generation sequencing methods were performed to search for NPR2 gene variants. The results were evaluated using the American College of Medical Genetics and Genomics guidelines. The GH treatment response (growth velocity improvement and height standard deviation score development over the first 5 years of treatment) was evaluated.

Results
In 5/87 children (5.7%), a (likely) pathogenic variant in the NPR2 gene was identified (p.Ile558Thr [in 2], p.Arg205*, p.Arg557His, p.Ser603Thr). Two children had disproportionate short-limbed short stature, 1 a dysplastic 5th finger phalanx. The growth velocity in the first year of GH treatment accelerated by 3.6 to 4.2 cm/year; the height improved by 1.2 to 1.8 SD over 5 years of treatment.

Conclusions
NPR2 gene variants cause FSS in a significant proportion of children. Their GH treatment response is promising. Studies including final height data are necessary to assess the long-term efficacy of this therapy.
Effects of Preoperative Gum Chewing on Sore Throat After General Anesthesia With a Supraglottic Airway Device: A Randomized Controlled Trial
Authors: Wang Tingting , Wang Qi , Zhou Haiyang , Huang Shaoqiang 
Published: January 2020

BACKGROUND:
Postoperative sore throat (POST) is not uncommon after general anesthesia with a supraglottic airway (SGA) device. Although it was reported that some pharmacological and nonpharmacological measures can reduce POST, because of limitations and variable success rates, we need to find a simpler and more effective way to alleviate POST.

METHODS:
This prospective, observer-blinded, randomized controlled study enrolled 140 patients who required general anesthesia administered via a streamlined liner of the pharyngeal airway (SLIPA) for <60 minutes. They were randomly divided into the gum (group G, n = 70) and control (group C, n = 70) groups. Before the induction of general anesthesia for 5–10 minutes, the patients in group G chewed gum for 2 minutes. Group C was asked to swallow twice without any additional treatment. A standard anesthesia protocol was followed. The incidence and severity of sore throat were assessed up to 24 hours postoperatively. The primary outcome was the incidence of POST numerical rating scale (NRS) scores >3 within 24 hours after surgery, and the secondary outcomes included the POST (NRS) scores 2, 6, and 24 hours after the surgery.

RESULTS:
The incidence of moderate/severe POST (NRS >3) within 24 hours after surgery was significantly lower in group G (10.1%, 7/69) than in group C (40.6%, 28/69) (odds ratio 0.386, 95% confidence interval [CI], 0.153–0.976; P = .044). The median (interquartile range [range]) scores at 2, 6, and 24 hours after anesthesia in group G were lower than those in the control group at the same times (2 hours: 0 [0–3 {0–4}] vs 3 [0–3 {0–6}], P = .048; 6 hours: 0 [0–3 {0–6}] vs 2 [0–4 {0–6}], P = .048; 24 hours: 0 [0–1 {0–7}] vs 0 [0–2 {0–6}]; P = .011). There were 14 patients (20.3%, 14/69) in group G who had blood stains on the SGA device, which was significantly lower than the number in group C (37.7%, 26/69) (P = .024). In patients with bloody SGA devices, the incidence of POST scores >3 was significantly lower in group G (14.3%, 2/14) than in group C (73.1%, 19/26) (P < .001), while there was no significant difference between the 2 groups in the incidence of POST score >3 in patients without bloody SGA devices (group G: 9.1%, 5/55; group C: 20.9%, 9/43; P = .145).

CONCLUSIONS:
Chewing gum before surgery can effectively reduce POST with a SGA device for hysteroscopic surgery, especially in patients with pharyngeal mucosal injury.