bluuebunny/crossref_metadata_2025_split huggingface dataset:
GABA
A
Receptor Coupling Junction and Pore GABRB3 Mutations are Linked to Early-Onset Epileptic Encephalopathy
Authors: Hernandez Ciria C. , Zhang Yujia , Hu Ningning , Shen Dingding , Shen Wangzhen , Liu Xiaoyan , Kong Weijing , Jiang Yuwu , Macdonald Robert L. 
Published: November 2017

AbstractGABAA receptors are brain inhibitory chloride ion channels. Here we show functional analyses and structural simulations for three de novo missense mutations in the GABAA receptor β3 subunit gene (GABRB3) identified in patients with early-onset epileptic encephalopathy (EOEE) and profound developmental delay. We sought to obtain insights into the molecular mechanisms that might link defects in GABAA receptor biophysics and biogenesis to patients with EOEE. The mutant residues are part of conserved structural domains such as the Cys-loop (L170R) and M2-M3 loop (A305V) that form the GABA binding/channel gating coupling junction and the channel pore (T288N), which are functionally coupled during receptor activation. The mutant coupling junction residues caused rearrangements and formation of new hydrogen bonds in the open state, while the mutant pore residue reshaped the pore cavity. Whereas mutant coupling junction residues uncoupled during activation and caused gain of function, the mutant pore residue favoured low conductance receptors and differential sensitivity to diazepam and loss of function. These data reveal novel molecular mechanisms by which EOEE-linked mutations affect GABAA receptor function.
Intravesicular administration of sodium hyaluronate ameliorates the inflammation and cell proliferation of cystitis cystica et glandularis involving interleukin-6/JAK2/Stat3 signaling pathway
Authors: Ni Yongliang , Zhao Shaohua , Yin Xiaoxuan , Wang Haixin , Guang Qianqian , Hu Guangxia , Yang Yi , Jiao Shoubin , Shi Benkang 
Published: November 2017

AbstractCystitis cystica et glandularis (CCEG) is a chronic cystitis that causes extreme agony in affected patients. However, there are lack of effective conservative treatments. In this study, it is evident that intravesicular sodium hyaluronate (SH) therapy significantly improved the clinical symptoms of CCEG patients and ameliorated the bladder mucosal inflammation and cell proliferation characteristics of the disease. Immunohistochemical staining showed that the staining intensities of hyaluronidase (HYAL 1/2), CD44, IL-6 and phosphorylated signal transducer and activator of transcription 3 (p-Stat3) in bladder mucosal tissue were significantly increased in CCEG patients compared with control patients and that intravesicular SH treatment suppressed these protein expression. We established a CCEG rat model by treating rats with E. coli intravesicularly, and we found that HYAL 1/2 and CD44 expression levels were significantly increased in the E. coli group compared with the NC group. Activation of the IL-6/JAK2/Stat3 pathway and the expression levels of the downstream pro-apoptotic proteins Mcl-1 and Bcl-xL were also significantly increased in the E. coli group compared with the NC group. The above changes were significantly mitigated by intravesicular SH treatment. Therefore, SH may serve as an effective therapy for CCEG by inhibiting bladder mucosal inflammation and proliferation.
Effect of aerobic exercise and diet on liver fat in pre-diabetic patients with non-alcoholic-fatty-liver-disease: A randomized controlled trial
Authors: Cheng Sulin , Ge Jun , Zhao Can , Le Shenglong , Yang Yifan , Ke Dandan , Wu Na , Tan Xiao , Zhang Xiaobo , Du Xiaming , Sun Jianqin , Wang Renwei , Shi Yongyong , Borra Ronald J. H. , Parkkola Riitta , Wiklund Petri , Lu Dajiang 
Published: November 2017

AbstractThe study aimed to assess whether aerobic exercise (AEx) training and a fibre-enriched diet can reduce hepatic fat content (HFC) and increase glycaemic control in pre-diabetic patients with non-alcoholic fatty liver disease (NAFLD). Six-hundred-and-three patients from seven clinics in Yangpu district, Shanghai, China were recruited. Of them 115 individuals aged 50–65-year fulfilled the inclusion criteria (NAFLD with impaired fasting glucose or impaired glucose tolerance) and were randomly assigned into exercise (AEx n = 29), diet (Diet n = 28), exercise plus diet (AED n = 29), or no-intervention (NI n = 29) groups. Progressive supervised AEx training (60–75% VO2max intensity) was given 2-3 times/week in 30–60 min/sessions, and the diet intervention was provided as lunch with 38% carbohydrate and diet fibre of 12 g/day for 8.6-month. HFC was assessed by 1H MRS. We found that HFC was significantly reduced in the AEx (−24.4%), diet (−23.2%), and AED (−47.9%) groups by contrast to the 20.9% increase in the NI group (p = 0.001 for all) after intervention. However, only AED group significantly decreased HbA1c (−4.4%, p = 0.01) compared with the NI group (−0.6%). Aerobic exercise training combined with fibre-enriched diet can reduce HFC more effectively than either exercise or increased fibre-intake alone in pre-diabetic patients with NAFLD.
miR-500a-5p regulates oxidative stress response genes in breast cancer and predicts cancer survival
Authors: Degli Esposti Davide , Aushev Vasily N. , Lee Eunjee , Cros Marie-Pierre , Zhu Jun , Herceg Zdenko , Chen Jia , Hernandez-Vargas Hector 
Published: November 2017

AbstractMicroRNAs (miRNAs) are small regulatory non-coding RNAs with a diversity of cellular functions, and are frequently dysregulated in cancer. Using a novel computational method (ActMir) that we recently developed, the “activity” of miRNA hsa-miR-500a was implicated in estrogen receptor (ER) positive breast cancer; however its targets and functional impact remain poorly understood. Here, we performed an extensive gene expression analysis in ER+ breast cancer cell lines, to reveal the targets of miR-500a-5p after experimental modulation of its levels. We found that among mRNAs targeted by miR-500a-5p there was enrichment in oxidative stress response genes. Moreover,in vitroexposure to oxidative stress using H2O2induces miR-500a-5p overexpression and downregulation of the oxidative stress targetsTXNRD1andNFE2L2. Finally, expression of several of the identified miR-500a-5p targets related to oxidative stress, includingTXNRD1, was associated with ER+ breast cancer survival in multiple datasets. Overall, we identify miR-500a-5p as an oxidative stress response miRNA whose activity may define breast cancer progression and survival.
Shear Stress Regulates TRPV4 Channel Clustering and Translocation from Adherens Junctions to the Basal Membrane
Authors: Baratchi Sara , Knoerzer Markus , Khoshmanesh Khashayar , Mitchell Arnan , McIntyre Peter 
Published: November 2017

AbstractLocalized Ca2+ influx via TRPV4 on the surface of endothelial cells greatly influences endothelial adaptation to blood flow, but how mechanical stress from blood flow controls TRPV4 integration into this physiological function is not fully understood. Here, we studied the spatial organization of TRPV4 and its relationship to the adherens junction component β-catenin using single- and dual-color direct stochastic optical reconstruction microscopy (dSTORM). In non-stimulated endothelial cells, TRPV4 is clustered in small protein islands, as is β-catenin. Using dual-color imaging, we found that TRPV4 and β-catenin reside in similar islands and can be found at both the basolateral and basal membranes. Following shear stress stimulation, TRPV4 molecules formed smaller clusters, with the majority residing outside of clusters. Further shear stress stimulation changed the molecular distribution of TRPV4 molecules, limiting them to the basal membrane. This redistribution and the smaller clusters resulted in the segregation of TRPV4 from β-catenin. Furthermore, TRPV4 trafficking was controlled by focal adhesion kinase and activation of the α5ß1 integrin. These highly differentiated spatial redistributions suggest that mechanotransduction of blood flow is controlled via a more complex hierarchy than previously thought.
Temporary Diverting Stoma Improves Recovery of Anastomotic Leakage after Anterior Resection for Rectal Cancer
Authors: Wu Yuchen , Zheng Hongtu , Guo Tianan , Keranmu Adili , Liu Fangqi , Xu Ye 
Published: November 2017

AbstractTemporary diverting stoma might be a protective factor for the prevention of anastomotic leakage (AL) after anterior resection. Its role in leakage recovery is unknown. This study aimed to evaluate the effect of temporary diverting stoma on anastomotic leakage severity and recovery. We analyzed 323 patients who underwent anterior resection for rectal cancer and developed anastomotic leakage, in which 44 had temporary diverting stoma. Association between diverting stoma and occurrence of anastomotic leakage, recovery time, length of hospital stay, overall costs, local and distant relapse-free survival were further studied. In non-severe AL group, temporary diverting stoma improved leakage recovery by 4 days (mean: 20.7 days vs. 16.1 days, p = 0.031), especially in patients who did not receive neoadjuvant treatment (mean time: 20.9 days vs. 14.4 days, p = 0.016). However, it did not delay the occurrence of anastomotic leakage. Moreover, no significant difference was found in the overall length of hospital stay and costs among patients with versus without a diverting stoma. In severe AL group, however, no difference was detected. The advantage of shortened leakage recovery did not reduce the local and distant relapse-free survival. In conclusion, our findings indicated the recovery benefit from diverting stoma in patients with anterior resection.
Phalloplasty in Female-to-Male Transsexuals by Gottlieb and Levine's Free Radial Forearm Flap Technique—A Long-Term Single-Center Experience Over More than Two Decades
Authors: Majenka Pawel , Kaufmann Melanie , Wellenbrock Sascha , Kasper Lara , Hüttinger Susanne , Djedovic Gabriel , Bozkurt Ahmet , Sohn Michael , Rieger Ulrich , Wirthmann Anna 
Published: November 2017

Background The free radial forearm flap phalloplasty is the most utilized method for penile reconstruction. Among the techniques described in the literature, evidence for the flap design after Gottlieb and Levine is poor.
Methods From January 1993 until December 2015, 402 phalloplasties were performed in our clinic. Among the 247 free radial forearm flap phalloplasties, 232 free radial forearm flap phalloplasties were performed after Gottlieb and Levine in 229 patients. Operation and patient-specific characteristics were evaluated.
Results This study presents the highest number of free radial forearm flap phalloplasties after Gottlieb and Levine. The rate of total flap failure was 3%; 46% of the patients were heavy smokers. Urinary fistulae and strictures are common. The revision rate for urinary fistulae and/or strictures was 1.3 per patient. The number of postoperative complications, such as bleeding (14.2%), thrombosis of the flap requiring revision (11.2%), or delayed wound healing (16.8%) was considering the high rate of nicotine abuse (45.9%) reasonable.
Conclusion The free radial forearm phalloplasty in the design by Gottlieb and Levine is well established at our institution and has proven safe and reliable since 1993. The operative results are satisfactory for both patients and surgeons even in the presence of relevant comorbidities and heavy smoking. We acknowledge the long ordeal and psychological pressure that our patients suffer from, before presenting in our outpatient clinic.
Sind die Arzneimittelprüfungen oder die klinischen  Erfahrungswerte ausschlaggebend?
Authors: Ravi Roy 
Published: November 2017

ZusammenfassungWährend die Arzneimittelprüfung die Grundrichtung einer Arznei deutlich aufzeigt – welche zusammenhängenden Symptome bei welcher Art von Pathologie bei der Arznei zugrunde liegen –, dient die genaue Analyse der klinischen Erfahrungen dazu, die unterschiedlichen, teilweise sogar widersprüchlichen Symptome den Krankheitsverläufen zuzuordnen. Aus einseitigen Darstellungen von Beobachtungen oder Prüfungen entstehen mitunter Lehrmeinungen, die womöglich keine Entsprechung mehr zu den Tatsachen beinhalten. Andererseits können durch eine wertschätzende Beachtung der klinischen Erfahrungen sogar ganz neue Erkenntnisse und Zusammenhänge gewonnen werden.
PIE: A prior knowledge guided integrated likelihood estimation method for bias reduction in association studies using electronic health records data
Authors: Huang Jing , Duan Rui , Hubbard Rebecca A , Wu Yonghui , Moore Jason H , Xu Hua , Chen Yong 
Published: November 2017

Abstract

Objectives
This study proposes a novelPrior knowledge guidedIntegrated likelihoodEstimation (PIE) method to correct bias in estimations of associations due to misclassification of electronic health record (EHR)-derived binary phenotypes, and evaluates the performance of the proposed method by comparing it to 2 methods in common practice.

Methods
We conducted simulation studies and data analysis of real EHR-derived data on diabetes from Kaiser Permanente Washington to compare the estimation bias of associations using the proposed method, the method ignoring phenotyping errors, the maximum likelihood method with misspecified sensitivity and specificity, and the maximum likelihood method with correctly specified sensitivity and specificity (gold standard). The proposed method effectively leverages available information on phenotyping accuracy to construct a prior distribution for sensitivity and specificity, and incorporates this prior information through the integrated likelihood for bias reduction.

Results
Our simulation studies and real data application demonstrated that the proposed method effectively reduces the estimation bias compared to the 2 current methods. It performed almost as well as the gold standard method when the prior had highest density around true sensitivity and specificity. The analysis of EHR data from Kaiser Permanente Washington showed that the estimated associations from PIE were very close to the estimates from the gold standard method and reduced bias by 60%–100% compared to the 2 commonly used methods in current practice for EHR data.

Conclusions
This study demonstrates that the proposed method can effectively reduce estimation bias caused by imperfect phenotyping in EHR-derived data by incorporating prior information through integrated likelihood.
Use of Antibiotic Prophylaxis for Tooth Extractions, Dental Implants, and Periodontal Surgical Procedures
Authors: Suda Katie J , Henschel Heather , Patel Ursula , Fitzpatrick Margaret A , Evans Charlesnika T 
Published: November 2017

Abstract

Background
Guidelines for antibiotics prior to dental procedures for patients with specific cardiac conditions and prosthetic joints have changed, reducing indications for antibiotic prophylaxis. In addition to guidelines focused on patient comorbidities, systematic reviews specific to dental extractions and implants support preprocedure antibiotics for all patients. However, data on dentist adherence to these recommendations are scarce.

Methods
This was a cross-sectional study of veterans undergoing tooth extractions, dental implants, and periodontal procedures. Patients receiving antibiotics for oral or nonoral infections were excluded. Data were collected through manual review of the health record.

Results
Of 183 veterans (mean age, 62 years; 94.5% male) undergoing the included procedures, 82.5% received antibiotic prophylaxis (mean duration, 7.1 ± 1.6 days). Amoxicillin (71.3% of antibiotics) and clindamycin (23.8%) were prescribed most frequently; 44.7% of patients prescribed clindamycin were not labeled as penicillin allergic. Of those who received prophylaxis, 92.1% received postprocedure antibiotics only, 2.6% received preprocedural antibiotics only, and 5.3% received pre- and postprocedure antibiotics. When prophylaxis was indicated, 87.3% of patients received an antibiotic. However, 84.9% received postprocedure antibiotics when preprocedure administration was indicated. While the majority of antibiotics were indicated, only 8.2% of patients received antibiotics appropriately. The primary reason was secondary to prolonged duration. Three months postprocedure, there were no occurrences of Clostridium difficile infection, infective endocarditis, prosthetic joint infections, or postprocedure oral infections.

Conclusion
The majority of patients undergoing a dental procedure received antibiotic prophylaxis as indicated. Although patients for whom antibiotic prophylaxis was indicated should have received a single preprocedure dose, most antibiotics were prescribed postprocedure. Dental stewardship efforts should ensure appropriate antibiotic timing, indication, and duration.
Quantitative Evaluation of Muscle Function, Gait, and Postural Control in People Experiencing Critical Illness After Discharge From the Intensive Care Unit
Authors: Kiriella Jeevaka B , Araujo Tamara , Vergara Martin , Lopez-Hernandez Laura , Cameron Jill I , Herridge Margaret , Gage William H , Mathur Sunita 
Published: November 2017

Abstract

Background
The path to recovery of muscle strength and mobility following discharge from the intensive care unit (ICU) has not been well described.

Objective
The study objective was to quantify muscle function, gait, and postural control at 3 and 6 months after discharge in people who were recovering from critical illness and who were ventilated for 7 days or more.

Design
This was a nested longitudinal study with continuous inclusion of individuals over a 2-year period and with age- and sex-matched controls.

Methods
Twenty-four people were tested at 3 months after ICU discharge; 16 of them (67%) were reevaluated at 6 months (post-ICU group). Healthy controls (n = 12) were tested at a single time point. Muscle function of the knee extensors (KEs), plantar flexors (PFs), and dorsiflexors (DFs) was assessed on a dynamometer. Gait was measured using an electronic walkway, and postural control was measured with 2 portable force plates.

Results
Muscle weakness was observed across all muscle groups at 3 months, with the greatest strength reductions in the ankle PFs (45%) and DFs (30%). Muscle power was reduced in the PFs and DFs but was not reduced in the KEs. Gait in the post-ICU group was characterized by a narrower step, longer stride, and longer double-support time than in the controls. Improvements were found in KE strength and in stride time and double-support time during gait at 6 months. Leg muscle strength and power had moderate associations with gait velocity, step width, and stride length (r = .44–.65).

Limitations
The small heterogeneous sample of people with a high level of function was a limitation of this study.

Conclusions
Muscle strength and power were impaired at 6 months after ICU discharge and were associated with gait parameters. Future studies are needed to examine the role of muscle strength and power training in post-ICU rehabilitation programs to improve mobility.
Exercise, Manual Therapy, and Booster Sessions in Knee Osteoarthritis: Cost-Effectiveness Analysis From a Multicenter Randomized Controlled Trial
Authors: Bove Allyn M , Smith Kenneth J , Bise Christopher G , Fritz Julie M , Childs John D , Brennan Gerard P , Abbott J Haxby , Fitzgerald G Kelley 
Published: November 2017

Abstract

Background
Limited information exists regarding the cost-effectiveness of rehabilitation strategies for individuals with knee osteoarthritis (OA).

Objective
The study objective was to compare the cost-effectiveness of 4 different combinations of exercise, manual therapy, and booster sessions for individuals with knee OA.

Design
This economic evaluation involved a cost-effectiveness analysis performed alongside a multicenter randomized controlled trial.

Setting
The study took place in Pittsburgh, Pennsylvania; Salt Lake City, Utah; and San Antonio, Texas.

Participants
The study participants were 300 individuals taking part in a randomized controlled trial investigating various physical therapy strategies for knee OA.

Intervention
Participants were randomized into 4 treatment groups: exercise only (EX), exercise plus booster sessions (EX+B), exercise plus manual therapy (EX+MT), and exercise plus manual therapy and booster sessions (EX+MT+B).

Measurements
For the 2-year base case scenario, a Markov model was constructed using the United States societal perspective and a 3% discount rate for costs and quality-adjusted life years (QALYs). Incremental cost-effectiveness ratios were calculated to compare differences in cost per QALY gained among the 4 treatment strategies.

Results
In the 2-year analysis, booster strategies (EX+MT+B and EX+B) dominated no-booster strategies, with both lower health care costs and greater effectiveness. EX+MT+B had the lowest total health care costs. EX+B cost${\$}$1061 more and gained 0.082 more QALYs than EX+MT+B, for an incremental cost-effectiveness ratio of${\$}$12,900/QALY gained.

Limitations
The small number of total knee arthroplasty surgeries received by individuals in this study made the assessment of whether any particular strategy was more successful at delaying or preventing surgery in individuals with knee OA difficult.

Conclusions
Spacing exercise-based physical therapy sessions over 12 months using periodic booster sessions was less costly and more effective over 2 years than strategies not containing booster sessions for individuals with knee OA.
Hearing Loss in Children With Otitis Media With Effusion: Actual and Simulated Effects on Speech Perception
Authors: Cai Ting , McPherson Bradley , Li Caiwei , Yang Feng 
Published: November 2017

Objective:
Conductive hearing loss simulations have attempted to estimate the speech-understanding difficulties of children with otitis media with effusion (OME). However, the validity of this approach has not been evaluated. The research aim of the present study was to investigate whether a simple, frequency-specific, attenuation-based simulation of OME-related hearing loss was able to reflect the actual effects of conductive hearing loss on speech perception.

Design:
Forty-one school-age children with OME-related hearing loss were recruited. Each child with OME was matched with a same sex and age counterpart with normal hearing to make a participant pair. Pure-tone threshold differences at octave frequencies from 125 to 8000 Hz for every participant pair were used as the simulation attenuation levels for the normal-hearing children. Another group of 41 school-age otologically normal children were recruited as a control group without actual or simulated hearing loss. The Mandarin Hearing in Noise Test was utilized, and sentence recall accuracy at four signal to noise ratios (SNR) considered representative of classroom-listening conditions were derived, as well as reception thresholds for sentences (RTS) in quiet and in noise using adaptive protocols.

Results:
The speech perception in quiet and in noise of children with simulated OME-related hearing loss was significantly poorer than that of otologically normal children. Analysis showed that RTS in quiet of children with OME-related hearing loss and of children with simulated OME-related hearing loss was significantly correlated and comparable. A repeated-measures analysis suggested that sentence recall accuracy obtained at 5-dB SNR, 0-dB SNR, and –5-dB SNR was similar between children with actual and simulated OME-related hearing loss. However, RTS in noise in children with OME was significantly better than that for children with simulated OME-related hearing loss.

Conclusions:
The present frequency-specific, attenuation-based simulation method reflected the effects of OME-related hearing loss on speech perception impairment in quiet environments. In noisy environments, the simulation method could only approximately estimate the effects of OME-related hearing loss on speech perception in typical classroom noise levels. Children with OME-related hearing loss may develop compensatory strategies to reduce the effects of hearing loss in adverse listening environments.