bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elagolix reduced dyspareunia and improved health-related quality of life in premenopausal women with endometriosis-associated pain
Authors: Leyland Nicholas , Taylor Hugh S , Archer David F , Peloso Paul M , Soliman Ahmed M , Palac Hannah L , Martinez Marisol , Abrao Mauricio S 
Published: September 2019

Objectives: The objective was to evaluate the effects of elagolix on dyspareunia in women with endometriosis-associated pain. Methods: Data were pooled from two similar, randomized, double-blind, placebo-controlled, 6-month phase 3 studies (Elaris Endometriosis-I and Elaris Endometriosis-II) of elagolix at two doses (150 mg QD and 200 mg BID) in women with endometriosis-associated pain. In this post hoc analysis, dyspareunia responders were defined as having a clinically meaningful decrease from baseline in the dyspareunia score and decreased or stable use of rescue analgesic agents, as recorded in a daily electronic diary. Sexual relationship was assessed using the 30-item Endometriosis Health Profile questionnaire sexual relationship module. Results: A total of 1384 women reported ⩾1 day of sexual activity at baseline (35 days prior to and including day 1 of treatment). Of these 1384 women, 1297 (94%) reported ⩾1 day of any dyspareunia (mild, moderate, or severe), of which 51% reported ⩾1 day of severe dyspareunia. Among sexually active women who reported any dyspareunia at baseline, both elagolix doses led to improvements in dyspareunia. Women in the 200-mg BID group showed more months at which the dyspareunia response rates were statistically significantly greater than placebo, particularly in a subgroup of women with severe dyspareunia at baseline. Compared to placebo, both elagolix doses led to statistically significantly greater improvements in the mean 30-item Endometriosis Health Profile sexual relationship module score. Conclusion: Up to 6 months of elagolix treatment improved dyspareunia in women with endometriosis-associated pain in a dose-dependent manner, with 200-mg BID dose showing the most significant improvements in dyspareunia and quality of sexual relationships compared with placebo.
Smartphone Applications for Assessing Ankle Range of Motion in Clinical Practice
Authors: Wang Kevin Y. , Hussaini S. Hanif , Teasdall Robert D. , Gwam Chukwuweike U. , Scott Aaron T. 
Published: September 2019

Background: Measuring ankle range of motion (ROM) following injury or intervention is necessary for monitoring recovery as well as for calculating permanent impairment ratings in workers’ compensation cases. In recent years, smartphone application developers have created applications (apps) that emulate ROM measurement tools like the universal goniometer. This study assessed the correlation between smartphone ROM measurements and universal goniometer measurements, as well as the reliability and usability of these apps in clinical practice. Methods: Three raters used the Goniometer app (Gonio), Clinometer app (Clino), DrGoniometer app (DrG), and a universal goniometer (UG) to assess the ankle ROM in plantarflexion and dorsiflexion of 24 patients with ankle pathology. Each patient completed a survey on the usability of the apps. Results: Lin’s concordance correlation coefficient test showed moderate correlation between the smartphone and UG measurements (Lin‘s correlation coefficient [rLC] = 0.931, 95% confidence interval [CI] = 0.911-0.946 for UG-Gonio; rLC = 0.908, 95% CI = 0.881-0.929 for UG-Clino; rLC = 0.935, 95% CI = 0.915-0.950 for UG-DrG). A 2-way mixed model showed good to excellent interrater reliability for each app for plantarflexion and dorsiflexion (ICCp = 0.836, ICCd = 0.912, P < .001 for Gonio; ICCp = 0.788, ICCd = 0.893, P < .001 for Clino; ICCp = 0.777, ICCd = 0.897, P < .001 for DrG). Most participants surveyed were very comfortable with having their ankle ROM measured by a smartphone. Conclusion: Smartphone apps may be a more convenient way to measure ankle ROM than UG. Physicians can use these apps to measure a patient’s ROM in clinic, a patient could send a picture of his or her dorsiflexed or plantarflexed ankle to the physician to remotely track ROM, or a patient could measure his or her own ROM at home using a personal smartphone. Level of Evidence: Level IV, case series.
Effects of dietary intervention on vitamin B12 status and cognitive level of 18-month-old toddlers in high-poverty areas: a cluster-randomized controlled trial
Authors: Sheng Xiaoyang , Wang Junli , Li Feng , Ouyang Fengxiu , Ma Jingqiu 
Published: September 2019

Abstract

Background
The local diet in high-poverty areas in China is mainly vegetarian, and children may be more vulnerable to vitamin B12 deficiency.

Objective
The aims of this study were to explore the vitamin B12 status of toddlers living in high-poverty areas of China and to observe the effects of different complementary foods on the vitamin B12 status and cognitive level of these toddlers.

Methods
The study was nested within a cluster-randomized controlled trial implemented in 60 administrative villages (clusters) of Xichou County in which infants aged 6 months old were randomized to receive 50 g/d of pork (meat group), an equi-caloric fortified cereal supplement (fortified cereal group) or local cereal supplement (local cereal group) for one year. At 18 months, a subsample of the 180 toddlers (60 from each group) was randomly tested for serum vitamin B12 and total homocysteine (tHcy) levels, and their neurodevelopment was evaluated.

Results
The median serum concentrations of vitamin B12 and tHcy were 360.0 pg/mL and 8.2 μmol/L, respectively, in children aged 18 months. Serum vitamin B12 concentrations less than 300 pg/mL were found in 62 (34.4%) children, and concentrations less than 200 pg/mL were found in 30 (16.7%) children. The median vitamin B12 concentration was significantly different among the three groups (P < 0.001). The highest vitamin B12 level was demonstrated in the fortified cereal group (509.5 pg/mL), followed by the meat group (338.0 pg/mL) and the local cereal group (241.0 pg/mL). Vitamin B12 concentration was positively correlated with the cognitive score (P < 0.001) and the fine motor score (P = 0.023) of the Bayley Scales of Infant Development, 3rd Edition (BSID III) screening test. Compared to the local cereal group, children in the meat group had higher cognitive scores (P < 0.05).

Conclusion
In poor rural areas of China, vitamin B12 deficiency in toddlers was common due to low dietary vitamin B12 intake. Fortified cereal and meat could help improve the vitamin B12 status of children and might improve their cognitive levels.

Trial registration
The larger trial in which this study was nested was registered at clinical trials.gov as NCT00726102. It was registered on July 31, 2008.
Quantitative MNase-seq accurately maps nucleosome occupancy levels
Authors: Chereji Răzvan V. , Bryson Terri D. , Henikoff Steven 
Published: September 2019

AbstractMicrococcal nuclease (MNase) is widely used to map nucleosomes. However, its aggressive endo-/exo-nuclease activities make MNase-seq unreliable for determining nucleosome occupancies, because cleavages within linker regions produce oligo- and mono-nucleosomes, whereas cleavages within nucleosomes destroy them. Here, we introduce a theoretical framework for predicting nucleosome occupancies and an experimental protocol with appropriate spike-in normalization that confirms our theory and provides accurate occupancy levels over an MNase digestion time course. As with human cells, we observe no overall differences in nucleosome occupancies betweenDrosophilaeuchromatin and heterochromatin, which implies that heterochromatic compaction does not reduce MNase accessibility of linker DNA.
Reconstruction of a dorsal thoracic wall defect with a dorsal intercostal artery perforator flap after removal of a bulky cutaneous squamous cell carcinoma: a case report
Authors: Lupon E. , Lellouch A. G. , Deilhes F. , Chaput B. , Berthier C. 
Published: September 2019

Abstract

Introduction
Surgical reconstruction of large soft tissue defects of the upper back is challenging. Although the usefulness of free perforator flaps has been demonstrated, local options remain limited. The dorsal intercostal artery perforator flap was recently described but its use is still uncommon.

Case report
An 88-year-old Causasian woman presented with a large, ulcerated, left prescapular cutaneous squamous cell carcinoma (T3N0M0). Complete excision was performed, and the resulting defect was reconstructed with a dorsal intercostal artery perforator flap based on two perforators. Postoperative recovery was uncomplicated and adjuvant radiotherapy commenced 10 weeks later.

Conclusion
Compared to conventional muscle flaps, the dorsal intercostal artery perforator flap offers greater protection of muscle function, is less invasive, and lowers donor site morbidity. Based on these advantages, this flap should be considered a useful local option for reconstructing large cutaneous defects of the upper back.
Look granulomatosis with polyangiitis (GPA) straight in the face: missed opportunities leading to a delayed diagnosis
Authors: Rolle N. , Muruganandam M. , Jan I. , Harji F. M. , Harrington J. , Konstantinov K. N. 
Published: September 2019

Abstract
Granulomatosis with polyangiitis (GPA) is a systemic vasculitis with a potential to involve any organ system. It remains an important cause of kidney related morbidity and mortality. Early diagnosis can be difficult and requires high index of suspicion in all patients, but especially in cases with atypical presentation. We report a case with GPA, which was diagnosed only after new and advancing symptoms belied the original diagnosis of bilateral facial palsy and aortic mural thrombus.
Feed nutritional value of brewers’ spent grain residue resulting from protease aided protein removal
Authors: Shen Yizhao , Abeynayake Ranithri , Sun Xin , Ran Tao , Li Jianguo , Chen Lingyun , Yang Wenzhu 
Published: September 2019

Abstract

Background
This study was conducted to evaluate the feed nutritional value of brewers’ spent grain (BSG) residue resulting from protease aided protein removal. The nutritional value was measured as nutrient content, gas production, nutrient digestibility and fermentation characteristics in batch culture.

Results
Protein extraction process decreased content of crude protein but concentrated the neutral detergent fibre (NDF) and ferulic acid in BSG residue. The changes in the chemical composition of BSG residue varied with enzyme and enzyme dosage. Digestibility of dry matter (DMD) and NDF of residue differed among proteases. Increasing alcalase dosage linearly decreased DMD, whereas, the DMD linearly increased as everlase or flavourzyme dosage increased. Compared with BSG, the DMD, gas production and fermentation acid concentration of BSG residues were lower, whereas NDF digestibility was higher.

Conclusions
The substantially increased NDF content and improved in vitro NDF digestibility due to protease hydrolysis suggest that BSG residue can be potentially exploited as a viable fibre source for ruminant feeding.
Perceptions and trends in the use of community pharmacies in Ghana
Authors: Okai Grace Adjei , Abekah-Nkrumah Gordon , Asuming Patrick Opoku 
Published: September 2019

AbstractObjectiveTo examine the patterns in utilization of community pharmacies and perceptions of the general public towards community pharmacists’ role in health services delivery.MethodA cross-sectional household survey was conducted in Ga West district. A total of 497 adults (18 years and above) were chosen using a three-stage cluster random sampling technique. information on respondents’ contact with community pharmacies (i.e. 12 months prior to the study), reasons for visiting the pharmacies, factors influencing the choice of a particular pharmacy and perception towards community pharmacists’ roles were collected. Data collected were analyzed using stata version 14.Key findingsOut of the 497 respondents, 415 indicated that they had used pharmacies within the last 12 months prior to the study, while 82 indicated that they had not used the facilities within the same time frame. majority of the pharmacy users (33.7%) visited community pharmacies once a month. Approximately 84% of the pharmacy users frequently visited community pharmacies to get treatment for minor ailments. most users (about 75%) chose to visit a particular pharmacy as it was close to their home/workplace/hospital/clinic. More than half of the pharmacy users identified the pharmacist as the first point of contact in case of any drug-related problem. Less than half of the respondents (44.9%) perceived community pharmacists as health professionals with a good balance between health and business matters.ConclusionThe findings of the study suggest that beside the fact that majority of the respondents believe that community pharmacists are responsive, friendlier and have the capacity to handle minor ailments, they are indeed using community pharmacies for the treatment of minor ailments. It will therefore be important to develop appropriate policy and regulations that enables community pharmacies to adequately participate in the delivery of primary care and thereby improve population health.
Cell-culture growth conditions resulting in the oxidation of a recombinant antigen-binding fragment
Authors: Siddiquee Khandaker , Zhao Cheng , Stemler Michelle A. , Zeck Bill , Fishpaugh Jeffrey R. , Allen Steven P. 
Published: September 2019

AbstractUse of Quality-by-Design (QbD) tools is becoming an important part of the bioprocessing industry when developing a process for manufacturing operations to ensure the robustness and reproducibility of the biologic product. In the present study, a QbD tool, Design of Experiments (DOE), was utilized to optimize a bioprocess for the production of a CHO recombinant antigen-binding fragment (rFab) in small-scale bioreactors. DOE studies evaluated percent dissolved oxygen, temperature, and feeding strategy specific to this Chinese Hamster Ovary (CHO) clone. It was determined that these factors influenced cell viability, yield of the recombinant protein, and metabolic byproduct formation. To ensure the quality of the target molecule in the cell-culture process, small-scale purifications and analytical evaluation of the target molecule were completed prior to cell-culture scale-up to ensure that oxidation of the rFab, presence of free light chain, and truncation of thiol group were not observed. Analysis of the purified rFab by mass spectrometry indicated that rFab oxidation occurred under poor cell-culture conditions. PCR profile array results also revealed increased transcription of the oxidative genes Superoxide Dismutase 3, Myeloperoxidase, Dual Oxidase Like 2, Nuclear Receptor Coactivator 7, NADPH Oxidase Organizer 1, Mitochondria Uncouple Protein 3, Eosinophil Peroxidase, Lactoperoxidase Like, Serum Albumin Like, and GlutathioneS-Transferase Pi 1 in this CHO strain. The present study suggests a mechanism and pathway for the oxidation of an rFab molecule during cell-culture bioprocess optimization. The present study also demonstrated the importance of utilizing the QbD tool of DOE to optimize the cell-culture bioprocess prior to scaling up into the large-scale production bioreactor.
Isomerization of glucose into fructose with homogenous amine-type base catalysts: amine structure, chain length, and kinetics
Authors: Zhang Libo , Deng Bailian , Li Nan , Zhong Hong 
Published: September 2019

Abstract
Three homogeneous organosilanes amine and aliphatic primary amine were used as amine catalysts to evaluate their catalytic activity and kinetic towards glucose isomerization. Catalysts structure (primary, secondary, tertiary amine), terminal groups and alkyl chain length were investigated and compared elaborately. Result showed organosilanes tertiary amine behaved the best and amine generated OH− and amine itself contributed the isomerization reaction. The generated acidic by-product not only decreased fructose selectivity but also affected glucose conversion kinetic. The effect of siloxane (–Si–O–CH3) substituent with methyl (–CH3) can be insignificant, but it provided guiding significance for selecting amine-type homogeneous or grafted amine catalysts for glucose isomerization reaction. Longer alkyl chain resulted in lower glucose conversion because of the alkyl chain curls that would weaken the amine catalytic effect and hydration ability. Catalyst loading and initial glucose concentration investigations further showed that amine would effectively catalyze the isomerization reaction under varied operational conditions. This work will provide more details about organic amine catalysts on glucose isomerization into fructose and promote synthesis of platform chemicals in the applications of biorenewable chemicals and fuel.
3D-bioprinted tracheal reconstruction: an overview
Authors: Frejo Lidia , Grande Daniel A. 
Published: September 2019

AbstractCongenital tracheomalacia and tracheal stenosis are commonly seen in premature infants. In adulthood, are typically related with chronic obstructive pulmonary disease, and can occur secondarily from tracheostomy, prolong intubation, trauma, infection and tumors. Both conditions are life-threatening when not managed properly. There are still some surgical limitations for certain pathologies, however tissue engineering is a promising approach to treat massive airway dysfunctions. 3D-bioprinting have contributed to current preclinical and clinical efforts in airway reconstruction. Several strategies have been used to overcome the difficulty of airway reconstruction such as scaffold materials, construct designs, cellular types, biologic components, hydrogels and animal models used in tracheal reconstruction. Nevertheless, additional long-term in vivo studies need to be performed to assess the efficacy and safety of tissue-engineered tracheal grafts in terms of mechanical properties, behavior and, the possibility of further stenosis development.
Smoking and the risk for bipolar disorder: evidence from a bidirectional Mendelian randomisation study
Authors: Vermeulen Jentien M. , Wootton Robyn E. , Treur Jorien L. , Sallis Hannah M. , Jones Hannah J. , Zammit Stanley , van den Brink Wim , Goodwin Guy M. , de Haan Lieuwe , Munafò Marcus R. 
Published: September 2019

BackgroundThere is increasing evidence that smoking is a risk factor for severe mental illness, including bipolar disorder. Conversely, patients with bipolar disorder might smoke more (often) as a result of the psychiatric disorder.AimsWe conducted a bidirectional Mendelian randomisation (MR) study to investigate the direction and evidence for a causal nature of the relationship between smoking and bipolar disorder.MethodWe used publicly available summary statistics from genome-wide association studies on bipolar disorder, smoking initiation, smoking heaviness, smoking cessation and lifetime smoking (i.e. a compound measure of heaviness, duration and cessation). We applied analytical methods with different, orthogonal assumptions to triangulate results, including inverse-variance weighted (IVW), MR-Egger, MR-Egger SIMEX, weighted-median, weighted-mode and Steiger-filtered analyses.ResultsAcross different methods of MR, consistent evidence was found for a positive effect of smoking on the odds of bipolar disorder (smoking initiation ORIVW = 1.46, 95% CI 1.28–1.66, P = 1.44 × 10−8, lifetime smoking ORIVW = 1.72, 95% CI 1.29–2.28, P = 1.8 × 10−4). The MR analyses of the effect of liability to bipolar disorder on smoking provided no clear evidence of a strong causal effect (smoking heaviness betaIVW = 0.028, 95% CI 0.003–0.053, P = 2.9 × 10−2).ConclusionsThese findings suggest that smoking initiation and lifetime smoking are likely to be a causal risk factor for developing bipolar disorder. We found some evidence that liability to bipolar disorder increased smoking heaviness. Given that smoking is a modifiable risk factor, these findings further support investment into smoking prevention and treatment in order to reduce mental health problems in future generations.
Contribution of Inherited DNA-Repair Gene Mutations to Hormone-Sensitive and Castrate-Resistant Metastatic Prostate Cancer and Implications for Clinical Outcome
Authors: Yadav Siddhartha , Hart Steven N. , Hu Chunling , Hillman David , Lee Kun Y. , Gnanaolivu Rohan , Na Jie , Polley Eric C. , Couch Fergus J. , Kohli Manish 
Published: September 2019

PURPOSE To compare the prevalence of germline mutations in metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castrate-resistant prostate cancer (mCRPC) and assess the impact of mutations on progression to castration resistance and overall survival. METHODS Targeted sequencing of germline DNA from 704 men (221 at the time of mHSPC and 483 at the time of mCRPC) enrolled in two advanced prostate cancer registries at Mayo Clinic between 2003 and 2013 was performed for 21 predisposition genes. Frequencies of pathogenic mutations were compared in patients and reference controls to identify genes enriched in metastatic prostate cancer. Multivariable Cox proportional hazards regression was used to identify predictors of progression to mCRPC and overall survival. RESULTS Sixty-eight germline mutations in 12 genes were identified in 66 men (9.4%). Mutations in ATM, BRCA2, CHEK2, FANCM, and TP53 were significantly enriched (odds ratio greater than 2.0) in the metastatic cohorts compared with reference controls. The frequency of germline mutations was similar for patients with mHSPC and mCRPC (11.8% v 8.3%; P = .16). The median time to progression from mHSPC to mCRPC was 23.1 and 32.5 months for patients with and without mutations, respectively ( P = .96). Although older age at diagnosis, Gleason score greater than 7, elevated alkaline phosphatase level, and high volume of disease were associated with shorter duration of progression to mCRPC and poor overall survival, mutation status was not (progression to mCRPC hazard ratio, 0.81; 95% CI, 0.61 to 1.09; P = .17; overall survival hazard ratio, 1.00; 95% CI, 0.75 to 1.34; P = .98). CONCLUSION Similarly elevated rates of germline predisposition gene mutations in mHSPC and mCRPC suggest that germline genetic testing may help to guide medical management for all patients with advanced metastatic prostate cancer. Mutation status was not associated with shorter progression to mCRPC or poor overall survival.