bluuebunny/crossref_metadata_2025_split huggingface dataset:
ClinGen Expert Clinical Validity Curation of 164 Hearing Loss Gene-Disease Pairs
Authors: DiStefano Marina T. , Hemphill Sarah E. , Oza Andrea M. , Siegert Rebecca K. , Grant Andrew R. , Hughes Madeline Y. , Cushman Brandon J. , Azaiez Hela , Booth Kevin T. , Chapin Alex , Duzkale Hatice , Matsunaga Tatsuo , Shen Jun , Zhang Wenying , Kenna Margaret , Schimmenti Lisa A. , Tekin Mustafa , Rehm Heidi L. , Tayoun Ahmad N. Abou , Amr Sami S. ,   on behalf of the ClinGen Hearing Loss Clinical Domain Working Group
Published: January 2019

AbstractPurposeProper interpretation of genomic variants is critical to successful medical decision making based on genetic testing results. A fundamental prerequisite to accurate variant interpretation is the clear understanding of the clinical validity of gene-disease relationships. The Clinical Genome Resource (ClinGen) has developed a semi-quantitative framework to assign clinical validity to gene-disease relationships.MethodsThe ClinGen Hearing Loss Gene Curation Expert Panel (HL GCEP) uses this framework to perform evidence-based curations of genes present on testing panels from 17 clinical laboratories in the Genetic Testing Registry. The HL GCEP curated and reviewed 142 genes and 164 gene-disease pairs, including 105 nonsyndromic and 59 syndromic forms of hearing loss.ResultsThe final outcome included 82 Definitive (50%), 12 Strong (7%), 25 Moderate (15%), 32 Limited (20%), 10 Disputed (6%), and 3 Refuted (2%) classifications. The summary of each curation is date stamped with the HL GCEP approval, is live, and will be kept up-to-date on the ClinGen website (https://search.clinicalgenome.org/kb/gene-validity).ConclusionThis gene curation approach serves to optimize the clinical sensitivity of genetic testing while reducing the rate of uncertain or ambiguous test results caused by the interrogation of genes with insufficient evidence of a disease link.
Emergent microscale gradients give rise to metabolic cross-feeding and antibiotic tolerance in clonal bacterial populations
Authors: Co Alma Dal , van Vliet Simon , Ackermann Martin 
Published: January 2019

AbstractBacteria often live in spatially structured groups such as biofilms. In these groups, cells can collectively generate gradients through the uptake and release of compounds. In turn, individual cells adapt their activities to the environment shaped by the whole group. Here we studied how these processes can generate phenotypic variation in clonal populations and how this variation contributes to the resilience of the population to antibiotics. We grew two-dimensional populations of Escherichia coli in microfluidic chambers where limiting amounts of glucose were supplied from one side. We found that the collective metabolic activity of cells created microscale gradients where nutrient concentration varied over a few cell lengths. As a result, growth rates and gene expression levels varied strongly between cells close in space. Furthermore, we found evidence for a metabolic cross-feeding interaction between glucose fermenting and acetate respiring subpopulations. Finally, we found that the populations were able to survive an antibiotic pulse that was lethal in well-mixed conditions, likely due to the presence of a slow growing subpopulation. Our work shows that emergent metabolic gradients can have important consequences for the functionality of bacterial populations as they create opportunities for metabolic interactions and increase the populations’ tolerance to environmental stressors.
The Piezo channel is used by migrating cells to sense compressive load
Authors: Srivastava Nishit , Traynor David , Kabla Alexandre J. , Kay Robert R. 
Published: January 2019

AbstractMigrating cells face varied mechanical and physical barriers in physiological environments, but how they sense and respond to them remains to be fully understood. We used a custom-built ‘cell squasher’ to apply uniaxial pressure to Dictyostelium cells migrating under soft agarose. Within 10 seconds of application, loads of as little as 100 Pa cause cells to move using blebs instead of pseudopods. Cells lose volume and surface area under pressure and their actin dynamics are perturbed. Myosin-II is recruited to the cortex, potentially increasing contractility and so driving blebbing. The blebbing response depends on extra-cellular calcium, is accompanied by increased cytosolic calcium and largely abrogated in null mutants of the Piezo stretch-operated channel. We propose that migrating cells sense mechanical force through mechano-sensitive channels, leading to an influx of calcium and cortical recruitment of myosin, thus re-directing the motile apparatus to produce blebs rather than pseudopods.
Stool-derived eukaryotic RNA biomarkers for detection of high-risk adenomas
Authors: Barnell Erica , Kang Yiming , Barnell Andrew , Campbell Katie , Kruse Kimberly R. , Wurtzler Elizabeth M. , Griffith Malachi , Chaudhuri Aadel A. , Griffith Obi L. 
Published: January 2019

AbstractBackground and aimsColorectal cancer (CRC) is the second leading cause of cancer related deaths in the United States. Mortality is largely attributable to low patient compliance with screening and a subsequent high frequency of late-stage diagnoses. Noninvasive methods, such as stool- or blood-based diagnostics could improve patient compliance, however, existing techniques cannot adequately detect high-risk adenomas (HRAs) and early-stage CRC.MethodsHere we apply cancer profiling using amplicon sequencing of stool-derived eukaryotic RNA for 275 patients undergoing prospective CRC screening. A training set of 154 samples was used to build a random forest model that included 4 feature types (differentially expressed amplicons, total RNA expression, demographic information, and fecal immunochemical test results). An independent hold out test set of 121 patients was used to assess model performance.ResultsWhen applied to the 121-patient hold out test set, the model attained a receiver operating characteristic (ROC) area under the curve (AUC) of 0.94 for CRC and a ROC AUC of 0.87 for CRC and HRAs. In aggregate, the model achieved a 91 % sensitivity for CRC and a 73% sensitivity for HRAs at an 89% specificity for all other findings (medium-risk adenomas, low-risk adenomas, benign polyps, and no findings on a colonoscopy).ConclusionCollectively, these results indicate that in addition to early CRC detection, stool-derived biomarkers can accurately and noninvasively identify HRAs, which could be harnessed to prevent CRC development for asymptomatic, average-risk patients.
Justifying students’ performance
Authors: Ukut Idorenyin Idorenyin Thomas , Krairit Donyaprueth 
Published: January 2019

PurposeThe purpose of this study is to compare students and instructors’ perspectives on students’ performance based on unified theory of acceptance and use of technology (UTAUT) framework. This study also aims to propose additional variables that might be used to extend the UTAUT model to make it more appropriate for the educational setting.Design/methodology/approachThe study was carried out using a three-pronged methodology, namely, literature review, expert interviews and self-administered survey of 430 students and 55 information and communication technology (ICT) instructors from tertiary institutions in Akwa Ibom State, Nigeria. Validity analysis were conducted using IBM SPSS version 24 and two structural equation models were finally obtained using AMOS version 24.FindingsThis study finds UTAUT constructs including social influence, facilitating condition and voluntariness of use to have direct and significant impact on students’ performance from the students and the instructors’ perspective. The result of the instructors’ perspective shows that ICT use behaviour of students have direct and significant impact on students’ performance, but the students’ result shows an insignificant direct effect of use behaviour on students’ performance. From the students and the instructors’ perspective, gender, age and experience have statistically significantly direct impact on performance expectancy in this study. The result also shows that additional variables including ICT instructors’ characteristics, motivation and personal environment directly affect students’ performance from the students’ perspective, but the result of the instructors’ perspective shows that the influence of ICT instructors’ characteristics, motivation and personal environment does not directly and significantly affect students’ performance.Research limitations/implicationsThis study was limited to tertiary institutions in Akwa Ibom State, Nigeria. Consequently, the findings of this study are limited to Akwa Ibom State, Nigeria, and may not be generalised to cover other countries.Originality/valueThis research shows that the students and instructors have different views on variables that impact on students’ performance. This study finds empirical evidence to support the direct impact of use behaviour on students’ performance from the instructors’ perspective, while the students disagree but indicated an empirical evidence to show that instructors’ characteristics, environment and motivation contribute a greater impact on students’ performance. From the students and the instructors’ perspective, gender, age and experience have statistically significantly direct impact on performance expectancy in this study. This adds to the findings in the original UTAUT that indicated that performance expectancy is moderated by gender and age.
Effect of effortful swallowing training on tongue strength and oropharyngeal swallowing function in stroke patients with dysphagia: a double‐blind, randomized controlled trial
Authors: Park Hee‐Su , Oh Dong‐Hwan , Yoon Taehyung , Park Ji‐Su 
Published: January 2019

AbstractBackgroundEffortful swallowing training (EST) is a remedial method for the training of swallowing‐related muscles in the oropharyngeal phase. However, clinical evidence of its effectiveness is insufficient.AimsTo investigate the effects of EST on tongue strength and swallowing function in patients with stroke.Methods & ProceduresStroke patients with dysphagia were randomly assigned to one of two groups: an experimental group (n = 12) and a control group (n = 12). The experimental group underwent EST, while the control group performed saliva swallowing. Training was conducted 5 days per week for 4 weeks. Both groups underwent conventional dysphagia treatment for 30 min/day, 5 days/week for 4 weeks.Outcomes & ResultsTongue strength was assessed using the Iowa Oral Performance Instrument. The Videofluoroscopic Dysphagia Scale (VDS), based on a videofluoroscopic swallowing study, was used to analyze oropharyngeal swallowing function. The experimental group showed greater improvements in anterior and posterior tongue strength compared with the control group (p = 0.046 and 0.042, respectively), and greater improvement in the oral phases of the VDS (p = 0.017).Conclusions & ImplicationsWe recommend EST as a remedial strategy for improving tongue strength and oral swallowing function in patients with stroke.
Sovereignty Beyond the State: Exception and Informality in a Western European City
Authors: Picker Giovanni 
Published: January 2019

AbstractBridging debates on urban sovereignty and urban informality, this paper argues that relationships between sovereignty and informality may not reside exclusively in the way the sovereign state decides to allow or forbid informality, but also in the way sovereignty is distributed among a range of state and non‐state actors. Drawing upon fieldwork on the early‐2010s management of displaced Romanian Romani families in two emergency camps in the city of Montreuil (France), the paper shows how the NGO responsible for managing one camp acted as sovereign power, allowing a number of informal activities to thrive within its confines. By contrast, inside the other camp, managed by another NGO that resolutely implemented state directives, only formal activities took place. Building on Dean's (2010) concept of ‘disaggregated sovereignty’, the paper mobilizes this disjuncture as a case for critically examining how the ‘state of exception’ takes shape beyond the state's grip. A subtext running throughout is the parallel between the very first camps for civilians in nineteenth‐century colonized territories and these twenty‐first‐century camps for Roma in Europe—both elicited a state of exception partially predicated on camp dwellers’ perceived ethnic/racial homogeneity.
A Comprehensive Review on Kiwifruit Allergy: Pathogenesis, Diagnosis, Management, and Potential Modification of Allergens Through Processing
Authors: Wang Jin , Vanga Sai Kranthi , McCusker Christine , Raghavan Vijaya 
Published: January 2019

AbstractKiwifruit is rich in bioactive components including dietary fibers, carbohydrates, natural sugars, vitamins, minerals, omega‐3 fatty acids, and antioxidants. These components are beneficial to boost the human immune system and prevent cancer and heart diseases. However, kiwifruit is emerging as one of the most common elicitors of food allergies worldwide. Kiwifruit allergy results from an abnormal immune response to kiwifruit proteins and occur after consuming this fruit. Symptoms range from the oral allergy syndrome (OAS) to the life‐threatening anaphylaxis. Thirteen different allergens have been identified in green kiwifruit and, among these allergens, Act d 1, Act d 2, Act d 8, Act d 11, and Act d 12 are defined as the “major allergens.” Act d 1 and Act d 2 are ripening‐related allergens and are found in abundance in fully ripe kiwifruit. Structures of several kiwifruit allergens may be altered under high temperatures or strong acidic conditions. This review discusses the pathogenesis, clinical features, and diagnosis of kiwifruit allergy and evaluates food processing methods including thermal, ultrasound, and chemical processing which may be used to reduce the allergenicity of kiwifruit. Management and medical treatments for kiwifruit allergy are also summarized.
Regional favoritism and tax avoidance: evidence from China
Authors: Chen Yunsen , Huang Jianqiao , Liu Hang , Wang Weimin 
Published: January 2019

AbstractThis paper investigates the effect of officials’ regional favoritism on corporate tax avoidance activity in China. We find that firms located in regions that were formerly administered by the current provincial governors have a higher level of tax avoidance than other firms in the province. Further evidence indicates that regional favoritism affects tax avoidance through two channels: regional politicians’ personal connections with the governor and firms’ political access to the governor. Overall, the findings support China's current official selection and promotion guidelines that restrict hometown favoritism. Our results further imply that favoritism can also extend to officials’ former administrative regions.
The Hepatitis C Awareness Through to Treatment (HepCATT) study: improving the cascade of care for hepatitis C virus‐infected people who inject drugs in England
Authors: Harrison Graham I. , Murray Karen , Gore Roxanne , Lee Penelope , Sreedharan Aravamuthan , Richardson Paul , Hughes Amanda J. , Wiselka Martin , Gelson Will , Unitt Esther , Ratcliff Karen , Orton Annette , Trinder Kerry , Simpson Charlotte , Ryder Stephen D. , Oelbaum Sandra , Foster Graham R. , Christian Archie , Smith Stuart , Thomson Brian J. , Reynolds Rosy , Harris Magdalena , Hickman Matthew , Irving William L. 
Published: January 2019

AbstractBackground and AimsPrevious studies have shown low rates of diagnosis and treatment of hepatitis C virus (HCV) infection in people who inject drugs (PWID). Our aims were to test the effect of a complex intervention [Hepatitis C Awareness Through to Treatment (HepCATT)] in drug and alcohol clinics—primarily, on engagement of HCV‐positive PWID with therapy and, secondarily, on testing for HCV, referral to hepatology services and start of HCV treatment.Design and settingA non‐randomized pilot study in three specialist addiction clinics in England comparing an intervention year (starting between September 2015 and February 2016) with a baseline year (2014), together with three control clinics.ParticipantsAnalysis included all attendees at the intervention and control specialist addiction clinics identified as PWID.InterventionThe intervention comprised the placement of a half‐time facilitator in each clinic for 12 months with the brief to increase diagnosis of HCV infection within clients at those services and the engagement of diagnosed individuals with an appropriate care pathway. The facilitator undertook various activities, which could include training of key workers, direct interaction with clients, streamlining and support for hepatology appointments and introduction of dried blood‐spot testing.MeasurementsFor each clinic and period, we obtained the total number of clients and, as relevant, their status as PWID, tested for HCV, known HCV‐positive, engaged with HCV therapy or treated.FindingsCompared with baseline, there was strong evidence that engagement with HCV therapy in the intervention year increased (P < 0.001) more in the HepCATT centres than controls, up +31 percentage points [95% confidence interval (CI) = 19–43] versus −12 (CI = –31 to +6) and odds ratio (OR) = 9.99 (CI = 4.42–22.6) versus 0.35 (CI = 0.08–1.56). HepCATT centres also had greater increases in HCV testing (OR = 3.06 versus 0.78, P < 0.001), referral to hepatology (OR = 9.60 versus 0.56, P < 0.001) and treatment initiation (OR = 9.5 versus 0.74, P < 0.001).ConclusionsIntroducing a half‐time facilitator into drug and alcohol clinics in England increased engagement of HCV‐positive people who inject drugs with hepatitis C virus care pathways, with increased uptake also of testing, referral to hepatology and initiation of treatment.
Clinical efficacy of concurrent bevacizumab for malignant ascites in nonsquamous cell carcinoma of the lung
Authors: Hsu Jui‐Feng , Lee Yen‐Lung , Chang Hsu‐Liang , Wei Po‐Ju , Shen Yu‐Ting , Lin Chi‐Min , Li Ching‐Yi , Chong Inn‐Wen , Yang Chih‐Jen 
Published: January 2019

AbstractPurposeLung cancer with malignant peritoneal carcinomatosis and malignant ascites is rare, often indicates the terminal stage, and is refractory to treatment. The median survival time of lung cancer patients with malignant ascites has been reported to be as short as 15 days to 2 months in retrospective studies.MethodsWe reviewed all lung cancer patients who had cytologically or pathologically proven malignant ascites and received aggressive therapy including chemotherapy, anti‐angiogenesis agents and target therapy at a Taiwan hospital from January 2015 to December 2017. In addition, we searched PubMed using the terms “lung cancer,” “peritoneal carcinomatosis” and “malignant ascites” to find other studies reporting experience of such treatment.ResultsThree consecutive lung cancer patients with malignant ascites (3/265, 1.13%) were included in this case series study, all of whom received bevacizumab with three other drugs (erlotinib, afatinib and gemcitabine). All of the patients showed a good response to treatment with a marked decrease in ascites. Two of the patients had a long progression‐free survival time of more than 5 months. In the literature review, several cases reports and case series documented the treatment efficacy, however no prospective or retrospective studies reported treatment strategies.ConclusionsAggressive treatment for lung cancer with malignant ascites is encouraged when possible. Bevacizumab‐based treatment may serve as one effective treatment strategy for non‐squamous cell lung carcinoma with malignant ascites. Further prospective trials are urgently needed.
Oral health of adolescents in the Colac‐Otway Shire
Authors: Mayze Lara , Pawlak Jacqui , Rogers Margaret , Smith Michael 
Published: January 2019

AbstractObjectiveAltruistically, the developmental stage of adolescence poses a unique time frame to instil positive oral health behaviours. Caries are commonly associated with lower socioeconomic populations and regional or rural regions and are often prevalent in adolescents. This research project assessed the patterns of oral health and oral health behaviours of adolescents and investigated any potentially changeable behaviours or ways in which health services might support improvement in their oral health.Design, setting and participantsAdolescents aged 11–17 years were recruited from four secondary schools in the Colac‐Otway Shire (n = 143). Students were screened for dental decay and the condition of tooth surfaces was recorded. Completion of a dental anxiety screening survey and a World Health Organization oral health behaviours survey was undertaken.Main outcome measureEarly carious lesions and advanced decay.ResultsEarly carious lesions were found in 86 (60%) of students and more advanced decay in 39 (28%). Dental decay was associated with consuming sweets and soft drinks, irregular dental check‐ups and students whose mother's highest education level was primary school. Consuming fruit was protective against decay.ConclusionThis study identified that adolescents were experiencing high percentage of decay and not regularly visiting the dentist for dental screening. Programs that take the oral health therapists to regional and rural areas and lower socioeconomic areas might be warranted to target secondary schools.
Atypical choroideremia presenting with early‐onset macular atrophy
Authors: Kontos Georgios , Kwan Jennifer , Xue Kanmin , Patrício Maria I. , Clouston Penny , Packham Emily , MacLaren Robert E. , Downes Susan M. 
Published: January 2019

AbstractChoroideremia is an X‐linked recessive retinal degeneration predominantly affecting hemizygous males. It is caused by mutations in the CHM gene that encodes the Rab escort protein‐1. Characteristic features include early nyctalopia followed by progressive constriction of peripheral visual fields and sparing of the central vision until late in life with a distinct fundoscopic appearance. We present the case of a 17‐year‐old male with a c.282delT in exon 4 of CHM that has not previously been reported. Phenotypically this patient presented with an atypical choroideremia phenotype of early central macular degeneration in addition to the classic peripheral fundus characteristic findings.
Influence of myopic macular degeneration severity on treatment outcomes with intravitreal aflibercept in the MYRROR study
Authors: Cheung Chui Ming Gemmy , Ohno‐Matsui Kyoko , Wong Tien Yin , Li Tummy , Asmus Friedrich , Leal Sérgio ,   MYRROR Study Investigators
Published: January 2019

AbstractPurposeTo determine the influence of baseline myopic macular degeneration (MMD) severity on outcomes with intravitreal aflibercept (IVT‐AFL) in patients with myopic choroidal neovascularization (CNV).MethodsMYRROR was a randomized, double‐masked study in patients with myopic CNV treated with IVT‐AFL/sham over 48 weeks. At baseline/week 48, images were retrospectively graded for MMD.ResultsAt baseline, 115 eyes had a valid MMD grading result; at week 48, grading results were available for 99 eyes [IVT‐AFL (n = 78)/sham (n = 21)]. Severity of baseline MMD was distributed as follows: category 1: 19/115 (17%); category 2: 67/115 (58%); category 3: 22/115 (19%); category 4: 7/115 (6%). Higher MMD category was associated with older age (nominal p = 0.007) and longer axial length (nominal p = 0.025). At week 48, patients in the mild and severe groups had visual acuity gains of +13.5 and +12.4 letters, respectively. Baseline MMD severity did not significantly affect visual/anatomical outcomes or number of treatments. Visual Functioning Questionnaire‐25 scores improved more in mild (+5.6) versus severe (+0.4) MMD (nominal p = 0.03). There were no new safety events.ConclusionsVisual acuity gains, morphological outcomes and dosing frequency were not affected by baseline MMD severity in patients treated with IVT‐AFL. A benefit with IVT‐AFL treatment was observed for all baseline MMD stages included in this study.