bluuebunny/crossref_metadata_2025_split huggingface dataset:
High genetic connectivity in a gastropod with long-lived planktonic larvae
Authors: Crocetta Fabio , Caputi Luigi , Paz-Sedano Sofia , Tanduo Valentina , Vazzana Angelo , Oliverio Marco 
Published: October 2019

AbstractGenetic connectivity plays a crucial role in shaping the geographic structure of species. Our aim in this study was to explore the pattern of genetic connectivity in Bursa scrobilator, an iconic marine caenogastropod with long-lived pelagic larvae. Our study was based on the analysis of DNA sequence data for the 658-bp barcoding fragment of the mitochondrial cytochrome c oxidase subunit I (COI) gene. This is the largest DNA sequence dataset assembled to date for B. scrobilator. These data confirm that the two recently described subspecies B. scrobilator scrobilator (Linnaeus, 1758), from the Mediterranean and Macaronesia, and B. s. coriacea (Reeve, 1844), from West Africa, constitute two evolutionarily significant units (ESUs). We found that for the nominal subspecies, the variation in morphology (shell, radula and gross anatomy) and DNA sequences was not geographically structured, and this agrees with what we would expect in a species with high connectivity at the larval stage. The divergence between the two subspecies cannot be easily explained by isolation by distance, and we would argue that one or more extrinsic factors may have played a role in isolating the two ESUs and maintaining that isolation.
Histone lysine demethylase KDM4B regulates the alternative splicing of the androgen receptor in response to androgen deprivation
Authors: Duan Lingling , Chen Zhenhua , Lu Jun , Liang Yanping , Wang Ming , Roggero Carlos M , Zhang Qing-Jun , Gao Jason , Fang Yong , Cao Jiazheng , Lu Jian , Zhao Hongwei , Dang Andrew , Pong Rey-Chen , Hernandez Elizabeth , Chang Chun-Mien , Hoang David T , Ahn Jung-Mo , Xiao Guanghua , Wang Rui-tao , Yu Kai-jiang , Kapur Payal , Rizo Josep , Hsieh Jer-Tsong , Luo Junhang , Liu Zhi-Ping 
Published: October 2019

AbstractAlternative splicing is emerging as an oncogenic mechanism. In prostate cancer, generation of constitutively active forms of androgen receptor (AR) variants including AR-V7 plays an important role in progression of castration-resistant prostate cancer (CRPC). AR-V7 is generated by alternative splicing that results in inclusion of cryptic exon CE3 and translation of truncated AR protein that lacks the ligand binding domain. Whether AR-V7 can be a driver for CRPC remains controversial as the oncogenic mechanism of AR-V7 activation remains elusive. Here, we found that KDM4B promotes AR-V7 and identified a novel regulatory mechanism. KDM4B is phosphorylated by protein kinase A under conditions that promote castration-resistance, eliciting its binding to the splicing factor SF3B3. KDM4B binds RNA specifically near the 5′-CE3, upregulates the chromatin accessibility, and couples the spliceosome to the chromatin. Our data suggest that KDM4B can function as a signal responsive trans-acting splicing factor and scaffold that recruits and stabilizes the spliceosome near the alternative exon, thus promoting its inclusion. Genome-wide profiling of KDM4B-regulated genes also identified additional alternative splicing events implicated in tumorigenesis. Our study defines KDM4B-regulated alternative splicing as a pivotal mechanism for generating AR-V7 and a contributing factor for CRPC, providing insight for mechanistic targeting of CRPC.
Survival of diffuse astrocytic glioma, IDH1/2 wildtype, with molecular features of glioblastoma, WHO grade IV: a confirmation of the cIMPACT-NOW criteria
Authors: Tesileanu C Mircea S , Dirven Linda , Wijnenga Maarten M J , Koekkoek Johan A F , Vincent Arnaud J P E , Dubbink Hendrikus J , Atmodimedjo Peggy N , Kros Johan M , van Duinen Sjoerd G , Smits Marion , Taphoorn Martin J B , French Pim J , van den Bent Martin J 
Published: October 2019

Abstract

Background
The Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) has recommended that isocitrate dehydrogenase 1 and 2 wildtype (IDH1/2wt) diffuse lower-grade gliomas (LGGs) World Health Organization (WHO) grade II or III that present with (i) a telomerase reverse transcriptase promoter mutation (pTERTmt), and/or (ii) gain of chromosome 7 combined with loss of chromosome 10, and/or (iii) epidermal growth factor receptor (EGFR) amplification should be reclassified as diffuse astrocytic glioma, IDH1/2 wildtype, with molecular features of glioblastoma, WHO grade IV (IDH1/2wt astrocytomas WHO IV). This paper describes the overall survival (OS) of IDH1/2wt astrocytoma WHO IV patients, and more in detail patients with tumors with pTERTmt only.

Methods
In this retrospective multicenter study, we compared the OS of 71 IDH1/2wt astrocytomas WHO IV patients, with radiological characteristics of LGGs, with the OS of 197 IDH1/2wt glioblastoma patients. Moreover, we compared the OS of 22 pTERTmt only astrocytoma patients with the OS of the IDH1/2wt glioblastoma patients.

Results
Median OS was similar for IDH1/2wt astrocytoma WHO IV patients (23.8 mo) and IDH1/2wt glioblastoma patients (19.2 mo) (Cox proportional hazards model: hazard ratio [HR] 1.27, 95% CI: 0.85–1.88, P = 0.242). OS was also similar in patients with IDH1/2wt astrocytomas WHO IV, pTERTmt only, and IDH1/2wt glioblastomas (HR 1.15, 95% CI: 0.64–2.10, P = 0.641).

Conclusions
The presented data confirm the cIMPACT-NOW recommendation and we propose that IDH1/2wt astrocytomas WHO IV in the absence of other qualifying mutations should be classified as IDH1/2wt glioblastomas.
De novoassembly of a Tibetan genome and identification of novel structural variants associated with high-altitude adaptation
Authors:   Ouzhuluobu, He Yaoxi , Lou Haiyi , Cui Chaoying , Deng Lian , Gao Yang , Zheng Wangshan , Guo Yongbo , Wang Xiaoji , Ning Zhilin , Li Jun , Li Bin , Bai Caijuan ,   Baimakangzhuo,   Gonggalanzi,   Dejiquzong,   Bianba,   Duojizhuoma, Liu Shiming , Wu Tianyi , Xu Shuhua , Qi Xuebin , Su Bing 
Published: October 2019

AbstractStructural variants (SVs) may play important roles in human adaptation to extreme environments such as high altitude but have been under-investigated. Here, combining long-read sequencing with multiple scaffolding techniques, we assembled a high-quality Tibetan genome (ZF1), with a contig N50 length of 24.57 mega-base pairs (Mb) and a scaffold N50 length of 58.80 Mb. The ZF1 assembly filled 80 remaining N-gaps (0.25 Mb in total length) in the reference human genome (GRCh38). Markedly, we detected 17 900 SVs, among which the ZF1-specific SVs are enriched in GTPase activity that is required for activation of the hypoxic pathway. Further population analysis uncovered a 163-bp intronic deletion in the MKL1 gene showing large divergence between highland Tibetans and lowland Han Chinese. This deletion is significantly associated with lower systolic pulmonary arterial pressure, one of the key adaptive physiological traits in Tibetans. Moreover, with the use of the high-quality de novo assembly, we observed a much higher rate of genome-wide archaic hominid (Altai Neanderthal and Denisovan) shared non-reference sequences in ZF1 (1.32%–1.53%) compared to other East Asian genomes (0.70%–0.98%), reflecting a unique genomic composition of Tibetans. One such archaic hominid shared sequence—a 662-bp intronic insertion in the SCUBE2 gene—is enriched and associated with better lung function (the FEV1/FVC ratio) in Tibetans. Collectively, we generated the first high-resolution Tibetan reference genome, and the identified SVs may serve as valuable resources for future evolutionary and medical studies.
Authority and the Future of Consent in Population-Level Biomedical Research
Authors: Sheehan Mark , Thompson Rachel , Fistein Jon , Davies Jim , Dunn Michael , Parker Michael , Savulescu Julian , Woods Kerrie 
Published: October 2019

Abstract
Population-level biomedical research has become crucial to the health system’s ability to improve the health of the population. This form of research raises a number of well-documented ethical concerns, perhaps the most significant of which is the inability of the researcher to obtain fully informed specific consent from participants. Two proposed technical solutions to this problem of consent in large-scale biomedical research that have become increasingly popular are meta-consent and dynamic consent. We critically examine the ethical and practical credentials of these proposals and find them lacking. We suggest that the consent problem is not solved by adopting a technology driven approach grounded in a notion of ‘specific’ consent but by taking seriously the role of research governance in combination with broader conceptions of consent. In our view, these approaches misconstrue the rightful location of authority in the way in which population-level biomedical research activities are structured and organized. We conclude by showing how and why the authority for determining the nature and shape of choice making about participation ought not to lie with individual participants, but rather with the researchers and the research governance process, and that this necessarily leads to the endorsement of a fully articulated broad consent approach.
The perspective of people with axial spondyloarthritis regarding physiotherapy: room for the implementation of a more active approach
Authors: Osthoff Anne-Kathrin Rausch , van der Giesen Florus , Meichtry André , Walker Beatrice , van Gaalen Floris A , Goekoop-Ruiterman Yvonne P M , Peeters Andreas J , Niedermann Karin , Vliet Vlieland Theodora P M 
Published: October 2019

Abstract

Objectives
Physiotherapy is recommended in the management of people with axial Spondyloarthritis (axSpA), with new insights into its preferred content and dosage evolving. This study aimed to describe the use and preferences regarding individual and group physiotherapy among people with axSpA.

Methods
A cross-sectional survey was conducted among people with axSpA living in the Netherlands (NL) and Switzerland (CH).

Results
713 people with axSpA participated (56.7% male, median age 55 years, median ASAS-Hi-score 4.2). Response rates were 45% (n = 206) in NL and 29% in CH (n = 507). 83.3% of participants were or had been using physiotherapy. Individual therapy only was or had been used by 36.7%, a combination of individual plus land- and water-based group therapy was or had been used by 29.1% and group therapy only by 5.3%. Only less than half participants attending individual therapy reported active therapy (like aerobic, muscle strength, flexibility exercises). Although the majority (75.9%) was not aware of the increased cardiovascular risk, participants showed an interest in cardiovascular training, either individually or in a supervised setting. If supervised, a majority, in CH (75.0%) more than in NL (55.7%), prefers supervision by a specialized physiotherapist.

Conclusion
The majority of people with axSpA uses or used physiotherapy, more often in an individual than in a group setting. The content of individual therapy should be more active; in both therapy settings aerobic exercises should be promoted. Especially, enabling people with axSpA to perform exercises independently would meet their needs and might enhance their daily physical activity.
Foucault on the Wards: Rediscovering Reflection as a Social Pediatrician in Training
Authors: Maynard Kevin 
Published: October 2019

The author states that as a second-year medical student with a liberal arts degree, it was often difficult for him to reconcile his former liberal arts education with the current demands of his training. Although the medical curriculum increasingly acknowledges the importance of a biopsychosocial model, the prioritization of knowledge remains the same: know your biological, pharmacological, and anatomical facts. However, the author’s experience with a social pediatrics research summer studentship moved him beyond this basic sciences mindset and provided a practical framework for the application of his liberal arts training. The experience was twofold: he worked on a research project while simultaneously shadowing a pediatrician twice a week. His project applied a Foucauldian critical discourse analysis (CDA) to an archive of texts that sought to better characterize the term social pediatrics. The author concludes that the thought-changing reflection, mentorship, and concrete clinical experiences made possible by the summer studentship expanded his worldview.
The author discusses the complementary relationship between CDA, clinical experience, and self-reflection in the developing clinician. The purpose of his essay is threefold. First, by drawing on concepts from Descartes’ Meditations and Plato’s allegory of the cave, he establishes educational continuity between his liberal arts and medical training. Second, using clinical examples, he explores the practicality of discourse analysis and how skills regarding empathy and bias awareness are transferrable to the wards. Last, he highlights the importance of cognitive dissonance and transformative learning in the maturing physician.
Comparison of Continuing Medical Education at U.S. Medical Schools and Other Accredited Organizations: A 20-Year Analysis
Authors: Rayburn William F. , Regnier Kate , McMahon Graham T. 
Published: October 2019

Purpose
To describe a long-term overview of accredited continuing medical education (CME) at M.D.-granting medical schools in the United States.

Method
Self-reported data about type, duration, and numbers of learner participants of accredited CME activities and income for CME units from each medical school were compiled annually by the Accreditation Council for Continuing Medical Education (ACCME) between 1998 and 2017. Comparisons were made with data from all other ACCME-accredited organizations.

Results
Between 1998 and 2017, medical schools represented 18%–19% of all ACCME-accredited organizations. CME activities, hours of instruction, learner participants, and income increased gradually until reaching the highest levels between 2008 and 2011 before remaining constant. In 2017, each school generated a median of 132 activities (interquartile range [IQR]: 66–266), of which 44% were courses and 31% were regularly scheduled series (RSS), and a median of 29,824 learner interactions (IQR: 8,464–46,255). Total income rose gradually until 2010 before declining. In 2017, each school reported a median annual income of $1.0 million (IQR: $0.2 million – $2.9 million) from CME activities, comprising 44% from registration fees, 39% from commercial support, and 14% from advertising and exhibits. Compared with other accredited organization types, medical schools generally developed more RSS activities and proportionally fewer interprofessional and online activities.

Conclusions
While medical schools represent less than 20% of all ACCME-accredited organizations, their role is pivotal and their influence far-reaching. For medical schools to fulfill their responsibility as education leaders, they need to prioritize support for CME offices and faculty development and implement new approaches to teaching and learning.
Perceptions of Ethical Decision-Making Climate Among Clinicians Working in European and U.S. ICUs: Differences Between Nurses and Physicians*
Authors: Jensen Hanne Irene , Hebsgaard Stine , Hansen Tina Charlotte Bitsch , Johnsen Rikke Frank Aagaard , Hartog Christiane S. , Soultati Ioanna , Szucs Orsolya , Wilson Michael E. , van den Bulcke Bo , Benoit Dominique D. , Piers Ruth 
Published: October 2019

Objectives:
To examine perceptions of nurses and physicians in regard to ethical decision-making climate in the ICU and to test the hypothesis that the worse the ethical decision-making climate, the greater the discordance between nurses’ and physicians’ rating of ethical decision-making climate with physicians hypothesized to rate the climate better than the nurses.

Design:
Prospective observational study.

Setting:
A total of 68 adult ICUs in 13 European countries and the United States.

Subjects:
ICU physicians and nurses.

Interventions:
None.

Measurements and Main Results:
Perceptions of ethical decision-making climate among clinicians were measured in April-May 2014, using a 35-items self-assessment questionnaire that evaluated seven factors (empowering leadership by physicians, interdisciplinary reflection, not avoiding end-of-life decisions, mutual respect within the interdisciplinary team, involvement of nurses in end-of-life care and decision-making, active decision-making by physicians, and ethical awareness). A total of 2,275 nurses and 717 physicians participated (response rate of 63%). Using cluster analysis, ICUs were categorized according to four ethical decision-making climates: good, average with nurses’ involvement at end-of-life, average without nurses’ involvement at end-of-life, and poor. Overall, physicians rated ethical decision-making climate more positively than nurses (p < 0.001 for all seven factors). Physicians had more positive perceptions of ethical decision-making climate than nurses in all 13 participating countries and in each individual participating ICU. Compared to ICUs with good or average ethical decision-making climates, ICUs with poor ethical decision-making climates had the greatest discordance between physicians and nurses. Although nurse/physician differences were found in all seven factors of ethical decision-making climate measurement, the factors with greatest discordance were regarding physician leadership, interdisciplinary reflection, and not avoiding end-of-life decisions.

Conclusions:
Physicians consistently perceived ICU ethical decision-making climate more positively than nurses. ICUs with poor ethical decision-making climates had the largest discrepancies.
Efficacy, Patient-Reported Outcomes, and Safety for Millennial Subjects Treated With OnabotulinumtoxinA for Moderate to Severe Horizontal Forehead Lines
Authors: Palm Melanie D. , Few Julius , Patel Tapan , Safa Marva , Drinkwater Adrienne , Mao Cheri , Garcia Julie K. 
Published: October 2019

BACKGROUND
Millennials (aged 18–34 years) represent a growing segment of the facial aesthetic market.

OBJECTIVE
To evaluate investigator-assessed efficacy, patient-reported outcomes (PROs), and safety for millennials versus subjects aged at least 35 years after onabotulinumtoxinA treatment of forehead lines (FHL) across 2 phase 3 studies.

METHODS
Eligible subjects with moderate to severe FHL received onabotulinumtoxinA (FHL: 20 U; glabellar lines: 20 U, with/without 24 U in crow's feet line regions) or placebo. All findings were pooled by the age group.

RESULTS
Millennials composed 15% of subjects (176/1,178). Day 30 responder rates of at least 1-grade Facial Wrinkle Scale improvement in FHL severity for millennials versus subjects aged 35 years and older were 100% versus 97.8% at maximum eyebrow elevation and 78.4% versus 83.5% at rest, respectively. Responder rates were significantly greater with onabotulinumtoxinA than placebo (p ≤ .015) for both groups through Day 180. Similar trends were observed for achieving none/mild severity. Both age groups reported high satisfaction rates and improved psychological impacts with onabotulinumtoxinA treatment. No new safety signals were detected.

CONCLUSION
OnabotulinumtoxinA treatment was well tolerated, and both age groups experienced significant improvements in FHL severity, high satisfaction, and improved psychological impacts after treatment. Millennials reported numerically greater improvements.
Risk Factors for Recurrent Community-associated Clostridiodes Difficile Infection in Children
Authors: Parmar Deepika , Dang Rebecca , Miranda-Katz Margot , Alabaster Amy , Greenhow Tara L. 
Published: October 2019

Background:
Recurrence of community-associated (CA) Clostridiodes difficile infection (CDI) approaches 30%. Studies on risk factors and treatment of choice for pediatric CA-CDI are scarce with variable recommendations.

Methods:
This was a retrospective cohort study of the electronic health records of children 1–17 years with stool specimens sent for C. difficile at Kaiser Permanente Northern California from January 01, 2012 to December 31, 2016. Children with (1) CA disease, (2) confirmatory C. difficile laboratory testing with no other identified causes of diarrhea and (3) clinical symptoms consistent with CDI were defined as cases. Recurrent CA-CDI was defined using the above-described case criteria and onset of diarrhea within 8 weeks of primary CA-CDI.

Results:
Of the 7350 children with stool samples sent for C. difficile testing, 408 had primary CA-CDI. Forty-five (11%) experienced a recurrence. Using multivariable logistic regression, inflammatory bowel disease [odds ratio (OR) 7.5; 95% confidence interval (CI): 2.6–21.1] and cancer (OR 6.3; 95% CI: 1.6–24.1) diagnoses were risk factors for recurrent disease. Compared with children of Caucasian race, those with multi/other/unknown race had an OR of 3.03 (95% CI: 1.04–8.82) of recurrence. There was no statistically significant difference in the type or duration of therapy as a predictor for recurrent CA CDI. Six percent of children who received metronidazole were switched to vancomycin due to subjective metronidazole allergy or intolerance or metronidazole treatment failure.

Conclusions:
Recurrent CA-CDI in children in our population is less common than previously reported. This study supports first-line treatment with the standard, short course metronidazole in most cases of primary CA-CDI.
Norovirus Activity and Genotypes in Sporadic Acute Diarrhea in Children in Shanghai During 2014–2018
Authors: Wang Xiangshi , Wei Zhongqiu , Guo Jiayin , Cai Jiehao , Chang Hailing , Ge Yanling , Zeng Mei 
Published: October 2019

Background:
Based on the impact public health of norovirus and the current progress in norovirus vaccine development, it is necessary to continuously monitor the epidemiology of norovirus infection, especially in children who are more susceptible to norovirus.

Objectives:
To monitor the activity and genotypes of norovirus infection in sporadic diarrhea in Shanghainese children during 2014–2018.

Study design:
Acute diarrheal cases were prospectively enrolled in the outpatient setting. Real-time reverse transcription-polymerase chain reaction was used for screening norovirus GI and GII genogroups. Dual norovirus genotypes were identified based on the partial capsid and polymerase gene sequences.

Results:
Of the 3422 children with diarrhea, 510 (14.9%) were positive for noroviruses with 13 (2.5%) strains being GI genogroup and 497 (97.5%) strains being GII genogroup. Five distinct capsid GII genotypes were identified, including GII.4-Sydney/2012 (71.8%), GII.3 (13.8%), GII.17 (7.8%), GII.2 (6.0%), GII.6 (0.3%) and GII.8 (0.3%). Seven polymerase GII genotypes were identified, including GII.Pe (77.0%), GII.P12 (11.0%), GII.P17 (9.0%), GII.P16 (2.1%), and GII.P7, GII.P8 and GII.P2 in each (0.3%). Eleven distinct polymerase/capsid genotypes were identified with GII.Pe/GII.4-Sydney/2012 (74.2%), GII.P12/GII.3 (11.7%) and GII.P17/GII.17 (7.7%) being common. GII.P17/GII.17 strains were detected since September 2014. Recombinant GII.P16/GII.2 strains were detected since December 2016.

Conclusions:
Norovirus is a major pathogen causing diarrhea in Shanghainese children. GII.Pe/GII.4-Sydney/2012 strains remained the predominant genotype. The emergence of GII.P17/GII.17 and GII.P16/GII.2 strains in sporadic diarrhea was consistent with norovirus-associated outbreaks attributable to these 2 novel variants in China. Continuous monitoring norovirus genotypes circulating in pediatric population is needed for current vaccine development.