bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fine-scale diversity patterns in belowground microbial communities are consistent across kingdoms
Authors: Aas Anders Bjørnsgaard , Andrew Carrie J , Blaalid Rakel , Vik Unni , Kauserud Håvard , Davey Marie L 
Published: April 2019

ABSTRACTThe belowground environment is heterogeneous and complex at fine spatial scales. Physical structures, biotic components and abiotic conditions create a patchwork mosaic of potential niches for microbes. Questions remain about mechanisms and patterns of community assembly belowground, including: Do fungal and bacterial communities assemble differently? How do microbes reach the roots of host plants? Within a 4 m2 plot in alpine vegetation, high throughput sequencing of the 16S (bacteria) and ITS1 (fungal) ribosomal RNA genes was used to characterise microbial community composition in roots and adjacent soil of a viviparous host plant (Bistorta vivipara). At fine spatial scales, beta-diversity patterns in belowground bacterial and fungal communities were consistent, although compositional change was greater in bacteria than fungi. Spatial structure and distance-decay relationships were also similar for bacteria and fungi, with significant spatial structure detected at &lt;50 cm among root- but not soil-associated microbes. Recruitment of root microbes from the soil community appeared limited at this sampling and sequencing depth. Possible explanations for this include recruitment from low-abundance populations of soil microbes, active recruitment from neighbouring plants and/or vertical transmission of symbionts to new clones, suggesting varied methods of microbial community assembly for viviparous plants. Our results suggest that even at relatively small spatial scales, deterministic processes play a significant role in belowground microbial community structure and assembly.
Patterns of Social Engagement Among Older Adults With Mild Cognitive Impairment
Authors: Amano Takashi , Morrow-Howell Nancy , Park Sojung 
Published: April 2019

AbstractObjectivesPromoting engagement in social activities may be an intervention that prevents or delays cognitive impairment. Nevertheless, little is known about social engagement among people with mild cognitive impairment (MCI). We aim to examine patterns of social engagement among people with MCI and to assess whether factors under 4 domains of the WHO’s ICF model (personal factors, environmental factors, body functions and structure, and health condition) associate with different patterns of social engagement.MethodData were drawn from the 2010 Health and Retirement Study. The final sample comprised 1,227 people with cognitive impairment no dementia (CIND). Latent class analysis and multinomial logistic regression were utilized.ResultsThree patterns of social engagement were identified: informal social engagement only, formal and informal social engagement, and low social engagement. Factors in each of the 4 ICF model domains were associated with the probability of class membership.DiscussionOur findings suggest that social engagement is heterogeneous among people with CIND and that some groups of people with CIND have possibilities of engaging in more social activities, especially in formal social activities. Results also indicate that providing informal social resources may be essential for social programs designed specifically for people with CIND to promote their formal social engagement. Future study is needed to examine possible differences in outcomes across groups with similar patterns of social engagement.
Microbiome Learning Repo (ML Repo): A public repository of microbiome regression and classification tasks
Authors: Vangay Pajau , Hillmann Benjamin M , Knights Dan 
Published: April 2019

Abstract
The use of machine learning in high-dimensional biological applications, such as the human microbiome, has grown exponentially in recent years, but algorithm developers often lack the domain expertise required for interpretation and curation of the heterogeneous microbiome datasets. We present Microbiome Learning Repo (ML Repo, available at https://knights-lab.github.io/MLRepo/), a public, web-based repository of 33 curated classification and regression tasks from 15 published human microbiome datasets. We highlight the use of ML Repo in several use cases to demonstrate its wide application, and we expect it to be an important resource for algorithm developers.
B lymphocytes inactivation by Ibrutinib limits endometriosis progression in mice
Authors: Riccio L G C , Jeljeli M , Santulli P , Chouzenoux S , Doridot L , Nicco C , Reis F M , Abrão M S , Chapron C , Batteux F 
Published: April 2019

Abstract

STUDY QUESTION
What are the effects of B lymphocyte inactivation or depletion on the progression of endometriosis?

SUMMARY ANSWER
Skewing activated B cells toward regulatory B cells (Bregs) by Bruton’s tyrosine kinase (Btk) inhibition using Ibrutinib prevents endometriosis progression in mice while B cell depletion using an anti-CD20 antibody has no effect.

WHAT IS KNOWN ALREADY
A polyclonal activation of B cells and the presence of anti-endometrial autoantibodies have been described in a large proportion of women with endometriosis though their exact role in the disease mechanisms remains unclear.

STUDY DESIGN, SIZE, DURATION
This study included comparison of endometriosis progression for 21 days in control mice versus animals treated with the anti-CD20 depleting antibody or with the Btk inhibitor Ibrutinib that prevents B cell activation.

PARTICIPANTS/MATERIALS, SETTING, METHODS
After syngeneic endometrial transplantation, murine endometriotic lesions were compared between treated and control mice using volume, weight, ultrasonography, histology and target genes expression in lesions. Phenotyping of activated and regulatory B cells, T lymphocytes and macrophages was performed by flow cytometry on isolated spleen and peritoneal cells. Cytokines were assayed by ELISA.

MAIN RESULTS AND THE ROLE OF CHANCE
Btk inhibitor Ibrutinib prevented lesion growth, reduced mRNA expression of cyclooxygenase-2, alpha smooth muscle actin and type I collagen in the lesions and skewed activated B cells toward Bregs in the spleen and peritoneal cavity of mice with endometriosis. In addition, the number of M2 macrophages decreased in the peritoneal cavity of Ibrutinib-treated mice compared to anti-CD20 and control mice. Depletion of B cells using an anti-CD20 antibody had no effect on activity and growth of endometriotic lesions and neither on the macrophages, compared to control mice.

LARGE SCALE DATA
N/A.

LIMITATIONS, REASONS FOR CAUTION
It is still unclear whether B cell depletion by the anti-CD20 or inactivation by Ibrutinib can prevent establishment and/or progression of endometriosis in humans.

WIDER IMPLICATIONS OF THE FINDINGS
Further investigation may contribute to clarifying the role of B cell subsets in human endometriosis.

STUDY FUNDING/COMPETING INTEREST(S)
This research was supported by a grant of Institut National de la Santé et de la Recherche Médicale and Paris Descartes University. None of the authors has any conflict of interest to disclose.
US Practice Patterns and Impact of Monitoring for Mucosal Inflammation After Biologic Initiation in Inflammatory Bowel Disease
Authors: Limketkai Berkeley N , Singh Siddharth , Jairath Vipul , Sandborn William J , Dulai Parambir S 
Published: April 2019

Abstract

Background
We assessed practice patterns for monitoring mucosal inflammation after biologic initiation and the association between monitoring approaches and development of disease-related complications for Crohn’s disease (CD) and ulcerative colitis (UC).

Methods
This study used a Truven Health MarketScan (2007–2016) query for CD and UC patients initiating biologic therapy. Cumulative 24-month disease-related complications (corticosteroids, change of biologic, hospitalization, surgery) in patients undergoing proactive disease monitoring with lower endoscopy, fecal calprotectin, or cross-sectional radiographic enterography (computed tomography enterography or magnetic resonance enterography) within 6 months of biologic initiation vs no early monitoring after biologic initiation were compared. Cox proportional hazard ratios (HRs with 95% confidence intervals [CIs]) adjusted for propensity score were used.

Results
Within the first 24 months after biologic initiation, monitoring (proactive or reactive) was performed in 56.4% of CD patients and 67.8% of UC patients, with considerable geographic variability. Early (within 6 months) proactive monitoring was endoscopy-based (87.9%), performed in 11% of CD (n = 2195/19,899) and 12.8% of UC (n = 925/7247) patients. Compared with no early monitoring, early proactive monitoring was associated with a reduction in disease-related complications for CD (adjusted HR [aHR], 0.90; 95% CI, 0.84–0.96) and UC (aHR, 0.87; 95% CI, 0.78–0.97) and predominately driven by a reduction in corticosteroid use (CD: aHR, 0.83; 95% CI, 0.77–0.90; UC: aHR, 0.77; 95% CI, 0.69–0.87). Results were consistent across multiple sensitivity analyses.

Conclusions
Early proactive monitoring of mucosal inflammation in CD and UC within 6 months of biologic initiation was associated with reduction in disease-related complications over 24 months, primarily related to reduced steroid utilization. Wide variation exists in practice patterns for monitoring of mucosal inflammation after biologic initiation.
Impacts of Fruit-Feeding Arthropod Pests on Oranges and Mandarins in California
Authors: Cass Bodil N , Hack Lindsey M , Grafton-Cardwell Elizabeth E , Rosenheim Jay A 
Published: April 2019

AbstractOne of the major challenges facing citrus integrated pest management (IPM) in California is the recent, sharp increase in the acreage of mandarins being planted. The current citrus IPM guidelines have been established from years of experiments and experience in oranges, with no specific guidelines for mandarins. In the absence of research into key arthropod pest effects in mandarins, the assumption that the pest management practices for oranges appropriately transfer for optimal production in mandarins has not been tested. We used a data mining or ‘ecoinformatics’ approach in which we compiled and analyzed production records collected by growers and pest control advisors to gain an overview of direct pest densities and their relationships with fruit damage for 202 commercial groves, each surveyed for 1–10 yr in the main production region of California. Pest densities were different among four commonly grown species of citrus marketed as mandarins (Citrus reticulata, C. clementina, C. unshiu, and C. tangelo) compared with the standard Citrus sinensis sweet oranges, for fork-tailed bush katydids (Scudderia furcata Brunner von Wattenwyl [Orthoptera: Tettigoniidae]), and citrus thrips (Scirtothrips citri Moulton [Thysanoptera: Thripidae]). Citrus reticulata had notably low levels of fruit damage, suggesting they have natural resistance to direct pests, especially fork-tailed bush katydids. These results suggest that mandarin-specific research and recommendations would improve citrus IPM. More broadly, this is an example of how an ecoinformatics approach can serve as a complement to traditional experimental methods to raise new and unexpected hypotheses that expand our understanding of agricultural systems.
Clearing the Air: Avoiding Conflicts of Interest Within the United Nations Framework Convention on Climate Change
Authors: Dambacher Brook M R , Stilwell Matthew T , McGee Jeffrey S 
Published: April 2019

Abstract
Conflicts of interest (COIs) have the capacity to undermine the integrity and legitimacy of decision-making in international legal fora. The issue of COIs has recently become a contentious issue within the international negotiations under the United Nations Framework Convention on Climate Change (UNFCCC). Despite an emerging debate on COIs, key issues regarding engagement with certain non-state actors, and the reforms that could be implemented in response, remain to be systematically addressed. This article therefore examines best practice for addressing COIs in international fora to see how this might inform management of the issue within the UNFCCC. We find that protecting the integrity and legitimacy of the UNFCCC will likely require its Conference of the Parties to clearly define COIs and to adopt a process for their management. This reform will bring the UNFCCC into line with best practices in global governance and improve prospects for more effective international law on climate change.
Recruitment and Trial-Finding Apps—Time for Rules of the Road
Authors: Morain Stephanie R , Largent Emily A 
Published: April 2019

Abstract
The problem of insufficient recruitment to clinical oncology trials is well known. Some stakeholders view mobile apps as a solution with the potential to make recruitment more efficient, lower trial costs, support patient-centeredness, and accelerate treatment advances. Recruitment and trial-finding apps seek to disrupt the traditional approach to recruitment in several ways, including aggregating information about ongoing trials and presenting it in a user-friendly format, curating information to tailor search results to prospective participants’ interests, facilitating direct contact between prospective participants and trial sites, and, in at least one case, analyzing individuals’ tumor samples and medical records to provide tailored recommendations both for approved treatments and clinical trials. Although recruitment and trial-finding apps respond to a real need, they raise ethical concerns. Here, we outline six domains of ethical concern: review of recruitment materials, privacy and confidentiality, constrained choice and conflicts of interest, therapeutic misbranding, payment for accessing research-related information, and disruptions to care and research. We offer several suggestions and encourage additional dialogue to improve the ethical acceptability of these apps because, as third parties increasingly promise to revolutionize clinical trial recruitment by connecting patients and investigators via recruitment and trial-finding apps, we need some rules of the road.
Uncovering the Role of RNA-Binding Protein hnRNP K in B-Cell Lymphomas
Authors: Gallardo Miguel , Malaney Prerna , Aitken Marisa J L , Zhang Xiaorui , Link Todd M , Shah Vrutant , Alybayev Sanzhar , Wu Meng-Han , Pageon Laura R , Ma Huaxian , Jacamo Rodrigo , Yu Li , Xu-Monette Zijun Y , Steinman Haley , Lee Hun Ju , Sarbassov Dos , Rapado Inmaculada , Barton Michelle C , Martinez-Lopez Joaquin , Bueso-Ramos Carlos , Young Ken H , Post Sean M 
Published: April 2019

Abstract

Background
Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is an RNA-binding protein that is aberrantly expressed in cancers. We and others have previously shown that reduced hnRNP K expression downmodulates tumor-suppressive programs. However, overexpression of hnRNP K is the more commonly observed clinical phenomenon, yet its functional consequences and clinical significance remain unknown.

Methods
Clinical implications of hnRNP K overexpression were examined through immunohistochemistry on samples from patients with diffuse large B-cell lymphoma who did not harbor MYC alterations (n = 75). A novel transgenic mouse model that overexpresses hnRNP K specifically in B cells was generated to directly examine the role of hnRNP K overexpression in mice (three transgenic lines). Molecular consequences of hnRNP K overexpression were determined through proteomics, formaldehyde-RNA-immunoprecipitation sequencing, and biochemical assays. Therapeutic response to BET-bromodomain inhibition in the context of hnRNP K overexpression was evaluated in vitro and in vivo (n = 3 per group). All statistical tests were two-sided.

Results
hnRNP K is overexpressed in diffuse large B-cell lymphoma patients without MYC genomic alterations. This overexpression is associated with dismal overall survival and progression-free survival (P &lt; .001). Overexpression of hnRNP K in transgenic mice resulted in the development of lymphomas and reduced survival (P &lt; .001 for all transgenic lines; Line 171[n = 30]: hazard ratio [HR] = 64.23, 95% confidence interval [CI] = 26.1 to 158.0; Line 173 [n = 31]: HR = 25.27, 95% CI = 10.3 to 62.1; Line 177 [n = 25]: HR = 119.5, 95% CI = 42.7 to 334.2, compared with wild-type mice). Clinical samples, mouse models, global screening assays, and biochemical studies revealed that hnRNP K’s oncogenic potential stems from its ability to posttranscriptionally and translationally regulate MYC. Consequently, Hnrnpk overexpression renders cells sensitive to BET-bromodomain-inhibition in both in vitro and transplantation models, which represents a strategy for mitigating hnRNP K-mediated c-Myc activation in patients.

Conclusion
Our findings indicate that hnRNP K is a bona fide oncogene when overexpressed and represents a novel mechanism for c-Myc activation in the absence of MYC lesions.
Performance Measures of Magnetic Resonance Imaging Plus Mammography in the High Risk Ontario Breast Screening Program
Authors: Chiarelli Anna M , Blackmore Kristina M , Muradali Derek , Done Susan J , Majpruz Vicky , Weerasinghe Ashini , Mirea Lucia , Eisen Andrea , Rabeneck Linda , Warner Ellen 
Published: April 2019

AbstractBackgroundThe Ontario Breast Screening Program expanded in July 2011 to screen high-risk women age 30–69 years with annual magnetic resonance imaging (MRI) and digital mammography. This study examined the benefits of screening with mammography and MRI by age and risk criteria.MethodsThis prospective cohort study included 8782 women age 30–69 years referred to the High Risk Ontario Breast Screening Program from July 2011 to June 2015, with final results to December 2016. Cancer detection rates, sensitivity, and specificity of MRI and mammography combined were compared with each modality individually within risk groups stratified by age using generalized estimating equation models. Prognostic features of screen-detected breast cancers were compared by modality using Fisher exact test. All P values are two-sided.ResultsAmong 20 053 screening episodes, there were 280 screen-detected breast cancers (cancer detection rate = 14.0 per 1000, 95% confidence interval [CI] = 12.4 to 15.7). The sensitivity of mammography was statistically significantly lower than that of MRI plus mammography (40.8%, 95% CI = 29.3% to 53.5% vs 96.0%, 95% CI = 92.2% to 98.0%, P &lt; .001). In mutation carriers age 30–39 years, sensitivity of the combination was comparable with MRI alone (100.0% vs 96.8%, 95% CI = 79.2% to 100.0%, P = .99) but with statistically significantly decreased specificity (78.0%, 95% CI = 74.7% to 80.9% vs 86.2%, 95% CI = 83.5% to 88.5%, P &lt; .001). In women age 50–69 years, combining MRI and mammography statistically significantly increased sensitivity compared with MRI alone (96.3%, 95% CI = 90.6% to 98.6% vs 90.9%, 95% CI = 83.6% to 95.1%, P = .02), with a small but statistically significant decrease in specificity (84.2%, 95% CI = 83.1% to 85.2% vs 90.0%, 95% CI = 89.2% to 90.9%, P &lt; .001).ConclusionsScreening high risk women age 30–39 years with annual MRI only may be sufficient for cancer detection and should be evaluated further, particularly for mutation carriers. Among women age 50–69 years, detection is most effective when mammography is included with annual MRI.
Universal Tumor DNA BRCA1/2 Testing of Ovarian Cancer: Prescreening PARPi Treatment and Genetic Predisposition
Authors: Vos Janet R , Fakkert Ingrid E , de Hullu Joanne A , van Altena Anne M , Sie Aisha S , Ouchene Hicham , Willems Riki W , Nagtegaal Iris D , Jongmans Marjolijn C J , Mensenkamp Arjen R , Woldringh Gwendolyn H , Bulten Johan , Leter Edward M , Kets C Marleen , Simons Michiel , Ligtenberg Marjolijn J L , Hoogerbrugge Nicoline ,   OPA Working Group, Ebisch Inge M W , de Kievit Ineke M , Laurens Nicole G , Ottevanger Nelleke , van Alphen Robbert J , Vos M Caroline , van den Wurff Anneke A M , van Kampen Roel , Mertens Helen J M M , Sastrowijoto Prapto , Engelen Mirjam J A , Lalisang Roy I , Slangen Brigitte F M , Kooreman Loes F S , Creemers Geert-Jan M , Piek Jurgen M J , Klinkhamer Paul , Jeuken Judith W M , Aalders Anette L , Aliredjo Riena P 
Published: April 2019

Abstract

Background
Women with epithelial ovarian cancer (OC) have a higher chance to benefit from poly (ADP-ribose) polymerase inhibitor (PARPi) therapy if their tumor has a somatic or hereditary BRCA1/2 pathogenic variant. Current guidelines advise BRCA1/2 genetic predisposition testing for all OC patients, though this does not detect somatic variants. We assessed the feasibility of a workflow for universal tumor DNA BRCA1/2 testing of all newly diagnosed OC patients as a prescreen for PARPi treatment and cancer predisposition testing.

Methods
Formalin-fixed paraffin-embedded tissue was obtained from OC patients in seven hospitals immediately after diagnosis or primary surgery. DNA was extracted, and universal tumor BRCA1/2 testing was then performed in a single site. Diagnostic yield, uptake, referral rates for genetic predisposition testing, and experiences of patients and gynecologists were evaluated.

Results
Tumor BRCA1/2 testing was performed for 315 (77.6%) of the 406 eligible OC samples, of which 305 (96.8%) were successful. In 51 of these patients, pathogenic variants were detected (16.7%). Most patients (88.2%) went on to have a genetic predisposition test. BRCA1/2 pathogenic variants were shown to be hereditary in 56.8% and somatic in 43.2% of patients. Participating gynecologists and patients were overwhelmingly positive about the workflow.

Conclusions
Universal tumor BRCA1/2 testing in all newly diagnosed OC patients is feasible, effective, and appreciated by patients and gynecologists. Because many variants cannot be detected in DNA from blood, testing tumor DNA as the first step can double the identification rate of patients who stand to benefit most from PARP inhibitors.
Addition of Platinum Derivatives to Fluoropyrimidine-Based Neoadjuvant Chemoradiotherapy for Stage II/III Rectal Cancer: Systematic Review and Meta-Analysis
Authors: Hüttner Felix J , Probst Pascal , Kalkum Eva , Hackbusch Matthes , Jensen Katrin , Ulrich Alexis , Debus Jürgen , Jäger Dirk , Diener Markus K 
Published: April 2019

Abstract

Background
Current guidelines recommend neoadjuvant therapy for patients with stage II or III rectal cancer. The addition of platinum derivatives to fluoropyrimidine-based chemoradiotherapy has been frequently investigated, but their role in this setting remains controversial.

Methods
PubMed, Cochrane Library, and Web of Science were systematically searched for randomized trials comparing chemoradiotherapy with or without platinum agents in stage II or III rectal cancer. Main outcome parameters were overall and disease-free survival, additional outcomes included pathological complete response, isolated local recurrence, distant recurrence, toxicity, and perioperative morbidity. Time-to-event data were pooled as hazard ratios (HRs) by the inverse variance method and binary outcomes as odds ratios (ORs) by the Peto method with their respective 95% confidence interval (CI). All statistical tests were two-sided.

Results
Ten randomized controlled trials with data on 5599 patients were included in the meta-analysis. Platinum derivatives did not statistically significantly improve overall survival (HR = 0.93, 95% CI = 0.82 to 1.05, P = .23), disease-free survival (HR = 0.91, 95% CI = 0.83 to 1.01, P = .07), or local recurrence (OR = 0.83, 95% CI = 0.66 to 1.05, P = .12). However, it led to a statistically significant increase of pathological complete response (OR = 1.31, 95% CI = 1.10 to 1.55, P = .002) and a statistically significant reduction of distant recurrence (OR = 0.78, 95% CI = 0.66 to 0.92, P = .004). Benefits were accompanied by higher rates of grade 3 or 4 toxicities.

Conclusions
Intensified neoadjuvant chemoradiotherapy with the addition of platinum derivatives cannot be recommended routinely because it did not improve overall or disease-free survival and was associated with increased toxicity. It needs to be elucidated whether the benefits in distant recurrence and pathological complete response may be advantageous for selected high-risk patients.