bluuebunny/crossref_metadata_2025_split huggingface dataset:
A culturally and linguistically salient pilot intervention to promote colorectal cancer screening among Latinos receiving care in a Federally Qualified Health Center
Authors: Gwede Clement K , Sutton Steven K , Chavarria Enmanuel A , Gutierrez Liliana , Abdulla Rania , Christy Shannon M , Lopez Diana , Sanchez Julian , Meade Cathy D 
Published: March 2019

Abstract
Despite established benefits, colorectal cancer (CRC) screening is underutilized among Latinos/Hispanics. We conducted a pilot 2-arm randomized controlled trial evaluating efficacy of two intervention conditions on CRC screening uptake among Latinos receiving care in community clinics. Participants (N = 76) were aged 50–75, most were foreign-born, preferred to receive their health information in Spanish, and not up-to-date with CRC screening. Participants were randomized to either a culturally linguistically targeted Spanish-language fotonovela booklet and DVD intervention plus fecal immunochemical test [FIT] (the LCARES, Latinos Colorectal Cancer Awareness, Research, Education and Screening intervention group); or a non-targeted intervention that included a standard Spanish-language booklet plus FIT (comparison group). Measures assessed socio-demographic variables, health literacy, CRC screening behavior, awareness and beliefs. Overall, FIT uptake was 87%, exceeding the National Colorectal Cancer Roundtable’s goal of 80% by 2018. The LCARES intervention group had higher FIT uptake than did the comparison group (90% versus 83%), albeit not statistically significant (P = 0.379). The LCARES intervention group was associated with greater increases in CRC awareness (P = 0.046) and susceptibility (P = 0.013). In contrast, cancer worry increased more in the comparison group (P = 0.045). Providing educational materials and a FIT kit to Spanish-language preferring Latinos receiving care in community clinics is a promising strategy to bolster CRC screening uptake to meet national targets.
Functional rescue in a mouse model of congenital muscular dystrophy with megaconial myopathy
Authors: Sayed-Zahid Ambreen A , Sher Roger B , Sukoff Rizzo Stacey J , Anderson Laura C , Patenaude Kathryn E , Cox Gregory A 
Published: March 2019

Abstract
Congenital muscular dystrophy with megaconial myopathy (MDCMC) is an autosomal recessive disorder characterized by progressive muscle weakness and wasting. The observation of megamitochondria in skeletal muscle biopsies is exclusive to this type of MD. The disease is caused by loss of function mutations in the choline kinase beta (CHKB) gene which results in dysfunction of the Kennedy pathway for the synthesis of phosphatidylcholine. We have previously reported a rostrocaudal MD (rmd) mouse with a deletion in the Chkb gene resulting in an MDCMC-like phenotype, and we used this mouse to test gene therapy strategies for the rescue and alleviation of the dystrophic phenotype. Introduction of a muscle-specific Chkb transgene completely rescues motor and behavioral function in the rmd mouse model, confirming the cell-autonomous nature of the disease. Intramuscular gene therapy post-disease onset using an adeno-associated viral 6 (AAV6) vector carrying a functional copy of Chkb is also capable of rescuing the dystrophy phenotype. In addition, we examined the ability of choline kinase alpha (Chka), a gene paralog of Chkb, to improve dystrophic phenotypes when upregulated in skeletal muscles of rmd mutant mice using a similar AAV6 vector. The sum of our results in a preclinical model of disease suggest that replacement of the Chkb gene or upregulation of endogenous Chka could serve as potential lines of therapy for MDCMC patients.
Performance of multispecies assessment models: insights on the influence of diet data
Authors: Trijoulet Vanessa , Fay Gavin , Curti Kiersten L , Smith Brian , Miller Timothy J 
Published: March 2019

Abstract
Multispecies stock assessment models require predator diet data, e.g. stomach samples. Diet data can be unavailable, sparse, of small sample size, or very noisy. It is unclear if multispecies interactions can be estimated without bias when interactions are weak. Research is needed about how model performance is affected by the availability or quality of diet data and by the method for fitting it. We developed seven age-structured operating models that simulate trophic interactions for two fish species and different scenarios of diet data availability or quality. The simulated data sets were fitted using four statistical catch-at-age models that estimated fishing, predation and residual natural mortality and differed in the way the diet data was fitted. Fitting the models to diet data averaged over time should be avoided since it resulted in estimation bias. Fitting annual diet composition per stomach produced bias estimates due to the occurrence of zeros in the observed proportions and the statistical assumptions for the diet model. Fitting to annual stomach proportions averaged across stomachs led to unbiased results even if the number of stomachs was small, the interactions were weak or some sampled years and ages were missing. These methods should be preferred when fitting multispecies models.
Measles, mumps and rubella vs diphtheria–tetanus–acellular-pertussis–inactivated-polio–Haemophilus influenzae type b as the most recent vaccine and risk of early ‘childhood asthma’
Authors: Rieckmann Andreas , Hærskjold Ann , Benn Christine Stabell , Aaby Peter , Lange Theis , Sørup Signe 
Published: March 2019

AbstractBackground and objectiveLive vaccines may have beneficial non-specific effects. We tested whether the live measles, mumps and rubella (MMR) vaccine compared with the non-live diphtheria–tetanus–acellular-pertussis–inactivated-polio–Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine as the most recent vaccine was associated with less childhood asthma and fewer acute hospital contacts for childhood asthma among boys and girls.MethodsThis study is a nationwide register-based cohort study of 338 761 Danish children born between 1999 and 2006. We compared (i) the incidence of first-registered childhood asthma based on hospital contacts and drug prescriptions and (ii) the incidence of severe asthma defined as acute hospital contacts for childhood asthma between the ages of 15 and 48 months among children whose last received vaccine was three doses of DTaP-IPV-Hib and then MMR with children whose last received vaccine was three doses of DTaP-IPV-Hib.ResultsFor boys, following the recommended vaccine schedule of MMR after DTaP-IPV-Hib3 compared with DTaP-IPV-Hib3 as the last received vaccine, MMR was associated with 8.1 (95% confidence interval 3.9–12.3) fewer childhood asthma cases per 1000 boys, corresponding to 10% (5–15%) reduction in the cumulative incidence of childhood asthma. MMR, when given last, was also associated with 16.3 (95% confidence interval 12.7–20.0) fewer acute hospital admissions for childhood asthma per 1000 boys, corresponding to a 27% (22–31%) reduction in the cumulative incidence. No associations were seen for girls.ConclusionMMR may have a protective effect against childhood asthma for boys. This calls for an understanding of whether non-specific effects of vaccines can be used to optimize our vaccine programmes.
A novel approach for exposing and sharing clinical data: the Translator Integrated Clinical and Environmental Exposures Service
Authors: Fecho Karamarie , Pfaff Emily , Xu Hao , Champion James , Cox Steve , Stillwell Lisa , Peden David B , Bizon Chris , Krishnamurthy Ashok , Tropsha Alexander , Ahalt Stanley C 
Published: March 2019

AbstractObjectiveThis study aimed to develop a novel, regulatory-compliant approach for openly exposing integrated clinical and environmental exposures data: the Integrated Clinical and Environmental Exposures Service (ICEES).Materials and MethodsThe driving clinical use case for research and development of ICEES was asthma, which is a common disease influenced by hundreds of genes and a plethora of environmental exposures, including exposures to airborne pollutants. We developed a pipeline for integrating clinical data on patients with asthma-like conditions with data on environmental exposures derived from multiple public data sources. The data were integrated at the patient and visit level and used to create de-identified, binned, “integrated feature tables,” which were then placed behind an OpenAPI.ResultsOur preliminary evaluation results demonstrate a relationship between exposure to high levels of particulate matter ≤2.5 µm in diameter (PM2.5) and the frequency of emergency department or inpatient visits for respiratory issues. For example, 16.73% of patients with average daily exposure to PM2.5 &gt;9.62 µg/m3 experienced 2 or more emergency department or inpatient visits for respiratory issues in year 2010 compared with 7.93% of patients with lower exposures (n = 23 093).DiscussionThe results validated our overall approach for openly exposing and sharing integrated clinical and environmental exposures data. We plan to iteratively refine and expand ICEES by including additional years of data, feature variables, and disease cohorts.ConclusionsWe believe that ICEES will serve as a regulatory-compliant model and approach for promoting open access to and sharing of integrated clinical and environmental exposures data.
A network model of activities in primary care consultations
Authors: Kocaballi Ahmet Baki , Coiera Enrico , Tong Huong Ly , White Sarah J , Quiroz Juan C , Rezazadegan Fahimeh , Willcock Simon , Laranjo Liliana 
Published: March 2019

AbstractObjectiveThe objective of this study is to characterize the dynamic structure of primary care consultations by identifying typical activities and their inter-relationships to inform the design of automated approaches to clinical documentation using natural language processing and summarization methods.Materials and MethodsThis is an observational study in Australian general practice involving 31 consultations with 4 primary care physicians. Consultations were audio-recorded, and computer interactions were recorded using screen capture. Physical interactions in consultation rooms were noted by observers. Brief interviews were conducted after consultations. Conversational transcripts were analyzed to identify different activities and their speech content as well as verbal cues signaling activity transitions. An activity transition analysis was then undertaken to generate a network of activities and transitions.ResultsObserved activity classes followed those described in well-known primary care consultation models. Activities were often fragmented across consultations, did not flow necessarily in a defined order, and the flow between activities was nonlinear. Modeling activities as a network revealed that discussing a patient’s present complaint was the most central activity and was highly connected to medical history taking, physical examination, and assessment, forming a highly interrelated bundle. Family history, allergy, and investigation discussions were less connected suggesting less dependency on other activities. Clear verbal signs were often identifiable at transitions between activities.DiscussionPrimary care consultations do not appear to follow a classic linear model of defined information seeking activities; rather, they are fragmented, highly interdependent, and can be reactively triggered.ConclusionThe nonlinearity of activities has significant implications for the design of automated information capture. Whereas dictation systems generate literal translation of speech into text, speech-based clinical summary systems will need to link disparate information fragments, merge their content, and abstract coherent information summaries.
Genome-Wide Association Study of Susceptibility Loci for T-Cell Acute Lymphoblastic Leukemia in Children
Authors: Qian Maoxiang , Zhao Xujie , Devidas Meenakshi , Yang Wenjian , Gocho Yoshihiro , Smith Colton , Gastier-Foster Julie M , Li Yizhen , Xu Heng , Zhang Shouyue , Jeha Sima , Zhai Xiaowen , Sanda Takaomi , Winter Stuart S , Dunsmore Kimberly P , Raetz Elizabeth A , Carroll William L , Winick Naomi J , Rabin Karen R , Zweidler-Mckay Patrick A , Wood Brent , Pui Ching-Hon , Evans William E , Hunger Stephen P , Mullighan Charles G , Relling Mary V , Loh Mignon L , Yang Jun J 
Published: March 2019

Abstract

Background
Acute lymphoblastic leukemia (ALL) is the most common cancer in children and can arise in B or T lymphoid lineages. Although risk loci have been identified for B-ALL, the inherited basis of T-ALL is mostly unknown, with a particular paucity of genome-wide investigation of susceptibility variants in large patient cohorts.

Methods
We performed a genome-wide association study (GWAS) in 1191 children with T-ALL and 12 178 controls, with independent replication using 117 cases and 5518 controls. The associations were tested using an additive logistic regression model. Top risk variants were tested for effects on enhancer activity using luciferase assay. All statistical tests were two sided.

Results
A novel risk locus in the USP7 gene (rs74010351, odds ratio [OR] = 1.44, 95% confidence interval [CI] = 1.27 to 1.65, P = 4.51 × 10–8) reached genome-wide significance in the discovery cohort, with independent validation (OR = 1.51, 95% CI = 1.03 to 2.22, P = .04). The USP7 risk allele was overrepresented in individuals of African descent, thus contributing to the higher incidence of T-ALL in this race/ethnic group. Genetic changes in USP7 (germline variants or somatic mutations) were observed in 56.4% of T-ALL with TAL1 overexpression, statistically significantly higher than in any other subtypes. Functional analyses suggested this T-ALL risk allele is located in a putative cis-regulatory DNA element with negative effects on USP7 transcription. Finally, comprehensive comparison of 14 susceptibility loci in T- vs B-ALL pointed to distinctive etiology of these leukemias.

Conclusions
These findings indicate strong associations between inherited genetic variation and T-ALL susceptibility in children and shed new light on the molecular etiology of ALL, particularly commonalities and differences in the biology of the two major subtypes (B- vs T-ALL).
The Landscape of Somatic Genetic Alterations in Breast Cancers from CHEK2 Germline Mutation Carriers
Authors: Mandelker Diana , Kumar Rahul , Pei Xin , Selenica Pier , Setton Jeremy , Arunachalam Sasi , Ceyhan-Birsoy Ozge , Brown David N , Norton Larry , Robson Mark E , Wen Hannah Y , Powell Simon , Riaz Nadeem , Weigelt Britta , Reis-Filho Jorge S 
Published: March 2019

Abstract
Pathogenic germline variants in checkpoint kinase 2 (CHEK2), which plays pivotal roles in DNA damage response and cell cycle regulation, confer an increased breast cancer (BC) risk. Here, we investigated the phenotypic and genomic characteristics of 33 BCs from CHEK2 germline mutation carriers (16 high-risk variants and 17 low-risk p.Ile157Thr variants). CHEK2-associated BCs from patients with high-risk germline variants were largely hormone receptor-positive (87%, 13/15), and 81% (13/16) exhibited loss of heterozygosity (LOH) of the CHEK2 wild-type allele. Conversely, CHEK2-associated BCs from patients with the low-risk p.Ile157Thr variant displayed less-frequent loss of heterozygosity (5/17, 29%) and higher levels of CHEK2 protein expression than those with high-risk germline variants. CHEK2-associated BCs lacked a dominant mutational signature 3, a genomics feature of homologous recombination DNA repair deficiency (HRD). Our findings indicate that CHEK2-associated BCs are generally hormone receptor-positive and lack HRD-related mutational signatures, recapitulating the features of ATM-associated BCs. Specific CHEK2 germline variants may have a distinct impact on tumor biology.
Platelet-derived microparticles from recurrent miscarriage associated with antiphospholipid antibody syndrome influence behaviours of trophoblast and endothelial cells
Authors: Zhou Qian , Lian Yan , Zhang Yan , Li Lei , Li Hongyan , Shen Di , Zhou Yu , Zhang Meihua , Lu Yuan , Liu Jing , Xia Yu , Wang Xietong 
Published: March 2019

AbstractPlatelet-derived microparticles (PMPs) are a type of microparticle budding from platelets undergoing activation or apoptosis in many autoimmune diseases, including antiphospholipid antibody syndrome (APS). PMPs may also contribute to recurrent miscarriage, although the exact mechanism is unclear. The aim of this study was to determine the potential biological mechanism by which abnormal PMP activation may affect recurrent miscarriage. PMPs were counted by fluorescence-activated cell sorting (FACS) and compared between the healthy control (HC) and recurrent miscarriage/APS groups. Different effects of PMPs isolated by FACS from patients with recurrent miscarriage/APS and HCs were explored. Capillary electrophoresis immunoquantification, RT-qPCR, Luminex xMAP and immunofluorescence staining were performed to investigate all these different effects of PMPs. We found that the difference in the counts of PMP was not significant. However the expression of the inflammatory cytokine tumour necrosis factor-α (TNF-α) and the adhesion molecules intracellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were increased by PMPs derived from the recurrent miscarriage/APS group. PMPs isolated from patients with recurrent miscarriage/APS also more potently stimulated monocyte recruitment, inhibited angiogenesis and promoted human umbilical vein endothelial cell (HUVEC) apoptosis, in comparison to PMPs from HCs matched for gestational week. Moreover, PMPs could be ternalized by HTR-8/SVneo cells and could increase apoptosis of these cells and decrease trophoblastic invasion and migration. To supplement our work, the limited sample size needs to be increased, and further in-vivo work is necessary. Findings from this study indicate that abnormal activation of PMPs contributes to recurrent miscarriage/APS progression and provides potential therapeutic targets.
A tunable assay for modulators of genome-destabilizing DNA structures
Authors: del Mundo Imee M A , Cho Eun Jeong , Dalby Kevin N , Vasquez Karen M 
Published: March 2019

AbstractRegions of genomic instability are not random and often co-localize with DNA sequences that can adopt alternative DNA structures (i.e. non-B DNA, such as H-DNA). Non-B DNA-forming sequences are highly enriched at translocation breakpoints in human cancer genomes, representing an endogenous source of genetic instability. However, a further understanding of the mechanisms involved in non-B DNA-induced genetic instability is needed. Small molecules that can modulate the formation/stability of non-B DNA structures, and therefore the subsequent mutagenic outcome, represent valuable tools to study DNA structure-induced genetic instability. To this end, we have developed a tunable Förster resonance energy transfer (FRET)-based assay to detect triplex/H-DNA-destabilizing and -stabilizing ligands. The assay was designed by incorporating a fluorophore-quencher pair in a naturally-occurring H-DNA-forming sequence from a chromosomal breakpoint hotspot in the human c-MYC oncogene. By tuning triplex stability via buffer composition, the assay functions as a dual-reporter that can identify stabilizers and destabilizers, simultaneously. The assay principle was demonstrated using known triplex stabilizers, BePI and coralyne, and a complementary oligonucleotide to mimic a destabilizer, MCRa2. The potential of the assay was validated in a 384-well plate with 320 custom-assembled compounds. The discovery of novel triplex stabilizers/destabilizers may allow the regulation of genetic instability in human genomes.
Prediction of the effect of dapagliflozin on kidney and heart failure outcomes based on short-term changes in multiple risk markers
Authors: Idzerda Nienke M A , Stefansson Bergur V , Pena Michelle J , Sjostrom David C , Wheeler David C , Heerspink Hiddo J L 
Published: March 2019

Abstract

Background
Besides improving glucose control, sodium-glucose co-transporter 2 inhibition with dapagliflozin reduces blood pressure, body weight and urinary albumin:creatinine ratio (UACR) in patients with type 2 diabetes (T2DM). The parameter response efficacy (PRE) score was developed to predict how short-term drug effects on cardiovascular risk markers translate into long-term changes in clinical outcomes. We applied the PRE score to clinical trials of dapagliflozin to model the effect of the drug on kidney and heart failure (HF) outcomes in patients with T2DM and impaired kidney function.

Methods
The relationships between multiple risk markers and long-term outcome were determined in a background population of patients with T2DM with a multivariable Cox model. These relationships were then applied to short-term changes in risk markers observed in a pooled database of dapagliflozin trials (n = 7) that recruited patients with albuminuria to predict the drug-induced changes to kidney and HF outcomes.

Results
A total of 132 and 350 patients had UACR &gt;200 mg/g and &gt;30 mg/g at baseline, respectively, and were selected for analysis. The PRE score predicted a risk change for kidney events of −40.8% [95% confidence interval (CI) −51.7 to −29.4) and −40.4% (95% CI −48.4 to −31.1) with dapagliflozin 10 mg compared with placebo for the UACR &gt;200 mg/g and &gt;30 mg/g subgroups. The predicted change in risk for HF events was −27.3% (95% CI −47.7 to −5.1) and −21.2% (95% CI −35.0 to −7.8), respectively. Simulation analyses showed that even with a smaller albuminuria-lowering effect of dapagliflozin (10% instead of the observed 35% in both groups), the estimated kidney risk reduction was still 26.5 and 26.8%, respectively.

Conclusions
The PRE score predicted clinically meaningful reductions in kidney and HF events associated with dapagliflozin therapy in patients with diabetic kidney disease. These results support a large long-term outcome trial in this population to confirm the benefits of the drug on these endpoints.
Association Between Spinal Cord Stimulation and Top-Down Nociceptive Inhibition in People With Failed Back Surgery Syndrome: A Cohort Study
Authors: Goudman Lisa , Brouns Raf , De Groote Sander , De Jaeger Mats , Huysmans Eva , Forget Patrice , Moens Maarten 
Published: March 2019

Abstract

Background
Descending nociceptive inhibitory pathways often malfunction in people with chronic pain. Conditioned pain modulation (CPM) is an experimental evaluation tool for assessing the functioning of these pathways. Spinal cord stimulation (SCS), a well-known treatment option for people with failed back surgery syndrome (FBSS), probably exerts its pain-relieving effect through a complex interplay of segmental and higher-order structures.

Objective
To the best of our knowledge, no clinical studies have thoroughly investigated the associations between SCS and CPM.

Design
This was a prospective cohort study in people with FBSS.

Methods
Seventeen people who had FBSS and were scheduled for SCS were enrolled in this study. The CPM model was evaluated at both sural nerves and was induced by electrical stimulation as the test stimulus and the cold pressor test as the conditioning stimulus.

Results
Before SCS, less than 30% of the participants with FBSS showed a CPM effect. Significant increases in the electrical detection threshold on the symptomatic side and the nonsymptomatic side were found. On the symptomatic side, no differences in the numbers of CPM responders before and after SCS could be found. On the nonsymptomatic side, more participants showed a CPM effect during SCS. Additionally, there were significant differences for CPM activation and SCS treatment.

Limitations
Limitations were the small sample size and the subjective outcome parameters in the CPM model.

Conclusions
This study revealed a bilateral effect of SCS that suggests the involvement of higher-order structures, such as the periaqueductal gray matter and rostroventromedial medulla (key regions in the descending pathways), as previously suggested by animal research.