bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prehabilitation
Authors: Harris Rachel E. , Duncan Hazel , Buchanan Elaine , Cardigan Tracey , Garrick Vikki , Curtis Lee , Gervais Lisa , Barclay Andrew , Haddock Graham , Hansen Richard , Tayler Rachel , Walker Gregor , Russell Richard K. 
Published: December 2019

ABSTRACTExclusive enteral nutrition (EEN) is effective in inducing remission in paediatric Crohn Disease (CD) and has been shown to reduce inflammation and improve outcomes in adult CD patients when used before resectional surgery. This retrospective study demonstrates that preoperative EEN is achievable in paediatric CD patients undergoing right hemicolectomy and is associated with positive peri‐operative outcomes. Seventeen patients (8 who received preoperative EEN and 9 who did not) were included in the study. Six of 8 (75.0%) managed EEN orally; 1 via nasogastric tube and another via a previously sited gastrostomy. Use of preoperative EEN was associated with a decreased rate of moderate/severe disease on resection pathology (5/8 [62.5%] vs 9/9 [100%]; P = 0.04). Larger studies are required to determine the wider potential benefits of preoperative EEN on postoperative outcomes within paediatric practice.
Psychotic Symptoms Predict Suicidal Behavior Postdischarge in High Risk Psychiatric Inpatients
Authors: BARZILAY SHIRA , ASSOUNGA KRYSTEL , KIM HAE-JOON , RUDNER ELVIRA , YASEEN ZIMRI , GALYNKER IGOR 
Published: December 2019

Background:
Psychotic disorders, as well as psychotic symptoms, are associated with a greater lifetime risk of suicidal behavior (SB). It is not known, however, whether psychotic symptoms are independent predictors for short-term SB.

Methods:
Data were collected from 201 psychiatric inpatients at Mount Sinai Beth Israel Hospital. Self-reported psychotic symptoms were assessed using the Brief Symptom Inventory (BSI). Postdischarge SB defined as an aborted, interrupted, or actual suicide attempt was assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS), during the 4 to 8 weeks following discharge from an inpatient psychiatric unit (n=127, 63% retention). Logistic regressions were performed to assess the relationships between psychotic symptoms and SB, controlling for primary psychiatric disorders.

Results:
Self-reported psychotic symptoms were associated with subsequent postdischarge SB. There was no significant difference between the SB versus no SB groups on the basis of primary psychiatric disorder. Self-reported psychotic symptoms remained an independent and significant predictor of postdischarge SB when the analysis controlled for primary psychiatric disorder.

Conclusions:
These results suggest that psychotic symptoms are a dimensional predictor of near-term postdischarge SB and are a necessary component of suicide risk assessment during inpatient hospitalization, independent of psychiatric diagnosis.
Kidney Transplant Outcomes in Patients With Adenine Phosphoribosyltransferase Deficiency
Authors: Runolfsdottir Hrafnhildur Linnet , Palsson Runolfur , Agustsdottir Inger M. Sch. , Indridason Olafur S. , Li Jennifer , Dao Myriam , Knebelmann Bertrand , Milliner Dawn S. , Edvardsson Vidar O. 
Published: December 2019

Background.
Adenine phosphoribosyltransferase (APRT) deficiency is a rare, hereditary cause of kidney stones and chronic kidney disease (CKD) which is characterized by 2,8-dihydroxyadenine renal parenchymal crystal deposition. The aim of this study was to examine outcomes of kidney transplantation in APRT deficiency patients.

Methods.
Included were 13 patients in the APRT Deficiency Registry of the Rare Kidney Stone Consortium, 2 from Westmead Hospital in Sydney, Australia, and 2 from Necker Hospital in Paris, France. The CKD-EPI and CKiD equations were used to calculate glomerular filtration rate estimates. Allograft survival was analyzed employing the Kaplan-Meier method. The Wilcoxon-Mann-Whitney test was used to compare alllograft outcomes according to xanthine oxidoreductase (XOR) inhibitor treatment status at transplantation.

Results.
Seventeen patients (9 females) received 22 kidney transplants. Age at first transplantation was 47.2 (14.9–67.0) years. Ten patients received XOR inhibitor therapy pretransplant (11 allografts), while 8 patients did not receive such treatment before transplantation (11 allografts). Two-year allograft survival was 91% and 55% in the 2 groups, respectively (P = 0.16). The median (range) estimated glomerular filtration rate at 2 years posttransplant was 61.3 (24.0–90.0) mL/min/1.73 m2 when XOR inhibitor therapy was initiated before transplantation, and 16.2 (10.0–39.0) mL/min/1.73 m2 (P = 0.009) when such treatment was not administered pretransplant.

Conclusions.
Kidney allograft outcomes are good in APRT deficiency patients beginning XOR inhibitor therapy pretransplant. Delay in such treatment is a major cause of premature graft loss in these patients. Increased awareness among clinicians is imperative, promoting early diagnosis of APRT deficiency and pharmacotherapy initiation before kidney transplantation.
The making of calibration sausage exemplified by recalibrating the transcriptomic timetree of jawed vertebrates
Authors: Marjanović David 
Published: December 2019

AbstractMolecular divergence dating has the potential to overcome the incompleteness of the fossil record in inferring when cladogenetic events (splits, divergences) happened, but needs to be calibrated by the fossil record. Ideally but unrealistically, this would require practitioners to be specialists in molecular evolution, in the phylogeny and the fossil record of all sampled taxa, and in the chronostratigraphy of the sites the fossils were found in. Paleontologists have therefore tried to help by publishing compendia of recommended calibrations, and molecular biologists unfamiliar with the fossil record have made heavy use of such works (in addition to using scattered primary sources and copying from each other). Using a recent example of a large node-dated timetree inferred from molecular data, I reevaluate all thirty calibrations in detail, present the current state of knowledge on them with its various uncertainties, rerun the dating analysis, and conclude that calibration dates cannot be taken from published compendia or other secondary or tertiary sources without risking strong distortions to the results, because all such sources become outdated faster than they are published: 50 of the sources I cite to constrain calibrations were published in 2019, half of the total of 276 after mid-2016, and 90% after mid-2005. It follows that the present work cannot serve as such a compendium either; in the slightly longer term, it can only highlight known and overlooked problems. Future authors will need to solve each of these problems anew through a thorough search of the primary paleobiological and chronostratigraphic literature on each calibration date every time they infer a new timetree; and that literature is not optimized for that task, but largely has other objectives.
The association of neurofibromatosis and autism symptomatology is confounded by behavioral problems
Authors: Morotti Hadley , Mastel Sarah , Keller Kory , Barnard Rebecca A. , Hall Trevor , O’Roak Brian J. , Fombonne Eric 
Published: December 2019

AbstractAimto evaluate if autism symptoms and diagnoses are raised in children with neurofibromatosis type 1 (NF1), to which levels, and to determine if co-occurring symptomatology accounts for this elevation.MethodWe interrogated our hospital electronic medical records. We collected parental reports of autism symptomatology, adaptive behavior, and co-occurring behavioral and emotional problems on a subsample of 45 children (9 years 2 months, 49% male). Age- and sex-matched controls with (N=180) or without ASD (N=180) were drawn from the Simons Simplex Collection and compared cross-sectionally to participants with NF1.ResultsDiagnoses of ADHD (8.8%), not of ASD (2.1%), were raised among 968 children with NF1 identified through electronic search. Mean Social Responsiveness Score (55.9) was below the cut-off of 60 for significant autism symptoms. Participants with NF1 had significantly more autism and behavioral symptoms than typically developing (TD) controls, and significantly less than controls with autism, with one exception: ADHD symptom levels were similar to those of autistic controls. When emotional, ADHD, and communication scores were covaried, the difference between participants with NF1 and TD controls disappeared almost entirely.InterpretationOur results do not support an association between NF1 and autism, both at the symptom and disorder levels.What this paper addsDiagnoses of ADHD, not of ASD, were raised among children with NF1.Increases in autism symptoms did not reach clinically significant thresholds.Co-occurring ADHD symptoms accounted for increased autism questionnaire scores.Adaptive behavior in NF1 participants showed normal socialization but lower communication proficiency.
Use of directed acyclic graphs (DAGs) in applied health research: review and recommendations
Authors: Tennant Peter WG , Harrison Wendy J , Murray Eleanor J , Arnold Kellyn F , Berrie Laurie , Fox Matthew P , Gadd Sarah C , Keeble Claire , Ranker Lynsie R , Textor Johannes , Tomova Georgia D , Gilthorpe Mark S , Ellison George TH 
Published: December 2019

ABSTRACTBackgroundDirected acyclic graphs (DAGs) are an increasingly popular approach for identifying confounding variables that require adjustment when estimating causal effects. This review examined the use of DAGs in applied health research to inform recommendations for improving their transparency and utility in future research.MethodsOriginal health research articles published during 1999-2017 mentioning “directed acyclic graphs” or similar or citing DAGitty were identified from Scopus, Web of Science, Medline, and Embase. Data were extracted on the reporting of: estimands, DAGs, and adjustment sets, alongside the characteristics of each article’s largest DAG.ResultsA total of 234 articles were identified that reported using DAGs. A fifth (n=48, 21%) reported their target estimand(s) and half (n=115, 48%) reported the adjustment set(s) implied by their DAG(s).Two-thirds of the articles (n=144, 62%) made at least one DAG available. Diagrams varied in size but averaged 12 nodes (IQR: 9-16, range: 3-28) and 29 arcs (IQR: 19-42, range: 3-99). The median saturation (i.e. percentage of total possible arcs) was 46% (IQR: 31-67, range: 12-100). 37% (n=53) of the DAGs included unobserved variables, 17% (n=25) included super-nodes (i.e. nodes containing more than one variable, and a 34% (n=49) were arranged so the constituent arcs flowed in a consistent direction.ConclusionsThere is substantial variation in the use and reporting of DAGs in applied health research. Although this partly reflects their flexibility, it also highlight some potential areas for improvement. This review hence offers several recommendations to improve the reporting and use of DAGs in future research.
Bone changes assessed with High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT) in early inflammatory arthritis: a 12-month cohort study
Authors: Brunet Scott C. , Finzel Stephanie , Engelke Klaus , Boyd Steven K. , Barnabe Cheryl , Manske Sarah L. 
Published: December 2019

ABSTRACTObjectivesWe sought to determine the sensitivity of high resolution peripheral quantitative computed tomography (HR-pQCT) to detect change and identify erosions in comparison with conventional radiography (CR) in early inflammatory arthritis patients. We also explored which prognostic factors contribute to bone damage assessed by HR-pQCT in the first year of diagnosis.Methods46 patients with arthritic symptoms less than one year, and a clinical diagnosis of inflammatory arthritis were prospectively imaged at baseline and 12-months. HR-pQCT scans of the 2nd and 3rd MCP joints and CR of the hands and feet were performed. Joint space width (JSW), total bone mineral density (Tt.BMD), erosion presence and volume were assessed with HR-pQCT. Scan-rescan precision was assessed to define an individual-level least significant change (LSC) criterion. Regression analyses explored prognostic factors for bone damage progression.ResultsWe observed no significant group-level changes in JSW, Tt.BMD or erosion volume. 20% or fewer joints demonstrated individual-level changes greater than the LSC criterion for mean JSW, Tt.BMD and erosion volume. HR-pQCT detected more erosions than CR in the 2nd and 3rd MCP. Increased symptom duration at diagnosis was associated (p < 0.10) with lower JSW minimum and higher JSW standard deviation.ConclusionsWe have demonstrated stability in erosion, bone density and JSW over 12-months in most patients receiving treatment for inflammatory arthritis using a LSC criterion, although patients with longer symptom duration prior to treatment initiation had demonstrable negative effects on JSW estimates. HR-pQCT captures bone damage and progression undetectable by CR in the imaged joints.
Lactoferrin Reverses Methotrexate Driven Epithelial Barrier Defect by Inhibiting TGF-β Mediated Epithelial to Mesenchymal Transition
Authors: Wallach Thomas E. , Srivastava Vasudha , Reyes Efren , Klein Ophir D. , Gartner Zev J. 
Published: December 2019

ABSTRACTBACKGROUND AND AIMSMethotrexate is an important tool in the arsenal of oncologists, gastroenterologists, and rheumatologists. At low doses it induces intestinal barrier dysfunction that may induce side effects such as gastrointestinal discomfort and liver injury. Previous studies suggest that lactoferrin can improve barrier function in a variety of contexts. This study set out to determine the mechanism of methotrexate induced barrier dysfunction and assess the effect of lactoferrin and other components of human breast milk on this dysfunction.METHODSUsing a murine enteroid model and Caco2 spheroids, we measured flux of basolateral-administered fluorescent dextran into the lumen. Barrier dysfunction was induced using methotrexate (220 nM) or lipopolysaccharide (20 nM). Human lactoferrin was added at 0.8 mg/ml (10 µM). RNAseq was performed on exposed samples.RESULTSLactoferrin blocks methotrexate-induced barrier dysfunction in murine enteroids. Similar results were observed when barrier dysfunction was induced in Caco2 spheroids with methotrexate and LPS, but not ML7. RNAseq revealed activation of TGF-β response genes and epithelial-mesenchymal transition (EMT) by methotrexate, which normalized in the presence of lactoferrin. TGF-β receptor inhibition (RepSox) blocked methotrexate induced barrier dysfunction in Caco2 spheroids. 20 nM TGF-β induced barrier dysfunction in Caco2 spheroids which was also inhibited by lactoferrin.CONCLUSIONSMethotrexate induces barrier dysfunction by activation of an EMT program promoted by TGF-β signaling and inhibited by lactoferrin. Lactoferrin is also protective of barrier function in an LPS-induced model. The likely mechanism of this effect is blockade of EMT programs induced by TGF-β.
NFIA regulates granule recruitment and exocytosis in the adult pancreas
Authors: Scavuzzo Marissa A. , Chmielowiec Jolanta , Teaw Jessica , Yang Diane , Hill Matthew C. , Waksmunski Andrea R. , Duraine Lita , Camunas-Soler Joan , Dai Xiaoqing , King Jordon C. , Quake Stephen R , MacDonald Patrick E. , Catic Andre , Borowiak Malgorzata 
Published: December 2019

SummaryAfter food ingestion, pancreatic cells secrete zymogen and hormone-containing granules to precisely control digestion and blood glucose levels. Identifying regulators of this process is paramount to combatting multiple pancreatic diseases. Here we show that pancreatic deletion of the transcription factor nuclear factor IA (NFIA) leads to hyperglycemia, hypoinsulinemia, and hypolipidemia. Surprisingly, insulin and digestive enzymes are produced in the absence of NFIA, however, they are not secreted properly and instead accumulate inside pancreatic cells. In NFIA-deficient mice we saw a reduction of insulin granules in the ready releasable pool and the first-phase insulin response was impaired. We found that NFIA binds to and activatesRab39b,a Rab GTPase critical for exocytosis. Re-expression ofRab39bin NFIA knockout islets restored glucose-stimulated insulin secretion. In sum, the NFIA-Rab39b axis regulates pancreatic physiology throughgranule recruitment and docking, linking NFIA to a new process with potential effects in diabetes, pancreatitis, and lipid disorders.
Antimetastatic dsRNA mimics identified by live imaging of pathogenic neolymphangiogenesis
Authors: Olmeda David , Cerezo-Wallis Daniela , Calvo Tonantzin G. , Alonso Direna , Cañón Estela , Ibarz Nuria , Muñoz Javier , Ortega Sagrario , Soengas María S. 
Published: December 2019

ABSTRACTThe crosstalk between cancer cells and the lymphatic vasculature has long been proposed to define competency for metastasis. Nevertheless, the discovery of selective blockers of lymphovascular niches has been compromised by the paucity of experimental systems for whole-body analyses of tumor progression. Here we present immunocompetent and immunodeficient mouse models for live imaging of melanoma-induced neolymphangiogenesis (driven by Vegfr3) as a cost-effective platform for drug screeningin vivo. Spatio-temporal analyses in autochthonous melanomas and patient-derived xenografts identified double stranded RNA mimics (dsRNA nanoplexes) as potent repressors of lymphangiogenesis and metastasis. Mechanistically, dsRNA nanoplexes were found to suppress lymphangiogenic drivers in both tumor cells and their associated lymphatic vasculature (via MIDKINE and Vegfr3, respectively). This dual inhibitory action, driven by type I interferon, was not shared by FDA-approved antimelanoma treatments or by lymphangiogenic blockers in clinical testing. These results underscore the power of Vegfr3-lymphoreporters for pharmacological testing in otherwise aggressive cancers.RELEVANCEAlthough tumor-induced lymphangiogenesis has long been associated with metastasis, selective targeting of this process has been compromised by the paucity of experimental platforms for whole-body imaging of tumor progression and drug response. Here we present animal models engineered for spatio-temporal analyses of neolymphangiogenesis in clinically relevant autochthonous melanomas and patient-derived xenografts, and identify a unique action of double stranded-RNA nanoplexes as potent repressors of lymphatic dissemination and metastatic relapse.
Prediction of condition-specific regulatory maps inArabidopsisusing integrated genomic data
Authors: Song Qi , Lee Jiyoung , Akter Shamima , Grene Ruth , Li Song 
Published: December 2019

AbstractRecent advances in genomic technologies have generated large-scale protein-DNA interaction data and open chromatic regions for multiple plant species. To predict condition specific gene regulatory networks using these data, we developed theConditionSpecificRegulatory network inference engine (ConSReg), which combines heterogeneous genomic data using sparse linear model followed by feature selection and stability selection to select key regulatory genes. UsingArabidopsisas a model system, we constructed maps of gene regulation under more than 50 experimental conditions including abiotic stresses, cell type-specific expression, and stress responses in individual cell types. Our results show that ConSReg accurately predicted gene expressions (average auROC of 0.84) across multiple testing datasets. We found that, (1) including open chromatin information from ATAC-seq data significantly improves the performance of ConSReg across all tested datasets; (2) choice of negative training samples and length of promoter regions are two key factors that affect model performance. We applied ConSReg toArabidopsissingle cell RNA-seq data of two root cell types (endodermis and cortex) and identified five regulators in two root cell types. Four out of the five regulators have additional experimental evidence to support their roles in regulating gene expression inArabidopsisroots. By comparing regulatory maps in abiotic stress responses and cell type-specific experiments, we revealed that transcription factors that regulate tissue levels abiotic stresses tend to also regulate stress responses in individual cell types in plants.
Conservative management of women with cervical intraepithelial neoplasia grade 2 in Denmark: a cohort study
Authors: Skorstengaard M , Lynge E , Suhr J , Napolitano G 
Published: December 2019

ObjectiveAssess the progression, persistence, and regression of cervical intraepithelial neoplasia grade 2 (CIN2) after new guidelines on conservative treatment, compared with previous practice.DesignNationwide register‐based cohort study.SettingDenmark.PopulationWomen aged 18–44 years diagnosed with CIN2 on biopsy: 6721 in 2008–2011 and 6399 in 2014–2017.MethodsRegister data were retrieved from before (2008–2011) and after (2014–2017) the introduction of new guidelines. Histology diagnoses at second visit were used to assess progression (CIN3+), persistence (CIN2), or regression (CIN1/normal).Main outcome measuresProportion of CIN2 by type of management. Relative risk (RR) and corresponding 95% confidence intervals (95% CIs) for progression, persistence, and regression at second visit in 2014–2017, versus 2008–2011.ResultsThe proportion of CIN2 managed conservatively increased from 29.6% in 2008–2011 to 53.3% in 2014–2017 (RR 1.81, 95% CI 1.73–1.89). Time to second visit increased by 2 months. Regression increased from 23.5 to 30.2% (RR 1.29, 95% CI 1.22–1.36), whereas persistence and progression decreased, from 42.6 to 34.9% (RR 0.82, 95% CI 0.78–0.86) and from 28.0 to 22.8% (RR 0.81, 95% CI 0.77–0.86), respectively. In 2008–2011, women managed conservatively had a regression rate of 41.8%, persistence rate of 40.9%, and progression rate of 16.6%. In 2014–2017, these rates were 46.7, 35.5, and 17.1%, respectively.ConclusionAfter implementation of the new guidelines, conservative management became more frequent, and is now used for more than half of women with CIN2. Lesion regression became more frequent, now experienced by 47% of women managed conservatively. Similar regression rates were seen in women younger and older than 30 years, suggesting that conservative management is justifiable for women of childbearing age.Tweetable abstractIn Denmark, more than half of women with CIN2 are managed conservatively, and half of these women experience lesion regression.