bluuebunny/crossref_metadata_2025_split huggingface dataset:
High crystalloid volumes negate benefit of hemostatic resuscitation in pediatric wartime trauma casualties
Authors: Schauer Steven G. , April Michael D. , Becker Tyson E. , Cap Andrew P. , Borgman Matthew A. 
Published: January 2020

BACKGROUND
Recent data for adult trauma patients suggest improved survival when using hemostatic resuscitation, which includes limiting crystalloids and using closer to 1:1 ratios for both fresh frozen plasma (FFP) and platelets (PLTs) relative to packed red blood cells (PRBCs). Pediatric studies have shown similar but mixed results and often lack measuring crystalloids. We seek to evaluate in-hospital survival based on crystalloid administration and different blood product ratios in pediatric casualties during the recent conflicts.

METHODS
We queried the Department of Defense Trauma Registry for all pediatric encounters in Iraq and Afghanistan from January 2007 to January 2016 and included those with at least 40 mL/kg of total blood products administered provided that they received at least 1 U of PRBC. We grouped children as younger (0–7 years) and older (8–17 years). We grouped low versus high ratios for FFP/PRBC (≤1:2 vs. >1:2) and PLT/PRBC (≤1:6 vs. >1.6). We used a threshold of 40 mL/kg to for high versus low crystalloid resuscitation.

RESULTS
During this time, there were 3,439 encounters in the registry with 521 (15.1%) that met the inclusion criteria. The median age of casualties that met the inclusion was 10 years (interquartile range, 5–13), most were male (73.5%), with a moderate median injury severity score (17; interquartile range, 13–25). We performed regression modeling with adjustments for mechanism of injury, composite injury severity score, and total blood product volume (mL/kg based), grouping children based on high versus low fluid resuscitation. In the low-volume crystalloid group, we found that higher (>1:2) FFP/PRBC was associated with improved survival (odds ratio [OR], 3.42). However, in the high fluid crystalloid resuscitation group, we found that that higher ratios for PLT/PRBC (>1:6) overall (OR, 0.46) and the FFP/PRBC (>1:2) in younger children (OR, 0.28) was associated with worse survival. The remaining associations were not statistically significant.

CONCLUSION
We found an association with survival in massively transfused pediatric trauma patients who received both a high FFP/PRBC ratio and low crystalloid administration. The benefit of this high ratio is negated, in patients receiving high crystalloid volumes, particularly among smaller children. Future studies on hemostatic resuscitation evaluating blood product ratios should also account for crystalloid and colloid administration.

LEVEL OF EVIDENCE
Retrospective, comparative, level III.
Surveillance for HCC After Liver Transplantation: Increased Monitoring May Yield Aggressive Treatment Options and Improved Postrecurrence Survival
Authors: Lee David D. , Sapisochin Gonzalo , Mehta Neil , Gorgen Andre , Musto Kaitlyn R. , Hajda Hana , Yao Francis Y. , Hodge David O. , Carter Rickey E. , Harnois Denise M. 
Published: January 2020

Background.
Currently, no surveillance guidelines for hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) exist. In this retrospective, multicenter study, we have investigated the role of surveillance imaging on postrecurrence outcomes.

Methods.
Patients with recurrent HCC after LT from 2002 to 2016 were reviewed from 3 transplant centers (University of California San Francisco, Mayo Clinic Florida, and University of Toronto). For this study, we proposed the term cumulative exposure to surveillance (CETS) as a way to define the cumulative sum of all the protected intervals that each surveillance test provides. In our analysis, CETS has been treated as a continuous variable in months.

Results.
Two hundred twenty-three patients from 3 centers had recurrent HCC post-LT. The median follow-up was 31.3 months, and median time to recurrence was 13.3 months. Increasing CETS was associated with improved postrecurrence survival (hazard ratio, 0.94; P < 0.01) as was treatment of recurrence with resection or ablation (hazard ratio, 0.31; P < 0.001). An receiver operating characteristic curve (area under the curve, 0.64) for CETS covariate showed that 252 days of coverage (or 3 surveillance scans) within the first 24 months provided the highest probability for aggressive postrecurrence treatment.

Conclusions.
In this review of 223 patients with post-LT HCC recurrence, we found that increasing CETS does lead to improved postrecurrence survival as well as a higher probability for aggressive recurrence treatment. We found that 252 days of monitoring (ie, 3 surveillance scans) in the first 24 months was associated with the ability to offer potentially curative treatment.
Antidepressant Effect of Adjunct Repetitive Transcranial Magnetic Stimulation in Inpatients 60 Years and Older
Authors: Qiao Ying , Wang JunJie , Zhu JunJuan , Cui HuiRu , Tang YingYing , Xu LiHua , Tang XiaoChen , Wei YanYan , Hui Li , Li ChunBo , Jia QiuFang , Zhu HongLiang , Wen Hui , Wang JiJun , Zhang TianHong 
Published: January 2020

Background
Repetitive transcranial magnetic stimulation (rTMS) is now an established, safe, and effective treatment for adults with depression. However, specific research in rTMS for use in elderly patients with acute depression is scarce.

Objective
The aim of the present study was to investigate the efficacy of add-on rTMS in a clinical sample of older adults experiencing an acute phase of depression.

Method
This study examined 114 patients (54 elderly [aged ≥60] and 60 adults [aged 18–59]) with acute depression who were drug free at baseline. They were treated with at least 10 sessions of rTMS for 4 weeks along with 1 antidepressant. Symptoms of depression were measured using the Hamilton Rating Scale for Depression at baseline and after 2 and 4 weeks of treatment. Clinical improvement and rates of response and remission were compared across groups.

Results
Significant improvement was noted after 2 and 4 weeks of treatment in both adult and elderly groups. Higher remission rates were found in adult patients but with no differences in response. The stimulation intensity and course of illness were significant predictors of remission after 4 weeks of rTMS treatment in the elderly.

Conclusions
The add-on rTMS treatment for elderly depression patients is promising with respect to safety and feasibility. This preliminary evidence supports the application of rTMS to this group during acute episodes.
Prospective Single Center Cohort Study for Early Diagnosis of Cardiac Dysfunction in Swiss Childhood Cancer Survivors: A Study Protocol
Authors: Schindera Christina , Kuehni Claudia E. , Pavlovic Mladen , Haegler-Laube Eva , Waespe Nicolas , Roessler Jochen , Suter Thomas M. , von der Weid Nicolas X. 
Published: January 2020

AbstractIntroductionCardiovascular disease is the leading nonmalignant cause of late deaths in childhood cancer survivors. Cardiovascular disease and cardiac dysfunction can remain asymptomatic for many years, but eventually lead to progressive disease with high morbidity and mortality. Early detection and intervention are therefore crucial to improve outcome. In our study, we aim to 1) assess the prevalence of early cardiac dysfunction in adult childhood cancer survivors using conventional and speckle tracking echocardiography, 2) determine the association between cardiac dysfunction and treatment-related risk factors (anthracyclines, alkylating agents, steroids, cardiac radiation) and modifiable cardiovascular risk factors (abdominal obesity, hypertension), 3) investigate the development of cardiac dysfunction longitudinally in a defined cohort, 4) study the association between cardiac dysfunction and other health outcomes like pulmonary, endocrine, and renal diseases, quality of life, fatigue, strength and endurance, and physical activity, and 5) gain experience conducting a clinical study of childhood cancer survivors that will be extended to a national, multicenter study of cardiac complications.MethodsWe will invite ≥5 year childhood cancer survivors who were treated at the University Children’s Hospital Bern, Switzerland with any chemotherapy and/or cardiac radiation since 1976 and who are ≥18 years of age at time of study for a cardiac assessment at the University Hospital Bern. This includes overall 544 childhood cancer survivors, of whom about half were treated with anthracyclines and/or cardiac radiation and half with any other chemotherapy. The standardized cardiac assessment includes a medical history focusing on signs of cardiovascular disease and its risk factors, a physical examination, anthropometry, vital parameters, the 1-minute sit-to-stand test, and an echocardiography including speckle tracking.ResultsWe will invite 544 eligible childhood cancer survivors for a cardiac assessment with a median age at study of 32.5 years and a median times since diagnosis of 25.0 years. Three hundred survivors (55%) are at high risk and 244 survivors (45%) are at standard risk for cardiac dysfunction.DiscussionThe results of this study will show the prevalence of early cardiac dysfunction in Swiss childhood cancer survivors, inform whether speckle tracking echocardiography is more sensitive to cardiac dysfunction than conventional echocardiography, and give a detailed picture of risk factors for cardiac dysfunction. The results will help improve primary treatment and follow-up care of children suffering from cancer.Trial registrationProspectively registered in ClinicalTrials.gov, Identifier: NCT03790943, registration date 25.06.2018.
Ideal Cardiovascular Health in Urban Jamaica: Prevalence Estimates and Relationship to Community Property Value, Household Assets and Educational Attainment
Authors: McKenzie Joette A. , Younger-Coleman Novie O. , Tulloch-Reid Marshall K. , Govia Ishtar , Bennett Nadia R. , McFarlane Shelly R. , Walters Renee , Francis Damian K. , Webster-Kerr Karen , Grant Andriene , Davidson Tamu , Wilks Rainford J. , Williams David R. , Ferguson Trevor S. 
Published: January 2020

ABSTRACTBACKGROUNDIdeal cardiovascular health (ICH) is associated with greater longevity and reduced morbidity, but no research on ICH has been conducted in Jamaica. We estimated the prevalence of ICH in urban Jamaica and evaluated associations between ICH and community, household and individual socioeconomic status (SES).METHODSCross-sectional study using data from 360 men and 665 women, age ≥20 years in urban Jamaica. ICH was defined as having seven characteristics: current non-smoking, healthy diet, moderate physical activity, and normal body mass index, blood pressure, glucose, and cholesterol. Logistic regression, weighted for survey design, quantified association between the outcome (≥5 ICH characteristics [ICH-5]), and exposure variables (tertiles of community median land value [MLV], tertiles of household assets and educational attainment).RESULTSPrevalence of ICH (7 characteristics) was 0.51%, while prevalence of ICH-5 was 22.9% (male 24.5%, female 21.5%, p=0.447). In sex-specific multivariable models adjusted for age, education, and household assets, men in the lower tertiles of community MLV had lower odds of ICH-5 compared to men in the upper tertile (lowest tertile: OR 0.33, 95%CI 0.12-0.91, p=0.032; middle tertile: OR 0.46 (0.20-1.04) p=0.062). Women from communities in the lower and middle tertiles of MLV also had lower odds of ICH-5, but association was not statistically significant. Educational attainment was inversely associated with ICH-5 among men and positively associated among women. No significant association was seen for household assets.CONCLUSIONPrevalence of ICH is low in urban Jamaica. Living in poorer communities was associated with lower odds of ICH-5 among men. Higher education was associated with higher odds of ICH-5 among women but lowers odds among men.
Locus coeruleus pathology in progressive supranuclear palsy, and its relation to disease severity
Authors: Kaalund Sanne Simone , Passamonti Luca , Allinson Kieren SJ , Murley Alexander G , Robbins Trevor W , Spillantini Maria Grazia , Rowe James B 
Published: January 2020

AbstractThe locus coeruleus is the major source of noradrenaline to the brain and contributes to a wide range of physiological and cognitive functions including arousal, attention, autonomic control, and adaptive behaviour. Neurodegeneration and pathological aggregation of tau protein in the locus coeruleus are early features of progressive supranuclear palsy (PSP). This pathology is proposed to contribute to the clinical expression of disease, including the PSP Richardson’s syndrome. We test the hypothesis that tau pathology and neuronal loss are associated with clinical heterogeneity and severity in PSP.We used immunohistochemistry in post mortem tissues from 31 patients with a clinical diagnosis of PSP (22 with Richardson’s syndrome) and 6 control cases. We quantified the presence of hyperphosphorylated tau, the number of pigmented cells indicative of noradrenergic neurons, and the percentage of pigmented neurons with tau-positive inclusions. Ante mortem assessment of clinical severity using the PSP rating scale was available within 1.8 (±0.9) years for 23 patients.We found an average 49% reduction of pigmented neurons in PSP patients relative to controls. The loss of pigmented neurons correlated with disease severity, even after adjusting for disease duration and the interval between clinical assessment and death. The degree of neuronal loss was associated with tau-positive inclusions, with an average of 44% of pigmented neurons displaying tau-inclusions.Degeneration and tau pathology in the locus coeruleus are related to clinical heterogeneity of PSP. The noradrenergic deficit in the locus coeruleus is a candidate target for pharmacological treatment. Recent developments in ultra-high field magnetic resonance imaging to quantify in vivo structural integrity of the locus coeruleus may provide biomarkers for noradrenergic experimental medicines studies in PSP.
Prognostic Imaging Biomarkers for Diabetic Kidney Disease (iBEAt): Study protocol
Authors: Gooding Kim M , Lienczewski Chrysta , Papale Massimo , Koivuviita Niina , Maziarz Marlena , Andersson Anna-Maria Dutius , Sharma Kanishka , Pontrelli Paola , Hernandez Alberto Garcia , Bailey Julie , Tobin Kay , Saunavaara Virva , Zetterqvist Anna , Shelley David , Teh Irvin , Ball Claire , Puppala Sapna , Ibberson Mark , Karihaloo Anil , Metsärinne Kaj , Banks Rosamonde , Gilmour Peter S , Mansfield Michael , Gilchrist Mark , de Zeeuw Dick , Heerspink Hiddo J.L. , Nuutila Pirjo , Kretzler Matthias , Wellberry-Smith Matthew , Gesualdo Loreto , Andress Dennis , Grenier Nicolas , Shore Angela C , Gomez Maria F. , Sourbron Steven ,   iBEAt investigators
Published: January 2020

ABSTRACTDiabetic kidney disease (DKD) is traditionally classified based on albuminuria and reduced kidney function (estimated glomerular filtration rate (eGFR)), but these have limitations as prognostic biomarkers due to the heterogeneity of DKD. Novel prognostic markers are needed to improve stratification of patients based on risk of disease progression.The iBEAT study, part of the BEAt-DKD consortium, aims to determine whether renal imaging biomarkers (magnetic resonance imaging (MRI) and ultrasound (US)) provide insight into the pathogenesis and heterogeneity of DKD (primary aim), and whether they have potential as prognostic biomarkers in DKD progression (secondary aim).iBEAT is a prospective multi-centre observational cohort study recruiting 500 patients with type 2 diabetes (T2D) and eGFR > 30ml/min/1.73m2. At baseline each participant will undergo quantitative renal MRI and US imaging with central processing for MRI images. Blood sampling, urine collection and clinical examinations will be performed and medical history obtained at baseline, and these assessments will be repeated annually for 3 years. Biological samples will be stored in a central laboratory for later biomarker and validation studies. All data will be stored in a central data depository. Data analysis will explore the potential associations between imaging biomarkers and renal function, and whether the imaging biomarkers may improve the prediction of DKD progression rates.Embedded within iBEAT are ancillary substudies that will (1) validate imaging biomarkers against renal histopathology; (2) validate MRI based renal blood flow against water-labelled positron-emission tomography (PET); (3) develop machine-learning methods for automated processing of renal MRI images; (4) examine longitudinal changes in imaging biomarkers; (5) examine whether the glycocalyx, microvascular function and structure are associated with imaging biomarkers and eGFR decline; (6) a pilot study to examine whether the findings in T2D can be extrapolated to type 1 diabetes.The iBEAT study, the largest DKD imaging study to date, will provide invaluable insights into the progression and heterogeneity of DKD, and aims to contribute to a more personalized approach to the management of DKD in patients with type 2 diabetes.
Common genetic risk variants identified in the SPARK cohort implicate DDHD2 as a novel autism risk gene
Authors: Matoba Nana , Liang Dan , Sun Huaigu , Aygün Nil , McAfee Jessica C. , Davis Jessica E. , Raffield Laura M. , Qian Huijun , Piven Joseph , Li Yun , Kosuri Sriam , Won Hyejung , Stein Jason L. 
Published: January 2020

AbstractBackgroundAutism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder. Large genetically informative cohorts of individuals with ASD have led to the identification of three common genome-wide significant (GWS) risk loci to date. However, many more common genetic variants are expected to contribute to ASD risk given the high heritability. Here, we performed a genome-wide association study (GWAS) using the Simons Foundation Powering Autism Research for Knowledge (SPARK) dataset to identify additional common genetic risk factors and molecular mechanisms underlying risk for ASD.MethodsWe performed an association study on 6,222 case-pseudocontrol pairs from SPARK and meta-analyzed with a previous GWAS. We integrated gene regulatory annotations to map non-coding risk variants to their regulated genes. Further, we performed a massively parallel reporter assay (MPRA) to identify causal variant(s) within a novel risk locus.ResultsWe identified one novel GWS locus from the SPARK GWAS. The meta-analysis identified four significant loci, including an additional novel locus. We observed significant enrichment of ASD heritability within regulatory regions of the developing cortex, indicating that disruption of gene regulation during neurodevelopment is critical for ASD risk. The MPRA identified one variant at the novel locus with strong impacts on gene regulation (rs7001340), and expression quantitative trait loci data demonstrated an association between the risk allele and decreased expression of DDHD2 (DDHD domain containing 2) in both adult and pre-natal brains.ConclusionsBy integrating genetic association data with multi-omic gene regulatory annotations and experimental validation, we fine-mapped a causal risk variant and demonstrated that DDHD2 is a novel gene associated with ASD risk.
Crowdsourcing digital health measures to predict Parkinson’s disease severity: the Parkinson’s Disease Digital Biomarker DREAM Challenge
Authors: Sieberts Solveig K. , Schaff Jennifer , Duda Marlena , Pataki Bálint Ármin , Sun Ming , Snyder Phil , Daneault Jean-Francois , Parisi Federico , Costante Gianluca , Rubin Udi , Banda Peter , Chae Yooree , Chaibub Neto Elias , Dorsey E. Ray , Aydın Zafer , Chen Aipeng , Elo Laura L. , Espino Carlos , Glaab Enrico , Goan Ethan , Golabchi Fatemeh Noushin , Görmez Yasin , Jaakkola Maria K. , Jonnagaddala Jitendra , Klén Riku , Li Dongmei , McDaniel Christian , Perrin Dimitri , Perumal Thanneer M. , Rad Nastaran Mohammadian , Rainaldi Erin , Sapienza Stefano , Schwab Patrick , Shokhirev Nikolai , Venäläinen Mikko S. , Vergara-Diaz Gloria , Zhang Yuqian ,   the Parkinson’s Disease Digital Biomarker Challenge Consortium, Wang Yuanjia , Guan Yuanfang , Brunner Daniela , Bonato Paolo , Mangravite Lara M. , Omberg Larsson 
Published: January 2020

AbstractMobile health, the collection of data using wearables and sensors, is a rapidly growing field in health research with many applications. Deriving validated measures of disease and severity that can be used clinically or as outcome measures in clinical trials, referred to as digital biomarkers, has proven difficult. In part due to the complicated analytical approaches necessary to develop these metrics. Here we describe the use of crowdsourcing to specifically evaluate and benchmark features derived from accelerometer and gyroscope data in two different datasets to predict the presence of Parkinson’s Disease (PD) and severity of three PD symptoms: tremor, dyskinesia and bradykinesia. Forty teams from around the world submitted features, and achieved drastically improved predictive performance for PD status (best AUROC=0.87), as well as tremor (best AUPR=0.75), dyskinesia (best AUPR=0.48) and bradykinesia (best AUPR=0.95) severity.
Nivolumab and Ipilimumab in Metastatic Melanoma Are Associated with Distinct Immune Landscape Changes and Response-Associated Immunophenotypes
Authors: Woods DM , Laino AS , Winters A , Alexandre J , Rao V , Adavani SS , Weber JS , Chattopadhyay PK 
Published: January 2020

AbstractThe reshaping of the immune landscape by nivolumab (NIVO) and ipilimumab (IPI) and its relation to patient outcomes is not well-described. We used high-parameter flow cytometry and a novel computational platform, CytoBrute, to define immunophenotypes of up to 15 markers to assess peripheral blood samples from metastatic melanoma patients receiving sequential NIVO>IPI or IPI>NIVO. The two treatments were associated with distinct immunophenotypic changes and had differing profiles associated with response. Only two immunophenotypes were shared but had opposing relationships to response/survival. To understand the impact of sequential treatment on response/survival, phenotypes that changed after the initial treatment and differentiated response in the other cohort were identified. Immunophenotypic changes occurring post-NIVO were predominately associated with response to IPI>NIVO, but changes occurring post-IPI were predominately associated with progression with NIVO>IPI. Among these changes, CD4+CD38+CD39+CD127-GARP- T-cell subsets were increased after IPI treatment and were negatively associated with response/survival for the NIVO>IPI cohort.