bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterizing CDK12-Mutated Prostate Cancers
Authors: Rescigno Pasquale , Gurel Bora , Pereira Rita , Crespo Mateus , Rekowski Jan , Rediti Mattia , Barrero Maialen , Mateo Joaquin , Bianchini Diletta , Messina Carlo , Fenor de la Maza Maria D. , Chandran Khobe , Carmichael Juliet , Guo Christina , Paschalis Alec , Sharp Adam , Seed George , Figueiredo Ines , Lambros Maryou , Miranda Susana , Ferreira Ana , Bertan Claudia , Riisnaes Ruth , Porta Nuria , Yuan Wei , Carreira Suzanne , de Bono Johann S. 
Published: September 2020

Abstract

Purpose:
Cyclin-dependent kinase 12 (CDK12) aberrations have been reported as a biomarker of response to immunotherapy for metastatic castration-resistant prostate cancer (mCRPC). Herein, we characterize CDK12-mutated mCRPC, presenting clinical, genomic, and tumor-infiltrating lymphocyte (TIL) data.

Experimental Design:
Patients with mCRPC consented to the molecular analyses of diagnostic and mCRPC biopsies. Genomic analyses involved targeted next-generation (MiSeq; Illumina) and exome sequencing (NovaSeq; Illumina). TILs were assessed by validated immunocytochemistry coupled with deep learning–based artificial intelligence analyses including multiplex immunofluorescence assays for CD4, CD8, and FOXP3 evaluating TIL subsets. The control group comprised a randomly selected mCRPC cohort with sequencing and clinical data available.

Results:
Biopsies from 913 patients underwent targeted sequencing between February 2015 and October 2019. Forty-three patients (4.7%) had tumors with CDK12 alterations. CDK12-altered cancers had distinctive features, with some revealing high chromosomal break numbers in exome sequencing. Biallelic CDK12-aberrant mCRPCs had shorter overall survival from diagnosis than controls [5.1 years (95% confidence interval (CI), 4.0–7.9) vs. 6.4 years (95% CI, 5.7–7.8); hazard ratio (HR), 1.65 (95% CI, 1.07–2.53); P = 0.02]. Median intratumoral CD3+ cell density was higher in CDK12 cancers, although this was not statistically significant (203.7 vs. 86.7 cells/mm2; P = 0.07). This infiltrate primarily comprised of CD4+FOXP3− cells (50.5 vs. 6.2 cells/mm2; P &lt; 0.0001), where high counts tended to be associated with worse survival from diagnosis (HR, 1.64; 95% CI, 0.95–2.84; P = 0.077) in the overall population.

Conclusions:
CDK12-altered mCRPCs have worse prognosis, with these tumors surprisingly being primarily enriched for CD4+FOXP3− cells that seem to associate with worse outcome and may be immunosuppressive.
See related commentary by Lotan and Antonarakis, p. 380
Evaluation of Trends and Prognosis Over Time in Patients with AML Relapsing After Allogeneic Hematopoietic Cell Transplant Reveals Improved Survival for Young Patients in Recent Years
Authors: Bazarbachi Ali , Schmid Christoph , Labopin Myriam , Beelen Dietrich , Wolfgang Blau Igor , Potter Victoria , Niittyvuopio Riitta , Socié Gerard , Blaise Didier , Sanz Jaime , Ciceri Fabio , Abou Dalle Iman , Spyridonidis Alexandros , Bug Gesine , Esteve Jordi , Savani Bipin N. , Nagler Arnon , Mohty Mohamad 
Published: September 2020

Abstract

Purpose:
Relapsed acute myeloid leukemia (AML) post allogeneic hematopoietic cell transplantation (allo-HCT) has a dismal prognosis.

Experimental Design:
To assess prognosis of patients with recurrent AML post allo-HCT over time, we analyzed European Society for Blood and Marrow Transplantation registry data of 8,162 adult patients with AML who relapsed between 2000 and 2018 after allo-HCT performed in first complete remission from matched sibling, unrelated, or haploidentical donors.

Results:
The 2-year overall survival (OS) rate from relapse was 17%. For 3,630 patients, &lt;50 years of age, the 2-year OS continuously increased from 16% between 2000 and 2004 to 18% for 2005–2009, to 21% for 2010–2014, and to 26% for 2015–2018 (P = 0.001). Improvement over time was noted both after relapse within and beyond 6 months from allo-HCT. On multivariate analysis among patients &lt;50 years of age, OS was positively affected by a later year of relapse (baseline: 2000–2004; HR, 0.82; P &lt; 0.02 for 2010–2014 and HR, 0.72; P = 0.0002 for 2015–2018), good performance status, favorable cytogenetics, and longer time from transplant to relapse, but negatively affected by increasing age. In contrast, among 4,532 patients, &gt;50 years of age, the year of relapse had no influence on OS (16% for 2000–2004 and 14% for 2015–2018; P = 0.56). Regarding treatment, encouraging results were observed after second allo-HCT, which was performed within 2 years after relapse in 17% of the entire cohort, resulting in a 2-year OS of 30.7%.

Conclusions:
Outcome after posttransplant relapse among younger patients has improved significantly in recent years, likely reflecting, among other factors, the efficacy of posttransplant salvage including second allo-HCT.
Molecular detection and occurrence of equine theileriosis in Arabian horses in Al-Najaf province/Iraq
Authors: Al-Rammahi Hayder Mohammad , Hatem Abdulameer Abed , Al-Atabi Asaad Chasib 
Published: September 2020

This study was designed to detect equine piroplasmosis using the molecular technique in Al-Najaf province during the season that showed an increment in tick activities. Blood samples were collected from 110 horses with more than two signs of piroplasmosis. After DNA extraction, the product was examined by a polymerase chain reaction to amplify 18SrRNA. The results showed that the overall percentage of equine theileriosis was 38.18%. According to gender, the percentage of infection was 43.48% and 29.27% in females and males, respectively. Significant variations appeared between infected horses according to age, and the percentage of infection was 50% and 35.22% in less than 2 years and more than 2 years age, respectively. Moreover, the percentage of infection was 62.5% and 19.35% in animals with and without acariasis, respectively. Significant variations were also seen in equine theileriosis according to geographical areas, and the higher percentage was reported in Hera district (60.87%), while the lowest percentage was in the center of Al-Najaf (21.43%). This difference may be due to different distribution of vector of disease (tick), which may be the availability of the suitable weather that helped in the multiplication of the intermediate vectors. In conclusion, this study proved the variations in the occurrences of equine piroplasmosis according to gender, age, and geographical areas.
Adrenal function evaluation in critically ill dogs with low doses of synthetic ACTH
Authors: Jericó Márcia Marques , Bento Fernando Mathias , Silva Ricardo Duarte , Cardozo Felipe Braz de Siqueira , Ponce Fabiano De Granville , Soila Rogério Márcio , Furtado Priscila Viau , Machado Fabrício Lorenzini Aranha 
Published: September 2020

The hypothalamus-pituitary-adrenal axis function may be impaired in patients with critical illnesses, especially cases of sepsis, named critical illness-related corticosteroid insufficiency (CIRCI). This study examined the function of the hypothalamic-pituitary-adrenal axis in normal dogs (n = 10) and dogs with critical diseases (n = 16), through determinations of endogenous ACTH (adrenocorticotropic hormone), basal cortisol and cortisol after stimulation in low doses of synthetic ACTH (1.0μg/kg/IV). The stimulation test with ACTH dose tested was verified as effective for evaluation of adrenal function in healthy and sick dogs. Ill dogs differed from healthy dogs by presenting higher basal cortisol values. Eight sick dogs presented a decrease in endogenous ACTH, basal cortisol, or Δ-cortisol. No significant differences were found between the control groups and critically ill dogs for the values of endogenous ACTH, cortisol after stimulation or Δ-cortisol. We concluded that the stimulation test with low-dose ACTH was effective for evaluation of adrenal function, as well as the fact that a considerable portion of critically ill dogs studied here, especially with sepsis, had evidence of inadequate corticosteroid response to stress.
Predicting the Risk of Right Ventricular Failure in Patients Undergoing Left Ventricular Assist Device Implantation
Authors: Frankfurter Claudia , Molinero Micaela , Vishram-Nielsen Julie K.K. , Foroutan Farid , Mak Susanna , Rao Vivek , Billia Filio , Orchanian-Cheff Ani , Alba Ana Carolina 
Published: September 2020

Background:
Right ventricular failure (RVF) is a cause of major morbidity and mortality after left ventricular assist device (LVAD) implantation. It is, therefore, integral to identify patients who may benefit from biventricular support early post-LVAD implantation. Our objective was to explore the performance of risk prediction models for RVF in adult patients undergoing LVAD implantation.

Methods:
A systematic search was performed on Medline, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews from inception until August 2019 for all relevant studies. Performance was assessed by discrimination (via C statistic) and calibration if reported. Study quality was assessed using the Prediction Model Risk of Bias Assessment Tool criteria.

Results:
After reviewing 3878 citations, 25 studies were included, featuring 20 distinctly derived models. Five models were derived from large multicenter cohorts: the European Registry for Patients With Mechanical Circulatory Support, Interagency Registry for Mechanically Assisted Circulatory Support, Kormos, Pittsburgh Bayesian, and Mechanical Circulatory Support Research Network RVF models. Seventeen studies (68%) were conducted in cohorts implanted with continuous-flow LVADs exclusively. The definition of RVF as an outcome was heterogenous among models. Seven derived models (28%) were validated in at least 2 cohorts, reporting limited discrimination (C-statistic range, 0.53–0.65). Calibration was reported in only 3 studies and was variable.

Conclusions:
Existing RVF prediction models exhibit heterogeneous derivation and validation methodologies, varying definitions of RVF, and are mostly derived from single centers. Validation studies of these prediction models demonstrate poor-to-modest discrimination. Newer models are derived in cohorts implanted with continuous-flow LVADs exclusively and exhibit modest discrimination. Derivation of enhanced discriminatory models and their validations in multicenter cohorts is needed.
Microanatomy of the Human Atherosclerotic Plaque by Single-Cell Transcriptomics
Authors: Depuydt Marie A.C. , Prange Koen H.M. , Slenders Lotte , Örd Tiit , Elbersen Danny , Boltjes Arjan , de Jager Saskia C.A. , Asselbergs Folkert W. , de Borst Gert J. , Aavik Einari , Lönnberg Tapio , Lutgens Esther , Glass Christopher K. , den Ruijter Hester M. , Kaikkonen Minna U. , Bot Ilze , Slütter Bram , van der Laan Sander W. , Yla-Herttuala Seppo , Mokry Michal , Kuiper Johan , de Winther Menno P.J. , Pasterkamp Gerard 
Published: September 2020

Rationale:
Atherosclerotic lesions are known for their cellular heterogeneity, yet the molecular complexity within the cells of human plaques has not been fully assessed.

Objective:
Using single-cell transcriptomics and chromatin accessibility, we gained a better understanding of the pathophysiology underlying human atherosclerosis.

Methods and Results:

We performed single-cell RNA and single-cell ATAC sequencing on human carotid atherosclerotic plaques to define the cells at play and determine their transcriptomic and epigenomic characteristics. We identified 14 distinct cell populations including endothelial cells, smooth muscle cells, mast cells, B cells, myeloid cells, and T cells and identified multiple cellular activation states and suggested cellular interconversions. Within the endothelial cell population, we defined subsets with angiogenic capacity plus clear signs of endothelial to mesenchymal transition. CD4
+
and CD8
+
T cells showed activation-based subclasses, each with a gradual decline from a cytotoxic to a more quiescent phenotype. Myeloid cells included 2 populations of proinflammatory macrophages showing IL (interleukin) 1B or TNF (tumor necrosis factor) expression as well as a foam cell-like population expressing TREM2 (triggering receptor expressed on myeloid cells 2) and displaying a fibrosis-promoting phenotype. ATACseq data identified specific transcription factors associated with the myeloid subpopulation and T cell cytokine profiles underlying mutual activation between both cell types. Finally, cardiovascular disease susceptibility genes identified using public genome-wide association studies data were particularly enriched in lesional macrophages, endothelial, and smooth muscle cells.

Conclusions:
This study provides a transcriptome-based cellular landscape of human atherosclerotic plaques and highlights cellular plasticity and intercellular communication at the site of disease. This detailed definition of cell communities at play in atherosclerosis will facilitate cell-based mapping of novel interventional targets with direct functional relevance for the treatment of human disease.
Are the Effects of Financial Market Disruptions Big or Small?
Authors: Barnichon Regis , Matthes Christian , Ziegenbein Alexander 
Published: September 2020

Abstract
While episodes of financial distress are followed by large and persistent drops in economic activity, structural time series analyses point to relatively mild and transitory effects of financial market disruptions. We argue that these seemingly contradictory findings are due to the asymmetric effects of financial shocks, which have been predicted theoretically but not taken into account empirically. We estimate a model designed to identify the (possibly asymmetric) effects of financial market disruptions, and we find that a favorable financial shock—an easing of financial conditions—has little effect on output, but an adverse shock has large and persistent effects. In a counterfactual exercise, we find that over two-thirds of the gap between current US GDP and its 207 precrisis trend was caused by the 2007–2008 financial shocks.
Tax-Preferred Savings Vehicles: Can Financial Education Improve Asset Location Decisions?
Authors: Boyer M. Martin , d'Astous Philippe , Michaud Pierre-Carl 
Published: September 2020

Abstract
In this study, we conduct a stated-choice experiment to analyze the decision to contribute to either a front- or back-loaded tax-preferred retirement savings account. Our experimental design includes a randomized financial education intervention that provides information on the tax implications of both types of account. Respondents who were exposed to the intervention have greater knowledge of these accounts and make contribution choices that increase their after-tax income. Using a well-defined benchmark, we show that on average, respondents who experienced the intervention increase their discounted welfare by about 4% of their contribution amount.
Potential multidimensional behavioural impacts of differential infection in two fish populations
Authors: Ruehle Brandon P. , Poulin Robert 
Published: September 2020

Abstract
Parasites can influence the behaviour of their hosts, however investigations on how they may shape multiple personality traits are uncommon. The flatworm parasite Tylodelphys darbyi resides in the eyes of common bully, Gobiomorphus cotidianus, a locally common fish host to a range of other parasites that could also influence their behaviour. Here we assess how parasitism may be related to personality traits of two G. cotidianus populations; one where T. darbyi is highly abundant and one where the parasite is absent. We hypothesized that T. darbyi would have a stronger association with the different personality traits than other parasite taxa, and that the effects of infection on personality traits would vary between populations. Our results demonstrate that T. darbyi infections correlate with boldness, exploration, and activity within and among individuals. Further, we show that the relationship and therefore possible influence of other parasites, e.g., Apatemon sp., on personality traits vary between two host populations. Our study has revealed potential patterns highlighting how parasitism may differentially contribute to behavioural and ecological divergence among host populations.
Terminal Wind Hazard Analyses Based on Assimilated Weather Data and Lagrangian Coherent Structures
Authors: Knutson Brent , Tang Wenbo , Chan Pak Wai 
Published: September 2020

AbstractThe operational light detection and ranging (lidar) data from the Hong Kong International Airport (HKIA) in China are assimilated in the six-nest, high-resolution Weather Research and Forecasting (WRF) Model. The existing radar data assimilation schemes in the WRF data assimilation (WRFDA) package have been adapted to accommodate the high temporal frequency and spatial resolution of the lidar observations. The weather data are then used to produce Lagrangian coherent structures to detect atmospheric hazards for flights. The coherent structures obtained from the various datasets are contrasted against flight data measured on aircraft. It is found that both WRF and WRFDA produce coherent structures that are more distinguishable than those obtained from two-dimensional retrieval, which may improve the detection of true wind shear hazards.
Western North Pacific Tropical Cyclones in the Met Office Global Seasonal Forecast System: Performance and ENSO Teleconnections
Authors: Feng Xiangbo , Klingaman Nicholas P. , Hodges Kevin I. , Guo Yi-Peng 
Published: September 2020

AbstractThe performance of the Met Office Global Seasonal Forecast System (GloSea5-GC2) for tropical cyclone (TC) frequency for the western North Pacific (WNP) in July–October is evaluated, using 23 years of ensemble forecasts (1993–2015). Compared to observations, GloSea5 overpredicts the climatological TC frequency in the eastern WNP and underpredicts it in the western and northern WNP. These biases are associated with an El Niño–type bias in TC-related environmental conditions (e.g., low-level convergence and steering flow), which encourages too many TCs to form throughout the tropical Pacific and slows TC propagation speed. For interannual TC frequency variability, GloSea5 overestimates the observed negative TC–ENSO teleconnection in the western and northern WNP, associated with an eastward shift in the ENSO teleconnection to environmental conditions. Consequently, GloSea5 fails to predict interannual TC variability in the northeast WNP (south of Japan); performance is higher in the southwest WNP (e.g., the South China Sea) where the sign of the TC–ENSO teleconnection is correct. This study suggests the need to reduce biases in environmental conditions and associated ENSO teleconnections in GloSea5 to improve the TC prediction performance in the NWP.
Management of Nonoperative Diverticulitis
Authors: Malizia Robert A. , Martinolich Jessica L. , Ata Ashar , Fitz Nicholas G. , Williams Kanwaldeep K. , Valerian Brian T. , Stain Steven C. , Lee Edward C. 
Published: September 2020

Background Institutional pathways (IPs) allow efficient utilization of health care resources. Recent literature reports decreased hospital length of stay (LOS), complications, and costs with the admittance of surgical disease to surgical services. Our study aimed to demonstrate that admission to surgery for nonoperative, acute diverticulitis reduces hospital LOS, and cost, with comparable complication rates. Methods In January 2017, we defined IPs for diverticulitis, mandating emergency department admission to a surgical service. Patients admitted from October 2015 to June 2016 (pre-protocol, control cohort) were compared with those admitted January 2017-September 2018 (post-protocol, IP cohort). Primary outcomes included hospital LOS, direct cost, indirect cost, total cost, and 30-day readmission. Student’s 2-tailed t-test and chi-square analysis were utilized, with statistical significance P < .05. Results Nonoperative management of acute diverticulitis occurred in 62 (74%) patients in the control cohort. One hundred and eleven patients (85%) were admitted to the IP cohort. Patient characteristics were similar, except for a higher percentage of surgical patients utilizing private insurance and younger in age. Interestingly, no difference in hospital LOS (3.8 vs 4.7 days; P = 0.07), direct cost ($2639.44 vs $3251.52; P = .19), or overall cost ($5968.67 vs $6404.08, P = .61) was found between cohorts. Thirty-day readmission rates were comparable at 8% and 11% ( P = .59). Conclusion Institutional policy mandating admissions for patients receiving nonoperative management of diverticulitis to surgical services does not reduce hospital LOS or cost. This argues that admission to medical services may be an acceptable practice. This raises the question, is acute diverticulitis always a surgical issue?
Highly challenging balance and gait training for individuals with Parkinson’s disease improves pace, rhythm and variability domains of gait – A secondary analysis from a randomized controlled trial
Authors: Rennie Linda , Opheim Arve , Dietrichs Espen , Löfgren Niklas , Franzén Erika 
Published: September 2020

Objective: Evaluate immediate and long-term effects of highly challenging balance and gait training on pace-, rhythm-, variability-, asymmetry-, and postural control domains of gait for individuals with Parkinson’s disease (PD). Design: Randomized controlled trial - a secondary analysis. Setting: University hospital setting. Participants: One-hundred older adults with mild to moderate PD (Hoehn & Yahr 2 and 3). Intervention: Training group ( n = 51): 10 weeks (3 times/week) of intensive balance and gait training, incorporating dual tasks. Control group ( n = 49): care as usual. Main outcome measures: Spatiotemporal gait variables collected during normal and fast walking on a pressure-sensitive mat. A linear mixed model was used to evaluate training effects post intervention and at the 6 and 12 month follow-up. Results: Immediate training effects in the pace domain of gait were increased step velocity (normal speed: 8.2 cm/s, P = 0.04; fast: 10.8 cm/s, P < 0.01), increased step length (normal speed: 3 cm, P = 0.05; fast: 2.3 cm, P = 0.05) and reduced swing time variability (fast speed: –2.5 ms, P = 0.02). In the rhythm domain reduced step time (fast speed: –19.3 ms, P = 0.02), stance time (normal: –24.3 ms, P = 0.01; fast: –29.6 ms, P = 0.02) and swing time (fast speed: –8.7 ms, P = 0.04) was seen. Relative to the variability domain, the training decreased step time variability (fast: –2.8 ms, P = 0.02) and stance time variability (fast: –3.9 ms, P = 0.02). No training effects were retained at 6 months. Conclusions: Highly challenging balance and gait training improved pace, rhythm and variability aspects of PD gait in the short-term, but effects are not retained long-term. Trial registration number: NCT01417598.
Changes of intestinal microflora in neonatal necrotizing enterocolitis: a single-center study
Authors: Duan Miao , Han Zunhua , Huang Nanqu 
Published: September 2020

Objective To investigate the changes in the diversity and dynamics of intestinal microflora in patients with neonatal necrotizing enterocolitis (NEC) in a single center in China. Methods In this prospective study conducted between 2016 and 2019, feces were collected from 28 neonates with NEC and 30 control neonates to analyze the species richness and Shannon’s diversity index of the bands, which were also sequenced via PCR-denaturing gradient gel electrophoresis. Results The species richness and Shannon’s diversity index were significantly lower in the NEC group than in the control group, indicating that the diversity of intestinal flora was reduced in NEC. The numbers of samples positive for Bacteroides and Klebsiella were higher in the NEC group, whereas Escherichia coli, Bifidobacterium, and Lactobacillus were less frequently detected in patients with NEC than in controls. The prevalence of intestinal bacteria normalized after the resolution of NEC. Conclusion The decrease of intestinal flora diversity in neonates with NEC, especially the decreased prevalence of probiotic bacteria, may be an important factor in the pathogenesis of NEC.