bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated preoperative C‐reactive protein is associated with renal functional decline and non‐cancer mortality in surgically treated renal cell carcinoma: analysis from the INternational Marker Consortium for Renal Cancer (INMARC)
Authors: Cotta Brittney H. , Meagher Margaret F. , Patil Dattatraya , Saito Kazutaka , Patel Sunil H. , Patel Devin N. , Miller Nathan , Dutt Raksha , Keiner Cathrine , Bradshaw Aaron W. , Wan Fang , Eldefrawy Ahmed , Yasuda Yosuke , Fujii Yasuhisa , Master Viraj , Derweesh Ithaar H. 
Published: August 2020

ObjectiveTo investigate association of preoperative C‐reactive protein (CRP) and non‐cancer mortality (NCM) in a cohort of patients undergoing surgery for localised renal cell carcinoma (RCC).Patients and MethodsRetrospective multicentre analysis of patients surgically treated for clinical Stage 1–2 RCC from 2006 to 2017, excluding all cases of cancer‐specific mortality. Descriptive analyses were obtained between the pre‐treatment normal‐CRP (≤5 mg/L) and elevated‐CRP (>5 mg/L) groups. The primary outcome was NCM. The secondary outcomes included progression to de novo chronic kidney disease Stages 3–4 (estimated glomerular filtration rate [eGFR] of <60, <45, and <30 mL/min/1.73 m2). Multivariable analyses (MVA) were performed to assess for risk factors associated with functional decline and NCM, and Kaplan–Meier analysis was used to obtain survival estimates for outcomes.ResultsA total of 1987 patients who underwent radical or partial nephrectomy were analysed (normal‐CRP group, n = 963; elevated‐CRP group, n = 1024). Groups were similar in age (59 vs 60 years, P = 0.079). An elevated CRP was more frequent in males (36.8% vs 27.8%, P < 0.001), African‐Americans (22.6% vs 2.9%, P < 0.001), and in those with a higher median body mass index (30 vs 25 kg/m2, P < 0.001) and larger median tumour size (4.5 vs 3.3 cm, P < 0.001). On MVA, an elevated CRP was independently associated with development of de novo eGFR of <60 mL/min/1.73 m2 (hazard ratio [HR] 1.32, P = 0.015), <45 mL/min/1.73 m2 (HR 1.41, P = 0.023) and <30 mL/min/1.73 m2 (odds ratio 2.23, P < 0.001). The MVA for factors associated with NCM demonstrated increasing age (HR 1.06, P < 0.001), preoperative elevated CRP (HR 2.18, P < 0.001) and an eGFR of <45 mL/min/1.73 m2 (HR 1.16; P = 0.021) as independent risk factors. Kaplan–Meier analysis revealed significantly higher 5‐year NCM in the elevated‐CRP group vs the normal‐CRP group (98% vs 80%, P < 0.001).ConclusionsPre‐treatment elevated CRP was independently associated with both progressive renal functional decline and NCM in patients undergoing surgery for Stage 1–2 RCC. Patients with elevated CRP and Stage 1 and 2 RCC may be considered as having indication for nephron‐sparing strategies, which may be prioritised if oncologically appropriate.
Clinical impact of a cancer genomic profiling test using an in‐house comprehensive targeted sequencing system
Authors: Hayashi Hideyuki , Tanishima Shigeki , Fujii Kyoko , Mori Ryo , Okada Chihiro , Yanagita Emmy , Shibata Yuka , Matsuoka Ryosuke , Amano Toraji , Yamada Takahiro , Yabe Ichiro , Kinoshita Ichiro , Komatsu Yoshito , Dosaka‐Akita Hirotoshi , Nishihara Hiroshi 
Published: August 2020

AbstractPrecision medicine is a promising strategy for cancer treatment. In this study, we developed an in‐house clinical sequencing system to perform a comprehensive cancer genomic profiling test as a clinical examination and analyzed the utility of this system. Genomic DNA was extracted from tumor tissues and peripheral blood cells collected from 161 patients with different stages and types of cancer. A comprehensive targeted amplicon exome sequencing for 160 cancer‐related genes was performed using next‐generation sequencing (NGS). The sequencing data were analyzed using an original bioinformatics pipeline, and multiple cancer‐specific gene alterations were identified. The success rate of our test was 99% (160/161), while re‐biopsy was required for 24% (39/161) of the cases. Potentially actionable and actionable gene alterations were detected in 91% (145/160) and 46% (73/160) of the patients, respectively. The actionable gene alterations were frequently detected in PIK3CA (9%), ERBB2 (8%), and EGFR (4%). High tumor mutation burden (TMB) (≥10 mut/Mb) was observed in 12% (19/160) of the patients. The secondary findings in germline variants considered to be associated with hereditary tumors were detected in 9% (15/160) of the patients. Seventeen patients (11%, 17/160) were treated with genotype‐matched therapeutic agents, and the response rate was 47% (8/17). The median turnaround time for physicians was 20 days, and the median survival time after the initial visit was 8.7 months. The results of the present study prove the feasibility of implementing in‐house clinical sequencing as a promising laboratory examination technique for precision cancer medicine.
Peptidomimetic‐based approach toward inhibitors of microbial trimethylamine lyases
Authors: Gabr Moustafa T. , Deganutti Giuseppe , Reynolds Christopher A. 
Published: August 2020

AbstractThe development of gut microbiota‐targeted small molecules represents a promising platform for the identification of new therapeutics based on the implication of human gut bacteria with different diseases. Bacterial trimethylamine (TMA)‐lyase (CutC) is expressed in gut bacteria and catalyzes the conversion of choline to TMA. The association of elevated TMA production with various disorders has directed research efforts toward identification of CutC inhibitors. Herein, we introduce peptidomimetics as a promising toolbox for the discovery of CutC inhibitors. Our approach starts with screening a library of peptidomimetics for intestinal metabolic stability followed by in vitro CutC inhibition. Compound 5 was identified from this screening platform with IC50 value of 5.9 ± 0.6 μM for CutC inhibition. Unlike previously reported CutC inhibitors, compound 5 possessed universal CutC inhibitory activity in different bacterial strains. Molecular dynamics simulations suggested a plausible binding site and inhibition mechanism for compound 5. Therefore, compound 5 is a promising lead for further structural optimization in the search for CutC‐targeted small molecules.
Expedient synthesis and anticancer evaluation of dual‐action 9‐anilinoacridine methyl triazene chimeras
Authors: Walunj Dipak , Egarmina Katarina , Tuchinsky Helena , Shpilberg Ofer , Hershkovitz‐Rokah Oshrat , Grynszpan Flavio , Gellerman Gary 
Published: August 2020

AbstractThe efficient synthesis of molecular hybrids including a DNA‐intercalating 9‐anilinoacridine (9‐AnA) core and a methyl triazene DNA‐methylating moiety is described. Nucleophilic aromatic substitution (SNAr) and electrophilic aromatic substitution (EAS) reactions using readily accessible starting materials provide a quick entry to novel bifunctional anticancer molecules. The chimeras were evaluated for their anticancer activity. Chimera 7b presented the highest antitumor activity at low micromolar IC50 values in antiproliferative assays performed with various cancer cell lines. In comparison, compound 7b outperformed DNA‐intercalating drugs like amsacrine and AHMA. Mechanistic studies of chimera 7b suggest a dual mechanism of action: methylation of the DNA‐repairing protein MGMT associated with the triazene structural portion and Topo II inhibition by intercalation of the acridine core.
A Two‐Generation Education Intervention and Children’s Attendance in Head Start
Authors: Sommer Teresa Eckrich , Schneider William , Chor Elise , Sabol Terri J. , Chase‐Lansdale P. Lindsay , Brooks‐Gunn Jeanne , Yoshikawa Hirokazu , Morris Amanda , King Christopher 
Published: August 2020

Two‐generation human capital programs seek to promote the education of parents and children simultaneously. This study examines relations between family participation in CareerAdvance, which recruits parents of Head Start children into a workforce training program, and children’s Head Start attendance. The sample included 293 children (on average 4 years old) and their parents. After one semester, CareerAdvance children demonstrated higher rates of attendance and lower rates of absence and chronic absence (missing 10% or more of school days) than matched comparison children. These associations were similar across a range of high‐ and low‐risk subgroups at baseline. These findings are discussed in terms of the implications of a family systems approach for improving children’s Head Start attendance.
Causal Effects of Parent Number Talk on Preschoolers’ Number Knowledge
Authors: Gibson Dominic J. , Gunderson Elizabeth A. , Levine Susan C. 
Published: August 2020

Individual differences in children’s number knowledge arise early and are associated with variation in parents’ number talk. However, there exists little experimental evidence of a causal link between parent number talk and children’s number knowledge. Parent number talk was manipulated by creating picture books which parents were asked to read with their children every day for 4 weeks. N = 100 two‐ to four‐year olds and their parents were randomly assigned to read either Small Number (1–3), Large Number (4–6), or Control (non‐numerical) books. Small Number books were particularly effective in promoting number knowledge relative to the Control books. However, children who began the study further along in their number development also benefited from reading the Large Number Books with their parents.
Learning From Video: A Meta‐Analysis of the Video Deficit in Children Ages 0 to 6 Years
Authors: Strouse Gabrielle A. , Samson Jennifer E. 
Published: August 2020

Young children often learn less from video than face‐to‐face presentations. Meta‐regression models were used to examine the average size of this difference (video deficit) and investigate moderators. An average deficit of about half of a standard deviation was reported across 122 independent effect sizes from 59 reports, involving children ages 0–6 years. Moderator analyses suggested (a) the deficit decreased with age, (b) object retrieval studies showed larger deficits than other domains, and (c) there was no difference between studies using live versus prerecorded video. Results are consistent with a multiple‐mechanism explanation for the deficit. However, the analyses highlighted potential quality and publication bias issues that may have resulted in overestimation of the effect and should be addressed by future researchers.
The Association Between Adverse Childhood Experiences and Child Telomere Length: Examining Self‐Regulation as a Behavioral Mediator
Authors: Sosnowski David W. , Kliewer Wendy , Valrie Cecelia R. , Winter Marcia A. , Serpell Zewelanji , Amstadter Ananda B. 
Published: August 2020

Childhood adversity is linked to shortened telomere length (TL), but behavioral indicators of telomere attrition remain unclear. This study examined the association between adverse childhood experiences (ACEs) and child TL, and if ACEs were indirectly associated with TL through children’s self‐regulatory abilities (i.e., effortful control and self‐control). Hypotheses were tested using national data from teachers, parents, and their children (N = 2,527; Mage = 9.35, SD = .36 years). More ACEs were uniquely associated with short TL, and low self‐control mediated the association between more ACEs and short TL. While longitudinal studies are needed to strengthen claims of causation, this study identifies a pathway from ACEs to TL that should be explored further.
The association of muscle size, strength and exercise capacity with all‐cause mortality in non‐dialysis‐dependent CKD patients
Authors: Watson Emma L. , Major Rupert W. , Wilkinson Thomas J. , Greening Neil J. , Gould Douglas W. , Barratt Jonathan , Smith Alice C. 
Published: August 2020

AbstractBackground/ObjectivePatients with chronic kidney disease (CKD) are commonly reported to exhibit skeletal muscle wasting, reduced strength and exercise capacity. Evidence from patients with end‐stage renal disease (ESRD) demonstrates these factors are associated with mortality, but it is unclear whether this relationship exists earlier in the illness. Our objective was to determine whether muscle size, strength or exercise capacity was associated with all‐cause mortality, unscheduled hospital admissions or time to ESRD in patients not requiring dialysis.MethodsThis is a prospective cohort study of 89 patients with CKD stages 3b‐5 not requiring renal replacement therapy with a mean follow‐up period of 3.3 years in which the contribution of predictors of rectus femoris muscle size, muscle strength, exercise capacity to all‐cause mortality rates, progression to ESRD and time to first hospitalization were investigated.ResultsUnadjusted analysis suggested each 1 cm2 increase in quadriceps muscle size (measured by ultrasonography cross‐sectional area) was associated with a 38% reduced risk for death (p = .006), and a 10 m improvement on the incremental shuttle walk test was associated with a 3% reduced risk for death (p = .04). However, this relationship was not present in analysis adjusted for age, gender and eGFR. No association was seen between any factor for the development of ESRD or time to first hospitalization.ConclusionThese results suggest that in this small cohort, muscle size and exercise capacity are associated with mortality when considered alone, but this relationship was not present in adjusted analyses. Further investigation in a larger patient group is warranted.
Mean platelet volume combined red cell distribution width as biomarker of chronic obstructive pulmonary disease with pulmonary heart disease
Authors: Bai Yu , Tao Xiao‐Nan 
Published: August 2020

AbstractBackground and objectivePlatelet activation, inflammatory reactions and oxidative stress are common pathogenesis of chronic obstructive pulmonary disease (COPD) with pulmonary heart disease (PHD). Mean platelet volume (MPV) and red blood cell distribution width (RDW) form part of the pathomechanisms of these conditions. Here, we investigated whether MPV and RDW can be biomarkers of PHD occurring secondary to COPD.Materials and methodsThis was a retrospective study on 229 participants with COPD. Among them, 69 had PHD. Complete blood count (CBC), blood gas analysis, pulmonary function tests and echocardiography were analyzed.ResultsMPV and RDW‐standard deviation (RDW‐SD) were significantly higher in patients with PHD than in patients without PHD (P ≤ 0.001). MPV and RDW‐SD were positively correlated with pulmonary artery pressure (PAP) and the size of the right ventricle (P ≤ 0.05). Multivariate regression analysis showed that the risk of PHD increased 3‐fold per unit rise in MPV (OR = 2.901, P ≤ 0.001). We observed that the risk of PHD increased 1.5 times per unit rise in RDW‐SD (OR = 1.371, P ≤ 0.001).The AUC of ROC curve for the combined MPV and RDW‐SD in predicting PHD among COPD patients was 0.900 (95％CI: 0.846‐0．954, P ≤ 0.001), with a sensitivity of 76.8% and a specificity of 99.4%.ConclusionsBoth MPV and RDW‐SD were significantly elevated and correlated with disease severity in COPD patients with PHD. A combination of these two parameters presents an effective biomarker of PHD.
Impact of temporary mechanical circulatory support for early graft failure on post–heart transplantation outcomes
Authors: Urban Marian , Lundgren Scott W. , Siddique Aleem , Ryan Timothy R. , Lowes Brian D. , Stoller Douglas A. , Um John Y. 
Published: August 2020

AbstractAlthough temporary mechanical circulatory support (tMCS) for hemodynamic failure following heart transplantation is associated with increased early morbidity and mortality, the impact of etiology of graft dysfunction and long‐term clinical implications are less well known. The objective of our study was to evaluate outcomes in patients who required venoarterial extracorporeal membrane oxygenation (VA ECMO) or temporary right ventricular assist device (RVAD) support for either primary or secondary early graft dysfunction. Hospital mortality in 27 patients who required tMCS following heart transplantation at our institution between 2007 and 2017 was 56%, 30% in patients with right ventricular dysfunction secondary to increased afterload, 60% in patients with primary graft dysfunction, and 100% in patients with graft failure secondary to coagulopathy with intraoperative bleeding or overwhelming sepsis. Conditional 1‐year and 5‐year survival was comparable between patients with, and without, the need for post‐transplantation support with tMCS (98% and 89%; 92% and 65% at 1 and 5 years, P = .21). Etiology of early graft failure plays an important part in determining the short‐term post–heart transplantation outcome. Although complications associated with tMCS use, such as renal dysfunction and infection, extend beyond index transplant hospitalization, long‐term conditional survival is not compromised.
Functional electrical stimulation cycling, goal‐directed training, and adapted cycling for children with cerebral palsy: a randomized controlled trial
Authors: Armstrong Ellen L , Boyd Roslyn N , Horan Sean A , Kentish Megan J , Ware Robert S , Carty Christopher P 
Published: August 2020

AimTo test the efficacy of functional electrical stimulation (FES) cycling, goal‐directed training, and adapted cycling, compared with usual care, to improve function in children with cerebral palsy (CP).MethodThe intervention was delivered between 2017 and 2019 and included three sessions per week for 8 weeks (2×1h sessions at a children’s hospital, and 1h home programme/week). Hospital sessions included 30 minutes of FES cycling and 30 minutes of goal‐directed training. Home programmes included goal‐directed training and adapted cycling. The comparison group continued usual care. Primary outcomes were gross motor function assessed by the Gross Motor Function Measure (GMFM) and goal performance/satisfaction assessed using the Canadian Occupational Performance Measure (COPM). Secondary outcomes were sit‐to‐stand and activity capacity, participation in home, school, and community activities, and power output. Linear regression was used to determine the between‐group mean difference immediately post‐training completion after adjusting for baseline scores.ResultsThis randomized controlled trial included 21 participants (mean age=10y 3mo, standard deviation [SD]=3y; Gross Motor Function Classification System level: II=7, III=6, IV=8) who were randomized to the intervention (n=11) or usual care group (n=10). Between‐group differences at T2 favoured the intervention group for GMFM‐88 (mean difference=7.4; 95% confidence interval [CI]: 2.3–12.6; p=0.007), GMFM‐66 (mean difference=5.9; 95% CI: 3.1–8.8; p<0.001), COPM performance (mean difference=4.4; 95% CI: 3.9–5.3; p<0.001) and satisfaction (mean difference=5.2; 95% CI: 4.0–6.4; p<0.001).InterpretationChildren with CP achieved meaningful functional improvements after FES cycling, goal‐directed training, and adapted cycling training. Cycling programmes for children with CP should be individualized and goal directed.
Effects of antidiabetic drugs on psoriasis: A meta‐analysis
Authors: Chi Ching‐Chi , Lee Chin‐Yu , Liu Chia‐Yu , Wang Shu‐Hui , Tien O’Donnell Felice , Tung Tao‐Hsin 
Published: August 2020

AbstractBackgroundPsoriasis, a chronic inflammatory skin disease, poses an elevated risk of developing diabetes mellitus.PurposeTo investigate the effects of antidiabetic medications on psoriasis.Data sources, study selection and data extractionWe conducted a systemic review and meta‐analysis and searched MEDLINE, EMBASE and CENTRAL for relevant randomized controlled trials. Our outcomes included 75% improvement in the psoriasis area and severity index from baseline (PASI 75), change in the psoriasis area and severity index (PASI) score, or change in the Dermatology Life Quality Index score under antidiabetic agents. Cochrane Collaboration's tool was used to evaluate the risk of bias of included studies. Subgroup analysis of different dosages of the antidiabetic agents was also performed.Data synthesisWe included 10 randomized controlled studies examining the effect of antidiabetic agents. Eight studies were rated high risk of bias. Pioglitazone demonstrated significant increase in PASI 75 (risk difference = 0.42; 95% CI: 0.18‐0.65) and decrease in mean PASI (mean difference = −3.82; 95% CI: −6.05‐1.ㄍ59). In subgroup analysis, 30 mg pioglitazone group demonstrated a significantly higher portion of PASI 75 than 15 mg pioglitazone group (P = .003).LimitationsSome biases are reported high risk in involved articles. The main limitation of the study is in the inclusion of only glitazones. The lack of effect was seen for rosiglitazone and metformin. In the case of metformin, there was only one study available, which is also an important issue.ConclusionsThe current evidence demonstrates therapeutic efficacy of pioglitazone, which may be a treatment option in patients with psoriasis and diabetes mellitus.
Features of severe COVID‐19: A systematic review and meta‐analysis
Authors: Del Sole Francesco , Farcomeni Alessio , Loffredo Lorenzo , Carnevale Roberto , Menichelli Danilo , Vicario Tommasa , Pignatelli Pasquale , Pastori Daniele 
Published: August 2020

AbstractBackgroundTo systematically review clinical and biochemical characteristics associated with the severity of the novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐related disease (COVID‐19).Materials and methodsSystematic review of observational studies from PubMed, ISI Web of Science, SCOPUS and Cochrane databases including people affected by COVID‐19 and reporting data according to the severity of the disease. Data were combined with odds ratio (OR) and metanalysed. Severe COVID‐19 was defined by acute respiratory distress syndrome, intensive care unit admission and death.ResultsWe included 12 studies with 2794 patients, of whom 596 (21.33%) had severe disease. A slightly higher age was found in severe vs non‐severe disease. We found that prevalent cerebrovascular disease (odds ratio [OR] 3.66, 95% confidence interval [CI] 1.73‐7.72), chronic obstructive pulmonary disease (OR: 2.39, 95% CI 1.10‐5.19), prevalent cardiovascular disease (OR: 2.84, 95% CI 1.59‐5.10), diabetes (OR: 2.78, 95% CI 2.09‐3.72), hypertension (OR: 2.24, 95% CI 1.63‐3.08), smoking (OR: 1.54, 95% CI 1.07‐2.22) and male sex (OR: 1.22, 95% CI 1.01‐1.49) were associated with severe disease. Furthermore, increased procalcitonin (OR: 8.21, 95% CI 4.48‐15.07), increased D‐Dimer (OR: 5.67, 95% CI 1.45‐22.16) and thrombocytopenia (OR: 3.61, 95% CI 2.62‐4.97) predicted severe infection.ConclusionCharacteristics associated with the severity of SARS‐CoV‐2 infection may allow an early identification and management of patients with poor outcomes.