bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sperm DNA methylation changes after short‐term nut supplementation in healthy men consuming a Western‐style diet
Authors: Salas‐Huetos Albert , James Emma R. , Salas‐Salvadó Jordi , Bulló Mònica , Aston Kenneth I. , Carrell Douglas T. , Jenkins Timothy G. 
Published: September 2020

AbstractBackgroundMany environmental and lifestyle factors have been implicated in the decline of sperm quality, with diet being one of the most plausible factors identified in recent years. Moreover, several studies have reported a close association between the alteration of specific sperm DNA methylation signatures and semen quality.ObjectivesTo evaluate the effect of tree nut consumption on sperm DNA methylation patterns in healthy individuals reporting eating a Western‐style diet.Material and methodsThis is a post hoc analysis conducted in a subset of participants (healthy, non‐smoking, and young) from the FERTINUTS 14‐wk randomized‐controlled, parallel trial, recruited between December 2015 and February 2017. The participants included in the current study (n = 72) were randomly selected in a proportion 2:1 from the original FERTINUTS trial between the 98 participants that completed the entire dietary intervention (nut group, n = 48; control group, n = 24). Sperm DNA methylation patterns were examined at baseline and after 14 weeks in 48 individuals consuming 60 g/d of mixed nuts (nut group) and in 24 individuals following the usual Western‐style diet avoiding consumption of nuts (control group).ResultsOver the course of the trial, no significant changes in global methylation were observed between groups. However, in the nut group, we identified 36 genomic regions that were significantly differentially methylated between the baseline and the end of the trial and 97.2% of the regions displayed hypermethylation. We identified no such change in the control group over the same period of time. We also utilized the recently developed germ line age calculator to determine if nut consumption resulted in alterations to the epigenetic age of cells and no significant differences were found.Discussion and conclusionAdding nuts to a regular Western‐style diet subtly impacts sperm DNA methylation in specific regions, demonstrating that there are some sperm epigenome regions that could respond to diet.
The clinical relevance of the microbiome when managing paediatric infectious diseases—Narrative review
Authors: Sainz Talía , Delgado Jaime , Mendez‐Echevarría Ana , Santiago Begoña , Lopez‐Varela Elisa , Aguilera‐Alonso David , Saavedra‐Lozano Jesús , Rodríguez‐Fernández Rosa , Holguín África , Navarro Marisa L. , Muñoz‐Fernández María Ángeles , Rivero‐Calle Irene , Solana María José , López‐Herce Jesús , Calvo Cristina 
Published: September 2020

AbstractIn recent years, the field of infectious diseases has been hit by the overwhelming amount of information generated while the human microbiome is being disentangled. Based on the interaction between the microbiota and the immune system, the implications regarding infectious diseases are probably major and remain a challenge.AimsThis review was conceived as a comprehensive tool to provide an overview of the available evidence regarding the influence of the microbiome on infectious diseases in children.MethodsWe present the main findings aroused from microbiome research in prevention, diagnosis and treatment of infectious disease under a paediatric perspective, to inform clinicians of the potential relevance of microbiome‐related knowledge for translation to clinical practice.Results and ConclusionThe evidence shown in this review highlights the numerous research gaps ahead and supports the need to move forward to integrating the so‐called microbiome thinking into our routine clinical practice.
Evaluating multiple surrogate markers with censored data
Authors: Parast Layla , Cai Tianxi , Tian Lu 
Published: September 2020

AbstractThe utilization of surrogate markers offers the opportunity to reduce the length of required follow‐up time and/or costs of a randomized trial examining the effectiveness of an intervention or treatment. There are many available methods for evaluating the utility of a single surrogate marker including both parametric and nonparametric approaches. However, as the dimension of the surrogate marker increases, a completely nonparametric procedure becomes infeasible due to the curse of dimensionality. In this paper, we define a quantity to assess the value of multiple surrogate markers in a time‐to‐event outcome setting and propose a robust estimation approach for censored data. We focus on surrogate markers that are measured at some landmark time, t0, which occurs earlier than the end of the study. Our approach is based on a dimension reduction procedure with an option to incorporate weights to guard against potential misspecification of the working model, resulting in three different proposed estimators, two of which can be shown to be double robust. We examine the finite sample performance of the estimators under various scenarios using a simulation study. We illustrate the estimation and inference procedures using data from the Diabetes Prevention Program (DPP) to examine multiple potential surrogate markers for diabetes.
Assessment of sexual dysfunction in patients with perianal Crohn's disease
Authors: Boudiaf R. , Bouchard D. , Rivière P. , Brochard C. , Laharie D. , Abramowitz L. , Pigot F. ,   the GREP members (Groupe de Recherche en Proctologie)
Published: September 2020

AbstractAimOver the past 10 years, several studies have focused on sexuality in patients with Crohn's disease. Very few of them specifically focused on perianal disease (PD). This study aimed to compare the prevalence of sexual dysfunction (SD) in Crohn's disease patients with active PD versus controls without active PD.MethodPatients from 14 French centres with active PD, defined by the presence of symptomatic ulceration, fistula or stenosis, were arbitrarily included. They were compared with controls from the existing SEXIA cohort. Men completed the International Index of Erectile Function (IIEF) and women the Female Sexual Function Index (FSFI). The primary end‐point was SD defined by FSFI < 26.55 in women and IIEF < 42.9 in men.ResultsNinety‐seven patients (64 women, 33 men) and 238 controls (131 women, 107 men) were included. SD was found in 66% of the female patients versus 50% of the controls (P = 0.04). In the male population, SD was found in 30% of the cases versus 16% of the controls (P = 0.06). Erectile dysfunction affected 46% of the male patients and 43% of the controls (P = 0.8). On multivariate analysis, the predictive factor most strongly associated with SD in women was severely active anal PD defined by a perineal disease activity index > 4 [OR = 13.05 (2.32–73.44)].ConclusionWomen with active PD had an increased prevalence of SD compared with controls without active PD. In the male population, the study was unable to determine whether there was a difference as it was underpowered.
Effect of liposomal bupivacaine on opioid requirements and length of stay in colorectal enhanced recovery pathways: A systematic review and network meta‐analysis
Authors: Byrnes Kevin Gerard , Sahebally Shaheel Mohammad , Burke John Patrick 
Published: September 2020

AbstractAimReducing postoperative opioid consumption is a key aim of enhanced recovery after colorectal surgery protocols. Potential solutions include anaesthetic techniques such as local infiltration of anaesthetic agents or transversus abdominis plane (TAP) blocks. This study aimed to assess the efficacy of liposomal bupivacaine (LB) for colorectal resections, across a variety of anaesthetic techniques.MethodsPubMed, Scopus and Embase databases were searched for relevant studies assessing LB, administered by any anaesthetic technique. The primary outcome was postoperative morphine consumed (milligrams) and the secondary outcome was length of stay (days). A Bayesian network meta‐analysis comparing LB versus non‐LB analgesia was performed alongside meta‐regression for different surgical approaches.ResultsTwelve trials were included, with a total of 2512 patients. LB‐based wound infiltration was most likely to reduce length of stay followed by TAP block with LB (sum under the cumulative ranking [SUCRA] 85.55 and 70.26, respectively). TAP block with LB was most likely to reduce morphine requirements, followed by wound infiltration with LB (SUCRA 83.94 and 75.73, respectively). Compared to standard analgesia, LB‐based wound infiltration reduced morphine usage (mean difference 36.64 mg, 95% credibility interval 15.64–59.20) and length of stay (mean difference 1.79 days, 95% credibility interval 0.59–3.81). On meta‐regression, the findings held for minimally invasive surgery only.ConclusionAlthough LB‐based interventions were associated with reduced postoperative morphine requirements and length of stay in this network meta‐analysis, the confidence in these estimates was graded as very low. Further well‐executed trials are required before LB can be recommended as a first‐line agent.
Analogical Comparison Promotes Theory‐of‐Mind Development
Authors: Hoyos Christian , Horton William S. , Simms Nina K. , Gentner Dedre 
Published: September 2020

AbstractTheory‐of‐mind (ToM) is an integral part of social cognition, but how it develops remains a critical question. There is evidence that children can gain insight into ToM through experience, including language training and explanatory interactions. But this still leaves open the question ofhowchildren gain these insights—what processes drive this learning? We propose that analogical comparison is a key mechanism in the development of ToM. In Experiment 1, children were shown true‐ and false‐belief scenarios and prompted to engage in multiple comparisons (e.g., belief vs. world). In Experiments 2a, 2b, and 3, children saw a series of true‐ and false‐belief events, varying in order and in their alignability. Across these experiments, we found that providing support for comparing true‐ and false‐belief scenarios led to increased performance on false‐belief tests. These findings show that analogical comparison can support ToM learning.
Syntactic Representations Are Both Abstract and Semantically Constrained: Evidence From Children’s and Adults’ Comprehension and Production/Priming of the English Passive
Authors: Bidgood Amy , Pine Julian M. , Rowland Caroline F. , Ambridge Ben 
Published: September 2020

AbstractAll accounts of language acquisition agree that, by around age 4, children’s knowledge of grammatical constructions is abstract, rather than tied solely to individual lexical items. The aim of the present research was to investigate, focusing on the passive, whether children’s and adults’ performance is additionally semantically constrained, varying according to the distance between the semantics of the verb and those of the construction. In a forced‐choice pointing study (Experiment 1), both 4‐ to 6‐year olds (N = 60) and adults (N = 60) showed support for the prediction of this semantic construction prototype account of an interaction such that the observed disadvantage for passives as compared to actives (i.e., fewer correct points/longer reaction time) was greater for experiencer‐theme verbs than for agent‐patient and theme‐experiencer verbs (e.g., Bob was seen/hit/frightened by Wendy). Similarly, in a production/priming study (Experiment 2), both 4‐ to 6‐year olds (N = 60) and adults (N = 60) produced fewer passives for experiencer‐theme verbs than for agent‐patient/theme‐experiencer verbs. We conclude that these findings are difficult to explain under accounts based on the notion of A(rgument) movement or of a monostratal, semantics‐free, level of syntax, and instead necessitate some form of semantic construction prototype account.
Mechanical force modulates periodontal ligament stem cell characteristics during bone remodelling via TRPV4
Authors: Jin Shan‐Shan , He Dan‐Qing , Wang Yu , Zhang Ting , Yu Hua‐Jie , Li Zi‐Xin , Zhu Li‐Sha , Zhou Yan‐Heng , Liu Yan 
Published: September 2020

AbstractObjectivesMechanical force plays an important role in modulating stem cell fate and behaviours. However, how periodontal ligament stem cells (PDLSCs) perceive mechanical stimulus and transfer it into biological signals, and thereby promote alveolar bone remodelling, is unclear.Materials and MethodsAn animal model of force‐induced tooth movement and a compressive force in vitro was used. After force application, tooth movement distance, mesenchymal stem cell and osteoclast number, and proinflammatory cytokine expression were detected in periodontal tissues. Then, rat primary PDLSCs with or without force loading were isolated, and their stem cell characteristics including clonogenicity, proliferation, multipotent differentiation and immunoregulatory properties were evaluated. Under compressive force in vitro, the effects of the ERK signalling pathway on PDLSC characteristics were evaluated by Western blotting.ResultsMechanical force in vivo induced PDLSC proliferation, which was accompanied with inflammatory cytokine accumulation, osteoclast differentiation and TRPV4 activation; the force‐stimulated PDLSCs showed greater clonogenicity and proliferation, reduced differentiation ability, improved induction of macrophage migration, osteoclast differentiation and proinflammatory factor expression. The biological changes induced by mechanical force could be partially suppressed by TRPV4 inhibition. Mechanistically, force‐induced activation of TRPV4 in PDLSCs regulated osteoclast differentiation by affecting the RANKL/OPG system via ERK signalling.ConclusionsTaken together, we show here that TRPV4 activation in PDLSCs under mechanical force contributes to changing their stem cell characteristics and modulates bone remodelling during tooth movement.
Substantially Increased Plasma Coproporphyrin‐I Concentrations Associated With OATP1B1*15 Allele in Japanese General Population
Authors: Suzuki Yosuke , Sasamoto Yuri , Koyama Teruhide , Yoshijima Chisato , Nakatochi Masahiro , Kubo Michiaki , Momozawa Yukihide , Uehara Ritei , Ohno Keiko 
Published: September 2020

Coproporphyrin‐I (CP‐I) in plasma is a sensitive and specific endogenous probe for phenotyping organic anion transporting polypeptides 1B (OATP1B, encoded by SLCO1B). A few small‐scale studies suggested that plasma CP‐I concentration is affected by OATP1B1 polymorphism, but detailed studies are lacking. In this large‐scale study, we measured plasma CP‐I concentrations in 391 subjects from the Japanese general population, and evaluated the relationship between plasma CP‐I concentrations and OATP1B1 polymorphisms to further assess the utility of plasma CP‐I concentrations as an endogenous OATP1B probe. Plasma CP‐I concentrations were 0.45 ± 0.12, 0.47 ± 0.16, 0.47 ± 0.20, 0.50 ± 0.15, 0.54 ± 0.14, and 0.74 ± 0.31 ng/mL in participants with OATP1B1*1b/*1b (n = 103), *1a/*1b (n = 122), *1a/*1a (n = 40), *1b/*15 (n = 74), *1a/*15 (n = 41), and *15/*15 (n = 11), respectively, showing an ascending rank order with significant difference (P < 0.0001). Post hoc analysis revealed significant increases in plasma CP‐I concentration in OATP1B1*1b/*15 (P = 0.036), *1a/*15 (P = 0.0005), and *15/*15 (P = 0.0003) groups compared with the OATP1B1*1b/*1b group. There was no significant difference among OATP1B genotypes in plasma concentration of 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid, a uremic toxin reported to decrease OATP1B activity in vivo. These findings confirm the utility of plasma CP‐I concentrations as an endogenous biomarker for phenotyping of OATP1B activity. Plasma CP‐I concentration is potentially useful for the study of drug‐drug interactions via OATP1B or individual dose adjustment of OATP1B substrates.
Efficacy and safety of polyethylene glycol loxenatide monotherapy in type 2 diabetes patients: A multicentre, randomized, double‐blind, placebo‐controlled phase 3a clinical trial
Authors: Shuai Ying , Yang Gangyi , Zhang Qiu , Li Wei , Luo Yong , Ma Jianhua , Chen Daoxiong , Yang Jialin , Wang Xinjun , Hu Ji , Xu Ning , Yang Wenying 
Published: September 2020

AbstractAimTo evaluate the efficacy and safety of polyethylene glycol loxenatide (PEX168) monotherapy in type 2 diabetes (T2D) patients in China.Materials and MethodsIn a multicentred, randomized, double‐blinded, placebo‐controlled phase 3a clinical trial, 361 patients with inadequate glycaemic control (HbA1c 7.0%‐10.5%, fasting plasma glucose <13.9 mmol/L) were randomized (1:1:1) for weekly subcutaneous injections: placebo, PEX168/100 μg or PEX168/200 μg. The 24‐week treatment was followed by a 28‐week extension, during which placebo‐treated patients were randomly assigned to PEX168/100 μg or PEX168/200 μg. The primary efficacy endpoint was the HbA1c change from baseline to week 24.ResultsThe three groups had similar demographics and baseline characteristics. The HbA1c least‐square mean (95% CI) change from baseline to week 24 was greater for PEX168/100 μg (−1.02% [−1.21%, −0.83%]) and PEX168/200 μg (−1.34% [−1.54%, −1.15%]) than for placebo (−0.17% [−0.36%, 0.02%]); (superiority: P < .0001). The proportions of patients with less than 7% HbA1c in the placebo, PEX168/100 μg and PEX168/200 μg groups were 15.7%, 34.7% and 46.6%, respectively. Common gastrointestinal adverse events (AEs) were nausea (5.6%, 10.0% and 0% for PEX168/100 μg, PEX168/200 μg and placebo, respectively) and vomiting (2.4%, 8.3% and 0% for PEX168/100 μg, PEX168/200 μg and placebo, respectively). Six (1.6%) patients (PEX168/100 μg: N = 2 [1.6%], PEX168/200 μg: N = 3 [2.5%] and placebo: N = 1 [0.8%]) discontinued treatment because of AEs. Four (1.2%) patients (PEX168/100 μg: N = 3 [2.5%] and PEX168/200 μg: N = 1 [0.9%]) developed PEX168 antidrug antibodies.ConclusionPEX168 monotherapy significantly improved glycaemic control in T2D patients with a safety profile resembling that of other glucagon‐like peptide‐1 receptor agonists.
Association between visit‐to‐visit HbA1c variability and the risk of cardiovascular disease in patients with type 2 diabetes
Authors: Shen Yun , Zhou Jian , Shi Lizheng , Nauman Elizabeth , Katzmarzyk Peter T. , Price‐Haywood Eboni G. , Horswell Ronald , Bazzano Alessandra N. , Nigam Somesh , Hu Gang 
Published: September 2020

AbstractAimTo investigate the association between visit‐to‐visit HbA1c variability and the risk of cardiovascular disease in patients with type 2 diabetes.Materials and methodsWe performed a retrospective cohort study of 29 260 patients with at least four HbA1c measurements obtained within 2 years of their first diagnosis of type 2 diabetes. Different HbA1c variability markers were calculated, including the standard deviation (SD), coefficient of variation (CV) and adjusted SD. Cox proportional hazards regression models were used to estimate the association of these HbA1c variability markers with incident cardiovascular disease.ResultsDuring a mean follow‐up of 4.18 years, a total of 3746 incident cardiovascular disease cases were diagnosed. Multivariate‐adjusted hazard ratios for cardiovascular disease across the first, second, third and fourth quartiles of HbA1c SD values were 1.00, 1.30 (95% confidence interval [CI] 1.18‐1.42), 1.40 (95% CI 1.26‐1.55) and 1.59 (95% CI 1.41‐1.77) (P for trend <.001), respectively. When we utilized HbA1c CV and adjusted HbA1c SD values as exposures, similar positive associations were observed. HbA1c variability was also associated with the risk of first and recurrent severe hypoglycaemic events. A mediating effect of severe hypoglycaemia was observed between HbA1c variability and incident cardiovascular disease.ConclusionsLarge visit‐to‐visit HbA1c variability is associated with an increased risk of cardiovascular disease in patients with type 2 diabetes. Severe hypoglycaemia may mediate the association between HbA1c variability and incident cardiovascular disease.
Health‐related quality of life in patients with untreated cavernous malformations of the central nervous system
Authors: Herten A. , Chen B. , Saban D. , Santos A. , Wrede K. , Jabbarli R. , Zhu Y. , Schmidt B. , Kleinschnitz C. , Forsting M. , Sure U. , Dammann P. 
Published: September 2020

Background and purposeTo estimate health‐related quality of life (HRQOL) in patients with untreated cavernous malformation of the CNS [cavernous cerebral malformations (CCMs)].MethodsWe performed a cross‐sectional observational study on patients with CCMs admitted to our department from 1 November 2017 to 10 January 2020 using standardized interviews [short‐form‐36 questionnaire, hospital anxiety and depression score (HADS‐A/D), CCM perception questionnaire]. Included criteria were diagnosis of an untreated CCM and information about the diagnosis in a specialized CCM consultation. Health‐related quality of life (HRQOL) data were analyzed and compared to the German normal population. Uni‐ and multivariate analyses were carried out to identify variables with impact on outcome.ResultsTwo hundred nineteen (93%) of 229 eligible patients were included. Mean age was 46.3 ± 14.7 (18–86) years; 136 (62%) were female. Ninety‐eight (45%) patients presented with symptomatic hemorrhage (SH), and 17 (8%) with repetitive SH. Ninety‐two (42%) patients were asymptomatic. Thirty‐seven patients (17%) suffered from cavernoma‐related epilepsy. Twenty‐eight patients (13%) suffered from familial CCMs. Patients showed significantly decreased component scores and subdomain scores compared to the normal population, with effects ranging from small to large. This accounted largely also for asymptomatic patients (except for physical component score and main physical subdomains). Multivariate regression analysis confirmed impact of functional impairment on physical component score. HADS‐A was significantly increased. HADS‐A/D strongly correlated with mental component score and individual perception of the CCM.ConclusionsPatients with the diagnosis of a CCM showed decreased HRQOL compared to the normal population even when not suffering functional impairment or neurological symptoms. Our data may function as benchmarks in evaluation of different (future) management strategies.
Stroke units could be a valid alternative to intensive care units for patients with low‐grade aneurysmal subarachnoid haemorrhage
Authors: Llull L. , Mayà G. , Torné R. , Mellado‐Artigas R. , Renú A. , López‐Rueda A. , Laredo C. , Culebras D. , Ferrando C. , Blasco J. , Amaro S. , Chamorro Á. 
Published: September 2020

Background and purposeAccording to current guidelines, patients with aneurysmal subarachnoid haemorrhage (aSAH) are mostly managed in intensive care units (ICUs) regardless of baseline severity. We aimed to assess the prognostic and economic implications of initial admission of patients with low‐grade aSAH into a stroke unit (SU) compared to initial ICU admission.MethodsWe reviewed prospectively registered data from consecutive aSAH patients with a World Federation of Neurosurgery Societies grade <3, admitted to our Comprehensive Stroke Centre between April 2013 and September 2018. Clinical and radiological baseline traits, in‐hospital complications, length of stay (LOS) and poor outcome at 90 days (modified Rankin Scale score > 2) were compared between the ICU and SU groups in the whole population and in a propensity‐score‐matched cohort.ResultsOf 131 patients, 74 (56%) were initially admitted to the ICU and 57 (44%) to the SU. In‐hospital complication rates were similar in the ICU and SU groups and included rebleeding (10% vs. 7%; P = 0.757), angiographic vasospasm (61% vs. 60%; P = 0.893), delayed cerebral ischaemia (12% vs. 12%; P = 0.984), pneumonia (6% vs. 4%; P = 0.697) and death (10% vs. 5%; P = 0.512). LOS did not differ between groups (median [interquartile range] 22 [16–30] vs. 19 [14–26] days; P = 0.160). In adjusted multivariate models, the location of initial admission was not associated with long‐term poor outcome either in the whole population (odds ratio [OR] 1.16, 95% confidence interval [CI] 0.32–4.19; P = 0.825) or in the matched cohort (OR 0.98, 95% CI 0.24–4.06; P = 0.974).ConclusionsA dedicated SU, with care from a multidisciplinary team, might be an optimal alternative to ICU for initial admission of patients with low‐risk aSAH.