bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying perceptions and barriers regarding vaccination in patients with rheumatoid arthritis: A Canadian perspective
Authors: Aberumand Babak , Dyck Bailey A. , Towheed Tanveer
Published: September 2020

Aim

Canadian guidelines recommend that patients with rheumatoid arthritis (RA) receive pneumococcal, influenza and shingles vaccinations. The aim of this study was to identify and understand vaccination rates in Canadian patients with RA.

Methods

We conducted an observational study to evaluate uptake of herpes zoster (HZ), influenza and pneumonia vaccination in a cross‐section of patients with RA in Kingston, Ontario, Canada. Data were collected using a self‐administered questionnaire in patients attending at an academic rheumatology clinic. If vaccination was not received, the reason was established.

Results

Ninety‐eight out of a total of 103 patients surveyed met the inclusion criteria and were evaluated: 72.4% had received the influenza vaccination in the past year encompassing a period of 2017‐2019. Of the 27.6% who did not, the most common chosen reason was personal preference not to get vaccinated (55.6%). Regarding HZ, 18.4% had received vaccination. Of the 2 available types of vaccines, more participants received Zostavax (66.7%) as compared to Shringrix (33.3%). For those not vaccinated (81.6%), “Other” was the most chosen option (37.5%) with the reasons subsequently specified as cost, concern over interaction with treatment and waiting until age ≥65 years. In terms of pneumococcal vaccination, 36.7% were vaccinated, with the majority being vaccinated with Pneumovax‐23 (63.9%) compared to Prevnar‐13 (16.7%) or both (19.4%). Of the 63.3% of the participants who did not receive vaccination, the most cited reason was they did not know they should receive pneumococcal vaccination (48.4%).

Conclusions

Vaccination rates among Canadian patients with RA are suboptimal.
MiR‐429 suppresses proliferation and invasion of breast cancer via inhibiting the Wnt/β‐catenin signaling pathway
Authors: Zhang Liping , Liu Qinghua , Mu Qingjie , Zhou Dandan , Li Hongli , Zhang Baogang , Yin Chonggao
Published: September 2020

Background

microRNAs (miRNAs) have been verified as molecular targets for regulating tumor proliferation, invasion, and metastasis in tumor progression. However, the relationship between miRNAs and cellular energy metabolism in breast cancer still needs to be clarified. This study aimed to investigate the role of miR‐429 in breast cancer progression.

Methods

Bioinformatic analyses were employed to detect the relationship between miR‐429 and cancer‐related signaling pathways. We used a Kaplan‐Meier curve to analyze survival rate in patients with high or low expression of miR‐429. We used real‐time quantitative PCR (RT‐qPCR) to detect the expression of miR‐429 in different cell lines. Sh‐con, over‐miR‐429, miR‐429 inhibitor, and sh‐inhibitor control were transfected. Colony formation and EDU assay were used to detect the proliferation of transfected cells. Wound healing and transwell assays were performed to detect the mobility and invasion ability of transfected cells. Western blot assay was used to detect relative protein expression in transfected cells and different tissues. Bioinformatic analyses were conducted to detect the target proteins expression in different breast cancer databases. Dual luciferase reporter assay was used to confirm the binding site between miR‐429 and fibronectin 1 (FN1).

Results

The results of our study indicate that MiR‐429 and its target genes are associated with cancer‐related signaling pathways and that higher miR‐429 expression corresponds with a better prognosis. When miR‐429 was overexpressed, the proliferation, invasion of MDA‐MB‐231 were inhibited. MiR‐429 was able to suppress the Wnt/β‐catenin signaling pathway, and FN1 overexpression could rescue the influence of over‐miR‐429.

Conclusions

The results of our study suggest that miR‐429 suppresses the proliferation and invasion of breast cancer via inhibiting the Wnt/β‐catenin signaling pathway.
DNA sonication inverse PCR for genome scale analysis of uncharacterized flanking sequences
Authors: Alquezar‐Planas David E. , Löber Ulrike , Cui Pin , Quedenau Claudia , Chen Wei , Greenwood Alex D.
Published: September 2020

There are few available tools to comprehensively and economically identify uncharacterized flanking regions that are not extremely labour intensive and which exploit the advantages of emerging long‐read sequencing platforms.

We describe SIP; a sonication‐based inverse PCR high‐throughput sequencing strategy to investigate uncharacterized flanking region sequences, including those flanking mobile DNA. SIP combines unbiased fragmentation by sonication and target enrichment by coupling outward facing PCR priming with long‐read sequencing technologies.

We demonstrate the effectiveness of SIP by determining retroviral integrations which are high copy and challenging to characterize. We further describe SIP's workflow, examine retroviral (proviral) enrichment and characterize viral structural variants identified. When SIP was coupled with long‐read sequencing using the PacBio RS II platform, proviral integration was extensively characterized at high sequence depth per integration. By interrogating the sequence data, we were also able to test several intrinsic factors including SIP's propensity to form chimeric sequences and adapter ligation efficiencies.

SIP is an adaption of a traditional molecular biology technique that can be used to characterize any unknown genomic flanking sequence or to extend any sequence for which only minimal sequence information is available. SIP can be applied broadly to study complex biological systems such as mobile genetic elements with high throughput.
Effects of thermal softening of endotracheal tubes on postoperative sore throat: A randomized double‐blinded trial
Authors: Yu Je Hyuk , Paik Hye‐Sun , Ryu Ho Geol , Lee Hannah
Published: September 2020

Background

Postoperative throat complications after intubation are undesirable but frequent outcomes. A randomized, double‐blinded study was performed to determine whether thermal softening of endotracheal tubes reduced throat complications after intubation.

Methods

Patients (n = 196) undergoing nasal surgery were randomly allocated into the control group and thermal softening groups. Sore throat and hoarseness were evaluated 1 and 24 hours after extubation. The severity of sore throat was evaluated using the numeric rating scale (NRS). The primary outcome was the incidence of sore throat 1 hour after extubation and sore throat was defined as a painful or scratchy feeling in the throat. The secondary outcomes were the incidence of hoarseness 1 hour after extubation, the incidence of sore throat and hoarseness 24 hours after extubation, severity of sore throat, and vocal cord injuries.

Results

The incidence of sore throat 1 hour after extubation was lower in the thermal softening group than in the control group (35.1% vs 52.7%, P = .02). Moreover, thermal softening decreased the mean NRS score for sore throat in the thermal softening group by 10% an hour after extubation (thermal softening group, 1.29 [95% CI, 0.88‐1.70] vs control group, 2.33 [95% CI, 1.77‐2.89]; P < .01). At 24 hours after extubation, the incidence of sore throat (38.3% vs 40.7%, P = .77) and hoarseness (34.0% vs 35.2%, 0.95 [0.52‐1.74], P = .74) were comparable between the two groups.

Conclusions

Intubation using endotracheal tubes with thermal softening significantly decreased the incidence of sore throat 1 hour after extubation when compared with endotracheal tubes without thermal softening.
Effects of different mean arterial pressure targets on plasma volume, ANP and glycocalyx—A randomized trial
Authors: Damén Tor , Saadati Sofia , Forssell‐Aronsson Eva , Hesse Camilla , Bentzer Peter , Ricksten Sven‐Erik , Nygren Andreas
Published: September 2020

Background

Arterial haematocrit (Hct) has been shown to decrease after anaesthesia induction, most probably because of an increased plasma volume (PV). The primary objective was to quantify change in PV if mean arterial pressure (MAP) was kept at baseline level or allowed to decrease to 60 mm Hg. Our secondary objective was to evaluate underlying mechanisms of this response.

Methods

Twenty‐four coronary artery bypass patients were randomized to a higher (90 mm Hg, intervention group) or lower (60 mm Hg, control group) MAP by titration of norepinephrine. During the experimental procedure, no fluids were administered. Baseline PV was measured by 125I‐albumin and the change in PV was calculated from the change in Hct. Changes in MAP, plasma 125I‐albumin, colloid osmotic pressure, albumin, Mid Regional‐pro Atrial Natriuretic Peptide (MR‐proANP) and endothelial glycocalyx components were measured from baseline to 50 minutes after anaesthesia induction.

Results

The MAP during the trial was 93 ± 9 mm Hg in the intervention group and 62 ± 5 mm Hg in the control group. PV increased with up to 420 ± 180 mL in the control group and 45 ± 130 mL in the intervention group (P < .001). Albumin and colloid osmotic pressure decreased significantly more in the control group. MR‐proANP increased in the control group but no shedding of the glycocalyx layer was detected in either of the groups.

Conclusion

Allowing mean arterial pressure to fall to 60 mm Hg during anaesthesia induction, increases the plasma volume due to reabsorption of interstitial water, with no ANP‐induced degradation of the endothelial glycocalyx.
Beers with Peers: Childhood ADHD and Risk for Correlated Change in Perceived Peer and Personal Alcohol Use Across Young Adulthood
Authors: Kennedy Traci M. , Walther Christine A.P. , Pedersen Sarah L. , McKone Kirsten M.P. , Gnagy Elizabeth M. , Pelham William E. , Molina Brooke S.G.
Published: September 2020

Background

ADHD poses risk for problematic alcohol use through adulthood. Perceived peer alcohol use, one of the strongest correlates of individuals’ own alcohol use, is especially salient for adolescents with ADHD. The extent to which this risk extends into young adulthood is unknown, as well as how change in these constructs is associated throughout young adulthood.

Methods

In the Pittsburgh ADHD Longitudinal Study, 358 individuals with childhood‐diagnosed ADHD and 239 without were prospectively followed from ages 18 to 29. Piecewise, bivariate longitudinal growth modeling was used to examine the change in both peer alcohol use and individuals’ heavy drinking (binge‐drinking frequency), their between‐person associations, and differences by ADHD group. The addition of structured residuals probed within‐person year‐to‐year change in peer and personal alcohol use and their prospective associations.

Results

Perceived peer alcohol use and individuals’ heavy drinking frequencies changed together over time concurrently—from ages 18 to 21 (piece 1) and 21 to 29 (piece 2). Prospectively, individuals who increased the most in heavy drinking from ages 18 to 21 reported more friends using alcohol at age 29, regardless of ADHD history. Within‐person increases in personal alcohol use likewise predicted increased perceived peer use the subsequent year within each age group (piece), regardless of ADHD history. However, while decreasing perceived peer use from ages 21 to 29 was related to more frequent heavy drinking at age 29 for those without ADHD, increasing perceived peer use from ages 18 to 21 predicted more frequent heavy drinking at age 29 for those with ADHD.

Conclusions

Young adult heavy drinking changes in tandem with perceived peer alcohol use across individuals and predicts selection of alcohol‐using peers from year to year within individuals, further into adulthood than previously documented. Findings suggest the centrality of relationships with alcohol‐consuming friends in relation to one’s heavy drinking, especially for young adults with ADHD histories, through the twenties.
Financial slack, institutional shareholding and enterprise innovation investment: evidence from China
Authors: Zhang Ke , Wang Jenny Jing , Sun Yanqi , Hossain Sarowar
Published: September 2020

This study examines how institutional shareholding affects the relationship between financial slack and corporate investment in innovation for Chinese A‐share listed companies. We find that financial slack significantly increases corporate innovation investment. Pressure‐resistant institutions do not moderate the relation but pressure‐sensitive institutions do moderate the relation negatively. We further find that financial slack affects beneficially results because of the employment of slack resources after an exogenous negative shock like COVID‐19/Global Financial Crisis. Our findings contribute to the literature on the cross‐sectional variation on the relationship between companies’ strategies and accounting choices in China.
Levered and inverse VIX ETP option contract adjustments: No harm, no foul?
Authors: Tengulov Angel , Whaley Robert E.
Published: September 2020

The terms of exchange‐traded stock option contracts are usually adjusted when corporate actions take place. These adjustments are made to safeguard the value of the outstanding option contracts. Recently, a new type of corporate event has appeared − levered and inverse exchange‐traded product issuers are reducing leverage ratios with increased frequency. While such changes directly affect option values, no contract adjustments are made, resulting in windfall transfers of wealth from outstanding long to outstanding short option holders. In one instance alone, the transfer was more than $US100 million. To remedy the problem, we offer a simple contract adjustment procedure.
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

Background

Many 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.

Objectives

To evaluate the effect of tree nut consumption on sperm DNA methylation patterns in healthy individuals reporting eating a Western‐style diet.

Material and methods

This 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).

Results

Over 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 conclusion

Adding 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

In 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.

Aims

This 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.

Methods

We 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 Conclusion

The 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

The 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

Aim

Over 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.

Method

Patients 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.

Results

Ninety‐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)].

Conclusion

Women 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

Aim

Reducing 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.

Methods

PubMed, 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.

Results

Twelve 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.

Conclusion

Although 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

Theory‐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

All 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

Objectives

Mechanical 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 Methods

An 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.

Results

Mechanical 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.

Conclusions

Taken 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

Aim

To evaluate the efficacy and safety of polyethylene glycol loxenatide (PEX168) monotherapy in type 2 diabetes (T2D) patients in China.

Materials and Methods

In 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.

Results

The 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.

Conclusion

PEX168 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

Aim

To investigate the association between visit‐to‐visit HbA1c variability and the risk of cardiovascular disease in patients with type 2 diabetes.

Materials and methods

We 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.

Results

During 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.

Conclusions

Large 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 purpose

To estimate health‐related quality of life (HRQOL) in patients with untreated cavernous malformation of the CNS [cavernous cerebral malformations (CCMs)].

Methods

We 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.

Results

Two 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.

Conclusions

Patients 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 purpose

According 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.

Methods

We 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.

Results

Of 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).

Conclusions

A dedicated SU, with care from a multidisciplinary team, might be an optimal alternative to ICU for initial admission of patients with low‐risk aSAH.
Eavesdropping of an African ground squirrel on the heterospecific alarm calls of a noisy ground‐nesting bird
Authors: Waterman Jane M. , Mai Monica
Published: September 2020

Animals gather information about their environment from a variety of sources to enable adaptive decision‐making behaviour. Eavesdropping on heterospecific alarm calls enhances predator avoidance, reduces time spent vigilant and allows for more time on daily activities such as foraging. If the information is relevant and reliable, individuals that respond to heterospecific signals may benefit from a wider range of information at a low marginal cost. The Cape ground squirrel (Xerus inauris) and crowned lapwing (Vanellus chilensis) are ground‐dwelling species that are taxonomically distant but share similar predators, habitat and anti‐predatory behaviours. We used playback experiments of the alarm calls produced by conspecifics and lapwings to investigate the vigilance responses of adult female Cape ground squirrels. Squirrels responded with greater vigilance to both squirrel and lapwing alarm calls, and no changes of vigilance levels were observed in response to a control sound. However, contrary to our predictions, changes in vigilance and time to relax did not differ between conspecific versus heterospecific playbacks. The results from our study suggest that squirrels perceive lapwing alarm calls as relevant and reliable information and that responding to it could increase their survival.
Emotion Regulation and Personality as Predictors of Mothers' Emotion Socialization Practices
Authors: Cabecinha‐Alati Sarah , Malikin Hagit , Montreuil Tina C.
Published: September 2020

Background

Parental emotion regulation (ER) and emotion socialization have been identified as key factors contributing to children's emotional competence; however, only a handful of studies have assessed the relationship between these constructs.

Objective

The goal of the present study was to determine whether parental ER would predict parents' self‐reported emotion socialization practices above and beyond the influence of personality.

Method

Parents completed a series of self‐report measures online. After data cleaning, 104 mothers of children between the ages of 8 and 12 years were retained for analyses.

Results

Hierarchal regressions revealed that mothers who reported higher levels of ER skills and more frequent use of cognitive reappraisal were more likely to report engaging in supportive response behaviors when controlling for personality. Moreover, maternal reappraisal was significantly and inversely associated with reports of unsupportive emotion socialization.

Conclusion

Findings provide evidence to support the association between maternal ER and emotion socialization behaviors.

Implications

Results are discussed with respect to their implications for emotion‐focused interventions aimed at promoting supportive parenting practices.
Frequency‐specific modification of locomotor components by the white gene in Drosophila melanogaster adult flies
Authors: Xiao Chengfeng , Qiu Shuang
Published: September 2020

The classic eye‐color gene white (w) in Drosophila melanogaster (fruitfly) has unexpected behavioral consequences. How w affects locomotion of adult flies is largely unknown. Here, we show that a mutant allele (w1118) selectively increases locomotor components at relatively high frequencies (> 0.1 Hz). The w1118 flies had reduced transcripts of w+ from the 5′ end of the gene. Male flies of w1118 walked continuously in circular arenas while the wildtype Canton‐S walked intermittently. Through careful control of genetic and cytoplasmic backgrounds, we found that the w1118 locus was associated with continuous walking. w1118‐carrying male flies showed increased median values of path length per second (PPS) and 5‐min path length compared with w+‐carrying males. Additionally, flies carrying 2–4 genomic copies of mini‐white+ (mw+) in the w1118 background showed suppressed median PPSs and decreased 5‐min path length compared with controls, and the suppression was dependent on the copy number of mw+. Analysis of the time‐series (i.e., PPSs over time) by Fourier transform indicated that w1118 was associated with increased locomotor components at relatively high frequencies (> 0.1 Hz). The addition of multiple genomic copies of mw+ (2–4 copies) suppressed the high‐frequency components. Lastly, the downregulation of w+ in neurons but not glial cells resulted in increased high‐frequency components. We concluded that mutation of w modified the locomotion in adult flies by selectively increasing high‐frequency locomotor components.
Polypharmacy at admission prolongs length of hospitalization in gastrointestinal surgery patients
Authors: Abe Natsuki , Kakamu Takeyasu , Kumagai Tomohiro , Hidaka Tomoo , Masuishi Yusuke , Endo Shota , Kasuga Hideaki , Fukushima Tetsuhito
Published: September 2020

Aim

Polypharmacy in elderly people is a social issue and has been reported to cause not only drug adverse events, but also falls, dysfunction and cognitive decline. Those events may trigger prolonged length of hospitalization. Therefore, the aim of this study was to investigate whether polypharmacy has a prolonging effect on hospitalization.

Methods

The study subjects were 584 patients in a university hospital in Japan who had been admitted for hepatectomy, pancreaticoduodenectomy, gastrectomy or colectomy, and to whom clinical pathways had been applied. In this study, polypharmacy was defined as taking five or more regular oral medications, and prolonged hospitalization was defined as hospitalization longer than that determined by the clinical pathway. Multiple logistic regression analysis was performed to investigate whether polypharmacy affects the length of hospitalization.

Results

The subjects were 348 males and 236 females, mean ± SD age of 65.8 ± 12.9 years. Among all subjects, 228 (39.0%) were receiving polypharmacy at admission, and the number of patients with prolonged hospitalization was 262 (44.9%). Multiple logistic regression analysis revealed that the following variables were significantly associated with prolonged hospitalization; polypharmacy (odds ratio = 1.532; 95% confidence interval = 1.010–2.327), age 50–59; 2.971 (1.216–7.7758), age 60–69; 2.405 (1.059–5.909), organ pancreas; 0.298 (0.122–0.708), operation time ≥386 min; 2.050 (1.233–3.432), intraoperative bleeding volume ≥401 mL; 2.440 (1.489–4.038), postoperative delirium; 2.395 (1.240–4.734), postoperative infection; 10.715 (4.270–33.059).

Conclusion

The current study revealed that polypharmacy at admission was an independent factor for prolonged hospitalization. In future, measures against polypharmacy are required, collaborating with outpatient clinics, family doctors and dispensing pharmacies. Geriatr Gerontol Int 2020; 20: 1085–1090..
Who leads? Village development committees and local governance in Southern Malawi
Authors: Maiden Emily , Guzman Danice Brown , Bleck Jaimie
Published: September 2020

Since the 1980s, many developing countries have enacted policies of decentralization to create localized, representative forms of government. A highly under‐studied body of local governance are village development committees (VDCs). Utilizing a mixed‐method approach in three districts of Southern Malawi, we combine surveys, focus groups, and interviews to examine the role of VDCs in local politics. Selected by their peers, VDC members navigate a complicated landscape including: local and central politicians, government bureaucrats, NGOs and special interest groups, and traditional authorities. We find that citizens are accurately able to evaluate the development work that VDCs are doing and consistently rate their trust in these institutions higher than their trust in elected authorities. Still, challenges persist: members receive no standardized training and there are consistent gender gaps in the experiences of men and women members of the VDCs.
Comparative effectiveness of antiretroviral drug classes for the treatment of HIV infection in patients with high viral loads: a multicentre retrospective cohort study
Authors: Adams JL , Murray M , Patel N , Sawkin MT , Boardman RC , Pham C , Kaur H , Patel D , Yager JL , Pontiggia L , Baxter J
Published: September 2020

Objectives

We aimed to compare the effectiveness of antiretroviral therapy (ART) classes for achieving HIV RNA suppression to < 50 HIV‐1 RNA copies/mL within 6 months of initiation with high viral loads (VLs). Secondary objectives were to compare viral suppression (VS) at 12 weeks and 12 months, partial HIV RNA suppression to < 200 copies/mL, time to VS, time to rebound, and change in CD4 cell count.

Methods

This was a multicentre, retrospective, observational study. Adult patients were included if they initiated ART between January 2005 and December 2016 with a VL ≥ 100 000 copies/mL.

Results

There were 220 patients included in the study. The median VL was 252 919 [interquartile range (IQR) 149 472–500 000] copies/mL. Nonnucleoside reverse transcriptase inhibitor (NNRTI) recipients were more likely to achieve VS by 6 months compared to those initiating ART containing protease inhibitors (PIs) [75.4% vs. 44.1%, respectively; odds ratio (OR) 3.34; 95% confidence interval (CI) 1.62–6.90] or integrase strand transfer inhibitors (INSTIs) (75.4% vs. 55.8%, respectively; OR 2.40; 95% CI 1.03–5.58). VS at 12 weeks was more frequent with INSTI‐containing regimens than with PIs (28.9% vs. 9.0%, respectively; OR 4.10; 95% CI 1.69–9.92). VS at 12 months did not significantly differ between treatment regimens. Median time to complete VS for INSTI, PI and NNRTI recipients was 22.3 (95% CI 13.4–33), 30.1 (95% CI 25–36) and 19.9 (95% CI 16–22.3) weeks, respectively. There were no significant differences in time to viral rebound or change in CD4 cell counts.

Conclusions

Patients with high VLs initiated on NNRTIs were more likely to achieve VS by 6 months on ART compared to INSTI and PI recipients.