bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sodium‐glucose co‐transporter‐2 inhibitors and major adverse limb events: A trial‐level meta‐analysis including 51 713 individuals
Authors: Huang Chen‐Yu , Lee Jen‐Kuang 
Published: August 2020

AbstractAimTo analyse large‐scale cardiovascular outcome trials of sodium‐glucose co‐transporter‐2 (SGLT‐2) inhibitors to evaluate whether there are safety concerns with respect to major adverse limb events overall or among various high‐risk subgroups of patients.MethodsWe performed a quantitative meta‐analysis of randomized, placebo‐controlled, cardiovascular outcome trials of SGLT‐2 inhibitors in patients with type 2 diabetes. We searched the PubMed, Embase and Cochrane databases for trials published up until 30 June 2020. The efficacy outcomes analysed included amputations and were stratified by several subgroup variables, including age, duration of diabetes, glucose control, renal function, established peripheral artery disease and diabetes microvascular complications. This review was registered before completing the analysis.ResultsAmong 383 records identified, six studies assessing the following three SGLT‐2 inhibitors met our inclusion criteria: empagliflozin (EMPA‐REG OUTCOME study), canagliflozin (CANVAS Program and CREDENCE study), dapagliflozin (DECLARE‐TIMI 58 and DAPA‐HF trials) and ertugliflozin (VERTIS CV study). Of a total of 51 713 participants, 858 required amputation operations. The event rates of amputation were 2.0% (535/26 778) and 1.3% (323/24 927) in the SGLT‐2 inhibitor and control groups, respectively. The random effects model revealed that SGLT‐2 inhibitors were not significantly associated with an increased risk of amputation with substantial heterogeneity (pooled risk ratio, 1.24; 95% confidence interval, 0.96 to 1.60; I2 = 67.5%). This neutral effect of SGLT‐2 inhibitors was also consistent across different levels of subgroups, including subgroups with or without established peripheral artery disease (PAD).ConclusionsSGLT‐2 inhibitors are not associated with increased risks of amputation operations even among various high‐risk subgroups, including patients with PAD. The amputation events primarily arise from critical limb ischaemia and infection instead of acute limb ischaemia. A multi‐centre study focused on major adverse limb events with a longer follow‐up is needed to confirm these results and provide guidelines for clinical practice.
Cardiovascular outcomes trials with glucagon‐like peptide‐1 receptor agonists: A comparison of study designs, populations and results
Authors: Pantalone Kevin M. , Munir Kashif , Hasenour Clinton M. , Atisso Charles M. , Varnado Oralee J. , Maldonado Juan M. , Konig Manige 
Published: August 2020

AbstractDespite treatment advances leading to improved outcomes over the past 2 decades, cardiovascular (CV) disease (CVD) remains the leading cause of morbidity and mortality in people with diabetes. People with type 2 diabetes (T2D) have a 2‐ to 4‐fold increased risk of CVD and CV death. Individuals with T2D have not seen the same improvements in CV morbidity and mortality as those without T2D. Given this, it is important to understand the CV impact of drugs used to treat T2D. In patients with T2D, glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) have shown a reduction in HbA1c and body weight regardless of their differences in chemical structure and pharmacokinetic variables. Glycaemic efficacy, accompanied by the potential for weight reduction and a low risk of hypoglycaemia, has moved GLP‐1 RAs to the first treatment of choice following metformin monotherapy in the latest American Diabetes Association treatment guidelines. Additionally, all GLP‐1 RAs have shown CV safety and several have proven CV benefit. GLP‐1 RAs have been evaluated in cardiovascular outcomes trials (CVOTs) of varying sizes, designs and patient populations with differing reported effects on CV outcomes. The purpose of this article is to review the completed GLP‐1 RA CVOTs with special attention to how their design, size, patient populations and conduct may influence the interpretation of results.
Measuring vergence and fixation disparity in 3D space
Authors: Duchesne Jean , Coubard Olivier A. 
Published: August 2020

AbstractAs the eyes continuously move in 3D space, they rarely converge at the exact depth of the plane even when fixating a 2D image or computer screen. Rather, the lines of gaze measured by eye movement recordings show some misalignment so‐called fixation disparity. Fixation disparity occurs in front of or behind the plane, and the eyes may also be lagged vertically. For those reasons, vision research requires mathematical tools to calculate where exactly the lines of gaze cross the stimulus plane. Seminal research on vergence eye movements targeting stimuli lying on isovergence curves has been content with simple computation of the difference between the two eye rotation angles. Recently, the need of new calculations has emerged with the increasing use of eye‐trackers providing the eye coordinates on a computer screen. Previous studies have made this attempt but with restrictions. We introduce here a complete calculation of fixation disparity in 3D space allowing vision researchers to study the precision of gaze regardless of the stimulus location in 3D space and of whether the eyes lag horizontally and/or vertically.
A parietal region processing numerosity of observed actions: An FMRI study
Authors: Sawamura Hiromasa , Urgen Burcu A. , Corbo Daniele , Orban Guy A. 
Published: August 2020

AbstractWhen observing others' behavior, it is important to perceive not only the identity of the observed actions (OAs), but also the number of times they were performed. Given the mounting evidence implicating posterior parietal cortex in action observation, and in particular that of manipulative actions, the aim of this study was to identify the parietal region, if any, that contributes to the processing of observed manipulative action (OMA) numerosity, using the functional magnetic resonance imaging technique. Twenty‐one right‐handed healthy volunteers performed two discrimination tasks while in the scanner, responding to video stimuli in which an actor performed manipulative actions on colored target balls that appeared four times consecutively. The subjects discriminated between two small numerosities of either OMAs (“Action” condition) or colors of balls (“Ball” condition). A significant difference between the “Action” and “Ball” conditions was observed in occipito‐temporal cortex and the putative human anterior intraparietal sulcus (phAIP) area as well as the third topographic map of numerosity‐selective neurons at the post‐central sulcus (NPC3) of the left parietal cortex. A further region of interest analysis of the group‐average data showed that at the single voxel level the latter area, more than any other parietal or occipito‐temporal numerosity map, favored numerosity of OAs. These results suggest that phAIP processes the identity of OMAs, while neighboring NPC3 likely processes the numerosity of the identified OAs.
Identification of putative phenotype‐modifying genetic factors associated with phenotypic diversity in Brooke‐Spiegler syndrome
Authors: Pap Éva Melinda , Farkas Katalin , Széll Márta , Németh Gábor , Rajan Neil , Nagy Nikoletta 
Published: August 2020

AbstractBrooke‐Spiegler syndrome (BSS, OMIM 605041) is a rare monogenic skin disease characterized by the development of skin appendage tumors caused by mutations in the cylindromatosis gene. We recently investigated a Hungarian and an Anglo‐Saxon pedigrees affected by Brooke‐Spiegler syndrome. Despite carrying the same disease‐causing mutation (c.2806C>T, p.Arg936X) of the cylindromatosis (CYLD) gene, the affected family members of the two pedigrees exhibit striking differences in their phenotypes. To identify phenotype‐modifying genetic factors, whole exome sequencing was performed and the data from the Hungarian and Anglo‐Saxon BSS patients were compared. Three putative phenotype‐modifying genetic variants were identified: the rs1053023 SNP of the signal transducer and activator of transcription 3 (STAT3) gene, the rs1131877 SNP of the tumor necrosis factor receptor‐associated factor 3 (TRAF3) gene and the rs202122812 SNP of the neighbour of BRCA1 gene 1 (NBR1) gene. Our study contributes to the accumulating evidence for the clinical importance of phenotype‐modifying genetic factors, which are potentially important for the elucidation of disease prognosis.
Season‐long, mixed stocking of a cool‐temperate pasture
Authors: Mata‐Padrino Domingo J. , Pena‐Yewtukhiw Eugenia M. , Belesky David P. , Bryan William B. , Bowdridge Scott A. 
Published: August 2020

AbstractMixed‐species grazing offers a means to diversify livestock production systems for cool‐temperate regions typified by the Appalachian plateau of the USA. Our objective was to determine how mixed grazing influenced herbage and animal production, and sward botanical composition of three grazing systems including cattle and sheep. Three replicated systems were as follows: (A) cattle only with winter grazing; (B) cattle and sheep with winter grazing; and (C) cattle and sheep without winter grazing. Herbage mass and growth rate differed by grazing period; system C had the lowest growth rate and showed an interaction of system and grazing period. The proportion of grass in the sward differed by period, and the legume component was influenced by an interaction of system and period. Forbs and dead were influenced by period and sampling location. Herbage crude protein was not influenced by treatment. Herbage fiber components and lignin were consistently higher during the second grazing period. Steers performed similarly in all systems, but total gains varied with year. Lambs in the system without a winter grazing component were heavier than lambs in the system with a winter grazing component. Live weight gains were modest. Lamb fecal egg count was higher in the system with a winter grazing component; however, the fecal egg count per gram was relatively low throughout the experiment. Animal productivity differed with year and tended to be slightly greater for the system without a winter grazing component. Our findings suggest that livestock production systems that included mixed‐species grazing and extended‐season grazing practices contributed to desirable changes in botanical composition and improved herbage productivity patterns, especially in years with ample precipitation. The practices could be used to drive pasture composition by modifying relative abundance of various plant functional groups.
Antibiotic allergy labels and optimal antimicrobial stewardship
Authors: Chakravorty Arindam , Binder Elene , Rawlins Matthew , Trevenen Michelle , Ingram Paul R. , McKeogh Anna , Murray Kevin , Dyer John , Lucas Michaela 
Published: August 2020

AbstractBackgroundAlthough common, antimicrobial allergy labels (AAL) rarely reflect immunologically‐mediated hypersensitivity and can lead to poorer outcomes from alternative antimicrobial agents. Antimicrobial stewardship programs are ideally placed to assess AAL early as a means of improving antimicrobial use.AimsTo quantify the prevalence of AAL in patients referred for antimicrobial stewardship review and assess their impact on antibiotic prescribing, patient mortality, hospital length of stay, readmission and rates of multidrug‐resistant infections.MethodsWe conducted a retrospective analysis of adult patients referred for inpatient antimicrobial prospective audit and feedback rounds (PAFR) through an electronic referral system (eReferrals) over a 12‐month period in 2015. Outcome data were collected for a period of 36 months following the initial review.ResultsOf the 639 patient records reviewed, 630 met inclusion criteria; 103 (16%) had an AAL, of which 82 (13%) had reported allergies to β‐lactam antibiotics. Those with AAL were significantly less likely to be receiving guideline‐recommended antimicrobial therapy (50% vs 64%, P = 0.0311); however, there were no significant difference in mortality, hospital length of stay, readmission or increased incidence of multidrug‐resistant infections.ConclusionsOur cohort demonstrated that AAL was associated with reduced adherence to antibiotic guidelines. The lack of association with adverse outcomes may reflect limitations within the study including retrospective cohort study numbers and observational nature, further skewed by high rates of poor documentation. A clear opportunity exists for antimicrobial stewardship programs to incorporate allergy assessment, de‐labelling, challenge and referral into these rounds.
Palliative care physicians' preparation and planning for the implementation of the Voluntary Assisted Dying Act in Victoria
Authors: Philip Jennifer , Holmes Alex , Benson Melanie , Boughey Mark , Yoong Jaclyn , Clinch Alexandra , Moran Juli 
Published: August 2020

AbstractBackgroundIn November 2017, the Victorian Voluntary Assisted Dying (VAD) Act was passed enabling people with a progressive terminal illness to end their life voluntarily. Heated debate abounded including, to some extent within palliative care, which was also challenged with developing processes around the legislation enactment.AimIn response, the lead author convened a series of meetings of palliative care physicians to: (i) share ideas about preparations being undertaken within services; and (ii) re‐establish professional cohesion following the divide that the legislation had presented.MethodsA series of three closed meetings were held between the legislation passage and its implementation, with all Victorian palliative care physicians invited to attend. Meetings were facilitated by an experienced psychiatrist from outside the field.ResultsThese meetings proved very valuable as physicians collectively sought to define and respond to challenges, simultaneously reflecting on the personal and professional implications for individuals and the field. Key areas raised including gauging institutional ‘readiness’ for the legislation through staff surveys; the educational role of palliative care staff of the legislation implications; communication skills training; the role (if any) of palliative care in the processes of VAD; and the perceptions of palliative care itself in health services and the community. It was during the processes of discussing challenges and sharing solutions that the attendees appeared to reaffirm their professional interconnections.ConclusionA description of the key elements of these discussions may be useful to others who may yet face similar circumstances with the introduction of VAD legislation.
Effectiveness of a couple‐based psychosocial intervention on patients with prostate cancer and their partners: A quasi‐experimental study
Authors: Chien Ching‐Hui , Chung Hsiao‐Jen , Liu Kuan‐Lin , Pang See‐Tong , Wu Chun‐Te , Chang Ying‐Hsu , Huang Xuan‐Yi , Chang Yen‐Hwa , Lin Tzu‐Ping , Lin Wei‐Yu , Chuang Cheng‐Keng 
Published: August 2020

AbstractAimsTo understand the effectiveness of a couple‐based psychosocial information package (PIP) and multimedia psychosocial intervention (MPI) on patients with prostate cancer and their partners.DesignA random assignment and quasi‐experimental design were used.MethodsFrom August 2015–March 2018, 103 newly diagnosed patients with prostate cancer and their partners were divided into a control group (CG) (N = 50), PIP group (N = 25) and MPI group (N = 28). The CG received usual care, the PIP group received information manuals and telephone counselling for 6‐week and the MPI group received multimedia films and manuals and professional support for 6 weeks. The three groups were posttested 6, 10, 18 and 24 weeks after the pre‐test. The outcome measurements included disease appraisals, emotion status, relationship satisfaction, health‐related quality of life (HRQOL) and satisfaction with MPI.Results/FindingsPartners in the MPI and PIP groups experienced significant improvements in positive and negative affect or mental HRQOL as compared with the CG. The effectiveness of MPI and PIP on negative affect, mental HRQOL, however, were not statistically significant in patients with prostate cancer. Nevertheless, patients were satisfied with the MPI.ConclusionNurses can provide different types of interventions for partners, depending on personal preferences and available resources.IMPACTThere is a lack of studies that focus on the effectiveness of couple‐based psychosocial intervention on both the patients with prostate cancer and their partners in Asia. Partners in the multimedia psychosocial intervention group and psychosocial information package group experienced improvements in positive affect, negative affect or health‐related quality of life as compared with the control group. Patients in both intervention groups experienced similar negative affect and health‐related quality of life as compared with the control group. The couple‐based psychosocial interventions can be provided by nurses based on partners’ preferences and available resources.
Inhibition of PTEN activity promotes IB4‐positive sensory neuronal axon growth
Authors: Zhou Li‐Yu , Han Feng , Qi Shi‐Bin , Ma Jin‐Jin , Ma Yan‐Xia , Xie Ji‐Le , Zhang Hong‐Cheng , Fu Xin‐Ya , Chen Jian‐Quan , Li Bin , Yang Hui‐Lin , Zhou Feng , Saijilafu  
Published: August 2020

AbstractTraumatic nerve injuries have become a common clinical problem, and axon regeneration is a critical process in the successful functional recovery of the injured nervous system. In this study, we found that peripheral axotomy reduces PTEN expression in adult sensory neurons; however, it did not alter the expression level of PTEN in IB4‐positive sensory neurons. Additionally, our results indicate that the artificial inhibition of PTEN markedly promotes adult sensory axon regeneration, including IB4‐positive neuronal axon growth. Thus, our results provide strong evidence that PTEN is a prominent repressor of adult sensory axon regeneration, especially in IB4‐positive neurons.
Diagnostic utility of corneal confocal microscopy in type 2 diabetic peripheral neuropathy
Authors: Wang Meijian , Zhang Cong , Zuo Anju , Li Lili , Chen Li , Hou Xinguo 
Published: August 2020

AbstractAims/IntroductionThe early pathological changes of diabetic peripheral neuropathy (DPN) are mainly small nerve fiber injuries. Corneal confocal microscopy (CCM) is an easy, rapid, non‐invasive and repeatable technique to detect the damage of small nerve fibers. The purpose of this study was to explore the application of CCM in DPN and other chronic complications of type 2 diabetes mellitus.Materials and MethodsA total of 220 individuals (48 normal healthy control participants and 172 patients with type 2 diabetes mellitus) were included in the study. All participants were assessed and scored for neurological symptoms and neurological deficits, quantitative sensory test, neuroelectrophysiological test, and CCM.ResultsCorneal nerve fiber density, corneal nerve fiber length and corneal nerve branch density were significantly reduced in patients with type 2 diabetes mellitus compared with normal healthy control subjects (P < 0.001, P < 0.001 and P < 0.001, respectively). In the DPN group, corneal nerve fiber density, corneal nerve branch density and corneal nerve fiber length were significantly lower than for patients without DPN (P < 0.001, P < 0.001 and P < 0.001, respectively). Receiver operating characteristic analysis showed that the optimal cut‐off values were 24.68, 39 and 15.315, respectively, in which corneal nerve fiber density and corneal nerve fiber length had moderate sensitivity and specificity.ConclusionThis study provides more support for the clinical use of CCM to diagnose type 2 diabetes mellitus‐related complications, especially DPN.
Undernutrition is associated with change in severe dental caries
Authors: Shen Anqi , Bernabé Eduardo , Sabbah Wael 
Published: August 2020

AbstractObjectivesTo examine the association of baseline prevalence of thinness or stunting and the incidence of dental caries among preschool children in Liaoning Province, China.MethodsChildren were recruited from 15 kindergartens in Liaoning Province. A total of 772 children were assessed at baseline and follow‐up. The mean age of children at baseline was 50.82 months, and the median follow‐up time was 10.12 months. Anthropometric measurement, dental caries, and questionnaire were assessed overtime, whereas only baseline questionnaire was used in the data analysis. z‐Score for body mass index (BMI)‐for‐age, weight‐for‐age, and height‐for‐age were calculated using World Health Organisation (WHO) Child Growth Standards. Dental caries was assessed according to the fifth WHO Basic Methods for Oral Health Surveys. The presence of pulpal involvement, ulceration, fistula, and abscess (pufa) were used to indicate severe dental caries in deciduous teeth. A structured questionnaire mainly based on the fifth WHO Oral Health Surveys was used to collect sociodemographic and behavior data. Logistic regression was constructed to assess the association between change in severe dental caries and prevalence of thinness and stunting.ResultsThere was a positive association between prevalence of stunting and incidence of severe caries in the fully adjusted model [odds ratios 2.88; 95 percent confidence interval (CI): 1.01, 8.27]. Prevalence of thinness showed insignificant positive association with incidence of severe caries.ConclusionsWhile undernutrition indicated by stunting appeared to be a risk factor for severe dental caries, it could also be a marker for other determinants of progress of dental caries including socioeconomic factors and lack of use of dental services.
Canine orosomucoid (alpha‐1 acid glycoprotein) variants and their influence on drug plasma protein binding
Authors: Costa Ana P. , Court Michael H. , Villarino Nicolas F. , Burke Neal S. , Mealey Katrina L. 
Published: August 2020

AbstractOrosomucoid polymorphisms influence plasma drug binding in humans; however, canine variants and their effect on drug plasma protein binding have not yet been reported. In this study, the orosomucoid gene (ORM1) was sequenced in 100 dogs to identify the most common variant and its allele frequency determined in 1,464 dogs (from 64 breeds and mixed‐breed dogs). Plasma protein binding extent of amitriptyline, indinavir, verapamil, and lidocaine were evaluated by equilibrium dialysis using plasma from ORM1 genotyped dogs (n = 12). Free and total drug plasma concentrations were quantified by liquid chromatography–mass spectrometry. From the five polymorphisms identified in canine ORM1, two were nonsynonymous. The most common was c.70G>A (p.Ala24Thr) with an allele frequency of 11.2% (n = 1464). Variant allele frequencies varied by breed, reaching 74% in Shetland Sheepdogs (n = 21). Free drug fractions did not differ significantly (p > .05; Mann‐Whitney U) between plasma collected from dogs with c.70AA (n = 4) and those with c.70GG (n = 8) genotypes. While c.70G>A did not affect the extent of plasma protein binding in our study, the potential biological and pharmacological implication of this newly discovered ORM1 variant in dogs should be further investigated.