bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of type 2 diabetes mellitus on efficacy and safety of therapeutic apheresis for severe hypertriglyceridemia
Authors: Bagir Gulay Simsek , Bakiner Okan Sefa , Haydardedeoglu Filiz Eksi , Araz Filiz , Ertorer Melek Eda , Kozanoglu İlknur 
Published: October 2020

AbstractThe efficacy and safety of triglyceride (TG) apheresis in patients with type 2 diabetes mellitus (DM) is unclear. Diabetic complications may predispose patients to adverse events (AEs) associated with the apheresis procedure, and diabetic dyslipidemia may negatively affect the efficacy of therapeutic apheresis (TA). We investigated the effect of DM on the efficacy and complications of TA. Patients with severe hypertriglyceridemia who underwent apheresis for treatment or for the prevention of acute pancreatitis were included in this retrospective study. Epidemiological data, lipid parameters, and AEs were recorded before and after each therapeutic session. A total of 166 procedures were performed in 27 patients. Group 1 included 17 patients with type 2 DM, and Group 2 included 10 patients without DM. The mean percentage decrease in TG levels (TG%) was higher in Group 1 (71.9% vs 60.6%, P < .001). The TG% was negatively correlated with the duration of DM in Group 1 (r = −.49, P < .001). The total number of TA sessions was 142 in patients who underwent double filtration plasmapheresis and 24 in patients who underwent therapeutic plasma exchange. We observed 9 (5.4%) mild‐to‐moderate AEs. No intergroup difference was observed in the total number of AEs (P = .06). TA is safe and effective in patients with type 2 DM with severe hypertriglyceridemia.
Disturbed sensory physiology underlies poor balance and disrupts activities of daily living in alcohol use disorder
Authors: Sullivan Edith V. , Zahr Natalie M. , Sassoon Stephanie A. , Pfefferbaum Adolf 
Published: October 2020

AbstractPostural stability is a multi‐factorial skill maintained implicitly. Components of quiet standing can decline with Alcohol Use Disorder (AUD), cause instability, and disrupt activities of daily living (ADL). To examine how stability factors contribute to ADL and balance, 638 force platform testing sessions measured sway paths acquired during quiet standing in 151 AUD and 96 control men and women, age 25–75. Structural equation (seq) path analysis estimated contributions from age, diagnosis, and sensory perception to sway and measures of ADL and roadside ataxia testing. Whether eyes were open or closed, older AUD and control participants had longer sway paths than younger ones; older men had longer sway paths than older women. Although each sensory ability tested declined with aging, different factor constellations influenced ADL, ataxia scores, or sway path. Seq‐path analysis indicated that ADL was strongly dependent on sensory (but not cognitive) systems with sway‐path length accounting for upwards of 25% of variance. Within the AUD group, an index of historically‐experienced withdrawal symptoms was a common predictor of stability regardless of vision condition. The greatest variance measured by the seq‐path model was for predicting platform sway and simple ataxia testing of one‐leg standing even though these measures were affected by different predictor variables: strong predictors of one‐leg standing were diagnosis and age (R2 = 39.6%–43.2%), whereas strong predictors of sway‐path length were sensory factors and withdrawal index (R2 = 22.0%–22.9%). These findings present evidence for appreciating selective factors that contribute to declining postural stability and to liability for compromised quality of life in AUD.
The role of withdrawal in mesocorticolimbic drug cue reactivity in opioid use disorder
Authors: Shi Zhenhao , Jagannathan Kanchana , Padley James H. , Wang An‐Li , Fairchild Victoria P. , O'Brien Charles P. , Childress Anna Rose , Langleben Daniel D. 
Published: October 2020

AbstractOpioid use disorder (OUD) is characterized by heightened cognitive, physiological, and neural responses to opioid‐related cues that are mediated by mesocorticolimbic brain pathways. Craving and withdrawal are key symptoms of addiction that persist during physiological abstinence. The present study evaluated the relationship between the brain response to drug cues in OUD and baseline levels of craving and withdrawal. We used functional magnetic resonance imaging (fMRI) to examine brain responses to opioid‐related pictures and control pictures in 29 OUD patients. Baseline measures of drug use severity, opioid craving, and withdrawal symptoms were assessed prior to cue exposure and correlated with subsequent brain responses to drug cues. Mediation analysis was conducted to test the indirect effect of drug use severity on brain cue reactivity through craving and withdrawal symptoms. We found that baseline drug use severity and opioid withdrawal symptoms, but not craving, were positively associated with the neural response to drug cues in the nucleus accumbens, orbitofrontal cortex, and amygdala. Withdrawal, but not craving, mediated the effect of drug use severity on the nucleus accumbens' response to drug cues. We did not find similar effects for the neural responses to stimuli unrelated to drugs. Our findings emphasize the central role of withdrawal symptoms as the mediator between the clinical severity of OUD and the brain correlates of sensitization to opioid‐related cues. They suggest that in OUD, baseline withdrawal symptoms signal a high vulnerability to drug cues.
Pregnancy‐specific continuous reference intervals for haematology parameters from an Australian dataset: A step toward dynamic continuous reference intervals
Authors: Markus Corey , Flores Cindy , Saxon Ben , Osborn Kym 
Published: October 2020

BackgroundPregnancy is a time of dynamic physiological changes occurring as a continuous spectrum. Smoothed centile curves describe the distribution of measurements as a function of age. There has been no application of centile charts in pregnancy for haematological parameters.AimsTo derive gestational age‐specific centile curves for six haematological parameters and compare these with published reference intervals.Materials and MethodsAn LMS approach was used with haematology results from an obstetric hospital laboratory database. After application of exclusion criteria, smoothed centiles conditional on gestational age were obtained by a two‐step process: (i) finding the best model within four response distributions using Bayesian information criteria, and (ii) selecting the best model among the response distributions based on test‐dataset global deviance.ResultsIn total, 11 255 deliveries were extracted from 10 813 patients. There was little difference between distributions, and Box‐Cox power exponential was selected overall. Red cell parameters showed similar trends: values fell until the second trimester and increased thereafter. Leukocyte and neutrophil counts rapidly increased and plateaued around 15 weeks. Platelets exhibited a gradual fall with advancing gestation.ConclusionsThis is the first study to use an LMS approach to model gestational age‐dependent variations in haematological parameters. Proposed haemoglobin reference intervals were lower than those published but reflect our patient population. Serial monitoring of antenatal patients, as is the standard of care, in conjunction with these centile charts, may highlight trends in red cell changes with advancing gestation, allowing early identification of adverse pregnancy outcomes and evolving anaemia.
Efficacy and safety of breast milk eye drops in infants with eye discharge
Authors: Sugimura Tetsu , Seo Tomoko , Terasaki Nami , Ozaki Yukiko , Rikitake Noriko , Okabe Rumiko , Matsushita Masami 
Published: October 2020

AbstractAimBreast milk (BM) contains various protective components, such as immunoglobulins, lactoferrin, lysozyme, oligosaccharides and immune cell subsets. We evaluated the effectiveness of BM eye drops in infants with eye discharge in a randomised controlled study.MethodsSubjects were breastfed infants aged ≤180 days, with eye discharge. We randomly assigned patients to receive eye drops of BM or sodium azulene sulphonate hydrate 0.02% ophthalmic solution (OS). The patients received drop of BM or OS for 7 days. Improvement score of eye discharge in the groups was compared using a non‐inferiority test.ResultsThe number of patients improved eye discharge was 119/155 (76.8%) and 119/157 (75.8%) in BM and OS groups, respectively. There were no significant differences between groups. The improvement score in eye discharge was 1.76 ± 0.91 in the BM group and 1.71 ± 0.96 in the OS group. The BM group was considered non‐inferior to the OS group.ConclusionsThis study demonstrated that BM is no less effective than OS in infants with eye discharge aged ≤6 months. The results suggested that the use of breast milk as eye drops could be considered as a first‐line treatment for infants aged ≤6 months with eye discharge.
Body mass index trajectories up to preschool age in a multi‐ethnic population; relations with maternal gestational diabetes, BMI and gestational weight gain
Authors: Toftemo Ingun , Jenum Anne Karen , Sletner Line 
Published: October 2020

AbstractAimIndependent effects of gestational diabetes (GDM), maternal prepregnant obesity and gestational weight gain on offspring BMI and obesity are scarcely documented. We examined associations between GDM and children's BMI trajectories from birth to 4‐5 years age, and effects of prepregnant obesity and gestational weight gain not mediated through GDM.MethodsWe included 734 children from a population‐based, multi‐ethnic cohort of women and their offspring followed from early pregnancy. All women were screened for GDM. Using linear mixed models, we explored associations between maternal factors and children's BMI development through seven serial measurements.ResultsAt birth and age 4‐5 years, BMI of children exposed to GDM was similar to those not exposed. However, they had slower BMI growth (B = −0.1 BMI units/month (95% CI: −0.17, −0.04)) during first 6 months, and faster BMI growth from 6 months to 4‐5 years. Maternal prepregnant obesity was associated with higher child BMI at birth, and thereafter persistently higher BMI. High gestational weight gain was associated with faster BMI growth from 6 months to 4‐5 years.ConclusionEffects of maternal GDM, prepregnant obesity, and gestational weight gain on children's BMI and BMI trajectories from birth to preschool age differed in relation to effect size, timing and direction.
GLP‐1 modulates insulin‐induced relaxation response through β‐arrestin2 regulation in diabetic mice aortas
Authors: Taguchi Kumiko , Kaneko Nozomu , Okudaira Kanami , Matsumoto Takayuki , Kobayashi Tsuneo 
Published: October 2020

AbstractAimsDiabetes impairs insulin‐induced endothelium‐dependent relaxation by reducing nitric oxide (NO) production. GLP‐1, an incretin hormone, has been shown to prevent the development of endothelial dysfunction. In this study, we hypothesized that GLP‐1 would improve the impaired insulin‐induced relaxation response in diabetic mice. We also examined the underlying mechanisms.MethodsUsing aortic rings from ob/ob mice, an animal model of obesity and type 2 diabetes, and from lean mice, vascular relaxation responses and protein expressions were evaluated using insulin, GLP‐1, and pathway‐specific inhibitors to elucidate the mechanisms of response. In parallel experiments, β‐arrestin2 siRNA‐transfected aortas were treated with GLP‐1 to evaluate its effects on aortic response pathways.ResultsWhen compared to that of untreated ob/ob aortas, GLP‐1 increased insulin‐induced vasorelaxation and NO production. AMPK inhibition did not alter this vasorelaxation in both GLP‐1‐treated lean and ob/ob aortas, while Akt inhibition reduced vasorelaxation in both groups, and co‐treatment with GLP‐1 and insulin caused Akt/eNOS activation. Additionally, GLP‐1 decreased GRK2 activity and enhanced β‐arrestin2 translocation from the cytosol to membrane in ob/ob aortas. β‐Arrestin2 siRNA decreased insulin‐induced relaxation both in lean aortas and GLP‐1‐treated ob/ob aortas.ConclusionsWe demonstrated that insulin‐induced relaxation is dependent on β‐arrestin2 translocation and Akt activation via GLP‐1‐stimulated GRK2 inactivation in ob/ob aortas. We showed a novel cross‐talk between GLP‐1‐responsive β‐arrestin2 and insulin signalling in diabetic aortas.
Development of a brief psychological intervention for perinatal depression (BIND‐P)
Authors: Ransing Ramdas , Kukreti Prerna , Raghuveer Pracheth , Mahadevaiah Mahesh , Puri Manju , Pemde Harish , Karkal Ravichandra , Patil Suvarna , Nirgude Abhay , Kataria Dinesh , Sagvekar Shraddha , Deshpande Smita N. 
Published: October 2020

AbstractBackgroundLack of recognition in national programs, poor referral system, and non‐availability of trained human resources are the important barriers for the delivery of perinatal depression (PND) services in low‐ and middle‐income countries (LAMICs). To address this there is an urgent need to develop an integrative and non‐specialist‐based stepped care model. As part of its research thrust on target areas of India's National Mental Health Programme (NMHP), the Indian Council of Medical Research funded a research project on the outcome of PND at four sites. In this article, we describe the development of the primary health care worker‐based stepped care model and brief psychological intervention for PND.MethodsA literature review focused on various aspects of PND was conducted to develop a model of care and intervention under NMHP. A panel of national and international experts and stakeholders reviewed the literature, opinions, perspectives, and proposal for different models and interventions, using a consensus method and WHO implementation toolkit.ResultsA consensus was reached to develop an ANM (Auxillary nurse midwife)‐based stepped‐care model consisting of the components of care, training, and referral services for PND. Furthermore, a brief psychological intervention (BIND‐P) was developed, which includes the components of the low‐intensity intervention (eg, exercise, sleep hygiene).ConclusionThe BIND‐P model and intervention provide a practical approach that may facilitate effective identification, treatment, and support women with PND. We are currently evaluating this model across four study sites in India, which may help in the early detection and provision of appropriate and integrative care for PND.
Hospitalization for COVID‐19 in patients treated with selected immunosuppressant and immunomodulating agents, compared to the general population: A Danish cohort study
Authors: Nørgård Bente Mertz , Nielsen Jan , Knudsen Torben , Nielsen Rasmus Gaardskær , Larsen Michael Due , Jølving Line Riis , Kjeldsen Jens 
Published: October 2020

AimsIn the Danish population, we examined whether patients treated with thiopurines, methotrexate, systemic corticosteroids, anti‐tumour necrosis factor (TNF)‐α agents, anti‐interleukin therapeutic agents, selective immunosuppressive agents and cyclosporine/tacrolimus had an increased risk of hospitalization for COVID‐ 19, compared to the background population.MethodsA nationwide cohort study including all people alive in Denmark on 1 March 2020. Exposed patients constituted those exposed to thiopurines (n =5484), methotrexate (n =17 977), systemic corticosteroids (n =55 868), anti‐TNF‐α agents (n =17 857), anti‐interleukin therapeutic agents (n =3744), selective immunosuppressive agents (n =3026) and cyclosporine/tacrolimus (n =1143) in a period of 12 months prior to 1 March 2020 (estimated time of outbreak in Denmark). We estimated the adjusted risk of hospitalization for COVID‐19 for patients treated with the above‐mentioned categories of medications, compared to the rest of the population.ResultsThe adjusted odds ratios of hospitalization in patients treated with corticosteroids and cyclosporine/tacrolimus were 1.64 (95% confidence interval [CI] 1.35 to 2.00) and 4.75 (95% CI 1.96 to 11.49), respectively. The risks of hospitalization in patients treated with thiopurines, methotrexate, and anti‐TNF‐α agents, were 1.93 (95% CI 0.91 to 4.08), 0.74 (95% CI 0.43 to 1.28), 1.00 (95% CI 0.52 to 1.94), respectively. The number of outcomes in patients treated with anti‐interleukin therapeutic agents and selective immunosuppressive agents was too small for analysis.ConclusionPatients treated with systemic corticosteroids and cyclosporine/tacrolimus had a significantly increased risk of being hospitalized for COVID‐19. Our study does not uncover whether the increased risk is related to the drug itself, the underlying condition for which the patient is treated or other factors.
Alterations in plasma kynurenine pathway metabolites in children and adolescents with bipolar disorder and unaffected offspring of bipolar parents: A preliminary study
Authors: Benevenuto Deborah , Saxena Kirti , Fries Gabriel R. , Valvassori Samira S. , Kahlon Ramandeep , Saxena Johanna , Kurian Sherin , Zeni Cristian P. , Kazimi Iram F. , Scaini Giselli , Soares Jair C. , Quevedo João 
Published: October 2020

AbstractBackgroundThere has been growing scientific evidence in recent years that bipolar disorder (BD) is associated with alterations in the kynurenine (KYN) pathway. However, many of these studies have been limited by their focus on adults. Thus, this preliminary study investigated differences in the peripheral levels of KYN metabolites in children and adolescents with BD, unaffected offspring of parents with BD, and healthy controls (HCs).MethodsPlasma samples were collected from 49 youths with BD, 19 bipolar offspring, and 31 HCs. Tryptophan (TRP), KYN, and kynurenic acid (KYNA) were separated using electrospray ionization.ResultsOne‐Way ANCOVA after controlling for age, gender, race, BMI‐for‐age, and smoking status showed that BD had lower levels of KYN, while unaffected high‐risk offspring subjects had lower levels of TRP, KYN, and KYNA when compared to HCs. Moreover, we found that KYN, KYN/TRP, and KYNA/KYN levels predicted the severity of depressive symptoms, while the YMRS score was not associated with any metabolite.ConclusionsIn summary, this preliminary study has shown that KYN metabolites are decreased in both affected and unaffected subjects, strengthening the idea that the KYN pathway might underlie the familial risk of BD shown by high‐risk offspring individuals. However, longitudinal studies are needed to examine whether the alterations observed in this study represent early markers of risk for later developing BD.
Molecular regulatory mechanisms underlying the adaptability of polyploid plants
Authors: Scarrow Margaret , Wang Yiling , Sun Genlou 
Published: October 2020

ABSTRACTPolyploidization influences the genetic composition and gene expression of an organism. This multi‐level genetic change allows the formation of new regulatory pathways leading to increased adaptability. Although both forms of polyploidization provide advantages, autopolyploids were long thought to have little impact on plant divergence compared to allopolyploids due to their formation through genome duplication only, rather than in combination with hybridization. Recent advances have begun to clarify the molecular regulatory mechanisms such as microRNAs, alternative splicing, RNA‐binding proteins, histone modifications, chromatin remodelling, DNA methylation, and N6‐methyladenosine (m6A) RNA methylation underlying the evolutionary success of polyploids. Such research is expanding our understanding of the evolutionary adaptability of polyploids and the regulatory pathways that allow adaptive plasticity in a variety of plant species. Herein we review the roles of individual molecular regulatory mechanisms and their potential synergistic pathways underlying plant evolution and adaptation. Notably, increasing interest in m6A methylation has provided a new component in potential mechanistic coordination that is still predominantly unexplored. Future research should attempt to identify and functionally characterize the evolutionary impact of both individual and synergistic pathways in polyploid plant species.
Radiographic features and poor prognostic factors of interstitial lung disease with nivolumab for non–small cell lung cancer
Authors: Saito Yoshinobu , Sasaki Shinichi , Oikado Katsunori , Tominaga Junya , Sata Masafumi , Sakai Fumikazu , Kato Terufumi , Iwasawa Tae , Kenmotsu Hirotsugu , Kusumoto Masahiko , Baba Tomohisa , Endo Masahiro , Fujiwara Yutaka , Sugiura Hiroaki , Yanagawa Noriyo , Ito Yoshihiko , Sakamoto Takahiko , Ohe Yuichiro , Kuwano Kazuyoshi 
Published: October 2020

AbstractNivolumab can cause interstitial lung disease (ILD), which may be fatal; however, mortality risk factors have not been identified. This postmarketing study evaluated the poor prognostic factors of ILD in nivolumab‐treated patients with non–small cell lung cancer (NSCLC) in Japan. Clinical and chest imaging findings for each ILD case were assessed by an expert central review committee, and prognosis was evaluated by radiographic findings, including the presence/absence of peritumoral ground‐glass opacity (peritumoral‐GGO). Poor prognostic factors were identified by univariate and multivariate Cox regression analysis. Of the 238 patients with nivolumab‐induced ILD, 37 died. The main radiographic patterns of ILD were cryptogenic organizing pneumonia/chronic eosinophilic pneumonia–like (53.4%), faint infiltration pattern/acute hypersensitivity pneumonia–like (20.2%), diffuse alveolar damage (DAD)‐like (10.9%), and nonspecific interstitial pneumonia–like (6.3%). The main poor prognostic factors identified were DAD‐like pattern (highest hazard ratio: 10.72), ≤60 days from the start of nivolumab treatment to the onset of ILD, pleural effusion before treatment, lesion distribution contralateral or bilateral to the tumor, and abnormal change in C‐reactive protein (CRP) levels. Of the 37 deaths due to ILD, 17 had DAD‐like radiographic pattern, three had peritumoral‐GGO, and five had a change in radiographic pattern from non‐DAD at the onset to DAD‐like. Patients with NSCLC who develop ILD during nivolumab treatment should be managed carefully if they have poor prognostic factors such as DAD‐like radiographic pattern, onset of ILD ≤60 days from nivolumab initiation, pleural effusion before nivolumab treatment, lesion distribution contralateral or bilateral to the tumor, and abnormal changes in CRP levels.