bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of drugs acting on adrenergic receptors in the treatment for tobacco or alcohol use disorders: systematic review and meta‐analysis
Authors: Vanderkam Paul , Solinas Marcello , Ingrand Isabelle , Doux Nicolas , Ebrahimighavam Soghra , Jaafari Nematollah , Lafay‐Chebassier Claire 
Published: September 2020

AbstractAimTo assess the efficacy of drugs directly acting on alpha‐ and beta‐adrenergic receptors in the treatment of patients suffering from tobacco or alcohol use disorder.MethodsUsing Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines, studies were identified through PUBMED, EMBASE, the Cochrane Central Register of Controlled Trials and clinicaltrial.gov. We selected only randomized controlled trials with adult patients with tobacco or alcohol use disorders according to DSM‐5 criteria. Interventions included any molecule having a direct pharmacological action on alpha‐ or beta‐adrenergic receptors (agonist or antagonist). Comparators were placebo or other validated pharmacotherapies. The duration of the intervention was a minimum of 1 month, with 3 months of follow‐up. Measurements included smoking cessation for tobacco; for alcohol, we selected abstinence, alcohol consumption (drinks per day or week) and heavy drinking days (HDD). Ten studies with tobacco and six with alcohol use disorder were included in the qualitative synthesis and fifteen studies in the quantitative analysis.ResultsWe found that clonidine, an alpha‐2 agonist, significantly increased smoking abstinence [relative risk = 1.39 with a 95% confidence interval (CI) = 1.04, 1.84]. Beta‐blockers had no significant effect on smoking abstinence. The alpha‐1 antagonists prazosin and doxazosin decreased alcohol consumption [SMD = −0.32 (−0.56, −0.07)] but had no effect on abstinence or HDD.ConclusionsThe noradrenaline system may represent a promising mechanism to target in tobacco and alcohol use disorders.
Venous hepatic segmentation in dogs (Canis lupus familiaris—L. 1758)
Authors: de Morais‐Pinto Luciano , Pereira Vítor Pires , de Souza Vencato Marina , de Oliveira Alzido , Miglino Maria Angelica 
Published: September 2020

AbstractThe external shape of the liver is varied and determines specific vascular arrangements. This morphological relationship is important to establish hepatic segmentation in different species submitted to surgeries that aim to preserve a larger area of liver parenchyma. After observing 60 livers injected with Neoprene Latex and three plastic moulds obtained by corrosion, eight hepatic venous segments were identified, drained by six hepatic veins agrouped into segmental veins, which drained one sector (segments I, VI, VII and VIII) and intersegmental veins, which drained more than one sector (segments II/III and IV/V). They were described as follows: left intersegmental vein, formed by a segmental vein from the papillary process (segment I), two to three lateral left segmental veins that drained the segment II, and one to five left paramedian segmental veins that drained the segment III; sagittal intersegmental vein, formed by the confluence between segmental vein of the quadrate lobe (segment IV) and the medial right paramedian segmental vein, which derived from the segment V; lateral right paramedian vein drained the dorsocranial sector of the segment VI; the lateral right segmental vein, formed by one to four vessels that drained segment VII, and the segmental vein of the caudate process, which drained the segment VIII. Understanding the number and disposition of the hepatic veins in lobate livers is essential to reduce bleeding risks in surgeries. The nomenclature based on segmentation analogy of non‐lobate liver could be less confusing and, therefore, be more useful in the surgical approaches of lobate livers.
Circulating CD14+HLA‐DRlo/− monocytic cells as a biomarker for epithelial ovarian cancer progression
Authors: Stenzel Ashley E. , Abrams Scott I. , Joseph Janine M. , Goode Ellen L. , Tario Joseph D. , Wallace Paul K. , Kaur Divjot , Adamson Anna‐Kay , Buas Matthew F. , Lugade Amit A. , Laslavic Angela , Taylor Sarah E. , Orr Brian , Edwards Robert P. , Elishaev Esther , Odunsi Kunle , Mongiovi Jennifer M. , Etter John Lewis , Winham Stacey J. , Kaufmann Scott H. , Modugno Francesmary , Moysich Kirsten B. 
Published: September 2020

AbstractProblemPrevious studies identified circulating CD14+HLA‐DRlo/− monocytic cells as an immune suppressive subset in solid malignancies, such as prostate, renal cell carcinoma, and pancreatic cancer. Such monocytic cells have been implicated not only in tumour progression but also as a potential barrier for immunotherapy. This study examined the relationship between the frequency of circulating monocytic cells and epithelial ovarian cancer (EOC) progression pre‐ and post‐frontline chemotherapy, defined by disease stage, which is a leading prognostic factor for this malignancy.Method of studyIncident cases of 236 women with EOC were recruited and comprehensive flow cytometry was utilized to assess the frequency of peripheral blood CD33+CD11b+HLA‐DR−/lowCD14+CD15− monocytic cells, henceforth termed CD14+HLA‐DRlo/− monocytic cells, prior to and after completion of frontline chemotherapy. Multivariable odds ratios (OR) were used to estimate the association between CD14+HLA‐DRlo/− monocytic cell percentages and disease stage. Wilcoxon signed‐rank tests evaluated changes in these monocytic cell levels pre‐ and post‐chemotherapy in a patient subset (n = 70).ResultsPatients with elevated frequencies of circulating CD14+HLA‐DRlo/− monocytic cells at diagnosis were at 3.33‐fold greater odds of having advanced stage (III/IV) EOC (CI: 1.04‐10.64), with a significant trend in increasing CD14+HLA‐DRlo/−monocytic cell levels (P = .04). There was a 2.02% median decrease of these monocytic cells post‐chemotherapy among a subset of patients with advanced stage disease (P < .0001).ConclusionThese findings support the potential clinical relevance of CD14+HLA‐DRlo/−monocytic cells in EOC for prognosis and may indicate a non‐invasive biomarker to measure disease progression.
Assessment of nest building and social interaction behavior in mice exposed to acute social defeat stress using a three‐dimensional depth camera
Authors: Otabi Hikari , Okayama Tsuyoshi , Toyoda Atsushi 
Published: September 2020

AbstractNest building is an instinctive behavior toward protection from predators, body temperature regulation, and courtship. Previously, we discovered that acute and chronic social defeat stress suppresses the onset of nest‐building behavior in male mice (C57BL/6J). Here, we analyzed nest building and other behavioral deficits induced by acute social defeat stress (ASDS). We utilized a customized cage and specifically developed observational programs for nest building, social avoidance, and other behaviors using an infrared depth camera to acquire three‐dimensional (3D) data of animal behavior (Negura system). We determined the volume of nesting materials from these 3D depth images. Mice exposed to ASDS showed increased spontaneous activities, decreased rearing, and delayed nest building; however, nest‐building activity was gradually recovered during the dark period of the 24 hr observation interval. At the endpoint following 24 hr, the ASDS and control groups showed no differences in nest volumes. Furthermore, we observed the time courses of both nest building and social avoidance behaviors and their relationship using the Negura system. Our data demonstrated a weak positive correlation between nest‐building delay and social avoidance in ASDS mice. The Negura system can observe various behaviors that reflect the effects of social defeat stress.
Effects of ear corn silage supplementation on milk production and milk fatty acid profiles in grazing dairy farms
Authors: Mitani Tomohiro , Asakuma Sadaki , Shinoda Yuka , Ueda Yasuko , Aoki Yasuhiro , Oshita Tomoko 
Published: September 2020

AbstractThis study investigated the effects of substituting ear corn silage (ECS) for commercial formula feed on milk production and milk fatty acid profiles in grazing dairy farms during the summer season. A field survey was conducted on five grazing dairy farms in every summer month of 2017, 2018, and 2019. Three of the five farms substituted fresh ECS for the commercial formula feed at a ratio of 2:1 from July of each year (ECS farms). Other farms maintained the same feeding management as before (non‐ECS farms). An interview survey was conducted on each farm to calculate feed intake and milk yield per cow. Feed and milk samples were collected in each survey. Milk compositions and milk fatty acid profiles were determined. The substitution of ECS for the commercial formula feed did not affect milk yield or milk composition, but ECS farms maintained low levels of milk urea compared with non‐ECS farms (p < .01). The ECS substitution also influenced some of the milk fatty acid proportions; C16:0 and C16:1 increased, and trans‐11 C18:1, cis‐9,trans‐11 C18:2, and the sum of polyunsaturated fatty acids decreased, while these fatty acid proportions were maintained in non‐ECS farms throughout the summer season (p < .05).
Impact of the Goal‐directed Medication Review Electronic Decision Support System on Drug Burden Index: A cluster‐randomised clinical trial in primary care
Authors: Kouladjian O'Donnell Lisa , Gnjidic Danijela , Sawan Mouna , Reeve Emily , Kelly Patrick J. , Chen Timothy F. , Bell J. Simon , Hilmer Sarah N. 
Published: September 2020

AimsThe Goal‐directed Medication Review Electronic Decision Support System (G‐MEDSS) assesses and reports a patient's goals, attitudes to deprescribing and Drug Burden Index (DBI) score, a measure of cumulative exposure to anticholinergic and sedative medications. This study evaluated the effect of implementing G‐MEDSS in home medicines reviews (HMRs) on DBI exposure and clinical outcomes.MethodsA cluster‐randomised clinical trial was performed across Australia. Accredited clinical pharmacists were randomised into intervention (G‐MEDSS with usual care HMR) or comparison groups (usual care HMR alone). Patients were recruited by pharmacists from those routinely referred by general practitioners for HMR. The primary outcome was the proportion of patients with any reduction in DBI at 3‐months follow‐up. Secondary outcomes included change in DBI continuous score at 3‐months, HMR recommendations to change DBI and clinical outcomes.ResultsThere were 201 patient participants at baseline (n = 88 intervention, n = 113 comparison), with 159 followed‐up at 3‐months (n = 63 intervention, n = 96 comparison). The proportion of patients with a reduction in DBI was not significantly different at 3‐months (intervention 17%, comparison 11%; adjusted odds ratio 1.44, 95% confidence interval 0.56–3.80). Regarding secondary outcomes, there was no difference in change in DBI score at 3‐months. However, the HMR report made recommendations to reduce DBI for a significantly greater proportion of patients in the intervention than in the comparison group (intervention 37%, comparison 14%; adjusted odds ratio 3.20, 95% confidence interval 1.50–6.90). No changes were observed in clinical outcomes.ConclusionImplementation of G‐MEDSS within HMR did not reduce patients' DBI at 3 months compared with usual care HMR.
Characterization of rapid cycling bipolar patients presenting with major depressive episode within the BRIDGE‐II‐MIX study
Authors: Antonietta Furio Maria , Popovic Dina , Vieta Eduard , Stukalin Yelena , Hagin Michal , Torrent Carla , Azorin Jean‐Michel , Angst Jules , Bowden Charles L. , Mosolov Sergey , Young Allan H. , Perugi Giulio ,   for the BRIDGE‐II‐Mix Study Group
Published: September 2020

AbstractObjectivesThe “Bipolar Disorders: Improving Diagnosis, Guidance, and Education” (BRIDGE‐II‐Mix) study aimed to estimate the frequency of mixed states in patients with a major depressive episode (MDE) according to different definitions and to compare their clinical validity, looking into specific features such as rapid cycling (RC).MethodsPsychiatric symptoms, socio‐demographic, and clinical variables were collected from a sample of 2811 MDE patients, of which 726 (25.8%) were diagnosed with bipolar disorder (BD). The characteristics of bipolar patients with RC (BD‐RC) and without (BD‐NRC) RC were compared.ResultsOf 726 BD patients, 159 (21.9%) met DSM‐5 criteria for RC. BD‐RC group presented a higher number of lifetime depressive episodes (p < 0.001) with shorter duration of depressive episodes, and more psychiatric comorbidities, as well as higher rates of atypical features (p = 0.016) and concomitant (hypo)manic symptoms (irritable mood (p = 0.001); risky behavior (p = 0.005); impulsivity (p = 0.006); and psychomotor agitation (p = 0.029)). Patients with RC had a worse functioning (p = 0.033), more obesity (p = 0.003), and were significantly more likely to be treated with three or more drugs (p = 0.007).ConclusionsImportant clinical differences between bipolar patients with and without a RC include more depressive morbidity, higher incidence of anxiety disorders, addiction, bulimia, and borderline personality disorder, as well as atypical features during depression and symptoms such as irritability, risky behavior, impulsivity, and agitation. RC patients had poorer functioning than patients without RC, more obesity, and had to be treated with more drugs.
Using the “Hidden” genome to improve classification of cancer types
Authors: Chakraborty Saptarshi , Begg Colin B. , Shen Ronglai 
Published: September 2020

AbstractIt is increasingly common clinically for cancer specimens to be examined using techniques that identify somatic mutations. In principle, these mutational profiles can be used to diagnose the tissue of origin, a critical task for the 3% to 5% of tumors that have an unknown primary site. Diagnosis of primary site is also critical for screening tests that employ circulating DNA. However, most mutations observed in any new tumor are very rarely occurring mutations, and indeed the preponderance of these may never have been observed in any previous recorded tumor. To create a viable diagnostic tool we need to harness the information content in this “hidden genome” of variants for which no direct information is available. To accomplish this we propose a multilevel meta‐feature regression to extract the critical information from rare variants in the training data in a way that permits us to also extract diagnostic information from any previously unobserved variants in the new tumor sample. A scalable implementation of the model is obtained by combining a high‐dimensional feature screening approach with a group‐lasso penalized maximum likelihood approach based on an equivalent mixed‐effect representation of the multilevel model. We apply the method to the Cancer Genome Atlas whole‐exome sequencing data set including 3702 tumor samples across seven common cancer sites. Results show that our multilevel approach can harness substantial diagnostic information from the hidden genome.
Optimism, pessimism, and health biomarkers in older couples
Authors: Arbel Reout , Segel‐Karpas Dikla , Chopik William 
Published: September 2020

ObjectiveStudies have demonstrated the importance of optimism in predicting perceived general health. However, the handful of studies focusing on cardiovascular biomarkers show inconsistent effects. Additionally, no study examined whether spousal levels of optimism and pessimism affect an individual’s biological markers of cardiovascular health. Thus, our objectives were to examine whether partners’ optimism and pessimism affect individual biological markers, differentiating between between‐dyad associations and within‐dyad predictive processes.MethodsThree waves of the Health and Retirement Study collected in 2006, 2010, and 2014 were used to test actor and partner effects of optimism and pessimism on C‐reactive protein (CRP) and high‐density lipoprotein. Multilevel longitudinal actor–partner models were used to examine the contribution of a partner’s optimism and pessimism to each biomarker, adjusting for respondent's age, sex, depression, body mass index, daily activity levels, and a summary score of respondent's doctor‐diagnosed chronic conditions.ResultsPartners’ pessimism and optimism levels were moderately associated. Results for within‐person effects were all non‐significant, both within and across waves. Associations at the between‐person level were also non‐significant, with the exception of a positive association between husbands’ pessimism and their own CRP, and husbands’ optimism and their wives’ CRP.ConclusionsResults suggest that optimism and pessimism may not play a pertinent role in within variability of biomarkers of cardiovascular diseases and have a minor role in predicting to between‐person variability of biomarkers of cardiovascular diseases.
Distinct microglial and macrophage distribution patterns in the concentric and lamellar lesions in Baló's disease and neuromyelitis optica spectrum disorders
Authors: Hayashida Shotaro , Masaki Katsuhisa , Suzuki Satoshi O. , Yamasaki Ryo , Watanabe Mitsuru , Koyama Sachiko , Isobe Noriko , Matsushita Takuya , Takahashi Kazuya , Tabira Takeshi , Iwaki Toru , Kira Jun‐ichi 
Published: September 2020

AbstractTMEM119 and purinergic receptor P2Y12 (P2RY12), which are not expressed by recruited peripheral blood macrophages, are proposed to discriminate microglia from macrophages. Therefore, we investigated the distribution patterns of microglia and macrophages in 10 concentric lesions from four autopsied Baló's disease cases and one neuromyelitis optica spectrum disorder (NMOSD) case, using quantitative immunohistochemistry for the markers TMEM119, P2RY12, CD68, CD163 and GLUT5. Three cases with Baló's disease had distal oligodendrogliopathy (DO) showing preferential loss of myelin‐associated glycoprotein and early active demyelination in the outermost demyelinating layer (termed DMY‐MO). In DMY‐MO with DO, TMEM119‐positive activated microglia expressing upregulated GLUT5 but markedly downregulated P2RY12 were significantly increased. These activated microglia expressed inducible nitric oxide synthase. Oligodendrocytes and their precursors showed apoptotic‐like nuclear condensation in DMY‐MO. TMEM119‐negative and CD68/CD163‐positive macrophages were distributed throughout the lesion center of DMY‐MO with DO and these cells demonstrated foamy morphology only in the inner portion but not in the outer portion. In concentric demyelinating lesions from another Baló's case and lamellar demyelinating lesions in an NMOSD case, which had late active demyelination without DO, the densities of TMEM119‐, GLUT5‐ and P2RY12‐positive microglia with ramified morphology were significantly increased in myelinated layers but not in demyelinating layers. In particular, in the NMOSD case, TMEM119‐positive microglia were confined to the outer portion of the myelinated layers. CD68‐positive macrophages with foamy morphology also expressing CD163 accumulated in myelinated as well as in demyelinated layers. These findings suggest that activated microglia expressing TMEM119 and GLUT5, but not P2RY12, are associated with apoptosis of oligodendrocytes in the leading edge of Baló's concentric lesions with DO, whereas TMEM119‐, GLUT5‐ and P2RY12‐positive microglia with ramified morphology are associated with myelin preservation in concentric lesions without DO in Baló's disease and NMOSD. These two types of microglia appear to play distinct roles in the formation of concentric lesions.
Discovery and characterization of ORM‐11372, a novel inhibitor of the sodium‐calcium exchanger with positive inotropic activity
Authors: Otsomaa Leena , Levijoki Jouko , Wohlfahrt Gerd , Chapman Hugh , Koivisto Ari‐Pekka , Syrjänen Kaisa , Koskelainen Tuula , Peltokorpi Saara‐Elisa , Finckenberg Piet , Heikkilä Aira , Abi‐Gerges Najah , Ghetti Andre , Miller Paul E. , Page Guy , Mervaala Eero , Nagy Norbert , Kohajda Zsófia , Jost Norbert , Virág László , Varró András , Papp Julius Gy. 
Published: September 2020

Background and PurposeThe lack of selective sodium–calcium exchanger (NCX) inhibitors has hampered the exploration of physiological and pathophysiological roles of cardiac NCX 1.1. We aimed to discover more potent and selective drug like NCX 1.1 inhibitor.Experimental ApproachA flavan series‐based pharmacophore model was constructed. Virtual screening helped us identify a novel scaffold for NCX inhibition. A distinctively different NCX 1.1 inhibitor, ORM‐11372, was discovered after lead optimization. Its potency against human and rat NCX 1.1 and selectivity against other ion channels was assessed. The cardiovascular effects of ORM‐11372 were studied in normal and infarcted rats and rabbits. Human cardiac safety was studied ex vivo using human ventricular trabeculae.Key ResultsORM‐11372 inhibited human NCX 1.1 reverse and forward currents; IC50 values were 5 and 6 nM respectively. ORM‐11372 inhibited human cardiac sodium 1.5 (INa) and hERG KV11.1 currents (IhERG) in a concentration‐dependent manner; IC50 values were 23.2 and 10.0 μM. ORM‐11372 caused no changes in action potential duration; short‐term variability and triangulation were observed for concentrations of up to 10 μM. ORM‐11372 induced positive inotropic effects of 18 ± 6% and 35 ± 8% in anaesthetized rats with myocardial infarctions and in healthy rabbits respectively; no other haemodynamic effects were observed, except improved relaxation at the lowest dose.Conclusion and ImplicationsORM‐11372, a unique, novel, and potent inhibitor of human and rat NCX 1.1, is a positive inotropic compound. NCX inhibition can induce clinically relevant improvements in left ventricular contractions without affecting relaxation, heart rate, or BP, without pro‐arrhythmic risk.
Preclinical studies investigating the neural mechanisms involved in the co‐morbidity of migraine and temporomandibular disorders: the role of CGRP
Authors: Akerman Simon , Romero‐Reyes Marcela 
Published: September 2020

AbstractBackground and PurposeTemporomandibular disorders (TMD) and migraine can be co‐morbid. This can be a significant factor in exacerbating and increasing the prevalence of migraine‐like symptoms. However, the underlying mechanisms involved are unknown. Our objective was to investigate these neural mechanisms and the role of CGRP as a key modulator in this co‐morbidity.Experimental ApproachWe combined experimental approaches using CGRP, which triggers a migraine‐like response in patients, with that of masseteric muscle injection of complete Freund's adjuvant (CFA), to model myofascial TMD‐like inflammation. Using validated electrophysiological methods to assess each of the above approaches independently or in combination, we examined their effects on the response properties of migraine‐like dural‐trigeminocervical neurons.Key ResultsIndependently, in ~2/3 of animals (rats) each approach caused delayed migraine‐like activation and sensitisation of dural‐trigeminocervical neurons. The response to masseteric‐CFA was attenuated by a selective CGRP receptor antagonist. The combination approach caused a migraine‐like neuronal response in all animals tested, with somatosensory‐evoked cranial hypersensitivity significantly exacerbated.Conclusion and ImplicationsThe data demonstrate a neuronal phenotype that translates to the exacerbated clinical co‐morbid phenotype, supporting this combination approach as a relevant model to study the mechanisms involved. It provides a pathophysiological rationale for this exacerbated phenotype, strongly implicating the involvement of CGRP. The results provide support for targeting the CGRP pathway as a novel monotherapy approach for treating this co‐morbid condition. This has key implications into our understanding of this co‐morbid condition, as well as potentially addressing the major unmet need for novel and effective therapeutic approaches.