bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amelioration of age‐related brain function decline by Bruton's tyrosine kinase inhibition
Authors: Ekpenyong‐Akiba Akang E. , Poblocka Marta , Althubiti Mohammad , Rada Miran , Jurk Diana , Germano Sandra , Kocsis‐Fodor Gabriella , Shi Yu , Canales Juan J. , Macip Salvador 
Published: November 2019

AbstractOne of the hallmarks of aging is the progressive accumulation of senescent cells in organisms, which has been proposed to be a contributing factor to age‐dependent organ dysfunction. We recently reported that Bruton's tyrosine kinase (BTK) is an upstream component of the p53 responses to DNA damage. BTK binds to and phosphorylates p53 and MDM2, which results in increased p53 activity. Consistent with this, blocking BTK impairs p53‐induced senescence. This suggests that sustained BTK inhibition could have an effect on organismal aging by reducing the presence of senescent cells in tissues. Here, we show that ibrutinib, a clinically approved covalent inhibitor of BTK, prolonged the maximum lifespan of a Zmpste24−/− progeroid mice, which also showed a reduction in general age‐related fitness loss. Importantly, we found that certain brain functions were preserved, as seen by reduced anxiety‐like behaviour and better long‐term spatial memory. This was concomitant to a decrease in the expression of specific markers of senescence in the brain, which confirms a lower accumulation of senescent cells after BTK inhibition. Our data show that blocking BTK has a modest increase in lifespan in Zmpste24−/− mice and protects them from a decline in brain performance. This suggests that specific inhibitors could be used in humans to treat progeroid syndromes and prevent the age‐related degeneration of organs such as the brain.
Stress‐related suppression of peripheral cytokines predicts future relapse in alcohol‐dependent individuals with and without subclinical depression
Authors: Fox Helen C. , Milivojevic Verica , MacDougall Alicia , LaVallee Heather , Simpson Christine , Angarita Gustavo A. , Sinha Rajita 
Published: November 2019

AbstractChronic alcohol abuse and depressive symptoms are both associated with peripheral cytokine changes. Despite this, cytokine adaptations have not been assessed in co‐morbid populations or prospectively as predictors of relapse. We examine cytokine responses to stress in alcohol‐dependent individuals and social drinkers, both with and without subclinical depression. We also examine the potential link between cytokine adaptations in response to stress and prospective alcohol relapse risk. Thirty‐three, alcohol‐dependent individuals (21 with and 12 without high depressive symptoms) and 37 controls (16 with and 21 without high depressive symptoms) were exposed to two 5‐minute personalized guided imagery conditions (stress and neutral) across consecutive days in a randomized and counterbalanced order. Alcohol craving and serum measures of tumor necrosis factor alpha (TNFα), tumor necrosis factor receptor 1 (TNFR1), interleukin‐6 (IL‐6), and interleukin‐1 receptor antagonist (IL‐1ra) were collected prior to and following imagery exposure. Following treatment discharge, follow‐up interviews were conducted over 90 days to assess relapse. Dampened IL‐1ra and IL‐6 in response to stress was observed as a function of alcohol dependence and not moderated by depressive symptoms. Lower levels of IL‐6 following stress also predicted greater drinking days following treatment. Conversely, high depressive symptomatology was associated solely with pro‐inflammatory adaptations. Stress‐related suppression of TNFα predicted drinking severity only in alcohol‐dependent individuals with subclinical depression, and suppressed TNFR1 following stress was only seen in individuals with subclinical depression. Stress‐induced suppression of pro‐inflammatory TNF markers may indicate a risk factor for alcohol‐dependent individuals with co‐occurring depressive symptoms.
Constructing who can be Japanese: A study of social markers of acceptance in Japan
Authors: Komisarof Adam , Leong Chan‐Hoong , Teng Eugene 
Published: November 2019

Social markers of acceptance are socially constructed indicators of adaptation (e.g., language skills or adherence to social norms) that recipient nationals use in deciding whether to view an immigrant as a host community member. This study had two objectives: (a) to distill the markers considered important by Japanese undergraduates to accept immigrants in Japanese society and (b) to test the premises of integrated threat and social identity theories by ascertaining the effects on marker endorsement of perceived immigrant threat, contribution, relative social status, and intergroup permeability. Native‐born Japanese (the term “native‐born Japanese” is used throughout this article to refer to people born as Japanese citizens—differentiating them from immigrants who are Japanese citizens naturalized after birth) from 12 Japanese universities (N = 428) completed an online survey. Marker importance ratings were factor‐analyzed, and three latent dimensions were found representing sociolinguistic, ethnic, and socioeconomic markers. Multiple hierarchical regressions discerned the main effects of immigrants’ perceived threat and contribution on social markers as well as their interactions with intergroup permeability and immigrant relative status. The results underscored perceived threat’s consistent role in increasing marker importance and suggested divergent paths to acceptance: Immigrants perceived as “low‐status” were expected to conform to sociolinguistic and ethnic markers, whereas socioeconomic markers were stressed more for “high‐status” immigrants when perceived immigrant threat increased and intergroup boundaries were considered less permeable.
Cholesterol accumulation, lipid droplet formation, and steroid production in Leydig cells: Role of translocator protein (18‐kDa)
Authors: Chung Jin‐Yong , Chen Haolin , Papadopoulos Vassilios , Zirkin Barry 
Published: November 2019

AbstractBackgroundCholesterol import into the mitochondria of steroid‐producing cells is the rate‐determining step in steroidogenesis. Numerous studies have provided evidence that the cholesterol‐binding translocator protein (18 kDa TSPO) plays an important role in cholesterol translocation into mitochondria and that it also might act on cholesterol homeostasis. Several TSPO‐specific ligands have been shown to increase steroid production in vitro and in vivo.ObjectivesThe present study assessed the effects of the TSPO drug ligand FGIN‐1‐27 on cholesterol accumulation and lipid droplet formation in relationship to steroid formation.Materials and MethodsUsing MA‐10 and primary Leydig cells, immunocytochemical and molecular methods were used to examine cholesterol accumulation, the formation of lipid droplets, and steroid formation in response to LH and FGIN‐1‐27. Additionally, we determined the effects of Tspo knockout by CRISPR/Cas9, and of siRNA knockdowns of Tspo and Plin2 (Perilipin 2; also known as adipose differentiation‐related protein, ADFP) on LH‐ and FGIN‐1‐27‐induced steroidogenesis.ResultsIn response to LH and FGIN‐1‐27, cultured MA‐10 cells and primary Leydig cells increased steroid formation, cholesterol accumulation, and lipid droplet formation. Cholesterol accumulation in the lipid droplets also was increased in Tspo knockout cells. Knockout of Tspo or its knockdown in MA‐10 cells resulted in reduced progesterone formation in response to both LH and FGIN‐1‐27, as did knockdown of Plin2. Steroid production also was inhibited by the cholesteryl ester hydrolase inhibitor diethylumbelliferyl phosphate.Discussion and ConclusionThese results support the conclusion that FGIN‐1‐27 stimulates steroid formation by increasing TSPO‐mediated cholesterol translocation into the inner mitochondria for steroidogenesis, as well as into the cytosol for lipid droplet formation. FGIN‐1‐27 also increased steroid formation at least in part by inducing the conversion of cholesteryl ester located in lipid droplets to cholesterol, thus making available more substrate for steroid formation.
A distinct retinal pigment epithelial cell autofluorescence pattern in choroideremia predicts early involvement of overlying photoreceptors
Authors: Stevanovic Marta , Cehajic Kapetanovic Jasmina , Jolly Jasleen K. , MacLaren Robert E. 
Published: November 2019

AbstractPurposeChoroideremia is an X‐linked retinal disease characterized by early retinal pigment epithelium (RPE) loss and subsequent retinal degeneration. The RPE adopts either a smooth or mottled appearance on fundus autofluorescence (FAF). It is not known how RPE changes predict the health of the overlying ellipsoid zone (EZ).MethodsA retrospective review of FAF and optical coherence tomography (OCT) images from 20 patients with choroideremia was performed. The percentage of intact EZ in each smooth and mottled FAF region was determined using one horizontal trans‐foveal OCT section.ResultsFourteen out of 20 patients had distinct smooth and mottled areas in both eyes and were included in the sub‐analysis. On average, 62.5 ± 10.1% of the EZ in each smooth region of the right eyes was intact compared to 10.0 ± 4.3% in the mottled areas. The same trend was observed in left eyes: 76.5 ± 7.2% of the EZ was intact in the smooth regions versus 9.8 ± 3.9% in the mottled areas (two‐way anova, p < 0.0001). Thus, the mottled FAF regions were associated with EZ disruption more so than the smooth areas.ConclusionRetinal pigment epithelium (RPE) changes correlate with the health of the overlying EZ in choroideremia. The smooth FAF region likely represents early stages of the disease, with most of the area containing preserved EZ, whereas the mottled zone indicates more advanced stages and has mostly disrupted EZ. Because of the clear relationship between FAF findings and EZ integrity, FAF imaging can be used to monitor disease progression and identify areas of preserved EZ that could be rescued by gene therapy.
Recent advances in risk factors associated with ocular exfoliation syndrome
Authors: Ghaffari Sharaf Mehdi , Damji Karim F. , Unsworth Larry D. 
Published: November 2019

AbstractExfoliation syndrome is generally considered a progressive age‐related systemic disorder of the extracellular matrix, which is clinically characterized through the observation of flaky white aggregates on ocular tissues. Exfoliation syndrome is directly linked to exfoliative glaucoma in elderly patients, where it is known as the most common identifiable cause of open‐angle glaucoma. Despite the identification of various risk factors associated with exfoliation syndrome, the exact pathogenesis of this syndrome has not been fully elucidated. There is a growing number of genome‐wide association studies in different populations around the world to identify genetic factors underlying exfoliation syndrome. Besides variants in LOXL1 and CACNA1A genes, new loci have been recently identified which are believed to be associated with exfoliation syndrome. Among different genetic factors, functional variants might help to better understand mechanisms underlying this systemic disorder. Besides genetic factors, epigenetic regulation of different gene expression patterns has been thought to play a role in its pathogenesis. Other factors have been also considered to be involved in the development of exfoliation syndrome at cellular organelles level where mitochondrial impairment and autophagy dysfunction have been suggested in relation to exfoliation syndrome. This review addresses the most recent findings on genetic factors as well as cellular and molecular mechanisms involved in both the development and progression of exfoliation syndrome.
Flanged intraocular lens fixation via 27‐gauge trocars using a double‐needle technique decreases surgical wounds without losing its therapeutic effect
Authors: Ishikawa Hiroto , Fukuyama Hisashi , Komuku Yuki , Araki Takashi , Gomi Fumi 
Published: November 2019

AbstractPurposeIntraocular lens (IOL) fixation using a sutureless 27‐gauge needle intrascleral IOL implantation technique requires six surgical wounds. We developed a modified technique using two 27‐gauge trocars for vitrectomy and indwelling flanged IOL haptics to reduce the number of surgical wounds.SettingDepartment of Ophthalmology, Hyogo College of Medicine.DesignThis retrospective study enrolled 54 patients who had undergone IOL scleral fixation between January 2016 and April 2019.MethodsPatients who underwent IOL scleral fixation and were observed for >12 weeks were analysed using medical record data. Before October 2017, patients underwent normal flanged IOL scleral fixation. Between November 2017 and April 2019, patients underwent the modified method (flanged IOL via 27‐gauge trocars with double‐needle technique). Primary end‐point was superiority or non‐inferiority of modified IOL scleral fixation compared with normal IOL scleral fixation for visual acuity (VA). Changes in corneal endothelium cell number, refractivity, astigmatisms and surgery‐related complications, were secondary end‐points.ResultsThere were no significant differences in baseline characteristics between groups. Raw VA and best collected VA (BCVA) were significantly improved in all eyes (p−). There were no statistical significances in raw VA, BCVA and surgery‐related complications between groups.ConclusionsResults of the modified technique were not inferior compared with the original technique although it was less invasive. Therefore, flanged IOL fixation via trocars using a double‐needle technique is a useful technique for IOL implantation.
Providing a framework of principles for conceptualising the Fontan circulation
Authors: Gewillig Marc , Brown Stephen C. , van de Bruaene Alexander , Rychik Jack 
Published: November 2019

AbstractThe Fontan operation remains the final palliation for thousands of patients with complex congenital heart disease. By creating a Fontan circuit, control of cardiac output and congestion is wrested away from the ventricle and new haemodynamic forces take control. Understanding how to control the flow in the Fontan circuit will enable clinicians to improve patient management and possibly prevent future complications.ConclusionThis review proposes a framework of principles to conceptualise the functionality and limitations of a Fontan circulation.
Prediction of and surgical strategy for adherent hilar lymph nodes in thoracoscopic surgery
Authors: Matsuura Yosuke , Ichinose Junji , Nakao Masayuki , Okumura Sakae , Mun Mingyon 
Published: November 2019

AbstractIntroductionAdhesions between the hilar lymph nodes (HLN) and pulmonary artery are challenging during thoracoscopic surgery. Preoperative assessment of appropriate surgical access and feasibility of thoracoscopic surgery for lobectomy are crucial. However, there have been only a few reports of this issue. We investigated the association between the radiological features and the presence of HLN adhesions and validated the possibility of preoperatively predicting their presence. The types of adhesions were classified, and surgical strategies for each category were summarized.MethodsWe retrospectively identified 19 patients with adherent HLN (group A) from 1134 patients who had undergone thoracoscopic surgery for lobectomy between January 2008 and December 2017. One case in group A was matched to two cases with normal HLN (group N) by propensity score matching. We compared the radiological features of HLN between the two groups on preoperative CT scans. For group A, we assessed the recurrence of regional lymph nodes (RLNs) and classified the types of adhesions.ResultsAdherent HLN were larger and had higher CT values than normal HLN. Calcification in the RLNs indicated the possibility of adhesions in HLN. Group A had adhesions due to inflammation but no postoperative recurrence of RLNs.ConclusionsAdhesion of HLN to the pulmonary artery may be predicted to some extent by using preoperative CT scans. Our findings may contribute to improving the safety of thoracoscopic surgery.
Symptom trajectories in the months before and after a suicide attempt in individuals with bipolar disorder: A STEP‐BD study
Authors: Ballard Elizabeth D. , Farmer Cristan A. , Shovestul Bridget , Vande Voort Jennifer , Machado‐Vieira Rodrigo , Park Lawrence , Merikangas Kathleen R. , Zarate Carlos A. 
Published: November 2019

AbstractObjectivesThe suicide crisis is a relatively short‐lived psychiatric emergency, with transient symptoms that ebb and flow around the suicide attempt. Understanding the dynamic processes of symptoms before and after suicide attempt may aid future prevention efforts.MethodsData were drawn from the NIMH STEP‐BD study, which followed 4,360 patients with bipolar disorder; a subset attempted suicide during the trial (245/4100 or 5.97% of the sample eligible for analysis). This analysis focused on change in suicidal ideation (SI) in the 120 days before and 120 days after suicide attempt; similar analyses were conducted for other depressive symptoms. Generalized linear mixed models with a two‐piece linear function of time corresponding to pre‐ and post‐suicide attempt trends were used.ResultsSI ratings from 216 individuals were analyzed (n = 1,231 total; n = 395 pre‐attempt, n = 126 circa‐attempt, n = 710 post‐attempt) and compared to data from a matched sample of 648 non‐attempters. SI worsened in the 120 days pre‐attempt but improved afterwards, reaching non‐attempter levels by 90 days post‐attempt. A similar pattern was found for other depressive symptoms, including depressed mood, loss of interest, guilt, and self‐esteem. Pre/post differences in tension/activating symptoms of depression—anxiety, agitation, and irritability—were less pronounced and more time‐limited.ConclusionsThe suicide crisis is dynamic, and the days before and after suicide attempt may be particularly critical. The findings extend previous research on proximal symptoms of suicide and underscore that some SI and affective/cognitive symptoms of depression can remain elevated up to 90 days post‐attempt in individuals with bipolar disorder.
Breastfeeding experiences of same‐sex mothers
Authors: Juntereal Nina A. , Spatz Diane L. 
Published: November 2019

AbstractBackgroundFamily structures are diversifying in the United States, and more same‐sex female couples are building families. For two‐mother families, complexity exists for breastfeeding as more than one mother can provide human milk. The purpose of this study was to explore the lactation experience and level of lactation support of birth mothers in a same‐sex (two female) relationship.MethodsThis study consists of a mixed methods design using an online survey to identify the demographic of same‐sex mothers and qualitative interviews to provide an in‐depth understanding of the mothers' experiences. Qualitative content analysis is applied to develop themes from the interviews.ResultsSixty‐eight participants completed the online survey. Thirty‐seven mothers (59%) reported breastfeeding for more than one year. Fourteen (21%) respondents reported accessing induced lactation information for the nongestational parent from their health care practitioner. Forty‐three (63%) respondents reported receiving breastfeeding and induced lactation information from other sources. Only nine (13%) nongestational parents underwent induced lactation. Eighteen gestational mothers participated in qualitative interviews. Five themes emerged from the qualitative data: (a) committed to a year, (b) deciding “how to do it,” (c) sources of information, (d) involvement of partner, and (e) need for inclusive and educated health care practitioners.ConclusionsSame‐sex mothers have strong intentions to breastfeed and are resourceful in educating themselves for induced lactation and conursing. Nongestational parents are essential support partners and equivalent in motherhood. Providers need to better equip themselves and incorporate inclusive language in breastfeeding policy statements to support lactation outcomes.
Molecular tools for coral reef restoration: Beyond biomarker discovery
Authors: Parkinson John Everett , Baker Andrew C. , Baums Iliana B. , Davies Sarah W. , Grottoli Andréa G. , Kitchen Sheila A. , Matz Mikhail V. , Miller Margaret W. , Shantz Andrew A. , Kenkel Carly D. 
Published: November 2019

AbstractAs coral reefs continue to decline due to climate change and other stressors, scientists have proposed adopting genomic tools, such as biomarkers, to aid in the conservation and restoration of these threatened ecosystems. Biomarkers are easily measured indicators of biological processes that can be used to predict or diagnose health, resilience, and other key performance metrics. The ultimate goal of developing biomarkers is to determine the conservation value and utility of a given coral colony, including the host animal, its algal symbionts, and their microbial partners. However, this goal remains distant because most efforts have not yet moved beyond the initial discovery phase. We review recent progress in the development of coral molecular biomarkers from a practical standpoint and consider the many challenges that remain as roadblocks to large‐scale implementation. We caution practitioners that, while biomarkers are a promising technology, they are unlikely to be available for field application in the near future barring a rapid shift in research focus from discovery to subsequent validation and field trials. To facilitate such a shift, we propose a stepwise framework to guide additional study in this area, with the aim of accelerating practical molecular biomarker development to enhance coral restoration practice.
Inhibition of lysine‐specific demethylase 1A suppresses neointimal hyperplasia by targeting bone morphogenetic protein 2 and mediating vascular smooth muscle cell phenotype
Authors: Zhang Xiaobo , Huang Tao , Zhai Heng , Peng Wenpeng , Zhou Yong , Li Qi , Yang Haifeng 
Published: November 2019

AbstractObjectivesVascular disorders are associated with phenotypical switching of vascular smooth muscle cells (VSMCs). We investigated the effect of bone morphogenetic protein (BMP)‐2 in controlling VSMC phenotype and vascular disorder progression. Lysine (K)‐specific demethylase 1A (KDM1A) has been identified to target BMP‐2 and is employed as a therapeutic means of regulating BMP‐2 expression in VSMCs.Materials and methodsVSMCs were stimulated with angiotensin II, and the expression of KDM1A and BMP‐2 was detected. VSMC proliferation, apoptosis, and phenotype were evaluated. An in vivo aortic injury model was established, and VSMC behaviour was evaluated by the expression of key markers. The activation of BMP‐2–associated signalling pathways was examined.ResultsWe confirmed the inhibitory effect of KDM1A on BMP‐2 activity and demonstrated that KDM1A inhibition prevented VSMC transformation from a contractile to synthetic phenotype. In angiotensin II‐treated VSMCs, KDM1A inhibition triggered a decrease in cell proliferation and inflammatory response. In vivo, KDM1A inhibition alleviated post‐surgery neointimal formation and collagen deposition, preventing VSMCs from switching into a synthetic phenotype and suppressing disease onset. These processes were mediated by BMP‐2 through canonical small mothers against decapentaplegic signalling, which was associated with the activation of BMP receptors 1A and 1B.ConclusionsThe regulatory correlation between KDM1A and BMP‐2 offers insights into vascular remodelling and VSMC phenotypic modulation. The reported findings contribute to the development of innovative strategies against vascular disorders.