bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serotonin transporter gene polymorphisms may be associated with poststroke neurological recovery after escitalopram use
Authors: Lee Eun-Jae , Oh Mi-Sun , Kim Jong S , Chang Dae-Il , Park Jong-Ho , Cha Jae-Kwan , Heo Ji Hoe , Sohn Sung-Il , Kim Dong-Eog , Kim Hahn Young , Kim Jei , Seo Woo-Keun , Lee Jun , Park Sang-Won , Kim Yun Joong , Lee Byung-Chul 
Published: October 2017

ObjectiveSelective serotonin reuptake inhibitors (SSRIs) putatively improve neurological recovery after stroke. We aimed to investigate whether serotonin transporter (SERT) gene polymorphisms are related to the responsiveness to SSRIs in the poststroke neurological recovery.MethodsThis was a post hoc analysis of the EMOTION study (ClinicalTrials.gov NCT01278498), a randomised, placebo-controlled, double-blind trial examining the efficacy of escitalopram on emotional and neurological disturbances after acute stroke. Patients with no/minimal disability initially (modified Rankin Scale (mRS) 0–1) were excluded. Of the participants, 301 underwent genetic studies of the STin2 (a variable number tandem repeat (VNTR) in intron 2) (STin2 12/10 and STin2 12/12 genotypes) and 5-HTTLPR (a variable-length repeat in the promoter region) polymorphisms of SERT. We explored whether neurological function (National Institutes of Health Stroke Scale (NIHSS) score and mRS) at 3 months would differ according to SERT polymorphisms within each treatment arm (escitalopram and placebo).ResultsAmong the escitalopram users (n=159), neurological function in subjects with STin2 12/10 (n=29) improved significantly more than that in STin2 12/12 carriers (n=130) at 3 months. After adjusting for age, initial NIHSS and depression, STin2 12/10 independently predicted a good clinical outcome (mRS 0–1) (OR 2.99, 95% CI 1.04 to 8.58) at 3 months. However, differences between STin2 polymorphisms were not shown in the placebo group (n=142). 5-HTTLPR polymorphisms were not associated with neurological recovery in any treatment group.ConclusionSTin2 VNTR polymorphisms may be associated with poststroke neurological recovery after SSRI therapy. Further studies are needed to identify the role of serotonin in neurological recovery after stroke.
Macrophage overexpression of matrix metalloproteinase-9 in aged mice improves diastolic physiology and cardiac wound healing after myocardial infarction
Authors: Meschiari Cesar A. , Jung Mira , Iyer Rugmani Padmanabhan , Yabluchanskiy Andriy , Toba Hiroe , Garrett Michael R. , Lindsey Merry L. 
Published: October 2017

Matrix metalloproteinase (MMP)-9 increases in the myocardium with advanced age and after myocardial infarction (MI). Because young transgenic (TG) mice overexpressing human MMP-9 only in macrophages show better outcomes post-MI, whereas aged TG mice show a worse aging phenotype, we wanted to evaluate the effect of aging superimposed on MI to see if the detrimental effect of aging counteracted the benefits of macrophage MMP-9 overexpression. We used 17- to 28-mo-old male and female C57BL/6J wild-type (WT) and TG mice ( n = 10–21 mice/group) to evaluate the effects of aging superimposed on MI. Despite similar infarct areas and mortality rates at day 7 post-MI, aging TG mice showed improved diastolic properties and remodeling index compared with WT mice (both P < 0.05). Macrophage numbers were higher in TG than WT mice at days 0 and 7 post-MI, and the post-MI increase was due to elevated cluster of differentiation 18 protein levels (all P < 0.05). RNA sequencing analysis of cardiac macrophages isolated from day 7 post-MI infarcts identified 1,276 statistically different (all P < 0.05) genes (994 increased and 282 decreased in TG mice). Reduced expression of vascular endothelial growth factor A, platelet-derived growth factor subunit A, and transforming growth factor-β3, along with elevated expression of tissue inhibitor of MMP-4, in macrophages revealed mechanisms of indirect downstream effects on fibroblasts and neovascularization. While collagen accumulation was enhanced in TG mice compared with WT mice at days 0 and 7 post-MI ( P < 0.05 for both), the post-MI collagen cross-linking ratio was higher in WT mice ( P < 0.05), consistent with increased diastolic volumes. Vessel numbers [by Griffonia ( Bandeiraea) simplicifolia lectin I staining] were decreased in TG mice compared with WT mice at days 0 and 7 post-MI ( P < 0.05 for both). In conclusion, macrophage-derived MMP-9 improved post-MI cardiac wound healing through direct and indirect mechanisms to improve diastolic physiology and remodeling.NEW & NOTEWORTHY Aging mice with macrophage overexpression of matrix metalloproteinase-9 have increased macrophage numbers 7 days after myocardial infarction, resulting in improved diastolic physiology and left ventricular remodeling through effects on cardiac wound healing.
Right Ventricular Pacing Increases Risk of Appropriate Implantable Cardioverter–Defibrillator Shocks Asymmetrically
Authors: Cronin Edmond M. , Jones Paul , Seth Milan C. , Varma Niraj 
Published: October 2017

Background:
Right ventricular pacing (RVP) increases risk of atrial fibrillation in patients with implantable cardioverter–defibrillators (ICDs), but ventricular proarrhythmia is less clear. We analyzed a large remote monitoring database to assess this question.

Methods and Results:

Patients with single- or dual-chamber ICDs, engaged in remote monitoring for at least 6 months and with unchanged tachycardia programming, were included. %RVP was derived for each weekly transmission. ICD electrograms preceding the first shock were adjudicated. Among 425 625 transmissions received from 8435 patients, 389 appropriate shocks occurred over a mean follow-up of 15.0±8.8 months. In a time-dependent Cox proportional hazards model, transmissions with 80% to 98% RVP were associated with a hazard ratio of 1.56 for an appropriate shock in the subsequent week compared with <1% RVP (95% CI, 1.01–2.41;
P
=0.04). By contrast, ≥98% RVP trended toward a lower risk of an appropriate shock (hazard ratio, 0.61; 95% CI, 0.33–1.12;
P
=0.108). Lifetime cumulative %RVP was closely correlated with weekly %RVP (
R
2
=0.907) and was similarly associated with increased risk of appropriate shocks at 80% to 98% RVP (hazard ratio, 1.57; 95% CI, 1.01–2.44;
P
=0.046) but not at ≥98% RVP (hazard ratio, 0.49; 95% CI, 0.24–1.01;
P
=0.052). These results were driven by dual-chamber devices, but unaffected by PVC counts or programming. Male sex and age were also associated with appropriate ICD shocks.

Conclusions:
Increasing frequency of RVP is associated with a progressively increased risk of appropriate ICD shocks until ≥98% RVP. RVP may have ventricular proarrhythmia because of competition of paced and intrinsic rhythm in ICD patients.
Extracellular Matrix Proteomics Reveals Interplay of Aggrecan and Aggrecanases in Vascular Remodeling of Stented Coronary Arteries
Authors: Suna Gonca , Wojakowski Wojciech , Lynch Marc , Barallobre-Barreiro Javier , Yin Xiaoke , Mayr Ursula , Baig Ferheen , Lu Ruifang , Fava Marika , Hayward Robert , Molenaar Chris , White Stephen J. , Roleder Tomasz , Milewski Krzysztof P. , Gasior Pawel , Buszman Piotr P. , Buszman Pawel , Jahangiri Marjan , Shanahan Catherine M. , Hill Jonathan , Mayr Manuel 
Published: October 2017

Background:
Extracellular matrix (ECM) remodeling contributes to in-stent restenosis and thrombosis. Despite its important clinical implications, little is known about ECM changes post–stent implantation.

Methods:
Bare-metal and drug-eluting stents were implanted in pig coronary arteries with an overstretch under optical coherence tomography guidance. Stented segments were harvested 1, 3, 7, 14, and 28 days post-stenting for proteomics analysis of the media and neointima.

Results:

A total of 151 ECM and ECM-associated proteins were identified by mass spectrometry. After stent implantation, proteins involved in regulating calcification were upregulated in the neointima of drug-eluting stents. The earliest changes in the media were proteins involved in inflammation and thrombosis, followed by changes in regulatory ECM proteins. By day 28, basement membrane proteins were reduced in drug-eluting stents in comparison with bare-metal stents. In contrast, the large aggregating proteoglycan aggrecan was increased. Aggrecanases of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family contribute to the catabolism of vascular proteoglycans. An increase in ADAMTS-specific aggrecan fragments was accompanied by a notable shift from
ADAMTS1
and
ADAMTS5
to
ADAMTS4
gene expression after stent implantation. Immunostaining in human stented coronary arteries confirmed the presence of aggrecan and aggrecan fragments, in particular, at the contacts of the stent struts with the artery. Further investigation of aggrecan presence in the human vasculature revealed that aggrecan and aggrecan cleavage were more abundant in human arteries than in human veins. In addition, aggrecan synthesis was induced on grafting a vein into the arterial circulation, suggesting an important role for aggrecan in vascular plasticity. Finally, lack of ADAMTS-5 activity in mice resulted in an accumulation of aggrecan and a dilation of the thoracic aorta, confirming that aggrecanase activity regulates aggrecan abundance in the arterial wall and contributes to vascular remodeling.

Conclusions:

Significant differences were identified by proteomics in the ECM of coronary arteries after bare-metal and drug-eluting stent implantation, most notably an upregulation of aggrecan, a major ECM component of cartilaginous tissues that confers resistance to compression. The accumulation of aggrecan coincided with a shift in
ADAMTS
gene expression. This study provides the first evidence implicating aggrecan and aggrecanases in the vascular injury response after stenting.
Randomized Controlled Trial of Early Versus Delayed Statin Therapy in Patients With Acute Ischemic Stroke
Authors: Yoshimura Shinichi , Uchida Kazutaka , Daimon Takashi , Takashima Ryuzo , Kimura Kazuhiro , Morimoto Takeshi , Tanada Shuichi , Iida Tomoko , Kuroda Junko , Nose Akinori , Tatebayashi Kotaro , Shimizu Fuminori , Tsudaka Shun , Takeuchi Masataka , Hiyama Nagayasu , Oki Yoshiharu , Hagii Joji , Saito Shin , Matsumoto Tsuyoshi , Tanaka Yasue , Kuramoto Yoji , Mikami Kazuyuki , Shinoda Narihide , Shimo Daisuke , Soneda Junichi , Tokuda Kou , Matsuda Kenichi , Hiroto Kakita , Yamaura Ikuya , Okada Takashi , Hirano Teruyuki , Kuwayama Naoya , Teramukai Satoshi 
Published: October 2017

Background and Purpose—
Several studies suggested that statins during hospitalization were associated with better disability outcomes in patients with acute ischemic stroke, but only 1 small randomized trial is available.

Methods—
We conducted a multicenter, open-label, randomized controlled trial in patients with acute ischemic strokes in 11 hospitals in Japan. Patients with acute ischemic stroke and dyslipidemia randomly received statins within 24 hours after admission in the early group or on the seventh day in the delayed group, in a 1:1 ratio. Statins were administered for 12 weeks. The primary outcome was patient disability assessed by modified Rankin Scale at 90 days.

Results—

A total of 257 patients were randomized and analyzed (early 131, delayed 126). At 90 days, modified Rankin Scale score distribution did not differ between groups (
P
=0.68), and the adjusted common odds ratio of the early statin group was 0.84 (95% confidence interval, 0.53–1.3;
P
=0.46) compared with the delayed statin group. There were 3 deaths at 90 days (2 in the early group, 1 in the delayed group) because of malignancy. Ischemic stroke recurred in 9 patients (6.9%) in the early group and 5 patients (4.0%) in the delayed group. The safety profile was similar between groups.

Conclusions—
Our randomized trial involving patients with acute ischemic stroke and dyslipidemia did not show any superiority of early statin therapy within 24 hours of admission compared with delayed statin therapy 7 days after admission to alleviate the degree of disability at 90 days after onset.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02549846.
Early Postoperative Infection Following Open Reduction Internal Fixation Repair of Closed Malleolar Fractures
Authors: Schade Meredith A. , Hollenbeak Christopher S. 
Published: October 2017

Background: Early postoperative infection (EPI) following hardware placement in patients with malleolar fractures is a serious complication. Identifying factors that place patients at risk for early infection may help target interventions to prevent infections. Methods: Data for the study included all adult patients who underwent operative management for closed malleolar fracture from 2006 to 2013 in the National Surgical Quality Improvement Program database. Characteristics of patients with and without EPI were compared using univariate tests. Logistic regression was used to perform a multivariable analysis of risk factors for EPI while controlling for covariates. Length of stay was analyzed using a generalized linear model. Results: The analysis sample included 7054 patients, of whom 116 developed EPI. Patients with EPI were slightly older on average, more likely to have diabetes, and had higher anesthesia class. Multivariable analysis identified several risk factors for EPI, including diabetes (odds ratio [OR] = 2.6; 95% CI = 1.5-4.5; P < .0001), American Society of Anaesthesiology (ASA) class 3+ (OR = 2.3; 95% CI = 1.03-5.0; P = .04), unclean surgery (OR = 2.4; 95% CI = 1.3-4.2; P < .0001), and inpatient location (OR 1.7, 1.1-2.7; P = .01). After controlling for other factors, EPI was not significantly associated with a longer hospital stay (0.2 days, P = .55). Conclusion: In the 30 days after hardware placement for malleolar fracture, infection occurs with increased frequency in older patients, diabetics, those with higher anesthesia class, and in the setting of unclean surgery and inpatient operative location. Patients with the identified risk factors should be followed closely for development of infection. Levels of Evidence: Level III: Retrospective cohort study
Vanadian and chromian garnet- and epidote-supergroup minerals in metamorphosed Paleozoic black shales from Čierna Lehota, Strážovské vrchy Mountains, Slovakia: crystal chemistry and evolution
Authors: Bačík Peter , Uher Pavel , Kozáková Petra , Števko Martin , Ozdín Daniel , Vaculovič Tomáš 
Published: October 2017

AbstractSilicate minerals enriched in V, Cr and Mn including garnets and epidote-supergroup members, in association with amphiboles, albite, hyalophane, titanite, chamosite, sulfides and other minerals occur in Devonian black shales near Čierna Lehota in the Strážovské vrchy Mountains, Slovakia. The garnets have high concentrations of V, Cr and Mn (up to 17 wt.% V2O3, ≤11 wt.% Cr2O3and ≤ 21 wt.% MnO) and several compositional types. Vanadian-chromian grossular (Grs 1) usually preserves primary metamorphic oscillatory zoning, whereas solid solutions between goldmanite (Gld 2A,B), V- and Cr-rich grossular and spessartine (Grs 2A,B, Sps 2) form irregular domains or crystals with variable zoning. Dominant substitutions in the garnets include CaMn–1and (V,Cr)Al–1, resulting in coupled Ca(V,Cr)Mn–1Al–1. Epidote-supergroup minerals occur as abundant anhedral crystals with variable compositional zoning. Nearly all crystals have a complete zoning sequence beginning withREE-rich allanite-(La), followed by mukhinite and by V- and Cr-rich clinozoisite to mukhinite and V- and Cr-poor clinozoisite. In common with garnets, the epidote-supergroup minerals are enriched in V, Cr and Mn (<7 wt.% V2O3, <5 wt.% Cr2O3and <3 wt.% MnO). Lanthanum is the dominantREE(up to 11.5 wt.% La2O3) in allanite-(La). The composition of epidote-supergroup minerals is controlled byREEFe2+(CaAl)–1,REEMg(CaAl)–1,REEMn2+(CaAl)–1andREEFe2+(CaFe3+)–1substitutions introducingREE, together with VAl–1and CrAl–1substitutions. The negative Ce and slightly positive Eu anomalies displayed in chondrite-normalized patterns and enrichment in V, Cr and Mn are ascribed to the geochemical properties of the protolith. The minerals investigated exhibit multi-stage evolution: (1) presumed low-grade greenschist-facies metamorphism; and (2) development of V- and Cr-rich zones in both garnet- and epidote-supergroup minerals which result from late-Variscan contact metamorphism due to granitic intrusion of the Suchý Massif. Decreased temperature following the metamorphic peak probably resulted in the formation ofREE-, V- and Cr-poor clinozoisite and secondary garnet.
HSC extrinsic sex-related and intrinsic autoimmune disease–related human B-cell variation is recapitulated in humanized mice
Authors: Borsotti Chiara , Danzl Nichole M. , Nauman Grace , Hölzl Markus A. , French Clare , Chavez Estefania , Khosravi-Maharlooei Mohsen , Glauzy Salome , Delmotte Fabien R. , Meffre Eric , Savage David G. , Campbell Sean R. , Goland Robin , Greenberg Ellen , Bi Jing , Satwani Prakash , Yang Suxiao , Bathon Joan , Winchester Robert , Sykes Megan 
Published: October 2017

Key PointsIncreased human B-cell reconstitution is seen in female compared to male mice in multiple humanized mouse models. The PI mouse model recapitulates HSC-intrinsic autoimmune defects from T1D and RA bone marrow donors.
Exendin-4, a Glucagonlike Peptide-1 Receptor Agonist, Attenuates Breast Cancer Growth by Inhibiting NF-κB Activation
Authors: Iwaya Chikayo , Nomiyama Takashi , Komatsu Shiho , Kawanami Takako , Tsutsumi Yoko , Hamaguchi Yuriko , Horikawa Tsuyoshi , Yoshinaga Yasuteru , Yamashita Shinichi , Tanaka Tomoko , Terawaki Yuichi , Tanabe Makito , Nabeshima Kazuki , Iwasaki Akinori , Yanase Toshihiko 
Published: October 2017

Abstract
Incretin therapies have received much attention because of their tissue-protective effects, which extend beyond those associated with glycemic control. Cancer is a primary cause of death in patients who have diabetes mellitus. We previously reported antiprostate cancer effects of the glucagonlike peptide-1 (GLP-1) receptor (GLP-1R) agonist exendin-4 (Ex-4). Breast cancer is one of the most common cancers in female patients who have type 2 diabetes mellitus and obesity. Thus, we examined whether GLP-1 action could attenuate breast cancer. GLP-1R was expressed in human breast cancer tissue and MCF-7, MDA-MB-231, and KPL-1 cell lines. We found that 0.1 to 10 nM Ex-4 significantly decreased the number of breast cancer cells in a dose-dependent manner. Although Ex-4 did not induce apoptosis, it attenuated breast cancer cell proliferation significantly and dose-dependently. However, the dipeptidyl peptidase-4 inhibitor linagliptin did not affect breast cancer cell proliferation. When MCF-7 cells were transplanted into athymic mice, Ex-4 decreased MCF-7 tumor size in vivo. Ki67 immunohistochemistry revealed that breast cancer cell proliferation was significantly reduced in tumors extracted from Ex-4-treated mice. In MCF-7 cells, Ex-4 significantly inhibited nuclear factor κB (NF-κB ) nuclear translocation and target gene expression. Furthermore, Ex-4 decreased both Akt and IκB phosphorylation. These results suggest that GLP-1 could attenuate breast cancer cell proliferation via activation of GLP-1R and subsequent inhibition of NF-κB activation.
Neurokinin B Regulates Gonadotropin Secretion, Ovarian Follicle Growth, and the Timing of Ovulation in Healthy Women
Authors: Skorupskaite Karolina , George Jyothis T , Veldhuis Johannes D , Anderson Richard A 
Published: October 2017

Abstract

Context
Neurokinin B (NKB) is obligate for human puberty, but its role in adult female gonadotropin secretion and ovarian follicle growth is unknown.

Objective
To investigate antagonism of NKB on pulsatile gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretion and ovarian follicle development in healthy women.

Design
Open investigation of the effects of a neurokinin-3 receptor (NK3R) antagonist (NK3Ra) vs a no-treatment control cycle.

Setting
Clinical research facility.

Patients or other participants
Healthy women with regular menses (n = 13).

Intervention(s)
NK3Ra MLE4901 40 mg taken orally twice daily from cycle day 5 to 6 for 7 days.

Main outcome measure(s)
LH secretion, ovarian follicle growth, and timing of ovulation.

Results
NK3Ra administration reduced basal LH secretion without a change in pulse frequency and delayed the LH surge by 7 days, the duration of treatment [mean cycle day ± standard error of the mean (SEM), 22 ± 1 days vs 15 ± 1 days in control cycles; P = 0.0006]. Follicle growth (mean diameter at the end of administration of NK3Ra administration ± SEM, 9.3 ± 0.4 mm vs 15.1 ± 0.9 mm in control cycles; P &lt; 0.0001) and rising estradiol concentrations (mean ± SEM, 166 ± 29 pmol/L vs 446 ± 86 pmol/L in control cycles; P &lt; 0.0001) were prevented. After treatment, follicle development resumed and normal preovulatory follicle diameter and estradiol concentrations were demonstrated. Postovulatory progesterone rise was similarly delayed (peak cycle day, 30 ± 2 vs 22 ± 1; P = 0.002) and cycle length was prolonged (35 ± 1 days vs 29 ± 1 days in control cycles; P = 0.0003) but luteal progesterone excretion was unaffected by the NK3Ra (LH surge day +7 mean urinary progesterone levels ± SEM, 58 ± 10 pmol/mol vs 48±7 pmol/mol creatinine in control cycles; nonsignificant).

Conclusion
These data demonstrate the involvement of NKB-NK3R signaling in the physiological regulation of GnRH/LH secretion, determining normal follicle development in women.
Bronchiectasis—a growing respiratory problem
Authors: Cope Graham 
Published: October 2017

Bronchiectasis is the irreversible, pathological dilatation of the small and medium-sized bronchi. It is not a disease in its own right, but a final common pathway of a cycle of inflammation, bacterial colonisation and infection ( Altenburg et al, 2015 ). It occurs in a variety of pathologic processes that are associated with recurrent or acute infection and inflammation, such as cystic fibrosis, chronic obstructive pulmonary disease and asthma leading to permanent structural changes in the airways. Bronchiectasis can result in substantial morbidity, usually secondary to recurrent infection, but in severe cases can lead to death ( Milliron et al, 2015 ). The main symptom of bronchiectasis is a chronic productive cough, over-production of mucus and the dilation of the bronchus, which causes each cough to be less effective, leading to inefficient clearance of secretions with the potential for chronic or recurrent infections ( Currie et al, 1987 ). The main treatments aim to suppress the inflammation and prevent infections, and in the case of exacerbations, to reduce the sputum volume, viscosity and purulence and to lessen the cough, dyspnoea and fever ( Abo-Leyah and Chalmers, 2017 ).