bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of autonomic nervous activity, as measured by heart rate variability, on the effect of mortality in disabled older adults with low blood pressure in long‐term care
Authors: Shibasaki Koji , Ogawa Sumito , Yamada Shizuru , Ouchi Yasuyoshi , Akishita Masahiro 
Published: April 2018

AimPrevious studies have shown the relationship between low blood pressure and high mortality in frail, disabled older adults in long‐term care. However, the mechanism of this relationship is still unclear. We hypothesized that autonomic nervous activity decline is involved in the relationship between low blood pressure and high mortality.MethodsThe present prospective cohort study recruited 61 participants aged ≥75 years. The data from 24‐h Holter monitoring and blood pressure recorded by ambulatory blood pressure monitoring were collected. Measured data were divided into three categories: 24‐h, daytime and night‐time. From power spectral density in the electrocardiogram, low frequency, high frequency and low frequency/high frequency ratio were calculated. The primary end‐point was death.ResultsHigh blood pressure was connected to both high daytime low frequency and high frequency (partial correlation coefficients: 0.42, P < 0.05 and 0.35, P < 0.05, respectively). In addition, the low blood pressure group had higher mortality than the high blood pressure group, and disabled older adults in long‐term care and those with elevated daytime systolic and diastolic blood pressure had less risk of mortality compared with those without (systolic: hazard ratio 0.89, 95% confidence interval 0.83–0.96, P = 0.003; diastolic: hazard ratio 0.98, 95% confidence interval 0.79–1.00, P = 0.049). The average blood pressures in the high blood pressure groups were approximately 140/80 mmHg and were connected to low mortality.ConclusionsAttenuated autonomic nervous activity might lead to low blood pressure in the daytime and high mortality in disabled older adults in long‐term care. Geriatr Gerontol Int 2018; 18: 1153–1158.
Oncological impact of neoadjuvant hormonal therapy on permanent iodine‐125 seed brachytherapy in patients with low‐ and intermediate‐risk prostate cancer
Authors: Takamoto Atsushi , Tanimoto Ryuta , Bekku Kensuke , Araki Motoo , Sadahira Takuya , Wada Koichiro , Ebara Shin , Katayama Norihisa , Yanai Hiroyuki , Nasu Yasutomo 
Published: April 2018

ObjectivesTo determine whether neoadjuvant hormonal therapy improves oncological outcomes of patients with localized prostate cancer treated with permanent brachytherapy.MethodsBetween January 2004 and November 2014, 564 patients underwent transperineal ultrasonography‐guided permanent iodine‐125 seed brachytherapy. We retrospectively analyzed low‐ or intermediate‐risk prostate cancer based on the National Comprehensive Cancer Network guidelines. The clinical variables were evaluated for influence on biochemical recurrence‐free survival, progression‐free survival, cancer‐specific survival and overall survival.ResultsA total of 484 patients with low‐risk (259 patients) or intermediate‐risk disease (225 patients) were evaluated. Of these, 188 received neoadjuvant hormonal therapy. With a median follow up of 71 months, the 5‐year actuarial biochemical recurrence‐free survival rates of patients who did and did not receive neoadjuvant hormonal therapy were 92.9% and 93.6%, respectively (P = 0.2843). When patients were stratified by risk group, neoadjuvant hormonal therapy did not improve biochemical recurrence‐free survival outcomes in low‐ (P = 0.8949) or intermediate‐risk (P = 0.1989) patients. The duration or type of hormonal therapy was not significant in predicting biochemical recurrence. In a multivariate analysis, Gleason score, pretreatment prostate‐specific antigen, clinical T stage, and prostate dosimetry, primary Gleason score and positive core rate were significant predictive factors of biochemical recurrence‐free survival, whereas neoadjuvant hormonal therapy was insignificant. Furthermore, neoadjuvant hormonal therapy did not significantly influence progression‐free survival, cancer‐specific survival or overall survival.ConclusionsIn patients with low‐ or intermediate‐risk disease treated with permanent prostate brachytherapy, neoadjuvant hormonal therapy does not improve oncological outcomes. Its use should be restricted to patients who require prostate volume reduction.
Acid‐suppressive drugs and risk of kidney disease: A systematic review and meta‐analysis
Authors: Qiu Tingting , Zhou Junwen , Zhang Chao 
Published: April 2018

AbstractBackground and AimMore concerns had been raised about the risk of kidney disease (KD) associated with acid‐suppressive drugs. But whether they could directly increase such risk remained unclear. Meta‐analysis was conducted to comprehensively investigate this relationship.MethodsPubMed, EMBASE, Cochrane Central Register of Controlled Trials, and three Chinese databases were searched until April 2017 for observational studies investigating the associations between acid‐suppressive drugs and KD. Pooled log (odds ratios [ORs]) or log (hazard ratios [HRs]) with standard errors for KD risk were calculated using the generic inverse variance method and random‐effect model.ResultsTen studies involving 128 020 KD patients were included. Proton pump inhibitor (PPI) therapy was associated with higher risks of acute interstitial nephritis (OR, 2.78; 95% confidence interval [CI], 1.25–6.17), acute kidney injury (AKI) (HR, 1.85; 95% CI, 1.33–2.59), chronic kidney disease (CKD) (HR, 1.47; 95% CI, 1.03–2.09), and end‐stage renal disease (ESRD) (HR, 1.61; 95% CI, 1.26–2.04) than non‐PPI therapy. Additionally, PPI significantly increased the risks of AKI (HR, 1.32; 95% CI, 1.16–1.51), CKD (HR, 1.28; 95% CI, 1.24–1.33), and ESRD (HR, 1.96; 95% CI, 1.21–3.17) compared with histamine 2 receptor antagonist (H2RA). Relationship between H2RA therapy and AKI (OR, 0.98; 95% CI, 0.90–1.07) or CKD (OR, 1.00; 95% CI, 0.89–1.11) was not found.ConclusionsProton pump inhibitor therapy significantly increased the risks of acute interstitial nephritis, AKI, CKD, and ESRD. Similar risks were not identified for H2RA therapy. More clinical trials are needed to confirm our findings.
A survey on author profiling, deception, and irony detection for the Arabic language
Authors: Rosso Paolo , Rangel Francisco , Farías Irazu Hernández , Cagnina Leticia , Zaghouani Wajdi , Charfi Anis 
Published: April 2018

AbstractThe possibility of knowing people traits on the basis of what they write is a field of growing interest named author profiling. To infer a user's gender, age, native language, language variety, or even when the user lies, simply by analyzing her texts, opens a wide range of possibilities from the point of view of security. In this paper, we review the state of the art about some of the main author profiling problems, as well as deception and irony detection, especially focusing on the Arabic language.
Correlation between novel 3D high‐resolution manometry esophagogastric junction metrics and pH‐metry in reflux disease patients
Authors: Xiao Y. , Lin Z. , Li Y. , Pandolfino J. E. , Chen M. , Kahrilas P. J. 
Published: April 2018

AbstractBackground and aimsWe recently developed 2 novel 3D high‐resolution manometry (HRM) metrics of esophagogastric junction (EGJ) contractility to differentiate the lower esophageal sphincter (LES) and crural diaphragm (CD) elements of EGJ pressure. This study aimed to compare these metrics to the EGJ‐contractile integral (EGJ‐CI) and to analyze their correlation with esophageal acid exposure time (AET) on pH‐metry.MethodsThirty‐one gastro‐oesophageal reflux disease (GERD) patients and 20 control subjects underwent 24‐hour pH‐metry and HRM using a 3D‐HRM catheter. EGJ metrics were calculated during 3 consecutive respiratory cycles at rest. The EGJ‐CI was calculated using the DCI tool in the ManoView software. 3D LES pressure (3D‐LESP) and 3D‐DHA, a metric quantifying the CD component of the 3D‐HRM pressure topography, were calculated using a MATLAB program. Pearson correlation was used to calculate correlations with AET.Key Results3D‐LESP, 3D‐DHA, and EGJ‐CI were all significantly lower in GERD patients than in control subjects (P < .05) and all were significantly correlated with AET (R = −.48, −.42, −.52, respectively, all P < .01). The 3D‐DHA and EGJ‐CI also strongly correlated with each other (R = .84, P < .001).Conclusions & InferencesBoth 3D‐EGJ metrics were correlated with AET emphasizing the importance of both LES and CD function as a determinant of EGJ competence. 3D‐DHA also strongly correlated with the EGJ‐CI suggesting that EGJ‐CI is strongly driven by the asymmetrical CD pressure component.
Arabidopsis ANGUSTIFOLIA3 (AN3) is associated with the promoter of CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) to regulate light‐mediated stomatal development
Authors: Meng Lai‐Sheng , Li Cong , Xu Meng‐Ke , Sun Xu‐Dong , Wan Wen , Cao Xiao‐Ying , Zhang Jin‐Lin , Chen Kun‐Ming 
Published: April 2018

AbstractLight signals are perceived by multiple photoreceptors that converge to suppress the RING E3 ubiquitin ligase CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) for the regulation of stomatal development. Thus, COP1 is a point of integration between light signaling and stomatal patterning. However, how light signaling is collected into COP1 for the production and spacing of stomata is still unknown. Here, we report that the loss‐of‐function mutant of ANGUSTIFOLIA3 (AN3) delays asymmetric cell division, which leads to decreased stomatal index. Furthermore, overexpression of AN3 accelerates asymmetric cell division, which results in clusters of stomata. In addition, the stomatal development through AN3 regulation is mediated by light signaling. Finally, we find that an3 is a light‐signaling mutant, and that AN3 protein is light regulated. Self‐activation by AN3 contributes to the control of AN3 expression. Thus, AN3 is a point of collection between light signaling and stomatal patterning. Target‐gene analysis indicates that AN3 is associated with COP1 promoter for the regulation of light‐controlling stomatal development. Together, these components for regulating stomatal development form an AN3–COP1–E3 ubiquitin ligase complex, allowing the integration of light signaling into the production and spacing of stomata.
Insights to plant–microbe interactions provide opportunities to improve resistance breeding against root diseases in grain legumes
Authors: Wille Lukas , Messmer Monika M. , Studer Bruno , Hohmann Pierre 
Published: April 2018

AbstractRoot and foot diseases severely impede grain legume cultivation worldwide. Breeding lines with resistance against individual pathogens exist, but these resistances are often overcome by the interaction of multiple pathogens in field situations. Novel tools allow to decipher plant–microbiome interactions in unprecedented detail and provide insights into resistance mechanisms that consider both simultaneous attacks of various pathogens and the interplay with beneficial microbes. Although it has become clear that plant‐associated microbes play a key role in plant health, a systematic picture of how and to what extent plants can shape their own detrimental or beneficial microbiome remains to be drawn. There is increasing evidence for the existence of genetic variation in the regulation of plant–microbe interactions that can be exploited by plant breeders. We propose to consider the entire plant holobiont in resistance breeding strategies in order to unravel hidden parts of complex defence mechanisms. This review summarizes (a) the current knowledge of resistance against soil‐borne pathogens in grain legumes, (b) evidence for genetic variation for rhizosphere‐related traits, (c) the role of root exudation in microbe‐mediated disease resistance and elaborates (d) how these traits can be incorporated in resistance breeding programmes.
Interstitial Lung Diseases in the U.S. Mining Industry: Using MSHA Data to Examine Trends and the Prevention Effects of Compliance with Health Regulations, 1996–2015
Authors: Yorio Patrick L. , Laney A. Scott , Halldin Cara N. , Blackley David J. , Moore Susan M. , Wizner Kerri , Radonovich Lewis J. , Greenawald Lee A. 
Published: April 2018

AbstractGiven the recent increase in dust‐induced lung disease among U.S. coal miners and the respiratory hazards encountered across the U.S. mining industry, it is important to enhance an understanding of lung disease trends and the organizational contexts that precede these events. In addition to exploring overall trends reported to the Mine Safety and Health Administration (MSHA), the current study uses MSHA's enforcement database to examine whether or not compliance with health regulations resulted in fewer mine‐level counts of these diseases over time. The findings suggest that interstitial lung diseases were more prevalent in coal mines compared to other mining commodities, in Appalachian coal mines compared to the rest of the United States, and in underground compared to surface coal mines. Mines that followed a relevant subset of MSHA's health regulations were less likely to report a lung disease over time. The findings are discussed from a lung disease prevention strategy perspective.
Randomization‐based statistical inference: A resampling and simulation infrastructure
Authors: Dinov Ivo D. , Palanimalai Selvam , Khare Ashwini , Christou Nicolas 
Published: April 2018

SummaryStatistical inference involves drawing scientifically‐based conclusions describing natural processes or observable phenomena from datasets with intrinsic random variation. We designed, implemented, and validated a new portable randomization‐based statistical inference infrastructure (http://socr.umich.edu/HTML5/Resampling_Webapp) that blends research‐driven data analytics and interactive learning, and provides a backend computational library for managing large amounts of simulated or user‐provided data.We designed, implemented and validated a new portable randomization‐based statistical inference infrastructure (http://socr.umich.edu/HTML5/Resampling_Webapp) that blends research‐driven data analytics and interactive learning, and provides a backend computational library for managing large amounts of simulated or user‐provided data. The core of this framework is a modern randomization webapp, which may be invoked on any device supporting a JavaScript‐enabled web browser. We demonstrate the use of these resources to analyse proportion, mean and other statistics using simulated (virtual experiments) and observed (e.g. Acute Myocardial Infarction, Job Rankings) data. Finally, we draw parallels between parametric inference methods and their distribution‐free alternatives.The Randomization and Resampling webapp can be used for data analytics, as well as for formal, in‐class and informal, out‐of‐the‐classroom learning and teaching of different scientific concepts. Such concepts include sampling, random variation, computational statistical inference and data‐driven analytics. The entire scientific community may utilize, test, expand, modify or embed these resources (data, source‐code, learning activity, webapp) without any restrictions.
Central and peripheral chemoreceptors in sudden infant death syndrome
Authors: Porzionato Andrea , Macchi Veronica , De Caro Raffaele 
Published: April 2018

AbstractThe pathogenesis of sudden infant death syndrome (SIDS) has been ascribed to an underlying biological vulnerability to stressors during a critical period of development. This paper reviews the main data in the literature supporting the role of central (e.g. retrotrapezoid nucleus, serotoninergic raphe nuclei, locus coeruleus, orexinergic neurons, ventral medullary surface, solitary tract nucleus) and peripheral (e.g. carotid body) chemoreceptors in the pathogenesis of SIDS. Clinical and experimental studies indicate that central and peripheral chemoreceptors undergo critical development during the initial postnatal period, consistent with the age range of SIDS (<1 year). Most of the risk factors for SIDS (gender, genetic factors, prematurity, hypoxic/hyperoxic stimuli, inflammation, perinatal exposure to cigarette smoke and/or substance abuse) may structurally and functionally affect the developmental plasticity of central and peripheral chemoreceptors, strongly suggesting the involvement of these structures in the pathogenesis of SIDS. Morphometric and neurochemical changes have been found in the carotid body and brainstem respiratory chemoreceptors of SIDS victims, together with functional signs of chemoreception impairment in some clinical studies. However, the methodological problems of SIDS research will have to be addressed in the future, requiring large and highly standardized case series. Up‐to‐date autopsy protocols should be produced, involving substantial, and exhaustive sampling of all potentially involved structures (including peripheral arterial chemoreceptors). Morphometric approaches should include unbiased stereological methods with three‐dimensional probes. Prospective clinical studies addressing functional tests and risk factors (including genetic traits) would probably be the gold standard, allowing markers of intrinsic or acquired vulnerability to be properly identified.
MitoCPR—A surveillance pathway that protects mitochondria in response to protein import stress
Authors: Weidberg Hilla , Amon Angelika 
Published: April 2018

The mitoCPR unclogs mitochondria
The import of proteins into mitochondria is essential for cell viability. How cells respond when mitochondrial protein import is impaired is poorly understood. Weidberg and Amon showed that upon mitochondrial import stress, yeast cells mounted a response known as the mitoCPR. mitoCPR was activated when mitochondrial protein import was impaired and unimported precursors accumulated on the organelle's surface. mitoCPR restored mitochondrial functions by clearing stalled proteins from the import channels. It did this by inducing expression of Cis1, which recruited the adenosine triphosphatase Msp1 to import channels to remove unimported precursors and target them for degradation by the proteasome.

Science
, this issue p.
eaan4146
Plasticity of Aminoglycoside Binding to Antibiotic Kinase APH(2″)-Ia
Authors: Caldwell Shane J. , Berghuis Albert M. 
Published: April 2018

ABSTRACT
The APH(2″)-Ia aminoglycoside resistance enzyme forms the C-terminal domain of the bifunctional AAC(6′)-Ie/APH(2″)-Ia enzyme and confers high-level resistance to natural 4,6-disubstituted aminoglycosides. In addition, reports have suggested that the enzyme can phosphorylate 4,5-disubstituted compounds and aminoglycosides with substitutions at the N1 position. Previously determined structures of the enzyme with bound aminoglycosides have not indicated how these noncanonical substrates may bind and be modified by the enzyme. We carried out crystallographic studies to directly observe the interactions of these compounds with the aminoglycoside binding site and to probe the means by which these noncanonical substrates interact with the enzyme. We find that APH(2″)-Ia maintains a preferred mode of binding aminoglycosides by using the conserved neamine rings when possible, with flexibility that allows it to accommodate additional rings. However, if this binding mode is made impossible because of additional substitutions to the standard 4,5- or 4,6-disubstituted aminoglycoside architecture, as in lividomycin A or the N1-substituted aminoglycosides, it is still possible for these aminoglycosides to bind to the antibiotic binding site by using alternate binding modes, which explains the low rates of noncanonical phosphorylation activities seen in enzyme assays. Furthermore, structural studies of a clinically observed arbekacin-resistant mutant of APH(2″)-Ia revealed an altered aminoglycoside binding site that can stabilize an alternative binding mode for N1-substituted aminoglycosides. This mutation may alter and expand the aminoglycoside resistance spectrum of the wild-type enzyme in response to newly developed aminoglycosides.
Treating Anthrax-Induced Meningitis in Rabbits
Authors: Ben-Shmuel Amir , Glinert Itai , Sittner Assa , Bar-David Elad , Schlomovitz Josef , Brosh Tal , Kobiler David , Weiss Shay , Levy Haim 
Published: April 2018

ABSTRACT
Treatment of anthrax is challenging, especially during the advanced stages of the disease. Recently, the Centers for Disease Control and Prevention (CDC) updated its recommendations for postexposure prophylaxis and treatment of exposed populations (before and after symptom onset). These recommendations distinguished, for the first time, between systemic disease with and without meningitis, a common and serious complication of anthrax. The CDC considers all systemic cases meningeal unless positively proven otherwise. The treatment of patients suffering from systemic anthrax with suspected or confirmed meningitis includes the combination of three antibiotics, i.e., a fluoroquinolone (levofloxacin or ciprofloxacin), a β-lactam (meropenem or imipenem), and a protein synthesis inhibitor (linezolid or clindamycin). In addition, treatment with an antitoxin (anti-protective antigen antibodies) and dexamethasone should be applied. Since the efficacy of most of these treatments has not been demonstrated, especially in animal meningitis models, we developed an anthrax meningitis model in rabbits and tested several of these recommendations. We demonstrated that, in this model, ciprofloxacin, linezolid, and meropenem were ineffective as single treatments, while clindamycin was highly effective. Furthermore, combined treatments of ciprofloxacin and linezolid or ciprofloxacin and dexamethasone failed in treating rabbits with meningitis. We demonstrated that dexamethasone actually hindered blood-brain barrier penetration by antibiotics, reducing the effectiveness of antibiotic treatment of anthrax meningitis in this rabbit model.
SUN1 Regulates HIV-1 Nuclear Import in a Manner Dependent on the Interaction between the Viral Capsid and Cellular Cyclophilin A
Authors: Luo Xinlong , Yang Wei , Gao Guangxia 
Published: April 2018

ABSTRACT
Human immunodeficiency virus type 1 (HIV-1) can infect nondividing cells via passing through the nuclear pore complex. The nuclear membrane-imbedded protein SUN2 was recently reported to be involved in the nuclear import of HIV-1. Whether SUN1, which shares many functional similarities with SUN2, is involved in this process remained to be explored. Here we report that overexpression of SUN1 specifically inhibited infection by HIV-1 but not that by simian immunodeficiency virus (SIV) or murine leukemia virus (MLV). Overexpression of SUN1 did not affect reverse transcription but led to reduced accumulation of the 2-long-terminal-repeat (2-LTR) circular DNA and integrated viral DNA, suggesting a block in the process of nuclear import. HIV-1 CA was mapped as a determinant for viral sensitivity to SUN1. Treatment of SUN1-expressing cells with cyclosporine (CsA) significantly reduced the sensitivity of the virus to SUN1, and an HIV-1 mutant containing CA-G89A, which does not interact with cyclophilin A (CypA), was resistant to SUN1 overexpression. Downregulation of endogenous SUN1 inhibited the nuclear entry of the wild-type virus but not that of the G89A mutant. These results indicate that SUN1 participates in the HIV-1 nuclear entry process in a manner dependent on the interaction of CA with CypA.

IMPORTANCE
HIV-1 infects both dividing and nondividing cells. The viral preintegration complex (PIC) can enter the nucleus through the nuclear pore complex. It has been well known that the viral protein CA plays an important role in determining the pathways by which the PIC enters the nucleus. In addition, the interaction between CA and the cellular protein CypA has been reported to be important in the selection of nuclear entry pathways, though the underlying mechanisms are not very clear. Here we show that both SUN1 overexpression and downregulation inhibited HIV-1 nuclear entry. CA played an important role in determining the sensitivity of the virus to SUN1: the regulatory activity of SUN1 toward HIV-1 relied on the interaction between CA and CypA. These results help to explain how SUN1 is involved in the HIV-1 nuclear entry process.