bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pro-Resolution Potency of Resolvins D1, D2 and E1 on Neutrophil Migration and in Dermal Wound Healing
Authors: Menon Riyesh , Krzyszczyk Paulina , Berthiaume François 
Published: February 2017

An exuberant inflammatory response may exacerbate the primary tissue damage caused by injuries to the skin due to burns, surgery, excessive pressure, and other etiologies, thus increasing the time to heal. We hypothesized that application of factors that decrease inflammation would allow the skin to more quickly restore its barrier function, and promote the return to homeostasis. Resolvins are endogenous, pro-resolving lipid mediators derived from omega-3 fatty acids that serve to inhibit neutrophil migration and enhance macrophage phagocytosis, thus promoting the resolution of inflammation and the beginning of the proliferative phase of wound healing. Resolvins are derived either from docosahexaenoic (D-series) or eicosapentaenoic (E-series) acid. Herein, we compare the effects of resolvins D1 (RvD1), D2 (RvD2) and E1 (RvE1) on their abilities to inhibit neutrophil migration in vitro and to promote wound healing in vivo. In Transwell experiments, all resolvins inhibited neutrophil migration, with RvE1 being the most effective at a 2000[Formula: see text]nM concentration. In an in vivo murine excisional wound (1[Formula: see text]cm[Formula: see text][Formula: see text][Formula: see text]1[Formula: see text]cm) healing model, topically applied resolvins accelerated wound closure. RvE1-treated wounds healed by 19.4[Formula: see text][Formula: see text][Formula: see text]1.5 days post-wounding, which was significantly shorter than the RvD2-treated and RvD1-treated groups ([Formula: see text]0.05), which closed by an average of 22.8[Formula: see text][Formula: see text][Formula: see text]1.8 and 24.4[Formula: see text][Formula: see text][Formula: see text]2.2 days, respectively. Furthermore, all resolvin-treated groups healed faster than vehicle controls ([Formula: see text]0.05), which closed at 28.6[Formula: see text][Formula: see text][Formula: see text]1.5 days. There was a strong linear correlation ([Formula: see text]0.9384) between each resolvin’s potency in inhibiting neutrophil migration in vitro versus accelerating wound healing in vivo. Furthermore, upon histological analysis, the RvE1-treated group exhibited more mature collagen organization and re-epithelialization.
Temporal dissociation between the minimal distal-to-aortic pressure ratio and peak hyperemia during intravenous adenosine infusion
Authors: Casadonte Lorena , Marques Koen M. , Spaan Jos A. E. , Siebes Maria 
Published: February 2017

The present study sought to compare the temporal relation between maximal coronary flow (peak hyperemia) and minimal coronary-to-aortic pressure ratio (Pd/Pa) for intracoronary (IC) and intravenous (IV) adenosine administration. Peak hyperemia is assumed to coincide with the minimal Pd/Pa value. However, this has not been confirmed for systemic hemodynamic variations during IV adenosine infusion. Hemodynamic responses to IV and IC adenosine administration were obtained in 12 patients (14 lesions) using combined IC pressure and flow velocity measurements. A fluid dynamic model was used to predict the change in Pd/Pa for different stenosis severities and varying Pa. Hemodynamic variability during IV adenosine hyperemia was greater than during IC adenosine, as assessed by the coefficient of variation. During IV adenosine, flow velocity peaked 28 ± 4 (SE) s after the onset of hyperemia, while Pd/Pa reached a minimum (0.82 ± 0.01) 22 ± 7 s later ( P < 0.05), when Pa had declined by 6.1% and hyperemic velocity by 4.5% ( P < 0.01). Model outcomes corroborated the role of variable Pa in this dissociation. In contrast, maximal flow and minimal Pd/Pa coincided for IC adenosine, with IV-equivalent peak velocities and a higher Pd/Pa ratio (0.86 ± 0.01, P < 0.01). Hemodynamic variability during continuous IV adenosine infusion can lead to temporal dissociation of minimal Pd/Pa and peak hyperemia, in contrast to IC adenosine injection, where maximal velocity and minimal Pd/Pa coincide. Despite this variability, stenosis hemodynamics remained stable with both ways of adenosine administration. Our findings suggest advantages of IC over IV adenosine to identify maximal hyperemia from pressure-only measurements. NEW & NOTEWORTHY Systemic hemodynamic variability during intravenous adenosine infusion produces substantial temporal dissociation between peak hyperemia appraised by coronary flow velocity and the minimal distal-to-aortic pressure ratio commonly used to determine functional stenosis severity. This dissociation was absent for intracoronary adenosine administration and tended to be mitigated in patients receiving Ca2+ antagonists.
Quantitative MRI volumetry, diffusivity, cerebrovascular flow, and cranial hydrodynamics during head-down tilt and hypercapnia: the SPACECOT study
Authors: Kramer Larry A. , Hasan Khader M. , Sargsyan Ashot E. , Marshall-Goebel Karina , Rittweger Jörn , Donoviel Dorit , Higashi Saki , Mwangi Benson , Gerlach Darius A. , Bershad Eric M. ,   SPACECOT Investigators Group
Published: February 2017

To improve the pathophysiological understanding of visual changes observed in astronauts, we aimed to use quantitative MRI to measure anatomic and physiological responses during a ground-based spaceflight analog (head-down tilt, HDT) combined with increased ambient carbon dioxide (CO2). Six healthy, male subjects participated in the double-blinded, randomized crossover design study with two conditions: 26.5 h of −12° HDT with ambient air and with 0.5% CO2, both followed by 2.5-h exposure to 3% CO2. Volume and mean diffusivity quantification of the lateral ventricle and phase-contrast flow sequences of the internal carotid arteries and cerebral aqueduct were acquired at 3 T. Compared with supine baseline, HDT (ambient air) resulted in an increase in lateral ventricular volume ( P = 0.03). Cerebral blood flow, however, decreased with HDT in the presence of either ambient air or 0.5% CO2( P = 0.002 and P = 0.01, respectively); this was partially reversed by acute 3% CO2exposure. Following HDT (ambient air), exposure to 3% CO2increased aqueductal cerebral spinal fluid velocity amplitude ( P = 0.01) and lateral ventricle cerebrospinal fluid (CSF) mean diffusivity ( P = 0.001). We concluded that HDT causes alterations in cranial anatomy and physiology that are associated with decreased craniospinal compliance. Brief exposure to 3% CO2augments CSF pulsatility within the cerebral aqueduct and lateral ventricles.NEW & NOTEWORTHY Head-down tilt causes increased lateral ventricular volume and decreased cerebrovascular flow after 26.5 h. Additional short exposure to 3% ambient carbon dioxide levels causes increased cerebrovascular flow associated with increased cerebrospinal fluid pulsatility at the cerebral aqueduct. Head-down tilt with chronically elevated 0.5% ambient carbon dioxide and acutely elevated 3% ambient carbon dioxide causes increased mean diffusivity of cerebral spinal fluid within the lateral ventricles.
WNT/β-Catenin Directs Self-Renewal Symmetric Cell Division of hTERThigh Prostate Cancer Stem Cells
Authors: Zhang Kai , Guo Yanjing , Wang Xue , Zhao Huifang , Ji Zhongzhong , Cheng Chaping , Li Li , Fang Yuxiang , Xu Dawei , Zhu Helen He , Gao Wei-Qiang 
Published: February 2017

Abstract
Cancer stem-like cells (CSC) drive cancer progression and recurrence. Self-renewal expansion of CSC is achieved through symmetric cell division, yet how external stimuli affect intracellular regulatory programs of CSC division modes and stemness remains obscure. Here, we report that the hTERThigh prostate cancer cells exhibit CSC properties, including a stem cell–associated gene expression signature, long-term tumor-propagating capacity and epithelial-to-mesenchymal transition. In promoting the self-renewal symmetric division of hTERThigh prostate cancer cells, WNT3a dramatically decreased the ratio of hTERThigh prostate cancer cells undergoing asymmetric division. Increased WNT/β-catenin signal activation was also detected in hTERThigh prostate cancer cells. hTERT-mediated CSC properties were at least partially dependent on β-catenin. These findings provide novel cellular and molecular mechanisms for the self-renewal of CSC orchestrated by tumor microenvironmental stimuli and intracellular signals. Cancer Res; 77(9); 2534–47. ©2017 AACR.
Genetic Manipulation of Helicobacter pylori Virulence Function by Host Carcinogenic Phenotypes
Authors: Suarez Giovanni , Romero-Gallo Judith , Sierra Johanna C. , Piazuelo M. Blanca , Krishna Uma S. , Gomez Martin A. , Wilson Keith T. , Peek Richard M. 
Published: February 2017

Abstract
Helicobacter pylori is the strongest risk factor for gastric adenocarcinoma, yet only a minority of infected persons ever develop this malignancy. One cancer-linked locus is the cag type 4 secretion system (cagT4SS), which translocates an oncoprotein into host cells. A structural component of the cagT4SS is CagY, which becomes rapidly altered during in vivo adaptation in mice and rhesus monkeys, rendering the cagT4SS nonfunctional; however, these models rarely develop gastric cancer. We previously demonstrated that the H. pylori cag+ strain 7.13 rapidly induces gastric cancer in Mongolian gerbils. We now use this model, in conjunction with samples from patients with premalignant lesions, to define the effects of a carcinogenic host environment on the virulence phenotype of H. pylori to understand how only a subset of infected individuals develop cancer. H. pylori cagY sequence differences and cagT4SS function were directly related to the severity of inflammation in human gastric mucosa in either a synchronous or metachronous manner. Serial infections of Mongolian gerbils with H. pylori strain 7.13 identified an oscillating pattern of cagT4SS function. The development of dysplasia or cancer selected for attenuated virulence phenotypes, but robust cagT4SS function could be restored upon infection of new hosts. Changes in the genetic composition of cagY mirrored cagT4SS function, although the mechanisms of cagY alterations differed in human isolates (mutations) versus gerbil isolates (addition/deletion of motifs). These results indicate that host carcinogenic phenotypes modify cagT4SS function via altering cagY, allowing the bacteria to persist and induce carcinogenic consequences in the gastric niche. Cancer Res; 77(9); 2401–12. ©2017 AACR.
Lapatinib Resistance in Breast Cancer Cells Is Accompanied by Phosphorylation-Mediated Reprogramming of Glycolysis
Authors: Ruprecht Benjamin , Zaal Esther A. , Zecha Jana , Wu Wei , Berkers Celia R. , Kuster Bernhard , Lemeer Simone 
Published: February 2017

AbstractHER2/ERBB2–overexpressing breast cancers targeted effectively by the small-molecule kinase inhibitor lapatinib frequently acquire resistance to this drug. In this study, we employed explorative mass spectrometry to profile proteome, kinome, and phosphoproteome changes in an established model of lapatinib resistance to systematically investigate initial inhibitor response and subsequent reprogramming in resistance. The resulting dataset, which collectively contains quantitative data for &gt;7,800 proteins, &gt;300 protein kinases, and &gt;15,000 phosphopeptides, enabled deep insight into signaling recovery and molecular reprogramming upon resistance. Our data-driven approach confirmed previously described mechanisms of resistance (e.g., AXL overexpression and PIK3 reactivation), revealed novel pharmacologically actionable targets, and confirmed the expectation of significant heterogeneity in molecular resistance drivers inducing distinct phenotypic changes. Furthermore, our approach identified an extensive and exclusively phosphorylation-mediated reprogramming of glycolytic activity, supported additionally by widespread changes of corresponding metabolites and an increased sensitivity towards glycolysis inhibition. Collectively, our multi-omic analysis offers deeper perspectives on cancer drug resistance and suggests new biomarkers and treatment options for lapatinib-resistant cancers. Cancer Res; 77(8); 1842–53. ©2017 AACR.
Comparison of Carotid‐Femoral and Brachial‐Ankle Pulse‐Wave Velocity in Association With Target Organ Damage in the Community‐Dwelling Elderly Chinese: The Northern Shanghai Study
Authors: Lu Yuyan , Zhu Mengyun , Bai Bin , Chi Chen , Yu Shikai , Teliewubai Jiadela , Xu Henry , Wang Kai , Xiong Jing , Zhou Yiwu , Ji Hongwei , Fan Ximin , Yu Xuejing , Li Jue , Blacher Jacques , Zhang Yi , Xu Yawei 
Published: February 2017

Background
Carotid‐femoral pulse‐wave velocity (cf‐PWV) and brachial‐ankle PWV (ba‐PWV) are the 2 most frequently applied PWV measurements. However, little is known about the comparison of hypertensive target organ damage (TOD) with cf‐PWV and ba‐PWV.

Methods and Results

A total of 1599 community‐dwelling elderly subjects (age >65 years) in northern Shanghai were recruited from June 2014 to August 2015. Both cf‐PWV and ba‐PWV were measured using SphygmoCor and VP1000 systems, respectively. Within the framework of comprehensive cardiovascular examinations, risk factors were assessed, and asymptomatic TOD, including left ventricular mass index, peak transmitral pulsed Doppler velocity/early diastolic tissue Doppler velocity (E/Ea), carotid intima‐media thickness, arterial plaque, creatinine clearance rate, and urinary albumin‐creatinine ratio were all evaluated. Both PWVs were significantly associated with male sex, age, waist/hip circumference, fasting plasma glucose, and systolic blood pressure, and ba‐PWV was also significantly related to body mass index. Both PWVs were significantly correlated with most TOD. When cf‐PWV and ba‐PWV were both or separately put into the stepwise linear regression model together with cardiovascular risk factors and treatment, only cf‐PWV, but not ba‐PWV, was significantly associated with carotid intima‐media thickness and creatinine clearance rate (
P
<0.05). When cf‐PWV and ba‐PWV were both or separately put into the same full‐mode model after adjustment for confounders, only cf‐PWV, but not ba‐PWV, showed significant association with carotid intima‐media thickness and creatinine clearance rate (
P
<0.05). Similar results were observed in logistic regression analysis.

Conclusions
Taken together, in the community‐dwelling elderly Chinese, cf‐PWV seems to be more closely associated with hypertensive TOD, especially vascular and renal TOD, as compared with ba‐PWV.

Clinical Trial Registration

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02368938.
Information depends on context: behavioural response to chemical signals depends on sex and size in crayfish contests
Authors: Wofford Sarah J. , LaPlante Phillip M. , Moore Paul A. 
Published: February 2017

Securing information about oneself or an opponent can be crucial to update the likelihood of winning a contest and the relative costs of continuing or escalating. This information can subsequently reduce costly errors. However, information encoded in signals exchanged by opponents can differ based on context. We sought to unravel these differences by pairing male and female crayfish (Orconectes rusticus) under varying sex and size conditions. A pre-optimized technique was used to visualize a well-studied contest signal in crayfish (i.e., urine). Behavioural responses were quantified prior to and after the release of that signal. There was a characteristic de-escalation of behavioural intensity after an opponent released urine. However, behavioural changes after the release event were dependent on the sex and the relative size of the opponents. Urine also significantly altered both sender and receiver behaviour, but lack of behavioural differences suggests urine plays a role in both opponent and auto-communication.
Featured Article: Pharmacological postconditioning with delta opioid attenuates myocardial reperfusion injury in isolated porcine hearts
Authors: Seewald Maria , Coles James A , Sigg Daniel C , Iaizzo Paul A 
Published: February 2017

Ischemic preconditioning has been utilized to protect the heart from ischemia prior to ischemia onset, whereas postconditioning is employed to minimize the consequences of ischemia at the onset of reperfusion. The underlying mechanisms and pathways of ischemic pre- and postconditioning continue to be investigated as therapeutic targets. We evaluated the administration of a delta opioid agonist or cariporide on various parameters associated with myocardial reperfusion injury upon reperfusion of isolated porcine hearts. The hearts were reperfused in vitro with a Krebs buffer containing either: (1) 1 µM Deltorphin D (delta opioid specific agonist, n = 6); (2) 3 µM cariporide (sodium–hydrogen exchange inhibitor, n = 4); or (3) no treatment (control, n = 6). Subsequently, postischemic hemodynamic performance, arrhythmia burden, relative tissue perfusion, and development of necrosis were assessed over a 2 h reperfusion period. Postconditioning with Deltorphin D significantly improved diastolic relaxation (Tau, P < 0.05 versus controls) and decreased the incidence of ventricular arrhythmias during early reperfusion. Additionally, these treated hearts demonstrated increased tissue perfusion after 2 h ( P < 0.05 versus controls), suggesting improved microvascular function. Delta opioid agonists elicited the potential to attenuate reperfusion injury, suggesting a postconditioning effect of these agents. We hypothesize that the induced benefits of delta opioids, in part, are associated with decreased calcium influx on reperfusion, independent of sodium–hydrogen exchange inhibition. Such agents may have a potential role in minimizing reperfusion injury associated with coronary stenting, bypass surgery, myocardial infarction, cardiac transplantation, or with the utilization of heart preservation systems. Impact statement In this study, we found that postconditioning with Deltorphin D significantly improved diastolic relaxation and decreased the incidence of ventricular arrhythmias during early reperfusion. Furthermore, these treated hearts demonstrated increased tissue perfusion after 2 h, suggesting improved microvascular function. Delta opioid agonists attenuated reperfusion injury, suggestive of a postconditioning effect. Such agents may have a potential role in minimizing reperfusion injury associated with coronary stenting, bypass surgery, myocardial infarction, cardiac transplantation, or with the utilization of heart preservation systems.
Necrotizing Cutaneous Fungal Infection of the Breast in a Patient with Breast Implants
Authors: Velazco Cristine S , Mahabir Raman C , Kusne Shimon , Dicaudo David J , Gray Richard J 
Published: February 2017

Breast fungal infections are rare in nonlactating women. The present report is the first to describe a necrotizing cutaneous breast fungal infection. A 50-year-old woman with a remote history of breast cancer and autologous tissue reconstruction presented with a progressive cutaneous necrotic infection one year after implant augmentation of the reconstruction. Multiple eschars developed on the left breast, and pathological examination of debrided tissue revealed numerous fungal hyphae invading the epidermis, dermis and adipose tissue of the breast. Fungal cultures yielded Bipolaris species. She was treated with voriconazole. Five months later, the patient presented with an eschar on her back, indicative of disseminated disease. Bipolaris species are dematiaceous fungi; cutaneous or disseminated infections with Bipolaris species have rarely been reported in immunocompetent patients. Unresectable or recurrent lesions should be treated with antifun-gals. Cutaneous necrotizing breast fungal infections should be considered in patients who do not respond to antibacterial therapy.
Variations Among Physicians in Hospice Referrals of Patients With Advanced Cancer
Authors: Wang Xiao , Knight Louise S. , Evans Anne , Wang Jiangxia , Smith Thomas J. 
Published: February 2017

Purpose:The benefits of hospice for patients with end-stage disease are well established. Although hospice use is increasing, a growing number of patients are enrolled for ≤ 7 days, a marker of poor quality of care and patient and family dissatisfaction. In this study, we examined variations in referrals among individuals and groups of physicians to assess a potential source of suboptimal hospice use.Methods:We conducted a retrospective chart review of 452 patients with advanced cancer referred to hospice from a comprehensive cancer center. We analyzed patient length of service (LOS) under hospice care, looking specifically at median LOS and percent of short enrollments (%LOS ≤ 7), to examine the variation between individual oncologists and divisions of oncologists.Results:Of 394 successfully referred patients, median LOS was 14.5 days and %LOS ≤ 7 was 32.5%, consistent with national data. There was significant interdivisional variation in LOS, both by overall distribution and %LOS ≤ 7 ( P < .01). In addition, there was dramatic variation in median LOS by individual physician (range, 4 to 88 days for physicians with five or more patients), indicating differences in hospice referral practices between providers (coefficient of variation > 125%). As one example, median LOS of physicians in the Division of Thoracic Malignancies varied from 4 to 33 days, despite similarities in patient population.Conclusion:Nearly one in three patients with cancer who used hospice had LOS ≤ 7 days, a marker of poor quality. There was significant LOS variability among different divisions and different individual physicians, suggesting a need for increased education and training to meet recommended guidelines.
Microtubule-associated protein-4 controls nanovesicle dynamics and T cell activation
Authors: Bustos-Morán Eugenio , Blas-Rus Noelia , Martin-Cófreces Noa Beatriz , Sánchez-Madrid Francisco 
Published: February 2017

ABSTRACT
The immune synapse (IS) is a specialized structure formed at the contact area between T lymphocytes and antigen-presenting cells (APCs) that is essential for the adaptive immune response. Proper T cell activation requires its polarization towards the APC, which is highly dependent on the tubulin cytoskeleton. Microtubule-associated protein-4 (MAP4) is a microtubule (MT)-stabilizing protein that controls MTs in physiological processes, such as cell division, migration, vesicular transport or primary cilia formation. In this study, we assessed the role of MAP4 in T cell activation. MAP4 decorates the pericentrosomal area and MTs of the T cell, and it is involved in MT detyrosination and stable assembly in response to T cell activation. In addition, MAP4 prompts the timely translocation of the MT-organizing center (MTOC) towards the IS and the dynamics of signaling nanovesicles that sustains T cell activation. However, MAP4 acts as a negative regulator of other T cell activation-related signals, including diacylglycerol (DAG) production and IL2 secretion. Our data indicate that MAP4 acts as a checkpoint molecule that balances positive and negative hallmarks of T cell activation.
The New Form No. 2-Audit: What Is Good, What Is Bad
Authors: Гутцайт  , Guttsayt E. 
Published: February 2017

The article discusses a new variant Form of Federal statistical monitoring No. 2-audit «Information on audit
activity», approved by Rosstat on November 23, 2016. Constituent indicators, its advantages and disadvantages, its
differences from the previous version of this form are analyzed. Proposals for further improvement of this form are given.