bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carbonic anhydrase inhibition selectively prevents amyloid β neurovascular mitochondrial toxicity
Authors: Solesio María E. , Peixoto Pablo M. , Debure Ludovic , Madamba Stephen M. , de Leon Mony J. , Wisniewski Thomas , Pavlov Evgeny V. , Fossati Silvia 
Published: June 2018

SummaryMounting evidence suggests that mitochondrial dysfunction plays a causal role in the etiology and progression of Alzheimer's disease (AD). We recently showed that the carbonic anhydrase inhibitor (CAI) methazolamide (MTZ) prevents amyloid β (Aβ)‐mediated onset of apoptosis in the mouse brain. In this study, we used MTZ and, for the first time, the analog CAI acetazolamide (ATZ) in neuronal and cerebral vascular cells challenged with Aβ, to clarify their protective effects and mitochondrial molecular mechanism of action. The CAIs selectively inhibited mitochondrial dysfunction pathways induced by Aβ, without affecting metabolic function. ATZ was effective at concentrations 10 times lower than MTZ. Both MTZ and ATZ prevented mitochondrial membrane depolarization and H2O2 generation, with no effects on intracellular pH or ATP production. Importantly, the drugs did not primarily affect calcium homeostasis. This work suggests a new role for carbonic anhydrases (CAs) in the Aβ‐induced mitochondrial toxicity associated with AD and cerebral amyloid angiopathy (CAA), and paves the way to AD clinical trials for CAIs, FDA‐approved drugs with a well‐known profile of brain delivery.
The current status of multimodality treatment for unresectable locally advanced esophageal squamous cell carcinoma
Authors: Hirano Hidekazu , Boku Narikazu 
Published: June 2018

AbstractA multimodality approach plays a key role in the treatment of patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC). Currently, definitive chemoradiotherapy (dCRT) using 5‐fluorouracil (5‐FU) plus cisplatin with radiotherapy is the standard treatment in this population. dCRT regimens using 5‐FU plus leucovorin plus oxaliplatin (FOLFOX), and carboplatin plus paclitaxel have been investigated in prospective clinical trials. Anti‐epidermal growth factor receptor (EGFR) antibody has been evaluated in combination with dCRT; however, this combination has not revealed any additive benefits. Induction chemotherapy using docetaxel plus 5‐FU plus cisplatin has also been under investigation. Although long‐term survival and cure have been observed in some patients by dCRT, most patients experience local failure or distant metastasis and eventually die from the disease. Salvage surgery is an important option if the residual or recurrent tumors after dCRT can be resectable, but is associated with high postoperative morbidity and mortality. Introduction of radiotherapy using a new technique with dose escalation is expected to improve efficacy without increasing radiation‐related toxicities. Immunotherapy in combination with radiotherapy has also gathered attention. For the establishment of new and effective treatments in the field of unresectable locally advanced ESCC, a collaboration between clinical researchers and basic researchers is warranted.
International Constraints and Electoral Decisions: Does the Room to Maneuver Attenuate Economic Voting?
Authors: Kosmidis Spyros 
Published: June 2018

AbstractProminent studies of electoral accountability and economic voting suggest that government constraints and international financial structures decrease the economic vote. The proposed mechanism is often labeled as the “room to maneuver,” and it posits that because elected officials have limited space to propose and implement economic policy, politicians can shirk responsibility, and thus voters are less likely to place voting weights on the economy. However, results from elections that took place in Europe during the Great Recession and scholarly research on economic voting in these elections cast serious doubts on the causal mechanism. This article directly tests this mechanism with a survey experiment using data from Greece (the country most affected by the debt crisis). The results suggest that although the economic vote is strong and substantive, its size does not vary across the room to maneuver treatments. This finding informs the literature on economic voting and carries out important implications for party strategies with respect to exogenous policy impositions and their electoral effects.
Stakeholders' views and experiences of pharmacist prescribing: a systematic review
Authors: Jebara Tesnime , Cunningham Scott , MacLure Katie , Awaisu Ahmed , Pallivalapila Abdulrouf , Stewart Derek 
Published: June 2018

AimsThe aims of this systematic review were to: (1) critically appraise, synthesize and present the available evidence on the views and experiences of stakeholders on pharmacist prescribing and; (2) present the perceived facilitators and barriers for its global implementation.MethodsMedline, CINAHL, International Pharmaceutical Abstracts, PsychArticles and Google Scholar databases were searched. Study selection, quality assessment and data extraction were conducted independently by two reviewers. A narrative approach to data synthesis was undertaken due to heterogeneity, the nature of study types and outcome measures.ResultsSixty‐five studies were identified, mostly from the UK (n = 34), followed by Australia (n = 13), Canada (n = 6) and USA (n = 5). Twenty‐seven studies reported pharmacists' perspectives, with fewer studies focusing on patients' (n = 12), doctors' (n = 6), the general public's (n = 4), nurses' (n = 1), policymakers' (n = 1) and multiple stakeholders' (n = 14) perspectives. Most reported positive experiences and views, regardless of stage of implementation. The main benefits described were: ease of patient access to healthcare services, improved patient outcomes, better use of pharmacists' skills and knowledge, improved pharmacist job satisfaction, and reduced physician workload. Any lack of support for pharmacist prescribing was largely in relation to: accountability for prescribing, limited pharmacist diagnosis skills, lack of access to patient clinical records, and issues concerning organizational and financial support.ConclusionThere is an accumulation of global evidence of the positive views and experiences of diverse stakeholder groups and their perceptions of facilitators and barriers to pharmacist prescribing. There are, however, organizational issues to be tackled which may otherwise impede the implementation and sustainability of pharmacist prescribing.
Japanese Society of Medical Oncology Clinical Guidelines: Molecular Testing for Colorectal Cancer Treatment, Third Edition
Authors: Yamazaki Kentaro , Taniguchi Hiroya , Yoshino Takayuki , Akagi Kiwamu , Ishida Hideyuki , Ebi Hiromichi , Nakatani Kaname , Muro Kei , Yatabe Yasushi , Yamaguchi Kensei , Tsuchihara Katsuya 
Published: June 2018

The Japanese Society of Medical Oncology (JSMO) previously published 2 editions of the clinical guidelines: “Japanese guidelines for testing of KRAS gene mutation in colorectal cancer” in 2008 and “Japanese Society of Medical Oncology Clinical Guidelines: RAS (KRAS/NRAS) mutation testing in colorectal cancer patients” in 2014. These guidelines have contributed to the proper use of KRAS and RAS mutation testing, respectively. Recently, clinical utility, particularly for colorectal cancer (CRC) patients with BRAF V600E mutation or DNA mismatch‐repair (MMR) deficiency, has been established. Therefore, the guideline members decided these genetic alterations should also be involved. The aim of this revision is to properly carry out testing for BRAF V600E mutation and MMR deficiency in addition to RAS mutation. The revised guidelines include the basic requirements for testing for these genetic alterations based on recent scientific evidence. Furthermore, because clinical utility of comprehensive genetic testing using next‐generation sequencing and somatic gene testing of analyzing circulating tumor DNA has increasingly evolved with recent advancements in testing technology, we noted the current situation and prospects for these testing technologies and their clinical implementation in the revised guidelines.
CD47‐signal regulatory protein α signaling system and its application to cancer immunotherapy
Authors: Murata Yoji , Saito Yasuyuki , Kotani Takenori , Matozaki Takashi 
Published: June 2018

Tumor cells evade immune surveillance through direct or indirect interactions with various types of immune cell, with much recent attention being focused on modifying immune cell responses as the basis for the development of new cancer treatments. Signal regulatory protein α (SIRPα) and CD47 are both transmembrane proteins that interact with each other and constitute a cell‐cell communication system. SIRPα is particularly abundant in myeloid cells such as macrophages and dendritic cells, whereas CD47 is expressed ubiquitously and its expression level is elevated in cancer cells. Recent studies have shown that blockade of CD47‐SIRPα interaction enhances the phagocytic activity of phagocytes such as macrophages toward tumor cells in vitro as well as resulting in the efficient eradication of tumor cells in a variety of xenograft or syngeneic mouse models of cancer. Moreover, CD47 blockade has been shown to promote the stimulation of tumor‐specific cytotoxic T cells by macrophages or dendritic cells. Biological agents, such as Abs and recombinant proteins, that target human CD47 or SIRPα have been developed and are being tested in preclinical models of human cancer or in clinical trials with cancer patients. Preclinical studies have also suggested that CD47 or SIRPα blockade may have a synergistic antitumor effect in combination with immune checkpoint inhibitors that target the adaptive immune system. Targeting of the CD47‐SIRPα signaling system is thus a promising strategy for cancer treatment based on modulation of both innate and acquired immune responses to tumor cells.
Helping, Sharing, and Comforting in Young Children: Links to Individual Differences in Attachment
Authors: Beier Jonathan S. , Gross Jacquelyn T. , Brett Bonnie E. , Stern Jessica A. , Martin David R. , Cassidy Jude 
Published: June 2018

Although attachment theory has long posited a link between early experiences of care and children's prosocial behavior, investigations of this association have not embraced the multifaceted nature of prosociality. This study is the first to assess associations between child attachment and independent observations of helping, sharing, and comforting. Attachment quality in 3‐ to 5‐year‐old children (N = 137) was linked to all three prosocial behaviors. Additionally, bifactor analyses revealed distinct associations between attachment and children's general prosocial dispositions and their specific abilities to meet the unique challenges of helping and, marginally, comforting. These findings underscore the importance of considering multiple explanations for links between attachment and prosocial behavior and provide novel insights into sources of variation in children's prosociality.
Pulsus paradoxus
Authors: Sarkar Malay , Bhardwaj Rajeev , Madabhavi Irappa , Gowda Srinivas , Dogra Kushal 
Published: June 2018

AbstractObjectivesReviewed the etiologies, pathophysiologic mechanisms, detection and clinical significance of pulsus paradoxus in various conditions.Data sourceWe searched PubMed, EMBASE, and the CINAHL from inception to June 2017. We used the following search terms: Pulsus paradoxus, pericardial effusion, acute asthma, ventricular interdependence and so forth. All types of study were chosen.Results and conclusionLegendary physician Sir William Osler truly said that “Medicine is learned by the bedside and not in the classroom.” Bedside history taking and physical examination should be an integral component of clinical teaching curriculum imparted to medical students. Pulsus paradoxus is a valuable physical sign seen in many clinical conditions. Pulsus paradoxus is defined by an inspiratory fall in systolic blood pressure of greater than 10 mm Hg. Two prototype examples of pulsus paradoxus are cardiac tamponade and acute asthma. Exaggerated swings of intrapleural pressure, bi‐ventricular interactions and increase afterload of the left ventricle are few of the pathophysiological mechanisms involved in the causation of pulsus paradoxus. The sensitivity of pulsus paradoxus in the diagnosis of cardiac tamponade is very high. In acute asthma, it also correlates with the severity of airflow obstruction.
Prevalence and features of asthma‐COPD overlap in the United States 2007–2012
Authors: Mendy Angelico , Forno Erick , Niyonsenga Theophile , Carnahan Ryan , Gasana Janvier 
Published: June 2018

AbstractBackgroundPerceived to be distinct, asthma and chronic obstructive pulmonary disease (COPD) can co‐exist and potentially have a worse prognosis than the separate diseases. Yet, little is known about the exact prevalence and the characteristics of the Asthma‐COPD overlap (ACO) in the US population.AimsTo determine ACO prevalence in the United States, identify ACO predictors, examine ACO association with asthma and COPD severity, and describe distinctive spirometry and laboratory features of ACO.MethodsData on adult participants to the National Health and Nutrition Examination Surveys conducted from 2007 to 2012 was analyzed. ACO was defined as current asthma and post‐bronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) <0.7.ResultsOverall, 7,570 participants representing 98.58 million Americans were included in our study. From 2007 to 2012, the crude and age‐standardized ACO prevalence were, respectively, 0.96% (95% CI: 0.65%–1.26%) and 1.05% (0.74%–1.37%). In asthma, ACO predictors included older age, male gender, and smoking. In COPD, ACO predictors were non‐Hispanic Black race/ethnicity and obesity. ACO was associated with increased ER visits for asthma (OR = 3.46, 95% CI: 1.48–8.06]) and oxygen therapy in COPD (OR = 11.17, 95% CI: 5.17–24.12]). In spirometry, FEV1 and peak expiratory flow were lower in ACO than in asthma or COPD alone.ConclusionAge‐adjusted prevalence of ACO in the United States was 1.05% in 2007–2012, representing 0.94 (95% CI: 0.62–1.26) million Americans. It is much lower than previously reported. The overlap was associated with higher asthma and COPD severity as well as decreased lung function compared with COPD or asthma alone.
Prognostic evaluation of serum ferritin in acute exacerbation of idiopathic pulmonary fibrosis
Authors: Enomoto Noriyuki , Oyama Yoshiyuki , Enomoto Yasunori , Mikamo Masashi , Karayama Masato , Hozumi Hironao , Suzuki Yuzo , Kono Masato , Furuhashi Kazuki , Fujisawa Tomoyuki , Inui Naoki , Nakamura Yutaro , Suda Takafumi 
Published: June 2018

AbstractBackgroundAcute exacerbation of idiopathic pulmonary fibrosis (AE‐IPF) has an extremely poor prognosis. The role of ferritin in the pathogenesis of AE‐IPF is not well known while serum ferritin is a key prognostic indicator for patients with clinically amyopathic dermatomyositis with rapidly progressive interstitial pneumonia.ObjectiveTo elucidate the clinical importance of serum ferritin in patients with AE‐IPF.MethodsThirty‐seven patients (48 episodes), who were diagnosed with AE‐IPF and treated at our hospital between 1997 and 2015, were retrospectively studied.ResultsPatients with AE‐IPF had significantly higher levels of serum ferritin than baseline levels at the first diagnosis of IPF (P = 0.0017). Receiver operating characteristic analysis showed the cut‐off value 174 ng/mL for the separation of AE (area under the curve, 0.700). No patients with AE‐IPF were positive for anti‐ melanoma differentiation‐associated gene 5 antibody. Patients with AE‐IPF and higher ferritin (≥174 ng/mL) had lower %FVC and %DLCO before AE, and those with much higher ferritin (≥500 ng/mL) had significantly worse prognosis than those with lower ferritin (log‐rank, P = 0.024). Immunohistochemical staining in autopsy specimens showed alveolar macrophages that were producing ferritin. Finally, in multivariate Cox proportional hazards analyses, serum ferritin level of ≥500 ng/mL was a significant worse prognostic factor (hazard ratio 5.280, P = 0.046).ConclusionHigher serum ferritin may be related to a worse prognosis in patients with AE‐IPF.
What is psoriasis? – Perception and assessment of psoriasis among the German population
Authors: Sommer Rachel , Mrowietz Ulrich , Radtke Marc Alexander , Schäfer Ines , von Kiedrowski Ralph , Strömer Klaus , Enk Alexander , Maul Julia‐Tatjana , Reich Kristian , Zander Nicole , Augustin Matthias 
Published: June 2018

SummaryBackgroundDelivery of health care to psoriasis patients plays an important role in the field of dermatology. Following the 2014 WHO resolution and the 2016 WHO global report, there has been an increase in the awareness of psoriasis among the general public. However, the perception of psoriasis by the general population remains unclear. The goal of the present study was to investigate the perception and assessment of psoriasis among the German population.Patients and MethodsRepresentative telephone survey among 2,001 adults using a standardized questionnaire. Analyses with respect to place of residence, age, gender and level of education were conducted in a descriptive manner.ResultsTwenty‐nine percent of participants were familiar with the term “Psoriasis”; 86 %, with the German designation “Schuppenflechte”. Ninety‐three percent considered the disease to be a significant burden for affected individuals; 59 % stated that there were effective drugs available for psoriasis; 9 % considered the disease to be communicable. Ten percent reported that they would not want to live in the same household as an affected individual; 23 % did not want to share the same swimming pool; and 27 % did not want to be in a personal relationship with someone affected. Twelve percent stated to be familiar with the WHO resolution on psoriasis; 6 % with the World Psoriasis Day; and 3 % with the “Bitte berühren” (“Please touch”) campaign.ConclusionsAlthough a majority of the German population is familiar with the term “Schuppenflechte”, there is a significant lack of knowledge about the disease as well as prejudice toward affected individuals. Further measures are required to improve the level of information and decrease stigmatization.
Impact of red versus blue light on tolerability and efficacy of PDT: a randomized controlled trial
Authors: Gholam Patrick , Bosselmann Ina , Enk Alexander , Fink Christine 
Published: June 2018

SummaryVarious light sources may be used for photodynamic therapy of actinic keratosis since photosensitizing agents are activated by different wavelengths. However, the relative impact of red and blue light irradiation on the efficacy and tolerability of therapy is controversial.ObjectiveThe aim of this study is to compare the efficacy and tolerability of therapy with red versus blue light sources, as well as the patients’ evaluation of cosmetic results, clinical response, painfulness and preferred light source for future photodynamic treatments.MethodsThis is a prospective, single‐center, randomized, controlled, open‐label study with 28 patients undergoing elective photodynamic therapy.ResultsRed and blue light sources both showed very good results with a complete response rate of 84 % and 85 % respectively. Pain during photodynamic therapy was 6.1 vs. 5.4 (and 2.1 vs. 1.5 eight hours after therapy) on the visual analogue scale. Although these differences were statistically significant, the clinical relevance is low, since the number of therapy interruptions were equally distributed in both groups, and patients’ subjective evaluation of the treatment showed no personal preference towards the light sources.ConclusionBoth light sources showed very good clinical results and satisfactory tolerability in this study.
Differential diagnostic significance of epithelial and stromal CD10 expression in tumors of trichogenic origin
Authors: Kneitz Hermann , Fetzer Stefanie , Goebeler Matthias , Bröcker Eva‐Bettina 
Published: June 2018

SummaryBackground and objectivesThe histological differential diagnosis between benign trichogenic skin tumors and basal cell carcinoma may be challenging. We therefore set out to investigate whether expression of CD10, a cell surface protein with neutral endopeptidase activity, might be a suitable marker for the histological differential diagnosis of trichogenic skin tumors.Patients and methodsWe immunohistochemically analyzed 119 cases of benign trichogenic skin tumors and basal cell carcinoma. These included 28 nodular and 15 sclerosing basal cell carcinomas, 21 Pinkus tumors, 20 trichoblastomas, nine trichofolliculomas, eleven trichoepitheliomas, five desmoplastic trichoepitheliomas, and ten seborrheic keratoses.ResultsThe majority of nodular basal cell carcinomas expressed CD10 in tumor cells at the peripheral (22/28 [75 %]). On the other hand, trichoblastomas revealed peripheral CD10 expression in only 10 % (2/20) of cases, whereas 50 % showed central expression (10/20). Peripheral epithelial expression of CD10 was also found in Pinkus tumors (9/21 [42.9 %]) and trichoepithelioma (4/11 [36.4 %]). Desmoplastic trichoepithelioma showed no tumoral CD10 expression at all (0/5 [0 %]), while the majority of sclerosing basal cell carcinomas was positive for CD10 (13/15 [86.7 %]).ConclusionsOur findings suggest that epithelial expression of CD10 – and not peritumoral stromal CD10 expression, as has been postulated – may well be of differential diagnostic significance. The pattern of distribution of CD10‐positive neoplastic cells in particular can be useful in the diagnosis of trichogenic tumors.
Differenzialdiagnostische Bedeutung epithelialer und stromaler CD10‐Expression in Tumoren trichogenen Ursprungs
Authors: Kneitz Hermann , Fetzer Stefanie , Goebeler Matthias , Bröcker Eva‐Bettina 
Published: June 2018

ZusammenfassungHintergrund und ZieleDie histologische Differenzialdiagnose zwischen benignen trichogenen Hauttumoren und dem Basalzellkarzinom ist mitunter schwierig. Wir untersuchten in der vorliegenden Arbeit, ob CD10, ein Zelloberflächenprotein mit neutraler Endopeptidaseaktivität, ein geeigneter Marker für die histologische Differenzialdiagnose trichogener Hauttumoren sein könnte.Patienten und Methodik119 trichogene Hauttumoren und Basalzellkarzinome wurden immunhistologisch analysiert. Im Einzelnen handelte es sich um 28 solide und 15 sklerodermiforme Basalzellkarzinome, 21 Pinkus‐Tumoren, 20 Trichoblastome, neun Trichofollikulome, elf Trichoepitheliome, fünf desmoplastische Trichoepitheliome und zehn seborrhoische Keratosen.ErgebnisseDas solide Basalzellkarzinom exprimierte in den randständigen Zellen CD10 (22/28 [75 %]), während Trichoblastome nur in 10 % der Fälle (2/20) eine randständige Expression von CD10 aufwiesen und häufiger eine zentrale Expression zeigten (10/20 [50 %]). Eine randständige epitheliale Expression von CD10 war auch in Pinkus‐Tumoren (9/21 [42,9 %]) und Trichoepitheliomen (4/11 [36,4 %]) zu finden. Im desmoplastischen Trichoepitheliom war keine CD10‐Expression in den Tumorzellen zu erkennen (0/5 [0 %]), während die meisten sklerodermiformen Basalzellkarzinome CD10‐positiv waren.SchlussfolgerungenDie Befunde zeigen, dass eine epitheliale CD10–Expression durchaus eine differenzialdiagnostische Bedeutung hat, nicht aber, wie in der Literatur postuliert, die peritumorale, stromale Immunreaktivität. Besonders das Verteilungsmuster der CD10‐positiven Tumorzellen in trichogenen Tumoren kann eine diagnostische Hilfe sein.