bluuebunny/crossref_metadata_2025_split huggingface dataset:
EuroHYP-1: European Multicenter, Randomized, Phase III Clinical Trial of Therapeutic Hypothermia plus Best Medical Treatment vs. Best Medical Treatment Alone for Acute Ischemic Stroke
Authors: van der Worp H. Bart , Macleod Malcolm R. , Bath Philip M. W. , Demotes Jacques , Durand-Zaleski Isabelle , Gebhardt Bernd , Gluud Christian , Kollmar Rainer , Krieger Derk W. , Lees Kennedy R. , Molina Carlos , Montaner Joan , Roine Risto O. , Petersson Jesper , Staykov Dimitre , Szabo Istvan , Wardlaw Joanna M. , Schwab Stefan 
Published: May 2014

Rationale Cooling reduced infarct size and improved neurological outcomes in animal studies modeling ischemic stroke, and also improved outcome in randomized clinical trials in patients with hypoxic-ischemic brain injury after cardiac arrest. Cooling awake patients with ischemic stroke has been shown feasible in phase II clinical trials. Primary aim To determine whether systemic cooling to a target body temperature between 34·0 and 35·0°C, started within six-hours of symptom onset and maintained for 24 h, improves functional outcome at three-months in patients with acute ischemic stroke. Design International, multicenter, phase III, randomized, open-label clinical trial with blinded outcome assessment in 1500 patients aged 18 years or older with acute ischemic stroke and a National Institutes of Health Stroke Scale score of 6 up to and including 18. In patients randomized to hypothermia, cooling to a target body temperature of 34–35°C will be started within six-hours after symptom onset with rapid intravenous infusion of refrigerated normal saline or a surface cooling technique and maintained for 24 h with a surface or endovascular technique. Patients randomized to hypothermia will receive pethidine and buspirone to prevent shivering and discomfort. Primary outcome Score on the modified Rankin Scale at 91 days, as analyzed with ordinal logistic regression and expressed as a common odds ratio. Discussion With 750 patients per intervention group, this trial has 90% power to detect 7% absolute improvement at the 5% significance level. The full trial protocol is available at http://www.eurohyp1.eu . ClinicalTrials.gov Identifier: NCT01833312.
Prenatal depression and 5‐HTTLPR interact to predict dysregulation from 3 to 36 months – A differential susceptibility model
Authors: Babineau Vanessa , Green Cathryn Gordon , Jolicoeur‐Martineau Alexis , Bouvette‐Turcot Andrée‐Anne , Minde Klaus , Sassi Roberto , St‐André Martin , Carrey Normand , Atkinson Leslie , Kennedy James L. , Lydon John , Steiner Meir , Gaudreau Helene , Levitan Robert , Meaney Michael , Wazana Ashley ,   the MAVAN project
Published: May 2014

BackgroundChildhood dysregulation, which reflects deficits in the capacity to regulate or control one's thoughts, emotions and behaviours, is associated with psychopathology throughout childhood and into adulthood. Exposures to adversity during the prenatal period, including prenatal depression, can influence the development of dysregulation, and a number of candidate genes have been suggested as moderators of prenatal exposure, including polymorphisms in the promoter region of the serotonin transporter gene (5‐HTTLPR). We examined whether prenatal depression and child 5‐HTTLPR interact to predict childhood dysregulation.MethodSample of N = 213 mother–child pairs from the Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) project. Mothers reported the IBQ‐R at 3 and 6 months, and the ECBQ at 18 and 36 months, from which measures of dysregulation were extracted. Mothers' self‐reported symptoms of depression on the CES‐D at 24–36 weeks of gestation, and at 6, 12, 24 and 36 months postnatal. 5‐HTTLPR genotype was extracted from buccal swabs. Mixed‐model and confirmatory analyses were conducted.ResultsPrenatal depression and 5‐HTTLPR interacted to predict dysregulation from 3 to 36 months, within a model of strong differential susceptibility.ConclusionChildren with S or LG alleles, when exposed to prenatal depression, have higher levels of dysregulation, and when exposed to lower or little prenatal depression, have higher capacity for regulation. Our findings support efforts to identify, support and treat prenatal depression.
Cross-Sex Hormone Therapy in Trans Persons Is Safe and Effective at Short-Time Follow-Up: Results from the European Network for the Investigation of Gender Incongruence
Authors: Wierckx Katrien , Van Caenegem Eva , Schreiner Thomas , Haraldsen Ira , Fisher Alessandra , Toye Kaatje , Kaufman Jean Marc , T'Sjoen Guy 
Published: May 2014

Abstract

Introduction
Data on the effects of cross-sex hormone therapy (CHT) are limited due to the low prevalence of gender dysphoria, small number of subjects treated at each center, lack of prospective studies, and wide variations in treatment modalities.

Aim
The aim of this study is to report the short-term effects of CHT on hormonal and clinical changes, side effects, and adverse events in trans men (female-to-male gender dysphoric persons) and trans women (male-to-female gender dysphoric persons).

Methods
This was a multicenter 1-year prospective study in 53 trans men and 53 trans women. Trans men received injections of testosterone undecanoate every 3 months. Trans women younger than 45 years received 50 mg cyproterone acetate (CA) and 4 mg estradiol valerate daily, whereas those older than 45 years received 50 mg CA daily together with 100 μg/24 hours transdermal 17-β estradiol.

Main Outcome Measures
Sex steroids, prolactin, liver enzymes, lipids, hematocrit, blood pressure, anthropometrics, Ferriman and Gallwey score, and global acne grading scale were measured. Side effects, adverse events, and desired clinical changes were examined.

Results
No deaths or severe adverse events were observed. Two trans men developed erythrocytosis, and two had transient elevation of the liver enzymes. Trans men reported an increase in sexual desire, voice instability, and clitoral pain (all P ≤ 0.01). Testosterone therapy increased acne scores, facial and body hair, and prevalence of androgenetic alopecia. Waist–hip ratio, muscle mass, triglycerides, total cholesterol (C), and LDL-C increased, whereas total body fat mass and HDL-C decreased. Three trans women experienced transient elevation of liver enzymes. A significant increase in breast tenderness, hot flashes, emotionality, and low sex drive was observed (all P ≤ 0.02). Fasting insulin, total body fat mass, and prolactin levels increased, and waist–hip ratio, lean mass, total C, and LDL-C decreased.

Conclusions
Current treatment modalities were effective and carried a low risk for side effects and adverse events at short-time follow-up.
Which is a better predictor of plant traits: temperature or precipitation?
Authors: Moles Angela T. , Perkins Sarah E. , Laffan Shawn W. , Flores‐Moreno Habacuc , Awasthy Monica , Tindall Marianne L. , Sack Lawren , Pitman Andy , Kattge Jens , Aarssen Lonnie W. , Anand Madhur , Bahn Michael , Blonder Benjamin , Cavender‐Bares Jeannine , Cornelissen J. Hans C. , Cornwell Will K. , Díaz Sandra , Dickie John B. , Freschet Grégoire T. , Griffiths Joshua G. , Gutierrez Alvaro G. , Hemmings Frank A. , Hickler Thomas , Hitchcock Timothy D. , Keighery Matthew , Kleyer Michael , Kurokawa Hiroko , Leishman Michelle R. , Liu Kenwin , Niinemets Ülo , Onipchenko Vladimir , Onoda Yusuke , Penuelas Josep , Pillar Valério D. , Reich Peter B. , Shiodera Satomi , Siefert Andrew , Sosinski Enio E. , Soudzilovskaia Nadejda A. , Swaine Emily K. , Swenson Nathan G. , van Bodegom Peter M. , Warman Laura , Weiher Evan , Wright Ian J. , Zhang Hongxiang , Zobel Martin , Bonser Stephen P. 
Published: May 2014

AbstractQuestionAre plant traits more closely correlated with mean annual temperature, or with mean annual precipitation?LocationGlobal.MethodsWe quantified the strength of the relationships between temperature and precipitation and 21 plant traits from 447,961 species‐site combinations worldwide. We used meta‐analysis to provide an overall answer to our question.ResultsMean annual temperature was significantly more strongly correlated with plant traits than was mean annual precipitation.ConclusionsOur study provides support for some of the assumptions of classical vegetation theory, and points to many interesting directions for future research. The relatively low R2values for precipitation might reflect the weak link between mean annual precipitation and the availability of water to plants.
Extracellular vesicles produced by the Gram‐positive bacterium Bacillus subtilis are disrupted by the lipopeptide surfactin
Authors: Brown Lisa , Kessler Anne , Cabezas‐Sanchez Pablo , Luque‐Garcia Jose L. , Casadevall Arturo 
Published: May 2014

SummaryPreviously, extracellular vesicle production in Gram‐positive bacteria was dismissed due to the absence of an outer membrane, where Gram‐negative vesicles originate, and the difficulty in envisioning how such a process could occur through the cell wall. However, recent work has shown that Gram‐positive bacteria produce extracellular vesicles and that the vesicles are biologically active. In this study, we show that Bacillus subtilis produces extracellular vesicles similar in size and morphology to other bacteria, characterized vesicles using a variety of techniques, provide evidence that these vesicles are actively produced by cells, show differences in vesicle production between strains, and identified a mechanism for such differences based on vesicle disruption. We found that in wild strains of B. subtilis, surfactin disrupted vesicles while in laboratory strains harbouring a mutation in the gene sfp, vesicles accumulated in the culture supernatant. Surfactin not only lysed B. subtilis vesicles, but also vesicles from Bacillus anthracis, indicating a mechanism that crossed species boundaries. To our knowledge, this is the first time a gene and a mechanism has been identified in the active disruption of extracellular vesicles and subsequent release of vesicular cargo in Gram‐positive bacteria. We also identify a new mechanism of action for surfactin.
Our 2014 approach to mucormycosis
Authors: Tacke Daniela , Koehler Philipp , Markiefka Birgid , Cornely Oliver A. 
Published: May 2014

SummaryMucormycosis, previously termed as zygomycosis, is caused by fungi belonging to the order Mucorales and is a very severe disease in immunocompromised patients with an often unfavourable outcome. Given the high morbidity and mortality of mucormycosis, establishing a timely diagnosis followed by immediate treatment is of major importance. As randomised clinical trials are lacking, we present our current diagnostic and treatment pathways for mucormycosis in the immunocompromised host. Due to the difficulty to distinguish mucormycosis from other filamentous fungi, mucormycosis always has to be considered as differential diagnosis in predisposed patients. Diagnostic procedures comprise imaging, microscopy, culture and histopathology and need to be rigorously used. In patients with a high suspicion of mucormycosis, e.g. reversed halo sign on computed tomography scanning, our approach combines liposomal amphotericin B (LAmB) with surgical debridement. In light of the rapid deterioration and poor prognosis of these patients, we prefer a daily dose of LAmB of at least 5 mg kg−1 despite nephrotoxicity. In patients with stable disease we switch to posaconazole 200 mg four times per day. In case of progression antifungal combination is an option.
Vulvovaginal candidiasis: species distribution, fluconazole resistance and drug efflux pump gene overexpression
Authors: Zhang Jie‐Yu , Liu Jin‐Hui , Liu Fa‐Di , Xia Yan‐Hua , Wang Jing , Liu Xi , Zhang Zhi‐Qin , Zhu Na , Yan‐Yan   , Ying Ying , Huang Xiao‐Tian 
Published: May 2014

SummaryThe increasing incidence of vulvovaginal candidiasis (VVC) and the emergence of fluconazole resistance are an indisputable fact. However, little information is available regarding the correlation between fluconazole resistance in vaginal Candida albicans and the expression of drug efflux pump genes. In this study, we investigated the species distribution, fluconazole susceptibility profiles and the mechanisms of fluconazole resistance in Candida strains. In total, 785 clinical Candida isolates were collected from patients with VVC. C. albicans was the most frequently isolated species (n = 529) followed by C. glabrata (n = 164) and C. krusei (n = 57). Of all Candida isolates, 4.7% were resistant to fluconazole. We randomly selected 18 fluconazole‐resistant isolates of C. albicans to evaluate the expression of CDR1, CDR2, MDR1 and FLU1 genes. Compared with fluconazole‐susceptible C. albicans isolates, CDR1 gene expression displayed 3.16‐fold relative increase, which was statistically significant. CDR2, MDR1 and FLU1 overexpression was observed in several fluconazole‐resistant C. albicans isolates, but statistical significance was not achieved. These results demonstrate a high frequency of non‐albicans species (32.6%); however, C. albicans is the most common Candida species implicated in vaginitis, and this strain displays considerable fluconazole resistance. Meanwhile, our study further indicates that fluconazole resistance in C. albicans may correlate with CDR1 gene overexpression.
A new Hyperodapedon (Archosauromorpha, Rhynchosauria) from the Upper Triassic of India: implications for rhynchosaur phylogeny
Authors: Mukherjee Debarati , Ray Sanghamitra 
Published: May 2014

AbstractA new species of the rhynchosaur genus Hyperodapedon, namely H. tikiensis, is described from well‐preserved skeletal elements that were collected from the Upper Triassic Tiki Formation of India. Hyperodapedon tikiensis is diagnosed on the basis of several cranial and postcranial features including longer than wide basipterygoid process, crest‐shaped maxillary cross section lateral to the main longitudinal groove, deeply excavated neural arches of mid‐dorsal vertebrae, long scapular blade, a pronounced deltopectoral crest, proximal humeral end much broader than distal end, iliac length greater than iliac height, equal pre‐ and postacetabular iliac lengths and circular femoral cross section. Two distinct morphotypes of the maxillary tooth plates can be discerned, which are attributed to ontogenetic variations. A maximum‐parsimony analysis was carried out to show that the order Rhynchosauria is characterized by nine cranial and one postcranial character states. The analysis reveals that Otischalkia elderae is invalid and the basal forms, Howesia and Mesosuchus, are closely related. The Mid‐Triassic genus Ammorhynchus is more derived and forms a sister group to the Late Triassic subfamily Hyperodapedontinae. Isalorhynchus and Teyumbaita are basal to the pandemic genus Hyperodapedon. Twenty‐four characters that are not homoplasious document major patterns of skeletal evolution in rhynchosaurs. From laterally oriented scapula and slender propodials, the postcranial skeleton evolved into a more robust form as is evident from nearly vertical scapula and increase in the robustness of the propodials. Shortening of the femur is noted in the derived Late Triassic forms as exemplified in Hyperodapedon gordoni, Hyperodapedon huxleyi and H. tikiensis.
Conditional Inferential Models: Combining Information for Prior-Free Probabilistic Inference
Authors: Martin Ryan , Liu Chuanhai 
Published: May 2014

Summary
The inferential model (IM) framework provides valid prior-free probabilistic inference by focusing on predicting unobserved auxiliary variables. But, efficient IM-based inference can be challenging when the auxiliary variable is of higher dimension than the parameter. Here we show that features of the auxiliary variable are often fully observed and, in such cases, a simultaneous dimension reduction and information aggregation can be achieved by conditioning. This proposed conditioning strategy leads to efficient IM inference and casts new light on Fisher's notions of sufficiency, conditioning and also Bayesian inference. A differential-equation-driven selection of a conditional association is developed, and validity of the conditional IM is proved under some conditions. For problems that do not admit a conditional IM of the standard form, we propose a more flexible class of conditional IMs based on localization. Examples of local conditional IMs in a bivariate normal model and a normal variance components model are also given.
Loneliness and health care consumption among older people
Authors: Taube Elin , Kristensson Jimmie , Sandberg Magnus , Midlöv Patrik , Jakobsson Ulf 
Published: May 2014

Few studies have investigated loneliness in relation to health care consumption among frail older people. The aim of this study was to examine loneliness, health‐related quality of life (HRQoL), and health complaints in relation to health care consumption of in‐ and outpatient care among frail older people living at home. The study, with a cross‐sectional design, comprised a sample of 153 respondents aged from 65 years (mean age 81.5 years) or older, who lived at home and were frail. Data was collected utilising structured interviews in the respondent's home assessing demographic data, loneliness, HRQoL and health complaints. Patient administrative registers were used to collect data on health care consumption. Loneliness was the dependent variable in the majority of the analyses and dichotomised. For group comparisons Student′s t‐test, Mann–Whitney U‐test and Chi‐square test were used. The results showed that 60% of the respondents had experienced loneliness during the previous year, at least occasionally. The study identified that lonely respondents had a lower HRQoL (p = 0.022), with a higher total number of reported health complaints (p = 0.001), and used more outpatient services including more acute visits at the emergency department, compared to not lonely respondents (p = 0.026). Multiple linear regression analysis showed that a depressed mood was independently associated to total use of outpatient care (B = 7.4, p < 0.001). Therefore, it might not be loneliness, per se, that is the reason for seeking health care. However, reasons for using health care services are difficult to determine due to the complex situation for the frail older person. To avoid emergency department visits and to benefit the well‐being of the frail older person, interventions targeting the complex health situation, including loneliness, are suggested.
First report on the antibody verification of HLA‐ABC epitopes recorded in the website‐based HLA Epitope Registry
Authors: Duquesnoy R. J. , Marrari M. , Mulder A. , da Mata Sousa L. C. D. , da Silva A. S. , do Monte S. J. H. 
Published: May 2014

AbstractThe International Registry of Antibody‐Defined HLA Epitopes (
http://www.epregistry.com.br) has been recently established as a tool to understand humoral responses to human leukocyte antigen (HLA) mismatches. These epitopes are defined structurally by three‐dimensional molecular modeling and amino acid sequence differences between HLA antigens. So‐called eplets represent essential components of HLA epitopes and they are defined by polymorphic residues. A major goal is to identify HLA epitopes that have been verified experimentally with informative antibodies. Our analysis has also included data in many publications. As of 1 November 2013, 95 HLA‐ABC antibody‐verified epitopes have been recorded, 62 correspond to eplets and 33 are defined by eplets paired with other residue configurations. The Registry is still a work‐in‐progress and will become a useful resource for HLA professionals interested in histocompatibility testing at the epitope level and investigating antibody responses to HLA mismatches in transplant patients.
Serological and molecular evidence of a plausible transmission of hepatitis E virus through pooled plasma
Authors: Andonov A. , Rock G. , Lin L. , Borlang J. , Hooper J. , Grudeski E. , Wu J. ,   Members of the Canadian Apheresis Group (CAG)
Published: May 2014

Background and ObjectivesRecently, hepatitis E virus has been recognized as a new transfusion‐associated risk; however, its efficiency of transmission through blood products requires further investigation. Asymptomatic viremia of short duration has been observed in blood donors from several European countries to the rate of <1:10 000 and HEV transmission in recipients of blood products has been documented in Japan and Europe. Although HEV RNA was detected in large plasma fractionation pools used for manufacturing of plasma derived products, HEV transmission has not been demonstrated so far. In this study, we investigated the possibility of HEV transmission in patients with thrombotic thrombocytopenic purpura whose treatment included up to 40 l of plasma exchange.Materials and MethodsThirty‐six TTP patients received either solvent–detergent‐treated plasma prepared by pooling of 2500 single‐donor or cryosupernatant plasma. Three samples were collected from TTP patients at time 0, 1 and 6 months post‐treatment and tested for anti‐HEV antibodies. Patients with HEV seroconversion were also tested for viremia by PCR.ResultsTwo of seventeen TTP patients treated with SDP showed serological evidence of HEV infection. The 1‐month samples from these patients were also positive for HEV RNA. A distinct rise of anti‐HEV IgG level was detected in two other TTP patients with weak pre‐existing immunity to HEV; this observation is indicative of a possible immune response boost due to a breakthrough infection.ConclusionThis work provides, for the first time, indirect evidence of HEV transmission by pooled plasma and warrants further studies.
Comparison of the Immunogenicity and Safety of the Conventional Subunit, MF59-Adjuvanted, and Intradermal Influenza Vaccines in the Elderly
Authors: Seo Yu Bin , Choi Won Suk , Lee Jacob , Song Joon Young , Cheong Hee Jin , Kim Woo Joo 
Published: May 2014

ABSTRACT
The influenza vaccination is known as the most effective method for preventing influenza infection and its complications in the elderly. Conventional subunit (Agrippal S1; Novartis), MF59-adjuvanted (Fluad; Novartis), and intradermal (IDflu15; Sanofi Pasteur) influenza vaccines are widely used throughout South Korea. However, few comparative studies evaluating the safety and immunogenicity of these vaccines are available. Prior to the beginning of the 2011-2012 influenza season, 335 healthy elderly volunteers randomly received one of three seasonal trivalent influenza vaccines, the conventional subunit, MF59-adjuvanted, or intradermal influenza vaccine. Serum hemagglutination-inhibiting antibody levels were measured at the time of vaccination and at 1 and 6 months after vaccination. Adverse events were recorded prospectively. A total of 113 conventional subunit, 111 MF59-adjuvanted, and 111 intradermal influenza vaccine volunteers were followed up during a 6-month postvaccination period. One month after vaccination, all three vaccines satisfied Committee for Medical Products for Human Use (CHMP) immunogenicity criteria for the A/H1N1 and A/H3N2 strains but not for the B strain. Compared with the subunit vaccine, the intradermal vaccine exhibited noninferiority, while the MF59-adjuvanted vaccine exhibited superiority. Furthermore, the MF59-adjuvanted vaccine was more immunogenic against the A/H3N2 strain than was the subunit vaccine up to 6 months postvaccination. The most common local and systemic reactions to the conventional subunit, MF59-adjuvanted, and intradermal influenza vaccines were pain at the injection site (7.1%, 10.8%, and 6.3%, respectively) and generalized myalgia (0.9%, 8.1%, and 5.4%, respectively). Local and systemic reactions were similar among the three vaccine groups. MF59-adjuvanted vaccine exhibited superior immunogenicity compared with a conventional subunit vaccine and had a comparable safety profile. For older adults, the MF59-adjuvanted vaccine is preferable for providing superior immunogenicity.