bluuebunny/crossref_metadata_2025_split huggingface dataset:
Catecholamine-Modulated Novel Surface-Exposed Adhesin LIC20035 of Leptospira spp. Binds Host Extracellular Matrix Components and Is Recognized by the Host during Infection
Authors: Ghosh Karukriti Kaushik , Prakash Aman , Balamurugan Vinayagamurthy , Kumar Manish 
Published: February 2018

ABSTRACTIn this study, the effect of the host stress hormone catecholamine onLeptospiragene transcripts encoding outer membrane proteins was investigated. There was no impact of catecholamine supplementation on thein vitrogrowth pattern ofLeptospira interrogans; however, 7 genes out of 41 were differentially transcribed, and the effect was reversed to the basal level in the presence of the antagonist propranolol. Comprehensive analysis of one of the differentially regulated proteins, LIC20035 (in serovar Copenhageni)/LB047 (in serovar Lai) (due to catecholamine supplementation), revealed immunogenicity and ability to adhere to host extracellular matrices. Protease accessibility assay and phase partition of integral membrane proteins ofLeptospirashowed LIC20035/LB047 to be an outer membrane surface-exposed protein. The recombinant LIC20035 protein can be serologically detected using human/bovine sera positive for leptospirosis. Moreover, the recombinant LIC20035 can bind to diverse host extracellular matrices, with a higher affinity toward collagen and chondroitin sulfate.IMPORTANCELeptospirosis is a neglected tropical disease of global importance. This study aimed to identify outer membrane proteins of pathogenicLeptospiraresponding to host chemical signals like catecholamines, with the potential to serve as virulence factors, new serodiagnostic antigens, and vaccine candidates. This study mimicked the plausible means by whichLeptospiraduring infection and hormonal stress intercepts host catecholamines to disseminate in host tissues.
Design of a phase IV randomised, double-blind, placebo-controlled trial assessing the ImPact ofResidual Inflammation Detected via Imaging TEchniques,Drug Levels and Patient Characteristics on the Outcome of Dose TaperIng of Adalimumab inClinical Remission Rheumatoid ArThritis (RA) patients (PREDICTRA)
Authors: Emery Paul , Burmester Gerd R , Naredo Esperanza , Zhou Yijie , Hojnik Maja , Conaghan Philip G 
Published: February 2018

IntroductionThe current American College of Rheumatology and European League Against Rheumatism treatment recommendations advise tapering biological disease-modifying antirheumatic drug (bDMARD) therapy in patients with rheumatoid arthritis (RA) who achieve stable clinical remission while receiving bDMARDs. However, not all patients maintain remission or low disease activity after tapering or discontinuation of bDMARDs. The aim of the ImPact ofResidual Inflammation Detected via Imaging TEchniques,Drug Levels and Patient Characteristics on the Outcome of Dose TaperIng of Adalimumab inClinical Remission Rheumatoid ArThritis (RA) study, or PREDICTRA, is to generate data on patient and disease characteristics that may predict the clinical course of a fixed dose-tapering regimen with the bDMARD adalimumab.Methods and analysisPREDICTRA is an ongoing, multicentre, phase IV, randomised, double-blind, parallel-group study of adalimumab dose tapering controlled by withdrawal in participants with RA who achieved stable clinical remission while receiving adalimumab. The study includes a screening period, a 4-week lead-in period with open-label adalimumab 40 mg every other week and a subsequent 36-week double-blind period during which participants are randomised 5:1 to adalimumab 40 mg every 3 weeks (taper arm) or placebo (withdrawal arm). The primary explanatory efficacy variables are lead-in baseline hand and wrist MRI-detected synovitis and bone marrow oedema scores, as well as a composite of both scores; the dependent variable is the occurrence of flare up to week 40. Additional efficacy variables, safety, pharmacokinetics, biomarkers and immunogenicity will also be assessed, and an ultrasound substudy will be conducted.Ethics and disseminationThe study is conducted in accordance with the International Conference on Harmonisation guidelines, local laws and the ethical principles of the Declaration of Helsinki. All participants are required to sign a written informed consent statement before the start of any study procedures.Trial registration numberEudraCT 2014-001114-26 andNCT02198651; Pre-results.
Heritability of glaucoma and glaucoma-related endophenotypes: systematic review and meta-analysis protocol
Authors: Asefa Nigus Gebrmedhin , Neustaeter Anna , Jansonius Nomdo M , Snieder Harold 
Published: February 2018

IntroductionGlaucoma is the second leading cause of age-related vision loss worldwide; it is an umbrella term that is used to describe a set of complex ocular disorders with a multifactorial aetiology. Both genetic and lifestyle risk factors for glaucoma are well established. Thus far, however, systematic reviews on the heritability of glaucoma have focused on the heritability of primary open-angle glaucoma only. No systematic review has comprehensively reviewed or meta-analysed the heritability of other types of glaucoma, including glaucoma-related endophenotypes. The aim of this study will be to identify relevant scientific literature regarding the heritability of both glaucoma and related endophenotypes and summarise the evidence by performing a systematic review and meta-analysis.Methods and analysisThis systematic review will follow the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols 2015 checklist, which provides a standardised approach for carrying out systematic reviews. To capture as much literature as possible, a comprehensive step-by-step systematic search will be undertaken in MEDLINE (PubMed), EMBASE, Web of Science and ScienceDirect, and studies published until 31 December 2017 will be included. Two reviewers will independently search the articles for eligibility according to predefined selection criteria. A database will be used for screening of eligible articles. The quality of the included studies will be rated independently by two reviewers, using the National Health Institute Quality Assessment tool for Observational Cohort and Cross-Sectional Studies. A random-effects model will be used for the meta-analysis. This systematic review is registered with the International Prospective Register of Systematic Reviews with a registration number: CRD42017064504.Ethics and disseminationWe will use secondary data from peer-reviewed published articles, and hence there is no requirement for ethics approval. The results of this systematic review will be disseminated through publication in a peer-reviewed scientific journal.
Targeting Tumor Vasculature with TNF Leads Effector T Cells to the Tumor and Enhances Therapeutic Efficacy of Immune Checkpoint Blockers in Combination with Adoptive Cell Therapy
Authors: Elia Angela Rita , Grioni Matteo , Basso Veronica , Curnis Flavio , Freschi Massimo , Corti Angelo , Mondino Anna , Bellone Matteo 
Published: February 2018

Abstract
Purpose: Irregular blood flow and endothelial cell anergy, which characterize many solid tumors, hinder tumor infiltration by cytotoxic T lymphocytes (CTL). This confers resistance to cancer immunotherapy with monoclonal antibodies directed against regulatory pathways in T lymphocytes (i.e., immune checkpoint blockade, ICB). We investigated whether NGR-TNF, a TNF derivative capable of targeting the tumor vasculature, and improving intratumor infiltration by activated CTLs, could sensitize tumors to ICB with antibodies specific for the PD-1 and CTLA-4 receptors.
Experimental Design: Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with autochthonous prostate cancer and C57BL/6 mice with orthotopic B16 melanoma were treated with NGR-TNF, adoptive T-cell therapy (ACT), and ICB, and monitored for immune surveillance and disease progression.
Results: The combination of ACT, NGR-TNF, and ICB was the most effective in delaying disease progression, and in improving overall survival of mice bearing ICB-resistant prostate cancer or melanoma. Mechanistically, the therapeutic effects were associated with potent tumor infiltration, especially by endogenous but also by adoptively transferred PD-1+, granzyme B+, and interferon-γ+ CTLs. The therapeutic effects were also associated with favorable T-effector/regulatory T cell ratios.
Conclusions: Targeting the tumor vasculature with low-dose TNF in association with ACT may represent a novel strategy for enhancing T-cell infiltration in tumors and overcoming resistance to immune checkpoint blockers. Clin Cancer Res; 24(9); 2171–81. ©2018 AACR.
Combinations of Bevacizumab and Erlotinib Show Activity in Colorectal Cancer Independent of RAS Status
Authors: Mésange Paul , Bouygues Anaïs , Ferrand Nathalie , Sabbah Michèle , Escargueil Alexandre E. , Savina Ariel , Chibaudel Benoist , Tournigand Christophe , André Thierry , de Gramont Aimery , Larsen Annette K. 
Published: February 2018

Abstract
Purpose: There is extensive cross-talk between VEGF- and EGFR-pathway signaling in colorectal cancer. However, combinations of VEGF- and EGFR-targeted monoclonal antibodies (mAb) show disappointing activity, in particular for patients with mutant RAS. Previous results show that tyrosine kinase inhibitors (TKI) can be active in colorectal cancer models resistant to mAbs. This prompted us to examine whether the activity of bevacizumab can be increased by combination with erlotinib.
Experimental Design: The antitumor activity of bevacizumab, erlotinib, and their combination was determined in colorectal cancer models with different RAS status and bevacizumab sensitivity. EGFR/VEGF pathway activation was characterized by immunohistochemistry, Western blot, and ELISA assays. The influence of cetuximab and erlotinib on EGF-mediated migration and the EGFR–EGF ligand feedback loop was established in colorectal cancer cell lines with different RAS status.
Results: The addition of erlotinib increased bevacizumab activity in all models independent of RAS status. Bevacizumab exposure was accompanied by marked EGFR activation in tumor cells as well as in tumor-associated endothelial cells (TECs) and resulted in strong accumulation of intracellular EGFR, which could be attenuated by erlotinib. In cellular models, erlotinib was able to attenuate EGF-mediated functions in all cell lines independent of RAS status while cetuximab only showed activity in RAS wild-type cells.
Conclusions: These results should provide a molecular framework to better understand the increased activity of the bevacizumab–erlotinib combination, compared with bevacizumab alone, in the GERCOR DREAM phase III clinical trial. Differential activity of mAbs and TKIs targeting the same signaling pathway is likely applicable for other tumor types. Clin Cancer Res; 24(11); 2548–58. ©2018 AACR.
An uncommon habitat for a common salamander: Isthmura bellii in arid tropical scrub
Authors: Domínguez-Vega Hublester , Zuria Iriana , Fernández-Badillo Leonardo 
Published: February 2018

Abstract
Salamanders are usually seen as typical inhabitants of temperate and humid habitats. Among Plethodontids, Isthmura bellii has the broadest altitudinal range of any salamander in the world and it is considered a habitat generalist. Nonetheless, even for this species, dry environments are thought unsuitable. We report the first records of I. bellii in arid tropical scrub from two localities within central Mexico. We analyze the environmental differentiation of these new localities in relation to the known distribution range of the genus. Our study shows that among the new localities, there is at least one site where I. bellii appears to have established in arid tropical scrub. An environmental model reveals that these new localities present different conditions than most of the records of Isthmura spp.
Chasing the phantom: biogeography and conservation of Vipera latastei-monticola in the Maghreb (North Africa)
Authors: Freitas Inês , Fahd Soumia , Velo-Antón Guillermo , Martínez-Freiría Fernando 
Published: February 2018

Abstract
The Maghreb region (North Africa) constitutes a major component of the Mediterranean Basin biodiversity hotspot. During the last centuries, a consistent human population growth has led to an unprecedented rate of habitat transformation and loss in the region and thus, threatening its biodiversity. The Western Mediterranean viper Vipera latastei-monticola inhabits humid and subhumid areas in the main mountain ranges of the Maghreb, facing such threatening factors; however, its elusive character and rarity hindered data collection for distinct biological purposes. Here, we study the biogeographical patterns and conservation status of the Maghrebian V. latastei-monticola resulting from recent sampling campaigns in Morocco and Tunisia. We update species distribution, and integrate phylogeographic and ecological niche modelling analyses at both species and lineage level to identify suitable areas, and to evaluate the impact of anthropogenic transformation and level of protection of their suitable space. We identified four highly divergent mitochondrial lineages, including a new lineage endemic to the Western High Atlas, with allopatric distributions and restricted to mountain ranges, supporting the role of mountains as past climatic refugia. Despite the remoteness of suitable areas, we report widespread habitat degradation and identify the low effectiveness of the current protected areas system in preserving the species and lineages range. Our study shows the urgent need to apply management actions for the long-term conservation of this vulnerable species and suggests a revaluation of the specific status of V. monticola, as these populations likely represent an ecotype of V. latastei.
Monomia lucida sp. nov., a new swimming crab (Crustacea: Decapoda: Portunidae) from the South China Sea
Authors: KOCH MILAN , ĎURIŠ ZDENĚK 
Published: February 2018

A new species of the portunid genus, Monomia Gistel, 1848, is described from the South China Sea in Vietnam. Monomia lucida sp. nov. is morphologically most similar to M. argentata (A. Milne-Edwards, 1861), which was originally described from Sarawak, on the island of Borneo. In addition to the stout, forward-directed anterolateral teeth of the carapace, the subrectangular sixth segment of the male pleon, and the long and slender laterally bent first gonopods, adults of the new species reach a greater size, and can also be distinguished from M. argentata by the colour pattern on the natatory dactylus. The independent specific status of M. lucida sp. nov. is also supported by molecular evidence. Aside from a comparison of this new species with other known congeners, new photographs of the holotype of M. samoensis (Ward, 1939) are also provided.
Bowel Disease after Radiotherapy
Authors: Schofield Philip F , Holden D , Carr N D 
Published: February 2018

The clinical presentation, operative findings and outcome in 40 patients who required surgery for bowel disease after radiotherapy are presented. The type of presentation varied according to the time after radiotherapy. In the first month, many patients had a proctitis but none required surgery. Five patients were operated on within one month, 2 for radiation-induced acute ileitis and 3 for exacerbations of pre-existing disease (diverticular disease 2, ulcerative colitis 1). The commonest time of presentation was between 3 and 18 months after radiotherapy, when 20 patients needed surgery for bowel disease caused by radiation-induced local ischaemia. Twelve of these patients had chronic perforation, 6 had severe rectal bleeding and 2 had painful anorectal ulceration. Fifteen patients presented between 2 and 24 years after radiotherapy, usually with incomplete intestinal obstruction due to a fibrous stricture, but 2 patients had rectal carcinoma. Wide resection of the involved bowel was the principal method of treatment but any anastomosis was protected by a proximal defunctioning stoma. There was no operative mortality but 10 patients have died subsequently. The danger of dismissing these patients as having incurable malignancy is stressed because, although the condition is infrequent, it is usually amenable to adequate surgery.
The Role of the Hospital Consultant in General Practitioner Prescribing
Authors: Strickland-Hodge B , Jepson M H 
Published: February 2018

A questionnaire was designed and posted to 600 general medical practitioners in the West Midlands. The results indicated that the prescribers were reassured by the hospital consultant although independence was maintained in prescribing decisions. The hospital medical team was recognized for its expertise rather than the consultant alone. A table was constructed from the results to show the therapy areas in which doctors prefer to refer their patients. Consultant's influence in prescribing is most likely where communication between GP and consultant is optimal. The generalized influence of the consultant as implied by the Greenfield report remains unproven. Any influence is much more specific and may depend upon therapy area, the consultant specialty, and the standing of the hospital medical team. The innovativeness of the prescriber which was also considered may also have an influence as to how the consultant's recommendations will be accepted.
The use of Acrylic Bone Cement for Cervical Fusion in Patients with Rheumatoid Arthritis
Authors: Wilde G P , Hopkins J S 
Published: February 2018

We report on 14 patients with instability of the cervical spine secondary to rheumatoid arthritis treated by fusion using a combination of traditional bone grafting techniques and methylmethacrylate bone cement. Successful fusion was achieved in all cases with few complications. The high infection rate reported by other authors was avoided by reducing the bulk of the cement mass and the use of antibiotic impregnated cement. We recommend this method of fusion to all orthopaedic surgeons involved in the treatment of patients with rheumatoid arthritis.
Severe Herpetic Keratitis. II. The Costs Associated with Penetrating Keratoplasty
Authors: Menage M J , Claoué C M P 
Published: February 2018

We report a study on 100 patients with severe herpetic keratitis. Overall, one in three of the study group required a penetrating keratoplasty (PK). These patients required a mean of 18 days as an inpatient and 15 outpatient visits in the year the PK was performed; these figures fell to 1 inpatient day and 8 outpatient visits in the second year after surgery. The financial cost of such therapy is discussed.
Drug-Induced Epistaxis?
Authors: Watson M G , Shenoi P M 
Published: February 2018

To assess the aetiological contribution made to spontaneous epistaxis in adults over the age of 50 years by various groups of drugs, a controlled study was designed. Fifty-three consecutive epistaxis patients were compared with 50 controls. Significant differences were found between the groups in their consumption of warfarin, dipyridamole and non-steroidal anti-inflammatory drugs. Hypertension was equally common in the two groups, but tended to be less well controlled in the epistaxis patients compared to the controls. It is thought that the link between the use of non-steroidal anti-inflammatory drugs and the occurrence of epistaxis may be due to alteration of platelet function.
Controlled Trial of Automated External Defibrillators in the London Ambulance Service
Authors: Walters Geraldine , D'Auria D , Glucksman E E 
Published: February 2018

This controlled trial was performed in London and compared outcomes of patients treated by ambulance staff using either basic life support alone or an automated external defibrillator (AED) as an adjunct to basic life support. Five of the 212 (2%) patients were successfully resuscitated by crews using basic life support alone, compared with seven of 186 (4%) patients treated by crews equipped with the AED. Neurological outcomes in the AED group were better. However, meaningful statistical comparisons are not possible with so few survivors. The AED used (Lifepak 200, PhysioControl Corp) was found to be sensitive and specific, and ambulance staff operated the defibrillator correctly. The use of AEDs is an option to maximize the provision of defibrillators in the community and could readily be incorporated into basic ambulance training.
Medication in Police Custody
Authors: Busuttil A , Wallace N W 
Published: February 2018

Police Officers have an obligation to look after the welfare of the persons detained by them. As such persons may require to be given medication on a regular basis during their period of custody which may last a few days, the Police are also responsible for ensuring that this takes place. To identify the extent of this requirement, a survey was carried out by questionnaire in Edinburgh over a period of one month. Eighty five per cent of the 127 detainees were carrying with them a variety of drugs or required to be given medication on a regular basis. The problems associated with this practice are discussed.
Are Accident Flying Squads also Worthwhile for Medical Emergencies?
Authors: Cope A R , Dove A F , Kulendrarajah T , McLauchlan C A J 
Published: February 2018

A retrospective analysis of 208 flying squad attendances was performed to assess the effect of pre-hospital care by the team on outcome in emergency medical conditions, and in the trauma victim. Sixty-two (26%) of these cases were medical, but only 24 (11.5%) required immediate cardiopulmonary resuscitation. Only one out of the four successful resuscitations finally left hospital alive. In trauma, there was no significant enhancement of survival due to the presence of the team by comparing the expected against observed mortality and the injury severity score for age-matched groups. The value of flying squads as a training aid, perception of the local community and relationships with other emergency services are discussed. Alternative solutions to improving pre-hospital care include advanced trained ambulance and bystander resuscitation schemes. Although difficult to quantify the authors feel that flying squads are of benefit.
Vasomotion in Venous Disease
Authors: Cheatle T R , Shami S K , Stibe E , Smith P D Coleridge , Scurr J H 
Published: February 2018

Abnormalities of the capillary microcirculation may be important in the pathogenesis of venous ulceration. In this study the characteristics of capillary vasomotion in venous disease have been studied using laser Doppler flowmetry. The amplitude and frequency of vasomotion in the skin microcirculation as measured by laser Doppler flowmetry was determined in 101 subjects. These comprised 43 subjects with venous disease and lipodermatosclerosis (LDS), 14 subjects with uncomplicated varicose veins (VV), and 44 normal controls. In 43 of these 101 limbs, vasomotion was also measured after heating the skin to 43°C. The resting laser Doppler flux was significantly higher in the LDS group compared to the other two groups (LDS median=76, VV median=47 (P < 0.04), controls median=49 (P < 0.003)). The amplitude of vasomotive waves was significantly higher in the LDS group compared to controls (LDS median=20, VV median=8.3 (P < 0.007), controls median=14 (P < 0.007)), as was the frequency of vasomotion (LDS median=3.3 waves/min, VV median=2.5 (P=ns), controls median=2.7 (P < 0.007)). On heating the skin to 43 °C the frequency of the vasomotion increased significantly in the control (P < 0.004) and VV (P < 0.04) groups but not in the LDS group. The amplitude of the vaso-motion also increased significantly in the control (P < 0.01) and VV (P < 0.002) groups but not in the LDS group. Following heating, the frequency of vasomotive waves was significantly lower in the LDS group than in controls (P=0.05).