bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recombinant Immunotoxin with T-cell Epitope Mutations That Greatly Reduce Immunogenicity for Treatment of Mesothelin-Expressing Tumors
Authors: Mazor Ronit , Zhang Jingli , Xiang Laiman , Addissie Selamawit , Awuah Prince , Beers Richard , Hassan Raffit , Pastan Ira 
Published: October 2015

AbstractSS1P is a recombinant immunotoxin (RIT) that targets mesothelin. It consists of an antimesothelin Fv fused to a portion of Pseudomonas exotoxin A. In clinical studies, it has produced dramatic responses in patients with advanced mesothelioma, when combined with immunosuppressive therapy so that several treatment cycles could be given. Otherwise its activity is limited by its immunogenicity. In this work, we describe the development and characterization of LMB-T20, a highly potent RIT targeted at mesothelin-expressing cancers with low immunogenicity due to removal of its eight T-cell epitopes. LMB-T20 was more active than SS1P when tested on four different mesothelin-expressing cell lines as well as on cells obtained from patients with mesothelioma. It also has potent antitumor activity in mice, and has reduced immunogenicity as measured by cytokine secretion assays. In conclusion, LMB-T20 is a favorable candidate for evaluation in clinical trials due to its reduced immunogenicity and excellent activity. Mol Cancer Ther; 14(12); 2789–96. ©2015 AACR.
Quantifying the Benefit of Prehospital Rapid Treatment in Acute Stroke
Authors: Lorenz Matthias W. , Lauer Arne , Foerch Christian 
Published: October 2015

Background and Purpose—
In acute ischemic stroke, time from onset to tissue-type plasminogen activator treatment (OTT) is a major determinant of outcome. To reduce OTT, clinical trials have been undertaken evaluating prehospital cerebral imaging with mobile computed tomographic scanners. Furthermore, blood biomarkers may allow rapid differentiation between ischemic stroke and intracerebral hemorrhage before hospital admission. How such treatment strategies translate into clinical benefit has not been specifically evaluated.

Methods—
We constructed decision models to estimate the net clinical benefit yielded by shorter OTT. In different scenarios, we estimated the proportion of patients with favorable outcome and the average quality of life.

Results—
An OTT reduction of 60 minutes increases the probability of favorable outcome by 6.6% in a mixed stroke population. For comparison, the average effect of tissue-type plasminogen activator itself is 7.0%. Prehospital mobile computed tomography gaining 25 to 40 minutes increases the probability of favorable outcome by 3.0% to 4.6%. The additional benefit of prehospital computed tomography to deliver patients with large vessel occlusion directly to endovascular treatment centers increases the probability of favorable outcome by another 0.2% to 1.0%. A blood test discriminating ischemic stroke and intracerebral hemorrhage may beneficially substitute brain scan before tissue-type plasminogen activator if >32 to 40 minutes are gained and if sensitivity for intracerebral hemorrhage is >75% to 80%.

Conclusions—
Reducing the OTT has robust beneficial effects for acute stroke patients. Prehospital tissue-type plasminogen activator treatment without brain imaging may become conceivable under several preconditions, including a point-of-care test with >75% to 80% sensitivity to detect intracerebral hemorrhage and a time gain of >32 to 40 minutes. Ethical implications remain to be addressed.
Alteplase Reduces Downstream Microvascular Thrombosis and Improves the Benefit of Large Artery Recanalization in Stroke
Authors: Desilles Jean-Philippe , Loyau Stephane , Syvannarath Varouna , Gonzalez-Valcarcel Jaime , Cantier Marie , Louedec Liliane , Lapergue Bertrand , Amarenco Pierre , Ajzenberg Nadine , Jandrot-Perrus Martine , Michel Jean-Baptiste , Ho-Tin-Noe Benoit , Mazighi Mikael 
Published: October 2015

Background and Purpose—
Downstream microvascular thrombosis (DMT) is known to be a contributing factor to incomplete reperfusion in acute ischemic stroke. The aim of this study was to determine the timing of DMT with intravital imaging and to test the hypothesis that intravenous alteplase infusion could reduce DMT in a transient middle cerebral artery occlusion (MCAO) rat stroke model.

Methods—
Rats were subjected to 60-minute transient MCAO. Alteplase (10 mg/kg) was administered 30 minutes after the beginning of MCAO. Real-time intravital fluorescence microscopy through a dura-sparing craniotomy was used to visualize circulating blood cells and fibrinogen. Cerebral microvessel patency was quantitatively evaluated by fluorescein isothiocyanate-dextran perfusion.

Results—

Immediately after MCAO, platelet and leukocyte accumulation were observed mostly in the venous compartment. Within 30 minutes after MCAO, microthrombi and parietal fibrin deposits were detected in postcapillary microvessels. Alteplase treatment significantly (
P
=0.006) reduced infarct volume and increased the percentage of perfused vessels during MCAO (
P
=0.02) compared with saline. Plasma levels of fibrinogen from alteplase-treated rats showed a rapid and profound hypofibrinogenemia. In vitro platelet aggregation demonstrated that alteplase reduced platelet aggregation (
P
=0.0001) and facilitated platelet disaggregation (
P
=0.001). These effects were reversible in the presence of exogenous fibrinogen.

Conclusions—
Our data demonstrate that DMT is an early phenomenon initiated before recanalization. We further show that alteplase-dependent maintenance of downstream perfusion during MCAO improves acute ischemic stroke outcome through a fibrinogen-dependent platelet aggregation reduction. Our results indicate that early targeting of DMT represents a therapeutic strategy to improve the benefit of large artery recanalization in acute ischemic stroke.
Genetic differentiation among species of the genus Thermophis Malnate (Serpentes, Colubridae) and comments on T. shangrila
Authors: Hofmann Sylvia , Tillack Frank , Miehe Georg 
Published: October 2015

The genus Thermophis includes the two species, T. baileyi and T. zhaoermii, which differ morphologically, geographically and molecularly. Recently, a third Thermophis species was described from Shangri-La, northern Yunnan Province, China, and named T. shangrila. The new species was based on morphological and genetic data derived from three specimens. However, the morphological features used to delimit this species seem vague, because they may fall within the range of intraspecific variation of T. zhaoermii. Furthermore, the reported genetic differences in nuclear data are questionable. They likely resulted from a misinterpretation probably due to alignment/analytical flaws or sample/sequence mix-up. Here, we used partial sequences of three mitochondrial (CO1, ND4, cytb) genes and one nuclear (c-mos) gene to analyse the genetic variation between and within species of Thermophis. We inferred the phylogeny using Bayesian Inference and Maximum Likelihood approaches and present additional morphological data that contribute to the knowledge on intraspecific variation in the genus. Our results indicate lacking robustness in the distinguishing morphological features and in the genetic differentiation of T. shangrila and highlight the need for more detailed morphological and molecular studies from a substantially larger sample.
Epigenetics in Legg–Calvé–Perthes disease: A study of global DNA methylation
Authors: Zheng Pengfei , Yang Tao , Ju Li , Jiang Bo , Lou Yue 
Published: October 2015

Objective To examine the global methylation status of DNA in blood cells of children with Legg-Calvé-Perthes disease (LCPD), since the aetiopathogenesis of LCPD remains unclear, and many factors closely associated with DNA methylation may be linked to the occurrence of LCPD. Methods Children with LCPD and age-, sex- and body mass index-matched controls were evaluated. Methylation levels of the long interspersed nuclear element 1 (LINE-1), a biomarker of global DNA methylation, were quantified by methylation-specific polymerase chain reaction. Results Of 82 children with LCPD (68 male/14 female) and 120 matched controls (98 male/22 female), methylation of the LINE-1 promoter was significantly lower in patients with LCPD compared with controls. Subgroup analyses showed that methylation of the LINE-1 promoter was significantly lower in male patients with LCPD compared with male controls. No significant between-group differences were observed in female participants. Conclusions Reduced global DNA methylation may be associated with increased risk of LCPD in male children. Further research is required to understand whether detection of global DNA methylation may provide a basis for clinical diagnosis and early intervention of LCPD.
Pediatrician Ambiguity in Understanding Palliative Sedation at the End of Life
Authors: Henderson Carrie M. , FitzGerald Michael , Hoehn K. Sarah , Weidner Norbert 
Published: October 2015

Context: Palliative sedation is a means of relieving intractable symptoms at the end of life, however, guidelines about its use lack consistency. In addition, ethical concerns persist around the practice. There are reports of palliative sedation in the pediatric literature, which highlight various institutional perspectives. Objectives: This survey of 4786 pediatric providers sought to describe their knowledge of and current practices around pediatric palliative sedation. Methods: Our survey was administered to pediatricians who care for children at the end of life. The survey assessed agreement with a definition of palliative sedation, as well as thoughts about its alignment with aggressive symptom management. Bivariate analyses using χ2 and analysis of variance were calculated to determine the relationship between responses to closed-ended questions. Open-ended responses were thematically coded by the investigators and reviewed for agreement. Results: Nearly half (48.6%) of the respondents indicated that the stated definition of palliative sedation “completely” reflected their own views. Respondents were split when asked if they viewed any difference between palliative sedation and aggressive symptom management: Yes (46%) versus No (54%). Open-ended responses revealed specifics about the nature of variation in interpretation. Conclusions: Responses point to ambiguity surrounding the concept of palliative sedation. Pediatricians were concerned with a decreased level of consciousness as the goal of palliative sedation. Respondents were split on whether they view palliative sedation as a distinct entity or as one broad continuum of care, equivalent to aggressive symptom management. Institutional-based policies are essential to clarify acceptable practice, enable open communication, and promote further research.
Feasibility of a Modified Biopsy Needle for Irreversible Electroporation Ablation and Periprocedural Tissue Sampling
Authors: Wimmer Thomas , Srimathveeravalli Govindarajan , Silk Mikhail , Monette Sebastien , Gutta Narendra , Maybody Majid , Erinjery Joseph P. , Coleman Jonathan A. , Solomon Stephen B. , Sofocleous Constantinos T. 
Published: October 2015

Objectives: To test the feasibility of modified biopsy needles as probes for irreversible electroporation ablation and periprocedural biopsy. Methods: Core biopsy needles of 16-G/9-cm were customized to serve as experimental ablation probes. Computed tomography-guided percutaneous irreversible electroporation was performed in in vivo porcine kidneys with pairs of experimental (n = 10) or standard probes (n = 10) using a single parameter set (1667 V/cm, ninety 100 µs pulses). Two biopsy samples were taken immediately following ablation using the experimental probes (n = 20). Ablation outcomes were compared using computed tomography, simulation, and histology. Biopsy and necropsy histology were compared. Results: Simulation-suggested ablations with experimental probes were smaller than that with standard electrodes (455.23 vs 543.16 mm2), although both exhibited similar shape. Computed tomography (standard: 556 ± 61 mm2, experimental: 515 ± 67 mm2; P = .25) and histology (standard: 313 ± 77 mm2, experimental: 275 ± 75 mm2; P = .29) indicated ablations with experimental probes were not significantly different from the standard. Histopathology indicated similar morphological changes in both groups. Biopsies from the ablation zone yielded at least 1 core with sufficient tissue for analysis (11 of the 20). Conclusions: A combined probe for irreversible electroporation ablation and periprocedural tissue sampling from the ablation zone is feasible. Ablation outcomes are comparable to those of standard electrodes.
Fungal contamination of the respiratory tract and associated respiratory impairment among sawmill workers in India
Authors: Adhikari Asit , Sahu Subhashis , Bandyopadhyay Arghya , Blanc Paul D. , Moitra Subhabrata 
Published: October 2015

Wood processing workers are exposed to wood-associated microbiological contaminants, including fungi. Our aim was to study the potential association between sputum fungus and adverse respiratory effects in such workers.In a group of sawmill workers, we administered a respiratory questionnaire, performed lung function testing and quantified the proportions of leukocytes in spontaneously expectorated sputum samples. We identified fungal species by DNA sequencing.Of 54 sawmill workers, 19 yielded fungal positive sputum samples (mean age 42.5±10.4 years) and 35 were negative for fungus (mean age 36.9±5.2 years). The fungus was identified asCandidasp. in all samples. Those with fungal-positive sputum, compared to others, reported more cough (26%versus63%) and haemoptysis (6%versus37%) (both p<0.05), manifested reduced forced midexpiratory flow rates (FEF25–75%) (82.3±4.5versus69.2±9.9% predicted, p<0.001), and had higher sputum eosinophil counts (median 9.25versus3.25%, p<0.01). Reduction of FEF25–75%was associated both with fungus detection in sputum (−12.7%, 95% CI−8.5– −16.9%) and sputum eosinophils (−2.1% per 1% increase in eosinophils, 95% CI −1.5– −2.8%) (both p<0.001).In sawmill workers,Candidasp. detectable in sputum was associated with respiratory symptoms, sputum eosinophilia and reduced FEF25–75%.
Evaluation of district mental healthcare plans: The PRIME consortium methodology
Authors: De Silva Mary J. , Rathod Sujit D. , Hanlon Charlotte , Breuer Erica , Chisholm Dan , Fekadu Abebaw , Jordans Mark , Kigozi Fred , Petersen Inge , Shidhaye Rahul , Medhin Girmay , Ssebunnya Joshua , Prince Martin , Thornicroft Graham , Tomlinson Mark , Lund Crick , Patel Vikram 
Published: October 2015

BackgroundFew studies have evaluated the implementation and impact of real-world mental health programmes delivered at scale in low-resource settings.AimsTo describe the cross-country research methods used to evaluate district-level mental healthcare plans (MHCPs) in Ethiopia, India, Nepal, South Africa and Uganda.MethodMultidisciplinary methods conducted at community, health facility and district levels, embedded within a theory of change.ResultsThe following designs are employed to evaluate the MHCPs: (a) repeat community-based cross-sectional surveys to measure change in population-level contact coverage; (b) repeat facility-based surveys to assess change in detection of disorders; (c) disorder-specific cohorts to assess the effect on patient outcomes; and (d) multilevel case studies to evaluate the process of implementation.ConclusionsTo evaluate whether and how a health-system-level intervention is effective, multidisciplinary research methods are required at different population levels. Although challenging, such methods may be replicated across diverse settings.
Estimating the cost of implementing district mental healthcare plans in five low- and middle-income countries: The PRIME study
Authors: Chisholm Dan , Burman-Roy Soumitra , Fekadu Abebaw , Kathree Tasneem , Kizza Dorothy , Luitel Nagendra P. , Petersen Inge , Shidhaye Rahul , De Silva Mary , Lund Crick 
Published: October 2015

BackgroundAn essential element of mental health service scale up relates to an assessment of resource requirements and cost implications.AimsTo assess the expected resource needs of scaling up services in five districts in sub-Saharan Africa and south Asia.MethodThe resource quantities associated with each site's specified care package were identified and subsequently costed, both at current and target levels of coverage.ResultsThe cost of the care package at target coverage ranged from US$0.21 to 0.56 per head of population in four of the districts (in the higher-income context of South Africa, it was US$1.86). In all districts, the additional amount needed each year to reach target coverage goals after 10 years was below $0.10 per head of population.ConclusionsEstimation of resource needs and costs for district-level mental health services provides relevant information concerning the financial feasibility of locally developed plans for successful scale up.
Case Report: Pulmonary Kaposi Sarcoma in a non-HIV patient
Authors: Kodra Arber , Walczyszyn Maciej , Grossman Craig , Zapata Daniel , Rambhatla Tarak , Mina Bushra 
Published: October 2015

Kaposi Sarcoma (KS) is an angioproliferative tumor associated with human herpes virus 8 (HHV-8). Often known as one of the acquired immunodeficiency syndrome (AIDS)-defining skin diseases, pulmonary involvement in KS has only been discussed in a handful of case reports, rarely in a non-HIV patient. Herein we report the case of a 77 year-old- male who presented with a 6-week history of progressive dyspnea on exertion accompanied by productive cough of yellow sputum and intermittent hemoptysis. His past medical history was significant for Non-Hodgkin’s Follicular B-Cell Lymphoma (NHL). Patient also had biopsy-confirmed cutaneous KS. His physical exam was notable for a 2cm firm, non-tender, mobile right submandibular lymph node. Lungs were clear to auscultation. He had multiple violet non-tender skin lesions localized to the lower extremities. CT scan of the chest showed numerous nodular opacities and small pleural effusions in both lungs. A thoracenthesis was performed, showing sero-sanguineous exudative effusions. Histopathology failed to demonstrate malignant cells or lymphoma. A subsequent bronchoscopy revealed diffusely hyperemic, swollen mucosa of the lower airways with mucopurulent secretions. Bronchoalveolar lavage PCR for HHV-8 showed 5800 DNA copies/mL. It was believed that his pulmonary symptoms were likely due to disseminated KS. This case illustrates the potential for significant lung injury from KS. It also demonstrates the use of PCR for HHV-8 to diagnose KS in a bronchoalveolar lavage sample in a case when bronchoscopic biopsy was not safe. Furthermore, this case is unique in that the patient did not match the typical KS subgroups as HIV infection and other immune disorders were ruled out. Recognition of this syndrome is critical to the institution of appropriate therapy. As such, this case should be of interest to a broad readership across internal medicine including the specialties of Pulmonology and Critical Care.
A short history of the development of wound care dressings
Authors: Jones Menna Lloyd 
Published: October 2015

Over the past 40 years, the amount of advanced wound care dressings available on the market has grown at a phenomenal rate, not only in the different types of dressings, but also in the variety of shapes and sizes available. There is no doubt therefore that selecting the most appropriate wound care dressing from the plethora of dressings available today can present a huge challenge to clinicians.Wound care dressings have evolved over thousands of years, as humans attempted to try and find a solution to stop bleeding, speed up healing of acute wounds and cope with troublesome chronic wounds ( Gottrup and Leaper, 2004 ).The aim of this series is to provide a short history of dressings, alongside information on the different types of dressings available today.
Risk management in dementia care, Part 2/4: identifying hazards and risks
Authors: Nazarko Linda 
Published: October 2015

Dementia can affect a person's awareness of risks and his or her ability to do certain things. The type of dementia, stage of dementia and other factors, such as an infection or a hazardous environment, can increase the risk of the person with dementia suffering harm. This article, the second in a series, explains how risk assessments are carried out, the pitfalls of traditional assessment and how important it is to respect, enable and empower the person with dementia.
Exacerbations of Chronic Obstructive Pulmonary Disease and Implementation of Guidelines Gold 2011 in Practice
Authors: Osinová D , Sadloňová J. , Rozborilová E. 
Published: October 2015

Abstract
Background: Chronic obstructive pulmonary disease (COPD) is a disease that is characterized by a persistent blockage of airflow from the lungs. It is an under-diagnosed, life-threatening disease which is not fully reversible. COPD is not only global health problem, the disease is also serious economic problem.
Objective: The aim of this study was to evaluate the effects of implementation of new guidelines Global Initiative for Chronic Obstructive Lung Disease (GOLD) for diagnosis and treatment of chronic obstructive pulmonary disease (COPD).
Design: Consecutive, observational, retrospective, mono-centric study.
Methods: Into the study were included all patients admitted with COPD exacerbations to Department of Pneumology and Phtiseology, Jessenius Faculty of Medicine in Martin and University Hospital, separately in year 2008 and year 2013, who have satisfied the inclusion criteria. Those years were chosen specifically from the reason of biennial application of diagnosis and treatment, according to recommended guidelines GOLD 2006 and GOLD 2011, in practice. The study was focused on the basic anthropometric parameters, data of medical history, complications of underlying disease, comorbidities, laboratory parameters, treatment strategy of patients after release from hospital and mortality within one year were evaluated.
Results: Patients in group 2013, when were applied guidelines GOLD 2011 had a higher average oxygen saturation and higher pO2 at all stages of the disease, significantly in GOLD D. They had higher values of FEV1 and FVC significantly in GOLD B. There was decrease of overuse of inhalation corticosteroids in group GOLD B from 53.34% to 28.57%. There was a downturn in use of theophylline, significantly in GOLD C. The average number of exacerbations leading to hospitalizations was lower in group 2013 in all stages of the disease. One-year mortality of patients in group 2013 was lower.
Conclusions: The implementation and application of guidelines GOLD 2011 in practice is a challenging and complex process, which is in region of University hospital Martin gradually and successfully implemented. The achievement the objectives of the GOLD 2011 not only contributes to the efficiency of prevention and timely diagnosis, but mainly on setting of adequate treatment, improves survival and quality of life of patients with COPD.