bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Double-blind Randomized Comparative Clinical Trial to Evaluate the Safety and Efficacy of Dendritic Cell Vaccine Loaded with WT1 Peptides (TLP0-001) in Combination with S-1 in Patients with Advanced Pancreatic Cancer Refractory to Standard Chemotherapy
Authors: Katsuda Masahiro , Miyazawa Motoki , Ojima Toshiyasu , Katanuma Akio , Hakamada Kenichi , Sudo Kentaro , Asahara Shingo , Endo Itaru , Ueno Makoto , Hara Kazuo , Yamada Suguru , Fujii Tsutomu , Satoi Sohei , Ioka Tatsuya , Ohira Masaichi , Akahori Takahiro , Kitano Masayuki , Nagano Hiroaki , Furukawa Masayuki , Adachi Tomohiko , Yamaue Hiroki 
Published: February 2019

Abstract
Background: Pancreatic cancer is a refractory malignancy and the development of a new effective treatment strategy is needed. We generated a dendritic cell vaccine by culturing monocytes obtained by apheresis of blood from each patient, inducing their differentiation into dendritic cells, and pulsing with tumor antigen peptides. However, the clinical efficacy of the vaccine has not been established. We therefore decided to conduct an exploratory clinical trial of dendritic cell vaccine loaded with Wilms’ tumor gene 1 peptides (TLP0-001) as a potential new treatment for patients with advanced pancreatic cancer refractory to standard chemotherapy.
Methods: This is an investigator-initiated double-blind comparative trial. The patients were allocated to two groups in a 1:1 ratio through a central registration by dynamic allocation. A total of 185 patients with inoperable or metastatic pancreatic cancer who were refractory or intolerant to standard primary chemotherapy with gemcitabine plus nab-paclitaxel will be allocated to secondary treatment either with placebo in combination with S-1 (the control group) or TLP0-001 in combination with S-1 (the investigational product group). The primary objective of this trial is to evaluate the safety and efficacy (as measured by overall survival) of the investigational product by comparing the two groups. This clinical trial will be performed in accordance with Japanese Good Clinical Practice guidelines.
Discussion: Clinical trials of the standard regimen, including gemcitabine, for advanced pancreatic cancer are ongoing worldwide. However, a strategy for after the primary treatment has not been established. We therefore decided to conduct this study to evaluate the safety and efficacy of TLP0-001 as a secondary treatment for pancreatic cancer in anticipation of the approval of this new drug in Japan. This trial is conducted with full consideration of safety as it is the first-in-human clinical trial of TLP0-001; thus, the trial will be conducted only at the Second Department of Surgery at Wakayama Medical University until the safety is confirmed by interim analysis. We plan to conduct a multicenter trial at 18 institutions in Japan after confirmation of the safety.
Trial registration: University Hospital Medical Information Network Clinical Trials Registry, ID: UMIN000027179. Registered on 9 April 2017, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000031102
Delayed-Onset Interface Fluid Syndrome After LASIK Following Phacotrabeculectomy
Authors: Kim Chung Young , Jung Young Ho , Lee Eun Ji , Hyon Joon Young , Park Kyu Hyung , Kim Tae Woo 
Published: February 2019

Abstract
Background
Interface fluid syndrome (IFS) is an unusual complication after laser-assisted in-situ keratomileusis (LASIK). We report the first case of IFS after uncomplicated phacotrabeculectomy in a patient who had undergone LASIK 10 years previously. This case emphasizes the importance of intraocular pressure (IOP) interpretation in eyes that have undergone LASIK.

Case presentation
A 30-year-old woman with a history of LASIK surgery presented to glaucoma clinic due to uncontrolled IOP despite of maximally tolerable medical treatment. After receiving phacotrabeculectomy, IOP decreased to 3mmHg on the first postoperative day, but again increased up to 21mmHg and a diffuse corneal edema with cloudy flap interface was demonstrated by slit-lamp microscopy. Corneal edema was sustained even after the IOP was lowered to 14 mmHg. Spectral-domain optical coherence tomography scanning of the cornea revealed a diffuse, thin fluid pocket in the corneal interface. After laser lysis of the scleral flap sutures, IOP was further decreased to 9mmHg and interface fluid was resolved.

Conclusion
IFS should be considered as a possible cause of postoperative corneal edema despite of low IOP in the eyes that underwent LASIK surgery. Additional IOP lowering may be helpful for resolving the corneal edema.
Fabry disease causes angiitis of the central nervous system:a case report
Authors: Kong De-Zheng , Lian Ya-Hui , Wang Lin-Jing , Wang Chun-Mei , Meng Yang-Yang , Zhou Hong-Wei 
Published: February 2019

Abstract
Background

Fabry disease is rare, and often the diagnosis is delayed. Here, we describe a case of Fabry disease resulting in vasculopathy of the central nervous system. Magnetic resonance (MR) black-blood sequence (three-dimensional T1 volumetric isotropic turbo spin echo acquisition), with a unique advantage of imaging the vascular wall, facilitated a clear identification of the vasculopathy.

Case presentation

A 27-year-old man visited our hospital for the treatment of " double vision 6d." After a series of examinations, the patient was diagnosed with Fabry disease, which caused vasculopathy of the central nervous system. Subsequently, the patient was treated with corticosteroids and his symptoms were attenuated. Two months after the initial treatment, the initial lesion formed in the vascular vessel disappeared, however, a new lesion appeared. Similarly, four months after the initial treatment, although the previous lesion disappeared, a new lesion appeared.

Conclusions

This case highlights that clinicians should use MR black-blood sequence scan in a timely manner in case of young patients with repeated strokes and migratory lesions. In case of detection of a vascular lesion in combination with other systemic lesions, the possibility of Fabry disease should be considered.
Views of healthcare professionals on recruiting to trials of psychosocial research: a qualitative study
Authors: Aspden Trefor , Armstrong Megan , Serfaty Marc 
Published: February 2019

Abstract
Background: Randomised controlled trials, and in particular those of psychosocial interventions, often fail to recruit to target, resulting in underpowered trials with poor generalisability of findings. The objectives of this study was to explore the views of healthcare professionals on recruiting to psychosocial research studies, and to explore their views on factors that may hinder or facilitate recruitment.

Methods: We conducted 14 semi-structured interviews, with healthcare professionals who had been involved in recruitment into a randomised controlled trial of a talking therapy for depression in patients with advanced cancer. Interviews were transcribed and analysed using thematic analysis.

Results: Six primary themes were identified, comprised of 15 subthemes. Attitudes towards research were largely positive. Health care professionals identified lack of time and narrow screening criteria as barriers to recruitment, and also noted the tendency to withhold participants from research for reasons other than eligibility (e.g., gatekeeping). The engagement of the study team with the clinical recruitment site, and the frequent presence of a researcher in clinics, were noted as facilitating recruitment.

Conclusions: Healthcare professionals involved in recruiting to trials of psychosocial interventions hold generally positive views of psychosocial research, but report that constraints limit their ability to recruit. The findings from this study can inform how best to design trials, and in particular trials of psychosocial interventions, and train health care professionals for the study, to maximise recruitment.

Trial registration: Controlled Trials ISRCTN07622709, registered 15 July 2011
The REstart or STop Antithrombotics Randomised Trial (RESTART) after stroke due to intracerebral haemorrhage: statistical analysis plan for a randomised controlled trial
Authors: Salman Rustam Al-Shahi , Murray Gordon D. , Dennis Martin S. , Newby David E. , Sandercock Peter A.G. , Sprigg Nikola , Sudlow Cathie L.M. , Werring David J. , White Philip M. , Whiteley William N. 
Published: February 2019

Abstract
Background: For adults surviving stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) who had taken an antithrombotic (i.e. anticoagulant or antiplatelet) drug for the prevention of vaso-occlusive disease before the ICH, it is unclear whether starting antiplatelet drugs modifies the risks of recurrent ICH, haemorrhagic events, vaso-occlusive events, or a composite of all serious vascular events compared to avoiding antiplatelet drugs.
Methods/design: The REstart or STop Antithrombotics Randomised Trial (RESTART) is an investigator-led, parallel group, open, assessor-blind, randomised trial comparing starting versus avoiding antiplatelet drugs for adults surviving antithrombotic-associated ICH. Recruitment began on 22 May 2013 and ended on 31 May 2018. Follow-up ended on 30 November 2018. This update to the protocol describes the statistical analysis plan (version 1.7, finalised on 25 January 2019). Database lock and un-blinding occured on 29 January 2019, after which the un-blinded trial statistician conducted the final analyses according to this statistical analysis plan.
Discussion: Final results of RESTART will be analysed and disseminated in May 2019.
Trial registration: ISRCTN registry 71907627. Prospectively registered on 25 April 2013.
The trial is funded by a British Heart Foundation special project grant (SP/12/2/29422) and a travel fellowship (FS/13/72/30531). The trial sponsor is the Academic and Clinical Central Office for Research and Development (ACCORD), which is a partnership between the University of Edinburgh and NHS Lothian Health Board.
Antithrombin Supplementation during Extracorporeal Membrane Oxygenation: Study Protocol for a Pilot Randomized Clinical Trial
Authors: Panigada Mauro , Spinelli Elena , Cucino Alberto , Cipriani Elisa , De Falco Stefano , Panarello Giovanna , Occhipinti Giovanna , Arcadipane Antonio , Sales Gabriele , Fanelli Vito , Brazzi Luca , Novembrino Cristina , Consonni Dario , Pesenti Antonio , Grasselli Giacomo 
Published: February 2019

Abstract
Background: Normal levels of plasma antithrombin (AT) activity might decrease heparin requirements to achieve an adequate level of anticoagulation during treatment with extracorporeal membrane oxygenation (ECMO). Acquired AT deficiency during ECMO is common, but formal recommendation on target, timing, and rate of AT supplementation is lacking. Thus, we conceived a pilot trial to evaluate the feasibility and safety of prolonged AT supplementation in patients requiring veno-venous ECMO for respiratory failure.
Methods: GATRA is a phase 3, prospective, randomized, single blinded multicenter controlled two-arm trial. Patients undergoing veno-venous ECMO will be randomized to either receive AT supplementation to maintain a functional AT level between 80%-120% (AT supplementation group) or not (control group) for the entire ECMO course. In both study groups anticoagulation will be provided with unfractionated heparin following a standardized protocol. The primary endpoint will be the dose of heparin required to maintain ratio of activated partial thromboplastin time between 1.5-2. Secondary endpoints will be the adequacy of anticoagulation and the incidence of hemorrhagic and thrombotic complications.
Discussion: GATRA is a pilot trial that will test the efficacy of a protocol of AT supplementation in decreasing the heparin dose and improving anticoagulation adequacy during ECMO. If positive, it might provide the basis for a future larger trial aimed at verifying the impact of AT supplementation on a composite outcome endpoint including hemorrhagic events, transfusion requirements and mortality.

Trial registration

ClinicalTrials.gov, NCT03208270. Registered on 5 July 2017.
Expert panel process to optimise the design of a randomised controlled trial in chronic rhinosinusitis (the MACRO programme).
Authors: Vennik Jane , Blackshaw Helen , Philpott Carl , Thomas Mike , Eyles Caroline , Carpenter James , Clarke Caroline S , Morris Stephen , Schilder Anne , Lund Valerie , Little Paul , Durham Stephen , Denaxas Spiros , Williamson Elizabeth , Beard David , Cook Jonathan , Conte Steffi Le , Airey Kim , Boardman Jim , Hopkins Claire 
Published: February 2019

Abstract
Background

MACRO (Defining best Management for Adults with Chronic RhinOsinusitis) is an NIHR-funded programme of work designed to establish best practice for adults with chronic rhinosinusitis (CRS). The 7-year programme comprises three consecutive workstreams, designed to explore NHS care pathways through analysis of primary and secondary data sources, and to undertake a randomised controlled trial to evaluate a longer-term course of macrolide antibiotics and endoscopic sinus surgery for patients with CRS. A number of outstanding elements still required clarification at the funding stage. This paper reports an expert panel review process designed to agree and finalise the MACRO trial design, ensuring relevance to patients and clinicians whilst maximising trial recruitment and retention.

Methods

An expert panel consisting of the MACRO programme management group, independent advisors, and patient contributors, was convened to review current evidence and the mixed method data collected as part of the programme, and reach agreement on MACRO trial design. Specifically, agreement was sought for selection of macrolide antibiotic, use of oral steroids, inclusion of CRS phenotypes (with/without nasal polyps), and overall trial design.

Results

A 12-week course of clarithromycin was agreed as the main trial comparator, due to its increasing use as a first and second line treatment for patients with CRS, and the perceived need to establish its role in CRS management. Oral steroids will be used as a rescue medication during the trial, rather than routinely either pre or post trial randomisation, to limit any potential effects on surgical outcomes and better reflect current UK prescribing habits. Both CRS phenotypes will be included in a single trial to ensure the MACRO trial is both pragmatic and generalisable to primary care. A modified 3-arm trial design was agreed after intense discussions and further exploratory work. Inclusion criteria were amended to ensure that patients recruited would be considered eligible for the treatment offered in the trial, due to having already received appropriate medical therapy as deemed suitable by their ENT surgeon. A proposed 6-week run-in period prior to randomisation was removed due to the new criteria prior to randomisation.

Conclusion

The expert panel review process resulted in agreement on key elements and an optimal design for the MACRO trial, considered most likely to be successful in terms of both recruitment potential and ability to establish best management of patients with CRS.
A Predictive Model for the US Non-profit Market; A Macro to a Micro Perspective
Authors: Quevedo Francisco J , Quevedo-Prince Andrea Katherine 
Published: February 2019

The Non-Profit Sector contributes almost $1 trillion to the US economy, representing 5.4% of GDP, and generating over 12 million jobs in 2017. Researchers suggest that a better understanding of the factors that affect fundraising would be of great interest to policy makers and fundraisers. However, the workings of the sector are subject of much debate. Some relate its size to the Theory of Government Failure, while others propose that government funding does have a positive effect on revenues. Some have suggested they swing with Gross Domestic Product (GDP), but others contradict this view and contend that macroeconomic variables do not affect short-run dynamics. Some research found that non-profit revenues react more to economic upswings than downturns, but nationwide organizations relate the ups-and-downs to certain events, as they influence public awareness. Predictive modeling overall has focused on big-donor analytics, aimed at identifying potential sponsors. Our research set out instead to define a working model for the US Non-Profit Sector. After an exhausting search, we located complete time series for an emblematic segment, the environmental cause, Factor Analysis allowed us to pinpoint the independent variables. We found that Non-Profit Revenues (NPR) depend largely on Public Awareness, as measured by TV coverage, and on Disposable Personal Income (DPI), specifically: NPR = -4401.542 + 528.327(DPI) +23.121(TVCoverage) + Ɛ We replicated prior research, which sought out relationships between macro-economic variables and NPR. That study had discarded the correlation between GDP and NPR as obvious, but did not explore DPI as the determining factor, and stuck to single variable searches, finding a correlation between the Standard & Poors index and lagged NPR figures, with a correlation coefficient of 0.636. Our model’s Pearson's R came up to 0.935, with perfect significance levels. Confirmatory Factor Analysis reaffirmed the fit of our equation, with an R² of 0.87.
Redesigning the ventilated improved pit latrine for use in built-up low-income settings
Authors: Obeng Peter A. , Oduro-Kwarteng Sampson , Keraita Bernard , Bregnhøj Henrik , Abaidoo Robert C. , Awuah Esi , Konradsen Flemming 
Published: February 2019

Abstract
The ventilated improved pit (VIP) latrine has the potential to address the challenge of access to improved sanitation in built-up low-income settings. However, its conventional technical design fails to address the needs and preferences of some users. The objective of this paper was to test the technical performance of modified engineering designs of the technology to respond to some preferences of toilet users. The entry of air from multiple windows in the superstructure and installation of insect screens in windows were tested in an experimental VIP latrine. The modified design achieved the recommended ventilation rate of 20 m3/h when a vent pipe diameter of 150 mm was used. The study concludes that adopting a multidirectional airflow design leads to a lower ventilation rate as compared to the conventional design. However, when fitted with the recommended size of vent pipe, this modified design achieves more than twice the recommended ventilation rate with or without an insect screen installed in the windows. Nevertheless, the practice in which 100 mm diameter vent pipes are used with insect screens installed in windows is likely to lead to odour problems due to inadequate ventilation through the vent pipe.
Flood disaster evaluation based on adaptive fuzzy clustering iterative model and hybrid differential evolution algorithm
Authors: Qiang Zou , Li Liao , Hui Qin 
Published: February 2019

Abstract
In order to reasonably and rapidly evaluate flood disaster, based on a fuzzy clustering iterative model (FCI) and differential evolution algorithm (DE), an adaptive fuzzy clustering iterative model using a hybrid differential evolution algorithm (AFCI-HDE) is proposed, which has three advantages: firstly, the decision-maker's subjective preference was considered to flexibly modify the objective function; secondly, HDE was introduced to optimize the index weight vector of AFCI; thirdly, the validity of its clustering effect was more credible than that of FCI. Finally, the case study revealed that AFCI-HDE is feasible and effective by comparing the optimal fitness and clustering validity values with other approaches, which could reflect various decision-maker's preferences by simple adaptive adjustments and rapidly obtain reasonable evaluation results, thus providing a new effective approach in flood risk management.
Nitrogen removal and responses of bacterial communities in activated sludge under different operational manipulations
Authors: Yasong Chen , Junling Lu , Zheng Zhao , Huiping Chen , Yuke Peng , Lin Xiao 
Published: February 2019

Abstract
Operational conditions are often manipulated to improve the nitrogen removal performance of wastewater treatment, yet the impacts of operational conditions on microbial communities were still not well understood. There is a pressing need to understand the microbial mechanisms that link operation manipulation and nitrogen removal performance. In this study, high-throughput analysis of 16S rDNA and quantitative polymerase chain reaction of functional genes were used to identify the microbial response to operational manipulations. The results showed that alteration of operational parameters could change the bacterial communities at the genera level and denitrification guild gradually dominated in the activated sludge bacterial communities. Heterotrophic Hyphomicrobium and Chromatiaceae drove the kinetic of dominant genera and denitrification guild. Carbon source supplement was the most efficient strategy for improving nitrogen removal, and greatly increased the abundance of denitrifiers and denitrification genes. However, carbon source supplement inhibited expression activities of denitrification genes, as well as the proliferation of autotrophic denitrifiers, and it was supposed to be unfavorable in terms of cost over the long term. The result should bring new inspiration for improving the effect of WWTP performance through the manipulation of operational parameters.
Genitourinary Tumors: Update on Molecular Biomarkers for Diagnosis, Prognosis and Prediction of Response to Therapy
Authors: Cimadamore Alessia , Scarpelli Marina , Santoni Matteo , Massari Francesco , Tartari Francesca , Cerqueti Roy , Lopez-Beltran Antonio , Cheng Liang , Montironi Rodolfo 
Published: February 2019

Background:Research of biomarkers in genitourinary tumors goes along with the development of complex emerging techniques ranging from next generation sequencing platforms, applied to archival pathology specimens, cytological samples, liquid biopsies, and to patient-derived tumor models.Methods:This contribution is an update on molecular biomarkers for diagnosis, prognosis and prediction of response to therapy in genitourinary tumors. The following major topics are dealt with: Immunological biomarkers, including the microbiome, and their potential role and caveats in renal cell carcinoma, bladder and prostate cancers and testicular germ cell tumors; Tissue biomarkers for imaging and therapy, with emphasis on Prostate-specific membrane antigen in prostate cancer; Liquid biomarkers in prostate cancer, including circulating tumor cell isolation and characterization in renal cell carcinoma, bladder cancer with emphasis on biomarkers detectable in the urine and testicular germ cell tumors; and Biomarkers and economic sustainability.Conclusion:The identification of effective biomarkers has become a major focus in cancer research, mainly due to the necessity of selecting potentially responsive patients in order to improve their outcomes, as well as to reduce the toxicity and costs related to ineffective treatments.
Neurometabolic Diseases in Children: Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy Features
Authors: Aksoy Direnç Özlem , Alkan Alpay 
Published: February 2019

Background:Neurometabolic diseases are a group of diseases secondary to disorders in different metabolic pathways, which lead to white and/or gray matter of the brain involvement. </P><P> Discussion: Neurometabolic disorders are divided in two groups as dysmyelinating and demyelinating diseases. Because of wide spectrum of these disorders, there are many different classifications of neurometabolic diseases. We used the classification according to brain involvement areas. In radiological evaluation, MRI provides useful information for these disseases.Conclusion:Magnetic Resonance Spectroscopy (MRS) provides additional metabolic information for diagnosis and follow ups in childhood with neurometabolic diseases.