bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assertive outreach treatment versus care as usual for the treatment of high-need, high-cost alcohol related frequent attenders: study protocol for a randomised controlled trial
Authors: Blackwood R. , Wolstenholme A. , Kimergård A. , Fincham-Campbell S. , Khadjesari Z. , Coulton S. , Byford S. , Deluca P. , Jennings S. , Currell E. , Dunne J. , O’Toole J. , Winnington J. , Finch E. , Drummond C. 
Published: March 2020

AbstractBackgroundAlcohol-related hospital admissions have doubled in the last ten years to > 1.2 m per year in England. High-need, high-cost (HNHC) alcohol-related frequent attenders (ARFA) are a relatively small subgroup of patients, having multiple admissions or attendances from alcohol during a short time period. This trial aims to test the effectiveness of an assertive outreach treatment (AOT) approach in improving clinical outcomes for ARFA, and reducing resource use in the acute setting.MethodsOne hundred and sixty ARFA patients will be recruited and following baseline assessment, randomly assigned to AOT plus care as usual (CAU) or CAU alone in equal numbers. Baseline assessment includes alcohol consumption and related problems, physical and mental health comorbidity and health and social care service use in the previous 6 months using standard validated tools, plus a measure of resource use. Follow-up assessments at 6 and 12 months after randomization includes the same tools as baseline plus standard measure of patient satisfaction. Outcomes for CAU + AOT and CAU at 6 and 12 months will be compared, controlling for pre-specified baseline measures. Primary outcome will be percentage of days abstinent at 12 months. Secondary outcomes include emergency department (ED) attendance, number and length of hospital admissions, alcohol consumption, alcohol-related problems, other health service use, mental and physical comorbidity 6 and 12 months post intervention. Health economic analysis will estimate the economic impact of AOT from health, social care and societal perspectives and explore cost-effectiveness in terms of quality adjusted life years and alcohol consumption at 12-month follow-up.DiscussionAOT models piloted with alcohol dependent patients have demonstrated significant reductions in alcohol consumption and use of unplanned National Health Service (NHS) care, with increased engagement with alcohol treatment services, compared with patients receiving CAU. While AOT interventions are costlier per case than current standard care in the UK, the rationale for targeting HNHC ARFAs is because of their disproportionate contribution to overall alcohol burden on the NHS. No previous studies have evaluated the clinical and cost-effectiveness of AOT for HNHC ARFAs: this randomized controlled trial (RCT) targeting ARFAs across five South London NHS Trusts is the first.Trial registrationInternational standard randomized controlled trial number (ISRCTN) registry:ISRCTN67000214, retrospectively registered 26/11/2016.
Circulating matrix metalloproteinases and tissue metalloproteinase inhibitors in patients with idiopathic pulmonary fibrosis in the multicenter IPF-PRO Registry cohort
Authors:   on behalf of the IPF-PRO Registry investigators, Todd Jamie L. , Vinisko Richard , Liu Yi , Neely Megan L. , Overton Robert , Flaherty Kevin R. , Noth Imre , Newby L. Kristin , Lasky Joseph A. , Olman Mitchell A. , Hesslinger Christian , Leonard Thomas B. , Palmer Scott M. , Belperio John A. 
Published: March 2020

AbstractBackgroundMatrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) play important roles in the turnover of extracellular matrix and in the pathogenesis of idiopathic pulmonary fibrosis (IPF). This study aimed to determine the utility of circulating MMPs and TIMPs in distinguishing patients with IPF from controls and to explore associations between MMPs/TIMPs and measures of disease severity in patients with IPF.MethodsThe IPF cohort (n = 300) came from the IPF-PRO Registry, an observational multicenter registry of patients with IPF that was diagnosed or confirmed at the enrolling center in the past 6 months. Controls (n = 100) without known lung disease came from a population-based registry. Generalized linear models were used to compare circulating concentrations of MMPs 1, 2, 3, 7, 8, 9, 12, and 13 and TIMPs 1, 2, and 4 between patients with IPF and controls, and to investigate associations between circulating levels of these proteins and measures of IPF severity. Multivariable models were fit to identify the MMP/TIMPs that best distinguished patients with IPF from controls.ResultsAll the MMP/TIMPs analyzed were present at significantly higher levels in patients with IPF compared with controls except for TIMP2. Multivariable analyses selected MMP8, MMP9 and TIMP1 as top candidates for distinguishing patients with IPF from controls. Higher concentrations of MMP7, MMP12, MMP13 and TIMP4 were significantly associated with lower diffusion capacity of the lung for carbon monoxide (DLCO) % predicted and higher composite physiologic index (worse disease). MMP9 was associated with the composite physiologic index. No MMP/TIMPs were associated with forced vital capacity % predicted.ConclusionsCirculating MMPs and TIMPs were broadly elevated among patients with IPF. Select MMP/TIMPs strongly associated with measures of disease severity. Our results identify potential MMP/TIMP targets for further development as disease-related biomarkers.
TKA in the treatment of bilateral dysplasia epiphysealis hemimelica (Trevor’s Disease) of the knee in a 50-year-old man: a case report
Authors: Gao Fei , Chen Guo , Wang Ruoyu , Huang Pan , Wang Jing , Xu Weihua 
Published: March 2020

Abstract
Background
Dysplasia epiphysealis hemimelica (DEH), also known as Trevor’s disease, is a rare skeletal developmental disorder affecting the epiphyses in pediatric patients. DEH is characterized by an asymmetric osteochondral overgrowth arising from either the medial or lateral portion of an epiphysis and usually occurs in the joints of lower limbs, most commonly in the knees and ankles. However, bilateral involvement in an adult is extremely rare, and total knee arthroplasty (TKA) for a patient with DEH has been reported only once before.

Case presentation
Here, we present a case of bilateral DEH of the knees that caused varus deformity and dysfunction of the lower limbs in a 50-year-old man. TKA was performed for treatment, and the patient had satisfactory function with no angular knee deformity and a normal range of motion after 1 year of follow-up.

Conclusions
The patient in this case exhibited its specific clinical and radiological features of late-term DEH and TKA was proved to be an appropriate procedure for treating the severe deformity caused by this rare disease.
Accuracy of pedicle screw insertion for unilateral open transforaminal lumbar interbody fusion: a side-by-side comparison of percutaneous and conventional open techniques in the same patients
Authors: Sumiya Satoshi , Numano Fujiki , Ogawa Takahisa , Yoshii Toshitaka , Okawa Atsushi , Komori Hiromichi 
Published: March 2020

Abstract
Background
The aim of the study was to compare the accuracy of percutaneous pedicle screw (PPS) insertion (P-side) with that of conventional open screw insertion (O-side) during unilateral open transforaminal lumbar interbody fusion (TLIF) in the same patients. We also sought to determine the incidence of pedicle screw misplacement and to identify relevant risk factors.

Methods
The study was a retrospective analysis of prospectively collected data for 766 pedicle screws placed in 181 consecutive patients who underwent a unilateral open-TLIF procedure in the lumbosacral spine. Our minimally invasive TLIF was performed by unilateral open freehand insertion of pedicle screws for decompression on one side and PPS on the opposite side. Using this approach, we were able to compare the accuracy of PPS insertion with that of conventional open screw insertion in the same patients. There were 383 PPSs and 383 screws inserted by the open method. The accuracy of screw placement was evaluated on reconstructed computed tomography images obtained postoperatively, and screw misplacement was classified. Potential risk factors for screw misplacement were investigated in three-level mixed-effects logistic regression analysis.

Results
Thirty-four screws (8.9%) were misplaced on the P-side and 37 (9.5%) were misplaced on the O-side; the difference was not statistically significant (P = 0.803). Subclassification analysis revealed minor perforation of 28 screws (7.3%) on the P-side and 32 (8.4%) on the O-side, moderate perforation of 5 screws (1.3%) on the P-side and 4 (1.0%) on the O-side, and severe perforation of 1 screw (0.3%) on each side. Three-level mixed-effects logistic regression analysis identified body mass index as a significant risk factor for screw misplacement on the P-side (odds ratio 1.194, 95% confidence interval 1.066–1.338).

Conclusions
Accuracy of pedicle screw insertion was not significantly different between PPS insertion and conventional open screw insertion in the same patients. Body mass index had a significant influence on the risk of screw misplacement in PPS insertion.
A novel family of expression vectors with multiple affinity tags for wheat germ cell-free protein expression
Authors: Nagy Szilvia Krisztina , Kállai Brigitta Margit , András Judit , Mészáros Tamás 
Published: March 2020

Abstract
Background
Cell-free protein expression has become a widely used alternative of in vivo, cell-based systems in functional and structural studies of proteins. The wheat germ-based method outstands from the commercially available eukaryotic in vitro translation systems by its flexibility, high translation efficiency and success rate of properly folded eukaryotic protein synthesis. The original T7 promoter containing pEU3-NII vector was improved previously by addition of a ligation-independent cloning site, His6- and GST-tags, and a TEV protease cleavage site to facilitate the creation of recombinant plasmids, permit affinity purification, and enable production of purified, tag-free target proteins, respectively.

Results
Here, we describe a further development of pEU3-NII vector by inserting the rare-cutting, NotI restriction enzyme cleavage site to simplify vector linearization step prior to in vitro transcription. Additionally, His12, FLAG, and Halo affinity tag coding vectors have been created to increase detection sensitivity, specificity of interaction studies, and provide covalently linkable ligands for pull-down assays, respectively. Finally, the presented GST-His6, and GST-biotin double-tagging vectors could broaden the range of possibilities of protein-protein interaction studies.

Conclusions
The new generation of pEU3-NII vector family allows a more rapid production of translationally active mRNA and wheat germ cell-free expression of target proteins with a wide variety of affinity tags thus enables designing flexible and diverse experimental arrangement for in vitro studies of proteins.
Cyclooxygenase enzyme and PGE2 expression in patients with functional and non-functional pituitary adenomas
Authors: Akbari Nasrin , Ghorbani Mohammad , Salimi Vahid , Alimohammadi Alimohammad , Khamseh Mohammad E. , Akbari Hamideh , Nourbakhsh Mitra , Sheikhi Alireza , Taghavi S. Fahimeh , Tavakoli-Yaraki Masoumeh 
Published: March 2020

Abstract
Background
Pituitary adenomas as multifactorial intracranial neoplasms impose a massive burden of morbidity on patients and characterizing the molecular mechanism underlying their pathogenesis has received considerable attention. Despite the appealing role of cyclooxygenase enzymes and their bioactive lipid products in cancer pathogenesis, their relevance to pituitary adenoma pathogenesis is debated and yet to be determined. Thus, the current study perused this relevance.

Methods
The expression level of the isoforms of cyclooxygenase (COX-1 and COX-2) was evaluated in hormone-secreting and in-active pituitary adenoma tumors and normal pituitary tissues through Real-Time PCR. The level of PGE2, as the main product of enzymes, was assessed using enzyme immunoassay kits in patients and healthy subjects.

Results
The results of the current study demonstrated that COX-1 and COX-2 expression levels were increased in pituitary tumors including non-functional pituitary adenoma (NFPA), acromegaly, Cushing’s disease and prolactinoma compared with normal pituitary tissues. A significant expression level of COX-2 was observed in NFPA compared with the other pituitary tumors. Furthermore, the COX-2 expression level was significantly increased in macroadenoma and invasive tumors. The level of PGE2 was consistent with COX enzymes enhanced in pituitary adenoma tumors compared with healthy pituitary tissue. A significant elevation in the PGE2 level was detected in NFPA compared with hormone-secreting pituitary tumors. Additionally, the PGE2 level was increased in macroadenoma compared with microadenoma and in invasive compared with non-invasive pituitary tumors. The diagnostic values of cyclooxygenase isoforms and PGE2 were considerable between patients and healthy groups; however, COX-2 revealed more value in distinguishing endocrinologically active and non-active pituitary tumors.

Conclusions
Data from the current study provides expression patterns of COX-1, COX-2 and PGE2 in prevalent pituitary tumors and their association with patients’ clinical features which may open up new molecular targets for early diagnosis/follow up of pituitary tumor growth.
A pilot study: a possible implication of Candida as an etiologically endogenous pathogen for oral lichen planus
Authors: He Hong , Xia Xinyu , Yang Haiping , Peng Qiao , Zheng Jiaoer 
Published: March 2020

Abstract
Background
The aim of this study was to investigate the prevalence and genotypic profiles of Candida albicans in patients with oral lichen planus (OLP).

Materials and methods
Positive rates and genotypic profiles of Candida albicans strains from OLP patients and healthy controls were analyzed. Random amplified polymorphic DNA and internal transcribed spacer of ribosome DNA polymerase chain reactions were used to sequence the DNA of these strains, and then their genetic similarity was measured using BLAST, UIV Band, and Vector NTI Suite Sequence Analyses Software.

Results
The prevalence of C. albicans strains detected from erosive-OLP, non-erosive OLP, and normal individuals was 18.87, 18.75, and 7.92%, respectively. Four different genotypes were revealed by the two methods. To be specific, type I was found only in the healthy subjects; type II a and II b were found in non-erosive OLP, and type III was identified in erosive OLP. Intragroup similarity coefficients, i.e. SAB were 100%, and inter-groups similarity coefficients, i.e. SAB were less than 30%.

Conclusions
The genotypic results of C. albicans in OLP revealed an endogenous rather than exogenous infection of C. albicans. In addition, a possible pathogenic role of C. albicans in OLP, with the etiologic sense contributing to a more proper recognition on the pathogenesis, development, and progression of OLP, as well as some strategies for its diagnosis and treatment were identified.
Incidence trend of breast Cancer in women of eastern Mediterranean region countries from 1998 to 2019: A systematic review and meta-analysis
Authors: Zahedi Razieh , Molavi Vardanjani Hossein , Baneshi Mohammad Reza , Haghdoost Ali Akbar , Malekpour Afshar Reza , Ershad Sarabi Roghayeh , Tavakoli Fatemeh , Zolala Farzaneh 
Published: March 2020

Abstract
Background
This study was conducted to provide evidence on the current status of breast cancer and its incidence trend in Eastern Mediterranean Region during 1998–2019. Also, this study aimed to investigate the association between the incidence of breast cancer and Human Development Index and some factors related to this index, including total fertility rate, and obesity, using a meta-analysis.

Method
Data on incidence of breast cancer were collected from various sources, including PubMed, Embase, Web of Science, and WHO, from 1998 to 2019 using systematic review and meta-analysis. Pooled age standardized rate was calculated based on study duration and quality of data using a subgroup analysis and random effect meta-analysis.

Results
A total of 80 studies (545 data points) were analyzed. Pooled age standardized rate of breast cancer for Eastern Mediterranean Region was 37.1 per 100,000 person-year (95% confidence interval [CI], 34.5, 39.8) during 2011–2019. age standardized rate of breast cancer had an upward trend in Eastern Mediterranean Region from 2005 to 2019. However, the increasing trend was found to be slightly different in various regions based on quality of data. Moreover, pooled age standardized rate had a significant association with Human Development Index [− 89.2 (95% CI, − 119.8, − 58.7)] and obesity [1.2 (95% CI, 0.9, 1.5)].

Conclusion
Pooled age standardized rate of breast cancer in Eastern Mediterranean Region was lower than the global average. Also, the age standardized rate value and its incremental trend have been higher in countries with high-quality data than in other countries of this region in recent years. Data quality or physiological factors, such as increase in obesity rates, could be the reasons for this incremental trend.
Attitudes of Israeli medical students towards the medical treatment of uninsured migrants
Authors: Mor Zohar , Cadesky Adam , Halleluyan Ran , Sheffer Rivka 
Published: March 2020

Abstract
Background
Undocumented migration to developed countries poses practical concerns, as migrants are not medically insured. This cross-sectional study aims to appraise the attitudes of Israeli medical students towards the uninsured migrant population.

Methods
Participants from five medical schools in Israel completed anonymous questionnaires in Hebrew, based on the “Medical Students’ Attitudes Toward the Underserved” (MSATU), which assessed students’ attitudes regarding the professional responsibility and societal expectations towards the migrants. It also evaluated students’ views of the migrants as eligible for expensive medical procedures.

Results
A total of 891 students completed the survey with a median age of 28 years. The majority were Jews (N = 816, 91.6%) and singles (N = 681, 68.5%). Participants in the pre-clinical years were likely to be female and unmarried compared to those in clinical training. They also demonstrated higher scores on professional responsibilities and societal expectations than students in clinical training, but no significant differences were found in their views on expensive medical services. Students of minorities (non-Jews and migrants) scored higher on professional responsibilities and societal expectations.
The scores for professional responsibilities and societal expectations decreased as students progressed in their medical training (Spearman coefficient p = 0.04 and p = 0.01, respectively). This trend was more apparent in males rather than females.

Conclusion
MSATU scores declined as students progressed through medical school, with females maintaining more favorable attitudes than males. Medical schools should attempt to maintain the enthusiasm and idealism that students possess as they enter medical training and provide clinical experience with migrant populations that allows for cross-cultural communication.
Disease awareness or subtle product placement? Orphan diseases featured in the television series “House, M.D.” - a cross-sectional analysis
Authors: Mechler Konstantin , Rausch Juliane , Mountford William K. , Ries Markus 
Published: March 2020

Abstract
Background
Approximately 7% of the general population is affected by an orphan disease, which, in the United States, is defined as affecting fewer than 1 in 1500 people. Disease awareness is often low and time-to-diagnosis delayed. Different legislations worldwide have created incentives for pharmaceutical companies to develop drugs for orphan diseases. A journalistic article in Bloomberg Businessweek has claimed that pharmaceutical companies have tried marketing orphan drugs by placing a specific disease into the popular television series “House, M.D.” which features diagnostic journeys and was produced between 2004 and 2012. This study aimed to describe the presentation of orphan diseases in the television series “House, M.D.”, to test in an exploratory fashion the hypothesis that treatable orphan conditions are overrepresented in “House, M.D.” and to discuss whether such marketing practices may or may not be ethical.

Methods
A list of all medical cases depicted in the television series “House, M.D.” was obtained and classified as orphan or non-orphan according to the Orphanet database. The ratios of orphan diseases among all diseases, such with an orphan drug designation and such with an orphan drug approval by the FDA were then compared with conservative approximations of real world conditions (chi-squared tests for equality of proportions). STROBE criteria were respected.

Results
Out of a total of n = 181 different medical diagnoses, n = 42 (23.2%) were orphan diseases. The difference in percentages in between “House, M.D.” and reality was not statistically significant for orphan diseases overall (p = 0.96), yet was statistically significantly higher for both orphan diseases with one or more orphan drug designations (p = 0.0192) and such with one or more approved orphan drugs (p < 0.0001).

Conclusions
Orphan diseases with a designated and/or approved orphan drug were overrepresented in the television series “House, M.D.” with statistical significance while orphan diseases overall were not. This may be explained by (so far) undocumented efforts of pharmaceutical companies to place their orphan drugs in the television series, as described in the article in Bloomberg Businessweek. Further research is needed into marketing practices in popular and emerging media formats.