bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Satisfaction With Comorbid Depression Care Models Among Low-Income Patients With Diabetes
Authors: Evanson Olivia , Wu Shinyi 
Published: October 2019

Introduction: Patient satisfaction is a patient-reported outcome with the potential to assess and improve the quality of newer care-management models such as remote patient monitoring using telecommunication technology. Objective: To evaluate differences in patient satisfaction among 3 care management groups in a comparative effectiveness trial. Methods: This study analyzed a comparative effectiveness trial that tested automated remote assessment technology–facilitated comorbid depression care-management (TC, n = 254) in comparison to team-supported depression care (SC, n = 228) and usual primary care (UC, n = 218) among low-income patients with type 2 diabetes. Relationships between patient satisfaction and care group were evaluated at each 6-month phase up to 18 months using linear regression models that controlled for depression status, diabetes symptoms, patient characteristics, and study group differences. Results: While receiving care management, SC and TC patients were significantly more satisfied with depression care than UC patients. No consistently significant associations between patient satisfaction and patient characteristics or disease symptoms were found. Conclusions: Patient satisfaction was found to be influenced by elements of care-management, not by patient characteristics or disease symptoms. Results suggest greater patient satisfaction with depression care in a care-management model than UC, whether through clinician team support or automated remote monitoring technology.
Analysis of the cost-effectiveness of treatment strategies for CML with incorporation of treatment discontinuation
Authors: Yamamoto Chihiro , Nakashima Hirotomo , Ikeda Takashi , Kawaguchi Shin-ichiro , Toda Yumiko , Ito Shoko , Mashima Kiyomi , Nagayama Takashi , Umino Kento , Minakata Daisuke , Nakano Hirofumi , Morita Kaoru , Yamasaki Ryoko , Sugimoto Miyuki , Ishihara Yuko , Ashizawa Masahiro , Hatano Kaoru , Sato Kazuya , Oh Iekuni , Fujiwara Shin-ichiro , Ueda Masuzu , Ohmine Ken , Muroi Kazuo , Kanda Yoshinobu 
Published: October 2019

Key Points
The cost of TKI for treatment of CML can be substantially saved by treatment discontinuation in patients who achieved DMR. Starting treatment with imatinib is the most cost-effective strategy even after incorporation of treatment discontinuation.
Determinants of ADL and IADL disability in older adults in southeastern Poland
Authors: Ćwirlej-Sozańska Agnieszka , Wiśniowska-Szurlej Agnieszka , Wilmowska-Pietruszyńska Anna , Sozański Bernard 
Published: October 2019

Abstract

Background
The extension of the life span has led to an increase in the number of older people and an increase in the prevalence of disability in people over 60 years of age. The aim of this study was to assess the prevalence of ADL and IADL disability and to analyze its determinants among people aged 60 and older living in southeastern Poland.

Methods
This cross-sectional study was carried out among a randomly selected, representative population of people aged 60 and older living in southeastern Poland. Disability was assessed using the Katz Index of Independence in Basic Activities of Daily Living and Instrumental Activities of Daily Living. Logistic regression models were used to identify the factors related to ADLs and IADLs. For the variables that were included in the above models, their clustered influence on the increase in the odds ratio for the occurrence of an ADL or IADL limitation was also examined.

Results
The research results show that 35.75% of the participants reported at least one problem with IADLs. At least one problem with ADLs was reported by 17.13% of the participants. The most significant modifiable factors influencing the occurrence of disability were the presence of barriers in the participant’s environment, poor relations with relatives, a lack of social contacts, multimorbidity and pain. A multiple increase in the odds ratio of disability was found with the presence of pairs of analyzed factors. The highest odds ratio of at least one ADL limitation was observed for the combination of barriers in the participant’s environment with multimorbidity (OR 74.07). With regard to IADL disability, the highest odds ratio was observed for the combination of pain on the VAS scale ≥3 points with older age (OR 19.47).

Conclusions
The study showed a high prevalence of ADL and IADL disability in older people living in southeastern Poland. It also indicated the extent to which modifiable factors influenced the occurrence of disability and the extent to which the risk of disability increased with the presence of pairs of factors, especially those that included environmental barriers in the participant’s environment.
Probable progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome with immunosuppressant dose reduction following lung transplantation: a case report and literature review
Authors: Ishii Kazuhiro , Yamamoto Fumiko , Homma Shinsuke , Okada Yoshinori , Nakamichi Kazuo , Saijo Masayuki , Tamaoka Akira 
Published: October 2019

Abstract

Background
Progressive multifocal leukoencephalopathy (PML) is a rapidly developing demyelinating disease in the cerebral white matter and is often caused by JC polyomavirus (JCV). PML after lung transplantation is rare and has a poor prognosis, with no established therapies. Reducing the patient’s immunosuppressant doses, thereby restoring immunity, could be used to treat PML. However, some patients develop immune reconstitution inflammatory syndrome (IRIS) with this treatment, an immune-induced inflammatory response to JCV that results in serious neuronal damage. We herein report a case of a 60-year-old female who suffered from PML 5 years after lung transplantation, had worsened brain lesions thought to be related to PML-IRIS at the time of immunosuppressant reduction, and missed treatment opportunities.

Case presentation
A 60-year-old female developed PML 5 years after lung transplantation. Fluid-attenuated inversion recovery and diffusion-weighted brain magnetic resonance imaging (MRI) revealed multiple high-signal lesions, mainly in the cerebral white matter. Polymerase chain reaction found 0.32 million copies/mL of JCV in the cerebrospinal fluid. Thus, she was given a diagnosis of PML. Mycophenolate mofetil and tacrolimus dosages were reduced, and CD4-positive cell counts and the blood concentration of each immunosuppressant were monitored. Mefloquine was also orally administered at a daily dose of 275 mg for 3 days and was then administered at a dose of 275 mg per week. Although the patient’s CD4-positive cell counts increased and her immune system recovered, her symptoms and brain MRI findings worsened. We suspected PML progression or a transition to PML-IRIS. Steroid pulse therapy to suppress the inflammatory lesions was not possible but was retrospectively indicated. The patient rapidly began to exhibit akinetic mutism and died 4 months after the onset of neurologic symptoms.

Conclusions
When neurologic symptoms and abnormal brain MRI findings are noted during immune recovery, it is often difficult to distinguish between progressed PML and PML-IRIS. However, the pathogenesis of brain lesions usually involves inflammation and immune-reactive mechanisms for JCV. Steroid pulse therapy, which can reduce inflammation, should thus be administered in organ transplantation cases with differential diagnoses including PML-IRIS.
Tumor cell sensitivity to vemurafenib can be predicted from protein expression in a BRAF-V600E basket trial setting
Authors: Carroll Molly J. , Parent Carl R. , Page David , Kreeger Pamela K. 
Published: October 2019

AbstractBackgroundGenetics-based basket trials have emerged to test targeted therapeutics across multiple cancer types. However, while vemurafenib is FDA-approved forBRAF-V600E melanomas, the non-melanoma basket trial was unsuccessful, suggesting mutation status is insufficient to predict response. We hypothesized that proteomic data would complement mutation status to identify vemurafenib-sensitive tumors and effective co-treatments forBRAF-V600E tumors with inherent resistance.MethodsReverse Phase Proteomic Array (RPPA, MD Anderson Cell Lines Project), RNAseq (Cancer Cell Line Encyclopedia) and vemurafenib sensitivity (Cancer Therapeutic Response Portal) data forBRAF-V600E cancer cell lines were curated. Linear and nonlinear regression models using RPPA protein or RNAseq were evaluated and compared based on their ability to predictBRAF-V600E cell line sensitivity (area under the dose response curve). Accuracies of all models were evaluated using hold-out testing. CausalPath software was used to identify protein-protein interaction networks that could explain differential protein expression in resistant cells. Human examination of features employed by the model, the identified protein interaction networks, and model simulation suggested anti-ErbB co-therapy would counter intrinsic resistance to vemurafenib. To validate this potential co-therapy, cell lines were treated with vemurafenib and dacomitinib (a pan-ErbB inhibitor) and the number of viable cells was measured.ResultsOrthogonal partial least squares (O-PLS) predicted vemurafenib sensitivity with greater accuracy in both melanoma and non-melanomaBRAF-V600E cell lines than other leading machine learning methods, specifically Random Forests, Support Vector Regression (linear and quadratic kernels) and LASSO-penalized regression. Additionally, use of transcriptomic in place of proteomic data weakened model performance. Model analysis revealed that resistant lines had elevated expression and activation of ErbB receptors, suggesting ErbB inhibition could improve vemurafenib response. As predicted, experimental evaluation of vemurafenib plus dacomitinb demonstrated improved efficacy relative to monotherapies.Conclusions: Combined, our results support that inclusion of proteomics can predict drug response and identify co-therapies in a basket setting.
Short-term treatment with high dose liraglutide improves lipid and lipoprotein profile and changes hormonal mediators of lipid metabolism in obese patients with no overt type 2 diabetes mellitus: a randomized, placebo-controlled, cross-over, double-blind clinical trial
Authors: Peradze Natia , Farr Olivia M. , Perakakis Nikolaos , Lázaro Iolanda , Sala-Vila Aleix , Mantzoros Christos S. 
Published: October 2019

Abstract
Objective
Long-term treatment with up to 1.8 mg liraglutide improves cardiovascular and all-cause mortality in patients with type 2 diabetes at high risk for cardiovascular disease (CVD) and is currently under investigation in subjects without diabetes. Aim of our study was to investigate whether high dose (3 mg) short-term (5 weeks) treatment with liraglutide in obese patients with no overt type 2 diabetes affects metabolites, lipid and lipoprotein profile and components of activin–follistatin axis in cardiovascular beneficial or detrimental way.

Research design and methods
Twenty obese patients participated in a randomized, placebo-controlled, cross-over, double-blind study and were administrated liraglutide 3 mg or placebo for 5 weeks. Metabolites, fatty acids, lipid–lipoprotein profile and concentrations of activins and follistatins (250 parameters) were assessed in serum at start and completion of each treatment.

Results
Concentrations of important cardiovascular markers such as total, free and remnant cholesterol were reduced with liraglutide before and after adjusting for weight loss. Similarly, reductions in number of small and medium size LDL particles and in their total lipid concentration were observed with liraglutide and partially weight-loss related. Tyrosine levels were reduced and behenic acid levels were increased whereas only minor changes were observed in HDL, VLDL and IDL. Concentrations of activin AB and follistatin were significantly reduced in liraglutide-treated group.

Conclusions
Treatment of obese patients without overt type 2 diabetes with high dose of liraglutide for a short period of time induces changes in lipid–lipoprotein and hormonal profile that are suggestive of lower risk of atherosclerosis and CVD.
Trial registration ClinicalTrials.gov Identifier: NCT02944500. Study ID Number 2015P000327. Registered November 2016
Luseogliflozin attenuates neointimal hyperplasia after wire injury in high-fat diet-fed mice via inhibition of perivascular adipose tissue remodeling
Authors: Mori Yusaku , Terasaki Michishige , Hiromura Munenori , Saito Tomomi , Kushima Hideki , Koshibu Masakazu , Osaka Naoya , Ohara Makoto , Fukui Tomoyasu , Ohtaki Hirokazu , Tsutomu Hirano , Yamagishi Sho-ichi 
Published: October 2019

AbstractBackgroundExcess fat deposition could induce phenotypic changes of perivascular adipose tissue (PVAT remodeling), which may promote the progression of atherosclerosis via modulation of adipocytokine secretion. However, it remains unclear whether and how suppression of PVAT remodeling could attenuate vascular injury. In this study, we examined the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitor, luseogliflozin on PVAT remodeling and neointima formation after wire injury in mice.MethodsWilt-type mice fed with low-fat diet (LFD) or high-fat diet (HFD) received oral administration of luseogliflozin (18 mg/kg/day) or vehicle. Mice underwent bilateral femoral artery wire injury followed by unilateral removal of surrounding PVAT. After 25 days, injured femoral arteries and surrounding PVAT were analyzed.ResultsIn LFD-fed lean mice, neither luseogliflozin treatment or PVAT removal attenuated the intima-to-media (I/M) ratio of injured arteries. However, in HFD-fed mice, luseogliflozin or PVAT removal reduced the I/M ratio, whereas their combination showed no additive reduction. In PVAT surrounding injured femoral arteries of HFD-fed mice, luseogliflozin treatment decreased the adipocyte sizes. Furthermore, luseogliflozin reduced accumulation of macrophages expressing platelet-derived growth factor-B (PDGF-B) and increasedadiponectingene expression. Gene expression levels ofPdgf-bin PVAT were correlated with the I/M ratio.ConclusionsOur present study suggests that luseogliflozin could attenuate neointimal hyperplasia after wire injury in HFD-fed mice partly via suppression of macrophage PDGF-B expression in PVAT. Inhibition of PVAT remodeling by luseogliflozin may be a novel therapeutic target for vascular remodeling after angioplasty.
Association of statin use and clinical outcomes in heart failure patients: a systematic review and meta-analysis
Authors: Bielecka-Dabrowa Agata , Bytyçi Ibadete , Von Haehling Stephan , Anker Stefan , Jozwiak Jacek , Rysz Jacek , Hernandez Adrian V. , Bajraktari Gani , Mikhalidis Dimitri P. , Banach Maciej 
Published: October 2019

Abstract

Background
The role of statins in patients with heart failure (HF) of different levels of left ventricular ejection fraction (LVEF) remains unclear especially in the light of the absence of prospective data from randomized controlled trials (RCTs) in non-ischemic HF, and taking into account potential statins’ prosarcopenic effects. We assessed the association of statin use with clinical outcomes in patients with HF.

Methods
We searched PubMed, EMBASE, Scopus, Google Scholar and Cochrane Central until August 2018 for RCTs and prospective cohorts comparing clinical outcomes with statin vs non-statin use in patients with HF at different LVEF levels. We followed the guidelines of the 2009 PRISMA statement for reporting and applied independent extraction by multiple observers. Meta-analyses of hazard ratios (HRs) of effects of statins on clinical outcomes used generic inverse variance method and random model effects. Clinical outcomes were all-cause mortality, cardiovascular (CV) mortality and CV hospitalization.

Results
Finally we included 17 studies (n = 88,100; 2 RCTs and 15 cohorts) comparing statin vs non-statin users (mean follow-up 36 months). Compared with non-statin use, statin use was associated with lower risk of all-cause mortality (HR 0.77, 95% confidence interval [CI], 0.72–0.83, P < 0.0001, I2 = 63%), CV mortality (HR 0.82, 95% CI: 0.76–0.88, P < 0.0001, I2 = 63%), and CV hospitalization (HR 0.78, 95% CI: 0.69–0.89, P = 0.0003, I2 = 36%). All-cause mortality was reduced on statin therapy in HF with both EF < 40% and ≥ 40% (HR: 0.77, 95% Cl: 0.68–0.86, P < 0.00001, and HR 0.75, 95% CI: 0.69–0.82, P < 0.00001, respectively). Similarly, CV mortality (HR 0.86, 95% CI: 0.79–0.93, P = 0.0003, and HR 0.83, 95% CI: 0.77–0.90, P < 0.00001, respectively), and CV hospitalizations (HR 0.80 95% CI: 0.64–0.99, P = 0.04 and HR 0.76 95% CI: 0.61–0.93, P = 0.009, respectively) were reduced in these EF subgroups. Significant effects on all clinical outcomes were also found in cohort studies’ analyses; the effect was also larger and significant for lipophilic than hydrophilic statins.

Conclusions
In conclusion, statins may have a beneficial effect on CV outcomes irrespective of HF etiology and LVEF level. Lipophilic statins seem to be much more favorable for patients with heart failure.
Correction to: The small molecule WNT/β-catenin inhibitor CWP232291 blocks the growth of castration-resistant prostate cancer by activating the endoplasmic reticulum stress pathway
Authors: Pak Sahyun , Park Sejun , Kim Yunlim , Park Jung-Hyuck , Park Chan-Hee , Lee Kyoung-June , Kim Choung-soo , Ahn Hanjong 
Published: October 2019

In the original publication of this article [1], there are mistakes in Fig. 4d. The corrected Fig. 4 should be:
A green and facile synthesis of an industrially important quaternary heterocyclic intermediates for baricitinib
Authors: Cui Xin , Du Junming , Jia Zongqing , Wang Xilong , Jia Haiyong 
Published: October 2019

Abstract

Background
Baricitinib, with a 2-(1-(ethylsulfonyl)azetidin-3-yl)acetonitrile moiety at N-2 position of the pyrazol skeleton, is an oral and selective reversible inhibitor of the JAK1 and JAK2 and displays potent anti-inflammatory activity. Several research-scale synthetic methods have been reported for the preparation of key quaternary heterocyclic intermediates of baricitinib. However, they were all associated with several drawbacks, such as the expensive materials, usage of pollutional reagents, and poor yields.

Results
In this manuscript, we established a green and cost-effective synthesis of 2-(1-(ethylsulfonyl)azetidin-3-ylidene)acetonitrile and tert-butyl 3-(cyanomethylene)azetidine-1-carboxylate for further scale-up production of baricitinib. This synthetic method employs commercially available and low-cost starting material benzylamine and an industry-oriented reaction of green oxidation reaction in microchannel reactor to yield important quaternary heterocyclic intermediates.

Conclusion
Generally, this procedure is reasonable, green and suitable for industrial production.
Evolving liver inflammation in biochemically normal individuals with anti-mitochondria antibodies
Authors: Baldo Danielle Cristiane , Dellavance Alessandra , Ferraz Maria Lucia Gomes , Andrade Luis Eduardo C. 
Published: October 2019

Abstract

Background
Anti-mitochondria autoantibodies (AMA) occur in > 95% primary biliary cholangitis (PBC) patients. Biochemically normal AMA-positive (BN/AMA+) individuals, occasionally noticed by indirect immunofluorescence (IIF) on HEp-2 cells and confirmed in AMA-specific assays, may represent early stages of PBC. The Enhanced Liver Fibrosis (ELF) score is a surrogate marker for liver fibrosis. This prospective study investigated the ELF score in BN/AMA+ individuals and PBC patients, considering autoantibody avidity and serum levels along the years.

Methods
327 samples from 35 PBC and 59 BN/AMA+ were prospectively obtained in average 3.83 (range 0.50–7.40) years apart. Samples were tested by IIF on rat-kidney (IIF-AMA), western-blot for AMA (WB-AMA), and ELISA for antibodies against pyruvate-dehydrogenase (PDC-E2), gp210, sp100 and CENP-A/B. Anti-PDC-E2 avidity was determined by 6 M urea-elution ELISA. Alkaline phosphatase (ALP), gamma glutamyl transferase (ɣGT) and ELF score were measured by automated methods.

Results
Along the follow-up period BN/AMA+ subjects and PBC patients presented significant increase in serum anti-PDC-E2 (mean 10.45% and 8.86% per year; respectively), anti-PDC-E2 avidity (3.02% and 4.94%/year) and ELF score (3.24% and 2.71%/year). IIF-AMA and ɣGT increased in BN/AMA+ (6.59% and 2.36%) and decreased in PBC (− 4.89%/year and − 3.88%/year). In BN/AMA+ individuals there was positive correlation of ELF with IIF-AMA titer (r = 0.465; p < 0.001) and with anti-PDC-E2 levels (r = 0.239; p < 0.001). Expansion of autoantibody targets along time occurred in 39% BN/AMA+ and 49% PBC patients. The frequency of BN/AMA+ with high probability of having established PBC increased from 7 to 14%.

Conclusions
BN/AMA+ individuals present an orchestrated increase in ELF score and humoral autoimmune response over time, indicating an opportunity for early therapeutic intervention and prevention in autoimmunity.
Identification of novel B cell epitopes in the fiber protein of serotype 8 Fowl adenovirus
Authors: Lu Hao , Shao Hongxia , Chen Hongjun , Zhang Jianjun , Wang Weikang , Li Tuofan , Xie Quan , Qin Aijian , Ye Jianqiang 
Published: October 2019

Abstract
In recent years, hepatitis-hydropericardium syndrome (HHS) and inclusion body hepatitis (IBH) caused by fowl adenovirus (FAdV) infection have resulted in significant economic losses to the poultry industry worldwide. Epidemiological analysis revealed that serotype FAdV-8 is one of the major pathogenic FAdVs currently prevalent in domestic flocks. Although the fiber protein of FAdV plays vital roles in viral infection and pathogenesis, the B cell epitope in the fiber protein is less known. In this study, two monoclonal antibodies (mAbs) specific to fiber protein of FAdV-8, designated as 4D9 and 5F10, were prepared. Although the mAb 4D9 and 5F10 could not neutralize FAdV-8 infection, 4D9 and 5F10 showed good activities of indirect immunofluorescence, western blot and immunoprecipitation. Epitope analysis revealed that mAb 5F10 recognized 187–219aa in the fiber whereas mAb 4D9 recognized 113–149aa in the fiber. Sequence analysis showed that the epitope recognized by mAb 5F10 was conserve across serotypes FAdV-7, 8a and 8b whereas that for mAb 4D9 was only conserve in FAdV-8b. The generation of mAbs specific to fiber of FAdV-8 and the identification of the novel B cell epitopes here lay the foundation for further studying the antigenicity of the fiber and developing specific diagnosis for FAdV-8.