bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment With Treprostinil and Metformin Normalizes Hyperglycemia and Improves Cardiac Function in Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection Fraction
Authors: Wang Longfei , Halliday Gunner , Huot Joshua R. , Satoh Taijyu , Baust Jeffrey J. , Fisher Amanda , Cook Todd , Hu Jian , Avolio Theodore , Goncharov Dmitry A. , Bai Yang , Vanderpool Rebecca R. , Considine Robert V. , Bonetto Andrea , Tan Jiangning , Bachman Timothy N. , Sebastiani Andrea , McTiernan Charles F. , Mora Ana L. , Machado Roberto F. , Goncharova Elena A. , Gladwin Mark T. , Lai Yen-Chun 
Published: April 2020

Objective:
Pulmonary hypertension (PH) due to left heart disease (group 2), especially in the setting of heart failure with preserved ejection fraction (HFpEF), is the most common cause of PH worldwide; however, at present, there is no proven effective therapy available for its treatment. PH-HFpEF is associated with insulin resistance and features of metabolic syndrome. The stable prostacyclin analog, treprostinil, is an effective and widely used Food and Drug Administration-approved drug for the treatment of pulmonary arterial hypertension. While the effect of treprostinil on metabolic syndrome is unknown, a recent study suggests that the prostacyclin analog beraprost can improve glucose intolerance and insulin sensitivity. We sought to evaluate the effectiveness of treprostinil in the treatment of metabolic syndrome-associated PH-HFpEF.

Approach and Results:
Treprostinil treatment was given to mice with mild metabolic syndrome-associated PH-HFpEF induced by high-fat diet and to SU5416/obese ZSF1 rats, a model created by the treatment of rats with a more profound metabolic syndrome due to double leptin receptor defect (obese ZSF1) with a vascular endothelial growth factor receptor blocker SU5416. In high-fat diet-exposed mice, chronic treatment with treprostinil reduced hyperglycemia and pulmonary hypertension. In SU5416/Obese ZSF1 rats, treprostinil improved hyperglycemia with similar efficacy to that of metformin (a first-line drug for type 2 diabetes mellitus); the glucose-lowering effect of treprostinil was further potentiated by the combined treatment with metformin. Early treatment with treprostinil in SU5416/Obese ZSF1 rats lowered pulmonary pressures, and a late treatment with treprostinil together with metformin improved pulmonary artery acceleration time to ejection time ratio and tricuspid annular plane systolic excursion with AMPK (AMP-activated protein kinase) activation in skeletal muscle and the right ventricle.

Conclusions:
Our data suggest a potential use of treprostinil as an early treatment for mild metabolic syndrome-associated PH-HFpEF and that combined treatment with treprostinil and metformin may improve hyperglycemia and cardiac function in a more severe disease.
Endothelial Scaffolding Protein ENH (Enigma Homolog Protein) Promotes PHLPP2 (Pleckstrin Homology Domain and Leucine-Rich Repeat Protein Phosphatase 2)-Mediated Dephosphorylation of AKT1 and eNOS (Endothelial NO Synthase) Promoting Vascular Remodeling
Authors: Huang Jiaqi , Cai Changhong , Zheng Tianyu , Wu Xinyan , Wang Dongfei , Zhang Kaijie , Xu Bocheng , Yan Ruochen , Gong Hui , Zhang Jie , Shi Yueli , Xu Zhiyong , Zhang Xue , Zhang Xuemin , Shang Tao , Zhou Jianhong , Guo Xiaogang , Zeng Chunlai , Lai En Yin , Xiao Changchun , Chen Ju , Wan Shu , Liu Wen-Hsien , Ke Yuehai , Cheng Hongqiang 
Published: April 2020

Objective:
A decrease in nitric oxide, leading to vascular smooth muscle cell proliferation, is a common pathological feature of vascular proliferative diseases. Nitric oxide synthesis by eNOS (endothelial nitric oxide synthase) is precisely regulated by protein kinases including AKT1. ENH (enigma homolog protein) is a scaffolding protein for multiple protein kinases, but whether it regulates eNOS activation and vascular remodeling remains unknown.

Approach and Results:
ENH was upregulated in injured mouse arteries and human atherosclerotic plaques and was associated with coronary artery disease. Neointima formation in carotid arteries, induced by ligation or wire injury, was greatly decreased in endothelium-specific ENH-knockout mice. Vascular ligation reduced AKT and eNOS phosphorylation and nitric oxide production in the endothelium of control but not ENH-knockout mice. ENH was found to interact with AKT1 and its phosphatase PHLPP2 (pleckstrin homology domain and leucine-rich repeat protein phosphatase 2). AKT and eNOS activation were prolonged in VEGF (vascular endothelial growth factor)-induced ENH- or PHLPP2-deficient endothelial cells. Inhibitors of either AKT or eNOS effectively restored ligation-induced neointima formation in ENH-knockout mice. Moreover, endothelium-specific PHLPP2-knockout mice displayed reduced ligation-induced neointima formation. Finally, PHLPP2 was increased in the endothelia of human atherosclerotic plaques and blood cells from patients with coronary artery disease.

Conclusions:
ENH forms a complex with AKT1 and its phosphatase PHLPP2 to negatively regulate AKT1 activation in the artery endothelium. AKT1 deactivation, a decrease in nitric oxide generation, and subsequent neointima formation induced by vascular injury are mediated by ENH and PHLPP2. ENH and PHLPP2 are thus new proatherosclerotic factors that could be therapeutically targeted.
Cracking the EMDR code: Recruitment of sensory, memory and emotional networks during bilateral alternating auditory stimulation
Authors: Rousseau Pierre-François , Boukezzi Sarah , Garcia René , Chaminade Thierry , Khalfa Stéphanie 
Published: April 2020

Introduction: The inability to extinguish a conditioned fear is thought to be at the core of post-traumatic stress disorder. Eye movement desensitization and reprocessing therapy has been efficacious for post-traumatic stress disorder, but the brain mechanisms underlying the effect are still unknown. The core effect of eye movement desensitization and reprocessing therapy seems to rely on the simultaneous association of bilateral alternating stimulation and the recall of the traumatic memory. To shed light on how eye movement desensitization and reprocessing therapy functions, we aimed to highlight the structures activated by bilateral alternating stimulation during fear extinction and its recall. Methods: We included 38 healthy participants in this study. Participants were examined twice in functional magnetic resonance imaging, over 2 consecutive days. On the first day, they performed two fear conditioning and extinction procedures, one with and one without the bilateral alternating stimulation during the fear extinction learning phase in a counter-balanced order across the participants. On the second day, participants completed the fear extinction recall procedure, in the same order as the previous day. Statistical significance of maps was set at p < 0.05 after correction for family-wise error at the cluster level. Results: The analysis revealed significant activation with versus without bilateral alternating stimulation at the early extinction in the bilateral auditory areas, the right precuneus, and the left medial frontal gyrus. The same pattern was found in the early recall on the second day. The connectivity analysis found a significant increase in connectivity during bilateral alternating stimulation versus without bilateral alternating stimulation in the early extinction and recall between the two superior temporal gyri, the precuneus, the middle frontal gyrus and a set of structures involved in multisensory integration, executive control, emotional processing, salience and memory. Conclusion: We show for the first time that in the eye movement desensitization and reprocessing therapy the bilateral alternating stimulation is not a simple sensory signal and can activate large emotional neural networks.
The global management of leg ulceration: Pre early venous reflux ablation trial
Authors: Heatley Francine , Onida Sarah , Davies Alun H 
Published: April 2020

Background Various guidelines exist worldwide for the diagnosis and management of venous leg ulcers; however, these are difficult to implement resulting in disparate treatment of patients globally. Method An online, 26-question survey was designed to evaluate the current global management of venous leg ulceration and was emailed globally to approximately 15,000 participants (November 2017–February 2018). Results Overall, 799 responses were received from 86 countries, with a 5% response rate. The respondent physicians saw a median of 10 (interquartile range 5–20) patients per month, with a median time to referral from primary to secondary care of six weeks. Of the respondents, 61% arranged an ankle brachial pressure index on first visit and 84% performed a venous duplex, with 95% prescribing compression for those in whom it was not contraindicated. Fifty-nine percent performed endovenous intervention or surgery prior to ulcer healing. Conclusions The survey showed a diversity of treatment pathways. The need to develop a robust, clear pathway for patients with leg ulceration is clearly required.
Differential diagnosis of chromophobe renal cell carcinoma and papillary renal cell carcinoma with dual-energy spectral computed tomography
Authors: Wang Dan , Huang Xiaoyu , Bai Liangcai , Zhang Xueling , Wei Jinyan , Zhou Junlin 
Published: April 2020

Background Computed tomography (CT) image features of chromophobe renal cell carcinoma (ChRCC) and papillary renal cell carcinoma (PRCC) are, occasionally, sometimes difficult to identify. However, spectral CT might provide quantitative parameters to differentiate them. Purpose To differentiate between ChRCC and PRCC with quantitative parameters using spectral CT. Material and Methods Forty cases of RCC confirmed with pathological tests were analyzed retrospectively (27 cases of PRCC and 13 cases of ChRCC). All patients underwent non-enhanced CT and dual-phase contrast-enhanced CT scans. For each lesion, the CT value of monochromatic images as well as iodine and water concentrations were measured, and the slope of spectrum curve was calculated. Data were analyzed using Student’s t-test. Sensitivity and specificity of the quantitative parameters were analyzed using the receiver operating characteristic (ROC) curve. Results During the cortex phase (CP) and parenchyma phase (PP), the CT value and slope of spectrum curve of ChRCC were higher than those of PRCC, and significant differences were observed at low energy levels (40–70 keV). Normalized iodine concentration of ChRCC and that of PRCC was significantly different during CP and PP ( P < 0.05). The water (iodine) concentrations of ChRCC and PRCC in CP and PP were not statistically different ( P > 0.05). All the ROCs for parameters were above the reference line. Conclusion Spectral CT may help increase the diagnostic accuracy of differentiating PRCC from ChRCC using a quantitative analysis.
Occupational therapists’ experiences and perspectives towards occupation-based practice in Thailand: A mixed-methods study
Authors: Kaunnil Anuchart , Khemthong Supalak , Sriphetcharawut Sarinya , Thichanpiang Peeradech , Sansri Veerawat , Thongchoomsin Surachart , Permpoonputtana Kannika , Smith Cristina R 
Published: April 2020

Introduction Occupation-based practice is a core tenet of occupational therapy. This study explores perspectives and experiences with occupation-based practice among Thai occupational therapists. Method Using mixed methods, a focus group was conducted with eight occupational therapists, and the results were interpreted using thematic analysis. A questionnaire survey was also completed concerning practitioner perspectives ( n = 216). Findings Three major themes were identified: (a) perspectives on occupation-based practice were related to practice areas and felt to strengthen the identity of occupational therapy (52% strongly agree), leading to improved services and better outcomes for clients (44% strongly agree); (b) approaches focused on activities of daily living were appropriate for cross-practice areas; and (c) occupation-based practice is consistent with integrated medical sciences and occupations for clients (52% strongly agree). Conclusion Implementing occupation-based practice will be of value to clients, provide benefits as a compass to direct processes, and enhance clinical reasoning and outcomes.
Role of Various DW MRI and DCE MRI Parameters as Predictors of Malignancy in Solid Pulmonary Lesions
Authors: Kumar Neeraj , Sharma Mini , Aggarwal Neeti , Sharma Sanjiv , Sarkar Malay , Singh Balraj , Sharma Navneet 
Published: April 2020

Purpose: We aimed to evaluate various diffusion and dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) parameters in differentiating malignant from benign pulmonary lesions. Methods: We enrolled 31 (22 males) patients who had solid pulmonary lesion(s) >2 cm in our cross sectional study. Of these, 23 (74.2%) were found to be malignant on histopathology. Dynamic contrast-enhanced MRI was performed using 36 dynamic measurements (volumetric interpolated breath-hold examination). Diffusion-weighted MRI (DW MRI) performed at b value of 800 s/mm2. We measured different diffusion and perfusion parameters, for example, diffusion-weighted imaging (DWI) SI, mean apparent diffusion coefficient (ADC), minimum ADC, lesion-to-spinal cord ratio, DWI score, T2 score, Ktrans, Kep, and Ve. We stratified values of each parameter as high if it was >median of values observed in our data set and low if it was ≤median. Normally distributed data were compared by unpaired t test, whereas non-normal continuous data were compared by Kruskal Wallis-H test. We applied Wilson score method to calculate sensitivity, specificity, and predictive values of parameters that were statistically significant by type of lesion with reference to histopathological examination as gold standard. Results: Diffusion-weighted imaging SI, mean ADC, minimum ADC, DWI score and Ktrans values were found to be significantly different ( P value < .05) by type of lesion. Ktrans was found to have the highest diagnostic accuracy (74.2%) among these parameters. Conclusion: Ktrans and mean ADC had similar sensitivity of 65.2%. However, Ktrans had highest diagnostic accuracy among various DWI and DCE MRI parameters in predicting malignancy in solid pulmonary lesions. In our study, we found a cutoff value 0.251 min−1 for Ktrans as 100% specific.
Assessing biosimilar education needs among oncology pharmacy practitioners worldwide: An ISOPP membership survey
Authors: Chan Alexandre , Patel Himanshu , Siderov Jim , Bubalo Joseph , Foreman Emma 
Published: April 2020

Background The International Society of Oncology Pharmacy Practitioners (ISOPP) Biosimilar Task Force was charged to develop educational resources to address the learning needs related to biosimilars use of oncology pharmacy practitioners. To facilitate the process, the task force conducted a survey in order to identify unmet education needs as well as barriers for obtaining biosimilar education among oncology pharmacy practitioners. Methods A cross sectional survey was conducted between 10 December 2018 and 18 February 2019. Members of International Society of Oncology Pharmacy Practitioners and national oncology pharmacy groups were invited to complete the survey. The survey contained 22 items and consisted of four sections. Descriptive statistics were utilized to analyze the survey results. Results A total of 363 International Society of Oncology Pharmacy Practitioners members were surveyed, with 75 members providing a response (response rate = 21%). In addition, 11 non-International Society of Oncology Pharmacy Practitioners members also participated in the survey, bringing the total to 86 respondents. The top three areas in which respondents reported learning needs included evaluating comparative efficacy of a biosimilar to an originator’s product (74.4%), managing the switchover to a biosimilar from the original product (74.4%), and understanding medication safety issues in relation to biosimilars use (73.3%). The most common challenges faced in obtaining education on biosimilars included limited financial support for education on biosimilar products (38.4%), heavy workload (31.4%), and inadequate educational resources (27.9%). Conclusion This survey has identified numerous biosimilar learning needs as well as challenges faced in obtaining biosimilars education among oncology pharmacy practitioners. Educational activities should be created to address these learning needs, and innovative strategies should be considered to overcome practitioner’s barriers in obtaining biosimilars education.
A survey of global biosimilar implementation practice conducted by the International Society of Oncology Pharmacy Practitioners
Authors: Foreman Emma , Patel Himanshu , Siderov Jim , Harchowal Jatinder , Bubalo Joseph , Chan Alexandre 
Published: April 2020

Background The International Society of Oncology Pharmacy Practitioners (ISOPP) Biosimilars Task Force was charged to develop educational activities and resources to assist members when implementing biosimilar medicines into their local practice. To facilitate the process, the task force conducted a survey in order to understand biosimilar implementation practice by ISOPP members across the world and the challenges that oncology pharmacists face when adopting biosimilars into their clinical practice. Methods A cross-sectional survey was conducted between 20 April 2019 and 27 May 2019. Members of ISOPP and a number of national oncology pharmacy groups were invited to complete the survey. The survey contained 29 items and consisted of three sections: respondents’ demographics, respondents’ institutional practice relating to biosimilar implementation and post implementation practice at the respondents’ institutions. Descriptive statistics were utilized to analyze the survey results. Results A total of 265 ISOPP members were surveyed, with 50 members providing a response (response rate = 19%). In addition, 40 nonmembers participated in the survey, bringing the total to 90 respondents. The most common factors that influence the decision to implement use of a biosimilar as reported by respondents are medication costs/pricing (92%), available clinical data (73%), and product availability (63%). Respondents also commented on the barriers to biosimilar implementation at their institutions, which included a reluctance of prescribers to use biosimilars (due to the lack of familiarity or perceived inferiority), a reluctance to switch established patients from an originator to a biosimilar and the preferences of insurance companies or funding bodies. Conclusion The results of this survey reinforce the need for greater education and training for health care professionals in the use of biosimilars, the importance of sharing good practice, and a need for standardization.
A single parathyroid hormone measurement two hours after a thyroidectomy reliably predicts permanent hypoparathyroidism
Authors: Palmhag David , Brydolf Jacob , Zedenius Jan , Bränström Robert , Nilsson Inga-Lena 
Published: April 2020

Introduction: Hypoparathyroidism is the most common complication following thyroidectomy, and various algorithms for early detection have been suggested. The aim of this study was to evaluate the predictive value of measuring the parathyroid hormone level 2 h after thyroidectomy and whether determination of the perioperative decline in parathyroid hormone added diagnostic value. Methods: Patients subjected to thyroidectomy for benign thyroid disorders were analyzed in (1) a retrospective register-based study (366 consecutive patients treated during 2015–2016) and (2) a prospective observational study (39 patients treated during 2018). Optimal cut-off values for postoperative parathyroid hormone and perioperative decline (%) in parathyroid hormone were determined by receiver operating characteristics and area under the curve. Sensitivity, specificity, positive and negative predictive values were calculated using cross tabulation. Results: The prevalence of hypoparathyroidism the first day after thyroidectomy was higher among patients treated for hyperthyroidism (30% vs 20%; P = 0.03). The optimal cut-off level for postoperative parathyroid hormone was 1.1 pmol/L (area under the curve = 0.887, 95% confidence interval: 0.839–0.934; positive predictive value: 88%, negative predictive value: 93%) for the entire cohort. When the groups were analyzed separately, the optimal cut-off was 1.05 for the non-hyperfunctioning group and 1.55 pmol/L for the group with hyperthyroidism. Twelve months after thyroidectomy, 3% were defined as having permanent hypoparathyroidism. Measurement of parathyroid hormone decline added diagnostic value for one patient with preoperative parathyroid-hormone-elevation associated with vitamin D deficiency. Conclusions: For patients with vitamin D sufficiency, the diagnostic accuracy of a single measurement of parathyroid hormone 2 h after thyroidectomy is an excellent indicator for predicting transient hypoparathyroidism.
A Systematic Review Evaluating Psychometric Properties of Parent or Caregiver Report Instruments on Child Maltreatment: Part 2: Internal Consistency, Reliability, Measurement Error, Structural Validity, Hypothesis Testing, Cross-Cultural Validity, and Criterion Validity
Authors: Yoon Sangwon , Speyer Renée , Cordier Reinie , Aunio Pirjo , Hakkarainen Airi 
Published: April 2020

Aims: Child maltreatment (CM) is global public health issue with devastating lifelong consequences. Global organizations have endeavored to eliminate CM; however, there is lack of consensus on what instruments are most suitable for the investigation and prevention of CM. This systematic review aimed to appraise the psychometric properties (other than content validity) of all current parent- or caregiver-reported CM instruments and recommend the most suitable for use. Method: A systematic search of the CINAHL, Embase, ERIC, PsycINFO, PubMed, and Sociological Abstracts databases was performed. The evaluation of psychometric properties was conducted according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines for systematic reviews of patient-report outcome measures. Responsiveness was beyond the scope of this systematic review, and content validity has been reported on in a companion paper (Part 1). Only instruments developed and published in English were included. Results: Twenty-five studies reported on selected psychometric properties of 15 identified instruments. The methodological quality of the studies was overall adequate. The psychometric properties of the instruments were generally indeterminate or not reported due to incomplete or missing psychometric data; high-quality evidence on the psychometric properties was limited. Conclusions: No instruments could be recommended as most suitable for use in clinic and research. Nine instruments were identified as promising based on current psychometric data but would need further psychometric evidence for them to be recommended.