bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dickkopf-related protein 3 is a novel biomarker for chronic GVHD after allogeneic hematopoietic cell transplantation
Authors: Inamoto Yoshihiro , Martin Paul J. , Lee Stephanie J. , Momin Amin A. , Tabellini Laura , Onstad Lynn E. , Pidala Joseph , Flowers Mary E. D. , Lawler Richard L. , Katayama Hiroyuki , Hanash Samir , Hansen John A. 
Published: June 2020

Abstract
To identify plasma biomarkers associated with fibrotic mechanisms of chronic graft-versus-host disease (GVHD), we used multiplex mass spectrometry with pooled samples for biomarker discovery in comparing proteomic profiles between patients with newly diagnosed sclerotic chronic GVHD (n = 21), those with newly diagnosed nonsclerotic chronic GVHD (n = 33), and those without chronic GVHD (n = 20). Immunoassay was used to measure protein concentrations of individual discovery samples and 186 independent verification samples. The discovery mass spectrometry analysis identified 2 candidate proteins with at least 1.5-fold difference in sclerotic GVHD: Dickkopf-related protein 3 (DKK3) and interleukin-1 receptor accessory protein (IL1RAP). Analysis of individual discovery samples by immunoassay showed that DKK3, a modulator of the Wnt signaling pathway, was a biomarker for both sclerotic and nonsclerotic chronic GVHD. Verification analysis of 186 patients confirmed that elevated plasma DKK3 concentrations were associated with chronic GVHD, regardless of the presence or absence of sclerosis, and that the area under the receiver operating characteristic curve was 0.85 for association of DKK3 concentrations with chronic GVHD. Multiple linear regression analysis showed that chronic GVHD with or without steroid treatment and patient age were independently associated with DKK3 concentrations. Patients with high DKK3 concentrations had a higher nonrelapse mortality than those with low concentrations. The lower IL1RAP concentrations in patients with sclerotic GVHD compared with other conditions in the discovery cohort were not confirmed in the verification cohort. DKK3 is a novel biomarker for chronic GVHD. Further studies are needed to determine the biological functions of DKK3 in the pathogenesis of chronic GVHD.
Hard flaccid syndrome: state of current knowledge
Authors: Abdessater Maher , Kanbar Anthony , Akakpo William , Beley Sebastien 
Published: June 2020

Abstract
Introduction
Hard-flaccid syndrome is gaining increased interest among male sexual dysfunctions in the last years. It is poorly understood and defined. Most of the information comes from online forums. This paper is a review of current knowledge on the clinical presentation, diagnosis, pathophysiological mechanisms and treatments of this newly recognized condition.

Material and methods
A literature review was conducted on MEDLINE, CENTRAL, PASCAL databases and google scholar, using the terms: hard, flaccid, syndrome. The research identified 16 articles published between 2018 and February 2019. After reference lists review and duplicates removal, 7 full text references were eligible and useful for our review that follows PRISMA guidelines.

Results
The condition is acquired, chronic and painful. It is characterized by a constantly semi-rigid penis at the flaccid state and a loss in erectile rigidity. Patients have penile sensory changes, urinary symptoms, erectile dysfunction, pelvic floor muscles contraction and psychological distress. Symptoms are worse in standing position. The majority of the cases aged between their second and third decades. A traumatic injury at the base of an erect penis is the initial event. Neurovascular structures damage and subsequent sensory, muscular and vascular changes follow. Initial symptoms trigger emotional distress and reactional sympathetic stimulation that worsen symptoms. Diagnosis is based on patient’s history. Imaging and blood tests are normal. Differential diagnosis includes high-flow priapism and non-erecting erections. A multimodal treatment has been so far the most beneficial strategy, consisting of behavioral modifications to reduce stress and decrease pelvic floor muscles contraction, evaluation and treatment of the associated psychological conditions, and medical therapy for pain control and the treatment of the associated erectile dysfunction.

Conclusion
Hard-flaccid syndrome is poorly recognized in the daily clinical experience and not well defined. A multimodal approach seems so far the most efficient strategy for treatment. Additional evidence based studies with better quality are needed to define the exact pathophysiological mechanisms and subsequently more efficient therapeutic strategies.
Prejudices against the unemployed—empirical evidence from Germany
Authors: Gross Christiane , Gurr Thomas , Jungbauer-Gans Monika , Lang Sebastian 
Published: June 2020

AbstractPrejudices against the unemployed pose an enormous threat to their self-confidence and can make it difficult for them to re-enter the labour market, resulting in further long-term unemployment. Given these high costs for the unemployed and for society as a whole, our knowledge of prejudices against the unemployed is surprisingly scarce. We focus on the question of what determines the strength of prejudice among employees. By applying social identity theory, we assume that people who are disadvantaged in the labour market in general, also hold stronger prejudices. In addition, we assume that social status mediates this association and that self-efficacy moderates it. We use data from the German panel study “Labour Market and Social Security” (PASS) and show that some groups of people who are themselves disadvantaged in the labour market (women and first-generation immigrants) have more prejudices against the unemployed; however, people with poor mental health have even fewer prejudices. Low social status (in terms of educational background, income, and job status) is associated with strong prejudices; however, social status does work as mediator to a minor degree only. People with low self-efficacy in general (main “effect”) and first-generation immigrants in particular (moderating “effect”) have stronger prejudices. These results can be a starting point for developing measures to reduce prejudice and for the onset of a debate about the origins of prejudices against the unemployed.
The MYB transcription factor CiMYB42 regulates limonoids biosynthesis in citrus
Authors: Zhang Pan , Liu Xiaofeng , Yu Xin , Wang Fusheng , Long Junhong , Shen Wanxia , Jiang Dong , Zhao Xiaochun 
Published: June 2020

Abstract
Background
Limonoids are major bioactive compounds that are produced by the triterpenoid metabolic pathway. The detailed biochemical process of limonoid biosynthesis and the mechanism of its molecular regulation remain elusive. The identification of transcription factors that regulate limonoid biosynthetic pathways is very important for understanding the underlying regulatory mechanisms. This information could also provide tools for manipulating biosynthesis genes to modulate limonoid production.

Results
In this study, the CiMYB42 transcription factor was isolated to identify its role in limonoid biosynthesis. Multiple alignment analysis and phylogenetic analysis demonstrated that CiMYB42 is a typical R2R3MYB transcription factor that shares high similarity of its amino acid sequence with AtMYB42. Limonoids contents were higher in Citrus sinensis and Citrus grandis than in other species. Limonoid accumulation during leaf development also showed diverse trends in different genotypes. The expression of CiMYB42 was significantly related to the limonoid content and the expression of CiOSC in some citrus accessions. The overexpression of CiMYB42 in sweet orange resulted in significant accumulation of limonin, whereas the downregulation of CiMYB42 by RNAi resulted in a dwarf phenotype and less nomilin accumulation. Furthermore, the results of a yeast one-hybrid assay and EMSA indicated that CiMYB42 binds exclusively to the TTGTTG sequence (type II MYB core) in the promoter of CiOSC. Together, these results suggest that CiMYB42 positively regulates limonoid biosynthesis by regulating the expression of CiOSC by binding to the TTGTTG sequence (type II MYB core) of its promoter.

Conclusions
CiMYB42 is an important transcription activator involved in limonoid biosynthesis that regulates the expression of CiOSC by binding to the TTGTTG sequence (type II MYB core).
Diagnostic and prognostic nomograms for bone metastasis in hepatocellular carcinoma
Authors: Hu Chuan , Yang Jiaxin , Huang Zhangheng , Liu Chuan , Lin Yijun , Tong Yuexin , Fan Zhiyi , Chen Bo , Wang Cailin , Zhao Cheng-Liang 
Published: June 2020

Abstract
Background
Bone metastasis (BM) is one of the common sites of hepatocellular carcinoma (HCC), and the prognosis of BM patients is worse than patients without it. Our study aimed to identify predictors and prognostic factors of BM in HCC patients and develop two nomograms to quantify the risk of BM and the prognosis of HCC patients with BM.

Methods
We retrospectively reviewed the data of patients who were diagnosed as HCC between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. Independent predictors for BM from HCC patients were determined by the univariate and multivariate logistic regression analysis. Independent prognostic factors for HCC patients with BM were identified by univariate and multivariate Cox regression analysis. Two nomograms were established and evaluated by calibration curves, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA).

Results
Nine thousand and forty-seven patients were included. The independent risk factors of BM in newly diagnosed HCC patients are sex, grade, T stage, and N stage. The independent prognostic factors for HCC patients with BM are radiotherapy, chemotherapy, and lung metastasis. The AUC of diagnostic nomogram were 0.726 in the training set and 0.629 in the testing set. For the prognostic nomogram, the AUCs of 6-, 9-, and 12-months were 0.753, 0.799, and 0.732 in the training set and 0.698, 0.770, and 0.823 in the validation set. The calibration curve and DCA indicated the good performance of the nomogram.

Conclusions
Two nomograms were established to predict the incidence of BM in HCC patients and the prognosis of HCC patients with BM, respectively. Both nomograms have satisfactory accuracy, and clinical utility may benefit for clinical decision-making.
The findings of corneal specular microscopy in patients with type-2 diabetes mellitus
Authors: Taşlı Nurdan Gamze , Icel Erel , Karakurt Yücel , Ucak Turgay , Ugurlu Adem , Yilmaz Hayati , Akbas Emin Murat 
Published: June 2020

Abstract
Background
We aimed to compare the morphological characteristics of corneal endothelial cells in type 2 diabetic patients and age-matched healthy subjects by specular microscopy.
We also aimed to determine the association of corneal morphological features with the general characteristics and laboratory data of diabetic patients, including disease duration, haemoglobin A1c (HbA1c) levels and urine albumin creatinine ratio.

Methods
A total of 195 diabetic patients and 100 healthy controls were enrolled in the study. All participants underwent a complete ophthalmological examination. Corneal endothelial measurements were performed using a noncontact specular microscopy. Laboratory data including serum fasting glucose, haemoglobin A1c levels, creatinine levels, and the urinary albumin-to-creatinine ratio were recorded. Diabetic patients were further subdivided into 3 groups according to the presence and stage of diabetic retinopathy. Specular microscopy findings and central corneal thickness of all patients were compared.

Results
The ECD and hexagonal cell ratio were significantly lower, while the average cell size, CV%, and central corneal thickness were determined to be significantly higher in diabetic patients than in healthy controls (p = 0.001). With the presence and advancement of diabetic retinopathy, the ECD and hexagonal cell ratio decreased, while the average cell size, CV%, and central corneal thickness increased. When correlation analysis was performed between corneal morphological features and laboratory data of diabetic patients, ECD showed a significant negative correlation with diabetes duration (p = 0.028). HbA1c levels, urinary albumin-creatinine ratio (p = 0.041), average cell size and CV showed a positive correlation with these parameters.

Conclusion
In conclusion, keratopathy is an important complication of type 2 diabetes. With an increase in the stage of diabetic retinopathy, alterations in corneal findings also increased. In that respect, we can suggest that keratopathy should be evaluated more cautiously in diabetic patients.
Access to health care for people with disabilities in rural Malawi: what are the barriers?
Authors: Harrison Josephine A. K. , Thomson Rachael , Banda Hastings T. , Mbera Grace B. , Gregorius Stefanie , Stenberg Berthe , Marshall Tim 
Published: June 2020

Abstract
Background
People with disabilities experience significant health inequalities. In Malawi, where most individuals live in low-income rural settings, many of these inequalities are exacerbated by restricted access to health care services. This qualitative study explores the barriers to health care access experienced by individuals with a mobility or sensory impairment, or both, living in rural villages in Dowa district, central Malawi. In addition, the impact of a chronic lung condition, alongside a mobility or sensory impairment, on health care accessibility is explored.

Methods
Using data from survey responses obtained through the Research for Equity And Community Health (REACH) Trust’s randomised control trial in Malawi, 12 adult participants, with scores of either 3 or 4 in the Washington Group Short Set (WGSS) questions, were recruited. The WGSS questions concern a person’s ability in core functional domains (including seeing, hearing and moving), and a score of 3 indicates ‘a lot of difficulty’ whilst 4 means ‘cannot do at all’. People with cognitive impairments were not included in this study. All who were selected for the study participated in an individual in-depth interview and full recordings of these were then transcribed and translated.

Results
Through thematic analysis of the transcripts, three main barriers to timely and adequate health care were identified: 1) Cost of transport, drugs and services, 2) Insufficient health care resources, and 3) Dependence on others. Attitudinal factors were explored and, whilst unfavourable health seeking behaviour was found to act as an access barrier for some participants, community and health care workers’ attitudes towards disability were not reported to influence health care accessibility in this study.

Conclusions
This study finds that health care access for people with disabilities in rural Malawi is hindered by closely interconnected financial, practical and social barriers. There is a clear requirement for policy makers to consider the challenges identified here, and in similar studies, and to address them through improved social security systems and health system infrastructure, including outreach services, in a drive for equitable health care access and provision.
Influence of gender in monocrotaline and chronic hypoxia induced pulmonary hypertension in obese rats and mice
Authors: Neupane Balram , Sydykov Akylbek , Pradhan Kabita , Vroom Christina , Herden Christiane , Karnati Srikanth , Ghofrani Hossein Ardeschir , Avdeev Sergey , Ergün Süleyman , Schermuly Ralph Theo , Kosanovic Djuro 
Published: June 2020

Abstract
Background
Obesity and pulmonary hypertension (PH) share common characteristics, such as augmented inflammation and oxidative stress. However, the exact role of obesity in the pathology of PH is largely uninvestigated. Therefore, we have hypothesized that in the context of obesity the gender difference may have influence on development of PH in animal models of this disease.

Methods
Animal experiments were conducted in monocrotaline (MCT) and chronic hypoxia (HOX) models of PH. Lean and obese Zucker rats or B6 mice of both genders were used for MCT or HOX models, respectively. Echocardiography, hemodynamic measurements, histology and immuno-histochemistry were performed to analyze various parameters, such as right ventricular function and hypertrophy, hemodynamics, pulmonary vascular remodeling and lung inflammation.

Results
Both lean and obese male and female Zucker rats developed PH after a single MCT injection. However, negligible differences were seen between lean and obese male rats in terms of PH severity at the end stage of disease. Conversely, a more prominent and severe PH was observed in obese female rats compared to their lean counterparts. In contrast, HOX induced PH in lean and obese, male and female mice did not show any apparent differences.

Conclusion
Gender influences PH severity in obese MCT-injected rats. It is also an important factor associated with altered inflammation. However, further research is necessary to investigate and reveal the underlying mechanisms.
Local expression profiles of vitamin D-related genes in airways of COPD patients
Authors: Mathyssen Carolien , Aelbrecht Celine , Serré Jef , Everaerts Stephanie , Maes Karen , Gayan-Ramirez Ghislaine , Vanaudenaerde Bart , Janssens Wim 
Published: June 2020

AbstractTreatment of Chronic Obstructive Pulmonary Disease (COPD) is based on bronchodilation, with inhaled corticosteroids or azithromycin associated when frequent exacerbations occur. Despite the proven benefits of current treatment regimens, the need for new interventions in delineated subgroups remains. There is convincing evidence for oral vitamin D supplementation in reducing exacerbations in COPD patients severely deficient for circulating vitamin D. However, little is known about local vitamin D metabolism in the airways and studies examining expression of the vitamin D receptor (VDR), the activating enzyme (CYP27B1) and inactivating enzyme (CYP24A1) of vitamin D in lung tissue of COPD patients are lacking. Therefore, the expression and localization of key enzymes and the receptor of the vitamin D pathway were examined in tissue of 10 unused donor lungs and 10 COPD explant lungs. No differences in the expression of CYP27B1 and CYP24A1 were found. Although protein expression of VDR was significantly lower in COPD explant tissue, there was no difference in downstream expression of the antimicrobial peptide cathelicidin. Whereas CYP27B1 and CYP24A1 were present in all layers of the bronchial epithelium, VDR was only expressed at the apical layer of a fully differentiated bronchial epithelium with no expression in vascular endothelial cells. By contrast, CYP24A1 expression was highly present in lung endothelial cells suggesting that systemic vitamin D can be inactivated before reaching the epithelial compartment and the tissue immune cells. These data support the idea of exploring the role of vitamin D inhalation in patients with COPD.
Using force data to self-pace an instrumented treadmill and measure self-selected walking speed
Authors: Song Seungmoon , Choi Hojung , Collins Steven H. 
Published: June 2020

Abstract
Background
Self-selected speed is an important functional index of walking. A self-pacing controller that reliably matches walking speed without additional hardware can be useful for measuring self-selected speed in a treadmill-based laboratory.

Methods
We adapted a previously proposed self-pacing controller for force-instrumented treadmills and validated its use for measuring self-selected speeds. We first evaluated the controller’s estimation of subject speed and position from the force-plates by comparing it to those from motion capture data. We then compared five tests of self-selected speed. Ten healthy adults completed a standard 10-meter walk test, a 150-meter walk test, a commonly used manual treadmill speed selection test, a two-minute self-paced treadmill test, and a 150-meter self-paced treadmill test. In each case, subjects were instructed to walk at or select their comfortable speed. We also assessed the time taken for a trial and a survey on comfort and ease of choosing a speed in all the tests.

Results
The self-pacing algorithm estimated subject speed and position accurately, with root mean square differences compared to motion capture of 0.023 m s −1 and 0.014 m, respectively. Self-selected speeds from both self-paced treadmill tests correlated well with those from the 10-meter walk test (R>0.93,p<1×10−13). Subjects walked slower on average in the self-paced treadmill tests (1.23±0.27 ms−1) than in the 10-meter walk test (1.32±0.18 ms−1) but the speed differences within subjects were consistent. These correlations and walking speeds are comparable to those from the manual treadmill speed selection test (R=0.89,p=3×10−11;1.18±0.24 ms−1). Comfort and ease of speed selection were similar in the self-paced tests and the manual speed selection test, but the self-paced tests required only about a third of the time to complete. Our results demonstrate that these self-paced treadmill tests can be a strong alternative to the commonly used manual treadmill speed selection test.

Conclusions
The self-paced force-instrumented treadmill well adapts to subject walking speed and reliably measures self-selected walking speeds. We provide the self-pacing software to facilitate use by gait researchers and clinicians.
Prevention of tumor risk associated with the reprogramming of human pluripotent stem cells
Authors: Wuputra Kenly , Ku Chia-Chen , Wu Deng-Chyang , Lin Ying-Chu , Saito Shigeo , Yokoyama Kazunari K. 
Published: June 2020

AbstractHuman pluripotent embryonic stem cells have two special features: self-renewal and pluripotency. It is important to understand the properties of pluripotent stem cells and reprogrammed stem cells. One of the major problems is the risk of reprogrammed stem cells developing into tumors. To understand the process of differentiation through which stem cells develop into cancer cells, investigators have attempted to identify the key factors that generate tumors in humans. The most effective method for the prevention of tumorigenesis is the exclusion of cancer cells during cell reprogramming. The risk of cancer formation is dependent on mutations of oncogenes and tumor suppressor genes during the conversion of stem cells to cancer cells and on the environmental effects of pluripotent stem cells. Dissecting the processes of epigenetic regulation and chromatin regulation may be helpful for achieving correct cell reprogramming without inducing tumor formation and for developing new drugs for cancer treatment. This review focuses on the risk of tumor formation by human pluripotent stem cells, and on the possible treatment options if it occurs. Potential new techniques that target epigenetic processes and chromatin regulation provide opportunities for human cancer modeling and clinical applications of regenerative medicine.