bluuebunny/crossref_metadata_2025_split huggingface dataset:
Care patterns and TCM constitution as factors of depression and anxiety in systemic scleroderma: a cross- sectional study during the COVID-19 pandemic
Authors: Kong Qi , Chen Li-Ming , Dai Zong-Hao , Tang Yun-Zhe , Zhou Yu-Yang , Tu Wen-Zhen , Zhao Yin-Huan , Zhang Jia-Qian 
Published: April 2022

Abstract
Background: Care patterns and TCM constitution affects systemic scleroderma (SSc) patients’ emotion and health while the prevalence of covid-19 may aggravate this situation. Thus, we investigated depression and anxiety level in SSc patients during the COVID-19 pandemic to identify the correlation between care patterns, TCM constitution and patients' emotion. Methods: This was a cross-sectional study. SSc patients and healthy individuals were surveyed through the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, the Constitution in Chinese Medicine Questionnaire and a modified care pattern questionnaire. Factors correlated with depression and anxiety were screened by univariate and multivariate logistic regression. Results: A total of 273 SSc patients and 111 healthy individuals were included. The median age was 45 years in both patient and healthy groups. 74.36% of SSc patients were in depression and 51.65% were in anxiety. 69.60% worked remotely and 50.92% experienced a decrease in income, which were both higher than in the healthy group (38.74%, 29.73%). The proportion of income reduction in the online group (56.19%) was higher than that in the hospital group (33.33%) (P = 0.001). 36.99% of SSc patients had disease progression during the pandemic. Yang-deficiency constitution (82.05%) was the TCM constitution characteristic of SSc patients, while Qi-deficiency(73.63%) and Blood-stasis constitution (57.14%) were also more common. TCM constitution of patients from different sources distributed roughly similar. Qi-deficiency (adjusted OR=2.250) and Qi-stagnation (adjusted OR= 3.824) constitution were significantly associated with depression. The major constitution of dampness-heat was associated with a decrease in depression (adjusted OR=0.160). Remote work during the outbreak (adjusted OR= 1.920), decreasing in income (adjusted OR=3.556), and disease progression (P=0.030) were associated with the occurrence of depression. Conclusion: Chinese SSc patients have a high prevalence of depression and anxiety. The COVID-19 pandemic has changed the care patterns of Chinese SSc patients in terms of work, income, and ways of getting medical support. Within the care patterns, work, income, disease and change of medications were correlates of depression or anxiety in SSc patients. Qi-stagnation and Qi-deficiency constitution were associated with depression, and Qi-stagnation constitution was associated with anxiety in SSc patients. Further research is needed. Trial registration: ChiCTR, ChiCTR2000038796, Registered 02 October 2020, http://www.chictr.org.cn/showproj.aspx?proj=62301
Accurate prediction of molecular targets using a self-supervised image representation learning framework
Authors: Zeng Xiangxiang , Xiang Hongxin , Yu Linhui , Wang Jianmin , Li Kenli , Nussinov Ruth , Cheng Feixiong 
Published: April 2022

Abstract
The clinical efficacy and safety of a drug is determined by its molecular targets in the human proteome. However, proteome-wide evaluation of all compounds in human, or even animal models, is challenging. In this study, we present an unsupervised pre-training deep learning framework, termed ImageMol, from 8.5 million unlabeled drug-like molecules to predict molecular targets of candidate compounds. The ImageMol framework is designed to pretrain chemical representations from unlabeled molecular images based on local- and global-structural characteristics of molecules from pixels. We demonstrate high performance of ImageMol in evaluation of molecular properties (i.e., drug’s metabolism, brain penetration and toxicity) and molecular target profiles (i.e., human immunodeficiency virus) across 10 benchmark datasets. ImageMol shows high accuracy in identifying anti-SARS-CoV-2 molecules across 13 high-throughput experimental datasets from the National Center for Advancing Translational Sciences (NCATS) and we re-prioritized candidate clinical 3CL inhibitors for potential treatment of COVID-19. In summary, ImageMol is an active self-supervised image processing-based strategy that offers a powerful toolbox for computational drug discovery in a variety of human diseases, including COVID-19.
A patient with hepatitis B virus infection had hepatic epithelioid angiomyolipoma scattered in the liver which was not suitable for surgical resection: A case report
Authors: Cai Xiangren , Sun Shuchuan , Deng Yuxin , Pan Siyuan 
Published: April 2022

Abstract
Hepatic epithelioid angiomyolipoma (HEAML) is a rare tumor of mesenchymal tissue with a malignant tendency. It most frequently occurs in women. According to incomplete statistics, the incidence in men and women is approximately 1:5. Most HEAML lesions are single, and the lesions are generally located in the right lobe of the liver. In rare cases, the occurrence and development of the disease is hidden, the lesions are generally found by chance by patients, there are no special signs, and imaging has no specificity in the diagnosis of the disease. In addition, the misdiagnosis rate is very high with an accuracy rate of < 32%. Therefore, it has led to great difficulties in our diagnosis and treatment. This patient was a middle-aged female with a history of hepatitis B and no other special symptoms. She is a patient with multiple intrahepatic angiomyolipoma. Due to the small and scattered foci, complete resection was impossible, and due to her history of hepatitis B, conservative treatment was taken, and regular follow-up was performed. There was no tumor neogenesis or metastasis at the one-year follow-up.
Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion
Authors: Giroux Nicholas S. , Ding Shengli , McClain Micah T. , Burke Thomas W. , Petzold Elizabeth , Chung Hong A. , Rivera Grecia O. , Wang Ergang , Xi Rui , Bose Shree , Rotstein Tomer , Nicholson Bradly P. , Chen Tianyi , Henao Ricardo , Sempowski Gregory D. , Denny Thomas N. , De Ussel Maria Iglesias , Satterwhite Lisa L. , Ko Emily R. , Ginsburg Geoffrey S. , Kraft Bryan D. , Tsalik Ephraim L. , Shen Xiling , Woods Christopher 
Published: April 2022

Abstract
SARS-CoV-2 infection triggers profound and variable immune responses in human hosts. Chromatin remodeling has been observed in individuals severely ill or convalescing with COVID-19, but chromatin remodeling early in disease prior to anti-spike protein IgG seroconversion has not been defined. We performed the Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) and RNA-seq on peripheral blood mononuclear cells (PBMCs) from outpatients with mild or moderate symptom severity at different stages of clinical illness. Early in the disease course prior to IgG seroconversion, modifications in chromatin accessibility associate with mild or moderate symptoms are already robust and include severity-associated changes in accessibility of genes in interleukin signaling, regulation of cell differentiation and cell morphology. Furthermore, single-cell analyses revealed evolution of the chromatin accessibility landscape and transcription factor motif accessibility for individual PBMC cell types over time. The most extensive remodeling occurred in CD14+ monocytes, where sub-populations with distinct chromatin accessibility profiles were observed prior to seroconversion. Mild symptom severity is marked by upregulation classical antiviral pathways including those regulating IRF1 and IRF7, whereas in moderate disease these classical antiviral signals diminish suggesting dysregulated and less effective responses. Together, these observations offer novel insight into the epigenome of early mild SARS-CoV-2 infection and suggest that detection of chromatin remodeling in early disease may offer promise for a new class of diagnostic tools for COVID-19.
Appreciation of the personalized BETER lifestyle intervention for overweight: a case series design
Authors: Kanera Iris Maria , Kleynen Melanie , Schroën Yan , Luxzenburg Tanja Johanna Jacques de Jong van , Braun Susy Michelle 
Published: April 2022

Abstract
Background: Obesity is an epidemic affecting many citizens worldwide. Behavior change through lifestyle interventions can be effective, but success rates vary. Personalized interventions based on a systems biology approach might represent the individual variety of characteristics and underlying pathways in this target population better. Five subtypes of overweight were used for a personalized lifestyle program called BETER. This pilot study aimed to assess the degree of appreciation for the BETER program and to observe changes in vitality, lifestyle and body mass index (BMI).Methods: A case series design was applied. In a sample of people with overweight an evaluation of the appreciation of the program and a comparison of vitality, lifestyle, and BMI were performed. Data collection through questionnaires and clinical measurements were performed at baseline, after three and six months. The data were analyzed descriptively. Results: Seventy-nine adults (31 males, range average BMI: 28.4-31.3, range age: 19-65 years) reported promising results: a high degree of appreciation (8 out of 10), low dropout rates (9%), short term self-reported positive changes in lifestyle behaviors (adoption of lifestyle recommendations: physical activity: range 50-100%; nutrition: range 50-90%), increased perceived vitality (range participants ‘positive’ 67-81%) and a positive trend was seen in BMI reduction. Decline in adherence at follow-up was observed.Conclusion: The BETER lifestyle program was greatly appreciated and contributed to self-reported positive lifestyle changes and weight loss. Further research is needed to investigate whether the use of subtypes from a systems biology approach can provide key elements to increase the success rate of lifestyle interventions for obesity and chronic diseases, also on the long term.
P66Shc-mediated reactive oxygen species and autophagy disrupts brain microvascular endothelial cell function in response to hyperglycemia
Authors: Wang Lin , Yang Mengzhen , Wu Chao , Hu Hanyang , Ji Lulu , Lai Rujie , Peng Min , Huang Shenghe 
Published: April 2022

Abstract
Diabetes mellitus is a metabolic disease characterized by hyperglycemia, which can lead to serious central nervous system complications. The blood-brain barrier(BBB) is essential for maintaining the environmental stability of the central nervous system. Hyperglycemia may cause blood-brain barrier dysfunction and lead to central nervous system complications, but the mechanism is not clear. To explore the molecular mechanism of BBB injury caused by high glucose (HG), we hypothesize that p66Shc damaged BBB by promoting ROS production and autophagy. Human brain microvascular endothelial cells (HBMEC) were treated with different concentrations of glucose, Mito-tempo (MT), autophagy inhibitor (3-MA), autophagy inducer rapamycin (RAP), and P66Shc siRNA. Western blot was used to detect the expression of LC3, P62, ZO-1, claudin-5, and P66Shc in HBMEC. Autophagosomes were observed by transmission electron microscopy (TEM). Immunofluorescence staining was used to observe the expression of ZO-1, occludin, and ROS. The autophagy level was enhanced by HG. HG decreased the expression of ZO-1 and increased the expression of P66Shc and ROS. Inhibition of ROS levels under HG reversed the high level of autophagy induced by HG and increased the expression of ZO-1. The autophagy level was negatively correlated with the ZO-1 expression in HG. In HG, inhibit the expression of P66Shc reduced the ROS and autophagy levels and increased the ZO-1 expression. HG increased the autophagy level and destroyed the integrity of the tight junctions between HBMEC. Silencing P66Shc repaired HG damaged-HBMEC by inhibiting ROS production and reducing autophagy. To explore the molecular mechanism of BBB injury caused by high glucose (HG), we hypothesize that p66Shc damaged BBB by promoting ROS production and autophagy.
Importance of urodynamic evaluation of bladder function after untethering in spina bifida patients – Single center experience of 30 years
Authors: Lingnau Anja , Ciesla Luise , Schneider Joanna , Marco Beatriz Bañuelos , Schulz Matthias , Thomale Ulrich-Wilhelm , Geppert Tamara , Trojan Katharina C. , Kaindl Angela M. 
Published: April 2022

Abstract
Introduction: A TCS after primary closure of meningomyeloceles is a known complication of the spina bifida disease. Data on the outcome after SSCU surgery is heterogeneous and lacking standardization. Thus we aimed to find a reliable system for assessment of the bladder function before and after SSCU surgery and document postoperative outcome.Methods: A retrospective study was performed on a cohort of 306 patients with spina bifida diagnosis. In total, 130 patients underwent 182 SSCU surgeries, 56 of those met our inclusion criteria. A classification system, including two different methods, was used. The AC system used baseline pressure and detrusor over activity to define three levels of bladder dysfunction, the second method ranked the severity of bladder dysfunction by awarding points from 0 to 2 for bladder capacity, maximal detrusor pressure during autonomous contractions, leak point pressure and vesicoureteral reflux A high score is correlated with a severe bladder dysfunction.Results: Gender distribution was equally (male: n=29; 51,8%; female: n=27; 48,2%). The median age at SSCU was 9,02 years (range 0,5 – 22,8 years).After SSCU, the stage improved in 11 patients (19.6%), worsened in 11 (19.6%) patients and remained the same in 34 patients (60.7%) after intervention (AC score). Non-worsening was observed in a total of 45 cases (80.4%) (p<0.001).MHS score (n=27, 48,2%) improved, remained unchanged (n=12, 21.4%), 17 patients worsened (30.4%). Non-worsening in postoperative bladder functional outcome was demonstrated in 39 cases (69,6%) over all (p<0.005).Regardless of whether bladder function is categorized by AC or MHS, postoperative outcome worsened significantly when SSCU was performed due to increasing deterioration in motor function alone (p<0.05). Of the 24 cases with NOD as indication, 22 (91,7%) had an unchanged (n=10; 41,7%) or improved (n=12; 50,0%), meaning positive neuro-orthopedic outcome, only 2 (8,3%) deteriorated (p<0,001).Conclusion: Our study presents reliable evaluation systems for bladder function in spina bifida patients. Since indications for SSCU surgery differ, it is important to know the possible effects on bladder function after this surgical procedure. Even a mild impairment of bladder function has a risk to deteriorate after SSCU surgery. Particularly interesting becomes this with regard to the fact that the prevalence of TCS might become more frequent with the rising numbers of prenatal closures of meningomyeloceles.
Successful salvage urethroplasty with pedicled soft tissue reinforcement for failed hypospadias repair.
Authors: Seo Shogo , Miyake Yuichiro , Takeda Masahiro , Yazaki Yuta , Ochi Takanori , Miyano Go , Koga Hiroyuki , Lane Geoffrey J. , Yamataka Atsuyuki 
Published: April 2022

Abstract
Purpose: The high incidence of scarring and vascular compromise after failed hypospadias repair greatly compromises salvage urethroplasty. Pedicled soft tissue reinforcement (STR) is presented for enhancing the potential for success.Methods: The impact of lateral reinforcement of the scarred urethral plate to boost thickness and perfusion at the time of curvature correction (called CHARGE by the authors) and covering the neourethra at the time of urethroplasty (NUC) used as STR during salvage tubularized incised plate urethroplasty performed between 2003 and 2019 were assessed by retrospective review of the medical records of 8 cases of failed hypospadias repair. Results: Types of hypospadias were perineal/penoscrotal (n=7), and mid-shaft (n=1). Indications for salvage surgery included residual penile curvature (n=5), urethral diverticulum >15mm (n=3), urethral dehiscence (n=1), and urethral stricture (n=1). Salvage surgery was single-stage (urethroplasty at the same of curvature correction; n=1) or multi-stage (n=7; two-stage: n=4, three-stage: n=3). All cases had NUC and 4/8 had CHARGE. All salvage repairs were successful with no incidence of postoperative complications after mean follow-up of 3.9 years (range: 1.6-6.4 years) after the last procedure.Conclusion: STR most likely enhanced tissue perfusion/pliability which ensured the success of salvage urethroplasty for failed hypospadias repair.
Hypoxic microenvironment as a crucial factor triggering events leading to rupture of intracranial aneurysm
Authors: Aoki Tomohiro , Ono Isao , Kayahara Tomomichi , Kawashima Akitsugu , Okada Akihiro , Miyamoto Susumu , Kataoka Hiroharu , Kurita Hiroki , Ishii Akira 
Published: April 2022

Abstract
Background: Subarachnoid hemorrhage being the rupture of intracranial aneurysm (IA) as a major cause has a high mortality rate in spite of technical advancement in treatment interventions. Thereby, it is mandatory for social health to clarify mechanisms regulating rupture of IAs and to develop a novel therapeutic strategy to prevent rupture. Following the recent experimental studies, we and others have clarified the formation of vasa vasorum in IA lesions presumably for inflammatory cells to infiltrate in lesions as the potential histopathological alternation leading to rupture. Main Body: We first clarified the origin of vasa vasorum as arteries located at the brain surface in 3D-immunohistochemistry with tissue transparency. We then found the presence of hypoxic microenvironment mainly at the adventitia of intracranial arteries where IA is induced by using the Pimonidazole-based probe in vivo. Among angiogenic factors potentially responsible for the formation of vasa vasorum, the production of vascular endothelial growth factor (VEGF) from cultured macrophages in such a hypoxic condition was identified in vitro and in vivo experiment using rupture-prone IA lesions induced in a rat model reproduced the production of VEGF from infiltrating macrophages. We further examined VEGF production in human unruptured IA lesions and found the accumulation of VEGF in the lesions, supporting the production of VEGF in situ. Finally, the VEGF-dependent induction of neovessels from arteries on brain surface was confirmed in experiments placing the sheet for the slow-release of VEGF on brain surface. Here, because intracranial arteries histologically lack vasa vasorum and are surrounded by cerebrospinal fluid space, the formation of the hypoxic microenvironment could be a character of intracranial arteries and inflammatory responses there could further facilitate such a condition to induce vasa vasorum. In addition, the enlargement of the lesions and the disruption of physical barrier like arachnoid might be a necessary factor for the migration of vasa vasorum into subarachnoid space from arteries on brain surface.Conclusions: The findings from the present study have revealed the potential role of hypoxic microenvironment and hypoxia-induced VEGF production as a machinery triggering rupture of IAs via providing root for inflammatory cells in lesions to exacerbate inflammation.
The density of Crown-Like Structures in epicardial adipose tissue could play a role in cardiovascular diseases
Authors: Malavazos Alexis Elias , Vincenzo Angelica Di , Iacobellis Gianluca , Basilico Sara , Dubini Carola , Morricone Lelio , Menicanti Lorenzo , Luca Tonia , Giordano Antonio , Castorina Sergio , Carruba Michele , Nisoli Enzo , Prato Stefano Del , Cinti Saverio 
Published: April 2022

Abstract
Purpose The visceral fat of patients affected by abdominal obesity is inflamed, and the main histopathologic feature is the high density of crown-like structures (CLS). Epicardial adipose tissue (EAT) is a visceral fat of paramount importance for its relationships with coronary vessels and myocardium. Its inflammation in patients with abdominal obesity could be of clinical relevance, but histopathological studies on CLS density in EAT are lacking. This study aimed to assess the histopathology of EAT biopsies obtained from patients undergoing open-heart surgery. Methods We collected EAT biopsies from 10 patients undergoing open-heart surgery for elective coronary artery bypass grafting (CABG) (n=5) or valvular replacement (VR) (n=5). Biopsies were treated for light microscopy and immunohistochemistry. We quantify the CLS density in each EAT sample. Results Despite all patients having abdominal obesity, in EAT samples, no CLS were detected in the VR group; in contrast, CLS were detected in the CABG group (about 17 CLS/104 adipocytes vs. 0,0 CLS/104 adipocytes, CABG vs. VR group, respectively). An impressive density of CLS (100 times that of other patients) was found in one patient (LS) in the CABG group that had a relevant anamnestic aspect: relatively rapid increase of weight gain, especially in abdominal adipose tissue, coincident with myocardial infarction. Conclusion CLS density could be an important predictive tool for cardiovascular diseases. Furthermore, the LS case implies a role for timing in weight gain.Level of evidence: No level of evidence; this is a basic science study.
Emicizumab in children: bleeding episodes and outcome before and after transition to Emicizumab
Authors: Glonnegger Hannah , Andresen Felicia , Kapp Friedrich , Malvestiti Stefano , Büchsel Martin , Zieger Barbara 
Published: April 2022

Abstract
Purpose: Real-world data and study data regarding therapy with Emicizumab in pediatric cohorts with haemophilia A is scarce. Especially, data on previously untreated pediatric patients (PUPs) and minimally treated patients (MTPs) are missing.Methods: 14 pediatric patients with haemophilia A and treatment with Emicizumab were retrospectively evaluated for Annual Bleeding Rates (ABR) pre-and post-Emicizumab treatment. Safety data and data on management of minor surgery as well as laboratory results were collected. Additionally, we describe the clinical features of two PUPs and one MTP that are included in our cohort.Results: Median age at initiation of Emicizumab was 5.9 (0.26-21.34) years, three patients were younger than one year at initiation of treatment with Emicizumab. Median follow-up time on Emicizumab was 24 (0.7-40) months. Total ABR (p=0.006) as well as spontaneous (p=0.018), traumatic (p=0.012), and joint (p=0.018) ABR reduced significantly post-Emicizumab transition. Safety profile was favourable as only one local site reaction occurred; no cessation of treatment was necessary. Surgery was successfully performed in three patients receiving rFVlla pre- and post-surgery. Emicizumab trough levels showed a median of 43.4 mg/ml (23.9-72.1) after three doses of 3 mg/kg and 53.9 mg/ml (30.4-75) at first follow-up with 1.5 mg/kg. Conclusion: Emicizumab is safe and efficient in pediatric patients with and without inhibitors. More data on larger multicenter cohorts and especially on PUPs/MTPs are still needed.