bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of ISG15 and ZFP36 as novel hypoxia- and immune-related gene signatures contributing to a new perspective for the treatment of prostate cancer by bioinformatics and experimental verification
Authors: Lyu Fang , Li Yunxue , Yan Zhecheng , He Qingliu , Cheng Lulin , Zhang Pu , Liu Bing , Liu Chunyu , Song Yarong , Xing Yifei 
Published: May 2022

AbstractBackgroundProstatic cancer (PCa) is one of the most common malignant tumors in men worldwide. Emerging evidence indicates significance of hypoxia and immunity in PCa invasion and metastasis. This study aimed to develop a hypoxia- and immune-related gene risk signature and explore the molecular mechanisms to formulate a better prognostic tool for PCa patients.MethodsThe hypoxia and immune scores of all PCa patients in The Cancer Genome Atlas (TCGA) dataset were calculated via the maximally selected rank statistics method and the ESTIMATE algorithm. From common genes identified overlapping hypoxia- and immune-related differentially expressed genes (DE-HRGs and DE-IRGs), a hypoxia- and immune-related gene risk signature was developed utilizing univariate and multivariate Cox regression analyses, and validated in the Memorial Sloan Kettering Cancer Centre (MSKCC) database. The immune cell infiltration level of PCa samples were evaluated with ssGSEA algorithm. Differential expression of prognostic genes was evidenced by immunohistochemistry and western blot (WB) in paired PCa samples. Expression levels of these genes and their variations under regular and hypoxic conditions were examined in cell lines. The functional effects of the prognostic gene on PCa cells were examined by wound healing and transwell assays.ResultsA hypoxia- and immune-related gene risk signature constructed by ISG15 and ZFP36 displays significant predictive potency, with higher risk score representing worse survival. A nomogram based on independent prognostic factors including the risk score and Gleason score exhibited excellent clinical value in the survival prediction of PCa. Infiltration levels of eosinophils, neutrophils, Tcm, Tem, TFH, Th1 cells, and Th17 cells were significantly lower in the high-risk group. Conversely, aDC, pDC, T helper cells, and Tregs were significantly higher. Additionally, the two prognostic genes were closely correlated with the tumor-infiltrating immune cell subset in PCa progression. RT-qPCR and WB presented higher and lower expression of ISG15 and ZFP36 in PCa cells, respectively. They were correspondingly increased and decreased in PCa cells under hypoxic conditions. Wound healing and transwell assays showed that over-expression of ISG15 promoted the migration and invasion of PCa cells.ConclusionOur study identified a novel hypoxia- and immune-related gene signature, contributing a new perspective to the treatment of PCa
The PDE4 inhibitor tanimilast shows distinct immunomodulatory properties associated with a type 2 endotype and CD141 upregulation
Authors: Nguyen Hoang Oanh , Salvi Valentina , Tiberio Laura , Facchinetti Fabrizio , Govoni Mirco , Villetti Gino , Civelli Maurizio , Barbazza Ilaria , Gaudenzi Carolina , Passari Mauro , Schioppa Tiziana , Sozio Francesca , Del Prete Annalisa , Sozzani Silvano , Bosisio Daniela 
Published: May 2022

AbstractBackgroundTanimilast is a novel and selective inhaled inhibitor of phosphodiesterase-4 in advanced clinical development for chronic obstructive pulmonary disease (COPD). Tanimilast is known to exert prominent anti-inflammatory activity when tested in preclinical experimental models as well as in human clinical studies. Recently, we have demonstrated that it also finely tunes, rather than suppressing, the cytokine network secreted by activated dendritic cells (DCs). This study was designed to characterize the effects of tanimilast on T-cell polarizing properties of DCs and to investigate additional functional and phenotypical features induced by tanimilast.MethodsDCs at day 6 of culture were stimulated with LPS in the presence or absence of tanimilast or the control drug budesonide. After 24 h, DCs were analyzed for the expression of surface markers of maturation and activation by flow cytometry and cocultured with T cells to investigate cell proliferation and activation/polarization. The regulation of type 2-skewing mediators was investigated by real-time PCR in DCs and compared to results obtained in vivo in a randomized placebo-controlled trial on COPD patients treated with tanimilast.ResultsOur results show that both tanimilast and budesonide reduced the production of the immunostimulatory cytokine IFN-γ by CD4+T cells. However, the two drugs acted at different levels since budesonide mainly blocked T cell proliferation, while tanimilast skewed T cells towards a Th2 phenotype without affecting cell proliferation. In addition, only DCs matured in the presence of tanimilast displayed increased CD86/CD80 ratio and CD141 expression, which correlated with Th2 T cell induction and dead cell uptake respectively. These cells also upregulated cAMP-dependent immunosuppressive molecules such as IDO1, TSP1, VEGF-A and Amphiregulin. Notably, the translational value of these data was confirmed by the finding that these same genes were upregulated also in sputum cells of COPD patients treated with tanimilast as add-on to inhaled glucocorticoids and bronchodilators.ConclusionTaken together, these findings demonstrate distinct immunomodulatory properties of tanimilast associated with a type 2 endotype and CD141 upregulation in DCs and provide a mechanistic rationale for the administration of tanimilast on top of inhaled corticosteroids.
Gastric antral vascular ectasia in systemic sclerosis: a study of its epidemiology, disease characteristics and impact on survival
Authors: Morrisroe Kathleen , Hansen Dylan , Stevens Wendy , Sahhar Joanne , Ngian Gene-Siew , Hill Catherine , Roddy Janet , Walker Jennifer , Proudman Susanna , Nikpour Mandana 
Published: May 2022

Abstract
Background
To describe the epidemiology, determinants and survival impact of gastric antral vascular ectasia (GAVE) in systemic sclerosis (SSc).

Methods
Consecutive SSc patients prospectively enrolled in the Australian Scleroderma Cohort Study (ASCS) were included. Univariable and multivariable logistic regression were used to determine the associations of GAVE with clinical manifestations and serological parameters. Kaplan-Meier (K-M) survival curves were used to estimate survival.

Results
The prevalence of GAVE in this SSc cohort of 2039 SSc patients was 10.6% (n = 216) over a median follow-up period of 4.3(1.7–8.4) years. SSc patients with a history of GAVE compared with those without a history of GAVE were older at SSc onset [49.5 (40.0–58.2) vs 46.7 (36.0–56.7) years, p = 0.05]; more likely to have diffuse disease subtype (dcSSc) (35.3% vs 24.1%, p < 0.001); be negative for Scl-70, U1RNP and Scl/PM antibody (4.0% vs 16.1%, p < 0.001, 3.5% vs 7.4%, p = 0.041, 0.0% vs 2.0%, p = 0.042; and respectively) and positive for RNAP III antibody (24.9% vs 8.3%, p < 0.001). Those with GAVE had a worse HRQoL (p = 0.002). Independent determinants of GAVE included the presence of RNAP III antibody (OR 3.46, p < 0.001), absence of Scl-70 antibody (OR 0.23, p = 0.001), presence of GIT dysmotility (OR 1.64, p = 0.004), and digital ulcers; pits; or digital amputation (OR 1.59, p = 0.014).

Conclusions
GAVE is an underestimated and underappreciated SSc manifestation of SSc, which occurs with a relatively high frequency. Identifying an at-risk GAVE phenotype, as presented herein, is of practical importance as screening may prove advantageous given GAVE can be easily diagnosed and treated.
The course of primary progressive aphasia diagnosis: a cross-sectional study
Authors: Mouton A. , Plonka A. , Fabre R. , Tran T. M. , Robert P. , Macoir J. , Manera V. , Gros A. 
Published: May 2022

AbstractBackgroundThe primary progressive aphasia (PPA) diagnosis trajectory is debated, as several changes in diagnosis occur during PPA course, due to phenotype evolution from isolated language alterations to global cognitive impairment.The goal of the present study, based on a French cohort, was to describe the demographics and the evolution of subjects with (PPA) in comparison with Alzheimer’s disease (AD) on a period of 7 years.MethodsWe conducted a repeated cross-sectional study. The study population comprised individuals with PPA and AD diagnosis (N=167,191) from 2010 to 2016 in the French National data Bank (BNA). Demographic variables, MMSE scores, diagnosis status at each visit and prescribed treatments were considered.ResultsFrom 2010 to 2016, 5186 patients were initially diagnosed with PPA, 162,005 with AD. Compared to AD subjects, significant differences were found concerning age (younger at first diagnosis for PPA), gender (more balanced in PPA), education level (higher in PPA) and MMSE score (higher of 1 point in PPA).Percentage of pending diagnosis, delay between first consultation and first diagnosis and the number of different diagnoses before the diagnosis of interest were significantly higher in PPA group compared to AD group. Pharmacological and non-pharmacological treatments were significatively more recommended following PPA than AD diagnosis.ConclusionThis study improves the knowledge of PPA epidemiology and has the potential to help adopting appropriate public health service policies. It supports the hypothesis that PPA is diagnosed later than AD. The PPA diagnosis increases the prescription of non-pharmacological treatments, especially speech and language therapy (SLT) that is the main treatment available and most effective when at the initial stage.Trial registrationClinicalTrials.gov identifierNCT03687112
Intraocular pressure improvement in patients receiving teprotumumab for the treatment of thyroid eye disease: a case series
Authors: Chu Matthew , Sung Jonathan , Song Michael , Song Alice , Song Julia 
Published: May 2022

Abstract
Background
Teprotumumab is a novel treatment that reduces inflammation and symptoms caused by thyroid eye disease. There are limited data on teprotumumab’s effect on intraocular pressure.

Case presentation
We report nine patients diagnosed with thyroid eye disease whose intraocular pressure decreased during teprotumumab treatment for 8 weeks: patient 1, a 67-year-old Hispanic woman; patient 2, an 86-year-old African-American man; patient 3, a 71-year-old Caucasian woman; patient 4, a 72-year-old Hispanic woman; patient 5, a 65-year-old Caucasian woman; patient 6, a 54-year-old Caucasian man; patient 7, a 54-year-old Asian man; patient 8, a 31-year-old Asian woman; patient 9, a 60-year-old Caucasian woman. The diagnosis of thyroid eye disease was based on increased redness, swelling, and excessive tearing; abnormal proptosis, lid retraction, and diplopia measurements were also taken during physical examination. Intraocular pressure in primary, lateral gaze, and upgaze was documented. There was significant (p = 0.0397) improvement of primary gaze eye pressure from pre-teprotumumab infusions (baseline) to completion of the treatment course.

Conclusions
Teprotumumab significantly decreased the intraocular pressure for patients during the duration of the study. Teprotumumab is a novel medication that is approved for the primary treatment of thyroid eye disease in both acute and chronic thyroid eye disease. Previous treatments used to treat thyroid eye disease include glucocorticoids, radiotherapy, or orbital decompression surgery; however, these treatments all have significant limitations. Teprotumumab is an effective noninvasive alternative for decreasing symptoms of thyroid eye disease and, as shown, also lowers intraocular pressure. However, teprotumumab should not be used as a substitute for glaucoma medications; its ability to lower intraocular pressure may be in addition to lowering periorbital pressure and retro-orbital pressure.
Whole-exome sequencing in a subject with fluctuating neuropsychiatric symptoms, immunoglobulin G1 deficiency, and subsequent development of Crohn’s disease: a case report
Authors: Jyonouchi Harumi , Geng Lee 
Published: May 2022

Abstract
Background
Mutations or polymorphisms of genes that are associated with inflammasome functions are known to predispose individuals to Crohn’s disease and likely affect clinical presentations and responses to therapeutic agents in patients with Crohn’s disease. The presence of additional gene mutations/polymorphisms that can modify immune responses may further affect clinical features, making diagnosis and management of Crohn’s disease even more challenging. Whole-exome sequencing is expected to be instrumental in understanding atypical presentations of Crohn’s disease and the selection of therapeutic measures, especially when multiple gene mutations/polymorphisms affect patients with Crohn’s disease.

Case summary
We report the case of a non-Hispanic Caucasian female patient with Crohn’s disease who was initially diagnosed with pediatric acute-onset neuropsychiatric syndrome with fluctuating anxiety symptoms at 9 years of age. This patient was initially managed with pulse oral corticosteroid treatment and then intravenous immunoglobulin due to her immunoglobulin G1 deficiency. At 15 years of age, she was diagnosed with Crohn’s disease, following onset of acute abdomen. Treatment with oral corticosteroid and then tumor necrosis factor-α blockers (adalimumab and infliximab) led to remission of Crohn’s disease. However, she continued to suffer from chronic abdominal pain, persistent headache, general fatigue, and joint ache involving multiple joints. Extensive gastrointestinal workup was unrevealing, but whole-exome sequencing identified two autosomal dominant gene variants: NLRP12 (loss of function) and IRF2BP2 (gain of function). Based on whole-exome sequencing findings, infliximab was discontinued and anakinra, an interleukin-1β blocker, was started, rendering marked improvement of her clinical symptoms. However, Crohn’s disease lesions recurred following Yersinia enterocolitis. The patient was successfully treated with a blocker of interleukin-12p40 (ustekinumab), and anakinra was discontinued following remission of her Crohn’s disease lesions.

Conclusion
Loss-of-function mutation of NRLRP12 gene augments production of interleukin-1β and tumor necrosis factor-α, while gain-of-function mutation of IRF2BP2 impairs cytokine production and B cell differentiation. We propose that the presence of these two autosomal dominant variants caused an atypical clinical presentation of Crohn’s disease.
The inertial iterative extragradient methods for solving pseudomonotone equilibrium programming in Hilbert spaces
Authors: Rehman Habib ur , Kumam Poom , Argyros Ioannis K. , Kumam Wiyada , Shutaywi Meshal 
Published: May 2022

AbstractIn this paper, we present new iterative techniques for approximating the solution of an equilibrium problem involving a pseudomonotone and a Lipschitz-type bifunction in Hilbert spaces. These techniques consist of two computing steps of a proximal-type mapping with an inertial term. Improved simplified stepsize rules that do not involve line search are investigated, allowing the method to be implemented more quickly without knowing the Lipschitz-type constants of a bifunction. The iterative sequences converge weakly on a specific solution to the problem when the control parameter conditions are properly specified. The numerical tests were carried out, and the results demonstrated the applicability and quick convergence of innovative approaches over earlier ones.
Body weight at 1.5- and 3-year health checks and body fat at 14 years of age: a population-based retrospective cohort study using dual-energy X-ray absorptiometry
Authors: Kouda Katsuyasu , Fujita Yuki , Ohara Kumiko , Nakamura Harunobu , Dorjravdan Munkhjargal , Nakama Chikako , Nishiyama Toshimasa , Iki Masayuki 
Published: May 2022

Abstract
Background
In Japan, height and weight measurements, taken for all children at birth and 1.5- and 3-year health checks, are recorded in the Mother and Child Health (MCH) Handbook, as required by the law. The present population-based retrospective cohort study aimed to evaluate the diagnostic performance of height and weight records in the Handbook for predicting excessive adiposity in adolescents.

Methods
The source population consisted of 8th grade students (800 students aged 14 years) registered at two public junior high schools. Of these, we excluded students who were born at a gestational age < 37 weeks or > 42 weeks. The present analyses included 435 participants who provided complete information. Body mass index (BMI) was calculated using height and weight records. Body fat mass at 14 years of age was measured by dual-energy X-ray absorptiometry (DXA). Diagnostic performance of BMI calculated from the MCH Handbook records to discriminate between the presence and absence of excessive adiposity at 14 years of age was evaluated using receiver operating characteristic (ROC) curve analysis. The area under the ROC curve (AUC) was used to quantify the diagnostic accuracy of BMI.

Results
With regard to the prediction of excessive fat at 14 years of age, AUCs and 95% confidence intervals for BMI at 1.5 and 3 years of age were greater than 0.5. Meanwhile, the AUC of BMI at birth was not significantly greater than 0.5.

Conclusion
The present study findings indicate that BMI values calculated using MCH Handbook data have potential ability to distinguish between the presence and absence of excessive fat at 14 years of age.
A total infectome approach to understand the etiology of infectious disease in pigs
Authors: Huang Xinyi , Wu Weichen , Tian Xiaoxiao , Hou Xin , Cui Xingyang , Xiao Yihong , Jiao Qiulin , Zhou Pei , Liu Liqiang , Shi Weilin , Chen Ligong , Sun Yue , Yang Yongbo , Chen Jianxin , Zhang Guihong , Liu Jinling , Holmes Edward C. , Cai Xuehui , An Tongqing , Shi Mang 
Published: May 2022

AbstractBackgroundThe global pork industry is continuously affected by infectious diseases that can result in large-scale mortality, trade restrictions, and major reductions in production. Nevertheless, the cause of many infectious diseases in pigs remains unclear, largely because commonly used diagnostic tools fail to capture the full diversity of potential pathogens and because pathogen co-infection is common.ResultsWe used a meta-transcriptomic approach to systematically characterize the pathogens in 136 clinical cases representing different disease syndromes in pigs, as well as in 12 non-diseased controls. This enabled us to simultaneously determine the diversity, abundance, genomic information, and detailed epidemiological history of a wide range of potential pathogens. We identified 34 species of RNA viruses, nine species of DNA viruses, seven species of bacteria, and three species of fungi, including two novel divergent members of the genusPneumocystis. While most of these pathogens were only apparent in diseased animals or were at higher abundance in diseased animals than in healthy animals, others were present in healthy controls, suggesting opportunistic infections. Importantly, most of the cases examined here were characterized by co-infection with more than two species of viral, bacterial, or fungal pathogens, some with highly correlated occurrence and abundance levels. Examination of clinical signs and necropsy results in the context of relevant pathogens revealed that a multiple-pathogen model was better associated with the data than a single-pathogen model was.ConclusionsOur data demonstrate that most of the pig diseases examined were better explained by the presence of multiple rather than single pathogens and that infection with one pathogen can facilitate infection or increase the prevalence/abundance of another. Consequently, it is generally preferable to consider the cause of a disease based on a panel of co-infecting pathogens rather than on individual infectious agents.
Postoperative chylous ascites after total gastrectomy successfully treated using peritoneovenous (Denver) shunt: a case report
Authors: Sakamoto Shinya , Takata Nobuo , Noda Yoshihiro , Ozaki Kazuhide , Okabayashi Takehiro 
Published: May 2022

Abstract
Background
Chylous ascites (CA) is a rare complication of gastrectomy for gastric cancer. While most cases of postoperative CA improve with medication or nutritional support, some are refractory to conservative treatment. A peritoneovenous shunt (PVS) may help patients who are poor candidates for surgery. However, PVS placement for postoperative CA after gastroenterological surgery has been rarely reported. Herein, we present a case of postoperative CA following total gastrectomy with para-aortic lymphadenectomy, treated successfully by PVS placement.

Case presentation
A 74-year-old man who underwent total gastrectomy with para-aortic lymph node dissection was hospitalised because of insufficient oral intake and dehydration. His abdomen was markedly distended with severe bilateral lower extremity oedema. On admission, abdominal computed tomography (CT) showed a high volume of ascites and no signs of cancer recurrence. Accordingly, postoperative CA resulting from drainage of fluid on paracentesis was diagnosed. Despite nutritional support, diuretics, and octreotide administration, his abdominal distension and nutritional status did not improve. We could not identify the sites of lymphatic leakage in the three intranodal lymphangiographies followed by CT. Although we considered a surgical treatment in our patient, we decided against it. Because we could not identify lymphatic leakage site during lymphangiography, surgical treatment might have a potential failure of detection and closure of leakage site. Furthermore, the patient’s general condition was poor because of malnutrition resulting from the loss of lymphatic fluid. Consequently, we decided to place PVS. After PVS placement, his abdominal distension improved rapidly, and he was discharged without serious complications. Thirteen months after PVS, patient has no relapse of abdominal distention and nutrition status has improved.

Conclusion
PVS might be a good option to manage refractory postoperative CA, as the leakage point cannot be detected on lymphangiography.