bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of novel biomarkers in Hunner’s interstitial cystitis using the CIBERSORT, an algorithm based on machine learning
Authors: Lu Kaining , Wei Shan , Wang Zhengyi , Wu Kerong , Jiang Junhui , Yan Zejun , Cheng Yue 
Published: August 2021

Abstract
Background
Hunner’s interstitial cystitis (HIC) is a complex disorder characterized by pelvic pain, disrupted urine storage, and Hunner lesions seen on cystoscopy. There are few effective diagnostic biomarkers. In the present study, we used the novel machine learning tool CIBERSORT to measure immune cell subset infiltration and potential novel diagnostic biomarkers for HIC.

Methods
The GSE11783 and GSE57560 datasets were downloaded from the Gene Expression Omnibus for analysis. Ten HIC and six healthy samples from GSE11783 were analyzed using the CIBERSORT algorithm. Gene Set Enrichment Analysis (GSEA) was performed to identify biological processes that occur during HIC pathogenesis. Finally, expression levels of 11 T cell follicular helper cell (Tfh) markers were compared between three healthy individuals and four patients from GSE57560.

Results
Six types of immune cells in HIC from GSE11783 showed significant differences, including resting mast cells, CD4+ memory-activated T cells (CD3+ CD4+ HLA-DR+ cells), M0 and M2 macrophages, Tfh cells, and activated natural killer cells. Except for plasma cells, there were no significant differences between Hunner’s lesion and non-Hunner’s lesion areas in HIC. The GSEA revealed significantly altered biological processes, including antigen–antibody reactions, autoimmune diseases, and infections of viruses, bacteria, and parasites. There were 11 Tfh cell markers with elevated expression in patients from GSE57560.

Conclusion
This was the first demonstration of Tfh cells and CD3+ CD4+ HLA-DR+ cells with elevated expression in HIC. These cells might serve as novel diagnostic biomarkers.
Pharmacists’ clinical knowledge and practice in the safe use of contraceptives: real knowledge vs. self-perception and the implications
Authors: Jelić Ana Golić , Tasić Ljiljana , Škrbić Ranko , Marinković Valentina , Šatara Svjetlana Stoisavljević , Stojaković Nataša , Peković Vanda Marković , Godman Brian 
Published: August 2021

AbstractBackgroundPharmacists are often the first healthcare professionals that patients contact with their illnesses and requests for medical information, which is enhanced following the recent COVID-19 pandemic. Community pharmacists are expected and required to possess a broad spectrum of knowledge and skills. Self-assessment of these competencies is needed for their self-improvement.Purpose of the studyTo assess pharmacists’ clinical knowledge and practice in the safe use of contraceptives, and to compare the scores obtained by external observation with pharmacists’ self-assessment of their knowledge as well as investigate the significance of preceptorship experiences. Contraceptives was chosen as the subject area in view of high rates of abortions as a means of contraception in Bosnia and Herzegovina.MethodsA questionnaire approach was used. The questionnaire included the following: the first domain contained two case scenarios (safe use of contraceptives), which evaluated clinical knowledge, a second domain in which pharmacists self-assessed their knowledge to resolve cases from the first domain and a third domain that measured the demographics of pharmacists (including experience in preceptorship). Dispensing practice was evaluated in the second domain. The questionnaires were distributed to a convenient sample of 100 pharmacists at the Annual Meeting of Bosnia and Herzegovina Pharmacists. The results were presented as counts (%). The groups (preceptors and non-preceptors) were compared using Mann-Whitney U test, paired assessments were analyzed by Wilcoxon signed-rank test and Spearman’s correlation was used to assess the correlation between variables.ResultsOf the 100 pharmacists invited to participate, 84 completed the questionnaire (84 % response rate). There was no agreement between pharmacists’ real knowledge (average score -case 1: 2.71,case 2: 3.3) and their self-assessment (average score -case 1: 3.77,case 2: 3.91). There was no statistically significant difference in the actual knowledge of pharmacists (experienced/non-experienced in precepting), while the difference in the self-assessment was significant between these two groups.ConclusionPharmacists appear to overrate themselves, which leads to self-enhancement bias, in which the experience in precepting has some influence. Pharmacists’ capability in performing an objective self-assessment of their clinical knowledge needs to be carefully studied in the future to fully benefit patients.
Cost-utility analysis of trabecular micro-bypass stents (TBS) in patients with mild-to-moderate open-angle Glaucoma in Italy
Authors: Fea Antonio Maria , Cattel Francesco , Gandolfi Stefano , Buseghin Giorgio , Furneri Gianluca , Costagliola Ciro 
Published: August 2021

Abstract
Background
Glaucoma is a disease characterized by progressive damage of the optic nerve. Several therapeutic options are available to lower intraocular pressure (IOP). In primary open-angle glaucoma (POAG) patients with inadequate IOP control (or controlled with multiple medical therapies or for whom medical therapy is contraindicated), the implantation of micro-invasive glaucoma surgery devices (MIGS) and concomitant cataract surgery has proved to be more effective in reducing intraocular pressure (IOP), as compared to cataract surgery alone. The objective of this study was to assess the cost-effectiveness of iStent inject® device with concurrent cataract surgery vs. cataract surgery alone, in patients with mild-to-moderate POAG, adopting the Italian National Health Service (NHS) perspective.

Methods
Simulation of outcomes and costs was undertaken using a Markov model with 4 health states and one-month cycles, that is used to simulate the prognosis of these patients. Efficacy data were obtained from the randomized clinical trial (RCT). A lifetime horizon was adopted in the analysis. A discount rate of 3.5% was applied to both costs and effects. The Italian National Healthcare Service (NHS) perspective was considered, therefore only healthcare direct costs (acquisition of main interventions and subsequent procedures; medications; monitoring and follow-up; adverse events). Model robustness was tested through sensitivity analyses.

Results
Results of the base-case analysis showed that the total lifetime costs were higher in the iStent inject® + concurrent cataract surgery, compared with the cataract surgery alone group (€8368.51 vs. €7134.71 respectively). iStent inject® + concurrent cataract surgery was cost-effective vs. cataract surgery alone, with an incremental cost-effectiveness ratio of €13,037.01 per quality-adjusted life year (QALY) gained. Both one-way deterministic and probabilistic sensitivity analyses confirmed robustness of base-case results. The cost-effectiveness accessibility curve (CEAC) showed that iStent inject® + cataract surgery would have a 98% probability of being cost-effective, compared to cataract surgery alone, when the willingness to pay (WTP) is equal to €50,000 per QALY gained.

Conclusions
The results of the cost-utility analysis confirm that iStent inject® + cataract surgery is a cost-effective option for the treatment of patients affected by mild-to-moderate POAG, compared with cataract surgery alone, when evaluated from the Italian NHS perspective.
Temporal change in Syndecan-1 as a therapeutic target and a biomarker for the severity classification of COVID-19
Authors: Ogawa Fumihiro , Oi Yasufumi , Nakajima Kento , Matsumura Reo , Nakagawa Tomoki , Miyagawa Takao , Sakai Kazuya , Saji Ryo , Taniguchi Hayato , Takahashi Kohei , Abe Takeru , Iwashita Masayuki , Nishii Mototsugu , Takeuchi Ichiro 
Published: August 2021

Abstract
Background
Coronavirus disease 2019 (COVID-19) pneumonitis associated with severe respiratory failure is associated with high mortality. The pathogenesis of COVID-19 is associated with microembolism or microvascular endothelial injuries. Here, we report that syndecan-1 (SDC-1), a component of the endothelial glycocalyx, may be a biomarker of severity classification for COVID-19 related to endothelial injury.

Methods and analysis
We analyzed the data of COVID-19 patients for 1 year from February 2020 at Yokohama City University Hospital and Yokohama City University Medical Center Hospital. We selected COVID-19 patients who required admission care, including intensive care, and analyzed the classification of severe and critical COVID-19 retrospectively, using various clinical data and laboratory data with SDC-1 by ELISA.

Results
We analyzed clinical and laboratory data with SDC-1 in five severe COVID-19 and ten critical COVID-19 patients. In the two groups, their backgrounds were almost the same. In laboratory data, the LDH, CHE, and CRP levels showed significant differences in each group (P = 0.032, P < 0.0001, and P = 0.007, respectively) with no significant differences in coagulation-related factors (platelet, PT-INR, d-dimer, ISTH score; P = 0.200, 0.277, 0.655, and 0.36, respectively). For the clinical data, the SOFA score was significantly different from admission day to day 14 of admission (p < 0.0001). The SDC-1 levels of critical COVID-19 patients were significantly higher on admission day and all-time course compared with the levels of severe COVID-19 patients (P = 0.009 and P < 0.0001, respectively).

Conclusions
Temporal change of SDC-1 levels closely reflect the severity of COVID-19, therefore, SDC-1 may be a therapeutic target and a biomarker for the severity classification of Covid-19.
Morphological neurite changes induced by porcupine inhibition are rescued by Wnt ligands
Authors: Godoy Juan A. , Espinoza-Caicedo Jasson , Inestrosa Nibaldo C. 
Published: August 2021

Abstract
Background
Wnt signaling plays key roles in cellular and physiological processes, including cell proliferation, differentiation and migration during development and tissue homeostasis in adults. This pathway can be defined as Wnt/β-catenin-dependent or β-catenin-independent or “non-canonical”, both signaling are involved in neurite and synapse development/maintenance. Porcupine (PORCN), an acylase that o-acylates Wnt ligands, a major modification in secretion and interaction with its receptors. We use Wnt-C59, a specific PORCN inhibitor, to block the secretion of endogenous Wnts in embryonic hippocampal neurons (DIV 4). Under these conditions, the activity of exogenous Wnt ligands on the complexity of the dendritic tree and axonal polarity were evaluated

Methods
Cultured primary embryonic hippocampal neurons obtained from Sprague–Dawley rat fetuses (E18), were cultured until day in vitro (DIV) 4 (according to Banker´s protocol) and treated with Wnt-C59 for 24 h, Wnt ligands were added to the cultures on DIV 3 for 24 h. Dendritic arbors and neurites were analysis by fluorescence microscopy. Transfection with Lipofectamine 2000 on DIV 2 of plasmid expressing eGFP and KIF5-Cherry was carried out to evaluate neuronal polarity. Immunostaining was performed with MAP1B and Tau protein. Immunoblot analysis was carried out with Wnt3a, β-catenin and GSK-3β (p-Ser9). Quantitative analysis of dendrite morphology was carried out with ImageJ (NIH) software with Neuron J Plugin.

Results
We report, here, that Wnt-C59 treatment changed the morphology of the dendritic arbors and neurites of embryonic hippocampal neurons, with decreases β-catenin and Wnt3a and an apparent increase in GSK-3β (p-Ser9) levels. No effect was observed on axonal polarity. In sister cultures, addition of exogenous Wnt3a, 5a and 7a ligands rescued the changes in neuronal morphology. Wnt3a restored the length of neurites to near that of the control, but Wnt7a increased the neurite length beyond that of the control. Wnt5a also restored the length of neurites relative to Wnt concentrations.

Conclusions
Results indicated that Wnt ligands, added exogenously, restored dendritic arbor complexity in embryonic hippocampal neurons, previously treated with a high affinity specific Porcupine inhibitor. We proposed that PORCN is an emerging molecular target of interest in the search for preclinical options to study and treat Wnt-related diseases.
Urinary metabolomic changes and microbiotic alterations in presenilin1/2 conditional double knockout mice
Authors: Gao Jie , Zhou Nian , Wu Yongkang , Lu Mengna , Wang Qixue , Xia Chenyi , Zhou Mingmei , Xu Ying 
Published: August 2021

Abstract
Background
Given the clinical low efficient treatment based on mono-brain-target design in Alzheimer’s disease (AD) and an increasing emphasis on microbiome-gut-brain axis which was considered as a crucial pathway to affect the progress of AD along with metabolic changes, integrative metabolomic signatures and microbiotic community profilings were applied on the early age (2-month) and mature age (6-month) of presenilin1/2 conditional double knockout (PS cDKO) mice which exhibit a series of AD-like phenotypes, comparing with gender and age-matched C57BL/6 wild-type (WT) mice to clarify the relationship between microbiota and metabolomic changes during the disease progression of AD.

Materials and methods
Urinary and fecal samples from PS cDKO mice and gender-matched C57BL/6 wild-type (WT) mice both at age of 2 and 6 months were collected. Urinary metabolomic signatures were measured by the gas chromatography-time-of-flight mass spectrometer, as well as 16S rRNA sequence analysis was performed to analyse the microbiota composition at both ages. Furthermore, combining microbiotic functional prediction and Spearman’s correlation coefficient analysis to explore the relationship between differential urinary metabolites and gut microbiota.

Results
In addition to memory impairment, PS cDKO mice displayed metabolic and microbiotic changes at both of early and mature ages. By longitudinal study, xylitol and glycine were reduced at both ages. The disturbed metabolic pathways were involved in glycine, serine and threonine metabolism, glyoxylate and dicarboxylate metabolism, pentose and glucuronate interconversions, starch and sucrose metabolism, and citrate cycle, which were consistent with functional metabolic pathway predicted by the gut microbiome, including energy metabolism, lipid metabolism, glycan biosynthesis and metabolism. Besides reduced richness and evenness in gut microbiome, PS cDKO mice displayed increases in Lactobacillus, while decreases in norank_f_Muribaculaceae, Lachnospiraceae_NK4A136_group, Mucispirillum, and Odoribacter. Those altered microbiota were exceedingly associated with the levels of differential metabolites.

Conclusions
The urinary metabolomics of AD may be partially mediated by the gut microbiota. The integrated analysis between gut microbes and host metabolism may provide a reference for the pathogenesis of AD.
Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling
Authors: Cheng Demin , Xu Qi , Wang Yue , Li Guanru , Sun Wenqing , Ma Dongyu , Zhou Siyun , Liu Yi , Han Lei , Ni Chunhui 
Published: August 2021

Abstract
Background
Silicosis is one of the most common occupational pulmonary fibrosis caused by respirable silica-based particle exposure, with no ideal drugs at present. Metformin, a commonly used biguanide antidiabetic agent, could activate AMP-activated protein kinase (AMPK) to exert its pharmacological action. Therefore, we sought to investigate the role of metformin in silica-induced lung fibrosis.

Methods
The anti-fibrotic role of metformin was assessed in 50 mg/kg silica-induced lung fibrosis model. Silicon dioxide (SiO2)-stimulated lung epithelial cells/macrophages and transforming growth factor-beta 1 (TGF-β1)-induced differentiated lung fibroblasts were used for in vitro models.

Results
At the concentration of 300 mg/kg in the mouse model, metformin significantly reduced lung inflammation and fibrosis in SiO2-instilled mice at the early and late fibrotic stages. Besides, metformin (range 2–10 mM) reversed SiO2-induced cell toxicity, oxidative stress, and epithelial-mesenchymal transition process in epithelial cells (A549 and HBE), inhibited inflammation response in macrophages (THP-1), and alleviated TGF-β1-stimulated fibroblast activation in lung fibroblasts (MRC-5) via an AMPK-dependent pathway.

Conclusions
In this study, we identified that metformin might be a potential drug for silicosis treatment.
Sarcopenia and dosimetric parameters in relation to treatment-related leukopenia and survival in anal cancer
Authors: Nilsson Martin P. , Johnsson Anders , Scherman Jonas 
Published: August 2021

Abstract
Background
Treatment-related white blood cell (WBC) toxicity has been associated with an inferior prognosis in different malignancies, including anal cancer. The aim of the present study was to investigate predictors of WBC grade ≥ 3 (G3+) toxicity during chemoradiotherapy (CRT) of anal cancer.

Methods
Consecutive patients with locally advanced (T2 ≥ 4 cm—T4 or N+) anal cancer scheduled for two cycles of concomitant 5-fluorouracil and mitomycin C chemotherapy were selected from an institutional database (n = 106). All received intensity modulated radiotherapy (IMRT; mean dose primary tumor 59.5 Gy; mean dose elective lymph nodes 45.1 Gy). Clinical data were extracted from medical records. The highest-grade WBC toxicity was recorded according to CTCAE version 5.0. Pelvic bone marrow (PBM) was retrospectively contoured and dose-volume histograms were generated. The planning CT was used to measure sarcopenia. Dosimetric, anthropometric, and clinical variables were tested for associations with WBC G3+ toxicity using the Mann–Whitney test and logistic regression. Cox proportional hazard regression was used to assess predictors for overall survival (OS) and anal cancer specific survival (ACSS).

Results
WBC G3+ was seen in 50.9% of the patients, and 38.7% were sarcopenic. None of the dosimetric parameters showed an association with WBC G3+ toxicity. The most significant predictor of WBC G3+ toxicity was sarcopenia (adjusted OR 4.0; P = 0.002). Sarcopenia was also associated with an inferior OS (adjusted HR 3.9; P = 0.01), but not ACSS (P = 0.07). Sensitivity analysis did not suggest that the inferior prognosis for sarcopenic patients was a consequence of reduced doses of chemotherapy or a prolonged radiation treatment time. Patients who experienced WBC G3+ toxicity had an inferior OS and ACSS, even after adjustment for sarcopenia.

Conclusions
Sarcopenia was associated with increased risks of both WBC G3+ toxicity and death following CRT for locally advanced anal cancer. In this study, radiation dose to PBM was not associated with WBC G3+ toxicity. However, PBM was not used as an organ at risk for radiotherapy planning purposes and doses to PBM were high, which may have obscured any dose–response relationships.
Efficacy of management of associated dysfunctions on rotator cuff and long head of the biceps: systematic review
Authors: Aldon-Villegas Rocio , Perez-Cabezas Veronica , Chamorro-Moriana Gema 
Published: August 2021

AbstractBackgroundThe important functional role the rotator cuff (RC) and biceps play in the shoulder, the close anatomical relationship between them and the high incidence of injuries require an appropriate multidisciplinary therapeutic approach after a rigorous assessment. The objective is to identify and analyze surgical interventions, whether or not followed by a postsurgical one, of associated dysfunctions on the RC and long head of the biceps (LHB) and their effectiveness in improving shoulder functionality.MethodsA systematic review based on PRISMA protocol was conducted using PubMed, Web of Science, PEDro, Scopus, CINAHL, and Dialnet until 22 April 2021. The main inclusion criteria were as follows: randomized clinical trials including subjects diagnosed with RC and LHB lesions who had surgical and/not post-surgical treatments. The methodological quality of trials was evaluated by the PEDro scale. Data were shown in 3 pre-established tables: (1)sample data, diagnostic methods, dysfunctions and injury frequency, interventions, outcome measures and results; (2)significance and effectiveness of interventions; and (3)comparison of the effectiveness of interventions.ResultsEleven studies were selected. The methodological quality of ten of them was assessed asgoodand oneexcellent(PEDro scale). All articles had surgical treatments and ten had postoperative management. All trials used arthroscopy and two open surgery too. Single-row, double-row and transosseous repair were used for RC lesions, while SLAP repair, tenotomy, and tenodesis were applied to LHB injuries. Measured parameters were functionality, pain, Popeye’s sign, strength, range of motion, satisfaction degree, biceps cramping, and quality of life. All approaches in general, surgical plus postsurgical, were always effective to the parameters measured in each study. Seven trials compared tenotomy and tenodesis: four of them obtained statistically significant differences in favor of tenodesis in Popeye’s sign, cramping, satisfaction degree, and/or forearm supination strength; and one, in favor of tenotomy in cramping. All studies measured functionality using functional assessment scales. The most widely used was the Constant Score.ConclusionsSurgical plus post-surgical interventions in associated dysfunctions on RC and LHB were effective. Tenodesis obtained better results than tenotomy in Popeye’s sign, satisfaction, and forearm supination strength. However, there was no difference regarding biceps cramping.
Two progressed malignant phyllodes tumors of the breast harbor alterations in genes frequently involved in other advanced cancers
Authors: Reinisch Mattea , Kuemmel Sherko , Breit Elisabeth , Theuerkauf Ingo , Harrach Hakima , Schindowski Dorothea , Moka Detlef , Bettstetter Marcus , Bruzas Simona , Chiari Ouafaa 
Published: August 2021

AbstractBackgroundThe genomic landscape of phyllodes tumors (PTs) of the breast is not well defined, especially in patients with advanced disease. To shed light on this topic, paired primary and progressed tumor samples from two patients with malignant PTs were subjected to next-generation sequencing (NGS) followed by functional analysis of genetic alterations using two prediction tools.MethodsThe DNA of both the primary tumor and distant metastases of Patient 1 and the primary and recurrent tumor of Patient 2 were subjected to molecular profiling. NGS with the FoundationOne® assay was performed in a commercial molecular pathology laboratory. Two in silico prediction tools were used to estimate the pathogenicity of indicated genetic alterations.ResultsIn total, 38 genomic alterations were detected, of which 11 were predicted to be probably benign. In Patient 1, 14 aberrations were identified in the primary tumor and 17 in pulmonary metastases, 12 of which were identical. In the primary and recurrent tumor of Patient 2, 17 and 15 sequence variants, respectively, were found, with 13 overlapping findings. Affected genes included seven (TP53,TERT,APC,ARID1A,EGFR,KMT2D, andRB1) of the top 10 most frequently altered genes in other advanced cancer entities, as well as four actionable therapeutic targets (EGFR,KIT,PDGFRA, andBRIP1). Of note, seven genes coding for receptor tyrosine kinases were affected: three in Patient 1 and four in Patient 2. Several genes (e.g.EPHA3,EPHA7, andEPHB1) were shown to be altered for the first time in PTs.ConclusionsThe two progressed malignant PTs investigated here share some of the major genetic events occurring in other advanced cancers.