bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pilot Study of Combination Gemogenovatucel-T (Vigil) and Durvalumab in Women With Relapsed BRCA-wt Triple-Negative Breast or Ovarian Cancer
Authors: Barve Minal , Aaron Phylicia , Manning Luisa , Bognar Ernest , Wallraven Gladice , Horvath Staci , Stanbery Laura , Nemunaitis John 
Published: August 2022

Background: Gemogenovatucel-T (Vigil) is a triple-function autologous tumor cell immunotherapy which expresses granulocyte-macrophage colony-stimulating factor and decreases expression of furin and downstream TGF-β1 and TGF-β2. Vigil has suggested survival benefit in frontline maintenance ovarian cancer patients who are BRCA-wt. In addition, Vigil demonstrates relapse-free and overall survival advantage in homologous recombination-proficient patients with OC. Further evidence of clinical benefit and safety has been demonstrated in combination with atezolizumab. Methods: In this pilot study (NCT02725489), the concurrent combination of the programmed death-ligand 1 (PD-L1) inhibitor durvalumab and Vigil was explored in advanced BRCA-wt relapsed triple-negative breast cancer (TNBC) patients and stage III-IV recurrent/refractory OC patients. Patients received the combination regimen of Vigil (1 × 10e6-10e7 cells/dose intradermally, up to 12 doses) and durvalumab (1500 mg/dose intravenous infusion, up to 12 months) once every 4 weeks. The primary objective was to evaluate safety of this combination. The study included 13 BRCA-wt patients (TNBC, n = 8; OC, n = 5). Results: The most common treatment-emergent adverse events (⩾20%) in all patients included injection-site reaction (92.3%), myalgia (38.5%), bruise at injection site (23.1%), and pruritus (23.1%). Three grade 3 treatment-related adverse events were observed and related to durvalumab. There were no grade 4/5 treatment-related adverse events. Median progression-free survival was 7.1 months and the median overall survival was not reached. Prolonged progression-free survival was improved in patients with PD-L1+ tumors (n = 8, hazard ratio = 0.304, 95% confidence interval, 0.0593-1.56, 1-sided P = .04715) compared with those with PD-L1− tumors. Conclusions: Vigil plus durvalumab was well tolerated and showed promising clinical activity in advanced BRCA-wt TNBC and stage III-IV recurrent/refractory OC patients.
Analogy and similarity as a resource in new speaker styles of Basque
Authors: Lantto Hanna 
Published: August 2022

Aims and Objectives/Purpose/Research Questions: The study examines contact between the Basque standard variety, Spanish, and Basque dialects in the speech of new speakers of Basque, euskaldun berriak, who have Spanish as their language of primary socialization and who have learned standard Basque in classroom contexts. The overall goal of the study is to determine what linguistic features new speakers draw from in the construction of a colloquial style of Basque. Design/Methodology/Approach: The study combines third-wave approaches of sociolinguistic variation with cognitive, usage-based approaches to language contact. The study is based on ethnographic fieldwork conducted in the city of Bilbao between 2016 and 2017. Data and Analysis: Forty-seven new speakers of Basque participated in metalinguistic interviews. Many others were observed in the larger context of the ethnographic fieldwork. The data consist of field notes and more than 30 hours of recordings. The analysis combines the metalinguistic commentary of the participants with observation of their linguistic practices. Findings/Conclusions: New speakers’ morphosyntactic and stylistic variation in constructing a colloquial style is explained through analogy and similarity, as they draw from interlingual and intralingual analogies and similarities in the process of register construction. The variation can be largely explained by the speakers’ social networks and their involvement in the Basque-speaking cultural sphere. Originality: This study examines the role of new speakers in linguistic change. The study presents a novel approach by combining analyses of common cognitive processes with an understanding of shared social language practices that are influenced by language ideologies. Significance/Implications: An integrated approach of cognitive processes and the social meaning of language change allow the examination of the interplay of social competence and human faculty. Variationist studies can benefit from studies conducted at the sites of language revitalization with complex indexical fields and rapidly changing social dynamics.
Effect of combining anticoagulant and glucocorticoid therapy on mortality in patients with severe COVID-19
Authors: Shi Can , Wu Tian , Hu Jing , Guo Ren , Liu Zuoliang 
Published: August 2022

Introduction Coronavirus disease (COVID-19) has spread rapidly to more than 200 countries and regions worldwide. Although several options have been implemented in attempts to control the rate of COVID-19 infection, the mortality rates remain high. The aim of this study is to evaluate whether patients with severe COVID-19 will benefit from the combination of anticoagulant and glucocorticoid therapy. Methods A single-center retrospective cohort study of patients with COVID-19 was performed. Several factors influencing patients with COVID-19 have been analyzed retrospectively, including basic conditions, inflammatory factors, coagulation parameters, medications, and outcomes. Continuous and categorical variables have been evaluated via binary logistic regression analysis to predict mortality. The association between anticoagulant treatment and outcomes has also been evaluated, stratifying patients according to glucocorticoid treatment. Results 61 patients with severe COVID-19, including 23 critically ill patients have been enrolled in the study. In those with severe and critical illness COVID-19, mortality rate was lower in those who received combined anticoagulant and glucocorticoid with odds ratio of 0.003 ( p = 0.042) and 0.031 ( p = 0.046), respectively. In cases of severe COVID-19, those who were treated with both anticoagulant and glucocorticoid had lower mortality (17.6%) than those treated with glucocorticoid alone (31.8%), although this did not reach statistical significance ( p = 0.321). In the critically ill COVID-19 patients who received both anticoagulant and glucocorticoid, there was significantly lower mortality (30%) than those who received glucocorticoid alone (77.8%) ( p = 0.047). Seventy-five percent of non-survivors of COVID-19 met the International Society on Thrombosis and Haemostasis criteria of disseminated intravascular coagulation (total points ≥5). Conclusion Patients with severe COVID-19 or critically ill patients with COVID-19 may benefit from the combination therapy of anticoagulant and glucocorticoid. As the disease getting severe, more benefits may be obtained from the combination therapy.
Astaxanthin suppresses End MT by LOX-1 pathway in ox-LDL-induced HUVECs
Authors: Zhu Zhongsheng , Li Jinyu , Tong Rui , Zhang Xiaorong , Yu Bo 
Published: August 2022

Introduction Astaxanthin (ASX) is carotenoid with the highest antioxidant activity in various cell types and reverse atherosclerosis. However, the roles and detailed mechanisms of ASX in atherosclerosis associated endothelial injury remains unclear. Methods In vitro atherosclerosis model was established in HUVECs by incubation with oxidized low-density lipoprotein (ox-LDL). Cell viability and oxidative stress were measured. The mRNA and protein expressions of lectin-like ox-LDL receptor (LOX-1) and other related genes were determined. Results ox-LDL reduced cell viability of HUVECs, and induced oxidative stress, as evidenced by elevated cellular malondialdehyde (MDA) and decreased superoxide dismutase (SOD). Pretreatment with ASX (50, 100, 200, and 400 μM) markedly reversed the reduction in cell viability and an increase in migration of HUVECs induced by ox-LDL (50 μg/mL). ASX attenuated the increase in the endothelial-to-mesenchymal transition (EndMT) process, as evidenced by increased CD31 and decreased α-SMA and vimentin proteins by ASX treatment in HUVECs. Furthermore, ASX attenuated the increase in MDA and decrease in SOD induced by ox-LDL, increased supernatant NO production, attenuated the increase in iNOS and decrease in eNOS in HUVECs with ox-LDL. ASX enhanced mRNA and protein expressions of the lectin-like ox-LDL receptor (LOX-1), which was dependent on ASX’s antioxidant activity. The inhibitory effect of ASX on EndMT could be abolished by overexpression of LOX-1 in HUVECs induced by ox-LDL. Conclusions Our data speculate that ASX prevents ox-LDL-induced endothelial cell injury and EndMT by inducing antioxidant property (SOD and NO) and decreasing LOX-1 expression.
Self-Reported Outcomes in Early Postoperative Management After Shoulder Surgery Using a Home-Based Strengthening and Stabilization System With Telehealth
Authors: Greiner Justin J. , Drain Nicholas P. , Lesniak Bryson P. , Lin Albert , Musahl Volker , Irrgang James J. , Popchak Adam J. 
Published: August 2022

Background: Multiple rehabilitation protocols after shoulder surgery have been proposed. The coronavirus pandemic adds an extra layer of complexity to postoperative rehabilitation after shoulder surgery. Hypothesis: The combined use of a home-based rehabilitation system, the Shoulder Strengthening and Stabilization System (SSS), and telehealth visits will lead to acceptable patient self-reported outcomes and satisfaction after shoulder surgery. Study Design: Prospective observational cohort. Level of Evidence: Level 4. Methods: A total of 132 patients were prescribed SSS after shoulder surgery. A virtual clinical specialist monitored patients through telehealth visits as prescribed by the treating physician. Data were collected prospectively during each telehealth visit. Patients completed an exit survey during their last telehealth visit. Results: The use of SSS with telehealth revealed a positive impact on postoperative shoulder rehabilitation (96%), pain (71%), and stiffness (92%) as reported by patients. Both pain scores and pain medication use decreased from the 1st to 8th postoperative telehealth session ( P < 0.01). Nearly all (93%) patients recommended SSS after shoulder surgery upon completing the SSS protocol. Conclusion: Postoperative management of shoulder surgery with SSS combined with telehealth results in a reduction in patient pain levels in the early postoperative period. Patients reported high levels of improvement with SSS in shoulder rehabilitation, pain, and stiffness. The overwhelming majority (93%) of patients recommended SSS for postoperative shoulder rehabilitation and SSS yielded high patient satisfaction scores. Elucidating the impact of SSS on clinical outcomes and function in comparison with traditional rehabilitation protocols is warranted. Clinical Relevance: SSS in combination with telehealth was tolerated well by patients and may represent an alternative or adjunct to traditional rehabilitation protocols.
Evaluation of the Anti-Inflammatory and Chondroprotective Effect of Celecoxib on CartilageEx Vivoand in a Rat Osteoarthritis Model
Authors: Haartmans Mirella J.J. , Timur Ufuk Tan , Emanuel Kaj S. , Caron Marjolein M.J. , Jeuken Ralph M. , Welting Tim J.M. , van Osch Gerjo J.V.M. , Heeren Ron M.A. , Cillero-Pastor Berta , Emans Pieter J. 
Published: August 2022

ObjectiveThe potential chondroprotective effect of celecoxib, a nonsteroidal anti-inflammatory drug and selective cyclooxygenase-2 inhibitor used to reduce pain and inflammation in knee osteoarthritis patients, is disputed. This study aimed at investigating the chondroprotective effects of celecoxib on (1) human articular cartilage explants and (2) in an in vivo osteoarthritis rat model.DesignArticular cartilage explants from 16 osteoarthritis patients were cultured for 24 hours with celecoxib or vehicle. Secreted prostaglandins (prostaglandin E2, prostaglandin F2α, prostaglandin D2) and thromboxane B2 (TXB2) concentrations were determined in medium by ELISA, and protein regulation was measured with label-free proteomics. Cartilage samples from 7 of these patients were analyzed for gene expression using real-time quantitative polymerase chain reaction. To investigate the chondroprotective effect of celecoxib in vivo, 14 rats received an intra-articular injection of celecoxib or 0.9% NaCl after osteoarthritis induction by anterior cruciate ligament transection and partial medial meniscectomy (ACLT/pMMx model). Histopathological scoring was used to evaluate osteoarthritis severity 12 weeks after injection.ResultsSecretion of prostaglandins, target of Nesh-SH3 (ABI3BP), and osteonectin proteins decreased, whereas tissue inhibitor of metalloproteinase 2 (TIMP-2) increased significantly after celecoxib treatment in the human ( ex vivo) explant culture. Gene expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5 (ADAMTS4/5) and metalloproteinase 13 (MMP13) was significantly reduced after celecoxib treatment in human cartilage explants. Cartilage degeneration was reduced significantly in an in vivo osteoarthritis knee rat model.ConclusionsOur data demonstrated that celecoxib acts chondroprotective on cartilage ex vivo and a single intra-articular bolus injection has a chondroprotective effect in vivo.
Outcome of spongioplasty alone as second layer of tubularised incised plate urethroplasty in patients with hypospadias
Authors: Maheshwari Mudit , Gite Venkat Arjun , Agrawal Mayank , Sankapal Prakash , Shaw Vivek , Sharma Shashank , Dias Sabby 
Published: August 2022

Abstract
Background
Spongioplasty alone or in combination with local tissue flaps can be used as a second layer for the prevention of complications of tubularised incised plate urethroplasty (TIPU) of hypospadias repair. It can be used when wide urethral plate and well-developed robust spongiosum are present. This study aims to review the success rate and complications of TIPU performed utilising spongioplasty alone as a second layer in Type 3 well-developed robust spongiosum.

Methods
This is a retrospective observational study conducted between January 2015 and December 2019 at a tertiary care centre. A total of 21 patients aged 4–15.4 years with primary hypospadias having a Type 3 well-developed robust spongiosum, Glans score ≤ 2, Meatal score ≤ 4, and Shaft score ≤ 3 underwent TIPU using spongioplasty alone as a second layer. The hospital stay ranged from 10 to 14 days and follow-up from 12 to 36 months.

Results
Hypospadias was distal in 12 (57.1%), mid in 5 (23.8%), and proximal penile in 4 (19.1%) patients. The mean Glans Meatus Shaft score was 6.1 (G = 1.25, M = 2.95, S = 1.9) with a range of 3–9. An early post-operative complication of preputial oedema and bladder spasm developed in 1 (4.7%) patient each. Meatal stenosis developed in 1 (4.7%) patient. None developed urethrocutaneous fistula. At 3 months all patients had good urinary flow (> 15 ml/s) and good cosmesis. All the patients/parents (in case of minors) were satisfied with the result.

Conclusion
Spongioplasty alone as the second layer after TIPU for primary penile hypospadias in patients with well-developed robust spongiosal tissue is associated with minimal, easily manageable complications.
Collagen-induced assembly of adenosine monophosphate-modified gold nanoparticles for photothermal cancer therapy
Authors: Qu Xinyu , Chen Yixing , Cai Zhuyun , Zhao Xinyu , Zeng Hua , Liu Xiaohao , Tan Shuo , Lu Bingqiang , Gao Rui , Chen Feng 
Published: August 2022

Abstract
Background
Photothermal therapy (PTT) has become an attractive approach for cancer treatment due to its merits of minimal invasiveness, location selectivity, and suitability for various cancer types. In PTT, photosensitizers are usually adopted to convert light to heat at tumor site, thereby generating heat-induced necroptosis or apoptosis. Therefore, the performance of photosensitizer (e.g., photothermal conversion efficiency (PCE), surface property, tumor accumulation and retention, etc.) determines the clinical manifestation of PTT. Currently, the poor tumor retention and potential long-term toxicity are two main obstacles for developing efficient photosensitizers. To address these issues, we have developed an in vivo tumor microenvironment stimuli-responsive self-assembled photosensitizer, which consists of a biomolecule, adenosine monophosphate (AMP) modified gold nanoparticles (AAu NPs), to enhance the accumulation and retention within tumor tissue for efficient PTT.

Results
The obtained AAu NPs with a hydrodynamic diameter of 9.12 ± 0.82 nm have excellent colloidal stability in aqueous solution. No sediments can be observed in the AAu NPs aqueous phase even after several months. The temperature of AAu aqueous suspension is elevated to 53.0 ℃ within 8 min at a low particle concentration of 80 μg/mL. A high PCE of 62.8% is obtained for AAu NPs based on the temperature change curves. The near-infrared (NIR) absorption and PCE of AAu NPs are enhanced compared to the surfactant-free Au NPs, enabling excellent photothermal cell-killing in vitro. When the AAu NPs arrive at the tumor tissue, they quickly form large aggregates via a collagen-induced assembly, leading to enhanced NIR absorption and improved tumor accumulation and retention, which enables a high PTT efficacy in vivo at a low photosensitizer dose of 40 μg and a low laser power density of 1.91 W/cm2.

Conclusions
A collagen-induced self-assembled gold photosensitizer for efficient PTT has been synthesized based on a biomolecule, AMP modification method. The synthesized AAu NPs with high PTT efficacy, superior biosafety and fast excretion from the body is an effective therapeutic agent in photothermal cancer therapy.
Improved prediction of gene expression through integrating cell signalling models with machine learning
Authors: Al taweraqi Nada , King Ross D. 
Published: August 2022

Abstract
Background
A key problem in bioinformatics is that of predicting gene expression levels. There are two broad approaches: use of mechanistic models that aim to directly simulate the underlying biology, and use of machine learning (ML) to empirically predict expression levels from descriptors of the experiments. There are advantages and disadvantages to both approaches: mechanistic models more directly reflect the underlying biological causation, but do not directly utilize the available empirical data; while ML methods do not fully utilize existing biological knowledge.

Results
Here, we investigate overcoming these disadvantages by integrating mechanistic cell signalling models with ML. Our approach to integration is to augment ML with similarity features (attributes) computed from cell signalling models. Seven sets of different similarity feature were generated using graph theory. Each set of features was in turn used to learn multi-target regression models. All the features have significantly improved accuracy over the baseline model - without the similarity features. Finally, the seven multi-target regression models were stacked together to form an overall prediction model that was significantly better than the baseline on 95% of genes on an independent test set. The similarity features enable this stacking model to provide interpretable knowledge about cancer, e.g. the role of ERBB3 in the MCF7 breast cancer cell line.

Conclusion
Integrating mechanistic models as graphs helps to both improve the predictive results of machine learning models, and to provide biological knowledge about genes that can help in building state-of-the-art mechanistic models.
Effects of an inhibitor of the SHH signaling pathway on endometrial cells of patients with endometriosis
Authors: He Yanan , Wang J. , Jiang Xinyan , Gao Jianhua , Cheng Yan , Liang Tian , Zhou Jun , Sun Liyuan , Zhang Guangmei 
Published: August 2022

Abstract
Background
Endometriosis is one of the most common gynecological diseases, and seriously reduces the quality of life of patients. However, the pathogenesis of this disease is unclear. Therefore, more studies are needed to elucidate its pathogenesis. Our previous publication found that the Sonic Hedgehog (SHH) signaling pathway was activated in endometriosis. This study tested whether SHH signaling in endometrial stromal cells (ESCs) was critical for the pathogenesis of endometriosis.

Methods
To examine the effect of inhibiting the SHH signaling pathway on endometriosis, we first isolated ESCs from eutopic endometrial tissues of patients with or without endometriosis and identified the extracted cells by morphological observation and immunofluorescence. Then, we treated ESCs with the GLI inhibitor GANT61 and used CCK-8, wound healing and invasion assays to detect cell activities, such as proliferation, invasion and metastasis. Furthermore, we detected the expression of key proteins and proliferation markers of the SHH signaling pathway in the lesions of nude mice using immunochemistry.

Results
We demonstrated that higher concentrations of GANT61 decreased the proliferation rate and migration distance of ESCs. We observed that GANT61 inhibited the invasion of ESCs. In addition, blockage of the SHH signaling pathway significantly reduced cell proliferation in vitro.

Conclusions
Our study suggested that inhibition of the SHH pathway is involved in cell proliferation and invasive growth in the pathogenesis of endometriosis.
Genome-wide identification and expression analysis of the cucumber PP2C gene family
Authors: Zhang Guobin , Zhang Zeyu , Luo Shilei , Li Xia , Lyu Jian , Liu Zeci , Wan Zilong , Yu Jihua 
Published: August 2022

Abstract
Background
Type 2C protein phosphatase (PP2C) is a negative regulator of ABA signaling pathway, which plays important roles in stress signal transduction in plants. However, little research on the PP2C genes family of cucumber (Cucumis sativus L.), as an important economic vegetable, has been conducted.

Results
This study conducted a genome-wide investigation of the CsPP2C gene family. Through bioinformatics analysis, 56 CsPP2C genes were identified in cucumber. Based on phylogenetic analysis, the PP2C genes of cucumber and Arabidopsis were divided into 13 groups. Gene structure and conserved motif analysis showed that CsPP2C genes in the same group had similar gene structure and conserved domains. Collinearity analysis showed that segmental duplication events played a key role in the expansion of the cucumber PP2C genes family. In addition, the expression of CsPP2Cs under different abiotic treatments was analyzed by qRT-PCR. The results reveal that CsPP2C family genes showed different expression patterns under ABA, drought, salt, and cold treatment, and that CsPP2C3, 11–17, 23, 45, 54 and 55 responded significantly to the four stresses. By predicting the cis-elements in the promoter, we found that all CsPP2C members contained ABA response elements and drought response elements. Additionally, the expression patterns of CsPP2C genes were specific in different tissues.

Conclusions
The results of this study provide a reference for the genome-wide identification of the PP2C gene family in other species and provide a basis for future studies on the function of PP2C genes in cucumber.