bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening of CXC chemokines in the microenvironment of ovarian cancer and the biological function of CXCL10
Authors: Li Weiyuan , Ma Ji-Ao , Sheng Xun , Xiao Chunjie 
Published: November 2021

Abstract
Background
This study aims to screen and identify the biological functions and prognostic value of CXC chemokines in ovarian cancer (OC) through bioinformatics and molecular biology methods, and to provide data support for the selection of biomarkers and prognostic analysis of OC.

Methods
In this study, GEO, ONCOMINE, GEPIA, cBioPortal, GeneMANIA, Metascape, STRING, TRRUST, and TIMER databases were used to study CXC chemokines. Angiogenesis and T cell killing assay were used to detect the effect of CXCL10 on tumor cell immunity and angiogenesis. Real-time quantitative PCR (qRT-PCR), immunoblotting, and ectopic tumor formation experiments were used to verify the effect of CXCL10 on ovarian cancer tumors.

Results
We found that CXCL1, CXCL10, CXCL11, CXCL13, and CXCL14 were significantly upregulated in OC samples compared with normal tissues. Our data showed that there was a relationship between the expression of CXC chemokines and the infiltration of six types of immune cells significant correlation. In vitro assay confirmed that overexpression of CXCL10 could enhance the killing effect of T cells and inhibit angiogenesis. Further in vivo assay had shown that CXCL10 could affect the progression of ovarian cancer by increasing the expression of cytotoxic T cells and inhibiting angiogenesis.

Conclusion
In conclusion, we hope that our data will provide new insights into the development of immunotherapy and the selection of prognostic markers for patients with OC.
Monitoring the tissue perfusion during hemorrhagic shock and resuscitation: tissue-to-arterial carbon dioxide partial pressure gradient in a pig model
Authors: Endo Yusuke , Hirokawa Taku , Miyasho Taku , Takegawa Ryosuke , Shinozaki Koichiro , Rolston Daniel M. , Becker Lance B. , Hayashida Kei 
Published: November 2021

Abstract
Background
Despite much evidence supporting the monitoring of the divergence of transcutaneous partial pressure of carbon dioxide (tcPCO2) from arterial partial pressure carbon dioxide (artPCO2) as an indicator of the shock status, data are limited on the relationships of the gradient between tcPCO2 and artPCO2 (tc-artPCO2) with the systemic oxygen metabolism and hemodynamic parameters. Our study aimed to test the hypothesis that tc-artPCO2 can detect inadequate tissue perfusion during hemorrhagic shock and resuscitation.

Methods
This prospective animal study was performed using female pigs at a university-based experimental laboratory. Progressive massive hemorrhagic shock was induced in mechanically ventilated pigs by stepwise blood withdrawal. All animals were then resuscitated by transfusing the stored blood in stages. A transcutaneous monitor was attached to their ears to measure tcPCO2. A pulmonary artery catheter (PAC) and pulse index continuous cardiac output (PiCCO) were used to monitor cardiac output (CO) and several hemodynamic parameters. The relationships of tc-artPCO2 with the study parameters and systemic oxygen delivery (DO2) were analyzed.

Results
Hemorrhage and blood transfusion precisely impacted hemodynamic and laboratory data as expected. The tc-artPCO2 level markedly increased as CO decreased. There were significant correlations of tc-artPCO2 with DO2 and COs (DO2: r = − 0.83, CO by PAC: r = − 0.79; CO by PiCCO: r = − 0.74; all P < 0.0001). The critical level of oxygen delivery (DO2crit) was 11.72 mL/kg/min according to transcutaneous partial pressure of oxygen (threshold of 30 mmHg). Receiver operating characteristic curve analyses revealed that the value of tc-artPCO2 for discrimination of DO2crit was highest with an area under the curve (AUC) of 0.94, followed by shock index (AUC = 0.78; P < 0.04 vs tc-artPCO2), and lactate (AUC = 0.65; P < 0.001 vs tc-artPCO2).

Conclusions
Our observations suggest the less-invasive tc-artPCO2 monitoring can sensitively detect inadequate systemic oxygen supply during hemorrhagic shock. Further evaluations are required in different forms of shock in other large animal models and in humans to assess its usefulness, safety, and ability to predict outcomes in critical illnesses.
Serotype-dependent recombinant adeno-associated vector (AAV) infection of Epstein–Barr virus-positive B-cells, towards recombinant AAV-based therapy of focal EBV + lymphoproliferative disorders
Authors: Ahmadi Elham , Ravanshad Mehrdad , Xie Jun , Panigrahi Rajesh , Jubbal Sandeep S. , Guru Santosh Kumar , Guangping Gao , Ziyaeyan Mazyar , Fingeroth Joyce 
Published: November 2021

Abstract
Background
B-cell proliferative disorders, such as post-transplant lymphoproliferative disease (PTLD), are increased among persons afflicted by T-cell compromise. Most are Epstein–Barr virus (EBV) + and can first present with a focal lesion. Direct introduction of oncolytic viruses into localized tumors provides theoretical advantages over chemotherapy, immunotherapy and radiation therapy by reducing systemic toxicity. Despite extensive study as a vehicle for gene therapy, adeno-associated viruses (AAV) have rarely been applied to human cancer research due to technical and theoretical obstacles. Moreover, human B-cells have historically been described as resistant to AAV infection. Nonetheless, advances using different recombinant (r)AAV serotypes with unique tropisms to deliver cytotoxic therapy suggested a localized anti-tumor approach was feasible.

Methods
As a prelude to the development of a therapeutic vehicle, the ability of fifteen distinct EGFP-bearing rAAV serotypes to transduce human B-cells, including primary, immortalized, and B-cell tumor lines ± EBV was assessed by confocal microscopy, flow cytometry and subsequently cell viability assay.

Results
Rank order analysis revealed augmented transduction by rAAV6.2 and closely related virions. EBV infection of EBV-negative B-cell tumor lines and EBV immortalization of primary B-cells increased susceptibility to rAAV6.2 transduction. As a proof of concept, transduction by rAAV6.2 encoding herpes simplex virus type 1 (HSV1)-thymidine kinase (TK) eliminated TK-negative rhabdomyosarcoma cells and diminished viability of transduced B-cell lines upon incubation with ganciclovir.

Conclusions
rAAV serotypes differentially transduce human B-cell lines reversing the dogma that human B-cells are refractory to AAV infection. EBV + B-cells display increased susceptibility to rAAV6.2 infection, uncovering a new method for improved nucleic acid transfer into transfection-resistant B-cell lines. The introduction of a functional suicide gene into the rAAV6.2 genome identifies a candidate vector for the development of rAAV-based oncolytic therapy targeting focal EBV-bearing B-lymphoproliferative disorders.
Explore association of genes in PDL1/PD1 pathway to radiotherapy survival benefit based on interaction model strategy
Authors: Shen Junjie , Liu Jingfang , Li Huijun , Bai Lu , Du Zixuan , Geng Ruirui , Cao Jianping , Sun Peng , Tang Zaixiang 
Published: November 2021

Abstract
Purpose
To explore the association of genes in “PD-L1 expression and PD-1 check point pathway in cancer” to radiotherapy survival benefit.

Methods and materials
Gene expression data and clinical information of cancers were downloaded from TCGA. Radiotherapy survival benefit was defined based on interaction model. Fast backward multivariate Cox regression was performed using stacking multiple interpolation data to identify radio-sensitive (RS) genes.

Results
Among the 73 genes in PD-L1/PD-1 pathway, we identified 24 RS genes in BRCA data set, 25 RS genes in STAD data set and 20 RS genes in HNSC data set, with some crossover genes. Theoretically, there are two types of RS genes. The expression level of Type I RS genes did not affect patients' overall survival (OS), but when receiving radiotherapy, patients with different expression level of Type I RS genes had varied survival benefit. Oppositely, Type II RS genes affected patients' OS. And when receiving radiotherapy, those with lower OS could benefit a lot. Type II RS genes in BRCA had strong positive correlation and closely biological interactions. When performing cluster analysis using these related Type II RS genes, patients could be divided into RS group and non-RS group in BRCA and METABRIC data sets.

Conclusions
Our study explored potential radio-sensitive biomarkers of several main cancer types in an important tumor immune checkpoint pathway and revealed a strong association between this pathway and radiotherapy survival benefit. New types of RS genes could be identified based on expanded definition to RS genes.
A 24-month retrospective update: follow-up hospitalization charges and readmissions in US lumbar fusion surgeries using a cellular bone allograft (CBA) versus recombinant human bone morphogenetic protein-2 (rhBMP-2)
Authors: Wetzell Bradley , McLean Julie B. , Dorsch Kimberly , Moore Mark A. 
Published: November 2021

Abstract
Background
The objectives of this study were to build upon previously-reported 12-month findings by retrospectively comparing 24-month follow-up hospitalization charges and potentially-relevant readmissions in US lumbar fusion surgeries that employed either recombinant human bone morphogenetic protein-2 (rhBMP-2) or a cellular bone allograft comprised of viable lineage-committed bone cells (V-CBA) via a nationwide healthcare system database.

Methods
A total of 16,172 patients underwent lumbar fusion surgery using V-CBA or rhBMP-2 in the original study, of whom 3,792 patients (23.4%) were identified in the current study with all-cause readmissions during the 24-month follow-up period. Confounding baseline patient, procedure, and hospital characteristics found in the original study were used to adjust multivariate regression models comparing differences in 24-month follow-up hospitalization charges (in 2020 US dollars) and lengths of stay (LOS; in days) between the groups. Differences in potentially-relevant follow-up readmissions were also compared, and all analyses were repeated in the subset of patients who only received treatment at a single level of the spine.

Results
The adjusted cumulative mean 24-month follow-up hospitalization charges in the full cohort were significantly lower in the V-CBA group ($99,087) versus the rhBMP-2 group ($124,389; P < 0.0001), and this pattern remained in the single-level cohort (V-CBA = $104,906 vs rhBMP-2 = $125,311; P = 0.0006). There were no differences between groups in adjusted cumulative mean LOS in either cohort. Differences in the rates of follow-up readmissions aligned with baseline comorbidities originally reported for the initial procedure. Subsequent lumbar fusion rates were significantly lower for V-CBA patients in the full cohort (10.12% vs 12.00%; P = 0.0002) and similar between groups in the single-level cohort, in spite of V-CBA patients having significantly higher rates of baseline comorbidities that could negatively impact clinical outcomes, including bony fusion.

Conclusions
The results of this study suggest that use of V-CBA for lumbar fusion surgeries performed in the US is associated with substantially lower 24-month follow-up hospitalization charges versus rhBMP-2, with both exhibiting similar rates of subsequent lumbar fusion procedures and potentially-relevant readmissions.
Occult pleural dissemination detected intraoperatively in patients with thymic tumors: a retrospective analysis
Authors: Song Zuodong , Zhu Shu , Chen Tangbing , Zhao Weigang 
Published: November 2021

Abstract
Background
Thymic tumors usually present with adjacent organ invasion or pleural dissemination, but very few studies have reported on occult pleural dissemination detected intraoperatively. This study aimed to investigate the risk factors that can predict pleural dissemination preoperatively.

Methods
Consecutive patients with thymic tumors who underwent surgery from January 2010 to January 2017 were reviewed. Only patients without pleural dissemination detected preoperatively were included in this study. Demographic, clinical, pathological, and survival data were collected for statistical analysis. Further analyses were performed to find the risk factors of occult pleural dissemination.

Results
A total of 352 patients with thymic tumors were included in this study. Seven patients had pleural dissemination detected intraoperatively. All pleural dissemination cases were in clinical Masaoka-Koga stage III, and most underwent the video-assisted thoracoscopic surgery (VATS) approach (or VATS exploration). Univariate analysis showed that positive squamous cell carcinoma (SCC) antigen was the only predictor of pleural dissemination (p = 0.009). Tiny nodules close to the diaphragm were detected in the computed tomography scans of 1 case after reviewing the imaging data. Tumor recurrence occurred in 5 patients during follow-up. The disease-free survival rates were better in patients with a solitary nodule than those with multiple nodules (p = 0.019). No significant difference was detected in terms of disease-free survival rates between SCC antigen positive and SCC antigen negative patients.

Conclusions
Positive SCC antigen was the only detected risk factor for predicting pleural dissemination in thymic tumors preoperatively in this study. The VATS approach (including VATS exploration) is suggested for patients with clinical Masaoka-Koga stage III and SCC antigen positive thymic tumors, according to our experience.
Extranodal natural killer/T-cell lymphoma of the breast: a retrospective clinicopathological analysis of a consecutive 11-year case series
Authors: Liu Wei , Chen Zihang , Li Fanglan , Zhang Wenyan , Liu Weiping , Zhao Sha 
Published: November 2021

Abstract
Background
Extranodal NK/T-cell lymphoma of the breast (ENKTL-Breast) is rarely detected in clinical practice, and its clinicopathological features remain unclear.

Results
A consecutive 11-year (2010–2020) ENKTL-Breast case series was retrospectively analyzed. Eight cases of ENKTL-Breast were selected, with three primary and five secondary lesions, accounting for 3.5% (8/228) of all breast lymphomas. All patients were female with a median age of 46 years. Lesions presented as solid breast masses (8/8, 100%) and were usually located in the upper outer quadrant of the breast (7/8, 87.5%). B-symptoms were observed in seven (7/8, 87.5%) cases. Two primary ENKTL-Breast cases showed concomitant diseases (IgA nephropathy and chronic active hepatitis B). Histological and immunohistochemical features of ENKTL-Breast were similar to those of ENKTL at other sites. T-cell receptor rearrangement revealed clonality in all examined primary cases (2/2, 100%), but only in one secondary case (1/5, 20%). The disease progressed rapidly in two primary cases and both patients died within 3 and 9 months. For secondary cases, the disease manifested as a disseminated disease, with a median survival time of 6 months.

Conclusions
Our data suggested that ENKTL-Breast clinically mimics breast cancer to some extent, though B-symptoms might serve as a distinguishing factor. ENKTL-Breast is highly aggressive and patients with this disease exhibit a short survival time. Primary ENKTL-Breast tends to originate from activated cytotoxic T-cells, and immune-related diseases may be involved in its pathogenesis and development.
Identification and treatment of primary cervical gestational trophoblastic neoplasia: a retrospective study of 13 patients and literature review
Authors: Wang Xiaoyu , Yang Junjun , Wan Xirun , Feng Fengzhi , Zhao Jun , Ren Tong , Xiang Yang 
Published: November 2021

Abstract
Background
Primary cervical gestational trophoblastic neoplasias (GTNs) are extremely rare ectopic GTNs. Such lesions are difficult to diagnose clinically because of their rarity, with abnormal vaginal bleeding of a non-specific cause being the most common symptom. To that end, this retrospective study aimed to identify the clinical characteristics of cervical GTN and to explore diagnostic and therapeutic strategies.

Results
Thirteen patients diagnosed with primary cervical GTN at the Department of Gynecology, Peking Union Medical College Hospital, Beijing, China, between June 1, 1988 and May 31, 2020 were included in the study. All patients had irregular vaginal bleeding, including six who presented with massive bleeding. Seven patients (53.8%) were initially misdiagnosed with a cervical pregnancy. All patients received chemotherapy; 11 (84.6%) also underwent hysterectomy because of chemoresistant lesions or uncontrolled bleeding. All patients achieved complete remission; however, two women (15.4%) experienced a relapse during the median follow-up period of 35 months. A comprehensive review of English-language literature published between 1980 and 2020 identified 22 case reports encompassing 27 patients. The definitive diagnosis was achieved via pathology in 26 of them (96.3%), and hysterectomy was performed in 21 (77.8%).

Conclusions
Owing to its rarity and nonspecific symptoms, the diagnosis of primary cervical GTN is challenging and often relies on pathology. The combination of chemotherapy and hysterectomy is the main therapeutic strategy for this disease.
In vitro functional rescue by ivacaftor of an ABCB11 variant involved in PFIC2 and intrahepatic cholestasis of pregnancy
Authors: Mareux Elodie , Lapalus Martine , Ben-Saad Amel , Callebaut Isabelle , Falguières Thomas , Gonzales Emmanuel , Jacquemin Emmanuel 
Published: November 2021

Abstract
Background
ABCB11 variations are responsible for a spectrum of rare liver diseases, including progressive familial intrahepatic cholestasis type 2 (PFIC2) and intrahepatic cholestasis of pregnancy (ICP). Current medical treatment of these conditions mostly relies on ursodeoxycholic acid with limited efficacy. We report on the in vitro study of the p.A257V missense variant of ABCB11 identified in a PFIC2 patient and in her mother who experienced ICP.

Results
The Ala257 residue is located outside the ATP-binding site of ABCB11. We show that the p.A257V variant of ABCB11 is correctly expressed at the canalicular membrane of HepG2 cells but that its function significantly decreased when studied in MDCK cells. This functional defect can be fully rescued by Ivacaftor.

Conclusion
Ivacaftor could be considered as a new pharmacological tool able to respond to an unmet medical need for patients with ICP and PFIC2 due to ABCB11 variations affecting ABCB11 function, even when the residue involved is not located in an ATP-binding site of ABCB11.
An exploratory study of the barriers and facilitators to the implementation of community health worker programmes in conflict-affected South Sudan
Authors: Lutwama George William , Kok Maryse , Jacobs Eelco 
Published: November 2021

Abstract
Background
Community health workers (CHWs) are crucial for increasing access to health services to communities. Due to decades of conflict and under-funding, access to health care in South Sudan remains severely limited. To improve equitable access to healthcare, the government has introduced “the Boma Health Initiative (BHI)”, a strategy to harmonise community health programmes across the country. In order to scale up the BHI, it is necessary to assess the recent CHW programmes and draw lessons for future implementation. This study aimed to explore the characteristics, barriers, and facilitators to the implementation of CHW interventions in South Sudan between 2011 and 2019.

Methods
The study used a qualitative approach drawing from 26 key informant interviews and a scoping review of 21 Health Pooled Fund (HPF) programme reports from October 2016 to June 2018 and policy documents from 2011 to 2019. The results were thematically analysed based on a conceptual framework on factors influencing the performance of CHWs.

Results
Funding of CHW programmes has come from international donors, channelled through non-governmental organisations (NGOs) that have implemented a variety of CHW programmes. Communities have been participating in the selection of voluntary CHWs, intervention areas, and occasionally in the supervision of activities performed by CHWs. The coordination mechanisms among stakeholders have been weak, leading to wastage and duplication of resources. Although training of CHWs is done, training duration was short, and refresher-trainings were rare. There were and still are disparities in the type of incentives provided to CHWs. Monitoring and supportive supervision activities have been insufficient; drug misuse and stock-outs were common.

Conclusion
Despite their challenges, CHW programmes can be implemented in conflict-affected South Sudan if the local human capital is leveraged and engaged by NGOs as implementing partners. Robust coordination efforts are required to build synergies among stakeholders for the effective implementation of the BHI strategy.
LncRNA Snhg6 regulates the differentiation of MDSCs by regulating the ubiquitination of EZH2
Authors: Lu Wei , Cao Fenghua , Feng Lili , Song Ge , Chang Yi , Chu Ying , Chen Zhihong , Shen Bo , Xu Huaxi , Wang Shengjun , Ma Jie 
Published: November 2021

AbstractMyeloid-derived suppressor cells (MDSCs) are derived from bone marrow progenitor cells commonly, which is a heterogeneous cell group composed of immature granulocytes, dendritic cells, macrophages and early undifferentiated bone marrow precursor cells. Its differentiation and immunosuppressive function are regulated by complex network signals, but the specific regulation mechanisms are not yet fully understood. In this study, we found that in mouse of Lewis lung cancer xenograft, long non-coding RNA Snhg6 (lncRNA Snhg6) was highly expressed in tumor-derived MDSCs compared with spleen-derived MDSCs. LncRNA Snhg6 facilitated the differentiation of CD11b+ Ly6G− Ly6Chigh monocytic MDSCs (Mo-MDSCs) rather than CD11b+ Ly6G+ Ly6Clow polymorphonuclear MDSCs (PMN-MDSCs), but did not affect the immunosuppressive function of MDSCs. Notably, lncRNA Snhg6 could inhibit the expression of EZH2 by ubiquitination pathway at protein level rather than mRNA level during the differentiation of mouse bone marrow cells into MDSCs in vitro. EZH2 may be an important factor in the regulation of lncRNA Snhg6 to promote the differentiation of Mo-MDSCs. So what we found may provide new ideas and targets for anti-tumor immunotherapy targeting MDSCs.