bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR-502-5p affects gastric cancer progression by targeting PD-L1
Authors: You Wendao , Liu Xiaoyu , Yu Yang , Chen Chen , Xiong Yujia , Liu Yiting , Sun Yibin , Tan Chenhuan , Zhang Hanshuo , Wang Yadong , Li Rui 
Published: August 2020

Abstract
Background
Studies have shown that miR-502-5p functions as a tumor suppressor and is associated with tumor growth and metastasis. This study intends to uncover the potential mechanism of miR-502-5p functioning as a tumor suppressor in gastric cancer.

Methods
Expression levels of miR-502-5p and PD-L1 were measured by using qRT-PCR. Cell proliferation abilities were examined by EDU incorporation assay. Cell migration, invasion and cell cycle analysis of cells were determined by transwell assay, transwell-matrigel assay and flow cytometry, respectively. The relationship between miR-502-5p expression and the overall survival of xenograft tumor mice was statistically analyzed. Bioinformatics analysis and luciferase reporter assays were applied to analyze the relationship between miR-502-5p and CD40, STAT3 or PD-L1. Expressions of CD40, STAT3 and PD-L1 at protein level were detected by western blot.

Results
The results showed that miR-502-5p was significantly downregulated in gastric cancer tumor tissues compared with adjacent normal tissues. Overexpression of miR-502-5p significantly attenuated the proliferation, migration/invasion and induced the G1 phase arrest of gastric cancer cells. Consistently, miR-502-5p suppressed tumor growth and metastasis in vivo. Mechanically, we demonstrated that miR-502-5p had inhibited the malignant behaviour of gastric cancer by down-regulating PD-L1 expression at transcriptional level and post-transcriptional levels.

Conclusions
These findings suggest that miR-502-5p acts as a tumor suppressor in gastric cancer (GC). MiR-502-5p/PD-L1 may be a novel therapeutic target in GC treatment.
LncRNA KCNQ1OT1 sponges miR-15a to promote immune evasion and malignant progression of prostate cancer via up-regulating PD-L1
Authors: Chen Qi-Hua , Li Bo , Liu De-Guo , Zhang Biao , Yang Xian , Tu Ya-Ling 
Published: August 2020

AbstractBackgroundWe focused on the KCNQ1OT1/miR-15a/PD-L1 axis and explored its significance in regulating immune evasion and malignant behaviors of prostate cancer (PC) cells.MethodsThe expression levels of KCNQ1OT1, miR-15a, PD-L1, and CD8 in cells or tissues were examined by RT-qPCR, western blot or immunohistochemistry (IHC) assays. The direct regulations between KCNQ1OT1, miR-15a and PD-L1 were validated by luciferase reporter assay. PC cells were co-cultured with CD8+T cells to study the immune evasion. Proliferation, apoptosis, migration and invasion abilities were detected by MTT, flow cytometry, wound healing and Transwell assays, respectively. The cytotoxicity of CD8+T cells was determined by LDH cytotoxicity Kit. Epithelial–mesenchymal transition (EMT) and Ras/ERK signaling markers were evaluated by western blot.ResultsKCNQ1OT1, PD-L1 and CD8 were increased, while miR-15a was decreased in PC tissues. MiR-15a directly bound to the 3′-UTR of PD-L1 and inhibited the expression of PD-L1. Overexpressing miR-15a in PC cells was sufficient to promote cytotoxicity and proliferation, while inhibit apoptosis of CD8+T cells, and also suppressed viability, migration, invasion and EMT while promoted apoptosis of PC cells. The above anti-tumor effects of miR-15a were reversed by overexpressing PD-L1. KCNQ1OT1 sponged miR-15a and released its inhibition on PD-L1. Functionally, KCNQ1OT1 in PC cells was essential for suppressing the cytotoxicity of CD8+T cells and maintaining multiple malignant phenotypes of PC cells. The Ras/ERK signaling was suppressed after overexpressing miR-15a or knocking down KCNQ1OT1.ConclusionsLncRNA KCNQ1OT1 sponges miR-15a to promote immune evasion and malignant progression of PC via up-regulating PD-L1.
The challenges of COVID-19 in the Brazilian Amazonian communities and the importance of seroepidemiological surveillance studies
Authors: Vallinoto Antonio Carlos Rosário , da Silva Torres Maria Karoliny , Vallinoto Mariana Cayres , Cayres Vallinoto Izaura M. V. 
Published: August 2020

AbstractThe emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has alarmed the world with its high rate of transmission and the ability to cause severe and fatal disease. The impact of this pandemic may be even greater in populations where the absence of health services is a chronic aspect, as reported with populations living in the Brazilian Amazon. In this article, we address the perspective of possible impacts of the pandemic on these populations and the importance of conducting seroepidemiological surveillance studies.
Segmental artery clamping versus main renal artery clamping in nephron-sparing surgery: updated meta-analysis
Authors: Xu Jinhong , Xu Shuxiong , Yao Biao , Xu Run , Xu Yuangao , Sun Fa , Qiu Qian , Shi Hua 
Published: August 2020

AbstractObjectivesIschemia–reperfusion injury is harmful in partial nephrectomy (PN) in renal cell carcinoma. Choosing an appropriate surgical method is important to reduce ischemia–reperfusion injury. This study aimed to compare the effect of segmental artery clamping (SAC) and main renal artery clamping (MAC) on patients who underwent PN.MethodsStudies from January 2008 to November 2019 were identified by an electronic search of English and Chinese databases, including PubMed, Excerpt Medica Database, Cochrane Library, Wanfang, VIP, and Chinese National Knowledge Internet, without language restriction. Two reviewers were involved in the trial. The effects on operation time (OT), warm ischemia time (WIT), length of hospital stay (LOS), blood transfusion rate, postoperative complication rate, Clavien classification (≥ 3), and positive surgery margin (PSM) were evaluated using Stata software. Standardized mean difference (SMD, for continuous data) and pooled odds ratios (for count data) with 95% confidence interval (CI) were used as effect indicators.ResultsThirty-two studies were included. SAC decreased the 1-week (SMD = − 0.973; 95% CI = − 1.414, − 0.532;P= 0.000), 1-month (SMD = − 0.411; 95% CI = − 0.769, − 0.053;P= 0.025), and 3-month (affected kidney: SMD = − 0.914; 95% CI = − 1.662, − 0.617;P= 0.000) percentages of postoperative changes in renal function (estimated glomerular filtration rate) between the SAC and MAC groups. Sub-group analysis showed that the SAC group had longer OT (SMD = 0.562; 95% CI = 0.252, 0.871;P= 0.000) than the MAC group. However, no differences were observed in the OT, WIT, LOS, blood transfusion rate, postoperative complication rate, Clavien classification (≥ 3), and PSM between the two groups.ConclusionsSAC is superior to MAC in terms of short-term postoperative renal function recovery. The use of SAC or MAC depends on tumor size, location, surgical modality, and surgeon’s judgments.
Stage-dependent angiopoietin-Tie2 and nitric oxide signaling of erythrocytes in response to surgical trauma in head and neck cancer
Authors: Wu Hsiang-Ling , Chu You-Hsiang , Tai Ying-Hsuan , Tsou Mei-Yung , Wu Cheng-Hsien , Lo Wen-Liang , Tai Shyh-Kuan , Yeh Chun-Chang , Lu Chih-Cherng 
Published: August 2020

AbstractBackgroundAngiopoietin-Tie2 and nitric oxide pathway is crucial in tumor angiogenesis and closely correlates with tumor development, growth, and metastasis. This study aimed to investigate the angiopoietin-Tie2 and nitric oxide signaling of the erythrocyte membrane in response to surgical trauma in head and neck cancer.MethodsWe prospectively enrolled the patients with histology-proven head and neck squamous cell carcinoma undergoing surgical resection of primary tumors at the medical center between August and November 2019. We measured the preoperative and postoperative levels of angiopoietin-1, angiopoietin-2 in plasma using enzyme-linked immunosorbent assays, nitric oxide in plasma using nitrate/nitrite colorimetric assays, and Tie2 phosphorylation in erythrocyte membrane using Western blotting.ResultsThe plasma angiopoietin-1 was downregulated from the median 971.3 pg/mL (interquartile range [IQR] 532.1–1569.3) to 417.9 (IQR 270.5–597.3) after tumor resection (p= 0.0020). Conversely, the plasma angiopoietin-2 was enhanced from 1173.6 pg/mL (IQR 977.7–1450.2) to 2353.7 (IQR 1352.4–2954.3) after surgery (p= 0.0021), with a concomitant increase in plasma nitric oxide level from 7.73 μM (IQR 5.39–10.06) to 10.50 (IQR 7.65–14.18) after surgical resection (p= 0.0093). Subgroup analyses further showed the angiopoietin-Tie2 and nitric oxide signaling was significant only in stage III and IV cancer.ConclusionsThe dynamic change of angiopoietin-Tie2 signaling in the erythrocyte membrane along with the enhanced nitric oxide in plasma after tumor resection suggests erythrocytes play a significant role in modulating surgery-induced angiogenesis, which may provide a novel marker for cancer surveillance and control.
A single-center experience with pancreatic cystic neuroendocrine tumors
Authors: Khalil Ange , Ewald Jacques , Marchese Ugo , Autret Aurélie , Garnier Jonathan , Niccoli Patricia , Piana Gilles , Poizat Flora , Giovannini Marc , Delpero Jean-Robert , Turrini Olivier 
Published: August 2020

Abstract
Background
Pancreatic neuroendocrine tumors (PNET) are rare, with a significant malignant potential. This study aimed to determine outcomes of patients with resected PNETs according to the cystic component and confirm the accuracy of preoperative staging.

Methods
From 1997 to 2016, 106 patients underwent resection of PNETs, including 73 purely solid (S-PNETs, 69%), 21 mixed (M-PNETs, 20%), and 12 purely cystic lesions (C-PNETs, 11%). To ensure consistent comparisons of overall (OS) and disease-free (DFS) survival outcomes between the 3 groups, the patients were matched according to the World Health Organization (WHO) grade and tumor height.

Results
Overall, the rate of correlation between the preoperative and pathological diagnoses was low in the C-PNET group (33%, P = 0.03). None of the 24 patients (23%) with metastatic disease at the time of surgery were in the C-PNET group. Furthermore, significantly more parenchyma-sparing resections (P = 0.039) and fewer enlarged resections (P = 0.019) were achieved in the C-PNET group. C-PNET group had a significantly lower node invasion rate than the S-PNET and M-PNET groups (8% vs. 41% and 24%, P = 0.004). Although median OS was comparable in all 3 groups before (P = 0.3) and after (P = 0.18) matching, higher median DFS was observed in the C-PNET group than in the other groups after matching (P = 0.038).

Conclusion
C-PNET was associated with a better prognosis than PNET with a solid component. The results support a wait-and-see policy in cases wherein a reliable preoperative diagnosis remains challenging.
Establishment of a WHO Reference Reagent for anti-Mullerian hormone
Authors: Ferguson Jackie , Hockley Jason , Rigsby Peter , Burns Chris 
Published: August 2020

Abstract
Background
There is a need for a reference material to support the development and ensure the quality of immunoassays for human AMH. A batch of ampoules, coded 16/190, containing lyophilised recombinant AMH was evaluated in a WHO Collaborative Study. The aims of the study were to determine the AMH content in terms of the calibration of each immunoassay method, to predict long-term stability and to assess the suitability of the preparation to calibrate AMH immunoassays.

Methods
Study participants were asked to report the AMH content of specific dilutions of coded ampoules of 16/190 and a comparator preparation containing approximately half the AMH content. In each assay, participants also reported the AMH content of 22 patient samples to assess commutability. A robust all-laboratory geometric mean of the content estimates was determined using the laboratory geometric mean estimates. Commutability was assessed using a difference in bias approach. Stability was predicted by the measurement of thermally accelerated degradation samples.

Results
Seven laboratories performed twenty-one immunoassay method-platform combinations, sixteen of which provided data which met the validity criteria, giving a consensus geometric mean estimate of AMH content of 511 ng/ampoule (95% CI, 426–612, n = 16, GCV 42%) and a robust geometric mean of 489 ng/ampoule. By contrast, the GCV% for the all-laboratory geometric mean of the relative content estimates for the comparator sample to 16/190 was 12%. Commutability was assessed using 20 of the 22 representative patient samples. Of the valid assays, 16/190 was within the limits of acceptable commutability for 6 methods, partially commutable for a further 3 methods and non-commutable when measured by 7 methods. The preparation was predicted to be highly stable when stored at − 20 °C.

Conclusion
The majority of methods met the validity criteria. Content estimates showed a high between-method variability, yet assays exhibited a similar proportionality of response as demonstrated using the comparator sample. 16/190 was commutable in some but not all methods. On the basis of these results, it was agreed by the WHO Expert Committee on Biological Standardization to establish 16/190 as a WHO Reference Reagent for AMH with a content defined by consensus immunoassay of 489 ng/ampoule.
Lactobacillus sakei suppresses collagen-induced arthritis and modulates the differentiation of T helper 17 cells and regulatory B cells
Authors: Jhun Jooyeon , Min Hong Ki , Ryu Jaeyoon , Lee Seon-Yeong , Ryu Jun-Geol , Choi Jeong Won , Na Hyun Sik , Lee Seung Yoon , Jung Yunju , Park Sang-Jun , Park Myeong Soo , Kwon Bin , Ji Geun Eog , Cho Mi-La , Park Sung-Hwan 
Published: August 2020

Abstract
Background
To evaluate the immunomodulatory effect of Lactobacillus sakei in a mouse model of rheumatoid arthritis (RA) and in human immune cells.

Methods
We evaluated whether L. sakei reduced the severity of collagen-induced arthritis (CIA) and modulated interleukin (IL)-17 and IL-10 levels, as well as whether it affected the differentiation of CD4+ T cells and regulatory B cells. We evaluated osteoclastogenesis after culturing bone marrow-derived mononuclear cells with L. sakei.

Results
The differentiation of T helper 17 cells and the serum level of IL-17 were suppressed by L. sakei in both human peripheral blood mononuclear cells and mouse splenocytes. The serum level of IL-10 was significantly increased in the L. sakei-treated group, whereas the regulatory T cell population was unchanged. The population of regulatory B cells significantly increased the in L. sakei-treated group. Oral administration of L. sakei reduced the arthritis incidence and score in mice with CIA. Finally, osteoclastogenesis and the mRNA levels of osteoclast-related genes were suppressed in the L. sakei-treated group.

Conclusion
L. sakei exerted an anti-inflammatory effect in an animal model of RA, regulated Th17 and regulatory B cell differentiation, and suppressed osteoclastogenesis. Our findings suggest that L. sakei has therapeutic potential for RA.
Hemodynamics during the 10-minute NASA Lean Test: evidence of circulatory decompensation in a subset of ME/CFS patients
Authors: Lee Jihyun , Vernon Suzanne D. , Jeys Patricia , Ali Weam , Campos Andrea , Unutmaz Derya , Yellman Brayden , Bateman Lucinda 
Published: August 2020

Abstract
Background
Lightheadedness, fatigue, weakness, heart palpitations, cognitive dysfunction, muscle pain, and exercise intolerance are some of the symptoms of orthostatic intolerance (OI). There is substantial comorbidity of OI in ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome). The 10-minute NASA Lean Test (NLT) is a simple, point-of-care method that can aid ME/CFS diagnosis and guide management and treatment of OI. The objective of this study was to understand the hemodynamic changes that occur in ME/CFS patients during the 10-minute NLT.

Methods
A total of 150 ME/CFS patients and 75 age, gender and race matched healthy controls (HCs) were enrolled. We recruited 75 ME/CFS patients who had been sick for less than 4 years (< 4 ME/CFS) and 75 ME/CFS patients sick for more than 10 years (> 10 ME/CFS). The 10-minute NLT involves measurement of blood pressure and heart rate while resting supine and every minute for 10 min while standing with shoulder-blades on the wall for a relaxed stance. Spontaneously reported symptoms are recorded during the test. ANOVA and regression analysis were used to test for differences and relationships in hemodynamics, symptoms and upright activity between groups.

Results
At least 5 min of the 10-minute NLT were required to detect hemodynamic changes. The < 4 ME/CFS group had significantly higher heart rate and abnormally narrowed pulse pressure compared to > 10 ME/CFS and HCs. The < 4 ME/CFS group experienced significantly more OI symptoms compared to > 10 ME/CFS and HCs. The circulatory decompensation observed in the < 4 ME/CFS group was not related to age or medication use.

Conclusions
Circulatory decompensation characterized by increased heart rate and abnormally narrow pulse pressure was identified in a subgroup of ME/CFS patients who have been sick for < 4 years. This suggests inadequate ventricular filling from low venous pressure. The 10-minute NLT can be used to diagnose and treat the circulatory decompensation in this newly recognized subgroup of ME/CFS patients. The > 10 ME/CFS group had less pronounced hemodynamic changes during the NLT possibly from adaptation and compensation that occurs over time. The 10-minute NLT is a simple and clinically useful point-of-care method that can be used for early diagnosis of ME/CFS and help guide OI treatment.
Cancer patients and coronavirus disease 2019: evidence in context
Authors: Barba Maddalena , Krasniqi Eriseld , Ciliberto Gennaro , Vici Patrizia 
Published: August 2020

AbstractIn the rapidly evolving coronavirus disease 2019 (COVID-19) outbreak, inherent literature has been increasing at an impressive rate. Such a dynamic scenario imposes the necessity to define a new framework for cancer care. The first emerging evidence has transmitted contrasting messages with regards to cancer care management. Some authors have hypothesized an increased infection risk for cancer patients, with a more severe disease, requiring a reorganization of health care system that could disrupt an established high quality cancer care routine in many developed countries. Other authors have attempted to interpret data related to cancer patients by better defining their “active status”. We herein present our point of view in the light of current evidence and based on the experience matured at our cancer institute in managing cancer patients during the COVID-19 pandemic. Our core idea is that “active cancer” may be considered a proxy of more recent exposure to diagnostic or therapeutic procedures, and the frequency of access to health care facilities can be predicted as a function of the severity of cancer symptoms. Hence, COVID-19 screening program and the adjustment of cancer care provision in a cancer institutions should be led by this risk model, while awaiting new evidence.
A novel rabbit derived anti-HER2 antibody with pronounced therapeutic effectiveness on HER2-positive breast cancer cells in vitro and in humanized tumor mice (HTM)
Authors: Wege Anja Kathrin , Kirchhammer Nicole , Kazandjian Linda Veronique , Prassl Sandra , Brandt Michael , Piendl Gerhard , Ortmann Olaf , Fischer Stephan , Brockhoff Gero 
Published: August 2020

AbstractBackgroundAntibody based cancer therapies have achieved convincing success rates combining enhanced tumor specificity and reduced side effects in patients. Trastuzumab that targets the human epidermal growth factor related receptor 2 (HER2) is one of the greatest success stories in this field. For decades, trastuzumab based treatment regimens are significantly improving the prognosis of HER2-positive breast cancer patients both in the metastatic and the (neo-) adjuvant setting. Nevertheless, ≥ 50% of trastuzumab treated patients experiencede-novoor acquired resistance. Therefore, an enhanced anti-HER2 targeting with improved treatment efficiency is still aspired.MethodsHere, we determined cellular and molecular mechanisms involved in the treatment of HER2-positive BC cells with a new rabbit derived HER2 specific chimeric monoclonal antibody called “B100″. We evaluated the B100 treatment efficiency of HER2-positive BC cells with different sensitivity to trastuzumab both in vitro and in the presence of a human immune system in humanized tumor mice.ResultsB100 not only efficiently blocks cell proliferation but more importantly induces apoptotic tumor cell death. Detailed in vitro analyses of B100 in comparison to trastuzumab (and pertuzumab) revealed equivalent HER2 internalization and recycling capacity, similar Fc receptor signaling, but different HER2 epitope recognition with high binding and treatment efficiency. In trastuzumab resistant SK-BR-3 based humanized tumor mice the B100 treatment eliminated the primary tumor but even more importantly eradicated metastasized tumor cells in lung, liver, brain, and bone marrow.ConclusionOverall, B100 demonstrated an enhanced anti-tumor activity both in vitro and in an enhanced preclinical HTM in vivo model compared to trastuzumab or pertuzumab. Thus, the use of B100 is a promising option to complement and to enhance established treatment regimens for HER2-positive (breast) cancer and to overcome trastuzumab resistance. Extended preclinical analyses using appropriate models and clinical investigations are warranted.
T cell infiltration and upregulation of MHCII in microglia leads to accelerated neuronal loss in an α-synuclein rat model of Parkinson’s disease
Authors: Subbarayan Meena S. , Hudson Charles , Moss Lauren D. , Nash Kevin R. , Bickford Paula C. 
Published: August 2020

AbstractBackgroundParkinson’s disease (PD) is the second most prevalent movement disorder characterized by up to 80% loss of dopamine (DA) neurons and accumulation of Lewy body deposits composed of α-synuclein (α-syn). Accumulation of α-syn is associated with microglial activation, leading to a pro-inflammatory environment linked with the pathogenesis of PD. Along with microglia, CD4 and CD8 T cells are observed in SNpc. The contribution of T-cells to PD development remains unclear with studies demonstrating that they may mediate neurodegeneration or act in a neuroprotective manner.MethodsHere, we assessed the contribution of T cells to PD neurodegeneration using an adeno-associated virus (AAV) coding human wild-type α-syn or GFP injected into the substantia nigra pars compacta (SNpc) in T cell deficient (athymic nude) and T cell competent (heterozygous) rats. The rats were behaviorally assessed with cylinder test to test paw bias. Following behavior testing, brains were collected and analyzed for markers of dopamine neuron, microglial activation, T cells, and α-syn expression.ResultsInjection of AAV9-α-syn unilaterally into the SN of T cell competent rats resulted in a significant paw bias in comparison to the controls at 60 days post-injection. Conversely, T cell-deficient rats injected with AAV9-α-syn showed no deficit in paw bias. As expected, injected T cell competent rats demonstrated a significant increase in microglial activation (MHCII staining) as well as significant dopaminergic neuron loss. In contrast, the T cell-deficient counterparts did not show a significant increase in microglial activation or significant neuron loss compared to the control animals. We also observed CD4 and CD8 T cells in SNpc following microglial MHCII expression and dopaminergic neuron loss. The time course of T cell entry correlates with upregulation of MHCII and the peak loss of TH+ cells in the SNpc.ConclusionThese data demonstrate that T cell infiltration and microglial upregulation of MHCII are involved in α-synuclein-mediated DA neuron loss in this rat model of PD.