bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistent T Cell Repertoire Perturbation and T Cell Activation in HIV After Long Term Treatment
Authors: Turner Carolin T. , Brown James , Shaw Emily , Uddin Imran , Tsaliki Evdokia , Roe Jennifer K. , Pollara Gabriele , Sun Yuxin , Heather James M. , Lipman Marc , Chain Benny , Noursadeghi Mahdad 
Published: February 2021

ObjectiveIn people living with HIV (PLHIV), we sought to test the hypothesis that long term anti-retroviral therapy restores the normal T cell repertoire, and investigate the functional relationship of residual repertoire abnormalities to persistent immune system dysregulation.MethodsWe conducted a case-control study in PLHIV and HIV-negative volunteers, of circulating T cell receptor repertoires and whole blood transcriptomes by RNA sequencing, complemented by metadata from routinely collected health care records.ResultsT cell receptor sequencing revealed persistent abnormalities in the clonal T cell repertoire of PLHIV, characterized by reduced repertoire diversity and oligoclonal T cell expansion correlated with elevated CD8 T cell counts. We found no evidence that these expansions were driven by cytomegalovirus or another common antigen. Increased frequency of long CDR3 sequences and reduced frequency of public sequences among the expanded clones implicated abnormal thymic selection as a contributing factor. These abnormalities in the repertoire correlated with systems level evidence of persistent T cell activation in genome-wide blood transcriptomes.ConclusionsThe diversity of T cell receptor repertoires in PLHIV on long term anti-retroviral therapy remains significantly depleted, and skewed by idiosyncratic clones, partly attributable to altered thymic output and associated with T cell mediated chronic immune activation. Further investigation of thymic function and the antigenic drivers of T cell clonal selection in PLHIV are critical to efforts to fully re-establish normal immune function.
In vitro Antibacterial Activity of an FDA-Approved H+-ATPase Inhibitor, Bedaquiline, Against Streptococcus mutans in Acidic Milieus
Authors: Zhang Meng , Yu Wenqian , Zhou Shujing , Zhang Bing , Lo Edward Chin Man , Xu Xin , Zhang Dongjiao 
Published: February 2021

BackgroundDental caries is an acid-related disease. Current anti-caries agents mainly focus on the bacteriostatic effect in a neutral environment and do not target acid-resistant microorganisms related to caries in acidic milieus.ObjectivesTo assess thein vitroantibacterial activities of bedaquiline against oral pathogens in acidic milieus.MethodsStreptococcus mutans,Streptococcus sanguinis, andStreptococcus salivariuswere used to prepare the mono-/multiple suspension and biofilm. The MIC and IC50of bedaquiline againstS. mutanswere determined by the broth microdilution method. Bedaquiline was compared regarding (i) the inhibitory activity in pH 4–7 and at different time points against planktonic and biofilm; (ii) the effect on the production of lactic acid, extracellular polysaccharide, and pH ofS. mutansbiofilm; (iii) the cytotoxicity effects; and (iv) the activity on H+-ATPase enzyme ofS. mutans.ResultsIn pH 5 BHI, 2.5 mg/L (IC50) and 4 mg/L (MIC) of bedaquiline inhibited the proliferation and biofilm generation ofS. mutansand Mix in a dose-dependent and time-dependent manner, but it was invalid in a neutral environment. The lactic acid production, polysaccharide production, and pH drop range reduced with the incorporation of bedaquiline in a pH 5 environment. Its inhibitory effect (&gt;56 mg/L) against H+-ATPase enzyme inS. mutansand its non-toxic effect (&lt;10 mg/L) on periodontal ligament stem cells were also confirmed.ConclusionBedaquiline is efficient in inhibiting the proliferation and biofilm generation ofS. mutansand other oral pathogens in an acidic environment. Its high targeting property and non-cytotoxicity also promote its clinical application potential in preventing caries. Further investigation of its specific action sites and drug modification are warranted.
Reduced Superficial Capillary Density in Cerebral Infarction Is Inversely Correlated With the NIHSS Score
Authors: Kwapong William Robert , Yan Yuying , Hao Zilong , Wu Bo 
Published: February 2021

Purpose: The retina and the brain share similar neuronal and microvascular features, therein we aimed to assess the structural and microvascular changes in the macula and choriocapillaris (CC) in patients with cerebral infarction when compared with healthy controls using optical coherence tomography angiography (OCTA).Methods: OCTA was used to image and measure the capillary density in the radial peripapillary capillaries (RPC), superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris (CC), and mean area of the foveal avascular zone (FAZ) in all participants. Twenty-two cerebral infarction patients based on their magnetic resonance imaging (MRI) and 25 healthy controls were included in our study.Results: Density of the RPC (P &lt; 0.001), SCP (P = 0.001), DCP (P &lt; 0.001) and CC (P &lt; 0.001) were significantly reduced in cerebral infarction patients when compared with healthy controls, respectively. Retinal thickness measurements (P &lt; 0.05) were significantly reduced in cerebral infarction patients when compared with healthy controls. The mean FAZ area was significantly larger (P = 0.012) in cerebral infarction patients when compared with healthy controls. National Institute of HealthStroke Scale (NIHSS) inversely correlated with SCP density in cerebral infarction patients (Rho = −0.409, P = 0.001). Receiver operating characteristics curve analysis showed that the blood flow of the choriocapillaris had the highest index [area under the receiver operatingcharacteristic (AUROC) = 0.964] to discriminate cerebral infarction patients from the healthy controls.Conclusions: Our study suggests that cerebral microcirculation dysfunction which occurs in cerebral infarction is mirrored in the macula and choroidal microcirculation. OCTA has the potential to non-invasively characterize the macula and choroidal changes in cerebral infarction in vivo.
Lung Cancer Attributed Mortality Among 316,336 Early Stage Breast Cancer Cases Treated by Radiotherapy and/or Chemotherapy, 2000–2015: Evidence From the SEER Database
Authors: Abera Semaw Ferede , Mikolajczyk Rafael T. , Kantelhardt Eva Johanna , Efremov Ljupcho , Bedir Ahmed , Ostheimer Christian , Glowka André , Vordermark Dirk , Medenwald Daniel 
Published: February 2021

ObjectiveTo estimate the risk of death from lung cancer in patients treated for breast cancer (BC) in relation to the general population.MethodsBC data, covering 2000 to 2015, were extracted from the Surveillance, Epidemiology and End Results-18 (SEER-18) cancer registry database. A comparison of lung cancer attributed mortality between BC patients and the general population was performed using standardized mortality ratios (SMRs) and SMRs conditional on survival length (cSMRs). Prognostic factors of lung cancer mortality were identified using flexible parametric modelling. Our model adjusts the effect of downstream (histopathological BC tumor grade and hormone receptor status) and upstream (age at diagnosis, ethnicity, and marital status) factors.ResultsThe median follow-up was 6.4 years (interquartile range, 3.0–10.3 years). BC cases who received only radiotherapy (cSMR = 0.93; 95%CI: 0.77–1.13), only chemotherapy (cSMR = 0.91; 0.62–1.33), and radio-and chemotherapy (cSMR = 1.04; 0.77–1.39) had no evidence of increased lung cancer mortality relative to the general population. The adjusted model identified that lung cancer mortality was higher for women who were older at diagnosis compared to those &lt;50 years (ranging from HR50-59 = 3.41 [95%CI: 2.72–4.28] to HR70-79 = 10.53 [95%CI: 8.44–13.13]) and for cases with negative estrogen and progesterone receptors (HR =1.38; 95% CI: 1.21–1.57). Compared to married cases, widowed, divorced, single or others had a 76%, 45%, and 25% higher hazard of lung cancer mortality, respectively. Lung cancer mortality was lower for American Indian/Alaska Native and Asian/Pacific Islander ethnicities (HR = 0.51; 95% CI: 0.40–0.64) compared to BC cases with white ethnic background.ConclusionsThere is no evidence for a higher lung cancer mortality in BC patients when compared to the general population.
Hypoxia-Induced miR-137 Inhibition Increased Glioblastoma Multiforme Growth and Chemoresistance Through LRP6
Authors: Li Dong-Mei , Chen Qiu-Dan , Wei Gui-Ning , Wei Jie , Yin Jian-Xing , He Jun-Hui , Ge Xin , Shi Zhu-Mei 
Published: February 2021

PurposeGlioblastoma multiforme (GBM) is one of the deadliest tumors, which is involved in numerous dysregulated microRNAs including miR-137. However, the mechanism of how miR-137 suppression associated with cancer progression and chemoresistance still remains to be elucidated.MethodsQuantitative reverse transcriptase-PCR (qRT-PCR), DNA methylation analysis, cell proliferation assay, flow cytometric analysis, invasion assay, in situ tumor formation experiment were performed to test the expression levels and functions of miR-137 in GBM. Bioinformatics analysis, luciferase reporter assay, qRT-PCR, immunoblotting, immunofluorescence, and immunohistochemistry assay were used to identify and verify the target of miR-137.ResultsWe found that miR-137 was downregulated in primary and recurrent GBM compared with normal brain tissues. Overexpression of miR-137 inhibited cell invasion and enhanced cell chemosensitivity to temozolomide (TMZ) by directly targeting low-density lipoprotein receptor-related protein 6 (LRP6) in GBM. Forced expression of LRP6 cDNA without its 3’-UTR region partly restored the effects of miR-137 in vitro and in vivo. Hypoxia-induced miR-137 methylation was responsible for the miR-137 suppression, leading to the cell chemoresistance and poor prognosis of GBM.ConclusionsThese findings demonstrated the detailed molecular mechanism of miR-137 in regulating GBM growth and chemoresistance in hypoxia microenvironment, suggesting the potentiality of miR-137 as a therapeutic target for GBM.
Comparison of the Gross Target Volumes Based on Diagnostic PET/CT for Primary Esophageal Cancer
Authors: Shi Jingzhen , Li Jianbin , Li Fengxiang , Zhang Yingjie , Guo Yanluan , Wang Wei , Wang Jinzhi 
Published: February 2021

BackgroundClinically, many esophageal cancer patients who planned for radiation therapy have already undergone diagnostic Positron-emission tomography/computed tomography (PET/CT) imaging, but it remains unclear whether these imaging results can be used to delineate the gross target volume (GTV) of the primary tumor for thoracic esophageal cancer (EC).MethodsSeventy-two patients diagnosed with thoracic EC had undergone prior PET/CT for diagnosis and three-dimensional CT (3DCT) for simulation. The GTV3D was contoured on the 3DCT image without referencing the PET/CT image. The GTVPET-ref was contoured on the 3DCT image referencing the PET/CT image. The GTVPET-reg was contoured on the deformed registration image derived from 3DCT and PET/CT. Differences in the position, volume, length, conformity index (CI), and degree of inclusion (DI) among the target volumes were determined.ResultsThe centroid distance in the three directions between two different GTVs showed no significant difference (P &gt; 0.05). No significant difference was found among the groups in the tumor volume (P &gt; 0.05). The median DI values of the GTVPET-reg and GTVPET-ref in the GTV3D were 0.82 and 0.86, respectively (P = 0.006). The median CI values of the GTV3D in the GTVPET-reg and GTVPET-ref were 0.68 and 0.72, respectively (P = 0.006).ConclusionsPET/CT can be used to optimize the definition of the target volume in EC. However, no significant difference was found between the GTVs delineated based on visual referencing or deformable registration whether using the volume or position. So, in the absence of planning PET–CT images, it is also feasible to delineate the GTV of primary thoracic EC with reference to the diagnostic PET–CT image.
PAFAH1B3 Expression Is Correlated With Gastric Cancer Cell Proliferation and Immune Infiltration
Authors: Xie Tianyu , Guo Xin , Wu Di , Li Shuo , Lu Yixun , Wang Xinxin , Chen Lin 
Published: February 2021

BackgroundPlatelet activating factor acetylhydrolase 1b catalytic subunit 3 (PAFAH1B3) is associated with a variety of human diseases. However, its function in gastric cancer remains uncertain.MethodsPAFAH1B3 expression was analyzed in The Cancer Genome Atlas (TCGA) and genotype-tissue expression pan-cancer data. The association between PAFAH1B3 expression and patient prognosis was evaluated using TCGA clinical survival data. Enrichment analysis of PAFAH1B3 was performed using the clusterProfiler R software package. Moreover, the correlation between PAFAH1B3 expression and immune cell infiltration were evaluated by analyzing TCGA database. CCK8 assay and colony-formation assay were performed to assess the effect of PAFAH1B3 on the proliferation of gastric cancer cells. Transwell assay was used to evaluate the impact of PAFAH1B3 on gastric cancer cell migration. Western blot was performed to evaluate the role of PAFAH1B3 on signaling pathways in gastric cancer cells.ResultsPAFAH1B3 was highly expressed in many types of tumors including gastric cancer. High PAFAH1B3 expression was significantly correlated with proliferation-related gene sets involved in DNA replication, the cell cycle, and cell cycle checkpoints. Further analysis showed that high PAFAH1B3 expression was associated with high M1 macrophage and CD8-positive T cell infiltration scores. PAFAH1B3 knockdown inhibited the proliferation, migration, and the activation of oncogenic signaling in gastric cancer cells.ConclusionsOur findings suggest that PAFAH1B3 may be an oncogene in gastric cancer.
Fragile Gene WWOX Guides TFAP2A/TFAP2C-Dependent Actions Against Tumor Progression in Grade II Bladder Cancer
Authors: Kołat Damian , Kałuzińska Żaneta , Bednarek Andrzej K. , Płuciennik Elżbieta 
Published: February 2021

IntroductionThe presence of common fragile sites is associated with no-accidental chromosomal instability which occurs prior to carcinogenesis. TheWWOXgene spans the second most active fragile site: FRA16D. Chromosomal breakage at this site is more common in bladder cancer patients who are tobacco smokers which suggests the importance ofWWOXgene loss regarding bladder carcinogenesis. Tryptophan domains of WWOX are known to recognize motifs of other proteins such as AP-2α and AP-2γ allowing protein-protein interactions. While the roles of both AP-2 transcription factors are important for bladder carcinogenesis, their nature is different. Based on the literature, AP-2γ appears to be oncogenic, whereas AP-2α mainly exhibits tumor suppressor character. Presumably, the interaction between WWOX and both transcription factors regulates thousands of genes, hence the aim of the present study was to determine WWOX, AP-2α, and AP-2γ function in modulating biological processes of bladder cancer.MethodsRT-112 cell line (grade II bladder cancer) was subjected to two stable lentiviral transductions. Overall, this resulted in six variants to investigate distinct WWOX, AP-2α, or AP-2γ function as well as WWOX in collaboration with a particular transcription factor. Cellular models were examined with immunocytochemical staining and in terms of differences in biological processes using assays investigating cell viability, proliferation, apoptosis, adhesion, clonogenicity, migration, activity of metalloproteinases and 3D culture growth.ResultsWWOX overexpression increased apoptosis but decreased cell viability, migration and large spatial colonies. AP-2α overexpression decreased tumor cell viability, migratory potential, matrix metalloproteinase-2 activity and clonogenicity. AP-2γ overexpression decreased matrix metalloproteinase-2 activity but increased wound healing, adhesion, clonogenicity and spatial colony formation. WWOX and AP-2α overexpression induced apoptosis but decreased cell viability, adhesion, matrix metalloproteinase-2 activity, overall number of cultured colonies and migration rate. WWOX and AP-2γ overexpression decreased tumor cell viability, proliferation potential, adhesion, clonogenicity and the ability to create spatial structures, but also increased apoptosis or migration rate.ConclusionCo-overexpression of WWOX with AP-2α or WWOX with AP-2γ resulted in a net anti-tumor effect. However, considering this research findings and the difference between AP-2α and AP-2γ, we suggest that this similarity is due to a divergent behavior of WWOX.
Differences in Importance Attached to Drug Effects Between Patients With Type 2 Diabetes From the Netherlands and Turkey: A Preference Study
Authors: Roldan Munoz Sonia , Postmus Douwe , de Vries Sieta T. , Arnardottir Arna H. , Dolu İlknur , Hillege Hans , Mol Peter G. M. 
Published: February 2021

Objective: The aim of this study was to compare the importance that patients with type 2 diabetes mellitus from the Netherlands and Turkey attach to certain drug effects of oral anti-diabetic drugs.Methods: Data were collected through a cross-sectional survey containing demographic questions and a discrete choice experiment assessing preferences for oral anti-diabetic drugs. Adults from the Netherlands and Turkey were included if they had type 2 diabetes mellitus and had received a prescription of an oral anti-diabetic drug in the last 4 months. The oral anti-diabetic drugs in the discrete choice experiment were described in terms of six attributes: effects on HbA1c, cardiovascular diseases, weight change, gastrointestinal adverse drug events hypoglycemic events, and bladder cancer. Multinomial logit models with country as an interaction factor were fitted.Results: In total, 381 patients were included, 199 from the Netherlands and 182 from Turkey. Patients’ preferences toward drug effects varied between the countries. Turkish patients attached the highest importance to reducing the risk of cardiovascular diseases (relative weight: 0.51, 95% CI 0.45–0.55), followed by reducing hypoglycemic events (relative weight: 0.16, 95% CI 0.11–0.22), and reducing gastrointestinal adverse drug events (relative weight: 0.11, 95% CI 0.07–0.18). Patients from the Netherlands attached the highest importance to gastrointestinal ADEs (relative weight: 0.22, 95% CI 0.14–0.39), followed by reducing hypoglycemic events (relative weight: 0.22, 95% CI 0.16–0.25), and reducing the risk of cardiovascular diseases (relative weight: 0.20, 95% CI 0.13–0.23).Conclusion: Patient preferences may differ across countries. Such differences should be acknowledged in regulatory decisions and clinical practice.
Is a Brief Online Booklet Sufficient to Reduce Fear of Cancer Recurrence or Progression in Women With Ovarian Cancer?
Authors: Pradhan Poorva , Sharpe Louise , Butow Phyllis N. , Smith Allan Ben , Russell Hayley 
Published: February 2021

Background: Fear of cancer recurrence or progression (FCR/P) is a common challenge experienced by people living with and beyond cancer and is frequently endorsed as the highest unmet psychosocial need amongst survivors. This has prompted many cancer organizations to develop self-help resources for survivors to better manage these fears through psychoeducation, but little is known about whether they help reduce FCR/P.Method: We recruited 62 women with ovarian cancer. Women reported on their medical history and demographic characteristics and completed the Fear of Progression Questionnaire-Short Form (FoP-Q-SF). They then read a booklet on FCR specifically created for Ovarian Cancer Australia by two of the authors (ABS and PB). One week after reading the booklet, 50/62 women (81%) completed the FoP-Q-SF and answered questions about their satisfaction with the booklet.Results: More than half of the women (35/62; 56.5%) scored in the clinical range for FCR/P at baseline. Of the completers, 93% said that they would recommend the booklet to other women. Satisfaction with the booklet was relatively high (75.3/100) and more than two-thirds of women rated it as moderately helpful or better. However, FCR/P did not change significantly over the week following reading the booklet [t(49) = 1.71, p = 0.09]. There was also no difference in change in FCR/P between women in the clinical vs. non-clinical range on the FoP-Q. Women high in FCR/P rated the booklet as less helpful in managing FCR/P (r = −0.316, p = 0.03), but overall satisfaction with the booklet was not associated with degree of FCR/P (r = −0.24, p = 0.10).Conclusions: These results suggest that a simple online FCR booklet is acceptable to women with ovarian cancer and they are satisfied with the booklet, but, it was insufficient to change in FCR/P levels. These results suggest that such resources are valued by women with ovarian cancer, but more potent interventions are necessary to reduce FCR in this population.
Mild to Severe Depressive Symptoms in Elderly Stroke Survivors and Its Associated Factors: Evidence From a Cross-Sectional Study in Zhejiang Province, China
Authors: Wang Xinyi , Li Fudong , Zhang Tao , He Fan , Lin Junfen , Zhai Yujia , Yu Min 
Published: February 2021

Objective: The objective of the study is to explore the prevalence of mild to severe depressive symptoms in elderly stroke survivors and its associated factors.Methods: We did data analyses of 335 elders with stroke history. Data were collected in a survey conducted between 2014 and 2015, among permanent residents aged 60 and older in Zhejiang Province, China. Prevalence of mild to severe depressive symptoms among stroke survivors were calculated, and univariate analyses and multilevel logistic regression were used to explore its associated factors.Results: Prevalence of mild to severe depressive symptoms was 22.09% (95% CI: 17.65–26.53%) in elders with stroke history, more than twice compared to their counterparts not suffering stroke (9.77%, P &lt; 0.001). In multilevel logistic regression, we found that elderly stroke survivors who were illiterate (OR = 2.33, p = 0.008), or had limitation in activities of daily living (OR = 3.04, p = 0.001) were more likely to be present with mild to severe depressive symptoms, respectively, while those with more fresh vegetable consumption were at lower odds (OR = 0.82, p = 0.047).Conclusions: Prevalence of mild to severe depressive symptoms was high in elderly stroke survivors. Targeted screening might be needed for those being illiterate, disabled in activities of daily living, and having little consumption of fresh vegetable. The association between fresh vegetable consumption and depressive symptom in stroke patients calls for further research.