bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atrial fibrillation and breast cancer—Vicious twins? A systematic review and meta-analysis
Authors: Yao Xiongda , Hu Qingwen , Liu Xiao , Ling Qing , Leng Yurong , Zhao Huilei , Yu Peng , Ma Jianyong , Zhao Yujie , Liu Menglu , Yang Renqiang 
Published: March 2023

BackgroundEpidemiological studies suggest a bidirectional association between atrial fibrillation and breast cancer. This study aimed to conduct a meta-analysis to elucidate the prevalence of atrial fibrillation among breast cancer patients, and the bidirectional association between atrial fibrillation and breast cancer.MethodsPubMed, the Cochrane Library, and Embase were searched to identify studies reporting the prevalence, incidence, and bidirectional association between atrial fibrillation and breast cancer. The study was registered with PROSPERO (CRD42022313251). Levels of evidence and recommendations were assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE).ResultsTwenty-three studies (17 retrospective cohort studies, 5 case-control studies and 1 cross-sectional study) involving 8,537,551 participants were included. Among patients with breast cancer, the prevalence of atrial fibrillation was 3% (11 studies; 95% CI: 0.6 to 7.1%) and the incidence was 2.7% (6 studies; 95% CI: 1.1 to 4.9%). Breast cancer was associated with increased risk of atrial fibrillation (5 studies; hazard ratio [HR]: 1.43, 95% CI: 1.12 to 1.82, I2 = 98%). Atrial fibrillation was also significantly associated elevated risk of breast cancer (5 studies HR: 1.18, 95% CI: 1.14 to 1.22, I2 = 0%). Grade assessment shown low certainty of the evidence for the risk of atrial fibrillation and moderate certainty of the evidence for the risk of breast cancer.ConclusionAtrial fibrillation is not uncommon in patients with breast cancer and vice versa. There is a bidirectional association between atrial fibrillation (low certainty) and breast cancer (moderate certainty).
The RGD region of bone sialoprotein affects metabolic activity in mice
Authors: Nagasaki Karin , Nagasaki Atsuhiro , Taylor Jocelyn M. , Kear Bernice D. , Ma Yinyan , Somerman Martha J. , Gavrilova Oksana 
Published: March 2023

IntroductionBone sialoprotein (BSP) is a key regulator of mineralized tissue formation. Previously, we generated BSP-KAE knock-in mice (KAEKI mice) by substituting a non-function KAE (lysine-alanine-glutamic acid) for the integrin-binding RGD (arginine-glycine-aspartic acid) sequence and reported a vital role of the BSP-RGD motif in modulating the periodontal ligament (PDL). Specifically, a histological disorganization of the PDL was noted, resulting in a weakened function of the PDL as measured by dynamic mechanical analysis. Intriguingly, also noted was a weight gain as KAEKI mice aged. While several proteins associated with mineralized tissues are reported to affect energy metabolism, the metabolic role of the BSP-RGD region has yet to be elucidated. Here we focus on defining the role of the BSP-RGD region in metabolic activity.MethodsBody weight, body composition, and caloric intake were measured in wild type (WT) and KAEKI mice. Energy expenditure was estimated using energy balance technique. Epididymal fat, interscapular fat, and liver were harvested for histological analysis. The systemic metabolic phenotype was assessed by sera analyses, insulin tolerance and glucose tolerance tests.ResultsThe results showed that KAEKI mice developed mild obesity starting from 13 weeks postnatal (wpn). The increase in body weight correlated with an increase in lean mass and visceral adiposity. Histological examination revealed adipocyte hypertrophy in white epididymal fat and interscapular brown fat in KAEKI vs. WT mice at 17 wpn. Metabolic profiling indicated that KAEKI mice had dyslipidemia and hyperleptinemia but no significant changes in glucose metabolism. Energy balance analyses revealed that hyperphagia preceded weight gain in KAEKI mice.ConclusionThese data suggest that the RGD region of BSP affects energy metabolism by regulating food intake, with further studies warranted to uncover the underlying mechanisms.
Prognostic predictors of adrenocortical carcinoma: A single-center thirty-year experience
Authors: Pan Li-Hsin , Yen Chueh-Chuan , Huang Chun-Jui , Ng Xin-Ning , Lin Liang-Yu 
Published: March 2023

BackgroundThe prognosis of adrenocortical carcinoma (ACC) is poor but highly variable. The present study aimed to characterize patients with ACC at a single center in Taiwan and to determine the prognostic predictors of overall and progression-free survival.MethodsMedical records of patients, who were diagnosed with ACC at Taipei Veterans General Hospital between January 1992 and June 2021, were reviewed. Patient demographics, tumor characteristics, and subsequent treatment were analyzed with regard to overall survival and progression-free survival using Kaplan-Meier methods and a Cox regression model.ResultsSixty-seven patients were included. Females (65.7%) were more susceptible to ACC, with a younger onset and active hormonal secretion. One-half of the patients exhibited distant metastases at the time of diagnosis. The European Network for the Study of Adrenal Tumours (ENSAT) stage (hazard ratio [HR] 3.60 [95% confidence interval (CI) 1.25–10.38]; p=0.018), large vessel invasion (HR 5.19 [95% CI 1.75–15.37]; p=0.003), and mitotane use (HR 0.27 [95% CI 0.11–0.70]; p=0.007) were significantly associated with overall survival (OS). There was no single factor independently associated with progression-free survival.ConclusionENSAT stage had a substantial impact on overall survival though there was no difference in OS between patients with stage II and stage III ACC. Large vessel invasion portended poor prognosis and influenced OS significantly. Moreover, mitotane only improved clinical outcomes of patients with stage IV disease.
A novel endothelial-related prognostic index by integrating single-cell and bulk RNA sequencing data for patients with kidney renal clear cell carcinoma
Authors: Li Deng-Xiong , Yu Qing-Xin , Zeng Chui-Xuan , Ye Lu-Xia , Guo Yi-Qing , Liu Jun-Fei , Zheng Hai-Hong , Feng Dechao , Wei Wuran 
Published: March 2023

Background: Endothelial cells in the tumor microenvironment play an important role in the development of kidney renal clear cell carcinoma (KIRC). We wanted to further identify the function of endothelial cells in KIRC patients by integrating single-cell and bulk RNA sequencing data.Methods: Online databases provide the original data of this study. An endothelial-related prognostic index (ERPI) was constructed and validated by R version 3.6.3 and relative packages.Results: The ERPI consisted of three genes (CCND1, MALL, and VWF). Patients with high ERPI scores were significantly correlated with worse prognosis than those with low ERPI scores in the TCGA training group, TCGA test group, and GSE29609 group. A positive correlation was identified between the ERPI score and poor clinical features. The results of functional analysis indicated that ERPI was significantly associated with immune-related activities. We suggested that patients with high ERPI scores were more likely to benefit from immunotherapy based on the results of immune checkpoints, tumor microenvironment, stemness index, and TCIA, while patients with low ERPI scores were sensitive to gemcitabine, docetaxel, paclitaxel, axitinib, pazopanib, sorafenib, and temsirolimus according to the results of the “pRRophetic” algorithm. Therefore, this ERPI may help doctors choose the optimal treatment for patients with KIRC.Conclusion: By integrating single-cell and bulk RNA sequencing data from KIRC patients, we successfully identified the key genes from the perspective of endothelial cells in the tumor microenvironment and constructed ERPIs that had positive implications in precision medicine.
Positive cfDNA screening results for 22q11.2 deletion syndrome—Clinical and laboratory considerations
Authors: Soster Erica , Dyr Brittany , Rafalko Jill , Almasri Eyad , Cacheris Phillip 
Published: March 2023

Introduction: Non-invasive prenatal screening (NIPS) via cell-free DNA (cfDNA) screens for fetal chromosome disorders using maternal plasma, including 22q11.2 deletion syndrome (22q11.2DS). While it is the commonest microdeletion syndrome and has potential implications for perinatal management, prenatal screening for 22q11.2DS carries some inherent technical, biological, and counseling challenges, including varying deletion sizes/locations, maternal 22q11.2 deletions, confirmatory test choice, and variable phenotype.Materials and methods: This study addresses these considerations utilizing a retrospective cohort of 307 samples with screen-positive 22q11.2 NIPS results on a massively parallel sequencing (MPS) platform.Results: Approximately half of the cases reported ultrasound findings at some point during pregnancy. In 63.2% of cases with diagnostic testing, observed positive predictive values were 90.7%–99.4%. cfDNA identified deletions ranging from &lt;1 Mb to 3.55 Mb, with significant differences in confirmed fetal versus maternal deletion sizes; estimated cfDNA deletion size was highly concordant with microarray findings. Mosaicism ratio proved useful in predicting the origin of a deletion (fetal versus maternal). Prediction of deletion size, location, and origin may help guide confirmatory testing.Discussion: The data shows that MPS-based NIPS can screen for 22q11.2DS with a high PPV, and that collaboration between the laboratory and clinicians allows consideration of additional metrics that may guide diagnostic testing and subsequent management.
CD27+ microparticle interactions and immunoregulation of CD4+ T lymphocytes
Authors: Cagnet Léonie , Neyrinck-Leglantier Déborah , Tamagne Marie , Berradhia Lylia , Khelfa Mehdi , Cleophax Sabine , Pirenne France , Vingert Benoît 
Published: March 2023

IntroductionAplasia and hematological malignancies are treated with platelet transfusions, which can have major immunomodulatory effects. Platelet concentrates (PCs) contain many immunomodulatory elements, including the platelets themselves, residual leukocytes, extracellular vesicles, such as microparticles (MPs), cytokines and other soluble elements. Two of these components, MPs and a soluble form of CD27 (sCD27), have been shown to play a particularly important role in immune system modulation. The loss of CD27 expression is an irreversible marker of terminal effector CD3+ T-lymphocyte (TL) differentiation, and the CD27+ MPs present in PCs may maintain CD27 expression on the surface of TLs, and, thus, the activation of these cells.MethodsIn this study, we phenotyped the CD27-expressing MPs present in PCs by microscale flow cytometry and investigated the interaction of these particles with CD4+ TLs. We cocultured MPs and PBMCs and determined the origin of the CD27 expressed on the surface of CD4+ TLs with the aid of two fluorochromes (BV510 for CD27 originating from MPs and BV786 for cellular CD27).ResultsWe showed that the binding of CD27- expressing MPs involved the CD70 molecule, which was also present on these MPs. Finally, the maintenance of CD27 expression on the surface of TLs by sorted CD27+ MPs led to activation levels lower than those observed with other types of MPs.DiscussionThese results for CD27-expressing MPs and their CD70-mediated targeting open up new possibilities for immunotherapy based on the use of MPs to maintain a phenotype or to target immune cells, for example. Moreover, decreasing the levels of CD27-expressing MPs in transfused platelets might also increase the chances of success for anti-CD27 monoclonal immunotherapy.
Peripheral CD8+CD28+ T lymphocytes predict the efficacy and safety of PD-1/PD-L1 inhibitors in cancer patients
Authors: Geng Ruixuan , Tang Hui , You Tingting , Xu Xiuxiu , Li Sijian , Li Zepeng , Liu Yuan , Qiu Wei , Zhou Na , Li Ningning , Ge Yuping , Guo Fuping , Sun Yuhong , Wang Yingyi , Li Taisheng , Bai Chunmei 
Published: March 2023

BackgroundProgrammed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors works by reactivating immune cells. Considering the accessibility of noninvasive liquid biopsies, it is advisable to employ peripheral blood lymphocyte subsets to predict immunotherapy outcomes.MethodsWe retrospectively enrolled 87 patients with available baseline circulating lymphocyte subset data who received first-line PD-1/PD-L1 inhibitors at Peking Union Medical College Hospital between May 2018 and April 2022. Immune cell counts were determined by flow cytometry.ResultsPatients who responded to PD-1/PD-L1 inhibitors had significantly higher circulating CD8+CD28+ T-cell counts (median [range] count: 236 [30-536] versus 138 [36-460]/μL, p &lt; 0.001). Using 190/μL as the cutoff value, the sensitivity and specificity of CD8+CD28+ T cells for predicting immunotherapy response were 0.689 and 0.714, respectively. Furthermore, the median progression-free survival (PFS, not reached versus 8.7 months, p &lt; 0.001) and overall survival (OS, not reached versus 16.2 months, p &lt; 0.001) were significantly longer in the patients with higher CD8+CD28+ T-cell counts. However, the CD8+CD28+ T-cell level was also associated with the incidence of grade 3-4 immune-related adverse events (irAEs). The sensitivity and specificity of CD8+CD28+ T cells for predicting irAEs of grade 3-4 were 0.846 and 0.667, respectively, at the threshold of CD8+CD28+ T cells ≥ 309/μL.ConclusionsHigh circulating CD8+CD28+ T-cell levels is a potential biomarker for immunotherapy response and better prognosis, while excessive CD8+CD28+ T cells (≥ 309/μL) may also indicate the emergence of severe irAEs.
Survival of Escherichia coli after high-antibiotic stress is dependent on both the pregrown physiological state and incubation conditions
Authors: Thorfinnsdottir Lilja Brekke , Bø Gaute Hovde , Booth James Alexander , Bruheim Per 
Published: March 2023

IntroductionThe survival of bacterial cells exposed to antibiotics depends on the mode of action, the antibiotics concentration, and the duration of treatment. However, it also depends on the physiological state of the cells and the environmental conditions. In addition, bacterial cultures contain sub-populations that can survive high antibiotic concentrations, so-called persisters. Research on persisters is challenging due to multiple mechanisms for their formation and low fractions, down to and below one millionth of the total cell population. Here, we present an improved version of the persister assay used to enumerate the amount of persisters in a cell population.MethodsThe persister assay with high antibiotic stress exposure was performed at both growth supporting and non-supporting conditions. Escherichia coli cells were pregrown to various growth stages in shake flasks and bench-top bioreactors. In addition, the physiological state of E. coli before antibiotic treatment was determined by quantitative mass spectrometry-based metabolite profiling.ResultsSurvival of E. coli strongly depended on whether the persister assay medium supported growth or not. The results were also highly dependent on the type of antibiotic and pregrown physiological state of the cells. Therefore, applying the same conditions is critical for consistent and comparable results. No direct connection was observed between antibiotic efficacy to the metabolic state. This also includes the energetic state (i.e., the intracellular concentration of ATP and the adenylate energy charge), which has earlier been hypothesized to be decisive for persister formation.DiscussionThe study provides guides and suggestions for the design of future experimentation in the research fields of persisters and antibiotic tolerance.
Effect of home-based, overground robotic-assisted gait training on vascular health in people with chronic stroke
Authors: Faulkner James , Wright Amy , Stone Keeron , Fryer Simon , Martinelli Louis , Lambrick Danielle , Paine Eloise , Stoner Lee 
Published: March 2023

Overground robotic-assisted gait training (O-RAGT) has been shown to improve clinical functional outcomes in people living with stroke. The purpose of this study was to identify whether a home-based O-RAGT program, in combination with usual care physiotherapy, would demonstrate improvements in vascular health in individuals with chronic stroke, and, whether any changes in vascular outcomes would be sustained 3 months after completing the program. Thirty-four participants with chronic stroke (between 3 months and 5 years post-stroke) were randomized to either a 10-week O-RAGT program in combination with usual care physiotherapy, or to a usual care physiotherapy only control group. Participants' (n = 31) pulse wave analysis (PWA), and regional [carotid-femoral pulse wave analysis (cfPWV)] and local (carotid) measures of arterial stiffness were assessed at baseline, post-intervention, and 3-month post-intervention. Analysis of covariance demonstrated a significant reduction (improvement) in cfPWV between BL and PI for O-RAGT (8.81 ± 2.51 vs. 7.92 ± 2.17 m/s, respectively), whilst the control group remained unchanged (9.87 ± 2.46 vs. 9.84 ± 1.76 m/s, respectively; p &lt; 0.05; ηp2 = 0.14). The improvement in cfPWV was maintained 3 months after completing the O-RAGT program. There were no significant Condition by Time interactions for all PWA and carotid arterial stiffness measures (p &gt; 0.05). A significant increase in physical activity, as determined by the time spent stepping, was observed for O-RAGT between baseline and post-intervention assessments (3.2 ± 3.0–5.2 ± 3.3%, respectively) but not for CON (p &lt; 0.05). The improvement in cfPWV, in combination with an increase in physical activity whilst wearing the O-RAGT and concomitant reduction in sedentary behavior, are important positive findings when considering the application of this technology for “at home” rehabilitation therapy for stroke survivors. Further research is needed to determine whether implementing “at home” O-RAGT programs should be a part of the stroke treatment pathway.Clinical trial registrationhttps://clinicaltrials.gov, identifier NCT03104127.
Prognostic significance of serum NLRC4 in patients with acute supratentorial intracerebral hemorrhage: A prospective longitudinal cohort study
Authors: Li Wei , Lv Xuan , Ma Yijun , Cai Yong , Zhu Suijun 
Published: March 2023

ObjectiveCaspase activation and recruitment domain-containing protein 4 (NLRC4) is implicated in neuroinflammation. The aim of the study was to discern the potential ability of serum NLRC4 in assessment of prognosis after intracerebral hemorrhage (ICH).MethodsIn this prospective, observational study, serum NLRC4 levels were quantified in 148 acute supratentorial ICH patients and 148 controls. Severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) and hematoma volume, and poststroke 6-month functional outcome was estimated according to the modified Rankin Scale (mRS). Early neurologic deterioration (END) and 6-month poor outcome (mRS 3–6) were deemed as the two prognostic parameters. Multivariate models were established for investigating associations, and receiver operating characteristic (ROC) curves were configured to indicate predictive capability.ResultsPatients had substantially higher serum NLRC4 levels than controls (median, 363.2 pg/ml vs. 74.7 pg/ml). Serum NLRC4 levels had independent correlation with NIHSS scores [β, 0.308; 95% confidence interval (CI), 0.088–0.520], hematoma volume (β, 0.527; 95% CI, 0.385–0.675), serum C-reactive protein levels (β, 0.288; 95% CI, 0.109–0.341) and 6-month mRS scores (β, 0.239; 95% CI, 0.100–0.474). Serum NLRC4 levels above 363.2 pg/ml were independently predictive of END (odds ratio, 3.148; 95% CI, 1.278–7.752) and 6-month poor outcome (odds ratio, 2.468; 95% CI, 1.036–5.878). Serum NLRC4 levels significantly distinguished END risk [area under ROC curve (AUC), 0.765; 95% CI, 0.685–0.846] and 6-month poor outcome (AUC, 0.795; 95% CI, 0.721–0.870). In terms of predictive ability for 6-month poor outcome, serum NLRC4 levels combined with NIHSS scores and hematoma volume was superior to NIHSS scores combined with hematoma volume, NIHSS scores and hematoma volume (AUC, 0.913 vs. 0.870, 0.864 and 0.835; all P &lt; 0.05). Nomograms were built to reflect prognosis and END risk of combination models, where serum NLRC4, NIHSS scores and hematoma volume were enforced. Calibration curves confirmed stability of combination models.ConclusionsMarkedly raised serum NLRC4 levels following ICH, in close relation to illness severity, are independently associated with poor prognosis. Such results are indicative of the notion that determination of serum NLRC4 may aid in severity assessment and prediction of functional outcome of ICH patients.
Case Report: MSS colorectal extrahepatic (non-liver) metastases as the dominant population for immunotherapy combined with multi-target tyrosine kinase inhibitors
Authors: Liu Jiayin , Li Dan , Han Jing , Zhang Yin , Zhang Xue , Fan Zhisong , Feng Li , Wang Long , Jin Hui , Zuo Jing , Wang Yudong 
Published: March 2023

BackgroundThe microsatellite stability(MSS) subtype of Colorectal Cancer(CRC) represents approximately 95% of mCRC cases. Immunotherapy was not as encouraging as the data for MSS mCRC cancer. We report the treatment of a series of patients with extrahepatic metastasis of MSS colorectal cancer, which can provide reference and guidance for the treatment of non-hepatic metastasis of MSS colorectal.Case presentationThis report describes 8 typical cases of successful MSS treatment with lung metastases of CRC. We systematically reviewed the clinical data and detailed medical history of one of these patients with extrahepatic metastasis from MSS colorectal cancer, and reviewed the literature to analyze and discuss the related epidemiological features, mechanisms and recent research findings of the special subgroup of the population.ConclusionsAlthough MSS colon rectal cancer is still known as a cold tumor in the industry, immunotherapy combined with multi-targeted anti-vascular tyrosine kinase inhibitors had brought clinical benefits to patients with non-hepatic metastases from MSS colorectal cancer.