bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methylation of SDC2/TFPI2 and Its Diagnostic Value in Colorectal Tumorous Lesions
Authors: Zhang Lianglu , Dong Lanlan , Lu Changming , Huang Wenxian , Yang Cuiping , Wang Qian , Wang Qian , Lei Ruixue , Sun Rui , Wan Kangkang , Li Tingting , Sun Fan , Gan Tian , Lin Jun , Yin Lei 
Published: December 2021

Background:SDC2 methylation is a feasible biomarker for colorectal cancer detection. Its specificity for colorectal cancer is higher than 90%, but the sensitivity is normally lower than 90%. This study aims to improve the sensitivity of SDC2 detection through finding a high positive target from the false-negative samples of SDC2 detection based on analysis of the bowel subsite difference in methylation.Methods: Hypermethylated TFPI2 was identified in SDC2 hypomethylated colorectal cancer samples retrieved from TCGA database with the methylation level lower than 0.2. The methylation-specific PCR assay was developed and then evaluated using tissue samples (184 cancer and 54 healthy control samples) and stool samples (289 cancer, 190 adenoma, and 217 healthy control samples).Results:TFPI2 was hypermethylated in most SDC2 hypomethylated colorectal cancer samples. When the SDC2/TFPI2-combined PCR assay was performed in stool specimens, the AUC value of cancer vs. control was 0.98, with the specificity of 96.40% and sensitivity of 96.60%, and the AUC value of adenoma vs. control was 0.87, with the specificity of 95.70% and the sensitivity of 80.00%. The improvement in sensitivity was the most momentous in the left colon. As the detection index, the Ct value was better in improving the sensitivity of detection than the methylation level based on the 2−ΔΔCt value.Conclusion:TFPI2 can improve the sensitivity of SDC2 methylation–specific detection of colorectal tumorous lesions while maintaining high specificity, in particular reducing the missed detection of left colon cancer and adenoma.
Healthy Lifestyle Factors, Cancer Family History, and Gastric Cancer Risk: A Population-Based Case-Control Study in China
Authors: Man Jinyu , Ni Yingchun , Yang Xiaorong , Zhang Tongchao , Yuan Ziyu , Chen Hui , Chen Xingdong , Lu Ming , Ye Weimin 
Published: December 2021

Background: We aimed to explore the relationship between lifestyle factors, cancer family history, and gastric cancer risk.Methods: We examined the association between lifestyle factors, cancer family history, and gastric cancer risk based on a population-based case-control study in Taixing, China, with 870 cases and 1928 controls. A lifestyle score was constructed considering body shape, smoking, alcohol drinking, tooth brushing habit, and food storage method. Unconditional logistic regression models were used to calculate odd ratios (ORs) and 95% confidence intervals (CIs).Results: Compared with participants with a lifestyle score of 0, subjects with a lifestyle score of 1 (OR 0.59, 95%CI 0.43–0.83), 2 (OR 0.42, 95%CI 0.30–0.59), 3 (OR 0.29, 95%CI 0.20–0.41), 4 (OR 0.20, 95%CI 0.13–0.32), or 5 (OR 0.10, 95%CI 0.04–0.22) had a lower risk of gastric cancer (P for trend &lt; 0.001). Overall, 34% of gastric cancer cases (95%CI 27–41%) can be attributed to non-compliance with ≥3 healthy lifestyle. Family history of early-onset cancer is closely related to the occurrence of gastric cancer, with an OR ranging from 1.77 to 3.27. Regardless of family history, a good lifestyle is associated with a reduced risk of gastric cancer, with an OR value between 0.38 and 0.70.Conclusions: The early-onset cancer family history is closely related to the occurrence of gastric cancer and a good lifestyle is associated with a reduced risk of gastric cancer regardless of family history. Our results provide a basis for identifying and providing behavior guidance of high-risk groups of gastric cancer.
The Relationship Between Body Mass Index and Different Regional Patterns of Lymph Node Involvement in Papillary Thyroid Cancers
Authors: Li Changlin , Dionigi Gianlorenzo , Liang Nan , Guan Haixia , Sun Hui 
Published: December 2021

IntroductionLymph node (LN) metastasis is the first site of metastasis of papillary thyroid cancer (PTC). LN status influences clinical management and the prognosis of patients. We explored the relationship between patient obesity and regional patterns of LN involvement in PTC.Materials and MethodsThis study retrospectively analyzed the data from 12,772 PTC patients. The rate of LN metastasis, number of LN metastasis, maximum diameter of positive LN, number of dissected LN, and LN ratios (LNR) were compared between normal-weight and obese patients. Statistical methods have been adjusted for the confounders in hypothesis testing.ResultsOverweight and obesity were independent risk factor for metastatic LNs (OR1 = 1.125, 95% CI 1.042-1.214, P1 = 0.003; OR2 = 1.554, 95% CI 1.339-1.802, P2&lt;0.001). Obesity was an independent risk factor for the number of metastatic CLNs (OR=1.159, 95% CI 0.975-1.377, P=0.045), however not for number of metastatic lateral LNs (P=0.907). Furthermore, obesity was not an independent risk factor for number of CLNs when dissected more than five (P=0.653), still an independent risk factors for number of metastatic lateral LNs when more than six (OR=1.185, 95% CI 1.010-1.391, P=0.037). As for LNR, obesity was an independent risk factor for the central LNR when more than 0.12 (OR adjusted 1 = 1.099, 95% CI 1.011-1.194, P1 = 0.027; OR adjusted 2 = 1.177, 95% CI 1.003-1.381, P2 = 0.045), for the lateral LNR more than 0.05 (P2 = 0.283).ConclusionsObesity was associated with poor prognoses with PTC respecting LNs. Surgeons should be extreme caution when performing central neck dissection in obese patients.
Clinical Complete Remission of An Advanced Gastric Adenocarcinoma After Camrelizumab Plus Chemotherapy Followed by Camrelizumab Plus Capecitabine: A Case Report
Authors: Lin Jieheng , Yang Jianying , Wang Wenping , Lin Xiaotong , Cao Yang 
Published: December 2021

We report a rare case of PDL1-negative advanced gastric adenocarcinoma that improved significantly after camrelizumab plus chemotherapy followed by camrelizumab plus capecitabine as first-line therapy. A 65-year-old woman was diagnosed with a gastric adenocarcinoma in 2017 via contrast-enhanced computed tomography (CT) and endoscopic biopsy. She stabilised after preoperative neoadjuvant chemotherapy, surgery, and postoperative adjuvant chemotherapy. In September 2019, positron emission tomography (PET)/CT re-examination suggested a peritoneal metastasis and multiple lymph node metastases. She then received six cycles of camrelizumab plus chemotherapy. PET/CT indicated that the metastatic foci had disappeared and that she had achieved a clinical complete response(CCR). She was followed-up with camrelizumab plus capecitabine (maintenance therapy). At the time of writing, her progression-free survival is more than 14 months and her quality of life is good. Thus, camrelizumab plus chemotherapy is a useful first-line treatment for HER2- and PD-L1-negative advanced gastric adenocarcinoma.
Pre-Birth and Early-Life Factors Associated With the Timing of Adiposity Peak and Rebound: A Large Population-Based Longitudinal Study
Authors: Lin Dan , Chen Didi , Huang Jun , Li Yun , Wen Xiaosa , Wang Ling , Shi Huijing 
Published: December 2021

Background: The late occurrence of adiposity peak (AP) and the early occurrence of adiposity rebound (AR) are considered the earliest indicators for obesity and its related health conditions later in life. However, there is still limited information for their upstream factors. Therefore, in this study, we aimed to identify the parental and child factors associated with the timing of AP and AR in the early stage of life.Methods: This is a population-based longitudinal study conducted in Shanghai, China. The BMI data of children born between September 2010 and October 2013 were followed from birth to 80 months. Subject-specific body mass index trajectories were fitted by non-linear mixed-effect models with natural cubic spline functions, and the individual's age at AP and AR was estimated. The generalized linear regression models were applied to identify the upstream factors of late occurrence of AP and early occurrence AR.Results: For 7,292 children with estimated AP, boys were less likely to have a late AP [adjusted risk ratio (RR) = 0.83, 95% confidence interval (CI): 0.77–0.90, p &lt; 0.001], but preterm born children had a higher risk of a late AP (adjusted RR = 1.25, 95% CI: 1.07–1.47, p &lt; 0.01). For 10,985 children with estimated AR, children with breastfeeding longer than 4 months were less likely to have an early AR (adjusted RR = 0.80, 95% CI: 0.73–0.87, p &lt; 0.001), but children who were born to advanced-age mothers and who were born small for gestational age had a higher risk of having an early AR (adjusted RR = 1.21, 95% CI: 1.07–1.36, p &lt; 0.01; adjusted RR = 1.20, 95% CI: 1.04–1.39, p = 0.01).Conclusions: Modifiable pre-birth or early-life factors associated with the timing of AP or AR were found. Our findings may help develop prevention and intervention strategies at the earliest stage of life to control later obesity and the health conditions and diseases linked to it.
Respiratory Adherence Care Enhancer Questionnaire: Identifying Self-Management Barriers of Inhalation Corticosteroids in Asthma
Authors: Visser Claire D. , Linthorst Jip M. , Kuipers Esther , Sont Jacob K. , Lacroix Joyca P. W. , Guchelaar Henk-Jan , Teichert Martina 
Published: December 2021

Introduction: Suboptimal self-management of inhaled corticosteroids (ICS) in asthma patients is frequently observed in clinical practice and associated with poor asthma control. Driving factors for suboptimal self-management are complex and consist of a range of behavioral barriers (cognitive, affective and practical) with a considerable inter-individual variability. Identification of individual barriers facilitates the use of corresponding behavior change techniques and tailored care to improve asthma treatment outcomes.Objective: This study describes the development and validation of the ‘Respiratory Adherence Care Enhancer’ (RACE) questionnaire to identify individual barriers to self-management of ICS therapy in asthma patients.Methods: The development included: 1) an inventory of self-management barriers based on a literature review, 2) expert assessment on relevance and completeness of this set, linking these barriers to behavioral domains of the Theoretical Domains Framework (TDF) and 3) the formulation of corresponding questions assessing each of the barriers. A cross-sectional study was performed for validation. Primary care asthma patients were invited to fill out the RACE-questionnaire prior to a semi-structured telephonic interview as golden standard. Barriers detected from the questionnaire were compared to those mentioned in the interview.Results: The developed questionnaire is made up of 6 TDF-domains, covering 10 self-management barriers with 23 questions. For the validation 64 patients completed the questionnaire, of whom 61 patients were interviewed. Cronbach’s alpha for the consistency of questions within the barriers ranged from 0.58 to 0.90. Optimal cut-off values for the presence of barriers were determined at a specificity between 67 and 92% with a sensitivity between 41 and 83%. Significant Areas Under the Receiver Operating Curves values were observed for 9 barriers with values between 0.69 and 0.86 (p-value &lt;0.05), except for ‘Knowledge of ICS medication’ with an insignificant value of 0.53.Conclusion: The RACE-questionnaire yields adequate psychometric characteristics to identify individual barriers to self-management of ICS therapy in asthma patients, facilitating tailored care.
Insights Into Amentoflavone: A Natural Multifunctional Biflavonoid
Authors: Xiong Xifeng , Tang Nan , Lai Xudong , Zhang Jinli , Wen Weilun , Li Xiaojian , Li Aiguo , Wu Yanhua , Liu Zhihe 
Published: December 2021

Amentoflavone is an active phenolic compound isolated fromSelaginella tamariscinaover 40 years. Amentoflavone has been extensively recorded as a molecule which displays multifunctional biological activities. Especially, amentoflavone involves in anti-cancer activity by mediating various signaling pathways such as extracellular signal-regulated kinase (ERK), nuclear factor kappa-B (NF-κB) and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), and emerges anti-SARS-CoV-2 effect via binding towards the main protease (Mpro/3CLpro), spike protein receptor binding domain (RBD) and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. Therefore, amentoflavone is considered to be a promising therapeutic agent for clinical research. Considering the multifunction of amentoflavone, the current review comprehensively discuss the chemistry, the progress in its diverse biological activities, including anti-inflammatory, anti-oxidation, anti-microorganism, metabolism regulation, neuroprotection, radioprotection, musculoskeletal protection and antidepressant, specially the fascinating role against various types of cancers. In addition, the bioavailability and drug delivery of amentoflavone, the molecular mechanisms underlying the activities of amentoflavone, the molecular docking simulation of amentoflavone throughin silicoapproach and anti-SARS-CoV-2 effect of amentoflavone are discussed.
Autoimmune Progressive Fibrosing Interstitial Lung Disease: Predictors of Fast Decline
Authors: Nagy Alexandra , Nagy Tamas , Kolonics-Farkas Abigel Margit , Eszes Noemi , Vincze Krisztina , Barczi Eniko , Tarnoki Adam Domonkos , Tarnoki David Laszlo , Nagy György , Kiss Emese , Maurovich-Horvat Pal , Bohacs Aniko , Müller Veronika 
Published: December 2021

A subset of interstitial lung diseases (ILDs) with autoimmune traits—including connective tissue disease-associated ILD (CTD-ILD) and interstitial pneumonia with autoimmune features (IPAF)—develops progressive fibrosing (PF)-ILD. The aim of our study was to evaluate the clinical characteristics and predictors of longitudinal lung function (LF) changes in autoimmune PF-ILD patients in a real-world setting. All ILD cases with confirmed or suspected autoimmunity discussed by a multidisciplinary team (MDT) between January 2017 and June 2019 (n = 511) were reviewed, including 63 CTD-ILD and 44 IPAF patients. Detailed medical history, LF test, diffusing capacity of the lung for carbon monoxide (DLCO), 6-min walk test (6MWT), blood gas analysis (BGA), and high-resolution computer tomography (HRCT) were performed. Longitudinal follow-up for functional parameters was at least 2 years. Women were overrepresented (70.1%), and the age of the IPAF group was significantly higher as compared to the CTD-ILD group (p &lt; 0.001). Dyspnea, crackles, and weight loss were significantly more common in the IPAF group as compared to the CTD-ILD group (84.1% vs. 58.7%, p = 0.006; 72.7% vs. 49.2%, p = 0.017; 29.6% vs. 4.8%, p = 0.001). Forced vital capacity (FVC) yearly decline was more pronounced in IPAF (53.1 ± 0.3 vs. 16.7 ± 0.2 ml; p = 0.294), while the majority of patients (IPAF: 68% and CTD-ILD 82%) did not deteriorate. Factors influencing progression included malignancy as a comorbidity, anti-SS-A antibodies, and post-exercise pulse increase at 6MWT. Antifibrotic therapy was administered significantly more often in IPAF as compared to CTD-ILD patients (n = 13, 29.5% vs. n = 5, 7.9%; p = 0.007), and importantly, this treatment reduced lung function decline when compared to non-treated patients. Majority of patients improved or were stable regarding lung function, and autoimmune-associated PF-ILD was more common in patients having IPAF. Functional decline predictors were anti-SS-A antibodies and marked post-exercise pulse increase at 6MWT. Antifibrotic treatments reduced progression in progressive fibrosing CTD-ILD and IPAF, emphasizing the need for guidelines including optimal treatment start and combination therapies in this special patient group.
Impact of the Pilot Volume-Based Drug Purchasing Policy in China: Interrupted Time-Series Analysis with Controls
Authors: Chen Yilin , Ji Xu , Xiao Hong , Unger Joseph M , Cai Yi , Mao Zongfu , Yeung Kai 
Published: December 2021

Centralizing procurement for prescription drugs has the potential to reduce drug spending by creating economies of scale and by improving purchasing power. In March 2019, the Chinese government launched a volume-based purchasing (VBP) pilot program using a competitive bidding process to purchase accredited generic drugs for which branded drug substitutes were available. We performed an interrupted time-series design to estimate the change in monthly drug purchase quantity and spending comparing 14 months before and 7 months after the VBP pilot. We obtained monthly prescription drug purchase data for all purchases from public medical institutions in the three large pilot cities (Beijing, Shanghai and Xi’an) and two non-pilot cities (Changsha and Zhengzhou) between January 2018 to September 2019. We used negative binomial regression and log-linked Gamma Generalized Linear Model for purchase quantity and spending respectively. We evaluated heterogeneity of impact by pilot city, drug type (selected or non-selected drugs), and therapeutic class (cardiovascular disease, mental disorder and cancer) separately. The implementation of the pilot reform was associated with a 132% (95%-CI: 104–165%, p &lt; 0.001) increase in the purchase quantity of selected drugs in pilot cities compared to an 17% decrease (95%-CI: 9–25%, p &lt; 0.001) in control cities. In contrast, the purchase quantity of branded and other drugs in pilot cities decreased by 38% (95%-CI: 27–46%, p &lt; 0.001) and 77% (95%-CI: 71–81%, p &lt; 0.001), respectively; while in control cities, these remained at similar levels. Overall, in pilot cities, there was a 35% (95%-CI: 28–41%, p &lt; 0.001) decrease in the purchase spending for all drugs in the first post-policy month, from 8.1 billion CNY estimated in the absence of VBP down to 5.3 billion CNY; in control cities, the change was negligible. The largest reduction in spending occurred for drugs for the treatment of cardiovascular diseases. The evidence suggests a positive impact of the VBP pilot in reducing overall drug spending and increasing the use of accredited generics in three pilot cities. This overall trend is not observed in two non-pilot cities. Assessments of long-term impact of the VBP policy on additional key outcomes including drug prescriptions, drug utilization, patients’ health outcomes and payments on drugs are needed.
Attention Deficit/Hyperactivity Disorder Symptoms Impair Adaptive and Social Function in Children With Autism Spectrum Disorder
Authors: Liu Yu , Wang Luxi , Xie Shu , Pan Shixu , Zhao Jingyi , Zou Mingyang , Sun Caihong 
Published: December 2021

Background: Autism spectrum disorder (ASD) often co-exists with attention deficit/hyperactivity disorder (ADHD), which may aggravate functional impairment. However, it is unclear how comorbid ADHD symptoms influence the adaptive behavior and social interaction deficits of children with ASD.Methods: The study enrolled 340 children (ranging from 2 to 14 years) with ASD, with comorbid ASD and ADHD, or with typical development (TD). A psychological evaluation involving adaptive behavior and social function was conducted using the Vineland Adaptive Behavior Scale, Second Edition (VABS-II) and the Social Responsiveness Scale (SRS).Results: There was a high prevalence of ADHD symptoms (46.6%) in children with ASD, and children with ASD + ADHD presented the worse profile of ASD symptoms. The ASD + ADHD group had higher scores on VABS and lower scores on SRS in comparison with the ASD alone group and TD group. The regression analysis revealed that ASD symptoms and ADHD symptoms were significantly associated with greater impairments in adaptive behavior and social function. The ADHD symptoms were responsible for an additional 0.8% of the variance in adaptive behavior, and 9.5% of the variance in social function.Conclusions: More severe ASD symptoms and greater impairment in adaptive function and social ability were found in children with ASD and comorbid ADHD, highlighting the need to identify ADHD comorbidities early on in children with ASD and to reduce their negative impact on functioning.
The Effects of Bipolar Disorder Risk on a Mobile Phone Keystroke Dynamics Based Biomarker of Brain Age
Authors: Zulueta John , Demos Alexander Pantelis , Vesel Claudia , Ross Mindy , Piscitello Andrea , Hussain Faraz , Langenecker Scott A. , McInnis Melvin , Nelson Peter , Ryan Kelly , Leow Alex , Ajilore Olusola 
Published: December 2021

Background: Research by our group and others have demonstrated the feasibility of using mobile phone derived metadata to model mood and cognition. Given the effects of age and mood on cognitive performance, it was hypothesized that using such data a model could be built to predict chronological age and that differences between predicted age and actual age could be a marker of pathology.Methods: These data were collected via the ongoing BiAffect study. Participants complete the Mood Disorders Questionnaire (MDQ), a screening questionnaire for bipolar disorder, and self-reported their birth year. Data were split into training and validation sets. Features derived from the smartphone kinematics were used to train random forest regression models to predict age. Prediction errors were compared between participants screening positive and negative on the MDQ.Results: Three hundred forty-four participants had analyzable data of which 227 had positive screens for bipolar disorder and 117 had negative screens. The absolute prediction error tended to be lower for participants with positive screens (median 4.50 years) than those with negative screens (median 7.92 years) (W = 508, p = 0.0049). The raw prediction error tended to be lower for participants with negative screens (median = −5.95 years) than those with positive screens (median = 0.55 years) (W = 1,037, p= 0.037).Conclusions: The tendency to underestimate the chronological age of participants screening negative for bipolar disorder compared to those screening positive is consistent with the finding that bipolar disorder may be associated with brain changes that could reflect pathological aging. This interesting result could also reflect that those who screen negative for bipolar disorder and who engaged in the study were more likely to have higher premorbid functioning. This work demonstrates that age-related changes may be detected via a passive smartphone kinematics based digital biomarker.