bluuebunny/crossref_metadata_2025_split huggingface dataset:
A liquid biopsy signature of circulating exosome-derived mRNAs, miRNAs and lncRNAs predict therapeutic efficacy to neoadjuvant chemotherapy in patients with advanced gastric cancer
Authors: Guo Ting , Tang Xiao-Huan , Gao Xiang-Yu , Zhou Yuan , Jin Bo , Deng Zi-Qian , Hu Ying , Xing Xiao-Fang , Li Zi-Yu , Ji Jia-Fu 
Published: December 2022

AbstractAt present, there is no validated marker to identify the subpopulation of patients with advanced gastric cancer (AGC) who might benefit from neoadjuvant chemotherapy (NACT). In view of this clinical challenge, the identification of non-invasive biomarkers for efficacy prediction of NACT in patients with AGC is imperative. Herein, we aimed to develop a non-invasive, liquid-biopsy-based assay by using an exosome-derived RNAs model based on multi-omics characteristics of RNAs. We firstly used a multi-omics strategy to characterize the mRNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) profiles of circulating exosome enriched fractions in responders to NACT paired with non-responders, using RNA sequencing. Finally, numerous miRNAs, mRNAs and lncRNAs were identified to be associated with the response to NACT in patients with AGC, and it was validated in an independent cohort with promising AUC values. Furthermore, we established a 6-exosome-RNA panel that could robustly identified responders from non-responders treated with fluorouracil-based neoadjuvant chemotherapy.
Prognostic value of elastic lamina staining in patients with stage III colon cancer
Authors: Bi Feifei , Li Xiaoyan , Zhang Yong , Wang Zekun , Dong Qian , Zhang Jingdong , Sun Deyu 
Published: December 2022

Abstract
Objective
The objectives of this study were to analyze the difference between the preoperative radiological and postoperative pathological stages of colorectal cancer (CRC) and explore the feasibility of elastic lamina invasion (ELI) as a prognostic marker for patients with stage III colon cancer.

Methods
A total of 105 consecutive patients underwent radical surgery (R0 resection) for stage III colon cancer at the Cancer Hospital of China Medical University between January 2015 and December 2017. Clinicopathological features, including radiological stage and elastic lamina staining, were analyzed for prognostic significance in stage III colon cancer.

Results
A total of 105 patients with stage III colon cancer who met the criteria and had complete data available were included. The median follow-up period of survivors was 41 months. During the follow-up period, 33 (31.4%) patients experienced recurrence after radical resection, and the 3-year disease-free survival (DFS) rate was 64.8%. The consistency between preoperative radiological and postoperative pathological staging was poor (κ = 0.232, P < 0.001). The accuracy of ≤ T2 stage diagnoses was 97.1% (102/105), that of T3 stage was 60.9% (64/105), that of T4a stage was 68.6% (72/105) and that of T4b stage was 91.4% (96/105). The DFS rate of T3 ELI (+) patients was significantly lower than that of both T3 ELI (−) patients (P = 0.000) and pT4a patients (P = 0.013). The DFS rate of T3 ELI (−) patients was significantly higher than that of pT4b patients (P=0.018). T3 ELI (+) (HR (Hazard ratio), 8.444 [95% CI, 1.736–41.067]; P = 0.008), T4b (HR, 57.727[95% CI, 5.547-600.754]; P = 0.001), N2 stage (HR, 10.629 [95% CI, 3.858–29.286]; P < 0.001), stage III (HR, 0.136 [95% CI, 0.31–0.589]; P = 0.008) and perineural invasion (PNI) (HR, 8.393 [95% CI, 2.094–33.637]; P = 0.003) were independent risk factors for postoperative recurrence of stage III colon cancer.

Conclusions
The consistency between preoperative radiological and postoperative pathological staging was poor, especially for tumors located in the ascending colon and descending colon. Elastic lamina staining is expected to become a stratified indicator of recurrence risk for patients with stage III colon cancer and a guide for individualized adjuvant chemotherapy, thus improving patient prognosis.
Comparative single-center study between modified laparoscopic radical hysterectomy and open radical hysterectomy for early-stage cervical cancer
Authors: Li Xuqing , Pei Xueting , Li Hongyan , Wang Yan , Zhou Youwei , Wei Zhaolian , Yin Zongzhi 
Published: December 2022

Abstract
Background
Since the release of the LACC trial results in 2018, the safety of laparoscopic radical hysterectomy (LRH) for cervical cancer has received huge attention and heated discussion. We developed modified laparoscopic radical hysterectomy (MLRH) incorporating a series of measures to prevent tumor spillage, which has been performed in our center since 2015.

Objective
Present study retrospectively analyzed relevant indicators of MLRH and evaluated disease-free survival (DFS) primarily in the treatment of early cervical cancer compared with open surgery.

Methods
Patients with 2014 International Federation of Gynecology and Obstetrics clinical stages 1B1 and 2A1 cervical cancer who underwent radical hysterectomy in the gynecological department of our hospital from October 2015 to June 2018 were enrolled retrospectively in this study. Patients were divided into two groups based on the surgical procedure: open radical hysterectomy (ORH) group (n = 336) and MLRH group (n = 302). Clinical characteristics, surgical indices, and survival prognosis were analyzed, including 2.5-year overall survival (OS) rate, 2.5-year DFS rate, recurrence rate, and recurrence pattern.

Results
Compared to the ORH group, the MLRH group exhibited a longer operative time, longer normal bladder function recovery time, less intraoperative blood loss volume, and more harvested pelvic lymph nodes (P < 0.05). No significant differences were observed in postoperative complications, the 2.5-year OS, 2.5-year DFS, and recurrence rate between the two groups (P > 0.05); however, the recurrence pattern was significantly different (P < 0.05). The MLRH group mainly exhibited local single metastasis (7/11), whereas the ORH group mainly exhibited distant multiple metastases (14/16). Stratified analysis revealed that overall survival rate was higher in the MLRH group than in the ORH group in patients with stage 1B1 and middle invasion (P < 0.05).

Conclusion
MLRH does not show a survival disadvantage in the treatment of early-stage cervical cancer when compared with open surgery. In addition, MLRH shows a survival advantage in patients with stage 1B1 and middle 1/3 invasion. Considering this is a retrospective study, further prospective study is necessary for more sufficient data support.

Trial registration
Present research is a retrospective study. The study had retrospectively registered on Chinese Clinical Trial Registry (http://www.chictr.org.cn/), and the registered number is ChiCTR1900026306.
Association between physical activity and cancer risk among Chinese adults: a 10-year prospective study
Authors: Su Jian , Jiang Yuchen , Fan Xikang , Tao Ran , Wu Ming , Lu Yan , Hua Yujie , Jin Jianrong , Guo Yu , Lv Jun , Pei Pei , Chen Zhengming , Li Liming , Zhou Jinyi 
Published: December 2022

Abstract
Background
In China, the quantity of physical activity differs from that in Western countries. Substantial uncertainty remains about the relevance of physical activity for cancer subtypes among Chinese adults.

Objective
This study aimed to investigate the association between total daily physical activity and the incidence of common types of cancer.

Methods
A total of 53,269 participants aged 30–79 years were derived from the Wuzhong subcohort of the China Kadoorie Biobank study during 2004–2008. We included 52,938 cancer-free participants in the final analysis. Incident cancers were identified through linkage with the health insurance system and death registries. Cox proportional hazard models were introduced to assess the associations of total daily physical activity with the incidence of 6 common types of cancer.

Results
During a follow-up of 10.1 years, 3,674 cases of cancer were identified, including 794 (21.6%) from stomach cancer, 722 (19.7%) from lung cancer, 458 (12.5%) from colorectal cancer, 338 (9.2%) from liver cancer, 250 (6.8%) from breast cancer, and 231 (6.3%) from oesophageal cancer. Compared to the participants in the lowest quartile of physical activity levels, those in the highest quartile had an 11% lower risk for total cancer incidence (hazard ratio [HR]: 0.89, 95% confidence interval [CI]: 0.81–0.99), 25% lower risk for lung cancer incidence (HR: 0.75, 95% CI: 0.60–0.94), and 26% lower risk for colorectal cancer incidence (HR: 0.74, 95% CI: 0.55–1.00). There were significant interactions of physical activity with sex and smoking on total cancer (both P for interaction < 0.005), showing a lower risk for females and never smokers (HR: 0.92, 95% CI: 0.87–0.98 and HR: 0.93, 95% CI: 0.87–0.98, respectively).

Conclusions
Higher physical activity levels are associated with a reduced risk of total, lung, and colorectal cancer.
Genome-wide association study reveals ethnicity-specific SNPs associated with ankylosing spondylitis in the Taiwanese population
Authors: Ko Ching-Lung , Lin Wei-Zhi , Lee Meng-Ting , Chang Yu-Tien , Lin Hung-Che , Wu Yi-Syuan , Lin Jun-Fu , Pan Ke-Ting , Chang Yu-Chuan , Lee Ko-Han , Lee Yi-Lun , Hsieh Tsung-Ting , Huang Jia-Hsin , Wang Chih-Hung , Yang Sung-Sen , Chen Hsiang-Cheng , Chu Chi-Ming 
Published: December 2022

Abstract
Background
Ankylosing spondylitis (AS) is an autoimmune disease affecting mainly spine and sacroiliac joints and adjacent soft tissues. Genome-wide association studies (GWASs) are used to evaluate genetic associations and to predict genetic risk factors that determine the biological basis of disease susceptibility.
We aimed to explore the race-specific SNP susceptibility of AS in Taiwanese individuals and to investigate the association between HLA-B27 and AS susceptibility SNPs in Taiwan.

Methods
Genotyping data were collected from a medical center participating in the Taiwan Precision Medicine Initiative (TPMI) in the northern district of Taiwan. We designed a case–control study to identify AS susceptibility SNPs through GWAS. We searched the genome browser to find the corresponding susceptibility genes and used the GTEx database to confirm the regulation of gene expression. A polygenic risk score approach was also applied to evaluate the genetic variants in the prediction of developing AS.

Results
The results showed that the SNPs located on the sixth chromosome were related to higher susceptibility in the AS group. There was no overlap between our results and the susceptibility SNPs found in other races. The 12 tag SNPs located in the MHC region that were found through the linkage disequilibrium method had higher gene expression. Furthermore, Taiwanese people with HLA-B27 positivity had a higher proportion of minor alleles. This might be the reason that the AS prevalence is higher in Taiwan than in other countries. We developed AS polygenic risk score models with six different methods in which those with the top 10% polygenic risk had a fivefold increased risk of developing AS compared to the remaining group with low risk.

Conclusion
A total of 147 SNPs in the Taiwanese population were found to be statistically significantly associated with AS on the sixth pair of chromosomes and did not overlap with previously published sites in the GWAS Catalog. Whether those genes mapped by AS-associated SNPs are involved in AS and what the pathogenic mechanism of the mapped genes is remain to be further studied.
Impact of disease-modifying therapy on dendritic cells and exploring their immunotherapeutic potential in multiple sclerosis
Authors: Liu Caiyun , Zhu Jie , Mi Yan , Jin Tao 
Published: December 2022

AbstractDendritic cells (DCs) are the most potent professional antigen-presenting cells (APCs), which play a pivotal role in inducing either inflammatory or tolerogenic response based on their subtypes and environmental signals. Emerging evidence indicates that DCs are critical for initiation and progression of autoimmune diseases, including multiple sclerosis (MS). Current disease-modifying therapies (DMT) for MS can significantly affect DCs’ functions. However, the study on the impact of DMT on DCs is rare, unlike T and B lymphocytes that are the most commonly discussed targets of these therapies. Induction of tolerogenic DCs (tolDCs) with powerful therapeutic potential has been well-established to combat autoimmune responses in laboratory models and early clinical trials. In contrast to in vitro tolDC induction, in vivo elicitation by specifically targeting multiple cell-surface receptors has shown greater promise with more advantages. Here, we summarize the role of DCs in governing immune tolerance and in the process of initiating and perpetuating MS as well as the effects of current DMT drugs on DCs. We then highlight the most promising cell-surface receptors expressed on DCs currently being explored as the viable pharmacological targets through antigen delivery to generate tolDCs in vivo.
Effect of a communication intervention on alcohol use during pregnancy in post conflict Northern Uganda: a quasi experimental study
Authors: Agiresaasi Apophia , Nassanga Goretti , Maina Gakenia Wamuyu , Kiguli Juliet , Nabiwemba Elizabeth , Kiwanuka Noah , Mukose Aggrey , Tumwesigye Nazarius Mbona 
Published: December 2022

AbstractBackgroundAlcohol use during pregnancy is a preventable risk factor for Fetal Alcohol Spectrum disorders. Psycho-social and educational interventions have been reported to enable women reduce alcohol intake levels during pregnancy and help improve some health outcomes of unhealthy alcohol use. We set out to assess the effect of a communication intervention on alcohol use during pregnancy in post conflict northern Uganda.MethodsThe study employed a quasi - experimental design to assess the effect of a community health worker led communication strategy on pregnant women’s knowledge, attitudes and various patterns of alcohol use using Difference in Difference(DiD). 420 respondents were recruited at baseline as at endline.ResultsThe communication messages were significantly associated with reduced odds of binge drinking (P = 0.018; OR = 0.09; CI = 0.012–0.66). Also those who received the intervention were less likely to drink frequently (P = 0.80; OR = 0.75; 95%CI = 0.074–7.5) or be harmful alcohol users(P = 0.948). The intervention also positively influenced having fair (β =0.49;P = 0.217;RRR =1.63)or adequate knowledge(β = 0.89;P = 0.25;RRR = 2.44) and having positive(β = 0.37;RRR =1.44;P = 0.46) or fair attitude(β = 0.19;RRR = 1.21;P = 0.693) although not to a significant level.ConclusionsThe communication intervention affected some patterns of alcohol use among pregnant women and not others. Our results contribute to existing evidence that communication interventions are a promising approach in reduction of alcohol exposed pregnancies. Interventions aimed at promoting alcohol abstinence during pregnancy should be implemented alongside other strategies that address factors that influence pregnant women to drink to achieve maximum results.
Thoracic injuries in trauma patients: epidemiology and its influence on mortality
Authors: Lundin Andrea , Akram Shahzad K. , Berg Lena , Göransson Katarina E. , Enocson Anders 
Published: December 2022

Abstract
Background
Thoracic injuries are common among trauma patients. Studies on trauma patients with thoracic injuries have reported considerable differences in morbidity and mortality, and there is limited research on comparison between trauma patients with and without thoracic injuries, particularly in the Scandinavian population. Thoracic injuries in trauma patients should be identified early and need special attention since the differences in injury patterns among patient population are important as they entail different treatment regimens and influence patient outcomes. The aim of the study was to describe the epidemiology of trauma patients with and without thoracic injuries and its influence on 30-day mortality.

Methods
Patients were identified through the Karolinska Trauma Register. The Abbreviated Injury Scale (AIS) system was used to find patients with thoracic injuries. Logistic regression analysis was performed to evaluate factors [age, gender, ASA class, GCS (Glasgow Coma Scale), NISS (New Injury Severity Score) and thoracic injury] associated with 30-day mortality.

Results
A total of 2397 patients were included. Of those, 768 patients (32%) had a thoracic injury. The mean (± SD, range) age of all patients (n = 2397) was 46 (20, 18–98) years, and the majority (n = 1709, 71%) of the patients were males. There was a greater proportion of patients with rib fractures among older (≥ 60 years) patients, whereas younger patients had a higher proportion of injuries to the internal thoracic organs. The 30-day mortality was 11% (n = 87) in patients with thoracic injury and 4.3% (n = 71) in patients without. After multivariable adjustment, a thoracic injury was found to be associated with an increased risk of 30-day mortality (OR 1.9, 95% CI 1.3–3.0); as was age ≥ 60 years (OR 3.7, 95% CI 2.3–6.0), ASA class 3–4 (OR 2.3, 95% CI 1.4–3.6), GCS 1–8 (OR 21, 95% CI 13–33) and NISS > 15 (OR 4.2, 2.4–7.3).

Conclusion
Thoracic injury was an independent predictor of 30-day mortality after adjustment for relevant key variables. We also found a difference in injury patterns with older patients having a higher proportion of rib fractures, whilst younger patients suffered more internal thoracic organ injuries.
Analysis and comparison of web searches in Google Trends in the business and industrial category for the word’s “resilience” and “wellbeing" during COVID-19
Authors: Truong Hang , McLachlan Craig Steven 
Published: December 2022

AbstractObjectiveThe comparison of Google internet searches for worker wellbeing and resilience during COVID has not previously been undertaken. It is important to understand interest in wellbeing and resilience as both constructs influence health and burnout. Our objective to investigate internet interest in both wellbeing and resilience during COVID. Using Google Trends, data on global search English word queries we compared “worker wellbeing” or “wellbeing” versus “resilience” or “psychological resilience”. Two time periods were compared, the last 5 years and the last 12 months, both up until the end of April 2022. The relationship between web search interest, reflected by search volume index (SVI) for all categories versus the business and industrial category evaluated.ResultsOpen category searches on Google trends for the key words “worker wellbeing” or “wellbeing” demonstrated increased SVI peaks for COVID periods. Sub-group analyses demonstrated the category business and industrial had less web search interest in wellbeing and an increase in search terms related to resilience but not psychological resilience. Online interest in wellbeing and resilience represents a complex search metric. There are differing search interests depending on whether the category business and industrial is chosen versus the general Google Trends category.
The impact of Hyssop (Hyssopus officinalis) extract on activation of endosomal toll like receptors and their downstream signaling pathways
Authors: Ghasempour Masoumeh , Hosseini Maryam , Soltani-Zangbar Mohammad Sadegh , Motavalli Roza , Aghebati-Maleki Leili , Dolati Sanam , Mehdizadeh Amir , Yousefi Mehdi , Ahmadian Heris Javad 
Published: December 2022

Abstract
Objectives
From the ancient, medicinal benefits of Hyssop (Hyssopus officinalis L.) have been implicated for respiratory and digestive diseases despite the effects of Hyssop on viral infections have not been mechanistically investigated. In this study, we examined whether the Hyssop extract activated anti-viral innate immunity, as a sentinel for immune system, through activation of endosomal TLRs recognizing nucleic acids and their downstream signaling. The Hyssop herb extracts was prepared and co-cultured with healthy individual’s peripheral blood mononuclear cells (PBMCs). After viability assay, gene expression levels of TLR3,7,8,9, as well as MyD88 and NF-κB, were evaluated in treated PBMCs using Real-time PCR. Next, the secretion level of immune related cytokines was quantified via ELISA.

Results
Post 24 h, 40 µg/ml of the extract significantly inhibited the viability of less than 50% of cells compared to the control and had a maximum effect on cellular function. The Hyssop-treated PBMCs demonstrated an elevated expression of endosomal TLRs genes, as well as MyD88 and NF-κB. Moreover, the release of INF-α and β notably enhanced in cell culture supernatant, while the content of inflammatory cytokines remarkably diminished (P < 0.05). The Hyssop extract was capable of inducing antiviral innate immune responses so can be promising in antiviral drug strategies.
Underlying IPEX syndrome in a patient with idiopathic juvenile arthritis and vitiligo
Authors: Mendonça Leonardo Oliveira , dos Reis Chuster Adriana Pitchon , Dorna Mayra Barros , Barros Samar Freschi , Alves Janaina Baptista , Gonçalves Victor Lucas , Yang Ariana Campos , Kalil Jorge , Toledo-Barros Myrthes Anna Maragna , Kokron Cristina Maria 
Published: December 2022

Abstract
Background
IPEX syndrome is an X-linked inborn error of immunity clinically characterized by the triad of: enteropathy, polyendocrinopathy and eczema. However many other clinical presentations lacking the triad above described have been reported what underpin the need of careful clinical suspicion, immunological evaluation and genetic sequencing.

Case presentation
Here we report a case of a Brazilian boy with severe eczema as the first and only presentation requiring cyclosporin therapy. Progressive and cumulative symptoms of arthritis and enteropathy lead to the suspicion of an inborn error of immunity. Peripheral FOXP3 expression was normal (CD127−/CD4+/CD25+/FOXP3+—396 cells—63%) and a pathogenic mutation in FOXP3 gene (c.1150G>A; p.Ala384Thr), confirmed the diagnosis of IPEX syndrome.

Conclusions
IPEX syndrome should be suspected in patients presenting with severe eczema associated or not with other autoimmune/hyper inflammatory diseases in life. Our study also reinforces that FOXP3 expression by flowcytometry seems not to be a good screening method, and genetic sequencing is mandatory even in those with high suspicion and normal peripheral FOXP3 expression.
ReMODE: a deep learning-based web server for target-specific drug design
Authors: Wang Mingyang , Wang Jike , Weng Gaoqi , Kang Yu , Pan Peichen , Li Dan , Deng Yafeng , Li Honglin , Hsieh Chang-Yu , Hou Tingjun 
Published: December 2022

AbstractDeep learning (DL) and machine learning contribute significantly to basic biology research and drug discovery in the past few decades. Recent advances in DL-based generative models have led to superior developments in de novo drug design. However, data availability, deep data processing, and the lack of user-friendly DL tools and interfaces make it difficult to apply these DL techniques to drug design. We hereby present ReMODE (Receptor-based MOlecular DEsign), a new web server based on DL algorithm for target-specific ligand design, which integrates different functional modules to enable users to develop customizable drug design tasks. As designed, the ReMODE sever can construct the target-specific tasks toward the protein targets selected by users. Meanwhile, the server also provides some extensions: users can optimize the drug-likeness or synthetic accessibility of the generated molecules, and control other physicochemical properties; users can also choose a sub-structure/scaffold as a starting point for fragment-based drug design. The ReMODE server also enables users to optimize the pharmacophore matching and docking conformations of the generated molecules. We believe that the ReMODE server will benefit researchers for drug discovery. ReMODE is publicly available at http://cadd.zju.edu.cn/relation/remode/.
Graphical Abstract