bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive analysis of cuproptosis-related lncRNAs in immune infiltration and prognosis in hepatocellular carcinoma
Authors: Liu Chunhua , Wu Simin , Lai Liying , Liu Jinyu , Guo Zhaofu , Ye Zegen , Chen Xiang 
Published: January 2023

Abstract
Background
Being among the most common malignancies worldwide, hepatocellular carcinoma (HCC) accounting for the third cause of cancer mortality. The regulation of cell death is the most crucial step in tumor progression and has become a crucial target for nearly all therapeutic options. Cuproptosis, a copper-induced cell death, was recently reported in Science. However, its primary function in carcinogenesis is still unclear.

Methods
Cuproptosis-related lncRNAs significantly associated with overall survival (OS) were screened by stepwise univariate Cox regression. The signature of cuproptosis-related lncRNAs for HCC prognosis was constructed by the LASSO algorithm and multivariate Cox regression. Further Kaplan–Meier analysis, proportional hazards model, and ROC analysis were performed. Functional annotation was performed using gene set enrichment analysis (GSEA). The relationship between prognostic cuproptosis-related lncRNAs and HCC prognosis was further explored by GEPIA(http://gepia.cancer-pku.cn/) online analysis tool. Finally, we used the ESTIMATE and XCELL algorithms to estimate stromal and immune cells in tumor tissue and cast each sample to infer the underlying mechanism of cuproptosis-related lncRNAs in the tumor immune microenvironment (TIME) of HCC patients.

Results
Four cuproptosis-related lncRNAs were used to construct a prognostic lncRNA signature, which was an independent factor in predicting OS in HCC patients. Kaplan–Meier curves showed significant differences in survival rates between risk subgroups (p = 0.002). At the same time, we found that the expression levels of most immune checkpoint genes increased with increasing risk scores. Tumorigenesis and immunological-related pathways were primarily enhanced in the high-risk group, as determined by GSEA. The results of drug sensitivity analysis showed that compared with patients in the high-risk group, the IC50 values of erlotinib and lapatinib were lower in patients in the low-risk group, while the opposite was true for sunitinib, paclitaxel, gemcitabine, and imatinib. We also found that elevated AL133243.2 expression was significantly associated with worse OS and disease-free survival (DFS), more advanced T stage and higher tumor grade, and reduced immune cell infiltration, suggesting that HCC patients with low AL133243.2 expression in tumor tissues may have a better response to immunotherapy.

Conclusion
Collectively, the cuproptosis-associated lncRNA signature can serve as an independent predictor to guide individual treatment strategies. Furthermore, AL133243.2 is a promising marker for predicting immunotherapy response in HCC patients. This data may facilitate further exploration of more effective immunotherapy strategies for HCC.
A gene based combination test using GWAS summary data
Authors: Zhang Jianjun , Liang Xiaoyu , Gonzales Samantha , Liu Jianguo , Gao Xiaoyi Raymond , Wang Xuexia 
Published: January 2023

AbstractBackgroundGene-based association tests provide a useful alternative and complement to the usual single marker association tests, especially in genome-wide association studies (GWAS). The way of weighting for variants in a gene plays an important role in boosting the power of a gene-based association test. Appropriate weights can boost statistical power, especially when detecting genetic variants with weak effects on a trait. One major limitation of existing gene-based association tests lies in using weights that are predetermined biologically or empirically. This limitation often attenuates the power of a test. On another hand, effect sizes or directions of causal genetic variants in real data are usually unknown, driving a need for a flexible yet robust methodology of gene based association tests. Furthermore, access to individual-level data is often limited, while thousands of GWAS summary data are publicly and freely available.ResultsTo resolve these limitations, we propose a combination test named as OWC which is based on summary statistics from GWAS data. Several traditional methods including burden test, weighted sum of squared score test [SSU], weighted sum statistic [WSS], SNP-set Kernel Association Test [SKAT], and the score test are special cases of OWC. To evaluate the performance of OWC, we perform extensive simulation studies. Results of simulation studies demonstrate that OWC outperforms several existing popular methods. We further show that OWC outperforms comparison methods in real-world data analyses using schizophrenia GWAS summary data and a fasting glucose GWAS meta-analysis data. The proposed method is implemented in an R package available athttps://github.com/Xuexia-Wang/OWC-R-packageConclusionsWe propose a novel gene-based association test that incorporates four different weighting schemes (two constant weights and two weights proportional to normal statisticZ) and includes several popular methods as its special cases. Results of the simulation studies and real data analyses illustrate that the proposed test, OWC, outperforms comparable methods in most scenarios. These results demonstrate that OWC is a useful tool that adapts to the underlying biological model for a disease by weighting appropriately genetic variants and combination of well-known gene-based tests.
Individual patient data to allow a more elaborated comparison of trial results with real-world outcomes from second-line immunotherapy in NSCLC
Authors: Ismail R. K. , Schramel F. M. N. H. , van Dartel M. , Pasmooij A. M. G. , Cramer-van der Welle C. M. , Hilarius D. L. , de Boer A. , Wouters M. W. J. M. , van de Garde E. M. W. 
Published: January 2023

Abstract
Background
Many studies have compared real-world clinical outcomes of immunotherapy in patients with metastatic non-small cell lung cancer (NSCLC) with reported outcomes data from pivotal trials. However, any differences observed could be only limitedly explored further for causation because of the unavailability of individual patient data (IPD) from trial participants. The present study aims to explore the additional benefit of comparison with IPD.

Methods
This study compares progression free survival (PFS) and overall survival (OS) of metastatic NSCLC patients treated with second line nivolumab in real-world clinical practice (n = 141) with IPD from participants in the Checkmate-057 clinical trial (n = 292). Univariate and multivariate Cox proportional hazards models were used to construct HRs for real-world practice versus clinical trial.

Results
Real-world patients were older (64 vs. 61 years), had more often ECOG PS ≥ 2 (5 vs. 0%) and were less often treated with subsequent anti-cancer treatment (28.4 vs. 42.5%) compared to trial patients. The median PFS in real-world patients was longer (3.84 (95%CI: 3.19-5.49) vs 2.30 (2.20-3.50) months) and the OS shorter than in trial participants (8.25 (6.93-13.2) vs. 12.2 (9.90-15.1) months). Adjustment with available patient characteristics, led to a shift in the hazard ratio (HR) for OS, but not for PFS (HRs from 1.13 (0.88-1.44) to 1.07 (0.83-1.38), and from 0.82 (0.66-1.03) to 0.79 (0.63-1.00), respectively).

Conclusions
This study is an example how IPD from both real-world and trial patients can be applied to search for factors that could explain an efficacy-effectiveness gap. Making IPD from clinical trials available to the international research community allows this.
Anti-IgLON5 disease complicated with rectal adenocarcinoma: a case report
Authors: Li Yi , Zhang Lili , Wang Yuzhong 
Published: January 2023

Abstract
Background
Anti-IgLON5 disease is a rare chronic autoimmune-mediated tauopathy, featured by the sleep disturbance. Several studies have described its clinical characteristics, however, the simultaneous occurrence of anti-IgLON5 disease and rectal cancer has not been reported. We described an unusual entity of anti-IgLON5 disease complicated with rectal cancer.

Case presentation
A 76-year-old man initially presented with slurred speech and limb tremors, followed by epileptic-like seizures, lethargy, and sleep apnea. IgG anti-IgLON5 antibodies were positive in both serum and cerebrospinal fluid. The patient responded well to the treatment of plasma exchange and a pulse and gradual reduction of steroids therapy. When the oral steroids started, mycophenolate mofetil was added. Two months later, the patient had bloody stools and pathological-confirmed moderately differentiated adenocarcinoma of the rectum.

Conclusions
Whereas sleep disturbance is the most common feature in patients with anti-IgLON5 disease, our case presented with slurred speech and limb tremors. Anti-IgLON5 disease complicated with rectal cancer is very rare. Tumor screening should be considered in patients with anti-IgLON5 disease to investigate the association between tumor and this disease.
Clinical characteristics and prognostic factors affecting survival after radical radiotherapy for early and late post-treatment metastatic nasopharyngeal carcinoma
Authors: Jia Guo-Dong , Sun Xue-Song , Li Xiao-Yun , Liu Sai-Lan , Yang Jin-Hao , Chen Qiu-Yan , Yuan Li , Mai Hai-Qiang 
Published: January 2023

Abstract
Objective
We compared the clinical characteristics and survival outcomes after radical radiotherapy between nasopharyngeal carcinoma (NPC) with early and late metastases based on a relatively large cohort, which provides valuable data for the planning of clinical surveillance strategies.

Methods
This was a single-center retrospective analysis of 10,566 patients who received radical radiotherapy in China from January 2000 to December 2016. Overall survival was the primary endpoint. Kaplan–Meier survival analysis and log-rank tests were applied to investigate the association between early or late metastasis and the endpoints. The prognostic value of clinicopathological features was identified using univariate and multivariate Cox proportional hazards models.

Results
The cutoff value for time to metastasis was based on ROC analysis. A total of 559 (5.3%) patients developed distant metastases, 297 (53.1%) of which developed early metastatic disease, with the rest (46.9%) developing late metastatic disease. The K-M analysis showed that the patients with late metastatic foci had significantly better post-metastatic OS (P = 0.0056). Multivariate analysis indicated that age, liver metastasis, the number of metastatic foci and time to metastasis (P = 0.013) are independent prognostic factors for OS. After analyzing the impact of different treatment methods, we found that local treatment was an independent protective factor for LM, while local treatment was not associated with a survival benefit for EM disease.

Conclusions
The time to metastasis after radical radiotherapy affected the prognosis of NPC patients and local treatment was an independent protective factor that could improve the survival of late metastatic NPC patients.
Varenicline induced auditory hallucinations in a young female with bipolar disorder: a case report
Authors: Tsang Vivian W. L. , Bhanot Saundarai , Jia Lingsa 
Published: January 2023

Abstract
Background
Creating appropriate and sustainable treatment plans for patients with concurrent disorders presents a challenge to psychiatrists and addiction medicine specialists alike. Although varenicline has been found to be the most effective medication for smoking cessation and abstinence when compared to results from placebo medications, nicotine patches and bupropion, caution is needed when starting patients on this medication. With the high prevalence of concurrent mental health and substance use disorders in vulnerably-housed populations in Canada, it becomes increasingly important to advocate for increased guidance and research into treating concurrent disorders.

Case presentation
In this case, a young female patient provisionally diagnosed with bipolar I disorder was hospitalized for a manic episode in the context of substance use and medication noncompliance. She also endorsed a long history of tobacco, alcohol, cocaine, cannabis and ketamine use. Perceptual abnormalities, including auditory hallucinations, were not recorded at admission. In addition to being stabilized for bipolar diagnosis, the patient was started on nicotine replacement therapy on Day 7 of admission followed by initiation of varenicline for smoking cessation on Day 14 of admission. Soon after the varenicline treatment was started, the patient developed auditory hallucinations, paranoia and referential beliefs. However, her insight was intact, and she had minimal thought form disorganization. In this case, these symptoms were thought to be secondary to varenicline after the consideration of potential alternative contributors.

Conclusion
The occurrence of side effects as a result of varenicline use in patients with diagnosed mental health conditions is rare and underlying psychiatric illness is not labeled as an absolute contraindication in the prescription of varenicline. However, it is important to advocate for increased guidance and research on the treatment of substance use disorders in patients with bipolar I disorder. Patients may also benefit from increased collaboration between psychiatric and addiction services as that may allow for earlier recognition and intervention of symptoms to minimize distress.
Policy to expand hospital utilization in disadvantaged areas in Indonesia: who should be the target?
Authors: Laksono Agung Dwi , Megatsari Hario , Senewe Felly Philipus , Latifah Leny , Ashar Hadi 
Published: January 2023

Abstract
Background
The disadvantaged areas are one of the government’s focuses in accelerating development in Indonesia, including the health sector. The study aims to determine the target for expanding hospital utilization in disadvantaged areas in Indonesia.

Methods
The study employed the 2018 Indonesian Basic Health Survey data. This cross-sectional study analyzed 42,644 respondents. The study used nine independent variables: residence, age, gender, marital, education, employment, wealth, insurance, and travel time, in addition to hospital utilization, as a dependent variable. The study employed binary logistic regression to evaluate the data.

Results
The results found that average hospital utilization in disadvantaged areas in Indonesia in 2018 was 3.7%. Urban areas are 1.045 times more likely than rural areas to utilize the hospital (95% CI 1.032–1.058). The study also found age has a relationship with hospital utilization. Females are 1.656 times more likely than males to use the hospital (95% CI 1.639–1.673). Moreover, the study found marital status has a relationship with hospital utilization. The higher the education level, the higher the hospital utilization. Employed individuals have a 0.748 possibility to use the hospital compared with those unemployed (95% CI 0.740–0.757). Wealthy individuals have more chances of using the hospital than poor individuals. Individuals with all insurance types are more likely to utilize the hospital than those uninsured. Individuals with travel times of ≤ 1 h are 2.510 more likely to use the hospital than those with > 1 h (95% CI 2.483–2.537).

Conclusion
The specific targets to accelerate the increase in hospital utilization in disadvantaged areas in Indonesia are living in a rural area, being male, never in a union, having no education, being employed, being the poorest, uninsured, and having a travel time of > 1 h. The government should make a policy addressing the problem based on the research findings.
Association of internalised homonegativity with partner notification after diagnosis of syphilis or gonorrhoea among men having sex with men in 49 countries across four continents
Authors: Marcus Ulrich , Jonas Kai , Berg Rigmor , Veras Maria Amelia , Caceres Carlos F. , Casabona Jordi , Schink Susanne B. , Schmidt Axel J. 
Published: January 2023

AbstractBackgroundPartner notification (PN) after a sexually transmitted infection (STI) diagnosis is being promoted as a means to interrupt transmission chains. We investigated whether Internalised Homonegativity (IH) is associated with PN among men having sex with men (MSM).MethodsPN, defined as notifying at least one partner after diagnosis of syphilis and gonorrhoea, was queried in two internet-based self-completion surveys conducted between Oct 2017 and May 2018 in 68 countries in Europe, Latin America, Canada, and the Philippines. IH is defined by a man’s level of agreement or disagreement with negative social beliefs about male homosexuality. Covariates included in a multivariate regression model with a random intercept at country level were age, HIV diagnosis, partnership status, sexual self-efficacy, HIV serostatus communication during last sex with a non-steady partner, place where this partner was met, and PN-related socio-historical background of the country of residence. We grouped countries in three areas: North- and Central-Western European countries plus Canada, former socialist countries, and Latin-American/Mediterranean countries plus the Philippines. In each of the three areas individuals were assigned to 4 subgroups based on IH quartiles and PN rates were determined for each subgroup.ResultsPN rates were calculated for 49 countries (excluding countries with less than 10 diagnoses). Mean proportions of MSM notifying their partners were 68.1% and 72.9% after syphilis and gonorrhoea diagnoses, respectively. PN rates were lower in Latin American countries and the Philippines compared to European countries. Within Europe, a North–South divide with lower PN rates in Mediterranean countries was observed. In each of the three regions we mostly observed a stepwise increase of PN rates with decreasing IH.Regression analysis showed lower IH scores associated with higher PN rates. Higher perceived self-efficacy, living in a partnership, and HIV status communication were positively associated with PN. Men who had met their last partner in a gay social venue were more likely to have notified their partners of a syphilis diagnosis compared to men who had met this partner online. Men with diagnosed HIV were less likely to report PN.ConclusionsWe could demonstrate that IH was associated with PN among MSM across all countries included in our analysis. Reducing cultural homophobia and ensuring inclusive policies may contribute to STI prevention and control.
Relationship between BMI and risk of impaired glucose tolerance and impaired fasting glucose in Chinese adults: a prospective study
Authors: Zhang Xin , Yue Yankun , Liu Shaobo , Cong Xiangfeng , Wang Wenjuan , Li Jianhong 
Published: January 2023

Abstract
Background
Current studies in most Western countries have largely focused on body mass index (BMI) as an important risk factor for impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), which have different pathophysiological bases. In people with obesity, the prevalence of IGT is higher and the prevalence of IFG is lower. The prevalence of IGT in the Asian population is higher than that in the white population, and the obesity rate in China is still increasing. However, few cohort studies explore the relationship between BMI and the incidence of IGT and IFG in China. We aimed to explore the relationship between BMI and the risk of IGT and IFG in Chinese adults and analyze the differences between them.

Methods
The baseline data were obtained from the 2010 China Chronic Disease and Risk Factor Surveillance, of which 20 surveillance sites were followed up from 2016 to 2017. Finally, in this study, a total of 5,578 studies were grouped into BMI categories of underweight (BMI < 18.5 kg/m2), normal weight (18.5–23.9 kg/m2), overweight (24.0–27.9 kg/m2), and obesity (≥ 28.0 kg/m2). We used the unconditional logistic regression model to analyze the relationship between BMI and the risk of IGT and IFG.

Results
During an average follow-up of 6.4 years, 562 developed IGT and 257 developed IFG. After age, gender, urban and rural areas, physical activity, family history of diabetes, hypertension, abdominal obesity, dyslipidemia, and other factors were adjusted, overweight increased the risk of IGT by 35% [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.08–1.70], and obesity increased the risk of IGT by 77% (OR 1.77, 95% CI 1.27–1.47). After the factors consistent with the above were adjusted, only obesity increased the risk of IFG by 122% (OR 2.22, 95% CI 1.39–3.54).

Conclusions
In China, obesity is an important risk factor for IGT and IFG, and the risk of IGT increases during the overweight stage.
Technical aspects of virtual augmented reality-based rehabilitation systems for musculoskeletal disorders of the lower limbs: a systematic review
Authors: Kiani Shamim , Rezaei Iman , Abasi Sanaz , Zakerabasali Somayyeh , Yazdani Azita 
Published: January 2023

AbstractIntroductionMusculoskeletal disorders are one of the most common causes of physical disability. The rehabilitation process after musculoskeletal disorders is long and tedious, and patients are not motivated to follow rehabilitation protocols. Therefore, new systems must be used to increase patient motivation. Virtual reality (VR) and augmented reality (AR) technologies can be used in this regard. In developing such systems, various technologies and methods of movement recognition are used; therefore, this study aims to summarize the technical aspects of using VR/AR in rehabilitation and evaluate and discuss efficient methods of investigating studies using the Statement of Standards for Reporting Implementation Studies (StaRI).MethodsSearch in four scientific databases was done systematically based on PRISMA through online search engines from inception to June 2021. These databases include Medline (PubMed), Scopus, IEEE, and Web of Science. An updated search was also conducted on 17 December 2021. The research used keywords and MeSH terms associated with VR/AR, musculoskeletal disorder, and rehabilitation. Selected articles were evaluated qualitatively using the Standards for Reporting Implementation Studies (StaRI) statement.ResultsA total of 2343 articles were found, and 20 studies were included. We found that 11 (55%) studies used Kinect technology as input tools, and 15 (75%) studies have described the techniques used to analyze human movements, such as dynamic time warping (DTW) and support vector machines (SVM). In 10 (50%) studies, the Unity game engine was used for visualization. In 8 studies (40%), usability was assessed, and high usability was reported. Similarly, the results of the review of studies according to the StaRI checklist showed poor reporting in the title and discussion of the studies.ConclusionsWe found that academic studies did not describe the technical aspects of rehabilitation systems. Therefore, a good description of the technical aspects of the system in such studies should be considered to provide repeatability and generalizability of these systems for investigations by other researchers.