bluuebunny/crossref_metadata_2025 huggingface dataset:
The correlation between different antihypertensive treatments and prognosis of cardiovascular disease in hypertensive patients
Authors: Liu Shengnan , Li Fei , Zhang Chao , Wei Baozhu , Wan Jing , Shao Hua
Published: July 2023

Objective

To determine the association between different antihypertensive regimens and cardiovascular disease (CVD) outcomes in hypertensive patients.

Method

This single center retrospective cohort study analyzed 602 hypertensive patients with complete medical records at Zhongnan Hospital of Wuhan University, China, from January 2016 to November 2022. Baseline data and follow-up data of the included patients were collected, including demographic and clinical characteristics and laboratory results.

Results

During the 5-year follow-up period, CVD outcomes occurred in 244 hypertensive patients (40.53%). Compared with patients receiving regular antihypertensive treatment, the incidence of adverse cardiovascular events in patients receiving irregular antihypertensive treatment was significantly higher (62 [55.86%] vs 182 [37.07%], HR 1.642, 95% CI 1.227–2.197, p < 0.001). In subgroup analysis, the results showed that the incidence of CVD was not identical (χ2 = 9.170, p = 0.010). The incidence of adverse cardiovascular events was highest in the single-drug antihypertensive treatment group (43.60%), followed by the multi-drug combination group (41.51%), and lowest in the two-drug combination group (29.58%). Kaplan–Meier curve showed that hypertensive patients treated with two-drug combination antihypertensive had longer overall survival time. We further compared the incidence of CVD between standard blood pressure and intensive blood pressure control, and found no significant difference in the incidence of adverse cardiovascular events between treatment to a systolic blood pressure (SBP) target of less than 140 mmHg compared with a SBP target of less than 120 mmHg (105 [43.93%] vs 35 [29.66%], HR 1.334, 95% CI 0.908–1.961, p = 0.142).

Conclusion

The incidence of adverse cardiovascular events was significantly different among different antihypertension treatments. Kaplan–Meier survival curve showed that hypertensive patients receiving two-drug combination antihypertensive treatment had longer overall survival time.
Evaluation of Bayesian spatiotemporal infectious disease models for prospective surveillance analysis
Authors: Kim Joanne , Lawson Andrew B. , Neelon Brian , Korte Jeffrey E. , Eberth Jan M. , Chowell Gerardo
Published: July 2023

Background

COVID-19 brought enormous challenges to public health surveillance and underscored the importance of developing and maintaining robust systems for accurate surveillance. As public health data collection efforts expand, there is a critical need for infectious disease modeling researchers to continue to develop prospective surveillance metrics and statistical models to accommodate the modeling of large disease counts and variability. This paper evaluated different likelihoods for the disease count model and various spatiotemporal mean models for prospective surveillance.

Methods

We evaluated Bayesian spatiotemporal models, which are the foundation for model-based infectious disease surveillance metrics. Bayesian spatiotemporal mean models based on the Poisson and the negative binomial likelihoods were evaluated with the different lengths of past data usage. We compared their goodness of fit and short-term prediction performance with both simulated epidemic data and real data from the COVID-19 pandemic.

Results

The simulation results show that the negative binomial likelihood-based models show better goodness of fit results than Poisson likelihood-based models as deemed by smaller deviance information criteria (DIC) values. However, Poisson models yield smaller mean square error (MSE) and mean absolute one-step prediction error (MAOSPE) results when we use a shorter length of the past data such as 7 and 3 time periods. Real COVID-19 data analysis of New Jersey and South Carolina shows similar results for the goodness of fit and short-term prediction results. Negative binomial-based mean models showed better performance when we used the past data of 52 time periods. Poisson-based mean models showed comparable goodness of fit performance and smaller MSE and MAOSPE results when we used the past data of 7 and 3 time periods.

Conclusion

We evaluate these models and provide future infectious disease outbreak modeling guidelines for Bayesian spatiotemporal analysis. Our choice of the likelihood and spatiotemporal mean models was influenced by both historical data length and variability. With a longer length of past data usage and more over-dispersed data, the negative binomial likelihood shows a better model fit than the Poisson likelihood. However, as we use a shorter length of the past data for our surveillance analysis, the difference between the Poisson and the negative binomial models becomes smaller. In this case, the Poisson likelihood shows robust posterior mean estimate and short-term prediction results.
Comparison of discrimination and calibration performance of ECG-based machine learning models for prediction of new-onset atrial fibrillation
Authors: Baj Giovanni , Gandin Ilaria , Scagnetto Arjuna , Bortolussi Luca , Cappelletto Chiara , Di Lenarda Andrea , Barbati Giulia
Published: July 2023

Background

Machine learning (ML) methods to build prediction models starting from electrocardiogram (ECG) signals are an emerging research field. The aim of the present study is to investigate the performances of two ML approaches based on ECGs for the prediction of new-onset atrial fibrillation (AF), in terms of discrimination, calibration and sample size dependence.

Methods

We trained two models to predict new-onset AF: a convolutional neural network (CNN), that takes as input the raw ECG signals, and an eXtreme Gradient Boosting model (XGB), that uses the signal’s extracted features. A penalized logistic regression model (LR) was used as a benchmark. Discrimination was evaluated with the area under the ROC curve, while calibration with the integrated calibration index. We investigated the dependence of models’ performances on the sample size and on class imbalance corrections introduced with random under-sampling.

Results

CNN's discrimination was the most affected by the sample size, outperforming XGB and LR only aroundn = 10.000 observations. Calibration showed only a small dependence on the sample size for all the models considered.

Balancing the training set with random undersampling did not improve discrimination in any of the models. Instead, the main effect of imbalance corrections was to worsen the models’ calibration (for CNN, integrated calibration index from 0.014 [0.01, 0.018] to 0.17 [0.16, 0.19]).

The sample size emerged as a fundamental point for developing the CNN model, especially in terms of discrimination (AUC = 0.75 [0.73, 0.77] whenn = 10.000, AUC = 0.80 [0.79, 0.81] whenn = 150.000). The effect of the sample size on the other two models was weaker. Imbalance corrections led to poorly calibrated models, for all the approaches considered, reducing the clinical utility of the models.

Conclusions

Our results suggest that the choice of approach in the analysis of ECG should be based on the amount of data available, preferring more standard models for small datasets. Moreover, imbalance correction methods should be avoided when developing clinical prediction models, where calibration is crucial.
KLHL3-dependent WNK4 degradation affected by potassium through the neddylation and autophagy pathway
Authors: Ying Siqi , Guo Qin , Zhang Chong
Published: July 2023

Background

Studies reported that kelch-like protein 3 (KLHL3)-Cullin3(CUL3) E3 ligase ubiquitinated with-no-lysine kinase 4 (WNK4). Impaired WNK4 ubiquitination plays a key role in Familial hyperkalemic hypertension (FHHt, also called pseudohypoaldosteronism type II) which results from overaction of thiazide-sensitive sodium chloride cotransport (NCC). In addition, researchers have also found that dietary potassium deficiency activates NCC along the renal distal convoluted tubule (DCT). However, the underlying mechanism remains unclear about the relationship between potassium and WNK4.

Methods

In the present study, we conducted in vitro and in vivo experiments to confirm that KLHL3-dependent WNK4 degradation is affected by potassium through the neddylation and autophagy pathway. In vitro, the WNK4 and KLHL3 plasmids were cotransfected into HEK293 cell lines by lipofectamine 2000, and then incubated with different potassium concentrations (1mmol/L and 10mmol/L) for 24 h, and further treated with MLN4924 or the autophagy inhibitor or both of MLN4924 and the autophagy inhibitor for another 24 h respectively. In vivo, we created mice that were fed with low or high potassium diets and then were injected MLN4924 in the experimental groups. The expression of WNK4, pWNK4, KLHL3, NEDD8, LC3 ,and P62 was detected by western blotting in vitro and vivo experiments.

Results

We found that the abundance and phosphorylation of WNK4 increase when neddylation is inhibited both in vitro and vivo. Furthermore, the abundance of pWNK4, WNK4, NEDD8, and KLHL3 was increased in the low potassium (LK) group. Inhibiting autophagy can ameliorate the effect of potassium on the abundance and activity of WNK4 to some extent.

Conclusion

These findings suggest a complex regulation of potassium in the degradation of WNK4. Low potassium can activate WNK4, which may be related to neddylation and autophagy, but the mechanism needs to be further studied.
An examination of the factors associated with male partner attendance in antenatal care in India
Authors: Paul Pooja L. , Pandey Shanta
Published: July 2023

Background

A growing body of literature indicates that including male partners in antenatal care can be instrumental to improving women’s health service utilization and maternal and child health outcomes. Despite this, very few studies have documented overall trends in male partner attendance and what factors influence this involvement within the Indian context. In this study, we used nationally representative data to examine levels of male partner attendance in antenatal care and the factors associated with male partner attendance.

Methods

Data were used from the National Family Health Survey (NFHS-4) conducted in 2015-16. Weighted (probability weights) descriptive statistics were conducted to summarize the level of male partner attendance in antenatal care in India, and multivariable logistic regression models were constructed to estimate the factors associated with male partner attendance in antenatal care.

Results

In 2015, of the women who had attended at least one antenatal care contact during their pregnancy, about 85% reported that their male partners had accompanied them to antenatal care contacts, with variations across regions. Level of education, household wealth, knowledge of pregnancy-related issues, men’s age at marriage, region, and women’s level of autonomy emerged as significant predictors of male partner attendance in antenatal care.

Conclusions

The results of this study highlight the multiple influences that shape male partners’ attendance in antenatal care. The findings underscore the need for a multi-faceted approach to programs and interventions aimed at encouraging male partner involvement; recognizing men both as individuals, as well as being situated within the family/household and community.
Patient-derived organoids for precision oncology: a platform to facilitate clinical decision making
Authors: Chitrangi Swati , Vaity Pooja , Jamdar Aishwarya , Bhatt Shweta
Published: July 2023

Background

Despite recent advances in research, there are still critical lacunae in our basic understanding of the cause, pathogenesis, and natural history of many cancers, especially heterogeneity in patient response to drugs and mediators in the transition from malignant to invasive phenotypes. The explication of the pathogenesis of cancer has been constrained by limited access to patient samples, tumor heterogeneity and lack of reliable biological models. Amelioration in cancer treatment depends on further understanding of the etiologic, genetic, biological, and clinical heterogeneity of tumor microenvironment. Patient-derived organoids recapitulate the basic features of primary tumors, including histological complexity and genetic heterogeneity, which is instrumental in predicting patient response to drugs.

Methods

Human iPSCs from healthy donors, breast and ovarian cancer patients were successfully differentiated towards isogenic hepatic, cardiac, neural and endothelial lineages. Multicellular organoids were established using Primary cells isolated from tumor tissues, histologically normal tissues adjacent to the tumors (NATs) and adipose tissues (source of Mesenchymal Stem Cells) from ovarian and breast cancer patients. Further these organoids were propagated and used for drug resistance/sensitivity studies.

Results

Ovarian and breast cancer patients’ organoids showed heterogeneity in drug resistance and sensitivity. iPSCs-derived cardiomyocytes, hepatocytes and neurons showed donor–to-donor variability of chemotherapeutic drug sensitivity in ovarian cancer patients, breast cancer patients and healthy donors.

Conclusion

We report development of a novel integrated platform to facilitate clinical decision-making using the patient's primary cells, iPSCs and derivatives, to clinically relevant models for oncology research.
Association of social isolation and cognitive performance: a longitudinal study using a four-wave nationwide survey
Authors: Duan Yanran , Jiang Shuai , Yin Zhao , Wang Sufan , Gao Jinghong , Yang Mengyu , Chen Changying , Fu Hang , Wang Chengzeng
Published: July 2023

Background

This study aimed to examine the bidirectional relationship between social isolation and cognitive performance among Chinese middle-aged and older adults.

Methods

We used four waves of data from the China Health and Retirement Longitudinal Study. A latent growth model (LGM) was applied to examine the association between social isolation and cognitive performance across different characteristics.

Results

In the analysis, we ultimately included 9,367 participants after excluding respondents with missing key variables. Social isolation and cognitive performance showed significant differences across time. After adjusting for the confounders, there was a significant association between higher social isolation and poor cognitive performance (β = −1.38, p < 0.001), and higher levels of social isolation resulted in a more pronounced decline in cognition over time (β = 0.17, p < 0.001). Additionally, the path coefficient between the initial level of cognition at baseline and the slope of social isolation was − 0.07 (p < 0.001) and 0.01 (p = 0.021), respectively. For the correlation between slopes, our study found that females’ cognition scores were more susceptible to social isolation (β = − 2.78, p < 0.001). Similarly, regarding cognition scores, the influence of social isolation was greater among people with education below the primary level (β = − 2.89, p = 0.002) or a greater number of chronic diseases (β = − 2.56, p = 0.001).

Conclusion

Our findings support the bidirectional association between social isolation and cognition. Specifically, higher baseline social isolation and its rate of increase over time contribute to an intensification of cognitive decline at follow-up. Besides, poorer cognitive performance predicted higher social isolation.
Prevalence of diagnosable depression in patients awaiting orthopaedic specialist consultation: a cross-sectional analysis
Authors: Patten Rhiannon K. , Asilioglu Alev , Levinger Itamar , Tacey Alexander , Pascoe Michaela , Tran Phong , McKenna Michael J. , Said Catherine M. , Coric Natali , De Gori Mary , Lane Rebecca , Apostolopoulos Vasso , Woessner Mary N. , Parker Alexandra
Published: July 2023

Background

Musculoskeletal conditions, including osteoarthritis (OA), are a leading cause of disability and chronic pain, and are associated with high rates of comorbid depression. However, signs of depression are often masked by pain. The aim of this study was to determine the prevalence and severity of depression and pain in individuals awaiting specialist orthopaedic consultation. A secondary objective was to determine the relationship between pain and depression, irrespective of demographic factors and clinical diagnosis.

Methods

Cross-sectional analysis of individuals awaiting orthopaedic consultation at a public hospital in Melbourne, Australia. Relevant data were extracted from medical records and questionnaires. Descriptive statistics were used to summarise participant characteristics. The patient health questionnaire (PHQ-9) was used to assess depression and a numerical rating scale (NRS) was used to assess pain severity. Multiple linear regression analyses were used to establish the relationship between pain and depression.

Results

Nine hundred and eighty-six adults (mean ± standard deviation, age = 54.1 ± 15.7 years, 53.2% women) participated in the study. OA was present in 56% of the population and 34% of the entire population had moderate depression or greater, 19% of which met the criteria for major depressive disorder. Moderate-to-severe pain was present in 79% of individuals with OA and 55% of individuals with other musculoskeletal complaints. Pain was significantly associated with depression scores (β = 0.84, adjusted R2 = 0.13, P < 0.001), and this relationship remained significant after accounting for gender, age, education and employment status, OA status, number of joints affected and waiting time (β = 0.91, adjusted R2 = 0.19, P < 0.001).

Conclusions

Depression affects one-third of individuals on an orthopaedic waitlist. A strong link between pain and depression in patients awaiting specialist orthopaedic consultation exists, indicating a need for an integrated approach in addressing pain management and depression to manage this complex and comorbid presentation.
Association between C-Reactive protein and periodontitis in an obese population from the NHANES 2009–2010
Authors: Sun Jiangling , Wang Wang , Li Dongdong , Song Jukun , Chen Zhu , Chen Liming , Smeets Ralf , Beikler Thomas , Strenge Jan , Yang Zhe , Friedrich Reinhard E.
Published: July 2023

Background

Various data have been obtained on the relationship between body mass index (BMI) and C-reactive protein (CRP) and periodontitis. The aim of this study was to determine whether CRP/BMI are associated with periodontitis using data from the National Health and Nutrition Examination Survey (NHANES) database.

Methods

A cross-sectional analysis of data from 3602 participants in the 2009–2010 NHANES cycle was performed. The definition of periodontitis was used to divide participants into four groups according to the criteria of Eke. Correlations between CRP/BMI and periodontitis were tested for statistical significance by means of descriptive statistics, multivariate regression, and subgroup-stratified analyses, with and without adjustments for confounders (such as age and sex).

Results

There were no statistically significant differences (p > 0.05) regarding BMI and the development of periodontitis. After adjustment for age, sex, race, marital status, annual family income, alcohol consumption, hypertension, smoking, chronic pulmonary disease, cardiovascular disease, diabetes, flossing, and arthritis, CRP correlated significantly with the development of periodontitis in the subgroups stratified by obesity, with an odds ratio (OR) of 1.2 (95% CI, 1.0 to 1.5).

Conclusion

Through data analysis, we found an association between CRP levels and periodontitis prevalence in the American population, although this association was only present in the obese population. While there are several hypotheses about the underlying mechanism, further studies are needed to validate these findings.
Physical, mechanical, and biological properties of collagen membranes for guided bone regeneration: a comparative in vitro study
Authors: Shi Xiaolu , Li Xianjing , Tian Ye , Qu Xinyao , Zhai Shaobo , Liu Yang , Jia Wei , Cui Yan , Chu Shunli
Published: July 2023

Background

To provide a reference for clinical selection of collagen membranes by analyzing the properties of three kinds of collagen membranes widely used in clinics: Bio-Gide membrane from porcine dermis (PD), Heal-All membrane from bovine dermis (BD), and Lyoplant membrane from bovine pericardium (BP).

Methods

The barrier function of three kinds of collagen membranes were evaluated by testing the surface morphology, mechanical properties, hydrophilicity, and degradation rate of collagen membranes in collagenase and artificial saliva. In addition, the bioactivity of each collagen membrane as well as the proliferation and osteogenesis of MC3T3-E1 cells were evaluated. Mass spectrometry was also used to analyze the degradation products.

Results

The BP membrane had the highest tensile strength and Young’s modulus as well as the largest water contact angle. The PD membrane exhibited the highest elongation at break, the smallest water contact angle, and the lowest degradation weight loss. The BD membrane had the highest degradation weight loss, the highest number of proteins in its degradation product, the strongest effect on the proliferation of MC3T3-E1 cells, and the highest expression level of osteogenic genes.

Conclusions

The PD membrane is the best choice for shaping and maintenance time, while the BD membrane is good for osteogenesis, and the BP membrane is suitable for spatial maintenance. To meet the clinical requirements of guided bone regeneration, using two different kinds of collagen membranes concurrently to exert their respective advantages is an option worth considering.
Health care providers’ early experiences of assisted dying in Aotearoa New Zealand: an evolving clinical service
Authors: Snelling Jeanne , Young Jessica , Beaumont Sophie , Diesfeld Kate , White Ben , Willmott Lindy , Robinson Jacqualine , Moeke-Maxwell Tess
Published: July 2023

Background

In November 2021, assisted dying (AD) became lawful in Aotearoa New Zealand. A terminally ill person may now request, and receive, pharmacological assistance (self-administered or provided by a medical practitioner/nurse practitioner) to end their life, subject to specific legal criteria and processes. Exploring the experiences of health providers in the initial stage of the implementation of the End of Life Choice Act 2019 is vital to inform the ongoing development of safe and effective AD practice, policy and law.

Aim

To explore the early experiences of health care providers (HCPs) who do and do not provide AD services seven months after legalisation of AD to provide the first empirical account of how the AD service is operating in New Zealand’s distinctive healthcare environment and cultural context.

Design

Qualitative exploratory design using semi-structured individual and focus group interviewing with a range of HCPs.

Results

Twenty-six HCPs participated in the study. Through a process of thematic analysis four key themes were identified: (1) Difference in organisational response to AD; (2) challenges in applying the law; (3) experiences at the coal face; and (4) functionality of the AD system.

Conclusion

A range of barriers and enablers to successful implementation of AD were described. Adoption of open and transparent organisational policies, ongoing education of the workforce, and measures to reduce stigma associated with AD are necessary to facilitate high quality AD service provision. Future research into the factors that influence responses to, and experience of AD; the impact of institutional objection; and the extent to which HCP perspectives evolve over time would be beneficial. In addition, further research into the integration of AD within Māori health organisations is required.
Application of bilingual simulated patients in the medical history collection for international medical students in China
Authors: Zou Liping , Su Juan , Li Jiao , Wang Jing , Kang Jian , Yin Anning , Ren Haixia , Jiang Xiaoda , Ding Yijuan , An Ping
Published: July 2023

Background

In all international medical student (IMS) programs in China, language barriers between IMSs and Chinese patients greatly reduced the learning in clinical practice and brought great challenges to IMSs in their transition from preclinical to clinical practice. This study aimed to investigate the role of bilingual simulated patients (B-SPs) in IMSs learning of medical history collection in China.

Methods

48 IMSs of grade 4 between October 2020 to Jan 2021 were enrolled in this study. During the training of medical history collection, students were randomly arranged into two groups trained with either B-SPs (B-SP group) or English-speaking SP (E-SP group). All SPs in Objective Structured Clinical Exam station (OSCE) were trained in the Affiliated Hospital of Wuhan University. Clinical skills in medical history collection were assessed by instructors during pre-clinical, post-clinical OSCE and clinical rotations.

Results

The scores of IMSs in each group were analyzed in terms of medical history collection including the ability to effectively consult for information and key communication skills related to patient care. Our results indicated that IMS in B-SP group obtained similar scores in preclinical training for history collection (67.3 ± 8.46 vs 67.69 ± 8.86, P < 0.05) compared to E-SP group, while obtaining significantly higher score improvements between pre- and post-OSCE (17.22 (95% CI 12.74 to 21.70) vs 10.84 (95% CI 3.53 to 18.15), P = 0.0007).

Conclusion

B-SPs are more conducive to doctor-patient communication and actually improve IMSs learning in medical history collection in China.
To donate or not to donate? Future healthcare professionals’ opinions on biobanking of human biological material for research purposes
Authors: Domaradzki Jan , Czekajewska Justyna , Walkowiak Dariusz
Published: July 2023

Background

Over the last few decades biobanks have been recognised as institutions that may revolutionise biomedical research and the development of personalised medicine. Poland, however, still lacks clear regulations regarding the running of biobanks and the conducting of biomedical research. While the awareness of the general public regarding biobanks is low, healthcare professions and medical students also lack basic knowledge regarding biobanks, and such ignorance may affect their support for biobanks.

Methods

This study is aimed at assessing the knowledge and attitudes of future healthcare professionals towards the donation of human biological material for research purposes and is based on a sample of 865 Polish medical students at Poznań University of Medical Sciences.

Results

This research has shown that the awareness of medical students’ regarding biobanks is low. It has also shown that while the majority of future healthcare professionals enrolled in this study supported the idea of biobank research and declared themselves willing to donate, still many students felt ambivalent about the biobanking of human biological material for research purposes and expressed concerns over biobanking research. While the primarily motivation to participate in biobank research was the desire to help advance science and to develop innovative therapies, the most common reason for a refusal was the fear that the government, insurance companies or employers, might have access to the samples. Concerns over unethical use of samples and data safety were also prevalent. More than half of students opted for a study-specific model of consent and only a few opted for broad consent.

Conclusions

This research suggests that a lack of knowledge about biobanks, their role and activities may affect medical students’ support for biobanks and their active participation in the collection and management of biospecimens for research purposes. Since in the future medical, nursing and pharmacy students will be involved in the collection, storage, testing and analysis of biospecimens from their patients, medical students in all professional fields should be trained regarding the concept, purposes and operational procedures of biobanks, as well as the ethical, legal and social implications of biobank research.
Quality indices for topic model selection and evaluation: a literature review and case study
Authors: Meaney Christopher , Stukel Therese A. , Austin Peter C. , Moineddin Rahim , Greiver Michelle , Escobar Michael
Published: July 2023

Background

Topic models are a class of unsupervised machine learning models, which facilitate summarization, browsing and retrieval from large unstructured document collections. This study reviews several methods for assessing the quality of unsupervised topic models estimated using non-negative matrix factorization. Techniques for topic model validation have been developed across disparate fields. We synthesize this literature, discuss the advantages and disadvantages of different techniques for topic model validation, and illustrate their usefulness for guiding model selection on a large clinical text corpus.

Design, setting and data

Using a retrospective cohort design, we curated a text corpus containing 382,666 clinical notes collected between 01/01/2017 through 12/31/2020 from primary care electronic medical records in Toronto Canada.

Methods

Several topic model quality metrics have been proposed to assess different aspects of model fit. We explored the following metrics: reconstruction error, topic coherence, rank biased overlap, Kendall’s weighted tau, partition coefficient, partition entropy and the Xie-Beni statistic. Depending on context, cross-validation and/or bootstrap stability analysis were used to estimate these metrics on our corpus.

Results

Cross-validated reconstruction error favored large topic models (K ≥ 100 topics) on our corpus. Stability analysis using topic coherence and the Xie-Beni statistic also favored large models (K = 100 topics). Rank biased overlap and Kendall’s weighted tau favored small models (K = 5 topics). Few model evaluation metrics suggested mid-sized topic models (25 ≤ K ≤ 75) as being optimal. However, human judgement suggested that mid-sized topic models produced expressive low-dimensional summarizations of the corpus.

Conclusions

Topic model quality indices are transparent quantitative tools for guiding model selection and evaluation. Our empirical illustration demonstrated that different topic model quality indices favor models of different complexity; and may not select models aligning with human judgment. This suggests that different metrics capture different aspects of model goodness of fit. A combination of topic model quality indices, coupled with human validation, may be useful in appraising unsupervised topic models.
Comparison of SGLT2 inhibitors with DPP-4 inhibitors combined with metformin in patients with acute myocardial infarction and diabetes mellitus
Authors: Lyu Young Sang , Oh Seok , Kim Jin Hwa , Kim Sang Yong , Jeong Myung Ho
Published: July 2023

Background

Although sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated cardiovascular benefits in patients with type 2 diabetes mellitus, real-world evidence regarding their benefits to diabetic patients with acute myocardial infarction (AMI) is insufficient. This study evaluated cardiovascular outcomes by comparing SGLT2i with dipeptidyl peptidase-4 inhibitors (DPP-4i) in combination with metformin in diabetic patients with AMI.

Methods

This study involved 779 diabetic participants with AMI from a Korean nationwide multicenter observational cohort, who were divided into two groups: (1) metformin plus SGLT2i group (SGLT2i group, n = 186) and (2) metformin plus DPP-4i (DPP-4i group, n = 593). The primary endpoint was one year of major adverse composite events (MACEs), a composite outcome of all-cause mortality, non-fatal myocardial infarction, any revascularization, cerebrovascular accident, and stent thrombosis. To balance the baseline differences, inverse probability of treatment weighting (IPTW) was performed.

Results

After IPTW, the rate of MACEs in the SGLT2i group was not significantly lower than that in the DPP-4i group (hazard ratio [HR], 0.99; 95% confidence interval [Cl], 0.46 to 2.14, p = 0.983). In the unadjusted and adjusted analyses, all items for clinical outcomes were comparable between the two groups. In our exploratory analysis, the left ventricular ejection fraction showed a significant improvement in the SGLT2i group than in the DPP-4i group before achieving statistical balancing (6.10 ± 8.30 versus 2.95 ± 10.34, p = 0.007) and after IPTW adjustment (6.91 ± 8.91 versus 3.13 ± 10.41, p = 0.027).

Conclusions

Our findings demonstrated that SGLT2i did not influence the rate of MACEs compared with DPP-4i in combination with metformin in diabetic patients with AMI but did improve left ventricular ejection fraction.

Trial registration

Not applicable (retrospectively registered).
Cardiac Troponin T (TNNT2) plays a potential oncogenic role in colorectal carcinogenesis
Authors: Liu Yifan , Meng Ze , Niu Junqiang , Tian Le , Chen Yishan , Meng Qingju , Liu Yibing , Zhou Zhiguo
Published: July 2023

Purpose

Colorectal cancer (CRC) is the third most common cancer in the world. The purpose of this study was to investigate the role of TNNT2 in the proliferation, migration and invasion of CRC cells and its expression in CRC tissues to better understand the regulatory role of TNNT2 in CRC.

Methods

Western blotting (WB) and qPCR were used to detect the expression of TNNT2 in colorectal cancer tissues and paracancerous tissues. CCK-8, colony formation, Transwell and other experiments were used to clarify the role of TNNT2 in the proliferation, migration and invasion of colorectal cancer cells. Changes in TNNT2, EGFR and HER2 mRNA transcription levels were detected by SYBR Real-Time PCR assay, and the effects of TNNT2 overexpression or knockdown on the expression of EGFR, HER2 and EMT-related proteins in CRC cells were determined by WB. TNNT2 and EGFR intreaction was carried out in HCT116 cells by coimmunoprecipitation experiments.

Results

The protein and mRNA expression level of TNNT2 in CRC tissues were higher than those in paracancerous tissues. The CCK-8 results suggested that overexpression of TNNT2 significantly promoted the proliferation of HCT116 and RKO cells, and TNNT2 konckdown gets the opposite result; and the colony formation results were the same as tthose of CCK-8 assay. Transwell invasion and migration experiments showed that overexpression of TNNT2 promoted the migration and invasion of HCT116 and PKO cells, and TNNT2 konckdown suppressed the migration and invasion of the these cells. The SYBR Green I real-time PCR method revealed that them RNA levels of TNNT2, EGFR and HER2 in the TNNT2 overexpression group were higher than those in RKO cells. WB showed that overexpressing TNNT2 increased the expression of EGFR and HER2 in HCT16 and RKO cells,decreased the expression of EMT marker E-cadherin, and increased the expression of Vimentin and N-cadherin. Konckdown of TNNT2 decreased the expression of EGFR and HER2, increased the expression of E-cadherin, and decreased the expression of Vimentin and N-cadherin in HCT16 and RKO cells. The immunocoprecipitation experiment showed that there was an interaction between EGFR and TNNT2.

Conclusion

TNNT2 can promote the proliferation, invasion and metastasis of colorectal cancer cells. There is an interaction between TNNT2 and EGFR protein. TNNT2 can upregulate EGFR and HER2-related proteins in colorectal cancer cells and promote the occurrence of EMT. Therefore, TNNT2 can promote the invasion and metastasis of CRC cells through the EGFR/HER2/EMT signal axis, suggesting that TNNT2 is a potential target of CRC treatment.
Extracellular vesicle-circEHD2 promotes the progression of renal cell carcinoma by activating cancer-associated fibroblasts
Authors: He Tao , Zhang Qiansheng , Xu Peng , Tao Wen , Lin Fuyang , Liu Renfei , Li Mingzhao , Duan Xiaolu , Cai Chao , Gu Di , Zeng Guohua , Liu Yongda
Published: July 2023

Background

The encapsulation of circular RNAs (circRNAs) into extracellular vesicles (EVs) enables their involvement in intercellular communication and exerts an influence on the malignant advancement of various tumors. However, the regulatory role of EVs-circRNA in renal cell carcinoma (RCC) remains elusive.

Methods

The in vitro and in vivo functional experiments were implemented to measure the effects of circEHD2 on the phenotype of RCC. The functional role of EVs-circEHD2 on the activation of fibroblasts was assessed by collagen contraction assay, western blotting, and enzyme-linked immunosorbent assay (ELISA). The mechanism was investigated by RNA pull-down assay, RNA immunoprecipitation, chromatin isolation by RNA purification, luciferase assay, and co-immunoprecipitation assay.

Results

We demonstrated that circEHD2 was upregulated in RCC tissues and serum EVs of RCC patients with metastasis. Silencing circEHD2 inhibited tumor growth in vitro and in vivo. Mechanistic studies indicated that FUS RNA -binding protein (FUS) accelerated the cyclization of circEHD2, then circEHD2 interacts with tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH), which acts as a bridge to recruit circEHD2 and Yes1-associated transcriptional regulator (YAP) to the promoter of SRY-box transcription factor 9 (SOX9); this results in the sustained activation of SOX9. Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) regulates the package of circEHD2 into EVs, then EVs-circEHD2 transmits to fibroblasts, converting fibroblasts to cancer-associated fibroblasts (CAFs). Activated CAFs promote the metastasis of RCC by secreting pro-inflammatory cytokines such as IL-6. Furthermore, antisense oligonucleotides (ASOs) targeting circEHD2 exhibited a strong inhibition of tumor growth in vivo.

Conclusions

The circEHD2/YWHAH/YAP/SOX9 signaling pathway accelerates the growth of RCC. EVs-circEHD2 facilitates the metastasis of RCC by converting fibroblasts to CAFs. Our results suggest that EVs-circEHD2 may be a useful biomarker and therapeutic target for RCC.
Association between body fat composition and disease duration, clinical activity, and intravenous corticosteroid-induced response in inflammatory bowel disease
Authors: He Shubei , Huang Yuxia , Peng Ying , Chai Jin , Chen Kun
Published: July 2023

Background

Body fat composition is believed to be associated with the progression, medical response, and prognosis of inflammatory bowel disease (IBD). Hence, we conducted this study to explore if fat metrics were associated with the disease activity of severe IBD and the response to intravenous corticosteroids (IVCS).

Methods

We included 69 patients with ulcerative colitis (UC) and 72 patients with Crohn's disease (CD) who had previously received IVCS during hospitalization. We quantified individual fat distribution using abdominal computed tomography slices. The correlations between fat parameters and disease activity were available with Spearman correlation analysis. The prediction model was developed using independent risk factors derived from multivariable logistic regression analysis. Model discrimination was evaluated leveraging the receiver operating characteristic curve. 1000 bootstrap resamples internally validated the model's prediction performance.

Results

Notable differences in age, nutritional status, serum cytomegalovirus replication, stool condition, and extraintestinal involvement between UC and CD patients were observed. UC subjects who responded to IVCS had higher subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI), and mesorectal adipose tissue index (MATI) than non-responders. IVCS-responding CD individuals had lower VATI and mesenteric fat index (MFI) than non-responders. CD patients with a prolonged disease duration had a decreased SATI and an elevated MFI. VATI and MATI were reduced as UC clinically progressed, while more prominent clinical activity in CD correlated with increased VATI, MATI, and MFI. A high SATI indicated that patients with UC were more prone to be IVCS responders. For patients with CD, levels of VATI and MFI were negatively associated with effective IVCS treatment. The established models showed a discriminative accuracy of 0.834 [95% confidence interval (CI) 0.740–0.928] in the UC cohort and 0.871 (95% CI 0.793–0.949) in the CD cohort. Repeated samples supported the reliability of the developed models (AUCUC = 0.836, 95% CI 0.735–0.919; AUCCD = 0.876, 95% CI 0.785–0.946).

Conclusion

Human fat indexes represent novel imaging biomarkers for identifying IBD patients who respond to IVCS, thus building accelerated therapy regimens and avoiding the adverse effects of ineffective IVCS.
Gambling harm prevention and harm reduction in online environments: a call for action
Authors: Marionneau Virve , Ruohio Heidi , Karlsson Nina
Published: July 2023

Background

Gambling is increasingly offered and consumed in online and mobile environments. The digitalisation of the gambling industry poses new challenges on harm prevention and harm reduction. The digital environment differs from traditional, land-based gambling environments. It increases many risk-factors in gambling, including availability, ease-of-access, but also game characteristics such as speed and intensity. Furthermore, data collected on those gambling in digital environments makes gambling offer increasingly personalised and targeted.

Main results

This paper discusses how harm prevention and harm reduction efforts need to address gambling in online environments. We review existing literature on universal, selective, and indicated harm reduction and harm prevention efforts for online gambling and discuss ways forward. The discussion shows that there are several avenues forward for online gambling harm prevention and reduction at each of the universal, selective, and indicated levels. No measure is likely to be sufficient on its own and multi-modal as well as multi-level interventions are needed. Harm prevention and harm reduction measures online also differ from traditional land-based efforts. Online gambling providers utilise a variety of strategies to enable, market, and personalise their products using data and the wider online ecosystem.

Conclusion

We argue that these same tools and channels should also be used for preventive work to better prevent and reduce the public health harms caused by online gambling.
Hypoxia-based classification and prognostic signature for clinical management of hepatocellular carcinoma
Authors: Li Ke , Yang Yanfang , Ma Mingwei , Lu Suping , Li Junjie
Published: July 2023

Objective

Intratumoral hypoxia is an essential feature of hepatocellular carcinoma (HCC). Herein, we investigated the hypoxia-based heterogeneity and relevant clinical implication in HCC.

Methods

Three HCC cohorts: TCGA-LIHC, LICA-FR, and LIRI-JP were retrospectively gathered. Consensus clustering analysis was utilized for hypoxia-based classification based upon transcriptome of hypoxia genes. Through LASSO algorithm, a hypoxia-relevant prognostic signature was built. Immunotherapeutic response was inferred through analyzing immune checkpoints, T cell inflamed score, TIDE score, and TMB score. RNF145 expression was measured in normoxic or hypoxic HCC cells. In RNF145-knockout cells, CCK-8, TUNEL, and scratch tests were implemented.

Results

HCC patients were classified into two hypoxia subtypes, with more advanced stages and poorer prognosis in cluster2 than cluster1. The heterogeneity in tumor infiltrating immune cells and genetic mutation was found between subtypes. The hypoxia-relevant prognostic model was proposed, composed of ANLN, CBX2, DLGAP5, FBLN2, FTCD, HMOX1, IGLV1-44, IL33, LCAT, LPCAT1, MKI67, PFN2, RNF145, S100A9, and SPP1). It was predicted that high-risk patients presented worse prognosis with an independent and reliable manner. Based upon high expression of immune checkpoints (CD209, CTLA4, HAVCR2, SIRPA, TNFRSF18, TNFRSF4, and TNFRSF9), high T cell inflamed score, low TIDE score and high TMB score, high-risk patients might respond to immunotherapy. Experimental validation showed that RNF145 was upregulated in hypoxic HCC cells, RNF145 knockdown attenuated proliferation and migration, but aggravated apoptosis in HCC cells.

Conclusion

Altogether, the hypoxia-based classification and prognostic signature might be useful for prognostication and guiding treatment of HCC.
Comparison of the Y-pouch orthotopic neobladder and the Studer technique after radical cystectomy: surgical and functional outcomes from a single-center series
Authors: Boonchai Sarayuth , Tanthanuch Monthira , Bejrananda Tanan
Published: July 2023

Background

To explore a method of constructing an orthotopic ileal neobladder (ONB) in the Y-pouch configuration. We describe the steps followed to create the Y-pouch ileal orthotopic neobladder (ONB) and compared the perioperative, functional, and urodynamics outcomes with the Studer neobladder technique.

Methods

A retrospective cohort study of 90 bladder cancer patients, who received open radical cystectomy with the ONB performed at a hospital from June 2009 to May 2020. These patients were divided into two groups—the Y-pouch and the Studer neobladder groups. Perioperative, functional outcome, complication, renal function data outcomes, and pressure–volume study were used to evaluate the treatment outcomes after a radical cystectomy.

Results

Ninety patients (54 Studer and 36 Y-pouch neobladder) were enrolled. The median patient age was 62.6 (± 11) years. The mean operative time for the Studer technique was 290 (242.5–350) min, and the Y-pouch technique was 300 (271.2–335) min) (p = 0.826). At 30 days postoperatively, the Clavien-Dindo classification of surgical complications revealed grade-2 urinary infections in two patients (5.6%) and six patients (11.1%) for the Y-pouch and Studer techniques, respectively. Intermediate complications (30–90 days) were reported in 4 (11.1%) and 18 patients (44.4%) in the Y-pouch and the Studer techniques, respectively (p = 0.062). In the urodynamics study (UDS), the Y-pouch group had a mean postvoid residual volume of 20 mL and Studer of 40 ml (p = 0.06). A mean capacity of 462 (380–600) mL compares to the Studer neobladder group with 495 (400–628) mL. The average mean compliance of the Studer group was 35.5 (28–52) ml/cm H2O and 33 (30–43) ml/cm H2O for Y pouch, and most patients had > 30 ml/cm H2O compliance (80/90 patients).

Conclusions

The Y-pouch neobladder technique in an RC with an orthotopic neobladder provides perioperative and functional outcomes compared to those of the Studer orthotopic neobladder resulting in similar intermediate-term. Therefore, the Y-pouch ileal neobladder is both feasible and safe to be used as a standard neobladder technique for urinary diversion in patients with bladder cancer undergoing radical cystectomy and needs confirmation with long-term results.