bluuebunny/crossref_metadata_2025 huggingface dataset:
Dimensionality of genomic information and its impact on genome-wide associations and variant selection for genomic prediction: a simulation study
Authors: Jang Sungbong , Tsuruta Shogo , Leite Natalia Galoro , Misztal Ignacy , Lourenco Daniela
Published: July 2023

Background

Identifying true positive variants in genome-wide associations (GWA) depends on several factors, including the number of genotyped individuals. The limited dimensionality of genomic information may give insights into the optimal number of individuals to be used in GWA. This study investigated different discovery set sizes based on the number of largest eigenvalues explaining a certain proportion of variance in the genomic relationship matrix (G). In addition, we investigated the impact on the prediction accuracy by adding variants, which were selected based on different set sizes, to the regular single nucleotide polymorphism (SNP) chips used for genomic prediction.

Methods

We simulated sequence data that included 500k SNPs with 200 or 2000 quantitative trait nucleotides (QTN). A regular 50k panel included one in every ten simulated SNPs. Effective population size (Ne) was set to 20 or 200. GWA were performed using a number of genotyped animals equivalent to the number of largest eigenvalues of G (EIG) explaining 50, 60, 70, 80, 90, 95, 98, and 99% of the variance. In addition, the largest discovery set consisted of 30k genotyped animals. Limited or extensive phenotypic information was mimicked by changing the trait heritability. Significant and large-effect size SNPs were added to the 50k panel and used for single-step genomic best linear unbiased prediction (ssGBLUP).

Results

Using a number of genotyped animals corresponding to at least EIG98 allowed the identification of QTN with the largest effect sizes when Ne was large. Populations with smaller Ne required more than EIG98. Furthermore, including genotyped animals with a higher reliability (i.e., a higher trait heritability) improved the identification of the most informative QTN. Prediction accuracy was highest when the significant or the large-effect SNPs representing twice the number of simulated QTN were added to the 50k panel.

Conclusions

Accurately identifying causative variants from sequence data depends on the effective population size and, therefore, on the dimensionality of genomic information. This dimensionality can help identify the most suitable sample size for GWA and could be considered for variant selection, especially when resources are restricted. Even when variants are accurately identified, their inclusion in prediction models has limited benefits.
A mutation responsible for impaired detection by the Xpert SARS-CoV-2 assay independently emerged in different lineages during the SARS-CoV-2 pandemic
Authors: Peñas-Utrilla Daniel , Sanz Amadeo , Catalán Pilar , Veintimilla Cristina , Alcalá Luis , Alonso Roberto , Muñoz Patricia , Pérez-Lago Laura , García de Viedma Darío ,   on behalf of the Gregorio Marañón Microbiology-ID COVID 19 Study Group, Aldámiz Teresa , Álvarez-Uría Ana , Bermúdez Elena , Bouza Emilio , Buenestado-Serrano Sergio , Burillo Almudena , Carrillo Raquel , Catalán Pilar , Cercenado Emilia , Cobos Alejandro , Díez Cristina , Escribano Pilar , Estévez Agustín , Fanciulli Chiara , Galar Alicia , García Mª Dolores , Gijón Paloma , Guillén Helmuth , Guinea Jesús , Herranz Marta , Irigoyen Álvaro , Kestler Martha , López Juan Carlos , Machado Marina , Marín Mercedes , Martín-Rabadán Pablo , Molero-Salinas Andrea , Montilla Pedro , Padilla Belén , Palomino-Cabrera Rosalía , Palomo María , Pérez-Granda María Jesús , Pérez Leire , Reigadas Elena , Rincón Cristina , Rodríguez Belén , Rodríguez Sara , Rodríguez-Grande Cristina , Rojas Adriana , Ruiz-Serrano María Jesús , Sánchez Carlos , Sánchez Mar , Serrano Julia , Tejerina Francisco , Valerio Maricela , Veintimilla Mª Cristina , Vesperinas Lara , Vicente Teresa , de la Villa Sofía
Published: July 2023

Background

COVID-19 diagnosis lies on the detection of SARS-CoV-2 on nasopharyngeal specimens by RT-PCR. The Xpert-Xpress SARS-CoV-2 assay provides results in less than one hour from specimen reception, which makes it suitable for clinical/epidemiological circumstances that require faster responses. The analysis of a COVID-19 outbreak suspected in the neonatology ward from our institution showed that the Ct values obtained for the targeted genes in the Xpert assay were markedly different within each specimen (N Ct value > 20 cycles above the E Ct value).

Results

We identified the mutation C29200T in the N gene as responsible for an impairment in the N gene amplification by performing whole genome sequencing of the specimens involved in the outbreak (Omicron variant). Subsequently, a retrospective analysis of all specimens sequenced in our institution allowed us to identify the same SNP as responsible for similar impairments in another 12 cases (42% of the total cases reported in the literature). Finally, we found that the same SNP emerged in five different lineages independently, throughout almost all the COVID-19 pandemic.

Conclusions

We demonstrated for the first time the impact of this SNP on the Xpert assay, when harbored by new Omicron variants. We extend our observation period throughout almost all the COVID-19 pandemic, offering the most updated observations of this phenomenon, including sequences from the seventh pandemic wave, until now absent in the reports related to this issue. Continuous monitoring of emerging SNPs that could affect the performance of the most commonly used diagnostic tests, is required to redesign the tests to restore their correct performance.
Prevalence and mechanisms of ciprofloxacin resistance in Escherichia coli isolated from hospitalized patients, healthy carriers, and wastewaters in Iran
Authors: Neyestani Zohreh , Khademi Farzad , Teimourpour Roghayeh , Amani Mojtaba , Arzanlou Mohsen
Published: July 2023

Background

This study was aimed to evaluate the prevalence and molecular characteristics of ciprofloxacin resistance among 346 Escherichia coli isolates collected from clinical specimens (n = 82), healthy children (n = 176), municipal wastewater (n = 34), hospital wastewater (n = 33), poultry slaughterhouse wastewater (n = 12) and livestock (n = 9) slaughterhouse wastewater in Iran.

Methods

Ciprofloxacin minimum inhibitory concentration (MIC) was determined by agar dilution assay. Phylogroups and plasmid-mediated quinolone resistance (PMQR) genes were identified using PCR. Mutations in gyrA, gyrB, parC, and parE genes and amino acid alterations were screened through sequencing assay. The effect of efflux pump inhibitor (PAβN) on ciprofloxacin MICs in ciprofloxacin-resistant isolates was investigated using the microdilution method.

Results

In total, 28.03% of E. coli isolates were phenotypically resistant to ciprofloxacin. Based on sources of isolation, 64.63%, 51.51%, 33.33%, 14.70%, 10.22% and 8.33% of isolates from clinical specimens, hospital wastewater, livestock wastewater, municipal wastewater, healthy children and poultry wastewater were ciprofloxacin-resistant, respectively. Eighty-one point eighty-one percent (Ser-83 → Leu + Asp-87 → Asn; 78.78% and Ser-83 → Leu only; 3.03% (of ciprofloxacin-resistant E. coli isolates showed missense mutation in GyrA subunit of DNA gyrase, while no amino-acid substitution was noted in the GyrB subunit. DNA sequence analyses of the ParC and ParE subunits of topoisomerase IV exhibited amino-acid changes in 30.30% (Ser-80 → Ile + Glu-84 → Val; 18.18%, Ser-80 → Ile only; 9.10% and Glu-84 → Val only; 3.03%0 (and 15.38% (Ser-458 → Ala) of ciprofloxacin-resistant E. coli isolates, respectively. The PMQR genes, aac(6')-Ib-cr, qnrS, qnrB, oqxA, oqxB, and qepA were detected in 43.29%, 74.22%, 9.27%, 14.43%, 30.92% and 1.03% of ciprofloxacin-resistant isolates, respectively. No isolate was found to be positive for qnrA and qnrD genes. In isolates harboring the OqxA/B efflux pump, the MIC of ciprofloxacin was reduced twofold in the presence of PAβN, as an efflux pump inhibitor. The phylogroups B2 (48.45%) and A (20.65%) were the most predominant groups identified in ciprofloxacin-resistant isolates.

Conclusions

This study proved the high incidence of ciprofloxacin-resistant E. coli isolates in both clinical and non-clinical settings in Iran. Chromosomal gene mutations and PMQR genes were identified in ciprofloxacin resistance among E. coli population.
Concomitant aortic regurgitation predicts better left ventricular reverse remodeling after transcatheter aortic valve replacement
Authors: Yang Hao-Ran , Xiong Tian-Yuan , Zhang Yi , He Jing-Jing , Feng Yuan , Chen Mao
Published: July 2023

Background

We aim to determine predictors of inadequate left ventricular mass index (LVMi) regression at mid-term after transcatheter aortic valve replacement (TAVR), including the potential role of epicardial adipose tissue (EAT).

Methods

We retrospectively reviewed patients with both echocardiographic assessments and multi-slice computed tomography (MSCT) obtained one year after TAVR. The change of LVMi, the volume and the average CT attenuation of EAT from baseline to one-year follow-up was calculated. Patients were divided into two groups by the percentage change of LVMi at a cut-off of 15%.

Results

A total of 152 patients were included with a median age of 74 years (interquartile range [IQR] 69–78 years) and 56.6% being male. LVMi decreased (P < 0.0001) while EAT volume increased and the average CT attenuation decreased (both P < 0.0001) at one year. Baseline atrial fibrillation (P = 0.042), mitral regurgitation ≥ mild (P = 0.006), aortic regurgitation (AR) > mild (P = 0.001) and the change in the average CT attenuation of EAT (P = 0.026) were different between the decrease of LVMi ≥ 15% and < 15%. AR > mild at baseline was the only statistically significant predictor of a decrease of LVMi < 15% at one year (OR 0.33, 95% CI: 0.13 to 0.84, P = 0.021) in multivariate regression.

Conclusions

Concomitant more-than-mild AR might predict better left ventricular reverse remodeling regression after TAVR.
Single-center experience with catheter-directed thrombolysis and balloon angioplasty for acute upper-extremity deep vein thrombosis: a case series study
Authors: Jenab Yaser , Tofighi Saeed , Ayati Aryan , Rezvanimehr Ali , Moosavi Najme-sadat , Jalaie Houman , Barbati Mohammad Esmaeil
Published: July 2023

Background

Effective treatment of upper extremity deep vein thrombosis (UEDVT) is crucial to prevent further complications. Various treatments, including percutaneous mechanical thrombectomy (PMT), catheter-directed thrombolysis (CDT), decompression surgery, and venoplasty are suggested for UEDVT. However, no prospective study has yet favored any of these treatments. This study presents a review of our experience with CDT followed by balloon venoplasty in patients with acute primary UEDVT.

Methods

We enrolled all patients diagnosed with acute UEDVT from January 2020 to June 2021. Subjects with UEDVT due to secondary causes like malignancies, indwelling catheters, or leads were excluded. CDT was performed through brachial vein access, using a perfusion catheter, and rt-PA administration. Balloon venoplasty was performed if the treated segment had remaining stenosis after CDT. Patients were followed up at the vein clinic for any signs and symptoms in the upper extremity and lifestyle changes. Follow-up ultrasonography was done 12 months after discharge.

Results

Twelve patients with a mean age of 41.08 ± 14.0 years were included in the study. The mean duration of CDT was 25.00 ± 10.56 h. After CDT, all patients had remaining occlusions, with seven having more than 50% remaining stenosis. However, after balloon venoplasty, no patient had significant (more than 50%) stenosis. There was no serious complication after both procedures. Patients were followed up for a mean duration of twelve months after their admission, with a mean time of maintenance anticoagulation was 10.73 ± 5.77 months. Only one patient had recurrent symptoms in his target limb which required a decompression surgery, while the rest were free of symptoms in their treated extremity. No subject developed pulmonary emboli (PE) during admission or the follow-up period. There was no evidence of hospital readmission for any reason. Upper extremity color-doppler sonography of the patients at twelve months after their procedure showed normal venous flow without any significant stenosis in 8 (66.7%), and partially normal flow with patent target vein in 4 (33.3%) patients.

Conclusions

CDT followed by balloon venoplasty may be an effective treatment for selected patients with acute primary UEDVT, providing desirable long-term results and potentially avoiding the need for decompression surgery in the short or long term.
Direct comparison of diagnostic and clinical values between Tc-99 m DPD and Tc-99 m PYP scintigraphy in patients with cardiac amyloidosis
Authors: Park Yong-Jin , Lee Joohee , Kim Darae , Choi Jin-Oh , Kim Seok Jin , Kim Kihyun , Choi Joon Young
Published: July 2023

Background

Technetium-99 m 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) and technetium-99 m sodium pyrophosphate (PYP) are the two most commonly used radiotracers for cardiac amyloidosis (CA), but no studies have directly compared them. Therefore, in this study, we directly compared the diagnostic and clinical utility of DPD and PYP scintigraphy in patients with CA.

Methods

Ten patients with CA were enrolled. Eight clinical variables and 12 scintigraphic parameters were used. Clinical variables were age, sex, estimated glomerular filtration rate (eGFR), N-terminal pro brain natriuretic peptide (NT-proBNP), and the results of electromyography (EMG), a sensory test, electrocardiogram, and echocardiography (EchoCG). Four heart retention ratios (heart/whole-body profile, heart/pelvis, heart/skull, and heart/contralateral lung) were calculated from the DPD and PYP scans and two visual scoring systems (Perugini and Dorbala systems) were used. Comparative analyses were performed between radiotracers and between visual scoring systems using clinical variables and scintigraphic parameters.

Results

Twenty DPD parameters and nine PYP parameters had significant associations with age, eGFR, NT-proBNP, EchoCG, and EMG. DPD parameters had more frequent significant associations with clinical variables than PYP parameters. Compared to visual scores in the DPD scan, the proportion of patients with higher visual scores in the PYP scan was relatively greater than those with lower visual scores, and there were more patients with a visual score of 2 or higher in PYP scans than DPD scans.

Conclusions

DPD scintigraphy may reflect the disease severity of CA better than PYP scintigraphy, whereas PYP scintigraphy may be a more sensitive imaging modality for identifying CA involvement.
Stroke in women: experience in a developing country
Authors: El Nahas Nevine , Aref Hany , Kenawy Fatma Fathalla , Georgy Shady , Abushady Eman Mones , Dawood Noha Lotfy , Hamdy Sara , Abdelmohsen Nourhan , Hassan Abdel Hamid Yasmine , Roushdy Tamer , Shokri Hossam
Published: July 2023

Background

Several studies have addressed gender differences in stroke. Yet, results are diverse, and research is still required in different populations. So, this study investigates variation in stroke according to gender in a developing country.

Methods

This is a registry-based, retrospective observational cross-sectional study comparing men and women as regards age, risk factors, stroke severity, quality of services, and stroke outcome.

Results

Data analyzed comprised 4620 patients. It was found that men outnumbered women, while women had an older age, more prevalence of hypertension and atrial fibrillation, with severer strokes and worse outcomes. However, there was no gender difference in promptness nor frequency of administration of revascularization therapies.

Conclusion

Despite the gender difference in risk factors and stroke severity, we could not detect any significant disparity in acute stroke services provided to either gender. Among age categories in women, we identified differences in acute ischemic stroke subtypes, and acute management in favor of older age.
Dissecting antenatal care inequalities in western Nepal: insights from a community-based cohort study
Authors: Khanal Vishnu , Bista Sangita , Mishra Shiva Raj , Lee Andy H.
Published: July 2023

Background

Antenatal care (ANC) ensures continuity of care in maternal and foetal health. Understanding the quality and timing of antenatal care (ANC) is important to further progress maternal health in Nepal. This study aimed to investigate the proportion of and factors associated with, key ANC services in western Nepal.

Methods

Data from a community-based cohort study were utilized to evaluate the major ANC service outcomes: (i) three or less ANC visits (underutilization) (ii) late initiation (≥ 4 months) and (iii) suboptimal ANC (< 8 quality indicators). Mothers were recruited and interviewed within 30 days of childbirth. The outcomes and the factors associated with them were reported using frequency distribution and multiple logistic regressions, respectively.

Results

Only 7.5% of 735 mothers reported not attending any ANC visits. While only a quarter (23.77%) of mothers reported under-utilizing ANC, more than half of the women (55.21%) initiated ANC visits late, and one-third (33.8%) received suboptimal ANC quality. A total of seven factors were associated with the suboptimal ANC. Mothers with lower education attainment, residing in rural areas, and those who received service at home, were more likely to attain three or less ANC visits, late initiation of ANC, and report receiving suboptimal ANC. Furthermore, mothers from poor family backgrounds appeared to initiate ANC late. Mothers from disadvantaged Madhesi communities tended to receive suboptimal ANC.

Conclusions

Despite a high ANC attendance, a significant proportion of mothers had initiated ANC late and received suboptimal care. There is a need to tailor ANC services to better support women from Madhesi ethnic community, as well as those with poor and less educated backgrounds to reduce the inequalities in maternal health care.
Relationship between insomnia and working from home among Korean domestic workers: results from the 5th Korean working condition survey
Authors: Lee Lei , Nam Ok Hyung , Lee Ko Eun , Lee Chunui
Published: July 2023

Background

Social distancing has been increasingly implemented following the COVID-19 pandemic and more people have been working from home. Consequently, the screen time has increased, which can disrupt the natural sleep-wake cycle and delay sleep onset. Given that studies on the health of employees who work from home remain insufficient, particularly with respect to the risk of sleep disorders including insomnia, this study aimed to assess the relationship between working from home and insomnia among workers using data from the 5th Working Conditions Survey conducted in Korea.

Methods

Of 30,108 wage workers, we enrolled 818 employees who worked from home and 4,090 employees who worked from the office, a 1:5 pair sample based on sex and occupational group. Personal and occupational characteristics, working from home, and insomnia were included in the analysis. Age, education, employment status, working years, working hours per week, work-life balance, self-perceived health, depression, and anxiety were all adjusted as potential confounding variables. Conditional logistic regression analysis was performed using working from home as an independent variable and insomnia as a dependent variable to determine the correlation between working from home and insomnia.

Results

Working from home was associated with sleep onset latency disorder, OR = 3.23 (95% CI: 2.67–3.91), sleep maintenance disorder, OR = 3.67 (95% CI: 3.02–4.45), and non-restorative sleep, OR = 3.01 (95% CI: 2.46–3.67); working from home had a statistically significant relationship with all three types of insomnia.

Conclusions

Within the limits of the study, these findings can be used as a fundamental basis for the implementation of policies and guidelines to prevent insomnia in workers who work from home.
Re-defining reproductive coercion using a socio-ecological lens: a scoping review
Authors: Graham Melissa , Haintz Greer Lamaro , Bugden Megan , de Moel-Mandel Caroline , Donnelly Arielle , McKenzie Hayley
Published: July 2023

Background

Reproductive coercion is a significant public health issue in Australia which has mainly been conceptualised as a form of violence at the interpersonal level. This limited scope ignores the role of the gendered drivers of violence and fails to encompass a socio-ecological lens which is necessary to consider the multiple interacting layers that create the context in which reproductive coercion occurs. The aim of the scoping review was to explore how the reproductive coercion is defined by international research. Specifically, how is reproductive coercion defined at the social-cultural-systems-structural levels, and are the definitions of reproductive coercion inclusive of the conditions and contexts in which reproductive coercion occurs?

Methods

A scoping review was undertaken to explore existing definitions of reproductive coercion. Searches were conducted on Embase, Cochrane Library, Informit Health Collection, and the EBSCOHost platform. Google was also searched for relevant grey literature. Articles were included if they were: theoretical research, reviews, empirical primary research, grey literature or books; published between January 2018 and May 2022; written in English; and focused on females aged 18–50 years. Data from eligible articles were deductively extracted and inductively thematically analysed to identify themes describing how reproductive coercion is defined.

Results

A total of 24 articles were included in the scoping review. Most research defined reproductive coercion at the interpersonal level with only eight articles partially considering and four articles fully considering the socio-cultural-systems-structural level. Thematic analysis identified four main themes in reproductive coercion definitions: Individual external exertion of control over a woman’s reproductive autonomy; Systems and structures; Social and cultural determinants; and Freedom from external forces to achieve reproductive autonomy.

Conclusions

We argue for and propose a more inclusive definition of reproductive coercion that considers the gendered nature of reproductive coercion, and is linked to power, oppression and inequality, which is and can be perpetrated and/or facilitated at the interpersonal, community, organisational, institutional, systems, and societal levels as well as by the state.
Global incidence, prevalence and disease burden of silicosis: 30 years’ overview and forecasted trends
Authors: Liu Xin , Jiang Qingtao , Wu Peihong , Han Lei , Zhou Peng
Published: July 2023

Background

Globally, silicosis accounts for 90% of all pneumoconiosis cases and is a serious public health issue. It is characterized by progressive inflammation and irreversible pulmonary fibrosis. A comprehensive analysis at temporal, spatial and population levels with the most updated data from GBD 2019 is provided in this study to estimate the disease burden of silicosis from 1990 to 2019 and make predictions to 2029.

Methods

We delineated silicosis data on incidence, prevalence, and disability-adjusted life years (DALYs) as well as age-standardized rates (ASRs) across 30 years from GBD 2019. Joinpoint regression analysis was employed to detect temporal changes and estimate annual percentage change (APC) of each trend segment. Measures were stratified by time, location, age, and sociodemographic index (SDI). Back propagation artificial neural network (BP-ANN) model was applied to elaborate ASR trends from 1990 to 2019 and projections to the next 10 years.

Results

Globally, silicosis incident, prevalent cases, and DALYs increased by 64.6%, 91.4%, and 20.8%, respectively. However, all the corresponding ASRs showed overall downward trends with an estimated average APC (AAPC) of -0.5(-0.7 to -0.3), -0.2(-0.5 to 0.0), and − 2.0(-2.2 to -1.8), respectively. Middle and high-middle SDI regions carried the heaviest disease burden. The highest disease burden of silicosis was mainly transferred to the older from 1990 to 2019. The trend of ASRs demonstrated a rapid decline between 2005 and 2019, followed by a continuous decline until 2029.

Conclusion

Though disease burden of silicosis has been on a decline in general from 1990 to 2019, which shows a promising prospect but cannot be ignored. We should pay more attention to implementing preventive tactics and improving the life quality of present sufferers.
Association of demographics, cardiovascular indicators and disability characteristics with 7-year coronary heart disease incident in persons with disabilities
Authors: Li Husheng , Wang Yiyan , Xue Yan , Li Yao , Wu Hengjing , Wu Jing
Published: July 2023

Objective

Previous studies had demonstrated that disability increases mortality in patients with coronary heart disease (CHD). However, for people who had been disabled but do not have baseline cardiovascular disease, there is still limited data on how they might develop CHD. This study aimed to investigate the incidence and predictors of CHD in people with disabilities.

Methods

We conducted a 7-year retrospective study utilizing data from the Shanghai Comprehensive Information Platform for Persons with Disabilities Rehabilitation. Subjects aged over 18 years with at least four annual complete electronic health records were included. The primary outcome was CHD, defined as ischemic heart disease or myocardial infarction. Kaplan–Meier analysis and log-rank tests were used to compare cumulative CHD for sub-populations, stratified by age, gender, and the classification of disabilities. Cox regression was used to identify the potentially important factors.

Results

Out of 6419 persons with disabilities, 688 CHD cases (mean age 52.95 ± 7.17 years, male 52.2%) were identified, with a cumulative incidence of 10.72% and an incidence density of 15.15/1000 person-years. The incidence density of CHD is higher in the male gender, people over 45 years, and those with physical disabilities. Male (HR = 1.294, 95% CI, 1.111–1.506), hypertension (HR = 1.683, 95% CI, 1.405–2.009), diabetes mellitus (HR = 1.488, 95% CI, 1.140–1.934), total cholesterol (HR = 1.110, 95% CI, 1.023–1.204), and physical disabilities (HR = 1.122, 95% CI, 1.019–1.414) were independently associated with CHD.

Conclusion

The findings indicate that the incidence of CHD differs across disability categories rather than the severity of disability. People with physical disabilities had significantly higher risks for the development of CHD. The underlying physiological and pathological factors need to be further studied.
Machine learning applications for early detection of esophageal cancer: a systematic review
Authors: Hosseini Farhang , Asadi Farkhondeh , Emami Hassan , Ebnali Mahdi
Published: July 2023

Introduction

Esophageal cancer (EC) is a significant global health problem, with an estimated 7th highest incidence and 6th highest mortality rate. Timely diagnosis and treatment are critical for improving patients’ outcomes, as over 40% of patients with EC are diagnosed after metastasis. Recent advances in machine learning (ML) techniques, particularly in computer vision, have demonstrated promising applications in medical image processing, assisting clinicians in making more accurate and faster diagnostic decisions. Given the significance of early detection of EC, this systematic review aims to summarize and discuss the current state of research on ML-based methods for the early detection of EC.

Methods

We conducted a comprehensive systematic search of five databases (PubMed, Scopus, Web of Science, Wiley, and IEEE) using search terms such as “ML”, “Deep Learning (DL (“, “Neural Networks (NN)”, “Esophagus”, “EC” and “Early Detection”. After applying inclusion and exclusion criteria, 31 articles were retained for full review.

Results

The results of this review highlight the potential of ML-based methods in the early detection of EC. The average accuracy of the reviewed methods in the analysis of endoscopic and computed tomography (CT (images of the esophagus was over 89%, indicating a high impact on early detection of EC. Additionally, the highest percentage of clinical images used in the early detection of EC with the use of ML was related to white light imaging (WLI) images. Among all ML techniques, methods based on convolutional neural networks (CNN) achieved higher accuracy and sensitivity in the early detection of EC compared to other methods.

Conclusion

Our findings suggest that ML methods may improve accuracy in the early detection of EC, potentially supporting radiologists, endoscopists, and pathologists in diagnosis and treatment planning. However, the current literature is limited, and more studies are needed to investigate the clinical applications of these methods in early detection of EC. Furthermore, many studies suffer from class imbalance and biases, highlighting the need for validation of detection algorithms across organizations in longitudinal studies.
Assessment of cardio-renal-hepatic function in patients with valvular heart disease: a multi-biomarker approach—the cardio-renal-hepatic score
Authors: Lv Junxing , Zhang Bin , Ye Yunqing , Li Zhe , Wang Weiwei , Zhao Qinghao , Liu Qingrong , Zhao Zhenyan , Zhang Haitong , Wang Bincheng , Yu Zikai , Duan Zhenya , Guo Shuai , Zhao Yanyan , Gao Runlin , Xu Haiyan , Wu Yongjian ,   for the CHINA-VHD collaborators
Published: July 2023

Background

Valvular heart disease (VHD) can cause damage to extra-cardiac organs, and lead to multi-organ dysfunction. However, little is known about the cardio-renal-hepatic co-dysfunction, as well as its prognostic implications in patients with VHD. The study sought to develop a multi-biomarker index to assess heart, kidney, and liver function in an integrative fashion, and investigate the prognostic role of cardio-renal-hepatic function in VHD.

Methods

Using a large, contemporary, prospective cohort of 6004 patients with VHD, the study developed a multi-biomarker score for predicting all-cause mortality based on biomarkers reflecting heart, kidney, and liver function (N-terminal pro-B-type natriuretic peptide [NT-proBNP], creatinine, and albumin). The score was externally validated in another contemporary, prospective cohort of 3156 patients with VHD.

Results

During a median follow up of 731 (704–748) days, 594 (9.9%) deaths occurred. Increasing levels of NT-proBNP, creatinine, and albumin were independently and monotonically associated with mortality, and a weighted multi-biomarker index, named the cardio-renal-hepatic (CRH) score, was developed based on Cox regression coefficients of these biomarkers. The CRH score was a strong and independent predictor of mortality, with 1-point increase carrying over two times of mortality risk (overall adjusted hazard ratio [95% confidence interval]: 2.095 [1.891–2.320], P < 0.001). The score provided complementary prognostic information beyond conventional risk factors (C index: 0.78 vs 0.81; overall net reclassification improvement index [95% confidence interval]: 0.255 [0.204–0.299]; likelihood ratio test P < 0.001), and was identified as the most important predictor of mortality by the proportion of explainable log-likelihood ratio χ2 statistics, the best subset analysis, as well as the random survival forest analysis in most types of VHD. The predictive performance of the score was also demonstrated in patients under conservative treatment, with normal left ventricular systolic function, or with primary VHD. It achieved satisfactory discrimination (C index: 0.78 and 0.72) and calibration in both derivation and validation cohorts.

Conclusions

A multi-biomarker index was developed to assess cardio-renal-hepatic function in patients with VHD. The cardio-renal-hepatic co-dysfunction is a powerful predictor of mortality and should be considered in clinical management decisions.
A multifunctional ‘golden cicada’ nanoplatform breaks the thermoresistance barrier to launch cascade augmented synergistic effects of photothermal/gene therapy
Authors: Yang Wen , Wang Ning , Yang Jin , Liu Chao , Ma Shuang , Wang Xiye , Li Wenzhen , Shen Meiling , Wu Qinjie , Gong Changyang
Published: July 2023

Background

Photothermal therapy (PTT) is taken as a promising strategy for cancer therapy, however, its applicability is hampered by cellular thermoresistance of heat shock response and insufficient accumulation of photothermal transduction agents in the tumor region. In consideration of those limitations, a multifunctional “Golden Cicada” nanoplatform (MGCN) with efficient gene delivery ability and excellent photothermal effects is constructed, overcoming the thermoresistance of tumor cells and improving the accumulation of indocyanine green (ICG).

Results

Down-regulation of heat shock protein 70 (HSP70) makes tumor cells more susceptible to PTT, and a better therapeutic effect is achieved through such cascade augmented synergistic effects. MGCN has attractive features with prolonged circulation in blood, dual-targeting capability of CD44 and sialic acid (SA) receptors, and agile responsiveness of enzyme achieving size and charge double-variable transformation. It proves that, on the one hand, MGCN performs excellent capability for HSP70-shRNA delivery, resulting in breaking the cellular thermoresistance mechanism, on the other hand, ICG enriches in tumor site specifically and possesses a great thermal property to promoted PTT.

Conclusions

In short, MGCN breaks the protective mechanism of cellular heat stress response by downregulating the expression of HSP70 proteins and significantly augments synergistic effects of photothermal/gene therapy via cascade augmented synergistic effects.
TGF-β1 dominates stromal fibroblast-mediated EMT via the FAP/VCAN axis in bladder cancer cells
Authors: Ping Qinrong , Wang Chunhui , Cheng Xin , Zhong Yiming , Yan Ruping , Yang Meng , Shi Yunqiang , Li Xiangmeng , Li Xiao , Huang Wenwen , Wang Liqiong , Bi Xiaofang , Hu Libing , Yang Yang , Wang Yingbao , Gong Rui , Tan Jun , Li Rui , Li Hui , Li Jian , Wang Wenju , Li Ruhong
Published: July 2023

Background

Bladder cancer is one of the most common malignant tumors of the urinary system and is associated with a poor prognosis once invasion and distant metastases occur. Epithelial-mesenchymal transition (EMT) drives metastasis and invasion in bladder cancer. Transforming growth factor β1 (TGF-β1) and stromal fibroblasts, especially cancer-associated fibroblasts (CAFs), are positive regulators of EMT in bladder cancer. However, it remains unclear how TGF-β1 mediates crosstalk between bladder cancer cells and CAFs and how it induces stromal fibroblast-mediated EMT in bladder cancer. We aimed to investigate the mechanism of TGF-β1 regulation of stromal fibroblast-mediated EMT in bladder cancer cells.

Methods

Primary CAFs with high expression of fibroblast activation protein (FAP) were isolated from bladder cancer tissue samples. Subsequently, different conditioned media were used to stimulate the bladder cancer cell line T24 in a co-culture system. Gene set enrichment analysis, a human cytokine antibody array, and cytological assays were performed to investigate the mechanism of TGF-β1 regulation of stromal fibroblast-mediated EMT in bladder cancer cells.

Results

Among the TGF-β family, TGF-β1 was the most highly expressed factor in bladder cancer tissue and primary stromal fibroblast supernatant. In the tumor microenvironment, TGF-β1 was mainly derived from stromal fibroblasts, especially CAFs. In stimulated bladder cells, stromal fibroblast-derived TGF-β1 promoted bladder cancer cell migration, invasion, and EMT. Furthermore, TGF-β1 promoted the activation of stromal fibroblasts, inducing CAF-like features, by upregulating FAP in primary normal fibroblasts and a normal fibroblast cell line. Stromal fibroblast-mediated EMT was induced in bladder cancer cells by TGF-β1/FAP. Versican (VCAN), a downstream molecule of FAP, plays an essential role in TGF-β1/FAP axis-induced EMT in bladder cancer cells. VCAN may also function through the PI3K/AKT1 signaling pathway.

Conclusions

TGF-β1 is a critical mediator of crosstalk between stromal fibroblasts and bladder cancer cells. We revealed a new mechanism whereby TGF-β1 dominated stromal fibroblast-mediated EMT of bladder cancer cells via the FAP/VCAN axis and identified potential biomarkers (FAP, VCAN, N-cadherin, and Vimentin) of bladder cancer. These results enhance our understanding of bladder cancer invasion and metastasis and provide potential strategies for diagnosis, treatment, and prognosis.
Comparison of immunotherapy mediated by apoptotic bodies, microvesicles and exosomes: apoptotic bodies’ unique anti-inflammatory potential
Authors: Wen Jing , Creaven Dale , Luan Xiangshu , Wang Jiemin
Published: July 2023

Immunotherapy, including immunostimulation and immunosuppression, has seen significant development in the last 10 years. Immunostimulation has been verified as effective in anti-cancer treatment, while immunosuppression is used in the treatment of autoimmune disease and inflammation. Currently, with the update of newly-invented simplified isolation methods and the findings of potent triggered immune responses, extracellular vesicle-based immunotherapy is very eye-catching. However, the research on three main types of extracellular vesicles, exosomes, microvesicles and apoptotic bodies, needs to be more balanced. These three subtypes share a certain level of similarity, and at the same time, they have their own properties caused by the different methods of biogensis. Herein, we summarized respectively the status of immunotherapy based on each kind of vesicle and discuss the possible involved mechanisms. In conclusion, we highlighted that the effect of the apoptotic body is clear and strong. Apoptotic bodies have an excellent potential in immunosuppressive and anti-inflammatory therapies .
IL-1RA promotes oral squamous cell carcinoma malignancy through mitochondrial metabolism-mediated EGFR/JNK/SOX2 pathway
Authors: Yuan Shyng-Shiou F. , Wang Yun-Ming , Chan Leong-Perng , Hung Amos C. , Nguyen Hieu D. H. , Chen Yuk-Kwan , Hu Stephen Chu‐Sung , Lo Steven , Wang Yen-Yun
Published: July 2023

Background

Interleukin-1 receptor antagonist (IL-1RA), a member of the IL-1 family, has diverse roles in cancer development. However, the role of IL-1RA in oral squamous cell carcinoma (OSCC), in particular the underlying mechanisms, remains to be elucidated.

Methods

Tumor tissues from OSCC patients were assessed for protein expression by immunohistochemistry. Patient survival was evaluated by Kaplan–Meier curve analysis. Impact of differential IL-1RA expression on cultured OSCC cell lines was assessed in vitro by clonogenic survival, tumorsphere formation, soft agar colony formation, and transwell cell migration and invasion assays. Oxygen consumption rate was measured by Seahorse analyzer or multi-mode plate reader. PCR array was applied to screen human cancer stem cell-related genes, proteome array for phosphorylation status of kinases, and Western blot for protein expression in cultured cells. In vivo tumor growth was investigated by orthotopic xenograft in mice, and protein expression in xenograft tumors assessed by immunohistochemistry.

Results

Clinical analysis revealed that elevated IL-1RA expression in OSCC tumor tissues was associated with increased tumor size and cancer stage, and reduced survival in the patient group receiving adjuvant radiotherapy compared to the patient group without adjuvant radiotherapy. In vitro data supported these observations, showing that overexpression of IL-1RA increased OSCC cell growth, migration/invasion abilities, and resistance to ionizing radiation, whereas knockdown of IL-1RA had largely the opposite effects. Additionally, we identified that EGFR/JNK activation and SOX2 expression were modulated by differential IL-1RA expression downstream of mitochondrial metabolism, with application of mitochondrial complex inhibitors suppressing these pathways. Furthermore, in vivo data revealed that treatment with cisplatin or metformin—a mitochondrial complex inhibitor and conventional therapy for type 2 diabetes—reduced IL-1RA-associated xenograft tumor growth as well as EGFR/JNK activation and SOX2 expression. This inhibitory effect was further augmented by combination treatment with cisplatin and metformin.

Conclusions

The current study suggests that IL-1RA promoted OSCC malignancy through mitochondrial metabolism-mediated EGFR/JNK activation and SOX2 expression. Inhibition of this mitochondrial metabolic pathway may present a potential therapeutic strategy in OSCC.
Transcriptional activity of the long control region in human papillomavirus type 33 intratype variants
Authors: Gyöngyösi Eszter , László Brigitta , Szalmás Anita , Kónya József , Veress György
Published: July 2023

Background

High-risk human papillomaviruses (HPVs) are responsible for the development of cervical and other anogenital cancers. Intratype sequence variants of certain high-risk HPV types (e.g. 16, 18 and 31) are thought to have different oncogenic potential, partly due to nucleotide sequence variation in the viral long control region (LCR). The LCR has an important role in the regulation of viral replication and transcription. The purpose of this study was to explore sequence variation in the LCR of HPV 33 intratype variants in Hungary and to see whether there are differences in the transcriptional activities of the variants.

Methods

The complete HPV 33 LCR was amplified from HPV 33 positive cervical samples. After sequencing the LCR variants, multiple sequence alignment and phylogenetic analyses were carried out. Representative HPV 33 LCR sequence variants were selected for cloning and functional analysis. After transient transfection of HeLa cells, luciferase reporter assays were used to analyse the transcriptional activities of different LCR variants.

Results

Altogether 10 different variants were identified by sequence analysis of the HPV 33 LCR. The results of phylogenetic analysis showed that 3 variants belonged to sublineage A1, while the other 7 variants clustered with sublineage A2. Variants belonging to sublineage A2 had significantly lower transcriptional activities than variants belonging to sublineage A1. Within sublineage A2, the two variants analysed had significantly different transcriptional activities, which was shown to be caused by the A7879G variation.

Conclusions

Nucleotide variation in the HPV 33 LCR can result in altered transcriptional activity of the intratype variants. Our results can help to understand the correlation between LCR polymorphism and the oncogenic potential of HPV 33 variants.
The incidence and severity of open gingival embrasures in adults treated with clear aligners and fixed appliances: a retrospective cohort study
Authors: Yang Tianrui , Jiang Lishan , Sun Weiman , Zhu Meng , Jiang Ke , Li Houxuan , Lei Lang
Published: July 2023

Background

To evaluate the incidence and severity of open gingival embrasures (OGEs) in adult patients treated with clear aligners and fixed appliances.

Methods

Two hundred non-extraction adult subjects with less than 5 mm of crowding (mean age, 24.6 ± 3.8 years) were enrolled in this retrospective study. The subjects were divided into the clear aligner (n = 100) and fixed appliance group (n = 100). The intraoral photographs were utilized to determine the incidence of OGEs in the upper arch between maxillary central incisors, as well as the lower arch between mandibular central incisors. Crown overlap, crown shape, posttreatment root angulation, the distance from the interproximal contact point (ICP) to the alveolar bone crest (ABC) after treatment and interproximal enamel reduction (IPR) were determined in the two groups.

Results

The incidence of OGEs between maxillary and mandibular central incisors after orthodontic treatment was 35.0% and 38.0% in the clear aligner group, respectively, significantly higher than that (18.0% and 24.0%) in the fixed appliance group (P < 0.05). The average area of an OGE after clear aligner treatment was larger both in the maxilla (0.16 ± 0.12mm2) and mandible (0.21 ± 0.24mm2) compared with that (0.05 ± 0.03mm2and 0.05 ± 0.06mm2) after fixed appliance treatment (P < 0.05). No difference was found regarding pretreatment crown overlap, crown shape, treatment duration, posttreatment root angulation, amount and distribution of IPR and the distance from ICP to ABC.

Conclusions

The incidence and severity of OGEs were higher in adults treated with clear aligners. Clinicians should be aware of the risk of OGEs during treatment with clear aligners.
Three-dimensional design custom-made uncemented stem for revision of cemented distal femoral endoprosthesis due to aseptic loosening
Authors: Li Zhuangzhuang , Lu Minxun , Zhou Yong , Min Li , Tu Chongqi
Published: July 2023

Background

Revision of cemented distal femoral replacement (DFR) due to aseptic loosening is challenging because of the resultant femoral bone loss. This paper aims to examine the outcomes of three-dimensional (3D) design custom-made uncemented stems for revision.

Methods

Between January 2014 and December 2020, 17 patients received 3D design uncemented stems for revision of loosed cemented DFR. The femoral bone loss was classified into four Grades, and four types of uncemented stems were designed correspondingly. The revision stems were custom-made for each patient by measuring the diameter of the medullary cavity and the anterior curvature of the femur.

Results

The patient counts with their corresponding Grades of femoral bone loss were as follows: Grade I, 8 patients; Grade II, 5 patients; Grade III, 3 patients; and Grade IV, 1 patient. During the mean follow-up of 80 months, no revision failure was detected. The postoperative radiographic showed that the stem matched the femoral anterior curvature well. The femoral bone defect was completely filled by the 3D design stem in 10 of the 17 cases postoperatively. In the remaining cases, the persistent peri-stem defect was filled or partially restored during the follow-up.

Conclusion

3D design custom-made uncemented stem created precise, stable, and durable fixation and provided satisfactory clinical outcomes, which seems to be a viable method for cemented DFR revision.
Energy stress-induced circZFR enhances oxidative phosphorylation in lung adenocarcinoma via regulating alternative splicing
Authors: Ma Zhifei , Chen Hao , Xia Zhijun , You Jing , Han Chencheng , Wang Siwei , Xia Wenjia , Bai Yongkang , Liu Tongyan , Xu Lin , Zhou Guoren , Xu Youtao , Yin Rong
Published: July 2023

Background

Circular RNAs (circRNAs) contribute to multiple biological functions and are also involved in pathological conditions such as cancer. However, the role of circRNAs in metabolic reprogramming, especially upon energy stress in lung adenocarcinoma (LUAD), remains largely unknown.

Methods

Energy stress-induced circRNA was screened by circRNA profiling and glucose deprivation assays. RNA-seq, real-time cell analyzer system (RTCA) and measurement of oxygen consumption rate (OCR) were performed to explore the biological functions of circZFR in LUAD. The underlying mechanisms were investigated using circRNA pull-down, RNA immunoprecipitation, immunoprecipitation and bioinformatics analysis of alternative splicing. Clinical implications of circZFR were assessed in 92 pairs of LUAD tissues and adjacent non-tumor tissues, validated in established patient-derived tumor xenograft (PDTX) model.

Results

CircZFR is induced by glucose deprivation and is significantly upregulated in LUAD compared to adjacent non-tumor tissues, enhancing oxidative phosphorylation (OXPHOS) for adaptation to energy stress. CircZFR is strongly associated with higher T stage and poor prognosis in patients with LUAD. Mechanistically, circZFR protects heterogeneous nuclear ribonucleoprotein L-like (HNRNPLL) from degradation by ubiquitination to regulate alternative splicing, such as myosin IB (MYO1B), and subsequently activates the AKT-mTOR pathway to facilitate OXPHOS.

Conclusion

Our study provides new insights into the role of circRNAs in anticancer metabolic therapies and expands our understanding of alternative splicing.