bluuebunny/crossref_metadata_2025 huggingface dataset:
Super-resolution deep learning reconstruction at coronary computed tomography angiography to evaluate the coronary arteries and in-stent lumen: an initial experience
Authors: Orii Makoto , Sone Misato , Osaki Takeshi , Ueyama Yuta , Chiba Takuya , Sasaki Tadashi , Yoshioka Kunihiro
Published: October 2023

A super-resolution deep learning reconstruction (SR-DLR) algorithm trained using data acquired on the ultrahigh spatial resolution computed tomography (UHRCT) has the potential to provide better image quality of coronary arteries on the whole-heart, single-rotation cardiac coverage on a 320-detector row CT scanner. However, the advantages of SR-DLR at coronary computed tomography angiography (CCTA) have not been fully investigated. The present study aimed to compare the image quality of the coronary arteries and in-stent lumen between SR-DLR and model-based iterative reconstruction (MBIR). We prospectively enrolled 70 patients (median age, 69 years; interquartile range [IQR], 59–75 years; 50 men) who underwent CCTA using a 320-detector row CT scanner between January and August 2022. The image noise in the ascending aorta, left atrium, and septal wall of the ventricle was measured, and the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in the proximal coronary arteries were calculated. Of the twenty stents, stent strut thickness and luminal diameter were quantitatively evaluated. The image noise on SR-DLR was significantly lower than that on MBIR (median 22.1 HU; IQR, 19.3–24.9 HU vs. 27.4 HU; IQR, 24.2–31.2 HU, p < 0.01), whereas the SNR (median 16.3; IQR, 11.8–21.8 vs. 13.7; IQR, 9.9–18.4, p = 0.01) and CNR (median 24.4; IQR, 15.5–30.2 vs. 19.2; IQR, 14.1–23.2, p < 0.01) on SR-DLR were significantly higher than that on MBIR. Stent struts were significantly thinner (median, 0.68 mm; IQR, 0.61–0.78 mm vs. 0.81 mm; IQR, 0.72–0.96 mm, p < 0.01) and in-stent lumens were significantly larger (median, 1.84 mm; IQR, 1.65–2.26 mm vs. 1.52 mm; IQR, 1.28–2.25 mm, p < 0.01) on SR-DLR than on MBIR. Although further large-scale studies using invasive coronary angiography as the reference standard, comparative studies with UHRCT, and studies in more challenging population for CCTA are needed, this study’s initial experience with SR-DLR would improve the utility of CCTA in daily clinical practice due to the better image quality of the coronary arteries and in-stent lumen at CCTA compared with conventional MBIR.
Knowledge, attitude, and practice toward postpartum depression among the pregnant and lying-in women
Authors: Wang Kai , Li Rui , Li Qingqing , Li Zhenzhen , Li Ning , Yang Yandong , Wang Jia
Published: October 2023

Background

Postpartum depression (PPD) is considered an important public health problem, and early recognition of PPD in pregnant and lactating women is critical. This study investigated the knowledge, attitude, and practice (KAP) toward PPD among pregnant and lying-in women.

Methods

This cross-sectional study was conducted at Binzhou Medical University Hospital between September 2022 and November 2022 and included pregnant and lying-in women as study participants. A questionnaire was designed by the researchers that included demographic data and knowledge, attitude, and practice dimensions. Correlations between knowledge, attitude, and practice scores were evaluated by Pearson correlation analysis. Factors associated with practice scores were identified by multivariable logistic regression.

Results

All participants scored 6.27 ± 2.45, 36.37 ± 4.16, and 38.54 ± 7.93 93 from three sub-dimensions of knowledge, attitudes, and practices regarding PPD, respectively, with statistical differences in the three scores by age, education, and job status (p < 0.05). There were no significant differences between maternal (6.24 ± 2.34, 36.67 ± 3.82 and 38.31 ± 7.27, respectively) and pregnant women (6.30 ± 2.49, 36.00 ± 4.53 and 38.83 ± 8.69, respectively) in the total scores of knowledge, attitude, and practice dimensions. According to the results of multivariate logistic regression, the knowledge (OR = 1.235[1.128–1.353], P < 0.001) and attitude (OR = 1.052[1.005–1.102], P = 0.030) dimension scores were factors influencing the practice dimension scores.

Conclusion

The KAP of pregnant and lying-in women toward PPD is low. This study suggests that maternal awareness of PPD should be increased through the knowledge and attitudinal dimensions. Preventing PPD in pregnant and lying-in women can be achieved by improving both dimensions, thus enhancing practice.
Role of neutrophil / lymphocyte ratio, uric acid / albumin ratio and uric acid / creatinine ratio as predictors to severity of preeclampsia
Authors: Mohamed Rayan Abdelraheem , Ali Ibrahim Abdelrhim
Published: October 2023

Background

Pre-eclampsia (PE) is an intractable obstetric disorder with high mortality and morbidity, affecting 6–8% of pregnancies worldwide. As its etiology and pathogenesis remain unclear, there are no specific prevention or treatment options. This study aimed to determine the association between neutrophil to lymphocyte ratio (NLR), uric acid to albumin ratio (UAR) and uric acid to creatinine ratio (UA/Cr) and severity of pre-eclampsia.

Methods

A cross-sectional hospital-based study was conducted among pre-eclamptic women in Kosti Maternity Hospital from September to December 2022. Forty-five pre-eclamptic women were enrolled in this study and were classified according to the WHO classification of PE into mild PE (23 PE patients) and severe PE (22 PE patients). Data were collected using a semi-structured questionnaire covering medical history and clinical assessment. A blood sample was taken from each participant for measurements of the complete blood count (CBC), liver functions test (LFT) with enzymes, renal functions test (RFT) with electrolytes, and uric acid by standard techniques.

Results

NLR was found to be statistically significantly higher in mothers with severe PE (6.3–9.9) than in those with mild PE (2.2–1.5) (p-value 0.048). Alanine aminotransferase (ALT) was significantly higher in women with severe PE than in those with mild PE (p-value = 0.02). The total means of platelet-lymphocyte ratio (PLR), UA/Cr, and UAR were insignificantly higher in women with severe PE compared with those with mild PE (p-values 0.666, 0.427, and 0.525, respectively). The means of uric acid and serum creatinine showed insignificant statistical elevation in women with severe PE compared with mild PE (p-values of 0.27 and 0.44, respectively). Serum albumin was found to be insignificantly lower in mothers with severe PE (3.3 ± 0.6 g/dl) than in those with mild PE (3.6 ± 0.6 g/dl); p-value = 0.21.

Conclusions

PE showed a significant statistical increase in WBC, neutrophils, alanine transaminase (ALT), and NLR in severe PE compared to mild PE and a significant statistical decrease in lymphocyte count in severe PE compared to mild PE. The measurement of NLR may be a useful laboratory marker for predicting the severity of PE.
Safety and efficacy of 0.01% and 0.1% low-dose atropine eye drop regimens for reduction of myopia progression in Danish children: a randomized clinical trial examining one-year effect and safety
Authors: Hansen Niklas Cyril , Hvid-Hansen Anders , Møller Flemming , Bek Toke , Larsen Dorte Ancher , Jacobsen Nina , Kessel Line
Published: October 2023

Background

To investigate the efficacy and safety of 0.1% and 0.01% low-dose atropine eye drops in reducing myopia progression in Danish children.

Methods

Investigator-initiated, placebo-controlled, double-masked, randomized clinical trial. Ninety-seven six- to twelve-year old myopic participants were randomized to 0.1% loading dose for six months followed by 0.01% for six months (loading dose group, Number (N) = 33), 0.01% for twelve months (0.01% group, N = 32) or vehicle for twelve months (placebo, N = 32). Primary outcomes were axial length and spherical equivalent refraction. Secondary outcomes included adverse events and reactions, choroidal thickness and ocular biometry. Outcomes were measured at baseline and three-month intervals. Data was analyzed with linear-mixed model analysis according to intention-to-treat.

Results

Mean axial elongation was 0.10 mm less (95% confidence interval (CI): 0.17; 0.02, adjusted-p = 0.06) in the 0.1% loading dose and 0.07 mm less (95% CI: 0.15; 0.00, adjusted-p = 0.16) in the 0.01% group at twelve months compared to placebo. Mean spherical equivalent refraction progression was 0.24 D (95% CI: 0.05; 0.42) less in the loading dose and 0.19 D (95% CI: 0.00; 0.38) less in the 0.01% groups at twelve months, compared to placebo (adjusted-p = 0.06 and 0.14, respectively). A total of 108 adverse events were reported during the initial six-month loading dose period, primarily in the loading dose group, and 14 were reported in the six months following dose switching, all deemed mild except two serious adverse events, unrelated to the intervention.

Conclusions

Low-dose atropine eye drops are safe over twelve months in otherwise healthy children. There may be a modest but clinically relevant reduction in myopia progression in Danish children after twelve months treatment, but the effect was statistically non-significant after multiple comparisons adjustment. After dose-switching at six months the loading dose group approached the 0.01% group, potentially indicating an early “rebound-effect”.

Trial registration

this study was registered in the European Clinical Trials Database (EudraCT, number: 2018-001286-16) 05/11/2018 and first posted atwww.clinicaltrials.gov(NCT03911271) 11/04/2019, prior to initiation.
Cerebral Palsy – Early Diagnosis and Intervention Trial: protocol for the prospective multicentre CP-EDIT study with focus on diagnosis, prognostic factors, and intervention
Authors: Hoei-Hansen Christina Engel , Weber Lene , Johansen Mette , Fabricius Rebecca , Hansen Jonas Kjeldbjerg , Viuff Anne-Cathrine F. , Rønde Gitte , Hahn Gitte Holst , Østergaard Elsebet , Duno Morten , Larsen Vibeke Andrée , Madsen Camilla Gøbel , Røhder Katrine , Elvrum Ann-Kristin Gunnes , Laugesen Britt , Ganz Melanie , Madsen Kathrine Skak , Willerslev-Olsen Maria , Debes Nanette Mol , Christensen Jan , Christensen Robin , Rackauskaite Gija
Published: October 2023

Background

Early diagnosis of cerebral palsy (CP) is important to enable intervention at a time when neuroplasticity is at its highest. Current mean age at diagnosis is 13 months in Denmark. Recent research has documented that an early-diagnosis set-up can lower diagnostic age in high-risk infants. The aim of the current study is to lower diagnostic age of CP regardless of neonatal risk factors. Additionally, we want to investigate if an early intervention program added to standard care is superior to standard care alone.

Methods

The current multicentre study CP-EDIT (Early Diagnosis and Intervention Trial) with the GO-PLAY intervention included (Goal Oriented ParentaL supported home ActivitY program), aims at testing the feasibility of an early diagnosis set-up and the GO-PLAY early intervention. CP-EDIT is a prospective cohort study, consecutively assessing approximately 500 infants at risk of CP. We will systematically collect data at inclusion (age 3–11 months) and follow a subset of participants (n = 300) with CP or at high risk of CP until the age of two years. The GO-PLAY early intervention will be tested in 80 infants with CP or high risk of CP.

Focus is on eight areas related to implementation and perspectives of the families: early cerebral magnetic resonance imaging (MRI), early genetic testing, implementation of the General Movements Assessment method, analysis of the GO-PLAY early intervention, parental perspective of early intervention and early diagnosis, early prediction of CP, and comparative analysis of the Hand Assessment for Infants, Hammersmith Infant Neurological Examination, MRI, and the General Movements method.

Discussion

Early screening for CP is increasingly possible and an interim diagnosis of “high risk of CP” is recommended but not currently used in clinical care in Denmark. Additionally, there is a need to accelerate identification in mild or ambiguous cases to facilitate appropriate therapy early. Most studies on early diagnosis focus on identifying CP in infants below five months corrected age. Little is known about early diagnosis in the 50% of all CP cases that are discernible later in infancy. The current study aims at improving care of patients with CP even before they have an established diagnosis.

Trial registration

ClinicalTrials.gov ID 22013292 (reg. date 31/MAR/2023) for the CP-EDIT cohort and ID 22041835 (reg. date 31/MAR/2023) for the GO-PLAY trial.
Examining the secondary impacts of the COVID-19 pandemic on syndemic production and PrEP use among gay, bisexual and other men who have sex with men (GBM) in Vancouver, Canada
Authors: Sang Jordan M. , Moore David M. , Wang Lu , Chia Jason , Toy Junine , Montaner Julio , Skakoon-Sparling Shayna , Cox Joseph , Lambert Gilles , Grace Daniel , Hart Trevor A. , Lal Allan , Jollimore Jody , Lachowsky Nathan J.
Published: October 2023

Background

The secondary impacts of the COVID-19 pandemic may disproportionately affect gay, bisexual, and other men who have sex with men (GBM), particularly related to HIV prevention and treatment outcomes. We applied syndemic theory to examine PrEP disruptions during the during the height of the COVID-19 pandemic in Vancouver, Canada.

Methods

Sexually-active GBM, aged 16 + years, were enrolled through respondent-driven sampling (RDS) from February 2017 to August 2019. Participants completed a Computer-Assisted Self-Interview every six months and data were linked to the BC PrEP Program (program responsible for publicly funded PrEP in the province) to directly measure PrEP disruptions. The analysis period for this study was from March 2018-April 2021. We used univariable generalized linear mixed models to examine (1) six-month trends for syndemic conditions: the prevalence of moderate/severe depressive or anxiety symptoms, polysubstance use, harmful alcohol consumption, intimate partner violence, and (2) six-month trends for PrEP interruptions among HIV-negative/unknown GBM. We also applied 3-level mixed-effects logistic regression with RDS clustering to examine whether syndemic factors were associated with PrEP interruptions.

Results

Our study included 766 participants, with 593 participants who had at least one follow-up visit. The proportion of respondents with abnormal depressive symptoms increased over the study period (OR = 1.35; 95%CI = 1.17, 1.56), but we found decreased prevalence for polysubstance use (OR = 0.89; 95%CI = 0.82, 0.97) and binge drinking (OR = 0.74; 95%CI = 0.67, 0.81). We also found an increase in PrEP interruptions (OR = 2.33; 95%CI = 1.85, 2.94). GBM with moderate/severe depressive symptoms had higher odds (aOR = 4.80; 95%CI = 1.43, 16.16) of PrEP interruptions, while GBM with experiences of IPV had lower odds (aOR = 0.38; 95%CI = 0.15, 0.95) of PrEP interruptions. GBM who met clinical eligibility for PrEP had lower odds of experiencing PrEP interruptions (aOR = 0.25; 95%CI = 0.11, 0.60).

Conclusion

There were increasing PrEP interruptions since March 2020. However, those most at risk for HIV were less likely to have interruptions. Additional mental health services and targeted follow-up for PrEP continuation may help to mitigate the impacts of the COVID-19 pandemic on GBM.
A political economy analysis of strengthening health information system in Tanzania
Authors: Kuwawenaruwa August , Mollel Henry , Machonchoryo John Matiko , Margini Federica , Jaribu Jennie , Binyaruka Peter
Published: October 2023

Background

Many countries’ health systems are implementing reforms to improve the functioning and performance of the Health Management Information System (HMIS) to facilitate evidence-based decisions for delivery of accessible and quality health services. However, in some countries such efforts and initiatives have led to a complex HMIS ecosystem characterized by multiple and fragmented sub-systems. We undertook an in-depth analysis of the HMIS ecosystem in Tanzania to inform the ongoing initiatives, by understanding the relationship and power differences among stakeholders, as well as drivers and barriers to HMIS investment and strengthening.

Methodology

This was a qualitative research method incorporating data collection through document review and key informant interviews guided by political economy analytical framework. A total of 17 key informant interviews were conducted between April and May 2022. A thematic content analysis was used during data analysis.

Results

Good relationship between the government and stakeholders dealing/supporting HMIS ecosystem was noted as there are technical working groups which brings stakeholders together to discuss and harmonize HMIS activities. The ‘need for the data’ has been the driving force toward investment in the HMIS ecosystem. The analysis showed that the government is the main stakeholder within the HMIS ecosystem and responsible for identifying the needs for improvement and has the power to approve or reject systems which are not in line with the government priority as stipulated with the HMIS investment roadmap/strategy. Moreover, partners with long relationship are powerful in influencing HMIS investment decision-making compared to those who are recently coming to support. It was further noted shortage of staff with technical competence, inadequate financial resources, and the development of fact that some of the existing systems have not been developed to their full capacity and have hindered the whole systems’ integration and interoperability exercise of ensuring integration and interoperability of the systems.

Conclusion

A need-based assessment of staff capacity at the sub-national level is equally important to identify available capabilities and the knowledge gap to strengthen the HMIS ecosystem. Strong coordination of the ideas and resources intended to strengthen the HMIS ecosystem would help to reduce fragmentation. In addition, there is a need to mobilize resources within and outside the country to facilitate the integration and interoperability process smoothly.
KAMPNet: multi-source medical knowledge augmented medication prediction network with multi-level graph contrastive learning
Authors: An Yang , Tang Haocheng , Jin Bo , Xu Yi , Wei Xiaopeng
Published: October 2023

Backgrounds

Predicting medications is a crucial task in intelligent healthcare systems, aiding doctors in making informed decisions based on electronic medical records (EMR). However, medication prediction faces challenges due to complex relations within heterogeneous medical data. Existing studies primarily focus on the supervised mining of hierarchical relations between homogeneous codes in medical ontology graphs, such as diagnosis codes. Few studies consider the valuable relations, including synergistic relations between medications, concurrent relations between diseases, and therapeutic relations between medications and diseases from historical EMR. This limitation restricts prediction performance and application scenarios.

Methods

To address these limitations, we propose KAMPNet, a multi-sourced medical knowledge augmented medication prediction network. KAMPNet captures diverse relations between medical codes using a multi-level graph contrastive learning framework. Firstly, unsupervised graph contrastive learning with a graph attention network encoder captures implicit relations within homogeneous medical codes from the medical ontology graph, generating knowledge augmented medical code embedding vectors. Then, unsupervised graph contrastive learning with a weighted graph convolutional network encoder captures correlative relations between homogeneous or heterogeneous medical codes from the constructed medical codes relation graph, producing relation augmented medical code embedding vectors. Finally, the augmented medical code embedding vectors, along with supervised medical code embedding vectors, are fed into a sequential learning network to capture temporal relations of medical codes and predict medications for patients.

Results

Experimental results on the public MIMIC-III dataset demonstrate the superior performance of our KAMPNet model over several baseline models, as measured by Jaccard, F1 score, and PR-AUC for medication prediction.

Conclusions

Our KAMPNet model can effectively capture the valuable relations between medical codes inherent in multi-sourced medical knowledge using the proposed multi-level graph contrastive learning framework. Moreover, The multi-channel sequence learning network facilitates capturing temporal relations between medical codes, enabling comprehensive patient representations for downstream tasks such as medication prediction.
Investigating the relationship between resilience and professional ethics in nurses: a cross-sectional study in southern Iran
Authors: Asadi Yasaman , Molazem Zahra , Mohebbi Zinat , Ghaemmaghami Parvin
Published: October 2023

Introduction

All businesses that deal directly with clients need to observe ethics, but in the nursing profession due to its nature, compliance with professional ethics becomes more necessary. On the other hand, nurses face tensions and difficult conditions in their daily work environment. Resilience is one of the most important abilities of human beings, which in difficult conditions causes effective adaptation to stress-causing factors. Therefore, the relationship between resilience and professional ethics becomes important.

The aim of the study

The present study was conducted to investigate the relationship between resilience and professional ethics in nurses of Shahid Ganji Hospital, Borazjan 2022–2023.

Methods

The current study is a cross-sectional descriptive-analytical study. The study environment was Shahid Ganji Hospital in Borazjan, Bushehr, Iran. The research method of the current study was census, so all 400 nurses of this hospital were invited to participate in the study. Finally, 340 of them were included in the study based on the inclusion criteria. Data collection tools included a demographic information form, Connor-Davidson questionnaire, and Cadozier professional ethics questionnaire. Data analysis was done using SPSS version 22 software.

Results

Most of the participants were between 25 and 30 years old. The average overall score of resilience and professional ethics of nurses participating in the study was 64.1 ± 16.3 and 34.3 ± 9.4, respectively. No significant difference was observed between the demographic characteristics of nurses with resilience and professional ethics. The Spearman correlation coefficient indicated a statistically significant and inverse relationship between professional ethics and resilience levels (r = -0.265, P < 0.001).

Conclusion

The present study demonstrated a significant and inverse relationship between professional ethics and resilience among nurses. Furthermore, professional ethics were at a moderate level, while resilience was at a good level. Therefore, it is recommended that enhancing professional ethics skills through the organization of educational workshops for nurses should be considered by nursing managers.
Knowledge needs in patients with Liver Disease: a qualitative study
Authors: Jacobsen Birgitte Gade , Lauridsen Mette Munk , Grønkjaer Lea Ladegaard
Published: October 2023

Background

Knowledge is essential for patients’ disease management strategies and a critical component of healthcare. The importance of increasing patients level of knowledge has become more widely acknowledge in liver disease management in recent years, but further studies are needed to address patients experiences of unmet knowledge needs to develop appropriate patient education strategies. Therefore, the aim of this study was to explore knowledge needs in patients’ with liver disease of different etiology and severity.

Methods

A qualitative study was designed and an inductive method was chosen. Thirty-three patients with liver disease of different etiology and severity were interviewed using a semi-structured interview guide. Content analysis was used as an inspiration to describe and compare patients’ needs for knowledge across disease etiology and severity. The reporting followed consolidated criteria for reporting qualitative research.

Results

The analysis generated three categories and nine subcategories. In general, the patients described lack of knowledge related to their liver disease, which made it difficult for them to manage their disease. Patients wished to be more involved in care and treatment of the liver disease. However, patients’ had difficulties to assess and understand the importance of the information they received from healthcare professionals. Due to lack of knowledge, patients’ had a misconception of the liver disease. Patients’ had variation in knowledge needs depending on liver disease etiology and severity.

Conclusion

Within liver disease management, knowledge of patients’ experiences is vital to meet patients’ knowledge needs and to develop appropriate patient education strategies. Therefore, it is important to ascertain a patient-centered approach to accommodate patients’ individual knowledge needs, involve patients in care and treatment, and insure understanding to strengthen their self-management and give the patients the necessary skills to manage their disease and everyday life.

Registration number

Open Science Framework registration DOI https://doi.org/10.17605/OSF.IO/W28RC.
Genetic heterogeneity of cardiomyopathy and its correlation with patient care
Authors: Kim Mi Jin , Cha Seulgi , Baek Jae Suk , Yu Jeong Jin , Seo Go Hun , Kang Minji , Do Hyo-Sang , Lee Sang Eun , Lee Beom Hee
Published: October 2023

Background

Cardiomyopathy, which is a genetically and phenotypically heterogeneous pathological condition, is associated with increased morbidity and mortality. Genetic diagnosis of cardiomyopathy enables accurate phenotypic classification and optimum patient management and counseling. This study investigated the genetic spectrum of cardiomyopathy and its correlation with the clinical course of the disease.

Methods

The samples of 72 Korean patients with cardiomyopathy (43 males and 29 females) were subjected to whole-exome sequencing (WES). The familial information and clinical characteristics of the patients were reviewed and analyzed according to their genotypes.

Results

Dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), left ventricular non-compaction cardiomyopathy, and restrictive cardiomyopathy was detected in 41 (56.9%), 25 (34.7%), 4 (5.6%), and 2 (2.8%) patients, respectively. WES analysis revealed positive results in 37 (51.4%) patients. Subsequent familial testing identified ten additional familial cases. Among DCM cases, 19 (46.3%) patients exhibited positive results, with TTN variants being the most common alteration, followed by LMNA and MYH7 variants. Meanwhile, among HCM cases, 15 (60%) patients exhibited positive results with MYH7 variants being the most common alteration. In six patients with positive results, extracardiac surveillance was warranted based on disease information. The incidence of worse outcomes, such as mortality and life-threatening arrhythmic events, in patients with DCM harboring LMNA variants, was higher than that in patients with DCM harboring TTN or MYH7 variants.

Conclusions

Diverse genotypes were identified in a substantial proportion of patients with cardiomyopathy. Genetic diagnosis enables personalized disease surveillance and management.
A novel proteomic-based model for predicting colorectal cancer with Schistosoma japonicum co‐infection by integrated bioinformatics analysis and machine learning
Authors: Li Shan , Sun Xuguang , Li Ting , Shi Yanqing , Xu Binjie , Deng Yuyong , Wang Sifan
Published: October 2023

Schistosoma japonicum infection is an important public health problem and the S. japonicum infection is associated with a variety of diseases, including colorectal cancer. We collected the paraffin samples of CRC patients with or without S. japonicum infection according to standard procedures. Data-Independent Acquisition was used to identify differentially expressed proteins (DEPs), protein–protein interaction (PPI) network construction, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis and machine learning algorithms (least absolute shrinkage and selection operator (LASSO) regression) were used to identify candidate genes for diagnosing CRC with S. japonicum infection. To assess the diagnostic value, the nomogram and receiver operating characteristic (ROC) curve were developed. A total of 115 DEPs were screened, the DEPs that were discovered were mostly related with biological process in generation of precursor metabolites and energy,energy derivation by oxidation of organic compounds, carboxylic acid metabolic process, oxoacid metabolic process, cellular respiration aerobic respiration according to the analyses. Enrichment analysis showed that these compounds might regulate oxidoreductase activity, transporter activity, transmembrane transporter activity, ion transmembrane transporter activity and inorganic molecular entity transmembrane transporter activity. Following the development of PPI network and LASSO, 13 genes (hsd17b4, h2ac4, hla-c, pc, epx, rpia, tor1aip1, mindy1, dpysl5, nucks1, cnot2, ndufa13 and dnm3) were filtered, and 3 candidate hub genes were chosen for nomogram building and diagnostic value evaluation after machine learning. The nomogram and all 3 candidate hub genes (hsd17b4, rpia and cnot2) had high diagnostic values (area under the curve is 0.9556). The results of our study indicate that the combination of hsd17b4, rpia, and cnot2 may become a predictive model for the occurrence of CRC in combination with S. japonicum infection. This study also provides new clues for the mechanism research of S. japonicum infection and CRC.
Phenotypic variability in two female siblings with oocyte maturation arrest due to a TUBB8 variant
Authors: Dou Qian , Xu HongEn , Ma LiYing , Tan Li , Tang WenXue
Published: October 2023

Tubulin beta-8 (TUBB8) is expressed exclusively in the oocyte and early embryo, encoding a beta-tubulin polypeptide that participates in the assembly of microtubules.TUBB8was first attributed to being responsible for oocyte MI arrest. Further studies have demonstrated that patients with different pathogenic variants have variable phenotypes. We report aTUBB8variant (c.10 A > C) in two siblings who presented different clinical features of primary infertility. The younger sister showed severe oocyte maturation arrest with abnormal morphology, whereas a few mature oocytes and zygotes could be retrieved from the older sister, but no embryo was available for transfer. This variant was previously reported without in vitro functional assays. In the present study, RT‒qPCR and western blot analyses revealed that c.10 A > C reducesTUBB8mRNA and protein levels; however, immunofluorescence demonstrated that this variant does not change the localization of the protein. These findings confirm the pathogenicity of the c.10 A > C variant and support the relationship between the variant and phenotype in the patients.
FSTL3 partially mediates the association of increased nonalcoholic fatty liver disease fibrosis risk with acute myocardial infarction in patients with type 2 diabetes mellitus
Authors: Duan Wenfei , Shi Ruixiao , Yang Fang , Zhou Zhoujunhao , Wang Lihong , Huang Zhe , Zang Shufei
Published: October 2023

Background

The study aimed to investigate an association of increased liver fibrosis with acute myocardial infarction (AMI), and to investigate the mediating effect of serum follistatin-like protein 3 (FSTL3) on the association in patients with type 2 diabetes mellitus (T2DM).

Method

A total of 1424 participants were included in this study, and were firstly divided into two groups: 429 T2DM patients and 995 T2DM patients with NAFLD to assess the association of NAFLD and AMI. Then 995 T2DM co-existent NAFLD patients were categorized by NAFLD fibrosis risk to explore the association between NAFLD fibrosis risk and AMI. Immunohistochemistry staining and semi-quantitative analysis of liver FSTL3 were performed in 60 patients with NAFLD. There were 323 individuals (191 without AMI and 132 with AMI) in T2DM co-existent NAFLD patients who had serum samples, and serum FSTL3 was tested and mediation effect of FSTL3 in association of NAFLD fibrosis and AMI was performed.

Results

First, increased NAFLD fibrosis risk was an independent risk factor for AMI in patients with T2DM and co-existent NAFLD. In addition, analysis of Gene Expression Omnibus (GEO) database and immunohistochemical staining confirmed the increased expression of FSTL3 in the liver of NAFLD patients with fibrosis. Serum FSTL3 significantly increased in patients with high NAFLD fibrosis risk and AMI, and closely associated with NAFLD fibrosis and AMI severity in T2DM patients with co-existent NAFLD. Most importantly, analysis of the level of mediation revealed that increased serum FSTL3 partially mediated the association of increased NAFLD fibrosis risk with AMI in T2DM patients with co-existent NAFLD.

Conclusions

NAFLD fibrosis was closely associated with AMI in T2DM patients. FSTL3 expression was enriched in the liver of NAFLD patients with significant and advanced fibrosis, and serum FSTL3 partially mediated the association of increased liver fibrosis risk with AMI in T2DM patients.
M2 macrophage-secreted exosomes promote metastasis and increase vascular permeability in hepatocellular carcinoma
Authors: Lu Yiwei , Han Guoyong , Zhang Yao , Zhang Long , Li Zhi , Wang Qingyuan , Chen Zhiqiang , Wang Xuehao , Wu Jindao
Published: October 2023

Background

Metastasis is a key feature of malignant tumors and significantly contributes to their high mortality, particularly in hepatocellular carcinoma (HCC). Therefore, it is imperative to explore the mechanism of tumor metastasis. Recently, tumor-associated macrophages (TAMs) have been demonstrated to promote tumor progression, while TAM-derived molecules involved in HCC metastasis warrant further investigation.

Methods

THP-1 was treated with IL-4 (Interleukin-4) and IL-13 (Interleukin-13) for M2 polarized macrophages. Exosomes derived from M2 macrophages were characterized. Then, HCC cells or human umbilical vein endothelial cells (HUVECs) were co-cultured with M2 macrophages or treated with M2 macrophage-secreted exosomes. Next, Transwell®, Scratch assay, tube formation, and endothelial permeability assays were performed. Moreover, RT-PCR, western blotting, immunofluorescence, and ELISA were used to assess mRNA and protein expression levels. Finally, the miRNA expression profiles of exosomes derived from M2 and M0 macrophages were analyzed.

Results

M2 macrophage infiltration was correlated with metastasis and a poor prognosis in HCC patients. M2-derived exosomes were absorbed by HCC and HUVEC cells and promoted the epithelial-mesenchymal transition (EMT), vascular permeability, and angiogenesis. Notably, MiR-23a-3p levels were significantly higher in M2-derived exosomes and hnRNPA1 mediated miR-23a-3p packaging into exosomes. Phosphatase and tensin homolog (PTEN) and tight junction protein 1 (TJP1) were the targets of miR-23a-3p, as confirmed by luciferase reporter assays. Lastly, HCC cells co-cultured with M2-derived exosomes secreted more GM-CSF, VEGF, G-CSF, MCP-1, and IL-4, which in turn further recruited M2 macrophages.

Conclusions

Our findings suggest that M2 macrophage-derived miR-23a-3p enhances HCC metastasis by promoting EMT and angiogenesis, as well as increasing vascular permeability.
LRRK2 is involved in the chemotaxis of neutrophils and differentiated HL-60 cells, and the inhibition of LRRK2 kinase activity increases fMLP-induced chemotactic activity
Authors: Mazaki Yuichi , Handa Haruka , Fumoto Yoshizuki , Horinouchi Takahiro , Onodera Yasuhito
Published: October 2023

Background

Neutrophils depend heavily on glycolysis for energy production under normal conditions. In contrast, neutrophils require energy supplied by mitochondrial oxidative phosphorylation (OXPHOS) during chemotaxis. However, the mechanism by which the energy supply changes from glycolysis to OXPHOS remains unknown. Leucine-rich repeat kinase 2 (LRRK2) is partially present in the outer mitochondrial membrane fraction. Lrrk2-deficient cells show mitochondrial fragmentation and reduced OXPHOS activity. We have previously reported that mitofusin (MFN) 2 is involved in chemotaxis and OXPHOS activation upon chemoattractant N-formyl-Met-Leu-Phe (fMLP) stimulation in differentiated HL-60 (dHL-60) cells. It has been previously reported that LRRK2 binds to MFN2 and partially colocalizes with MFN2 at the mitochondrial membranes. This study investigated the involvement of LRRK2 in chemotaxis and MFN2 activation in neutrophils and dHL-60 cells.

Methods

Lrrk2 knockout neutrophils and Lrrk2 knockdown dHL-60 cells were used to examine the possible involvement of LRRK2 in chemotaxis. Lrrk2 knockdown dHL-60 cells were used a tetracycline-inducible small hairpin RNA (shRNA) system to minimize the effects of LRRK2 knockdown during cell culture. The relationship between LRRK2 and MFN2 was investigated by measuring the GTP-binding activity of MFN2 in Lrrk2 knockdown dHL-60 cells. The effects of LRRK2 kinase activity on chemotaxis were examined using the LRRK2 kinase inhibitor MLi-2.

Results

fMLP-induced chemotactic activity was reduced in Lrrk2 knockout neutrophils in vitro and in vivo. Lrrk2 knockdown in dHL-60 cells expressing Lrrk2 shRNA also reduced fMLP-induced chemotactic activity. Lrrk2 knockdown dHL-60 cells showed reduced OXPHOS activity and suppressed mitochondrial morphological change, similar to Mfn2 knockdown dHL-60 cells. The amount of LRRK2 in the mitochondrial fraction and the GTP-binding activity of MFN2 increased upon fMLP stimulation, and the MFN2 GTP-binding activity was suppressed in Lrrk2 knockdown dHL-60 cells. Furthermore, the kinase activity of LRRK2 and Ser935 phosphorylation of LRRK2 were reduced upon fMLP stimulation, and LRRK2 kinase inhibition by MLi-2 increased the migration to fMLP.

Conclusions

LRRK2 is involved in neutrophil chemotaxis and the GTP-binding activity of MFN2 upon fMLP stimulation. On the other hand, the kinase activity of LRRK2 shows a negative regulatory effect on fMLP-induced chemotactic activity in dHL-60 cells.
Multipredictor risk models for predicting individual risk of Alzheimer’s disease
Authors: Hou Xiao-He , Suckling John , Shen Xue-Ning , Liu Yong , Zuo Chuan-Tao , Huang Yu-Yuan , Li Hong-Qi , Wang Hui-Fu , Tan Chen-Chen , Cui Mei , Dong Qiang , Tan Lan , Yu Jin-Tai ,   Alzheimer’s Disease Neuroimaging Initiative
Published: October 2023

Background

Early prevention of Alzheimer’s disease (AD) is a feasible way to delay AD onset and progression. Information on AD prediction at the individual patient level will be useful in AD prevention. In this study, we aim to develop risk models for predicting AD onset at individual level using optimal set of predictors from multiple features.

Methods

A total of 487 cognitively normal (CN) individuals and 796 mild cognitive impairment (MCI) patients were included from Alzheimer's Disease Neuroimaging Initiative. All the participants were assessed for clinical, cognitive, magnetic resonance imaging and cerebrospinal fluid (CSF) markers and followed for mean periods of 5.6 years for CN individuals and 4.6 years for MCI patients to ascertain progression from CN to incident prodromal stage of AD or from MCI to AD dementia. Least Absolute Shrinkage and Selection Operator Cox regression was applied for predictors selection and model construction.

Results

During the follow-up periods, 139 CN participants had progressed to prodromal AD (CDR ≥ 0.5) and 321 MCI patients had progressed to AD dementia. In the prediction of individual risk of incident prodromal stage of AD in CN individuals, the AUC of the final CN model was 0.81 within 5 years. The final MCI model predicted individual risk of AD dementia in MCI patients with an AUC of 0.92 within 5 years. The models were also associated with longitudinal change of Mini-Mental State Examination (p < 0.001 for CN and MCI models). An Alzheimer’s continuum model was developed which could predict the Alzheimer’s continuum for individuals with normal AD biomarkers within 3 years with high accuracy (AUC = 0.91).

Conclusions

The risk models were able to provide personalized risk for AD onset at each year after evaluation. The models may be useful for better prevention of AD.
Dose-effect relationship of linear accelerator based stereotactic radiotherapy for brain metastases
Authors: Wu Ning , Wang Zhiqiang , Guo Xin , Zhao Hongfu
Published: October 2023

Objective

The purpose of this study is to reveal the dose-effect relationship of linear accelerator (LINAC)-based stereotactic radiotherapy (SRT) in patients with brain metastases (BM).

Materials and methods

The PubMed, Cochrane, and Web of Science databases were used to identify studies that reported local tumour control after LINAC-based SRT in patients with BMs. Studies of other approaches that could affect local tumour control, such as whole brain radiotherapy, targeted therapy, and immunotherapy, were excluded from the dose-effect relationship analysis. Data extracted included patient and treatment characteristics and tumour local control. Probit model in XLSTAT 2016 was used for regression analysis, and P < 0.05 was set as the statistically significant level.

Results

After literature screening, 19 eligible studies involving 1523 patients were included in the probit model regression analysis. There was no significant dose-effect relationship between nominal BED10 and peripheral BED10 versus 12-month local control probability. There were significant dose effect relationships between the centre BED10 and the average BED10 versus the 12-month local control probability, with P values of 0.015 and 0.011, respectively. According to the model, the central BED10 and the average BED10 corresponding to probabilities of 90% 12-month local control were 109.2 GyBED10 (95% confidence interval (CI): 88.7–245.9 GyBED10) and 87.8 GyBED10 (95% CI: 74.3–161.5 GyBED10), respectively. A 12-month local control rate of 86.9% (95% CI: 81.7–89.7%) and 85.5% (95% CI: 81.2–89.2%) can be expected at a centre BED10 of 80 Gy and an average BED10 of 60 Gy, respectively.

Conclusion

For patients with BM treated with LINAC-based SRT, more attention should be given to the central and average doses of PTV. A clear definition of the dose prescription should be established to ensure the effectiveness and comparability of treatment.
Circulating small extracellular vesicle-derived splicing factor 3b subunit 4 as a non-invasive diagnostic biomarker of early hepatocellular carcinoma
Authors: Son Ju A , Weon Ji Hyang , Baek Geum Ok , Ahn Hye Ri , Choi Ji Yi , Yoon Moon Gyeong , Cho Hyo Jung , Cheong Jae Youn , Eun Jung Woo , Kim Soon Sun
Published: October 2023

Background

Hepatocellular carcinoma (HCC) accounts for a majority of primary liver cancer cases and related deaths. The purpose of this study was to assess the diagnostic value of splicing factor 3b subunit 4 (SF3B4) as a novel non-invasive biomarker for HCC and determine the association between SF3B4 expression and immune cell infiltration.

Methods

An enzyme-linked immunosorbent assay (ELISA) was used to detect SF3B4 levels in plasma samples obtained from healthy controls (HCs) and patients with chronic hepatitis, liver cirrhosis, and HCC. The expression levels of autoantibodies that detect SF3B4 in the plasma samples of each group of patients were measured. Small extracellular vesicles (EVs) were isolated from patient sera, and the expression levels of EV-SF3B4 were measured using quantitative reverse transcription PCR.

Results

ELISA results confirmed that the expression levels of SF3B4 proteins and autoantibodies in the plasma of patients with HCC were higher than those in HCs. However, their diagnostic performance was not better than that of alpha-fetoprotein (AFP). The mRNA expression of SF3B4 in serum EV increased but not in the buffy coat or serum of patients with HCC. Serum EV-SF3B4 displayed better diagnostic power than AFP for all stages of HCC (AUC = 0.968 vs. 0.816), including early-stage HCC (AUC = 0.960 vs. 0.842), and this was consistent in the external cohort. Single-cell RNA sequencing indicated that SF3B4 expression was correlated with myeloid-derived suppressor cells. The Tumor Immune Estimation Resource database reconfirmed the correlation between SF3B4 expression and immune cell infiltration in HCC.

Conclusions

SF3B4 may be associated with tumor immune infiltration in HCC, and EV-SF3B4 shows potential as a novel non-invasive diagnostic biomarker of HCC.
CHESS 3: an improved, comprehensive catalog of human genes and transcripts based on large-scale expression data, phylogenetic analysis, and protein structure
Authors: Varabyou Ales , Sommer Markus J. , Erdogdu Beril , Shinder Ida , Minkin Ilia , Chao Kuan-Hao , Park Sukhwan , Heinz Jakob , Pockrandt Christopher , Shumate Alaina , Rincon Natalia , Puiu Daniela , Steinegger Martin , Salzberg Steven L. , Pertea Mihaela
Published: October 2023

CHESS 3 represents an improved human gene catalog based on nearly 10,000 RNA-seq experiments across 54 body sites. It significantly improves current genome annotation by integrating the latest reference data and algorithms, machine learning techniques for noise filtering, and new protein structure prediction methods. CHESS 3 contains 41,356 genes, including 19,839 protein-coding genes and 158,377 transcripts, with 14,863 protein-coding transcripts not in other catalogs. It includes all MANE transcripts and at least one transcript for most RefSeq and GENCODE genes. On the CHM13 human genome, the CHESS 3 catalog contains an additional 129 protein-coding genes. CHESS 3 is available at http://ccb.jhu.edu/chess.
Identification of RNA reads encoding different channels in isolated rat ventricular myocytes and the effect of cell stretching on L-type Ca2+current
Authors: Kamkin Andre G. , Kamkina Olga V. , Kazansky Viktor E. , Mitrokhin Vadim M. , Bilichenko Andrey , Nasedkina Elizaveta A. , Shileiko Stanislav A. , Rodina Anastasia S. , Zolotareva Alexandra D. , Zolotarev Valentin I. , Sutyagin Pavel V. , Mladenov Mitko I.
Published: October 2023

Background

The study aimed to identify transcripts of specific ion channels in rat ventricular cardiomyocytes and determine their potential role in the regulation of ionic currents in response to mechanical stimulation. The gene expression levels of various ion channels in freshly isolated rat ventricular cardiomyocytes were investigated using the RNA-seq technique. We also measured changes in current through CaV1.2 channels under cell stretching using the whole-cell patch-clamp method.

Results

Among channels that showed mechanosensitivity, significant amounts of TRPM7, TRPC1, and TRPM4 transcripts were found. We suppose that the recorded L-type Ca2+ current is probably expressed through CaV1.2. Furthermore, stretching cells by 6, 8, and 10 μm, which increases ISAC through the TRPM7, TRPC1, and TRPM4 channels, also decreased ICa,L through the CaV1.2 channels in K+ in/K+ out, Cs+ in/K+ out, K+ in/Cs+ out, and Cs+ in/Cs+ out solutions. The application of a nonspecific ISAC blocker, Gd3+, during cell stretching eliminated ISAC through nonselective cation channels and ICa,L through CaV1.2 channels. Since the response to Gd3+ was maintained in Cs+ in/Cs+ out solutions, we suggest that voltage-gated CaV1.2 channels in the ventricular myocytes of adult rats also exhibit mechanosensitive properties.

Conclusions

Our findings suggest that TRPM7, TRPC1, and TRPM4 channels represent stretch-activated nonselective cation channels in rat ventricular myocytes. Probably the CaV1.2 channels in these cells exhibit mechanosensitive properties. Our results provide insight into the molecular mechanisms underlying stretch-induced responses in rat ventricular myocytes, which may have implications for understanding cardiac physiology and pathophysiology.