bluuebunny/crossref_metadata_2025 huggingface dataset:
U-shaped association between triglyceride-glucose index and all-cause mortality among critically ill pediatrics: a population-based retrospective cohort study
Authors: Gao Qi , Luo Fan , Yu Hongxue , Lin Yuxin , Xu Ruqi , Li Pingping , Zhang Yuping , Liu Jiao , Su Licong , Li Yanqin
Published: June 2024

Background

Previous studies have shown that an elevated triglyceride-glucose (TyG) index was associated with all-cause mortality in both general adult individuals and critically ill adult patients. However, the relationship between the TyG index and clinical prognosis in pediatric patients admitted to the intensive care unit (ICU) remains unknown. We aimed to investigate the association of the TyG index with in-hospital all-cause mortality in critically ill pediatric patients.

Methods

A total of 5706 patients in the Pediatric Intensive Care database were enrolled in this study. The primary outcome was 30-day in-hospital all-cause mortality, and secondary outcome was 30-day in-ICU all-cause mortality. The restricted cubic spline (RCS) curves and two-piecewise multivariate Cox hazard regression models were performed to explore the relationship between the TyG index and outcomes.

Results

The median age of the study population was 20.5 [interquartile range (IQR): 4.8, 63.0] months, and 3269 (57.3%) of the patients were male. The mean TyG index level was 8.6 ± 0.7. A total of 244 (4.3%) patients died within 30 days of hospitalization during a median follow-up of 11 [7, 18] days, and 236 (4.1%) patients died in ICU within 30 days of hospitalization during a median follow-up of 6 [3, 11] days. The RCS curves indicated a U-shape association between the TyG index and 30-day in-hospital and in-ICU all-cause mortality (both P values for non-linear < 0.001). The risk of 30-day in-hospital all-cause mortality was negatively correlated with the TyG index until it bottoms out at 8.6 (adjusted hazard ratio [HR], 0.72, 95% confidence interval [CI] 0.55–0.93). However, when the TyG index was higher than 8.6, the risk of primary outcome increased significantly (adjusted HR, 1.51, 95% CI 1.16–1.96]). For 30-day in-ICU all-cause mortality, we also found a similar relationship (TyG < 8.6: adjusted HR, 0.75, 95% CI 0.57–0.98; TyG ≥ 8.6: adjusted HR, 1.42, 95% CI 1.08–1.85). Those results were consistent in subgroups and various sensitivity analysis.

Conclusions

Our study showed that the association between the TyG index and 30-day in-hospital and in-ICU all-cause mortality was nonlinear U-shaped, with a cutoff point at the TyG index of 8.6 in critically ill pediatric patients. Our findings suggest that the TyG index may be a novel and important factor for the short-term clinical prognosis in pediatric patients.
Challenges and opportunities in the management of type 2 diabetes in patients with lower extremity peripheral artery disease: a tailored diagnosis and treatment review
Authors: Mahé Guillaume , Aboyans Victor , Cosson Emmanuel , Mohammedi Kamel , Sarlon-Bartoli Gabrielle , Lanéelle Damien , Mirault Tristan , Darmon Patrice
Published: June 2024

Lower extremity peripheral artery disease (PAD) often results from atherosclerosis, and is highly prevalent in patients with type 2 diabetes mellitus (T2DM). Individuals with T2DM exhibit a more severe manifestation and a more distal distribution of PAD compared to those without diabetes, adding complexity to the therapeutic management of PAD in this particular patient population. Indeed, the management of PAD in patients with T2DM requires a multidisciplinary and individualized approach that addresses both the systemic effects of diabetes and the specific vascular complications of PAD. Hence, cardiovascular prevention is of the utmost importance in patients with T2DM and PAD, and encompasses smoking cessation, a healthy diet, structured exercise, careful foot monitoring, and adherence to routine preventive treatments such as statins, antiplatelet agents, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. It is also recommended to incorporate glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) in the medical management of patients with T2DM and PAD, due to their demonstrated cardiovascular benefits. However, the specific impact of these novel glucose-lowering agents for individuals with PAD remains obscured within the background of cardiovascular outcome trials (CVOTs). In this review article, we distil evidence, through a comprehensive literature search of CVOTs and clinical guidelines, to offer key directions for the optimal medical management of individuals with T2DM and lower extremity PAD in the era of GLP-1RA and SGLT2i.
Antiproliferative effect of indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogues on IL-6 mediated STAT3 and role of the apoptotic pathway in albino Wistar rats of ethyl carbamate-induced lung carcinoma: In-silico, In-vitro, and In-vivo study
Authors: Sonkar Archana Bharti , Verma Abhishek , Yadav Sneha , Kumar Rohit , Singh Jyoti , Keshari Amit K. , Rani Soniya , Kumar Anurag , Kumar Dharmendra , Shrivastava Neeraj Kumar , Rastogi Shubham , Alamoudi Mariam K. , Ansari Mohd Nazam , Saeedan Abdulaziz S. , Kaithwas Gaurav , Saha Sudipta
Published: June 2024

Lung cancer (LC) ranks second most prevalent cancer in females after breast cancer and second in males after prostate cancer. Based on the GLOBOCAN 2020 report, India represented 5.9% of LC cases and 8.1% of deaths caused by the disease. Several clinical studies have shown that LC occurs because of biological and morphological abnormalities and the involvement of altered level of antioxidants, cytokines, and apoptotic markers. In the present study, we explored the antiproliferative activity of indeno[1,2-d]thiazolo[3,2-a]pyrimidine analogues against LC using in-vitro, in-silico, and in-vivo models. In-vitro screening against A549 cells revealed compounds 9B (8-methoxy-5-(3,4,5-trimethoxyphenyl)-5,6-dihydroindeno[1,2-d]thiazolo[3,2-a]pyrimidine) and 12B (5-(4-chlorophenyl)-5,6-dihydroindeno[1,2-d]thiazolo[3,2-a]pyrimidine) as potential pyrimidine analogues against LC. Compounds 9B and 12B were docked with different molecular targets IL-6, Cyt-C, Caspase9, and Caspase3 using AutoDock Vina 4.1 to evaluate the binding affinity. Subsequently, in-vivo studies were conducted in albino Wistar rats through ethyl-carbamate (EC)- induced LC. 9B and 12B imparted significant effects on physiological (weight variation), and biochemical (anti-oxidant [TBAR’s, SOD, ProC, and GSH), lipid (TC, TG, LDL, VLDL, and HDL)], and cytokine (IL-2, IL-6, IL-10, and IL-1β) markers in EC-induced LC in albino Wistar rats. Morphological examination (SEM and H&E) and western blotting (IL-6, STAT3, Cyt-C, BAX, Bcl-2, Caspase3, and caspase9) showed that compounds 9B and 12B had antiproliferative effects. Accordingly, from the in-vitro, in-silico, and in-vivo experimental findings, we concluded that 9B and 12B have significant antiproliferative potential and are potential candidates for further evaluation to meet the requirements of investigation of new drug application.
Investigation of antimicrobial susceptibility patterns, risk factors and their impact on mortality in cancer patients at a tertiary care cancer hospital- A prospective study
Authors: Shelke Akshay , Priya Pallavi , Mishra Shiwani , Chauhan Richa , Murti Krishna , Ravichandiran V. , Dhingra Sameer
Published: June 2024

Background

Cancer patients are vulnerable to infections due to immunosuppression caused by cancer itself and its treatment. The emergence of antimicrobial-resistant bacteria further complicates the treatment of infections and increases the mortality and hospital stays. This study aimed to investigate the microbial spectrum, antimicrobial resistance patterns, risk factors, and their impact on clinical outcomes in these patients.

Methods

A prospective study was conducted at a tertiary care cancer hospital in Patna, Bihar, India, which included cancer patients aged 18 years and older with positive microbial cultures.

Results

This study analysed 440 patients, 53% (234) of whom were females, with an average age of 49.27 (± 14.73) years. A total of 541 isolates were identified, among which 48.01% (242) were multidrug resistant (MDR), 29.76% (150) were extensively drug resistant (XDR), and 19.84% (112) were sensitive. This study revealed that patients who underwent surgery, chemotherapy, were hospitalized, had a history of antibiotic exposure, and had severe neutropenia were more susceptible to MDR and XDR infections. The average hospital stays were 16.90 (± 10.23), 18.30 (± 11.14), and 22.83 (± 13.22) days for patients with sensitive, MDR, and XDR infections, respectively. The study also revealed overall 30-day mortality rate of 31.81% (140), whereas the MDR and XDR group exhibited 38.92% and 50.29% rates of 30-day mortality respectively (P < 0.001). Possible risk factors identified that could lead to mortality, were cancer recurrence, sepsis, chemotherapy, indwelling invasive devices such as foley catheter, Central venous catheter and ryles tube, MASCC score (< 21) and pneumonia.

Conclusions

This study emphasizes the necessity for personalized interventions among cancer patients, such as identifying patients at risk of infection, judicious antibiotic use, infection control measures, and the implementation of antimicrobial stewardship programs to reduce the rate of antimicrobial-resistant infection and associated mortality and hospital length of stay.
Deciphering the tumor immune microenvironment from a multidimensional omics perspective: insight into next-generation CAR-T cell immunotherapy and beyond
Authors: Zhou Zhaokai , Wang Jiahui , Wang Jiaojiao , Yang Shuai , Wang Ruizhi , Zhang Ge , Li Zhengrui , Shi Run , Wang Zhan , Lu Qiong
Published: June 2024

Tumor immune microenvironment (TIME) consists of intra-tumor immunological components and plays a significant role in tumor initiation, progression, metastasis, and response to therapy. Chimeric antigen receptor (CAR)-T cell immunotherapy has revolutionized the cancer treatment paradigm. Although CAR-T cell immunotherapy has emerged as a successful treatment for hematologic malignancies, it remains a conundrum for solid tumors. The heterogeneity of TIME is responsible for poor outcomes in CAR-T cell immunotherapy against solid tumors. The advancement of highly sophisticated technology enhances our exploration in TIME from a multi-omics perspective. In the era of machine learning, multi-omics studies could reveal the characteristics of TIME and its immune resistance mechanism. Therefore, the clinical efficacy of CAR-T cell immunotherapy in solid tumors could be further improved with strategies that target unfavorable conditions in TIME. Herein, this review seeks to investigate the factors influencing TIME formation and propose strategies for improving the effectiveness of CAR-T cell immunotherapy through a multi-omics perspective, with the ultimate goal of developing personalized therapeutic approaches.
Advanced gene nanocarriers/scaffolds in nonviral-mediated delivery system for tissue regeneration and repair
Authors: Zhang Wanheng , Hou Yan , Yin Shiyi , Miao Qi , Lee Kyubae , Zhou Xiaojian , Wang Yongtao
Published: June 2024

Tissue regeneration technology has been rapidly developed and widely applied in tissue engineering and repair. Compared with traditional approaches like surgical treatment, the rising gene therapy is able to have a durable effect on tissue regeneration, such as impaired bone regeneration, articular cartilage repair and cancer-resected tissue repair. Gene therapy can also facilitate the production of in situ therapeutic factors, thus minimizing the diffusion or loss of gene complexes and enabling spatiotemporally controlled release of gene products for tissue regeneration. Among different gene delivery vectors and supportive gene-activated matrices, advanced gene/drug nanocarriers attract exceptional attraction due to their tunable physiochemical properties, as well as excellent adaptive performance in gene therapy for tissue regeneration, such as bone, cartilage, blood vessel, nerve and cancer-resected tissue repair. This paper reviews the recent advances on nonviral-mediated gene delivery systems with an emphasis on the important role of advanced nanocarriers in gene therapy and tissue regeneration.
9-cis-retinoic acid signaling in Sertoli cells regulates their immunomodulatory function to control lymphocyte physiology and Treg differentiation
Authors: Kamińska Alicja , Pardyak Laura , Lustofin Sylwia , Gielata Karolina , Arent Zbigniew , Pietsch-Fulbiszewska Agnieszka , Hejmej Anna
Published: June 2024

Background

Testis is an immune privileged organ, which prevents the immune response against sperm antigens and inflammation. Testicular cells responsible for immune tolerance are mainly Sertoli cells, which form the blood-testis barrier and produce immunosuppressive factors. Sertoli cells prevent inflammation in the testis and maintain immune tolerance by inhibiting proliferation and inducing lymphocyte apoptosis. It has been shown that 9-cis-retinoic acid (9cRA) blocks ex vivo apoptosis of peripheral blood lymphocytes and promotes the differentiation of Treg cells in the gut. However, the role of retinoid signaling in regulating the immune privilege of the testes remains unknown.

Objective

The aim of this study was to determine whether 9cRA, acting via the retinoic acid receptors (RAR) and the retinoic X receptors (RXR), controls the immunomodulatory functions of Sertoli cells by influencing the secretion of anti-inflammatory/pro-inflammatory factors, lymphocyte physiology and Treg cell differentiation.

Methods

Experiments were performed using in vitro model of co-cultures of murine Sertoli cells and T lymphocytes. Agonists and antagonists of retinoic acid receptors were used to inhibit/stimulate retinoid signaling in Sertoli cells.

Results

Our results have demonstrated that 9cRA inhibits the expression of immunosuppressive genes and enhances the expression of pro-inflammatory factors in Sertoli cells and lymphocytes, increases lymphocyte viability and decreases apoptosis rate. Moreover, we have found that 9cRA blocks lymphocyte apoptosis acting through both RAR and RXR and inhibiting FasL/Fas/Caspase 8 and Bax/Bcl-2/Caspase 9 pathways. Finally, we have shown that 9cRA signaling in Sertoli cells inhibits Treg differentiation.

Conclusion

Collectively, our results indicate that retinoid signaling negatively regulates immunologically privileged functions of Sertoli cells, crucial for ensuring male fertility. 9cRA inhibits lymphocyte apoptosis, which can be related to the development of autoimmunity, inflammation, and, in consequence, infertility.
TGF-β signaling: critical nexus of fibrogenesis and cancer
Authors: Giarratana Anna O. , Prendergast Conor M. , Salvatore Mary M. , Capaccione Kathleen M.
Published: June 2024

The transforming growth factor-beta (TGF-β) signaling pathway is a vital regulator of cell proliferation, differentiation, apoptosis, and extracellular matrix production. It functions through canonical SMAD-mediated processes and noncanonical pathways involving MAPK cascades, PI3K/AKT, Rho-like GTPases, and NF-κB signaling. This intricate signaling system is finely tuned by interactions between canonical and noncanonical pathways and plays key roles in both physiologic and pathologic conditions including tissue homeostasis, fibrosis, and cancer progression. TGF-β signaling is known to have paradoxical actions. Under normal physiologic conditions, TGF-β signaling promotes cell quiescence and apoptosis, acting as a tumor suppressor. In contrast, in pathological states such as inflammation and cancer, it triggers processes that facilitate cancer progression and tissue remodeling, thus promoting tumor development and fibrosis. Here, we detail the role that TGF-β plays in cancer and fibrosis and highlight the potential for future theranostics targeting this pathway.
Intestinal mRNA expression profiles associated with mucosal healing in ustekinumab-treated Crohn's disease patients: bioinformatics analysis and prospective cohort validation
Authors: Li Qing , Huang Zicheng , Yang Hongsheng , Tang Jian , Zuo Tao , Yang Qingfan , Huang Zhaopeng , Guo Qin , Li Miao , Gao Xiang , Chao Kang
Published: June 2024

Background

Variations exist in the response of patients with Crohn’s disease (CD) to ustekinumab (UST) treatment, but the underlying cause remains unknown. Our objective was to investigate the involvement of immune cells and identify potential biomarkers that could predict the response to interleukin (IL) 12/23 inhibitors in patients with CD.

Methods

The GSE207022 dataset, which consisted of 54 non-responders and 9 responders to UST in a CD cohort, was analyzed. Differentially expressed genes (DEGs) were identified and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Least absolute shrinkage and selection operator (LASSO) regression was used to screen the most powerful hub genes. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performances of these genes. Single-sample Gene Set Enrichment Analysis (ssGSEA) was used to estimate the proportions of immune cell types. These significantly altered genes were subjected to cluster analysis into immune cell-related infiltration. To validate the reliability of the candidates, patients prescribed UST as a first-line biologic in a prospective cohort were included as an independent validation dataset.

Results

A total of 99 DEGs were identified in the integrated dataset. GO and KEGG analyses revealed significant enrichment of immune response pathways in patients with CD. Thirteen genes (SOCS3, CD55, KDM5D, IGFBP5, LCN2, SLC15A1, XPNPEP2, HLA-DQA2, HMGCS2, DDX3Y, ITGB2, CDKN2B and HLA-DQA1), which were primarily associated with the response versus nonresponse patients, were identified and included in the LASSO analysis. These genes accurately predicted treatment response, with an area under the curve (AUC) of 0.938. T helper cell type 1 (Th1) cell polarization was comparatively strong in nonresponse individuals. Positive connections were observed between Th1 cells and the LCN2 and KDM5D genes. Furthermore, we employed an independent validation dataset and early experimental verification to validate the LCN2 and KDM5D genes as effective predictive markers.

Conclusions

Th1 cell polarization is an important cause of nonresponse to UST therapy in patients with CD. LCN2 and KDM5D can be used as predictive markers to effectively identify nonresponse patients.

Trial registration: Trial registration number: NCT05542459; Date of registration: 2022-09-14; URL: https://www.clinicaltrials.gov.
Adoptive NK cell therapy: a potential revolutionary approach in longevity therapeutics
Authors: Deng Xuewen , Terunuma Hiroshi
Published: June 2024

The aging process intricately involves immune system dynamics, with a crucial role in managing senescent cells (SNCs) and their senescence-associated secretory phenotypes (SASPs). Unfortunately, immunosenescence, a progressively dysregulated immunity with age, hampers effective SNC elimination, leading to accumulation, coupled with the release of SASPs, which, in turn, inhibits immunity and heightened susceptibility to aging-associated diseases (AADs). Natural killer (NK) cells, integral to the innate immune system, play a pivotal role in addressing SNCs swiftly. These cells also coordinate with other components of both innate and adaptive immunity to surveil and eliminate these cells. Accordingly, preserving NK cell function during aging is crucial for evading AADs and promoting healthy aging. Alternatively, NK-cell-based therapies present promising avenues for addressing the challenges associated with aging. Notable, recent studies in adoptive NK cell therapy have shown promise in rejuvenating immunosenescence, eliminating SNCs, and alleviating SASPs. This progress provides the proof-concept of adoptive NK cell therapy for senotherapy and holds promise as an emerging revolution in longevity therapeutics.
Knowledge, attitude and practice of healthcare workers on isoniazid preventive treatment in Tanzania; a health facility-based cross-sectional study
Authors: Mshiu Johnson Jeremia , Alexander Felix Christopher , Rushaigo Anelisa Martin , Nyigo Vitus Alberto , Majaha Melkisedeck Lolakeha , Maokola Werner Meinrad , Ngowi Bernard James , Wiketye Victor Enock , Kimbute Omari Abdallah , Mgina Erick Josephat , Makasi Charles Elias , Range Nyagosya Segere , Kilale Andrew Martin
Published: June 2024

Background

Tuberculosis (TB) remains a significant public health concern globally, particularly in regions with a high prevalence of HIV/AIDS. In Tanzania, the co-occurrence of TB and HIV poses a substantial challenge to healthcare systems. Isoniazid Preventive Therapy (IPT) has become an important intervention to mitigate the risk of TB infection among individuals living with HIV. Despite its proven efficacy, the extent of knowledge, attitude, and practice of healthcare workers (HCWs) in Tanzania is not well-documented. This study aimed to evaluate the levels of knowledge, attitude, and practice regarding IPT among healthcare workers.

Methods

A cross-sectional study was carried out among healthcare workers working at TB/HIV clinics in 12 regions of Tanzania mainland. A semi-structured questionnaire was administered to the respondents consisting of social demographic characteristics, knowledge, attitude, and practice questions. Data were analyzed using Stata version 14.0.

Results

A total of 464 respondents were interviewed, with 282 (60.8%) being female. The mean age was 36.4 years (SD = 11.0). Among the interviewed, 255 (55.0%) were nurses. Regarding knowledge, attitude, and practice on IPT, 217 (46.8%), 220 (47.0%), and 422 (90.9%) respondents respectively demonstrated adequacy in these domains. Factors such as gender, university education, professional role in healthcare practice, cumulative work experience of one year or more, tenure at a TB/HIV clinic of one year or longer, and attendance at IPT-related training emerged as significant determinants. These factors influence respondents' knowledge, attitude, and practice towards IPT.

Conclusion

The findings underscored a notable knowledge gap and a less favourable attitude towards IPT among HCWs, despite commendable practices. Addressing this disparity through targeted training interventions for healthcare workers holds promise for enhancing their understanding and attitude toward IPT, thereby fostering increased acceptance and utilization of this preventive therapy.
CircRNA_101491 regulated the radiation sensitivity of esophageal squamous cell carcinomas via sponging miR-125a-5p
Authors: Lin Chen , Huang Xianfeng , Qian Yuchen , Li Jiayi , He Youdi , Su Huafang
Published: June 2024

Background

At present, it has been found that many patients have acquired resistance to radiotherapy, which greatly reduces the effect of radiotherapy and further affects the prognosis. CircRNAs is involved in the regulation of radiosensitivity of many kinds of tumor cells. Therefore, the main purpose of this study is to explore the regulatory effect of CircRNA_101491 on radiosensitivity of ESCC and its related mechanism.

Methods

We established ESCC radiation-resistant cell line (KYSE150R cell) by gradient dose method, and tested the difference of KYSE150 between KYSE150R cell and parent cell in vitro. Then, after knocking down the expression of CircRNA_101491, a series of in vitro experiments were conducted to verify the effects of CircRNA_101491 on the phenotype and radiosensitivity of KYSE150R cells, and further analyzed the related regulatory mechanism. In addition, we also used the model of transplanted tumor in nude mice to investigate the effect of CircRNA_101491 on the radiosensitivity of ESCC in vivo.

Results

According to a series of in vitro experiments, we confirmed that KYSE150R cells lost the epithelial phenotype and obtained interstitial cell-like phenotype, and found that CircRNA_101491 was highly expressed in KYSE150R cells. In addition, we found that knocking down the expression of CircRNA_101491 will lift the inhibition of miR-125a-5p, and then reverse the process of EMT, accelerate the process of apoptosis, thus play a role in radiosensitization. The in vivo experiment of transplanted tumor in nude mice also showed that knocking down the expression of CircRNA_101491 could enhance the radiosensitivity of ESCC.

Conclusion

In conclusion, we confirmed that interfering with the expression of CircRNA_101491 can relieve the inhibition of miR-125a-5p, thus reverse the process of interstitial phenotype, accelerate the process of apoptosis, and enhance the radiosensitivity of ESCC.
Development and validation of a machine learning predictive model for perioperative myocardial injury in cardiac surgery with cardiopulmonary bypass
Authors: Li Qian , Lv Hong , Chen Yuye , Shen Jingjia , shi Jia , Zhou Chenghui
Published: June 2024

Background

Perioperative myocardial injury (PMI) with different cut-off values has showed to be associated with different prognostic effect after cardiac surgery. Machine learning (ML) method has been widely used in perioperative risk predictions during cardiac surgery. However, the utilization of ML in PMI has not been studied yet. Therefore, we sought to develop and validate the performances of ML for PMI with different cut-off values in cardiac surgery with cardiopulmonary bypass (CPB).

Methods

This was a second analysis of a multicenter clinical trial (OPTIMAL) and requirement for written informed consent was waived due to the retrospective design. Patients aged 18–70 undergoing elective cardiac surgery with CPB from December 2018 to April 2021 were enrolled in China. The models were developed using the data from Fuwai Hospital and externally validated by the other three cardiac centres. Traditional logistic regression (LR) and eleven ML models were constructed. The primary outcome was PMI, defined as the postoperative maximum cardiac Troponin I beyond different times of upper reference limit (40x, 70x, 100x, 130x) We measured the model performance by examining the area under the receiver operating characteristic curve (AUROC), precision-recall curve (AUPRC), and calibration brier score.

Results

A total of 2983 eligible patients eventually participated in both the model development (n = 2420) and external validation (n = 563). The CatboostClassifier and RandomForestClassifier emerged as potential alternatives to the LR model for predicting PMI. The AUROC demonstrated an increase with each of the four cutoffs, peaking at 100x URL in the testing dataset and at 70x URL in the external validation dataset. However, it’s worth noting that the AUPRC decreased with each cutoff increment. Additionally, the Brier loss score decreased as the cutoffs increased, reaching its lowest point at 0.16 with a 130x URL cutoff. Moreover, extended CPB time, aortic duration, elevated preoperative N-terminal brain sodium peptide, reduced preoperative neutrophil count, higher body mass index, and increased high-sensitivity C-reactive protein levels were identified as risk factors for PMI across all four cutoff values.

Conclusions

The CatboostClassifier and RandomForestClassifer algorithms could be an alternative for LR in prediction of PMI. Furthermore, preoperative higher N-terminal brain sodium peptide and lower high-sensitivity C-reactive protein were strong risk factor for PMI, the underlying mechanism require further investigation.
Pulmonary, aorta, and coronary arteries post-arterial switch in transposition of great arteries: intermediate-term surveillance utilizing conventional echocardiography and cardiac multislice computed tomography
Authors: Rakha Shaimaa , Batouty Nihal M. , ElDerie Ahmad AbdelAleem , Hussein Amira
Published: June 2024

Background

Arterial switch operation (ASO) is the standard surgical choice for D-transposition of great arteries (D-TGA). However, the implications of ASO on pulmonaries, coronaries, and aorta have not been adequately investigated. The current study evaluates arterial morphologic changes post-ASO at intermediate-term surveillance.

Methods

From May 2021 to May 2022, patients with D-TGA who underwent ASO for more than six months were recruited. Preoperative and operative data were collected. Patients were assessed using echocardiography (ECHO) and multislice CT angiography (MSCT) to evaluate pulmonary, coronary, and aortic arterial anatomy.

Results

Twenty patients were included with median age of 11 (10-23.25) days at ASO and 14 (7.25–32.75) months on last follow-up. Neo-aortic regurgitation was detected in 12(60%) and neo-pulmonary regurgitation in 3 (15%). Using ECHO, complete evaluation of pulmonary arteries (PAs) was not achieved in 35% and incomplete coronaries assessment in 40% of cases. No stenosis was detected in coronaries using MSCT, although coronary anomalies were found in 9/20 (45%). Dilated Aortic annulus was detected in 16/20 (80%), dilated aortic root in 18/20 (90%), and dilated sinotubular junction in 70%. Right PA stenosis was diagnosed in 10/20 (50%) and left PA(LPA) stenosis in 7/20 (35%). Although Z-score of PAs did not correlate with aortic data, LPA bending angle was positively correlated to neo-aortic root diameter and Z-score (rho = 0.65,p = 0.016; rho = 0.69,p = 0.01), respectively.

Conclusion

Echocardiography alone is not a conclusive surveillance tool for detecting late post-ASO anatomic changes in D-TGA patients. Cardiac MSCT should be considered for comprehensive evaluation on the intermediate-term follow-up post-ASO to accurately track morphologic abnormalities in the aorta, pulmonary, and coronary arteries.
Is comorbidity alone responsible for changes in health-related quality of life among critical care survivors? A purpose-specific review
Authors: Orwelius Lotti , Wilhelms Susanne , Sjöberg Folke
Published: June 2024

Background

Health-related quality of life (HRQoL) is one of the most important outcome variables for assessing the effectiveness of intensive care, together with mortality and survival, where comorbidity is suggested to have high impact. However, studies are lacking that examine to what extent HRQoL is affected after a general ICU period, beyond that of the effects that may be claimed to be due to comorbidities.

Design

Purpose-specific literature review including literature searches in PubMed, Cinahl, Scopus, and Cochrane library between 2010 and 2021.

Measurements and results

This Purpose-specific, i.e., task focused review examines HRQoL (assessed by either SF-36 or EQ-5D, > 30 days after leaving the hospital) in adult patients (≥ 18 years) having an ICU length of stay > 24 h. Further, the HRQoL comparisons were adjusted for age or comorbidity. A total of 11 publications were found. A majority comprised observational, prospective cohort studies, except three that were either case–control, cross-sectional comparison, or retrospective cohort studies. A total of 18,566 critically ill patients were included, and the response rate ranged from 16 to 94%. In all studies, a recurrent relevant finding was that HRQoL after ICU care was affected by pre-ICU comorbidities. In three studies (n = 3), which included a comorbidity adjusted control group, there were no effect of the critical care period itself on the registered HRQoL after the critical care period.

Conclusion

Health-Related Quality of Life (HRQoL) in former ICU patients appears to be primarily influenced by comorbidity. A notable limitation in this field of research is the high heterogeneity observed in the studies reviewed, particularly in terms of the HRQoL measurement tool employed, the duration of follow-up, the methodology for comorbidity assessment, and the adjustments for age and sex. Despite these variations and the limited number of studies in the review, the findings suggest a minimal HRQoL impact beyond the effects of comorbidity. Given the significant dearth of comprehensive studies in this domain, there is an escalating call for more thorough and detailed research endeavours.

Graphical abstract
Immune evasion impacts the landscape of driver genes during cancer evolution
Authors: Gourmet Lucie , Sottoriva Andrea , Walker-Samuel Simon , Secrier Maria , Zapata Luis
Published: June 2024

Background

Carcinogenesis is driven by interactions between genetic mutations and the local tumor microenvironment. Recent research has identified hundreds of cancer driver genes; however, these studies often include a mixture of different molecular subtypes and ecological niches and ignore the impact of the immune system.

Results

In this study, we compare the landscape of driver genes in tumors that escaped the immune system (escape +) versus those that did not (escape −). We analyze 9896 primary tumors from The Cancer Genome Atlas using the ratio of non-synonymous to synonymous mutations (dN/dS) and find 85 driver genes, including 27 and 16 novel genes, in escape − and escape + tumors, respectively. The dN/dS of driver genes in immune escaped tumors is significantly lower and closer to neutrality than in non-escaped tumors, suggesting selection buffering in driver genes fueled by immune escape. Additionally, we find that immune evasion leads to more mutated sites, a diverse array of mutational signatures and is linked to tumor prognosis.

Conclusions

Our findings highlight the need for improved patient stratification to identify new therapeutic targets for cancer treatment.
Ecology and geography of Cache Valley virus assessed using ecological niche modeling
Authors: Muller John A. , López Krisangel , Escobar Luis E. , Auguste Albert J.
Published: June 2024

Background

Cache Valley virus (CVV) is an understudied Orthobunyavirus with a high spillover transmission potential due to its wide geographical distribution and large number of associated hosts and vectors. Although CVV is known to be widely distributed throughout North America, no studies have explored its geography or employed computational methods to explore the mammal and mosquito species likely participating in the CVV sylvatic cycle.

Methods

We used a literature review and online databases to compile locality data for CVV and its potential vectors and hosts. We linked location data points with climatic data via ecological niche modeling to estimate the geographical range of CVV and hotspots of transmission risk. We used background similarity tests to identify likely CVV mosquito vectors and mammal hosts to detect ecological signals from CVV sylvatic transmission.

Results

CVV distribution maps revealed a widespread potential viral occurrence throughout North America. Ecological niche models identified areas with climate, vectors, and hosts suitable to maintain CVV transmission. Our background similarity tests identified Aedes vexans, Culiseta inornata, and Culex tarsalis as the most likely vectors and Odocoileus virginianus (white-tailed deer) as the most likely host sustaining sylvatic transmission.

Conclusions

CVV has a continental-level, widespread transmission potential. Large areas of North America have suitable climate, vectors, and hosts for CVV emergence, establishment, and spread. We identified geographical hotspots that have no confirmed CVV reports to date and, in view of CVV misdiagnosis or underreporting, can guide future surveillance to specific localities and species.

Graphical Abstract
Identification of transposable element families from pangenome polymorphisms
Authors: Sierra Pío , Durbin Richard
Published: June 2024

Background

Transposable Elements (TEs) are segments of DNA, typically a few hundred base pairs up to several tens of thousands bases long, that have the ability to generate new copies of themselves in the genome. Most existing methods used to identify TEs in a newly sequenced genome are based on their repetitive character, together with detection based on homology and structural features. As new high quality assemblies become more common, including the availability of multiple independent assemblies from the same species, an alternative strategy for identification of TE families becomes possible in which we focus on the polymorphism at insertion sites caused by TE mobility.

Results

We develop the idea of using the structural polymorphisms found in pangenomes to create a library of the TE families recently active in a species, or in a closely related group of species. We present a tool, pantera, that achieves this task, and illustrate its use both on species with well-curated libraries, and on new assemblies.

Conclusions

Our results show that pantera is sensitive and accurate, tending to correctly identify complete elements with precise boundaries, and is particularly well suited to detect larger, low copy number TEs that are often undetected with existing de novo methods.
A feasibility study of in vivo quantitative ultra-short echo time-MRI for detecting early cartilage degeneration
Authors: Su Xiaolian , Wang Yitong , Chen Jieying , Liang Zonghui , Wan Lidi , Tang Guangyu
Published: June 2024

Objectives

To explore the feasibility of Ultra-short echo time (UTE) – MRI quantitative imaging in detecting early cartilage degeneration in vivo and underlying pathological and biochemical basis.

Methods

Twenty volunteers with osteoarthritis (OA) planning for total knee arthroplasty (TKA) were prospectively recruited. UTE-MRI sequences and conventional sequences were performed preoperatively. Regions of interests (ROIs) were manually drawn on the tibial plateau and lateral femoral condyle images to calculate MRI values. Cartilage samples were collected during TKA according to the preset positions corresponding to MR images. Pathological and biochemical components of the corresponding ROI, including histological grading, glycosaminoglycan (GAG) content, collagen integrity, and water content were obtained.

Results

91 ROIs from volunteers of 7 males (age range: 68 to 78 years; 74 ± 3 years) and 13 females (age range: 57 to 79 years; 67 ± 6 years) were evaluated. UTE-MTR (r = −0.619, p < 0.001), UTE-AdiabT1ρ (r = 0.568, p < 0.001), and UTE-T2* values (r = −0.495, p < 0.001) showed higher correlation with Mankin scores than T2 (r = 0.287, p = 0.006) and T1ρ (r = 0.435, p < 0.001) values. Of them, UTE-MTR had the highest diagnostic performance (AUC = 0.824, p < 0.001). UTE-MTR, UTE-AdiabT1ρ and UTE-T2* value was mainly related to collagen structural integrity, PG content and water content, respectively (r = 0.536, −0.652, −0.518, p < 0.001, respectively).

Conclusion

UTE-MRI have shown greater in vivo diagnostic value for early cartilage degeneration compared to conventional T2 and T1ρ values. Of them, UTE-MTR has the highest diagnostic efficiency. UTE-MTR, UTE-AdiabT1ρ, and UTE-T2* value mainly reflect different aspects of cartilage degeneration--integrity of collagen structure, PG content, and water content, respectively.

Critical relevance statement

Ultra-short echo time (UTE)-MRI has the potential to be a novel image biomarkers for detecting early cartilage degeneration in vivo and was correlated with biochemical changes of early cartilage degeneration.

Key Points

Conventional MR may miss some early cartilage changes due to relatively long echo times.

Ultra-short echo time (UTE)-MRI showed the ability in identifying early cartilage degeneration in vivo.

UTE-MT, UTE-AdiabT1ρ, and UTE-T2* mapping mainly reflect different aspects of cartilage degeneration.

Graphical Abstract
Hepatitis A virus infection associated with bilateral pleural effusion, ascites, and acalculous cholecystitis in childhood: a case report
Authors: Breim Fatima , Roumi Jamal Bakri , Kanaa Lama , Bourghol Saleh , Jazmati Besher , Dadah Samia
Published: June 2024

Background

Acute hepatitis A infection is common among children in developing nations. The clinical presentation in children is usually asymptomatic and anicteric, and it is a self-limiting infection. Rarely, it can be associated with extrahepatic complications such as pleural effusion, acalculous cholecystitis, and ascites.

Case presentation

An 8-year-old middle eastern child presented with abdominal pain, jaundice in the sclera, yellowish color of urine, and poor appetite. In the last two days, abdominal distension developed. After conducting diagnostic investigations, the child was diagnosed with HAV hepatitis associated with bilateral pleural effusion, acalculous cholecystitis, and ascites. He was managed conservatively with vitamin K supplementation and supportive parenteral fluids. After 4 days, clinical improvement was observed.

Conclusion

Hepatitis A infections presented with extrahepatic manifestations like pleural effusion, acalculous cholecystitis, and ascites are very rare, especially in children. There have been some reports of these manifestations occurring in isolation, but for them to co-exist to our knowledge, this has only been reported in two cases in the literature, and this is the third case with all these three rare complications being presented simultaneously in a single child. Although HAV infection is an asymptomatic and self-limiting viral disease in childhood, it can manifest with rare extrahepatic complications, so pediatricians should be aware of this rare association to avoid unnecessary investigations.
A prospective clinical study of the influence of oral protein intake on [18F]FET-PET uptake and test–retest repeatability in glioma
Authors: Chehri Sarah , Henriksen Otto Mølby , Marner Lisbeth , Christensen Mette , Muhic Aida , Poulsen Hans Skovgaard , Law Ian
Published: June 2024

Background

O-(2-[18F]fluoroethyl)-l-tyrosine positron emission tomography ([18F]FET PET) scanning is used in routine clinical management and evaluation of gliomas with a recommended 4 h prior fasting. Knowledge of test–retest variation of [18F]FET PET imaging uptake metrics and the impact of accidental protein intake can be critical for interpretation. The aim of this study was to investigate the repeatability of [18F]FET-PET metrics and to assess the impact of protein-intake prior to [18F]FET PET scanning of gliomas.

Results

Test–retest variability in the non-protein group was good with absolute (and relative) upper and lower limits of agreement of + 0.15 and − 0.13 (+ 9.7% and − 9.0%) for mean tumour-to-background ratio (TBRmean), + 0.43 and − 0.28 (+ 19.6% and − 11.8%) for maximal tumour-to-background ratio (TBRmax), and + 2.14 cm3 and − 1.53 ml (+ 219.8% and − 57.3%) for biological tumour volume (BTV). Variation was lower for uptake ratios than for BTV. Protein intake was associated with a 27% increase in the total sum of plasma concentration of the l-type amino acid transporter 1 (LAT1) relevant amino acids and with decreased standardized uptake value (SUV) in both healthy appearing background brain tissue (mean SUV − 25%) and in tumour (maximal SUV − 14%). Oral intake of 24 g of protein 1 h prior to injection of tracer tended to increase variability, but the effects on derived tumour metrics TBRmean and TBRmax were only borderline significant, and changes generally within the variability observed in the group with no protein intake.

Conclusion

The test–retest repeatability was found to be good, and better for TBRmax and TBRmean than BTV, with the methodological limitation that tumour growth may have influenced results. Oral intake of 24 g of protein one hour before a [18F]FET PET scan decreases uptake of [18F]FET in both tumour and in healthy appearing brain, with no clinically significant difference on the most commonly used tumour metrics.
Diversity, composition, and structure of a 1-hectare tree plot in the cloud forest of the Sierra Nevada de Santa Marta, Colombia
Authors: Fortier Riley P. , Bernal-Escobar Manuel , Kullberg Alyssa T. , Osorio Ospina Juan Camilo , Herrera Medina Yeison , Aragón Lina , Palacios Hurtado Camilo , Contreras Maria Paula
Published: June 2024

Key Message

We present data from a new delimited 1-ha forest plot on the Sierra Nevada de Santa Marta in Colombia and describe its tree diversity, composition, and structure. This data can be used in regional analyses and help to refine remote sensing models. Future censuses will provide data on the demographics of rare, endangered, and endemic trees that can be used for their conservation. Dataset access is at https://doi.org/10.15472/ftwol2. Associated metadata are available at https://metadata-afs.nancy.inra.fr/geonetwork/srv/fre/catalog.search#/metadata/a4a7855f-4cb2-459b-a1a2-287bd1e6d587.
The emerging and diverse roles of F-box proteins in spermatogenesis and male infertility
Authors: Zhuang Xuan , Ruan Jun , Zhou Canquan , Li Zhiming
Published: June 2024

F-box proteins play essential roles in various cellular processes of spermatogenesis by means of ubiquitylation and subsequent target protein degradation. They are the substrate-recognition subunits of SKP1–cullin 1–F-box protein (SCF) E3 ligase complexes. Dysregulation of F‑box protein‑mediated proteolysis could lead to male infertility in humans and mice. The emerging studies revealed the physiological function, pathological evidence, and biochemical substrates of F-box proteins in the development of male germ cells, which urging us to review the current understanding of how F‑box proteins contribute to spermatogenesis. More functional and mechanistic study will be helpful to define the roles of F-box protein in spermatogenesis, which will pave the way for the logical design of F-box protein-targeted diagnosis and therapies for male infertility, as the spermatogenic role of many F-box proteins remains elusive.
Fake speech detection using VGGish with attention block
Authors: Kanwal Tahira , Mahum Rabbia , AlSalman Abdul Malik , Sharaf Mohamed , Hassan Haseeb
Published: June 2024

While deep learning technologies have made remarkable progress in generating deepfakes, their misuse has become a well-known concern. As a result, the ubiquitous usage of deepfakes for increasing false information poses significant risks to the security and privacy of individuals. The primary objective of audio spoofing detection is to identify audio generated through numerous AI-based techniques. Several techniques for fake audio detection already exist using machine learning algorithms. However, they lack generalization and may not identify all types of AI-synthesized audios such as replay attacks, voice conversion, and text-to-speech (TTS). In this paper, a deep layered model, i.e., VGGish, along with an attention block, namely Convolutional Block Attention Module (CBAM) for spoofing detection, is introduced. Our suggested model successfully classifies input audio into two classes: Fake and Real, converting them into mel-spectrograms, and extracting their most representative features due to the attention block. Our model is a significant technique to utilize for audio spoofing detection due to a simple layered architecture. It captures complex relationships in audio signals due to both spatial and channel features present in an attention module. To evaluate the effectiveness of our model, we have conducted in-depth testing using the ASVspoof 2019 dataset. The proposed technique achieved an EER of 0.52% for Physical Access (PA) attacks and 0.07 % for Logical Access (LA) attacks.