bluuebunny/crossref_metadata_2025 huggingface dataset:
MUC1 aptamer-tethered H40-TEPA-PEG nanoconjugates for targeted siRNA-delivery and gene silencing in breast cancer cells
Authors: Salve Rajesh , Haldar Niladri , Shaikh Aazam , Samanta Rajkumar , Sengar Devyani , Patra Surajit , Gajbhiye Virendra
Published: April 2024

With a prevalence of 12.5% of all new cancer cases annually, breast cancer stands as the most common form of cancer worldwide. The current therapies utilized for breast cancer are constrained and ineffective in addressing the condition. siRNA-based gene silencing is a promising method for treating breast cancer. We have developed an aptamer-conjugated dendritic multilayered nanoconjugate to treat breast cancer. Initially, we transformed the hydroxyl groups of the hyperbranched bis-MPA polyester dendrimer into carboxylic groups. Subsequently, we linked these carboxylic groups to tetraethylenepentamine to form a positively charged dendrimer. In addition, the mucin-1 (MUC1) aptamer was attached to the dendrimer using a heterobifunctional polyethylene glycol. Characterizing dendrimers involved 1H NMR and dynamic light scattering techniques at every production stage. A gel retardation experiment was conducted to evaluate the successful binding of siRNA with targeted and non-targeted dendrimers. The targeted dendrimers exhibited no harmful effects on the NIH-3T3 fibroblast cells and RBCs, indicating their biocompatible characteristics. Confocal microscopy demonstrated significant higher uptake of targeted dendrimers than non-targeted dendrimers in MCF-7 breast cancer cells. The real-time PCR results demonstrated that the targeted dendrimers exhibited the most pronounced inhibition of the target gene expression compared to the non-targeted dendrimers and lipofectamine-2000. The caspase activation study confirmed the functional effect of survivin silencing by dendrimer, which led to the induction of apoptosis in breast cancer cells. The findings indicated that Mucin-1 targeted hyperbranched bis-MPA polyester dendrimer carrying siRNA could successfully suppress the expression of the target gene in breast cancer cells.
Zebrafish cobll1a regulates lipid homeostasis via the RA signaling pathway
Authors: Zeng Ting , Lv Jinrui , Liang Jiaxin , Xie Binling , Liu Ling , Tan Yuanyuan , Zhu Junwei , Jiang Jifan , Xie Huaping
Published: April 2024

Background:

The COBLL1 gene has been implicated in human central obesity, fasting insulin levels, type 2 diabetes, and blood lipid profiles. However, its molecular mechanisms remain largely unexplored.

Methods:

In this study, we established cobll1a mutant lines using the CRISPR/Cas9-mediated gene knockout technique. To further dissect the molecular underpinnings of cobll1a during early development, transcriptome sequencing and bioinformatics analysis was employed.

Results:

Our study showed that compared to the control, cobll1a−/− zebrafish embryos exhibited impaired development of digestive organs, including the liver, intestine, and pancreas, at 4 days post-fertilization (dpf). Transcriptome sequencing and bioinformatics analysis results showed that in cobll1a knockout group, the expression level of genes in the Retinoic Acid (RA) signaling pathway was affected, and the expression level of lipid metabolism-related genes (fasn, scd, elovl2, elovl6, dgat1a, srebf1 and srebf2) were significantly changed (p < 0.01), leading to increased lipid synthesis and decreased lipid catabolism. The expression level of apolipoprotein genes (apoa1a, apoa1b, apoa2, apoa4a, apoa4b, and apoea) genes were downregulated.

Conclusion:

Our study suggest that the loss of cobll1a resulted in disrupted RA metabolism, reduced lipoprotein expression, and abnormal lipid transport, therefore contributing to lipid accumulation and deleterious effects on early liver development.
Designing, implementing and testing an intervention of affective intelligent agents in nursing virtual reality teaching simulations—a qualitative study
Authors: Loizou Michael , Arnab Sylvester , Lameras Petros , Hartley Thomas , Loizides Fernando , Kumar Praveen , Sumilo Dana
Published: April 2024

Emotions play an important role in human-computer interaction, but there is limited research on affective and emotional virtual agent design in the area of teaching simulations for healthcare provision. The purpose of this work is twofold: firstly, to describe the process for designing affective intelligent agents that are engaged in automated communications such as person to computer conversations, and secondly to test a bespoke prototype digital intervention which implements such agents. The presented study tests two distinct virtual learning environments, one of which was enhanced with affective virtual patients, with nine 3rd year nursing students specialising in mental health, during their professional practice stage. All (100%) of the participants reported that, when using the enhanced scenario, they experienced a more realistic representation of carer/patient interaction; better recognition of the patients' feelings; recognition and assessment of emotions; a better realisation of how feelings can affect patients' emotional state and how they could better empathise with the patients.
Theoretical study on the mechanism of stick-slip instability occurrence on deep coal-rock structure
Authors: Zhang Zhenpei , Yang Guanyu , Lü Yulei , Chen Yulong , Yang Chao , Zheng Jianwei
Published: April 2024

Dynamic disasters seriously threaten the safety and effectiveness in deep mining. The mechanism of stick-slip instability occurrence on the deep coal-rock structure was studied in this paper through analyzing the occurrence condition of stick-slip in the weak surface and discussing the friction constitutive of the coal-rock structure. The result indicated that the grinding slip and the soft interlayer formation occurred in weak plane in the coal-rock structure in the process of diagenesis and strata movement, which is more likely to satisfy the stick-slip condition and then trigger dynamic disaster. Based on the mechanism study of coal-rock structure failure caused by stick-slip, it is proposed that the horizontal compression pulse caused by local stick-slip in coal seam could lead the layer-crack and fly out with the broken fragments. At the same time, it is pointed out that the scattering effect of the plane compression pulse in the propagation process induces the serial sliding instability of the coal-rock structure in many places, forming a large range of dynamic disasters. By means of numerical simulation of coal bump accident in a roadway in Yima Coal Mines, the dynamic process of sliding-slip instability of coal and rock mass is inverted, and the mechanism of sliding-slip instability of coal and rock structure is verified.
First-line surgery versus first-line assisted reproductive technology for women with deep infiltrating endometriosis: a systematic review and meta-analysis
Authors: Liang Ying , Liu Min , Zhang Jianmei , Mao Zenghui
Published: April 2024

Background

The efficiency of different first-line treatments, such as first-line surgery and assisted reproductive technology (ART), in women with deep infiltrating endometriosis (DIE) is still unclear due to a lack of direct comparative trials. This systematic review and meta-analysis aim to elucidate and compare the efficacies of first-line treatments in patients with DIE, with an emphasis on fertility outcomes.

Methods

An exhaustive search of PubMed Central, SCOPUS, EMBASE, MEDLINE, Cochrane trial registry, Google Scholar, and Clinicaltrials.gov databases was done to identify studies directly comparing first-line surgery and assisted reproductive technology (ART) for DIE, and reporting fertility-related outcomes. Pooled estimates for each of the binary outcomes were reported as odds ratios (ORs) with 95% confidence intervals (CIs). The results were pooled using a random-effects model with the Mantel-Haenszel technique.

Results

Our results show that pregnancy rate per patient (OR, 1.47; 95% CI, 0.59 to 3.63), pregnancy rate per cycle (OR, 1.16; 95% CI, 0.45 to 2.99), and live births per patient (OR, 1.66; 95% CI, 0.56 to 4.91) were comparable in DIE patients, treated with surgery or ART as a first line of treatment. When both complete and incomplete surgical DIE excision procedures were taken into account, surgery was associated with a significant enhancement in the pregnancy rate per patient (OR, 1.63; 95% CI, 1.11 to 2.40).

Conclusion

The available evidence suggests that both first-line surgery and ART can be effective DIE treatments with similar fertility outcomes. However, further analysis reveals that excluding studies involving endometriomas significantly alters the understanding of treatment efficacy between surgery and ART for DIE-associated infertility.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=426061, identifier CRD42023426061.
Positive association between blood ethylene oxide levels and metabolic syndrome: NHANES 2013-2020
Authors: Zhou Chunqi , Wang Senlin , Ju Lingling , Zhang Ruimin , Yang Yunning , Liu Yanjun
Published: April 2024

Purpose

The exposure of Ethylene oxide (EO) is linked to systemic inflammatory response and various cardiovascular risk factors. Hemoglobin’s binding to ethylene oxide (HbEO) was used to measure serum EO level. This research aims to explore the association between metabolic syndrome (MetS) and HbEO, and between HbEO and components of metabolic syndrome.

Method

This research included 1842 participants from 2013 to 2020 in National Health and Nutrition Examination Survey (NHANES) database. Weighted logistic regression models were used to analyze the relationship between HbEO and metabolic syndrome risk, using odds ratio (OR) and 95% confidence interval (CI). The restricted cubic spline plot explores whether there is a dose-response relationship between HbEO and MetS risk. Subgroup analysis was performed to analyze study heterogeneity.

Results

Significant differences were found in gender, educational level, marital status, diabetes status and hypertension among different groups (P < 0.001, P = 0.007, P = 0.003, P < 0.001, P < 0.001, respectively). The serum HbEO level exhibited positive correlation with metabolic syndrome risk in Q2 level (OR=1.64, 1.04~2.48), Q3 level (OR=1.99, 1.29~3.08), and Q4 level (OR=2.89, 1.92~4.34). The dose-response association suggested a possible linear association between serum HbEO and metabolic syndrome risk (P-overall=0.0359, P-non-linear=0.179). L-shaped association was found between HbEO and the risk of MetS in female population, obese population and mid-age and elder population (P-overall<0.001, P-non-linear=0.0024; P-overall=0.0107, P-non-linear=0.0055 P-overall<0.001 P-non-linear=0.0157).

Conclusion

This study indicates a linear correlation between MetS and HbEO, with MetS risk escalating as HbEO levels increase. The prevalence of MetS varies depending on BMI, age and gender, and these factors can also influence MetS prevalence when exposed to EO.
Single-cell and bulk RNAseq unveils the immune infiltration landscape and targeted therapeutic biomarkers of psoriasis
Authors: Deng Wenhui , Yan Yijiao , Shi Chengzhi , Sui Daoshun
Published: April 2024

Background:

Psoriasis represents a multifaceted and debilitating immune-mediated systemic ailment afflicting millions globally. Despite the continuous discovery of biomarkers associated with psoriasis, identifying lysosomal biomarkers, pivotal as cellular metabolic hubs, remains elusive.

Methods:

We employed a combination of differential expression analysis and weighted gene co-expression network analysis (WGCNA) to initially identify lysosomal genes. Subsequently, to mitigate overfitting and eliminate collinear genes, we applied 12 machine learning algorithms to screen robust lysosomal genes. These genes underwent further refinement through random forest (RF) and Lasso algorithms to ascertain the final hub lysosomal genes. To assess their predictive efficacy, we conducted receiver operating characteristic (ROC) analysis and verified the expression of diagnostic biomarkers at both bulk and single-cell levels. Furthermore, we utilized single-sample gene set enrichment analysis (ssGSEA), CIBERSORT, and Pearson’s correlation analysis to elucidate the association between immune phenotypes and hub lysosomal genes in psoriatic samples. Finally, employing the Cellchat algorithm, we explored potential mechanisms underlying the participation of these hub lysosomal genes in cell-cell communication.

Results:

Functional enrichment analyses revealed a close association between psoriasis and lysosomal functions. Subsequent intersection analysis identified 19 key lysosomal genes, derived from DEGs, phenotypic genes of WGCNA, and lysosomal gene sets. Following the exclusion of collinear genes, we identified 11 robust genes, further refined through RF and Lasso, yielding 3 hub lysosomal genes (S100A7, SERPINB13, and PLBD1) closely linked to disease occurrence, with high predictive capability for disease diagnosis. Concurrently, we validated their relative expression in separate bulk datasets and single-cell datasets. A nomogram based on these hub genes may offer clinical advantages for patients. Notably, these three hub genes facilitated patient classification into two subtypes, namely metabolic-immune subtype 1 and signaling subtype 2. CMap analysis suggested butein and arachidonic fasudil as preferred treatment agents for subtype 1 and subtype 2, respectively. Finally, through Cellchat and correlation analysis, we identified PRSS3-F2R as potentially promoting the expression of hub genes in the psoriasis group, thereby enhancing keratinocyte-fibroblast interaction, ultimately driving psoriasis occurrence and progression.

Conclusion:

Our study identifies S100A7, SERPINB13, and PLBD1 as potential diagnostic biomarkers, offering promising prospects for more precisely tailored psoriatic immunotherapy designs.
Impact of sexual and reproductive health interventions among young people in sub-Saharan Africa: a scoping review
Authors: Chipako Isaac , Singhal Saurabh , Hollingsworth Bruce
Published: April 2024

Objectives

The aim of this scoping review was to identify and provide an overview of the impact of sexual and reproductive health (SRH) interventions on reproductive health outcomes among young people in sub-Saharan Africa.

Methods

Searches were carried out in five data bases. The databases were searched using variations and combinations of the following keywords: contraception, family planning, birth control, young people and adolescents. The Cochrane risk-of-bias 2 and Risk of Bias in Non-Randomized Studies-of-Interventions tools were used to assess risk of bias for articles included.

Results

Community-based programs, mHealth, SRH education, counselling, community health workers, youth friendly health services, economic support and mass media interventions generally had a positive effect on childbirth spacing, modern contraceptive knowledge, modern contraceptive use/uptake, adolescent sexual abstinence, pregnancy and myths and misperceptions about modern contraception.

Conclusion

Sexual and reproductive health interventions have a positive impact on sexual and reproductive health outcomes. With the increasing popularity of mHealth coupled with the effectiveness of youth friendly health services, future youth SRH interventions could integrate both strategies to improve SRH services access and utilization.
Bone mineral density as an individual prognostic biomarker in NSCLC patients treated with immune checkpoint inhibitors
Authors: Lou Jie , Gong Bingxin , Li Yi , Guo Yusheng , Li Lin , Wang Jing , Liu Weiwei , You Ziang , Zhang Hongyong , Pan Feng , Liang Bo , Yang Lian , Zhou Guofeng
Published: April 2024

Background

Immune checkpoint inhibitors (ICIs) have left a deep impression in the treatment of non-small cell lung cancer (NSCLC), however, not all patients benefit from it. The purpose of this study was to investigate the prognostic value of baseline bone mineral density (BMD) derived from chest computed tomography (CT) scans in NSCLC patients treated with ICIs.

Methods

This study included patients with advanced NSCLC who underwent ICI treatment at the Wuhan Union Hospital from March 2020 to October 2022. Baseline BMD was evaluated at non-contrast chest CT at the level of first lumbar vertebra. Patients were divided into BMD-lower group and BMD-higher group according to the optimal cutoff value calculated by X-tile software. Baseline characteristics of the two groups were compared and variables between the two groups were balanced by propensity score matching (PSM) analysis. We calculated the objective response rate (ORR) and disease control rate (DCR) of the two groups and analyzed overall survival (OS) and progression-free survival (PFS) using BMD and other clinical indexes through Cox regression models and Kaplan-Meier survival curves.

Results

A total of 479 patients were included in this study, and all patients were divided into BMD-lower group (n=270) and BMD-higher group (n=209). After PSM analysis, each group consisted of 150 patients. ORR (43.3% vs. 43.5% before PSM, P = 0.964; 44.7% vs. 44.7% after PSM, P = 1.000) and DCR (91.1% vs. 94.3% before PSM, P = 0.195; 93.3% vs. 96.7% after PSM, P =0.190) were similar in two groups. There was no statistically significant relationship between BMD degree and PFS before (16.0 months vs. 18.0 months, P = 0.067) and after PSM analysis (17.0 months vs. 19.0 months, P = 0.095). However, lower BMD was associated with shorter OS both before (20.5 months vs. 23.0 months, P< 0.001) and after PSM analysis (20.0 months vs. 23.0 months, P = 0.008).

Conclusion

Lower baseline BMD is associated with worse clinical outcomes in NSCLC patients treated with ICIs. As a reliable and easily obtained individual prognostic biomarker, BMD can become a routine detection indicator before immunotherapy.
Major endothelial damage markers identified from hemadsorption filters derived from treated patients with septic shock – endoplasmic reticulum stress and bikunin may play a role
Authors: Kasper Robin , Rodriguez-Alfonso Armando , Ständker Ludger , Wiese Sebastian , Schneider E. Marion
Published: April 2024

Introduction

In septic patients the damage of the endothelial barrier is decisive leading to circulatory septic shock with disseminated vascular coagulation, edema and multiorgan failure. Hemadsorption therapy leads to rapid resolution of clinical symptoms. We propose that the isolation of proteins adsorbed to hemadsorption devices contributes to the identification of mediators responsible for endothelial barrier dysfunction.

Material and methods

Plasma materials enriched to hemadsorption filters (CytoSorb®) after therapy of patients in septic shock were fractionated and functionally characterized for their effect on cell integrity, viability, proliferation and ROS formation by human endothelial cells. Fractions were further studied for their contents of oxidized nucleic acids as well as peptides and proteins by mass spectrometry.

Results

Individual fractions exhibited a strong effect on endothelial cell viability, the endothelial layer morphology, and ROS formation. Fractions with high amounts of DNA and oxidized DNA correlated with ROS formation in the target endothelium. In addition, defined proteins such as defensins (HNP-1), SAA1, CXCL7, and the peptide bikunin were linked to the strongest additive effects in endothelial damage.

Conclusion

Our results indicate that hemadsorption is efficient to transiently remove strong endothelial damage mediators from the blood of patients with septic shock, which explains a rapid clinical improvement of inflammation and endothelial function. The current work indicates that a combination of stressors leads to the most detrimental effects. Oxidized ssDNA, likely derived from mitochondria, SAA1, the chemokine CXCL7 and the human neutrophil peptide alpha-defensin 1 (HNP-1) were unique for their significant negative effect on endothelial cell viability. However, the strongest damage effect occurred, when, bikunin – cleaved off from alpha-1-microglobulin was present in high relative amounts (>65%) of protein contents in the most active fraction. Thus, a relevant combination of stressors appears to be removed by hemadsorption therapy which results in fulminant and rapid, though only transient, clinical restitution.
Prevalence and clinical markers of herpes simplex virus infection in oral lesions of bullous pemphigoid
Authors: Zhang Hanmei , Yu Meiwen , Liang Guirong , Li Suo , Zhao Chenjing , Jing Ke , Feng Suying
Published: April 2024

Background

The manifestations of bullous pemphigoid (BP) and herpes simplex virus (HSV) infection are similar in oral mucosa, and the laboratory detection of HSV has some limitations, making it difficult to identify the HSV infection in oral lesions of BP. In addition, the treatments for BP and HSV infection have contradictory aspects. Thus, it is important to identify the HSV infection in BP patients in time.

Objective

To identify the prevalence and clinical markers of HSV infection in oral lesions of BP.

Methods

This prospective cross-sectional descriptive analytical study was conducted on 42 BP patients with oral lesions. A total of 32 BP patients without oral lesions and 41 healthy individuals were enrolled as control groups. Polymerase chain reaction was used to detect HSV. Clinical and laboratory characteristics of patients with HSV infection were compared with those without infection.

Results

A total of 19 (45.2%) BP patients with oral lesions, none (0.0%) BP patients without oral lesions, and four (9.8%) healthy individuals were positive for HSV on oral mucosa. Among BP patients with oral lesions, the inconsistent activity between oral and skin lesions (p=0.001), absence of blister/blood blister in oral lesions (p=0.020), and pain for oral lesions (p=0.014) were more often seen in HSV-positive than HSV-negative BP patients; the dosage of glucocorticoid (p=0.023) and the accumulated glucocorticoid dosage in the last 2 weeks (2-week AGC dosage) (p=0.018) were higher in HSV-positive BP patients. Combining the above five variables as test variable, the AUC was 0.898 (p<0.001) with HSV infection as state variable in ROC analysis. The absence of blister/blood blister in oral lesions (p=0.030) and pain for oral lesions (p=0.038) were found to be independent predictors of HSV infection in multivariable analysis. A total of 14 (73.7%) HSV-positive BP patients were treated with 2-week famciclovir and the oral mucosa BPDAI scores significantly decreased (p<0.001).

Conclusion

HSV infection is common in BP oral lesions. The inconsistent activity between oral and skin lesions, absence of blister in oral lesions, pain for oral lesions, higher currently used glucocorticoid dosage, and higher 2-week AGC dosage in BP patients should alert physicians to HSV infection in oral lesions and treat them with 2-week famciclovir in time.
Case report: Effectiveness of low-dose methotrexate monotherapy in post-essential thrombocythemia myelofibrosis
Authors: Francis Sebastian , King Tom , Zeidler Martin P.
Published: April 2024

JAK/STAT pathway signalling is associated with both chronic inflammatory conditions such as psoriasis and haematological malignancies such as the myeloproliferative neoplasms (MPNs). Here we describe a 73yo female patient with a history of chronic plaque psoriasis, post-essential thrombocythemia myelofibrosis (MF) and a quality of life substantially impacted by both conditions. We report that 15 mg oral Methotrexate (MTX) weekly as a monotherapy is well tolerated, provides a substantial clinical improvement for both conditions and significantly improves quality of life. We suggest that the recently identified mechanism of action of MTX as a JAK inhibitor is likely to explain this efficacy and suggest that repurposing MTX for MPNs may represent a clinical- and cost-effective therapeutic option.
Effectiveness of the acute stroke care map program in reducing in-hospital delay for acute ischemic stroke in a Chinese urban area: an interrupted time series analysis
Authors: Wen Rui , Wang Miaoran , Bian Wei , Zhu Haoyue , Xiao Ying , Zeng Jing , He Qian , Wang Yu , Liu Xiaoqing , Shi Yangdi , Hong Zhe , Xu Bing
Published: April 2024

Background

Timely intravenous thrombolysis (IVT) is crucial for improving outcomes in acute ischemic stroke (AIS) patients. This study evaluates the effectiveness of the Acute Stroke Care Map (ASCaM) initiative in Shenyang, aimed at reducing door-to-needle times (DNT) and thus improving the timeliness of care for AIS patients.

Methods

An retrospective cohort study was conducted from April 2019 to December 2021 in 30 hospitals participating in the ASCaM initiative in Shenyang. The ASCaM bundle included strategies such as EMS prenotification, rapid stroke triage, on-call stroke neurologists, immediate neuroimaging interpretation, and the innovative Pre-hospital Emergency Call and Location Identification feature. An interrupted time series analysis (ITSA) was used to assess the impact of ASCaM on DNT, comparing 9 months pre-intervention with 24 months post-intervention.

Results

Data from 9,680 IVT-treated ischemic stroke patients were analyzed, including 2,401 in the pre-intervention phase and 7,279 post-intervention. The ITSA revealed a significant reduction in monthly DNT by −1.12 min and a level change of −5.727 min post-ASCaM implementation.

Conclusion

The ASCaM initiative significantly reduced in-hospital delays for AIS patients, demonstrating its effectiveness as a comprehensive stroke care improvement strategy in urban settings. These findings highlight the potential of coordinated care interventions to enhance timely access to reperfusion therapies and overall stroke prognosis.
Case report: Headache as the sole neurological symptom in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy
Authors: Shosha Eslam , Connolly Colleen , Budhram Adrian
Published: April 2024

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a recently emerging autoimmune disease of the central nervous system (CNS); GFAP astrocytopathy is characterized by optic neuritis and meningoencephalomyelitis. We report the case of a 55-year-old man, otherwise healthy, who presented with isolated headaches for three months, without other features of meningoencephalitis or myelitis. His neurological examination and fundoscopy were unremarkable. Gadolinium-enhanced brain MRI demonstrated increased T2 hyperintensity within the right sub-lenticular basal ganglia, with additional leptomeningeal enhancement along the bilateral perisylvian regions and mesial temporal lobes. Cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis, elevated protein, matching oligoclonal bands, and a negative infectious and cytological workup. Cell-based assays for anti-aquaporin-4, anti-myelin oligodendrocyte glycoprotein, autoimmune encephalitis panel, and vasculitis workup were all negative, except for CSF positivity for GFAP α antibody. Oncological screening, including CT of the chest, abdomen, pelvis, and scrotal US, was unremarkable. Immunotherapy with high-dose intravenous steroids for five days and subsequent single four-weekly doses resulted in the resolution of both clinical and radiographic features, with a maintained status 24 months after onset. This case highlights isolated headache and basal ganglia, mesial temporal lobe involvement as a rare presentation of autoimmune GFAP astrocytopathy.
A contemporary review of breast cancer risk factors and the role of artificial intelligence
Authors: Nicolis Orietta , De Los Angeles Denisse , Taramasco Carla
Published: April 2024

Background

Breast cancer continues to be a significant global health issue, necessitating advancements in prevention and early detection strategies. This review aims to assess and synthesize research conducted from 2020 to the present, focusing on breast cancer risk factors, including genetic, lifestyle, and environmental aspects, as well as the innovative role of artificial intelligence (AI) in prediction and diagnostics.

Methods

A comprehensive literature search, covering studies from 2020 to the present, was conducted to evaluate the diversity of breast cancer risk factors and the latest advances in Artificial Intelligence (AI) in this field. The review prioritized high-quality peer-reviewed research articles and meta-analyses.

Results

Our analysis reveals a complex interplay of genetic, lifestyle, and environmental risk factors for breast cancer, with significant variability across different populations. Furthermore, AI has emerged as a promising tool in enhancing the accuracy of breast cancer risk prediction and the personalization of prevention strategies.

Conclusion

The review highlights the necessity for personalized breast cancer prevention and detection approaches that account for individual risk factor profiles. It underscores the potential of AI to revolutionize these strategies, offering clear recommendations for future research directions and clinical practice improvements.
Non-coding RNAs as regulators of the Hippo pathway in cardiac development and cardiovascular disease
Authors: Song Mengyang , Wang He , Liu Caixia , Jin Sijie , Liu Bin , Sun Wei
Published: April 2024

Cardiovascular diseases pose a serious threat to human health. The onset of cardiovascular diseases involves the comprehensive effects of multiple genes and environmental factors, and multiple signaling pathways are involved in regulating the occurrence and development of cardiovascular diseases. The Hippo pathway is a highly conserved signaling pathway involved in the regulation of cell proliferation, apoptosis, and differentiation. Recently, it has been widely studied in the fields of cardiovascular disease, cancer, and cell regeneration. Non-coding RNA (ncRNAs), which are important small molecules for the regulation of gene expression in cells, can directly target genes and have diverse regulatory functions. Recent studies have found that ncRNAs interact with Hippo pathway components to regulate myocardial fibrosis, cardiomyocyte proliferation, apoptosis, and hypertrophy and play an important role in cardiovascular disease. In this review, we describe the mode of action of ncRNAs in regulating the Hippo pathway, provide new ideas for further research, and identify molecules involved in the mechanism of action of ncRNAs and the Hippo pathway as potential therapeutic targets, with the aim of finding new modes of action for the treatment and prevention of cardiovascular diseases.
Analyzing the role of reducible molecular descriptors and thermodynamic aspects of anti-tuberculosis drugs via QSPR study
Authors: Alam Sajid Mahboob , Nigar Niat , Rasheed Muhammad Waheed , Amin Laiba
Published: April 2024

Mycobacterium tuberculosis is an organism that causes tuberculosis (TB), a common infectious disease that has a high death and morbidity rate. Topological indices are mathematical tools used to describe the structural properties of molecules or networks. They provide a quantitative measure of the connectivity and complexity of a system, and play a crucial role in numerous area such as biochemistry and bioinformatics. The purpose of topological indices is to simplify complex structures into numerical values that can be easily analyzed and compared. QSPR modeling is a technique in chemistry that relates the structure of a chemical compound to its physical or chemical properties. It is used to predict properties like boiling points, solubilities, toxicities, and even biological activities of compounds. This saves time, resources, and enables researchers to make informed decisions in drug discovery, material science, and many other areas. In this study, we conducted an analysis of several drugs used for the treatment of tuberculosis. We focused on computing the reducible topological indices based on their degrees. Several techniques and approaches are employed. To perform calculations, we used edge partition methodology, analytical techniques, theoretical graph utilities, and degree counting method. Additionally, we examined six physicochemical properties of these drugs. To establish quantitative structure-property relationship models and evaluate their effectiveness, we employed linear, quadratic, and logarithmic regression analysis. By analyzing the reducible topological indices and physicochemical properties, we aimed to gain a deeper understanding of the drugs’ characteristics and their potential impact on tuberculosis treatment. This study established a significant relationship between the defined indices with two key properties: molar mass and collision cross section. The correlation coefficients for molar mass range from 0.7 to 0.9, while the collision cross section range from 0.8 to 0.9. These results demonstrate a strong association between the indices and the properties under investigation. Furthermore, it is worth noting that both molar mass and collision cross section satisfy the requirements for p-value and F-test value across all indices. This indicates the statistical significance of the observed correlations and the reliability of our findings.
The effects of Core Stability Exercises and Mulligan’s mobilization with movement techniques on sacroiliac joint dysfunction
Authors: Yan Huiqian , Zhao Peng , Guo Xuanhui , Zhou Xiao
Published: April 2024

Purpose:

Sacroiliac joint dysfunction (SIJD), while being the primary contributor to low back pain, is still disregarded and treated as low back pain. Mulligan’s Mobilization with Movement (MWM) Techniques and Core Stability Exercises (CSE) are often used to treat low back pain. There is not much evidence that it is effective in SIJD. To evaluate the effectiveness of CSE coupled with MWM (CSE + MWM) in the treatment of SIJD.

Methods:

39 patients with SIJD were recruited and randomly divided into distinct groups as follows: control group (n = 13), CSE group (n = 13) and CSE + MWM group (n = 13). The Numerical Pain Rating Scale (NPRS), the Roland Morris Disability Questionnaire (RMDQ), the Range of Motion (ROM), the Pressure Pain Threshold (PPT) and the pelvic tilt angle asymmetry ratio in the sagittal plane (PTAR) were used to gauge the intervention’s success both before (M0) and after (M1) it. All experimental data were statistically analyzed.

Results:

The SIJ-related pain metric significantly decreased in both the CSE + MWM group and the CSE group between M0 and M1, as determined by the NPRS and RMDQ. Between M0 and M1, The CSE group’s left axial rotation ROM and lumbar flexion ROM were significantly decreased. The CSE + MWM group’s extension ROM and left lateral flexion ROM both significantly increased between M0 and M1. In the difference variable (M1-M0), the CSE + MWM group substantially outperformed control group in the left lateral flexion ROM and outperformed the CSE group in the left axial rotation ROM.

Conclusion:

In individuals with SIJD, CSE + MWM is beneficial in lowering pain, disability, and function. Treatment with CSE and MWM approaches for SIJ appears to boost this efficacy.
Plasticity of bone marrow-derived cell differentiation depending on microenvironments in the skin
Authors: Okano Junko , Nakagawa Takahiko , Kojima Hideto
Published: April 2024

Bone marrow-derived cells (BMDCs) are heterogeneous populations in which not only pluripotent stem cells, namely, hematopoietic stem cells (HSCs), mesenchymal stem cells (MSC) but also endothelial progenitor cells (EPC) are involved. BMDCs contribute to the maintenance of homeostasis and recovery from disrupted homeostasis as the immune, endocrine, and nervous systems. The skin is the largest organ in which various tissues, such as the epidermis, dermis, skin appendages (i.e., hair follicles), fats, muscles, and vessels, are tightly and systematically packed. It functions as a physical barrier to block the invasion of harmful substances and pathogenic microorganisms and properly regulate water evaporation. The skin is exposed to injuries from external stimuli because it is the outermost layer and owing to its specificity. Recovery from physical injuries and DNA mutations occurs constantly in the skin, but medical treatments are required for impaired wound healing. Recently, conservative treatments utilizing scaffolds have attracted attention as alternatives to surgical therapy, which is highly invasive. Against this background, numerous scaffolds are available in a clinical setting, although they have not surpassed surgery because of their distinct disadvantages. Here, we discuss the plasticity of BMDCs in the skin to maintain homeostasis, in addition to their critical roles on recovery from disrupted homeostasis. We also share our perspective on how scaffolds can be developed to establish scaffolds beyond surgery to regenerate skin structure during wound healing by maximally utilizing the plasticity of BMDCs.
Childhood unpredictability and sleep quality in adulthood: the mediating roles of life history strategy and perceived stress
Authors: Qi Wei , He Xiangyang , Wang Zhechen
Published: April 2024

Background

Early environmental risk have been found to be related to lifelong health. However, the impact of childhood unpredictability, a type of early environmental risk, on health, especially on sleep quality in adulthood, has not been adequately studied. The present study aimed to examine the relationship between childhood unpredictability and sleep quality in adulthood and to explore the possible mediating roles of life history strategy and perceived stress.

Methods

A cross-sectional study was conducted on 472 participants from a university in Zhejiang Province, China. The questionnaire inquired about demography, childhood unpredictability, life history strategy (Mini-K), perceived stress (14-item Perceived Stress Scale), and Sleep Quality (Pittsburgh Global Sleep Quality Index).

Results

Higher childhood unpredictability was significantly associated with worse sleep quality in adulthood. Moreover, the link between higher childhood unpredictability and worse sleep quality in adulthood was explained by the chain mediation of life history strategy and perceived stress.

Conclusion

In line with the life history theory, individuals who have experienced higher unpredictability in childhood tend to develop a faster life history strategy and become more sensitive to stress in adulthood, and subsequently suffer a decrease in sleep quality.
Preference of primary care patients for home-based healthcare and support services: a discrete choice experiment in China
Authors: Liu Yaqing , Du Sixian , Liu Chaojie , Xue Tianqin , Tang Yuqing
Published: April 2024

Importance

This research, utilizing discrete choice experiments, examines the preferences and willingness to pay for home-based healthcare and support services among residents in China, a country grappling with severe aging population, an area often underexplored in international scholarship.

Objectives

This study aims to solicit the preferences of primary care patients for home-based healthcare and support services in China.

Design, setting, and participants

A discrete choice experiment (DCE) was conducted on 312 primary care patients recruited from 13 community health centers in Wuhan and Kunming between January and May 2023. The experimental choice sets were generated using NGene, covering five attributes: Scope of services, health professionals, institutions, insurance reimbursements, and visiting fees.

Main outcomes and measures

The choice sets were further divided into three blocks, and each participant was asked to complete one block containing 12 choice tasks. Mixed logit models were established to estimate the relevant importance coefficients of and willingness to pay for different choices, while Latent Class Logit (LCL) modeling was conducted to capture possible preferences heterogeneity.

Results

The relevant importance of the scope of services reached 67.33%, compared with 19.84% for service institutions and 12.42% for health professionals. Overall, respondents preferred physician-led diagnostic and treatment services. LCL categorized the respondents into three groups: Group one (60.20%) was most concerned about the scope of services, prioritizing disease diagnosis and treatment over preventive care and mental health, while group two (16.60%) was most concerned about care providers (hospitals and medical doctors were preferred), and group three (23.20%) was most concerned about financial burdens.

Conclusion

Primary care patients prefer physical health and medical interventions for home-based healthcare and support services. However, heterogeneity in preferences is evident, indicating potential disparities in healthcare and support at home services in China.
A population health approach to workplace mental health: rationale, implementation and engagement
Authors: Woodard Kaylee T. , Bailey Allison M. , Esagoff Aaron I. , Fragala Maren S. , Hayward Joanna I. , Hunter Jennifer L. , Hsu Yea-Jen , Kim Paul M. , Peters Matthew E. , Carr Susan M.
Published: April 2024

Objectives

To describe a population health-based program to support employee and dependent mental health and learn from engagement trends.

Methods

Retrospective analysis of a program utilizing an assessment of mental health risk. For scoring “at risk,” a Care Concierge is offered to connect users with resources.

Results

Participation was offered to 56,442 employees and dependents. Eight thousand seven hundred thirty-one completed the assessment (15%). Of those, 4,644 (53%) scored moderate or higher. A total of 418 (9%) engaged the Care Concierge. Factors that negatively influenced the decision to engage care included bodily pain, financial concerns. Positive influences were younger age, high stress, anxiety, PTSD and low social support.

Conclusion

Proactive assessment plus access to a Care Concierge facilitates mental healthcare utilization. Several factors influence likelihood to engage in care. A better understanding of these factors may allow for more targeted outreach and improved engagement.
Retention in Junior Giants, a sport-based youth development program: what factors are associated with intentions to return?
Authors: Bolter Nicole D. , Kipp Lindsay E. , Greenwood P. Brian
Published: April 2024

Introduction

While evaluation research shows that physical activity-based youth development (PA-PYD) programs can have a positive impact on social and emotional growth, less is known about which participants return year after year and what factors are associated with their continued participation. The Junior Giants is a sport-based youth development program for 5–18-year-old boys and girls that is non-competitive and free to participate. The 8-week program uses baseball and softball as platforms for teaching life skills and fostering social emotional competencies. This mixed-methods study evaluated quantitative factors associated with intentions to return to the program the following year and qualitative reasons why parents/caregivers intended not to re-enroll their child.

Method

Parents/caregivers of Junior Giants participants (N = 8,495) completed online surveys about their child's demographics, social emotional climate and learning, character development, and intentions to return the following year.

Results

Descriptive data illustrated that parents/caregivers reported quite positive outcomes and experiences for their child. Chi-square and t-test analyses revealed significant differences (p < .001) between intended returners (n = 7,179, 84.5%) and those who reported no/undecided on returning (n = 1,316, 15.5%). Intended returners were significantly more likely to be identified as Latino and be in their second year of participation. Significant predictors of a binomial logistic regression [χ2 (df = 22) = 1,463.25, p < .001] included age, race/ethnicity, years played, character development, reading, league experiences, physical activity, and perceived support, with small to medium effect sizes. Using responses from a subset of 217 parents/caregivers who reported their child would not return to the program, a thematic analysis resulted in seven themes: Lack of Organization and Communication; Dissatisfied with Coaching, Didn't Learn Baseball/Softball, Not Competitive Enough, Skill Levels Not Matched, Aged Out, and Non-Program Related Reasons.

Discussion

Quantitative results contribute to the literature on predictors of retention in youth development programs, while qualitative findings echo common motives cited for dropout in youth sport. Both provide opportunities for reflection and potential changes to future programming.
Investigating the stretch-shortening cycle fatigue response to a high-intensity stressful phase of training in collegiate men's basketball
Authors: Philipp Nicolas M. , Nijem Ramsey M. , Cabarkapa Dimitrije , Hollwedel Charles M. , Fry Andrew C.
Published: April 2024

Introduction

While using force-plate derived measures of vertical jump performance, reflective of stretch-shortening-cycle (SSC) efficiency is common practice in sport science, there is limited evidence as to which tests and measures may be most sensitive toward neuromuscular fatigue. The aim of this study was to explore the SSC fatigue response to a one-week high-intensity fatiguing phase of training in National Collegiate Athletic Association (NCAA) Division-I basketball players.

Methods

The study timeline consisted of three weeks of baseline measures, one week of high-intensity training, and two weeks of follow-up testing. Countermovement jumps (CMJ) and 10-5 hop tests were performed at baseline, as well as at two time-points during, and three time-points following the fatiguing training period, allowing for performance-comparisons with baseline.

Results

Compared to the weekly training sum at baseline, during the high intensity training phase, athletes were exposed to very large increases in selected external load metrics (ES = 1.44–3.16), suggesting that athletes experienced fatigue acutely, as well as potential longer lasting reductions in performance. Vertical jump data suggested that in the CMJ, traditional metrics such as jump height, as well as metrics reflecting kinetic outputs and movement strategies, were sensitive to the stark increase in high-intensity training exposure. The 10-5 hop test suggested a fatigue-induced loss of tolerance to ground impact reflected by performance reductions in metrics related to jump height and reactive strength qualities.

Discussion

These findings emphasize that when monitoring neuromuscular fatigue, variables and assessments may not be looked at individually, but rather as part of a more global monitoring approach.
Interactions of the Immune System with Human Kidney Organoids
Authors: Shankar Anusha S. , Tejeda-Mora Hector , Du Zhaoyu , Nlandu Quincy , Palomares-Cabeza Virginia , van den Bosch Thierry P. P. , Korevaar Sander S. , Da Costa Gonçalves Fabiany , Bindels Eric M. J. , Kramann R. , Reinders Marlies E. J. , Clahsen-van Groningen Marian C. , Hoorn Ewout J. , Gribnau Joost , Baan Carla C. , Hoogduijn Martin J.
Published: April 2024

Kidney organoids are an innovative tool in transplantation research. The aim of the present study was to investigate whether kidney organoids are susceptible for allo-immune attack and whether they can be used as a model to study allo-immunity in kidney transplantation. Human induced pluripotent stem cell-derived kidney organoids were co-cultured with human peripheral blood mononuclear cells (PBMC), which resulted in invasion of allogeneic T-cells around nephron structures and macrophages in the stromal cell compartment of the organoids. This process was associated with the induction of fibrosis. Subcutaneous implantation of kidney organoids in immune-deficient mice followed by adoptive transfer of human PBMC led to the invasion of diverse T-cell subsets. Single cell transcriptomic analysis revealed that stromal cells in the organoids upregulated expression of immune response genes upon immune cell invasion. Moreover, immune regulatory PD-L1 protein was elevated in epithelial cells while genes related to nephron differentiation and function were downregulated. This study characterized the interaction between immune cells and kidney organoids, which will advance the use of kidney organoids for transplantation research.