bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of autophagy induced by tetrandrine promotes the accumulation of reactive oxygen species and sensitizes efficacy of tetrandrine in pancreatic cancer
Authors: Wang Yiwei , Xu Ting , Wang Hongcheng , Xia Guanggai , Huang Xinyu 
Published: July 2024

AbstractPancreatic cancer, characterized by its poor prognosis, exhibits a marked resistance to conventional chemotherapy and immunotherapy, underscoring the urgent need for more effective treatment modalities. In light of this, the present study is designed to assess the potential antineoplastic efficacy of a combined regimen involving tetrandrine, a plant-derived alkaloid, and autophagy inhibitors in the context of pancreatic cancer. Electron microscopy and immunoblots showed that tetrandrine promoted the formation of autophagosomes and the upregulation of LC3II and the downregulation of p62 expression, indicating that tetrandrine induced autophagy in pancreatic cancer cells. Western blot revealed that tetrandrine inhibited the phosphorylation of AKT and mTOR, as well as the expression of Bcl-2, while upregulating Beclin-1 expression. Moreover, tetrandrine promoted the transcription and protein expression of ATG7. Following the combination of autophagy inhibitors and tetrandrine, the apoptotic rate and cell death significantly increased in pancreatic cancer cells. Consistent results were obtained when ATG7 was silenced. Additionally, tetrandrine induced the generation of ROS, which was involved in the activation of autophagy and apoptosis. Further investigation revealed that upon autophagy inhibition, ROS accumulated in pancreatic cancer cells, resulting in decreased mitochondrial membrane potential and further induction of apoptosis. The results of treating subcutaneous xenograft tumors with a combination of tetrandrine and chloroquine validated that autophagy inhibition enhances the toxicity of tetrandrine against pancreatic cancer in vivo. Altogether, our study demonstrates that tetrandrine induces cytoprotective autophagy in pancreatic cancer cells. Inhibiting tetrandrine-induced autophagy promotes the accumulation of ROS and enhances its toxicity against pancreatic cancer.
Examining geographical inequalities for malaria outcomes and spending on malaria in 40 malaria-endemic countries, 2010–2020
Authors: Apeagyei Angela E. , Patel Nishali K. , Cogswell Ian , O’Rourke Kevin , Tsakalos Golsum , Dieleman Joseph 
Published: July 2024

Abstract
Background
While substantial gains have been made in the fight against malaria over the past 20 years, malaria morbidity and mortality are marked by inequality. The equitable elimination of malaria within countries will be determined in part by greater spending on malaria interventions, and how those investments are allocated. This study aims to identify potential drivers of malaria outcome inequality and to demonstrate how spending through different mechanisms might lead to greater health equity.

Methods
Using the Gini index, subnational estimates of malaria incidence and mortality rates from 2010 to 2020 were used to quantify the degree of inequality in malaria burden within countries with incidence rates above 5000 cases per 100,000 people in 2020. Estimates of Gini indices represent within-country distributions of disease burden, with high values corresponding to inequitable distributions of malaria burden within a country. Time series analyses were used to quantify associations of malaria inequality with malaria spending, controlling for country socioeconomic and population characteristics.

Results
Between 2010 and 2020, varying levels of inequality in malaria burden within malaria-endemic countries was found. In 2020, values of the Gini index ranged from 0.06 to 0.73 for incidence, 0.07 to 0.73 for mortality, and 0.00 to 0.36 for case fatality. Greater total malaria spending, spending on health systems strengthening for malaria, healthcare access and quality, and national malaria incidence were associated with reductions in malaria outcomes inequality within countries. In addition, government expenditure on malaria, aggregated government and donor spending on treatment, and maternal educational attainment were also associated with changes in malaria outcome inequality among countries with the greatest malaria burden.

Conclusions
The findings from this study suggest that prioritizing health systems strengthening in malaria spending and malaria spending in general especially from governments will help to reduce inequality of the malaria burden within countries. Given heterogeneity in outcomes in countries currently fighting to control malaria, and the challenges in increasing both domestic and international funding allocated to control and eliminate malaria, the efficient targeting of limited resources is critical to attain global malaria eradication goals.
Adverse events profile associated with intermittent fasting in adults with overweight or obesity: a systematic review and meta-analysis of randomized controlled trials
Authors: Zhong Fan , Zhu Ting , Jin Xingyi , Chen Xiangjun , Wu Ruipeng , Shao Li , Wang Shaokang 
Published: July 2024

Abstract
Background
There is little evidence to comprehensively summarize the adverse events (AEs) profile of intermittent fasting (IF) despite its widespread use in patients with overweight or obesity.

Methods
We searched the main electronic databases and registry websites to identify eligible randomized controlled trials (RCTs) comparing IF versus control groups. A direct meta-analysis using a fixed-effect model was conducted to pool the risk differences regarding common AEs and dropouts. Study quality was assessed by using the Jadad scale. Pre-specified subgroup and sensitivity analyses were conducted to explore potential heterogeneity.

Results
A total of 15 RCTs involving 1,365 adult individuals were included. Findings did not show a significant difference between IF and Control in risk rate of fatigue [0%, 95% confidence interval (CI), -1% to 2%; P = 0.61], headache [0%, 95%CI: -1% to 2%; P = 0.86] and dropout [1%, 95%CI: -2% to 4%; P = 0.51]. However, a numerically higher risk of dizziness was noted among the IF alone subgroup with non-early time restricted eating [3%, 95%CI: -0% to 6%; P = 0.08].

Conclusions
This meta-analysis suggested that IF was not associated with a greater risk of AEs in adult patients affected by overweight or obesity. Additional large-scale RCTs stratified by key confounders and designed to evaluate the long-term effects of various IF regimens are needed to ascertain these AEs profile.
Unmutated RRAS2 emerges as a key oncogene in post-partum-associated triple negative breast cancer
Authors: Cifuentes Claudia , Oeste Clara L. , Fernández-Pisonero Isabel , Hortal Alejandro M. , García-Macías Carmen , Hochart Jeanne , Rubira Regina , Horndler Lydia , Horndler Carlos , Bustelo Xosé R. , Alarcón Balbino 
Published: July 2024

Abstract
Background
Breast cancer (BC) is the most common cancer in women, with triple negative BC (TNBC) accounting for 20% of cases. While early detection and targeted therapies have improved overall life expectancy, TNBC remains resistant to current treatments. Although parity reduces the lifetime risk of developing BC, pregnancy increases the risk of developing TNBC for years after childbirth. Although numerous gene mutations have been associated with BC, no single gene alteration has been identified as a universal driver. RRAS2 is a RAS-related GTPase rarely found mutated in cancer.

Methods
Conditional knock-in mice were generated to overexpress wild type human RRAS2 in mammary epithelial cells. A human sample cohort was analyzed by RT-qPCR to measure RRAS2 transcriptional expression and to determine the frequency of both a single-nucleotide polymorphism (SNP rs8570) in the 3’UTR region of RRAS2 and of genomic DNA amplification in tumoral and non-tumoral human BC samples.

Results
Here we show that overexpression of wild-type RRAS2 in mice is sufficient to develop TNBC in 100% of females in a pregnancy-dependent manner. In human BC, wild-type RRAS2 is overexpressed in 68% of tumors across grade, location, and molecular type, surpassing the prevalence of any previously implicated alteration. Still, RRAS2 overexpression is notably higher and more frequent in TNBC and young parous patients. The increased prevalence of the alternate C allele at the SNP position in tumor samples, along with frequent RRAS2 gene amplification in both tumors and blood of BC patients, suggests a cause-and-effect relationship between RRAS2 overexpression and breast cancer.

Conclusions
Higher than normal expression of RRAS2 not bearing activating mutations is a key driver in the majority of breast cancers, especially those of the triple-negative type and those linked to pregnancy.
Macrophage-derived exosomes promote telomere fragility and senescence in tubular epithelial cells by delivering miR-155
Authors: Yin Qing , Tang Tao-Tao , Lu Xiao-Yu , Ni Wei-Jie , Yin Di , Zhang Yi-Lin , Jiang Wei , Zhang Yue , Li Zuo-Lin , Wen Yi , Gan Wei-Hua , Zhang Ai-Qing , Lv Lin-Li , Wang Bin , Liu Bi-Cheng 
Published: July 2024

Abstract
Background
Chronic kidney disease (CKD) is highly prevalent worldwide, and its global burden is substantial and growing. CKD displays a number of features of accelerated senescence. Tubular cell senescence is a common biological process that contributes to CKD progression. Tubulointerstitial inflammation is a driver of tubular cell senescence and a common characteristic of CKD. However, the mechanism by which the interstitial inflammation drives tubular cell senescence remains unclear. This paper aims to explore the role of exosomal miRNAs derived from macrophages in the development of tubular cell senescence.

Methods
Among the identified inflammation-related miRNAs, miR-155 is considered to be one of the most important miRNAs involved in the inflammatory response. Macrophages, the primary immune cells that mediate inflammatory processes, contain a high abundance of miR-155 in their released exosomes. We assessed the potential role of miR-155 in tubular cell senescence and renal fibrosis. We subjected miR-155−/− mice and wild-type controls, as well as tubular epithelial cells (TECs), to angiotensin II (AngII)-induced kidney injury. We assessed kidney function and injury using standard techniques. TECs were evaluated for cell senescence and telomere dysfunction in vivo and in vitro. Telomeres were measured by the fluorescence in situ hybridization.

Results
Compared with normal controls, miR-155 was up-regulated in proximal renal tubule cells in CKD patients and mouse models of CKD. Moreover, the expression of miR-155 was positively correlated with the extent of renal fibrosis, eGFR decline and p16INK4A expression. The overexpression of miR-155 exacerbated tubular senescence, evidenced by increased detection of p16INK4A/p21expression and senescence-associated β-galactosidase activity. Notably, miR-155 knockout attenuates renal fibrosis and tubule cell senescence in vivo. Interestingly, once released, macrophages-derived exosomal miR-155 was internalized by TECs, leading to telomere shortening and dysfunction through targeting TRF1. A dual-luciferase reporter assay confirmed that TRF1 was the direct target of miR-155. Thus, our study clearly demonstrates that exosomal miR-155 may mediate communication between macrophages and TECs, subsequently inducing telomere dysfunction and senescence in TECs.

Conclusions
Our work suggests a new mechanism by which macrophage exosomes are involved in the development of tubule senescence and renal fibrosis, in part by delivering miR-155 to target TRF1 to promote telomere dysfunction. Our study may provide novel strategies for the treatment of AngII-induced kidney injury.
Pornography use, demographic and sexual health characteristics among university students: a gender-based comparative study of non-users, non-problematic users, and problematic users
Authors: Pouralijan Zeinab , Bőthe Beáta , Farnam Farnaz 
Published: July 2024

Abstract
Background
Limited gender-based research has compared sexual health among pornography users (PUs) and non-users, including non-problematic pornography users (non-PPUs) and problematic pornography users (PPUs), particularly in non-Western cultures.

Methods
A 2022 cross-sectional study involving 450 Iranian university students categorized participants as PUs or non-users based on 12 months of use. PUs were further classified as non-PPUs or PPUs using the 'Problematic Pornography Use Scale' cutoff point, with comparisons of demographic and sexual variables made between these groups.

Results
Pornography use was reported among 39.6% of students, including 51.7% of men and 33.6% of women. In general, 9.5% of participants were PPUs, including 17.4% of men and 5.6% of women. PUs were mainly men, had fewer children, shorter marriages, lower religiosity, and lower levels of education. Compared with non-users, PUs reported earlier sexual relationships, lower satisfaction with sex frequency and communication, and greater rates of extramarital relationships, masturbation, sexual desire, and sexual distress. PPUs reported more sexual desire, pornography use, masturbation, and extramarital affairs than non-PPUs. Similar patterns in demographics, sexual history, and health were observed in pornography use across genders. The regression indicated being male (OR: 2.42, 95% CI: 1.44–4.06), having lower education (OR: 0.89, 95% CI: 0.81–0.97), fewer children (OR: 0.64, 95% CI: 0.48–0.86), higher masturbation (OR: 1.31, 95% CI: 1.14–1.49), more extramarital relationship (OR: 1.69, 95% CI: 1.07–2.67), less religiosity (OR: 0.87, 95% CI: 0.82–0.93), more sexual excitement (OR: 0.79, 95% CI:0.62–1), and more sexual distress (OR: 1.20, 95% CI: 1.02–1.32) were associated with pornography use.
Two-way ANOVA found no significant effects of gender or pornography use on sexual satisfaction. Women had worse sexual function regardless of usage. Pornography users, regardless of gender, experienced higher sexual distress.
Scarlet fever epidemics, deaths, effects on society and precautions taken in the Ottoman Empire and the Early Turkish Republic
Authors: Erkmen Ayşe , Tüzün Nevim , Erkmen Osman 
Published: July 2024

Abstract
Background
Scarlet fever, one of the infectious diseases, has become an epidemic in some periods and has become an epidemic in history, causing thousands of people to die. In the Ottoman Empire and the early Republic of Turkey, there was not enough literature about the prevalence of the scarlet fever epidemic, the epidemic level, the mortality status and the fight against the disease.

Methods
The effects of scarlet fever on society during the early periods of the Ottoman Empire and the Republic of Turkey, as well as the measures taken to control the disease, have been researched in Ottoman archival documents.

Results
The number of scarlet fever patients is 1225 in Anatolian settlements; 429 (35.0%) of them were children, 76 (17.7%) of the children died, and 1796 (65.0%) of them were people, 49 (6.2%) of them died. The number of scarlet fever patients is 147 in Balkan settlements; 36 (24.5%) of them were children, 6 (16.7%) of the children died, and 111 (75.5%) of them were people, 48 (43.2%) of them died. The mortality rate from scarlet fever in the Ottoman Empire was 13.0%. In Ottoman documents, the demographic structure of the society is not detailed. It is only mentioned as adults and children. In a document, it is stated that an older woman died of scarlet fever. Most documents determined that scarlet fever was seen among poor people living in villages and cities. Scarlet fever spread, and more deaths occurred in the villages, mainly due to reasons such as unhygienic conditions, separation of people, and lack of medical personnel. In the early Republic of Turkey, 8865 patients were indicated, and 1681 of them (19.0%) died.

Conclusion
The main factors causing the emergence of epidemic diseases were wars and the disruption of society’s lifestyle, socioeconomic conditions and wars.

Public Interest Summary
Epidemic diseases have had and continue to have significant effects on public health from the past to the present. In our research, it was determined that scarlet fever causes a significant number of deaths in epidemics. It has been determined that some precautions were taken against the epidemic disease, which are still valid today, but they were less adequate than today’s measures. It has been determined that measures can be developed against current and future epidemics in line with the measures taken against the same disease in the past.
Outcomes of maze procedure and mitral valve surgery in atrial functional mitral regurgitation: a retrospective study
Authors: Song Kyungsub , Jang Woo Sung , Kim Yun Seok , Yoo Jonghoon 
Published: July 2024

Abstract
Background
Atrial functional mitral regurgitation (AFMR) is a newly discovered condition associated with longstanding atrial fibrillation. This retrospective study aimed to analyze the outcomes of the maze procedure and mitral regurgitation (MR) surgery in AFMR and atrial fibrillation in comparison with those in degenerative MR (DMR).

Methods
Patients who underwent mitral valve repair/replacement with a maze procedure at a hospital (July 2012–August 2021) were included. We excluded patients aged below 18 years undergoing concomitant coronary artery bypass grafting or atrial septal defect repair and those with MR etiology other than ARMR or DMR.

Results
We included 35 patients with AFMR and 50 patients with DMR. Patient characteristics and postoperative outcomes were not significantly different between the two groups. Long-term outcomes revealed no significant differences in the ratio of cardiac mortality, stroke, or hospital readmission. However, after the maze procedure, the sinus rhythm restoration rate was significantly lower (62% vs. 28.5%, p < 0.001), a junctional rhythm state (p < 0.001) and permanent pacemaker insertion for sick sinus syndrome (SSS) (p = 0.03) were significantly more common in AFMR than DMR. On postoperative transthoracic echocardiography (TTE), the pulmonary artery systolic pressure was significantly less decreased in the AFMR group than in the DMR group compared with that on preoperative TTE (p = 0.04).

Conclusions
AFMR showed excellent mitral valve surgery outcomes, similar to DMR, but had a significantly higher risk of pacemaker insertion for SSS after the maze procedure.
The crosstalk between immune cells and tumor pyroptosis: advancing cancer immunotherapy strategies
Authors: Hu Mengyuan , Deng Fengying , Song Xinlei , Zhao Hongkun , Yan Fei 
Published: July 2024

AbstractPyroptosis is a cell death process characterized by cell swelling until membrane rupture and release of intracellular contents. As an effective tumor treatment strategy, inducing tumor cell pyroptosis has received widespread attention. In this process, the immune components within the tumor microenvironment play a key regulatory role. By regulating and altering the functions of immune cells such as cytotoxic T lymphocytes, natural killer cells, tumor-associated macrophages, and neutrophils, tumor cell pyroptosis can be induced. This article provides a comprehensive review of the molecular mechanisms of cell pyroptosis, the impact of the tumor immune microenvironment on tumor cell pyroptosis, and its mechanisms. It aims to gain an in-depth understanding of the communication between the tumor immune microenvironment and tumor cells, and to provide theoretical support for the development of new tumor immunotherapies.
A proof of concept for microcirculation monitoring using machine learning based hyperspectral imaging in critically ill patients: a monocentric observational study
Authors: Kohnke Judith , Pattberg Kevin , Nensa Felix , Kuhlmann Henning , Brenner Thorsten , Schmidt Karsten , Hosch René , Espeter Florian 
Published: July 2024

Abstract
Background
Impaired microcirculation is a cornerstone of sepsis development and leads to reduced tissue oxygenation, influenced by fluid and catecholamine administration during treatment. Hyperspectral imaging (HSI) is a non-invasive bedside technology for visualizing physicochemical tissue characteristics. Machine learning (ML) for skin HSI might offer an automated approach for bedside microcirculation assessment, providing an individualized tissue fingerprint of critically ill patients in intensive care. The study aimed to determine if machine learning could be utilized to automatically identify regions of interest (ROIs) in the hand, thereby distinguishing between healthy individuals and critically ill patients with sepsis using HSI.

Methods
HSI raw data from 75 critically ill sepsis patients and from 30 healthy controls were recorded using TIVITA® Tissue System and analyzed using an automated ML approach. Additionally, patients were divided into two groups based on their SOFA scores for further subanalysis: less severely ill (SOFA ≤ 5) and severely ill (SOFA > 5). The analysis of the HSI raw data was fully-automated using MediaPipe for ROI detection (palm and fingertips) and feature extraction. HSI Features were statistically analyzed to highlight relevant wavelength combinations using Mann–Whitney-U test and Benjamini, Krieger, and Yekutieli (BKY) correction. In addition, Random Forest models were trained using bootstrapping, and feature importances were determined to gain insights regarding the wavelength importance for a model decision.

Results
An automated pipeline for generating ROIs and HSI feature extraction was successfully established. HSI raw data analysis accurately distinguished healthy controls from sepsis patients. Wavelengths at the fingertips differed in the ranges of 575–695 nm and 840–1000 nm. For the palm, significant differences were observed in the range of 925–1000 nm. Feature importance plots indicated relevant information in the same wavelength ranges. Combining palm and fingertip analysis provided the highest reliability, with an AUC of 0.92 to distinguish between sepsis patients and healthy controls.

Conclusion
Based on this proof of concept, the integration of automated and standardized ROIs along with automated skin HSI analyzes, was able to differentiate between healthy individuals and patients with sepsis. This approach offers a reliable and objective assessment of skin microcirculation, facilitating the rapid identification of critically ill patients.
sciMET-cap: high-throughput single-cell methylation analysis with a reduced sequencing burden
Authors: Acharya Sonia N. , Nichols Ruth V. , Rylaarsdam Lauren E. , O’Connell Brendan L. , Braun Theodore P. , Adey Andrew C. 
Published: July 2024

AbstractDNA methylation is a key component of the mammalian epigenome, playing a regulatory role in development, disease, and other processes. Robust, high-throughput single-cell DNA methylation assays are now possible (sciMET); however, the genome-wide nature of DNA methylation results in a high sequencing burden per cell. Here, we leverage target enrichment with sciMET to capture sufficient information per cell for cell type assignment using substantially fewer sequence reads (sciMET-cap). Accumulated off-target coverage enables genome-wide differentially methylated region (DMR) calling for clusters with as few as 115 cells. We characterize sciMET-cap on human PBMCs and brain (middle frontal gyrus).