bluuebunny/crossref_metadata_2025 huggingface dataset:
Too little or too much: nonlinear relationship between sleep duration and daily affective well-being in depressed adults
Authors: Lee Sun Ah , Mukherjee Dahlia , Rush Jonathan , Lee Soomi , Almeida David M.
Published: April 2024

Background

In addition to having higher negative affect and lower positive affect overall, depressed individuals exhibit heightened affective reactivity to external stimuli than non-depressed individuals. Sleep may contribute to day-to-day fluctuations in depressed individuals, given that sleep disturbance is a common symptom of depression. Yet, little is known about changes in daily affect as a function of nightly sleep duration in depressed adults and non-depressed adults. The current study examined whether and how naturally-occurring sleep duration is associated with negative and positive affect, and how these associations differ between depressed vs. non-depressed adults.

Methods

Data were drawn from the second wave of the National Study of Daily Experiences (NSDE), a daily diary project of the Midlife in the United States (MIDUS) study. The sample of 2,012 adults (Mage=56.5; 57% female; 84% white) completed eight-day diary interviews via telephone on their daily experiences including nightly sleep duration and negative and positive affect. They also completed assessments of the Composite International Diagnostic Interview-Short form, and depressed status was determined based on DSM-III. Multilevel regression models with linear, quadratic, and cubic terms of sleep duration examined the nonlinear relationship between nightly sleep duration and daily affect. Interaction terms with depression status were added to examine differences between depressed and non-depressed adults.

Results

Depressed adults exhibited significant and greater fluctuations in daily affect as a function of nightly sleep duration than non-depressed adults. Specifically, the degree of decrease in positive affect and increase in negative affect was greater when depressed adults slept 2 or more hours less or longer than their usual sleep hours. Non-depressed adults exhibited relatively stable daily affect regardless of their nightly sleep hours.

Conclusions

Sleep duration is nonlinearly associated with affect in daily lives of depressed adults, highlighting that both having too little sleep and excessive sleep are associated with adverse daily affective well-being. Implementing sleep interventions to promote an appropriate sleep duration may help improve daily affect among depressed adults.
Alterations in the fecal microbiota of methamphetamine users with bad sleep quality during abstinence
Authors: Deng Zijing , Liu Linzi , Liu Wen , Liu Ruina , Ma Tao , Xin Yide , Xie Yu , Zhang Yifan , Zhou Yifang , Tang Yanqing
Published: April 2024

Background

Methamphetamine (MA) abuse has resulted in a plethora of social issues. Sleep disturbance is a prominent issue about MA addiction, which serve as a risk factor for relapse, and the gut microbiota could play an important role in the pathophysiological mechanisms of sleep disturbances. Therefore, improving sleep quality can be beneficial for treating methamphetamine addiction, and interventions addressing the gut microbiota may represent a promising approach.

Method

We recruited 70 MA users to investigate the associations between sleep quality and fecal microbiota by the Pittsburgh Sleep Quality Index (PSQI), which was divided into MA-GS (PSQI score < 7, MA users with good sleep quality, n = 49) and MA-BS group (PSQI score ≥ 7, MA users with bad sleep quality, n = 21). In addition, we compared the gut microbiota between the MA-GS and healthy control (HC, n = 38) groups. 16S rRNA sequencing was applied to identify the gut bacteria.

Result

The study revealed that the relative abundances of the Thermoanaerobacterales at the order level differed between the MA-GS and MA-BS groups. Additionally, a positive correlation was found between the relative abundance of the genus Sutterella and daytime dysfunction. Furthermore, comparisons between MA users and HCs revealed differences in beta diversity and relative abundances of various bacterial taxa.

Conclusion

In conclusion, the study investigated alterations in the gut microbiota among MA users. Furthermore, we demonstrated that the genus Sutterella changes may be associated with daytime dysfunction, suggesting that the genus Sutterella may be a biomarker for bad sleep quality in MA users.
Analysis of the impact of pluronic acid on the thermal stability and infectivity of AAV6.2FF
Authors: Thomas Sylvia P. , Spinelli Marcus M. , Rghei Amira D. , Lopes Jordyn A. , Zielinska Nicole , McLeod Benjamin M. , Pei Yanlong , Zhang Wei , Thebaud Bernard , Karimi Khalil , Wootton Sarah K.
Published: April 2024

Background

The advancement of AAV vectors into clinical testing has accelerated rapidly over the past two decades. While many of the AAV vectors being utilized in clinical trials are derived from natural serotypes, engineered serotypes are progressing toward clinical translation due to their enhanced tissue tropism and immune evasive properties. However, novel AAV vectors require formulation and stability testing to determine optimal storage conditions prior to their use in a clinical setting.

Results

Here, we evaluated the thermal stability of AAV6.2FF, a rationally engineered capsid with strong tropism for lung and muscle, in two different buffer formulations; phosphate buffered saline (PBS), or PBS supplemented with 0.001% non-ionic surfactant Pluronic F68 (PF-68). Aliquots of AAV6.2FF vector encoding the firefly luciferase reporter gene (AAV6.2FF-ffLuc) were incubated at temperatures ranging from -20°C to 55°C for varying periods of time and the impact on infectivity and particle integrity evaluated. Additionally, the impact of several rounds of freeze-thaw treatments on the infectivity of AAV6.2FF was investigated. Vector infectivity was measured by quantifying firefly luciferase expression in HEK 293 cells and AAV particle integrity was measured by qPCR quantification of encapsidated viral DNA.

Conclusions

Our data demonstrate that formulating AAV6.2FF in PBS containing 0.001% PF-68 leads to increased stability and particle integrity at temperatures between -20℃ to 21℃ and protection against the destructive effects of freeze-thaw. Finally, AAV6.2FF-GFP formulated in PBS supplemented with 0.001% PF-68 displayed higher transduction efficiency in vivo in murine lung epithelial cells following intranasal administration than vector buffered in PBS alone further demonstrating the beneficial properties of PF-68.
Neuroprotective effect of acetoxypachydiol against oxidative stress through activation of the Keap1-Nrf2/HO-1 pathway
Authors: Qi Yu , Liu Ge , Jin Shengjie , Jian Rong , Zou Ziqiang , Wang Chenjing , Zhang Yuanlong , Zhao Min , Zhu Haoru , Yan Pengcheng
Published: April 2024

Background

Excessive oxidative stress in the brain is an important pathological factor in neurological diseases. Acetoxypachydiol (APHD) is a lipophilic germacrane-type diterpene extracted as a major component from different species of brown algae within the genus Dictyota. There have been no previous reports on the pharmacological activity of APHD. The present research aims to explore the potential neuroprotective properties of APHD and its underlying mechanisms.

Methods

The possible mechanism of APHD was predicted using a combination of molecular docking and network pharmacological analysis. PC12 cells were induced by H2O2 and oxygen–glucose deprivation/reoxygenation (OGD/R), respectively. Western blot, flow cytometry, immunofluorescence staining, and qRT-PCR were used to investigate the antioxidant activity of APHD. The HO-1 inhibitor ZnPP and Nrf2 gene silencing were employed to confirm the influence of APHD on the signaling cascade involving HO-1, Nrf2, and Keap1 in vitro.

Results

APHD exhibited antioxidant activity in both PC12 cells subjected to H2O2 and OGD/R conditions by downregulating the release of LDH, the concentrations of MDA, and ROS, and upregulating SOD, GSH-Px, and GSH concentrations. APHD could potentially initiate the Keap1-Nrf2/HO-1 signaling cascade, according to the findings from network pharmacology evaluation and molecular docking. Furthermore, APHD was observed to increase Nrf2 and HO-1 expression at both mRNA and protein levels, while downregulating the protein concentrations of Keap1. Both Nrf2 silencing and treatment with ZnPP reversed the neuroprotective effects of APHD.

Conclusions

APHD activated antioxidant enzymes and downregulated the levels of LDH, MDA, and ROS in two cell models. The neuroprotective effect is presumably reliant on upregulation of the Keap1-Nrf2/HO-1 pathway. Taken together, APHD from brown algae of the genus Dictyota shows potential as a candidate for novel neuroprotective agents.
Big five personality traits of medical students and workplace performance in the final clerkship year using an EPA framework
Authors: Peters Harm , Garbe Amelie , Breil Simon M. , Oberst Sebastian , Selch Susanne , Holzhausen Ylva
Published: April 2024

Background

The qualities of trainees play a key role in entrustment decisions by clinical supervisors for the assignments of professional tasks and levels of supervision. A recent body of qualitative research has shown that in addition to knowledge and skills, a number of personality traits are relevant in the workplace; however, the relevance of these traits has not been investigated empirically. The aim of this study was to analyse the workplace performance of final-year medical students using an Entrustable Professional Activity (EPA) framework in relation to their personality traits.

Methods

Medical students at the end of their final clerkship year were invited to participate in an online survey-based, cross-sectional field study. In the survey, the workplace performance was captured using a framework consisting of levels of experienced supervision and a defined set of 12 end-of-undergraduate medical training EPAs. The Big Five personality traits (extraversion, agreeableness, conscientiousness, neuroticism, and openness) of the participating medical students were measured using the Big Five Inventory-SOEP (BFI-S), which consists of 15 items that are rated on a seven-point Likert scale. The data were analysed using descriptive and inferential statistics.

Results

The study included 880 final-year medical students (mean age: 27.2 years, SD = 3.0; 65% female). The levels of supervision under which the final-year clerkship students carried out the EPAs varied considerably. Significant correlations were found between the levels of experienced supervision and all Big Five dimensions The correlations with the dimensions of extraversion, agreeableness, conscientiousness and openness were positive, and that for the neuroticism dimension was negative (range r = 0.17 to r = − 0.23). Multiple regression analyses showed that the combination of the Big Five personality traits accounted for 0.8–7.5% of the variance in supervision levels on individual EPAs.

Conclusions

Using the BFI-S, we found that the levels of supervision on a set of end-of-undergraduate medical training EPAs were related to the personality traits of final-year medical students. The results of this study confirm the existing body of research on the role of conscientiousness and extraversion in entrustment decision-making and, in particular, add the personality trait of neuroticism as a new and relevant trainee quality to be considered.
The impact of empathy on medical students: an integrative review
Authors: Chen Hao , Xuan Hanwen , Cai Jinquan , Liu Meichen , Shi Lei
Published: April 2024

Introduction

Empathy is considered the ability to understand or feel others emotions or experiences. As an important part of medical education, empathy can affect medical students in many ways. It is still lacking a comprehensive evaluation of the existing articles on empathy’s impact on medical students, despite the existence of many articles on the topic.

Objectives

To summarize the impact of empathy on medical students during medical education from four perspectives: mental health, academic performance, clinical competence, and specialty preference.

Methods

The search terms used for retrieval were “empathy”, “medical student”, “mental health”, “depression”, “anxiety”, “burnout”, “examinations”, “academic performance”, “clinical competence”, “specialty preference” on PubMed, EBSCO, and Web of Science before January 2024. The search was carried out by two reviewers. Titles and abstracts were screened independently and reviewed based on inclusion/exclusion criteria. A consensus was drawn on which articles were included.

Results

Our results indicated that high empathy was a positive factor for mental health, However, students with high affective empathy were more likely to suffer from depression, anxiety, and burnout. Empathy was found to be unrelated to academic performance, but positively correlated with clinical competence, particularly in terms of communication skills. Medical students with high levels of empathy tended to prefer people-oriented majors.

Conclusions

Medical students who score higher on the self-reported empathy scales often have better mental health, better communication skills, and tend to choose people-oriented specialties. But empathy is not related to academic performance. Additionally, the different dimensions of empathy have different impacts on medical students. It is necessary to design targeted courses and training for medical students to enhance their empathy.
Predictive model and risk analysis for coronary heart disease in people living with HIV using machine learning
Authors: Liu Zengjing , Meng Zhihao , Wei Di , Qin Yuan , Lv Yu , Xie Luman , Qiu Hong , Xie Bo , Li Lanxiang , Wei Xihua , Zhang Die , Liang Boying , Li Wen , Qin Shanfang , Yan Tengyue , Meng Qiuxia , Wei Huilin , Jiang Guiyang , Su Lingsong , Jiang Nili , Zhang Kai , Lv Jiannan , Hu Yanling
Published: April 2024

Objective

This study aimed to construct a coronary heart disease (CHD) risk-prediction model in people living with human immunodeficiency virus (PLHIV) with the help of machine learning (ML) per electronic medical records (EMRs).

Methods

Sixty-one medical characteristics (including demography information, laboratory measurements, and complicating disease) readily available from EMRs were retained for clinical analysis. These characteristics further aided the development of prediction models by using seven ML algorithms [light gradient-boosting machine (LightGBM), support vector machine (SVM), eXtreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), decision tree, multilayer perceptron (MLP), and logistic regression]. The performance of this model was assessed using the area under the receiver operating characteristic curve (AUC). Shapley additive explanation (SHAP) was further applied to interpret the findings of the best-performing model.

Results

The LightGBM model exhibited the highest AUC (0.849; 95% CI, 0.814–0.883). Additionally, the SHAP plot per the LightGBM depicted that age, heart failure, hypertension, glucose, serum creatinine, indirect bilirubin, serum uric acid, and amylase can help identify PLHIV who were at a high or low risk of developing CHD.

Conclusion

This study developed a CHD risk prediction model for PLHIV utilizing ML techniques and EMR data. The LightGBM model exhibited improved comprehensive performance and thus had higher reliability in assessing the risk predictors of CHD. Hence, it can potentially facilitate the development of clinical management techniques for PLHIV care in the era of EMRs.
Risk management and empirical study of the doctor-patient relationship: based on 1790 litigation cases of medical damage liability disputes in China
Authors: Li Hui , Li Limin , Liu Tong , Tan Meiqiong , He Wanwan , Luo Yuzhu , Zhong Xuerong , Zhang Liping , Sun Jiangjie
Published: April 2024

Background

Compensation for medical damage liability disputes (CMDLD) seriously hinders the healthy development of hospitals and undermines the harmony of the doctor-patient relationships (DPR). Risk management in the DPR has become an urgent issue of the day. The study aims to provide a comprehensive description of CMDLD in China and explore its influencing factors, and make corresponding recommendations for the management of risks in the DPR.

Methods

This study extracted data from the China Judgment Online - the official judicial search website with the most comprehensive coverage. Statistical analysis of 1,790 litigation cases of medical damage liability disputes (COMDLD) available from 2015 to 2021.

Results

COMDLD generally tended to increase with the year and was unevenly distributed by regions; the compensation rate was 52.46%, the median compensation was 134,900 yuan and the maximum was 2,234,666 yuan; the results of the single factor analysis showed that there were statistically significant differences between the compensation for different years, regions, treatment attributes, and trial procedures (P < 0.05); the correlation analysis showed that types of hospitals were significantly negatively associated with regions (R=-0.082, P < 0.05); trial procedures were significantly negatively correlated with years (R=-0.484, P < 0.001); compensat- ion was significantly positively correlated with years, regions, and treatment attributes (R = 0.098–0.294, P < 0.001) and negatively correlated with trial procedures (R=-0.090, P < 0.01); regression analysis showed that years, treatment attributes, and regions were the main factors affecting the CMDLD (P < 0.05).

Conclusions

Years, regions, treatment attributes, and trial procedures affect the outcome of CMDLD. This paper further puts forward relevant suggestions and countermeasures for the governance of doctor-patient risks based on the empirical results. Including rational allocation of medical resources to narrow the differences between regions; promoting the expansion and sinking of high-quality resources to improve the level of medical services in hospitals at all levels; and developing a third-party negotiation mechanism for medical disputes to reduce the cost of medical litigation.
Policies in Canada fail to address disparities in access to person-centred osteoarthritis care: a content analysis
Authors: Abbaticchio Angelina , Theodorlis Madeline , Marshall Deborah , MacKay Crystal , Borkhoff Cornelia M. , Hazlewood Glen Stewart , Battistella Marisa , Lofters Aisha , Ahluwalia Vandana , Gagliardi Anna R.
Published: April 2024

Background

Women are disproportionately impacted by osteoarthritis (OA) but less likely than men to access OA care, particularly racialized women. One way to reduce inequities is through policies that can influence healthcare services. We examined how OA-relevant policies in Canada address equitable, person-centred OA care for women.

Methods

We used content analysis to extract data from English-language OA-relevant documents referred to as policies or other synonymous terms published in 2000 or later identified by searching governmental and other web sites. We used summary statistics to describe policy characteristics, person-centred care using McCormack’s six-domain framework, and mention of OA prevalence, barriers and strategies to improve equitable access to OA care among women.

Results

We included 14 policies developed from 2004 to 2021. None comprehensively addressed all person-centred care domains, and few addressed individual domains: enable self-management (50%), share decisions (43%), exchange information (29%), respond to emotions (14%), foster a healing relationship (0%) and manage uncertainty (0%). Even when mentioned, content offered little guidance for how to achieve person-centred OA care. Few policies acknowledged greater prevalence of OA among women (36%), older (29%) or Indigenous persons (29%) and those of lower socioeconomic status (14%); or barriers to OA care among those of lower socioeconomic status (50%), in rural areas (43%), of older age (37%) or ethno-cultural groups (21%), or women (21%). Four (29%) policies recommended strategies for improving access to OA care at the patient (self-management education material in different languages and tailored to cultural norms), clinician (healthcare professional education) and system level (evaluate OA service equity, engage lay health leaders in delivering self-management programs, and offer self-management programs in a variety of formats). Five (36%) policies recommended research on how to improve OA care for equity-seeking groups.

Conclusions

Canadian OA-relevant policies lack guidance to overcome disparities in access to person-centred OA care for equity-seeking groups including women. This study identified several ways to strengthen policies. Ongoing research must identify the needs and preferences of equity-seeking persons with OA, and evaluate the impact of various models of service delivery, knowledge needed to influence OA-relevant policy.
Mini-dose methotrexate combined with methylprednisolone for the initial treatment of acute GVHD: a multicentre, randomized trial
Authors: Wang Yu , Liu Qi-Fa , Wu De-Pei , Xu Zheng-Li , Han Ting-Ting , Sun Yu-Qian , Huang Fen , Fan Zhi-Ping , Xu Na , Chen Feng , Zhao Ye , Kong Yuan , Mo Xiao-Dong , Xu Lan-Ping , Zhang Xiao-Hui , Liu Kai-Yan , Huang Xiao-Jun
Published: April 2024

Background

There is an urgent unmet need for effective initial treatment for acute graft-versus-host disease (aGVHD) adding to the standard first-line therapy with corticosteroids after allogeneic haematopoietic stem cell transplantation (allo-HSCT).

Methods

We performed a multicentre, open-label, randomized, phase 3 study. Eligible patients (aged 15 years or older, had received allo-HSCT for a haematological malignancy, developed aGVHD, and received no previous therapies for aGVHD) were randomly assigned (1:1) to receive either 5 mg/m2 MTX on Days 1, 3, or 8 and then combined with corticosteroids or corticosteroids alone weekly.

Results

The primary endpoint was the overall response rate (ORR) on Day 10. A total of 157 patients were randomly assigned to receive either MTX plus corticosteroids (n = 78; MTX group) or corticosteroids alone (n = 79; control group). The Day 10 ORR was 97% for the MTX group and 81% for the control group (p = .005). Among patients with mild aGVHD, the Day 10 ORR was 100% for the MTX group and 86% for the control group (p = .001). The 1-year estimated failure-free survival was 69% for the MTX group and 41% for the control group (p = .002). There were no differences in treatment-related adverse events between the two groups.

Conclusions

In conclusion, mini-dose MTX combined with corticosteroids can significantly improve the ORR in patients with aGVHD and is well tolerated, although it did not achieve the prespecified 20% improvement with the addition of MTX.

Trial registration

The trial was registered with clinicaltrials.gov (NCT04960644).
SLC27A2 is a potential immune biomarker for hematological tumors and significantly regulates the cell cycle progression of diffuse large B-cell lymphoma
Authors: Wang Yi , Chen Xue , Li Yun , Zhang Zhixue , Xia Leiming , Jiang Jiang , Chai Yuqin , Wang Ziming , Wan Yu , Li Tongyu , Jin Fengbo , Li Hongxia
Published: April 2024

Background

Research on the fatty acid metabolism related gene SLC27A2 is currently mainly focused on solid tumors, and its mechanism of action in hematological tumors has not been reported.

Method

This study aims to explore the pathological and immune mechanisms of the fatty acid metabolism related gene SLC27A2 in hematological tumors and verify its functional role in hematological tumors through cell experiments to improve treatment decisions and clinical outcomes of hematological tumors.

Result

This study identified the fatty acid metabolism related gene SLC27A2 as a common differentially expressed gene between DLBCL and AML. Immune microenvironment analysis showed that SLC27A2 was significantly positively correlated with T cell CD4 + , T cell CD8 + , endothelial cells, macrophages, and NK cells in DLBCL. In AML, there is a significant negative correlation between SLC27A2 and B cells, T cell CD8 + , and macrophages. SLC27A2 participates in the immune process of hematological tumors through T cell CD8 + and macrophages. The GESA results indicate that high expression of SLC27A2 is mainly involved in the fatty acid pathway, immune pathway, and cell cycle pathway of DLBCL. The low expression of SLC27A2 is mainly involved in the immune pathway of AML. Therefore, SLC27A2 is mainly involved in the pathological mechanisms of hematological tumors through immune pathways, and cell experiments have also confirmed that SLC27A2 is involved in the regulation of DLBCL cells.

Conclusion

In summary, our research results comprehensively report for the first time the mechanism of action of SLC27A2 in the immune microenvironment of DLBCL and AML, and for the first time verify the cycle and apoptotic effects of the fatty acid related gene SLC27A2 in DLBCL cells through cell experiments. Research can help improve the treatment of AML and DLBCL patients.
Human P2X7 receptor variants Gly150Arg and Arg276His polymorphisms have differential effects on risk association and cellular functions in pancreatic cancer
Authors: Magni Lara , Yu Haoran , Christensen Nynne M. , Poulsen Mette H. , Frueh Alexander , Deshar Ganga , Johansen Astrid Z. , Johansen Julia S. , Pless Stephan A. , Jørgensen Niklas R. , Novak Ivana
Published: April 2024

Background

The purinergic P2X7 receptor (P2X7R) plays an important role in the crosstalk between pancreatic stellate cells (PSCs) and cancer cells, thus promoting progression of pancreatic ductal adenocarcinoma (PDAC). Single nucleotide polymorphisms (SNPs) in the P2X7R have been reported for several cancers, but have not been explored in PDAC.

Materials and methods

Blood samples from PDAC patients and controls were genotyped for 11 non-synonymous SNPs in P2X7R and a risk analysis was performed. Relevant P2X7R-SNP GFP variants were expressed in PSCs and cancer cells and their function was assayed in the following tests. Responses in Ca2+ were studied with Fura-2 and dye uptake with YO-PRO-1. Cell migration was monitored by fluorescence microscopy. Released cytokines were measured with MSD assay.

Results

Risk analysis showed that two SNPs 474G>A and 853G>A (rs28360447, rs7958316), that lead to the Gly150Arg and Arg276His variants, had a significant but opposite risk association with PDAC development, protecting against and predisposing to the disease, respectively. In vitro experiments performed on cancer cells and PSCs expressing the Gly150Arg variant showed reduced intracellular Ca2+ response, fluorescent dye uptake, and cell migration, while the Arg276His variant reduced dye uptake but displayed WT-like Ca2+ responses. As predicted, P2X7R was involved in cytokine release (IL-6, IL-1β, IL-8, TNF-α), but the P2X7R inhibitors displayed varied effects.

Conclusion

In conclusion, we provide evidence for the P2X7R SNPs association with PDAC and propose that they could be considered as potential biomarkers.
Prospective study of malaria in pregnancy, placental and congenital malaria in Northwest Colombia
Authors: Cardona-Arias Jaiberth Antonio , Carmona-Fonseca Jaime
Published: April 2024

Background

Pregnancy Associated Malaria (PAM) include malaria in pregnancy (MiP), placental malaria (PM), and congenital malaria (CM). The evidence available in Colombia on PAM focuses on one of the presentations (MiP, PM or CM), and no study longitudinally analyses the infection from the pregnant woman, passing through the placenta, until culminating in the newborn. This study determined the frequency of MiP, PM, and CM caused by Plasmodium vivax, Plasmodium falciparum, or mixed infections, according to Thick Blood Smear (TBS) and quantitative Polymerase Chain Reaction (qPCR). Identifying associated factors of PAM and clinical-epidemiological outcomes in northwestern Colombia.

Methods

Prospective study of 431 pregnant women, their placenta, and newborns registered in the data bank of the research Group “Salud y Comunidad César Uribe Piedrahíta” which collected information between 2014 and 2020 in endemic municipalities of the departments of Córdoba and Antioquia. The frequency of infection was determined with 95% confidence intervals. Comparisons were made with the Chi-square test, Student t-test, prevalence ratios, and control for confounding variables by log-binomial regression.

Results

The frequency of MiP was 22.3% (4.6% using TBS), PM 24.8% (1.4% using TBS), and CM 11.8% (0% using TBS). Using TBS predominated P. vivax. Using qPCR the proportions of P. vivax and P. falciparum were similar for MiP and PM, but P. falciparum predominated in CM. The frequency was higher in nulliparous, and women with previous malaria. The main clinical effects of PAM were anaemia, low birth weight, and abnormal APGAR score.

Conclusions

The magnitude of infections was not detected with TBS because most cases were submicroscopic (TBS-negative, qPCR-positive). This confirmed the importance of improving the molecular detection of cases. PAM continue being underestimated in the country due to that in Colombia the control programme is based on TBS, despite its outcomes on maternal, and congenital health.
The incorporation of acetylated LAP-TGF-β1 proteins into exosomes promotes TNBC cell dissemination in lung micro-metastasis
Authors: Yu Pei , Han Yubao , Meng Lulu , Tang Zengying , Jin Zhiwei , Zhang Zhenzhen , Zhou Yunjiang , Luo Jun , Luo Jianguang , Han Chao , Zhang Chao , Kong Lingyi
Published: April 2024

Triple-negative breast cancer (TNBC) stands as the breast cancer subtype with the highest recurrence and mortality rates, with the lungs being the common site of metastasis. The pulmonary microenvironment plays a pivotal role in the colonization of disseminated tumor cells. Herein, this study highlights the crucial role of exosomal LAP-TGF-β1, the principal form of exosomal TGF-β1, in reshaping the pulmonary vascular niche, thereby facilitating TNBC lung metastasis. Although various strategies have been developed to block TGF-β signaling and have advanced clinically, their significant side effects have limited their therapeutic application. This study demonstrates that in lung metastatic sites, LAP-TGF-β1 within exosomes can remarkably reconfigure the pulmonary vascular niche at lower doses, bolstering the extravasation and colonization of TNBC cells in the lungs. Mechanistically, under the aegis of the acetyltransferase TIP60, a non-canonical KFERQ-like sequence in LAP-TGF-β1 undergoes acetylation at the K304 site, promoting its interaction with HSP90A and subsequent transport into exosomes. Concurrent inhibition of both HSP90A and TIP60 significantly diminishes the exosomal burden of LAP-TGF-β1, presenting a promising therapeutic avenue for TNBC lung metastasis. This study not only offers fresh insights into the molecular underpinnings of TNBC lung metastasis but also lays a foundation for innovative therapeutic strategies.
Young osteocyte-derived extracellular vesicles facilitate osteogenesis by transferring tropomyosin-1
Authors: Wang Zhen-Xing , Lin Xiao , Cao Jia , Liu Yi-Wei , Luo Zhong-Wei , Rao Shan-Shan , Wang Qiang , Wang Yi-Yi , Chen Chun-Yuan , Zhu Guo-Qiang , Li Fu-Xing-Zi , Tan Yi-Juan , Hu Yin , Yin Hao , Li You-You , He Ze-Hui , Liu Zheng-Zhao , Yuan Ling-Qing , Zhou Yong , Wang Zheng-Guang , Xie Hui
Published: April 2024

Background

Bone marrow mesenchymal stem cells (BMSCs) can undergo inadequate osteogenesis or excessive adipogenesis as they age due to changes in the bone microenvironment, ultimately resulting in decreased bone density and elevated risk of fractures in senile osteoporosis. This study aims to investigate the effects of osteocyte senescence on the bone microenvironment and its influence on BMSCs during aging.

Results

Primary osteocytes were isolated from 2-month-old and 16-month-old mice to obtain young osteocyte-derived extracellular vesicles (YO-EVs) and senescent osteocyte-derived EVs (SO-EVs), respectively. YO-EVs were found to significantly increase alkaline phosphatase activity, mineralization deposition, and the expression of osteogenesis-related genes in BMSCs, while SO-EVs promoted BMSC adipogenesis. Neither YO-EVs nor SO-EVs exerted an effect on the osteoclastogenesis of primary macrophages/monocytes. Our constructed transgenic mice, designed to trace osteocyte-derived EV distribution, revealed abundant osteocyte-derived EVs embedded in the bone matrix. Moreover, mature osteoclasts were found to release osteocyte-derived EVs from bone slices, playing a pivotal role in regulating the functions of the surrounding culture medium. Following intravenous injection into young and elderly mouse models, YO-EVs demonstrated a significant enhancement of bone mass and biomechanical strength compared to SO-EVs. Immunostaining of bone sections revealed that YO-EV treatment augmented the number of osteoblasts on the bone surface, while SO-EV treatment promoted adipocyte formation in the bone marrow. Proteomics analysis of YO-EVs and SO-EVs showed that tropomyosin-1 (TPM1) was enriched in YO-EVs, which increased the matrix stiffness of BMSCs, consequently promoting osteogenesis. Specifically, the siRNA-mediated depletion of Tpm1 eliminated pro-osteogenic activity of YO-EVs both in vitro and in vivo.

Conclusions

Our findings suggested that YO-EVs played a crucial role in maintaining the balance between bone resorption and formation, and their pro-osteogenic activity declining with aging. Therefore, YO-EVs and the delivered TPM1 hold potential as therapeutic targets for senile osteoporosis.

Graphical abstract
LIFU/MMP-2 dual-responsive release of repurposed drug disulfiram from nanodroplets for inhibiting vasculogenic mimicry and lung metastasis in triple-negative breast cancer
Authors: Liu Ying , Tang Rui , Cao Yuting , Wu Nianhong , Qin Qiaoxi , Chen Yuanyuan , Wei Xi , Ren Jianli , Sun Yang , Zhou Hong , Zhou Yang , Li Pan
Published: April 2024

Background

Vasculogenic mimicry (VM), when microvascular channels are formed by cancer cells independent of endothelial cells, often occurs in deep hypoxic areas of tumors and contributes to the aggressiveness and metastasis of triple-negative breast cancer (TNBC) cells. However, well-developed VM inhibitors exhibit inadequate efficacy due to their low drug utilization rate and limited deep penetration. Thus, a cost-effective VM inhibition strategy needs to be designed for TNBC treatment.

Results

Herein, we designed a low-intensity focused ultrasound (LIFU) and matrix metalloproteinase-2 (MMP-2) dual-responsive nanoplatform termed PFP@PDM-PEG for the cost-effective and efficient utilization of the drug disulfiram (DSF) as a VM inhibitor. The PFP@PDM-PEG nanodroplets effectively penetrated tumors and exhibited substantial accumulation facilitated by PEG deshielding in a LIFU-mediated and MMP-2-sensitive manner. Furthermore, upon exposure to LIFU irradiation, DSF was released controllably under ultrasound imaging guidance. This secure and controllable dual-response DSF delivery platform reduced VM formation by inhibiting COL1/pro-MMP-2 activity, thereby significantly inhibiting tumor progression and metastasis.

Conclusions

Considering the safety of the raw materials, controlled treatment process, and reliable repurposing of DSF, this dual-responsive nanoplatform represents a novel and effective VM-based therapeutic strategy for TNBC in clinical settings.

Graphical Abstract
Development and validation of machine learning models and nomograms for predicting the surgical difficulty of laparoscopic resection in rectal cancer
Authors: Li Xiangyong , Zhou Zeyang , Zhu Bing , Wu Yong , Xing Chungen
Published: April 2024

Background

The objective of this study is to develop and validate a machine learning (ML) prediction model for the assessment of laparoscopic total mesorectal excision (LaTME) surgery difficulty, as well as to identify independent risk factors that influence surgical difficulty. Establishing a nomogram aims to assist clinical practitioners in formulating more effective surgical plans before the procedure.

Methods

This study included 186 patients with rectal cancer who underwent LaTME from January 2018 to December 2020. They were divided into a training cohort (n = 131) versus a validation cohort (n = 55). The difficulty of LaTME was defined based on Escal’s et al. scoring criteria with modifications. We utilized Lasso regression to screen the preoperative clinical characteristic variables and intraoperative information most relevant to surgical difficulty for the development and validation of four ML models: logistic regression (LR), support vector machine (SVM), random forest (RF), and decision tree (DT). The performance of the model was assessed based on the area under the receiver operating characteristic curve(AUC), sensitivity, specificity, and accuracy. Logistic regression-based column-line plots were created to visualize the predictive model. Consistency statistics (C-statistic) and calibration curves were used to discriminate and calibrate the nomogram, respectively.

Results

In the validation cohort, all four ML models demonstrate good performance: SVM AUC = 0.987, RF AUC = 0.953, LR AUC = 0.950, and DT AUC = 0.904. To enhance visual evaluation, a logistic regression-based nomogram has been established. Predictive factors included in the nomogram are body mass index (BMI), distance between the tumor to the dentate line ≤ 10 cm, radiodensity of visceral adipose tissue (VAT), area of subcutaneous adipose tissue (SAT), tumor diameter >3 cm, and comorbid hypertension.

Conclusion

In this study, four ML models based on intraoperative and preoperative risk factors and a nomogram based on logistic regression may be of help to surgeons in evaluating the surgical difficulty before operation and adopting appropriate responses and surgical protocols.
Clinical outcomes and challenges of surgical extirpation for carotid body paraganglioma in South Korea: a single-center retrospective study
Authors: Shin Jiyoung , Yun Ji-sup , Kim Young-Wook
Published: April 2024

Background

Carotid body paraganglioma (CBP) is a rare, highly vascularized, and slow-growing neuroendocrine tumor. Surgical resection is the definitive treatment for CBP, however, it remains challenging due to the tumor’s proximity to critical blood vessels and cervical cranial nerves. This study aimed to document the characteristics of CBP and examine the clinical outcomes of patients following surgical extirpation of CBP.

Methods

This is a single-center retrospective review analyzed patients who underwent CBP extirpation. We examined the patient demographics, preoperative clinical features, tumor characteristics, levels of catecholamines and their metabolites in the serum and urine. Surgeries were performed by one vascular surgeon with follow-ups at 1,3,6 months and yearly thereafter. Logistic regression analysis was conducted to identify risk factors associated with the occurrence of either permanent or temporary cervival cranial nerve palsy (CNP).

Results

From September 2020 to February 2023, this study examined 21 cases of CBP removal surgeries that were carried out in 19 patients. The mean age of the patients was 38.9 ± 10.9 years and the percentage of males was 57.1% (n = 12). The most common preoperative clinical feature was painless neck mass (n = 12; 57.1%). Complete resection was achieved in 20 cases; excluding one case with pathologically proven sclerosing paraganglioma. Vascular procedures were performed in four cases (ECA resection, n = 2; primary repair of ICA tear without carotid shunting, n = 1; and ICA patch angioplasty with carotid shunting, n = 1). Temporary cranial neurologic complications, specifically aspiration and hoarseness occurred in four (19.0%), and three (14.3%) cases, respectively. Hoarseness associated with permanent CNP persisted for more than 6 months in two cases (9.5%). No recurrence or mortality was observed during the follow-up period.

Conclusions

Surgical resection is the primay treatment approach for CBP; however, it poses risks of vascular or cervical CNP. The intraoperative estimated blood loss was the only identified risk factor for CNP.
Kids SIPsmartER reduces sugar-sweetened beverages among Appalachian middle-school students and their caregivers: a cluster randomized controlled trial
Authors: Zoellner Jamie M. , You Wen , Porter Kathleen , Kirkpatrick Brittany , Reid Annie , Brock Donna , Chow Phillip , Ritterband Lee
Published: April 2024

Background

High consumption of sugar-sweetened beverages (SSB) is a global health concern. Additionally, sugar-sweetened beverage (SSB) consumption is disproportionately high among adolescents and adults in rural Appalachia. The primary study objective is to determine the intervention effects of Kids SIPsmartER on students’ SSB consumption. Secondary objectives focus on caregivers’ SSB consumption and secondary student and caregiver outcomes [e.g, body mass index (BMI), quality of life (QOL)].

Methods

This Type 1 hybrid, cluster randomized controlled trial includes 12 Appalachian middle schools (6 randomized to Kids SIPsmartER and 6 to control). Kids SIPsmartER is a 6-month, 12 lesson, multi-level, school-based, behavior and health literacy program aimed at reducing SSB among 7th grade middle school students. The program also incorporates a two-way text message strategy for caregivers. In this primary prevention intervention, all 7th grade students and their caregivers from participating schools were eligible to participate, regardless of baseline SSB consumption. Validated instruments were used to assess SSB behaviors and QOL. Height and weight were objectively measured in students and self-reported by caregivers. Analyses included modified two-part models with time fixed effects that controlled for relevant demographics and included school cluster robust standard errors.

Results

Of the 526 students and 220 caregivers, mean (SD) ages were 12.7 (0.5) and 40.6 (6.7) years, respectively. Students were 55% female. Caregivers were mostly female (95%) and White (93%); 25% had a high school education or less and 33% had an annual household income less than $50,000. Regardless of SSB intake at baseline and relative to control participants, SSB significantly decreased among students [-7.2 ounces/day (95% CI = -10.7, -3.7); p < 0.001, effect size (ES) = 0.35] and caregivers [-6.3 ounces/day (95% CI = -11.3, -1.3); p = 0.014, ES = 0.33]. Among students (42%) and caregivers (28%) who consumed > 24 SSB ounces/day at baseline (i.e., high consumers), the ES increased to 0.45 and 0.95, respectively. There were no significant effects for student or caregiver QOL indicators or objectively measured student BMI; however, caregiver self-reported BMI significantly decreased in the intervention versus control schools (p = 0.001).

Conclusions

Kids SIPsmartER was effective at reducing SSB consumption among students and their caregivers in the rural, medically underserved Appalachian region. Importantly, SSB effects were even stronger among students and caregivers who were high consumers at baseline.

Trial registration

Clincialtrials.gov: NCT03740113. Registered 14 November 2018– Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03740113.
Alpha-synuclein inclusion responsive microglia are resistant to CSF1R inhibition
Authors: Stoll Anna C. , Kemp Christopher J. , Patterson Joseph R. , Kubik Michael , Kuhn Nathan , Benskey Matthew , Duffy Megan F. , Luk Kelvin C. , Sortwell Caryl E.
Published: April 2024

Background

Parkinson’s disease (PD) is a neurodegenerative disorder that is characterized by the presence of proteinaceous alpha-synuclein (α-syn) inclusions (Lewy bodies), markers of neuroinflammation and the progressive loss of nigrostriatal dopamine (DA) neurons. These pathological features can be recapitulated in vivo using the α-syn preformed fibril (PFF) model of synucleinopathy. We have previously determined that microglia proximal to PFF-induced nigral α-syn inclusions increase in soma size, upregulate major-histocompatibility complex-II (MHC-II) expression, and increase expression of a suite of inflammation-associated transcripts. This microglial response is observed months prior to degeneration, suggesting that microglia reacting to α-syn inclusion may contribute to neurodegeneration and could represent a potential target for novel therapeutics. The goal of this study was to determine whether colony stimulating factor-1 receptor (CSF1R)-mediated microglial depletion impacts the magnitude of α-syn aggregation, nigrostriatal degeneration, or the response of microglial in the context of the α-syn PFF model.

Methods

Male Fischer 344 rats were injected intrastriatally with either α-syn PFFs or saline. Rats were continuously administered Pexidartinib (PLX3397B, 600 mg/kg), a CSF1R inhibitor, to deplete microglia for a period of either 2 or 6 months.

Results

CSF1R inhibition resulted in significant depletion (~ 43%) of ionized calcium-binding adapter molecule 1 immunoreactive (Iba-1ir) microglia within the SNpc. However, CSF1R inhibition did not impact the increase in microglial number, soma size, number of MHC-II immunoreactive microglia or microglial expression of Cd74, Cxcl10, Rt-1a2, Grn, Csf1r, Tyrobp, and Fcer1g associated with phosphorylated α-syn (pSyn) nigral inclusions. Further, accumulation of pSyn and degeneration of nigral neurons was not impacted by CSF1R inhibition. Paradoxically, long term CSF1R inhibition resulted in increased soma size of remaining Iba-1ir microglia in both control and PFF rats, as well as expression of MHC-II in extranigral regions.

Conclusions

Collectively, our results suggest that CSF1R inhibition does not impact the microglial response to nigral pSyn inclusions and that CSF1R inhibition is not a viable disease-modifying strategy for PD.
Influencing factors of length of stay among repeatedly hospitalized patients with mood disorders: a longitudinal study in China
Authors: Xu Feng , Cheng Peixia , Xu Jiaying , Wang Xiaonan , Jiang Zhen , Zhu Huiping , Fan Hua , Wang Qian , Gao Qi
Published: April 2024

Background

Patients with mood disorders usually require repeated and prolonged hospitalization, resulting in a heavy burden on healthcare resources. This study aims to identify variables associated with length of stay(LOS) of repeatedly hospitalized patients with mood disorders and to provide information for optimizing psychiatry management and healthcare resource allocation.

Methods

Electronic medical records (EMRs) of repeatedly hospitalized patients with mood disorders from January 2010 to December 2018 were collected and retrospectively analyzed. Chi-square and t-test were adopted to investigate the differences in characteristics between the two groups of short LOS and long LOS. Generalized estimating equation (GEE) was conducted to investigate potential factors influencing LOS.

Results

A total of 2,009 repeatedly hospitalized patients with mood disorders were enrolled, of which 797 (39.7%) had a long LOS and 1,212 (60.3%) had a short LOS. Adverse effects of treatment, continuous clinical manifestation, chronic onset type, suicide attempt, comorbidity and use of antidepressants were positively associated with long LOS among all repeatedly hospitalized patients with mood disorders (P < 0.050). For patients with depression, factors associated with long LOS consisted of age, monthly income, adverse effects of treatment, continuous clinical manifestation, suicide attempt and comorbidity (P < 0.050). Whereas, for patients with bipolar disorder (BD), adverse effects of treatment, four or more hospitalizations and use of antidepressants contributed to the long LOS (P < 0.050). Influencing factors of LOS also vary among patients with different effectiveness of treatment.

Conclusion

The LOS in repeatedly hospitalized patients with mood disorders was influenced by multiple factors. There were discrepancies in the factors affecting LOS in patients with different diagnoses and effectiveness of treatment, and specific factors should be addressed when evaluating the LOS.