bluuebunny/crossref_metadata_2025 huggingface dataset:
Utilization of partograph and associated factors among obstetric caregivers in Ethiopia: a systematic review and meta-analysis
Authors: Ayele Mulat , Lake Eyob Shitie , Yilak Gizachew , Kumie Getinet , Abate Biruk Beletew , Zemariam Alemu Birara , Tilahun Befkad Derese
Published: January 2025

Introduction

Effective use of the partograph is crucial in identifying abnormal labor (prolonged and obstructed labor) and taking appropriate actions. However, in Ethiopia, the prevalence of obstructed labor is much higher at 11.8% and contributes to 14.4% of the total maternal deaths due to underutilization of the partograph by obstetric caregivers. Although a previous systematic review and meta-analysis (SRMA) had been conducted, they were not representative on a national level as they included a limited number of studies and did not evaluate the current prevalence of partograph utilization beyond July 2019. Since then, there have been inconsistent studies assessing the proportion of partograph utilization and its associated factors. Therefore, this systematic review and meta-analysis aimed to estimate the pooled prevalence of partograph utilization and its associated factors in Ethiopia.

Method

Comprehensive literature searches were conducted in PubMed, Google Scholar, and HINARI from 1 September 2013 to 23 October 2023. A random-effects model was used to estimate pooled prevalence and adjusted odds ratio. Stata (version 11.0) was used to analyze the data. Cochrane I2 statistics were computed to assess heterogeneity among studies. A subgroup analysis was done based on the study region to minimize underlying heterogeneity. Funnel plot and Eggers test were conducted to assess publication bias.

Result

Overall, 661 articles were retrieved, and finally, 23 studies were included in this systematic review, including 7,649 participants. The pooled prevalence of partograph utilization was 54.92% (95% CI: 43.38–66.45). The subgroup analysis showed that partograph utilization was highest in the Dire Dawa region and lowest in the Amhara region. Factors such as partograph training [adjusted odds ratio (AOR) = 3.63, 95% CI: 2.57–5.25], good knowledge about partograph (AOR = 2.63, 95% CI: 1.62–4.26), a favorable attitude toward partograph (AOR = 1.95, 95% CI: 1.35–2.82), partograph availability (AOR = 0.89, 95% CI: 2.24–6.61), and being in the midwifery profession (AOR = 0.09, 95% CI: 1.78–5.25) were significantly associated with partograph utilization.

Conclusion

The pooled prevalence of partograph utilization in Ethiopia was low. Partograph training, good knowledge about partograph, favorable attitude toward partograph, partograph availability in the health facility, and being in the midwifery profession were significantly associated with partograph utilization.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier (CRD42023475818).
Metaheuristics for multi-objective scheduling problems in industry 4.0 and 5.0: a state-of-the-arts survey
Authors: Zhang Wenqiang , Bao Xuan , Hao Xinchang , Gen Mitsuo
Published: January 2025

The advent of Industry 4.0 and the emerging Industry 5.0 have fundamentally transformed manufacturing systems, introducing unprecedented levels of complexity in production scheduling. This complexity is further amplified by the integration of cyber-physical systems, Internet of Things, Artificial Intelligence, and human-centric approaches, necessitating more sophisticated optimization methods. This paper aims to provide a more comprehensive perspective on the application of metaheuristic algorithms in shop scheduling problems within the context of Industry 4.0 and Industry 5.0. Through a systematic review of recent literature (2015–2024), we analyze and categorize various metaheuristic approaches, including Evolutionary Algorithms (EAs), swarm intelligence, and hybrid methods, that have been applied to address complex scheduling challenges in smart manufacturing environments. We specifically examine how these algorithms handle multiple competing objectives such as makespan minimization, energy efficiency, production costs, and human-machine collaboration, which are crucial in modern industrial settings. Our survey reveals several key findings: 1) hybrid metaheuristics demonstrate superior performance in handling multi-objective optimization compared to standalone algorithms; 2) bio-inspired algorithms show promising results in addressing complex scheduling and multi-objective manufacturing environments; 3) tri-objective and higher-order multi-objective optimization problems warrant further in-depth exploration; and 4) there is an emerging trend towards incorporating human factors and sustainability objectives in scheduling optimization, aligned with Industry 5.0 principles. Additionally, we identify research gaps and propose future research directions, particularly in areas such as real-time scheduling adaptation, human-centric optimization, and sustainability-aware scheduling algorithms. This comprehensive review provides insights for researchers and practitioners in the field of industrial scheduling, offering a structured understanding of current methodologies and future challenges in the evolution from Industry 4.0 to 5.0.
Proteomic and serologic assessments of responses to mRNA-1273 and BNT162b2 vaccines in human recipient sera
Authors: Hickey Thomas E. , Mudunuri Uma , Hempel Heidi A. , Kemp Troy J. , Roche Nancy V. , Talsania Keyur , Sellers Brian A. , Cherry James M. , Pinto Ligia A.
Published: January 2025

Introduction

The first vaccines approved against SARS-CoV-2, mRNA-1273 and BNT162b2, utilized mRNA platforms. However, little is known about the proteomic markers and pathways associated with host immune responses to mRNA vaccination. In this proof-of-concept study, sera from male and female vaccine recipients were evaluated for proteomic and immunologic responses 1-month and 6-months following homologous third vaccination.

Methods

An aptamer-based (7,289 marker) proteomic assay coupled with traditional serology was leveraged to generate a comprehensive evaluation of systemic responsiveness in 64 and 68 healthy recipients of mRNA-1273 and BNT162b2 vaccines, respectively.

Results

Sera from female recipients of mRNA-1273 showed upregulated indicators of inflammatory and immunological responses at 1-month post-third vaccination, and sera from female recipients of BNT162b2 demonstrated upregulated negative regulators of RNA sensors at 1-month. Sera from male recipients of mRNA-1273 showed no significant upregulation of pathways at 1-month post-third vaccination, though there were multiple significantly upregulated proteomic markers. Sera from male recipients of BNT162b2 demonstrated upregulated markers of immune response to doublestranded RNA and cell-cycle G(2)/M transition at 1-month. Random Forest analysis of proteomic data from pre-third-dose sera identified 85 markers used to develop a model predictive of robust or weaker IgG responses and antibody levels to SARS-CoV-2 spike protein at 6-months following boost; no specific markers were individually predictive of 6-month IgG response. Thirty markers that contributed most to the model were associated with complement cascade and activation; IL-17, TNFR pro-apoptotic, and PI3K signaling; and cell cycle progression.

Discussion

These results demonstrate the utility of proteomics to evaluate correlates or predictors of serological responses to SARS-CoV-2 vaccination.
The liver’s dilemma: sensing real danger in a sea of PAMPs: the (arterial) sinusoidal segment theory
Authors: Henriques-Pons Andrea , Vacani-Martins Natália , dos Santos Carina de Lima Pereira , Meuser-Batista Marcelo
Published: January 2025

The liver is susceptible to viruses and bacterial infections, tumors, and sterile tissue damage, but immunological danger recognition in the liver is highly unconventional. When analyzing innate and adaptive immunity in the organ, the valid concepts that guide danger recognition and immune response in the periphery should be put aside. In the liver, the vascular anatomy is a game changer, as about 80% of the blood that percolates the organ arrives from the hepatic portal vein, draining blood rich in molecules from the intestinal flora. This 24/7 exposure to high amounts of pathogen-associated molecular pattern (PAMPs) molecules results in hepatic immunological tolerance. In the liver, dendritic, Kupffer (KC), liver sinusoidal endothelial cells (LSECs), and even hepatocytes express PD-L1, a T lymphocyte downregulatory molecule. Most cells express Fas-L, IL-10, TGF-β, low levels of co-stimulatory molecules, lack of or have low levels of MHC-I and/or MHC-II expression. Moreover, other negative regulators such as CTLA-4, IDO-1, and prostaglandin E2 (PGE2) are regularly expressed. Then, how can real danger be discerned and recognized in this sea of PAMPs? This is an open question. Here, we hypothesize that conventional immunological danger recognition can occur in the liver but in specific and minor arterial sinusoidal segments,. Then, in the portal triad, where the hepatic artery ramificates into the stroma and carries arterial blood with no gut-derived PAMPs, there is no evolutive or environmental pressure for immunosuppressive pathways, and conventional immunological danger recognition could occur. Therefore, in arterial sinusoidal segments with no sea of PAMPs, the liver could recognize real danger and support innate and adaptive immunity.
Systematic review and quantitative meta-analysis of age-dependent human T-lymphocyte homeostasis
Authors: Kulesh Victoria , Peskov Kirill , Helmlinger Gabriel , Bocharov Gennady
Published: January 2025

Objective

To evaluate and quantitatively describe age-dependent homeostasis for a broad range of total T-cells and specific T-lymphocyte subpopulations in healthy human subjects.

Methods

A systematic literature review was performed to identify and collect relevant quantitative information on T-lymphocyte counts in human blood and various organs. Both individual subject and grouped (aggregated) data on T-lymphocyte observations in absolute and relative values were digitized and curated; cell phenotypes, gating strategies for flow cytometry analyses, organs from which observations were obtained, subjects’ number and age were also systematically inventoried. Age-dependent homeostasis of each T-lymphocyte subpopulation was evaluated via a weighted average calculation within pre-specified age intervals, using a piece-wise equal-effect meta-analysis methodology.

Results

In total, 124 studies comprising 11722 unique observations from healthy subjects encompassing 20 different T-lymphocyte subpopulations – total CD45+ and CD3+ lymphocytes, as well as specific CD4+ and CD8+ naïve, recent thymic emigrants, activated, effector and various subpopulations of memory T-lymphocytes (total-memory, central-memory, effector-memory, resident-memory) – were systematically collected and included in the final database for a comprehensive analysis. Blood counts of most T-lymphocyte subpopulations demonstrate a decline with age, with a pronounced decrease within the first 10 years of life. Conversely, memory T-lymphocytes display a tendency to increase in older age groups, particularly after ~50 years of age. Notably, an increase in T-lymphocyte numbers is observed in neonates and infants (0 – 1 year of age) towards less differentiated T-lymphocyte subpopulations, while an increase into more differentiated subpopulations emerges later (1 – 5 years of age).

Conclusion

A comprehensive systematic review and meta-analysis of T-lymphocyte age-dependent homeostasis in healthy humans was performed, to evaluate immune T-cell profiles as a function of age and to characterize generalized estimates of T-lymphocyte counts across age groups. Our study introduces a quantitative description of the fundamental parameters characterizing the maintenance and evolution of T-cell subsets with age, based on a comprehensive integration of available organ-specific and systems-level flow cytometry datasets. Overall, it provides the most up-to-date view of physiological T-cell dynamics and its variance and may be used as a consistent reference for gaining further mechanistic understanding of the human immune status in health and disease.
Immunomodulatory effects of Lactiplantibacillus plantarum CCFM8661 + stachyose on cyclophosphamide-induced immunosuppression mice
Authors: Ma Weiwei , Sun Hang , Lian Lian , Guo Lidong , Wang Yanyan , Huang Lili
Published: January 2025

Introduction

The increasing stress of modern life has led to a decline in immunity, sparking widespread interest in new strategies to boost immune function. Lactiplantibacillus plantarum and stachyose have gained attention for their immune-regulating effects, but the mechanisms of their combined application remain unclear. This study aims to investigate the immunoregulatory effects of Lactiplantibacillus plantarum CCFM8661 combined with stachyose in cyclophosphamide-induced immunocompromised mice.

Methods

Mice were divided into the normal control group, model control group (normal saline), positive drug control group (levamisole hydrochloride, 10 mg/kg), and low, medium, and high-dose groups (1.5×105, 1.5×106, and 1.5×107 CFU of Lactiplantibacillus plantarum CCFM8661 + 1.5 mg stachyose). Each treatment group received continuous oral gavage administration for 28 days. On days 23 and 24, except for the normal control group, all other groups were intraperitoneally injected with cyclophosphamide (40 mg/kg) to establish an immunosuppressed model. On day 28, 30 minutes after the final administration, the mice were euthanized to collect the thymus, spleen, serum, ileum, and feces for subsequent analysis of immune indicators, intestinal barrier function, serum cytokines, and intestinal microbiota.

Results

The combination significantly improved immune organ atrophy, restored intestinal morphology, and normalized cytokine levels in immunosuppressed mice, indicating enhanced immune function. Additionally, it restored intestinal microbiota diversity by increasing the abundance of Muribaculaceae while reducing Lachnospiraceae, potentially promoting intestinal homeostasis.

Discussion

The combination of Lactiplantibacillus plantarum CCFM8661 and stachyose has immune-enhancing effects, potentially achieved by regulating inflammation levels and maintaining intestinal homeostasis.
A preoperative predictive model based on multi-modal features to predict pathological complete response after neoadjuvant chemoimmunotherapy in esophageal cancer patients
Authors: Qi Yana , Hu Yanran , Lin Chengting , Song Ge , Shi Liting , Zhu Hui
Published: January 2025

Background

This study aimed to develop a multi-modality model by incorporating pretreatment computed tomography (CT) radiomics and pathomics features along with clinical variables to predict pathologic complete response (pCR) to neoadjuvant chemoimmunotherapy in patients with locally advanced esophageal cancer (EC).

Method

A total of 223 EC patients who underwent neoadjuvant chemoimmunotherapy followed by surgical intervention between August 2021 and December 2023 were included in this study. Radiomics features were extracted from contrast-enhanced CT images using PyrRadiomics, while pathomics features were derived from whole-slide images (WSIs) of pathological specimens using a fine-tuned deep learning model (ResNet-50). After feature selection, three single-modality prediction models and a combined multi-modality model integrating two radiomics features, 11 pathomics features, and two clinicopathological features were constructed using the support vector machine (SVM) algorithm. The performance of the models were evaluated using receiver operating characteristic (ROC) analysis, calibration plots, and decision curve analysis (DCA). Shapley values were also utilized to explain the prediction model.

Results

The predictive capability of the multi-modality model in predicting pCR yielded an area under the curve (AUC) of 0.89 (95% confidence interval [CI], 0.75-1.00), outperforming the radiomics model (AUC 0.70 [95% CI 0.54-0.85]), pathomics model (AUC 0.77 [95% CI 0.53-1.00]), and clinical model (AUC 0.63 [95% CI 0.46-0.80]). Additionally, both the calibration plot and DCA curves support the clinical utility of the integrated multi-modality model.

Conclusions

The combined multi-modality model we propose can better predict the pCR status of esophageal cancer and help inform clinical treatment decisions.
A framework for the early detection and prediction of dengue outbreaks in the Republic of Panama
Authors: Ureña Grimaldo E. , Diaz Yamilka , Pascale Juan M. , López-Vergès Sandra , Sanchez-Galan Javier E.
Published: January 2025

The dengue virus (DENV) is endemic in most tropical regions of Central and South America. It is known that when the number of mosquito vectors (Aedes aegypti and Aedes albopictus) for this disease becomes abundant, the number of infectious cases increases. DENV has been known to be continuously circulating in Panama since 1993, with an increasing number of cases reported in recent years after the COVID-19 pandemic, as well as other vector-borne diseases. Preventing dengue outbreaks by having an early detection system is of the utmost importance. To tackle this task, we propose an overall surveillance system framework tailored to the Panamanian situation but applicable to many countries suffering the same maladies. This manuscript presents a transdisciplinary vision that encompasses aspects of sample management, vector surveillance, sharing of weather information, and georeferencing of cases in a Geographic Information System and defining data-driven software solutions for prediction of possible outbreaks.
Metazoan parasites associated with marine mollusks inhabiting the China Seas: a review
Authors: Du Xin , Sun Jing , Ju Huidong , Xu Zhen , Tang Xiaoli , Fang Xuedan , Chang Muhammad Saleem
Published: January 2025

Parasites in mollusks are often neglected by humans, while some species were reported to be harmful to economic mollusks and caused production decrease. Metazoan parasites of mollusk studies from the China Seas started relatively later than other countries. To promote long-term studies on the distribution and diversity of metazoan parasites of mollusks from the China Seas, a comprehensive review has been carried out based on the available literature. The purpose of this study was to perform a critical review about the metazoan parasites associated with mollusks that are useful for the discovery of new metazoans. This publication summarizes information on metazoan parasites of Chinese mollusks from 1932 to 2024. The information is presented and contains 128 species of parasites, distributed among the higher taxa as follows: Turbellaria (2 species), Trematoda (34 species), Cestoda (1 species), Annelida (38 species), Arthropoda (48 species), Porifera (2 species), Cnidaria (1 species), and Mollusca (2 species). Many records of parasites not identified to the species level are also included. Collectively, this review provides a synopsis of the known metazoan parasites of mollusks from the China Seas, as well as presents the known relationship between metazoan parasites and the mollusks, which will broaden our knowledge on the metazoan parasites of mollusks. It is important as it highlights the lack of metazoan parasite studies done in the China Seas and the need for more parasite biodiversity work.
Modeling the advective supply of Calanus finmarchicus to Stellwagen Bank as an indicator of sand lance foraging habitat, and the climate vulnerability of a National Marine Sanctuary
Authors: Thompson Cameron R. S. , Honda Isabel A. , Kritzer Jacob P. , Motyka Jackie , Runge Jeffrey A. , Ji Rubao
Published: January 2025

The northern sand lance (Ammodytes dubius), a key species in the food web supporting the Stellwagen Bank National Marine Sanctuary (SBNMS), feeds primarily on the lipid-rich copepod Calanus finmarchicus. Climate change poses a significant threat to this dynamic, as C. finmarchicus populations are at the southern edge of their subarctic distribution and are vulnerable to warming waters and changing oceanographic conditions. Declines in the advective supply of C. finmarchicus to Stellwagen Bank could adversely affect sand lance populations and, consequently, the ecological and economic resources that depend on them. To quantify the connectivity between SBNMS and potential sources of C. finmarchicus, we used the Finite-Volume Community Ocean Model (FVCOM) coupled with Lagrangian particle tracking over the years 1978 to 2016. Numerical experiments revealed that Stellwagen Bank is highly connected to upstream areas in the Maine Coastal Current (MCC), where existing time series monitoring stations observe C. finmarchicus populations. The connectivity exhibited strong seasonal patterns, with peak connectivity occurring during spring and early summer, aligning with the sand lance feeding period on C. finmarchicus. We found significant interannual variability, influenced by changes in the strength of the MCC and circulation patterns in the western Gulf of Maine. Years with stronger MCC flow showed higher connectivity and a greater potential supply of C. finmarchicus particles to Stellwagen Bank. Conversely, periods of reduced flow corresponded with decreased connectivity, potentially limiting the availability of C. finmarchicus to sand lance populations. Meanwhile, observations from drifters and buoys since 2001 have documented decreases in MCC current speed which has been linked to a climate driven strengthening of southwesterly winds. These findings underscore the importance of pelagic habitat connectivity in assessing the climate vulnerability of marine protected areas (MPAs) like SBNMS. Furthermore, monitoring C. finmarchicus populations at upstream time series stations can provide information on downstream foraging habitat in MPAs, and potentially in other vulnerable areas of ecological and socioeconomic interest. By incorporating these indicators of connectivity and upstream C. finmarchicus population abundance into decision support tools, Sanctuary managers and stakeholders can make informed decisions to mitigate potential climate impacts.
Analysis of small extracellular vesicles from dried blood spots
Authors: Bæk Rikke , Sloth Jenni Kathrine , Hasan Mohammad Mehedi , Midekessa Getnet , Jørgensen Malene Møller
Published: January 2025

This protocol paper describes how to extract small extracellular vesicles (sEVs) from dried blood spots (DBS). The methodology is described in detail and offers further evidence that the extracted particles are sEVs using western blotting (anti-CD9, CD63 and CD81) and fluorescence nanoparticle tracking analysis (fNTA). In addition, we present evidence that approximately 40% of the sEVs were recovered from DBS compared with EVs analyzed from plasma directly. The protocol proves to be robust, reliable and displays very interesting performances even after several weeks (up to 3 weeks) of storage of the DBS when analyzing the sEVs using protein microarray for the presence of the markers CD9, CD63, CD81, EpCAM, Flotilin-1, CD62E/P, CD142 and CD235a. These findings have important implications for using sEVs as future potential diagnostic tools by supporting the validity of less-invasive methods that can be implemented within vulnerable populations or in the field.
Recombinase-based amplification coupled with lateral flow chromatography for the specific and sensitive detection and identification of Leishmania major in cutaneous leishmaniasis patients
Authors: Bel Hadj Ali Insaf , Saadi-Ben Aoun Yusr , Khammeri Imen , Souguir Hejer , Harigua-Souiai Emna , Chouaieb Hamed , Chakroun Ahmed S. , Lemrani Meryem , Kallel Aicha , Kallel Kalthoum , Haddad Nabil , El Dbouni Oussaima , Coler Rhea N. , Reed Steven G. , Fathallah-Mili Akila , Guizani Ikram
Published: January 2025

Introduction

Cutaneous leishmaniases (CL), a wide range of cutaneous diseases caused by diverse species of Leishmania genus parasites, are among the most neglected infectious diseases. While they are non-fatal, CL are highly morbid with disfiguring lesions, which could be chronic, leaving lifelong unsightly scars; they are combined with psychological distress and social stigma. The efficiency of treatment highly depends on the infecting Leishmania species. Diagnosis is mainly based on microscopic direct examination (DE) of Giemsa-stained smears needing experienced microscopists. It can be laborious and time-consuming when the parasite load is low. DE is poorly sensitive and does not identify Leishmania species. So far, only DNA assays accurately identify the species. Despite their wide use for generic detection, PCR methods also require equipment and additional steps to identify causal Leishmania species. L. major is hyperendemic in many countries in Africa, the Middle East, and Asia, where other species co-occur with different endemicity levels according to the situations. This complicates disease management and treatment, particularly as distribution and epidemiology of leishmaniases remain poorly understood. Here, we aimed for a simple and rapid molecular diagnostic test to detect and identify L. major, a predominant CL causal species, which could be prone to become a control tool at the point of care, in endemic areas, using isothermal recombinase DNA amplification (recombinase polymerase amplification, RPA, or recombinase aided amplification, RAA) coupled to detection by the lateral flow (LF) chromatography on a PCRD cassette.

Methods

To develop an L. major species-specific RPA-LF assay, computational analysis of 70 Leishmania DNA targets, identified through bibliography and database searches, selected five targets. We designed and tested 7 primer pairs/probe sets to specifically amplify L. major DNAs. First, the primers were tested for species specificity and sensitivity using basic RPA chemistry. Then, to develop RPA-coupled LF detection, we shifted to the nfo chemistry.

Results

This way, we retained one set for further investigation, which confirmed it is L. major species-specific. Tested on 86 human cutaneous samples, this selected set was able to detect 100% of L. major infections in confirmed CL patients. We did not observe any cross-reactivity with lesions due to L. infantum or L. tropica.
Forging the future of nanotechnology: embracing greener practices for a resilient today and a sustainable tomorrow
Authors: Parab Ankita Rajendra , Ramlal Ayyagari , Gopinath Subash C. B. , Subramaniam Sreeramanan
Published: January 2025

Various chemical and physical methods have been proposed for the synthesis of nanoparticles (NPs). However, these methods have disadvantages, such as high energy loss and high capital requirements. To overcome these problems, alternative methods for NP synthesis, such as biological or green synthesis, are favoured to overcome these problems. Green synthesis of NPs is environmentally friendly, economical and non-toxic. This review examines the history of green synthesis, focusing on using environmentally friendly methods. The integration of machine learning into NP production and a range of NP applications in healthcare, disease treatment and the environment are also covered.
Brain anatomy differences in Chinese children who stutter: a preliminary study
Authors: Ma Dan , Wang Lingling , Liu Sai , Ma XinMao , Jia Fenglin , Hua Yimin , Liao Yi , Qu Haibo
Published: January 2025

Background and purpose

It is unknown the neural mechanisms of developmental stuttering (DS). The aim of this study was to investigate the changes in the structural morphology of the brain in Chinese children who stutter.

Methods

A case–control study was conducted to collect magnetic resonance imaging data from stuttering and non-stuttering children, thereby analyzing whole-brain gray matter volume and cortical morphological changes in stuttering children.

Results

A total of 108 subjects were recruited (stuttering group: control group = 1:1). Comparing to healthy controls, the gray matter volume was significantly decreased in right temporal gyrus and bilateral cerebellum. Additionally, there was a significant reduction in cortical folds in the right insula and right superior temporal gyrus. Moreover, the gray matter volume of the right cerebellum and right temporal gyrus is related to the severity score of stuttering.

Conclusion

The present study proposes that the neural mechanisms underlying DS are intricately linked to the cortico-basal ganglia-thalamo-cortical loop and the dorsal language pathway. This finding is expected to provide reference value for the clinical treatment of DS.
In vitro gastrointestinal digestion simulation screening of novel ACEI peptides from broccoli: mechanism in high glucose-induced VSMCs dysfunction
Authors: Zhang Shuzhi , Guo Jingjing , Suo Shikun , Ju Li , Jiang Zhaoqiang , Dong Pingshuan , Wang Yanli , Dang Yali , Du Laijing
Published: January 2025

Many natural angiotensin-converting enzyme inhibitory (ACEI) peptides have been widely studied. However, their stability in vivo is poor in most cases. In this study, peptides were initially digested from broccoli in vitro, and absorption was simulated by Caco2 cells transport and then analyzed by Peptideomics and molecular docking. Subsequently, the mechanisms were verified using a high glucose-induced vascular smooth muscle cells (VSMCs) dysfunction model. Results showed that ACEI activity of broccoli crude peptide increased by 70.73 ± 1.42% after digestion. The enzymatic hydrolysates of crude broccoli peptides before and after digestion were detected by HPLC. The digested crude peptides were highly stable (with a stability level > 90%) in the intestine and possessed a strong absorptive potential. Five peptides with high stability and strong permeability were first identified, including HLEVR, LTEVR, LEHGF, HLVNK, and LLDGR, which exhibited high activity with IC50 values of 3.19 ± 0.23 mM, 17.07 ± 1.37 mM, 0.64 ± 0.02 mM, 0.06 ± 0.01 mM, and 2.81 ± 0.12 mM, respectively. When the VSMCs model was exposed to Ang II, the expressions of PCNA, MMP2, and Bcl2 were increased, while the expression of BAX was inhibited. When the VSMCs was exposed to high glucose (HG), the Ang II concentration significantly increased. This indicates that HG elevated Ang II levels. Finally, five peptides significantly attenuated Ang II-induced VSMCs proliferation and migration by down-regulating AT1R expression and inhibiting ERK and p38 MAPK phosphorylation. Notably, in exploring VSMCs dysfunction on a high glucose-induced model, ACEI peptides resulted in down-regulation of ACE and up-regulation of ACE2 expression. Therefore, it can be further referenced for the functional food against hypertension and cardiovascular diseases.
Exploring the association between pro-inflammatory diets and chronic liver diseases: evidence from the UK Biobank
Authors: Pan Lili , Xu Zhengrong , Li Yining , Cai Guoen , Gao Haibing , Lin Shenglong
Published: January 2025

Background

Chronic liver diseases (CLD) continue to pose a significant global burden, potentially exacerbated by pro-inflammatory diets. This study explores the relationship between the Dietary Inflammatory Index (DII), a measure of dietary inflammatory potential, and CLD risk.

Methods

Utilizing data from the UK Biobank cohort, we assessed the dietary information and calculated the DII for each participant. Cox proportional hazards models and Fine-Gray competing risk models were employed to evaluate the association between DII and CLD incidence, adjusting for potential confounders.

Results

Our analysis included 121,329 participants with a median follow-up of 604.43 weeks, during which 4,018 developed CLD. A higher DII, indicating a more inflammatory diet, was associated with a 16% increased risk of CLD [hazard ratio (HR) = 1.162, P = 0.001], with each unit increase in DII elevating the risk by 3.3% (HR: 1.033, P < 0.001). A significant linear association between DII and CLD was observed. Competing risk analyses, which accounted for cirrhosis, liver cancer, and death, supported these findings. Subgroup analyses confirmed the robustness of the DII's association across various demographic and lifestyle factors. Moreover, a higher DII was positively associated with the progression of CLD to cirrhosis. Sensitivity analyses, including energy-adjusted DII and typical dietary DII, reinforced our results. Additionally, adherence to anti-inflammatory dietary patterns, as indicated by higher Healthy Eating Index 2020 and Mediterranean Diet Score values, was inversely associated with CLD risk.

Conclusion

Our study highlights the potential benefits of adopting anti-inflammatory diets as a strategy for the prevention and management of CLD. Comprehensive dietary interventions may play a pivotal role in mitigating the global burden of CLD.
Spontaneous rupture of a giant mature teratoma in the lateral ventricle: a case report
Authors: Xiao Yong , Liu Liang , Wang Ran , Wang Dong , Geng Liangyuan , Hu Xinhua , Liu Yong , Qian Chunfa , Zou Yuanjie
Published: January 2025

We present the case of an adolescent female patient diagnosed with a ruptured lateral ventricle teratoma. Distinctive radiological and microscopic findings revealed floating oily globules within the ventricles and subarachnoid space. The spontaneous rupture of the teratoma may be attributed to age-dependent hormonal changes, which increase glandular secretion, cyst content volume, and intra-cystic pressure. The patient underwent gross total resection of the tumor, and the subsequent pathological examination confirmed the diagnosis of mature teratoma. Postoperatively, she was managed with routine follow-up without adjuvant chemotherapy or radiotherapy. During the 1-year follow-up period, the patient remained asymptomatic with no evidence of tumor recurrence. Based on this case, we recommend that gross total resection followed by close monitoring, without adjunctive chemotherapy or radiotherapy, can be an effective treatment strategy for patients with similar presentations.
RET inhibition overcomes resistance to combined CDK4/6 inhibitor and endocrine therapy in ER+ breast cancer
Authors: Kindt Charlotte K. , Ehmsen Sidse , Traynor Sofie , Policastro Benedetta , Nissen Nikoline , Jakobsen Mie K. , Hundebøl Monique F. , Johansen Lene E. , Bak Martin , Arbajian Elsa , Staaf Johan , Ditzel Henrik J. , Alves Carla L.
Published: January 2025

Background

Combined CDK4/6 inhibitor (CDK4/6i) and endocrine therapy significantly improve the outcome of patients with advanced estrogen receptor-positive (ER+) breast cancer. However, resistance to this treatment and disease progression remains a major clinical challenge. High expression of the receptor tyrosine kinase REarranged during Transfection (RET) has been associated with resistance to endocrine therapy in breast cancer, but the role of RET in CDK4/6i treatment response/resistance remains unexplored.

Methods

To identify gene expression alterations associated with resistance to combined endocrine therapy and CDK4/6i, we performed RNA sequencing of two ER+ breast cancer cell models resistant to this combined therapy. The functional role of RET was assessed by siRNA-mediated RET silencing and targeted inhibition with the FDA/EMA-approved RET-selective inhibitor selpercatinib in resistant breast cancer cells and patient-derived organoids (PDOs). RET silencing was evaluated mechanistically using global gene expression and pathway analysis. The clinical relevance of RET expression in ER+ breast cancer was investigated by gene array analysis of primary tumors treated with endocrine therapy and by immunohistochemical scoring of metastatic lesions from patients who received combined CDK4/6i and endocrine therapy.

Results

We show that RET is upregulated in ER+ breast cancer cell lines resistant to combined CDK4/6i and fulvestrant compared to isogenic cells resistant to fulvestrant alone. siRNA-mediated silence of RET in high RET-expressing, combined CDK4/6i- and fulvestrant-resistant cells reduced their growth partially by affecting cell cycle regulators of the G2-M phase and E2F targets. Notably, targeting RET with selpercatinib in combination with CDK4/6i inhibited the growth of CDK4/6i-resistant cell lines and resensitized ER+ breast cancer patient-derived organoids resistant to CDK4/6i. Finally, analysis of RET expression in ER+ breast cancer patients treated with endocrine therapy showed that high RET expression correlated with poor clinical outcomes. We further observed a shorter median survival to combined CDK4/6i and endocrine therapy in patients with RET-positive compared to RET-negative tumors, but this difference did not reach statistical significance.

Conclusions

Our findings show that RET is overexpressed in ER+ metastatic breast cancer resistant to combined CDK4/6i and endocrine therapy, rendering RET inhibition a promising therapeutic approach for patients who experience disease progression on combined CDK4/6i and endocrine therapy.
Cardiac injury caused by iron overload in thalassemia
Authors: Fu Chunxi , Yang Xue
Published: January 2025

Cardiac iron overload affects approximately 25% of patients with β-thalassemia major, which is associated with increased morbidity and mortality. Two mechanisms are responsible for iron overload in β-thalassemia: increased iron absorption due to ineffective erythropoiesis and blood transfusions. This review examines the mechanisms of myocardial injury caused by cardiac iron overload and role of various clinical examination techniques in assessing cardiac iron burden and functional impairment. Early identification and intervention for cardiac injury and iron overload in β-thalassemia have the potential to prevent and reverse or delay its progression in the early stages, playing a crucial role in its prognosis.
Prognostic factors for successful extubation in newborns with congenital diaphragmatic hernia
Authors: Rannebro A. , Mesas-Burgos C. , Fläring U. , Eksborg S. , Berner J.
Published: January 2025

Introduction

Neonates with congenital diaphragmatic hernia (CDH) have an associated high mortality and morbidity. The European CDH EURO consortium has developed guidelines for initial and perioperative ventilatory management. There are, however, no recommendations on how to wean these patients from the ventilator. Extubation failure is more frequent in this group of patients than in other neonates. The aim of this study was to describe patient characteristics and risk factors for failed extubation and to evaluate predictive factors for successful weaning.

Methods

We performed a retrospective study in a single centre tertiary pediatric intensive care unit in Stockholm, Sweden. CDH-patients (n = 38), aged 0–28 days, with extubation events were identified from 2017 to 2019. Eight patients (21.1%) needed reintubation within 24 h after the first extubation attempt. Patient demographics, surgical repair with patch, oxygenation saturation index (OSI), rapid shallow breathing index (RSBI), ventilatory settings, fluid balance and sedation on the day of extubation were recorded.

Results

Patients in the failed extubation group (FE) had lower birth weight (p < 0.05), surgical patch repair (p < 0.05), longer length of stay in intensive care (p < 0.05), longer time on the ventilator (p < 0.05) and other comorbidities (p < 0.001). Using logistic regression we identified OSI, RSBI and inspiratory pressure (Pinsp) as factors predicting a successful extubation, AUCROC 0.95 (95% CI: 0.87 to 1.00). Patients in the FE-group had significantly more often pulmonary hypertension requiring treatment (p < 0.05), a higher fraction of inspired oxygen (FiO2) (p < 0.05) and hypercapnia (p < 0.001) prior to extubation and an oxygen demand exceeding 40% two hours after extubation (p < 0.05).

Conclusion

Useful predictors of successful extubation in CDH patients are OSI, RSBI and Pinsp. Low birth weight, patch repair and comorbidity also appear to be important factors. Prospective studies are required to confirm findings in the present study.
Incidence of hyperkalemia RAASi and SGLT-2i treatment in individuals with diabetic kidney disease: a systematic review and network meta-analysis
Authors: Yuan Yahui , Chen Chun , Lin Yuping , Luo Yehao , Yang Zhaojun , Guo Jingyi , Liu Qiaoyun , Sun Lu , Fan Guanjie
Published: January 2025

Background

This study aims to evaluate the incidence of hyperkalemia and serum potassium levels associated with the use of sodium-glucose cotransporter-2 inhibitors (SGLT-2i), renin‐angiotensin‐aldosterone system inhibitors (RAASi) and concurrent use of these medications in individuals with diabetic kidney disease (DKD).

Methods

A comprehensive systematic search was performed in EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, and PubMed database, covering studies up to March 2024. Relevant randomized controlled trials (RCT) included adults with DKD who were treated with SGLT-2i and RAASi or their combination, with a minimum follow-up duration of 12 weeks. The primary outcomes assessed were the incidence of hyperkalemia and serum potassium levels were the primary outcomes assessed. The surface under the cumulative ranking curves (SUCRA) was utilized for ranking purposes.

Results

The study included 36 trials, encompassing 45,120 participants, comparing various interventions. SGLT-2i (SUCRA = 88.5%) was found to significantly reduce the risk of hyperkalemia. In contrast, the combination of ACEI/ARB + MRA (SUCRA = 5.7%) increased the risk of hyperkalemia. However, when SGLT-2i was added to the ACEI/ARB + MRA regimen, the incidence of hyperkalemia was found to decrease. Subgroup analyses on MRA showed that ACEI/ARB + spironolactone posed the highest risk of hyperkalemia. ACEI/ARB + SGLT-2i mitigated serum potassium level.

Conclusion

SGLT-2i was effective in reducing the incidence of hyperkalemia incidence, whereas a combination of ACEI/ARB and MRA might elevate the incidence of hyperkalemia in individuals with DKD.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42024552810.
Evaluation of the antidiarrheal activity of the 80% hydromethanolic crude extract and solvent fractions of Terminalia brownii Fresen (Combretaceae) leaves in Swiss Albino mice
Authors: Kassaw Khalid Ibrahim , Wondafrash Dawit Zewdu , Yesuf Jibril Seid , Mengistie Mestayet Geta
Published: January 2025

Background

Although diarrhea is a preventable disease, it continues to have a significant impact on global health, with the burden being much greater in Sub-Saharan Africa. Medicinal plants represent affordable and locally available resources to address many diseases, including diarrhea. Thus, this study aimed to investigate the antidiarrheal activities of the 80% hydromethanolic crude extract and solvent fractions of Terminalia brownii Fresen (Combretaceae) leaves in Swiss Albino mice.

Methods

This study was carried out by administering the 80% hydromethanolic crude extract and solvent fractions from the crude extract, including the n-hexane fraction (NHF), ethyl acetate fraction (EAF), and aqueous fraction (AF) at doses of 100 mg/kg, 200 mg/kg, and 400 mg/kg, respectively, to the mice. The effects of these extracts and solvent fractions on reducing/delaying diarrhea were compared with the impact of the solvent used for reconstitution and a standard drug (loperamide 3 mg/kg or atropine 5 mg/kg), as well as with each other.

Results

The hydromethanolic crude extract and ethyl acetate fraction at all tested doses significantly reduced wet defecation (P < 0.05). In addition, total defecation was significantly reduced at a dose of 200 mg/kg (P < 0.05) and 400 mg/kg (P < 0.001) of the crude extract and ethyl acetate fraction at all tested doses (P < 0.01. The aqueous fraction at 200 mg/kg and 400 mg/kg and the n-hexane fraction at 400 mg/kg (P < 0.05) significantly inhibit wet and total defecation. Likewise, in the enteropooling test, the crude extract and ethyl acetate fractions showed a significant reduction in the weight and volume of intestinal contents at a dose of 200 mg/kg (P < 0.05) and 400 mg/kg (P < 0.05). Castor oil-induced intestinal motility was significantly reduced (p < 0.001) by the crude extract and ethyl acetate fractions at all tested doses.

Conclusion

The result from this study suggests significant antidiarrheal activity of Terminalia brownii leaves, which validates its traditional use. The 80% hydromethanolic crude extract and ethyl acetate solvent fractions of Terminalia brownii Fresen leaves have shown better antidiarrheal activity.
Enhanced bioavailability of Quercetin-loaded niosomal in situ gel for the management of Parkinson’s disease
Authors: Revankar Abhishek A. , Patil Archana S. , Karishetti Reshma , Chougule Krutuja R. , Patil Priyanka , Salokhe Abhijit
Published: January 2025

Background

Parkinson’s disease (PD) is the second most prevalent neurological disorder, characterized by motor symptoms such as tremor and rigidity due to the degeneration of dopaminergic neurons in the substantia nigra. This study investigates the formulation of quercetin, a natural bioflavonoid with potent antioxidant and anti-inflammatory properties, as niosomes for intranasal delivery to enhance its bioavailability and therapeutic potential for PD.

Methods

The niosomal formulation was optimized for critical parameters including particle size, entrapment efficiency, and zeta potential. Male Wistar rats were utilized to assess the effects of quercetin-loaded niosomes on motor function, dopaminergic neuron protection, and oxidative stress alleviation.

Results

The optimized niosomal formulation exhibited a particle size of 195 nm, a polydispersity index (PDI) of 0.29, a zeta potential (ZP) of −30.63 mV, and an entrapment efficiency (EE) of 82.77%. In vivo evaluations conducted using the haloperidol-induced PD model revealed significant enhancements in behavioural, biochemical, and histopathological outcomes when compared to both disease controls and the standard treatment group. Additionally, short-term stability tests confirmed the robustness of the formulation.

Conclusion

The findings suggest that the quercetin-loaded niosomal formulation offers improved drug delivery and efficacy, indicating its potential as a superior treatment option for PD compared to conventional dosage forms. This approach may pave the way for enhanced therapeutic strategies targeting the neurodegenerative processes underlying Parkinson’s disease.