bluuebunny/crossref_metadata_2025_split huggingface dataset:
Squalene epoxidase promotes the chemoresistance of colorectal cancer via (S)-2,3-epoxysqualene-activated NF-κB
Authors: Liu Qi , Zhang Yajuan , Li Huimin , Gao Hong , Zhou Yijie , Luo Dakui , Shan Zezhi , Yang Yufei , Weng Junyong , Li Qingguo , Yang Weiwei , Li Xinxiang 
Published: May 2024

Abstract
Background
While de novo cholesterol biosynthesis plays a crucial role in chemotherapy resistance of colorectal cancer (CRC), the underlying molecular mechanism remains poorly understood.

Methods
We conducted cell proliferation assays on CRC cells with or without depletion of squalene epoxidase (SQLE), with or without 5-fluorouracil (5-FU) treatment. Additionally, a xenograft mouse model was utilized to explore the impact of SQLE on the chemosensitivity of CRC to 5-FU. RNA-sequencing analysis and immunoblotting analysis were performed to clarify the mechanism. We further explore the effect of SQLE depletion on the ubiquitin of NF-κB inhibitor alpha (IκBα) and (S)-2,3-epoxysqualene on the binding of IκBα to beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC) by using immunoprecipitation assay. In addition, a cohort of 272 CRC patients were selected for our clinical analyses.

Results
Mechanistically, (S)-2,3-epoxysqualene promotes IκBα degradation and subsequent NF-κB activation by enhancing the interaction between BTRC and IκBα. Activated NF-κB upregulates the expression of baculoviral IAP repeat containing 3 (BIRC3), sustains tumor cell survival after 5-FU treatment and promotes 5-FU resistance of CRC in vivo. Notably, the treatment of terbinafine, an inhibitor of SQLE commonly used as antifungal drug in clinic, enhances the sensitivity of CRC to 5-FU in vivo. Additionally, the expression of SQLE is associated with the prognosis of human CRC patients with 5-FU-based chemotherapy.

Conclusions
Thus, our finding not only demonstrates a new role of SQLE in chemoresistance of CRC, but also reveals a novel mechanism of (S)-2,3-epoxysqualene-dependent NF-κB activation, implicating the combined potential of terbinafine for 5-FU-based CRC treatment.
Long non-coding RNA RP11-197K6.1 as ceRNA promotes colorectal cancer progression via miR-135a-5p/DLX5 axis
Authors: Wang Mingkun , Niu Xuben , Wang Maihuan , Zheng Peng , Liu Xiaoya , Cao Zhen , Zhang Chaojun 
Published: May 2024

Abstract
Background
Colorectal cancer (CRC) remains a major global health challenge, with high incidence and mortality rates. The role of long noncoding RNAs (lncRNAs) in cancer progression has received considerable attention. The present study aimed to investigate the function and mechanisms underlying the role of lncRNA RP11-197K6.1, microRNA-135a-5p (hsa-miR-135a-5p), and DLX5 in CRC development.

Methods
We analyzed RNA sequencing data from The Cancer Genome Atlas Colorectal Cancer dataset to identify the association between lncRNA RP11-197K6.1 and CRC progression. The expression levels of lncRNA RP11-197K6.1 and DLX5 in CRC samples and cell lines were determined by real-time quantitative PCR and western blotting assays. Fluorescence in situ hybridization was used to confirm the cellular localization of lncRNA RP11-197K6.1. Cell migration capabilities were assessed by Transwell and wound healing assays, and flow cytometry was performed to analyze apoptosis. The interaction between lncRNA RP11-197K6.1 and miR-135a-5p and its effect on DLX5 expression were investigated by the dual-luciferase reporter assay. Additionally, a xenograft mouse model was used to study the in vivo effects of lncRNA RP11-197K6.1 on tumor growth, and an immunohistochemical assay was performed to assess DLX5 expression in tumor tissues.

Results
lncRNA RP11-197K6.1 was significantly upregulated in CRC tissues and cell lines as compared to that in normal tissues, and its expression was inversely correlated with patient survival. It promoted the migration and metastasis of CRC cells by interacting with miR-135a-5p, alleviated suppression of DLX5 expression, and facilitated tumor growth.

Conclusion
This study demonstrated the regulatory network and mechanism of action of the lncRNA RP11-197K6.1/miR-135a-5p/DLX5 axis in CRC development. These findings provided insights into the molecular pathology of CRC and suggested potential therapeutic targets for more effective treatment of patients with CRC.
Therapeutic effects of orexin-A in sepsis-associated encephalopathy in mice
Authors: Guo Jing , Kong Zhuo , Yang Sha , Da Jingjing , Chu Liangzhao , Han Guoqiang , Liu Jian , Tan Ying , Zhang Jiqin 
Published: May 2024

Abstract
Background
Sepsis-associated encephalopathy (SAE) causes acute and long-term cognitive deficits. However, information on the prevention and treatment of cognitive dysfunction after sepsis is limited. The neuropeptide orexin-A (OXA) has been shown to play a protective role against neurological diseases by modulating the inflammatory response through the activation of OXR1 and OXR2 receptors. However, the role of OXA in mediating the neuroprotective effects of SAE has not yet been reported.

Methods
A mouse model of SAE was induced using cecal ligation perforation (CLP) and treated via intranasal administration of exogenous OXA after surgery. Mouse survival, in addition to cognitive and anxiety behaviors, were assessed. Changes in neurons, cerebral edema, blood-brain barrier (BBB) permeability, and brain ultrastructure were monitored. Levels of pro-inflammatory factors (IL-1β, TNF-α) and microglial activation were also measured. The underlying molecular mechanisms were investigated by proteomics analysis and western blotting.

Results
Intranasal OXA treatment reduced mortality, ameliorated cognitive and emotional deficits, and attenuated cerebral edema, BBB disruption, and ultrastructural brain damage in mice. In addition, OXA significantly reduced the expression of the pro-inflammatory factors IL-1β and TNF-α, and inhibited microglial activation. In addition, OXA downregulated the expression of the Rras and RAS proteins, and reduced the phosphorylation of P-38 and JNK, thus inhibiting activation of the MAPK pathway. JNJ-10,397,049 (an OXR2 blocker) reversed the effect of OXA, whereas SB-334,867 (an OXR1 blocker) did not.

Conclusion
This study demonstrated that the intranasal administration of moderate amounts of OXA protects the BBB and inhibits the activation of the OXR2/RAS/MAPK pathway to attenuate the outcome of SAE, suggesting that OXA may be a promising therapeutic approach for the management of SAE.
Automatic extraction of facial median sagittal plane for patients with asymmetry based on the EDMA alignment algorithm
Authors: Zhu Yujia , Wen Aonan , Xiao Ning , Gao Zixiang , Zheng Shengwen , Fu Xiangling , Zhao Yijiao , Wang Yong 
Published: May 2024

Abstract
Background
We aimed to establish a novel method for automatically constructing three-dimensional (3D) median sagittal plane (MSP) for mandibular deviation patients, which can increase the efficiency of aesthetic evaluating treatment progress. We developed a Euclidean weighted Procrustes analysis (EWPA) algorithm for extracting 3D facial MSP based on the Euclidean distance matrix analysis, automatically assigning weight to facial anatomical landmarks.

Methods
Forty patients with mandibular deviation were recruited, and the Procrustes analysis (PA) algorithm based on the original mirror alignment and EWPA algorithm developed in this study were used to construct the MSP of each facial model of the patient as experimental groups 1 and 2, respectively. The expert-defined regional iterative closest point algorithm was used to construct the MSP as the reference group. The angle errors of the two experimental groups were compared to those of the reference group to evaluate their clinical suitability.

Results
The angle errors of the MSP constructed by the two EWPA and PA algorithms for the 40 patients were 1.39 ± 0.85°, 1.39 ± 0.78°, and 1.91 ± 0.80°, respectively. The two EWPA algorithms performed best in patients with moderate facial asymmetry, and in patients with severe facial asymmetry, the angle error was below 2°, which was a significant improvement over the PA algorithm.

Conclusions
The clinical application of the EWPA algorithm based on 3D facial morphological analysis for constructing a 3D facial MSP for patients with mandibular deviated facial asymmetry deformity showed a significant improvement over the conventional PA algorithm and achieved the effect of a dental clinical expert-level diagnostic strategy.
Variants in the MS4A cluster interact with soluble TREM2 expression on biomarkers of neuropathology
Authors: Winfree Rebecca L. , Nolan Emma , Dumitrescu Logan , Blennow Kaj , Zetterberg Henrik , Gifford Katherine A. , Pechman Kimberly R. , Seto Mabel , Petyuk Vladislav A. , Wang Yanling , Schneider Julie , Bennett David A. , Jefferson Angela L. , Hohman Timothy J. ,   the Alzheimer’s Disease Neuroimaging Initiative*
Published: May 2024

AbstractRecent evidence suggests that Alzheimer’s disease (AD) genetic risk variants (rs1582763 and rs6591561) of the MS4A locus are genome-wide significant regulators of soluble TREM2 levels such that the minor allele of the protective variant (rs1582763) is associated with higher sTREM2 and lower AD risk while the minor allele of (rs6591561) relates to lower sTREM2 and higher AD risk. Our group previously found that higher sTREM2 relates to higher Aβ40, worse blood–brain barrier (BBB) integrity (measured with the CSF/plasma albumin ratio), and higher CSF tau, suggesting strong associations with amyloid abundance and both BBB and neurodegeneration complicate interpretation. We expand on this work by leveraging these common variants as genetic tools to tune the interpretation of high CSF sTREM2, and by exploring the potential modifying role of these variants on the well-established associations between CSF sTREM2 as well as TREM2 transcript levels in the brain with AD neuropathology. Biomarker analyses leveraged data from the Vanderbilt Memory & Aging Project (n = 127, age = 72 ± 6.43) and were replicated in the Alzheimer’s Disease Neuroimaging Initiative (n = 399, age = 73 ± 7.39). Autopsy analyses were performed leveraging data from the Religious Orders Study and Rush Memory and Aging Project (n = 577, age = 89 ± 6.46). We found that the protective variant rs1582763 attenuated the association between CSF sTREM2 and Aβ40 (β = -0.44, p-value = 0.017) and replicated this interaction in ADNI (β = -0.27, p = 0.017). We did not observe this same interaction effect between TREM2 mRNA levels and Aβ peptides in brain (Aβ total β = -0.14, p = 0.629; Aβ1-38, β = 0.11, p = 0.200). In contrast to the effects on Aβ, the minor allele of this same variant seemed to enhance the association with blood–brain barrier dysfunction (β = 7.0e-4, p = 0.009), suggesting that elevated sTREM2 may carry a much different interpretation in carriers vs. non-carriers of this allele. When evaluating the risk variant (rs6591561) across datasets, we did not observe a statistically significant interaction against any outcome in VMAP and observed opposing directions of associations in ADNI and ROS/MAP on Aβ levels. Together, our results suggest that the protective effect of rs1582763 may act by decoupling the associations between sTREM2 and amyloid abundance, providing important mechanistic insight into sTREM2 changes and highlighting the need to incorporate genetic context into the analysis of sTREM2 levels, particularly if leveraged as a clinical biomarker of disease in the future.
The impact of armed conflicts on HIV treatment outcomes in Sub-Saharan Africa: a systematic review and meta-analysis
Authors: Kebede Hafte Kahsay , Gesesew Hailay Abrha , Gebremedhin Amanuel Tesfay , Ward Paul 
Published: May 2024

Abstract
Background
Despite the fact that Sub-Saharan Africa bears a disproportionate burden of armed conflicts and HIV infection, there has been inadequate synthesis of the impact of armed conflict on HIV treatment outcomes. We summarized the available evidence on the impact of armed conflicts on HIV treatment outcomes in Sub-Saharan Africa from 2002 to 2022.

Methods
We searched four databases; MEDLINE, PubMed, CINHAL, and Scopus. We also explored grey literature sources and reviewed the bibliographies of all articles to identify any additional relevant studies. We included quantitative studies published in English from January 1, 2002 to December 30, 2022 that reported on HIV treatment outcomes for patients receiving antiretroviral therapy (ART) in conflict and post-conflict areas, IDP centers, or refugee camps, and reported on their treatment outcomes from sub-Saharan Africa. Studies published in languages other than English, reporting on non-ART patients and reporting on current or former military populations were excluded. We used EndNote X9 and Covidence to remove duplicates, extracted data using JBI-MAStARI, assessed risk of bias using AHRQ criteria, reported results using PRISMA checklist, and determined Statistical heterogeneity using Cochran Q test and Higgins I2, R- and RevMan-5 software were used for meta-analysis.

Results
The review included 16 studies with participant numbers ranging from 102 to 2572. Lost To Follow-Up (LTFU) percentages varied between 5.4% and 43.5%, virologic non-suppression rates ranged from 25 to 33%, adherence rates were over 88%, and mortality rates were between 4.2% and 13%. A pooled meta-analysis of virologic non-suppression rates from active conflict settings revealed a non-suppression rate of 30% (0.30 (0.26–0.33), I2 = 0.00%, p = 0.000). In contrast, a pooled meta-analysis of predictors of loss to follow-up (LTFU) from post-conflict settings identified a higher odds ratio for females compared to males (1.51 (1.05, 2.17), I2 = 0%, p = 0.03).

Conclusion
The review highlights a lack of research on the relationship between armed conflicts and HIV care outcomes in SSA. The available documents lack quality of designs and data sources, and the depth and diversity of subjects covered.
Association of low vitamin D level and full-term early-onset neonatal sepsis; a case-control study
Authors: Mohamed Shereen A. , Kamel Nermin R. , Fouda Aya E. , Elhawary Rabab E. , Abdelmegeid Mohamed A. 
Published: May 2024

Abstract
Background
Sepsis is one of the main causes of death in newborns worldwide. Vitamin D levels during fetal and neonatal periods have a significant role in the development of the immunological system. The study aims to evaluate the association between vitamin D levels and the risk of early-onset neonatal sepsis in full-term neonates in a developing country.

Methods
This case–control study was conducted at the Neonatal Intensive Care Units (NICUs) of Kasr Alainy Hospital, Cairo, Egypt. The study was composed of two groups; the sepsis group involved full-term neonates appropriate for gestational age with sepsis-related clinical signs. The control group included newborns with no signs of clinical/laboratory infection within 72 h of life. Blood samples were collected on admission during the first three days of life in both groups for the measurement of 25-hydroxyvitamin D levels, Complete Blood Count (CBC), C reactive protein (CRP), and blood culture.

Results
Forty-five newborns with clinical and laboratory findings of early-onset neonatal sepsis within 72 h of life were enrolled, and the control group included forty-five newborns with no evidence of sepsis. Vitamin D levels in the sepsis group were significantly lower than in the control group. Apgar score at the first minute was significantly lower in the sepsis group. 57.8% of neonates with sepsis had positive blood cultures. There was a statistical difference between deficient, insufficient, and sufficient vitamin D levels regarding the duration of the NICU stay, which was longer in neonates with deficient vitamin D levels. CRP was significantly higher in neonates with deficient vitamin D levels. The area under the receiver operating characteristic curve for serum vitamin D in the prediction of neonatal sepsis was 0.76 at a cutoff < 19.7(ng/ml).

Conclusion
In the current study, full-term newborns with EOS had considerably lower vitamin D levels than healthy controls. Through appropriate vitamin supplementation of the mothers during pregnancy, it could be possible to ensure adequate vitamin D levels for newborns. This may contribute to the reduction of the risk of EOS, together with the other well-known preventive measures (i.e. breastfeeding and intrapartum antibiotic prophylaxis).
Sero-antigen prevalence of lymphatic filariasis and risk factors of podoconiosis in Busiriba sub-county, Kamwenge district, Southwestern Uganda, August–September 2018
Authors: Mwesigye Vicent , Musinguzi Benson , Okongo Benson , Mucunguzi William , Kakaire Michael Nyende , Migisha Richard 
Published: May 2024

Abstract
Objective
Given the neglected nature of filariasis, especially in Uganda where data are scarce, this cross-sectional study aimed to determine the sero-antigen prevalence of lymphatic filariasis and risk factors associated with non-lymphatic filariasis (podoconiosis) in Busiriba Sub-county, Kamwenge District, Uganda, during August–September 2018, to inform targeted elimination efforts.

Results
We enrolled 101 participants, among whom 35 (34.7%) had podoconiosis. The sero-antigen prevalence of lymphatic filariasis was 1.0%. Older age and walking barefoot were associated with increased podoconiosis risk. Specifically, individuals aged 25–49 years with had 7.38 times higher odds of podoconiosis (adjusted odds ratio [aOR] = 7.38, 95% CI: 1.36–40.13) compared to those under 25 years, while those aged ≥ 50 years had even higher odds (aOR = 8.49, 95%CI: 1.44–50.15). Additionally, individuals who reported walking barefoot had 14 times higher odds of podoconiosis (aOR = 14.08; 95% CI: 2.49–79.50).
Monitoring monocyte HLA-DR expression and CD4 + T lymphocyte count in dexamethasone-treated severe COVID-19 patients
Authors: Monneret Guillaume , Voirin Nicolas , Richard Jean-Christophe , Cour Martin , Rimmelé Thomas , Garnier Lorna , Yonis Hodane , Coudereau Remy , Gossez Morgane , Malcus Christophe , Wallet Florent , Delignette Marie-Charlotte , Dailler Frederic , Buisson Marielle , Argaud Laurent , Lukaszewicz Anne-Claire , Venet Fabienne ,   for the RICO study group, Pescarmona Remi , Lombard Christine , Perret Magali , Villard Marine , Groussaud Marie , Itah Laetitia , Boussaha Inesse , Poitevin-Later Françoise , Simon Marie , Dargent Auguste , Bertrand Pierre-Jean , Stevic Neven , Provent Marion , Bignet Laurie , Cerro Valérie , Bitker Laurent , Mezidi Mehdi , Baboi Loredana 
Published: May 2024

Abstract
Background
A 10-day dexamethasone regimen has emerged as the internationally adopted standard-of-care for severe COVID-19 patients. However, the immune response triggered by SARS-CoV-2 infection remains a complex and dynamic phenomenon, leading to various immune profiles and trajectories. The immune status of severe COVID-19 patients following complete dexamethasone treatment has yet to be thoroughly documented.

Results
To analyze monocyte HLA-DR expression (mHLA-DR) and CD4 + T lymphocyte count (CD4) in critically ill COVID-19 patients after a dexamethasone course and evaluate their association with 28-day ICU mortality, adult COVID-19 patients (n = 176) with an ICU length of stay of at least 10 days and under dexamethasone treatment were included. Associations between each biomarker value (or in combination) measured at day 10 after ICU admission and 28-day mortality in ICU were evaluated. At day 10, the majority of patients presented decreased values of both parameters. A significant association between low mHLA-DR and 28-day mortality was observed. This association remained significant in a multivariate analysis including age, comorbidities or pre-existing immunosuppression (adjusted Hazard ratio (aHR) = 2.86 [1.30–6.32], p = 0.009). Similar results were obtained with decreased CD4 + T cell count (aHR = 2.10 [1.09–4.04], p = 0.027). When combining these biomarkers, patients with both decreased mHLA-DR and low CD4 presented with an independent and significant elevated risk of 28-day mortality (i.e., 60%, aHR = 4.83 (1.72–13.57), p = 0.001).

Conclusions
By using standardized immunomonitoring tools available in clinical practice, it is possible to identify a subgroup of patients at high risk of mortality at the end of a 10-day dexamethasone treatment. This emphasizes the significance of integrating immune monitoring into the surveillance of intensive care patients in order to guide further immumodulation approaches.
Enhancing multimedia management: cloud-based movie type recognition with hybrid deep learning architecture
Authors: Lin Fangru , Yuan Jie , Chen Zhiwei , Abiri Maryam 
Published: May 2024

AbstractFilm and movie genres play a pivotal role in captivating relevant audiences across interactive multimedia platforms. With a focus on entertainment, streaming providers are increasingly prioritizing the automatic generation of movie genres within cloud-based media services. In service management, the integration of a hybrid convolutional network proves to be instrumental in effectively distinguishing between a diverse array of video genres. This classification process not only facilitates more refined recommendations and content filtering but also enables targeted advertising. Furthermore, given the frequent amalgamation of components from various genres in cinema, there arises a need for social media networks to incorporate real-time video classification mechanisms for accurate genre identification. In this study, we propose a novel architecture leveraging deep learning techniques for the detection and classification of genres in video films. Our approach entails the utilization of a bidirectional long- and short-term memory (BiLSTM) network, augmented with video descriptors extracted from EfficientNet-B7, an ImageNet pre-trained convolutional neural network (CNN) model. By employing BiLSTM, the network acquires robust video representations and proficiently categorizes movies into multiple genres. Evaluation on the LMTD dataset demonstrates the substantial improvement in the performance of the movie genre classifier system achieved by our proposed architecture. Notably, our approach achieves both computational efficiency and precision, outperforming even the most sophisticated models. Experimental results reveal that EfficientNet-BiLSTM achieves a precision rate of 93.5%. Furthermore, our proposed architecture attains state-of-the-art performance, as evidenced by its F1 score of 0.9012.