bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sp1 promotes tumour progression by remodelling the mitochondrial network in cervical cancer
Authors: Xu Xu , Wang Xiaona , Chen Qihui , Zheng Aman , Li Donglu , Meng Ziqi , Li Xinran , Cai Hanchen , Li Wangzhi , Huang Shiyuan , Wang Fan 
Published: May 2023

Abstract
Background
Cervical cancer remains one of the most prevalent cancers worldwide. Accumulating evidence suggests that specificity protein 1 (Sp1) plays a pivotal role in tumour progression. The underlying role and mechanism of Sp1 in tumour progression remain unclear.

Methods
The protein level of Sp1 in tumour tissues was determined by immunohistochemistry. The effect of Sp1 expression on the biological characteristics of cervical cancer cells was assessed by colony, wound healing, transwell formation, EdU, and TUNEL assays. Finally, the underlying mechanisms and effects of Sp1 on the mitochondrial network and metabolism of cervical cancer were analysed both in vitro and in vivo.

Results
Sp1 expression was upregulated in cervical cancer. Sp1 knockdown suppressed cell proliferation both in vitro and in vivo, while overexpression of Sp1 had the opposite effects. Mechanistically, Sp1 facilitated mitochondrial remodelling by regulating mitofusin 1/2 (Mfn1/2), OPA1 mitochondrial dynamin-like GTPase (Opa1), and dynamin 1-like (Drp1). Additionally, the Sp1-mediated reprogramming of glucose metabolism played a critical role in the progression of cervical cancer cells.

Conclusions
Our study demonstrates that Sp1 plays a vital role in cervical tumorigenesis by regulating the mitochondrial network and reprogramming glucose metabolism. Targeting Sp1 could be an effective strategy for the treatment of cervical cancer.
SARS-CoV-2 envelope protein triggers depression-like behaviors and dysosmia via TLR2-mediated neuroinflammation in mice
Authors: Su Wenliang , Ju Jiahang , Gu Minghui , Wang Xinrui , Liu Shaozhuang , Yu Jiawen , Mu Dongliang 
Published: May 2023

Abstract
Background
Depression and dysosmia have been regarded as primary neurological symptoms in COVID-19 patients, the mechanism of which remains unclear. Current studies have demonstrated that the SARS-CoV-2 envelope (E) protein is a pro-inflammatory factor sensed by Toll-like receptor 2 (TLR2), suggesting the pathological feature of E protein is independent of viral infection. In this study, we aim to ascertain the role of E protein in depression, dysosmia and associated neuroinflammation in the central nervous system (CNS).

Methods
Depression-like behaviors and olfactory function were observed in both female and male mice receiving intracisternal injection of E protein. Immunohistochemistry was applied in conjunction with RT-PCR to evaluate glial activation, blood–brain barrier status and mediators synthesis in the cortex, hippocampus and olfactory bulb. TLR2 was pharmacologically blocked to determine its role in E protein-related depression-like behaviors and dysosmia in mice.

Results
Intracisternal injection of E protein evoked depression-like behaviors and dysosmia in both female and male mice. Immunohistochemistry suggested that the E protein upregulated IBA1 and GFAP in the cortex, hippocampus and olfactory bulb, while ZO-1 was downregulated. Moreover, IL-1β, TNF-α, IL-6, CCL2, MMP2 and CSF1 were upregulated in both cortex and hippocampus, whereas IL-1β, IL-6 and CCL2 were upregulated in the olfactory bulb. Furtherly, inhibiting microglia, rather than astrocytes, alleviated depression-like behaviors and dysosmia induced by E protein. Finally, RT-PCR and immunohistochemistry suggested that TLR2 was upregulated in the cortex, hippocampus and olfactory bulb, the blocking of which mitigated depression-like behaviors and dysosmia induced by E protein.

Conclusions
Our study demonstrates that envelope protein could directly induce depression-like behaviors, dysosmia, and obvious neuroinflammation in CNS. TLR2 mediated depression-like behaviors and dysosmia induced by envelope protein, which could serve as a promising therapeutic target for neurological manifestation in COVID-19 patients.
Role of combined use of mean platelet volume-to-lymphocyte ratio and monocyte to high-density lipoprotein cholesterol ratio in predicting patients with acute myocardial infarction
Authors: Cao Jianlei , Li Rui , He Tao , Zhang Lin , Liu Huixia , Wu Xiaoyan 
Published: May 2023

Abstract
Background
Atherosclerosis and thrombosis play important roles in the pathophysiology of acute coronary syndrome, with platelet activation and inflammation as the key and initiative factors. Recently mean platelet volume-to-lymphocyte ratio (MPVLR) and monocyte to high-density lipoprotein cholesterol ratio (MHR) have emerged as new prognostic indicators of cardiovascular diseases. However, the predicting effect of the combination of MPVLR and MHR in myocardial infarction has not been reported.

Objective
The aim of this study was to investigate the usefulness of combination of MPVLR and MHR in predicting patients with AMI.

Methods
375 patients who had chest pain or stuffiness were retrospectively enrolled in this study. According to the results of coronary angiography and cardiac troponin, patients were divided into AMI group (n = 284) and control group (n = 91). MPVLR, MHR, Gensini score and Grace score were calculated.

Results
MPVLR and MHR were significantly higher in AMI group than that in control group (6.47 (4.70–9.58) VS 4.88 (3.82–6.44), 13.56 (8.44–19.01) VS 9.14 (7.00–10.86), P < 0.001, respectively). Meanwhile, both were positively correlated with Gensini score and Grace score. Patients with a high level of MPVLR or MHR had an increased risk for AMI (odds ratio (OR) = 1.2, 95% confidence interval (CI) 1.1–1.4, OR = 1.2, 95% CI 1.2–1.3). Combination of MPVLR and MHR identified a greater ROC area than its individual parameters (P < 0.001).

Conclusion
Both MPVLR and MHR are independent predictors of AMI. Combination of MPVLR and MHR had higher predicting value in AMI, and thus appears to be a new risk factor and biomarker in the evaluation of risk and severity of atherosclerosis in AMI.
The short- and long-term effects of cognitive behavioral therapy on the glycemic control of diabetic patients: a systematic review and meta-analysis
Authors: Dong Na , Wang Xiaowei , Yang Liu 
Published: May 2023

Abstract
Background
Glycemic control is an important issue in the treatment of diabetic patients. However, traditional methods, such as medication (the usual treatment), have limitations. Cognitive behavioral therapy (CBT) might be a useful option to help control the glycemic condition. The effects can be revealed by systemic review or meta-analysis of randomized clinical trials (RCT).

Methods
A systematic search and a meta-analysis for the RCT were done of the short- and long-term effects of CBT on the glycemic control of diabetic patients in a comparison with the usual treatment. Nineteen RCT studies and 3,885 diabetic patients were enrolled in this meta-analysis. Subgroup analyses of types 1 and 2 diabetes and individual and group CBT were also performed.

Results
Patients treated with CBT showed no significant difference in HbA1c when compared to the usual treatment within six months. However, CBT was more effective in reducing HbA1c when compared to usual treatment with at least six months of treatment duration [standardized mean difference: -0.44 (95% confidence interval (CI): -0.63 ~ -0.25), Z = 4.49]. Subgroup analysis of type 1 and 2 diabetic patients supported a long-term effect of CBT on glycemic control [standardized mean difference: -0.85 (95% CI: -1.19 ~ -0.10), Z = 2.23, standardized mean difference: -0.33 (95% CI:-0.47 ~ -0.19), Z = 4.52, respectively].

Conclusions
CBT would be a useful option for improving the glycemic control of diabetic patients undergoing long-term treatment. The advantages of the long-term effects of CBT should be considered by clinicians and staff.
The effect on incisional hernia of absorbable barbed suture for midline fascial closure in minimally invasive surgery for colorectal and gastric cancers: study protocol for a randomized controlled trial
Authors: Lee Sejin , Han Se Wung , Lee Min Ro , Kim Chan-Young , Ha Gi Won 
Published: May 2023

Abstract
Background
Incisional hernia following abdominal surgery is a frequent complication of midline laparotomy. This complication is strongly associated with the technique and material used for suture. While a monofilament absorbable suture is recommended to prevent incisional hernia, it can lead to suture loosening or surgical-knot breakage. Although barbed sutures can be an alternative suture material in abdominal fascial closure, evidence for its safety and effectiveness is lacking. Therefore, we designed a prospective randomized trial to evaluate the safety and efficacy of absorbable barbed sutures for midline fascia closure in minimally invasive surgery for colorectal and gastric cancers in comparison with conventional absorbable monofilament sutures.

Methods
A total of 312 patients who underwent minimally invasive surgery for colorectal and gastric cancers will be randomly allocated to either the absorbable barbed or monofilament suture group for abdominal fascia closure in a 1:1 ratio. The primary outcome is incisional hernia rate within 3 years after surgery, as verified by physical examination and computed tomography. Postoperative complications, including surgical site infection, postoperative pain, and quality of life, will be compared between two groups as secondary outcomes. The investigator will examine the patients until discharge and at 6, 12, 18, 24, and 36 months postoperatively.

Discussion
This is the first randomized controlled trial to compare absorbable barbed sutures with monofilament sutures for midline fascia closure in minimally invasive surgery. If absorbable barbed sutures demonstrate superior results to those of monofilament sutures, this type of suture material may be recommended as an alternative option for abdominal fascia closure.

Trial registration
KCT0007069. Registered on January 30, 2023
Evaluation of a community-based integrated care model (CIE) for frail older people in rural Foshan, China: study protocol for a stepped-wedge cluster randomized controlled trial {1}
Authors: Xie Fengjiao , Wen Shuang , Deng Aiwen , Chen Jianhao , Xiong Ribo 
Published: May 2023

Abstract
Background
While community-based eldercare has proven to be effective in qualitative studies, there is limited evidence on the effectiveness of this geriatric care model in rural communities where caring for older people is traditionally the responsibility of family members, but a formal long-term care was recently introduced in China. CIE is a rural community-embedded intervention using multidisciplinary team, to provide evidenced-based integrated care services for frail older people including social care services and allied primary healthcare and community-based rehabilitation services.

Methods
CIE is a prospective stepped-wedge cluster randomized trial conducted at 5 community eldercare centers in rural China. The multifaceted CIE intervention, guided by chronic care model and integrated care model, consists of five components: comprehensive geriatric assessment, individualized care planning, community-based rehabilitation, interdisciplinary case management, and care coordination. The intervention is rolled out in a staggered manner in these clusters of centers at an interval of 1 month. The primary outcomes include functional status, quality of life, and social support. Process evaluation will also be conducted. Generalized linear mixed model is employed for binary outcomes.

Discussion
This study is expected to provide important new evidence on clinical effectiveness and implementation process of an integrated care model for frail older people. The CIE model is also unique as the first registered trial implementing a community-based eldercare model using multidisciplinary team to promote individualized social care services integrated with primary healthcare and community-based rehabilitation services for frail older people in rural China, where formal long-term care was recently introduced.

Trial registration {2a}
China Clinical Trials Register (http://www.chictr.org.cn/historyversionpub.aspx?regno=ChiCTR2200060326). May 28th, 2022.
Entorhinal cortex epigenome-wide association study highlights four novel loci showing differential methylation in Alzheimer’s disease
Authors: Sommerer Yasmine , Dobricic Valerija , Schilling Marcel , Ohlei Olena , Sabet Sanaz Sedghpour , Wesse Tanja , Fuß Janina , Franzenburg Sören , Franke Andre , Parkkinen Laura , Lill Christina M. , Bertram Lars 
Published: May 2023

AbstractBackgroundStudies on DNA methylation (DNAm) in Alzheimer’s disease (AD) have recently highlighted several genomic loci showing association with disease onset and progression.MethodsHere, we conducted an epigenome-wide association study (EWAS) using DNAm profiles in entorhinal cortex (EC) from 149 AD patients and control brains and combined these with two previously published EC datasets by meta-analysis (totaln = 337).ResultsWe identified 12 cytosine-phosphate-guanine (CpG) sites showing epigenome-wide significant association with either case–control status or Braak’s tau-staging. Four of these CpGs, located in proximity toCNFN/LIPE,TENT5A, PALD1/PRF1,andDIRAS1, represent novel findings. Integrating DNAm levels with RNA sequencing-based mRNA expression data generated in the same individuals showed significant DNAm-mRNA correlations for 6 of the 12 significant CpGs. Lastly, by calculating rates of epigenetic age acceleration using two recently proposed “epigenetic clock” estimators we found a significant association with accelerated epigenetic aging in the brains of AD patients vs. controls.ConclusionIn summary, our study represents the hitherto most comprehensive EWAS in AD using EC and highlights several novel differentially methylated loci with potential effects on gene expression.
Transcriptomic analysis of cave, surface, and hybrid samples of the isopod Asellus aquaticus and identification of chromosomal location of candidate genes for cave phenotype evolution
Authors: Lomheim Haeli J. , Reyes Rodas Lizet , Mulla Lubna , Freeborn Layla , Sun Dennis A. , Sanders Sheri A. , Protas Meredith E. 
Published: May 2023

Abstract
Background
Transcriptomic methods can be used to elucidate genes and pathways responsible for phenotypic differences between populations. Asellus aquaticus is a freshwater isopod crustacean with surface- and cave-dwelling ecomorphs that differ greatly in multiple phenotypes including pigmentation and eye size. Multiple genetic resources have been generated for this species, but the genes and pathways responsible for cave-specific characteristics have not yet been identified. Our goal was to generate transcriptomic resources in tandem with taking advantage of the species’ ability to interbreed and generate hybrid individuals.

Results
We generated transcriptomes of the Rakov Škocjan surface population and the Rak Channel of Planina Cave population that combined Illumina short-read assemblies and PacBio Iso-seq long-read sequences. We investigated differential expression at two different embryonic time points as well as allele-specific expression of F1 hybrids between cave and surface individuals. RNAseq of F2 hybrids, as well as genotyping of a backcross, allowed for positional information of multiple candidate genes from the differential expression and allele-specific analyses.

Conclusions
As expected, genes involved in phototransduction and ommochrome synthesis were under-expressed in the cave samples as compared to the surface samples. Allele-specific expression analysis of F1 hybrids identified genes with cave-biased (cave allele has higher mRNA levels than the surface allele) and surface-biased expression (surface allele has higher mRNA levels than the cave allele). RNAseq of F2 hybrids allowed for multiple genes to be placed to previously mapped genomic regions responsible for eye and pigmentation phenotypes. In the future, these transcriptomic resources will guide prioritization of candidates for functional analysis.
Cryptococcus neoformans osteomyelitis of the tibia: a case report and review of the literature
Authors: Papadakis Stamatios A. , Gourtzelidis Georgios , Pallis Dimitrios , Ampadiotaki Margarita-Michaela , Tatakis Fotios , Tsivelekas Konstantinos , Georgousi Kleoniki , Kokkinis Constantinos , Diamantopoulou Kalliopi , Lelekis Moyssis 
Published: May 2023

Abstract
Introduction
Osteomyelitis is a bone inflammation that can be related to various infectious agents. As with any other type of inflammation, the prevailing symptoms and signs may include redness, swelling, pain, and heat. Fungal osteomyelitis is rare and usually found in immune-compromised patients.

Case presentation
A non-human immunodeficiency virus immunocompromised Greek female patient, 82 years old, visited the emergency department due to a 3 day pain located mainly over the left tibia’s anterior surface, accompanied by swelling and redness. There was also a subcutaneous lesion of her left breast. Medical history revealed that the patient had an unmasked close contact with pigeons, a main host of the disease. Initial x-ray imaging showed an osteolytic area in the upper third of the tibial diaphysis. The patient was admitted and underwent a computed tomography-guided biopsy. The specimen revealed a Cryptococcus neoformans infection of the bone and the breast. She was treated with 400 mg fluconazole twice a day for 3 weeks while in hospital and 200 mg twice a day upon discharge for 9 months. After that, she underwent surgical debridement because of lasting local irritation. She was closely monitored in our outpatient office, and in her last visit, 1 year after the initial admission, inflammatory signs had regressed vastly.

Conclusions
To our knowledge, this is the ninth cryptococcal osteomyelitis of the tibia to be recorded since 1974, and the most unusual finding was the bifocal nature of the infection, affecting both the tibia and the breast.
DeepAR: a novel deep learning-based hybrid framework for the interpretable prediction of androgen receptor antagonists
Authors: Schaduangrat Nalini , Anuwongcharoen Nuttapat , Charoenkwan Phasit , Shoombuatong Watshara 
Published: May 2023

AbstractDrug resistance represents a major obstacle to therapeutic innovations and is a prevalent feature in prostate cancer (PCa). Androgen receptors (ARs) are the hallmark therapeutic target for prostate cancer modulation and AR antagonists have achieved great success. However, rapid emergence of resistance contributing to PCa progression is the ultimate burden of their long-term usage. Hence, the discovery and development of AR antagonists with capability to combat the resistance, remains an avenue for further exploration. Therefore, this study proposes a novel deep learning (DL)-based hybrid framework, named DeepAR, to accurately and rapidly identify AR antagonists by using only the SMILES notation. Specifically, DeepAR is capable of extracting and learning the key information embedded in AR antagonists. Firstly, we established a benchmark dataset by collecting active and inactive compounds against AR from the ChEMBL database. Based on this dataset, we developed and optimized a collection of baseline models by using a comprehensive set of well-known molecular descriptors and machine learning algorithms. Then, these baseline models were utilized for creating probabilistic features. Finally, these probabilistic features were combined and used for the construction of a meta-model based on a one-dimensional convolutional neural network. Experimental results indicated that DeepAR is a more accurate and stable approach for identifying AR antagonists in terms of the independent test dataset, by achieving an accuracy of 0.911 and MCC of 0.823. In addition, our proposed framework is able to provide feature importance information by leveraging a popular computational approach, named SHapley Additive exPlanations (SHAP). In the meanwhile, the characterization and analysis of potential AR antagonist candidates were achieved through the SHAP waterfall plot and molecular docking. The analysis inferred that N-heterocyclic moieties, halogenated substituents, and a cyano functional group were significant determinants of potential AR antagonists. Lastly, we implemented an online web server by using DeepAR (at http://pmlabstack.pythonanywhere.com/DeepAR). We anticipate that DeepAR could be a useful computational tool for community-wide facilitation of AR candidates from a large number of uncharacterized compounds.
Antibiotic stewardship in the ICU: time to shift into overdrive
Authors: Mokrani David , Chommeloux Juliette , Pineton de Chambrun Marc , Hékimian Guillaume , Luyt Charles-Edouard 
Published: May 2023

AbstractAntibiotic resistance is a major health problem and will be probably one of the leading causes of deaths in the coming years. One of the most effective ways to fight against resistance is to decrease antibiotic consumption. Intensive care units (ICUs) are places where antibiotics are widely prescribed, and where multidrug-resistant pathogens are frequently encountered. However, ICU physicians may have opportunities to decrease antibiotics consumption and to apply antimicrobial stewardship programs. The main measures that may be implemented include refraining from immediate prescription of antibiotics when infection is suspected (except in patients with shock, where immediate administration of antibiotics is essential); limiting empiric broad-spectrum antibiotics (including anti-MRSA antibiotics) in patients without risk factors for multidrug-resistant pathogens; switching to monotherapy instead of combination therapy and narrowing spectrum when culture and susceptibility tests results are available; limiting the use of carbapenems to extended-spectrum beta-lactamase-producing Enterobacteriaceae, and new beta-lactams to difficult-to-treat pathogen (when these news beta-lactams are the only available option); and shortening the duration of antimicrobial treatment, the use of procalcitonin being one tool to attain this goal. Antimicrobial stewardship programs should combine these measures rather than applying a single one. ICUs and ICU physicians should be at the frontline for developing antimicrobial stewardship programs.
Investigating the facilitating conditions, perceived ease of use and usefulness of mobile-assisted language learning
Authors: Ebadi Saman , Raygan Ali 
Published: May 2023

AbstractMobile technologies and factors influencing English as a foreign language (EFL) learners’ willingness to integrate them into their learning processes are significant. This study aims at investigating the role of facilitating conditions, perceived ease of use, and perceived usefulness as factors in predicting Iranian EFL learners’ perceptions toward mobile-assisted language learning (MALL). Accordingly, data were collected from 223 Iranian EFL learners who had their English language courses in the two major educational contexts (i.e., public schools and private institutes). Considering the first phase of the study, a statistically significant relationship was found between the three hypothesized factors (i.e., facilitating conditions, perceived ease of use, and perceived usefulness) and learners’ perceptions toward MALL. Furthermore, the facilitating conditions were associated with learners’ perceived ease of use. Regarding the second phase of the study, the analysis of the path coefficients indicated a significant predictive power of perceived usefulness on perceptions toward MALL. Also indicated in this study is the significant effect of facilitating conditions on learners’ perceived ease of use. The results are discussed in the light of the literature, and suggestions for further research are provided.