bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of BZW1 by CEBPB in macrophages promotes eIF2α phosphorylation-mediated metabolic reprogramming and endoplasmic reticulum stress in MRL/lpr lupus-prone mice
Authors: Qi Huimeng , Zheng Zhaoguo , Liu Qiang 
Published: October 2023

Abstract
Background
Lupus nephritis (LN) is associated with significant mortality and morbidity, while effective therapeutics and biomarkers are limited since the pathogenesis is complex. This study investigated the roles of the CEBPB/BZW1/eIF2α axis in metabolic reprogramming and endoplasmic reticulum stress in LN.

Method
The differentially expressed genes in LN were screened using bioinformatics tools. The expression of CEBPB in the renal tissue of patients with LN and its correlation with the levels of creatinine and urinary protein were analyzed. We used adenoviral vectors to construct LN mice with knockdown CEBPB using MRL/lpr lupus-prone mice and analyzed the physiological and autoimmune indices in mice. Chromatin immunoprecipitation quantitative polymerase chain reaction (ChIP–qPCR) and dual-luciferase reporter assays were conducted to explore the regulation of BZW1 by CEBPB, followed by glycolytic flux analysis, glucose uptake, and enzyme-linked immunosorbent assay (ELISA). Finally, the role of eIF2α phosphorylation by BZW1 in bone marrow-derived macrophages (BMDM) was explored using eIF2α phosphorylation and endoplasmic reticulum stress inhibitors.

Results
CEBPB was significantly increased in renal tissues of patients with LN and positively correlated with creatinine and urine protein levels in patients. Downregulation of CEBPB alleviated the autoimmune response and the development of nephritis in LN mice. Transcriptional activation of BZW1 by CEBPB-mediated glucose metabolic reprogramming in macrophages, and upregulation of BZW1 reversed the mitigating effect of CEBPB knockdown on LN. Regulation of eIF2α phosphorylation levels by BZW1 promoted endoplasmic reticulum stress-amplified inflammatory responses in BMDM.

Conclusion
Transcriptional activation of BZW1 by CEBPB promoted phosphorylation of eIF2α to promote macrophage glycolysis and endoplasmic reticulum stress in the development of LN.
Molecular characterization of tetracycline and vancomycin-resistant Enterococcus faecium isolates from healthy dogs in Egypt: a public health threat
Authors: El-Razik Khaled A. Abd , Ibrahim Eman S. , Arafa Amany A. , Hedia Riham H. , Younes Abdelgayed M. , Hasanain Mahmoud H. 
Published: October 2023

Abstract
Background
Vancomycin-resistant enterococci (VRE) are among the most common causative pathogens for nosocomial infections worldwide. Moreover, strains of VRE have been isolated from several domestic livestock in Egypt.

Methods
This study examined if healthy dogs are a potential source of VRE infection by isolating and characterizing Enterococcus faecium strains from stool samples on a morphological basis and biochemical activities. Subsequently, it was confirmed by genotypic characterization using polymerase chain reaction (PCR), followed by the detection of antibiotic resistance genes, virulence determinants, and genes contributing to enterocin production by PCR. Furthermore, the phylogenetic relationships among vanB and tetL genes were analyzed.

Results
All ten fecal samples were identified as E. faecium and confirmed by PCR. In addition, 90% of the isolates tested were positive for the virulence genes gelE and esp, and all the isolates tested were positive for the antibiotic resistance genes tetL and vanB. Only three of the five enterocin genes examined were detected. Ent As-48, bacteriocin 31, and Ent L50 were identified in 100%, 80%, and 60% of the samples, respectively.

Conclusion
Dogs should be regarded as a reservoir of E. faecium that carries vancomycin resistance and virulence determinants that may affect public health in Egypt, considering a "One Health" task force approach to restrict their spread.
Mitigating the risk of flow deterioration by deferring stent optimization in STEMI patients with large thrombus burden: Insights from a prospective cohort study
Authors: Cioffi Giacomo Maria , Zhi Yuan , Madanchi Mehdi , Seiler Thomas , Stutz Leah , Gjergjizi Varis , Romero Jean-Paul , Attinger-Toller Adrian , Bossard Matthias , Cuculi Florim 
Published: October 2023

Abstract
Objectives
It is uncertain, if omitting post-dilatation and stent oversizing (stent optimization) is safe and may decrease the risk for distal thrombus embolization (DTE) in STEMI patients with large thrombus burden (LTB).

Background
In patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) with stenting, (DTE) and flow deterioration are common and increase infarct size leading to worse outcomes.

Methods
From a prospective registry, 74 consecutive STEMI patients with LTB undergoing pPCI with stenting and intentionally deferred stent optimization were analyzed. Imaging data and outcomes up to 2 years follow-up were analyzed.

Results
Overall, 74 patients (18% females) underwent deferred stent optimization. Direct stenting was performed in 13 (18%) patients. No major complications occurred during pPCI. Staged stent optimization was performed after a median of 4 (interquartile range (IQR) 3; 7) days. On optical coherence tomography, under-expansion and residual thrombus were present in 59 (80%) and 27 (36%) cases, respectively. During deferred stent optimization, we encountered no case of flow deterioration (slow or no-reflow) or side branch occlusion. Minimal lumen area (mm2) and stent expansion (%) were corrected from 4.87±1.86mm to 6.82±2.36mm (p<0.05) and from 69±18% to 91±12% (p<0.001), respectively. During follow-up, 1 patient (1.4%) required target lesion revascularization and 1 (1.4%) patient succumbed from cardiovascular death.

Conclusions
Among STEMI patients with LTB, deferring stent optimization in the setting of pPCI appears safe and potentially mitigates the risk of DTE. The impact of this approach on infarct size and clinical outcomes warrants further investigation in a dedicated trial.
The application value of metagenomic next-generation sequencing in community-acquired purulent meningitis after antibiotic intervention
Authors: Shangguan Lijuan , Xue Lanping , Shang Jing , Wang Hailong 
Published: October 2023

Abstract
Background
Bacteria account for nearly one third of the causes of community-acquired central nervous system infections, and traditional diagnostic methods are based on culture results, which are time-consuming and have a low detection rate leading to delayed diagnosis and treatment. Since metagenomic next-generation sequencing (mNGS) has the advantages of high timeliness and only detecting microbial trace gene fragments, it has been used more widely in recent years. Based on this, we explored whether the application of cerebrospinal fluid (CSF) mNGS is advantageous in patients with community-acquired purulent meningitis, especially in people who have already used antibiotics.

Methods
This was a retrospective study of 63 patients with community-acquired purulent meningitis admitted to the Department of Neurology of Shanxi Bethune Hospital from March 2018 to November 2022. Data were systematically collected and classified into CSF culture group, blood culture group and CSF mNGS group according to different detection methods, and the total detection rate of each method was calculated. Each group of patients was divided into two subgroups according to whether antibiotics were used before sampling. The detection rates of the three groups were compared within and between groups to explore whether mNGS has advantages over traditional methods and the influence of antibiotic use on detection rates of the three methods.

Results
Among the 63 patients, the cases of CSF culture, blood culture and CSF mNGS were 56, 46, 44, respectively. The total detection rates of the three methods were 17.86%, 36.96%, 81.82%, with statistical differences (p < 0.05),suggesting that the detection rate of mNGS was higher than CSF culture (p < 0.05) and blood culture (p < 0.05),and the detection rate of blood culture higher than CSF culture (p < 0.05). Further grouping found that without antibiotics, the detection rates of CSF culture, blood culture and CSF mNGS were 28.57%, 56.25% and 88.89%, with statistical differences (p < 0.05), and the detection rate of CSF mNGS was higher than that of CSF culture (p < 0.05), but there was no statistical difference between CSF and blood culture (p > 0.05), nor between blood culture and CSF mNGS (p > 0.05). The detection rates of the three groups with antibiotics were 14.29%, 26.67% and 80.00%, with statistical differences (p < 0.05), and the detection rate of CSF mNGS was still higher than CSF culture (p < 0.05) and blood culture (p < 0.05). However, the detection rate of CSF mNGS also decreased after antibiotics were used for more than 3 days.

Conclusions
The detection rate of CSF mNGS in patients with purulent meningitis is higher than traditional methods, especially in patients who have been given antibiotics, but the detection rate will decrease with the extension of antibiotic use.
Cholinergic signaling influences the expression of immune checkpoint inhibitors, PD-L1 and PD-L2, and tumor hallmarks in human colorectal cancer tissues and cell lines
Authors: Kuol Nyanbol , Godlewski Janusz , Kmiec Zbigniew , Vogrin Sara , Fraser Sarah , Apostolopoulos Vasso , Nurgali Kulmira 
Published: October 2023

Abstract
Background
Cancer cells express immunosuppressive molecules, such as programmed death ligands (PD-L)1 and PD-L2, enabling evasion from the host’s immune system. Cancer cells synthesize and secrete acetylcholine (ACh), acting as an autocrine or paracrine hormone to promote their proliferation, differentiation, and migration.

Methods
We correlated the expression of PD-L1, PD-L2, cholinergic muscarinic receptor 3 (M3R), alpha 7 nicotinic receptor (α7nAChR), and choline acetyltransferase (ChAT) in colorectal cancer (CRC) tissues with the stage of disease, gender, age, risk, and patient survival. The effects of a muscarinic receptor blocker, atropine, and a selective M3R blocker, 4-DAMP, on the expression of immunosuppressive and cholinergic markers were evaluated in human CRC (LIM-2405, HT-29) cells.

Results
Increased expression of PD-L1, M3R, and ChAT at stages III-IV was associated with a high risk of CRC and poor survival outcomes independent of patients’ gender and age. α7nAChR and PD-L2 were not changed at any CRC stages. Atropine and 4-DAMP suppressed the proliferation and migration of human CRC cells, induced apoptosis, and decreased PD-L1, PD-L2, and M3R expression in CRC cells via inhibition of EGFR and phosphorylation of ERK.

Conclusions
The expression of immunosuppressive and cholinergic markers may increase the risk of recurrence of CRC. These markers might be used in determining prognosis and treatment regimens for CRC patients. Blocking cholinergic signaling may be a potential therapeutic for CRC through anti-proliferation and anti-migration via inhibition of EGFR and phosphorylation of ERK. These effects allow the immune system to recognize and eliminate cancer cells.
Associations between serum estradiol and IL-6/sIL-6R/sgp130 complex in female patients with major depressive disorder
Authors: Sun Ting , Chen Qian , Mei Junchi , Li Yan 
Published: October 2023

Abstract
Background
It has been hypothesized that the IL-6/sIL-6R/sgp130 complex, an inflammatory complex, plays a critical role in the pathogenesis of major depressive disorder (MDD). Estradiol (E2) is a sex steroid hormone involved in emotional regulation and MDD. This study aimed to investigate the relationship between E2 and IL-6/sIL-6R/sgp130 complex in patients with MDD.

Methods
Using enzyme-linked immunosorbent assay, the levels of IL-6, sIL-6Rα, and sgp130 were compared between 117 female patients with MDD and 122 healthy controls.The serum concentrations of E2 and other biomarkers were also measured.

Results
(1) The serum levels of IL-6 and sIL-6Rα in patients with MDD were significantly higher than those in the control group, while the serum levels of sgp130 and E2 were significantly lower (all P < 0.05). (2) Low levels of E2 were associated with high levels of IL-6 and low levels of sgp130 (all P < 0.01). (3) HAMD-24 score was positively correlated with the serum level of IL-6, but negatively correlated with the serum levels of sgp130 and E2(all P < 0.05). (4) IL-6 and sgp130 had certain prognostic values in MDD, and the combination of various indicators showed a significantly superior prognostic value.

Conclusions
The IL6/sIL-6R/sgp130 complex in female patients with MDD was closely related to E2 level. In addition, IL-6 and sgp130 may be valuable serum biomarkers for the diagnosis and prognosis of MDD in women.
Association between different insulin resistance surrogates and infertility in reproductive-aged females
Authors: Xia Weiting , Cai Yaoyao , Zhang Sisi , Wu Shenghao 
Published: October 2023

Abstract
Background
Obesity and metabolic syndrome are observed more frequently in infertile women, and insulin resistance (IR) is closely related to them. However, there are no studies that have examined the association between different IR surrogates and female infertility, hence we investigated the potential association between them in the general population.

Methods
This was a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES, 2013–2018). The association of different IR surrogates (HOMA-IR index, TyG index and TyG-BMI index) with female infertility was estimated by multivariable regression analysis.

Results
After adjusting for confounders, the HOMA-IR index and TyG index did not show an association with female infertility, while the TyG-BMI index was found to have a positive association with female infertility (OR = 1.01, 95% CI: 1.00, 1.01; P < 0.0001), and the OR of the TyG-BMI group T3 (≥ 255.55) was significantly different compared to the group T1 (< 185.31) (OR = 3.02, 95% CI: 1.62, 5.60). Similar results were seen in most of the subgroup participants by stratified analysis (P-interaction > 0.05). However, different IR surrogates did not show variability in their ability to predict infertility [TyG-BMI: 0.68 (95% CI: 0.62, 0.74) vs. TyG: 0.62 (95% CI: 0.57, 0.68) vs. HOMA-IR: 0.65 (95% CI: 0.60, 0.71)].

Conclusions
Our result suggests that high levels of TyG-BMI index were positively associated with female infertility in US reproductive-aged females.
A novel concentrated growth factor (CGF) and bio-oss based strategy for second molar protection after impacted mandibular third molar extraction: a randomized controlled clinical study
Authors: Sun Shoufu , Xu Xiaodong , Zhang Zhongxiao , Zhang Ying , Wei Wenjia , Guo Ke , Jiang Yunan N. 
Published: October 2023

Abstract
Background
The extraction of impacted mandibular third molars might cause large bone defects in the distal area of second molars. A new strategy was innovatively employed here combining autologous bone, Bio-Oss, concentrated growth factors (CGF) gel and CGF membrane for bone repair, and the present study aimed at exploring safety as well as short- and long-term efficacy of this new protocol clinically.

Materials and methods
A total of 66 participants were enrolled in this randomized single-blind clinical trial, and randomly allocated to control group (only blood clots), test A group (autogenous bone, Bio-Oss with barrier membrane) and test B group (autogenous bone, Bio-Oss, CGF gel with CGF membrane). The postoperative outcomes including PoSSe scale, periodontal probing depth (PD), degree of gingival recession and computed tomography measurements were assessed at 3rd, 6th, 12th month. A p-value < 0.05 was considered statistically significant.

Results
In PoSSe scale, no significant difference was observed except a significant alleviation of early-stage pain perception in test B group (p < 0.05). Also, test B group exhibited better effect on periodontal healing and gingival recession reduction after 6 months (p < 0.05). Both two test groups showed more new bone formation than the control group (p < 0.05). It is noteworthy that the bone repair of test B group was significantly better than that of test A at 3rd and 6th month (p < 0.05), yet no difference was observed at 12th month (p > 0.05).

Conclusion
Both two test groups could achieve stable long-term efficacy on bone defect repair. The use of CGF gel and CGF membrane could accelerate early-stage bone repair, alleviate short-term pain after surgery, reduce long-term probing depth and relieve economic cost for patients. This new bone repair protocol is worthy of promoting by clinicians.

Trial registration
This study was registered with the identification number ChiCTR2300068466 on 20/02/2023 at Chinese Clinical Trial Registry. Also, it was ethically approved from the institutional ethics committee at the Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (No:2023-010-01), and has been conducted in accordance to the guidelines of the declaration of Helsinki. Written informed consent was obtained from all participants in the study.
The applicability of the “surprise question” as a prognostic tool in patients with severe chronic comorbidities in a university teaching outpatient setting
Authors: Lin C. A. , Pires P. P. , Freitas L. V. , Reis P. V. S. , Silva F. D. , Herbst L. G. , Nunes R. , Lin C. J. , Nunes M. P. T. 
Published: October 2023

Abstract
Background
Life expectancy in recent decades has increased the prevalence of chronic diseases in the population, requiring an approach to new health topics, such as discussions on quality of life and expectations about death and dying. The concept of advance directives (ADs) gives individuals the opportunity to make known their decisions about the treatments they would like to receive at the end of life. Despite the recognition of relevance in clinical practice, the applicability of the concept presents challenges, including establishing the appropriate prognosis for each patient and the ideal time to approach the patient. Some prognostic tools were developed, such as the surprise question (SQ): “Would you be surprised if your patient died in 12 months?”, which is used in some clinical settings to predict patient deaths and to make decisions regarding ADs. The main objective of the present study was to evaluate the behavior of second-year resident physicians (PGY-2) when the SQ was applied.

Method
In our observational study, from July 1, 2016, to February 28, 2017, (PGY-2) in the Internal Medicine Residency Program (IMRP) applied SQ to all patients with multiple and varied chronic no communicable comorbidities, who were followed up at the general medicine outpatient clinic (GMOC) of a tertiary university hospital in São Paulo- Brazil. The frequency of the outcome (death or non-death within 12 months) was analyzed by correlating it with the clinical data (impact of the studied variables).

Results
Eight hundred forty patients entered the study. Fitfty-two of them (6.2%) died within one year. PGY-2 predicted that two hundred and fourteen patients (25.5% of total) would die within a year (answer No to SQ), of which, 32 (14.9%) did so. The correct residents’ prognosis for the subgroup of 626 patients (answer “Yes” to SQ) was NPV = 96.8% (CI = 95.4%-98.2%) and PPV = 14.9% (CI 10.1%-19, 6%). Answering “Yes” to SQ correlated negatively to addressing AD while the outcomes death and the answer No to SQ were positively correlated, according to the number of comorbidities.

Conclusion
The SQ, in addition to care, contributed to health education, communication and care planning shared by the doctor and patient.
Analysing the progress in service delivery towards achieving universal health coverage in Nigeria: a scoping review
Authors: Okeke Chinyere , Ezenwaka Uchenna , Ekenna Adanma , Onyedinma Chioma , Onwujekwe Obinna 
Published: October 2023

Abstract
Background
Attainment of universal health coverage (UHC) requires optimal utilization of health services. Poor coverage and inequitable access to healthcare could hinder improvement in service delivery towards UHC. The study analyzed the progress in service delivery coverage and equity in access to care within the Nigerian health systems based on the tracer indicators of the WHO framework for monitoring UHC.

Methods
We searched the literature in databases: PubMed, Scopus, Directory of Open Access Journals, Google Scholar, Science Direct and websites of relevant health Ministries, Agencies, and Organizations between March to December 2022. Search terms were identified in four broader themes: Service delivery coverage, equity, UHC and Nigeria. Data were collected through a review of 37 published articles (19 peer-reviewed articles and 8 grey documents). We synthesized the findings in thematic areas using the WHO framework for monitoring UHC.

Results
The findings show a slow improvement in service delivery coverage across the UHC tracer indicators; reproductive, maternal, newborn and child health, infectious diseases, non-communicable diseases and service capacity and access. With regards to equity in access to care across the tracer indicators, there has been a great disparity in the utilization of healthcare services among rural dwellers, lower educational level individuals and those with poor socio-economic status over 20 years. However, there was remarkable progress in the ownership and use of long-lasting insecticide-treated nets among rural and lowest-wealth quantile households than their urban counterpart.

Conclusion
There is poor coverage and persistent inequitable access to care among the tracer indicators for monitoring progress in service delivery. Attaining UHC requires concerted efforts and investment of more resources in service delivery to address inequitable access to care and sustainable service coverage for improved health outcomes.
Impact of a combination of pimobendan, furosemide, and enalapril on heart rate variability in naturally occurring, symptomatic, myxomatous mitral valve degeneration dogs
Authors: Pirintr Prapawadee , Saengklub Nakkawee , Boonpala Pakit , Hamlin Robert L. , Kijtawornrat Anusak 
Published: October 2023

AbstractBackgroundPimobendan, diuretics, and an angiotensin-converting enzyme inhibitor (ACEi) are widely used for the management of chronic valvular heart disease in dogs; however, the effects of that combination on heart rate variability (HRV) are unknown. The purpose of this study was to assess the HRV of symptomatic myxomatous mitral valve degeneration (MMVD) dogs in response to therapy with a combination of pimobendan, diuretics, and ACEi.ResultsMMVD stage C (n = 17) dogs were enrolled and a 1-hour Holter recording together with echocardiography, blood pressure measurement, and blood chemistry profiles were obtained before and 1, 3, and 6 months after oral treatment with pimobendan (0.25 mg/kg), enalapril (0.5 mg/kg), and furosemide (2 mg/kg) twice daily. The results revealed that MMVD stage C dogs at the baseline had lower values of time-domain indices, low frequency (LF), high frequency (HF), and total power, as well as higher value of LF/HF. Triple therapy significantly increases these parameters in MMVD stage C dogs (P < 0.05). A positive moderate correlation was observed between time domain parameters and a left ventricular internal diastole diameter normalized to body weight (P < 0.05).ConclusionsIt can be concluded that MMVD stage C dogs possess low HRV due to either the withdrawal of parasympathetic tone or enhanced sympathetic activation, and a combination therapy was shown to enhance cardiac autonomic modulation inferred from the increased heart rate variability. Therefore, a combination therapy may be useful for restoring normal autonomic nervous system activity in dogs with MMVD stage C.