bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronotherapeutic neuroprotective effect of verapamil against lipopolysaccharide-induced neuroinflammation in mice through modulation of calcium-dependent genes
Authors: Mosalam Esraa M. , Elberri Aya Ibrahim , Sallam Amany Said , Salem Heba Rady , Metwally Ebtehal M. , Abdallah Mahmoud S. , Shaldam Moataz A. , Mansour Hend E. Abo
Published: November 2022

Background

Neuroinflammation is a major mechanism in neurodegenerative diseases such as Alzheimer’s disease (AD), which is a major healthcare problem. Notwithstanding of ample researches figured out possible molecular mechanisms underlying the pathophysiology of AD, there is no definitive therapeutics that aid in neuroprotection. Therefore, searching for new agents and potential targets is a critical demand. We aimed to investigate the neuroprotective effect of verapamil (VRP) against lipopolysaccharide (LPS)-induced neuroinflammation in mice and whether the time of VRP administration could affect its efficacy.

Methods

Forty male albino mice were used and were divided into normal control, LPS only, morning VRP, and evening VRP. Y-maze and pole climbing test were performed as behavioral tests. Hematoxylin and eosin together with Bielschowsky silver staining were done to visualize neuroinflammation and phosphorylated tau protein (pTAU); respectively. Additionally, the state of mitochondria, the levels of microglia-activation markers, inflammatory cytokines, intracellular Ca2+, pTAU, and Ca2+-dependent genes involving Ca2+/ calmodulin dependent kinase II (CAMKII) isoforms, protein kinase A (PKA), cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF), with the level of VRP in the brain tissue were measured.

Results

LPS successfully induced neuroinflammation and hyperphosphorylation of tau protein, which was indicated by elevated levels of microglia markers, inflammatory cytokines, and intracellular Ca2+ with compromised mitochondria and downregulated CAMKII isoforms, PKA, CREB and BDNF. Pretreatment with VRP showed significant enhancement in the architecture of the brain and in the behavioral tests as indicated by the measured parameters. Moreover, morning VRP exhibited better neuroprotective profile compared to the evening therapy.

Conclusions

VRP highlighted a multilevel of neuroprotection through anti-inflammatory activity, Ca2+ blockage, and regulation of Ca2+-dependent genes. Furthermore, chronotherapy of VRP administration should be consider to achieve best therapeutic efficacy.

Graphical Abstract
Tetrandrine inhibits RANKL-induced osteoclastogenesis by promoting the degradation of TRAIL
Authors: Li Jiarui , Li Xiang , Zhou Shengji , Wang Yuxin , Lu Yang , Wang Quan , Zhao Fengchao
Published: November 2022

Background

Tetrandrine, a bisbenzylisoquinoline (BBI) alkaloid extracted from Stephania tetrandra (S. Moore), and is widely used in several diseases such as tuberculosis, hyperglycemia, malaria, and tumors. Tetrandrine was recently shown to prevent bone loss in ovariectomized mice. However, the specific mechanism underlying osteoclastogenesis inhibition remains unclear.

Methods

Tetrandrine’s cytotoxicity to cells was determined using the Cell Counting Kit-8 assay. Tartrate-resistant acid phosphatase staining, immunofluorescence and bone resorption assay were performed to evaluate osteoclasts’ differentiation and absorption capacity. The bone-forming capacity was assessed using alkaline phosphatase and Alizarin red S staining. qPCR and Western blotting were applied to assess the related genes and protein expression. Tetrandrine’s impact on TRAIL was demonstrated through a co-immunoprecipitation assay. Animal experiments were performed for the detection of the therapeutic effect of Tetrandrine on osteoporosis.

Results

Tetrandrine attenuated RANKL-induced osteoclastogenesis and decreased the related gene expression. The co-immunoprecipitation assay revealed that Tetrandrine administration accelerated the ubiquitination of TNF-related apoptosis-inducing ligand (TRAIL), which was subsequently degraded. Moreover, TRAIL overexpression was found to partially reverse the Tetrandrine-induced inhibition of osteoclastogenesis. Meanwhile, Tetrandrine significantly inhibited the phosphorylation of p38, p65, JNK, IKBα and IKKα/β, while the TRAIL overexpression weakened this effect. In addition, Tetrandrine promoted osteogenesis and inhibited the TRAIL expression in osteoblasts. Tetrandrine consistently improved bone destruction by stimulating bone formation and inhibiting bone resorption in an OVX-induced mouse model.

Conclusion

Tetrandrine inhibits RANKL-induced osteoclastogenesis by promoting TRAIL degradation and promotes osteoblast differentiation, suggesting its potential in antiosteopenia pharmacotherapy.
Modular networks and genomic variation during progression from stable angina pectoris through ischemic cardiomyopathy to chronic heart failure
Authors: Chen Lin , Yu Ya-Nan , Liu Jun , Chen Yin-ying , Wang Bo , Qi Yi-Fei , Guan Shuang , Liu Xi , Li Bing , Zhang Ying-Ying , Hu Yuanhui , Wang Zhong
Published: November 2022

Background

Analyzing disease–disease relationships plays an important role for understanding etiology, disease classification, and drug repositioning. However, as cardiovascular diseases with causative links, the molecular relationship among stable angina pectoris (SAP), ischemic cardiomyopathy (ICM) and chronic heart failure (CHF) is not clear.

Methods

In this study, by integrating the multi-database data, we constructed paired disease progression modules (PDPMs) to identified relationship among SAP, ICM and CHF based on module reconstruction pairs (MRPs) of K-value calculation (a Euclidean distance optimization by integrating module topology parameters and their weights) methods. Finally, enrichment analysis, literature validation and structural variation (SV) were performed to verify the relationship between the three diseases in PDPMs.

Results

Total 16 PDPMs were found with K > 0.3777 among SAP, ICM and CHF, in which 6 pairs in SAP–ICM, 5 pairs for both ICM–CHF and SAP–CHF. SAP–ICM was the most closely related by having the smallest average K-value (K = 0.3899) while the maximum is SAP–CHF (K = 0.4006). According to the function of the validation gene, inflammatory response were through each stage of SAP–ICM–CHF, while SAP–ICM was uniquely involved in fibrosis, and genes were related in affecting the upstream of PI3K–Akt signaling pathway. 4 of the 11 genes (FLT1, KDR, ANGPT2 and PGF) in SAP–ICM–CHF related to angiogenesis in HIF-1 signaling pathway. Furthermore, we identified 62.96% SVs were protein deletion in SAP–ICM–CHF, and 53.85% SVs were defined as protein replication in SAP–ICM, while ICM–CHF genes were mainly affected by protein deletion.

Conclusion

The PDPMs analysis approach combined with genomic structural variation provides a new avenue for determining target associations contributing to disease progression and reveals that inflammation and angiogenesis may be important links among SAP, ICM and CHF progression.
A comprehensive list of human microdeletion and microduplication syndromes
Authors: Wetzel Alyssa S. , Darbro Benjamin W.
Published: November 2022

Objective

The phenotypic spectrum of human microdeletion and microduplication syndromes (MMS) is heterogeneous but often involves intellectual disability, autism spectrum disorders, dysmorphic features and/or multiple congenital anomalies. While the common recurrent copy number variants (CNVs) which underlie these MMS have been well-studied, the expansion of clinical genomic testing has led to the identification of many rare non-recurrent MMS. To date, hundreds of unique MMS have been reported in the medical literature, and no single resource exists which compiles all these MMS in one location. This comprehensive list of MMS will aid further study of CNV disorders as well as serve as a resource for clinical laboratories performing diagnostic CNV testing.

Data description

Here we provide a comprehensive list of MMS which have been reported in the medical literature to date. This list is sorted by genomic location, and for each MMS, we provide a list of publications for referral, as well as the consensus coordinates, representative region, shortest regions of overlap (SRO), and/or subregions where applicable.
The potential use of acylglycerols on the thermal inactivation of lactic acid bacteria for the manufacture of long-life fermented products
Authors: Huerta-González Luis , López-Valdez Fernando , Luna-Suárez Silvia
Published: November 2022

The effect of acylglycerols on the thermal inactivation of lactic acid bacteria used in the production of fermented products was studied. The starting point was the observation of an increase in thermal sensitivity in the presence of an emulsifier based on mono- and diacylglycerols in the culture medium. Analysis of the emulsifier showed that monoacylglycerols were the compounds responsible for this effect, with monopalmitin being the main contributor. Monostearin, on the other hand, showed significantly less potentiating effect. Interestingly, monoacylglycerols showed a greater bactericidal effect when used individually than when used in combination. On the other hand, the rate of thermal inactivation observed in reconstituted skim milk emulsions was lower than in peptone water emulsions, showing that the presence of proteins and colloidal particles increased the resistance of bacteria to heat treatment. With respect to pH values, a reduction in pH from 6.6 to 5.5 promoted an increase in the rate of thermal death. However, at pH = 5.5, the enhancing bactericidal effect was only detectable when the heat treatment was performed at low temperatures but not at high temperatures. This finding is of interest, since it will allow the design of moderate heat treatments, combining the use of temperature with the addition of acylglycerols, to prolong the shelf life of products fermented with lactic acid bacteria, and minimizing the destruction of desirable compounds that were obtained by the fermentation process.
Antimicrobial activity of ceftobiprole and comparator agents when tested against gram-positive and -negative organisms collected across China (2016–2018)
Authors: Dandan Yin , Shi Wu , Yang Yang , Yonggui Zheng , Zhu Demei , Yan Guo , Hu Fupin
Published: November 2022

Background

Ceftobiprole is a fifth-generation cephalosporin which has been reported to have broad antibacterial spectrum when tested against bacteria collected from other countries except China. This study evaluated the in vitro activity of ceftobiprole in comparison with other comparators against clinically significant isolates collected across from China.

Results

Susceptibility testing of ceftobiprole and comparators against 1163 clinically isolated Gram-positive and Gram-negative bacteria was performed with broth micro dilution method following the CLSI guidelines. All 110 S. aureus were susceptible to ceftobiprole with MIC50/90 of 1/2 mg/L for MRSA and 0.5/1 mg/L for MSSA. For Coagulase-negative staphylococci (CNS), MIC50/90 of ceftobiprole for MRCNS and MSCNS was 1/2 mg/L and 0.25/0.5 mg/L. Ceftobiprole demonstrated good potency against E. faecalis (MIC50/90 of 0.5/1 mg/L) but limited activity against E. faecium (MIC50/90 of > 32/ > 32 mg/L). Ceftobiprole demonstrated potent activity against all 39 β-hemolytic Streptococcus spp. with MIC50/90 ≤ 0.015/ ≤ 0.015–2 mg/L and 110 of PSSP with 98.2% susceptibility. Ceftobiprole inhibited all isolates of H. influenzae and M. catarrhalis at ≤ 1 mg/L. 91.8% and 98.2% of the ESBL-negative E. coli and K. pneumoniae were susceptible to ceftobiprole, but most of the ESBL-positive or carbapenem-resistant strains were also resistant to ceftobiprole. Ceftobiprole inhibited 84.2% of carbapenem-susceptible P. aeruginosa and 94.1% of carbapenem-susceptible A. baumannii at ≤ 8 mg/L, but only 52.6% of carbapenem-resistant P. aeruginosa and 5.3% of carbapenem-resistant A. baumannii.

Conclusion

Ceftobiprole demonstrated good in vitro activity against a broad range of clinically relevant contemporary Gram-positive and Gram-negative bacterial isolates.
NLRP3 inflammasome regulates astrocyte transformation in brain injury induced by chronic intermittent hypoxia
Authors: She Ningning , Shi Yewen , Feng Yani , Ma Lina , Yuan Yuqi , Zhang Yitong , Cao Zine , Chen Xi , Zhao Bingjie , Liu Haiqin , Ren Xiaoyong
Published: November 2022

Background

Obstructive sleep apnea (OSA) is mainly characterized by sleep fragmentation and chronic intermittent hypoxia (CIH), the latter one being associated with multiple organ injury. Recently, OSA-induced cognition dysfunction has received extensive attention from scholars. Astrocytes are essential in neurocognitive deficits via A1/A2 phenotypic changes. Nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome is considered the most important factor inducing and maintaining neuroinflammation. However, whether the NLRP3 regulates the A1/A2 transformation of astrocytes in CIH-related brain injury remains unclear.

Methods

We constructed an OSA-related CIH animal model and assessed the rats' learning ability in the Morris water maze; the histopathological assessment was performed by HE and Nissl staining. The expression of GFAP (astrocyte marker), C3d (A1-type astrocyte marker), and S100a10 (A2-type astrocyte marker) were detected by immunohistochemistry and immunofluorescence. Western blotting and RT-qPCR were used to evaluate the changes of A1/A2 astrocyte-related protein and NLRP3/Caspase-1/ASC/IL-1β.

Results

The learning ability of rats decreased under CIH. Further pathological examination revealed that the neurocyte in the hippocampus were damaged. The cell nuclei were fragmented and dissolved, and Nissl bodies were reduced. Immunohistochemistry showed that astrocytes were activated, and morphology and number of astrocytes changed. Immunofluorescence, Western blotting and RT-qPCR showed that the expression of C3d was increased while S100a10 was decreased. Also, the expression of the inflammasome (NLRP3/Caspase-1/ASC/IL-1β) was increased. After treatment of MCC950 (a small molecule inhibitor of NLRP3), the damage of nerve cells was alleviated, the Nissl bodies increased, the activation of astrocytes was reduced, and the expression of A2-type astrocytes was increased. In contrast, A1-type astrocytes decreased, and the expression of inflammasome NLRP3/Caspase-1/ASC/IL-1β pathway-related proteins decreased.

Conclusion

The NLRP3 inflammasome could regulate the A1/A2 transformation of astrocytes in brain injury induced by CIH
A brief history of liver transplantation and transplant anesthesia
Authors: Sharma Sonal , Saner Fuat H. , Bezinover Dmitri
Published: November 2022

In this review, we describe the major milestones in the development of organ transplantation with a specific focus on hepatic transplantation. For many years, the barriers preventing successful organ transplantation in humans seemed insurmountable. Although advances in surgical technique provided the technical ability to perform organ transplantation, limited understanding of immunology prevented successful organ transplantation. The breakthrough to success was the result of several significant discoveries between 1950 and 1980 involving improved surgical techniques, the development of effective preservative solutions, and the suppression of cellular immunity to prevent graft rejection. After that, technical innovations and laboratory and clinical research developed rapidly. However, these advances alone could not have led to improved transplant outcomes without parallel advances in anesthesia and critical care. With increasing organ demand, it proved necessary to expand the donor pool, which has been achieved with the use of living donors, split grafts, extended criteria organs, and organs obtained through donation after cardiac death. Given this increased access to organs and organ resources, the number of transplantations performed every year has increased dramatically. New regulatory organizations and transplant societies provide critical oversight to ensure equitable organ distribution and a high standard of care and also perform outcome analyses. Establishing dedicated transplant anesthesia teams results in improved organ transplantation outcomes and provides a foundation for developing new standards for other subspecialties in anesthesiology, critical care, and medicine overall. Through a century of discovery, the success we enjoy at the present time is the result of the work of well-organized multidisciplinary teams following standardized protocols and thereby saving thousands of lives worldwide each year. With continuing innovation, the future is bright.
Clinical impact of physician staffing transition in intensive care units: a retrospective observational study
Authors: Fujii Yosuke , Hirota Kiichi , Muranishi Kentaro , Mori Yumiko , Kambara Kei , Nishikawa Yoshitaka , Hashiguchi Mitsuko
Published: November 2022

Background

Intensivists play an essential role in improving the outcomes of critically ill patients in intensive care units (ICUs). The transition of ICU physician staffing from low-intensity ICUs (elective intensivist or no intensivist consultation) to high-intensity ICUs (mandatory intensivist consultation or a closed ICU) improves clinical outcomes. However, whether a transition from high-intensity to low-intensity ICU staffing affects ICU outcomes and quality of care remains unknown.

Methods

A retrospective observational study was conducted to examine the impact of high- versus low-intensity staffing models on all-cause mortality in a suburban secondary community hospital with 400 general beds and 8 ICU beds. The ICU was switched from a high-intensity staffing model (high-former period) to low-intensity staffing in July 2019 (low-mid period) and then back to high-intensity staffing in March 2020 (high-latter period). Patients admitted from the emergency department, general ward, or operating room after emergency surgery were enrolled in these three periods and compared, balancing the predicted mortality and covariates of the patients. The primary outcome was all-cause mortality analyzed using hazard ratios (HRs) from Cox proportional hazards regression. An interrupted time-series analysis (ITSA) was also conducted to evaluate the effects of events (level change) and time.

Results

There were 962 eligible admissions, of which 251, 213, and 498 occurred in the high-former, low-mid, and high-latter periods, respectively. In the matched group (n = 600), the all-cause mortality rate comparing the high-former period with the low-mid period showed an HR of 0.88 [95% confidence interval (CI), 0.56, 1.39;p = 0.58] and that comparing the high-latter period with the low-mid period showed an HR of 0.84 [95% CI, 0.54, 1.30;p = 0.43]. The result for comparison between the three periods wasp = 0.80. ITSA showed level changes of 4.05% [95% CI, -13.1, 21.2;p = 0.63] when ICU staffing changed from the high-former to the low-mid period and 1.35% [95% CI, -13.8, 16.5;p = 0.86] when ICU staffing changed from the low-mid to the high-latter period.

Conclusion

There was no statistically significant difference in all-cause mortality among the three ICU staffing periods. This study suggests that low-intensity ICU staffing might not worsen clinical outcomes in the ICU in a medium-sized community hospital. Multiple factors, including the presence of an intensivist, other medical staff, and practical guidelines, influence the prognosis of critically ill patients.
Emergency tracheal intubation peri-operative risk factors and prognostic impact after esophagectomy
Authors: Liu Jun-Le , Jin Jian-Wen , Lin Li-Li , Lai Zhong-Meng , Wang Jie-Bo , Su Jian-Sheng , Zhang Liang-Cheng
Published: December 2022

Background

Emergent endotracheal intubation (ETI) is a serious complication after Oesophagectomy. It is still unclear that perioperative risk factors and prognosis of these patients with ETI.

Methods

Between January 2015 and December 2018, 21 patients who received ETI after esophagectomy were enrolled (ETI group) at the department of thoracic surgery, Fujian Union hospital, China. Each study subject matched one patient who underwent the same surgery in the current era were included (control group). Patient characteristics and perioperative factors were collected.

Results

Patients with ETI were older than those without ETI (p = 0.022). The patients with history of smoking in ETI group were significantly more than those in control group (p = 0.013). The stay-time of postanesthesia care unit (PACU) in ETI group was significantly longer than that in control group (p = 0.001). The incidence of anastomotic leak or electrolyte disorder in ETI group was also higher than that in control group (p = 0.014; p = 0.002). Logistic regression analysis indicated history of smoke (HR 6.43, 95%CI 1.39–29.76, p = 0.017) and longer stay time of PACU (HR 1.04, 95%CI 1.01–1.83, p = 0.020) both were independently associated with higher risks of ETI. The 3-year overall survival (OS) rates were 47.6% in patients with ETI and 85.7% in patients without ETI (HR 4.72, 95%CI 1.31-17.00, p = 0.018). COX regression analysis indicated ETI was an independent risk factor affecting the OS.

Conclusion

The study indicated that history of smoking and longer stay-time in PACU both were independently associated with higher risks of ETI; and ETI was an independent risk factor affecting the OS of patients after esophagectomy.

Trial registration

This trial was retrospectively registered with the registration number of ChiCTR2000038549.
Serial analysis of coronary artery disease progression by artificial intelligence assisted coronary computed tomography angiography: early clinical experience
Authors: Cho Geoffrey W. , Anderson Lauren , Quesada Carlos G. , Jennings Robert S. , Min James K. , Earls James P. , Karlsberg Ronald P.
Published: November 2022

Background

Studies have shown that quantitative evaluation of coronary artery plaque on Coronary Computed Tomography Angiography (CCTA) can identify patients at risk of cardiac events. Recent demonstration of artificial intelligence (AI) assisted CCTA shows that it allows for evaluation of CAD and plaque characteristics. Based on publications to date, we are the first group to perform AI augmented CCTA serial analysis of changes in coronary plaque characteristics over 13 years. We evaluated whether AI assisted CCTA can accurately assess changes in coronary plaque progression, which has potential clinical prognostic value in CAD management.

Case presentation

51-year-old male with hypertension, hyperlipidemia and family history of myocardial infarction, underwent CCTA exams for anginal symptom evaluation and CAD assessment. 5 CCTAs were performed between 2008 and 2021. Quantitative atherosclerosis plaque characterization (APC) using an AI platform (Cleerly), was performed to assess CAD burden. Total plaque volume (TPV) change-over-time demonstrated decreasing low-density non-calcified plaque (LD-NCP) with increasing overall NCP and calcified-plaque (CP). Examination of individual segments revealed a proximal-LAD lesion with decreasing NCP over-time and increasing CP. In contrast, although the D2/D1/ramus lesions showed increasing stenosis, CP, and total plaque, there were no significant differences in NCP over-time, with stable NCP and increased CP. Remarkably, we also consistently visualized small plaques, which typically readers may interpret as false positives due to artifacts. But in this case, they reappeared each study in the same locations, generally progressing in size and demonstrating expected plaque transformation over-time.

Conclusions

We performed the first AI augmented CCTA based serial analysis of changes in coronary plaque characteristics over 13 years. We were able to consistently assess progression of plaque volumes, stenosis, and APCs with this novel methodology. We found a significant increase in TPV composed of decreasing LD-NCP, and increasing NCP and CP, with variations in the evolution of APCs between vessels. Although the significance of evolving APCs needs to be investigated, this case demonstrates AI-based CCTA analysis can serve as valuable clinical tool to accurately define unique CAD characteristics over time. Prospective trails are needed to assess whether quantification of APCs provides prognostic capabilities to improve clinical care.
Effects of left atrial function on pulmonary arterial pressure in acute myocardial infarction, hypertrophic and dilated cardiomyopathy
Authors: Kim Minjeong , Chung Hyemoon , Kim In-Soo , Park Chul Hwan , Rim Se-Joong , Choi Eui-Young
Published: November 2022

Background

To investigate the differential contribution of the left atrial (LA) function and left ventricular (LV) fibrosis to pulmonary arterial systolic pressure (PASP) in hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) and reperfused acute myocardial infarction (AMI).

Methods

Data of 370 patients with HCM (n = 133), DCM (n = 114) and reperfused AMI (n = 123) who underwent both echocardiography and cardiovascular magnetic resonance (CMR) were comprehensively reviewed. Phasic LA volumes, LA-global longitudinal strain (GLS), LA stiffness index, defined as E/e′/LA-GLS and extracellular volume fraction (ECV) of LV were measured using CMR.

Results

E/e′ was correlated with PASP in all groups; however, the predicted value was significantly attenuated after adjusting for LA volume and LA strain in HCM and DCM, but remained significant in AMI. The LA stiffness index was related to PASP in HCM (p = 0.01) and DCM (p = 0.03) independent of LA volume index and E/e′, but not in AMI. In DCM, ECV was significantly related to PASP (p < 0.001) independent of LA volume index and E/e′. When subdivided according to the linear regression between PASP and E/e′, patients in the discrepantly high PASP group had lower total emptying fraction and reservoir fraction of left atrium in HCM and DCM but not in AMI.

Conclusions

The LA function in HCM and DCM and LV fibrosis in DCM correlated with PASP independent of E/e′ and LA size, contrary to that in AMI. These results suggest the presence of LA dysfunction in non-ischemic cardiomyopathies and usefulness of ECV measurement in DCM for the comprehensive evaluation of LV diastolic function.
Candidate genes and their alternative splicing may be potential biomarkers of acute myocardial infarction: a study of mouse model
Authors: Liu Xuemei , He Pengyi , Zhang Ze , Gong Pengfei , Niu Yunxia , Bao Zhen , Yang Yuchun , Gan Lin , Muhuyati
Published: November 2022

Background

Acute myocardial infarction (AMI) is one of the leading causes of death in human being, and an effective diagnostic biomarker is still lacking. Whilst some gene association with AMI has been identified by RNA sequencing (RNA-seq), the relationship between alternative splicing and AMI is not clear.

Methods

We retrieved myocardial tissues within 24 h from mice with induced AMI and sham, and analysed the differentially expressed genes (DEGs) and differential alternative splicing genes (DASGs) by RNA-seq. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein interaction network analysis were performed on DEGs-DASGs-overlap genes. PCR was used to verify the expression levels of representative genes and alternative splicing in myocardial tissues of AMI and sham mice.

Results

1367 DEGs were identified, including 242 up-regulated and 1125 down-regulated genes, among which there were 42 DASGs. GO analysis showed that the cellular component was primarily enriched in plasma membrane, cell membrane integrity and extracellular region. The molecular function was enriched in protein binding and metal ion binding. The biological process was primarily enriched in cell adhesion, immune system process and cell differentiation. KEGG analysis showed the enrichment was mainly in JAK-STAT and PI3K-AKT signalling pathway. Postn, Fhl1, and Fn1 were low-expressed while Postn alternative splicing was high-expressed in myocardial tissue of AMI mice, which was consistent with sequencing results.

Conclusions

The pathogenesis of AMI involves differentially expressed genes and differential alternative splicing. These differentially expressed genes and their alternative splicing, especially, Fhl1, Fn1 and Postn may become new biomarkers of AMI.
Evaluating the sensitivity of jurisdictional heterogeneity and jurisdictional mixing in national level HIV prevention analyses: context of the U.S. ending the HIV epidemic plan
Authors: Tatapudi Hanisha , Gopalappa Chaitra
Published: November 2022

Background

The U.S. Ending the HIV epidemic (EHE) plan aims to reduce annual HIV incidence by 90% by 2030, by first focusing interventions on 57 regions (EHE jurisdictions) that contributed to more than 50% of annual HIV diagnoses. Mathematical models that project HIV incidence evaluate the impact of interventions and inform intervention decisions. However, current models are either national level, which do not consider jurisdictional heterogeneity, or independent jurisdiction-specific, which do not consider cross jurisdictional interactions. Data suggests that a significant proportion of persons have sexual partnerships outside their own jurisdiction. However, the sensitivity of these jurisdictional interactions on model outcomes and intervention decisions hasn’t been studied.

Methods

We developed an ordinary differential equations based compartmental model to generate national-level projections of HIV in the U.S., through dynamic simulations of 96 epidemiological sub-models representing 54 EHE and 42 non-EHE jurisdictions. A Bernoulli equation modeled HIV-transmissions using a mixing matrix to simulate sexual partnerships within and outside jurisdictions. To evaluate sensitivity of jurisdictional interactions on model outputs, we analyzed 16 scenarios, combinations of a) proportion of sexual partnerships mixing outside jurisdiction: no-mixing, low-level-mixing-within-state, high-level-mixing-within-state, or high-level-mixing-within-and-outside-state; b) jurisdictional heterogeneity in care and demographics: homogenous or heterogeneous; and c) intervention assumptions for 2019–2030: baseline or EHE-plan (diagnose, treat, and prevent).

Results

Change in incidence in mixing compared to no-mixing scenarios varied by EHE and non-EHE jurisdictions and aggregation-level. When assuming jurisdictional heterogeneity and baseline-intervention, the change in aggregated incidence ranged from − 2 to 0% for EHE and 5 to 21% for non-EHE, but within each jurisdiction it ranged from − 31 to 46% for EHE and − 18 to 109% for non-EHE. Thus, incidence estimates were sensitive to jurisdictional mixing more at the jurisdictional level. As a result, jurisdiction-specific HIV-testing intervals inferred from the model to achieve the EHE-plan were also sensitive, e.g., when no-mixing scenarios suggested testing every 1 year (or 3 years), the three mixing-levels suggested testing every 0.8 to 1.2 years, 0.6 to 1.5 years, and 0.6 to 1.5 years, respectively (or 2.6 to 3.5 years, 2 to 4.8 years, and 2.2 to 4.1 years, respectively). Similar patterns were observed when assuming jurisdictional homogeneity, however, change in incidence in mixing compared to no-mixing scenarios were high even in aggregated incidence.

Conclusions

Accounting jurisdictional mixing and heterogeneity could improve model-based analyses.
Laboratory-based and office-based Globorisk scores to predict 10-year risk of cardiovascular diseases among Iranians: results from the Fasa PERSIAN cohort
Authors: Jahangiry Leila , Dehghan Azizallah , Farjam Mojtaba , Aune Dagfinn , Rezaei Fatemeh
Published: November 2022

Background

Globorisk is a novel risk prediction model for predicting cardiovascular disease (CVD). Globorisk is a country-specific risk prediction model that determines CVD risk for all countries. This model has two versions; laboratory-based and office-based. This study aimed to determine the agreement between laboratory-based and office-based models in a large sample of the general population.

Methods

Baseline data from the Fasa cohort study was used for the current study. In total, 6810 participants ≥ 40 years without any history of cardiovascular disease or stroke were included in the study. To determine the laboratory-based risk model, factors include age, sex, current smoking status, history of diabetes, systolic blood pressure (SBP), and total cholesterol. To estimate the office-based risk model, factors were age, sex, current smoking status, SBP, and body mass index (BMI). Kappa statistics was used to distinguish the agreement between grouped scores in these two models. Additionally, correlation coefficients and scatter plots were used to determine the linear correlation between the two models.

Results

In this study 46.53% of the participants were men. The mean age (SD) of participants was 51.08 (7.88) years. Agreements between the two models were moderate and substantial in all women and all men, respectively. The agreement between the two CVD risk groups was 90.15% (kappa = 0.717) in all men, 92.94% (kappa = 0.571) among men aged < 60 years and 77.60% (kappa = 0.645) in men aged ≥ 60 years. The agreement between the two CVD risk groups was 86.68% (kappa = 0.572) among all women, 93.96% (kappa = 0.274) among women aged < 60 years and 62.46% (kappa = 0.422) among women aged ≥ 60 years. A very strong positive correlation (r = 0.94) was found between the two risk scores in all men, and it was similar among men aged < 60 years (r = 0.84) and men aged > 60 years (r = 0.94). Among all women, there was a very strong positive correlation (r = 0.87), and the strong positive correlation remained among < 60 years old (r = 0.76) and women > 60 years old (r = 0.76).

Conclusion

The Globorisk office-based model which is easier to use as it does not require blood testing can determine the risk groups in this population. The Globorisk office-based model may be used for CVD risk screening in low-middle income countries where resources are limited.
Body Mass Index, sex, non-steroidal anti-inflammatory drug medications, smoking and alcohol are differentially associated with World Health Organisation criteria and colorectal cancer risk in people with Serrated Polyposis Syndrome: an Australian case-control study
Authors: Anthony Emma , Reece Jeanette C. , Milanzi Elasma , Joo Jihoon E. , Joseland Sharelle , Clendenning Mark , Whelan Amanda , Parry Susan , Arnold Julie , Vijay Varnika , Atkinson Nathan , Hopper John L. , Win Aung K. , Jenkins Mark A. , Macrae Finlay A. , Winship Ingrid M. , Rosty Christophe , Buchanan Daniel D. ,   for the Australasian Coloretal Cancer Family Registry,   the Family Cancer Clinics of Australia,   the Genetics of Colonic Polyposis Study
Published: November 2022

Objective

The unknown aetiology of Serrated Polyposis Syndrome (SPS) impedes risk prediction and prevention. We investigated risk factors for SPS, overall and stratified by World Health Organization (WHO)2010 clinical criteria and by colorectal cancer (CRC).

Method

A retrospective case-control study involving a cross-sectional analysis from 350 unrelated individuals with SPS from the Genetics of Colonic Polyposis Study and 714 controls from the Australasian Colorectal Cancer Family Registry. Univariate and multivariate logistic regression modelling was used to determine the association between risk factors and SPS and risk factors associated with CRC in SPS.

Results

Female biological sex (odds ratio (OR) = 4.54; 95%Confidence interval (CI) = 2.77–7.45), increasing body mass index (BMI) at age 20 years (OR = 1.09; 95%CI = 1.04–1.13), hormone replacement therapy (OR = 0.44; 95%CI = 0.20.98), and increasing weekly folate intake (OR = 0.82; 95%CI = 0.75–0.90) were associated with SPS by multivariate analysis. Increasing weekly calcium intake (OR = 0.79; 95%CI = 0.64–0.97) and smoking > 10 cigarettes daily (OR = 0.45; 95%CI = 0.23–0.86) were associated with WHO criterion I only. The consumption of 1-100 g of alcohol per week (OR = 0.39; 95%CI = 0.18–0.83) was associated with WHO criterion III only. Smoking 1–5 cigarettes daily (OR = 2.35; 95%CI = 1.09–5.05), weekly non-steroidal anti-inflammatory drug (NSAIDs) intake (OR = 0.88; 95%CI = 0.78–0.99), and increased height (OR = 1.09; 95% = 1.05–1.13), were associated with SPS fulfilling both WHO criteria I and III. Moreover, weekly NSAIDs intake (OR = 0.81; 95%CI = 0.67–0.98) was associated with a reduced likelihood of CRC in SPS.

Conclusion

We identified novel risk and potential protective factors associated with SPS, some specific for certain WHO2010 criteria. Weekly use of NSAIDs may reduce the risk of CRC in people with SPS.
Characterizing gastrointestinal dysfunction after pancreatic resection: a single-center retrospective study
Authors: Bromley-Dulfano Rebecca , August Auriel T. , Li Amy Y. , Park Walter , Visser Brendan
Published: November 2022

Background

There are many well-described potential gastrointestinal (GI) side effects of pancreatic resection that can cause patients to suffer from chronic malabsorption, diarrhea, and persistent nausea. These GI symptoms can affect postoperative recovery, initiation of adjuvant therapy, and overall quality of life (QOL). The purpose of this study is to quantify the incidence of post-procedural complications and identify patients at higher risk for experiencing GI dysfunction after pancreatectomy.

Methods

A retrospective review of patients who underwent pancreatic resection at a single institution between January 2014 and December 2019 was performed. Demographics, operative factors, and postoperative gastrointestinal symptomatology and treatments were obtained by chart review. Significance tests were performed to compare GI dysfunction between patient subgroups.

Results

A total of 545 patients underwent pancreatic resection; within the cohort 451 patients (83%) underwent a pancreaticoduodenectomy (PD) and the most common indication was pancreatic adenocarcinoma. Two-thirds of patients (67%) reported gastrointestinal symptoms persisting beyond hospitalization. Only 105 patients (20%) were referred to gastroenterology for evaluation with 30 patients (5.5%) receiving a formal diagnosis. Patients who underwent PD were more likely to report GI symptoms and patients who identified as Caucasian were more likely to be referred to gastroenterology for evaluation.

Conclusions

Gastrointestinal dysfunction after pancreatic resection occurs frequently yet only a small percentage of patients are referred for formal testing and diagnosis. There also appears to be a racial difference in referral patterns. Patients would benefit if earlier attention was dedicated to the diagnosis and corresponding treatment for postoperative digestive health disorders to optimize treatment planning and QOL.
Multimorbidity among inflammatory bowel disease patients in a tertiary care center: a retrospective study
Authors: Mosli Mahmoud H. , Alsahafi Majid , Alsanea Mohammad N , Alhasani Faisal , Ahmed Mohammad , Saadah Omar
Published: November 2022

Background and objectives

Inflammatory bowel disease (IBD) is a chronic systemic inflammatory condition that debilitate the quality of life. Multimorbidity, a concept only beginning to emerge in IBD, is defined as two or more comorbidities present in the same individual. Notably, we used the term multimorbidity to refer to two or more comorbidities excluding IBD. Multimorbidity is linked to decreased quality of life, poorer disease outcomes, increased hospitalizations, healthcare costs and polypharmacy complications. We aim to estimate the prevalence of multimorbidity and to explore its effect on IBD patients.

Methods

We retrospectively reviewed all IBD patients registered in a validated web-based registry since February 2018. Data on patient demographics, comorbidities, IBD and extraintestinal complications were obtained. We analyzed the date using univariate, bivariate and multivariable analysis.

Results

Among 767 IBD patients, 54.6% had Crohn’s disease (CD), 41.9% had ulcerative colitis (UC) and 3.5% had IBD unclassified. The median age at diagnosis was 22 years (IQR: 15–29). Males compromised 50.2% of patients. According to the Montréal IBD classification, most UC patients had moderate UC (47.8%) while most CD patients had non-stricturing non-penetrating CD (49.8%). Overall, 10.3% IBD patients had multimorbidity and 23.9% had at least one comorbidity. The most common comorbidity was diabetes mellitus (4.9%) followed by essential hypertension (4%) and iron deficiency anemia (3%). Female gender (P = 0.008) and UC (P = 0.005) were more likely to have multimorbidity. Multimorbid IBD patients were more likely to develop thrombosis than non-multimorbid peers (16.7% vs. 1.6%; P < 0.001). Higher age at diagnosis (OR = 1.04, 95%CI: 1.01–1.07) and having a history of thrombosis (OR = 7.82, 95% CI: 2.67–22.92) are associated with increased risk of multimorbidity.

Conclusion

Multimorbidity is not uncommon among IBD patients, especially females diagnosed with UC. Our findings indicate that future studies are needed to explore the effects of multimorbidity on IBD patients.
Relationships between children-related factors, basic psychological need satisfaction, and multiple happiness among urban empty-nesters in China: a structural equation modeling
Authors: Yu-ting Yang , Miao Yao , Yong-wei Yang , Qiong Ye , Ting Lin
Published: December 2022

Background

Aging and empty-nesting in China are becoming more and more serious. Empty-nesters refer to older adults who were not living with their children, were living alone, or were living independently with their spouses. The mental health of empty-nesters needs timely attention. Satisfying the needs of older adults is primarily dependent on their children. Therefore, this study aimed to explore relationships between children-related factors, basic psychological need satisfaction, and multiple happiness among urban empty-nesters in China.

Methods

This study employs the Children-related Factors Questionnaire (CFQ), the Chinese Version of the Basic Psychological Need Satisfaction (BPNS) Scale, and the Multiple Happiness Questionnaire (MHQ) to explore children-related factors, basic psychological need satisfaction and multiple happiness of urban empty-nesters in Fuzhou, China. A total of 507 samples were recruited by cluster sampling.

Results

Factors that affect BPNS include physical condition, the number of children, satisfaction with children's marriage, employment and income, retirement, gender, monthly personal income, and self-care have statistical differences (P < 0.05). Factors that affect MHQ include physical condition, the number of children, satisfaction with children's marriage, employment and income, gender, monthly personal income, living status, and self-care have statistical significances (P < 0.05). Structural equation model results showed that BPNS directly impacted MHQ, and factors about children indirectly affect MHQ through BPNS. The mediating role of BPNS in the relationship between children-related factors and MHQ.

Conclusion

We should encourage our children to spend more time with the empty-nesters and communicate with them, which could help them relieve their negative emotions, satisfy their psychological needs, and improve their well-being.

Trial registration

Reg date: 20/08/2021; No. ChiCTR2100050175.
Willingness to accept herpes zoster vaccines and the influencing factors in China
Authors: Jiang Binshan , Wang Qing , Wang Zhenzhong , Xu Yunshao , Yang Tao , Yang Weizhong , Jia Mengmeng , Feng Luzhao
Published: November 2022

Background

Herpes zoster increases the burden on the elderly in an aging society. Although an effective vaccine licensed by China Food and Drug Administration in 2019 was introduced into the market in June 2020, the willingness and influencing factors of herpes zoster vaccines in Chinese adults ≥ 50-years-old during coronavirus disease-2019 pandemic are yet to be elucidated.

Methods

An online questionnaire survey was conducted using a simple random sampling method in October 2021 for viewers of the broadcast program. A binary logistic regression and multiple response analysis were conducted for herpes zoster vaccine and vaccination willingness. Pareto’s graphs were plotted to present the multiple-choice questions of influencing factors.

Results

A total of 3838 eligible participants were included in this study. Among them, 43.02% intended to be vaccinated, including 10.34% self-reported about receiving at least one shot of shingles vaccine, 30.22% declined, and 26.76% were hesitant. This population comprised a large proportion of middle-aged and older people (≥ 50-years-old) who have not experienced an episode of herpes zoster (54.98%) or are unaware of the virus (33.22%). The strongest determinants of vaccine hesitancy among older people were education background of Master’s degree or above compared to senior high or equivalent and below, personal monthly income < 3000 RMB compared to 3000–5999 RMB, and living in a rural area.

Conclusions

The willingness to get shingles vaccines can be improved further. Professional education and credible recommendation might prompt the elderly to improve their willingness and reassure them of the safety and efficacy of the vaccine. Also, accessibility and affordability should also be improved in the future.
Prevalence and correlates of substance use and associations with HIV-related outcomes among trans women in the San Francisco Bay Area
Authors: Hsiang Elaine , Gyamerah Akua , Baguso Glenda , Jain Jennifer , McFarland Willi , Wilson Erin C. , Santos Glenn-Milo
Published: November 2022

Background

Trans women face tremendous social inequities as well as disproportionate rates of HIV and substance use, yet disaggregated substance use data specific to trans women remain limited.

Methods

We conducted a secondary analysis of baseline data from the Trans*National Study (2016–2017) surveying trans women in the San Francisco Bay Area (n = 629). Multivariable logistic regression was used to analyze socio-demographic and environmental correlates of substance use, and bivariate associations between substance use and HIV-associated outcomes are presented alongside prevalence data.

Results

Over half (52.9%) reported using substances in the prior year, most frequently marijuana, methamphetamine, and crack/cocaine. Those with unmet gender-affirming health care needs, lack of insurance, or a history of experiencing racial violence, transphobic violence, adult housing instability, or extreme poverty had higher odds of substance use. Sex work and condomless anal sex were also independently associated with substance use.

Conclusions

Among this sample of trans women, substance use and substance use concurrent with sex were highly prevalent, and associated with a number of socioeconomic and health care needs. These findings corroborate the need for holistic and intersectional efforts to reduce substance use and HIV risk.