bluuebunny/crossref_metadata_2025 huggingface dataset:
A functional mechanism for a non-coding variant near AGTR2 associated with risk for preterm birth
Authors: Wang Li , Rossi Robert M. , Chen Xiaoting , Chen Jing , Runyon Jilian , Chawla Mehak , Miller Daniel , Forney Carmy , Lynch Arthur , Zhang Xuzhe , Kong Fansheng , Jacobsson Bo , Kottyan Leah C. , Weirauch Matthew T. , Zhang Ge , Muglia Louis J.
Published: July 2023

Background

Preterm birth (PTB), defined as delivery before 37 gestational weeks, imposes significant public health burdens. A recent maternal genome-wide association study of spontaneous PTB identified a noncoding locus near the angiotensin II receptor type 2 (AGTR2) gene. Genotype-Tissue Expression data revealed that alleles associated with decreased AGTR2 expression in the uterus were linked to an increased risk of PTB and shortened gestational duration. We hypothesized that a causative variant in this locus modifies AGTR2 expression by altering transcription factor (TF) binding.

Methods

To investigate this hypothesis, we performed bioinformatics analyses and functional characterizations at the implicated locus. Potential causal single nucleotide polymorphisms (SNPs) were prioritized, and allele-dependent binding of TFs was predicted. Reporter assays were employed to assess the enhancer activity of the top PTB-associated non-coding variant, rs7889204, and its impact on TF binding.

Results

Our analyses revealed that rs7889204, a top PTB-associated non-coding genetic variant is one of the strongest eQTLs for the AGTR2 gene in uterine tissue samples. We observed differential binding of CEBPB (CCAAT enhancer binding protein beta) and HOXA10 (homeobox A10) to the alleles of rs7889204. Reporter assays demonstrated decreased enhancer activity for the rs7889204 risk “C” allele.

Conclusion

Collectively, these results demonstrate that decreased AGTR2 expression caused by reduced transcription factor binding increases the risk for PTB and suggest that enhancing AGTR2 activity may be a preventative measure in reducing PTB risk.
Elevated plasma factor XI predicts cardiovascular events in patients with type 2 diabetes: a long-term observational study
Authors: Paszek Elżbieta , Polak Maciej , Bryk-Wiązania Agata Hanna , Konieczyńska Małgorzata , Undas Anetta
Published: July 2023

Background

Type 2 diabetes mellitus (T2DM) patients are at high risk of cardiovascular (CV) events. Factor XI (FXI) is associated with arterial thromboembolism, including myocardial infarction (MI), stroke, and CV mortality. The role of FXI in T2DM is unknown. We investigated whether plasma FXI is associated with CV events in T2DM patients in long-term observation.

Methods

In 133 T2DM patients (aged 66 ± 8 years, 40.6% women, median T2DM duration 5 [2–10] years) we assessed plasma FXI levels, along with fibrin clot properties, thrombin generation, and fibrinolysis proteins. A composite endpoint of MI, stroke, or CV death, as well as CV mortality alone were assessed during a median follow-up of 72 months.

Results

Plasma FXI above the 120% upper normal limit was detected in 25 (18.8%) patients and showed positive association with LDL cholesterol and thrombin activatable fibrinolysis inhibitor, but not glycated hemoglobin, inflammatory markers or thrombin generation. The composite endpoint (n = 21, 15.8%) and CV death alone (n = 16, 12%) were more common in patients with elevated FXI (hazard ratio [HR] 10.94, 95% confidence interval [CI] 4.46–26.87, p < 0.001 and HR 7.11, 95% CI 2.61–19.31, p < 0.001, respectively). On multivariable analysis, FXI remained an independent predictor of the composite endpoint and CV death, regardless of concomitant coronary artery disease.

Conclusions

To our knowledge, this study is the first to show that in T2DM patients, elevated FXI could predict major CV events, including mortality, which suggest that anti-FXI agents might be a potential novel antithrombotic option in this disease.
Exosome-mediated miR-144-3p promotes ferroptosis to inhibit osteosarcoma proliferation, migration, and invasion through regulating ZEB1
Authors: Jiang Mingyang , Jike Yiji , Liu Kaicheng , Gan Fu , Zhang Ke , Xie Mingjing , Zhang Junlei , Chen Chuanliang , Zou Xiaochong , Jiang Xiaohong , Dai Yongheng , Chen Weikui , Qiu Yue , Bo Zhandong
Published: July 2023

Background

Osteosarcoma (OS) is the most prevalent orthopedic malignancy with a dismal prognosis. The high iron absorption rate in OS cells of patients suggests that ferroptosis may be related to the progression of OS, but its potential molecular regulatory role is still unclear. Based on the ability to couple with exosomes for targeted delivery of signals, exosome-derived micro ribonucleic acids (miRNAs) can potentially serve as diagnostic biomarkers for OS.

Methods

We identified ferroptosis-related miRNAs and messenger ribonucleic acids(mRNAs) in OS using bioinformatics analysis and performed survival analysis. Then we measured miRNA expression levels through exosome microarray sequencing, and used RT-qPCR and IHC to verify the expression level of miR-144-3p and ZEB1. Stable gene expression cell lines were fabricated for in vitro experiments. Cell viability, migration and invasion were determined by CCK-8 and transwell experiment. Use the corresponding reagent kit to detect GSH/GSSG ratio, Fe2+ level, MDA level and ROS level, and measure the expression levels of GPX4, ACSL4 and xCT through RT-qPCR and WB. We also constructed nude mice model for in vivo experiments. Finally, the stability of the miRNA/mRNA axis was verified through functional rescue experiments.

Results

Low expression of miR-144-3p and high expression of ZEB1 in OS cell lines and tissues was observed. Overexpression of miR-144-3p can promote ferroptosis, reduce the survival ability of OS cells, and prevent the progression of OS. In addition, overexpression of miR-144-3p can downregulate the expression of ZEB1 in cell lines and nude mice. Knockdown of miR-144-3p has the opposite effect. The functional rescue experiment validated that miR-144-3p can regulate downstream ZEB1, and participates in the occurrence and development of OS by interfering with redox homeostasis and iron metabolism.

Conclusions

MiR-144-3p can induce the occurrence of ferroptosis by negatively regulating the expression of ZEB1, thereby inhibiting the proliferation, migration, and invasion of OS cells.

Graphical Abstract
Pancreaticoduodenectomy combined gastroduodenal collateral reconstruction and preservation due to median arcuate ligament syndrome: technical notes with two surgical cases report (with video)
Authors: Nguyen Thanh Khiem , Nguyen Ham Hoi , Luong Tuan Hiep , Chantha Pisey , Ngo Gia Khanh , Le Van Duy , Dang Kim Khue , Tran Duc Huy , Nguyen Cuong Thinh
Published: July 2023

Introduction

Pancreaticoduodenectomy in patients with CA stenosis due to median arcuate ligament often required carefully collateral pathways management to avoid hepatic ischemic complications.

Cases presentation

Case 1: A 63-year-old man was referred to our department because of jaundice with distal common bile duct tumor. Pancreaticoduodenectomy with left posterior SMA first approach and circumferential lymphadenectomy was performed. Case 2: A 48-year-old man was referred to our department because of right-upper-quadrant abdominal pain with Vater tumor. Laparoscopic pancreaticoduodenectomy with left posterior SMA first approach and circumferential lymphadenectomy was performed. Postoperatively, in all two cases, three-dimensional reconstruction images showed developed collateral pathways around the pancreatic head, and the CA was stenosis in 75% and 70% due to MAL, respectively. Intraoperatively, in all two cases, we confirmed poor blood flow in the common hepatic artery (CHA) by palpation and observation. So that in the first case, we have decided to proceed a no-touch technique of GDA segmental resection en bloc with the tumor and reconstructed with an end-to-end GDA anastomosis; in the second cases, we have decided to proceed gastroduodenal collateral preservation. When preserving these collateral pathways, we confirmed that the PHA flow remained pulsatile as an indicator that the blood flow was adequate.

Conclusion

Celiac axis stenosis was a rare but difficult-to-managed condition associated with pancreaticoduodenectomy. Collateral pathways management depends on variety of collateral pathways.
Trends in insufficient physical activity among adults in China 2010–18: a population-based study
Authors: Zhang Mei , Ma Yanan , Xie Xili , Sun Ming , Huang Zhengjing , Zhao Zhenping , Zhang Xiao , Li Chun , Gao Xingxing , Wu Jing , Wang Limin , Zhou Maigeng , Wen Deliang
Published: July 2023

Background

The global prevalence of insufficient physical activity (PA) was reported to be 27.5% in 2016, and there were stable levels of insufficient PA worldwide between 2001 and 2016. The global target of a 10% reduction in insufficient PA by 2025 will not be met if the trends remain. The relevant data for trends in China were still scarce. This study aimed to determine nationwide temporal trends in insufficient PA among adults in China from 2010 to 2018.

Methods

645 903 adults aged 18 years or older were randomly selected from four nationally representative cross-sectional surveys of the China Chronic Disease and Risk Factor Surveillance conducted in 2010, 2013, 2015, and 2018. PA was measured using the Global Physical Activity Questionnaire. Temporal changes in insufficient PA prevalence and participation of domain-specific moderate- to vigorous-intensity PA (MVPA) were analyzed using logistic regression.

Results

From 2010 to 2018, the age-adjusted prevalence of insufficient PA in China increased from 17.9% (95% confidence interval 16.3% to 19.5%) in 2010 to 22.3% (20.9% to 23.8%) in 2018 (P for trend < 0.001). By age group, with a significant increase in insufficient PA in adults aged 18–34 years (P for trend < 0.001), which rose more rapidly than in adults aged ≥ 35 years (P for interaction < 0.001). Insufficient PA has increased significantly among adults engaged in agriculture-related work, non-manual work, and other manual work (all P for trend < 0.05). And among the occupational groups, those engaged in agriculture-related work had the fastest increase (P for interaction = 0.01). The percentage of adults participating in work-related MVPA decreased from 79.6% (77.8% to 81.5%) to 66.8% (64.9% to 68.7%) along with a decrease in time spent on work-related MVPA, while percentages of adults participating in recreation-related MVPA increased from 14.2% (12.5% to 15.9%) to 17.2% (16.0% to 18.4%) (all P for trend < 0.05).

Conclusions

Among Chinese adults, an increasing trend was found in insufficient PA from 2010 to 2018, with more than one-fifth of adults failing to achieve the recommendation of adequate PA. More targeted PA promotion strategies should be developed to improve population health.
Genetic characterization of dilated cardiomyopathy patients undergoing heart transplantation in the Chinese population by whole-exome sequencing
Authors: Lian Hong , Song Shen , Chen Wenzheng , Shi Anteng , Jiang Haobin , Hu Shengshou
Published: July 2023

Background

Dilated cardiomyopathy (DCM) is one of the most frequent causes of heart failure and heart transplantation (HTx). The genetic basis of DCM among patients undergoing HTx remains to be further studied. This study aimed to characterize the genetic basis of DCM HTx in the Chinese population.

Methods

In total, 208 unrelated DCM patients who underwent HTx at Fuwai Hospital between June 2004 and June 2017 were included in this study. Whole-exome sequencing (WES) was performed for all patients. Gene burden analysis, variant classification, and genotype–phenotype correlation analysis were subsequently performed.

Results

After completing the bioinformatics analysis, gene burden analysis suggested that titin (TTN), filamin C (FLNC) and lamin A/C (LMNA) were significantly enriched with rare protein-altering variants. The frequencies of TTN and FLNC truncating variants in our cohort were 18.8% and 8.7%, respectively. Among the 165 rare variants in high evidence DCM-related genes, 27 (16.4%) and 59 (35.8%) were interpreted as pathogenic (P) and likely pathogenic (LP), respectively. In addition, 41 (47.7%) and 16 (18.6%) of these 86 P/LP variants are located in TTN and FLNC, respectively. The FLNC group contained more patients with NYHA class IV than the P/LP-negative group (FLNC, 16/18 vs. P/LP-negative, 81/123, P = 0.049).

Conclusions

Based on WES, we provided a primary genetic spectrum of DCM patients undergoing HTx in the Chinese population. TTN and FLNC harbour the most P/LP variants. FLNC truncation may lead to severe clinical symptoms in DCM patients.
Unraveling the epigenetic landscape of pulmonary arterial hypertension: implications for personalized medicine development
Authors: Dave Jaydev , Jagana Vineeta , Janostiak Radoslav , Bisserier Malik
Published: July 2023

Pulmonary arterial hypertension (PAH) is a multifactorial disease associated with the remodeling of pulmonary blood vessels. If left unaddressed, PAH can lead to right heart failure and even death. Multiple biological processes, such as smooth muscle proliferation, endothelial dysfunction, inflammation, and resistance to apoptosis, are associated with PAH. Increasing evidence suggests that epigenetic factors play an important role in PAH by regulating the chromatin structure and altering the expression of critical genes. For example, aberrant DNA methylation and histone modifications such as histone acetylation and methylation have been observed in patients with PAH and are linked to vascular remodeling and pulmonary vascular dysfunction. In this review article, we provide a comprehensive overview of the role of key epigenetic targets in PAH pathogenesis, including DNA methyltransferase (DNMT), ten-eleven translocation enzymes (TET), switch-independent 3A (SIN3A), enhancer of zeste homolog 2 (EZH2), histone deacetylase (HDAC), and bromodomain-containing protein 4 (BRD4). Finally, we discuss the potential of multi-omics integration to better understand the molecular signature and profile of PAH patients and how this approach can help identify personalized treatment approaches.
Key person-centered care domains for residential substance use disorder treatment facilities: former clients’ perspectives
Authors: Andraka-Christou Barbara , Atkins Danielle N. , Shields Morgan C. , Golan Olivia K. , Totaram Rachel , Cortelyou Kendall , Lambie Glenn W. , Mazurenko Olena
Published: July 2023

Background

While person-centered care (PCC) includes multiple domains, residential substance use disorder (SUD) treatment clients may value certain domains over others. We sought to identify the PCC domains most valued by former residential SUD treatment clients. We also sought to explore conceptual distinctions between potential theoretical PCC subdomains.

Methods

We distributed an online survey via social media to a national convenience sample of former residential SUD treatment clients. Respondents were presented with ten PCC domains in an online survey: (a) access to evidence-based care; (b) integration of care; (c) diversity/respect for other cultures; (d) individualization of care; (e) emotional support; (f) family involvement in treatment; (g) transitional services; (h) aftercare; (i) physical comfort; and (j) information provision. Respondents were asked to select up to two domains they deemed most important to their residential SUD treatment experience. We used descriptive statistics to identify response frequencies and logistic regression to predict relationships between selected domains and respondents’ race, gender, relationship status, parenting status, and housing stability.

Results

Our final sample included 435 former residential SUD treatment clients. Diversity and respect for different cultures was the most frequently selected domain (29%), followed by integration of care (26%), emotional support (26%), and individualization of care (26%). Provision of information was the least frequently chosen domain (3%). Race and ethnicity were not predictive of selecting respect for diversity. Also, parental status, relationship status and gender were not predictive of selecting family integration. Employment and housing status were not predictive of selecting transitional services.

Conclusions

While residential SUD treatment facilities should seek to implement PCC across all domains, our results suggest facilities should prioritize (a) operationalizing diversity, (b) integration of care, and (c) emotional support. Significant heterogeneity exists regarding PCC domains deemed most important to clients. PCC domains valued by clients cannot be easily predicted based on client demographics.
Effectiveness of home-based exercise interventions on pain, physical function and quality of life in individuals with knee osteoarthritis: a systematic review and meta-analysis
Authors: Si Juncheng , Sun Lili , Li Zheng , Zhu Wenning , Yin Weidong , Peng Lina
Published: July 2023

Objective

The objective of the study was to evaluate the effectiveness of home-based exercise interventions on pain, physical function and quality of life in individuals with knee osteoarthritis (KOA).

Methods

Five databases (PubMed, Embase, Cochrane Library, CINAHL, Web of Science Core Collection) were searched for relevant randomized controlled trials (RCTs) published from database inception to 2 August 2022. The Cochrane Collaboration’s standards were followed for study selection, eligibility criteria, data extraction and statistics, using the Cochrane Collaboration Risk of Bias Tool and PEDro for quality assessment. A meta-analysis and subgroup analyses, stratified by control condition and intervention duration, were conducted using RevMan 5.4. The study was reported in compliance with the PRISMA statement.

Results

A total of 12 independent RCTs with 1442 participants were included. The meta-analysis showed that the home-based exercise interventions significantly reduced pain in individuals with KOA (SMD =  − 0.32, 95% CI [− 0.41, − 0.22], p < .01) and improved physical function (SMD =  − 0.25, 95% CI [− 0.47, − 0.02], p = .03) and quality of life (SMD = 0.63, 95% CI [0.41, 0.85], p < .001). Subgroup analysis revealed that home-based exercise interventions were superior to health education and no treatment, in terms of pain and physical function, and similar to clinic-based exercise and pharmacologic treatment.

Conclusions

The effect of home-based exercise intervention is significantly better than health education and no treatment for reducing knee pain and improving physical function, and was able to achieve the effects of clinic-based exercise treatment and pharmacologic treatment. With regard to quality of life, the unsupervised home strength exercise intervention showed a significant effect compared with the health education control and combined with cognitive behavioural therapies may produce better results. Although home-based intervention provides effective treatment options for individuals with clinical treatment limitations, individual disease complications and the dosimetry of exercise need to be considered in practice. Furthermore, growing evidence supports the effectiveness of Tai Chi in the rehabilitation of KOA.
High sensitivity troponin-I threshold to predict perioperative myocardial infarction
Authors: Friedman Tom , Leviner Dror B. , Chan Veronica , Yanagawa Bobby , Orbach Ady , Natour Abd El Haleem , Weis Anastasia , Sharoni Erez , Bolotin Gil
Published: July 2023

Background

High-sensitivity Troponin I (hs-cTnI) has largely replaced conventional troponin assays in an effort to improve detection of myocardial infarction. However, the mean displacement of hs-cTnI following coronary artery bypass graft (CABG) and the optimal threshold to detect perioperative myocardial infarction (MI) is unclear. Our objective is to describe mean hs-cTnI values at 6–12 h post-CABG and to determine the highest specificity while maintaining 100% sensitivity hs-cTnI cut-off values for diagnosis of perioperative or type-5 MI.

Methods

Between 2016 and 2018, 374 patients underwent non-emergent, isolated CABG. Pre-operative and 6 h post-operative hs-cTnI values were recorded as well as ECG, echocardiographic and angiographic data.

Results

Of 374 patients, 151 (40.3%) had normal and 224 (59.7%) had elevated preoperative hs-cTnI. Patients with normal preoperative hs-cTnI had a mean 6 h hs-cTnI of 9193 ng/l or 270X the upper normal value. Eleven patients (7.3%) presented with post-operative MI with a mean 6 h hs-cTnI of 50,218 ng/l or 1477X the upper normal value. Patients with elevated preoperative hs-cTnI had a mean 6 h hs-cTnI of 9449 ng/l or 292X the upper normal value. Eleven patients (4.9%) who presented with post-operative MI had a mean 6 h hs-cTnI of 26,823 ng/l or 789X the upper normal value.

Conclusions

We suggest hs-cTnI threshold of 80-fold in patients with normal pre-operative hs-cTnI and 2.7-fold in patients with elevated pre-operative hs-cTnI. These results have important implications for perioperative care and for surgical trial reporting.
Genomic analyses of germline and somatic variation in high-grade serous ovarian cancer
Authors: Adamson A. W. , Ding Y. C. , Steele L. , Leong L. A. , Morgan R. , Wakabayashi M. T. , Han E. S. , Dellinger T. H. , Lin P. S. , Hakim A. A. , Wilczynski S. , Warden C. D. , Tao S. , Bedell V. , Cristea M. C. , Neuhausen S. L.
Published: July 2023

Background

High-grade serous ovarian cancers (HGSCs) display a high degree of complex genetic alterations. In this study, we identified germline and somatic genetic alterations in HGSC and their association with relapse-free and overall survival. Using a targeted capture of 557 genes involved in DNA damage response and PI3K/AKT/mTOR pathways, we conducted next-generation sequencing of DNA from matched blood and tumor tissue from 71 HGSC participants. In addition, we performed the OncoScan assay on tumor DNA from 61 participants to examine somatic copy number alterations (SCNA).

Results

Approximately one-third of tumors had loss-of-function (LOF) germline (18/71, 25.4%) or somatic (7/71, 9.9%) variants in the DNA homologous recombination repair pathway genes BRCA1, BRCA2, CHEK2, MRE11A, BLM, and PALB2. LOF germline variants also were identified in other Fanconi anemia genes and in MAPK and PI3K/AKT/mTOR pathway genes. Most tumors harbored somatic TP53 variants (65/71, 91.5%). Using the OncoScan assay on tumor DNA from 61 participants, we identified focal homozygous deletions in BRCA1, BRCA2, MAP2K4, PTEN, RB1, SLX4, STK11, CREBBP, and NF1. In total, 38% (27/71) of HGSC patients harbored pathogenic variants in DNA homologous recombination repair genes. For patients with multiple tissues from the primary debulking or from multiple surgeries, the somatic mutations were maintained with few newly acquired point mutations suggesting that tumor evolution was not through somatic mutations. There was a significant association of LOF variants in homologous recombination repair pathway genes and high-amplitude somatic copy number alterations. Using GISTIC analysis, we identified NOTCH3, ZNF536, and PIK3R2 in these regions that were significantly associated with an increase in cancer recurrence and a reduction in overall survival.

Conclusions

From 71 patients with HGCS, we performed targeted germline and tumor sequencing and provided a comprehensive analysis of these 557 genes. We identified germline and somatic genetic alterations including somatic copy number alterations and analyzed their associations with relapse-free and overall survival. This single-site long-term follow-up study provides additional information on genetic alterations related to occurrence and outcome of HGSC. Our findings suggest that targeted treatments based on both variant and SCNA profile potentially could improve relapse-free and overall survival.
Hybridization of the effective pharmacophores for treatment of epilepsy: design, synthesis, in vivo anticonvulsant activity, and in silico studies of phenoxyphenyl-1,3,4-oxadiazole-thio-N-phenylacetamid hybrids
Authors: Fakhrioliaei Azadeh , Abedinifar Fahimeh , Salehi Darjani Pedram , Mohammadi-Khanaposhtani Maryam , Larijani Bagher , Ahangar Nematollah , Mahdavi Mohammad
Published: July 2023

Background

Epilepsy is a common neurological disorder. The available drugs for this disease only control convulsions in nearly 70% of patients, while bearing many side effects. In this study, a new series of phenoxyphenyl-1,3,4-oxadiazole-thio-N-phenylacetamid hybrids 8a-m was designed, synthesized, and evaluated as potent anticonvulsant agents.

Methods

Phenoxyphenyl-1,3,4-oxadiazole-thio-N-phenylacetamid derivatives 8a-m were synthesized with well-known chemical reactions and anticonvulsant activity of them was determined by pentylenetetrazole (PTZ) and maximal electroshock (MES) induced seizures in mice. Phenoxyphenyl-1,3,4-oxadiazole-thio-N-phenylacetamid scaffold has the necessary pharmacophores to be a benzodiazepine (BZD) receptor agonist, thus, the most potent anticonvulsant compounds were assayed in vivo and in silico as BZD receptor agonist. Furthermore, in vivo neurotoxicity evaluation and in silico physicochemical, pharmacokinetic, and toxicity study on the most potent compounds were also performed.

Results

Obtained results demonstrated that two compounds among the title new compounds have anticonvulsant activity in PTZ test while all of the new compounds are active in the MES test. The best anticonvulsant activities were obtained with nitro derivatives 8k and 8L. In vivo evaluation of flumazenil effect (a BZD receptor antagonist) on anticonvulsant activity of compound 8k confirmed that this compound is a BZD receptor agonist. The most potent compounds 8k and 8L interacted with the important residues of BZD-binding site of GABAA receptor. Furthermore, neurotoxicity of the latter compounds was lower than positive control diazepam.

Conclusion

According to these results, our designed scaffold can be a valuable lead structure for further structural developments and assessments to obtain a new potent anticonvulsant agent.
Syndecan-4 as a genetic determinant of the metabolic syndrome
Authors: Crocco Paolina , Vecchie Denise , Gopalkrishna Sreejit , Dato Serena , Passarino Giuseppe , Young Martin E. , Nagareddy Prabhakara R. , Rose Giuseppina , De Luca Maria
Published: July 2023

Background

Syndecan-4 (SDC4) is a member of the heparan sulfate proteoglycan family of cell-surface receptors. We and others previously reported that variation in the SDC4 gene was associated with several components of the metabolic syndrome, including intra-abdominal fat, fasting glucose and triglyceride levels, and hypertension, in human cohorts. Additionally, we demonstrated that high fat diet (HFD)-induced obese female mice with a Sdc4 genetic deletion had higher visceral adiposity and a worse metabolic profile than control mice. Here, we aimed to first investigate whether the mouse Sdc4 null mutation impacts metabolic phenotypes in a sex- and diet-dependent manner. We then tested whether SDC4 polymorphisms are related to the metabolic syndrome (MetS) in humans.

Methods

For the mouse experiment, Sdc4-deficient (Sdc4−/−) and wild-type (WT) mice were treated with 14-weeks of low-fat diet (LFD). Body composition, energy balance, and selected metabolic phenotypes were assessed. For the human genetic study, we used logistic regression models to test 11 SDC4 SNPs for association with the MetS and its components in a cohort of 274 (113 with MetS) elderly subjects from southern Italy.

Results

Following the dietary intervention in mice, we observed that the effects of the Sdc4 null mutation on several phenotypes were different from those previously reported in the mice kept on an HFD. Nonetheless, LFD-fed female Sdc4−/− mice, but not males, displayed higher levels of triglycerides and lower insulin sensitivity at fasting than WT mice, as seen earlier in the HFD conditions. In the parallel human study, we found that carriers of SDC4 rs2228384 allele C and rs2072785 allele T had reduced risk of MetS. The opposite was true for carriers of the SDC4 rs1981429 allele G. Additionally, the SNPs were found related to fasting triglyceride levels and triglyceride glucose (TyG) index, a reliable indicator of insulin resistance, with sex-stratified analysis detecting the association of rs1981429 with these phenotypes only in females.

Conclusions

Altogether, our results suggest that SDC4 is an evolutionary conserved genetic determinant of MetS and that its genetic variation is associated with fasting triglyceride levels in a female-specific manner.
The metabolic score for insulin resistance in the prediction of major adverse cardiovascular events in patients after coronary artery bypass surgery: a multicenter retrospective cohort study
Authors: Zhang Shuai , Wu Zhenguo , Zhuang Yifan , Sun Xiangfei , Wang Juan , Chen Sha , Guo Dachuan , Xu Panpan , Zhang Cheng , Yang Jianmin
Published: July 2023

Background

The metabolic score for insulin resistance (METS-IR) is a simple, convenient, and reliable marker for resistance insulin (IR), which has been regarded as a predictor of cardiovascular disease (CVD) and cardiovascular events. However, few studies examined the relationship between METS-IR and prognosis after coronary artery bypass graft (CABG). This study aimed to investigate the potential value of METS-IR as a prognostic indicator for the major adverse cardiovascular events (MACE) in patients after CABG.

Method

1100 CABG patients were enrolled in the study, including 760 men (69.1%) and 340 women (30.9%). The METS-IR was calculated as Ln [(2 × FPG (mg/dL) + fasting TG (mg/dL)] × BMI (kg/m2)/Ln [HDL-C (mg/dL)]. The primary endpoint of this study was the occurrence of major adverse cardiovascular events (MACE), including a composite of all-cause death, non-fatal myocardial infarction (MI), coronary artery revascularization, and stroke.

Result

The following-up time of this study was 49–101 months (median, 70 months; interquartile range, 62–78 months). During the follow-up period, there were 243 MACEs (22.1%). The probability of cumulative incidence of MACE increased incrementally across the quartiles of METS-IR (log-rank test, p < 0.001). Multivariate Cox regression analysis demonstrated a hazard ratio (95% CI) of 1.97 (1.36–2.86) for MACE in quartile 4 compared with participants in quartile 1. The addition of the METS-IR to the model with fully adjusting variables significantly improved its predictive value [C-statistic increased from 0.702 to 0.720, p < 0.001, continuous net reclassification improvement (NRI) = 0.305, < 0.001, integrated discrimination improvement (IDI) = 0.021, p < 0.001].

Conclusion

METS-IR is an independent and favorable risk factor for predicting the occurrence of MACE and can be used as a simple and reliable indicator that can be used for risk stratification and early intervention in patients after CABG.
The mirror like expression of genes involved in the FOXO signaling pathway could be effective in the pathogenesis of human lymphotropic virus type 1 (HTLV-1) through disruption of the downstream pathways
Authors: Yaslianifard Sahar , Movahedi Monireh , Yaslianifard Somayeh , Mozhgani Sayed‑Hamidreza
Published: July 2023

Objectives

Human lymphotropic virus type 1 (HTLV-1) is the cause of two major diseases, ATLL and HAM/TSP in a percentage of carriers. Despite progress in understanding the pathogenesis of these two diseases, the exact pathogenesis mechanism is still not well understood. High-throughput technologies have revolutionized medical research. This study aims to investigate the mechanism of pathogenesis of these two diseases using the results of high-throughput analysis of microarray datasets.

Results

A total of 100 differentially expressed genes were found between ATLL and HAM/TSP. After constructing protein-protein network and further analyzing, proteins including ATM, CD8, CXCR4, PIK3R1 and CD2 were found as the hub ones between ATLL and HAM/TSP. Finding the modules of the subnetwork revealed the enrichment of two common pathways including FOXO signaling pathway and Cell cycle with two common genes including ATM and CDKN2D. Unlike ATLL, ATM gene had higher expressions in HAM/TSP patients. The expression of CDKN2D was increased in ATLL patients. The results of this study could be helpful for understanding the pathogenic mechanism of these two diseases in the same signaling pathways.
Association of immune cell composition with the risk factors and incidence of acute coronary syndrome
Authors: Shi Xian , Qu Minghan , Jiang Yi , Zhu Ziwei , Dai Chengguqiu , Jiang Minghui , Ding Lin , Yan Yu , Wang Chaolong , Zhang Xiaomin , Cheng Shanshan , Hao Xingjie
Published: July 2023

Background

Although immune cells are involved in acute coronary syndrome (ACS), few studies have explored the association of incident ACS with the relative immune cell proportions. We aimed to investigate the association of immune cell proportions with the incidence and risk factors of ACS in the Dongfeng–Tongji cohort.

Methods

We conducted the analyses with 38,295 subjects from the first follow-up of the Dongfeng–Tongji cohort, including DNA methylation profiles for 1570 individuals. The proportions of immune cell types were observed from routine blood tests or estimated from DNA methylation profiles. For both observed and estimated immune cell proportions, we tested their associations with risk factors of ACS by multivariable linear regression models. In addition, the association of each immune cell proportion with incident ACS was assessed by the Cox regression model and conditional logistic regression model, respectively, adjusting for the risk factors of ACS.

Findings

The proportions of lymphocytes, monocytes, and neutrophils showed strong associations with sex, followed by diabetes. Moreover, sex and current smoking were the two factors with strongest association with the proportions of lymphocyte subtypes. The hazard ratio (HR) and 95% confidence interval (CI) of incident ACS per standard deviation (SD) increase in proportions of lymphocytes and neutrophils were 0.91 (0.85–0.96) and 1.10 (1.03–1.16), respectively. Furthermore, the OR (95% CI) of incident ACS per SD increase in proportions of NK cells, CD4+ T cells, and B cells were 0.88 (0.78–0.99), 1.15 (1.03–1.30), and 1.13 (1.00–1.26), respectively.

Interpretation

The proportions of immune cells were associated with several risk factors of ACS, including sex, diabetes, and current smoking. In addition, proportion of neutrophils had a risk effect, while proportion of lymphocytes had a protective effect on the incidence of ACS. The protective effect of lymphocytes was probably driven by NK cells.
Duck plague virus tegument protein vp22 plays a key role in the secondary envelopment and cell-to-cell spread
Authors: Wu Liping , Wang Mingshu , Cheng Anchun , Tian Bin , Huang Juan , Wu Ying , Yang Qiao , Ou Xumin , Sun Di , Zhang Shaqiu , Zhao Xinxin , Gao Qun , He Yu , Zhu Dekang , Chen Shun , Liu Mafeng , Jia Renyong
Published: July 2023

Duck plague virus (DPV) is one of the major infectious and fatal diseases of geese, ducks, and other wild waterfowl. The DPV UL49 gene product VP22 is one of the most abundant tegument proteins. However, the role of the DPV VP22 is enigmatic to be clarified. In this study, we found deletion of the UL49 gene resulted in reduced viral growth curve and smaller plaque size in duck embryo fibroblast (DEF) cells, confirming that DPV VP22 is required for efficient viral growth in vitro. In addition, deletion of the UL49 gene inhibited the secondary envelopment of the virus, the release of viral particles, and the spread of viruses between cells. Our study signified the importance of VP22 for DPV secondary envelopment, release, cell-to-cell spread, and accumulation of viral RNA. These findings provide a basis for further study of the function of VP22 in DPV or other herpesviruses.
A study of cadmium yellow paints from Joan Miró’s paintings and studio materials preserved at the Fundació Miró Mallorca
Authors: Gomez Lobon Mar , Ghirardello Marta , Juncosa Darder Enric , Palomino Cabello Carlos , Bauza Marta , Cotte Marine , Burnstock Aviva , Nevin Austin , Amato Silvia Rita , Izzo Francesca Caterina , Comelli Daniela
Published: July 2023

The deterioration of cadmium yellow paints in artworks by Joan Miró (1893–1983) and in painting materials from his studios in Mallorca (Spain) was investigated. Analysis of samples from Miró’s paintings and from paint tubes and palettes showed that degraded paints are composed of poorly crystalline cadmium sulfide/zinc cadmium sulfide (CdS/Cd1−xZnxS) with a low percentage of zinc, in an oil binding medium. Cadmium sulfates were identified as the main deterioration products, forming superficial white crusts detected using SR µXANES and µXRD techniques. Time-resolved photoluminescence measurements demonstrated that highly degraded samples display a pink/orange emission from the paint surface with a microsecond lifetime, a phenomenon observed in other degraded cadmium yellow paints. In agreement with recent studies on altered cadmium paints, these results suggest that the stability of the paint is related to its manufacturing method, which affects the degree of crystallinity of the resulting pigment. This, together with the environmental conditions in which artworks have been exposed, have induced the degradation of yellow paints in Miró’s artworks. It was finally noted that the paints exhibiting alteration in the analysed Miró artworks have a chemical composition that is very similar to the tube paint ‘Cadmium Yellow Lemon No. 1’ produced by Lucien Lefebvre-Foinet. Indeed, paint tubes from this brand were found in the studio, linking the use of this product with Miro’s degraded artworks.
Impact of multimodal intraoperative neurophysiological monitoring of the spinal cord during spine and spinal cord surgeries
Authors: Elwakil Walaa , Imam Mohamed , Hassan Marwa , Elsaadany Waleed , Gaber Omnia
Published: July 2023

Background

There is growing evidence of the valuable role of multimodal intraoperative neurophysiological monitoring (IONM) during spine and spinal cord surgeries, as it provides an opportunity to recognize functional changes of the neural elements, usually in the reversible stage, during complex surgical manipulations. Therefore, it may reduce the risk of postoperative neurological dysfunction and improve functional outcomes. The aim of the current study was to evaluate the efficacy of multimodal IONM for preventing and predicting iatrogenic neurological dysfunction during spinal cord and spine surgeries.

Results

Significant alerts had occurred in 9 out of 24 patients; however, all the changes were reversible and did not contribute to postoperative clinical deterioration. Only one case got worsened in the early postoperative follow-up period, with stable intraoperative monitoring.

Conclusion

Intraoperative monitoring is a valuable tool in spine and spinal cord surgeries. Combined transcranial motor-evoked potential (TcMEP), somatosensory-evoked potential (SSEP), and spontaneous electromyography (EMG) monitoring may prevent permanent motor deficit and enhance the postoperative outcomes.
Totally endoscopic trans-mitral removal of a left ventricular apical thrombus through right thoracotomy in a patient with subacute anterior myocardial infarction: a case report
Authors: Oda Ryoma , Oishi Atsumi , Kamikawa Yuki , Hata Hiroaki , Kajimoto Kan
Published: July 2023

Background

Left ventricular thrombosis confers a life-threatening risk of systemic embolism; therefore, it requires prompt intervention. Although anticoagulation is the primary treatment, surgery is indicated in instances of large or/and mobile thrombus or when there is potential for recovery of ventricular contraction. However, standard left ventriculoplasty with thrombectomy carries risks of cardiac dysfunction due to left ventriculotomy.

Case presentation

A 70-year-old man developed chest pain and vomiting 3 weeks before presenting to our hospital. A chest radiograph showed substantial cardiomegaly and mild pulmonary congestion; N-terminal pro-brain natriuretic peptide (5698 ng/L) was substantially increased, and troponin T (56 ng/L) levels were slightly above reference values. Transthoracic echocardiography showed akinesis of the anteroseptal and apical segments with an ejection fraction reduced to approximately 20%. We diagnosed subacute myocardial infarction and initiated pharmacotherapy. On hospital day 7, coronary angiography revealed a left anterior descending artery lesion with 99% stenosis; percutaneous coronary intervention was successfully performed the next day. That same day, transthoracic echocardiography revealed a large mobile left ventricular apical thrombus without any left ventricular aneurysm, and heparin therapy was initiated. On hospital day 10, three-dimensional computed tomography confirmed the location of an apical thrombus, and we planned a fourth intercostal approach. A thrombectomy was performed on hospital day 11 using an endoscopic trans-mitral approach with a right thoracotomy to avoid a left ventriculotomy. The patient was discharged from intensive care on postoperative day 2 under heparin and warfarin therapy. The subsequent postoperative course was uneventful, and he was discharged on postoperative day 14 with a vitamin K antagonist. At the 6-month follow-up, there was no recurrence of thrombus in the left ventricle and Ejection Fraction had improved to 46%.

Conclusions

Totally endoscopic thrombectomy via a trans-mitral approach through right thoracotomy was effective for a left ventricular thrombus. When concomitant coronary artery bypass grafting or left ventriculoplasty are not required, this procedure can be an effective option.
Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Systemic Cancer Therapy: ASCO Guideline Update
Authors: Dale William , Klepin Heidi D. , Williams Grant R. , Alibhai Shabbir M.H. , Bergerot Cristiane , Brintzenhofeszoc Karlynn , Hopkins Judith O. , Jhawer Minaxi P. , Katheria Vani , Loh Kah Poh , Lowenstein Lisa M. , McKoy June M. , Noronha Vanita , Phillips Tanyanika , Rosko Ashley E. , Ruegg Tracy , Schiaffino Melody K. , Simmons John F. , Subbiah Ishwaria , Tew William P. , Webb Tracy L. , Whitehead Mary , Somerfield Mark R. , Mohile Supriya G.
Published: July 2023

PURPOSE

To update the ASCO guideline (2018) on the practical assessment and management of age-associated vulnerabilities in older patients undergoing systemic cancer therapy.

METHODS

An Expert Panel conducted a systematic review to identify relevant randomized clinical trials (RCTs), systematic reviews, and meta-analyses from January 2016 to December 2022.

RESULTS

A total of 26 publications met eligibility criteria and form the evidentiary basis for the update.

RECOMMENDATIONS

The Expert Panel reiterates its overarching recommendation from the prior guideline that geriatric assessment (GA), including all essential domains, should be used to identify vulnerabilities or impairments that are not routinely captured in oncology assessments for all patients over 65 years old with cancer. Based on recently published RCTs demonstrating significantly improved clinical outcomes, all older adults with cancer (65+ years old) receiving systemic therapy with GA-identified deficits should have GA-guided management (GAM) included in their care plan. GAM includes using GA findings to inform cancer treatment decision-making as well as to address impairments through appropriate interventions, counseling, and/or referrals. A GA should include high priority aging-related domains known to be associated with outcomes in older adults with cancer: physical and cognitive function, emotional health, comorbid conditions, polypharmacy, nutrition, and social support. Clinical adaptation of the GA based on patient population, resources, and time is appropriate. The Panel recommends the Practical Geriatric Assessment as one option for this purpose ( https://old-prod.asco.org/sites/new-www.asco.org/files/content-files/practice-patients/documents/2023-PGA-Final.pdf ; https://youtu.be/jnaQIjOz2Dw ; https://youtu.be/nZXtwaGh0Z0 ). Additional information is available at www.asco.org/supportive-care-guidelines .
Crosstalk Between the Neuroendocrine System and Bone Homeostasis
Authors: Zhao Yuhu , Peng Xiaole , Wang Qing , Zhang Zhiyu , Wang Liangliang , Xu Yaozeng , Yang Huilin , Bai Jiaxiang , Geng Dechun
Published: July 2023

The homeostasis of bone microenvironment is the foundation of bone health and comprises 2 concerted events: bone formation by osteoblasts and bone resorption by osteoclasts. In the early 21st century, leptin, an adipocytes-derived hormone, was found to affect bone homeostasis through hypothalamic relay and the sympathetic nervous system, involving neurotransmitters like serotonin and norepinephrine. This discovery has provided a new perspective regarding the synergistic effects of endocrine and nervous systems on skeletal homeostasis. Since then, more studies have been conducted, gradually uncovering the complex neuroendocrine regulation underlying bone homeostasis. Intriguingly, bone is also considered as an endocrine organ that can produce regulatory factors that in turn exert effects on neuroendocrine activities. After decades of exploration into bone regulation mechanisms, separate bioactive factors have been extensively investigated, whereas few studies have systematically shown a global view of bone homeostasis regulation. Therefore, we summarized the previously studied regulatory patterns from the nervous system and endocrine system to bone. This review will provide readers with a panoramic view of the intimate relationship between the neuroendocrine system and bone, compensating for the current understanding of the regulation patterns of bone homeostasis, and probably developing new therapeutic strategies for its related disorders.
From mechanism to ecosystem: building bridges between ecoimmunology, psychoneuroimmunology and disease ecology
Authors: French Susannah S. , Demas Gregory E. , Lopes Patricia C.
Published: July 2023

Historically, the fields of ecoimmunology, psychoneuroimmunology and disease ecology have taken complementary yet disparate theoretical and experimental approaches, despite sharing critical common themes. Researchers in these areas have largely worked independently of one another to understand mechanistic immunological responses, organismal level immune performance, behavioral changes, and host and parasite/disease population dynamics, with few bridges across disciplines. Although efforts to strengthen and expand these bridges have been called for (and occasionally heeded) over the last decade, more integrative studies are only now beginning to emerge, with critical gaps remaining. Here, we briefly discuss the origins of these key fields, and their current state of integration, while highlighting several critical directions that we suggest will strengthen their connections into the future. Specifically, we highlight three key research areas that provide collaborative opportunities for integrative investigation across multiple levels of biological organization, from mechanisms to ecosystems: (1) parental effects of immunity, (2) microbiome and immune function and (3) sickness behaviors. By building new bridges among these fields, and strengthening existing ones, a truly integrative approach to understanding the role of host immunity on individual and community fitness is within our grasp.