bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosomal circ-ADRM1 promotes lung adenocarcinoma progression and induces macrophage M2 polarization through regulating MMP14 mRNA and protein
Authors: Qian Jun , Li Jie , Ma Haitao , Ji Wanyu 
Published: December 2022

Objective
Lung adenocarcinoma (LUAD) is one of the frequent subtypes of lung cancer, featuring high rates of incidence and mortality. Matrix metalloproteinase 14 (MMP14) is known as a regulator in multiple cancers, whereas its upstream molecular mechanism remains to be investigated. This study aims to reveal the upstream molecular mechanism of MMP14 in LUSC progression.

Methods
Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were conducted to examine the levels of MMP14 mRNA and protein in LUAD cells, respectively. Cell counting kit-8 (CCK-8), transwell assay and wound healing assay were implemented to unveil LUAD cell proliferation, migration and invasion after indicated transfections. Flow cytometry analysis was applied to evaluate macrophage polarization. Mechanism experiments such as western blot, co-immunoprecipitation (Co-IP), RNA pulldown assay, luciferase reporter assay and RNA-binding protein immunoprecipitation (RIP) assay were used to explore relevant molecular mechanisms.

Results
MMP14 facilitated LUAD cell proliferation, invasion and migration. MMP14 is the target gene of miR-1287-5p. Circ-ADRM1 upregulates MMP14 expression through sponging miR-1287-5p. Circ-ADRM1 recruits USP12 to impede the ubiquitination of MMP14 protein, thereby enhancing the stability of MMP14 protein. LUAD-derived exosomes induced macrophage M2 polarization by delivering circ-ADRM1.

Conclusions
Circ-ADRM1 promotes LUAD cell proliferation, invasion and migration through upregulating MMP14. Additionally, circ-ADRM1 induces macrophage M2 polarization in an exosome-dependent manner.
Are Detailed Behavioral, Psychosocial, and Environmental Variables Necessary to Control for Confounding in Pregnancy Weight Gain Research?
Authors: Bodnar Lisa M , Hutcheon Jennifer A 
Published: December 2022

Background:
Associations between pregnancy weight gain and adverse outcomes may be spurious owing to confounding by factors not typically measured in cohort studies. We determined the extent to which the addition of detailed behavioral, psychosocial, and environmental measurements to commonly available covariates improved control of confounding.

Methods:
We used data from a prospective US pregnancy cohort study (2010–2013, n = 8978). We calculated two propensity scores for low and high pregnancy weight gain (vs. adequate gain) using 11 standard confounders (e.g., age and education). We examined the balance of characteristics between weight gain groups before and after propensity score matching. We used negative binomial regression to estimate the association between weight gain and small- and large-for-gestational-age birth, preterm birth, and unplanned cesarean delivery, controlling for propensity score. To this model, we then added 17 detailed behavioral, psychosocial, and environmental measurements (“fully adjusted”). We calculated the risk ratio owing to confounding as the ratio of the standard confounder-adjusted risk ratio to the fully adjusted risk ratio.

Results:
There were minimal imbalances between weight gain groups in detailed measures after matching for a propensity score of standard covariates. Accordingly, the inclusion of detailed covariates had minimal impact on estimated associations between low or high pregnancy weight gain and adverse pregnancy outcomes: risk ratios owing to confounding were null for all outcomes (e.g., 1.1 [95% CI = 1.0, 1.1] for low weight gain and preterm birth).

Conclusions:
Adjustment for detailed behavioral, psychosocial, and environmental measurements had minimal impact on estimated associations between pregnancy weight gain and adverse perinatal outcomes.
Relationship of 24-h ambulatory blood pressure variability with micro and macrovascular parameters and hypertension status
Authors: Papadopoulou Stella-Lida , Gkaliagkousi Eugenia , Dipla Konstantina , Koletsos Nikolaos , Zafeiridis Andreas , Zabulis Xenophon , Lazaridis Antonios , Stergiou George , Douma Stella , Triantafyllou Areti 
Published: December 2022

Objectives:
Increased blood pressure variability (BPV) has been associated with an increased risk of subclinical organ damage and cardiovascular events, independently of elevated average BP values. We aimed to investigate the association of BPV indices with micro- and macrovascular parameters, some of them not previously studied.

Methods:
We evaluated 344 individuals (233 never-treated/newly diagnosed hypertensive and 111 normotensive individuals). BPV was assessed using average real variability (ARV) during 24-h, daytime and night-time ambulatory blood pressure monitoring, and systolic weighted standard deviation (wSD). Retinal microvascular diameter was assessed by nonmydriatic retinal photography. Arterial stiffness was assessed by pulse wave velocity (PWV) and aortic augmentation index (AIx); subendocardial variability ratio (SEVR) was used as an index of myocardial perfusion. Carotid intima-media thickness (cIMT) was measured by ultrasound. Data were analyzed using multiple regression analysis.

Results:
After adjusting for potential confounders, PWV and cIMT were independently associated with ARV components in the total sample (P < 0.023 and P < 0.014, respectively). Within hypertensives only PWV and cIMT were independently associated with ARV components (P < 0.002 for PWV and P < 0.003 for cIMT). In contrast, within normotensives, only retinal parameters and AIx were associated with ARV components (P < 0.017 and P = 0.013, respectively). None of the univariate correlations between vascular parameters and wSD remained significant after adjustment for potential confounders.

Conclusion:
Short-term BPV as assessed by ARV is independently associated with macrovascular parameters in untreated hypertensive patients, and with microvascular parameters in normotensive individuals.
Effects of minimally and ultra-processed foods on blood pressure in Brazilian adults: a two-year follow up of the CUME Project
Authors: Rezende-Alves Katiusse , Hermsdorff Helen Hermana Miranda , Miranda Aline Elizabeth da Silva , Bressan Josefina , Mendonça Raquel de Deus , de Oliveira Fernando Luiz Pereira , Pimenta Adriano Marçal 
Published: December 2022

Aim:
To assess the association of food consumption according to degree of processing with changes in systolic (SBP) and diastolic (DBP) blood pressure in adult participants of a Brazilian cohort.

Methods:
Longitudinal study with 2496 adult participants of the Cohort of Universities of Minas Gerais (CUME Project). Food consumption was categorized by food groups according to degree of processing following the NOVA grading system: unprocessed/minimally processed foods/culinary ingredients (U/MPF&CI), processed foods (PFs) and ultra-processed foods (UPFs). unprocessed/minimally processed foods/culinary ingredients (U/MPF&CI), processed foods (PFs) and ultra-processed foods (UPFs). Changes in SBP and DBP were categorized (decreased, maintained, increased). Independent associations between exposure and outcomes were verified using multiple generalized ordered logistic models adjusted for potential confounders.

Results:
After a two-year follow-up, the consumption of U/MPF&CI (% daily caloric intake) reduced the chance of increasing DBP (P for trend = 0.014), with a more evident effect among participants within the 5th quintile of this food group (odds ratio (OR) = 0.55; 95% confidence interval (CI): 0.34–0.97]. On the other hand, the consumption of UPFs (% daily caloric intake) raised the chance of increasing DBP (P for trend = 0.005) and was more evident among participants within the quintiles of higher consumption (4th quintile – OR = 1.97; 95% CI: 1.25–3.10; 5th quintile – OR = 1.79; 95% CI = 1.12–2.86). No associations were found between food consumption according to degree of processing and changes in SBP.

Conclusion:
Higher consumption of U/MPF&CI and UPFs were independently associated to lower and greater chances of increased DBP in adult participants from CUME Project.
Association of sodium intake with adverse left atrial function and left atrioventricular coupling in Chinese
Authors: Yin Lili , Mei Jiajie , Dong Jianli , Qu Xiaofeng , Jiang Yinong 
Published: December 2022

Objectives:
High sodium intake is strongly associated with hypertension and obesity. This study aims to investigate the relationship between 24-h urinary sodium (a surrogate measure of sodium intake), ambulatory blood pressure parameters, left atrial function, and left atrioventricular coupling. Further, we intend to examine whether blood pressure and BMI might be mediators of the relationship between 24-h urinary sodium and subclinical cardiac function.

Methods:
Our study had 398 participants, all of whom were subjected to 24-h urine collection, 24-h ambulatory blood pressure measurement, and cardiac magnetic resonance imaging.

Results:
The average age of the participants was 55.70 ± 11.30 years old. The mean urinary sodium of the participants was 172.01 ± 80.24 mmol/24 h. After adjusting for age, sex, history of diabetes, smoking status, alcohol consumption, and use of diuretics, 24-h urinary sodium was correlated with multiple ambulatory blood pressure parameters, BMI, left atrial function, and the left atrioventricular coupling index (LACI) (P < 0.05). Mediation analysis showed that BMI explained 16% of the indirect effect of 24-h urinary sodium and left atrial function and 30% of the indirect effect of LACI. Independent of the mediator, 24-h urinary sodium had a significant direct effect on left atrial function and left atrioventricular coupling.

Conclusions:
Higher 24-h urinary sodium was associated with a greater BMI as well as poor left atrial function and left atrioventricular coupling, and the BMI mediated the relationship between 24-h urinary sodium and subclinical left cardiac function. Furthermore, and more importantly, 24-h urinary sodium may have directly affected the left atrial function and left atrioventricular coupling independent of intermediary factors.
A Study on the Correlation of Big 5 Personality Traits in Asians With Facial Contour Surgery
Authors: Shi Jiadong , Ma Liping , Xu Haisong , Zhou Yanchun 
Published: December 2022

Purpose:
The purpose of this study is to explore the present situation and related factors of big 5 personality in Asian patients with facial contour surgery and to provide experience for clinical individualized medical care.

Methods:
Total 235 patients with facial contour surgery were selected in this study. The Neo Five-factor Inventory was used to investigate them.

Results:
The scores of conscientiousness and openness in the Neo Five-factor Inventory were higher than others, whereas neuroticism score was lowest in patients with facial contour surgery. The scores of extroversion and agreeableness were in the middle level. Among the big 5 personality the age, educational background, self-rated personality, the only child in a family and other cosmetic surgery history had significant differences in patients.

Conclusions:
Patients with facial contour surgery for different sex, different marital status, different body mass index, there is no significant difference in the big 5 personality through this study. However, older patients had higher score for conscientiousness, patients with higher educational background had higher scores in openness and patients with introverted personality had higher neuroticism score. The authors should take individualized personality traits during perioperative care to help the patients to establish a correct and healthy esthetic concept, as well as postoperative body image concept, to build their self-confidence and social competitiveness.
The relationship between blastocyst morphology and the sex ratio of singleton births in single blastocyst transfer cycles: A retrospective cohort study
Authors: Hu Jijun , Guan Yichun , Yang Rujing , Sun Lijun , Lou Hua , Wang Xingling 
Published: December 2022

AbstractBackgroundTo study the relationship between blastocyst morphology and the sex ratio of singleton births in single blastocyst transfer cylces.MethodsThis retrospective cohort study included women who underwentin vitrofertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) from January 2017 to December 2019 and obtained a single live baby following a single blastocyst transfer. The sex ratio which influenced by many possible factors were studied. Age-stratified analysis was performed for the maternal and paternal groups younger and older than 35 years. The 3108 cycles included here were grouped by sex at birth (male: 1777 cycles and female: 1331 cycles). Blastocysts were conceived via 2834 IVF and 274 ICSI treatments, and were used for 1054 fresh ET cycles and 2054 frozen-thawed embryo transfer (FET) cycles.ResultsSex ratio among singleton of poor blastocyst decreased significantly compared to those of good blastocyst (51.5% vs 60%,P<0.001). The results of multivariate logistic analysis showed that high-quality blastocysts had a 151% higher probability of being male singleton than poor-quality blastocysts (P<0.001). Further stratified analysis shows that in both group younger than 35 the sex ratio increased significantly in grades A and/or B trophectoderm (P<0.001) and good-quality blastocysts (P<0.001). While grade A inner cell mass (ICM) degree was significantly associated with a lower sex ratio than grade B (P<0.05).ConclusionsA single high-quality blastocyst transfer was significantly associated with a higher neonatal sex ratio. Grade A trophectoderm and grade B ICM contributed to improving the implantation potential of male blastocysts, especially in infertile men or women ≤35 years old.
Developing visit usage recommendations for outpatient rehabilitation after total knee arthroplasty: A Delphi study
Authors: Graber Jeremy , Churchill Laura , Struessel Tamara , O’Malley Shane , Bade Michael , Stevens-Lapsley Jennifer 
Published: December 2022

AbstractObjectiveNo consensus recommendations exist for rehabilitation visit usage (i.e., visit timing, visit frequency, duration of care) after total knee arthroplasty. In the absence of guiding evidence, rehabilitation visit usage varies considerably in the US, especially in the outpatient setting. We sought to develop expert consensus for visit usage recommendations in outpatient rehabilitation after total knee arthroplasty.MethodsWe used a 2-round Delphi process to develop expert consensus for visit usage recommendations. The Delphi panel consisted of surgeons, physical therapists, and advanced practice providers (N=29) with clinical and research expertise in recovery after total knee arthroplasty.ResultsThe panel reached consensus on eight visit frequency recommendations for use in the first three months after total knee arthroplasty. These recommendations are responsive to patients’ time since surgery and their recovery status relative to expected. Twelve additional complementary recommendations were developed to be used with the visit frequency recommendations.ConclusionsWe used the Delphi process to develop expert recommendations for visit usage in outpatient rehabilitation after total knee arthroplasty. We envision these recommendations may help to facilitate a more preference-sensitive approach to postoperative rehabilitation.
The impact of assortative mating, participation bias, and socioeconomic status on the polygenic risk of behavioral and psychiatric traits
Authors: Cabrera-Mendoza Brenda , Wendt Frank R , Pathak Gita A , Yengo Loic , Polimanti Renato 
Published: December 2022

AbstractTo investigate assortative mating (AM), participation bias, and socioeconomic status (SES) with respect to the genetics of behavioral and psychiatric traits, we analyzed gametic phase disequilibrium (GPD), within-spouses and within-siblings polygenic risk score (PRS) correlation, performing a SES conditional analysis. We observed genetic signatures of AM across multiple methods for traits related to substance use with SES conditioning increasing the within-spouses PRS correlation forFrequency of drinking alcohol(2.5% to 6%),Maximum habitual alcohol intake(1.33% to 4.43%), andEver taken cannabis(1.5% to 5.3%). Comparing UK Biobank mental health questionnaire responders vs. non-responders, major depressive disorder PRS showed significant GPD in both groups when based on the Million Veteran Program (3.2% vs. 3%), but only in responders when based on the Psychiatric Genomics Consortium (3.8% vs. 0.2%). These results highlight the impact of AM, participation bias, and SES on the polygenic risk of behavioral and psychiatric traits.
SARS-CoV-2 Envelope-mediated Golgi pH dysregulation interferes with ERAAP retention in cells
Authors: Vargas-Zapata Valerie , Geiger Kristina M. , Tran Dan , Ma Jessica , Mao Xiaowen , Puschnik Andreas S. , Coscoy Laurent 
Published: December 2022

AbstractEndoplasmic reticulum (ER) aminopeptidase associated with antigen processing (ERAAP) trims peptide precursors in the ER for presentation by major histocompatibility (MHC)-I molecules to surveying CD8+T-cells. This function allows ERAAP to regulate the nature and quality of the peptide repertoire and, accordingly, the resulting immune responses. We recently showed that infection with murine cytomegalovirus leads to a dramatic loss of ERAAP levels in infected cells. In mice, this loss is associated with the activation of QFL T-cells, a subset of T-cells that monitor ERAAP integrity and eliminate cells experiencing ERAAP dysfunction. In this study, we aimed to identify host factors that regulate ERAAP expression level and determine whether these could be manipulated during viral infections. We performed a CRISPR knockout screen and identified ERp44 as a factor promoting ERAAP retention in the ER. ERp44’s interaction with ERAAP is dependent on the pH gradient between the ER and Golgi. We hypothesized that viruses that disrupt the pH of the secretory pathway interfere with ERAAP retention. Here, we demonstrate that expression of the Envelope (E) protein from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) leads to Golgi pH neutralization and consequently decrease of ERAAP intracellular levels. Furthermore, SARS-CoV-2-induced ERAAP loss correlates with its release into the extracellular environment. ERAAP’s reliance on ERp44 and a functioning ER/Golgi pH gradient for proper localization and function led us to propose that ERAAP serves as a sensor of disturbances in the secretory pathway during infection and disease.
Genome-Wide Association Study of Obsessive-Compulsive Symptoms including 33 943 individuals from the general population
Authors: Strom Nora I. , Burton Christie L. , Iyegbe Conrad , Silzer Talisa , Antonyan Lilit , Pool René , Lemire Mathieu , Crowley James J. , Hottenga Jouke-Jan , Ivanov Volen Z. , Larsson Henrik , Lichtenstein Paul , Magnusson Patrik , Rück Christian , Schachar Russell , Wu Hei Man , Cath Danielle , Crosbie Jennifer , Mataix-Cols David , Boomsma Dorret I. , Mattheisen Manuel , Meier Sandra M. , Smit Dirk J.A. , Arnold Paul D. 
Published: December 2022

AbstractWhile 1-2% of individuals meet the criteria for a clinical diagnosis of obsessive-compulsive disorder (OCD), many more (∼15-40%) experience subclinical obsessive-compulsive symptoms (OCS) during their life. To characterize the genetic underpinnings of OCS and its genetic relationship to OCD, we conducted the largest genome-wide association study (GWAS) meta-analysis of parent- or self-reported OCS to date (N = 33,943 with complete phenotypic and genome-wide data), combining the results from seven large-scale population-based cohorts from Sweden, the Netherlands, England, and Canada (including six twin cohorts and one cohort of unrelated individuals). We found no genome-wide significant associations on the SNP or gene-level, but a polygenic risk score (PRS) based on the OCD GWAS previously published by the Psychiatric Genetics Consortium (PGC-OCD) was significantly associated with OCS (Pfixed= 3.06 ×10−5). Also, one curated gene set (Mootha Gluconeogenesis) reached Bonferroni-corrected significance (Ngenes= 28, Beta = 0.79, SE = 0.16, Pbon= 0.008). Expression of genes in this set is high at sites of insulin-mediated glucose disposal. Dysregulated insulin signaling in the etiology of OCS has been suggested by a previous study describing a genetic overlap of OCS with insulin signaling-related traits in children and adolescents. We report a SNP heritability of 4.1% (P = 0.0044) in the meta-analyzed GWAS, and heritability estimates based on the twin cohorts of 33% - 43%. Genetic correlation analysis showed that OCS were most strongly associated with OCD (rG= 0.72, p = 0.0007) among all tested psychiatric disorders (N = 11). Of all 97 tested phenotypes, 24 showed a significant genetic correlation with OCS, and 66 traits showed concordant directions of effect with OCS and OCD. OCS have a significant polygenic contribution and share genetic risk with diagnosed OCD, supporting the hypothesis that OCD represents the extreme end of widely distributed OCS in the population.
The imprinting effect of COVID-19 vaccines: an expected selection bias in observational studies
Authors: Monge Susana , Pastor-Barriuso Roberto , Hernán Miguel A. 
Published: December 2022

AbstractRecent observational studies have found a higher risk of reinfection with Omicron in people who received a third booster dose. This finding has been interpreted as evidence of immune imprinting of COVID-19 vaccines. We propose an alternative explanation: the increased risk of reinfection in individuals vaccinated with a vaccine booster compared with no booster is the result of selection bias and is expected to arise even if there is no immune imprinting. To clarify this alternative explanation, we describe how previous observational analyses were an attempt to estimate the direct effect of vaccine boosters on SARS-CoV-2 reinfections, an effect that cannot be correctly estimated with observational data. We use causal diagrams (directed acyclic graphs), data simulations and analysis of real data to illustrate the mechanism and magnitude of this bias, which is the result of conditioning on a collider.
A 2.8 Å structure of zoliflodacin in a DNA-cleavage complex withStaphylococcus aureusDNA gyrase
Authors: Morgan Harry , Lipka-Lloyd Magdalena , Warren Anna J. , Hughes Naomi , Holmes John , Burton Nicolas P. , Mahenthiralingam Eshwar , Bax Ben D. 
Published: December 2022

AbstractSince 2000 some thirteen quinolones/fluoroquinolones have been developed and come to market. The quinolones, one of the most successful classes of antibacterial drugs, stabilize DNA-cleavage complexes with DNA gyrase and topo IV, the two bacterial type IIA topoisomerases. The dual targeting of gyrase and topo IV helps decrease the likelihood of resistance developing. Here we report a 2.8 Å X-ray crystal structure which shows that zoliflodacin, a spiropyrimidinetrione antibiotic, binds in the same DNA-cleavage site(s) as quinolones sterically blocking DNA religation. The structure shows that zoliflodacin interacts with highly conserved residues on GyrB (and does not use the quinolone water-metal ion bridge to GyrA) suggesting it may be more difficult for bacteria to develop target mediated resistance. We found that zoliflodacin had an MIC of 4µg/mL againstAcinetobacter baumannii, an improvement of 4-fold over its progenitor QPT-1. The current phase III clinical trial of zoliflodacin for gonorrhea is due to be read out in 2023. Zoliflodacin, together with the unrelated novel bacterial topoisomerase inhibitor gepotidacin, are likely to become the first entirely novel chemical entities approved against Gram-negative bacteria in the 21st century. Zoliflodacin may also become the progenitor of a new safer class of antibacterial drugs against other problematic Gram-negative bacteria.