bluuebunny/crossref_metadata_2025 huggingface dataset:
A pilot study to evaluate tissue- and plasma-based DNA driver mutations in a cohort of patients with pancreatic intraductal papillary mucinous neoplasms
Authors: Park Margaret A , Zaw Thinzar , Yoder Sean J , Gomez Maria , Genilo-Delgado Maria , Basinski Toni , Katende Esther , Dam Aamir , Mok Shaffer R S , Monteiro Alvaro , Mohammadi Amir , Jeong Daniel K , Jiang Kun , Centeno Barbara A , Hodul Pamela , Malafa Mokenge , Fleming Jason , Chen Dung-Tsa , Mo Qianxing , Teer Jamie K , Permuth Jennifer B
Published: December 2022

Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions to pancreatic ductal adenocarcinoma that are challenging to manage due to limited imaging, cytologic, and molecular markers that accurately classify lesions, grade of dysplasia, or focus of invasion preoperatively. The objective of this pilot study was to determine the frequency and type of DNA mutations in a cohort of surgically resected, pathologically confirmed IPMN, and to determine if concordant mutations are detectable in paired pretreatment plasma samples. Formalin-fixed paraffin-embedded (FFPE) tissue from 46 surgically resected IPMNs (31 low-grade, 15 high-grade) and paired plasma from a subset of 15 IPMN cases (10 low-grade, 5 high-grade) were subjected to targeted mutation analysis using a QIAseq Targeted DNA Custom Panel. Common driver mutations were detected in FFPE from 44 of 46 (95.6%) IPMN cases spanning all grades; the most common DNA mutations included: KRAS (80%), RNF43 (24%), and GNAS (43%). Of note, we observed a significant increase in the frequency of RNF43 mutations from low-grade to high-grade IPMNs associated or concomitant with invasive carcinoma (trend test, P = 0.01). Among the subset of cases with paired plasma, driver mutations identified in the IPMNs were not detected in circulation. Overall, our results indicate that mutational burden for IPMNs is a common occurrence, even in low-grade IPMNs. Furthermore, although blood-based biopsies are an attractive, noninvasive method for detecting somatic DNA mutations, the QIAseq panel was not sensitive enough to detect driver mutations that existed in IPMN tissue using paired plasma in the volume we were able to retrieve for this retrospective study.
Identification of candidate genes responsible for innate fear behavior in the chicken
Authors: Ochiai Takayuki , Sakaguchi Marina , Kawakami Shin-Ichi , Ishikawa Akira
Published: December 2022

Identifying the genes responsible for quantitative traits remains a major challenge. We previously found a major QTL on chromosome 4 affecting several innate fear behavioral traits obtained by an open-field test in an F2 population between White Leghorn and Nagoya breeds of chickens (Gallus gallus). Here, an integrated approach of transcriptome, haplotype frequency, and association analyses was used to identify candidate genes for the QTL in phenotypically extreme individuals selected from the same segregating F2 population as that used in the initial QTL analysis. QTL mapping for the first principal component, which summarizes the variances of all affected behavioral traits in the F2 population, revealed the behavioral QTL located at 14–35 Mb on chromosome 4 with 333 genes. After RNA-seq analysis using two pooled RNAs from extreme F2 individuals, real-time qPCR analysis in the two parental breeds and their F1 individuals greatly reduced the number of candidate genes in the QTL interval from 333 to 16 genes. Haplotype frequency analysis in the two extreme F2 groups further reduced the number of candidate genes from 16 to 11. After comparing gene expression in the two extreme groups, a conditional correlation analysis of diplotypes between gene expression and phenotype of extreme individuals revealed that NPY5R and LOC101749214 genes were strong candidate genes for innate fear behavior. This study illustrates how the integrated approach can identify candidate genes more rapidly than fine mapping of the initial QTL interval and provides new information for studying the genetic basis of innate fear behavior in chickens.
Myxoid pleomorphic liposarcoma of the falciform ligament: a rare case report
Authors: AlObaid Bashayer , Alzahrani Nayef A , Shokor Nada , Alshammari Kanan
Published: December 2022

Liposarcomas are a group of malignancies that mainly affect adults. Myxoid pleomorphic liposarcoma (MPL) is a newly added subtype of liposarcomas [1]. It is extremely rare and mostly affects infants and children, and it has a predilection for the mediastinum. We report a case of a 58-years-old female with MPL originating from the falciform ligament who presented initially with vague abdominal pain. MPLs have an aggressive pathology and high metastasis and recurrence potential.
A multi-omic landscape of steatosis-to-NASH progression
Authors: Xiang Liping , Li Xiaoyan , Luo Yunchen , Zhou Bing , Liu Yuejun , Li Yao , Wu Duojiao , Jia Lijing , Zhu Pei-Wu , Zheng Ming-Hua , Wang Hua , Lu Yan
Published: December 2022

Nonalcoholic steatohepatitis (NASH) has emerged as a major cause of liver failure and hepatocellular carcinoma. Investigation into the molecular mechanisms that underlie steatosis-to-NASH progression is key to understanding the development of NASH pathophysiology. Here, we present comprehensive multi-omic profiles of preclinical animal models to identify genes, non-coding RNAs, proteins, and plasma metabolites involved in this progression. In particular, by transcriptomics analysis, we identified Growth Differentiation Factor 3 (GDF3) as a candidate noninvasive biomarker in NASH. Plasma GDF3 levels are associated with hepatic pathological features in patients with NASH, and differences in these levels provide a high diagnostic accuracy of NASH diagnosis (AUROC = 0.90; 95% confidence interval: 0.85−0.95) with a good sensitivity (90.7%) and specificity (86.4%). In addition, by developing integrated proteomic-metabolomic datasets and performing a subsequent pharmacological intervention in a mouse model of NASH, we show that ferroptosis may be a potential target to treat NASH. Moreover, by using competing endogenous RNAs network analysis, we found that several miRNAs, including miR-582-5p and miR-292a-3p, and lncRNAs, including XLOC-085738 and XLOC-041531, are associated with steatosis-to-NASH progression. Collectively, our data provide a valuable resource into the molecular characterization of NASH progression, leading to the novel insight that GDF3 may be a potential noninvasive diagnostic biomarker for NASH while further showing that ferroptosis is a therapeutic target for the disease.
GeneFriends: gene co-expression databases and tools for humans and model organisms
Authors: Raina Priyanka , Guinea Rodrigo , Chatsirisupachai Kasit , Lopes Inês , Farooq Zoya , Guinea Cristina , Solyom Csaba-Attila , de Magalhães João Pedro
Published: December 2022

Gene co-expression analysis has emerged as a powerful method to provide insights into gene function and regulation. The rapid growth of publicly available RNA-sequencing (RNA-seq) data has created opportunities for researchers to employ this abundant data to help decipher the complexity and biology of genomes. Co-expression networks have proven effective for inferring the relationship between the genes, for gene prioritization and for assigning function to poorly annotated genes based on their co-expressed partners. To facilitate such analyses we created previously an online co-expression tool for humans and mice entitled GeneFriends. To continue providing a valuable tool to the scientific community, we have now updated the GeneFriends database and website. Here, we present the new version of GeneFriends, which includes gene and transcript co-expression networks based on RNA-seq data from 46 475 human and 34 322 mouse samples. The new database also encompasses tissue-specific gene co-expression networks for 20 human and 21 mouse tissues, dataset-specific gene co-expression maps based on TCGA and GTEx projects and gene co-expression networks for additional seven model organisms (fruit fly, zebrafish, worm, rat, yeast, cow and chicken). GeneFriends is freely available at http://www.genefriends.org/.
SUMO conjugation regulates the activity of the Integrator complex
Authors: Bragado Laureano , Magalnik Melina , Mammi Pablo , Romero Agustín , Gaioli Nicolás , Pozzi Berta , Srebrow Anabella
Published: December 2022

RNA polymerase II (RNAPII) transcribes small nuclear RNA (snRNA) genes in close proximity to Cajal bodies, subnuclear compartments that depend on the SUMO isopeptidase USPL1 for their assembly. We show here that overexpression of USPL1 as well as of another nuclear SUMO isopeptidase, SENP6, alters snRNA 3′-end cleavage, a process carried out by the Integrator complex. Beyond its role in snRNA biogenesis, this complex is responsible for regulating the expression of different RNAPII transcripts. While several subunits of the complex are SUMO conjugation substrates, we found that the SUMOylation of the INTS11 subunit is regulated by USPL1 and SENP6. We defined Lys381, Lys462 and Lys475 as bona fide SUMO attachment sites on INTS11 and observed that SUMOylation of this protein modulates its subcellular localization and is required for Integrator activity. Moreover, while an INTS11 SUMOylation-deficient mutant is still capable of interacting with INTS4 and INTS9, its interaction with other subunits of the complex is affected. These findings point to a regulatory role for SUMO conjugation on Integrator activity and suggest the involvement of INTS11 SUMOylation in the assembly of the complex. Furthermore, this work adds Integrator-dependent RNA processing to the growing list of cellular processes regulated by SUMO conjugation.
Human DNA polymerase α has a strong mutagenic potential at the initial steps of DNA synthesis
Authors: Lisova Alisa E , Baranovskiy Andrey G , Morstadt Lucia M , Babayeva Nigar D , Tahirov Tahir H
Published: December 2022

DNA polymerase α (Polα) is essential for DNA replication initiation and makes a notable contribution to genome mutagenesis. The activity and fidelity of Polα during the early steps of DNA replication have not been well studied. Here we show that at the beginning of DNA synthesis, when extending the RNA primer received from primase, Polα is more mutagenic than during the later DNA elongation steps. Kinetic and binding studies revealed substantially higher activity and affinity to the template:primer when Polα interacts with ribonucleotides of a chimeric RNA–DNA primer. Polα activity greatly varies during first six steps of DNA synthesis, and the bias in the rates of correct and incorrect dNTP incorporation leads to impaired fidelity, especially upon the second step of RNA primer extension. Furthermore, increased activity and stability of Polα/template:primer complexes containing RNA–DNA primers result in higher efficiency of mismatch extension.
Pushing the limits of HiFi assemblies reveals centromere diversity between two Arabidopsis thaliana genomes
Authors: Rabanal Fernando A , Gräff Maike , Lanz Christa , Fritschi Katrin , Llaca Victor , Lang Michelle , Carbonell-Bejerano Pablo , Henderson Ian , Weigel Detlef
Published: December 2022

Although long-read sequencing can often enable chromosome-level reconstruction of genomes, it is still unclear how one can routinely obtain gapless assemblies. In the model plant Arabidopsis thaliana, other than the reference accession Col-0, all other accessions de novo assembled with long-reads until now have used PacBio continuous long reads (CLR). Although these assemblies sometimes achieved chromosome-arm level contigs, they inevitably broke near the centromeres, excluding megabases of DNA from analysis in pan-genome projects. Since PacBio high-fidelity (HiFi) reads circumvent the high error rate of CLR technologies, albeit at the expense of read length, we compared a CLR assembly of accession Eyach15-2 to HiFi assemblies of the same sample. The use of five different assemblers starting from subsampled data allowed us to evaluate the impact of coverage and read length. We found that centromeres and rDNA clusters are responsible for 71% of contig breaks in the CLR scaffolds, while relatively short stretches of GA/TC repeats are at the core of >85% of the unfilled gaps in our best HiFi assemblies. Since the HiFi technology consistently enabled us to reconstruct gapless centromeres and 5S rDNA clusters, we demonstrate the value of the approach by comparing these previously inaccessible regions of the genome between the Eyach15-2 accession and the reference accession Col-0.
Comparison of functional classification systems
Authors: Zeller Monika , Huson Daniel H
Published: December 2022

In microbiome analysis, functional profiling is based on assigning reads or contigs to terms or nodes in a functional classification system. There are a number of large, general-purpose functional classifications that are in use, such as eggNOG, KEGG, InterPro and SEED. Smaller, special-purpose classifications include CARD, EC, MetaCyc and VFDB. Here, we compare the different classifications in terms of their overlap, redundancy, structure and assignment rates. We also provide mappings between main concepts in different classifications. For the large classifications, we find that eggNOG performs the best with respect to sequence redundancy and structure, SEED has the cleanest hierarchy, whereas KEGG and InterPro:BP might be more informative for medical applications. We illustrate the practical assignment rates for different classifications using a number of metagenomic samples.
Strategies for knowledge exchange for action to address place-based determinants of health inequalities: an umbrella review
Authors: Halliday E , Tompson A , McGill E , Egan M , Popay J
Published: December 2022

Background

Place-based health inequalities persist despite decades of academics and other stakeholders generating ideas and evidence on how to reduce them. This may in part reflect a failure in effective knowledge exchange (KE). We aim to understand what KE strategies are effective in supporting actions on place-based determinants and the barriers and facilitators to this KE.

Methods

An umbrella review was undertaken to identify relevant KE strategies. Systematic reviews were identified by searching academic databases (Medline, Embase, Scopus, Web of Science) and handsearching. Synthesis involved charting and thematic analysis.

Results

Fourteen systematic reviews were included comprising 105 unique, relevant studies. Four approaches to KE were identified: improving access to knowledge, collaborative approaches, participatory models and KE as part of advocacy. While barriers and facilitators were reported, KE approaches were rarely evaluated for their effectiveness.

Conclusions

Based on these four approaches, our review produced a framework, which may support planning of future KE strategies. The findings also suggest the importance of attending to political context, including the ways in which this may impede a more upstream place-based focus in favour of behavioural interventions and the extent that researchers are willing to engage with politicized agendas.
Large-Scale Thalamocortical Triple Network Dysconnectivities in Patients With First-Episode Psychosis and Individuals at Risk for Psychosis
Authors: Kim Minah , Kim Taekwan , Ha Minji , Oh Harin , Moon Sun-Young , Kwon Jun Soo
Published: December 2022

Background and Hypothesis

Aberrant thalamocortical connectivity and large-scale network interactions among the default mode network (DMN), salience network (SN), and executive control network (ECN) (ie, triple networks) have been regarded as critical in schizophrenia pathophysiology. Despite the importance of network properties and the role of the thalamus as an integrative hub, large-scale thalamocortical triple network functional connectivities (FCs) in different stages of the psychotic disorder have not yet been reported.

Study Design

Thirty-nine first-episode psychosis (FEP) patients, 75 individuals at clinical high risk (CHR) for psychosis, 46 unaffected relatives (URs) of schizophrenia patients with high genetic loading, and 110 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Modular community detection was used to identify cortical and thalamic resting-state networks, and thalamocortical network interactions were compared across the groups.

Study Results

Thalamic triple networks included higher-order thalamic nuclei. Thalamic SN–cortical ECN FC was greater in the FEP group than in the CHR, UR, and HC groups. Thalamic DMN–cortical DMN and thalamic SN–cortical DMN FCs were greater in FEP and CHR participants. Thalamic ECN–cortical DMN and thalamic ECN–cortical SN FCs were greater in FEP patients and URs.

Conclusions

These results highlight critical modulatory functions of thalamic triple networks and the shared and distinct patterns of thalamocortical triple network dysconnectivities across different stages of psychotic disorders. The current study findings suggest that large-scale thalamocortical triple network dysconnectivities may be used as an integrative biomarker for extending our understanding of the psychosis pathophysiology and for targeting network-based neuromodulation therapeutics.
Substance Use and Sleep Problems in Patients With Psychotic Disorders
Authors: Cederlöf Erik , Holm Minna , Ahti Johan , Lähteenvuo Markku , Hietala Jarmo , Häkkinen Katja , Isometsä Erkki , Kampman Olli , Lahdensuo Kaisla , Lönnqvist Jouko , Suvisaari Jaana , Tiihonen Jari , Wegelius Asko , Veijola Juha , Palotie Aarno , Kieseppä Tuula , Niemelä Solja , Paunio Tiina
Published: December 2022

Background

Substance use and sleep problems are common in patients with psychotic disorders, but their associations in these patients have not been evaluated. We aimed to investigate associations between substance use and sleep problems in a large nationwide cohort of patients with a psychotic disorder.

Study Design

This study is part of the Finnish SUPER study, which belongs to the Stanley Global Neuropsychiatric Genomics Initiative. In this cross-sectional, multicenter study, participants (N = 8616) were recruited from primary and specialized healthcare. Patients with schizophrenia, schizoaffective disorder, bipolar disorder, and psychotic depression were included. Information on current alcohol (Alcohol Use Disorders Identification Test-Concise) and cigarette use as well as on lifetime illicit drug use, including cannabis, benzodiazepines, amphetamines, and opioids, was collected using questionnaires. The sleep outcomes in our logistic regression analysis were short (≤6 h) and long sleep (≥10 h) duration, difficulties initiating asleep, early morning awakenings, fatigue, and poor sleep quality (SQ).

Results

Self-reported substance use was associated with a higher prevalence of sleep problems. After adjustments with age, gender, diagnostic group, and living status, hazardous alcohol use (eg, poor SQ odds ratio [OR] = 1.80, 95% CI: 1.49 to 2.16, P < .001), current smoking (short sleep duration OR = 1.28, 95% CI: 1.08 to 1.52, P = .005), and lifetime benzodiazepine misuse (difficulties initiating sleep OR = 2.00, 95% CI: 1.55 to 2.48, P < .001) were associated with sleep problems.

Conclusions

Substance use was associated with sleep problems. Our findings underline the potential benefits of screening substance use when treating sleep problems in patients with psychotic disorders.
Draft Genome Sequence of Carrot Alternaria Leaf Blight Pathogen Alternaria dauci
Authors: Liu Xing , Zhao Donghang , Ou Chenggang , Hao Weidong , Zhang Yifan , He Yongheng , Zhao Zhiwei , Zhuang Feiyun
Published: December 2022

The fungal genus Alternaria, which causes a variety of crop diseases, is widely distributed in the world. Alternaria leaf blight, caused by Alternaria dauci, is one of the most common and destructive diseases in carrot. The infection of A. dauci leads to dramatic decay on both foliage and taproot in severe cases, which results in significant yield losses. In this study, we sequenced and assembled the genome of A. dauci isolate CALB1, which isolated from the major carrot producing areas of China. A total of 65 contigs were assembled, and the estimated genome size was 34.9 Mb. The draft genome of A. dauci can be used for comparative genomic analysis of Alternaria species and provide genetic information for further research on plant-pathogen interactions.
Which pediatric supracondylar humerus fractures are high risk for conversion to open reduction?
Authors: Latario Luke D. , Lubitz Marc G. , Narain Ankur S. , Swart Eric F. , Mortimer Errol S.
Published: December 2022

Supracondylar humerus fractures are common pediatric injuries encountered by orthopedic surgeons. Displaced fractures are treated operatively with closed reduction and percutaneous pinning or open reduction of injuries that cannot be adequately closed reduced. The purpose of this study is to identify preoperative injury characteristics associated with open reduction. Retrospective chart review was performed on all AO type 13A (Gartland type) supracondylar humerus fractures in patients 2–13 years old treated surgically at a single level 1 trauma center over 6 years. Preoperative demographics and radiographic parameters were obtained for all patients. Primary outcomes were closed reduction or conversion to open reduction of fractures prior to k-wire fixation. Initial bivariate analysis was done using Chi-square tests. Final multivariate analysis with Bonferonni correction was performed using a backward, stepwise regression model including potential predictor variables identified in the bivariate analysis. A total of 211 patients received surgical treatment and 18 of those patients (8.5%) failed closed reduction and underwent open reduction. Final multivariate analysis demonstrated that only flexion type [relative risk (RR), 10.2] and coronal displacement more than 7 mm (RR, 4.49) were significant preoperative factors for conversion to open reduction. Patients with significant coronal displacement and flexion-type injuries are markers of challenging reduction and are at high risk for conversion to open reduction.
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.
Pediatric Acute Lung Injury and Sepsis Investigators (PALISI): Evolution of an Investigator-Initiated Research Network
Authors: Randolph Adrienne G. , Bembea Melania M. , Cheifetz Ira M. , Curley Martha A. Q. , Flori Heidi R. , Khemani Robinder G. , Kudchadkar Sapna R. , Nishisaki Akira , Watson R. Scott , Tucci Marisa , Lacroix Jacques , Thompson Ann E. , Thomas Neal J. ,   for the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
Published: December 2022

The Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network originated over 20 years ago to foster research to optimize the care of critically ill infants and children. Over this period, PALISI has seen two major evolutions: formalization of our network infrastructure and a broadening of our clinical research focus. First, the network is unique in that its activities and meetings are funded by subscriptions from members who now comprise a multidisciplinary group of investigators from over 90 PICUs all over the United States (US) and Canada, with collaborations across the globe. In 2020, the network converted into a standalone, nonprofit organizational structure (501c3), making the PALISI Network formally independent of academic and clinical institutions or professional societies. Such an approach allows us to invest in infrastructure and future initiatives with broader opportunities for fund raising. Second, our research investigations have expanded beyond the original focus on sepsis and acute lung injury, to incorporate the whole field of pediatric critical care, for example, efficient liberation from mechanical ventilator support, prudent use of blood products, improved safety of intubation practices, optimal sedation practices and glucose control, and pandemic research on influenza and COVID-19. Our network approach in each field follows, where necessary, the full spectrum of clinical and translational research, including: immunobiology studies for understanding basic pathologic mechanisms; surveys to explore contemporary clinical practice; consensus conferences to establish agreement about literature evidence; observational prevalence and incidence studies to measure scale of a clinical issue or question; case control studies as preliminary best evidence for design of definitive prospective studies; and, randomized controlled trials for informing clinical care. As a research network, PALISI and its related subgroups have published over 350 peer-reviewed publications from 2002 through September 2022.
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

Background

To study the relationship between blastocyst morphology and the sex ratio of singleton births in single blastocyst transfer cylces.

Methods

This 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.

Results

Sex 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).

Conclusions

A 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

Objective

No 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.

Methods

We 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.

Results

The 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.

Conclusions

We 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

To 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

Endoplasmic 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

While 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

Recent 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

Since 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.