bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shared Genomic Architectures of COVID-19 and Antisocial Behavior
Authors: Adams Charleen D. , Tielbeek Jorim J. , Boutwell Brian B. 
Published: October 2021

AbstractLittle is known about the genetics of norm violation and aggression (ASB) in relation to coronavirus disease 2019 (COVID-19). To investigate this, we used summary statistics from genome-wide association studies and linkage disequilibrium score regression to calculate a matrix of genetic correlations (rgs) for ASB, COVID-19, and various health and behavioral traits. After false-discovery rate correction, ASB was genetically correlated with COVID-19 (rg = 0.51; P = 1.54E-02) and 19 other traits. ASB and COVID-19 were both positively genetically correlated with having a noisy workplace, doing heavy manual labor, chronic obstructive pulmonary disease, and genitourinary diseases. ASB and COVID-19 were both inversely genetically correlated with average income, education years, healthspan, verbal reasoning, lifespan, cheese intake, and being breastfed as a baby. But keep in mind that rgs are not necessarily causal. And, if causal, their prevailing directions of effect (which causes which) are indiscernible from rgs alone. Moreover, the SNP-heritability estimates for both measures of COVID-19 were very low, restricting the overlap of genetic variance in absolute terms between the two traits. Nonetheless, our findings suggest that those with antisocial tendencies possibly have a higher risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than those without antisocial tendencies. This may have been especially true early in the pandemic before vaccines against SARS-CoV-2 were available and before the emergence of the highly transmissible Omicron variant.
Association of Network Connectivity via Resting State Functional MRI with Consciousness, Mortality, and Outcomes in Neonatal Acute Brain Injury
Authors: Boerwinkle Varina L. , Sussman Bethany , Manjón Iliana , Mirea Lucia , Suleman Saher , Wyckoff Sarah N. , Bonnell Alexandra , Orgill Andrew , Tom Deborah 
Published: October 2021

AbstractBackgroundAn accurate and comprehensive test of integrated brain network function is needed for neonates during the acute brain injury period to inform on morbidity. This retrospective cohort study aimed to assess whether integrated brain network function by resting state functional MRI, acquired during the acute period in neonates with brain injury, is associated with acute exam, neonatal mortality, and 5-month outcomes.MethodsThis study included 40 consecutive neonates with resting state functional MRI acquired 1-22 days after suspected brain insult from March 2018 to July 2019 at Phoenix Childrens Hospital. Acute period exam and test results were assigned ordinal scores based on severity as documented by respective treating specialists. Analyses (Fisher exact, Wilcoxon-rank sum test, ordinal/multinomial logistic regression) examined association of resting state networks with demographics, presentation, neurological exam, electroencephalogram, anatomical MRI, magnetic resonance spectroscopy, passive task functional MRI, and outcomes of discharge condition, outpatient development, motor tone, seizure, and mortality.ResultsSubjects had a mean (standard deviation) gestational age of 37.8 (2.6) weeks, a majority were male (63%), with diagnosis of hypoxic ischemic encephalopathy (68%). Other findings at birth included mild distress (48%), moderately abnormal neurological exam (33%), and consciousness characterized as awake but irritable (40%). Significant associations after multiple testing corrections were detected for resting state networks: basal ganglia with outpatient developmental delay (odds ratio [OR], 14.5; 99.4% confidence interval [CI], 2.00-105; P<.001) and motor tone/weakness (OR, 9.98; 99.4% CI, 1.72-57.9; P<.001); language/frontal-parietal network with discharge condition (OR, 5.13; 99.4% CI, 1.22-21.5; P=.002) and outpatient developmental delay (OR, 4.77; 99.4% CI, 1.21-18.7; P=.002); default mode network with discharge condition (OR, 3.72; 99.4% CI, 1.01-13.78; P=.006) and neurological exam (P=.002 (FE); OR, 11.8; 99.4% CI, 0.73-191; P=.01 (OLR)); seizure onset zone with motor tone/weakness (OR, 3.31; 99.4% CI, 1.08-10.1; P=.003). Resting state networks were not detected in only three neonates, who died prior to discharge.ConclusionsThis study provides level 3 evidence (OCEBM Levels of Evidence Working Group) that the degree of abnormality of resting state networks in neonatal acute brain injury is associated with acute exam and outcomes. Total lack of brain network detection was only found in patients who did not survive.
Somatically mutated genes in fatty liver disease have minimal influence on germline risk
Authors: Mann Jake P. , Hoare Matthew 
Published: October 2021

AbstractBackgroundUnderstanding the genetics of liver disease has the potential to facilitate clinical risk stratification. We recently identified six genes and one lncRNA enriched for acquired somatic mutations in patients with NAFLD and alcohol-related liver disease. We hypothesised that germline variation in these genes would be associated with risk of liver disease development and contribute to prognostication.MethodsGenome-wide association study (GWAS) summary statistics were extracted from seven studies (>1.7 million participants) for variants near ACVR2A, ALB, CIDEB, FOXO1, GPAM, NEAT1 and TNRC6B for: aminotransferases, liver fat, HbA1c, diagnosis of NAFLD, ARLD, and cirrhosis. Findings were replicated using GWAS data from multiple independent cohorts. A phenome-wide association study was performed to examine for related metabolic traits, using both common and rare variants, including gene-burden testing.ResultsThere was no evidence of association between rare germline variants or SNPs near five genes (ACVR2A, ALB, CIDEB, FOXO1, and TNRC6B) and risk or severity of liver disease. Variants in GPAM were associated with liver fat (p=3.6×10-13), ALT (p=2.8×10-39), and serum lipid concentrations. Variants in NEAT1 demonstrated borderline significant associations with ALT (p=1.9×10-11) and HbA1c, but not with liver fat, as well as influencing waist-to-hip ratio, adjusted for BMI.ConclusionsDespite strong selective advantage to acquire somatic mutations at these loci, there was no evidence of an association between germline variation and markers of liver disease, except in GPAM. Polygenic risk scores based on germline variation alone will not capture prognostic data from genes affected by somatic mutations.
The association between smoking and anal human papillomavirus in the HPV infection in Men Study
Authors: Umutoni Victoria , Schabath Matthew B. , Nyitray Alan G. , Wilkin Timothy , Villa Luisa , Lazcano-Ponce Eduardo , Giuliano Anna R. , Sudenga Staci L. 
Published: October 2021

AbstractBackgroundPrevious studies show an association between smoking and anal cancer. The objective of this study was to assess the association between smoking and anal HPV prevalence in men.MethodsThe HPV infection in Men (HIM) Study is a multinational study that enrolled HIV-negative men. At baseline anal specimens were collected from 1994 participants. HPV genotyping was assessed by Linear Array. Prevalence ratios (PR) were used to assess the association between smoking and anal HPV prevalence.ResultsCurrent smokers have a higher prevalence of any anal HPV (adjusted PR (aPR)=1.36, 95%CI: 1.06-1.73) and LR-HPV (aPR=1.59, 95%CI: 1.20-2.12) compared to never smokers. There were no difference in the prevalence of anal HPV between former and never smokers.Smoking status was not associated with the prevalence of anal HPV among men that have sex with men (MSM). Among men that have sex with women (MSW), current smokers had an increased prevalence for LR-HPV (aPR=1.60 95% CI: 1.02-2.50) compared to never smokers.ConclusionsWhile there was no difference in anal HPV prevalence among MSM by smoking status, MSW that currently smoked had a higher prevalence of LR-HPV. Futher research is needed to assess the role smoking in anal HPV persistence.
Elevated antibody titers in Abdala vaccinees evaluated by Elecsys® anti-SARS-CoV-2 S highly correlate with UMELISA SARS-CoV-2 ANTI RBD, ACE-2 binding inhibition and viral neutralization assays
Authors: Lemos-Pérez Gilda , Chávez-Valdés Sheila , González-Formental Hany , Freyre-Corrales Giselle , Vázquez-Arteaga Amalia , Álvarez-Acevedo Beatriz , Ávila-Díaz Lismary , Martínez-Rosales Ricardo U. , Chacón-Quintero Yahima , Coizeau-Rodríguez Edelgis , Palenzuela-Díaz Ariel , Noa-Romero Enrique , Guillén-Nieto Gerardo E. 
Published: October 2021

AbstractSARS-CoV-2, a recently emerged coronavirus, is causing high morbidity and mortality worldwide since December 2019, posing an enormous health, social and economic problem. Obtaining effective treatments that can diminish deaths and sequelae and vaccines to slow or prevent viral transmission, and reduce disease severity and/or death are of utmost importance. Abdala is a Cuban vaccine based on the recombinant RBD subunit of the spike protein expressed in Pichia pastoris yeast. It demonstrated high efficacy (92.28 %) in phase III clinical trials for reducing transmission, and more than 90% effectiveness in reducing disease severity and mortality. Antibody titers were evaluated in 42 Abdala vaccinees using the Elecsys® Anti-SARS-CoV-2 S test. Fifteen days after immunization, sera from vaccinees showed high antibody titers (median of 1595 U/mL). The results obtained in this study also demonstrate correlation between the Cuban test UMELISA SARS-CoV-2 ANTI RBD used during the clinical trials and Elecsys® test results.HighlightsFifteen days after immunization with the Cuban Abdala vaccine, sera from vaccinees showed high antibody titers (median of 1595 U/mL).There was high correlation between the Cuban test UMELISA SARS-CoV-2 ANTI RBD used during the vaccine clinical trials and Roche’s Elecsys® test results.Abdala vaccinees reached antibody titers by the Elecsys® Anti-SARS-CoV-2 S test comparable to those of Pfizer/BionTech vaccine using the same test.
Assisted partner services for people who inject drugs: Index characteristics associated with untreated HIV in partners
Authors: Tseng Ashley S. , Sambai Betsy , Monroe-Wise Aliza , Mbogo Loice W. , Ludwig-Barron Natasha T. , Masyuko Sarah J. , Chohan Bhavna H. , Scott John D. , Sinkele William , Herbeck Joshua T. , Farquhar Carey , Guthrie Brandon L. 
Published: October 2021

ABSTRACTObjectiveIdentify characteristics of persons who inject drugs living with HIV (PWID-LWH) associated with greater assisted partner services (APS) efficiency in identifying partners in need of HIV care and treatment services.DesignProspective cohort studyMethodsPWID-LWH (index participants) were enrolled and asked to provide contact information for sexual and injecting partners who were traced and offered HIV testing. APS efficiency was assessed by the number of indexes needed to interview (NNTI) to find one additional partner who was unaware of their HIV status or not on ART. We defined index participant characteristics associated with greater efficiency, defined as lower NNTIs.ResultsAmong 783 indexes, the NNTI to identify one partner unaware of their HIV status was 7.1 and to identify one HIV-positive partner not on ART (regardless of status awareness) was 4.1. APS was provided to 977 partners and was more efficient in identifying partners who were not on ART (n=201) among indexes who were female (n=381, 49%; NNTI=2.9 vs. 5.7, p<0.001), unaware of their HIV status (n=74, 9.5%; NNTI=2.2 vs. 4.2, p=0.009), not on ART (n=158, 20%; NNTI=2.1 vs. 4.9; p<0.001), not enrolled in a methadone program (n=604, 77%; NNTI=3.3 vs. 10.4, p<0.001), reporting injecting <5 years (n=441, 56%; NNTI=3.3 vs. 5.0; p=0.005), or from Nairobi (n=452, 58%; NNTI=3.2 vs. 5.6, p<0.001).ConclusionsScaling up APS among PWID-LWH with certain characteristics could result in more efficient APS and greater partner engagement in HIV care.
Disrupted network segregation of the default mode network in autism spectrum disorder
Authors: Yang Bo , Wang Min , Zhou Weiran , Wang Xiuqin , Chen Shuaiyu , Yuan Lixia , Potenza Marc N. , Dong Guang-Heng 
Published: October 2021

ABSTRACTBackgroundChanges in the brain’s default mode network (DMN) in the resting state are closely related to autism spectrum disorder (ASD). Module segmentation can effectively elucidate the neural mechanism of ASD and explore the intra- and internetwork connections by means of the participation coefficient (PC).MethodsResting-state fMRI data from 269 ASD patients and 340 healthy controls (HCs) were used in the current study. The PC of brain network modules was calculated and compared between ASD subjects and HCs. In addition, we further explored the features according to different age groups and different subtypes of ASD. Intra- and internetwork differences were further calculated to find the potential mechanism underlying the results.ResultsASD subjects showed significantly higher PC of the DMN than HC subjects. This difference was caused by lower intramodule connections within the DMN and higher internetwork connections between the DMN and networks. When the subjects were split into age groups, the results were verified in the 7-12 and 12-18 age groups but not in the adult group (18-25). When the subjects were divided according to different subtypes of ASD, the results were also observed in the classic autism and pervasive developmental disorder groups, but not in the Asperger disorder group. In addition, compared with the HC group, the ASD group showed significantly increased intranetwork connections between the DMN and the frontoparietal network.ConclusionsLess developed network segregation in the DMN could be a valid biomarker for ASD, and this feature was validated with different measures. The current results provide new insights into the neural underpinnings of ASD and provide targets for potential interventions using brain modulation and behavioural training.
All-viral tracing of monosynaptic inputs to single birthdate-defined neurons in the intact brain
Authors: Jacobsen R Irene , Nair Rajeevkumar R , Obenhaus Horst A , Donato Flavio , Slettmoen Torstein , Moser May-Britt , Moser Edvard I 
Published: October 2021

SummaryNeuronal firing patterns are the result of inputs converging onto single cells. Identifying these inputs, anatomically and functionally, is essential to understand how neurons integrate information. Single-cell electroporation of helper genes and subsequent local injection of recombinant rabies viruses enable precise mapping of inputs to individual cells in superficial layers of the intact cortex. However, access to neurons in deeper structures requires more invasive procedures, including removal of overlying tissue. We have developed a method that through a combination of virus injections allows us to target ≤4 hippocampal cells 48% of the time and a single cell 16% of the time in wildtype mice without the use of electroporation or tissue aspiration. We identify local and distant monosynaptic inputs that can be functionally characterised in vivo. By expanding the toolbox for monosynaptic circuit tracing, this method will help further our understanding of neuronal integration at the level of single cells.
Computational Fluid Dynamics Modeling of Aerosol Particle Transport through Lung Airway Mucosa
Authors: Bartlett Blake A. , Feng Yu , Fromen Catherine A. , Ford Versypt Ashlee N. 
Published: October 2021

AbstractDelivery of aerosols to the lung has great potential for the treatment of various lung diseases. However, the lungs are coated by a protective mucus layer whose complex properties make this form of delivery difficult. Mucus is a non-Newtonian fluid and is cleared from the lungs over time by ciliated cells. Further, its gel-like structure hinders the diffusion of particles through it. Any aerosolized treatment of lung diseases must have certain properties to circumvent the mucosal barrier, and these properties may vary between diseases, drugs, and patients. Using computational fluid dynamics, a model of this mucus layer was constructed to simulate the convective and diffusive transport of impacted aerosol particles. The model predicts the dosage fraction of particles of a certain size that penetrate the mucus and reach the underlying tissue, as well as the distance downstream of the dosage site where epithelial concentration is maximized. Reactions that may occur in solution are also considered, with simulated data for the interaction of a model virus and antibody. The model is modular so that various lung regions and patient health states may be simulated.
Metabolic Potential of Microbial Communities in the Hypersaline Sediments of the Bonneville Salt Flats
Authors: McGonigle Julia M. , Bernau Jeremiah A. , Bowen Brenda B. , Brazelton William J. 
Published: October 2021

AbstractThe Bonneville Salt Flats (BSF) appear to be entirely desolate when viewed from above, but in reality they host rich microbial communities just below the surface salt crust. In this study, we investigate the metabolic potential of the BSF microbial ecosystem. The predicted and measured metabolic activities provide new insights into the ecosystem functions of evaporite landscapes and are an important analog for potential subsurface microbial ecosystems on ancient and modern Mars. Hypersaline and evaporite systems have been investigated previously as astrobiological analogs for Mars and other salty celestial bodies. Still, these studies have generally focused on aquatic systems and cultivation-dependent approaches. Here, we present an ecosystem-level examination of metabolic pathways within the shallow subsurface of evaporites. We detected aerobic and anaerobic respiration as well as methanogenesis in BSF sediments. Metagenome-assembled genomes (MAGs) of diverse bacteria and archaea encoded a remarkable diversity of metabolic pathways, including those associated with carbon fixation, carbon monoxide oxidation, acetogenesis, methanogenesis, sulfide oxidation, denitrification, and nitrogen fixation. These results demonstrate the potential for multiple energy sources and metabolic pathways in BSF and highlight the possibility for vibrant microbial ecosystems in the shallow subsurface of evaporites.
Preventing ovariectomy-induced weight gain decreases tumor burden in rodent models of obesity and postmenopausal breast cancer
Authors: Wellberg Elizabeth A , Corleto Karen A. , Checkley L. Allyson , Jindal Sonali , Johnson Ginger , Higgins Janine A. , Obeid Sarina , Anderson Steven M. , Thor Ann D. , Schedin Pepper J. , MacLean Paul S. , Giles Erin D. 
Published: October 2021

ABSTRACTObesity and adult weight gain are linked to increased breast cancer risk and poorer clinical outcomes in postmenopausal women, particularly for hormone-dependent tumors. Menopause is a time when significant weight gain occurs in many women, and clinical and preclinical studies have identified menopause (or ovariectomy) as a period of vulnerability for breast cancer development and promotion. We hypothesized that preventing weight gain after ovariectomy (OVX) may be sufficient to prevent the formation of new tumors and decrease growth of existing mammary tumors. Here, we tested this hypothesis in a rat model of obesity and carcinogen-induced postmenopausal mammary cancer and validated our findings in a murine xenograft model with implanted human tumors. In both models, preventing weight gain after OVX significantly decreased obesity-associated tumor development and growth. Importantly, we did not induce weight loss in these animals, but simply prevented weight gain. In both lean and obese rats, preventing weight gain reduced visceral fat accumulation and associated insulin resistance. Similarly, the intervention decreased circulating tumor-promoting growth factors and inflammatory cytokines (ie, BNDF, TNFα, FGF2), with greater effects in obese compared to lean rats. In obese rats, preventing weight gain decreased adipocyte size, adipose tissue macrophage infiltration, reduced expression of the tumor-promoting growth factor FGF-1, and reduced phosphorylated FGFR in tumors. Together, these findings suggest that the underlying mechanisms associated with the anti-tumor effects of weight maintenance are multifactorial, and that weight maintenance during the peri-/post-menopausal period may be a viable strategy for reducing obesity-associated breast cancer risk and progression in women.
Functional connectome of brainstem nuclei involved in autonomic, limbic, pain and sensory processing in living humans from 7 Tesla resting state fMRI
Authors: Cauzzo Simone , Singh Kavita , Stauder Matthew , García-Gomar María Guadalupe , Vanello Nicola , Passino Claudio , Staab Jeffrey , Indovina Iole , Bianciardi Marta 
Published: October 2021

AbstractDespite remarkable advances in mapping the functional connectivity of the cortex, the functional connectivity of subcortical regions is understudied in living humans. This is the case for brainstem nuclei that control vital processes, such as autonomic, limbic, nociceptive and sensory functions. This is because of the lack of precise brainstem nuclei localization, of adequate sensitivity and resolution in the deepest brain regions, as well as of optimized processing for the brainstem. To close the gap between the cortex and the brainstem, on 20 healthy subjects, we computed a correlation-based functional connectome of 15 brainstem nuclei involved in autonomic, limbic, nociceptive, and sensory function (superior and inferior colliculi, ventral tegmental area-parabrachial pigmented nucleus complex, microcellular tegmental nucleus-prabigeminal nucleus complex, lateral and medial parabrachial nuclei, vestibular and superior olivary complex, superior and inferior medullary reticular formation, viscerosensory motor nucleus, raphe magnus, pallidus, and obscurus, and parvicellular reticular nucleus – alpha part) with the rest of the brain. Specifically, we exploited 1.1mm isotropic resolution 7 Tesla resting-state fMRI, ad-hoc coregistration and physiological noise correction strategies, and a recently developed probabilistic template of brainstem nuclei. Further, we used 2.5mm isotropic resolution resting-state fMRI data acquired on a 3 Tesla scanner to assess the translatability of our results to conventional datasets. We report highly consistent correlation coefficients across subjects, confirming available literature on autonomic, limbic, nociceptive and sensory pathways, as well as high interconnectivity within the central autonomic network and the vestibular network. Interestingly, our results showed evidence of vestibulo-autonomic interactions in line with previous work. Comparison of 7 Tesla and 3 Tesla findings showed high translatability of results to conventional settings for brainstem-cortical connectivity and good yet weaker translatability for brainstem-brainstem connectivity. The brainstem functional connectome might bring new insight in the understanding of autonomic, limbic, nociceptive and sensory function in health and disease.