tbuckley/cabot-search huggingface dataset:
Increased Hepatic Expression of SARS-CoV-2 Entry Points and Proinflammatory Cytokines in Cirrhosis
Authors: Nathaly Limon-De La Rosa, Eduardo Cervantes-Alvarez, Nalu Navarro-Alvarez
Journal: Clinical Gastroenterology and Hepatology (2021)

It has been recently reported that patients with cirrhosis have significantly higher mortality following severe acute respiratory syndrome coronavrisu 2 (SARS-CoV-2) infection compared with those without.1,2 Specifically, it was demonstrated that mortality was greater in those with advanced cirrhosis (Child-Pugh B and C), and that from cirrhotic patients experiencing SARS-CoV-2 infection, close to half suffer acute decompensation including acute-on-chronic liver failure (ACLF).2 Unfortunately, the presence of hepatic decompensation at baseline has been shown to be an independent predictor of all-cause mortality in patients with coronavirus disease 2019 (COVID-19).1 Patients with decompensated cirrhosis contracting COVID-19 have a poor outcome, with an overall reported mortality of over 30%.1.
Three novel structural variations at the major histocompatibility complex and <i>IL12B</i> predispose to psoriasis*
Authors: Q. Zhen, Y. Zhang, Y. Yu, H. Yang, T. Zhang, X. Li, X. Mo, B. Li, J. Wu, Y. Liang, H. Ge, Q. Xu, W. Chen, W. Qian, H. Xu, G. Chen, B. Bai, J. Zhang, Y. Lu, S. Chen, H. Zhang, Y. Zhang, X. Chen, X. Li, X. Jin, X. Lin, L. Yong, M. Fang, J. Zhao, Y. Lu, S. Wu, D. Jiang, J. Shi, H. Cao, Y. Qiu, S. Li, X. Kang, J. Shen, H. Ma, S. Sun, Y. Fan, W. Chen, M. Bai, Q. Jiang, W. Li, C. Lv, S. Li, M. Chen, F. Li, Y. Li, L. Sun
Journal: British Journal of Dermatology (2021)

Structural variations (SVs; defined as DNA variants ≥ 50 base pairs) have been associated with various complex human diseases. However, research to screen the whole genome for SVs predisposing to psoriasis is lacking.To investigate the association of SVs and psoriasis.Using imputation, we performed a genome-wide screen of SVs on five independent cohorts with 45 386 participants from the Han Chinese population. Fine-mapping analysis, genetic interaction analysis and RNA expression analysis were conducted to explore the mechanism of SVs.In total, we obtained 4535 SVs and identified two novel deletions [esv3608550, odds ratio (OR) 2·73 (P < 2·00 × 10-308 ); esv3608542, OR 0·47 (P = 7·40 × 10-28 )] at 6q21·33 (major histocompatibility complex), one novel Alu element insertion [esv3607339; OR 1·22 (P = 1·18 × 10-35 )] at 5q33·3 (IL12B) and confirmed one previously reported deletion [esv3587563; OR 1·30 (P = 9·52 × 10-60 )] at 1q21·2 (late cornified envelope) for psoriasis. Fine-mapping analysis including single-nucleotide polymorphisms (SNPs) and small insertions/deletions revealed that esv3608550 and esv3608542 were independently associated with psoriasis, and a novel independent SNP [rs9378188; OR, 1·65 (P = 3·46 × 10-38 )] was identified at 6q21·33. By genetic interaction analysis and RNA expression analysis, we speculate that the association of two deletions at 6q21·33 with psoriasis might relate to their influence on the expression of HLA-C.We have constructed the most comprehensive SV map for psoriasis thus far and enriched the genetic architecture and pathogenesis of psoriasis, and highlight the non-negligible impact of SVs on complex diseases.
Quadrivalent human papillomavirus vaccination and non-targeted infectious disease hospitalisation: Population-based self-controlled case series analysis
Authors: Anders Hviid, Anna Laksafoss
Journal: The Lancet Regional Health - Europe (2021)

Claims of non-live vaccines having deleterious effects on non-targeted infectious disease and mortality among females persists. The majority of the available evidence is from West Africa and consists of observational studies and the interpretation and implications are controversial. Results from high-income countries have been conflicting. We evaluated the association between a human papillomavirus vaccine, a non-live vaccine primarily administered to pre-adolescent females, and non-targeted infectious disease in a high-income country.We constructed a nationwide cohort of all Danish females 10 to 29 years of age during 2007 to 2016 with information on quadrivalent human papillomavirus vaccination status and infectious disease hospital contacts using national registers. Nested in this cohort, we conducted a self-controlled case series (SCCS) analysis comparing the rates of hospitalisation in a 90-day main risk period following the latest vaccination to reference period rates with adjustment for age and season.We included 853,879 Danish-born females aged 10 to 29 years of age during the 2007 to 2016 study period in the study cohort. We identified a total of 65,293 infectious disease hospitalisations among 50,599 participants; 46,955 cases among 37,003 participants vaccinated during follow-up were included in the SCCS analysis. There was no statistically significantly increased risk of infectious disease hospitalisation in the 90-day main risk period (rate ratio 0.92, 95% CI 0.88 to 0.95).Reassuringly, our large well-controlled study does not support that human papillomavirus vaccination increases the risk of non-targeted infectious disease in any clinically meaningful way. While our study does not provide evidence against adverse effects of other non-live vaccines, it does provide evidence against the claim that all non-live vaccines increase risk of heterologous infections in females.The study was supported by the Novo Nordisk Foundation.
Genomic insights into the origin, domestication and diversification of Brassica juncea
Authors: Lei Kang, Lunwen Qian, Ming Zheng, Liyang Chen, Hao Chen, Liu Yang, Liang You, Bin Yang, Mingli Yan, Yuanguo Gu, Tianyi Wang, Sarah-Veronica Schiessl, Hong An, Paul Blischak, Xianjun Liu, Hongfeng Lu, Dawei Zhang, Yong Rao, Donghai Jia, Dinggang Zhou, Huagui Xiao, Yonggang Wang, Xinghua Xiong, Annaliese S. Mason, J. Chris Pires, Rod J. Snowdon, Wei Hua, Zhongsong Liu
Journal: Nature Genetics (2021)

Abstract Despite early domestication around 3000 BC, the evolutionary history of the ancient allotetraploid species Brassica juncea (L.) Czern &amp; Coss remains uncertain. Here, we report a chromosome-scale de novo assembly of a yellow-seeded B. juncea genome by integrating long-read and short-read sequencing, optical mapping and Hi-C technologies. Nuclear and organelle phylogenies of 480 accessions worldwide supported that B. juncea is most likely a single origin in West Asia, 8,000–14,000 years ago, via natural interspecific hybridization. Subsequently, new crop types evolved through spontaneous gene mutations and introgressions along three independent routes of eastward expansion. Selective sweeps, genome-wide trait associations and tissue-specific RNA-sequencing analysis shed light on the domestication history of flowering time and seed weight, and on human selection for morphological diversification in this versatile species. Our data provide a comprehensive insight into the origin and domestication and a foundation for genomics-based breeding of B. juncea .
Integrative Analysis of Genome, 3D Genome, and Transcriptome Alterations of Clinical Lung Cancer Samples
Authors: Tingting Li, Ruifeng Li, Xuan Dong, Lin Shi, Miao Lin, Ting Peng, Pengze Wu, Yuting Liu, Xiaoting Li, Xuheng He, Xu Han, Bin Kang, Yinan Wang, Zhiheng Liu, Qing Chen, Yue Shen, Mingxiang Feng, Xiangdong Wang, Duojiao Wu, Jian Wang, Cheng Li
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract Genomic studies of cancer cell alterations, such as mutations, copy number variations (CNVs), and translocations, greatly promote our understanding of the genesis and development of cancers. However, the 3D genome architecture of cancers remains less studied due to the complexity of cancer genomes and technical difficulties. To explore the 3D genome structure in clinical lung cancer, we performed Hi-C experiments using paired normal and tumor cells harvested from patients with lung cancer, combining with RNA sequenceing analysis. We demonstrated the feasibility of studying 3D genome of clinical lung cancer samples with a small number of cells (1 × 104), compared the genome architecture between clinical samples and cell lines of lung cancer, and identified conserved and changed spatial chromatin structures between normal and cancer samples. We also showed that Hi-C data can be used to infer CNVs and point mutations in cancer. By integrating those different types of cancer alterations, we showed significant associations between CNVs, 3D genome, and gene expression. We propose that 3D genome mediates the effects of cancer genomic alterations on gene expression through altering regulatory chromatin structures. Our study highlights the importance of analyzing 3D genomes of clinical cancer samples in addition to cancer cell lines and provides an integrative genomic analysis pipeline for future larger-scale studies in lung cancer and other cancers.
To Deprescribe or Not to Deprescribe Aspirin—A <i>Clear Indication</i> Is the Challenge
Authors: Tania Ahuja, Arun Manmadhan, Jeffrey S. Berger
Journal: JAMA Internal Medicine (2021)

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Stool microRNA profiling— dumpster diving for a master marker?
Authors: Anna Heintz-Buschart
Journal: Gut (2021)

The human gut constitutes a complex, dynamic ecosystem of trillions of microbial cells whose impact on their host’s health has been recognised in recent years. Moreover, inconceivable changes in gut physiology and the subsequent adaptations of the microbiome may offer a route to early diagnosis of diseases that are increasingly more difficult to treat the later they are detected and to monitor health in general. However, the released microbial cells may not hold the only informative molecules in stool. In Gut , Tarallo et al 1 combine gut microbiome profiling with an analysis of the stool microRNA profiles of the same healthy individuals. They investigate relationships between the two and their combined potential as biomarkers.

There is great potential in improving one’s health by taking good care of one’s microbes. Hence, the microbiome’s interactions with the immune system, diet and a multitude of other host factors are a field of lively study. It is becoming clear that the microbiome modulates the health effects of life styles, and especially of diet. Mechanisms of this modulation are being discovered. Moreover, the intimate relationship of the microbiome with its host …
Immuno-regenerative biomaterials for in situ cardiovascular tissue engineering – Do patient characteristics warrant precision engineering?
Authors: B.J. de Kort, S.E. Koch, T.B. Wissing, M.M. Krebber, C.V.C. Bouten, A.I.P.M. Smits
Journal: Advanced Drug Delivery Reviews (2021)

In situ tissue engineering using bioresorbable material implants - or scaffolds - that harness the patient's immune response while guiding neotissue formation at the site of implantation is emerging as a novel therapy to regenerate human tissues. For the cardiovascular system, the use of such implants, like blood vessels and heart valves, is gradually entering the stage of clinical translation. This opens up the question if and to what extent patient characteristics influence tissue outcomes, necessitating the precision engineering of scaffolds to guide patient-specific neo-tissue formation. Because of the current scarcity of human in vivo data, herein we review and evaluate in vitro and preclinical investigations to predict the potential role of patient-specific parameters like sex, age, ethnicity, hemodynamics, and a multifactorial disease profile, with special emphasis on their contribution to the inflammation-driven processes of in situ tissue engineering. We conclude that patient-specific conditions have a strong impact on key aspects of in situ cardiovascular tissue engineering, including inflammation, hemodynamic conditions, scaffold resorption, and tissue remodeling capacity, suggesting that a tailored approach may be required to engineer immuno-regenerative biomaterials for safe and predictive clinical applicability.
Human and herpesvirus microRNAs in periodontal disease
Authors: Afsar R. Naqvi, Jørgen Slots
Journal: Periodontology 2000 (2021)

Abstract Periodontitis is a multi‐etiologic infection characterized clinically by pathologic loss of the periodontal ligament and alveolar bone. Herpesviruses and specific bacterial species are major periodontal pathogens that cooperate synergistically in producing severe periodontitis. Cellular immunity against herpesviruses and humoral immunity against bacteria are key periodontal host defenses. Genetic, epigenetic, and environmental factors are modifiers of periodontal disease severity. MicroRNAs are a class of noncoding, gene expression‐based, posttranscriptional regulatory RNAs of great importance for maintaining tissue homeostasis. Aberrant expression of microRNAs has been associated with several medical diseases. Periodontal tissue cells and herpesviruses elaborate several microRNAs that are of current research interest. This review attempts to conceptualize the role of periodontal microRNAs in the pathogenesis of periodontitis. The diagnostic potential of salivary microRNAs is also addressed. Employment of microRNA technology in periodontics represents an interesting new preventive and therapeutic possibility.
Identification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming
Authors: Giorgia De Simone, Francesco Andreata, Camille Bleriot, Valeria Fumagalli, Chiara Laura, José M. Garcia-Manteiga, Pietro Di Lucia, Stefano Gilotto, Xenia Ficht, Federico F. De Ponti, Elisa B. Bono, Leonardo Giustini, Gioia Ambrosi, Marta Mainetti, Paola Zordan, Alexandre P. Bénéchet, Micol Ravà, Svetoslav Chakarov, Federica Moalli, Marc Bajenoff, Luca G. Guidotti, Florent Ginhoux, Matteo Iannacone
Journal: Immunity (2021)

Kupffer cells (KCs) are highly abundant, intravascular, liver-resident macrophages known for their scavenger and phagocytic functions. KCs can also present antigens to CD8+ T cells and promote either tolerance or effector differentiation, but the mechanisms underlying these discrepant outcomes are poorly understood. Here, we used a mouse model of hepatitis B virus (HBV) infection, in which HBV-specific naive CD8+ T cells recognizing hepatocellular antigens are driven into a state of immune dysfunction, to identify a subset of KCs (referred to as KC2) that cross-presents hepatocellular antigens upon interleukin-2 (IL-2) administration, thus improving the antiviral function of T cells. Removing MHC-I from all KCs, including KC2, or selectively depleting KC2 impaired the capacity of IL-2 to revert the T cell dysfunction induced by intrahepatic priming. In summary, by sensing IL-2 and cross-presenting hepatocellular antigens, KC2 overcome the tolerogenic potential of the hepatic microenvironment, suggesting new strategies for boosting hepatic T cell immunity.
Carrier-free micellar CpG interacting with cell membrane for enhanced immunological treatment of HIV-1
Authors: Haejoo Kim, Wei Zhang, Juyoung Hwang, Eun-Koung An, Yeol Kyo Choi, Eunyoung Moon, Mark Loznik, Yang Hoon Huh, Andreas Herrmann, Minseok Kwak, Jun-O Jin
Journal: Biomaterials (2021)
Estimating clinical SARS-CoV-2 infectiousness in Vero E6 and primary airway epithelial cells
Authors: Manel Essaidi-Laziosi, Francisco Javier Perez Rodriguez, Nicolas Hulo, Frederique Jacquerioz, Laurent Kaiser, Isabella Eckerle
Journal: The Lancet Microbe (2021)

emphasises the importance of the cell lines used for SARS-CoV-2 culture and supports the use of models closely mimicking the in-vivo situation for better understanding of SARS-CoV-2 transmission risks.We declare no competing interests.
Supraclavicular and Axillary Lymphadenopathy Induced by COVID-19 Vaccination on 18F-Fluorthanatrace, 68Ga-DOTATATE, and 18F-Fluciclovine PET/CT
Authors: Devaki Shilpa Sudha Surasi, Lilie Lin, Gregory Ravizzini, Franklin Wong
Journal: Clinical Nuclear Medicine (2021)

COVID-19 vaccination has started in most countries, and postvaccination imaging is inevitable in the oncologic population. The immune response to the vaccination in the form of reactive lymphadenopathy has been well documented on 18F-FDG PET/CT. We present the imaging findings of 3 patients who have undergone non-FDG PET/CT imaging including 18F-fluorthanatrace, 68Ga-DOTATATE, and 18F-fluciclovine PET/CT. It is crucial to recognize the timing and laterality of immunization to avoid false-positive findings.
Cannabinoid Formulations and Delivery Systems: Current and Future Options to Treat Pain
Authors: Barbara Stella, Francesca Baratta, Carlo Della Pepa, Silvia Arpicco, Daniela Gastaldi, Franco Dosio
Journal: Drugs (2021)

The field of Cannabis sativa L. research for medical purposes has been rapidly advancing in recent decades and a growing body of evidence suggests that phytocannabinoids are beneficial for a range of conditions. At the same time impressing development has been observed for formulations and delivery systems expanding the potential use of cannabinoids as an effective medical therapy. The objective of this review is to present the most recent results from pharmaceutical companies and research groups investigating methods to improve cannabinoid bioavailability and to clearly establish its therapeutic efficacy, dose ranges, safety and also improve the patient compliance. Particular focus is the application of cannabinoids in pain treatment, describing the principal cannabinoids employed, the most promising delivery systems for each administration routes and updating the clinical evaluations. To offer the reader a wider view, this review discusses the formulation starting from galenic preparation up to nanotechnology approaches, showing advantages, limits, requirements needed. Furthermore, the most recent clinical data and meta-analysis for cannabinoids used in different pain management are summarized, evaluating their real effectiveness, in order also to spare opioids and improve patients' quality of life. Promising evidence for pain treatments and for other important pathologies are also reviewed as likely future directions for cannabinoids formulations.
Adaptive immune determinants of viral clearance and protection in mouse models of SARS-CoV-2
Authors: Benjamin Israelow, Tianyang Mao, Jonathan Klein, Eric Song, Bridget Menasche, Saad B. Omer, Akiko Iwasaki
Journal: Science Immunology (2021)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than 160 million infections and more than 3 million deaths worldwide. Although effective vaccines are currently being deployed, the adaptive immune determinants that promote viral clearance and confer protection remain poorly defined. Using mouse models of SARS-CoV-2, we demonstrate that both humoral and cellular adaptive immunity contribute to viral clearance in the setting of primary infection. Furthermore, we find that either convalescent mice or mice that receive mRNA vaccination are protected from both homologous infection and infection with a variant of concern, B.1.351. In addition, we find that this protection is largely mediated by antibody response and not cellular immunity. These results highlight the in vivo protective capacity of antibodies generated to both vaccine and natural infection.
Insufficiency of non-canonical PRC1 synergizes with JAK2V617F in the development of myelofibrosis
Authors: Daisuke Shinoda, Yaeko Nakajima-Takagi, Motohiko Oshima, Shuhei Koide, Kazumasa Aoyama, Atsunori Saraya, Hironori Harada, Bahityar Rahmutulla, Atsushi Kaneda, Kiyoshi Yamaguchi, Yoichi Furukawa, Haruhiko Koseki, Kazuya Shimoda, Tomoaki Tanaka, Goro Sashida, Atsushi Iwama
Journal: Leukemia (2021)
Alpha Satellite Insertion Close to an Ancestral Centromeric Region
Authors: Giuliana Giannuzzi, Glennis A Logsdon, Nicolas Chatron, Danny E Miller, Julie Reversat, Katherine M Munson, Kendra Hoekzema, Marie-Noëlle Bonnet-Dupeyron, Pierre-Antoine Rollat-Farnier, Carl A Baker, Damien Sanlaville, Evan E Eichler, Caroline Schluth-Bolard, Alexandre Reymond
Journal: Molecular Biology and Evolution (2021)

Human centromeres are mainly composed of alpha satellite DNA hierarchically organized as higher-order repeats (HORs). Alpha satellite dynamics is shown by sequence homogenization in centromeric arrays and by its transfer to other centromeric locations, for example, during the maturation of new centromeres. We identified during prenatal aneuploidy diagnosis by fluorescent in situ hybridization a de novo insertion of alpha satellite DNA from the centromere of chromosome 18 (D18Z1) into cytoband 15q26. Although bound by CENP-B, this locus did not acquire centromeric functionality as demonstrated by the lack of constriction and the absence of CENP-A binding. The insertion was associated with a 2.8-kbp deletion and likely occurred in the paternal germline. The site was enriched in long terminal repeats and located ∼10 Mbp from the location where a centromere was ancestrally seeded and became inactive in the common ancestor of humans and apes 20-25 million years ago. Long-read mapping to the T2T-CHM13 human genome assembly revealed that the insertion derives from a specific region of chromosome 18 centromeric 12-mer HOR array in which the monomer size follows a regular pattern. The rearrangement did not directly disrupt any gene or predicted regulatory element and did not alter the methylation status of the surrounding region, consistent with the absence of phenotypic consequences in the carrier. This case demonstrates a likely rare but new class of structural variation that we name "alpha satellite insertion." It also expands our knowledge on alphoid DNA dynamics and conveys the possibility that alphoid arrays can relocate near vestigial centromeric sites.
Mitochondrial links between brain aging and Alzheimer’s disease
Authors: Heather M. Wilkins, Russell H. Swerdlow
Journal: Translational Neurodegeneration (2021)

Abstract Advancing age is a major risk factor for Alzheimer’s disease (AD). This raises the question of whether AD biology mechanistically diverges from aging biology or alternatively represents exaggerated aging. Correlative and modeling studies can inform this question, but without a firm grasp of what drives aging and AD it is difficult to definitively resolve this quandary. This review speculates over the relevance of a particular hallmark of aging, mitochondrial function, to AD, and further provides background information that is pertinent to and provides perspective on this speculation.