tbuckley/cabot-search huggingface dataset:
Altered faecal microbiome and metabolome in IgG4-related sclerosing cholangitis and primary sclerosing cholangitis
Authors: Qiaoyan Liu, Bo Li, Yikang Li, Yiran Wei, Bingyuan Huang, Jubo Liang, Zhengrui You, You Li, Qiwei Qian, Rui Wang, Jun Zhang, Ruiling Chen, Zhuwan Lyu, Yong Chen, Mingxia Shi, Xiao Xiao, Qixia Wang, Qi Miao, Jing-Yuan Fang, Merrill Eric Gershwin, Min Lian, Xiong Ma, Ruqi Tang
Journal: Gut (2021)

Multiple clinical similarities exist between IgG4-related sclerosing cholangitis (IgG4-SC) and primary sclerosing cholangitis (PSC), and while gut dysbiosis has been extensively studied in PSC, the role of the gut microbiota in IgG4-SC remains unknown. Herein, we aimed to evaluate alterations of the gut microbiome and metabolome in IgG4-SC and PSC.We performed 16S rRNA gene amplicon sequencing of faecal samples from 135 subjects with IgG4-SC (n=34), PSC (n=37) and healthy controls (n=64). A subset of the samples (31 IgG4-SC, 37 PSC and 45 controls) also underwent untargeted metabolomic profiling.Compared with controls, reduced alpha-diversity and shifted microbial community were observed in IgG4-SC and PSC. These changes were accompanied by differences in stool metabolomes. Importantly, despite some common variations in the microbiota composition and metabolic activity, integrative analyses identified distinct host-microbe associations in IgG4-SC and PSC. The disease-associated genera and metabolites tended to associate with the transaminases in IgG4-SC. Notable depletion of Blautia and elevated succinic acid may underlie hepatic inflammation in IgG4-SC. In comparison, potential links between the microbial or metabolic signatures and cholestatic parameters were detected in PSC. Particularly, concordant decrease of Eubacterium and microbiota-derived metabolites, including secondary bile acids, implicated novel host-microbial metabolic pathways involving cholestasis of PSC. Interestingly, the predictive models based on metabolites were more effective in discriminating disease status than those based on microbes.Our data reveal that IgG4-SC and PSC possess divergent host-microbe interplays that may be involved in disease pathogenesis. These data emphasise the uniqueness of IgG4-SC.
The OncoMasTR Test Predicts Distant Recurrence in Estrogen Receptor–Positive, HER2-Negative Early-Stage Breast Cancer: A Validation Study in ABCSG Trial 8
Authors: Martin Filipits, Margaretha Rudas, Verena Kainz, Christian F. Singer, Florian Fitzal, Zsuzsanna Bago-Horvath, Richard Greil, Marija Balic, Peter Regitnig, Stefan Halper, Wolfgang Hulla, Daniel Egle, Stephen Barron, Tony Loughman, Des O'Leary, William M. Gallagher, Dominik Hlauschek, Michael Gnant, Peter Dubsky
Journal: Clinical Cancer Research (2021)

Abstract Purpose: To validate the clinical performance of the OncoMasTR Risk Score in the biomarker cohort of Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 8. Experimental Design: We evaluated the OncoMasTR test in 1,200 formalin-fixed, paraffin-embedded (FFPE) surgical specimens from postmenopausal women with estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative primary breast cancer with 0 to 3 involved lymph nodes in the prospective, randomized ABCSG Trial 8. Time to distant recurrence (DR) was analyzed by Cox models. Results: The OncoMasTR Risk Score categorized 850 of 1,087 (78.2%) evaluable patients as “low risk”. At 10 years, the DR rate for patients in the low-risk group was 5.8% versus 21.1% for patients in the high-risk group (P &amp;lt; 0.0001, absolute risk reduction 15.3%). The OncoMasTR Risk Score was highly prognostic for prediction of DR in years 0 to 10 in all patients [HR 1.91, 95% confidence interval (CI) 1.62–2.26, P &amp;lt; 0.0001; C-index 0.73], in patients that were node negative (HR 1.79, 95% CI, 1.43–2.24, P &amp;lt; 0.0001; C-index 0.72), and in patients with 1 to 3 involved lymph nodes (HR 1.93, 95% CI, 1.44–2.58, P &amp;lt; 0.0001; C-index 0.71). The OncoMasTR Risk Score provided significant additional prognostic information beyond clinical parameters, Ki67, Nottingham Prognostic Index, and Clinical Treatment Score. Conclusions: OncoMasTR Risk Score is highly prognostic for DR in postmenopausal women with ER-positive, HER2-negative primary breast cancer with 0 to 3 involved lymph nodes. In combination with prior validation studies, this fully independent validation in ABCSG Trial 8 provides level 1B evidence for the prognostic capability of the OncoMasTR Risk Score.
Publisher Correction: SARS-CoV-2 and HIV-1 — a tale of two vaccines
Authors: Barton F. Haynes
Journal: Nature reviews. Immunology (2021)

The sentence "Like SARS-CoV-2-neutralizing antibodies, HIV-1 non-neutralizing antibodies are easily induced by any of a number of HIV-1 Env monomers or open trimerics" should read "Like SARS-CoV-2-neutralizing antibodies, HIV-1 non-neutralizing antibodies are easily induced by any of a number of HIV-1 Env monomers or open trimers".This correction was missed during the proofing process and has now been corrected in the HTML and PDF versions of the article in order to ensure correct scientific terminology.
Evolutionary Sparse Learning for Phylogenomics
Authors: Sudhir Kumar, Sudip Sharma
Journal: Molecular Biology and Evolution (2021)

We introduce a supervised machine learning approach with sparsity constraints for phylogenomics, referred to as evolutionary sparse learning (ESL). ESL builds models with genomic loci-such as genes, proteins, genomic segments, and positions-as parameters. Using the Least Absolute Shrinkage and Selection Operator, ESL selects only the most important genomic loci to explain a given phylogenetic hypothesis or presence/absence of a trait. ESL models do not directly involve conventional parameters such as rates of substitutions between nucleotides, rate variation among positions, and phylogeny branch lengths. Instead, ESL directly employs the concordance of variation across sequences in an alignment with the evolutionary hypothesis of interest. ESL provides a natural way to combine different molecular and nonmolecular data types and incorporate biological and functional annotations of genomic loci in model building. We propose positional, gene, function, and hypothesis sparsity scores, illustrate their use through an example, and suggest several applications of ESL. The ESL framework has the potential to drive the development of a new class of computational methods that will complement traditional approaches in evolutionary genomics, particularly for identifying influential loci and sequences given a phylogeny and building models to test hypotheses. ESL's fast computational times and small memory footprint will also help democratize big data analytics and improve scientific rigor in phylogenomics.
Induction of apoptosis in NK/T-cell lymphoma cell line, Hank-1 by genistein
Authors: Young A. Kim, Yoon-Kyung Jeon, Sung-Shin Park, Ji-Eun Kim, Yong-Nyun Kim, Chul-Woo Kim
Journal: Cancer Research (2004)

4874  Extranodal NK/T-cell lymphoma is more common among Orientals and recognized as a distinctive clinicopathologic entity. This lymphoma shows a highly aggressive clinical course and development of an effective chemotherapeutic modality is strongly advocated. Hank-1 is an NK/T-cell lymphoma cell line, which is derived from nasal type NK/T-cell lymphoma and a good candidate for the study of molecular characteristics of NK/T-cell lymphomas. Genistein is a major isoflavone of soybeans and has been documented to induce apoptosis in a variety of cells but there is no report of its effect on NK/T-cell lymphomas. In the present study, we investigated the effect and mechanism of action of genistein on Hank-1, NK/T-cell lymphoma cells. We found that genistein inhibits cell growth and induces apoptotic processes in Hank-1 cells but not in peripheral blood NK cells. Genistein treatment induced the reduction of mitochondrial membrane potential, the release of cytochrome c and apoptosis inducing factor from the mitochondria. Bcl-xL protein expression was decreased by genistein treatment whereas expression levels of Bax, Bid and Bcl-2 remained unchanged. Z-VAD-fmk, a general caspase inhibitor treatment significantly blocked genistein-induced apoptosis in these cells but z-DEVD-fmk, caspase 3 inhibitor did not. Western blot and enzyme activity assay revealed that caspase 3, -8, and –9 were not activated during genistein-induced apoptosis. These results collectively indicate that a post-mitochondrial caspase–dependent mechanism is involved in genistein-induced apoptosis. Moreover, genistein is a natural tyrosine kinase inhibitor and genistein treatment in Hank-1 cells significantly reduced Akt phosphorylation, which plays a critical role in controlling cell survival and apoptosis. These results suggest that genistein-induced apoptosis in Hank-1, NK/T-cell lymphoma cells occurs through partly caspase-dependent, but caspase 3-independent manner and via Akt signaling pathway. Therefore, genistein may be a potentially effective therapeutic agent against highly aggressive NK/T-cell lymphoma.
MAGE‐C3 promotes cancer metastasis by inducing epithelial‐mesenchymal transition and immunosuppression in esophageal squamous cell carcinoma
Authors: Qingnan Wu, Weimin Zhang, Yan Wang, Qingjie Min, Hongyue Zhang, Dezuo Dong, Qimin Zhan
Journal: Cancer Communications (2021)

Abstract Background Evading immune surveillance is necessary for tumor metastasis. Thus, there is an urgent need to better understand the interaction between metastasis and mechanisms of tumor immune evasion. In this study, we aimed to clarify a novel mechanism that link tumor metastasis and immunosuppression in the development of esophageal squamous cell carcinoma (ESCC). Methods The expression of melanoma‐associated antigen C3 (MAGE‐C3) was detected using immunohistochemistry. Transwell assays were used to evaluate the migration and invasion ability of esophageal squamous cell carcinoma (ESCC) cells. Metastasis assays in mice were used to evaluate metastatic ability in vivo . Lymphocyte‐mediated cytotoxicity assays were performed to visualize the immune suppression function on tumor cells. RNA sequencing was performed to identify differentially expressed genes between MAGE‐C3 overexpressing ESCC cells and control cells. Gene ontology (GO) enrichment analyses was performed to identify the most altered pathways influenced by MAGE‐C3. The activation of the interferon‐γ (IFN‐γ) pathway was analyzed using Western blotting, GAS luciferase reporter assays, immunofluorescence, and flow cytometry. The role of MAGE‐C3 in the IFN‐γ pathway was determined by Western blotting and immunoprecipitation. Furthermore, immunohistochemistry and flow cytometry analysis monitored the changes of infiltrated T cell populations in murine lung metastases. Results MAGE‐C3 was overexpressed in ESCC tissues. High expression of MAGE‐C3 had a significant association with the risk of lymphatic metastasis and poor survival in patients with ESCC. Functional experiments revealed that MAGE‐C3 promoted tumor metastasis by activating the epithelial‐mesenchymal transition (EMT). MAGE‐C3 repressed antitumor immunity and regulated cytokine secretion of T cells, implying an immunosuppressive function. Mechanistically, MAGE‐C3 facilitated IFN‐γ signaling and upregulated programmed cell death ligand 1 (PD­L1) by binding with IFN‐γ receptor 1 (IFNGR1) and strengthening the interaction between IFNGR1 and signal transducer and activator of transcription 1 (STAT1). Interestingly, MAGE‐C3 displayed higher tumorigenesis in immune‐competent mice than in immune‐deficient nude mice, confirming the immunosuppressive role of MAGE‐C3. Furthermore, mice bearing MAGE‐C3‐overexpressing tumors showed worse survival and more lung metastases with decreased CD8 + infiltrated T cells and increased programmed cell death 1 (PD‐1) + CD8 + infiltrated T cells. Conclusion MAGE‐C3 enhances tumor metastasis through promoting EMT and protecting tumors from immune surveillance, and could be a potential prognostic marker and therapeutic target.
Prognostication of Asymptomatic Penetrating Aortic Ulcers: A Modern Approach
Authors: Charles DeCarlo, Christopher A. Latz, Laura T. Boitano, Young Kim, Adam Tanious, Samuel I. Schwartz, Rushad Patell, Jahan Mohebali, Anahita Dua
Journal: Circulation (2021)

Literature detailing the natural history of asymptomatic penetrating aortic ulcers (PAUs) is sparse and lacks long-term follow-up. This study sought to determine the rate of asymptomatic PAU growth over time and adverse events from asymptomatic PAU.A cohort of patients with asymptomatic PAU from 2005 to 2020 was followed. One ulcer was followed per patient. Primary end points were change in size over time and the composite of symptoms, radiographic progression, rupture, and intervention; cumulative incidence function estimated the incidence of the composite outcome. Ulcer size and rate of change were modeled using a linear mixed-effects model. Patient and anatomic factors were evaluated as potential predictors of the outcomes.There were 273 patients identified. The mean age was 75.5±9.6 years; 66.4% were male. The majority of ulcers were in the descending thoracic aorta (53.9%), followed by abdominal aorta (41.4%) and aortic arch (4.8%). Fusiform aneurysmal disease was present in 21.6% of patients at a separate location; 2.6% had an associated intramural hematoma; 23.6% had at least 1 other PAU. Symptoms developed in 1 patient who ruptured; 8 patients (2.9%) underwent an intervention for PAU (1 for rupture, 2 for radiographic progression, 5 for size/growth) at a median of 3.1 years (interquartile range, 1.0-6.5) after diagnosis. Five- and 10-year cumulative incidence of the primary outcome, adjusted for competing risk of death, was 3.6% (95% CI, 1.6%-6.9%) and 6.5% (95% CI, 3.1%-11.4%), respectively. For 191 patients with multiple computed tomography scans (760 total computed tomographies) with a median radiographic follow-up of 3.50 years (interquartile range, 1.20-6.63 years), mean initial ulcer width, ulcer depth, and total diameter were 13.6 mm, 8.5 mm, and 31.4 mm, respectively. A small but statistically significant change over time was observed for ulcer width (0.23 mm/y) and total diameter (0.24 mm/y); ulcer depth did not significantly change over time. Hypertension, hyperlipidemia, diabetes, initial ulcer width >20 mm, thrombosed PAU, and associated saccular aneurysm were associated with larger changes in ulcer size over time; however, the magnitude of difference was small, ranging from 0.4 to 1.9 mm/y.Asymptomatic PAU displayed minimal growth and infrequent complications including rupture. Asymptomatic PAU may be conservatively managed with serial imaging and risk factor modification.
Endoscopic biliary access after pancreaticoduodenectomy following Imanaga’s procedure
Authors: Thomas Lambin, Jérôme Rivory, Mustapha Adham, Florian Rostain, Thierry Ponchon, Pierre Lafeuille, Mathieu Pioche
Journal: Endoscopy (2021)

Endoscopic retrograde cholangiopancreatography (ERCP) is the technique of choice to drain the main biliary duct with a high degree of technical success [1]. However, in the case of a pancreaticoduodenectomy, endoscopic biliary access can be challenging. Imanaga’s procedure is a pylorus-preserving pancreaticoduodenectomy procedure with the duodenojejunal, pancreaticojejunal, and hepaticojejunal anastomosis reconstructed in that order on the jejunal limb ([Fig. 1]) [2] [3]. This procedure is thought to allow easier endoscopic access to the hepaticojejunal anastomosis [4].
Outbreaks of COVID-19 variants in US prisons: a mathematical modelling analysis of vaccination and reopening policies
Authors: Theresa Ryckman, Elizabeth T Chin, Lea Prince, David Leidner, Elizabeth Long, David M Studdert, Joshua A Salomon, Fernando Alarid-Escudero, Jason R Andrews, Jeremy D Goldhaber-Fiebert
Journal: The Lancet Public Health (2021)

Residents of prisons have experienced disproportionate COVID-19-related health harms. To control outbreaks, many prisons in the USA restricted in-person activities, which are now resuming even as viral variants proliferate. This study aims to use mathematical modelling to assess the risks and harms of COVID-19 outbreaks in prisons under a range of policies, including resumption of activities.
Training the specialised youth athlete: a supportive classification model to keep them playing
Authors: Neeru Jayanthi, Heather Saffel, Tim Gabbett
Journal: British Journal of Sports Medicine (2021)

Sport specialisation, the year-round training in a single sport at the exclusion of other sports, is seen in approximately 30% of youth athletes.1 To reduce the risk of overuse injury and burnout, numerous organisations have recommended against such sport specialisation, particularly prior to adolescence.2 While some studies have suggested that sport specialisation is an independent risk factor for overuse injury,1 3 others consider training volume to be the underlying problem.4 However, single-sport training is a successful path for some and ‘it is possible to have positive experiences as a specialised athlete’.5

Many athletes continue to specialise, an accumulation of sport-specific practice hours is likely necessary to achieve elite level status,6 rather than just recommending multisport play. While sport specialisation and intense training may be discouraged in most youth athletes, there is still a need for a supportive model that (1) encourages training loads for the uninjured, specialised youth athlete and (2) adjusts training load progressions based on their individual load tolerance.

Recently, three simple concepts, of the ‘floor’, ‘ceiling’ and time have been described to safely progress athletes to peak performance.6 The floor represents …
Going with the Flow: The Promise of Plasma-Only Circulating Tumor DNA Assays
Authors: Alisha Bent, Scott Kopetz
Journal: Clinical Cancer Research (2021)

Abstract Circulating tumor DNA (ctDNA) has emerged as a noninvasive diagnostic and prognostic tool for colorectal cancer. Here, we discuss studies that evaluate the ability of plasma-only ctDNA assays to detect minimal residual disease and the potential benefit of integration of methylation into ctDNA assays. See related articles by Parikh et al., p. 5586 and Taieb et al., p. 5638
Optimizing Iron Overload Screening in a Pediatric Center for Cancer and Blood Disorders
Authors: Holly Pacenta, Rebecca Coughlin, Shelby Winzent, Joanne M. Hilden, Dianne Thornhill, Brian R. Branchford, Kelly Maloney, Nuechterlein Brandon, Amy Keating, Taizo Allen Nakano, Roger Giller, Christopher Michael McKinney
Journal: Blood (2017)
Case 24-2021: A 63-Year-Old Woman with Fever, Sore Throat, and Confusion
Authors: Robert H. Goldstein, William A. Mehan, Bailey Hutchison, Gregory K. Robbins
Journal: New England Journal of Medicine (2021)

A 63-year-old woman with hypertension was admitted during the Covid-19 pandemic because of fever, headache, sore throat, and confusion. She also reported a "lump" in the neck. Laboratory evaluation revealed lymphopenia and elevated levels of aspartate aminotransferase and alanine aminotransferase. A diagnostic test was performed.
RdRp or RT, That is the Question
Authors: Mahtab Peyambari, Shengxi Guan, Marilyn J Roossinck
Journal: Molecular Biology and Evolution (2021)

The RNA-dependent RNA polymerase (RdRp) of all known double-stranded RNA viruses is located within the viral particle and is responsible for the transcription and replication of the viral genome. Through an RT-PCR assay, we determined that purified virions, in vitro translated RdRp proteins, and purified recombinant RdRp proteins of partitiviruses also have reverse transcriptase (RT) function. We show that partitivirus RdRps 1) synthesized DNA from homologous and heterologous dsRNA templates; 2) are active using both ssRNA and dsRNA templates; and 3) are active at lower temperatures compared to an optimal reaction temperature of commercial RT enzymes. This finding poses an intriguing question: why do partitiviruses, with dsRNA genomes, have a polymerase with RT functions? In comparison, 3Dpol, the RdRp of poliovirus, did not show any RT activity. Our findings lead us to propose a new evolutionary model for RNA viruses where the RdRp of dsRNA viruses could be the ancestor of RdRps.
The Influence of Front-of-Package Nutrition Labeling on Consumer Behavior and Product Reformulation
Authors: Christina A. Roberto, Shu Wen Ng, Montserrat Ganderats-Fuentes, David Hammond, Simon Barquera, Alejandra Jauregui, Lindsey Smith Taillie
Journal: Annual Review of Nutrition (2021)

Countries worldwide have implemented mandatory or voluntary front-of-package nutrition labeling systems. We provide a narrative review of (a) real-world evaluations of front-of-package nutrition labels that analyze objective sales data and (b) studies that objectively assess product reformulation in response to a front-of-package nutrition label implementation. We argue that there is sufficient scientific evidence to recommend that governments implement mandatory front-of-package nutrition labeling systems to improvepopulation health. We also present a conceptual framework to describe front-of-package label influence and provide recommendations for the optimal label design, emphasizing that labeling systems should be highly visible and salient, be simple and easy to understand, leverage automatic associations, and integrate informational and emotional messaging. The existing research suggests that Guideline Daily Amount labels should be avoided and that the Health Star Rating and Nutri-Score systems are promising but that systems with warning labels like the one in Chile are likely to produce the largest public health benefits.
Association of 1 Vaping Session With Cellular Oxidative Stress in Otherwise Healthy Young People With No History of Smoking or Vaping
Authors: Theodoros Kelesidis, Elizabeth Tran, Randy Nguyen, Yuyan Zhang, Grace Sosa, Holly R. Middlekauff
Journal: JAMA Pediatrics (2021)

This randomized clinical crossover trial evaluates the association of a single session of electronic cigarette vaping with cellular oxidative stress in healthy young people who do not smoke compared with individuals with long-term tobacco cigarette or electronic cigarette use.
Gender differences in countries' adaptation to societal ageing: an international cross-sectional comparison
Authors: Cynthia Chen, Kenwin Maung, John W Rowe, John W Rowe, Toni Antonucci, Lisa Berkman, Axel Börsch-Supan, Laura Carstensen, Dana P Goldman, Linda Fried, Frank Furstenberg, James Jackson, Martin Kohli, Jay Olshansky, David Rehkopf, John Rother, Julie Zissimopoulos
Journal: The Lancet Healthy Longevity (2021)