tbuckley/cabot-search huggingface dataset:
Integrating Genomic and Transcriptomic Data to Reveal Genetic Mechanisms Underlying Piao Chicken Rumpless Trait
Authors: Yun-Mei Wang, Saber Khederzadeh, Shi-Rong Li, Newton Otieno Otecko, David M. Irwin, Mukesh Thakur, Xiao-Die Ren, Ming-Shan Wang, Dong-Dong Wu, Ya-Ping Zhang
Journal: Genomics Proteomics & Bioinformatics (2021)

Piao chicken, a rare Chinese native poultry breed, lacks primary tail structures, such as pygostyle, caudal vertebra, uropygial gland, and tail feathers. So far, the molecular mechanisms underlying tail absence in this breed remain unclear. In this study, we comprehensively employed comparative transcriptomic and genomic analyses to unravel potential genetic underpinnings of rumplessness in Piao chicken. Our results reveal many biological factors involved in tail development and several genomic regions under strong positive selection in this breed. These regions contain candidate genes associated with rumplessness, including Irx4, Il18, Hspb2, and Cryab. Retrieval of quantitative trait loci (QTL) and gene functions implies that rumplessness might be consciously or unconsciously selected along with the high-yield traits in Piao chicken. We hypothesize that strong selection pressures on regulatory elements might lead to changes in gene activity in mesenchymal stem cells of the tail bud. The ectopic activity could eventually result in tail truncation by impeding differentiation and proliferation of the stem cells. Our study provides fundamental insights into early initiation and genetic basis of the rumpless phenotype in Piao chicken.
Abstract 15389: Effect of Icosapent Ethyl on Changes in Coronary Plaque Characteristics at 9 Months in Patients With Elevated Triglycerides on Statin Therapy: Insights From EVAPORATE
Authors: Suvasini Lakshmanan, Andrew Buckler, Deepak L Bhatt, April Kinninger, Ilana Golub, Joseph B Muhlestein, Viet T Le, Heidi T May, Kashif Shaikh, Chandana Shekar, Sion K Roy, John Tayek, John R Nelson, Matthew J Budoff
Journal: Circulation (2020)

Background: Residual cardiovascular (CV) risk persists despite statin therapy. In REDUCE-IT, icosapent ethyl (IPE) reduced total CV events by 30%, but the mechanisms of benefit are not fully understood. The EVAPORATE trial evaluated the effects of IPE as adjunct to statins on adverse atherosclerotic plaque characteristics by CCTA. Here we use a novel software validated using histology to evaluate the effect of IPE on vulnerable plaque features. Methods: The EVAPORATE trial randomized statin-treated patients, with high TG (135-499 mg/dL), and known atherosclerosis to IPE 4 g/d or placebo. Plaque characteristics including lipid rich necrotic core (LRNC), fibrous cap thickness, and intraplaque hemorrhage (IPH) were assessed using vascuCAP ® (Elucid Bioimaging Inc., Boston, MA). Per-patient multivariable models robust with respect to physiological variation were used to evaluate plaque progression. Results: A total of 60 patients had interpretable images. Relative to placebo, patients on IPE demonstrated decreased wall volume (-7.2 vs. +28.4 mm 3 ), LRNC (-1.4 vs. +9.7 mm 3 ), and IPH (-0.02 vs. +0.3 mm 3 ), as well as increased cap thickness (+100 vs. -290 microns), indicating a migration to more stable phenotypes (p&gt;0.05).Statistical significance was achieved when incorporated into an optimized neural network model of lipid-rich phenotype (p = 0.04), AUROC=0.7[0.63,0.77], sensitivity=0.66[0.59,0.74], specificity=0.64 [0.56,0.72], and Cohen’s kappa=0.3 [0.19,0.41]. Operating points when used as a per-patient measure of response are presented in Figure 1. Conclusions: This study demonstrated that IPE, when added to statin therapy, is associated with reduction in vulnerable plaque, moving patients to a more stable plaque phenotype.
Expert Knowledge, Attitudes, and Practices in Management of Hidradenitis Suppurativa Pain
Authors: Mark J. Jedrzejczak, John R. Ingram, Michelle A. Lowes, Haley B. Naik, Anne Marie McKenzie-Brown, Suephy C. Chen, Lauren A. V. Orenstein
Journal: JAMA Dermatology (2021)

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that may cause recurrent scarring abscesses and tunnels and may lead to worse quality of life and greater pain than most dermatologic diseases.1 Patients rate HS pain as the most important symptom,2 yet its mechanism is unknown. Approved biologics only modestly decrease HS pain, and most patients live with moderate or worse pain.3 Although international guidelines recommend measuring HS pain,4 therapeutic recommendations are sparse.5 Because expert approaches to HS pain remain poorly described, this study aimed to characterize specialists’ knowledge, attitudes, and practices.
Complement activation promoted by the lectin pathway mediates C3aR-dependent sarcoma progression and immunosuppression
Authors: Elena Magrini, Sabrina Di Marco, Sarah N. Mapelli, Chiara Perucchini, Fabio Pasqualini, Alessia Donato, Maria de la Luz Guevara Lopez, Roberta Carriero, Andrea Ponzetta, Piergiuseppe Colombo, Ferdinando Cananzi, Domenico Supino, Edimara S. Reis, Clelia Peano, Antonio Inforzato, Sebastien Jaillon, Andrea Doni, John D. Lambris, Alberto Mantovani, Cecilia Garlanda
Journal: Nature Cancer (2021)
Muscle Krüppel-like factor 15 regulates lipid flux and systemic metabolic homeostasis
Authors: Liyan Fan, David R. Sweet, Domenick A. Prosdocimo, Vinesh Vinayachandran, Ernest R. Chan, Rongli Zhang, Olga Ilkayeva, Yuan Lu, Komal S. Keerthy, Chloe E. Booth, Christopher B. Newgard, Mukesh K. Jain
Journal: Journal of Clinical Investigation (2021)

Skeletal muscle is a major determinant of systemic metabolic homeostasis that plays a critical role in glucose metabolism and insulin sensitivity. By contrast, despite being a major user of fatty acids, and evidence that muscular disorders can lead to abnormal lipid deposition (e.g., nonalcoholic fatty liver disease in myopathies), our understanding of skeletal muscle regulation of systemic lipid homeostasis is not well understood. Here we show that skeletal muscle Krüppel-like factor 15 (KLF15) coordinates pathways central to systemic lipid homeostasis under basal conditions and in response to nutrient overload. Mice with skeletal muscle-specific KLF15 deletion demonstrated (a) reduced expression of key targets involved in lipid uptake, mitochondrial transport, and utilization, (b) elevated circulating lipids, (c) insulin resistance/glucose intolerance, and (d) increased lipid deposition in white adipose tissue and liver. Strikingly, a diet rich in short-chain fatty acids bypassed these defects in lipid flux and ameliorated aspects of metabolic dysregulation. Together, these findings establish skeletal muscle control of lipid flux as critical to systemic lipid homeostasis and metabolic health.
Balancing Watching vs Waiting During Imaging Surveillance of Small Abdominal Aortic Aneurysms
Authors: Gloria Y. Kim, Matthew A. Corriere
Journal: JAMA Surgery (2021)

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The Association of Tumor Burden by 18F-FDG PET/CT and Survival in Vulvar Carcinoma
Authors: Kgomotso M.G. Mokoala, Ismaheel O. Lawal, Thabo Lengana, Gbenga O. Popoola, Tebatso M.G. Boshomane, Neo P. Mokgoro, Mariza Vorster, Mike M. Sathekge
Journal: Clinical Nuclear Medicine (2021)

The aim of this study was to assess the impact of 18F-FDG PET/CT metabolic parameters obtained at initial staging of vulva carcinoma on survival in women with and without HIV infection.
A unique subset of glycolytic tumour-propagating cells drives squamous cell carcinoma
Authors: Jee-Eun Choi, Carlos Sebastian, Christina M. Ferrer, Caroline A. Lewis, Moshe Sade-Feldman, Thomas LaSalle, Anna Gonye, Begona G. C. Lopez, Walid M. Abdelmoula, Michael S. Regan, Murat Cetinbas, Gloria Pascual, Gregory R. Wojtkiewicz, Giorgia G. Silveira, Ruben Boon, Kenneth N. Ross, Itay Tirosh, Srinivas V. Saladi, Leif W. Ellisen, Ruslan I. Sadreyev, Salvador Aznar Benitah, Nathalie Y. R. Agar, Nir Hacohen, Raul Mostoslavsky
Journal: Nature Metabolism (2021)
Exploring the structural distribution of genetic variation in SARS-CoV-2 with the COVID-3D online resource (vol 52, pg 999, 2020)
Authors: Stephanie Portelli, Moshe Olshansky, Carlos Hm Rodrigues, Elston N D'Souza, Yoochan Myung, Michael Silk, Azadeh Alavi, Douglas Ev Pires, David B Ascher
Journal: Nature Genetics (2021)
1,N6-ethenodeoxyadenosine,a lipid peroxidation induced DNA adduct in alcoholic liver disease
Authors: Jagadeesan Nair, Alexander Frank, Claudia Haas, Helmut K. Seitz, Helmut Bartsch
Journal: Cancer Research (2004)

1967  Increased oxidative stress and lipid peroxidation (LPO) are implicated in multistage carcinogenesis. LPO-derived reactive hydroxyalkenals can form promutagenic exocyclic etheno-DNA adducts in vivo. Such DNA damage was found to be increased in the liver of patients with cancer prone metal storage diseases, primary hemochromatosis and Wilson’s disease. In non- endemic areas of hepatitis B virus infection, alcohol abuse is one of the main cause of liver cancer which is preceded by alcoholic fatty liver and fibrosis. We have investigated the levels of 1,N6-ethenodeoxyadenosine (edA) in human liver samples obtained from patients diagnosed with alcohol induced fatty liver and fibrosis and then compared with primary hemochromatosis and Wilson’s disease. Using an immunohistochemical method (Yang et al., 2000), the relative mean pixel intensity of randomly selected nuclei was measured by imaging software; positively stained cell nuclei (arbitrary mean pixel intensity > 0.5) were counted. Prevalence of edA (%) was calculated from the ratio: number of positively stained cell nuclei over total number of cells counted. When compared to normal livers (3.1%), the % prevalence (means) was significantly higher (p
Mutations in the IFNγ-JAK-STAT Pathway Causing Resistance to Immune Checkpoint Inhibitors in Melanoma Increase Sensitivity to Oncolytic Virus Treatment
Authors: Tan-Trieu Nguyen, LeeAnn Ramsay, Mozhdeh Ahanfeshar-Adams, Mathieu Lajoie, Dirk Schadendorf, Tommy Alain, Ian R. Watson
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Next-generation sequencing studies and CRISPR-Cas9 screens have established mutations in the IFNγ-JAK-STAT pathway as an immune checkpoint inhibitor (ICI) resistance mechanism in a subset of patients with melanoma. We hypothesized ICI resistance mutations in the IFNγ pathway would simultaneously render melanomas susceptible to oncolytic virus (OV) therapy. Experimental Design: Cytotoxicity experiments were performed with a number of OVs on a matched melanoma cell line pair generated from a baseline biopsy and a progressing lesion with complete JAK2 loss from a patient that relapsed on anti-PD-1 therapy, in melanoma lines following JAK1/2 RNA interference (RNAi) and pharmacologic inhibition and in Jak2 knockout (KO) B16-F10 mouse melanomas. Furthermore, we estimated the frequency of genetic alterations in the IFNγ-JAK-STAT pathway in human melanomas. Results: The melanoma line from an anti-PD-1 progressing lesion was 7- and 22-fold more sensitive to the modified OVs, herpes simplex virus 1 (HSV1-dICP0) and vesicular stomatitis virus (VSV-Δ51), respectively, compared with the line from the baseline biopsy. RNAi, JAK1/2 inhibitor studies, and in vivo studies of Jak2 KOs B16-F10 melanomas revealed a significant increase in VSV-Δ51 sensitivity with JAK/STAT pathway inhibition. Our analysis of The Cancer Genome Atlas data estimated that approximately 11% of ICI-naïve cutaneous melanomas have alterations in IFNγ pathway genes that may confer OV susceptibility. Conclusions: We provide mechanistic support for the use of OVs as a precision medicine strategy for both salvage therapy in ICI-resistant and first-line treatment in melanomas with IFNγ-JAK-STAT pathway mutations. Our study also supports JAK inhibitor–OV combination therapy for treatment-naïve melanomas without IFN signaling defects. See related commentary by Kaufman, p. 3278
County‐Level Variation in Hepatitis C Virus Mortality and Trends in the United States, 2005‐2017
Authors: Eric W. Hall, Sarah Schillie, Adam S. Vaughan, Jeb Jones, Heather Bradley, Ben Lopman, Eli S. Rosenberg, Patrick S. Sullivan
Journal: Hepatology (2021)

BACKGROUND AND AIMS Since 2013, the national hepatitis C virus (HCV) death rate has steadily declined, but this decline has not been quantified or described on a local level. APPROACH AND RESULTS We estimated county‐level HCV death rates and assessed trends in HCV mortality from 2005 to 2013 and from 2013 to 2017. We used mortality data from the National Vital Statistics System and used a Bayesian multivariate space–time conditional autoregressive model to estimate age‐standardized HCV death rates from 2005 through 2017 for 3,115 U.S. counties. Additionally, we estimated county‐level, age‐standardized rates for persons &lt;40 and 40+ years of age. We used log‐linear regression models to estimate the average annual percent change in HCV mortality during periods of interest and compared county‐level trends with national trends. Nationally, the age‐adjusted HCV death rate peaked in 2013 at 5.20 HCV deaths per 100,000 persons (95% credible interval [CI], 5.12, 5.26) before decreasing to 4.34 per 100,000 persons (95% CI, 4.28, 4.41) in 2017 (average annual percent change = −4.69; 95% CI, −5.01, −4.33). County‐level rates revealed heterogeneity in HCV mortality (2017 median rate = 3.6; interdecile range, 2.19, 6.77), with the highest rates being concentrated in the West, Southwest, Appalachia, and northern Florida. Between 2013 and 2017, HCV mortality decreased in 80.0% (n = 2,274) of all U.S. counties with a reliable trend estimate, with 25.8% (n = 803) of all counties experiencing a decrease larger than the national decline. CONCLUSIONS Although many counties have experienced a shift in HCV mortality trends since 2013, the magnitude and composition of that shift have varied by place. These data provide a better understanding of geographic differences in HCV mortality and can be used by local jurisdictions to evaluate HCV mortality in their areas relative to surrounding areas and the nation.
Serum potassium and outcomes in heart failure with preserved ejection fraction: a post‐hoc analysis of the <scp>PARAGON‐HF</scp> trial
Authors: João Pedro Ferreira, Brian L. Claggett, Jiankang Liu, Akshay S. Desai, Marc A. Pfeffer, Inder S. Anand, Dirk J. van Veldhuisen, Lars Kober, John G.F. Cleland, Jean L. Rouleau, Milton Packer, Michael R. Zile, Victor C. Shi, Martin P. Lefkowitz, Sanjiv J. Shah, Orly Vardeny, Faiez Zannad, Scott D. Solomon, John J.V. McMurray
Journal: European Journal of Heart Failure (2021)
Exploring the multifunctional role of melatonin in regulating autophagy and sleep to mitigate Alzheimer’s disease neuropathology
Authors: Md. Farhad Hossain, Ni Wang, Ruijun Chen, Siwen Li, Jaydeep Roy, Md. Giash Uddin, Zhong Li, Lee Wei Lim, You-Qiang Song
Journal: Ageing Research Reviews (2021)
Abstract PS13-12: Apatinib combined with taxanes and platinum neoadjuvant chemotherapy for patients with triple-negative and HER2-positive breast cancer: A multicenter, randomized, open-label, phase II trial
Authors: Yunjiang Liu, Xiangmei Zhang, Li Wang, Miao Cao, Shuo Zhang, Hui Zhang, Yarong Zhou, Jintian Wang
Journal: Cancer Research (2021)

Abstract Background: Apatinib, a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR2), has demonstrated a promising efficacy in patients with metastatic breast cancer. For triple-negative and HER2-positive subtypes, increasing the pathological complete response (pCR) of neoadjuvant therapy may benefit their clinical outcomes. Here, we assessed whether the combination of Apatinib with neoadjuvant chemotherapy elevate the pCR rate in locally advanced breast cancer. Method: In this multicenter, open-label trial, we randomized 53 patients into TP neoadjuvant chemotherapy (docetaxel 75 mg/m2 or nab-paclitaxel 260 mg/m2 or paclitaxel liposome 175 mg/m2 day 1, and carboplatin AUC=6 or cisplatin 75 mg/m2 or lobaplatin 30 mg/m2 day 1), or combined with apatinib (500mg day 1-21) . Trastuzumab was added to neoadjuvant therapy in HER2-positive subtype. Six cycles were repeated every 3 weeks. Results: In total patients with stage IIb-IIIc triple-negative and HER2-positive breast cancer, the addition of apatinib to TP neoadjuvant chemotherapy (Apa+TP) significantly increased the pCR rate (70.8%, 17/24), compared with TP along (41.4%, 12/29), P=0.032. When separating patients into triple-negative (Apa+TP 66.7% (8/12) vs. TP 42.9% (3/7)) and HER2-positve (Apa+TP 75% (9/12) vs. TP 40.9% (9/22)) subtypes, the effect of apatinib on pCR was also improved though no significant differences were found (P=0.377; P=0.080 separately) compared with control group. The most common Grade 3-4 adverse events (AE) included hypertension (Apa+TP 12.5% vs. TP 0%, P=0.173), hand-foot syndrome (Apa+TP 8.3% vs. TP 0%, P=0.389) and erythra (Apa+TP 4.2% vs. TP 0%, P=0.924). No significant differences of toxic effects were found between Apa+TP and control group. Conclusion: Apatinib combined with TP neoadjuvant chemotherapy significantly increased the pCR rate in patients with locally advanced triple-negative and HER2-positive breast cancer, indicating an applicable strategy in the future. EfficacyTriple-negative breast cancer efficacyHer2-positive breast cancer efficacySafety Citation Format: Yunjiang Liu, Xiangmei Zhang, Li Wang, Miao Cao, Shuo Zhang, Hui Zhang, Yarong Zhou, Jintian Wang. Apatinib combined with taxanes and platinum neoadjuvant chemotherapy for patients with triple-negative and HER2-positive breast cancer: A multicenter, randomized, open-label, phase II trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-12.
Arterial and venous thromboembolism in COVID-19: a study-level meta-analysis
Authors: Boun Kim Tan, Sabine Mainbourg, Arnaud Friggeri, Laurent Bertoletti, Marion Douplat, Yesim Dargaud, Claire Grange, Hervé Lobbes, Steeve Provencher, Jean-Christophe Lega
Journal: Thorax (2021)

Background The prevalence of venous thromboembolic event (VTE) and arterial thromboembolic event (ATE) thromboembolic events in patients with COVID-19 remains largely unknown. Methods In this meta-analysis, we systematically searched for observational studies describing the prevalence of VTE and ATE in COVID-19 up to 30 September 2020. Results We analysed findings from 102 studies (64 503 patients). The frequency of COVID-19-related VTE was 14.7% (95% CI 12.1% to 17.6%, I 2 =94%; 56 studies; 16 507 patients). The overall prevalence rates of pulmonary embolism (PE) and leg deep vein thrombosis were 7.8% (95% CI 6.2% to 9.4%, I 2 =94%; 66 studies; 23 117 patients) and 11.2% (95% CI 8.4% to 14.3%, I 2 =95%; 48 studies; 13 824 patients), respectively. Few were isolated subsegmental PE. The VTE prevalence was significantly higher in intensive care unit (ICU) (23.2%, 95% CI 17.5% to 29.6%, I 2 =92%, vs 9.0%, 95% CI 6.9% to 11.4%, I 2 =95%; p interaction &lt;0.0001) and in series systematically screening patients compared with series testing symptomatic patients (25.2% vs 12.7%, p interaction =0.04). The frequency rates of overall ATE, acute coronary syndrome, stroke and other ATE were 3.9% (95% CI 2.0% to to 3.0%, I 2 =96%; 16 studies; 7939 patients), 1.6% (95% CI 1.0% to 2.2%, I 2 =93%; 27 studies; 40 597 patients) and 0.9% (95% CI 0.5% to 1.5%, I 2 =84%; 17 studies; 20 139 patients), respectively. Metaregression and subgroup analyses failed to explain heterogeneity of overall ATE. High heterogeneity limited the value of estimates. Conclusions Patients admitted in the ICU for severe COVID-19 had a high risk of VTE. Conversely, further studies are needed to determine the specific effects of COVID-19 on the risk of ATE or VTE in less severe forms of the disease.
Mining Unknown Porcine Protein Isoforms by Tissue-Based Map of Proteome Enhances Pig Genome Annotation
Authors: Pengju Zhao, Xianrui Zheng, Ying Yu, Zhuocheng Hou, Chenguang Diao, Haifei Wang, Huimin Kang, Chao Ning, Junhui Li, Wen Feng, Wen Wang, George E. Liu, Bugao Li, Jacqueline Smith, Yangzom Chamba, Jian-Feng Liu
Journal: Genomics Proteomics & Bioinformatics (2021)

A lack of the complete pig proteome has left a gap in our knowledge of the pig genome and has restricted the feasibility of using pigs as a biomedical model. In this study, we developed a tissue-based proteome map using 34 major normal pig tissues. A total of 5841 unknown protein isoforms were identified and systematically characterized, including 2225 novel protein isoforms, 669 protein isoforms from 460 genes symbolized beginning with LOC, and 2947 protein isoforms without clear NCBI annotation in the current pig reference genome. These newly identified protein isoforms were functionally annotated through profiling the pig transcriptome with high-throughput RNA sequencing of the same pig tissues, further improving the genome annotation of the corresponding protein-coding genes. Combining the well-annotated genes that have parallel expression pattern and subcellular witness, we predicted the tissue-related subcellularlocations and potential functions for these unknown proteins. Finally, we mined 3081 orthologous genes for 52.7% of unknown protein isoforms across multiple species, referring to 68 KEGG pathways as well as 23 disease signaling pathways. These findings provide valuable insights and a rich resource for enhancing studies of pig genomics and biology, as well as biomedical model application to human medicine.
LPS刺激性マクロファージにおいてT-lymphocytotropic CXCカモカインを抑制することでTリンパ球補充を制御するアディポネクチン(抗炎症性アディキサイトカイン)-アディポネクチンの潜在的な抗アテローム生成機能
Authors: Okamoto Y, Shimizu K, Colvin R, Minami M, Kihara S, Funahashi T, Luster A, Libby P
Journal: Circulation (2006)