tbuckley/cabot-search huggingface dataset:
Molecular characteristics of synchronous multiple gastric cancer
Authors: Anqiang Wang, Zhongwu Li, Meng Wang, Shuqin Jia, Jiahu Chen, Ke Ji, Xin Ji, Xianglong Zong, Xiaojiang Wu, Ji Zhang, Ziyu Li, Lianhai Zhang, Ying Hu, Zhaode Bu, Qi Zheng, Jiafu Ji
Journal: Theranostics (2020)

Rationale: Multiple gastric cancer (MGC) is characterized by the presence of more than two different tumors in the stomach.However, the clonal relationship and carcinogenesis of MGC remain unclear.We investigated the clonal relationship and role of germline mutations in the carcinogenesis of MGC.Methods: We gathered 16 multiple gastric cancer patients.Thirty-three tumor samples and sixteen normal gastric tissue or blood samples were obtained from January 2016 to December 2017.We also conducted analyses for 208 gastric cancer and 49 esophagogastric junction cancer (GC-EGJ) tumors from TCGA.DNA extraction from our samples was conducted for whole-exome sequencing (WES).Results: Tumor mutation burden (TMB) was not statistically significant within database and our data in the GC-EGJ (P=0.0591) and GC groups (P=0.3113).The mutation spectrum and signatures also showed uniform distributions in GC and GC-EGJ groups within our data and TCGA database.Among sixteen patients, four were identified as monoclonal, in which 11, 10, 26 and 6 somatic mutations were shared within different tumors of P7, P8, P9 and P16, respectively.However, no common mutation between different tumors of the same patient was found among the other 12 patients.After identifying predisposing genes, we found that germline MSH2 and NCOR2 mutations were significantly dominant in 8/12 and 10/12 of genetic MGC patients.Additionally, all patients were identified with MSH2 mutations in cancer samples of those genetic MGC patients.Taking genetic MGCs as a whole, we identified that TP53 were significantly mutated in 14 of 25 tumor samples.Main conclusions: WES analyses are suggestive of monoclonal and polyclonal origin of MGC, which may promote the classification of MGC into genetic and metastatic MGC.For patients with genetic MGC, germline MSH2 X314_splice variants may contribute to carcinogenesis, thus prompting the consideration of more radical surgery and/or anti-PD-1/PD-L1 therapy.
A prospective, randomized trial of thrombin versus cyanoacrylate injection in the control of acute gastric variceal hemorrhage
Authors: Gin-Ho Lo, Chih-Wen Lin, Chi-Ming Tai, Daw-Shyong Perng, I-Lin Chen, Jen-Hao Yeh, Hui-Chen Lin
Journal: Endoscopy (2020)

Background Acute gastric variceal hemorrhage (AGVH) is a serious complication of portal hypertension. Endoscopic cyanoacrylate glue injection is standard therapy for acute hemostasis; however, it may be associated with serious complications. The role of thrombin injection has not been confirmed. This study compared endoscopic thrombin and glue injections in the hemostasis of AGVH. Methods 68 eligible patients with AGVH were randomized to receive thrombin injection (33 patients) or glue injection (35 patients). The primary end point was injection-induced gastric ulcers. Secondary end points were acute hemostasis, rebleeding, and mortality within 42 days. Results Both groups had comparable baseline data. Hemostasis of active bleeding at endoscopy was 90.0 % (9/10) in the thrombin group and 90.9 % (10/11) in the glue group (P = 0.58), and 48-hour hemostasis was achieved in 93.9 % (31/33) and 97.1 % (34/35), respectively (P = 0.60). Treatment failure at 5 days occurred in two patients (6.1 %) in the thrombin group and two patients (5.7 %) in the glue group (P &gt; 0.99). Gastric ulcers occurred in none of the thrombin group and 11/30 (36.7 %) of the glue group (P &lt; 0.001, 95 % confidence interval [CI] 8 % – 27 %). Complications occurred in 4 (12.1 %) and 18 (51.4 %) patients in the thrombin and glue groups, respectively (P &lt; 0.001, 95 %CI 22 % – 45 %). Two patients who received glue had post-treatment gastric ulcer bleeding. One patient in each group died. Conclusions Endoscopic thrombin injection was similar to glue injection in achieving successful hemostasis of AGVH. However, a higher incidence of complications may be associated with glue injection.
Identification of a novel microRNA-141-3p/Forkhead box C1/β-catenin axis associated with rheumatoid arthritis synovial fibroblast function in vivo and in vitro
Authors: Jun Wang, Yin Wang, Hui Zhang, Jun Chang, Ming Lu, Weilu Gao, Wendong Liu, Yetian Li, Li Yin, Xiaohe Wang, Yuejun Wang, Mengru Gao, Zongsheng Yin
Journal: Theranostics (2020)

Rationale: Rheumatoid arthritis (RA) is a prototype of inflammatory arthritis in which synovial fibroblasts (SFs) play key roles in cartilage and bone destruction through tumor-like proliferation, migration, invasion and inflammation. This study aimed to research forkhead box protein C1 (FoxC1) and microRNA (miR)-141-3p, which modulate pathological changes in the synovial membrane, to find possible strategies for treating RA. Methods: FoxC1, β-catenin and miR-141-3p gene expression in synovial tissues and SFs was quantified by real-time PCR; FoxC1 and β-catenin protein levels were evaluated by immunohistochemistry, immunofluorescence, and Western blotting. We transiently transfected human SFs with FoxC1 and β-catenin overexpression and silencing vectors and assessed proliferation, migration, invasion and inflammation by cell function and enzyme-linked immunosorbent assays. We also assessed downstream signaling activation using immunofluorescence, real-time PCR and Western blotting. Double luciferase, coimmunoprecipitation and chromatin immunoprecipitation assays were used to verify miR-141-3p, FoxC1 and β-catenin gene and protein combinations. Finally, the therapeutic effects of FoxC1 silencing and miR-141-3p overexpression were evaluated in type II collagen-induced arthritis (CIA) rats. Results: We found that FoxC1 expression was significantly upregulated in synovium and SFs in both RA patients and rats with collagen-induced arthritis (CIA). FoxC1 overexpression increased β-catenin messenger RNA (mRNA) and protein levels and upregulated cyclin D1, c-Myc, fibronectin and matrix metalloproteinase 3 (MMP3) mRNA and protein expression in RA SFs (RASFs). In contrast, FoxC1 knockdown reduced β-catenin mRNA and protein levels as well as cyclin D1, c-Myc, and fibronectin mRNA and protein levels in RASFs. Furthermore, altering FoxC1 expression did not significantly change GSK3β and pGSK3β levels. FoxC1 overexpression promoted proliferation, migration, invasion and proinflammatory cytokine (interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α)) production and reduced anti-inflammatory cytokine (IL-10) levels in RASFs. FoxC1 bound to the β-catenin promoter, and β-catenin mediated the FoxC1-induced pathological changes. We also observed downregulated microRNA (miR)-141-3p expression in SFs from both RA patients and CIA rats and further found that miR-141-3p bound to the FoxC1 3'UTR and suppressed FoxC1 expression. Intra-ankle miR-141-3p agomir or FoxC1-specific siRNA injection hindered CIA development in rats. Conclusions: FoxC1 and miR-141-3p participate in RA pathogenesis by mediating inflammation and SF proliferation, migration, and invasion and thus could be novel targets for RA therapy as a nonimmunosuppressive approach.
Liquid biopsy for infectious diseases: a focus on microbial cell-free DNA sequencing
Authors: Dongsheng Han, Rui Li, Jiping Shi, Ping Tan, Rui Zhang, Jinming Li
Journal: Theranostics (2020)

Metagenomic next-generation sequencing (mNGS) of microbial cell-free DNA (mcfDNA sequencing) is becoming an attractive diagnostic modality for infectious diseases, allowing broad-range pathogen detection, noninvasive sampling, and rapid diagnosis. At this key juncture in the translation of metagenomics into clinical practice, an integrative perspective is needed to understand the significance of emerging mcfDNA sequencing technology. In this review, we summarized the actual performance of the mcfDNA sequencing tests recently used in health care settings for the diagnosis of a variety of infectious diseases and further focused on the practice considerations (challenges and solutions) for improving the accuracy and clinical relevance of the results produced by this evolving technique. Such knowledge will be helpful for physicians, microbiologists and researchers to understand what is going on in this quickly progressing field of non-invasive pathogen diagnosis by mcfDNA sequencing and promote the routine implementation of this technique in the diagnosis of infectious disease.
ACE-2 expression in the small airway epithelia of smokers and COPD patients: implications for COVID-19
Authors: Janice M. Leung, Chen X. Yang, Anthony Tam, Tawimas Shaipanich, Tillie-Louise Hackett, Gurpreet K. Singhera, Delbert R. Dorscheid, Don D. Sin
Journal: European Respiratory Journal (2020)

<b>Smokers and those with COPD have increased airway expression of ACE-2, which is the entry receptor for the COVID-19 virus. This may explain the increased risk of severe COVID-19 in these subpopulations and highlight the importance of smoking cessation.</b>https://bit.ly/3bC29es
Abstract 19528: Parent of Origin Effect in Lipid Profiles
Authors: Irene Predazzi, Jessica Lilley, William Bush, Macrae Linton, Sergio Fazio, Scott Williams
Journal: Circulation (2012)

Even though heritability estimates for lipid traits are high (40-60% for HDL and 40-50% for LDL), genetic contributions to lipid expression are complex and are not fully understood. Part of this variability may be due to epigenetic influences such as genomic imprinting; maternal hypercholesterolemia is thought to influence in offspring cardiovascular outcomes even in adult life. Such epigenetic factors can be observed as parent of origin effects within families. To explore this mechanism in lipid traits, we examined natural lipid variation that can be explained by parent of origin effects in the general population. We performed linear regressions in the second and third generations from the Framingham Cohort (n= 9,219 participants) to compare lipid trait correlations between mothers and daughter, mothers and sons, fathers and daughters, and fathers and sons with the goal of identifying sex-specific transmission effects. Models were adjusted for BMI, age, smoking status, treatment, and menopausal status of both parent and offspring. We performed a likelihood ratio test to compare a reduced model (containing offspring and parent covariates only) to a full model that includes parent lipid values as a risk factor. As anticipated, we observe that a significant amount of offspring HDL and LDL is explained by parent HDL/LDL levels. However, we also note that maternal HDL and LDL levels explain significantly more variance in daughter HDL and LDL compared to other models of other parent/offspring pairs, with the full model showing R2=0.19 versus a reduced model with R2=0.12 (chi2 = 104.9 and p=1.285e-24) for HDL a full model showing R2=0.17 versus a reduced model with R2=0.11 (chi2 = 84.0 and p=4.948e-20) for LDL. By contrast, the relationship between maternal HDL explains only 2% of the son’s HDL (LR=19.74, p&lt;8.872e-6) and the relationship between maternal LDL explains only 3% of the son’s LDL.
Midkine signaling maintains the self-renewal and tumorigenic capacity of glioma initiating cells
Authors: Israel López-Valero, David Dávila, José González-Martínez, Nélida Salvador-Tormo, Mar Lorente, Cristina Saiz-Ladera, Sofía Torres, Estibaliz Gabicagogeascoa, Sonia Hernández-Tiedra, Elena García-Taboada, Marina Mendiburu-Eliçabe, Fátima Rodríguez-Fornés, Rebeca Sánchez-Domínguez, José Carlos Segovia, Pilar Sánchez-Gómez, Ander Matheu, Juan M. Sepúlveda, Guillermo Velasco
Journal: Theranostics (2020)

Glioblastoma (GBM) is one of the most aggressive forms of cancer. It has been proposed that the presence within these tumors of a population of cells with stem-like features termed Glioma Initiating Cells (GICs) is responsible for the relapses that take place in the patients with this disease. Targeting this cell population is therefore an issue of great therapeutic interest in neuro-oncology. We had previously found that the neurotrophic factor MIDKINE (MDK) promotes resistance to glioma cell death. The main objective of this work is therefore investigating the role of MDK in the regulation of GICs. Methods: Assays of gene and protein expression, self-renewal capacity, autophagy and apoptosis in cultures of GICs derived from GBM samples subjected to different treatments. Analysis of the growth of GICs-derived xenografts generated in mice upon blockade of the MDK and its receptor the ALK receptor tyrosine kinase (ALK) upon exposure to different treatments. Results: Genetic or pharmacological inhibition of MDK or ALK decreases the self-renewal and tumorigenic capacity of GICs via the autophagic degradation of the transcription factor SOX9. Blockade of the MDK/ALK axis in combination with temozolomide depletes the population of GICs in vitro and has a potent anticancer activity in xenografts derived from GICs. Conclusions: The MDK/ALK axis regulates the self-renewal capacity of GICs by controlling the autophagic degradation of the transcription factor SOX9. Inhibition of the MDK/ALK axis may be a therapeutic strategy to target GICs in GBM patients.
Ex ante coherence shifts
Authors: Dan Simon, Keith J Holyoak
Journal: Behavioral and Brain Sciences (2020)

Abstract Cushman characterizes rationalization as the inverse of rational reasoning, but this distinction is psychologically questionable. Coherence-based reasoning highlights a subtler form of bidirectionality: By distorting task attributes to make one course of action appear superior to its rivals, a patina of rationality is bestowed on the choice. This mechanism drives choice and action, rather than just following in their wake.
Prognostic impact of typical and probable usual interstitial pneumonia pattern in idiopathic pulmonary fibrosis: is the debate about biopsy a <i>Star Wars</i> saga?
Authors: Martin Kolb, Ganesh Raghu, Athol Wells
Journal: European Respiratory Journal (2020)

<b>The debate about the benefit of performing a surgical lung biopsy in patients with the probable UIP pattern needs every case to be viewed on an individual basis. This editorial attempts to bring some clarity to treating physicians and confused patients.</b>http://bit.ly/2Qk517r
Human Leukocyte Antigen B*14:01 and B*35:01 Are Associated With Trimethoprim‐Sulfamethoxazole Induced Liver Injury
Authors: Yi‐Ju Li, Elizabeth J. Phillips, Andrew Dellinger, Paola Nicoletti, Ryan Schutte, Danmeng Li, David A. Ostrov, Robert J. Fontana, Paul B. Watkins, Andrew Stolz, Ann K Daly, Guruprasad P Aithal, Huiman Barnhart, Naga Chalasani
Journal: Hepatology (2020)

Background and Aims Trimethoprim (TMP)–sulfamethoxazole (SMX) is an important cause of idiosyncratic drug‐induced liver injury (DILI), but its genetic risk factors are not well understood. This study investigated the relationship between variants in the human leukocyte antigen (HLA) class 1 and 2 genes and well‐characterized cases of TMP‐SMX DILI. Approach and Results European American and African American persons with TMP‐SMX DILI were compared with respective population controls. HLA sequencing was performed by Illumina MiSeq (Illumina, San Diego, CA) for cases. The HLA genotype imputation with attribute bagging program was used to impute HLA alleles for controls. The allele frequency difference between case patients and controls was tested by Fisher’s exact tests for each ethnic group. For European Americans, multivariable logistic regression with Firth penalization was used to test the HLA allelic effect after adjusting for age and the top two principal components. Molecular docking was performed to assess HLA binding with TMP and SMX. The European American subset had 51 case patients and 12,156 controls, whereas the African American subset had 10 case patients and 5,439 controls. Four HLA alleles were significantly associated in the European American subset, with HLA‐B*14:01 ranking at the top (odds ratio, 9.20; 95% confidence interval, 3.16, 22.35; P = 0.0003) after covariate adjustment. All carriers of HLA‐B*14:01 with TMP‐SMX DILI possessed HLA‐C*08:02 , another significant allele ( P = 0.0026). This pattern was supported by HLA‐B*14:01–HLA‐C*08:02 haplotype association ( P = 1.33 × 10 −5 ). For the African American patients, HLA‐B*35:01 had 2.8‐fold higher frequency in case patients than in controls, with 5 of 10 patients carrying this allele. Molecular docking showed cysteine at position 67 in HLA‐B*14:01 and phenylalanine at position 67 in HLA‐B*35:01 to be the predictive binding sites for SMX metabolites. Conclusions HLA‐B*14:01 is associated with TMP‐SMX DILI in European Americans, and HLA‐B*35:01 may be a potential genetic risk factor for African Americans.
e-Cigarette Use Among Young Adult Cancer Survivors Relative to the US Population
Authors: Helen M. Parsons, Patricia I. Jewett, Karim Sadak, Lucie M. Turcotte, Rachel I. Vogel, Anne H. Blaes
Journal: JAMA Oncology (2020)

This survey study uses data from the 2018 Behavioral Risk Factor Surveillance System survey to evaluate e-cigarette use in young adults who have a history of cancer relative to young adults without cancer.
Risk of Suicide, Homicide, and Unintentional Firearm Deaths in the Home
Authors: Elissa K. Butler, Hanne M. Boveng, Richard C. Harruff, Jeffrey S. Duchin, Monica S. Vavilala, Frederick P. Rivara, Ali Rowhani-Rahbar
Journal: JAMA Internal Medicine (2020)

Risk of Suicide, Homicide, and Unintentional Firearm Deaths in the HomePersonal protection is a frequently cited reason for firearm ownership. 1However, access to firearms in the home has been associated with an increased risk of death from suicide and homicide among household members. 2 In 1986, Kellermann and Reay 3 reviewed all the gunshot deaths in King County, Washington, from 1978 to 1983, including 398 that occurred in the residence where the firearm was kept.They found that for every self-protection homicide involving a firearm kept in the home, there were 1.3 accidental deaths, 4.6 criminal homicides, and 37 suicides involving firearms.We sought to update this study, using King County data from 2011 to 2018. Methods |The study was a population-based case series of firearm deaths in homes in King County, Washington, from 2011 to 2018 (population 2 233 163 in 2018). 4 We used King County Medical Examiner's Office (KCMEO) records and linked these records to the Washington Office of the Attorney General Homicide Investigation Tracking System (HITS) for homicides.Cases were excluded if the incident did not occur in a home, occurred outside of King County, occurred more than 1 year prior to death, or if the person was shot by the police.The eMethods in the Supplement provide details on case linking and definitions.We categorized deaths as suicide, criminal homicide, selfdefense homicide, unintentional death, or undetermined based on KCMEO and HITS records (eMethods in the Supplement).
Abstract 12851: Efficacy and Safety of Rilonacept in Recurrent Pericarditis: A Multicenter Phase 2 Clinical Trial
Authors: Allan Klein, David Lin, Paul Cremer, Saifullah Nasir, S Allen Luis, Antonio Abbate, Asif Akhtar, Andrew Ertel, Martin M Lewinter, Anna Beutler, John F Paolini, Fang Fang, Steven Chang, Larisa Collins, Randy Perrin, Kasia Warchol, Sharon Crugnale
Journal: Circulation (2019)

Introduction: Interleukin-1 (IL-1) mediates innate autoinflammation and is implicated in recurrent pericarditis (RP). We report final data from a Phase 2 study of rilonacept (IL-1α/IL-1β inhibitor)...
pH responsive superporogen combined with PDT based on poly Ce6 ionic liquid grafted on SiO<sub>2</sub> for combating MRSA biofilm infection
Authors: Chaoli Wang, Peng Chen, Youbei Qiao, Yuan Kang, Chaoren Yan, Zhe Yu, Jian Wang, Xin He, Hong Wu
Journal: Theranostics (2020)

Background: Biofilm infection caused by multidrug-resistant bacteria is difficult to eradicate by conventional therapies. Photodynamic therapy (PDT) is an effective antibacterial method for fighting against biofilm infection. However, the blocked photosensitizers outside of biofilm greatly limit the efficacy of PDT. Methods: Herein, a novel acid-responsive superporogen and photosensitizer (SiO2-PCe6-IL) was developed. Because of the protonation of the photosensitizer and the high binding energy of the polyionic liquid, SiO2-PCe6-IL changed to positive SiO2-PIL+ in an acidic microenvironment of biofilm infection. SiO2-PIL+ could combine with negatively charged extracellular polymeric substances (EPS) and create holes to remove the biofilm barrier. To strengthen the interaction between SiO2-PIL+ and EPS, SiO2-PIL+ of high charge density was prepared by grafting the high-density initiation site of ATRP onto the surface of the SiO2 base. Results: Due to the rapid protonation rate of COO- and the strong binding energy of SiO2-PIL+ with EPS, SiO2-PCe6-IL could release 90% of Ce6 in 10 s. With the stronger electrostatic and hydrophobic interaction of SiO2-PIL+ with EPS, the surface potential, hydrophobicity, adhesion and mechanical strength of biofilm were changed, and holes in the biofilm were created in 10 min. Combining with the release of photosensitizers and the porous structure of the biofilm, Ce6 was efficiently concentrated in the biofilm. The in vitro and in vivo antibacterial experiments proved that SiO2-PCe6-IL dramatically improved the PDT efficacy against MRSA biofilm infection. Conclusion: These findings suggest that SiO2-PCe6-IL could rapidly increase the concentration of photosensitizer in biofilm and it is an effective therapy for combating biofilm infection.
Genetic Associations Between Childhood Psychopathology and Adult Depression and Associated Traits in 42 998 Individuals
Authors: Wonuola A. Akingbuwa, Anke R. Hammerschlag, Eshim S. Jami, Andrea G. Allegrini, Ville Karhunen, Hannah Sallis, Helga Ask, Ragna B. Askeland, Bart Baselmans, Elizabeth Diemer, Fiona A. Hagenbeek, Alexandra Havdahl, Jouke-Jan Hottenga, Hamdi Mbarek, Fernando Rivadeneira, Martin Tesli, Catharina van Beijsterveldt, Gerome Breen, Cathryn M. Lewis, Anita Thapar, Dorret I. Boomsma, Ralf Kuja-Halkola, Ted Reichborn-Kjennerud, Per Magnus, Kaili Rimfeld, EIVIND Ystrom, Marjo-Riitta Jarvelin, Paul Lichtenstein, Sebastian Lundstrom, Marcus R. Munafò, Robert Plomin, Henning Tiemeier, Michel G. Nivard, Meike Bartels, Christel M. Middeldorp
Journal: JAMA Psychiatry (2020)

Adult mood disorders are often preceded by behavioral and emotional problems in childhood. It is yet unclear what explains the associations between childhood psychopathology and adult traits.