tbuckley/cabot-search huggingface dataset:
Endoscopic submucosal dissection of a subepithelial neuroendocrine tumor located in the duodenum using a countertraction technique
Authors: Thomas Lambin, Clara Yzet, Jérémie Albouys, Pierre Lafeuille, Florian Rostain, Jérôme Rivory, Mathieu Pioche
Journal: Endoscopy (2021)

Endoscopic submucosal dissection (ESD) is the technique of choice to remove large superficial neoplasms of the esophagus, stomach, colon, and rectum [1]. In the duodenum, for non-ampullary lesions, it has been associated with a high risk of perforation [2] owing to the relative thinness of the duodenal wall. Data with regard to ESD for subepithelial lesions are scarce. One study described a low rate of curative treatment for duodenal neuroendocrine tumors (NETs), but few patients were included [3]. Techniques such as countertraction using a rubber band [4] and anchoring the clips to close the scar [5] can be considered to secure the procedure.
Rapid dissonant grunting, or, but why does music sound the way it does?
Authors: Beau R Sievers, Thalia Wheatley
Journal: Behavioral and Brain Sciences (2021)

Abstract Each target article contributes important proto-musical building blocks that constrain music as-we-know-it. However, neither the credible signaling nor social bonding accounts elucidate the central mystery of why music sounds the way it does. Getting there requires working out how proto-musical building blocks combine and interact to create the complex, rich, and affecting music humans create and enjoy.
CREBBP Histone Acetyltransferase Domain Mutations Result in Dexamethasone Resistance in B-Progenitor Acute Lymphoblastic Leukemia
Authors: Yunchao Chang, David W. Woessner, Wenwei Lin, Taosheng Chen, Beisi Xu, Yiping Fan, Haiyan Tan, Junmin Peng, Lawryn Kasper, Michelle L. Churchman, Mignon L. Loh, Stephen P. Hunger, Aman Seth, Karen Gascoigne, Paul K Brindle, Charles G. Mullighan
Journal: Blood (2017)
Profile of phospho-proteins according to LKB1 gene status in lung cancer cells
Authors: Akiko Hisamoto, Eisei Kondo, Katsuyuki Kiura, Toshiaki Okada, Shinobu Hosokawa, Hideki Katayama, Kenji Nishii, Masahiro Tabata, Hiroshi Ueoka, Mitsune Tanimoto
Journal: Cancer Research (2005)

5735  Germ-line mutations at LKB1, also called STK11, are the cause of the Peutz-Jeghers syndrome (PJS), which is characterized by an increased in the risk of several types of cancer. We recently discovered that LKB1 is also somatically inactivated by point mutations or partial gene deletions in sporadic lung carcinomas of the adenocarcinoma histological type. These observations clearly evidence that LKB1 mutations are no circumscribed to the PJS and further highlights the role of LKB1 in cancer development. The LKB1 protein is a serine-threonine kinase that has been implicated in several cell functions such as cell polarity and signal transduction. Moreover, LKB1 appears to be the long-sought kinase that phosphorylates and activates AMP-activated protein kinase (AMPK) and that inhibit mTOR activity through the activation of TSC2. Given the previously described background we used a panel of 9 lung adenocarcinoma cell lines (4 wild type and 5 mutant for LKB1) and phospho-specific antibodies to perform western blot analysis and determine the basal profile of protein phosphorylation among components of the AMPK and PI3K/PTEN signal transduction pathways (AMPK, ACC, AKT, TSC-2, mTOR and S6K). Moreover, we evaluated the status of STRAD, which interacts with LKB1 and activates its kinase activity. Our results revealed that total levels of STRAD protein were very low in LKB1-mutant cells and that LKB1 reintroduction was able to restore STRAD expression in one LKB1-mutant cell line. However, phosphorylation of AKT at Ser473 and mTOR at Ser2448 appeared to be independent of the LKB1 status. Following treatment with AICAR, the LKB1-mutant cell line A427, was able to phosphorylate AMPK (at Ser172), suggesting that in these cells it must exist another mechanism for AMPK phosphorylation that is independent of LKB1. To further evaluate the role of LKB1 in lung cancer cells, we have stably expressed recombinant LKB1 with inducible activity in some LKB1-deficient cell lines. At present we are investigating the ability of ectopic LKB1 to activate AMPK and to inhibit mTOR pathway in this system. In conclusion, our work will provide evidence on whether absence of LKB1 promotes the constitutive activation of the AMPK-TSC-mTOR signal transduction pathway in lung tumorigenesis.
AB0086 PREGNANCY OUTCOMES IN SYSTEMIC LUPUS ERYTEMATOSUS (SLE)
Authors: Z. Alekberova, R. Goloeva, T. Popkova
Journal: Annals of the Rheumatic Diseases (2021)

Background: There’s no doubt that SLE has negative effect not only on the course of pregnancy, but also on maternal and fetal outcomes. Objectives: To clarify pregnancy outcomes in patients with SLE by means of retrospective analysis. Methods: The study group included 12 women with SLE aged 20-40 years, and the control group - 15 age-matching healthy women. SLE diagnosis was established based on the EULAR/ACR classification criteria, 2019. The SLEDAI 2K was used to evaluate disease activity, and the SLICC index – to evaluate damage. Completed by all women issue-specific questionnaire covered clinical symptoms of SLE and details of obstetric history (characteristics of menstrual and reproductive function, presence of genital and extragenital pathology, previous pregnancies outcomes; previous intrauterine interventions, a history of coagulopathy). Results: SLE patients’ mean age was 33.5 [29;38] years, and control group subjects’ - 32.0 [26;35] years. Mean disease duration was 11.5 [2.8;18] years. Acute, subacute and chronic SLE was established in 33%, 17%, and 50%, respectively. Disease activity according to SLEDAI 2K was low in 25%, moderate – in 33%, and high – in 42% of pts. The SLICC damage baseline evaluation: no damage – 17%, low – 50%, medium – 16.5%, high-16.5%. Past pregnancies were documented in 7 out of 12 SLE patients and 6 healthy subjects from the control group. Table 1. Pregnancy outcomes Pregnancy, n SLE, n=16 Control, n=15 p Birth 9 (56,3%) 13 (87%) 0,00 Abortion 2 (12,5%) 0 0,00 Unfavorable pregnancy outcome 5 (31,2%) 2 (13%) 0,00 Missed miscarriage 4 (25%) 0 0,00 Spontaneous abortion 1 (6%) 2 (13%) ns Spontaneous vaginal delivery of a full-term baby was documented in both groups. Unfavorable pregnancy outcomes were significantly more frequent in SLE pts (31% vs 13% in the control group, p = 0.001). Two SLE pts after cyclophosphane therapy (10.6 and 18.4 g cumulative dose) and low AMH levels (&lt; 1 ng/ml) failed to become pregnant, although never used contraception. Analysis of gynecological history indicate that episodes of menstrual disorders were significantly more often reported in SLE pts (50% vs 20% in controls, p =0.001), similarly, gynecological diseases were also documented in 50% of SLE pts (chronic salpyngo-oophoritis, colpitis, endometriosis and uterine endometrioma, subserous uterine myoma, cervical dysplasia, cervical erosion), meanwhile low AMH was found only in 4 SLE pts; there was only 1 subject with gynecological condition – teratoma of the ovaries – in the control group (favorable outcome – surgical removal, preserved fertility and two births after surgery). Conclusion: The incidence of unfavorable pregnancy outcomes is significantly higher in patients with SLE compared to the control group of healthy women. Disclosure of Interests: None declared
The microbiota in cirrhosis and its role in hepatic decompensation
Authors: Jonel Trebicka, Jane Macnaughtan, Bernd Schnabl, Debbie L. Shawcross, Jasmohan S. Bajaj
Journal: Journal of Hepatology (2021)

Cirrhosis - the common end-stage of chronic liver disease - is associated with a cascade of events, of which intestinal bacterial overgrowth and dysbiosis are central. Bacterial toxins entering the portal or systemic circulation can directly cause hepatocyte death, while dysbiosis also affects gut barrier function and increases bacterial translocation, leading to infections, systemic inflammation and vasodilation, which contribute to acute decompensation and organ failure. Acute decompensation and its severe forms, pre-acute-on-chronic liver failure (ACLF) and ACLF, are characterised by sudden organ dysfunction (and failure) and high short-term mortality. Patients with pre-ACLF and ACLF present with high-grade systemic inflammation, usually precipitated by proven bacterial infection and/or severe alcoholic hepatitis. However, no precipitant is identified in 30% of these patients, in whom bacterial translocation from the gut microbiota is assumed to be responsible for systemic inflammation and decompensation. Different microbiota profiles may influence the rate of decompensation and thereby outcome in these patients. Thus, targeting the microbiota is a promising strategy for the prevention and treatment of acute decompensation, pre-ACLF and ACLF. Approaches include the use of antibiotics such as rifaximin, faecal microbial transplantation and enterosorbents (e.g. Yaq-001), which bind microbial factors without exerting a direct effect on bacterial growth kinetics. This review focuses on the role of microbiota in decompensation and strategies targeting microbiota to prevent acute decompensation.
제5차 대한간학회 춘계학술대회 초록집 : 포스터 토의 순서 ; 간모세포종에서 P73, APC, P53의 이종접합성 소실과 G1세포주기 조절단백의 발현
Authors: 김한성 ( Kim Han Seong ), 정영미 ( Jeong Yeong Mi ), 김미란 ( Kim Mi Lan ), 이정용 ( Lee Jeong Yong ), 장자준 ( Jang Ja Jun )
Journal: Clinical and Molecular Hepatology (1999)
POS0415 BLOOD-DERIVED DNA METHYLATION EPI-SIGNATURES ASSOCIATED WITH ANKYLOSING SPONDYLITIS
Authors: M. Xiao, J. Gu
Journal: Annals of the Rheumatic Diseases (2021)

Background: Most (~90%) of the ankylosing spondylitis (AS) susceptibility loci are undefined and located in non-coding regions. Epigenetic changes may alter the expression of genes involved in AS and explain part of the missing heritability. 1 Objectives: To identify novel DNA methylation sites significant for AS and comprehensively understand the underlying pathological mechanism. Methods: Genome-wide DNA methylation of blood samples from 30 AS patients and 15 health controls was measured on the Infinium® MethylationEPIC BeadChip microarray. Methylome data were analyzed with ChAMP package in R. Results: The epigenome-wide association analysis identified 4,794 differentially methylated positions (DMPs) (FDR &lt;0.05 and delta β &gt;0.05), including 3,294 (68.7%) hypermethylated and 1,500 (31.3%) hypomethylated positions in AS patients (Figure 1A). The identified DMPs allowed clear distinction of most AS cases from controls in the PCA (Figure 1B) and unsupervised hierarchical clustering (Figure 1C). KEGG pathway analysis of AS associated DMPs enriched in T cell receptor signaling pathway, Th1 and Th2 cell differentiation. Besides, a total of 1,048 differentially variable positions (DVPs) were identified, the majority of which (974, 92.9%) were hypervariable in AS, while only 74 DVPs were hypovariable. The increased DNA methylation variability in disease were in line with the previous observation in other diseases, indicating the intrinsic heterogeneity in AS patients, which might be influenced by diverse factors, such as disease activity and treatment. Figure 1. Conclusion: Peripheral blood mononuclear cells from AS patients display aberrant DNA methylome and increased DNA methylation variability. The results enhanced our understanding of the important role of DNA methylation in pathology of AS and offered the possibility of identifying new targets for intervention. References: [1]Whyte JM, Ellis JJ, Brown MA, et al. Best practices in DNA methylation: lessons from inflammatory bowel disease, psoriasis and ankylosing spondylitis. Arthritis Res Ther 2019; 21:133. Acknowledgements: We appreciate all the staff members of the department of rheumatology of the Third Affiliated Hospital of Sun Yat-sen University for assistance and support in the patient’s recruitment and sample collection. Disclosure of Interests: None declared
Long-term modulation of airway remodelling in severe asthma following bronchial thermoplasty
Authors: Nicholas Jendzjowsky, Austin Laing, Michelle Malig, John Matyas, Elaine de Heuvel, Curtis Dumonceaux, Elaine Dumoulin, Alain Tremblay, Richard Leigh, Alex Chee, Margaret M. Kelly
Journal: European Respiratory Journal (2021)

Rationale Bronchial thermoplasty is a mechanical therapeutic intervention that has been advocated as an effective treatment option for severe asthma. The mechanism is promoted as being related to the attenuation of airway smooth muscle which has been shown to occur in the short-term. However, long-term studies of the effects of bronchial thermoplasty on airway remodelling are few, with only limited assessment of airway remodelling indices. Objectives To evaluate the effect of bronchial thermoplasty on 1) airway epithelial and smooth muscle cells in culture and 2) airway remodelling in patients with severe asthma who have been prescribed bronchial thermoplasty up to 12 months post-treatment. Methods The distribution of heat within the airway by bronchial thermoplasty was assessed in a porcine model. Culture of human airway smooth muscle cells and bronchial epithelial cells evaluated the impact of thermal injury. Histological evaluation and morphometric assessment were performed on bronchial biopsies obtained from severe asthma patients at baseline, 6 weeks and 12 months following bronchial thermoplasty. Results Bronchial thermoplasty resulted in heterogeneous heating of the airway wall. Airway smooth muscle cell cultures sustained thermal injury, whilst bronchial epithelial cells were relatively resistant to heat. Airway smooth muscle and neural bundles were significantly reduced at 6 weeks and 12 months post-treatment. At 6 weeks post-treatment, submucosal collagen was reduced and vessel density increased, with both indices returning to baseline at 12 months. Goblet cell numbers, submucosal gland area and sub-basement membrane thickness were not significantly altered at any time point examined. Conclusions Bronchial thermoplasty primarily affects airway smooth muscle and nerves with the effects still present at 12 months post-treatment.
Systemic Sirolimus Therapy for Infants and Children With Pulmonary Vein Stenosis
Authors: Jay D. Patel, Michael Briones, Mansi Mandhani, Shannon Jones, Divya Suthar, Rosemary Gray, Joelle Pettus, Courtney McCracken, Amanda Thomas, Christopher J. Petit
Journal: Journal of the American College of Cardiology (2021)
Genetically Encoded Elastin‐Like Polypeptides for Drug Delivery
Authors: Irene C. Jenkins, Joshua J. Milligan, Ashutosh Chilkoti
Journal: Advanced Healthcare Materials (2021)

Abstract Elastin‐like polypeptides (ELPs) are thermally responsive biopolymers that consist of a repeated amino acid motif derived from human tropoelastin. These peptides exhibit temperature‐dependent phase behavior that can be harnessed to produce stimuli‐responsive biomaterials, such as nanoparticles or injectable drug delivery depots. As ELPs are genetically encoded, the properties of ELP‐based biomaterials can be controlled with a precision that is unattainable with synthetic polymers. Unique ELP architectures, such as spherical or rod‐like micelles or injectable coacervates, can be designed by manipulating the ELP amino acid sequence and length. ELPs can be loaded with drugs to create controlled, intelligent drug delivery systems. ELPs are biodegradable, nonimmunogenic, and tolerant of therapeutic additives. These qualities make ELPs exquisitely well‐suited to address current challenges in drug delivery and have spurred the development of ELP‐based therapeutics to treat diseases—such as cancer and diabetes—and to promote wound healing. This review focuses on the use of ELPs in drug delivery systems.
RNA sequence analysis reveals ITGAL/CD11A as a stromal regulator of murine low-grade glioma growth
Authors: Amanda De Andrade Costa, Jit Chatterjee, Olivia Cobb, Shilpa Sanapala, Suzanne Scheaffer, Xiaofan Guo, Sonika Dahiya, David H Gutmann
Journal: Neuro-Oncology (2021)

Emerging insights from numerous laboratories have revealed important roles for nonneoplastic cells in the development and progression of brain tumors. One of these nonneoplastic cellular constituents, glioma-associated microglia (GAM), represents a unique population of brain monocytes within the tumor microenvironment that have been reported to both promote and inhibit glioma proliferation. To elucidate the role of GAM in the setting of low-grade glioma (LGG), we leveraged RNA sequencing meta-analysis, genetically engineered mouse strains, and human biospecimens.
Effective and biocompatible antibacterial surfaces via facile synthesis and surface modification of peptide polymers
Authors: Ziyi Lu, Yueming Wu, Zihao Cong, Yuxin Qian, Xue Wu, Ning Shao, Zhongqian Qiao, Haodong Zhang, Yunrui She, Kang Chen, Hengxue Xiang, Bin Sun, Qian Yu, Yuan Yuan, Haodong Lin, Meifang Zhu, Runhui Liu
Journal: Bioactive Materials (2021)

It is an urgent need to tackle drug-resistance microbial infections that are associated with implantable biomedical devices. Host defense peptide-mimicking polymers have been actively explored in recent years to fight against drug-resistant microbes. Our recent report on lithium hexamethyldisilazide-initiated superfast polymerization on amino acid N-carboxyanhydrides enables the quick synthesis of host defense peptide-mimicking peptide polymers. Here we reported a facile and cost-effective thermoplastic polyurethane (TPU) surface modification of peptide polymer (DLL: BLG = 90 : 10) using plasma surface activation and substitution reaction between thiol and bromide groups. The peptide polymer-modified TPU surfaces exhibited board-spectrum antibacterial property as well as effective contact-killing ability in vitro. Furthermore, the peptide polymer-modified TPU surfaces showed excellent biocompatibility, displaying no hemolysis and cytotoxicity. In vivo study using methicillin-resistant Staphylococcus aureus (MRSA) for subcutaneous implantation infectious model showed that peptide polymer-modified TPU surfaces revealed obvious suppression of infection and great histocompatibility, compared to bare TPU surfaces. We further explored the antimicrobial mechanism of the peptide polymer-modified TPU surfaces, which revealed a surface contact-killing mechanism by disrupting the bacterial membrane. These results demonstrated great potential of the peptide-modified TPU surfaces for practical application to combat bacterial infections that are associated with implantable materials and devices.
An open-label randomized controlled trial of the effect of lopinavir/ritonavir, lopinavir/ritonavir plus IFN-β-1a and hydroxychloroquine in hospitalized patients with COVID-19
Authors: Florence Ader, Nathan Peiffer-Smadja, Julien Poissy, Maude Bouscambert-Duchamp, Drifa Belhadi, Alpha Diallo, Christelle Delmas, Juliette Saillard, Aline Dechanet, Noémie Mercier, Axelle Dupont, Toni Alfaiate, François-Xavier Lescure, François Raffi, François Goehringer, Antoine Kimmoun, Stéphane Jaureguiberry, Jean Reignier, Saad Nseir, François Danion, Raphael Clere-Jehl, Kévin Bouiller, Jean-Christophe Navellou, Violaine Tolsma, André Cabié, Clément Dubost, Johan Courjon, Sylvie Leroy, Joy Mootien, Rostane Gaci, Bruno Mourvillier, Emmanuel Faure, Valérie Pourcher, Sébastien Gallien, Odile Launay, Karine Lacombe, Jean-Philippe Lanoix, Alain Makinson, Guillaume Martin-Blondel, Lila Bouadma, Elisabeth Botelho-Nevers, Amandine Gagneux-Brunon, Olivier Epaulard, Lionel Piroth, Florent Wallet, Jean-Christophe Richard, Jean Reuter, Thérèse Staub, Bruno Lina, Marion Noret, Claire Andrejak, Minh Patrick Lê, Gilles Peytavin, Maya Hites, Dominique Costagliola, Yazdan Yazdanpanah, Charles Burdet, France Mentré
Journal: Clinical Microbiology and Infection (2021)
Oncogenic Mutations in PI3K/AKT/mTOR Pathway Effectors Associate with Worse Prognosis in <i>BRAFV600E</i>-Driven Papillary Thyroid Cancer Patients
Authors: Theodora Pappa, Sara Ahmadi, Ellen Marqusee, Hannah L. Johnson, Matthew A. Nehs, Nancy L. Cho, Justine A. Barletta, Jochen H. Lorch, Gerard M. Doherty, Neal I. Lindeman, Erik K. Alexander, Iñigo Landa
Journal: Clinical Cancer Research (2021)

Abstract Purpose: The extent to which routine genomic sequencing can identify relevant secondary genomic alterations among BRAFV600E-mutant papillary thyroid carcinoma (PTC) is unknown. Such markers would prove highly valuable for prognostic purposes. Experimental Design: We reviewed clinicopathologic data of 225 patients with BRAFV600E-mutant PTC and integrated them with genomic data derived from targeted next-generation sequencing (NGS) on tumor specimens. We defined patient subgroups based on bona fide secondary oncogenic events (separate from BRAFV600E) and compared their clinical features and outcomes with those without additional oncogenic alterations. Results: Additional oncogenic alterations were identified in 16% of tumors. Patients in the “BRAF+additional mutations” group were more likely to be at high American Thyroid Association (ATA) risk of recurrence (48.6% vs. 17.6%; P = 0.0009), had larger baseline tumor (2.7 vs. 1.9 cm; P = 0.0005) and more advanced stage at presentation (14.3% vs. 1.1% stage 4; P &amp;lt; 0.0001). Importantly, over a 65-month follow-up, disease-specific mortality (DSM) was increased when additional mutations were identified (13.8% vs. 1.4% in the BRAF-only group; P = 0.005). Separately, we identified a subcluster of patients harboring oncogenic mutations in key effectors of the PI3K/AKT/mTOR pathway, which were independently associated with DSM (OR = 47.9; 95% confidence interval, 3.5–1,246.5; P = 0.0043). Conclusions: Identification of additional PIK3/AKT/mTOR alterations in patients with BRAFV600E-mutant PTC provides important and actionable prognostic risk stratification. These data support genomic profiling of PTC tumors to inform prognosis and clinical strategy.
Human plasma proteomic profiles indicative of cardiorespiratory fitness
Authors: Jeremy M. Robbins, Bennet Peterson, Daniela Schranner, Usman A. Tahir, Theresa Rienmüller, Shuliang Deng, Michelle J. Keyes, Daniel H. Katz, Pierre M. Jean Beltran, Jacob L. Barber, Christian Baumgartner, Steven A. Carr, Sujoy Ghosh, Changyu Shen, Lori L. Jennings, Robert Ross, Mark A. Sarzynski, Claude Bouchard, Robert E. Gerszten
Journal: Nature Metabolism (2021)
The Combined Effect of Vaccination and Nonpharmaceutical Public Health Interventions—Ending the COVID-19 Pandemic
Authors: Alexander Doroshenko
Journal: JAMA Network Open (2021)

Mehul D. Patel, PhD; Erik Rosenstrom, BS; Julie S. Ivy, PhD; Maria E. Mayorga, PhD; Pinar Keskinocak, PhD; Ross M. Boyce, MD, MSc; Kristen Hassmiller Lich, PhD; Raymond L. Smith III, PhD; Karl T. Johnson, BA; Paul L. Delamater, PhD; Julie L. Swann, PhD