tbuckley/cabot-search huggingface dataset:
Deficient Chaperone-Mediated Autophagy Promotes Inflammation and Atherosclerosis
Authors: Lei Qiao, Jing Ma, Zihao Zhang, Wenhai Sui, Chungang Zhai, Dan Xu, Zunzhe Wang, Huixia Lu, Meng Zhang, Cheng Zhang, Wenqiang Chen, Yun Zhang
Journal: Circulation Research (2021)

The NLRP3 (NLR [NOD-like receptor] family, pyrin domain containing 3) inflammasome is an important driver of atherosclerosis. Our previous study shows that chaperone-mediated autophagy (CMA), one of the main lysosomal degradative process, has a regulatory role in lipid metabolism of macrophages. However, whether the NLRP3 inflammasome is regulated by CMA, and the role of CMA in atherosclerosis remains unclear.To determine the role of CMA in the regulation of NLRP3 inflammasome and atherosclerosis.The expression of CMA marker, LAMP-2A (lysosome-associated membrane protein type 2A), was first analyzed in ApoE-/- mouse aortas and human coronary atherosclerotic plaques, and a significant downregulation of LAMP-2A in advanced atherosclerosis in both mice and humans was observed. To selectively block CMA, we generated macrophage-specific conditional LAMP-2A knockout mouse strains in C57BL/6 mice and ApoE-/- mice. Deletion of macrophage LAMP-2A accelerated atherosclerotic lesion formation in the aortic root and the whole aorta in ApoE-/- mice. Mechanistically, LAMP-2A deficiency promoted NLRP3 inflammasome activation and subsequent release of mature IL (interleukin)-1β in macrophages and atherosclerotic plaques. Furthermore, gain-of-function studies verified that restoration of LAMP-2A levels in LAMP-2A-deficient macrophages greatly attenuated NLRP3 inflammasome activation. Importantly, we identified the NLRP3 protein as a CMA substrate and demonstrated that LAMP-2A deficiency did not affect the NLRP3 mRNA levels but hindered degradation of the NLRP3 protein through CMA pathway.CMA function becomes impaired during the progression of atherosclerosis, which increases NLRP3 inflammasome activation and secretion of IL-1β, promoting vascular inflammation and atherosclerosis progression. Our study unveils a new mechanism by which NLRP3 inflammasome is regulated in macrophages and atherosclerosis, thus providing a new insight into the role of autophagy-lysosomal pathway in atherosclerosis. Pharmacological activation of CMA may provide a novel therapeutic strategy for atherosclerosis and other NLRP3 inflammasome/IL-1β-driven diseases.
Discovery of the pancreatic basal cell: a new candidate for an adult stem cell emerges
Authors: Simone Benitz, Howard Crawford
Journal: Gut (2021)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease and the seventh cause of cancer-related death worldwide.1 Notably, clinical characteristics, response to chemotherapy and progression of PDAC can vary among patients. Thus, huge efforts on the molecular profiling of cancer specimens have been undertaken during the last decade. Large-scale gene expression studies defined two main PDAC subtypes with either a ‘classical’ or ‘basal-like’ transcriptional signature, with patients with the basal-like subtype having a significantly poorer overall survival.2–4

Basal cells are a cell type predominantly located in the basal layer of stratified and pseudostratified epithelia in several tissues, including the skin, oesophagus, lung and breast. Common basal cell markers include keratin5 ( KRT5 ) and tumour protein P63 ( TP63 ), a member of the TP53 transcription factor family. In the pulmonary airway, the oesophagus and the mammary gland, basal cells serve as multipotent stem cells or progenitor-like cells which can give rise to organ-specific, terminally differentiated cells and thus have an important role in tissue regeneration on injury.5 6

Though basal cells have been found in several glandular organs, the pancreas is …
Incorporation of natriuretic peptides with clinical risk scores to predict heart failure among individuals with dysglycaemia
Authors: Matthew W. Segar, Muhammad Shahzeb Khan, Kershaw V. Patel, Muthiah Vaduganathan, Vaishnavi Kannan, Duwayne Willett, Eric Peterson, W.H. Wilson Tang, Javed Butler, Brendan M. Everett, Gregg C. Fonarow, Thomas J. Wang, Darren K. McGuire, Ambarish Pandey
Journal: European Journal of Heart Failure (2021)
TCT-163 Optical Coherence Tomography Characterization of Eccentric Versus Concentric Calcium Treated With Shockwave Intravascular Lithotripsy: Patient-Level Pooled Analysis of the Disrupt CAD OCT Substudies
Authors: Ziad Ali, Jonathan Hill, Shigeru Saito, Nieves Gonzalo, Carlo di Mario, Robert Riley, Benjamin Honton, Akiko Maehara, Mitsuaki Matsumura, Dean Kereiakes, Gregg Stone, Richard Shlofmitz
Journal: Journal of the American College of Cardiology (2021)
IgA Nephropathy Post COVID-19 Vaccination
Authors: Prakrati C. Acharya, Chirag Acharya, Juan A. Medaura
Journal: Journal of the American Society of Nephrology (2021)

Introduction: Inclusion of patients with kidney disease in COVID vaccine trials remains low. It is important to report association of disease exacerbation so that patients may undergo post vaccination monitoring. We hereby present a case of worsening IgA nephropathy temporarily associated with COVID vaccination Case Description: 63-year-old Hispanic female with past medical history of hypertension, psoriatic arthritis presented to the hospital with gross hematuria for 6 weeks starting 3 days after 2nd dose of Pfizer COVID vaccine. Her PCP had sent her to ER 5 days after onset of hematuria as had noted a creatinine (Cr) of 1.6 with 3+ protein and >20 RBCs on urinalysis suspicious for nephritic syndrome. On review she had serum Cr of 0.5 about 4 months ago with no proteinuria or hematuria before. In the ER she was given antibiotics for urinary tract infection and outpatient referral for nephrology. She could not make the outpatient appointment and with continued gross hematuria for a month, she presented to the ER again where she was noted to have Cr of 10 mg/dl and urine protein:cr ratio of 7.3gm/gm. Renal imaging including CT urogram was normal. Renal biopsy showed IgA nephropathy, M1S0E0T1C1 with a fibrocellular crescent and acute tubular necrosis likely secondary to lyzed red cells in setting of multiple RBC casts in the tubules. She was put on 250 mg Solumedrol for 3 doses followed by 1 mg/kg of Prednisone with eventual downtrend in Cr to 4.5 in 15 days. Discussion: There have been 2 cases reported in literature with known IgA nephropathy who developed gross hematuria post COVID 19 vaccination. SARS-COV 2 vaccines use nucleoside modified purified mRNA which does elicit higher neutralizing antibody titre and strong cluster of differentiation response leading to production of several proinflammatory cytokines. Thus, there is a concern that vaccines might exacerbate immune mediated glomerular diseases. IgA1 is involved in the pathogenesis of IgA nephropathy and patients with IgA nephropathy have higher than normal IgA1 response to other vaccines like influenza. Also while studying the antibody response to COVID 19 illness patients with IgA nephropathy are known to express higher IgA response compared to IgG and IgM along with reports of concurrent worsening of the glomerulonephritis. Nephrologists should closely follow patients with IgA nephropathy to establish the frequency of disease activation post vaccination.
TCT-279 Impact of Body Composition Indices on Ten-Year Mortality After Revascularization of Complex Coronary Artery Disease (From the Syntax Extended Survival Trial)
Authors: Masafumi Ono, Hideyuki Kawashima, Hironori Hara, Neil O’Leary, Chao Gao, Rutao Wang, Kuniaki Takahashi, Michael Mack, David Holmes, Marie-Claude Morice, Pieter Kappetein, Daniel Thuijs, Thilo Noack, Friedrich-Wilhelm Mohr, Piroze Davierwala, John McEvoy, Yoshinobu Onuma, Patrick Serruys
Journal: Journal of the American College of Cardiology (2021)
TCT-296 Atrial Fibrillation in Patients Undergoing Transcatheter Aortic Valve Implantation Is Associated With Increased Mortality
Authors: Astrid van Nieuwkerk, Roberto Blanco, Didier Tchetche, Fabio Brito, Marco Barbanti, Ran Kornowski, Azeem Latib, Augusto D'Onofrio, Flavio Ribichini, Juan Francisco Oteo Dominguez, Nicolas Dumonteil, Alexandre Abizaid, Jan Baan, Samantha Sartori, Paola D'Errigo, Giuseppe Tarantini, Mattia Lunardi, Katia Orvin, Angie Ghattas, Matteo Pagnesi, George Dangas, Roxana Mehran, Ronak Delewi
Journal: Journal of the American College of Cardiology (2021)
Continued therapy with ABI-H0731+NRTI results in sequential reduction/loss of HBV DNA, HBV RNA, HBeAg, HBcrAg and HBsAg in HBeAg positive patients
Authors: Sulkowski, K Agarwal, SK Fung, Rmf Yuen, XL Ma, JP Lalezari, TT Nguyen, HS Bae, ER Schiff, T Hassanein, Hwl Hann, M Elkhashab, DT Dieterich, PY Kwo, R Nahass, A Ramji, JS Park, N Ravendhran, S Chan, F Weilert, Shb Han, WS Ayoub, EJ Gane, IM Jacobson, M Bennett, M Bonacini, H Zayed, K Alves, Huey, Q Huang, E Ruby, DM Qiang, S Knox, R Colonno
Journal: Hepatology (2019)
Distinct contributions of metabolic dysfunction and genetic risk factors in the pathogenesis of non-alcoholic fatty liver disease
Authors: Panu K. Luukkonen, Sami Qadri, Noora Ahlholm, Kimmo Porthan, Ville Männistö, Henna Sammalkorpi, Anne K. Penttilä, Antti Hakkarainen, Tiina E. Lehtimäki, Melania Gaggini, Amalia Gastaldelli, Mika Ala-Korpela, Marju Orho-Melander, Johanna Arola, Anne Juuti, Jussi Pihlajamäki, Leanne Hodson, Hannele Yki-Järvinen
Journal: Journal of Hepatology (2021)

There is substantial inter-individual variability in the risk of non-alcoholic fatty liver disease (NAFLD). Part of which is explained by insulin resistance (IR) ('MetComp') and part by common modifiers of genetic risk ('GenComp'). We examined how IR on the one hand and genetic risk on the other contribute to the pathogenesis of NAFLD.
Procedure-specific Risks of Thrombosis and Bleeding in Urological Cancer Surgery: Systematic Review and Meta-analysis
Authors: Kari A.O. Tikkinen, Samantha Craigie, Arnav Agarwal, Philippe D. Violette, Giacomo Novara, Rufus Cartwright, Richard Naspro, Reed A.C. Siemieniuk, Bassel Ali, Leyla Eryuzlu, Johanna Geraci, Judi Winkup, Daniel Yoo, Michael K. Gould, Per Morten Sandset, Gordon H. Guyatt
Journal: European Urology (2017)

Pharmacological thromboprophylaxis involves balancing a lower risk of venous thromboembolism (VTE) against a higher risk of bleeding, a trade-off that critically depends on the risks of VTE and bleeding in the absence of prophylaxis (baseline risk).To provide estimates of the baseline risk of symptomatic VTE and bleeding requiring reoperation in urological cancer surgery.We identified contemporary observational studies reporting symptomatic VTE or bleeding after urological procedures. We used studies with the lowest risk of bias and accounted for use of thromboprophylaxis and length of follow-up to derive best estimates of the baseline risks within 4 wk of surgery. We used the GRADE approach to assess the quality of the evidence.We included 71 studies reporting on 14 urological cancer procedures. The quality of the evidence was generally moderate for prostatectomy and cystectomy, and low or very low for other procedures. The duration of thromboprophylaxis was highly variable. The risk of VTE in cystectomies was high (2.6-11.6% across risk groups) whereas the risk of bleeding was low (0.3%). The risk of VTE in prostatectomies varied by procedure, from 0.2-0.9% in robotic prostatectomy without pelvic lymph node dissection (PLND) to 3.9-15.7% in open prostatectomy with extended PLND. The risk of bleeding was 0.1-1.0%. The risk of VTE following renal procedures was 0.7-2.9% for low-risk patients and 2.6-11.6% for high-risk patients; the risk of bleeding was 0.1-2.0%.Extended thromboprophylaxis is warranted in some procedures (eg, open and robotic cystectomy) but not others (eg, robotic prostatectomy without PLND in low-risk patients). For "close call" procedures, decisions will depend on values and preferences with regard to VTE and bleeding.Clinicians often give blood thinners to patients to prevent blood clots after surgery for urological cancer. Unfortunately, blood thinners also increase bleeding. This study provides information on the risk of clots and bleeding that is crucial in deciding for or against giving blood thinners.
Characteristics of Workplace Psychosocial Resources and Risk of Diabetes: A Prospective Cohort Study
Authors: Tianwei Xu, Alice J. Clark, Jaana Pentti, Reiner Rugulies, Theis Lange, Jussi Vahtera, Linda L. Magnusson Hanson, Hugo Westerlund, Mika Kivimäki, Naja H. Rod
Journal: Diabetes Care (2021)

OBJECTIVE To examine whether characteristics of workplace psychosocial resources are associated with the risk of type 2 diabetes among employees. RESEARCH DESIGN AND METHODS Participants were 49,835 employees (77% women, aged 40–65 years, and diabetes free at baseline) from the Finnish Public Sector cohort study. Characteristics of horizontal (culture of collaboration and support from colleagues) and vertical (leadership quality and organizational procedural justice) psychosocial resources were self-reported. Incident type 2 diabetes (n = 2,148) was ascertained through linkage to electronic health records from national registers. We used latent class modeling to assess the clustering of resource characteristics. Cox proportional hazards models were used to examine the relationship between the identified clusters and risk of type 2 diabetes during 10.9 years of follow-up, adjusting for age, sex, marital status, educational level, type of employment contract, comorbidity, and diagnosed mental disorders. RESULTS We identified four patterns of workplace psychosocial resources: unfavorable, favorable vertical, favorable horizontal, and favorable vertical and horizontal. Compared with unfavorable, favorable vertical (hazard ratio 0.87 [95% CI 0.78; 0.97]), favorable horizontal (0.77 [0.67; 0.88]), and favorable vertical and horizontal (0.77 [0.68; 0.86]) resources were associated with a lower risk of type 2 diabetes, with the strongest associations seen in employees at age ≥55 years (Pinteraction = 0.03). These associations were robust to multivariable adjustments and were not explained by reverse causation. CONCLUSIONS A favorable culture of collaboration, support from colleagues, leadership quality, and organizational procedural justice are associated with a lower risk of employees developing type 2 diabetes than in those without such favorable workplace psychosocial resources.
12p gain is predominantly observed in non-germinomatous germ cell tumors and identifies an unfavorable subgroup of central nervous system germ cell tumors
Authors: Kaishi Satomi, Hirokazu Takami, Shintaro Fukushima, Satoshi Yamashita, Yuko Matsushita, Yoichi Nakazato, Tomonari Suzuki, Shota Tanaka, Akitake Mukasa, Nobuhito Saito, Masayuki Kanamori, Toshihiro Kumabe, Teiji Tominaga, Keiichi Kobayashi, Motoo Nagane, Toshihiko Iuchi, Koji Yoshimoto, Kaoru Tamura, Taketoshi Maehara, Keiichi Sakai, Kazuhiko Sugiyama, Kiyotaka Yokogami, Hideo Takeshima, Masahiro Nonaka, Akio Asai, Toshikazu Ushijima, Masao Matsutani, Ryo Nishikawa, Koichi Ichimura
Journal: Neuro-Oncology (2021)

Central nervous system (CNS) germ cell tumors (GCTs) are neoplasms predominantly arising in pediatric and young adult populations. While germinomas generally respond to chemotherapy and radiation, non-germinomatous GCTs (NGGCTs) require more intensive treatment. This study aimed to determine whether 12p gain could predict the prognosis of CNS GCTs.Eighty-two CNS GCTs were included in this study. The 12p gain was defined by an additional 12p in the background of potential polyploidy or polysomy. Cases were analyzed using an Illumina methylation 450K array for copy number investigations and validated by fluorescence in situ hybridization (FISH).A 12p gain was found in 25-out-of-82 cases (30%) and was more frequent in NGGCTs (12% of germinoma cases and 50% of NGGCT cases), particularly in cases with malignant components, such as immature teratoma, yolk sac tumor, choriocarcinoma, and embryonal carcinoma. 12p gain and KIT mutation were mutually exclusive events. The presence of 12p gain correlated with shorter progression-free (PFS) and overall survival (OS) (10-year OS: 59% vs. 94%, with and without 12p gain, respectively, P = 0.0002), even with histology and tumor markers incorporated in the multivariate analysis. Among NGGCTs, 12p gain still had prognostic significance for PFS and OS (10-year OS: 47% vs. 90%, respectively, P = 0.02). The 12p copy number status was shared among histological components in mixed GCTs.12p gain may predict the presence of malignant components of NGGCTs, and poor prognosis of the patients. It may be associated with early tumorigenesis of CNS GCT.
Telestration and Augmented Reality in Minimally Invasive Surgery
Authors: Felix Nickel, Amila Cizmic, Manish Chand
Journal: JAMA Surgery (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Electronic health record-based genome-wide meta-analysis provides insights on the genetic architecture of non-alcoholic fatty liver disease
Authors: Nooshin Ghodsian, Erik Abner, Connor A. Emdin, Émilie Gobeil, Nele Taba, Mary E. Haas, Nicolas Perrot, Hasanga D. Manikpurage, Éloi Gagnon, Jérôme Bourgault, Alexis St-Amand, Christian Couture, Patricia L. Mitchell, Yohan Bossé, Patrick Mathieu, Marie-Claude Vohl, André Tchernof, Sébastien Thériault, Amit V. Khera, Tõnu Esko, Benoit J. Arsenault
Journal: Cell Reports Medicine (2021)

Non-alcoholic fatty liver disease (NAFLD) is a complex disease linked to several chronic diseases. We aimed at identifying genetic variants associated with NAFLD and evaluating their functional consequences. We performed a genome-wide meta-analysis of 4 cohorts of electronic health record-documented NAFLD in participants of European ancestry (8,434 cases and 770,180 controls). We identify 5 potential susceptibility loci for NAFLD (located at or near GCKR, TR1B1, MAU2/TM6SF2, APOE, and PNPLA3). We also report a potentially causal effect of lower LPL expression in adipose tissue on NAFLD susceptibility and an effect of the FTO genotype on NAFLD. Positive genetic correlations between NAFLD and cardiometabolic diseases and risk factors such as body fat accumulation/distribution, lipoprotein-lipid levels, insulin resistance, and coronary artery disease and negative genetic correlations with parental lifespan, socio-economic status, and acetoacetate levels are observed. This large GWAS meta-analysis reveals insights into the genetic architecture of NAFLD.
Fractional Flow Reserve–Guided PCI as Compared with Coronary Bypass Surgery
Authors: William F. Fearon, Frederik M. Zimmermann, Bernard De Bruyne, Zsolt Piroth, Albert H.M. van Straten, Laszlo Szekely, Giedrius Davidavičius, Gintaras Kalinauskas, Samer Mansour, Rajesh Kharbanda, Nikolaos Östlund-Papadogeorgos, Adel Aminian, Keith G. Oldroyd, Nawwar Al-Attar, Nikola Jagic, Jan-Henk E. Dambrink, Petr Kala, Oskar Angerås, Philip MacCarthy, Olaf Wendler, Filip Casselman, Nils Witt, Kreton Mavromatis, Steven E.S. Miner, Jaydeep Sarma, Thomas Engstrøm, Evald H. Christiansen, Pim A.L. Tonino, Michael J. Reardon, Di Lu, Victoria Y. Ding, Yuhei Kobayashi, Mark A. Hlatky, Kenneth W. Mahaffey, Manisha Desai, Y. Joseph Woo, Alan C. Yeung, Nico H.J. Pijls
Journal: New England Journal of Medicine (2021)

Patients with three-vessel coronary artery disease have been found to have better outcomes with coronary-artery bypass grafting (CABG) than with percutaneous coronary intervention (PCI), but studies in which PCI is guided by measurement of fractional flow reserve (FFR) have been lacking.
A regulatory perspective on recombinant collagen-based medical devices
Authors: Wenbo Liu, Hai Lin, Peng Zhao, Lina Xing, Jie Li, Zehua Wang, Shan Ju, XinLi Shi, Yinghui Liu, Gang Deng, Guobiao Gao, Lei Sun, Xindong Zhang
Journal: Bioactive Materials (2021)

As a class of novel biomaterials manufactured by synthetic biology technologies, recombinant collagens are candidates for a variety of medical applications. In this article, a regulatory scientific perspective on recombinant collagens and their medical devices is presented with a focus on the definition, translation, classification and technical review. Recombinant collagens are categorized as recombinant human collagen, recombinant humanized collagen and recombinant collagen-like protein, as differentiated by specific compositions and structures. Based on their intended uses and associated risks, recombinant collagen-based medical devices are generally classified as Class Ⅱ or Ⅲ in China. The regulatory review of recombinant collagen-based medical devices aims to assess their safety and efficacy demonstrated by scientific evidences generated from preclinical and clinical evaluations. Taken together, opportunities as well as challenges for their future clinical translation of recombinant collagen-based medical devices abound, which highlights the essential role of regulatory science to provide new tools, standards, guidelines and methods to evaluate the safety and efficacy of medical products.
One-pot preparation of nanodispersion with readily available components for localized tumor photothermal and photodynamic therapy
Authors: Anpu Yang, Yanan Sun, Bochen Lyu, Binlong Chen, Zhipu Fan, Minghui Li, Yao Zhao, Jijun Fu, Bing He, Hua Zhang, Xueqing Wang, Wenbing Dai, Qiang Zhang
Journal: Asian Journal of Pharmaceutical Sciences (2021)

Photothermal (PTT) and photodynamic (PDT) combined therapy has been hindered to clinical translation, due to the lack of available biomaterials, difficult designs of functions, and complex chemical synthetic or preparation procedures. To actualize a high-efficiency combination therapy for cancer via a feasible approach, three readily available materials are simply associated together in one-pot, namely the single-walled carbon nanohorns (SWCNH), zinc phthalocyanine (ZnPc), and surfactant TPGS. The established nanodispersion is recorded as PCT. The association of SWCNH/ZnPc/TPGS was confirmed by energy dispersive spectrum, Raman spectrum and thermogravimetric analysis. Under lighting, PCT induced a temperature rising up to about 60 °C due to the presence of SWCNH, production a 7-folds of singlet oxygen level elevation because of ZnPc, which destroyed almost all 4T1 tumor cells in vitro. The photothermal effect of PCT depended on both laser intensity and nanodispersion concentration in a linear and nonlinear manner, respectively. After a single peritumoral injection in mice and laser treatment, PCT exhibited the highest tumor temperature rise (to 65 °C) among all test groups, completely destroyed primary tumor without obvious toxicity, and inhibited distant site tumor. Generally, this study demonstrated the high potential of PCT nanodispersion in tumor combined therapy.