tbuckley/cabot-search huggingface dataset:
Preclinical evaluation of a dual magnetic and fluorescence-guided approach for sentinel lymph node biopsy in the stomach.
Authors: Anil Shetty, Aidan Cousins, Shridhar Krishnan, Nguyen Pham, Valentina Milanova, Giri Krishnan, Melanie Nelson, Naruhiko Ikoma, Benjamin Thierry
Journal: Journal of Clinical Oncology (2022)

337 Background: Gastrectomy with extended (D2) lymphadenectomy is considered as a standard of care for gastric cancer to provide best possible outcomes and pathologic staging. However, D2 gastrectomy is technically demanding operation and reported to be associated with increased complications, including bleeding, pancreatitis, abscess, chylous ascites, and mortality. Application of sentinel lymph node mapping in gastric cancer has the potential to reduce patient morbidity, while facilitating detailed pathology processing required to accurately identify nodal metastases. However, sentinel lymph node biopsy techniques are not established for gastrectomy because of a lack of practical tracers; an effective and convenient tracer that exclusively accumulates in sentinel lymph nodes is critically needed. Methods: A lymphotropic tracer solution consisting of mannose-labelled magnetic nanoparticles (SPIONs) and a fluorescent dye (indocyanine green, ICG) was injected laparoscopically into the stomach submucosa of 6 healthy female domesticated pigs while under general anaesthesia. Intraoperative laparoscopic fluorescence imaging was used to highlight draining lymphatic pathways containing ICG, while a combination of T2-weighted MRI and magnetometer probe detection were used to identify nodes containing SPIONs. Results: Mixing the ICG dye and SPIONs ensured concurrence of fluorescent and magnetic signals in the sentinel nodes. Average tracer accumulation time before dissection was 5 hours. On average 4.5 fluorescent nodes (range 2–7) were removed, of which 2 (average) were also magnetic (range 1–4). Magnetic nodes could be identified using both preoperative MRI and intraoperative magnetometer probe. The mannose label of the SPIONs produced a strong binding affinity to macrophages, and in combination with particle size (80 nm) results in enhanced retention in the sentinel nodes. On average, after 5 hours accumulation time, the sentinel nodes contained 4.1% of the SPION injected dose and 88% of the magnetometer counts. Conclusions: Through the co-injection of fluorescent and mannose-labelled magnetic tracers, lymphatic drainage pathways can be determined preoperatively with MRI, visualised with intraoperative fluorescence cameras, and SLNs confirmed with magnetometer. Although ICG flows through multiple echelons, in doing so it creates a lymphatic roadmap to guide surgeons. The addition of magnetic particles provides sentinel node discrimination, so in combination, these two tracers could greatly enhance the capability to detect SLNs in gastric cancer.
Abstract 404: NLR Family, Pyrin Domain-containing 3 Knockout Rescues Cardiac Dysfunction Induced by High-fat Diet Feeding
Authors: Matthew R Peterson, Samantha Haller, Tracy Ta, Luiza Bosch, Aspen Smith, Alyssa Sanders, Jelard Aquino, Guanglong He
Journal: Circulation Research (2017)

NLR family, pyrin domain-containing 3 (NLRP3) is a pattern recognition receptor responsible for perpetuating an inflammatory response through production of pro-inflammatory cytokines IL-1β and IL-18. It has been implicated in the sustained inflammatory response in obesity and multiple cardiovascular disease conditions. In order to investigate NLRP3 as a potential therapeutic target in metabolic syndrome, C57BL/6 wild-type (WT) and NLRP3 knockout (NLRP3-\-) mice were fed a normal diet (ND; 12% fat chow) or a high fat diet (HFD; 45% fat chow) for 5 months. At 5 months, echocardiography and glucose tolerance tests (GTTs) were performed. Cardiac function assessed by fractional shortening (FS) was significantly impaired by HFD feeding in the WT group (0.335 HFD vs. 0.456 ND; p&lt;0.05) but not in the NLRP3-\- (0.449 HFD vs. 0.492 ND; p&gt;0.05). FS was higher in NLRP3-\-HFD than in WT-HFD (p&lt;0.05). Two-dimensional analysis shows the FS difference between NLRP3-\-HFD and WT-HFD was primarily explained by the difference in left ventricular end-systolic dimension (0.2716 cm WT vs. 0.1883 cm NLRP3-\-; p&lt;0.05). Glucose tolerance measured by area under the curve (AUC) was significantly impaired by HFD feeding for both WT (23183 ND vs. 57298 HFD; p&lt;0.001) and NLRP3-\- (23197 ND vs. 44626 HFD; p&lt;0.001), but significantly better in the NLRP3-\-HFD than in WT-HFD (p&lt;0.01). HFD feeding increased fasting blood glucose (FBG) for both WT (97.7 mg . dl -1 ND vs. 164.7 mg . dl -1 HFD; p&lt;0.01) and NLRP3-\- (80.50 mg . dl -1 ND vs. 108.8 mg . dl -1 HFD; p&lt;0.05), but significantly less in NLRP3-\- mice (NLRP3-\- vs. WT; p&lt;0.05). For GTTs, body weight was significantly higher in the WT than NLRP3-\- fed HFD (47.93 g vs. 36.5 g; p&lt;0.001). Body weight explained 92% of variation in glucose tolerance (p&lt;0.0001) and 69% of variation in fasting blood glucose (p&lt;0.0001). WT-HFD averaged 1.31X heavier than NLRP3-\-HFD, while the AUC for the IGTT was 1.28X larger for the WT-HFD than NLRP3-\-HFD. Body weights were not significantly different between genotypes at the time of echo. The results suggest that knockout of NLRP3 may be protective against HFD induced cardiovascular dysfunction. A protective effect on glucose tolerance is not strongly supported.
Secreted acid sphingomyelinase as a potential gene therapy for limb girdle muscular dystrophy 2B
Authors: Daniel C. Bittel, Sen Chandra Sreetama, Goutam Chandra, Robin Ziegler, Kanneboyina Nagaraju, Jack H. Van der Meulen, Jyoti K. Jaiswal
Journal: Journal of Clinical Investigation (2022)

Efficient sarcolemmal repair is required for muscle cell survival, with deficits in this process leading to muscle degeneration. Lack of the sarcolemmal protein dysferlin impairs sarcolemmal repair by reducing secretion of the enzyme acid sphingomyelinase (ASM), and causes limb girdle muscular dystrophy 2B (LGMD2B). The large size of the dysferlin gene poses a challenge for LGMD2B gene therapy efforts aimed at restoring dysferlin expression in skeletal muscle fibers. Here, we present an alternative gene therapy approach targeting reduced ASM secretion, the consequence of dysferlin deficit. We showed that the bulk endocytic ability is compromised in LGMD2B patient cells, which was addressed by extracellularly treating cells with ASM. Expression of secreted human ASM (hASM) using a liver-specific adeno-associated virus (AAV) vector restored membrane repair capacity of patient cells to healthy levels. A single in vivo dose of hASM-AAV in the LGMD2B mouse model restored myofiber repair capacity, enabling efficient recovery of myofibers from focal or lengthening contraction-induced injury. hASM-AAV treatment was safe, attenuated fibro-fatty muscle degeneration, increased myofiber size, and restored muscle strength, similar to dysferlin gene therapy. These findings elucidate the role of ASM in dysferlin-mediated plasma membrane repair and to our knowledge offer the first non-muscle-targeted gene therapy for LGMD2B.
Incorrect Statement
Journal: JAMA (1989)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Can low molecular heparin dalteparin inhibit in-stent neointimal hyperplasia following repeated PTCA to treat in-stent restenosis? A randomized trial followed by serial IVUS analysis Jun-ichi Kotani, Shinsuke Nanto, Tomoki Ohara, Takakazu Morozumi, Tetsuya Watanabe, Masashi Fujita, Mayu Nishio, Seiki Nagata. Kansai Rosai Hospital, Amagasaki, Japan
Journal: Journal of the American College of Cardiology (2001)
Functional-related distribution of $beta;3-adrenergic receptor in cardiac chambers Heng-Jie Cheng, Zhu-Shan Zhang, Tomohiko Ukai, Hideo Tachibana, Akihiko Igawa, David Sane, Che-Ping Cheng. Wake Forest University School of Medicine, Winston-Salem, NC
Journal: Journal of the American College of Cardiology (2001)
Real-world clinical outcomes of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with liposomal irinotecan-based regimens: Impact of prior irinotecan (IRI) exposure.
Authors: Kenneth H. Yu, Paul Cockrum, Andy Surinach, Neil Lamarre, Shu Wang, Eileen Mary O'Reilly
Journal: Journal of Clinical Oncology (2022)

580 Background: Subgroup analyses of the NAPOLI-1 study identified that among patients who were IRI naïve prior to entering the clinical trial, a survival benefit was observed between the study arm and control arm (overall survival (OS): 6.7 months vs 4.2 months). This treatment benefit was not observed among those previously exposed to IRI (OS: 4.6 months in study arm vs 4.8 months in control arm). This study sought to understand the impact of prior exposure to IRI on clinical outcomes among patients treated with liposomal irinotecan in the real-world setting. Methods: This retrospective observational study utilized the Flatiron Health EHR database. Data were analyzed for adult patients with mPDAC treated with liposomal irinotecan -based regimens between January 2016 and October 2020. Patient characteristics, OS and progression-free survival (PFS) were assessed. Prior IRI was defined as IRI given in a prior regimen in the metastatic setting. Cox proportional hazard (PH) methods were used to calculate hazard ratios (HRs). HRs were adjusted to account for demographics and relevant clinical covariates. Patients without prior exposure to IRI were used as the reference population for the Cox PH model (an HR &lt; 1 represents worse survival for unexposed patients relative to the exposed). Results: 675 patients with mPDAC treated with a liposomal irinotecan-based regimen were included. Median age at treatment initiation was 69 (IQR: 62 – 75) years and among patients with available ECOG performance status (PS), 77.4% had a PS of 0-1. 181 (27%) patients were previously exposed to IRI in the metastatic setting (Table). The unadjusted OS HR was 1.3 (95% CI: 1.1 – 1.6, p &lt; 0.001) and the unadjusted PFS HR was 1.4 (95%CI: 1.2 – 1.7, p &lt; 0.001). After adjustment for baseline characteristics the adjusted OS HR was 1.0 (95% CI: 0.8 – 1.3, p = 0.8836) and the adjusted PFS HR was 1.1 (95%: 0.8 – 1.4, p = 0.5626). Conclusions: The results of this study suggest prior exposure to IRI is not a predictor of worse clinical outcomes for patients treated with liposomal irinotecan-based treatment when accounting for key clinical characteristics in a multivariable model. The results from this real-world study can be used to support treatment sequencing decisions for patients with mPDAC following first line therapy. This is the largest real-world evidence study to date of patients with mPDAC treated with liposomal irinotecan.[Table: see text]
The Yin and Yang of ERBB4: Tumor Suppressor and Oncoprotein
Authors: Lauren M. Lucas, Vipasha Dwivedi, Jared I. Senfeld, Richard L. Cullum, Christopher P. Mill, J. Tyler Piazza, Ianthe N. Bryant, Laura J. Cook, S. Tyler Miller, James H. Lott, Connor M. Kelley, Elizabeth L. Knerr, Jessica A. Markham, David P. Kaufmann, Megan A. Jacobi, Jianzhong Shen, David J. Riese
Journal: Pharmacological Reviews (2022)

ERBB4 (HER4) is a member of the ERBB family of receptor tyrosine kinases, a family that includes the epidermal growth factor receptor (EGFR/ERBB1/HER1), ERBB2 (Neu/HER2), and ERBB3 (HER3). EGFR and ERBB2 are oncoproteins and validated targets for therapeutic intervention in a variety of solid tumors. In contrast, the role that ERBB4 plays in human malignancies is ambiguous. Thus, here we review the literature regarding ERBB4 function in human malignancies. We review the mechanisms of ERBB4 signaling with an emphasis on mechanisms of signaling specificity. In the context of this signaling specificity, we discuss the hypothesis that ERBB4 appears to function as a tumor suppressor protein and as an oncoprotein. Next, we review the literature that describes the role of ERBB4 in tumors of the bladder, liver, prostate, brain, colon, stomach, lung, bone, ovary, thyroid, hematopoietic tissues, pancreas, breast, skin, head, and neck. Whenever possible, we discuss the possibility that ERBB4 mutants function as biomarkers in these tumors. Finally, we discuss the potential roles of ERBB4 mutants in the staging of human tumors and how ERBB4 function may dictate the treatment of human tumors. <h3>Significance Statement</h3> This articles reviews ERBB4 function in the context of the mechanistic model that ERBB4 homodimers function as tumor suppressors, whereas ERBB4-EGFR or ERBB4-ERBB2 heterodimers act as oncogenes. Thus, this review serves as a mechanistic framework for clinicians and scientists to consider the role of ERBB4 and <i>ERBB4</i> mutants in staging and treating human tumors.
How is the outcome of coronary stenting in the elderly compared to younger patients? Daniela Trabattoni, Piero Montorsi, Alessandro Loaldi, Franco Fabbiocchi, Stefano Galli, Luca Grancini, Paolo Ravagnani, Sergio Cozzi, Antonio L. Bartorelli. Centro Cardiologico Monzino, IRCCS, Institute of Cardiology, University of Milan, Milan, Italy
Journal: Journal of the American College of Cardiology (2001)
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Journal: JAMA (1991)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
TCT-197: Multi Center, Prospective, Randomized, Single Blind, Consecutive Enrollment Evaluation of the Elixir DESyneTM BD Novolimus-Eluting Coronary Stent System with Bioabsorbable Polymer Compared to the Endeavor Zotarolimus- Eluting Coronary Stent System: 6- Month Clinical Angiographic and IVUS Results: The EXCELLA BD Study
Journal: Journal of the American College of Cardiology (2011)
Myocyte contractility and quabain toxicity in transgenic mice which overexpress the alpha3 isoform of the Na,K-ATPase Glenn T. Wetzel, Raphael Zahler, Shahla Jilani, Fuhua Chen. Mattel Children's Hospital at UCLA, Los Angeles, CA, Kaiser Permanente, Los Angeles, CA
Journal: Journal of the American College of Cardiology (2001)
Varied skin reactions after COVID-19 vaccination
Journal: British Journal of Dermatology (2022)

Abstract Linked Article: Català et al. Br J Dermatol 2022; 186:142–152. COVID-19 vaccination has been associated with skin reactions in clinical trials. The most frequent was the so-called ‘COVID arm’, consisting of redness, swelling and pain at the injection site in the arm. After approval and during mass vaccination, other rashes beyond the injection site have been reported but have been poorly described. The researchers, working with dermatologists across Spain using an online survey, collected information about 405 rashes occurring within 21 days after any dose of any COVID-19 vaccine approved at the time of the study (Pfizer, Moderna and AstraZeneca). All the skin reactions were described and classified by agreement between the authors and with the help of pictures. The results have shown that rashes after these vaccines are varied and more frequent in women. The most observed skin reaction was ‘COVID arm’, which occurs especially after the Moderna vaccine and was the reaction most often associated with general symptoms. In addition, other more extensive rashes were described that were usually itchy and consisted of wheals (urticaria), small red bumps or blisters, red scaly patches, measles-like rashes or purple lesions. In addition, there were reactivations of herpetic infections (mainly shingles), especially after the Pfizer-BioNTech vaccine. The most described skin reaction after the AstraZeneca vaccine was wheals. Most of these rashes were mild, required treatment with antihistamines and/or corticosteroids, and resolved on average within 12 days. This study may help healthcare workers to recognize these rashes better and to be able to advise and reassure the population during mass vaccination campaigns against COVID-19. Linked Article: Català et al. Br J Dermatol 2022; 186:142–152.
The Health Care Workforce Under Stress—Clinician Heal Thyself
Authors: Bernard P. Chang
Journal: JAMA Network Open (2022)

Daniel T. Myran, MD, MPH; Nathan Cantor, MSc; Emily Rhodes, MSc; Michael Pugliese, MSc; Jennifer Hensel, MD, MSc; Monica Taljaard, PhD; Robert Talarico, MSc; Amit X. Garg, MD, PhD; Eric McArthur, MSc; Cheng-Wei Liu, MD; Nivethika Jeyakumar, MSc; Christopher Simon, PhD; Taylor McFadden, PhD; Caroline Gerin-Lajoie, MD; Manish M. Sood, MD, MSc; Peter Tanuseputro, MD, MHSc
Selected Articles from This Issue
Journal: Clinical Cancer Research (2022)

The prognosis for patients diagnosed with epithelial ovarian cancer remains poor, especially in those patients resistant to platinum therapy. Evidence has suggested that the Wee1 inhibitor adavosertib may be efficacious in combination with chemotherapy. Moore and colleagues conducted a clinical trial of adavosertib combined with four commonly used chemotherapeutics in patients with primary platinum-resistant ovarian cancer. Combinations were effective, with 3% of patients achieving a complete response and 29% of patients with partial response. The response rate was highest with adavosertib plus carboplatin, while the longest duration of response was observed in patients treated with adavosertib plus paclitaxel. However, many patients experienced toxicity. These results indicate that although adavosertib may have promise for the treatment of ovarian cancer, further clinical study is necessary to minimize toxicity.Checkpoint inhibitors have improved outcomes in patients with many cancer subtypes, but resistance to treatment remains a challenge. In this clinical trial, Siu and colleagues assessed MK-4830, a first-in-class monoclonal antibody targeting the immunoglobulin-like transcrip. R (ILT4) receptor, either as monotherapy or in combination with the PD-1 inhibitor pembrolizumab. No dose-limiting toxicities were observed, and maximum-tolerated dose was not reached. Furthermore, promising clinical activity was observed with 11/34 patients receiving combination therapy achieving objective responses. Patients with evidence of T-cell inflammation were more likely to respond. Further study of this novel agent is warranted in additional clinical trials.Preclinical work has suggested that OX40 agonism may promote anti-tumor immunity, leading to effective antitumor responses. In this study, Diab and colleagues conducted a clinical trial assessing ivuxolimab, a monoclonal antibody against OX40, in patients with advanced solid tumors. Ivuxolimab was well tolerated, with no dose-limiting toxicities. Preliminary antitumor activity was observed, with disease control occuring in 56% of patients. Evidence of immune activation was observed in peripheral blood, as well as in on-treatment biopsies. Further clinical trials of ivuxolimab are warranted, especially in the combination setting.Stereotactic body radiotherapy (SBRT) is an emerging local treatment strategy for pancreatic ductal adenocarcinoma (PDAC). To characterize SBRT effects on the human tumor immune microenvironment, Mills and colleagues analyzed resected PDAC tissue a median seven days post-treatment. SBRT induced immunogenic cell death and initiated antitumor immune responses; however, treatment failed to lessen or reprogram abundant immune suppressor populations. SBRT did not improve clinical survival outcomes, but the augmentation of antitumor immunity supports and informs the continued development of SBRT/immunotherapy combinations for PDAC.
High-sensitive cardiac troponin after CPAP in obstructive sleep apnoea: the adjusted analytical change limit (adjACL) for small variations at low concentrations
Authors: Denis Monneret
Journal: European Respiratory Journal (2022)

<b>Interpreting change in cardiac troponin after CPAP in OSA is challenging, especially since the lower the troponin concentration, the higher the analytical imprecision. In such cases, the adjusted analytical change limit (adjACL) should be used.</b>https://bit.ly/3eaHcuq
Cancer-Associated SF3B1 Mutations Confer a BRCA-Like Cellular Phenotype and Synthetic Lethality to PARP Inhibitors
Authors: Katrina M. Lappin, Eliana M. Barros, Satpal S. Jhujh, Gareth W. Irwin, Hayley McMillan, Fabio G. Liberante, Cheryl Latimer, Melissa J. La Bonte, Ken I. Mills, D. Paul Harkin, Grant S. Stewart, Kienan I. Savage
Journal: Cancer Research (2022)

Mutations in SF3B1 have been identified across several cancer types. This key spliceosome component promotes the efficient mRNA splicing of thousands of genes including those with crucial roles in the cellular response to DNA damage. Here, we demonstrate that depletion of SF3B1 specifically compromises homologous recombination (HR) and is epistatic with loss of BRCA1. More importantly, the most prevalent cancer-associated mutation in SF3B1, K700E, also affects HR efficiency and as a consequence, increases the cellular sensitivity to ionizing radiation and a variety of chemotherapeutic agents, including PARP inhibitors. In addition, the SF3B1 K700E mutation induced unscheduled R-loop formation, replication fork stalling, increased fork degradation, and defective replication fork restart. Taken together, these data suggest that tumor-associated mutations in SF3B1 induce a BRCA-like cellular phenotype that confers synthetic lethality to DNA-damaging agents and PARP inhibitors, which can be exploited therapeutically.The cancer-associated SF3B1K700E mutation induces DNA damage via generation of genotoxic R-loops and stalled replication forks, defective homologous recombination, and increased replication fork degradation, which can be targeted with PARP inhibitors.