tbuckley/cabot-search huggingface dataset:
Dietary Geranylgeranyl Pyrophosphate Counteracts the Benefits of Statin Therapy in Experimental Pulmonary Hypertension
Authors: Liping Zhu, Fangbo Liu, Qiang Hao, Tian Feng, Zeshuai Chen, Shengquan Luo, Rui Xiao, Mengxiang Sun, Ting Zhang, Xiaohang Fan, Xianqin Zeng, Jianguo He, Ping Yuan, Jinming Liu, Matthieu Ruiz, Jocelyn Dupuis, Qinghua Hu
Journal: Circulation (2021)

The mevalonate pathway generates endogenous cholesterol and intermediates including geranylgeranyl pyrophosphate (GGPP). By reducing GGPP production, statins exert pleiotropic or cholesterol-independent effects. The potential regulation of GGPP homeostasis through dietary intake and the interaction with concomitant statin therapy is unknown.We developed a sensitive high-pressure liquid chromatography technique to quantify dietary GGPP and conducted proteomics, qualitative real-time polymerase chain reaction screening, and Western blot to determine signaling cascades, gene expression, protein-protein interaction, and protein membrane trafficking in wild-type and transgenic rats.GGPP contents were highly variable depending on food source that differentially regulated blood GGPP levels in rats. Diets containing intermediate and high GGPP reduced or abolished the effects of statins in rats with hypoxia- and monocrotaline-induced pulmonary hypertension: this was rescuable by methyl-allylthiosulfinate and methyl-allylthiosulfinate-rich garlic extracts. In human pulmonary artery smooth muscle cells treated with statins, hypoxia activated RhoA in an extracellular GGPP-dependent manner. Hypoxia-induced ROCK2 (Rho associated coiled-coil containing protein kinase 2)/Rab10 (Ras-related protein rab-10) signaling was prevented by statin and recovered by exogenous GGPP. The hypoxia-activated RhoA/ROCK2 pathway in rat and human pulmonary artery smooth muscle cells upregulated the expression of Ca2+-sensing receptor (CaSR) and HIMF (hypoxia-induced mitogenic factor), a mechanism attenuated by statin treatment and regained with exogenous GGPP. Rab10 knockdown almost abrogated hypoxia-promoted CaSR membrane trafficking, a process diminished by statin and resumed by exogenous GGPP. Hypoxia-induced pulmonary hypertension was reduced in rats with CaSR mutated at the binding motif of HIMF and the interaction between dietary GGPP and statin efficiency was abolished. In humans fed a high GGPP diet, blood GGPP levels were increased. This abolished statin-lowering effects on plasma GGPP, and also on hypoxia-enhanced RhoA activity of blood monocytes that was rescued by garlic extracts.There is important dietary regulation of GGPP levels that interferes with the effects of statin therapy in experimental pulmonary hypertension. These observations rely on a key and central role of RhoA-ROCK2 cascade activation and Rab10-faciliated CaSR membrane trafficking with subsequent overexpression and binding of HIMF to CaSR. These findings warrant clinical investigation for the treatment of pulmonary hypertension and perhaps other diseases by combining statin with garlic-derived methyl-allylthiosulfinate or garlic extracts and thus circumventing dietary GGPP variations.
Adolescents and Young Adults Living With an Uncertain or Poor Cancer Prognosis: The “New” Lost Tribe
Authors: Vivian W.G. Burgers, Winette T.A. van der Graaf, Daniël J. van der Meer, Martin G. McCabe, Anita W. Rijneveld, Martin J. van den Bent, Olga Husson
Journal: Journal of the National Comprehensive Cancer Network (2021)

Historically, adolescent and young adult (AYA) patients with cancer, diagnosed for the first time at age 15 through 39 years, have often been identified as a “lost tribe” without a medical “home”; neither pediatric nor adult oncology services were able to provide age-appropriate care to this specific group. Internationally, AYA care programs are being established to bridge the gap between the age-defined healthcare worlds and to address the specific needs of AYAs with cancer. However, AYA care programs mostly focus on improving cure rates and addressing survivorship issues, and direct less attention to the unique needs of those living with an uncertain and/or poor cancer prognosis. Additionally, palliative care services are typically poorly equipped to address the age-specific needs of this group. Given that increasingly more AYAs with an uncertain and/or poor cancer prognosis are gaining life years because of novel treatments, and sometimes even face the prospect of long-term disease control, AYA care programs should address the unique palliative care needs of this “new” lost tribe within AYA oncology. This report provides a definition and description of the AYA population living with an uncertain and/or poor cancer prognosis in terms of epidemiologic, clinical, and psychosocial characteristics and challenges, and provides perspectives for future research and care initiatives. It also highlights the need to comprehensively examine the experience of AYAs who are living with uncertain and/or poor cancer prognosis to adjust best care practices for this unique group.
Abstract PO007: Role of PI3K pathway in reprogramming the tumor niche of angiosarcoma
Authors: Sophia Wenthe, Ashley J. Schulte, Mathew G. Angelos, Dan S. Kaufman, Jaime F. Modiano, Jong Hyuk Kim
Journal: Cancer Research (2021)

Abstract Angiosarcoma (AS) is a highly aggressive, rare soft-tissue sarcoma that forms malignant blood vessels. Approximately half of patients have metastatic or unresectable disease with a median overall survival of less than 6 months, and tumor-related mortality is high. Inflamed tissue is frequently seen in angiosarcomas, and immune cells are key components that contribute to the landscape of the tumor microenvironment. Hemangiosarcoma (HSA) occurs commonly in companion dogs, and it shares clinical and morphological features with human AS. Recurrent mutations in TP53 and genes involved in PI3K pathway such as PIK3CA, and PIK3R1 were observed in both human AS and canine HSA, and the mutational landscape was associated with distinct molecular tumor subtypes; in particular, differing immunophenotypes. Recently, we have shown that human AS and canine HSA establish convergent transcriptional programs driven by angiogenic fusion genes and TP53 mutation. However, these vascular tumors are genomically complex, and molecular mechanisms that establish the tumor microenvironment are incompletely known. In this study, we analyzed RNA-seq transcriptomic data generated from human AS tissues (n=13) and canine HSA tissues (n=76) and HSA cell lines (n=11). The data showed that the tumors of both species enriched gene signatures associated with maintenance of hematopoietic stem cells. Then, we found that canine HSA cells supported expansion and differentiation of human CD34+ umbilical cord blood cells using long-term culture-initiating cell and colony-forming unit assays. We also developed xenograft models of canine HSA that facilitate myelopoiesis and macrophage infiltration in the tumor tissue. Our data showed that gene signatures of monocytes and naïve macrophages were detectable in canine HSA cells. In human ASs, macrophage-associated genes, in particular M2 macrophage signatures were significantly enriched, compared to normal tissues. Collectively, our data suggest that human AS and canine HSA have cell-autonomous capacity to govern hematopoietic progenitors and immune cells, potentially establishing the tumor immune niche. We engineered HSA cells to induce homozygous H1047R mutations in PIK3CA gene using CRISPR-Cas9 system. Our ongoing work is to determine if regulating PI3K pathway in the tumor cells contributes to the molecular programs that create the tumor niche of the vascular malignancy. Citation Format: Sophia Wenthe, Ashley J. Schulte, Mathew G. Angelos, Dan S. Kaufman, Jaime F. Modiano, Jong Hyuk Kim. Role of PI3K pathway in reprogramming the tumor niche of angiosarcoma [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr PO007.
Androgen deprivation therapy and risk of SARS-CoV-2 infection in men with prostate cancer: A University of California (UC) Health System registry study.
Authors: Daniel Kwon, Rohit Vashisht, Hala Borno, Rahul Raj Aggarwal, Eric Jay Small, Atul Butte, Franklin W. Huang
Journal: Journal of Clinical Oncology (2021)

37 Background: SARS-CoV-2 entry into host cells is facilitated by the transmembrane protease TMPRSS2. TMPRSS2 expression can be modulated by the androgen receptor. It is unclear whether androgen deprivation therapy (ADT) may partially protect from SARS-CoV-2 infection. Methods: A retrospective registry study of adult men with prostate cancer who underwent testing for SARS-CoV-2 in the UC Health System between February 1, 2020 and October 6, 2020 was performed. The University of California Health COVID Research Data Set (UC CORDS), which includes electronic health data of all patients who underwent testing for SARS-CoV-2 at 5 UC academic medical centers (UC Davis, UC Irvine, UC Los Angeles, UC San Diego, and UC San Francisco) and 12 affiliated hospitals across California, was used. Association of SARS-CoV-2 infection and receipt of ADT (GnRH agonist or antagonist) within 90 days of COVID testing was determined using the Chi-Squared test. Analyses (Chi-Squared or Fisher’s exact tests) were also performed in race/ethnicity subgroups. Results: Overall, 2,948 men with prostate cancer who underwent SARS-CoV-2 testing were identified, of whom 59 (2.0%) tested positive. Of the 2,948 men, 2,124 (72%) were White; 219 (7%) Black or African-American; 182 (6%) Asian or Native Hawaiian/Pacific-Islander; 176 (6%) Other race; and 247 (8%) Unknown race. There were 235 (8%) Hispanic or Latino men. Among the 444 men who received ADT in the entire cohort, 7 (1.6%) tested positive, and among the 2,504 men who did not receive ADT, 52 (2.1%) tested positive (OR 0.76, 95% CI 0.34-1.67, P = 0.49). No statistically significant association between ADT and SARS-CoV-2 positivity was found within race or ethnicity subgroups. Conclusions: No association between the use of ADT and the risk of testing positive for SARS-CoV-2 was identified in this study of a diverse patient population in the University of California Health System medical centers and hospitals. In this setting of an overall low prevalence of SARS-CoV-2 infection, thus far, there is no strong evidence of a protective benefit of ADT.
Are COVID-19 vaccines safe in pregnancy?
Authors: Victoria Male
Journal: Nature reviews. Immunology (2021)

As the COVID-19 vaccination programme starts to be rolled out, many young women are hesitant to accept the vaccine, citing concerns about fertility. Meanwhile, those offered the vaccine during pregnancy must decide whether they will accept, even though pregnant people were excluded from the clinical trials. Data on accidental pregnancies that occurred during the trials and, increasingly, outcomes in pregnant people who receive the vaccine can help these groups to make informed decisions. Reassuring data from accidental pregnancies that have occurred in the clinical trials of approved COVID-19 vaccines indicate that vaccination does not harm fertility or increase the rate of miscarriage.
Capsule endoscopies will be trialled in England
Authors: Zosia Kmietowicz
Journal: BMJ (2021)

Miniature cameras contained in a capsule for patients to swallow are set to be trialled throughout England to check for colorectal cancer and other bowel disorders such as Crohn’s disease.

The imaging technology, known as colon capsule endoscopy, takes two pictures a second as it passes through the body over about 5-8 hours and transmits the images to a data recorder worn on the patient’s waist. Patients can be …
A Randomized Trial of Albumin Infusions in Hospitalized Patients with Cirrhosis
Authors: Louise China, Nick Freemantle, Ewan Forrest, Yiannis Kallis, Stephen D. Ryder, Gavin Wright, Andrew J. Portal, Natalia Becares Salles, Derek W. Gilroy, Alastair O’Brien
Journal: New England Journal of Medicine (2021)

Infection and increased systemic inflammation cause organ dysfunction and death in patients with decompensated cirrhosis. Preclinical studies provide support for an antiinflammatory role of albumin, but confirmatory large-scale clinical trials are lacking. Whether targeting a serum albumin level of 30 g per liter or greater in these patients with repeated daily infusions of 20% human albumin solution, as compared with standard care, would reduce the incidences of infection, kidney dysfunction, and death is unknown.
Efficacy and Safety of Atezolizumab Plus Bevacizumab Following Disease Progression on Atezolizumab or Sunitinib Monotherapy in Patients with Metastatic Renal Cell Carcinoma in IMmotion150: A Randomized Phase 2 Clinical Trial
Authors: Thomas Powles, Michael B. Atkins, Bernard Escudier, Robert J. Motzer, Brian I. Rini, Lawrence Fong, Richard W. Joseph, Sumanta K. Pal, Mario Sznol, John Hainsworth, Walter M. Stadler, Thomas E. Hutson, Alain Ravaud, Sergio Bracarda, Cristina Suarez, Toni K. Choueiri, James Reeves, Allen Cohn, Beiying Ding, Ning Leng, Kenji Hashimoto, Mahrukh Huseni, Christina Schiff, David F. McDermott
Journal: European Urology (2021)
Abstract 13585: Clinical Outcomes and Predictors for Adverse Cardiac Events in Medically Treated Patients With Atrial Mitral Regurgitation
Authors: Kitae Kim, Misun Pak, Toshiaki Toyota, Yasuhiro Sasaki, Takeshi Kitai, Atsushi Kobori, Natsuhiko Ehara, Makoto Kinoshita, Shuichiro Kaji, Yutaka Furukawa
Journal: Circulation (2019)

Background: Atrial fibrillation (AF) causes functional mitral regurgitation (FMR) without left ventricular systolic dysfunction (atrial FMR). Little is known about the clinical outcomes and the pre...
Predictive factors for the development of leukemia in patients with transient abnormal myelopoiesis and Down syndrome
Authors: Genki Yamato, Takao Deguchi, Kiminori Terui, Tsutomu Toki, Tomoyuki Watanabe, Takahiro Imaizumi, Asahito Hama, Shotaro Iwamoto, Daisuke Hasegawa, Takahiro Ueda, Tomoko Yokosuka, Shiro Tanaka, Ryu Yanagisawa, Katsuyoshi Koh, Akiko M. Saito, Keizo Horibe, Yasuhide Hayashi, Souichi Adachi, Shuki Mizutani, Takashi Taga, Etsuro Ito, Kenichiro Watanabe, Hideki Muramatsu
Journal: Leukemia (2021)
Abstract PO-033: The impact of the variation of CT scanner on the prediction of HPV status in head &amp; neck cancer patients
Authors: Reza Reiazi, Collin Arrowsmith, Farnoosh Abbas-Aghababazadeh, Christopher Eles, Aria Rezaie, Scott V. Bratman, Andrew J. Hope, Benjamin Haibe-Kains
Journal: Clinical Cancer Research (2021)

Abstract Radiomics involves the use of high-dimensional quantitative imaging features for predictive purposes. However, studies showed that these radiomic features are sensitive to the variability of imaging parameters (e.g., scanner model). One of the major challenges in radiomics lies in improving the robustness of quantitative features against the variation in the imaging dataset in multi-center studies. Here, we assess the impact of scanner choice on the computed tomography (CT)-derived radiomic features to predict association of oropharyngeal squamous cell carcinoma with human papillomavirus (HPV), which has a well-established impact on CT-derived radiomic features. This experiment was performed on CT image datasets acquired with two different scanner types. We demonstrate strong scanner dependency by developing a machine learning model to classify HPV status from radiological images. These experiments revealed the effect of scanner type on the robustness of the radiomic features, and the extent of this dependency is reflected on the performance of HPV prediction models. The result of this study highlighted the importance of implementing an appropriate approach to reduce the impact of the imaging domain radiomic features and consequently on the machine learning models. Citation Format: Reza Reiazi, Collin Arrowsmith, Farnoosh Abbas-Aghababazadeh, Christopher Eles, Aria Rezaie, Scott V. Bratman, Andrew J. Hope, Benjamin Haibe-Kains. The impact of the variation of CT scanner on the prediction of HPV status in head &amp; neck cancer patients [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PO-033.
The Centers for Medicare &amp; Medicaid Services Requirement for Shared Decision-making for Lung Cancer Screening
Authors: Richard M. Hoffman, Daniel S. Reuland, Robert J. Volk
Journal: JAMA (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 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
Response to: ‘Correspondence on ‘MRI lesions in the sacroiliac joints of patients with spondyloarthritis: an update of definitions and validation by the ASAS MRI working group’’ by Jibri<i>et al</i>
Authors: Walter P Maksymowych, Robert GW Lambert, Mikkel Østergaard, Xenofon Baraliakos
Journal: Annals of the Rheumatic Diseases (2021)

Figure 1 Real-time iterative calibration tool for Spondyloarthritis Research Consortium of Canada Sacroiliac joint MRI inflammation scoring method (www.carearthritis.com/mriportal/sparccsij/index/).Short Tau Inversion Recovery (STIR) MRI scans conducted at two time points 12 weeks apart with schematics of sacroiliac joints scored for BME on a web-based interface.BME is scored as being present (1) or absent (0) in each sacroiliac joint quadrant.Blue coding of scores indicates concordance with expert reader consensus, while red coding indicates discordance.In particular, there is BME in the right upper sacrum and ilium of the right image that has not been scored by the naïve reader but was considered as being present by expert reader consensus.BME, bone marrow oedema.on July 31,
Platelet Reactivity in Patients With Acute Coronary Syndromes Awaiting Surgical Revascularization
Authors: Carlos A.K. Nakashima, Luis A.O. Dallan, Luiz A.F. Lisboa, Fabio B. Jatene, Ludhmila A. Hajjar, Alexandre M. Soeiro, Remo H.M. Furtado, Talia F. Dalçoquio, Luciano M. Baracioli, Felipe G. Lima, Roberto R.C.V. Giraldez, Bianca A. Silva, Mateus S.S. Costa, Celia M.C. Strunz, Luis R.P. Dallan, Carlos J.D.G. Barbosa, Flavia A.B. Britto, Michael E. Farkouh, Paul A. Gurbel, Jose C. Nicolau
Journal: Journal of the American College of Cardiology (2021)
Terlipressin and Intravenous Albumin in Advanced Cirrhosis — Friend and Foe
Authors: Guadalupe Garcia-Tsao
Journal: New England Journal of Medicine (2021)

Decompensated cirrhosis is defined by the presence of ascites, variceal hemorrhage, hepatic encephalopathy, or a combination of these disorders. A stage of further decompensation occurs with the development of complications of the complications, namely, refractory ascites, recurrent variceal hemorrhage, hepatorenal syndrome (HRS), or a combination thereof. HRS is a form of acute kidney injury that is associated with high mortality. Inflammatory states, most commonly bacterial infections or alcohol-induced hepatitis, are common precipitants of further decompensation and HRS. In this issue of the Journal, the results of two eagerly awaited multicenter, randomized, controlled trials evaluating the management of decompensated cirrhosis in . . .
The Synergy of Topographical Micropatterning and Ta|TaCu Bilayered Thin Film on Titanium Implants Enables Dual‐Functions of Enhanced Osteogenesis and Anti‐Infection
Authors: Mingyu Zhu, Ju Fang, Yulei Li, Chuanxin Zhong, Shihui Feng, Xiang Ge, Haixia Ye, Xiaofei Wang, Weiwei Zhu, Xiong Lu, Fuzeng Ren
Journal: Advanced Healthcare Materials (2021)

Abstract Poor osteogenesis and implant‐associated infection are the two leading causes of failure for dental and orthopedic implants. Surface design with enhanced osteogenesis often fails in antibacterial activity, or vice versa. Herein, a surface design strategy, which overcomes this trade‐off via the synergistic effects of topographical micropatterning and a bilayered nanostructured metallic thin film is presented. A specific microgrooved pattern is fabricated on the titanium surface, followed by sequential deposition of a nanostructured copper (Cu)‐containing tantalum (Ta) (TaCu) layer and a pure Ta cap layer. The microgrooved patterns coupled with the nanorough Ta cap layer shows strong contact guidance to preosteoblasts and significantly enhances the osteogenic differentiation in vitro, while the controlled local sustained release of Cu ions is responsible for high antibacterial activity. Importantly, rat calvarial defect models in vivo further confirm that the synergy of microgrooved patterns and the Ta|TaCu bilayered thin film on titanium surface could effectively promote bone regeneration. The present effective and versatile surface design strategy provides significant insight into intelligent surface engineering that can control biological response at the site of healing in dental and orthopedic implants.
Abstract 14755: Platelet Activity and Major Adverse Limb Events in Patients With Symptomatic Peripheral Artery Disease Undergoing Lower Extremity Revascularization
Authors: Gustavo Hernandez, Crystalann Rodriguez, Angela Lee, Elliot Luttrell-Williams, Michael A Nardi, Tessa Barrett, Yajaria Suarez, Glenn Jacobowitz, Thomas Maldonado, Judith S Hochman, Caron Rockman, Jeffrey S Berger
Journal: Circulation (2019)

Background: Peripheral artery disease (PAD) is an atherosclerotic disease affecting 200 million people worldwide. While lower extremity revascularization (LER) is often performed to improve morbidi...
Abstract 11107: The Association of Hospital Transfer on Outcomes of Newborns With Transposition of Great Arteries: Analysis of National Inpatient Sample Database Years of 2008-2016
Authors: Hasan F Othman, Mohammed Hamzah, Murad Almasri, Hany Aly
Journal: Circulation (2019)

Background: Surgical correction for transposition of great arteries (TGA) usually occurs in the first week of life. A significant number of neonates with TGA are transferred from their birth hospit...
Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study
Authors: Anthony R Mato, Nirav N Shah, Wojciech Jurczak, Chan Y Cheah, John M Pagel, Jennifer A Woyach, Bita Fakhri, Toby A Eyre, Nicole Lamanna, Manish R Patel, Alvaro Alencar, Ewa Lech-Maranda, William G Wierda, Catherine C Coombs, James N Gerson, Paolo Ghia, Steven Le Gouill, David John Lewis, Suchitra Sundaram, Jonathon B Cohen, Ian W Flinn, Constantine S Tam, Minal A Barve, Bryone Kuss, Justin Taylor, Omar Abdel-Wahab, Stephen J Schuster, M Lia Palomba, Katharine L Lewis, Lindsey E Roeker, Matthew S Davids, Xuan Ni Tan, Timothy S Fenske, Johan Wallin, Donald E Tsai, Nora C Ku, Edward Zhu, Jessica Chen, Ming Yin, Binoj Nair, Kevin Ebata, Narasimha Marella, Jennifer R Brown, Michael Wang
Journal: The Lancet (2021)