tbuckley/cabot-search huggingface dataset:
COVID-19 pathophysiology: looking beyond acute disease
Authors: None The Lancet Respiratory Medicine
Journal: The Lancet Respiratory Medicine (2021)

Careful descriptions of the clinical features of acute disease in patients infected with the novel coronavirus SARS-CoV-2 had begun to emerge before WHO declared the outbreak of COVID-19 a public health emergency of international concern on Jan 30, 2020. As the global pandemic took hold, the need for data to inform patient management drove research efforts to describe the clinical spectrum of COVID-19, the determinants of disease severity, the mechanisms underlying the multiorgan manifestations of SARS-CoV-2 infection, and the response to a range of interventions.
Erratum for the Research Article: “Acute kidney injury promotes development of papillary renal cell adenoma and carcinoma from renal progenitor cells” by A. J. Peired, G. Antonelli, M. L. Angelotti, M. Allinovi, F. Guzzi, A. Sisti, R. Semeraro, C. Conte, B. Mazzinghi, S. Nardi, M. E. Melica, L. De Chiara, E. Lazzeri, L. Lasagni, T. Lottini, S. Landini, S. Giglio, A. Mari, F. Di Maida, A. Antonelli, F. Porpiglia, R. Schiavina, V. Ficarra, D. Facchiano, M. Gacci, S. Serni, M. Carini, G. J. Netto…
Journal: Science Translational Medicine (2020)
Proteomic biomarkers of progressive fibrosing interstitial lung disease: a multicentre cohort analysis
Authors: Willis S Bowman, Chad A Newton, Angela L Linderholm, Megan L Neely, Janelle Vu Pugashetti, Bhavika Kaul, Vivian Vo, Gabrielle A Echt, William Leon, Rupal J Shah, Yong Huang, Christine Kim Garcia, Paul J Wolters, Justin M Oldham
Journal: The Lancet Respiratory Medicine (2022)
Five common skin manifestations of COVID‐19 identified
Journal: British Journal of Dermatology (2020)

COVID-19, also called coronavirus, is an infectious disease caused by SARS-CoV-2. First identified in December 2019, in March 2020 it was announced by the World Health Organisation that COVID-19 had become a global pandemic. The disease can affect different organ systems, and early reports have suggested skin symptoms. The researchers, working with dermatologists across Spain, reviewed 375 patients with suspected, or confirmed, COVID-19, with the aim of developing a detailed classification of the different types of skin symptoms associated with COVID-19 with corresponding images. An initial 120 images were reviewed by four dermatologists, without knowing any other clinical information, and they identified patterns of symptoms associated with COVID-19. These patterns were then applied to the rest of the images and further refined. Five common skin symptoms were identified this way. These symptoms are chilblain-like lesions, outbreaks of small blisters, wheals, rashes comprised of small flat and raised red bumps, and livedo and necrosis. Livedo is a skin condition where circulation is impaired within the blood vessels of the skin, necrosis refers to the premature death of skin tissue. These symptoms are associated with different severity of COVID-19 infection, from less severe disease in the chilblain-like lesions, to most severe in patients with livedo. The researchers noted that some of the skin symptoms associated with COVID-19 are common and can have many causes, particularly wheals and rashes. As such, they may not be particularly helpful as an aide to diagnosis.
Adverse outcomes in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: Follow‐up of patients diagnosed 2002–2017 in a complete coverage and nationwide agnostic register study
Authors: Torsten Dahlén, Gustaf Edgren, Per Ljungman, Hjalmar Flygt, Johan Richter, Ulla Olsson‐Strömberg, Hans Wadenvik, Arta Dreimane, Kristina Myhr‐Eriksson, Jingcheng Zhao, Anders Själander, Martin Höglund, Leif Stenke
Journal: American Journal of Hematology (2022)

Tyrosine kinase inhibitors (TKIs) have profoundly improved the clinical outcome for patients with chronic myeloid leukemia (CML), but their overall survival is still subnormal and the treatment is associated with adverse events. In a large cohort-study, we assessed the morbidity in 1328 Swedish CML chronic phase patients diagnosed 2002-2017 and treated with TKIs, as compared to that in carefully matched control individuals. Several Swedish patient registers with near-complete nationwide coverage were utilized for data acquisition. Median follow-up was 6 (IQR, 3-10) years with a total follow-up of 8510 person-years for the full cohort. Among 670 analyzed disease categories, the patient cohort showed a significantly increased risk in 142 while, strikingly, no category was more common in controls. Increased incidence rate ratios/IRR (95% CI) for more severe events among patients included acute myocardial infarction (AMI) 2.0 (1.5-2.6), heart failure 2.6 (2.2-3.2), pneumonia 2.8 (2.3-3.5), and unspecified sepsis 3.5 (2.6-4.7). When comparing patients on 2nd generation TKIs vs. imatinib in a within-cohort analysis, nilotinib generated elevated IRRs for AMI (2.9; 1.5-5.6) and chronic ischemic heart disease (2.2; 1.2-3.9), dasatinib for pleural effusion (11.6; 7.6-17.7) and infectious complications, for example, acute upper respiratory infections (3.0; 1.4-6.0). Our extensive real-world data reveal significant risk increases of severe morbidity in TKI-treated CML patients, as compared to matched controls, particularly for 2nd generation TKIs. Whether this increased morbidity may also translate into increased mortality, thus preventing CML patients to achieve a normalized overall survival, needs to be further explored.
Radioembolization with chemotherapy for liver-dominant colorectal cancer: Time to subsequent treatment and quality of life in the EPOCH trial.
Authors: Riad Salem, Mary Frances Mulcahy
Journal: Journal of Clinical Oncology (2022)

114 Background: The primary objective of the EPOCH trial evaluated potential benefit of adding second-line transarterial radioembolization (TARE) with yttrium-90 glass microspheres to chemotherapy compared to chemotherapy alone in patients with liver-dominant metastatic colorectal disease (mCRC). Secondary endpoints included time to deterioration of quality of life (TTDQoL). Methods: EPOCH was a 1:1 randomized, open-label, global, multicenter phase 3 trial. TTDQoL was assessed using the Functional Assessment of Cancer Therapy-colorectal (FACT-c) questionnaire and defined as the time from randomization to the change from baseline in FACT-c total score ≤ -7 points or date of death and was estimated using Kaplan-Meier analysis. Time to subsequent therapy was defined as the time from randomization to the start of subsequent therapy and was estimated using Kaplan-Meier analysis. Restricted mean survival time (RMST) analysis was used to estimate the area under Kaplan-Meier curves (AUC) for progression-free survival (PFS), hepatic PFS (hPFS), and TTDQoL, and the difference in AUC estimates between the two arms were assessed. The use of TheraSphere in the USA in the trial was under Investigational Device Exemption from FDA. Results: The EPOCH trial included 428 patients. Both primary endpoints of PFS (HR = 0.69, 95% CI: 0.54, 0.88; 1-sided p=0.0013) and hPFS (HR = 0.59, 95% CI: 0.46, 0.77; 1-sided p&lt;0.0001) were met in the EPOCH study. Median time to subsequent therapy in the TARE plus chemotherapy arm was 21.0 months, compared to 10.1 months in the chemotherapy only arm (HR = 0.49, 95% CI: 0.37, 0.67). TTDQoL before subsequent therapy was reported in 53.5% (115/215) patients in the TARE plus chemotherapy arm, compared to 43.7% of patients in the chemotherapy only arm (93/213). Median TTDQoL was 3.8 months in both the TARE plus chemotherapy arm and the chemotherapy alone arm (1-sided p=0.1513; HR = 0.86, 95% CI: 0.65, 1.14). AUC for PFS until 22.1 months was 9.4 months (95% CI: 8.4, 10.4) for the TARE plus chemotherapy arm, compared to 7.4 months (95% CI: 6.6, 8.1) for the chemotherapy only arm (1-sided p=0.0008). AUC for hPFS until 22.1 months was 10.3 months (95% CI: 9.2, 11.3) for the TARE plus chemotherapy arm, compared to 7.4 months (95% CI: 6.7, 8.2) for the chemotherapy only arm (1-sided p&lt;0.0001). AUC for TTDQoL until 18.5 months was 6.6 (95% CI: 5.6, 7.6) for the TARE plus chemotherapy arm, compared to 5.5 (95% CI: 4.4, 6.5) for the chemotherapy only arm (1-sided p=0.0663). Conclusions: These results suggest that the addition of TARE to second-line chemotherapy in patients with liver-dominant mCRC extended PFS, hPFS, and time to subsequent treatment without compromising quality of life. Clinical trial information: NCT01483027.
LONDON
Journal: JAMA (1933)

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
Selected Articles from This Issue
Journal: Clinical Cancer Research (2022)

Soft-tissue sarcoma (STS) is a rare mesenchymal tumor for which therapies are limited. Preclinical evidence has suggested that targeting MET and VEGF may be a therapeutic strategy in STS. To this end, Coyne and colleagues conducted a phase II clinical trial of single-agent cabozantinib, which targets both MET and VEGF signaling, in patients with advanced STS having progressed on prior systemic therapy. Although 11.1% of patients experienced objective responses, and the 6-month PFS was 49.3%, this study did not meet its primary endpoint. However, responses were observed in multiple subtypes of STS, suggesting that similar trials including multiple STS subtypes may be useful, given the rarity of this tumor type. Furthermore, additional clinical study of cabozantinib is warranted in STS to further refine patients who may benefit from this treatment.HR-positive/HER2-negative breast cancer is considered to be an immunologically cold tumor type. However, the utility of immunotherapy in this setting has been understudied. Dieci and colleagues conducted a phase II clinical trial of neoadjuvant immunotherapy in patients with HR-positive/HER2-negative Luminal B-like breast cancer. Anthracycline-based chemotherapy followed by nivolumab and endocrine therapy led to a pathologic complete response (pCR) in 16.3% of patients. Several features were found to associate with pCR, including basal subtype and tumor-infiltrating lymphocytes. These results suggest that immunotherapy may have efficacy in patients with HR-positive/HER2-negative breast cancer; additional clinical study is necessary to further understand the patient population that may most benefit from this treatment strategy.Prostate cancer has the greatest racial disparities in death rates of all cancers. Stopsack and colleagues demonstrate that prostate tumor genomics differ by both self-reported race and genetic ancestry. Although clinical characteristics of men who had access to tumor–normal sequencing varied by race, racial differences in tumor genomics persisted after adjusting for clinical characteristics. Tumors from Black men had more chr8q gains, which were associated with socioeconomic status and poor prognosis. This study underscores that differences in tumor genomes should neither be assumed to result solely from access to care nor solely from germline genetics.Plasma cell-free DNA (cfDNA) has emerged as a biomarker in cancer but has been understudied in neuroendocrine neoplasms (NEN). Boons and colleagues collected 195 plasma samples from well-differentiated, metastatic gastroenteropancreatic and lung NEN patients. cfDNA was subjected to shallow-whole genome sequencing to detect copy number alterations in circulating tumor DNA (ctDNA). The presence of ctDNA correlated with worse overall survival and could be followed over time to predict progression. Additionally, it allowed differentiating between pancreatic NEN and adenocarcinoma. This study demonstrates that plasma cfDNA is a minimally invasive biomarker with high specificity for diagnosis, prognosis, and follow-up in NENs.
Comparing the outcome of doublet therapy (gemcitabine and cisplatin) with triplet therapy (gemcitabine, cisplatin and nab paclitaxel) in locally advanced or metastatic gall bladder carcinoma patients: An open-label randomized control trial.
Authors: Chandrani Khatri, Pratap K. Das, Jayanta Patowary
Journal: Journal of Clinical Oncology (2022)

TPS497 Background: There are various studies evaluating the role of dual agent chemotherapy like gemcitabine and cisplatin in locally advanced or metastatic gall bladder cancer (1). This has been the standard of treatment up till now. Also there has been a single arm phase II trial of gemcitabine, cisplatin and nab-paclitaxel (triplet therapy) by Shroff et al (2) reporting an impressive data with RR (response rate) of 45 %, median PFS (progression free survival) of 11.8 months (5% CI; 6.0-15.6) and median OS (overall survival) was 19.2 months. This data was promising when compared to historical data of dual agents like gemcitabine and cisplatin. So it would be informative to conduct an RCT comparing doublet chemotherapy in locally advanced or metastatic GBC with triplet regimen chemotherapy. Methods: It is an open label randomized control study conducted in Indraprastha Apollo hospital New Delhi, India in newly diagnosed locally advanced or metastatic gall bladder cancer patients proven histologically and on imaging. The sample size calculated using the appropriate formula is, 27 in each arm that is total of 54 patients, but 60 patients will be enrolled in the study keeping in view 10% drop out rate. For simple randomization, we will use online computer generated random number table and then patients will be assigned in two groups, arms A and B. Arm A receiving two drugs gemcitabine 1,000mg/m2 i.v and cisplatin 25mg/m2 i.v on Day 1 and Day 8 of 21-day cycle and arm B receiving three drugs gemcitabine, 1,000 mg/m2, cisplatin, 25 mg/m2, and nab-paclitaxel, 125 mg/m2, on days 1 and 8 of 21-day cycle. Primary end point was response rates based on radiological response as per RECIST or PRECIST. Secondary end points were to determine median progression free survival and median overall survival and to evaluate the toxicities according to NCI-CTC v 4.0.Then response [on basis of RECIST or PRECIST criteria] will be seen after 3 and 6 cycles of chemotherapy are completed and at follow up of every 6 months for 2 years period for assessment of primary and secondary end points of the study. Statistical analysis for correlation between clinical and laboratory features and treatment outcomes will be done using the SPSS software. Till now we have enrolled 1 patient in each arm. CTRI/2021/09/036362. References: Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 2010;362:1273-81. Shroff RT, Javle MM, Xiao L, et al. Gemcitabine,Cisplatin, and nab-Paclitaxel for the Treatment of Advanced Biliary Tract Cancers: A Phase 2 Clinical Trial JAMA Oncol 2019. Clinical trial information: CTRI/2021/09/036362.
NAMPT-targeting PROTAC promotes antitumor immunity via suppressing myeloid-derived suppressor cell expansion
Authors: Ying Wu, Congying Pu, Yixian Fu, Guoqiang Dong, Min Huang, Chunquan Sheng
Journal: Acta Pharmaceutica Sinica B (2021)

Nicotinamide phosphoribosyl transferase (NAMPT) is considered as a promising target for cancer therapy given its critical engagement in cancer metabolism and inflammation. However, therapeutic benefit of NAMPT enzymatic inhibitors appears very limited, likely due to the failure to intervene non-enzymatic functions of NAMPT. Herein, we show that NAMPT dampens antitumor immunity by promoting the expansion of tumor infiltrating myeloid derived suppressive cells (MDSCs) via a mechanism independent of its enzymatic activity. Using proteolysis-targeting chimera (PROTAC) technology, PROTAC A7 is identified as a potent and selective degrader of NAMPT, which degrades intracellular NAMPT (iNAMPT) via the ubiquitin-proteasome system, and in turn decreases the secretion of extracellular NAMPT (eNAMPT), the major player of the non-enzymatic activity of NAMPT. In vivo, PROTAC A7 efficiently degrades NAMPT, inhibits tumor infiltrating MDSCs, and boosts antitumor efficacy. Of note, the anticancer activity of PROTAC A7 is superior to NAMPT enzymatic inhibitors that fail to achieve the same impact on MDSCs. Together, our findings uncover the new role of enzymatically-independent function of NAMPT in remodeling the immunosuppressive tumor microenvironment, and reports the first NAMPT PROTAC A7 that is able to block the pro-tumor function of both iNAMPT and eNAMPT, pointing out a new direction for the development of NAMPT-targeted therapies.
Percutaneous intervention in unstable plaques: The significance of temperature measurement in prognosis Christodoulos I. Stefanadis, Konstantinos Toutouzas, Eleftherios Tsiamis, Costas Stratos, Ioannis Kallikazaros, Manolis Vavuranakis, Costas Tentolouris, Dorothea Tsekoura, Pavlos Toutouzas. Hippokration Hospital, Athens, Greece
Journal: Journal of the American College of Cardiology (2001)
CRISPR screens uncover protective effect of PSTK as a regulator of chemotherapy-induced ferroptosis in hepatocellular carcinoma
Authors: Yiran Chen, Li Li, Jie Lan, Yang Cui, Xiaosong Rao, Jing Zhao, Tao Xing, Gaoda Ju, Guangtao Song, Jizhong Lou, Jun Liang
Journal: Molecular Cancer (2022)

Abstract Background Hepatocellular carcinoma (HCC) is among the most common forms of cancer and is associated with poor patient outcomes. The emergence of therapeutic resistance has hampered the efficacy of targeted treatments employed to treat HCC patients to date. In this study, we conducted a series of CRISPR/Cas9 screens to identify genes associated with synthetic lethality capable of improving HCC patient clinical responses. Methods CRISPR-based loss-of-function genetic screens were used to target 18,053 protein-coding genes in HCC cells to identify chemotherapy-related synthetic lethal genes in these cells. Synergistic effects were analyzed through in vitro and in vivo analyses, while related mechanisms were explored through RNA-seq and metabolomics analyses. Potential inhibitors of identified genetic targets were selected through high-throughput virtual screening. Results The inhibition of phosphoseryl-tRNA kinase (PSTK) was found to increase HCC cell sensitivity to chemotherapeutic treatment. PSTK was associated with the suppression of chemotherapy-induced ferroptosis in HCC cells, and the depletion of PSTK resulted in the inactivation of glutathione peroxidative 4 (GPX4) and the disruption of glutathione (GSH) metabolism owing to the inhibition of selenocysteine and cysteine synthesis, thus enhancing the induction of ferroptosis upon targeted chemotherapeutic treatment. Punicalin, an agent used to treat hepatitis B virus (HBV), was identified as a possible PSTK inhibitor that exhibited synergistic efficacy when applied together with Sorafenib to treat HCC in vitro and in vivo. Conclusions These results highlight a key role for PSTK as a mediator of resistance to targeted therapeutic treatment in HCC cells that functions by suppressing ferroptotic induction. PSTK inhibitors may thus represent ideal candidates for overcoming drug resistance in HCC.
Contents
Authors: Mo Tiwari, Chris Piech, Medina Baitemirova, Namperumalsamy Ba, Muthiah Prajna, Prajna Srinivasan, Natacha Lalitha, Niranjan Villegas, Janice Chua, Travis Redd, Thomas Lietman, Sebastian Thrun, Charles Lin, Ying Han, Alessandro Jammal, Samuel Berchuck, Eduardo Mariottoni, Angelo Tanna, Vital Costa, Felipe Medeiros, Jian Xiong, Fei Li, Diping Song, Guangxian Tang, Junjun He, Kai Gao, Hengli Zhang, Weijing Cheng, Yunhe Song, Fengbin Lin, Kun Hu, Peiyuan Wang, Ji-Peng Li, Tin Aung, Yu Qiao, Xiulan Zhang, Daniel Ting, Yu-Chieh Yang, Nai-Wei Hsu, Chiao-Yu Wang, Mong-Ping Shyong, Der-Chong Tsai, Leo Hahn, Mary Van Schooneveld, Nieneke Wesseling, Ralph Florijn, Jacoline Ten Brink, Birgit Lissenberg-Witte, Ine Strubbe, Magda Meester-Smoor, Alberta Thiadens, Roselie Diederen, Caroline Van Cauwenbergh, Julie De Zaeytijd, Sophie Walraedt, Elfride De Baere, Caroline Klaver, Jeannette Ossewaarde-Van Norel, Carel Hoyng, Maria Van Genderen, Paul Sieving, Bart Leroy, Arthur Bergen, J Boon, Kevin Chodnicki, Laurel Tanke, Jose Pulido, David Hodge, James Klaas, Timothy Olsen, M Tariq Bhatti, John Chen
Journal: Ophthalmology (2022)
Facing Sunsets
Authors: Farley Verner
Journal: Annals of Internal Medicine (1997)

Ad Libitum15 December 1997Facing SunsetsFarley Verner, MDFarley Verner, MDWaco, TX 76708Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-12-199712150-00014 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail A turn for the worsethey said he'd taken,so she turned, backinto the sun in its retreatbehind the hospital'shilltop station where hehad hid his own dis-ease by singing to comfortthose there to comfort him,like other days labors tosweep a neighbor's path,to measure another day'scycle's success by thesoundless beat of smileshis spirit coaxed fromthose he met andagain from his daughteras she turned to seehis last upward glance hadpainted the undersideof clouds the colorof a child's glad heart,a reminder in his absencehis daily lessona welcome grief. Author, Article, and Disclosure InformationAffiliations: Waco, TX 76708Corresponding Author: Farley Verner, MD, 2911 Herring, Suite 308, Waco, TX 76708. Previousarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 December 1997Volume 127, Issue 12Page: 1127KeywordsHeart ePublished: 15 August 2000 Issue Published: 15 December 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
AMA grams
Journal: JAMA (1966)

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