tbuckley/cabot-search huggingface dataset:
Abstract 1620: Efficacy and safety of ICIs in lung cancer patients with interstitial pneumonia
Authors: Yan Fu, Fuyu Gong
Journal: Cancer Research (2021)

Abstract Background: ICIs has demonstrated efficacy against metastatic lung cancer. However, immune-related adverse events can occur, among which pneumonitis is relatively common. Lung cancer patients with interstitial pneumonia (IP) have a higher risk of pneumonitis associated with anticancer therapy. We hypothesized that the benefit of ICIs may outweigh the risks of pneumonitis in patients with lung cancer who have IP. We performed a pilot trial to evaluate the safety of ICIs in lung cancer patients with IP. Methods: Previously treated, inoperable NSCLC patients with IP were enrolled. Patients received anti-PD-1/L1 as monotherapy or in combination with other agents, respectively. Results: A total of 21 lung cancer patients were selected, including 15 (71.4%) male and 6 (28.6%) female with a median age of 62. None experienced drug related nonhematologic grade 3/4 or hematologic grade 4 adverse events in the 12 weeks following the initiation of ICIs treatment. Furthermore, none of the patients had pneumonitis of any grade. At the time of analysis, all patients were alive, and 11 had experienced a partial response. Conclusion: ICIs therapy may be feasible in lung cancer patients with IP. Citation Format: Yan Fu, Fuyu Gong. Efficacy and safety of ICIs in lung cancer patients with interstitial pneumonia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1620.
A Review of Irritable Bowel Syndrome—Reply
Authors: Michael Camilleri
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
Comparison of two-year treatment adherence, persistence, discontinuation, reinitiation, and switching between psoriasis patients treated with ixekizumab or secukinumab in real-world settings
Authors: Andrew Blauvelt, Nianwen Shi, Najwa Somani, Russel Burge, Baojin Zhu, Terri L. Ridenour, Carolyn R. Lew, Nicole M. Zimmerman, Bilal Atiya, Mwangi J. Murage
Journal: Journal of the American Academy of Dermatology (2021)
Comparison of <scp>Levitt's CO</scp> breath test and the <scp><sup>15</sup>N</scp>‐glycine labeling technique for measuring the lifespan of human red blood cells
Authors: Lei Ye, Yongqiang Ji, Cong Zhou, Junfeng Luo, Li Zhang, Liping Jing, Xin Zhao, Jie Guo, Qingyan Gao, Guangxin Peng, Yang Li, Yuan Li, Jianping Li, Huihui Fan, Wenrui Yang, Yang Yang, Yongjian Ma, Fengkui Zhang
Journal: American Journal of Hematology (2021)

The red blood cell (RBC) lifespan is an important physiological indicator of clear significance in clinical research, used for the differential diagnosis of various diseases such as anemia, compensatory phase hemolysis, and polycythemia. The 15 N-glycine labeling technique is the gold standard method for determining RBC lifespans. However, the usefulness of this technique in clinical settings is seriously hindered by the several weeks required to complete the analyses. Levitt's CO breath test is another reliable technique for determining RBC lifespans, with a simpler protocol giving much faster results, making it more useful in clinical applications. We compared the CO breath test and 15 N-glycine labeling technique for measuring the human RBC lifespan. We investigated human RBC lifespans where each subject undertook both the 15 N-glycine labeling technique and the CO breath test. The correlation between the results from these two methods was analyzed. Eight of the ten subjects successfully completed the study. The RBC lifespan values obtained by Levitt's CO breath test were lower than those obtained by the 15 N-glycine labeling technique. The RBC lifespan values determined from the 15 N-glycine labeling technique and the CO breath test were significantly correlated, with a Pearson correlation coefficient of R = 0.98 (p < 0.05), while the R2 of the linear regression equation was 0.96. The CO breath test exhibits as good performance as the 15 N-glycine labelling technique in distinguishing healthy subjects from subjects with hemolysis. The result suggests that the CO breath test is a reliable method for quickly determining human RBC lifespans in clinical applications.
Comparison of early loosening vs. delayed section of mid-urethral slings for suspected bladder outlet obstruction
Authors: A. Gasmi, M. Pinsard, B. Brucker, P-L. Broux, J. Coiffic, A. Drain, J-P. Harlicot, N. Rosenblum, K. Nyangoh Timoh, J. Hascoet, A. Manunta, B. Peyronnet
Journal: European Urology (2021)
Prevalence and reasons for use of Heated Tobacco Products (HTP) in Europe: an analysis of Eurobarometer data in 28 countries
Authors: Anthony A. Laverty, Constantine I. Vardavas, Filippos T. Filippidis
Journal: The Lancet Regional Health - Europe (2021)

Heated Tobacco Products (HTP) are a relatively new class of tobacco products, with limited data on usage patterns. We assessed the prevalence and reasons for use among persons aged ≥15 years in 27 European Union member states and the United Kingdom·.
SARS-CoV-2 neutralizing antibodies: Longevity, breadth, and evasion by emerging viral variants
Authors: Fiona Tea, Alberto Ospina Stella, Anupriya Aggarwal, David Ross Darley, Deepti Pilli, Daniele Vitale, Vera Merheb, Fiona X. Z. Lee, Philip Cunningham, Gregory J. Walker, Christina Fichter, David A. Brown, William D. Rawlinson, Sonia R. Isaacs, Vennila Mathivanan, Markus Hoffmann, Stefan Pöhlman, Ohan Mazigi, Daniel Christ, Dominic E. Dwyer, Rebecca J. Rockett, Vitali Sintchenko, Veronica C. Hoad, David O. Irving, Gregory J. Dore, Iain B. Gosbell, Anthony D. Kelleher, Gail V. Matthews, Fabienne Brilot, Stuart G. Turville
Journal: PLoS Medicine (2021)

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibody neutralization response and its evasion by emerging viral variants and variant of concern (VOC) are unknown, but critical to understand reinfection risk and breakthrough infection following vaccination. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus–cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial samples from 233 reverse transcription polymerase chain reaction (RT-PCR)–confirmed Coronavirus Disease 2019 (COVID-19) individuals with detailed demographics and followed up to 7 months. A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization, was associated with COVID-19 severity. A subgroup of “high responders” maintained high neutralizing responses over time, representing ideal convalescent plasma donors. Antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants and VOC. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal responders and vaccine monitoring and design.
Abstract 934: Identification of a GPC3 specific RNA aptamer and its use in cell specific targeted killing of GPC3 expressing tumors
Authors: Kristin M. Thompson, Christina McGuire, Jin Yuan, Aaron Ball, Justin Sonberg, Yuxun Wang, Shuhao Zhu
Journal: Cancer Research (2021)

Abstract Aptamers are short oligonucleotides that recognize specific molecular targets due to their folded three-dimensional structures. Aptamers are generated against a target molecule using a process called SELEX. This method allows the in vitro evolution of nucleic acid molecules with highly specific binding to target molecules. Here we describe a nuclease stable, fully modified 2'OMethyl aptamer that recognizes Glypican-3 (GPC3) with high affinity and specificity. GPC3 is a heparan sulfate proteoglycan and cell surface oncofetal protein which is highly expressed on a variety of liver cancers, but not in healthy adult tissues. A conjugate comprising a GPC3 aptamer and Drug Maytansinoid (DM1), a membrane-permeable inhibitor of tubulin which can prevent cell division, is used to specifically target GPC3 expressing cells in vitro and in vivo. The aptamer-drug conjugate (GRX54) is capable of selectively killing a variety of GPC3 expressing liver cells in vitro and has significantly less toxicity in cells not expressing GPC3. The anti-tumor effect of GRX54 was tested in several tumor xenograft mouse models: Hep3B xenograft, Balb/c nude mice and NCI-H446 xenograft, Balb/c nude mice. GRX54 was administered at different doses via intraperitoneal injection (IP). For each group, mice were administered with vehicle or GRX54 once a day (QD) for 3, 5 or 7 days. Tumor weight and growth were measured. An anti-cancer drug Sorafenib Tosylate (30mg/kg, oral administration, once a day - Hep3B xenograft mouse model) or irinotecan (40mg/kg, i.p. twice a day for 4 days - NCI-H446 xenograft mouse model) were used as positive controls. GRX54 decreases Hep3B tumor volume in a Balb/c nude mouse xenograft model by ~30-45% depending on treatment schedule and NCI-H446 tumor volume by ~45-90% depending on treatment schedule. Together, our data show that GRX54 is a novel GPC3-targeting molecule capable of reducing tumor size with IP injection. Citation Format: Kristin M. Thompson, Christina McGuire, Jin Yuan, Aaron Ball, Justin Sonberg, Yuxun Wang, Shuhao Zhu. Identification of a GPC3 specific RNA aptamer and its use in cell specific targeted killing of GPC3 expressing tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 934.
An MRI guided active surveillance strategy. Can the PRECISE score exclude reclassification?
Authors: H.B. Luiting, R. Hogenhout, A. Rannikko, E.R. Boevé, V. Berge, K.H. Kully, R. Valdagni, C.H. Bangma, A. Semjonow, F. Staerman, M.J. Roobol
Journal: European Urology (2021)
Importance of internal and external validity in clinical research: comment on the article by Fatima et al
Authors: Yusuke Matsuo, Yoshie Yamada, Jun Miyata, Tetsuro Aita, Takashi Yoshioka
Journal: Arthritis & Rheumatology (2021)

In a recently published cohort study, Fatima et al. showed that the higher health assessment questionnaire (HAQ) score was associated with higher mortality among early rheumatoid arthritis (RA) patients.1 This study is prominent because the authors focused on early RA patientsâ€™ functional disability measured by HAQ, which is more strongly associated with mortality than disease activity and joint damage in patients with established RA.2
Antigen carbohydrate 125 as a biomarker in heart failure: a narrative review
Authors: Julio Núñez, Rafael de la Espriella, Gema Miñana, Enrique Santas, Pau Llácer, Eduardo Núñez, Patricia Palau, Vicent Bodí, Francisco J. Chorro, Juan Sanchis, Josep Lupón, Antoni Bayés‐Genís
Journal: European Journal of Heart Failure (2021)
Abstract 1948: Investigation of the effect of LLLT on glioblastoma multiforme
Authors: Rohini Atluri, Parsa Afkhami, Tae-Youl Choi, Denise P. Simmons
Journal: Cancer Research (2021)

Abstract Low-level Laser Treatment (LLLT) has a potential to alter tumor behavior such as proliferation in addition to therapeutic effects such as wound healing, inflammation reduction. Studies indicate that, different tumor cells respond distinctly to LLLT based on laser dose (J/sq. cm). GBM is an aggressive and invasive primary brain tumor which is heterogenic in nature and any treatment that could have a potential to kill or change tumor behavior or tumor microenvironment by making GBM sensitive to available treatments can help improve the survival rate. In this study, we investigated the effect of LLLT on human malignant glioma (U251) cells using He-Ne Laser (632.8 nm). The He-Ne laser parameters used for the treatment are power (14.87±0.3 mW), beam diameter (0.68 cm), and varying laser exposure times of 5 mins and 10 mins leading to variable doses of 12.28 J/sq.cm and 24.56 J/sq. cm respectively. The dose response of LLLT on U251 cells revealed that the dose 12.28 J/sq. cm lead to cell death of 17%, 24 hrs post treatment while the dose 24.56 J/sq. cm achieved cell death of 30%, 6 hrs post treatment along with some morphological changes such as vacuole formation in the heterogenic malignant glioma. Also, a biphasic response was observed post treatment with the dose of 24.56 J/sq. cm, as we observed increase in cell viability 18hrs post treatment along with neurite formation. Western analysis suggests the involvement of PARP and caspase 9 in killing LLL treated U251 cells. Thus, upon further study, LLLT could have a potential to be used as an adjunctive treatment when used with conventional treatments for malignant glioma. Citation Format: Rohini Atluri, Parsa Afkhami, Tae-Youl Choi, Denise P. Simmons. Investigation of the effect of LLLT on glioblastoma multiforme [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1948.
Abstract LB254: PKA signaling: a friend or foe to pediatric medulloblastoma
Authors: Itishree Kaushik, Sanjay Srivastava
Journal: Cancer Research (2021)

Abstract Pediatric brain tumor is the leading cause of cancer-related deaths in pediatric patients ranging 0-19 years of age. Medulloblastoma is one of the most commonly occurring brain tumor in children. Sonic hedgehog (Shh) activated subgroup of medulloblastoma is considered to be highly aggressive and metastatic in nature. Recent studies and oncomine, a cancer microarray database has shown that GABAA receptor is down regulated in pediatric medulloblastoma. In this study, we have evaluated the anti-cancer effects of an anthelminthic drug ‘moxidectin' a GABAA receptor agonist. Treatment of medulloblastoma cells with moxidectin, resulted in reduced Protein kinase A (PKA) activity. Leading to the inhibition of Gli1, a major transcription factor of non-canonical Shh signaling. Moxidectin has inhibited the proliferation of Daoy, UW426, UW228, ONS76, and PFSK1 medulloblastoma cells and significantly induced apoptosis in a concentration and time dependent manner in all the cell lines. Western blotting and immunofluorescence microscopy demonstrated that moxidectin treatment significantly induced GABAA receptor expression and inhibited cAMP mediated PKA signaling. As a result, the non-canonical activation of Gli1 and its downstream effector molecules such as Pax-6, Oct-4, Sox-2 and Nanog were also inhibited by moxidectin treatment. Efficacy of moxidectin was also evaluated in subcutaneous and intracranial medulloblastoma tumor models. Our results demonstrated that daily oral administration of 2.5 mg/kg moxidectin suppressed the growth of medulloblastoma tumors by 55-70% in subcutaneous and intracranial models. Ex-vivo analysis of tumors by western blotting, IHC, TUNEL and H&amp;E staining revealed that moxidectin suppressed medulloblastoma tumor progression by inhibiting PKA/Gli1 signaling axis indicating the significance of this pathway in medulloblastoma progression. To our knowledge, this study for the first time focuses on GABAA receptor agonist mediated PKA/Gli1 signaling inhibition. Most importantly, moxidectin is an FDA approved drug and is already in clinical use for the treatment of river blindness in humans with an established safety record, therefore any positive findings from our studies will prompt further clinical investigation into repositioning moxidectin for the treatment of MB patients. Citation Format: Itishree Kaushik, Sanjay Srivastava. PKA signaling: a friend or foe to pediatric medulloblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB254.
Abstract 2192: Transcriptomic classification of renal cancer: a machine learning approach
Authors: Khaled Bin Satter, Paul MH Tran, Sharad B. Purohit, Jin-Xiong She
Journal: Cancer Research (2021)

Abstract Introduction: Accurate diagnosis is essential for cancer treatment. Sometimes, it is difficult to confirm histological diagnosis due to inadequate tissue sample or preparation. Using molecular markers for classification would be ideal in such cases. For renal cell carcinoma(RCC), we developed a molecular classification based on transcriptomics to address these issues and aid current diagnostic workflow. Method: We obtained transcriptomic and phenotype data of renal cell carcinoma from The cancer genome atlas (TCGA) data repository. We developed an unsupervised algorithm, Density-based UMAP, based on two clustering methods, UMAP (Uniform manifold approximation and projection) and DBScan (Density-based spatial clustering of applications with noise). We iterated this algorithm 1000 times with random 1000 genes each time and classified each sample in each iteration. We used plurality voting of at least 70% of the iterations for consensus groups. The algorithm was able to identify all the major histological subtypes. We ran a differential expression analysis for each group. Finally, we developed a classification gene signature and a supervised algorithm to classify subtypes with fewer genes and implement this signature in an RCC metanalysis. Results: Density-based UMAP Algorithm classified the samples with 91.4% concordance with WHO 2016 classification. Among the discrepant cases, 4.4 % cases (46) were not diagnosed the same as their histological classification. 4.2 % (44) cases were shown a mixed expression profile. These cases are of further interest as they might respond better with a different treatment. Based on molecular characteristics they share with major subtypes, they are named ClCh, Clear 2, and Clear 3. ClCh and Clear 2 have shown to be indolent and, Clear 3 has shown to be very aggressive. We manually curated 328 genes for supervised learning from differential expression analysis between the groups and able to identify the groups in a metanalysis. Conclusion: Transcriptomic profiling is fast, robust and, simple. It can help in diagnosing histologically discrepant cases. This classifier would be a good edition in renal cancer diagnostic workflow and can complement current diagnostic guidelines for renal cancer. Citation Format: Khaled Bin Satter, Paul MH Tran, Sharad B. Purohit, Jin-Xiong She. Transcriptomic classification of renal cancer: a machine learning approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2192.
Abstract 243: Identification of novel epitopes of NY-ESO-1 for solid malignancies by Kiromic proprietary search engine Diamond
Authors: Lucia Piccotti, Leonardo Mirandola, Maurizio Chiriva-Internati
Journal: Cancer Research (2021)

Abstract Adoptive cell therapy has been proven a powerful approach for the cure of cancer and other diseases. In particular, the selection of appropriate immunogenic targets has been key to positive outcomes in clinical settings. The availability of RNA-Seq analysis, the accessibility to large data repositories such as TCGA and GTEx, and the creation of new bioinformatic tools have accelerated the process of neoantigen discovery. However, most of the current algorithms are encumbered by the intrinsic complexity of predicting antigen immunogenicity. Diamond™ is a novel artificial intelligence and cognitive machine and deep learning platform to predict peptide processing, HLA binding, and T cell activation. To validate the predictive value of DIAMOND algorithms, the meta-analyses of expression data of cancer-testis antigen New York Esophageal Squamous Cell Carcinoma 1 (NY-ESO-1) and predictions for the immunogenic peptides were compared to experimental data in the literature. In agreement with published clinical observations, DIAMOND metanalysis showed NY-ESO-1 genic overexpression in skin cutaneous melanoma, lung adenocarcinoma, and sarcoma. Moreover, DIAMOND predicted an MHC binding affinity of 0.289 with Supertype A2 for a new NY-ESO-1 peptide, which has been successfully targeted in clinical trials for patients with HLA-A*02:01, as well as it mirrored published data in its prediction of peptide affinity binding in NY-ESO-1–specific MHC II–restricted T cell receptors. Taken together these data support DIAMOND as a reliable platform for the discovery of new immunogenic targets for cancer therapy. Citation Format: Lucia Piccotti, Leonardo Mirandola, Maurizio Chiriva-Internati. Identification of novel epitopes of NY-ESO-1 for solid malignancies by Kiromic proprietary search engine Diamond [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 243.
Denser but Not Stronger? Fluoride-Induced Bone Growth and Increased Risk of Hip Fractures
Authors: Wendee Nicole
Journal: Environmental Health Perspectives (2021)

Left to right: Bone densitometry scan and X-ray of the same area of a left hip.High bone mass density does not necessarily make for strong bones."The hypothesis is that although fluoride stimulates bone formation, the bone that is formed has a lower quality and can more easily break," explains author Emilie Helte.