tbuckley/cabot-search huggingface dataset:
Impact of <i>#ASCO</i> Twitter impressions on the oncology community.
Authors: Gilberto Morgan, Toni K. Choueiri, Ronak Patel, Kavitha Balaji, Vivek Subbiah
Journal: Journal of Clinical Oncology (2021)

11039 Background: The oncology community is embracing social media (SM) platforms like Twitter to gain exposure to research, to network, and to engage in real-time discussions. The emergence of SM activity around the ASCO annual meetings has dramatically increased over the past 5 years, with factors such as the COVID-19 pandemic further accelerating use of digital platforms. This growth in SM engagement within the oncology community has previously been presented by totaling the quantity of tweets within a given time frame. Here, we explore the impact of specific trends through impression data. Methods: To evaluate activity trends among certain oncology stakeholders, we utilized an SM analytics platform, Symplur, to conduct a content analysis around ASCO conferences (2016-2020) using hashtags (#ASCOyy) as the search criterion. We focused our analysis on trends in impressions , defined by the theoretical maximum number of Twitter users a given tweet could have directly reached in a follower's timeline. We gathered impressions data to quantitatively assess overall ASCO engagement and evaluate topics of interest, and to discover common ASCO themes and reach within specific stakeholder groups. Results: Our results show the largest increase in impressions was during #ASCO20, despite a plateauing effect seen in the actual number of tweets (Table). The cumulative number of impressions for #ASCO16 was 468.2 million compared with approximately 1.12 billion for #ASCO20. Differentiating this result from the number of tweets related to ASCO, there was stabilization in the absolute number from #ASCO17 onward. When compiling impressions by doctors and by patient advocates, a similar trend emerged, with the most impressions captured during #ASCO20 (Table). Conclusions: As SM use continues to expand in the oncology community, stakeholders have turned to their digital voice to express views and opinions. The impact of impressions versus absolute number of tweets will continue to grow with a stakeholder’s follower count, thus building on the digital presence in oncology.[Table: see text]
Baseline Predictors of Glycemic Worsening in Youth and Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes in the Restoring Insulin Secretion (RISE) Study
Authors: Susan Sam, Sharon L. Edelstein, Silva A. Arslanian, Elena Barengolts, Thomas A. Buchanan, Sonia Caprio, David A. Ehrmann, Tamara S. Hannon, Ashley Hogan Tjaden, Steven E. Kahn, Kieren J. Mather, Mark Tripputi, Kristina M. Utzschneider, Anny H. Xiang, Kristen J. Nadeau, David A. Ehrmann, Karla A. Temple, Abby Rue, Elena Barengolts, Babak Mokhlesi, Eve Van Cauter, Susan Sam, M. Annette Miller, Steven E. Kahn, Karen M. Atkinson, Jerry P. Palmer, Kristina M. Utzschneider, Tsige Gebremedhin, Abigail Kernan-Schloss, Alexandra Kozedub, Brenda K. Montgomery, Emily J. Morse, Kieren J. Mather, Tammy Garrett, Tamara S. Hannon, Amale Lteif, Aniket Patel, Robin Chisholm, Karen Moore, Vivian Pirics, Linda Pratt, Kristen J. Nadeau, Susan Gross, Philip S. Zeitler, Jayne Williams, Melanie Cree-Green, Yesenia GarciaReyes, Krista Vissat, Silva A. Arslanian, Kathleen Brown, Nancy Guerra, Kristin Porter, Sonia Caprio, Mary Savoye, Bridget Pierpont, Thomas A. Buchanan, Anny H. Xiang, Enrique Trigo, Elizabeth Beale, Fadi N. Hendee, Namir Katkhouda, Krishan Nayak, Mayra Martinez, Cortney Montgomery, Xinhui Wang, Sharon L. Edelstein, John M. Lachin, Ashley N. Hogan, Santica Marcovina, Jessica Harting, John Albers, Dave Hill, Peter J. Savage, Ellen W. Leschek
Journal: Diabetes Care (2021)

To identify predictors of glycemic worsening among youth and adults with impaired glucose tolerance (IGT) or recently diagnosed type 2 diabetes in the Restoring Insulin Secretion (RISE) Study.
Cell microencapsulation technologies for sustained drug delivery: Latest advances in efficacy and biosafety
Authors: Tania B. Lopez-Mendez, Edorta Santos-Vizcaino, Jose Luis Pedraz, Gorka Orive, Rosa Maria Hernandez
Journal: Journal of Controlled Release (2021)

The development of cell microencapsulation systems began several decades ago. However, today few systems have been tested in clinical trials. For this reason, in the last years, researchers have directed efforts towards trying to solve some of the key aspects that still limit efficacy and biosafety, the two major criteria that must be satisfied to reach the clinical practice. Regarding the efficacy, which is closely related to biocompatibility, substantial improvements have been made, such as the purification or chemical modification of the alginates that normally form the microspheres. Each of the components that make up the microcapsules has been carefully selected to avoid toxicities that can damage the encapsulated cells or generate an immune response leading to pericapsular fibrosis. As for the biosafety, researchers have developed biological circuits capable of actively responding to the needs of the patients to precisely and accurately release the demanded drug dose. Furthermore, the structure of the devices has been subject of study to adequately protect the encapsulated cells and prevent their spread in the body. The objective of this review is to describe the latest advances made by scientist to improve the efficacy and biosafety of cell microencapsulation systems for sustained drug delivery, also highlighting those points that still need to be optimized.
The influence of alternating cyclic dynamic loads with different low frequencies on the bio-corrosion behaviors of AZ31B magnesium alloy in vitro
Authors: Linyuan Han, Zhenwei Zhang, Jianwei Dai, Xuan Li, Jing Bai, Zhihai Huang, Chao Guo, Feng Xue, Chenglin Chu
Journal: Bioactive Materials (2021)

The real physiological environment of human body is complicated with different degrees and forms of dynamic loads applied to implanted medical devices due to the daily activities of the patients, which would have impacts on the degradation behaviors of magnesium alloy implants. In this work, the bio-corrosion behaviors of AZ31B magnesium alloy under alternating cyclic dynamic loads with different low frequencies (0.1–2.5 Hz) were specially investigated. It was found that the bio-degradation performances under external dynamic stressed conditions were much severer than those under unstressed conditions and static loads. The corrosion rates were generally accelerated as the rise of cyclic frequency. Hereby a numerical model for the degradation process of Mg alloy was established. The corrosion current density icorr of Mg alloy and the applied loading frequency f matches a linear relationship of ln icorr ∝ f, which is the result of interactions between the cyclic alternating load and corrosive environment. This work could provide a theoretical reference and an experimental basis for further researches on the biodegradation behaviors of biomedical materials under dynamic conditions.
Prognostic disclosure: A scoping review on communication guidelines and their application in oncology.
Authors: Julie R Bloom, Deborah Catherine Marshall, Carlos Rodriguez-Russo, Emily J Martin, Joshua Adam Jones, Kavita Vyas Dharmarajan
Journal: Journal of Clinical Oncology (2021)

e24107 Background: Prognostic disclosure is essential to informed decision making in oncology, yet many oncologists are unsure how to successfully facilitate this discussion. This scoping review determines what prognostic communication guidelines exist, compares and contrasts these guidelines and explores the supporting evidence. Methods: A protocol was created using the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols extension for Scoping Reviews. Comprehensive literature searches of MEDLINE, EMBASE, PsychINFO, and Cochrane CENTRAL were performed to identify relevant publications between 1971 and 2020. Results: In total, 1532 articles were identified, of which 78 met inclusion criteria and contained 5 communication guidelines. Three guidelines have been validated in randomized control trials (Serious Illness Conversation Guide (SICG), The Four Habits Model and ADAPT) and demonstrated improved patient reported outcomes and objective communication measures. Among guidelines’ core principles, 3 concepts are common to all: patient’s understanding and preference, prognosis, and responding to emotion. Conclusions: Communicating prognosis is a core competency skill in cancer care, yet remains underprioritized in training and practice. This review highlights available models and acknowledges areas in need of further understanding including how to maintain learned communication skills for lifelong practice.[Table: see text]
MicroRNAs as predictors of future endometrial malignancies in endometrial hyperplasia without atypia.
Authors: Chyong-Huey Lai, Chiao-Yun Lin, Ren-Chin Wu, Lan-Yan Yang, Hsiao-Jung Tseng, Yun-Hsin Tang, Shih-Ming Jung, Shir-Hwa Ueng, Huei-Jean Huang, Angel Chao
Journal: Journal of Clinical Oncology (2021)

e17563 Background: The histological criteria of predicting risk of progression of endometrial hyperplasia (EH) to endometrial cancer (EC) is based on the degree of architectural crowding and nuclear atypia. We aim to investigate the cumulative rate of progression to EC in simple or complex hyperplasia without atypia (SH/CH-nonA) and the molecular biomarkers for risk of developing EC in women with SH/CH-nonA. Methods: EH tissues of EC patients with preceding SH/CH-nonA (case) were compared to SH/CH-nonA patients without progression to EC (control) using miRNA array, followed by reverse transcription and quantitative real-time polymerase chain reaction (RT-qPCR), and verified in an independent cohort. Results: The 10-year and 15-year cumulative rates were 8% and 10%, respectively by the hospital medical records. The median time from EH to EC was 8.71 years (range, 0.55-19.84). Twenty miRNAs (p &lt; 0.05, fold change &gt; 4) were significantly different in SH/CH-nonA cases (n = 6) compared to SH/CH-nonA controls (n = 12) by miRNA array. Multiplex RT-qPCR validation (51 SH/CH-nonA controls and 19 SH/CH-nonA cases) selected miR30a-3p, miR141, miR200a, and miR200b. Area under the curve values for tissue miR30a-3p (p = 0.043), miR141(p = 0.003), miR-200a (p &lt; 0.001), and miR200b (p = 0.004) in discriminating cases from controls were 0.658, 0.734, 0.811, and 0.710, and the sensitivity and specificity rates were 56.9% and 76.5%, 73.7% and 74.5%, and 68.4% and 100%, 47.4% and 100%, respectively. Conclusions: MiR30a-3p, miR141, miR-200a, and miR200b are useful tissue biomarkers for predicting future risk of developing EC for patients with SH/CH-nonA.
Differential gene expression of tight-junction proteins and their correlation with PRSS8 and prognosis in colorectal cancer.
Authors: Wancai Yang, Yongchen Guo, Jim Lu, Yonghua Bao
Journal: Journal of Clinical Oncology (2021)

e15548 Background: Intestinal epithelia cells are made up of tight junctions, adheren junctions and desmosomes. As integral membrane proteins, the tight junction proteins (TJPs) claudins (CLDNs) and occludin (OCLN) are the most important TJPs that play a major role in maintaining the integrity of the intestinal epithelia and regulate several key signaling pathways in cancers. Dysregulation of tight junction and adheren junction has been shown to be associated with disruption of mucosa barriers, chronic colitis, early onset of colorectal carcinogenesis, epithelial mesenchymal transition and cancer metastasis. Our recent studies have shown that intestinal conditional knockout of the Press8 (protease serine 8) gene causes disruption of intestinal epithelial homeostasis, spontaneous inflammation and tumorigenesis in mouse intestine. Whether these pathogeneses are resulted from TJPs alterations and their correlation with PRSS8 are largely unknown. Methods: PRSS8 overexpression plasmid was transfected into colon cancer cell line HCT116 cells and proteomics was conducted. The Cancer Genome Atlas colorectal cancer (CRC) data set was deeply mined, and the correlation between TJPs’ alterations, PRSS8 and prognosis was analyzed. Results: In vitro proteomics assay showed that increasing expression of PRSS8 led to differential expression of cellular TJPs and adheren proteins, including upregulation of E-cadherin, TJP1 (ZO-1) and OCLN, and downregulation of RAC1, CDC42, RHOA, CLDND1, ARHGAP1, CTNNB1 and CTNNBL1. TCGA data mining showed differential gene expression of tight junction proteins. For instance, similar as PRSS8, most colonic mucosal TJPs, such as TJP1 (ZO-1), TJP3, OLCN, CLDN7, CLDN8 and PTPRJ, were significantly decreased in CRC tissues (n = 215), compared to normal mucosa (n = 22). Moreover, these reduced expression of TJPs were positively correlated with the reduction of PRSS8 and were inversely associated with prognosis. In contrast, another group of TJPs, such as TJP2, CLDN1, CLDN2 and CLDN12, was significantly increased in CRC tissues in comparison with the normal mucosa. These increases of expression were negatively correlated with PRSS8 expression and poor outcomes. More interestingly, the PTPRJ, a newly identified tumor suppressor, was dramatically reduced in metastatic CRC, compared to the primary CRC. Furthermore, the reduced expression of PTPRJ was linked to poor prognosis in the CRC patients. The underlying mechanisms of regulatory interaction between PRSS8 and TJPs are under investigation. Conclusions: TJPs are differentially expressed in CRC and the alterations were well correlated with PRSS8 and prognosis. Therefore, these two opposite groups of TJPs could be used as biomarkers for the monitoring of early onset colorectal carcinogenesis, progression and for the prediction of prognosis.
<i>KEAP1</i> mutations in squamous cell lung cancer.
Authors: Sophia Koleczko, Axel Hillmer, Abdel Hakim Bayarassou, Christian Grohé, Martin Buchenroth, Britta Kaminsky, Clemens Schulte, Sebastian Yves Friedrich Michels, Diana Schaufler, Anna Kron, Richard Riedel, Theresa Westphal, Jan-Phillip Weber, Rieke Nila Fischer, Sabine Merkelbach-Bruse, Lucia Nogova, Reinhard Buettner, Juergen Wolf, Matthias Scheffler
Journal: Journal of Clinical Oncology (2021)

e21098 Background: KEAP1 mutations have been shown to decrease the efficacy of both chemotherapy (CTX) and immune-checkpoint inhibition (ICI) in lung adenocarcinoma. However, few is known about their impact on systemic treatment of squamous cell lung cancer (SqCC). The aim of this study was to assess the impact of KEAP1 mutations on systemic treatment outcome in SqCC. Methods: Tumor biopsies of SqCC patients were analyzed within the German Network Genomic Medicine (NGM) using a next-generation DNA sequencing (NGS) panel comprising 17 genes. In subsets, PD-L1 expression was tested with immunohistochemistry (IHC). MET amplification and FGFR1 amplification was tested with fluorescence in situ hybridization (FISH). Overall survival was estimated using Kaplan Meier statistics. For comparisons, we used log rank. A cohort with KEAP1 wild-type patients from the same panel served as control group. Results: Out of 1399 SqCC patients analyzed, 151 had a KEAP1 mutation (11%). The most common co-occurring mutations besides TP53 were PTEN, KRAS and NFE2L2. The median overall survival (OS) of stage IV KEAP1 mutated patients (n = 82) compared to stage IV control group patients (n = 82) was 7.3 vs. 11.4 months (hazard ratio (HR) 0.87 [95% confidence interval (CI) 0.62-1.23], p = 0.43). The addition of a second treatment line with ICI led to marked OS improvements in both KEAP1 mutant patient group (18.7 vs. 6.6 months, HR 0.11, [95% CI 0.04-0.25], p &lt; 0.0001) and control group (20.3 vs. 5.0 months, HR 0.12 [95% CI 0.06-0.24], p &lt; 0.0001). PD-L1 expression did not differ significantly in both groups. Conclusions: KEAP1 mutations occur commonly in SqCC patients and do not impact the efficacy of ICI in terms of OS. To identify prognostic markers for response to ICI further research is needed.
Healthcare utilization and outcomes in HIV versus non-HIV patients with anal cancer: A nationwide analysis.
Authors: Ikechukwu Achebe, Jennifer C Asotibe, Syed Ali Amir Sherazi, Okechukwu Obi, Bashar Attar, Shweta Gupta, Michael Russell Mullane
Journal: Journal of Clinical Oncology (2021)

e15505 Background: Anal cancer (AC) is the most common HPV-associated cancer in men with HIV. Nearly one third of men with anal cancer have HIV with HPV accounting for 88% of cases. Studies have reported mixed outcomes in HIV-Anal Cancer (HIV-AC) compared to non-HIV-AC patients with most studies being small and retrospective. There were no clear explanations for the differences in the outcomes in both groups. We studied HIV-AC patients from a national database and compared the outcomes and healthcare utilization with non-HIV AC cohort. Methods: We identified all adult patients with AC, with and without HIV, between 2016-2018 from the Healthcare Cost Utilization Project (HCUP) National Inpatient Sample (NIS) database. The groups were compared for socio-demographic differences, inpatient mortality, length of stay (LOS) and total hospital charges (THC). Secondary outcomes studied were rate of acute kidney injury (AKI), tumor lysis syndrome (TLS), lower GI Bleed (LGIB), anemia, tumor lysis (TLS), sepsis, septic shock (SS), neutropenia and protein energy malnutrition (PEM). Statistics was performed using the t-test, univariate and multivariate logistic regression using Stata software. Results: A total of 1235 inpatient admissions with HIV-AC and 10,415 with non-HIV-AC were identified. HIV-AC patients were significantly younger (mean age 50.2 vs 63 years, p &lt; 0.0001) with few over 65 years (8% vs 44.2%, p &lt; 0.0001), more men (82.6% vs 30.8%, p &lt; 0.001), more likely African Americans (AA) (47.8% VS 11.2%, p &lt; 0.0001) and significantly more likely to be treated at a teaching hospital (90.7% vs 9.3%, p &lt; 0.0001) compared to non-HIV-AC cohort. HIV-AC patients had significantly lower odds of inpatient mortality (aOR= 0.26, CI = 0.093 – 0.705, p = 0.008) but higher LOS (7.4 vs 6.5 days, p = 0.02) and higher THC ($74,131 vs $60,864, p = 0.005). Rates of sepsis were higher in HIV-AC (OR = 2.11, CI = 1.465 - 3.028, p &lt; 0.0001) compared to non-HIV-AC, but odds of AKI, TLS, LGIB, SS, anemia, neutropenia and PEM were similar. Conclusions: HIV-AC patients are more likely to be younger, AA, men and have significantly lower inpatient mortality compared to non-HIV-AC, despite higher rates of sepsis. HIV-AC patients being younger and overwhelmingly (90%) treated at teaching hospitals may be contributing to the observed lower mortality. However, the HIV-AC cohort was also a high inpatient healthcare utilizer with significantly increased hospital charges amounting to over $16 million over 3 years. The reversal of sex incidence likely reflects the different exposure to HPV in HIV and non-HIV cohorts. Prospective studies are needed to further evaluate outcomes in HIV-AC patients and identify underlying contributors of higher utilization.
Was William Harvey’s commitment to experimentation reflected in his clinical practice?
Authors: Andrew N Williams, Fred J O’Dell, Jeffrey K Aronson
Journal: Journal of the Royal Society of Medicine (2021)

The physician and physiologist Dr William Harvey is known for having discovered that the heart pumps arterial blood round the whole body and receives venous blood from the periphery, which it forwards to the lungs for reoxygenation. Harvey’s discovery was based on anatomical and physiological evidence and experiments using ligatures of varying tensions. As a clinician, however, Harvey does not appear to have appreciated the value of experiments in assessing treatment effects. Although he criticised Galenic views about the clinical value of experience and authority in the absence of accompanying empirical evidence, two handwritten prescriptions that he wrote for his friend and future biographer John Aubrey provide evidence that he conformed with Galenic theory when it came to drug therapy in clinical practice. This was consistent with his senior position in the College of Physicians, whose Pharmacopoeia Londinensis was based on Galenic principles, an appreciation of which was required for entry into the College. Harvey’s prescriptions reflect this and open a window onto 17th-century therapeutic practice and the personal elements on which such practice was sometimes based.
Immune landscape and subtypes in primary resectable oral squamous cell carcinoma: prognostic significance and predictive of therapeutic response
Authors: Pengfei Diao, Yue Jiang, Yuanyuan Li, Xiang Wu, Jin Li, Chen Zhou, Lei Jiang, Wei Zhang, Enshi Yan, Ping Zhang, Xu Ding, Heming Wu, Hua Yuan, Jinhai Ye, Xiaomeng Song, Linzhong Wan, Yunong Wu, Hongbing Jiang, Yanling Wang, Jie Cheng
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Immune landscape of cancer has been increasingly recognized as a key feature affecting disease progression, prognosis and therapeutic response. Here, we sought to comprehensively characterize the patterns of tumor-infiltrating immune cells (TIIs) in primary oral squamous cell carcinoma (OSCC) and develop immune features-derived models for prognostication and therapeutic prediction. Methods A total number of 392 patients with OSCC receiving ablative surgery at three independent centers were retrospectively enrolled and defined as training, testing and validation cohorts. Detailed features of 12 types of TIIs at center of tumor and invasive margin were assessed by immunohistochemistry coupled with digital quantification. TIIs abundance in OSCC was also estimated by bioinformatics approaches using multiple publicly available data sets. Prognostic models based on selected immune features were trained via machine learning approach, validated in independent cohorts and evaluated by time-dependent area under the curves and concordance index (C-index). Immune types of OSCC were further identified by consensus clustering and their associations with genetic, molecular features and patient survival were clarified. Results Patterns of TIIs infiltration varied among patients and dynamically evolved along with tumor progression. Prognostic models based on selected TIIs were identified as efficient and sensitive biomarkers to stratify patients into subgroups with favorable or inferior survival as well as responders or non-responders to postoperative radiotherapy or immunotherapy. These models outperformed multiple conventional biomarkers and immune-related scores in prognostic prediction. Furthermore, we identified two main immune subtypes of OSCC (immune-hot and immune-cold) which harbored characteristic TIIs infiltrations and genomic and molecular features, and associated with patient survival. Conclusions Our results delineated immune landscape and subtypes in OSCC, consolidated their clinical values as robust biomarkers to predict patient survival and therapeutic benefits and reinforced key roles of TIIs and tumor-immune interactions underlying oral tumorigenesis, ultimately facilitating development of tailed immunotherapeutic strategies.