tbuckley/cabot-search huggingface dataset:
The role of microneedle arrays in drug delivery and patient monitoring to prevent diabetes induced fibrosis
Authors: Emma McAlister, Melissa Kirkby, Juan Domínguez-Robles, Alejandro J. Paredes, Qonita Kurnia Anjani, Kurtis Moffatt, Lalitkumar K. Vora, Aaron R.J. Hutton, Peter E. McKenna, Eneko Larrañeta, Ryan F. Donnelly
Journal: Advanced Drug Delivery Reviews (2021)
Association of COVID-19 mRNA Vaccine With Ipsilateral Axillary Lymph Node Reactivity on Imaging
Authors: Mehmet Emin Adin, Edvin Isufi, Michal Kulon, Darko Pucar
Journal: JAMA Oncology (2021)

This cohort study examines ipsilateral axillary nodal reactivity seen on positron emission tomographic and computed tomographic imaging after intramuscular administration of the coronavirus 2019 mRNA vaccines.
CD101 genetic variants modify regulatory and conventional T cell phenotypes and functions
Authors: Laura E. Richert-Spuhler, Corinne M. Mar, Paurvi Shinde, Feinan Wu, Ting Hong, Evan Greene, Sharon Hou, Katherine Thomas, Raphael Gottardo, Nelly Mugo, Guy de Bruyn, Connie Celum, Jared M. Baeten, Jairam R. Lingappa, Jennifer M. Lund, Connie Celum, Anna Wald, Jairam R. Lingappa, Jared M. Baeten, Mary S. Campbell, Lawrence Corey, Robert W. Coombs, James P. Hughes, Amalia Magaret, M. Juliana McElrath, Rhoda Morrow, James I. Mullins, David Coetzee, Kenneth Fife, Edwin Were, Max Essex, Joseph Makhema, Elly Katabira, Allan Ronald, Elizabeth Bukusi, Craig Cohen, Saidi Kapiga, Rachel Manongi, Carey Farquhar, Grace John-Stewart, James Kiarie, Sinead Delany-Moretlwe, Helen Rees, Guy de Bruyn, Glenda Gray, James McIntyre, Nelly Rwamba Mugo, Connie Celum, Jared M. Baeten, Deborah Donnell, Robert W. Coombs, Lisa Frenkel, Craig W. Hendrix, Jairam R. Lingappa, M. Juliana McElrath, Kenneth Fife, Edwin Were, Elioda Tumwesigye, Patrick Ndase, Elly Katabira, Allan Ronald, Eliabeth Bukusi, Craig Cohen, Jonathan Wangisi, James Campbell, Jordan Tappero, James Kiarie, Carey Farquhar, Grace John-Stewart, Nelly Rwamba Mugo
Journal: Cell Reports Medicine (2021)

We recently reported that the risk of sexually acquired HIV-1 infection is increased significantly by variants in the gene encoding CD101, a protein thought to modify inflammatory responses. Using blood samples from individuals with and without these variants, we demonstrate that CD101 variants modify the prevalence of circulating inflammatory cell types and show that CD101 variants are associated with increased proinflammatory cytokine production by circulating T cells. One category of CD101 variants is associated with a reduced capacity of regulatory T cells to suppress T cell cytokine production, resulting in a reduction in the baseline level of immune quiescence. These data are supported by transcriptomics data revealing alterations in the intrinsic regulation of antiviral pathways and HIV resistance genes in individuals with CD101 variants. Our data support the hypothesis that CD101 contributes to homeostatic regulation of bystander inflammation, with CD101 variants altering heterosexual HIV-1 acquisition by facilitating increased prevalence and altered function of T cell subsets.
Preliminary results of niraparib and brivanib dual therapy evaluation in recurrent, metastatic and persistent cervical cancer (CQGOG0101): An open-label, phase II clinical trial.
Authors: Haixia Wang, Jin Shu, Dongling Zou, Qi Zhou
Journal: Journal of Clinical Oncology (2021)

e17506 Background: Early-stage cervical cancer (CC) has a good long-term prognosis, with 5-year survival rate more than 90% for localized disease. However, once the CC relapsed, patients lack effective solutions and usually die in less than one year. In this study (CQGOG0101), we aimed to assess the efficacy and safety of niraparib combined with brivanib or toripalimab in patients with recurrent CC. Herein, we report the cohort 1 portion of the study (patients recieving Niraparib 200mg and Brivanib 400mg orally).Findings for the cohort 2 of patients receiving niraparib and toripalimab will be reported separately. Methods: The cohort 1 of CQGOG0101 trial was to evaluate the safety and activity of Niraparib combined with Brivanib in patients with recurrent, metastatic, or persistent cervical cancer. 10 patients were planned to be enrolled (Actually nine patients). Eligible patients were aged 18–70 years with measurable lesions and had an ECOG performance status of 0-2. Patients received oral niraparib 200 mg and brivanib 400 mg once daily until disease progression, intolerable toxicity, or withdrawal of consent. Primary endpoint was the objective response rate (ORR) assessed by RECIST version 1.1. Secondary endpoints included disease control rate (DCR), duration of response (DOR) and safety. Results: Between May 8th, 2020 and Jan 22nd, 2021, 9 patients (median age, 50 years old [28-73]) were enrolled. Patients had received a median of two (1-3) previous lines of platinum-based therapy. All of nine patients had distant metastatic lesions and had underwent at least one post-baseline tumor assessment (To deadline for submission), including 1 confirmed partial response, 4 with stable disease, 4 with progressive disease. Median duration of treatment was 3.8 months (3-8.2), three patients were still on treatment. No drug-related grade 3 or worse treatment-emergent adverse events were detected, the most common grade 1-2 adverse events (AEs) included: neutropenia (4 of 9 patients), anemia (2 of 9 patients), thrombocytopenia (1 of 9 patients), hypertension (2 of 9 patients), proteinuria(1 of 9 patients), fatigue (1 of 9 patients), and increased ALT/AST (1 of 9 patients). Conclusions: This combo seems to show a similar efficacy compared to other recurrent cervical cancer late-line therapies. We are planning to initiate the cohort 2 to explore niraparib combined with anti-PD-1 antibody (Toripalimab) in recurrent CC in our trial later. Clinical trial information: NCT04395612.
A natural history comparison of SOD1-mutant patients with amyotrophic lateral sclerosis between Chinese and German populations
Authors: Lu Tang, Johannes Dorst, Lu Chen, Xiaolu Liu, Yan Ma, Kornelia Günther, Sebastian Michels, Kathrin Müller, Axel Freischmidt, Jochen H. Weishaupt, Dongsheng Fan, Albert C. Ludolph
Journal: Translational Neurodegeneration (2021)
Comparison of molecular signatures in small cell lung cancer with or without homologous recombination associated gene mutations.
Authors: Lili Fu, Feifei Li, Dandan Ren, Beibei Mao, Huan Chen, Pei Hao, Ji He
Journal: Journal of Clinical Oncology (2021)

e20580 Background: Small cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer with high mortality. Recently, Immune checkpoint inhibitors (ICIs) have been shown to have the potential to improve the prognosis of SCLC, but little is known about immunotherapeutic biomarkers. Homologous recombination deficiency (HRD) is demonstrated to be a response predictor to immunotherapies in gynecologic cancers, while limited studies were reported in small cell lung cancer. Herein, we analyze the mutational pattern of HRR related genes in a Chinese SCLC cohort and further analyze the relationship between HRR-gene mutations and tumor mutational burden. Methods: Target gene sequencing (543 genes) was performed in 133 Genecast cohort with small cell lung cancer. PD-L1 expression were evaluated for 90 among 133 patients using the SP142 PD-L1 immunohistochemistry assay. Results: Among 133 patients, 47 (35.3%) had HRR-gene mutations. ATM (8.3%), NBN (4.5%) and BRCA2 (4.5%) were the top 3 mutated HRR-gene in the cohort，followed by ATR (3.8%), BARD1 (3.8%), BRCA1 (3.8%), PALB2 (3.8%), RAD50 (3.8%), CHEK2 (3.0%), BLM (3.0%), BRIP1(2.3%), CHEK1(1.5%), RAD52(1.5%), and MRE11A (0.8%). Pathogenic somatic and germline mutations of HRR genes were identified in 11 (11/47, 23.4%) and 3 (3/47, 6.4%) patients, respectively. 1 (1/47, 2.1%) patient carried both germline and somatic variants. Genomic landscape revealed that TP53 and RB1 were commonly mutated genes in SCLC cohort. Mutations in KMT2D, AR and RTK-RAS pathway occurred more frequently in the HRR-Mut group, compared with the wildtype ones. Furthermore, we found that mutations in HRR-gene were associated with high TMB (Wilcoxon, p = 0.048), and patients with high TMB (≥median) showed a higher proportion of positive PD-L1 expression in 90 SCLC patients. Conclusions: Our data indicated that genomic alterations associated with HRR-genes have a positive correlation with high TMB, and detection of HRR-gene mutation status probably could help identify patients who might benefit from immune checkpoint blockade therapy. Keywords: Small cell lung cancer, Homologous recombination deficiency, Immunotherapy.
First-line treatment with a cyclin-dependent kinase 4/6 inhibitor combined with an aromatase inhibitor for hormone receptor-positive, human epidermal growth factor receptor-2 negative metastatic breast cancer: Population-based outcomes for patients treated in Alberta, Canada.
Authors: Carla Pires Amaro, Atul Batra, Sasha M. Lupichuk
Journal: Journal of Clinical Oncology (2021)

e13020 Background: Cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) in combination with an aromatase inhibitor (AI) has emerged as the standard first line treatment in patients with hormone receptor positive, human epidermal growth factor receptor-2 (HER-2) negative metastatic breast cancer (MBC). In this analysis, we describe population-based outcomes for first-line treatment with a CDK4/6i combined with an AI. Methods: All patients who were prescribed CDK4/6i + AI from January 2016 through June 2019 in a large Canadian province were included. Descriptive statistics were used to summarize patient demographics, tumor and treatment characteristics. Survival distributions were estimated using the Kaplan-Meier method. Multivariate analysis (MVA) using a Cox proportional hazards model was constructed to examine associations between potentially prognostic clinical variables and progression free survival (PFS). Results: A total of 316 patients were included. Median age was 61 years (interquartile range, 53-70 years), 82% were postmenopausal women, 39% had de novo MBC, and 48% had non-visceral disease. Palbociclib was prescribed in 94% of patients and the remaining patients received ribociclib. The CDK4/6i was dose-reduced upfront or during treatment in 47%. While 70% of the patients discontinued treatment due to progression, 30% stopped due to toxicity/patient preference/physician recommendation. With a median follow-up of 28.1 months, the median PFS was 37.9 months (95% CI, 26.7-NR). In the MVA, PR-negative tumour (HR, 2.37; 95% CI, 1.45-3.88; P = 0.001) and dose reduction of the CDK4/6i (HR, 1.51; 95% CI, 1.06-2.16; P = 0.022) predicted worse PFS. Median overall survival (OS) was not reached. The 30-month and 36-month OS rates were 74% and 68%, respectively. Of patients who progressed (n = 131), 89% received second-line treatment (chemotherapy in 46%, single agent hormonal therapy in 35%, hormonal therapy plus a targeted agent in 15%, and other in 4%). Median time to progression on second line chemotherapy was 9.0 (5.8-17.6) months and second line hormonal therapy +/- targeted agent was 4.0 (3.4-8.6) months (P = 0.012). Conclusions: The real-world outcomes of first-line use of CDK4/6i and AI are encouraging. PR negative tumors and dose reduction appear to be negative prognostic markers. CDK4/6i + AI as first-line treatment for HR-positive, HER2-negative MBC in Alberta is justified based on favorable PFS and early OS outcomes.
A retrospective collection of diagnostic data from the desmoid tumor research foundation natural history study.
Authors: Amanda Lucas, Danielle Braggio, Lynne Hernandez, Kelly Mercier
Journal: Journal of Clinical Oncology (2021)

e23549 Background: Desmoid tumors are a benign sarcoma diagnosed in 4-5 patients per million each year. The Desmoid Tumor Research Foundation (DTRF) launched the patient registry and natural history study (NHS) in 2017. This is a retrospective analysis of diagnostic data collected, tumor location, rates of misdiagnosis, how genetics testing is being incorporated into clinical practice, and additional clinical trial participation. Methods: The NHS launched September 2017 and contains 15 surveys covering diagnostics, disease, treatment, care management, and quality of life. Current reporting as of December 31, 2020, contains 619 participants or legally authorized representatives for which a subset have completed the surveys on desmoid tumor diagnoses. Results: Survey analysis documents that the most prevalent tumor locations were intra-abdominal 35.5% (220), joint / extremities 21.2% (131), and chest wall 14.7% (91). The majority of participants, 68.2%, reported that they had unifocal tumors (199/292), 19.5% reported that they had multifocal desmoid tumors (57). Biopsy procedures were the primary method of diagnosis according to 57.2% (167/292) of the participants, with needle biopsy comprising 19.8% (33/167). Biopsy as the primary method of diagnosis was most prevalent in tumors of the head and neck (18/26, 69.2%), chest wall (32/47, 68.1%) joint /extremities (50/90, 55.6%), and abdominal tumors (27/51, 52.9%). Additionally, imaging methods (CT, MRI) were the primary method of diagnosis in 22.6% (66/292) and surgical resection 14.4% (42/292). Misdiagnosis is common for this tumor type, as 41.0% (119/290) participants reported an incorrect initial diagnosis. The reported incorrect diagnoses are described in the table. Genetic testing is not standard of care for desmoid tumors but is increasing in practice. A total of 78 participants (28%) of 282 participants report they had genetic testing (germline or somatic) of their tumor tissue. The majority of those participants, 65.4% (51/78), reported having Familial Adenomatous Polyposis (FAP). Of the participants that had genetic testing, 89.0% live in the United States. 10.5% of participants (37/353) have reported having participated in clinical trials. The majority of participants (317/368, 86.1%) are willing to participate in other studies in the future, with 77.4% (285/368) willing to donate specimens for biomarker studies. Conclusions: Participants with desmoid tumors report many methods of diagnosis for their diverse tumor locations, high rates of misdiagnosis, and increased rates of genetic mutation testing. Data collection through the DTRF NHS is ongoing.[Table: see text]
Pandemic lessons from India: inappropriate prioritisation for vaccination
Authors: Peter Lloyd-Sherlock, Nidheesh Manee Kandiyil, Martin McKee, Arokiasamy Perianayagam, Sridhar Venkatapuram, Soumitra Pathare, Aravinda Meera Guntupali, Ramesh Kumar K, Soumitra Ghosh
Journal: BMJ (2021)

We welcome Reddy’s editorial on covid-19 in India,1 but want to emphasise one further issue: how India’s national government has inappropriately prioritised people for covid-19 vaccination.

In January 2021, India’s vaccination programme began with health professionals and “frontline workers.” In March, it was extended to people aged 60 or over and those aged 45 or over with comorbidities, and in April to anyone aged 45 or over. From 1 May, vaccine entitlement was extended to all people aged 18 or over, although people …
Influence of preoperative chemoradiation on tumor-infiltrating lymphocytes in locally advanced rectal cancer: The STAR-01 cohort.
Authors: Francesca Negri, Letizia Gnetti, Lorena Bottarelli, Nicoletta Campanini, Maria Emanuela Negru, Francesca Bergamo, Salvatore Siena, Michela Frisinghelli, Marija Petric, Germana Chiaulon, Valeria Smiroldo, Domenico C. Corsi, Giulia Anna Carmen Vita, Enrico Maria Silini, Cinzia Azzoni, Federica Gaiani, Luigi Laghi, Gian Luigi de'Angelis, Luca Boni, Carlo Aschele
Journal: Journal of Clinical Oncology (2021)

3611 Background: Preoperative chemoradiotherapy may increase antitumor immunity through enhancing T-cell activation and tumor infiltration. These effects could possibly sensitize tumors to immunotherapies, including checkpoint inhibitors. We explored whether preoperative chemoradiation for locally advanced rectal cancer induces immunologic changes and if the post-operative biological parameters are associated with tumor regression grade (TRG sec. Ryan –AJCC Eight ed.). Methods: The multicenter STAR-01 study compared a standard preoperative chemoradiotherapy regimen (50.4 Gy in 28 daily fractions with concomitant infused fluorouracil at the dose of 225 mg/m 2 /d) with the same regimen plus oxaliplatin given weekly at the dose of 60 mg/m 2 in patients with locally advanced rectal cancers. Paired pre- and post-operative specimens were available for 58 patients from this trial and were analyzed by immunohistochemistry. The immunoistochemical analysis was performed with a panel of immune cells and associated factors as CD3, CD20, CD4/CD8, PD1. The pattern of tumor infiltrating lymphocytes (TILs) and related infiltrating lymphocytes (RILs) was also evaluated. Response to pre-operative chemoradiotherapy was assessed according to TRG. Results: After therapy we observed a decreased CD4/CD8 ratio (p &lt; 0.001) and reduced expression level of CD20 (p &lt; 0.001). The expression level of CD3+ and PD-1+ cells after therapy did not change significantly. The relative increase of lymphocytes CD8+ inside CD4/CD8 ratio evaluated on post-operative samples was significantly associated with TRG 0 (p &lt; 0.001). Conclusions: Our data suggest that chemoradiation may induce an enrichment of CD8+ T lymphocytes and this translates in better response to chemoradiation. The new frontier of best treatment could be the use of specific immune cells (T lymphocytes) to trigger the system's immune response against disease.
Response by Schrage and Westermann to Letters Regarding Article, “Left Ventricular Unloading Is Associated With Lower Mortality in Patients With Cardiogenic Shock Treated With Venoarterial Extracorporeal Membrane Oxygenation: Results From an International, Multicenter Cohort Study”
Authors: Benedikt Schrage, Dirk Westermann
Journal: Circulation (2021)
Digital-Rapid On-site Examination in Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (DEBUT): a proof of concept study for the application of artificial intelligence in the bronchoscopy suite
Authors: Shahir Asfahan, Poonam Elhence, Naveen Dutt, Ram Niwas Jalandra, Nishant Kumar Chauhan
Journal: European Respiratory Journal (2021)

Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) has become the standard of care for sampling mediastinal and hilar lesions and is finding increased acceptance for diagnostic as well as staging purposes [1]. EBUS-TBNA is an expensive procedure due to the high cost of equipment [2]. A repeat procedure in case of an inconclusive outcome adds to the burgeoning expenditure. To circumvent this, rapid on-site examination (ROSE) has been adopted to reduce the number of needle punctures and decrease the requirement for additional procedures [3]. However, ROSE requires presence of a pathologist or cyto-technicians in the bronchoscopy suite. Artificial intelligence using open source deep neural network is able to classify on-site cytology smears during EBUS-TBNA procedure in the bronchoscopy suite <https://bit.ly/3vcRYX1>
Plasma and urine free glycosaminoglycans as monitoring and predictive biomarkers in metastatic renal cell carcinoma: A prospective observational study.
Authors: Francesco Gatto, Sinisa Bratulic, Eric Jonasch, Angelo Limeta, Francesca Maccari, Fabio Galeotti, Nicola Volpi, Sven Lundstam, Jens Nielsen, Ulrika Stierner
Journal: Journal of Clinical Oncology (2021)

e16540 Background: No liquid biomarkers are approved in renal cell carcinoma (RCC). In metastatic RCC (mRCC), there is a need to predict and monitor response noninvasively to guide the choice of treatment. Urine and plasma glycosaminoglycan (GAGs) profiles – or GAGomes - are promising biomarkers reflective of RCC metabolism. Here, we explored if GAGomes could predict and monitor response noninvasively. Methods: A single-center prospective consecutive series of mRCC patients elected for first-line therapy was enrolled between June 2016 - April 2019 at Sahlgrenska University Hospital, Gothenburg, Sweden. Response was assessed by the investigator as progressive disease (PD) versus non-PD. Plasma and urine GAGomes were measured at treatment start, after 6 weeks, and every 3 rd month in a blinded central laboratory. We conducted Bayesian estimation to correlate GAGomes to response and to design GAG scores to classify PD. So-trained GAG scores were validated to predict PD vs. non-PD at treatment start or after 6 weeks. Results: Fifty patients with treatment-naïve mRCC were enrolled (median age: 68.5 years, 33% female). All received tyrosine-kinase inhibitors (37 sunitinib, 4 pazopanib, 9 cabozantinib). The median follow-up time was 3.5 months, totaling 65 response evaluation visits - 23 PD and 42 non-PD. PD was compatible with alterations in 40% of the detectable GAGome features. These were used to design a plasma, urine, and combined GAG progression score to classify PD vs. non-PD at response evaluation. The area-under-the-curve (AUC) was 0.91 in plasma, 0.98 in urine, and 0.99 when combined. In validation, the AUC to predict PD at treatment start was 0.64 in plasma, 0.63 in urine, and 0.71 when combined (N = 50); and, after 6 weeks, 0.75 in plasma, 0.66 in urine, and 0.80 when combined (N = 47). The combined GAG progression score had 62% sensitivity and 86% specificity to PD at treatment start and 67% and 87% after 6 weeks. Conclusions: GAGomes correlated with treatment response in mRCC. GAG scores were validated for the early prediction of response. Their clinical utility remains to be ascertained. Clinical trial information: NCT02732665.