tbuckley/cabot-search huggingface dataset:
Amplified Pain—A Helpful Diagnosis
Authors: David D. Sherry
Journal: JAMA Pediatrics (2021)

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A Serum Marker for Early Pancreatic Cancer With a Possible Link to Diabetes
Authors: Hoonsik Nam, Soon-Sun Hong, Kyung Hee Jung, Sunmi Kang, Min Seok Park, Suyeon Kang, Han Sun Kim, Van-Hieu Mai, Juyoung Kim, Ho Lee, Woohyung Lee, Young Ju Suh, Joo Han Lim, Soo-Youl Kim, Song Cheol Kim, So Hun Kim, Sunghyouk Park
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background Pancreatic cancer (PC) has a grim prognosis, and an early diagnostic biomarker has been highly desired. The molecular link between diabetes and PC has not been well established. Methods Bioinformatics screening was performed for a serum PC marker. Experiments in cell lines (5 PC and 1 normal cell lines), mouse models, and human tissue staining (37 PC and 10 normal cases) were performed to test asprosin production from PC. Asprosin’s diagnostic performance was tested with serums from multi-center cohorts (347 PC, 209 normal, and 55 additional diabetic patients) and evaluated according to PC status, stages, and diabetic status, which was compared with that of CA19-9. Results Asprosin, a diabetes-related hormone, was found from the bioinformatics screening, and its production from PC was confirmed. Serum asprosin levels from multi-center cohorts yielded an age-adjusted diagnostic area under the curve (AUC) of 0.987 (95% confidence interval [CI] = 0.961 to 0.997), superior to that of CA19-9 (AUC = 0.876, 95% CI = 0.847 to 0.905), and a cut-off of 7.18 ng/mL, at which the validation set exhibited a sensitivity of 0.957 and a specificity of 0.924. Importantly, the performance was maintained in early-stage and non-metastatic PC, consistent with the tissue staining. A slightly lower performance against additional diabetic patients (n = 55) was restored by combining asprosin and CA19-9 (AUC = 0.985, 95% CI = 0.975 to 0.995). Conclusions Asprosin is presented as an early-stage PC serum marker that may provide clues for PC-induced diabetes. Larger prospective clinical studies are warranted to solidify its utility.
1360TiP First-line (1L) maintenance therapy with niraparib (nira) + pembrolizumab (pembro) vs placebo + pembro in advanced/metastatic non-small cell lung cancer (NSCLC): Phase III ZEAL-1L study
Authors: S.S. Ramalingam, G. de Castro, M.C.C. Garassino, J. Mazieres, R.E. Sanborn, E.F.F. Smit, D.R. Spigel, M. Thomas, V. Velcheti, E. Zhi, M. Whipple Neibauer, A. Stojadinovic, S. Peters
Journal: Annals of Oncology (2021)
643TiP Open-label, phase II study of ladiratuzumab vedotin (LV) for unresectable locally advanced or metastatic solid tumors
Authors: H-T. Arkenau, T. Guthrie, T. Mekhail, D. Cortinovis, L. Antonuzzo, J.Y. Bruce, N. Gabrail, I. Anderson, S.C. Oh, S.Y. Oh, L. Nott, M.A. Shah, R.E. Sanborn, D-Y. Oh, J.Y. Cho, C-C. Lin, A. Lee, Y. Wang, Z. Wang, A. Sher
Journal: Annals of Oncology (2021)
Epinephrine (adrenaline) compared to selective beta-2-agonist in adults or children with acute asthma: a systematic review and meta-analysis
Authors: Christina Baggott, Jo Katherine Hardy, Jenny Sparks, Doñah Sabbagh, Richard Beasley, Mark Weatherall, James Fingleton
Journal: Thorax (2021)

Background International asthma guidelines recommend against epinephrine (adrenaline) administration in acute asthma unless associated with anaphylaxis or angio-oedema. However, administration of intramuscular epinephrine in addition to nebulised selective β 2 -agonist is recommended for acute severe or life-threatening asthma in many prehospital guidelines. We conducted a systematic review to determine the efficacy of epinephrine in comparison to selective β 2 -agonist in acute asthma. Methods We included peer-reviewed publications of randomised controlled trials (RCTs) that enrolled children or adults in any healthcare setting and compared epinephrine by any route to selective β 2 -agonist by any route for an acute asthma exacerbation. The primary outcome was treatment failure, including hospitalisation, need for intubation or death. Results Thirty-eight of 1140 studies were included. Overall quality of evidence was low. Seventeen studies contributed data on 1299 participants to the meta-analysis. There was significant statistical heterogeneity, I 2 =56%. The pooled Peto’s OR for treatment failure with epinephrine versus selective β 2 -agonist was 0.99 (0.75 to 1.32), p=0.95. There was strong evidence that recruitment age group was associated with different estimates of the odds of treatment failure; with studies recruiting adults-only having lower odds of treatment failure with epinephrine. It was not possible to determine whether epinephrine in addition to selective β 2 -agonist improved outcomes. Conclusion The low-quality evidence available suggests that epinephrine and selective β 2 -agonists have similar efficacy in acute asthma. There is a need for high-quality double-blind RCTs to determine whether addition of intramuscular epinephrine to inhaled or nebulised selective β 2 -agonist improves outcome. PROSPERO registration number CRD42017079472.
Application of the CRISPR/Cas9-based gene editing technique in basic research, diagnosis, and therapy of cancer
Authors: Huimin Zhang, Chunhong Qin, Changming An, Xiwang Zheng, Shuxin Wen, Wenjie Chen, Xianfang Liu, Zhenghua Lv, Pingchang Yang, Wei Xu, Wei Gao, Yongyan Wu
Journal: Molecular Cancer (2021)

Abstract The 2020 Nobel Prize in Chemistry was awarded to Emmanuelle Charpentier and Jennifer Doudna for the development of the Clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease9 (CRISPR/Cas9) gene editing technology that provided new tools for precise gene editing. It is possible to target any genomic locus virtually using only a complex nuclease protein with short RNA as a site-specific endonuclease. Since cancer is caused by genomic changes in tumor cells, CRISPR/Cas9 can be used in the field of cancer research to edit genomes for exploration of the mechanisms of tumorigenesis and development. In recent years, the CRISPR/Cas9 system has been increasingly used in cancer research and treatment and remarkable results have been achieved. In this review, we introduced the mechanism and development of the CRISPR/Cas9-based gene editing system. Furthermore, we summarized current applications of this technique for basic research, diagnosis and therapy of cancer. Moreover, the potential applications of CRISPR/Cas9 in new emerging hotspots of oncology research were discussed, and the challenges and future directions were highlighted.
Cardiovascular consequences of viral infections: from COVID to other viral diseases
Authors: Heinz-Peter Schultheiss, Christian Baumeier, Heiko Pietsch, C -Thomas Bock, Wolfgang Poller, Felicitas Escher
Journal: Cardiovascular Research (2021)

Infection of the heart muscle with cardiotropic viruses is one of the major aetiologies of myocarditis and acute and chronic inflammatory cardiomyopathy (DCMi). However, viral myocarditis and subsequent dilated cardiomyopathy is still a challenging disease to diagnose and to treat and is therefore a significant public health issue globally. Advances in clinical examination and thorough molecular genetic analysis of intramyocardial viruses and their activation status have incrementally improved our understanding of molecular pathogenesis and pathophysiology of viral infections of the heart muscle. To date, several cardiotropic viruses have been implicated as causes of myocarditis and DCMi. These include, among others, classical cardiotropic enteroviruses (Coxsackieviruses B), the most commonly detected parvovirus B19, and human herpes virus 6. A newcomer is the respiratory virus that has triggered the worst pandemic in a century, SARS-CoV-2, whose involvement and impact in viral cardiovascular disease is under scrutiny. Despite extensive research into the pathomechanisms of viral infections of the cardiovascular system, our knowledge regarding their treatment and management is still incomplete. Accordingly, in this review, we aim to explore and summarize the current knowledge and available evidence on viral infections of the heart. We focus on diagnostics, clinical relevance and cardiovascular consequences, pathophysiology, and current and novel treatment strategies.
1383P Phase I study of the irreversible FGFR inhibitor futibatinib in Japanese patients with advanced solid tumors: Updated dose expansion results and activity in gastric cancer
Authors: Y. Kuboki, K. Shitara, C. Morizane, T. Kojima, K. Yoh, D. Sakai, M. Tahara, H. Hirai, Y. Kurokawa, T. Kato, T. Doi
Journal: Annals of Oncology (2021)
Use of Singing for Lung Health as an alternative training modality within pulmonary rehabilitation for COPD: a randomised controlled trial
Authors: Mette Kaasgaard, Daniel Bech Rasmussen, Karen Hjerrild Andreasson, Ole Hilberg, Anders Løkke, Peter Vuust, Uffe Bodtger
Journal: European Respiratory Journal (2021)

Background Pulmonary rehabilitation (PR) is a cornerstone in chronic obstructive pulmonary disease (COPD) management. However, PR adherence is generally low, and barriers include availability, economic issues, motivation and an inability to attend or perform physical training. Therefore, alternative, evidence-based PR activities are required. Singing may have benefits for quality of life (QoL), respiratory control and well-being in COPD, but the impact on the PR key outcome, physical exercise capacity, is uncertain. Methods In this randomised controlled trial ( NCT03280355 ), we investigated the effectiveness of 10 weeks of PR, including either “Singing for Lung Health” (SLH) training or standard physical exercise training (PExT). The primary outcome was a change in exercise capacity (6-min walk distance (6MWD)) from baseline to post-PR. Secondary outcomes were changes in QoL (St George's Respiratory Questionnaire (SGRQ)), Hospital Anxiety and Depression Score (HADS), lung function, dyspnoea and adherence. Results We included 270 COPD patients, and 195 completed the study. Demographics across groups were comparable, and both groups improved significantly in 6MWD and SGRQ score. SLH was non-inferior to PExT in improving 6MWD (mean± sd 13.1±36.3 m versus 14.1±32.3 m, p=0.81; difference 1.0 m, 95% CI −7.3–9.3 m) with 21.8% and 25.0%, respectively (p=0.57), reaching the 6MWD minimal important difference of 30 m. We found no significant between-group differences concerning SGRQ, HADS, lung function, dyspnoea or adherence. Conclusion Our study suggests that SLH is non-inferior to PExT in improving 6MWD during a 10-week PR programme. Future studies addressing reproducibility, long-term effects and health economics are needed.
Norovirus diarrhea is significantly associated with higher counts of fecal histo-blood group antigen expressing <i>Enterobacter cloacae</i> among black South African infants
Authors: Cliff A Magwira, Duncan Steele, ML Seheri
Journal: Gut Microbes (2021)

The study tested the hypothesis that harboring high levels of histo-blood group antigen-expressing Enerobactero cloacae is a risk factor for norovirus diarrhea. The fecal E. cloacae abundance in diarrheic norovirus positive (DNP), non-diarrheic norovirus negative (NDNN), diarrhea norovirus negative (DNN), and non-diarrhea norovirus positive (NDNP) infants was determined by qPCR, and the risk of norovirus diarrhea was assessed by logistical regression. DNP infants contained significantly higher counts of E. cloacae than NDNN and DNN infants, p = .0294, and 0.0001, respectively. The risk of norovirus diarrhea was significantly high in infants with higher counts of E. cloacae than those with lower counts, p = .009. Harboring higher counts of E. cloacae is a risk factor for norovirus diarrhea.
1361TiP Trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-mutated (HER2m) metastatic non-small cell lung cancer (NSCLC): A phase (ph) II study (DESTINY-Lung02)
Authors: E.F.F. Smit, B.T. Li, J. Mazieres, D. Planchard, K. Nakagawa, K. Goto, L. Paz-Ares, S. Novello, J.C-H. Yang, M-J. Ahn, G. Liu, K. O'Byrne, M. Aregay, R. Shiga, K. Saxena, G. Meinhardt, P.A. Jänne
Journal: Annals of Oncology (2021)
1236P Poziotinib in NSCLC harbouring EGFR or HER2 exon 20 insertion mutation
Authors: A. Prelaj, A. Bottiglieri, E. Galli, G. Lo Russo, R. Ferrara, G. Galli, A. De Toma, M. Brambilla, M. Occhipinti, S. Manglaviti, T. Beninato, E. Zattarin, G. Apollonio, M. Ganzinelli, R. Gallucci, R.M. Di Mauro, F. de Braud, V. Torri, M.C.C. Garassino, C. Proto
Journal: Annals of Oncology (2021)
1869TiP A phase II, multicenter, open-label study evaluating trastuzumab deruxtecan (T-DXd) for the treatment of select HER2-expressing solid tumors (DESTINY-PanTumor02)
Authors: F. Meric-Bernstam, C. Anoka, A. Dobrowolska, A. Chaudhry, J. Rowbottom, M. Gustavson, S. Puvvada
Journal: Annals of Oncology (2021)
Predictors and Dynamics of the Humoral and Cellular Immune Response to SARS-CoV-2 mRNA Vaccines in Hemodialysis Patients: A Multicenter Observational Study
Authors: Jens Van Praet, Marijke Reynders, Dirk De Bacquer, Liesbeth Viaene, Melanie K. Schoutteten, Rogier Caluwé, Peter Doubel, Line Heylen, Annelies V. De Bel, Bruno Van Vlem, Deborah Steensels, An S. De Vriese
Journal: Journal of the American Society of Nephrology (2021)

Preliminary evidence suggests patients on hemodialysis have a blunted early serological response to SARS-CoV-2 vaccination. Optimizing the vaccination strategy in this population requires a thorough understanding of predictors and dynamics of humoral and cellular immune responses to different SARS-CoV-2 vaccines.This prospective multicenter study of 543 patients on hemodialysis and 75 healthy volunteers evaluated the immune responses at 4 or 5 weeks and 8 or 9 weeks after administration of the BNT162b2 or mRNA-1273 vaccine, respectively. We assessed anti-SARS-CoV-2 spike antibodies and T cell responses by IFN-γ secretion of peripheral blood lymphocytes upon SARS-CoV-2 glycoprotein stimulation (QuantiFERON assay) and evaluated potential predictors of the responses.Compared with healthy volunteers, patients on hemodialysis had an incomplete, delayed humoral immune response and a blunted cellular immune response. Geometric mean antibody titers at both time points were significantly greater in patients vaccinated with mRNA-1273 versus BNT162b2, and a larger proportion of them achieved the threshold of 4160 AU/ml, corresponding with high neutralizing antibody titers in vitro (53.6% versus 31.8% at 8 or 9 weeks, P <0.0001). Patients vaccinated with mRNA-1273 versus BNT162b2 exhibited significantly greater median QuantiFERON responses at both time points, and a larger proportion achieved the threshold of 0.15 IU/ml (64.4% versus 46.9% at 8 or 9 weeks, P <0.0001). Multivariate analysis identified COVID-19 experience, vaccine type, use of immunosuppressive drugs, serum albumin, lymphocyte count, hepatitis B vaccine nonresponder status, and dialysis vintage as independent predictors of the humoral and cellular responses.The mRNA-1273 vaccine's greater immunogenicity may be related to its higher mRNA dose. This suggests a high-dose vaccine might improve the impaired immune response to SARS-CoV-2 vaccination in patients on hemodialysis.
1849P Ethnicity and socioeconomic deprivation in early phase clinical trials in a UK tertiary referral centre
Authors: N. Billy Graham Mariam, R. Rahman, H. Mistry, S. Aruketty, A. Adamson-Raieste, M. Church, J-A. Scott, L. Carter, F. Thistlethwaite, M.G. Krebs, N. Cook, D. Graham
Journal: Annals of Oncology (2021)
68P High blood concentration of circulating cancer stem cell-derived extracellular vesicles is associated with poor survival in advanced colorectal cancer patients
Authors: D. Brocco, P. Lanuti, P. Simeone, G. Bologna, P. Di Marino, M. De Tursi, A. Grassadonia, L. De Lellis, S. Veschi, P. Di Sebastiano, M. Marchisio, S. Miscia, A. Cama, N. Tinari
Journal: Annals of Oncology (2021)
PET/CT scan and biopsy-driven approach for safe anti-PD-1 therapy discontinuation in patients with advanced melanoma
Authors: Geoffrey T. Gibney, Jacob Zaemes, Shelly Shand, Neil J. Shah, David Swoboda, Kellie Gardner, Arash Radfar, Vesna Petronic-Rosic, Michael J. Reilly, Waddah B. Al-Refaie, Suthee Rapisuwon, Michael B. Atkins
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Limited data exist on safe discontinuation of antiprogrammed cell death protein 1 (PD-1) therapy in responding patients with advanced melanoma. The use of 18fluorodeoxyglucose ( 18 FDG)-PET/CT scan and tumor biopsy for assessment of active disease may be an effective predictive biomarker to guide such treatment decisions. Methods A retrospective study of 122 patients with advanced melanoma treated with anti-PD-1 monotherapy or anti-PD-1/anticytotoxic T-lymphocyte-associated protein 4 combination therapy at Georgetown Lombardi Comprehensive Cancer Center was conducted. Uveal melanoma patients and those receiving concurrent experimental therapy were excluded. Baseline characteristics, treatment outcomes, and survival were analyzed. Patients who decided to come off treatment typically after 12 months using CT scan radiographic complete response (CR), 18 FDG-PET/CT scan complete metabolic response (CMR) or tumor biopsy of a non-CR/CMR tumor site negative for active disease (possible pathological CR) were identified and compared with patients who discontinued treatment due to toxicity while their disease was in control. Event-free survival (EFS) was assessed from the last dose of anti-PD-1 therapy to progression requiring subsequent treatment (surgery, radiation, and/or systemic therapy) or referral to hospice/death due to melanoma. Results 24 (20%) patients discontinued treatment by choice with no active disease and 28 (23%) patients discontinued treatment due to toxicity with disease control after 12-month and 4-month median treatment durations, respectively. Similar baseline characteristics were observed between cohorts except higher prior receipt of ipilimumab (29% vs 7%; p=0.036) and fewer BRAF mutant positive disease (17% vs 41%; p=0.064) in patients off treatment by choice. Three-year EFS rates were 95% and 71%, respectively. No significant associations between EFS and sex, disease stage, lactate dehydrogenase elevation, BRAF status, prior systemic therapy, ECOG performance status, presence of brain metastases, or combination versus monotherapy were observed. Tumor biopsies led to alternative management in 3/10 patients due to active metastatic melanoma or second malignancy. Conclusions Anti-PD-1 therapy discontinuation after 12 months when no active disease is observed on CT scan, PET/CT scan or tumor biopsy may have low rates of disease relapse in patients with advanced melanoma. Biopsy of residual disease may frequently lead to a change in management. These findings are undergoing validation in the EA6192 trial.
84P Metastatic mismatch repair deficiency cancers: Hard to find, but a delight to treat!
Authors: A. Rauthan, N.Y. Murthy, P. Patil, S. Sampige Prasannakumar, S. Zaveri, G.R. Nigade, P. Vundemodalu, R. Ashwath, C. Jomi
Journal: Annals of Oncology (2021)
Conflating Race and Genetics Among Newborns With Neonatal Abstinence Syndrome
Authors: Rebecca R. S. Clark, Rachel French
Journal: JAMA Pediatrics (2021)

This Viewpoint discusses specific cases of the conflation of race and genetics in the neonatal abstinence syndrome literature to point out the history behind this conflation, why it is a fallacy, what it means for the individuals the research pertains to, and what needs to be done about it.
Epigenetic dynamics shaping melanophore and iridophore cell fate in zebrafish
Authors: Hyo Sik Jang, Yujie Chen, Jiaxin Ge, Alicia N. Wilkening, Yiran Hou, Hyung Joo Lee, You Rim Choi, Rebecca F. Lowdon, Xiaoyun Xing, Daofeng Li, Charles K. Kaufman, Stephen L. Johnson, Ting Wang
Journal: Genome biology (2021)

Abstract Background Zebrafish pigment cell differentiation provides an attractive model for studying cell fate progression as a neural crest progenitor engenders diverse cell types, including two morphologically distinct pigment cells: black melanophores and reflective iridophores. Nontrivial classical genetic and transcriptomic approaches have revealed essential molecular mechanisms and gene regulatory circuits that drive neural crest-derived cell fate decisions. However, how the epigenetic landscape contributes to pigment cell differentiation, especially in the context of iridophore cell fate, is poorly understood. Results We chart the global changes in the epigenetic landscape, including DNA methylation and chromatin accessibility, during neural crest differentiation into melanophores and iridophores to identify epigenetic determinants shaping cell type-specific gene expression. Motif enrichment in the epigenetically dynamic regions reveals putative transcription factors that might be responsible for driving pigment cell identity. Through this effort, in the relatively uncharacterized iridophores, we validate alx4a as a necessary and sufficient transcription factor for iridophore differentiation and present evidence on alx4a ’s potential regulatory role in guanine synthesis pathway. Conclusions Pigment cell fate is marked by substantial DNA demethylation events coupled with dynamic chromatin accessibility to potentiate gene regulation through cis-regulatory control. Here, we provide a multi-omic resource for neural crest differentiation into melanophores and iridophores. This work led to the discovery and validation of iridophore-specific alx4a transcription factor.