tbuckley/cabot-search huggingface dataset:
Adolescents and Young Adults With Cancer: CNS Tumors
Authors: Jing Wu, R. Elyse Heidelberg, Amar Gajjar
Journal: Journal of Clinical Oncology (2023)

Tumors of CNS are common in adolescents and young adults (AYAs). As the second leading cause of cancer-related death, CNS tumors in AYAs require improved clinical management. In this review, we discussed the current diagnostic approaches and recommended management strategies for malignant tumors in adult-type (IDH-mutant gliomas) and pediatric-type gliomas (pediatric high-grade gliomas), ependymoma and medulloblastoma, which commonly occur in AYAs. The impact of advanced molecular diagnostic approaches on the understanding of tumor biology of AYA CNS tumors is emphasized. To enhance participation in clinical trials, which poses a unique challenge in AYAs with CNS tumors, we propose encouraging referrals to neuro-oncology specialty care and improving collaboration between oncologists who care for both pediatric and adult patients. This will ensure better representation of AYA patients in research studies. Finally, we discussed the importance of considering neurocognitive and psychological function in AYAs with CNS tumor.
Glucagon-like peptide-1 receptor signaling modifies the extent of diabetic kidney disease through dampening the receptor for advanced glycation end products–induced inflammation
Authors: Karly C. Sourris, Yi Ding, Scott S. Maxwell, Annas Al-sharea, Phillip Kantharidis, Muthukumar Mohan, Carlos J. Rosado, Sally A. Penfold, Claus Haase, Yangsong Xu, Josephine M. Forbes, Simon Crawford, Georg Ramm, Brooke E. Harcourt, Karin Jandeleit-Dahm, Andrew Advani, Andrew J. Murphy, Daniel B. Timmermann, Anil Karihaloo, Lotte Bjerre Knudsen, Assam El-Osta, Daniel J. Drucker, Mark E. Cooper, Melinda T. Coughlan
Journal: Kidney International (2023)

Glucagon like peptide-1 (GLP-1) is a hormone produced and released by cells of the gastrointestinal tract following meal ingestion. GLP-1 receptor agonists (GLP-1RA) exhibit kidney-protective actions through poorly understood mechanisms. Here we interrogated whether the receptor for advanced glycation end products (RAGE) plays a role in mediating the actions of GLP-1 on inflammation and diabetic kidney disease. Mice with deletion of the GLP-1 receptor displayed an abnormal kidney phenotype that was accelerated by diabetes and improved with co-deletion of RAGE in vivo. Activation of the GLP-1 receptor pathway with liraglutide, an anti-diabetic treatment, downregulated kidney RAGE, reduced the expansion of bone marrow myeloid progenitors, promoted M2-like macrophage polarization and lessened markers of kidney damage in diabetic mice. Single cell transcriptomics revealed that liraglutide induced distinct transcriptional changes in kidney endothelial, proximal tubular, podocyte and macrophage cells, which were dominated by pathways involved in nutrient transport and utilization, redox sensing and the resolution of inflammation. The kidney-protective action of liraglutide was corroborated in a non-diabetic model of chronic kidney disease, the subtotal nephrectomised rat. Thus, our findings identify a novel glucose-independent kidney-protective action of GLP-1-based therapies in diabetic kidney disease and provide a valuable resource for exploring the cell-specific kidney transcriptional response ensuing from pharmacological GLP-1R agonism.
Corrigendum to “Pembrolizumab Plus Axitinib Versus Sunitinib as First-line Treatment of Advanced Renal Cell Carcinoma: 43-month Follow-up of the Phase 3 KEYNOTE-426 Study” [Eur Urol 84(5) (2023) 449–454]
Authors: Elizabeth R. Plimack, Thomas Powles, Viktor Stus, Rustem Gafanov, Dmitry Nosov, Tom Waddell, Boris Alekseev, Frédéric Pouliot, Bohuslav Melichar, Denis Soulières, Delphine Borchiellini, Raymond S. McDermott, Ihor Vynnychenko, Yen-Hwa Chang, Satoshi Tamada, Michael B. Atkins, Chenxiang Li, Rodolfo Perini, L. Rhoda Molife, Jens Bedke, Brian I. Rini
Journal: European Urology (2023)
Trends in smoking-attributable and smoking-unrelated lung cancer death rates in the United States, 1991-2018
Authors: Meredith S Shiels, Barry I Graubard, Timothy S McNeel, Lisa Kahle, Neal D Freedman
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background In the United States, lung cancer death rates have been declining for decades, primarily as a result of pronounced decreases in cigarette smoking. It is unclear, however, whether there have been similar declines in mortality rates of lung cancer unrelated to smoking. We estimated trends in US lung cancer death rates attributable and not attributable to smoking from 1991 to 2018. Methods The study included 30- to 79-year-olds in the National Health Interview Survey who were linked to the National Death Index, 1991-2014. Adjusted hazard ratios for smoking status and lung cancer death were estimated, and age-specific population attributable fractions were calculated. Annual population attributable fractions were multiplied by annual US national lung cancer mortality, partitioning rates into smoking-attributable and smoking-unrelated lung cancer deaths. All statistical tests were 2-sided. Results During 1991-2018, the proportion of never smokers increased among both men (35.1%-54.6%) and women (54.0%-65.4%). Compared with those who had ever smoked, those who had never smoked had 86% lower risk (hazard ratio = 0.14; 95% confidence interval [CI] = 0.12 to 0.16) of lung cancer death. The fraction of lung cancer deaths attributable to smoking decreased from 81.4% (95% CI = 78.9 to 81.4) to 74.7% (95% CI = 78.1 to 71.4). Smoking-attributable lung cancer death rates declined 2.7% per year (95% CI = ‒2.9% to ‒2.5%) and smoking-unrelated lung cancer death rates declined 1.8% per year (95% CI = ‒2.0% to ‒1.5%); these declines have accelerated in recent years. Conclusions An increasing proportion of lung cancer deaths are unrelated to smoking based on declines in smoking prevalence. Smoking-unrelated lung cancer death rates have declined, however, perhaps because of decreases in secondhand smoke and air pollution exposure as well as treatment improvements.
Organic cation transporters in psychiatric and substance use disorders
Authors: Lauren E. Honan, Rheaclare Fraser-Spears, Lynette C. Daws
Journal: Pharmacology & Therapeutics (2023)

Psychiatric and substance use disorders inflict major public health burdens worldwide. Their widespread burden is compounded by a dearth of effective treatments, underscoring a dire need to uncover novel therapeutic targets. In this review, we summarize the literature implicating organic cation transporters (OCTs), including three subtypes of OCTs (OCT1, OCT2, and OCT3) and the plasma membrane monoamine transporter (PMAT), in the neurobiology of psychiatric and substance use disorders with an emphasis on mood and anxiety disorders, alcohol use disorder, and psychostimulant use disorder. OCTs transport monoamines with a low affinity but high capacity, situating them to play a central role in regulating monoamine homeostasis. Preclinical evidence discussed here suggests that OCTs may serve as promising targets for treatment of psychiatric and substance use disorders and encourage future research into their therapeutic potential.
Tislelizumab plus zanubrutinib for Richter transformation: the phase 2 RT1 trial
Authors: Othman Al-Sawaf, Rudy Ligtvoet, Sandra Robrecht, Janina Stumpf, Anna-Maria Fink, Eugen Tausch, Christof Schneider, Sebastian Boettcher, Martin Mikusko, Matthias Ritgen, Johannes Schetelig, Julia von Tresckow, Ursula Vehling-Kaiser, Tobias Gaska, Clemens Martin Wendtner, Bjoern Chapuy, Kirsten Fischer, Karl-Anton Kreuzer, Stephan Stilgenbauer, Philipp Staber, Carsten Niemann, Michael Hallek, Barbara Eichhorst
Journal: Nature Medicine (2023)

In patients with chronic lymphocytic leukemia, Richter transformation (RT) reflects the development of an aggressive lymphoma that is associated with poor response to chemotherapy and short survival. We initiated an international, investigator-initiated, prospective, open-label phase 2 study in which patients with RT received a combination of the PD-1 inhibitor tislelizumab plus the BTK inhibitor zanubrutinib for 12 cycles. Patients responding to treatment underwent maintenance treatment with both agents. The primary end point was overall response rate after six cycles. Of 59 enrolled patients, 48 patients received at least two cycles of treatment and comprised the analysis population according to the study protocol. The median observation time was 13.9 months, the median age was 67 (range 45-82) years. Ten patients (20.8%) had received previous RT-directed therapy. In total, 28 out of 48 patients responded to induction therapy with an overall response rate of 58.3% (95% confidence interval (CI) 43.2-72.4), including 9 (18.8%) complete reponse and 19 (39.6%) partial response, meeting the study's primary end point by rejecting the predefined null hypothesis of 40% (P = 0.008). Secondary end points included duration of response, progression-free survival and overall survival. The median duration of response was not reached, the median progression-free survival was 10.0 months (95% CI 3.8-16.3). Median overall survival was not reached with a 12-month overall survival rate of 74.7% (95% CI 58.4-91.0). The most common adverse events were infections (18.0%), gastrointestinal disorders (13.0%) and hematological toxicities (11.4%). These data suggest that combined checkpoint and BTK inhibition by tislelizumab plus zanubrutinib is an effective and well-tolerated treatment strategy for patients with RT. ClinicalTrials.gov Identifier: NCT04271956 .
Final analysis of phase II results with cemiplimab in metastatic basal cell carcinoma after hedgehog pathway inhibitors
Authors: K.D. Lewis, K. Peris, A. Sekulic, A.J. Stratigos, L. Dunn, Z. Eroglu, A.L.S. Chang, M.R. Migden, S.-Y. Yoo, K. Mohan, E. Coates, E. Okoye, T. Bowler, J.-F. Baurain, O. Bechter, A. Hauschild, M.O. Butler, L. Hernandez-Aya, L. Licitra, R.I. Neves, E.S. Ruiz, F. Seebach, I. Lowy, P. Goncalves, M.G. Fury
Journal: Annals of Oncology (2023)

BackgroundMetastatic basal cell carcinoma (mBCC) is a rare condition with no effective second-line treatment options. Cemiplimab is an immune checkpoint inhibitor that blocks binding of programmed cell death-1 (PD-1) to its ligands, PD-L1 and PD-L2. Here, we present the final analysis of cemiplimab in patients with mBCC after first-line hedgehog pathway inhibitors (HHIs) (NCT03132636).Patients and methodsIn this open-label, single-arm, phase II study, adults with mBCC and Eastern Cooperative Oncology Group performance status ≤1, post-HHI treatment, received cemiplimab 350 mg intravenously every 3 weeks for ≤93 weeks or until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by independent central review (ICR). Duration of response (DOR) was a key secondary endpoint. Other secondary endpoints included ORR per investigator assessment (INV), progression-free survival (PFS), overall survival (OS), complete response (CR) rate, safety and tolerability.ResultsFifty-four patients were enrolled (70% male, median age 64 years [interquartile range (IQR) 57.0–73.0]). Median duration of follow-up was 8 months (IQR 4–21). ORR per ICR was 22% (95% confidence interval [CI] 12–36), with two CRs and 10 partial responses. Among responders, median time to response per ICR was 3 months (IQR 2–7). Estimated median DOR per ICR was not reached (95% CI 10 months–not evaluable [NE]). Disease control rate was 63% (95% CI 49–76) per ICR and 70% (95% CI 56–82) per INV. Median PFS per ICR was 10 months (95% CI 4–16); median OS was 50 months (95% CI 28–NE). The most common treatment-emergent adverse events were fatigue (23 [43%]) and diarrhoea (20 [37%]). There were no treatment-related deaths.ConclusionsCemiplimab demonstrated clinically meaningful antitumour activity, including durable responses, and an acceptable safety profile in patients with mBCC who had disease progression on or intolerance to HHI therapy.
Recapitulating primary immunodeficiencies with expanded potential stem cells: Proof of concept with STAT1 gain of function
Authors: Xueyan Liu, Vera S.F. Chan, Kenneth G.C. Smith, Chang Ming, Chung Sze Or, Faria T.W. Tsui, Bo Gao, Matthew C. Cook, Pentao Liu, Chak Sing Lau, Philip Hei Li
Journal: Journal of Allergy and Clinical Immunology (2023)
An insect sclerotization-inspired antifouling armor on biomedical devices combats thrombosis and embedding
Authors: Nan Lyu, Daihua Deng, Yuting Xiang, Zeyu Du, Xiaohui Mou, Qing Ma, Nan Huang, Jing Lu, Xin Li, Zhilu Yang, Wentai Zhang
Journal: Bioactive Materials (2023)

Thrombus formation and tissue embedding significantly impair the clinical efficacy and retrievability of temporary interventional medical devices. Herein, we report an insect sclerotization-inspired antifouling armor for tailoring temporary interventional devices with durable resistance to protein adsorption and the following protein-mediated complications. By mimicking the phenol-polyamine chemistry assisted by phenol oxidases during sclerotization, we develop a facile one-step method to crosslink bovine serum albumin (BSA) with oxidized hydrocaffeic acid (HCA), resulting in a stable and universal BSA@HCA armor. Furthermore, the surface of the BSA@HCA armor, enriched with carboxyl groups, supports the secondary grafting of polyethylene glycol (PEG), further enhancing both its antifouling performance and durability. The synergy of robustly immobilized BSA and covalently grafted PEG provide potent resistance to the adhesion of proteins, platelets, and vascular cells
Abnormal vascular structure and function within brain metastases is linked to pembrolizumab resistance
Authors: Albert E Kim, Kevin W Lou, Anita Giobbie-Hurder, Ken Chang, Mishka Gidwani, Katharina Hoebel, Jay B Patel, Mason C Cleveland, Praveer Singh, Christopher P Bridge, Syed Rakin Ahmed, Benjamin A Bearce, William Liu, Elies Fuster-Garcia, Eudocia Q Lee, Nancy U Lin, Beth Overmoyer, Patrick Y Wen, Lakshmi Nayak, Justine V Cohen, Jorg Dietrich, April Eichler, Rebecca Heist, Ian Krop, Donald Lawrence, Jennifer Ligibel, Sara Tolaney, Erica Mayer, Eric Winer, Carmen M Perrino, Elizabeth J Summers, Maura Mahar, Kevin Oh, Helen A Shih, Daniel P Cahill, Bruce R Rosen, Yi-Fen Yen, Jayashree Kalpathy-Cramer, Maria Martinez-Lage, Ryan J Sullivan, Priscilla K Brastianos, Kyrre E Emblem, Elizabeth R Gerstner
Journal: Neuro-Oncology (2023)

Abstract Background We recently conducted a phase 2 trial (NCT028865685) evaluating intracranial efficacy of pembrolizumab for brain metastases (BM) of diverse histologies. Our study met its primary efficacy endpoint and illustrates that pembrolizumab exerts promising activity in a select group of patients with BM. Given the importance of aberrant vasculature in mediating immunosuppression, we explored the relationship between immune checkpoint inhibitor (ICI) efficacy and vascular architecture in the hopes of identifying potential mechanisms of intracranial ICI response or resistance for BM. Methods Using Vessel Architectural Imaging, a histologically validated quantitative metric for in vivo tumor vascular physiology, we analyzed dual-echo DSC/DCE MRI for 44 patients on trial. Tumor and peri-tumor cerebral blood volume/flow, vessel size, arterial and venous dominance, and vascular permeability were measured before and after treatment with pembrolizumab. Results BM that progressed on ICI were characterized by a highly aberrant vasculature dominated by large-caliber vessels. In contrast, ICI-responsive BM possessed a more structurally balanced vasculature consisting of both small and large vessels, and there was a trend toward a decrease in under-perfused tissue, suggesting a reversal of the negative effects of hypoxia. In the peri-tumor region, the development of smaller blood vessels, consistent with neo-angiogenesis, was associated with tumor growth before radiographic evidence of contrast enhancement on anatomical MRI. Conclusions This study, one of the largest functional imaging studies for BM, suggests that vascular architecture is linked with ICI efficacy. Studies identifying modulators of vascular architecture, and effects on immune activity, are warranted and may inform future combination treatments.
Health-related quality of life with pembrolizumab plus chemotherapy vs placebo plus chemotherapy for advanced triple-negative breast cancer: KEYNOTE-355
Authors: David W Cescon, Peter Schmid, Hope S Rugo, Seock-Ah Im, Mastura Md. Yusof, Carlos Gallardo, Oleg Lipatov, Carlos H Barrios, Jose Perez-Garcia, Hiroji Iwata, Norikazu Masuda, Marco Torregroza Otero, Erhan Gokmen, Sherene Loi, Amin Haiderali, Xuan Zhou, Zifang Guo, Allison Martin Nguyen, Javier Cortes
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background In KEYNOTE-355 (NCT02819518), the addition of pembrolizumab to chemotherapy led to statistically significant improvements in progression-free survival and overall survival in patients with advanced triple-negative breast cancer with tumor programmed cell death ligand 1 (PD-L1) combined positive score of at least 10. We report patient-reported outcomes from KEYNOTE-355. Methods Patients were randomly assigned 2:1 to pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus investigator’s choice chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin). The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (QLQ-C30), Breast Cancer–Specific Quality of Life Questionnaire, and EuroQol 5-Dimension questionnaire visual analog scale were prespecified. Patient-reported outcomes were analyzed for patients who received at least 1 dose of study treatment and completed at least 1 patient-reported outcome assessment. Changes in patient-reported outcome scores from baseline were assessed at week 15 (latest time point at which completion and compliance rates were at least 60% and at least 80%, respectively). Time to deterioration in patient-reported outcomes was defined as time to first onset of at least a 10-point worsening in score from baseline. Results Patient-reported outcome analyses included 317 patients with tumor PD-L1 combined positive score of at least 10 (pembrolizumab plus chemotherapy: n = 217; placebo plus chemotherapy: n = 100). There were no between-group differences in change from baseline to week 15 in QLQ-C30 global health status/quality of life (QOL; least-squares mean difference = −1.81, 95% confidence interval [CI] = −6.92 to 3.30), emotional functioning (least-squares mean difference = −1.43, 95% CI = −7.03 to 4.16), physical functioning (least-squares mean difference = −1.05, 95% CI = −6.59 to 4.50), or EuroQol 5-Dimension questionnaire visual analog scale (least-squares mean difference = 0.18, 95% CI = −5.04 to 5.39) and no between-group difference in time to deterioration in QLQ-C30 global health status/QOL, emotional functioning, or physical functioning. Conclusions Together with the efficacy and safety findings, patient-reported outcome results from KEYNOTE-355 support pembrolizumab plus chemotherapy as a standard of care for patients with advanced triple-negative breast cancer with tumor PD-L1 expression (combined positive score ≥10).
Exploiting autophagy balance in T and NK cells as a new strategy to implement adoptive cell therapies
Authors: Manuela Giansanti, Tobias Theinert, Sarah Katharina Boeing, Dorothee Haas, Paul-Gerhardt Schlegel, Paola Vacca, Francesca Nazio, Ignazio Caruana
Journal: Molecular Cancer (2023)

Abstract Autophagy is an essential cellular homeostasis pathway initiated by multiple stimuli ranging from nutrient deprivation to viral infection, playing a key role in human health and disease. At present, a growing number of evidence suggests a role of autophagy as a primitive innate immune form of defense for eukaryotic cells, interacting with components of innate immune signaling pathways and regulating thymic selection, antigen presentation, cytokine production and T/NK cell homeostasis. In cancer, autophagy is intimately involved in the immunological control of tumor progression and response to therapy. However, very little is known about the role and impact of autophagy in T and NK cells, the main players in the active fight against infections and tumors. Important questions are emerging: what role does autophagy play on T/NK cells? Could its modulation lead to any advantages? Could specific targeting of autophagy on tumor cells (blocking) and T/NK cells (activation) be a new intervention strategy? In this review, we debate preclinical studies that have identified autophagy as a key regulator of immune responses by modulating the functions of different immune cells and discuss the redundancy or diversity among the subpopulations of both T and NK cells in physiologic context and in cancer.
Risk factors, mortality, and predictors of survival in COVID-19-associated pulmonary mucormycosis: a multicentre retrospective study from India
Authors: Valliappan Muthu, Ritesh Agarwal, Shivaprakash Mandya Rudramurthy, Deepak Thangaraju, Manoj Radhakishan Shevkani, Atul K. Patel, Prakash Srinivas Shastri, Ashwini Tayade, Sudhir Bhandari, Vishwanath Gella, Jayanthi Savio, Surabhi Madan, Vinaykumar Hallur, Venkata Nagarjuna Maturu, Arjun Srinivasan, Nandini Sethuraman, Raminder Pal Singh Sibia, Sanjay Pujari, Ravindra Mehta, Tanu Singhal, Puneet Saxena, Varsha Gupta, Vasant Nagvekar, Parikshit Prayag, Dharmesh Patel, Immaculata Xess, Pratik Savaj, Inderpaul Singh Sehgal, Naresh Panda, Gayathri Devi Rajagopal, Riya Sandeep Parwani, Kamlesh Patel, Anuradha Deshmukh, Aruna Vyas, Raghava Rao Gandra, Srinivas Kishore Sistla, Priyadarshini A. Padaki, Dharshni Ramar, Saurav Sarkar, Bharani Rachagulla, Pattabhiraman Vallandaramam, Krishna Prabha Premachandran, Sunil Pawar, Piyush Gugale, Pradeep Hosamani, Sunil Narayan Dutt, Satish Nair, Hariprasad Kalpakkam, Sanjiv Badhwar, Kiran Kumar Kompella, Nidhi Singla, Milind Navlakhe, Amrita Prayag, Gagandeep Singh, Poorvesh Dhakecha, Arunaloke Chakrabarti
Journal: Clinical Microbiology and Infection (2023)
Identifying critical quality metrics in Mohs Surgery: A national expert consensus process
Authors: Joseph A. Dodson, Sarah A. Ibrahim, Howard Rogers, M. Laurin Council, Kishwer S. Nehal, Rebecca Tung, David J. Leffell, Nathalie C. Zeitouni, Mariam B. Totonchy, Scott W. Fosko, Seaver Lee Soon, Travis W. Blalock, David G. Brodland, Elizabeth M. Billingsley, Jeffrey F. Scott, Brian C. Leach, Desiree Ratner, Carl Washington, C. William Hanke, Clark C. Otley, Nicholas Golda, Rajiv I. Nijhawan, Jerry Brewer, Addison Demer, Frederick Fish, Christopher B. Harmon, John Zitelli, Thomas Knackstedt, Gaurav Singh, Todd Mollet, David R. Carr, John G. Albertini, Brent R. Moody, Michel McDonald, Jeremy S. Bordeaux, Paul R. Massey, Mollie A. MacCormack, Allison Vidimos, Christopher J. Arpey, Sarah T. Arron, Omar A. Ibrahimi, S. Brian Jiang, Christopher J. Miller, Ian A. Maher, Ashley Wysong, Barry Leshin, Glenn D. Goldman, Nour Kibbi, Hao Feng, Lindsey Collins
Journal: Journal of the American Academy of Dermatology (2023)
Clinical advances in TNC delivery vectors and their conjugate agents
Authors: Wujun Chen, Yudong Wu, Jie Wang, Wanpeng Yu, Xin Shen, Kai Zhao, Bing Liang, Xiaokun Hu, Shuai Wang, Hongfei Jiang, Xinlin Liu, Miao Zhang, Xiaohui Xing, Chao Wang, Dongming Xing
Journal: Pharmacology & Therapeutics (2023)
Bona fide dendritic cells are pivotal precursors for osteoclasts
Authors: Antonia Puchner, Elisabeth Simader, Victoria Saferding, Melanie Hofmann, Markus Kieler, Julia Brunner, René Pfeifle, Birgit Niederreiter, Gerhard Krönke, Gernot Schabbauer, Philippe Georgel, Gretchen Diehl, Guenter Steiner, Silvia Hayer, Kurt Redlich, Josef S Smolen, Daniel Aletaha, Stephan Blüml
Journal: Annals of the Rheumatic Diseases (2023)

Osteoclasts (OCs) are myeloid-derived multinucleated cells uniquely able to degrade bone. However, the exact nature of their myeloid precursors is not yet defined.