tbuckley/cabot-search huggingface dataset:
MA11.08 Patient-Reported Outcomes from the Randomized Phase 3 CROWN Study of First-Line Lorlatinib versus Crizotinib in ALK+ NSCLC
Authors: J. Mazieres, L. Iadeluca, A. Shaw, B. Solomon, T. Bauer, F. De Marinis, E. Felip, Y. Goto, D. Kim, T. Mok, A. Reisman, H. Thurm, A. Polli, G. Liu
Journal: Journal of Thoracic Oncology (2021)
Renal Inflammation Induces Salt Sensitivity in Male db/db Mice through Dysregulation of ENaC
Authors: Luciana C. Veiras, Justin Z. Y. Shen, Ellen A. Bernstein, Giovanna C. Regis, DuoYao Cao, Derick Okwan-Duodu, Zakir Khan, David R. Gibb, Fernando P. Dominici, Kenneth E. Bernstein, Jorge F. Giani
Journal: Journal of the American Society of Nephrology (2021)

Significance Statement Men with diabetes have higher incidence of renal disease and hypertension than premenopausal women with diabetes. A mouse model investigated the mechanisms that predispose to salt-sensitive hypertension during diabetes. Male, 34-week-old, diabetic mice display hypertension when exposed to a high-salt diet, whereas females remain normotensive. Hypertension in males was associated with greater renal inflammation and no downregulation of the epithelial sodium channel (ENaC) compared with females. Blocking inflammation prevented the development of salt sensitivity and restored the normal regulation of ENaC in male diabetic mice. These findings indicate that inflammation is a key contributor to the sexual dimorphism associated with diabetic nephropathy. Understanding the mechanisms behind diabetes-associated salt sensitivity is critical to tailor rational therapies in a sex-specific manner. Background Hypertension is considered a major risk factor for the progression of diabetic kidney disease. Type 2 diabetes is associated with increased renal sodium reabsorption and salt-sensitive hypertension. Clinical studies show that men have higher risk than premenopausal women for the development of diabetic kidney disease. However, the renal mechanisms that predispose to salt sensitivity during diabetes and whether sexual dimorphism is associated with these mechanisms remains unknown. Methods Female and male db/db mice exposed to a high-salt diet were used to analyze the progression of diabetic kidney disease and the development of hypertension. Results Male, 34-week-old, db/db mice display hypertension when exposed to a 4-week high-salt treatment, whereas equivalently treated female db/db mice remain normotensive. Salt-sensitive hypertension in male mice was associated with no suppression of the epithelial sodium channel (ENaC) in response to a high-salt diet, despite downregulation of several components of the intrarenal renin-angiotensin system. Male db/db mice show higher levels of proinflammatory cytokines and more immune-cell infiltration in the kidney than do female db/db mice. Blocking inflammation, with either mycophenolate mofetil or by reducing IL-6 levels with a neutralizing anti–IL-6 antibody, prevented the development of salt sensitivity in male db/db mice. Conclusions The inflammatory response observed in male, but not in female, db/db mice induces salt-sensitive hypertension by impairing ENaC downregulation in response to high salt. These data provide a mechanistic explanation for the sexual dimorphism associated with the development of diabetic kidney disease and salt sensitivity.
The International Association for the Study of Lung Cancer Molecular Database Project: Objectives, Challenges, and Opportunities
Authors: Raymond U. Osarogiagbon, Ramon Rami-Porta, Ming Sound Tsao, Luis M. Montuenga, Katherine K. Nishimura, Dorothy J. Giroux, William Travis, Hisao Asamura, Valerie Rusch, David P. Carbone, Fred R. Hirsch
Journal: Journal of Thoracic Oncology (2021)
QIM21-090: The Expanding Role of an Oncology Urgent Care Clinic for the Management of Immune-Related Adverse Events
Authors: Kai-li Liang, Sean A. Tackett, Valerie Peterson, Tricia Patel, Michelle Turner, Sarah Sagorsky, Julie Brahmer, Christine Hann, Patrick Forde, Jarushka Naidoo, Kristen A. Marrone, David Ettinger, Ilene S. Browner, Vincent Lam, Russell K. Hales, Khinh R. Voong, Josephine L. Feliciano
Journal: Journal of the National Comprehensive Cancer Network (2021)
Histone lactylation drives oncogenesis by facilitating m6A reader protein YTHDF2 expression in ocular melanoma
Authors: Jie Yu, Peiwei Chai, Minyue Xie, Shengfang Ge, Jing Ruan, Xianqun Fan, Renbing Jia
Journal: Genome biology (2021)

Histone lactylation, a metabolic stress-related histone modification, plays an important role in the regulation of gene expression during M1 macrophage polarization. However, the role of histone lactylation in tumorigenesis remains unclear.Here, we show histone lactylation is elevated in tumors and is associated with poor prognosis of ocular melanoma. Target correction of aberrant histone lactylation triggers therapeutic efficacy both in vitro and in vivo. Mechanistically, histone lactylation contributes to tumorigenesis by facilitating YTHDF2 expression. Moreover, YTHDF2 recognizes the m6A modified PER1 and TP53 mRNAs and promotes their degradation, which accelerates tumorigenesis of ocular melanoma.We reveal the oncogenic role of histone lactylation, thereby providing novel therapeutic targets for ocular melanoma therapy. We also bridge histone modifications with RNA modifications, which provides novel understanding of epigenetic regulation in tumorigenesis.
Serous business: Delineating the broad spectrum of diseases with subretinal fluid in the macula
Authors: Elon H.C. van Dijk, Camiel J.F. Boon
Journal: Progress in Retinal and Eye Research (2021)

A wide range of ocular diseases can present with serous subretinal fluid in the macula and therefore clinically mimic central serous chorioretinopathy (CSC). In this manuscript, we categorise the diseases and conditions that are part of the differential diagnosis into 12 main pathogenic subgroups: neovascular diseases, vitelliform lesions, inflammatory diseases, ocular tumours, haematological malignancies, paraneoplastic syndromes, genetic diseases, ocular developmental anomalies, medication-related conditions and toxicity-related diseases, rhegmatogenous retinal detachment and tractional retinal detachment, retinal vascular diseases, and miscellaneous diseases. In addition, we describe 2 new clinical pictures associated with macular subretinal fluid accumulation, namely serous maculopathy with absence of retinal pigment epithelium (SMARPE) and serous maculopathy due to aspecific choroidopathy (SMACH). Differentiating between these various diseases and CSC can be challenging, and obtaining the correct diagnosis can have immediate therapeutic and prognostic consequences. Here, we describe the key differential diagnostic features of each disease within this clinical spectrum, including representative case examples. Moreover, we discuss the pathogenesis of each disease in order to facilitate the differentiation from typical CSC.
Unusual Complication of a Right Ventricular Support–Extracorporeal Membrane Oxygenation Cannula
Authors: Erin D. Unger, Ranya N. Sweis, Ankit Bharat
Journal: JAMA Cardiology (2021)

A previously healthy middle-aged man is diagnosed with respiratory failure requiring venovenous extracorporeal membrane oxygenation. Imaging showed abnormalities in the right coronary artery. What would you do next?
P72.03 Tumor Microenvironment Disparity in Multiple Primary Lung Cancers
Authors: M. Izumi, K. Sawa, J. Oyanagi, I. Noura, M. Fukui, K. Ogawa, Y. Matsumoto, Y. Tani, T. Suzumura, T. Watanabe, H. Kaneda, S. Mitsuoka, K. Asai, M. Ohsawa, N. Yamamoto, T. Kawaguchi, Y. Koh
Journal: Journal of Thoracic Oncology (2021)
A Phase I Dose-Escalation Study to Evaluate the Safety and Tolerability of Evofosfamide in Combination with Ipilimumab in Advanced Solid Malignancies
Authors: Aparna Hegde, Priyamvada Jayaprakash, Coline A. Couillault, Sarina Piha-Paul, Daniel Karp, Jordi Rodon, Shubham Pant, Siqing Fu, Ecaterina E. Dumbrava, Timothy A. Yap, Vivek Subbiah, Priya Bhosale, Cristian Coarfa, Jack P. Higgins, Eric T. Williams, Thomas F. Wilson, JoAnn Lim, Funda Meric-Bernstam, Elizabeth Sumner, Hira Zain, Di Nguyen, Ly M. Nguyen, Kimal Rajapakshe, Michael A. Curran, David S. Hong
Journal: Clinical Cancer Research (2021)

Abstract Purpose: As hypoxia can mediate resistance to immunotherapy, we investigated the safety, tolerability, and efficacy of combining evofosfamide, a prodrug that alleviates hypoxia, with ipilimumab, an immune checkpoint inhibitor, in immunologically “cold” cancers, which are intrinsically insensitive to immunotherapy, as well as in “hot/warm” metastatic cancers that are, atypical of such cancers, resistant to immunotherapy. Patients and Methods: In a phase I, 3+3 dose-escalation trial (NCT03098160), evofosfamide (400–640 mg/m2) and ipilimumab (3 mg/kg) were administered in four 3-week cycles. The former was administered on days 1 and 8 of cycles 1–2, while the latter was administered on day 8 of cycles 1–4. Response was assessed using immune-related RECIST and retreatment was allowed, if deemed beneficial, after completion of cycle 4 or at progression. Results: Twenty-two patients were enrolled, of whom 21 were evaluable, encompassing castration-resistant prostate cancer (n = 11), pancreatic cancer (n = 7), immunotherapy-resistant melanoma (n = 2), and human papillomavirus–negative head and neck cancer (n = 1). Drug-related hematologic toxicities, rash, fever, nausea, vomiting, and elevation of liver enzymes were observed in &amp;gt; 10% of patients. The most common drug-related grade 3 adverse event was alanine aminotransferase elevation (33.3%). Two patients discontinued ipilimumab and 4 required evofosfamide deescalation due to toxicity. Of 18 patients with measurable disease at baseline, 3 (16.7%) achieved partial response and 12 (66.7%) achieved stable disease. The best responses were observed at 560 mg/m2 evofosfamide. Preexisting immune gene signatures predicted response to therapy, while hypermetabolic tumors predicted progression. Responders also showed improved peripheral T-cell proliferation and increased intratumoral T-cell infiltration into hypoxia. Conclusions: No new or unexpected safety signals were observed from combining evofosfamide and ipilimumab, and evidence of therapeutic activity was noted.
Response to Comment on Tynjälä et al. Arterial Stiffness Predicts Mortality in Individuals With Type 1 Diabetes. Diabetes Care 2020;43:2266–2271
Authors: Anniina Tynjälä, Carol Forsblom, Valma Harjutsalo, Per-Henrik Groop, Daniel Gordin
Journal: Diabetes Care (2021)

We thank Gonzalez-Clemente et al. (1) for presenting an interesting perspective on arterial stiffness as a potential integrative risk factor for cardiovascular disease (CVD) in type 1 diabetes in the light of their findings in a cross-sectional cohort of 179 individuals (2). They demonstrated a strong correlation between aortic pulse wave velocity (PWV) and a CVD risk prediction score obtained from the Steno Type 1 Risk Engine (ST1RE) (3) and determined cutoff values for PWV as a marker of moderate/high (≥10%) and high (≥20%) risk of CVD in individuals with type 1 diabetes.

In the FinnDiane Study, we recently showed an independent association between augmentation index (AIx), another marker of arterial stiffness, and all-cause mortality as well as a composite cardiovascular and/or diabetes-related cause of death in a prospective analysis of 906 individuals with type 1 diabetes (4). Although the longitudinal data on PWV in our cohort …
MALT1 as a promising target to treat lymphoma and other diseases related to MALT1 anomalies
Authors: Xuewu Liang, YiChun Cao, Chunpu Li, Haolan Yu, Chenghua Yang, Hong Liu
Journal: Medicinal Research Reviews (2021)

Abstract Mucosa‐associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a key adaptor protein that regulates the NF‐κB pathway, in which MALT1 functions as a scaffold protein and protease to trigger downstream signals. The abnormal expression of MALT1 is closely associated with lymphomagenesis and other diseases, including solid tumors and autoimmune diseases. MALT1 is the only protease in the underlying pathogenesis of these diseases, and its proteolytic activity can be pharmacologically regulated. Therefore, MALT1 is a potential and promising target for anti‐lymphoma and other MALT1‐related disease treatments. Currently, the development of MALT1 inhibitors is still in its early stages. This review presents an overview of MALT1, particularly its X‐ray structures and biological functions, and elaborates on the pathogenesis of diseases associated with its dysregulation. We then summarize previously reported MALT1 inhibitors, focusing on their molecular structure, biological activity, structure–activity relationship, and limitations. Finally, we propose future research directions to accelerate the discovery of novel MALT1 inhibitors with clinical applications. Overall, this review provides a comprehensive and systematic overview of MALT1‐related research advances and serves as a theoretical basis for drug discovery and research.
Piggybacking on Niche Adaptation Improves the Maintenance of Multidrug-Resistance Plasmids
Authors: Julia Kloos, João A Gama, Joachim Hegstad, Ørjan Samuelsen, Pål J Johnsen
Journal: Molecular Biology and Evolution (2021)

Abstract The persistence of plasmids in bacterial populations represents a puzzling evolutionary problem with serious clinical implications due to their role in the ongoing antibiotic resistance crisis. Recently, major advancements have been made toward resolving this “plasmid paradox” but mainly in a nonclinical context. Here, we propose an additional explanation for the maintenance of multidrug-resistance plasmids in clinical Escherichia coli strains. After coevolving two multidrug-resistance plasmids encoding resistance to last resort carbapenems with an extraintestinal pathogenic E. coli strain, we observed that chromosomal media adaptive mutations in the global regulatory systems CCR (carbon catabolite repression) and ArcAB (aerobic respiration control) pleiotropically improved the maintenance of both plasmids. Mechanistically, a net downregulation of plasmid gene expression reduced the fitness cost. Our results suggest that global chromosomal transcriptional rewiring during bacterial niche adaptation may facilitate plasmid maintenance.
COVID-19 Postage Stamps—Messages in a Message
Authors: Bertrand Lefrère, Amélie Recoing, Hervé Delacour
Journal: JAMA (2021)

In living memory, no epidemic has generated a medical, scientific, social, and political response as massive, rapid, and global as that of COVID-19, which quickly became a global public health emergency recognized by the World Health Organization in January 2020  The commemoration of major events takes many forms, including the issuing of postage stamps  It is a mass medium used to commemorate events or raise public awareness about topics of wide social interest or influence  Educational and financial messages about infectious diseases on stamps appeared in 1904 when Danish postal clerk Einar Holboll developed the idea of raising money for tuberculosis by adding a surcharge to the sale of a Christmas seal stamp  With the rise of email the popular cultural significance of postage stamps has diminished, but they still remain a way for governments and nongovernment organizations to communicate on a broad scale and to raise funds
Circulating fibrocytes are not disease-specific prognosticators in idiopathic pulmonary fibrosis
Authors: Iain D. Stewart, Henry Nanji, Grazziela Figueredo, William A. Fahy, Toby M. Maher, Antje J. Ask, Shyam Maharaj, Kjetil Ask, Martin Kolb, Gisli R. Jenkins
Journal: European Respiratory Journal (2021)

<b>In people with idiopathic pulmonary fibrosis, circulating fibrocytes ≥2.2% were associated with a greater risk of mortality over a median 3 years of follow-up, but were not associated with disease-related decline in lung function or short-term progression.</b>https://bit.ly/3bWydwQ
P09.55 A Platform to Prospectively Link Real-World Clinico-Genomic, Imaging, and Outcomes Data for Patients With Lung Cancer
Authors: G. Walia, M. Lu, A. Bourla, E. Santos, K. Schulze, M. Cabili, E. Williams, N. Mirkovic, R. Dicecca, S. Lee, B. Fang, L. Schwartzberg, R. Herbst, A. Chiang
Journal: Journal of Thoracic Oncology (2021)
FP04.02 Feasibility of Radiotherapy Planning in the First 50 Patients Recruited to the ADSCaN Clinical Trial
Authors: R. Mir, C. Faivre-Finn, C. Lawless, E. Mccartney, C. Peedell, T. Pope, A. Shaw, R. Simoes, M. Hatton
Journal: Journal of Thoracic Oncology (2021)
On the bright side of PhD life: the perspectives of physiotherapist clinician–scientists
Authors: Carolyn A Emery, Christopher Napier
Journal: British Journal of Sports Medicine (2021)

Numerous cancer histopathology specimens have been collected and digitised as whole slide images over the past few decades. A comprehensive evaluation of the distribution of various cells in a section of tumour tissue can provide valuable information for understanding cancer and making accurate cancer diagnoses. Deep learning is one of the most suitable techniques to achieve these goals; however, the collection of large, unbiased training data has been a barrier to producing accurate segmentation models. Here, we developed a pipeline to generate SegPath, the largest annotation dataset that is over one order of magnitude larger than publicly available annotations, for the segmentation of haematoxylin and eosin (H&amp;E)-stained sections for eight major cell types. The pipeline used H&amp;E-stained sections that were destained and subsequently immunofluorescence-stained with carefully selected antibodies. The results showed that SegPath is comparable to, or significantly outperforms, conventional pathologist annotations. Moreover, we revealed that annotations by pathologists are biased toward typical morphologies; however, the model trained on the SegPath dataset can overcome this limitation. Our approach and SegPath will accelerate high-throughput computational pathology.
Correction: Hypoparathyroidism
Authors: Michael Mannstadt, John P. Bilezikian, Rajesh V. Thakker, Fadil M. Hannan, Bart L. Clarke, Lars Rejnmark, Deborah M. Mitchell, Tamara J. Vokes, Karen K. Winer, Dolores M. Shoback
Journal: Nature Reviews Disease Primers (2017)
Unique diagnostic signatures of concussion in the saliva of male athletes: the Study of Concussion in Rugby Union through MicroRNAs (SCRUM)
Authors: Valentina Di Pietro, Patrick O'Halloran, Callum N Watson, Ghazala Begum, Animesh Acharjee, Kamal M Yakoub, Conor Bentley, David J Davies, Paolo Iliceto, Gabriella Candilera, David K Menon, Matthew J Cross, Keith A Stokes, Simon PT Kemp, Antonio Belli
Journal: British Journal of Sports Medicine (2021)

Objective To investigate the role of salivary small non-coding RNAs (sncRNAs) in the diagnosis of sport-related concussion. Methods Saliva was obtained from male professional players in the top two tiers of England’s elite rugby union competition across two seasons (2017–2019). Samples were collected preseason from 1028 players, and during standardised head injury assessments (HIAs) at three time points (in-game, post-game, and 36–48 hours post-game) from 156 of these. Samples were also collected from controls (102 uninjured players and 66 players sustaining a musculoskeletal injury). Diagnostic sncRNAs were identified with next generation sequencing and validated using quantitative PCR in 702 samples. A predictive logistic regression model was built on 2017–2018 data (training dataset) and prospectively validated the following season (test dataset). Results The HIA process confirmed concussion in 106 players (HIA+) and excluded this in 50 (HIA−). 32 sncRNAs were significantly differentially expressed across these two groups, with let-7f-5p showing the highest area under the curve (AUC) at 36–48 hours. Additionally, a combined panel of 14 sncRNAs (let-7a-5p, miR-143-3p, miR-103a-3p, miR-34b-3p, RNU6-7, RNU6-45, Snora57, snoU13.120, tRNA18Arg-CCT, U6-168, U6-428, U6-1249, Uco22cjg1,YRNA_255) could differentiate concussed subjects from all other groups, including players who were HIA− and controls, immediately after the game (AUC 0.91, 95% CI 0.81 to 1) and 36–48 hours later (AUC 0.94, 95% CI 0.86 to 1). When prospectively tested, the panel confirmed high predictive accuracy (AUC 0.96, 95% CI 0.92 to 1 post-game and AUC 0.93, 95% CI 0.86 to 1 at 36–48 hours). Conclusions SCRUM, a large prospective observational study of non-invasive concussion biomarkers, has identified unique signatures of concussion in saliva of male athletes diagnosed with concussion.
P05.02 International Delphi Consensus on Radical Thoracic Re-Irradiation for Non-Small Cell Lung Cancer (NSCLC)
Authors: R. Rulach, M. Guckenberger, D. De Ruysscher, D. Palma, A. Louie, D. Ball, G. Hanna, S. Siva, A. Salem, G. Videtic, M. Dahele, D. Moghanaki, K. Franks, S. Harrow
Journal: Journal of Thoracic Oncology (2021)
Low expression of TRAF3IP2-AS1 promotes progression of NONO-TFE3 translocation renal cell carcinoma by stimulating N6-methyladenosine of PARP1 mRNA and downregulating PTEN
Authors: Lei Yang, Yi Chen, Ning Liu, QianCheng Shi, Xiaodong Han, Weidong Gan, Dongmei Li
Journal: Journal of Hematology & Oncology (2021)

Abstract Background NONO-TFE3 translocation renal cell carcinoma ( NONO-TFE3 tRCC) is one subtype of RCCs associated with Xp11.2 translocation/TFE3 gene fusions RCC (Xp11.2 tRCCs). Long non-coding RNA (lncRNA) has attracted great attention in cancer research. The function and mechanisms of TRAF3IP2 antisense RNA 1 (TRAF3IP2-AS1), a natural antisense lncRNA, in NONO-TFE3 tRCC remain poorly understood. Methods FISH and qRT-PCR were undertaken to study the expression, localization and clinical significance of TRAF3IP2-AS1 in Xp11.2 tRCC tissues and cells. The functions of TRAF3IP2-AS1 in tRCC were investigated by proliferation analysis, EdU staining, colony and sphere formation assay, Transwell assay and apoptosis analysis. The regulatory mechanisms among TRAF3IP2-AS1, PARP1, PTEN and miR-200a-3p/153-3p/141-3p were investigated by luciferase assay, RNA immunoprecipitation, Western blot and immunohistochemistry. Results The expression of TRAF3IP2-AS1 was suppressed by NONO-TFE3 fusion in NONO-TFE3 tRCC tissues and cells. Overexpression of TRAF3IP2-AS1 inhibited the proliferation, migration and invasion of UOK109 cells which were derived from cancer tissue of patient with NONO-TFE3 tRCC. Mechanistic studies revealed that TRAF3IP2-AS1 accelerated the decay of PARP1 mRNA by direct binding and recruitment of N 6 -methyladenosie methyltransferase complex. Meanwhile, TRAF3IP2-AS1 competitively bound to miR-200a-3p/153-3p/141-3p and prevented those from decreasing the level of PTEN. Conclusions TRAF3IP2-AS1 functions as a tumor suppressor in NONO-TFE3 tRCC progression and may serve as a novel target for NONO-TFE3 tRCC therapy. TRAF3IP2-AS1 expression has the potential to serve as a novel diagnostic and prognostic biomarker for NONO-TFE3 tRCC detection.
Gene replacement of α-globin with β-globin restores hemoglobin balance in β-thalassemia-derived hematopoietic stem and progenitor cells
Authors: M. Kyle Cromer, Joab Camarena, Renata M. Martin, Benjamin J. Lesch, Christopher A. Vakulskas, Nicole M. Bode, Gavin Kurgan, Michael A. Collingwood, Garrett R. Rettig, Mark A. Behlke, Viktor T. Lemgart, Yankai Zhang, Ankush Goyal, Feifei Zhao, Ezequiel Ponce, Waracharee Srifa, Rasmus O. Bak, Naoya Uchida, Ravindra Majeti, Vivien A. Sheehan, John F. Tisdale, Daniel P. Dever, Matthew H. Porteus
Journal: Nature Medicine (2021)
Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies
Authors: Delphine Planas, Timothée Bruel, Ludivine Grzelak, Florence Guivel-Benhassine, Isabelle Staropoli, Françoise Porrot, Cyril Planchais, Julian Buchrieser, Maaran Michael Rajah, Elodie Bishop, Mélanie Albert, Flora Donati, Matthieu Prot, Sylvie Behillil, Vincent Enouf, Marianne Maquart, Mounira Smati-Lafarge, Emmanuelle Varon, Frédérique Schortgen, Layla Yahyaoui, Maria Gonzalez, Jérôme De Sèze, Hélène Péré, David Veyer, Aymeric Sève, Etienne Simon-Lorière, Samira Fafi-Kremer, Karl Stefic, Hugo Mouquet, Laurent Hocqueloux, Sylvie van der Werf, Thierry Prazuck, Olivier Schwartz
Journal: Nature Medicine (2021)