tbuckley/cabot-search huggingface dataset:
Corneal in vivo confocal microscopy to detect belantamab mafodotin-induced ocular toxicity early and adjust the dose accordingly: a case report
Authors: Kevin Marquant, Anne Quinquenel, Carl Arndt, Alexandre Denoyer
Journal: Journal of Hematology & Oncology (2021)

Abstract Background New targeted antibody–drug conjugates (ADCs) against multiple myeloma are known to induce adverse effects that may lead to treatment discontinuation. Preclinical studies reported early severe ocular damage related to the use of belantamab mafodotin (belamaf), including ocular surface inflammation, severe dry eye, and a specific toxicity to the cornea, namely microcystic keratopathy. While belamaf-induced ocular changes have not been prospectively studied, a better understanding of mechanisms involved as well as kinetics may aid in anticipating dose adjustment rather than stopping the treatment once clinical ocular damage is too severe. Case presentation A 61-year-old woman scheduled for belamaf as a fifth-line treatment against multiple myeloma was prospectively included. Clinical examinations were performed before and every 3 weeks afterward, together with in vivo confocal microscopy (IVCM) of the cornea. Visual acuity, symptoms, slit-lamp examination, and ultrastructural changes of the cornea were recorded according to the received dose of belamaf. More precisely, kinetics, shape, density, and location of the toxic corneal lesions have been followed and analyzed using IVCM. Also, specific lesions at the sub-basal nerve plexus layer were detected and characterized for the first time. This advanced approach allowed a better understanding of the belamaf-induced toxicity, further balancing the dose to maintain good vision and eye health while continuing the treatment. Conclusions Systematic ultrastructural analysis and follow-up of the corneal state during ADCs treatment for multiple myeloma may open new avenues in the therapeutic approach. Early preclinical detection of ocular damage may accurately contribute to finding the correct dose for each patient and not stopping the treatment due to severe ocular adverse effects.
LBA48 DUBLIN-3 (BPI-2358-103): A global phase (Ph) III trial with the plinabulin/docetaxel (Plin/Doc) combination vs. Doc in 2nd/3rd Line NSCLC patients (pts) with EGFR-wild type (wt) progressing on a prior platinum-based regimen
Authors: B. Han, Y-K. Shi, T. Feinstein, D. Feng, D. Mitchell, Y. Lelorier, L. Du, L. Huang, R. Mohanlal, Y. Sun
Journal: Annals of Oncology (2021)
Retinal pigment epithelium 65 kDa protein (RPE65): An update
Authors: Philip D. Kiser
Journal: Progress in Retinal and Eye Research (2021)

Vertebrate vision critically depends on an 11-cis-retinoid renewal system known as the visual cycle. At the heart of this metabolic pathway is an enzyme known as retinal pigment epithelium 65 kDa protein (RPE65), which catalyzes an unusual, possibly biochemically unique, reaction consisting of a coupled all-trans-retinyl ester hydrolysis and alkene geometric isomerization to produce 11-cis-retinol. Early work on this isomerohydrolase demonstrated its membership to the carotenoid cleavage dioxygenase superfamily and its essentiality for 11-cis-retinal production in the vertebrate retina. Three independent studies published in 2005 established RPE65 as the actual isomerohydrolase instead of a retinoid-binding protein as previously believed. Since the last devoted review of RPE65 enzymology appeared in this journal, major advances have been made in a number of areas including our understanding of the mechanistic details of RPE65 isomerohydrolase activity, its phylogenetic origins, the relationship of its membrane binding affinity to its catalytic activity, its role in visual chromophore production for rods and cones, its modulation by macromolecules and small molecules, and the involvement of RPE65 mutations in the development of retinal diseases. In this article, I will review these areas of progress with the goal of integrating results from the varied experimental approaches to provide a comprehensive picture of RPE65 biochemistry. Key outstanding questions that may prove to be fruitful future research pursuits will also be highlighted.
6MO PCSK9 inhibitor evolocumab reduces cardiotoxicity and inflammation induced by doxorubicin-trastuzumab sequential treatment through MyD88/NF-kB/mTORC1 pathways
Authors: V. Quagliariello, S. Buccolo, M. Iovine, F. Cerrone, A. Paccone, N. Maurea
Journal: Annals of Oncology (2021)
Abstract 15241: Sex Difference in the Associations of Omega-6 Polyunsaturated Fatty Acids With Mortality in Patients With Stable Coronary Heart Disease: A Subanalysis of the ANOX Study
Authors: Hiromichi Wada, Masahiro Suzuki, Morihiro Matsuda, Yoichi Ajiro, Tsuyoshi Shinozaki, Satoru Sakagami, Kazuya Yonezawa, Masatoshi Shimizu, Junichi Funada, Takashi Takenaka, Yukiko Morita, Toshihiro Nakamura, Kazuteru Fujimoto, Hiromi Matsubara, Toru Kato, Takashi Unoki, Daisuke Takagi, Shuichi Ura, Kyohma Wada, Moritake Iguchi, Nobutoyo Masunaga, Mitsuru Ishii, Hajime Yamakage, Akira Shimatsu, Kazuhiko Kotani, Noriko Satoh-Asahara, Mitsuru Abe, Masaharu Akao, Koji Hasegawa
Journal: Circulation (2018)

Background: Omega-6 polyunsaturated fatty acids (PUFAs) are essential nutrients. However, the relationships between omega-6 PUFAs and the risk of mortality or cardiovascular events in patients with...
Spousal Concordance in the Development of Functional Limitations Among Married Adults in China
Authors: Jingwen Wang, Qian Wang, Xiang-Yu Hou, Sunan Chen, Zhen Guo, Wei Du, Lijun Fan
Journal: JAMA Network Open (2021)

Functional limitation is increasingly common as people age and is often associated with negative consequences. Evidence of the dynamics of functional limitation within couples in China is still inadequate.To examine whether functional limitation was associated within middle-aged and older couples and to explore sex differences in spousal associations.In this nationwide, population-based cohort study performed from January 1, 2011, to December 31, 2018, participants were selected using multistage probability sampling, and 5207 community-dwelling couples (10 414 individuals) 45 years or older were included in the nationally representative China Health and Retirement Longitudinal Study. Data analysis was performed from January 1 to February 28, 2021.The exposure variable was the presence of functional limitation in spouses. Functional limitation was measured by the activities of daily living (ADLs) and instrumental activities‎ of daily ‎living (IADLs) scales and was defined as having difficulty in independently performing at least 1 ADL or IADL item.The main outcome was functional limitation in index participants. Multivariable logistic regression with generalized estimating equations was used to estimate the reciprocal association of functional limitation within couples over time.A total of 5207 married, different-sex couples (mean [SD] age, 59.1 [8.8] years for husbands and 57.0 [8.2] years for wives) were included in the study. For husbands, the number (percentage) of participants classified with baseline functional limitation was 1140 (21.9%), the number (percentage) with ADL limitation was 684 (13.1%), and the number (percentage) with IADL limitation was 834 (16.0%). For wives, the number (percentage) of participants classified with baseline functional limitation was 1502 (28.8%), the number (percentage) with ADL limitation was 887 (17.0%), and the number (percentage) with IADL limitation was 1183 (22.7%). Longitudinal results demonstrated an association in spouses developing functional limitation (adjusted odds ratio [OR], 2.55; 95% CI, 2.41-2.69; P < .001), ADL limitation (adjusted OR, 2.26; 95% CI, 2.11-2.41; P < .001), and IADL limitation (adjusted OR, 2.58; 95% CI, 2.43-2.73; P < .001). Subgroup analyses by sex revealed similar patterns of spousal health concordance in terms of all studied outcomes, indicating no sex specificity.This population-based cohort study suggests that among Chinese middle-aged and older couples there is significant concordance in the development of functional limitation. This study of spousal functional ability from a dyadic perspective may help in the understanding of health risks within a wider familial context and offers novel insights for prioritizing policy focus from individual centered to couple based.
721O Relacorilant, a selective glucocorticoid receptor modulator, in combination with nab-paclitaxel improves progression-free survival in patients with recurrent platinum-resistant ovarian cancer: A 3-arm, randomized, open-label, phase II study
Authors: N. Colombo, D.D. Nguyen, G.F. Fleming, R.N. Grisham, D. Lorusso, T. Van Gorp, A. Oaknin, H.I. Pashova, A. Grauer
Journal: Annals of Oncology (2021)
Real-world safety data for the Pfizer BNT162b2 SARS-CoV-2 vaccine: historical cohort study
Authors: David Shasha, Ronen Bareket, Fabienne Hershkowitz Sikron, Omer Gertel, Judith Tsamir, David Dvir, David Mossinson, Anthony D. Heymann, Galia Zacay
Journal: Clinical Microbiology and Infection (2021)

ObjectiveThe Pfizer BNT162b2 vaccine showed a reassuring safety profile in clinical trials, but real-world data are scarce. Bell's palsy, herpes zoster, Guillain–Barré syndrome (GBS) and other neurological complaints in proximity to vaccination have received special public attention. We compared their rates among vaccinated and unvaccinated individuals.MethodsIndividuals ≥16 years vaccinated with at least one dose of BNT162b2 were eligible for this historical cohort study in a health maintenance organization insuring 1.2 million citizens. Each vaccinee was matched to a non-vaccinated control by sex, age, population sector (general Jewish, Arab, ultra-orthodox Jewish) and comorbidities. Diagnosis of Covid-19 before or after vaccination was an exclusion criterion. The outcome was a diagnosis of Bell's palsy, GBS, herpes zoster or symptoms of numbness or tingling, coded in the visit diagnosis field using ICD-9 codes. Diagnoses of Bell's palsy and GBS were verified by individual file review.ResultsOf 406 148 individuals vaccinated during the study period, 394 609 (97.2%) were eligible (11 539 excluded). A total of 233 159 (59.1%) were matched with unvaccinated controls. Mean follow was 43 ± 15.14 days. In vaccinated and unvaccinated individuals there were 23 versus 24 cases of Bell's palsy (RR 0.96, CI 0.54–1.70), one versus zero cases of GBS, 151 versus 141 cases of herpes zoster (RR 1.07, CI 0.85–1.35) and 605 versus 497 cases of numbness or tingling (RR 1.22, CI 1.08–1.37), respectively.DiscussionNo association was found between vaccination, Bell's palsy, herpes zoster or GBS. Symptoms of numbness or tingling were more common among vaccinees. This study adds reassuring data regarding the safety of the BNT162b2 vaccine.
Biologically relevant transfer learning improves transcription factor binding prediction
Authors: Gherman Novakovsky, Manu Saraswat, Oriol Fornes, Sara Mostafavi, Wyeth W. Wasserman
Journal: Genome biology (2021)

Abstract Background Deep learning has proven to be a powerful technique for transcription factor (TF) binding prediction but requires large training datasets. Transfer learning can reduce the amount of data required for deep learning, while improving overall model performance, compared to training a separate model for each new task. Results We assess a transfer learning strategy for TF binding prediction consisting of a pre-training step, wherein we train a multi-task model with multiple TFs, and a fine-tuning step, wherein we initialize single-task models for individual TFs with the weights learned by the multi-task model, after which the single-task models are trained at a lower learning rate. We corroborate that transfer learning improves model performance, especially if in the pre-training step the multi-task model is trained with biologically relevant TFs. We show the effectiveness of transfer learning for TFs with ~ 500 ChIP-seq peak regions. Using model interpretation techniques, we demonstrate that the features learned in the pre-training step are refined in the fine-tuning step to resemble the binding motif of the target TF (i.e., the recipient of transfer learning in the fine-tuning step). Moreover, pre-training with biologically relevant TFs allows single-task models in the fine-tuning step to learn useful features other than the motif of the target TF. Conclusions Our results confirm that transfer learning is a powerful technique for TF binding prediction.
1321P Real-world treatments and clinical outcomes in advanced NSCLC without actionable mutations after introduction of immunotherapy (IO) in Japan
Authors: H. Nokihara, M.L. Santorelli, K. Taniguchi, T. Kamitani, M. Irisawa, K. Kanda, M. Abe, T. Burke, Y. Goto
Journal: Annals of Oncology (2021)
462P Heterogeneity of mismatch repair status between primary tumors and matched metastases in metastatic colorectal cancer
Authors: D. Tougeron, G. Tachon, D. Sefrioui, S. Messina, E. Frouin, M-L. Auriault, R. Chautard, A. Zaanan, M. Jaffrelot, C. de la Fouchardiere, T. Aparicio, R. Coriat, J. Godet, V. Randrian, J.C. Sabourin, R. Guimbaud, E. Standley, T. Lecomte, L. Karayan Tapon, C. Evrard
Journal: Annals of Oncology (2021)
Re: Vicenç Ruiz de Porras, Xieng C. Wang, Luis Palomero, et al. Taxane-induced Attenuation of the CXCR2/BCL-2 Axis Sensitizes Prostate Cancer to Platinum-based Treatment. Eur Urol 2021;79:722–33
Authors: Shangqing Ren, Bo Yang, Dong Wang
Journal: European Urology (2021)
1194MO Canakinumab (CAN) + docetaxel (DTX) for the second- or third-line (2/3L) treatment of advanced non-small cell lung cancer (NSCLC): CANOPY-2 phase III results
Authors: L. Paz-Ares, Y. Goto, W.D.T. Lim, B. Halmos, B.C. Cho, M. Cobo Dols, J.L. Gonzalez-Larriba, C. Zhou, I. Demedts, A. Atmaca, S. Baka, B.P. Mookerjee, S. Portella, Z. Zhu, B. Dharan, M. Reck
Journal: Annals of Oncology (2021)
1623P Phase I clinical trials (CT) forge on despite COVID-19
Authors: M.J. Lostes Bardaji, E. Aliende, M. Moreno, H.K. Oberoi, I. Braña, O. Saavedra, M. Vieito Villar, G. Alonso, V. Galvao, N. Carballo, M. Beltran, P. Rovira, I. Cidoncha, C. Saura Manich, T. Macarulla Mercade, A. Oaknin, J. Carles Galceran, E. Felip, E. Garralda, S. Perez Pujol
Journal: Annals of Oncology (2021)
Diabetes Microvascular Disease Diagnosis and Treatment After High-Deductible Health Plan Enrollment
Authors: J. Frank Wharam, Jamie Wallace, Stephanie Argetsinger, Fang Zhang, Christine Y. Lu, Tomasz P. Stryjewski, Dennis Ross-Degnan, Joseph P. Newhouse
Journal: Diabetes Care (2021)

The Affordable Care Act mandates that primary preventive services have no out-of-pocket costs but does not exempt secondary prevention from out-of-pocket costs. Most commercially insured patients with diabetes have high-deductible health plans (HDHPs) that subject key microvascular disease-related services to high out-of-pocket costs. Brief treatment delays can significantly worsen microvascular disease outcomes.
652O Dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) or gemcitabine and cisplatin (GC) as perioperative chemotherapy for patients with muscle-invasive bladder cancer (MIBC): Results of the GETUG/AFU VESPER V05 phase III trial
Authors: C. Pfister, G. Gravis, A. Flechon, C.M. Chevreau, H. Mahammedi, B. Laguerre, A. Guillot, F. Joly, M. Soulie, Y. Allory, V. Harter, S. Culine
Journal: Annals of Oncology (2021)
931TiP Malnutrition based on the GLIM criteria and the response to concurrent chemoradiotherapy in patients with squamous cell carcinoma of the head and neck
Authors: M.J.P. de Sousa, M. Teixeira, C. Bento, I. Zorrinho, J. Correia Magalhães, R. Basto, C. Caramujo, A.R. Garcia, L. Khouri, I. Pires, F. Branquinho, A.R. Cardoso, A.P. Leite, G. Sousa
Journal: Annals of Oncology (2021)
The real-world <i>BRCA1/2</i> germline mutations in Chinese solid tumors.
Authors: Jian Chen, Zhaohua Gong, Dengjun Sun, Shujie Song, Weiwei Zhang, Ningning Luo, Qin Zhang, Guanghua Lu, Yingxue Qi, Yaqing Wu
Journal: Journal of Clinical Oncology (2021)

e22500 Background: Breast cancer susceptibility genes BRCA1 and 2 are tumor suppressor genes and they play an important role in DNA damage response and repair during homologous recombination. Hereditary breast and ovarian cancer (HBOC) syndrome is an autosomal dominant disease due to BRCA1 and 2 germline mutation. Germline mutations of BRCA1 and 2 genes significantly increase the risk of developing breast cancer, ovarian cancer, prostate cancer and a broad range of cancers. PARP inhibitor (PARPi) monotherapy and combinations have shown promising efficacy against a variety of cancer types with BRCA mutations. Nevertheless, the knowledge of incidence of BRCA1 and 2 germline mutations in solid tumor remains poorly understood. Herein, next generation sequencing of 539-gene profiling was performed to explore the incidence of BRCA1 and 2 germline mutations in Chinese solid tumors. Methods: We retrospectively analyzed the BRCA1 and BRCA2 germline mutations from a comprehensive 539-gene profiling of 8535 Chinese patients with pan-cancer. 539-gene profiling contains the somatic mutations in tumor tissue or blood ctDNA and the germline mutations in blood leukocyte. We screened out the pathogenic and likely pathogenic mutations in BRCA germline mutations, and calculated the mutation frequency and the median age in every cancer type. Results: In 8535 patients with pan-cancer, 110 patients were found pathogenic or likely pathogenic germline mutations in BRCA gene and the mutation frequency was 1.29%, of which 40 BRCA1 mutations and 70 BRCA2 mutations were found in patients, respectively. The total median age was 58.15. Eliminated a few types of cancers that had a smaller number (less than 50), the higher frequency of mutations contained ovarian cancer (14.78%, media age 58), prostatic cancer (6%, media age 58.33), breast cancer (5.2% media age 57.33). The details of the top 8 cancer types with mutation frequency and media age were shown in Table. Conclusions: This was the first report of the incidence of BRCA1 and 2 germline mutations in Chinese solid tumors, which expanded the understanding of BRCA1/2 and provided a direction for clinical trial design of PARPi monotherapy and combinations.[Table: see text]
Environmental risk factors and cardiovascular diseases: a comprehensive expert review
Authors: Thomas Münzel, Omar Hahad, Mette Sørensen, Jos Lelieveld, Georg Daniel Duerr, Mark Nieuwenhuijsen, Andreas Daiber
Journal: Cardiovascular Research (2021)

Abstract Non-communicable diseases (NCDs) are fatal for more than 38 million people each year and are thus the main contributors to the global burden of disease accounting for 70% of mortality. The majority of these deaths are caused by cardiovascular disease (CVD). The risk of NCDs is strongly associated with exposure to environmental stressors such as pollutants in the air, noise exposure, artificial light at night, and climate change, including heat extremes, desert storms, and wildfires. In addition to the traditional risk factors for CVD such as diabetes, arterial hypertension, smoking, hypercholesterolaemia, and genetic predisposition, there is a growing body of evidence showing that physicochemical factors in the environment contribute significantly to the high NCD numbers. Furthermore, urbanization is associated with accumulation and intensification of these stressors. This comprehensive expert review will summarize the epidemiology and pathophysiology of environmental stressors with a focus on cardiovascular NCDs. We will also discuss solutions and mitigation measures to lower the impact of environmental risk factors with focus on CVD.
723MO Tisotumab vedotin (TV) + carboplatin (Carbo) in first-line (1L) or + pembrolizumab (Pembro) in previously treated (2L/3L) recurrent or metastatic cervical cancer (r/mCC): Interim results of ENGOT-Cx8/GOG-3024/innovaTV 205 study
Authors: I.B. Vergote, B.J. Monk, R.E. O’Cearbhaill, A.M. Westermann, S. Banerjee, D.C. Collins, M.R. Mirza, D. O'Malley, C. Gennigens, S. Pignata, B. Melichar, A. Sadozye, F. Forget, K.S. Tewari, E. Gort, I. Soumaoro, C. Mondrup Andreassen, L.V. Nicacio, E. Van Nieuwenhuysen, D. Lorusso
Journal: Annals of Oncology (2021)
Generation of neutrophil extracellular traps in patients with acute liver failure is associated with poor outcome
Authors: Fien A. von Meijenfeldt, R. Todd Stravitz, Jingwen Zhang, Jelle Adelmeijer, Yoh Zen, Valerie Durkalski, William M. Lee, Ton Lisman
Journal: Hepatology (2021)

Acute liver failure (ALF) is characterized by significant changes in the hemostatic system and by systemic inflammation. The formation of neutrophil extracellular traps (NETs), in which an activated neutrophil expels its DNA, histones, and granular enzymes, such as myeloperoxidase (MPO), has been associated with immune-mediated and thrombotic diseases. We hypothesized that formation of NETs in patients with ALF contributes to progression of disease.A total of 676 patients with ALF (international normalized ratio [INR], ≥1.5) or severe acute liver injury (ALI; INR, ≥2.0) were recruited from the U.S. ALF Study Group Registry between 2011 and 2018, of whom 308 patients (45.6%) had acetaminophen-induced ALF. Up to 21 days after admission, 483 patients (71.5%) survived without liver transplantation (LT). Levels of cell-free DNA (cfDNA) and the specific NET marker MPO-DNA complexes were measured in plasma samples obtained on admission and compared to levels in healthy controls. In addition, liver tissue obtained at transplantation of 20 ALF patients was stained for NETs. Levels of cfDNA were 7.1-fold, and MPO-DNA complexes 2.5-fold, higher in patients with ALF compared to healthy controls. cfDNA levels were not associated with 21-day transplant-free survival, but were higher in those patients with more-severe disease on admission, as reflected by various laboratory and clinical parameters. MPO-DNA levels were 30% higher in patients with ALF who died or required urgent LT. Liver tissue of ALF patients stained positive for NETs in 12 of 18 evaluable patients.Here, we provide evidence for NET formation in patients with ALF. Elevated plasma levels of MPO-DNA complexes in patients with ALF were associated with poor outcome, which suggests that NET formation contributes to disease progression.