tbuckley/cabot-search huggingface dataset:
Tumor-agnostic transcriptome-based classifier identifies spatial infiltration patterns of CD8+T cells in the tumor microenvironment and predicts clinical outcome in early-phase and late-phase clinical trials
Authors: Andreas Roller, Iakov I Davydov, Petra C Schwalie, Martha L Serrano-Serrano, Astrid Heller, Nicolas Staedler, Cláudia S Ferreira, Gabriele Dietmann, Irina Klaman, Alberto Valdeolivas, Konstanty Korski, Michael A Cannarile
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background The immune status of a patient’s tumor microenvironment (TME) may guide therapeutic interventions with cancer immunotherapy and help identify potential resistance mechanisms. Currently, patients’ immune status is mostly classified based on CD8+tumor-infiltrating lymphocytes. An unmet need exists for comparable and reliable precision immunophenotyping tools that would facilitate clinical treatment-relevant decision-making and the understanding of how to overcome resistance mechanisms. Methods We systematically analyzed the CD8 immunophenotype of 2023 patients from 14 phase I–III clinical trials using immunohistochemistry (IHC) and additionally profiled gene expression by RNA-sequencing (RNA-seq). CD8 immunophenotypes were classified by pathologists into CD8-desert, CD8-excluded or CD8-inflamed tumors using CD8 IHC staining in epithelial and stromal areas of the tumor. Using regularized logistic regression, we developed an RNA-seq-based classifier as a surrogate to the IHC-based spatial classification of CD8+tumor-infiltrating lymphocytes in the TME. Results The CD8 immunophenotype and associated gene expression patterns varied across indications as well as across primary and metastatic lesions. Melanoma and kidney cancers were among the strongest inflamed indications, while CD8-desert phenotypes were most abundant in liver metastases across all tumor types. A good correspondence between the transcriptome and the IHC-based evaluation enabled us to develop a 92-gene classifier that accurately predicted the IHC-based CD8 immunophenotype in primary and metastatic samples (area under the curve inflamed=0.846; excluded=0.712; desert=0.855). The newly developed classifier was prognostic in The Cancer Genome Atlas (TCGA) data and predictive in lung cancer: patients with predicted CD8-inflamed tumors showed prolonged overall survival (OS) versus patients with CD8-desert tumors (HR 0.88; 95% CI 0.80 to 0.97) across TCGA, and longer OS on immune checkpoint inhibitor administration (phase III OAK study) in non-small-cell lung cancer (HR 0.75; 95% CI 0.58 to 0.97). Conclusions We provide a new precision immunophenotyping tool based on gene expression that reflects the spatial infiltration patterns of CD8+ lymphocytes in tumors. The classifier enables multiplex analyses and is easy to apply for retrospective, reverse translation approaches as well as for prospective patient enrichment to optimize the response to cancer immunotherapy.
Correspondence on 'Cardiovascular toxicities associated with bispecific T-cell engager therapy' by Sayed<i>et al</i>
Authors: Yoshihiro Noguchi, Miao Yan, Tomoya Tachi, Tomoaki Yoshimura
Journal: Journal for ImmunoTherapy of Cancer (2024)

We read with great interest the research article by Sayed et al .[1][1] Although it is very useful to understand the utilization of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) for cardiovascular toxicity associated with bispecific T-cell engagers (BTEs), there
Response to: Correspondence on 'Cardiovascular toxicities associated with bispecific T-cell engager therapy' by Noguchi<i>et al</i>
Authors: Ahmed Sayed, Malak Munir, Michael Poliner, Sana Sughra, Narendranath Epperla, Daniel Addison
Journal: Journal for ImmunoTherapy of Cancer (2024)

We would like to thank Dr Noguchi and his colleagues for their comments regarding our paper Cardiovascular toxicities associated with bispecific T-cell engager therapy . We agree that our analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS) database is subject to
Malignant Hypertension:A Systemic Cardiovascular Disease
Authors: Romain Boulestreau, Mateusz Śpiewak, Andrzej Januszewicz, Reinhold Kreutz, Tomasz J. Guzik, Magdalena Januszewicz, Maria Lorenza Muiesan, Alexandre Persu, Pantelis Sarafidis, Massimo Volpe, Anna Zaleska-Żmijewska, Bert-Jan H. van den Born, Franz H. Messerli
Journal: Journal of the American College of Cardiology (2024)
Evidence Supporting Criteria for Periprocedural Myocardial Infarction in Patients Undergoing Elective Percutaneous Coronary Intervention
Authors: Raffaele Piccolo, Domenico Angellotti, Fiorenzo Simonetti, Attilio Leone, Marisa Avvedimento, Luca Bardi, Giuliana Fortunato, Carmen Anna Maria Spaccarotella, Anna Franzone, Giovanni Esposito
Journal: Journal of the American College of Cardiology (2024)
Permanent Pacemaker Implantation and Long-Term Outcomes of Patients Undergoing Concomitant Mitral and Tricuspid Valve Surgery
Authors: Alexander Iribarne, Sundos H. Alabbadi, Alan J. Moskowitz, Gorav Ailawadi, Vinay Badhwar, Marc Gillinov, Vinod H. Thourani, Keith B. Allen, Michael E. Halkos, Nirav C. Patel, Robert S. Kramer, David D’Alessandro, Samantha Raymond, Helena L. Chang, Lopa Gupta, Kathleen N. Fenton, Wendy C. Taddei-Peters, Michael W.A. Chu, Volkmar Falk, Joanna Chikwe, Neal Jeffries, Emilia Bagiella, Patrick T. O’Gara, Annetine C. Gelijns, Natalia N. Egorova
Journal: Journal of the American College of Cardiology (2024)
Limb Outcomes With Ticagrelor Plus Aspirin in Patients With Diabetes Mellitus and Atherosclerosis
Authors: Marc P. Bonaca, Deepak L. Bhatt, Tabassome Simon, Kim Michael Fox, Shamir Mehta, Robert A. Harrington, Lawrence A. Leiter, Warren H. Capell, Claes Held, Anders Himmelmann, Wilhelm Ridderstråle, Jersey Chen, Jane J. Lee, Yang Song, Marielle Andersson, Jayne Prats, Mikhail Kosiborod, Darren K. McGuire, Ph. Gabriel Steg
Journal: Journal of the American College of Cardiology (2024)
Cardiovascular Disease in Hispanic Women
Authors: Odayme Quesada, Daniela Crousillat, Fatima Rodriguez, Katia Bravo-Jaimes, Joan Briller, Modele O. Ogunniyi, Deirdre J. Mattina, Niti R. Aggarwal, Carlos J. Rodriguez, Glaucia Maria Moraes De Oliveira, Gladys Velarde
Journal: Journal of the American College of Cardiology (2024)
Penetrance of Dilated Cardiomyopathy in Genotype-Positive Relatives
Authors: Eva Cabrera-Romero, Juan Pablo Ochoa, Roberto Barriales-Villa, Francisco José Bermúdez-Jiménez, Vicente Climent-Payá, Esther Zorio, María Angeles Espinosa, María Gallego-Delgado, Marina Navarro-Peñalver, Xabier Arana-Achaga, Jesús Piqueras-Flores, Victoria Espejo-Bares, José F. Rodríguez-Palomares, Gemma Lacuey-Lecumberri, Javier López, Coloma Tiron, María Luisa Peña-Peña, Jose M. García-Pinilla, Rebeca Lorca, Tomas Ripoll-Vera, Carles Díez-López, María Victoria Mogollon, Ana García-Álvarez, Luis Martínez-Dolz, María Brion, Jose María Larrañaga-Moreira, Juan Jiménez-Jáimez, María Isabel García-Álvarez, Silvia Vilches, Eduardo Villacorta, María Sabater-Molina, Itziar Solla-Ruiz, Ana Royuela, Fernando Domínguez, Jesús G. Mirelis, Pablo Garcia-Pavia
Journal: Journal of the American College of Cardiology (2024)

Disease penetrance in genotype-positive (G+) relatives of families with dilated cardiomyopathy (DCM) and the characteristics associated with DCM onset in these individuals are unknown. This study sought to determine the penetrance of new DCM diagnosis in G+ relatives and to identify factors associated with DCM development. The authors evaluated 779 G+ patients (age 35.8 ± 17.3 years; 459 [59%] females; 367 [47%] with variants in TTN) without DCM followed at 25 Spanish centers. After a median follow-up of 37.1 months (Q1-Q3: 16.3-63.8 months), 85 individuals (10.9%) developed DCM (incidence rate of 2.9 per 100 person-years; 95% CI: 2.3-3.5 per 100 person-years). DCM penetrance and age at DCM onset was different according to underlying gene group (log-rank P = 0.015 and P <0.01, respectively). In a multivariable model excluding CMR parameters, independent predictors of DCM development were: older age (HR per 1-year increase: 1.02; 95% CI: 1.0-1.04), an abnormal electrocardiogram (HR: 2.13; 95% CI: 1.38-3.29); presence of variants in motor sarcomeric genes (HR: 1.92; 95% CI: 1.05-3.50); lower left ventricular ejection fraction (HR per 1% increase: 0.86; 95% CI: 0.82-0.90) and larger left ventricular end-diastolic diameter (HR per 1-mm increase: 1.10; 95% CI: 1.06-1.13). Multivariable analysis in individuals with cardiac magnetic resonance and late gadolinium enhancement assessment (n = 360, 45%) identified late gadolinium enhancement as an additional independent predictor of DCM development (HR: 2.52; 95% CI: 1.43-4.45). Following a first negative screening, approximately 11% of G+ relatives developed DCM during a median follow-up of 3 years. Older age, an abnormal electrocardiogram, lower left ventricular ejection fraction, increased left ventricular end-diastolic diameter, motor sarcomeric genetic variants, and late gadolinium enhancement are associated with a higher risk of developing DCM.
The persistence of SARS-CoV-2 in tissues and its association with long COVID symptoms: a cross-sectional cohort study in China
Authors: Wenting Zuo, Di He, Chaoyang Liang, Shiyu Du, Zhan Hua, Qiangqiang Nie, Xiaofeng Zhou, Meng Yang, Haidong Tan, Jiuyang Xu, Yanbing Yu, Yuliang Zhan, Ying Zhang, Xiaoying Gu, Weijie Zhu, Hui Zhang, Hongyan Li, Weiliang Sun, Mingzhi Sun, Xiaolei Liu, Liguo Liu, Chuanzhen Cao, Rui Li, Jing Li, Yun Zhang, Yuting Zhang, Jing Guo, Ling Zhao, Chuan-Peng Zhang, Hongyu Liu, Shiyao Wang, Fei Xiao, Yeming Wang, Zai Wang, Haibo Li, Bin Cao
Journal: The Lancet Infectious Diseases (2024)

Growing evidence suggests that symptoms associated with post-COVID-19 condition (also known as long COVID) can affect multiple organs and systems in the human body, but their association with viral persistence is not clear. The aim of this study was to investigate the persistence of SARS-CoV-2 in diverse tissues at three timepoints following recovery from mild COVID-19, as well as its association with long COVID symptoms.
Gaza
Authors: Abdullah Al-Jamal
Journal: The Lancet Psychiatry (2024)

Before the war that began on Oct 7, 2023, we had in Gaza seven psychiatrists, three who had trained in Jordan, two in Qatar, one in Saudia Arabia, and one in Europe, most of whom had returned home to Gaza in the past 4 years. In August, 2021, we started a national programme for training in psychiatry (Board) under the umbrella of the Palestinian Medical Council. The programme received the recognition of the Arab Medical Council. Before the war, there were seven doctors in the programme, as well as dozens of mental health and social workers and psychiatric nurses.
Synchronized Expansion and Contraction of Olfactory, Vomeronasal, and Taste Receptor Gene Families in Hystricomorph Rodents
Authors: Yoshihito Niimura, Bhim B Biswa, Takushi Kishida, Atsushi Toyoda, Kazumichi Fujiwara, Masato Ito, Kazushige Touhara, Miho Inoue-Murayama, Scott H Jenkins, Christopher Adenyo, Boniface B Kayang, Tsuyoshi Koide
Journal: Molecular Biology and Evolution (2024)

Chemical senses, including olfaction, pheromones, and taste, are crucial for the survival of most animals. There has long been a debate about whether different types of senses might influence each other. For instance, primates with a strong sense of vision are thought to have weakened olfactory abilities, although the oversimplified trade-off theory is now being questioned. It is uncertain whether such interactions between different chemical senses occur during evolution. To address this question, we examined four receptor gene families related to olfaction, pheromones, and taste: olfactory receptor (OR), vomeronasal receptor type 1 and type 2 (V1R and V2R), and bitter taste receptor (T2R) genes in Hystricomorpha, which is morphologically and ecologically the most diverse group of rodents. We also sequenced and assembled the genome of the grasscutter, Thryonomys swinderianus. By examining 16 available genome assemblies alongside the grasscutter genome, we identified orthologous gene groups among hystricomorph rodents for these gene families to separate the gene gain and loss events in each phylogenetic branch of the Hystricomorpha evolutionary tree. Our analysis revealed that the expansion or contraction of the four gene families occurred synchronously, indicating that when one chemical sense develops or deteriorates, the others follow suit. The results also showed that V1R/V2R genes underwent the fastest evolution, followed by OR genes, and T2R genes were the most evolutionarily stable. This variation likely reflects the difference in ligands of V1R/V2Rs, ORs, and T2Rs: species-specific pheromones, environment-based scents, and toxic substances common to many animals, respectively.
Comparison of baseline patient characteristics in Italian oncology drug monitoring registries and clinical trials: a real-world cross-sectional study
Authors: Maria Lucia Iacovino, Simone Celant, Luca Tomassini, Laura Arenare, Andrea Caglio, Andrea Canciello, Flavio Salerno, Pier Paolo Olimpieri, Susanna Di Segni, Antonella Sferrazza, Maria Carmela Piccirillo, Giordano Domenico Beretta, Carmine Pinto, Livio Blasi, Saverio Cinieri, Luigi Cavanna, Massimo Di Maio, Pierluigi Russo, Francesco Perrone
Journal: The Lancet Regional Health - Europe (2024)

BackgroundGeneralizability of registrative clinical trials to real-world clinical practice is influenced by comparability of patients in the two settings. We compared characteristics of cancer patients in registrative trials with real-world clinical practice in Italy.MethodsData on age, sex and performance status (PS) were derived from web-based monitoring registries developed by Italian Medicines Agency (AIFA) and corresponding registrative trials reported in the European Public Assessment Reports (EPAR) of European Medicines Agency (EMA). Weighted means were calculated in registries and trials and differences were described. Multivariate analysis was performed using Principal Component Analysis and Cluster Analysis.FindingsFrom January, 2013 to April, 2023, 419,461 unique pairs of patients and therapeutic indications were recorded in 129 AIFA registries. Within 140 related trials, 87,452 patients had been enrolled. Median age and rate of elderly (≥65 years old) patients were higher in monitoring registries than in clinical trials [mean difference of median age 5.3 years, p < 0.001; mean difference of elderly rate 17.17% (95% CI 1.06, 1.48)]. Overall, rate of female patients was not different between registries and trials [mean difference −0.55% (95% CI –1.06, −0.05)]. Mean rate of patients with deteriorated PS was low both in trials (3.1%) and in registries (4.3%) with a mean difference of 1.27% (95% CI 1.06, 1.48). Two clusters were identified with multivariate analysis: one including more registries (higher median age and elderly rate, lower female rate, higher rate of deteriorated patients), the other more trials (lower median age and elderly rate, higher female rate, lower rate of deteriorated patients).InterpretationThis study supports that cancer patients enrolled in trials do only partially represent those who have been treated in Italy in clinical practice. Inclusiveness of registrative trials should be increased to ensure generalizability of results to real-world population.FundingPartially supported by Italian Ministry of Health.
Biomaterial-enhanced treg cell immunotherapy: A promising approach for transplant medicine and autoimmune disease treatment
Authors: Kazem Mashayekhi, Khashayarsha Khazaie, William A. Faubion, Gloria B. Kim
Journal: Bioactive Materials (2024)

Regulatory T cells (Tregs) are crucial for preserving tolerance in the body, rendering Treg immunotherapy a promising treatment option for both organ transplants and autoimmune diseases. Presently, organ transplant recipients must undergo lifelong immunosuppression to prevent allograft rejection, while autoimmune disorders lack definitive cures. In the last years, there has been notable advancement in comprehending the biology of both antigen-specific and polyclonal Tregs. Clinical trials involving Tregs have demonstrated their safety and effectiveness. To maximize the efficacy of Treg immunotherapy, it is essential for these cells to migrate to specific target tissues, maintain stability within local organs, bolster their suppressive capabilities, and ensure their intended function's longevity. In pursuit of these goals, the utilization of biomaterials emerges as an attractive supportive strategy for Treg immunotherapy in addressing these challenges. As a result, the prospect of employing biomaterial-enhanced Treg immunotherapy holds tremendous promise as a treatment option for organ transplant recipients and individuals grappling with autoimmune diseases in the near future. This paper introduces strategies based on biomaterial-assisted Treg immunotherapy to enhance transplant medicine and autoimmune treatments.
Cardiovascular risk in young people with childhood onset systemic lupus erythematosus
Authors: Coziana Ciurtin, George Robinson, Maryam Butt, Junjie Peng, Stacy Ardoin, Laura Schanberg, Alina Boteanu, Katerina Bouchalova, Selcan Demir, Elena Moraitis, Angela Migowa, Yvonne Glackin, Jenny Ainsworth, Eve Smith, Elizabeth Jury, Sezgin Sahin, Sylvia Kamphuis, Laura Lewandowski
Journal: The Lancet Rheumatology (2024)
The Florida Scoring System for stratifying children with suspected Sjögren's disease: a cross-sectional machine learning study
Authors: Wenjie Zeng, Akaluck Thatayatikom, Nicole Winn, Tyler C Lovelace, Indraneel Bhattacharyya, Thomas Schrepfer, Ankit Shah, Renato Gonik, Panayiotis V Benos, Seunghee Cha
Journal: The Lancet Rheumatology (2024)
Abstract 9624: Suppressive Effects of Irbesartan on Inflammation and Apoptosis in Atherosclerotic Plaques of Apoe <sup>-/-</sup> Mice: Molecular Imaging with <sup>14</sup> C-FDG and <sup>99m</sup> Tc-annexin A5
Authors: Yan Zhao, Songji Zhao, Yuji Kuge, Ayahisa Watanabe, Keita Fukao, Yoshikazu Tanaka, Toru Nakano, Hiroshi Takemoto, Nagara Tamaki
Journal: Circulation (2011)

Background: Although irbesartan, an angiotensin II subtype 1 receptor blocker, reportedly can suppress the progression of atherosclerosis, the mechanisms of the therapeutic effects remain unclear. FDG and annexin A5 are two promising molecular probes that can be used to image inflammation and apoptosis, respectively. Objectives: To clarify the relationship between the therapeutic effects of irbesartan and the inflammatory and apoptotic reactions in atherosclerotic plaques, using FDG and annexin A5. Methods: Female apoE −/− mice were administered a diet containing irbesartan (50 mg/kg/day) for 12 weeks. After 1 week of discontinuation of the treatment, the mice (n=11) were coinjected with 14 C-FDG and 99m Tc-annexin A5, and the cryostat sections of aortic root were prepared 2 h after the injection. The sections were used for dual-tracer autoradiography, and the uptake levels of 14 C-FDG and 99m Tc-annexin A5 in the plaques were evaluated (%ID×kg). Histological examination was performed with Mac-2 (macrophage infiltration), TUNEL (apoptosis), Movat's pentachrome (plaque size), and Oil Red O (lipid deposition) staining methods on serial sections. The same experiments were performed as control with age-matched mice on irbesartan-free diet (n=11). Results: Irbesartan treatment significantly ( p &lt;0.05) reduced the 14 C-FDG and 99m Tc-annexin A5 uptake levels in the plaque to 43.0% ± 18.6% and 45.9% ± 16.8% that of control, respectively. Histological examinations showed a significant reduction ( p &lt;0.05) of the intraplaque macrophage infiltration levels (61.9% ± 20.8% of control), number of apoptotic cells (14.5% ± 16.6%), and lipid deposition levels (53.6% ± 20.2%), as well as the plaque size (56.4% ± 11.1%). Positive correlations were observed between the 14 C-FDG uptake and macrophage infiltration levels (r=0.69, p &lt;0.001), and between the 99m Tc-annexin A5 uptake level and number of apoptotic cells (r=0.69, p &lt;0.001). Conclusions: Remissions of inflammation and apoptosis as the potential therapeutic effects of irbesartan on atherosclerosis were identified by histological examinations and molecular imaging with 14 C-FDG and 99m Tc-annexin A5. The accuracy and usefulness of molecular imaging for monitoring therapeutic effects are also suggested.
NOT lost in translation: translatome mapping as a novel approach to identify regulators of atherosclerosis
Authors: Ljubica Matic, Melody Chemaly, Helle F Jørgensen
Journal: Cardiovascular Research (2024)

NOT lost in translation: Translatome mapping as a novel approach to identify regulators of atherosclerosis Genome-wide association studies (GWAS) have identified hundreds of human genetic variants associated with increased risk of coronary artery disease (CAD) and stroke, the major causes of cardiovascular death.In addition to an orthogonal means of risk stratification, GWAS studies can
American Society of Nephrology Kidney Tutored Research and Education for Kidney Scholars (TREKS) Program
Authors: Molly Rubin, Stewart H. Lecker, Nirupama Ramkumar, Stephen M. Sozio, Robert S. Hoover, Mark L. Zeidel, Benjamin S. Ko
Journal: Journal of the American Society of Nephrology (2024)

In response to decreasing numbers of individuals entering into nephrology fellowships, the American Society of Nephrology launched Kidney Tutored Research and Education for Kidney Scholars (TREKS) to stimulate interest in nephrology among medical students, graduate students, and postdoctoral fellows. The program combines a 1-week intensive exposure to kidney physiology with a longitudinal mentorship program at the participants' home institutions. Ten years in, an analysis was conducted to assess its effectiveness. We surveyed participants to assess their opinions regarding nephrology before and after the course and followed them longitudinally to determine their career choices. TREKS applicants who were not selected to participate were used as a comparison group. Three hundred eighty-one people participated in the program, and 242 completed the survey. After TREKS, both medical students and graduate students showed increased interest in nephrology, with rank scores of 5.6±0.2 before to 7.5±0.1 after the course for medical students (mean±SD, n =189, P = 0.001) and 7.3±0.3 to 8.7±0.3 ( n =53, P = 0.001) for graduate students. In long-term follow-up, TREKS medical students chose a nephrology pipeline residency at a higher rate than medical students overall (57% versus 31%, P = 0.01) and TREKS applicants who did not participate (47% versus 31%, P = 0.04). Nephrology fellowship rates for these groups exceeded the general population but did not significantly differ between TREKS participants and applicants. Doctor of Philosophy students and postdoctoral TREKS participants had a higher rate of participation in nephrology research compared with TREKS applicants (66% versus 30%, P = 0.01). In summary, the American Society of Nephrology Kidney TREKS program has demonstrated that it can increase interest in nephrology in the short term and increase the number of individuals going into nephrology careers. This long-term effect is most evident in Doctor of Philosophy students and postdoctoral participants. Further study is needed to assess the impact of TREKS on enrollment in nephrology fellowship programs.