tbuckley/cabot-search huggingface dataset:
PF473 PEDIATRIC HODGKIN LYMPHOMA: DISPARITIES IN SURVIVAL BY RACE
Authors: K. Khullar, Z. Rivera‐Núñez, S. Jhawar, R. Drachtman, P. Cole, B. Hoppe, R. Parikh
Journal: HemaSphere (2019)

Background: The association between race and survival has not been well established for patients with pediatric Hodgkin Lymphoma (HL). Aims: The purpose of this study was to examine the disparities in overall survival (OS) by race in a large cohort of patients with pediatric HL. Methods: We evaluated clinical features and survival outcomes among patients ≤21 years of age diagnosed with stage I‐IV HL from 2004 to 2015 from the prospectively collected National Cancer DataBase (NCDB). The association between patient‐reported race and OS was assessed in a multivariable Cox proportional hazards model. Results: Among 11,546 patients with pediatric HL ≤21 years of age within the NCDB, a total of 9,285 patients with stage I‐IV disease were eligible for this study, with a median follow‐up of 5 years. The race status was as follows: 7,722 (83%) White; 1,136 (12%) Black, and 427 (5%) other. Black patients were found to be younger (&lt;15), lower stage at diagnosis, more commonly with “B” symptoms, less likely to have nodular‐sclerosis histology, more likely to be lower income and education quartiles, and under/uninsured (all p &lt; 0.01). Treatment interventions among races was similar (use of chemotherapy, radiation therapy, or combined modality therapy). Patients of Black race experienced a 5‐year OS of 91.5% vs. 95.9% compared to their White counterparts ( p &lt; 0.01). This difference in OS persisted across all stratified stages (I‐IV). When adjusting for all co‐variates, Black race was associated with significantly decreased OS (HR = 1.50; 95% CI, 1.12–1.99, p &lt; 0.01). In risk factor stratification by race,age &lt;15, stage IV disease, presence of B symptoms, use of radiation, and income were prognostic factors for OS in White patients, but not for Black patients. Effect measure modification was also utilized to assess the interaction between socioeconomic parameters (education/income/insurance status) and race and no significant interaction was found. In sensitivity analysis including age groups of ≤15 years, 16–18 years, and &gt;18 years of age, Black race was associated with poorer OS among all age groups compared to Whites with rates of 95.4% vs 97.7%, 87.1% vs 96.1%, and 91.6% vs 94.6% respectively. Summary/Conclusion: Our study reveals that among pediatric patients with HL, Black race was associated with lower overall survival, across all disease stages and pediatric age groups. To our knowledge, this study represents the largest dataset examining the role of race on survival for pediatric patients with HL. Further studies are necessary to elucidate the causes of these differences in order to facilitate optimal treatment of pediatric HL patients in the era of risk‐stratified, response‐based treatment. image
PF457 MECHANISM OF MORPHOLOGICAL REMODELING OF BONE MARROW ADIPOCYTES IN ACUTE MYELOID LEUKEMIA
Authors: S. Yang, W. Lu, C. Zhao, Y. Zhai, Y. Wei, J. Liu, Y. Yu, Z. Li, J. Shi
Journal: HemaSphere (2019)

Background: We have previously found that morphological remodeling of bone marrow adipocytes in acute myeloid leukemia (AML) patients is closely related to poor prognosis, and growth differentiation factor 15 (GDF15) may be a key factor in this pathological phenomenon. Aims: In this study, we further explored the mechanism of GDF15 regulating the bone marrow adipocyte remodeling from the perspective of calcium channel TRPV4. Methods: GDF15‐induced adipocytes were analyzed using gene expression profiling, and gene knockdown cells were generated by lentiviral‐mediated shRNA. Chip‐qPCR was used to evaluate the interaction between transcription factors and TRPV4. Signaling pathway downstream of GDF15 involved in adipocytes was analyzed by inhibitor experiments. An experimental AML mouse model was generated to investigate the role of TRPV4 in leukemia cell‐induced bone marrow adipocyte remodeling. Results: Western blot and RT‐qPCR showed that GDF15 could regulate TRPV4 expression in bone marrow adipocytes. In vitro , Transwell assay and neutralizing antibody assay further found that GDF15 secreted by leukemia cells regulated bone marrow adipocyte remodeling through TRPV4. The phenomenon was verified in obese C57/BL6 mice. Specific inhibition experiments showed that GDF15 secreted by leukemia cells combined with TGFβRII in bone marrow adipocytes, and then activated PI3K / AKT pathway. Using RNA‐Seq technique, we found that transcription factor FOXC1 mediated the inhibition of GDF15 on TRPV4 expression in bone marrow adipocytes, which causes the morphological remodeling of bone marrow adipocytes. Summary/Conclusion: GDF15 secreted by leukemia cells inhibits the expression of TRPV4 by regulating the transcription factor FOXC1 in bone marrow adipocytes, which promote the lipolysis of adipocytes. The free fatty acids released by this process provide energy support for the growth of leukemia cells. This paper provides a new perspective for the study of leukemia cell remodeling of bone marrow adipocyte microenvironment.
PF460 SINGLE CELL RNASEQ REVEALS THE IN VIVO DIFFERENTIATION POTENTIAL AND TRANSCRIPTIONAL DYNAMICS OF IMMATURE HUMAN THYMOCYTES
Authors: M. Lavaert, N. Vandamme, Y. Saeys, T. Taghon
Journal: HemaSphere (2019)

Background: T cell development depends on the colonization of the thymus by multipotent progenitor cells from the bone marrow. There, these precursor cells are gradually reprogrammed into committed T cell progenitors that have lost the developmental potential towards other hematopoietic lineages. While lineage tracing experiments in mice have provided evidence to which non T‐cell lineages these early T cell precursors differentiate in vivo , it remains unclear in human which blood cell lineages can originate from early T cell precursors. In vitro differentiation experiments have revealed erythroid, myeloid (DC, monocyte, granulocyte) and lymphoid (B, T, NK) differentiation potential, but whether this occurs in vivo is not clear. Aims: While lineage tracing experiments in mice have provided evidence to which non T‐cell lineages these early T cell precursors differentiate in vivo , it remains unclear in human which blood cell lineages can originate from early T cell precursors. In vitro differentiation experiments have revealed erythroid, myeloid (DC, monocyte, granulocyte) and lymphoid (B, T, NK) differentiation potential, but whether this occurs in vivo is not clear. Methods: Therefore, we have performed single cell RNA sequencing on more than 70.000 human CD34+lin‐ thymocytes that comprise the most immature thymocyte fraction of the human pediatric thymus. Results: Analysis of this dataset showed that cell cycle constitutes the majority of variation in the dataset, indicating less heterogeneity than anticipated. Indeed, using a strategy in which both clustering and trajectory inference were used, only limited branching was observed towards other, non T‐cell hematopoietic lineages, indicating a discrepancy between reported developmental potential and in vivo cell fate. Using these branching events, commitment was traced to coincide with loss of CD44 expression, confirming recent findings. In addition, we used CITEseq to correlate previously defined immature thymocyte subsets to these newly defined developmental cell states. Summary/Conclusion: In conclusion, our work suggests that the in vivo differentiation of immature human thymocytes is much more restricted compared to what in vitro differentiation experiments have suggested. In addition, we have delineated the transcriptional events that define the transition from multipotency toward T‐cell lineage commitment at the single cell level and redefine immature thymocyte subsets in human.
PF478 DOES ESCALATED BEACOP‐DACARBAZINE DO THE SAME AS ESCALATED BEACOP‐PROCARBAZINE FOR UNFAVORABLE HODGKIN'S LYMPHOMA?
Authors: R. Mansouri, K. Kacem, D. Jabr, M. Bchir, L. Aissaoui, E. Berred, S. Kefi, H. Ben Néji, M. Achour, Y. Ben Abdennebi, M. Bahri, B. Meddeb, R. Ben Lakhal
Journal: HemaSphere (2019)

Background: The management of Tunisian Adult Hodgkin's lymphoma (HL) has been standardized since 1999. Since 2008 we individualized four therapeutic groups according age, stage (Ann Arbor), EORTC criteria and GHSG criteria. So for patients aged less than 60 years we considered unfavorable group who have advanced stage III‐IV Ann Arbor and II stage with large mediastinal mass. This group received the escalated BEACOPP (esc‐BEACOPP) protocol differently to other three groups. Aims: We report in this study the therapeutic results of the national protocol of Adult HL (MDH2015) for this group and demonstrate the place of Dacarbazine. Methods: Our study is prospective monocentric interesting 76 patients followed between June 2015 and December 2017 for HL stage III‐IV and stage II with large mediastinal mass and treated according MDH2015 protocol. The median age was 29 years [14–58 years].B symptoms were found in 67% of our patients. Our patients were stage III‐IV Ann Arbor in 83% of cases and stage II with large mediastinal mass in 17%. For advanced stage, 68% of patients have IPS&gt;2. The MDH 2015 protocol is based on a strategy adapted to the therapeutic response to 2 cycles of esc‐BEACOPP. We considered as a primary failure, patients hadn’t achieved response≥75% after 4 cycles of esc‐BEACOPP.Our patients had received in this protocol Dacarbazine 250 mg/m2 three days/cycle instead of Procarbazine (esc‐BEACOPD). Results: Response≥75% to 2 courses of esc‐BEACOPD was achieved in 43% of patients and the response rate at the end of treatment was 92%. Fourteen patients (19%) had primary failure. In the multivariate analysis, the advanced stage Ann Arbor (III‐IV) and response&lt;75% after 2 cycles of esc‐BEACOPD were an independent predictive factor of primary failure, with respectively p = 0.01 and p &lt; 0.001. The relapse rate was 10%. The median follow‐up was 25 months [5–46 months]. Event free survival (EFS), relapse free survival (RFS) and overall survival (OS) at 2 years were respectively, 77%, 90% and 90%. In multivariate analysis, the prognostic factors for poor OS were large mediastinal mass (p = 0.05), response&lt;75% at 2 courses (p = 0.04). The EFS is better without large mediastinal mass (p = 0.03) and without lymphopenia (p = 0.02). Fifty per cent of neutropenia was happened. Febrile neutropenia was noted in 24% of cases. No treatment related mortality was noted. Summary/Conclusion: Compared to MDH 2008 (third version of Tunisian prospective protocol), the use of Dacarbazine instead of Procarbazine is equally effective in term of response rate and the survivals (EFS, RFS and OS). The toxicity is the same.
Transition Metal Oxide‐Decorated MXenes as Drugless Nanoarchitectonics for Enriched Nanocatalytic Chemodynamic Treatment
Authors: Hong‐Ying Xia, Bo‐Yi Li, Ying‐Tong Ye, Shi‐Bin Wang, Ai‐Zheng Chen, Ranjith Kumar Kankala
Journal: Advanced Healthcare Materials (2023)

Despite their unique characteristics, 2D MXenes with sole photothermal conversion ability are required to explore their superfluous abilities in biomedicine. The small-molecule-based chemotherapeutics suffer from various shortcomings of time-consuming and expensiveness concerning theoretical and performance (preclinical/clinical) checks. This study demonstrates the fabrication of Ti
The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023
Authors: Feng‐Hua Wang, Xiao‐Tian Zhang, Lei Tang, Qi Wu, Mu‐Yan Cai, Yuan‐Fang Li, Xiu‐Juan Qu, Hong Qiu, Yu‐Jing Zhang, Jie‐Er Ying, Jun Zhang, Ling‐Yu Sun, Rong‐Bo Lin, Chang Wang, Hao Liu, Miao‐Zhen Qiu, Wen‐Long Guan, Sheng‐Xiang Rao, Jia‐Fu Ji, Yan Xin, Wei‐Qi Sheng, Hui‐Mian Xu, Zhi‐Wei Zhou, Ai‐Ping Zhou, Jing Jin, Xiang‐Lin Yuan, Feng Bi, Tian‐Shu Liu, Han Liang, Yan‐Qiao Zhang, Guo‐Xin Li, Jun Liang, Bao‐Rui Liu, Lin Shen, Jin Li, Rui‐Hua Xu
Journal: Cancer Communications (2023)

Abstract The 2023 update of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China, reflecting the latest advancements in evidence‐based medicine, healthcare resource availability, and precision medicine. These updates address the differences in epidemiological characteristics, clinicopathological features, tumor biology, treatment patterns, and drug selections between Eastern and Western gastric cancer patients. Key revisions include a structured template for imaging diagnosis reports, updated standards for molecular marker testing in pathological diagnosis, and an elevated recommendation for neoadjuvant chemotherapy in stage III gastric cancer. For advanced metastatic gastric cancer, the guidelines introduce new recommendations for immunotherapy, anti‐angiogenic therapy and targeted drugs, along with updated management strategies for human epidermal growth factor receptor 2 (HER2)‐positive and deficient DNA mismatch repair (dMMR)/microsatellite instability‐high (MSI‐H) patients. Additionally, the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric cancer. The 2023 CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice, particularly in the heterogeneous healthcare landscape of China, while maintaining a commitment to scientific rigor, impartiality, and timely revisions.
SERS sensing for cancer biomarker: Approaches and directions
Authors: Lorena Vázquez-Iglesias, Giovanna Maria Stanfoca Casagrande, Daniel García-Lojo, Letícia Ferro Leal, Tien Anh Ngo, Jorge Pérez-Juste, Rui Manuel Reis, Krishna Kant, Isabel Pastoriza-Santos
Journal: Bioactive Materials (2023)

These days, cancer is thought to be more than just one illness, with several complex subtypes that require different screening approaches. These subtypes can be distinguished by the distinct markings left by metabolites, proteins, miRNA, and DNA. Personalized illness management may be possible if cancer is categorized according to its biomarkers. In order to stop cancer from spreading and posing a significant risk to patient survival, early detection and prompt treatment are essential. Traditional cancer screening techniques are tedious, time-consuming, and require expert personnel for analysis. This has led scientists to reevaluate screening methodologies and make use of emerging technologies to achieve better results. Using time and money saving techniques, these methodologies integrate the procedures from sample preparation to detection in small devices with high accuracy and sensitivity. With its proven potential for biomedical use, surface-enhanced Raman scattering (SERS) has been widely used in biosensing applications, particularly in biomarker identification. Consideration was given especially to the potential of SERS as a portable clinical diagnostic tool. The approaches to SERS-based sensing technologies for both invasive and non-invasive samples are reviewed in this article, along with sample preparation techniques and obstacles. Aside from these significant constraints in the detection approach and techniques, the review also takes into account the complexity of biological fluids, the availability of biomarkers, and their sensitivity and selectivity, which are generally lowered. Massive ways to maintain sensing capabilities in clinical samples are being developed recently to get over this restriction. SERS is known to be a reliable diagnostic method for treatment judgments. Nonetheless, there is still room for advancement in terms of portability, creation of diagnostic apps, and interdisciplinary AI-based applications. Therefore, we will outline the current state of technological maturity for SERS-based cancer biomarker detection in this article. The review will meet the demand for reviewing various sample types (invasive and non-invasive) of cancer biomarkers and their detection using SERS. It will also shed light on the growing body of research on portable methods for clinical application and quick cancer detection.
SARS-CoV-2 induced vascular endothelial dysfunction: direct or indirect effects?
Authors: Kathy O Lui, Zhangjing Ma, Stefanie Dimmeler
Journal: Cardiovascular Research (2023)

Clinical evidence reveals that manifestations of endothelial dysfunction are widely observed in COVID-19 and long-COVID patients. However, whether these detrimental effects are caused by direct infection of the endothelium or are indirectly mediated by systemic inflammation has been a matter of debate. It has been well acknowledged that endothelial cells (ECs) of the cardiovascular system ubiquitously express the SARS-CoV-2 entry receptor angiotensin-converting enzyme 2 (ACE2), yet accumulating evidence suggests that it is more predominantly expressed by pericytes and vascular smooth muscle cells of the mammalian blood vessel. Besides, replicative infection of ECs by SARS-CoV-2 has yet to be demonstrated both in vitro and in vivo. In this study, we review latest research on endothelial ACE2 expression in different vascular beds, and the heterogeneity in various EC subsets with differential ACE2 expression in response to SARS-CoV-2. We also discuss ACE2-independent alternative mechanisms underlying endothelial activation in COVID-19, and the clinical manifestations of SARS-CoV-2-induced endothelial dysfunction. Altogether, understanding ACE2-dependent and ACE2-independent mechanisms driving SARS-CoV-2-induced vascular dysfunction would shed light on strategies of more effective therapies targeting cardiovascular complications associated with COVID-19.
Injectable alginate-based in situ self-healable transparent hydrogel as a vitreous substitute with a tamponading function
Authors: Geunho Choi, Seoung Hyun An, Jae-Won Choi, Mee Sook Rho, Woo Chan Park, Woo jin Jeong, Hyung Joon Cha
Journal: Biomaterials (2024)
Resilience and Mental-Health Symptoms in ICU Healthcare Professionals Facing Repeated COVID-19 Waves
Authors: Elie Azoulay, Frédéric Pochard, Laurent Argaud, Alain Cariou, Raphael Clere-Jehl, Olivier Guisset, Vincent Labbé, Fabienne Tamion, Fabrice Bruneel, Mercé Jourdain, Danielle Reuter, Kada Klouche, Achille Kouatchet, Virginie Souppart, Alexandre Lautrette, Julien Bohé, Antoine Vieillard Baron, Jean Dellamonica, Laurent Papazian, Jean Reignier, Francois Barbier, Guillaume Dumas, Nancy Kentish-Barnes
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Rationale: Psychological resilience presents a potential protective mechanism against COVID-19-associated mental health symptoms in healthcare providers (HCPs). Objectives: to identify the determinants of HCP’s resilience in intensive care unit HCPs facing the fifth pandemic wave. Methods: Cross-sectional study in 21 ICUs. HCPs completed the CD-RISC10, HADS, and IES-R to assess resilience, symptoms of anxiety, depression and post-traumatic stress disorder (PTSD), respectively. Factors independently associated with resilience were identified. Measurements and Main Results:: The response rate was 73.1% (950/1300). The median CD-RISC10 score was 29 (25-32). Prevalence of symptoms of anxiety, depression and PTSD was 61%, 39%, and 36%, respectively. Infodemia was correlated with symptoms of depression and PTSD. Higher resilience was independently associated with lower prevalence of anxiety, depression and PTSD. Men, HCPs who faced the first waves, who managed >50 COVID-19 patients, who increased their working time and motivation, and who report that end-of-life decisions were more consensual compared to the previous waves had a higher resilience. Conversely, HCPs having managed >10 deaths during the ongoing wave, who described themselves as more frightened or isolated, or who reported more infodemia compared to the previous waves experienced a lower resilience. Conclusions: This study identifies modifiable determinants of resilience, framing the components of a training-skills based intervention to be properly evaluated. As HCP’s support remains a major unmet need, this study is holding accountable hospital administrators, directors, policymakers, and the ICU leadership, for their commitment in sharing the responsibility of preventing and mitigating mental health symptoms in HCPs. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Normal Lung Function and Mortality in World Trade Center Responders and NHANES III Participants
Authors: Madeline F. Cannon, David G. Goldfarb, Rachel A. Zeig-Owens, Charles B. Hall, Jaeun Choi, Hillel W. Cohen, David J. Prezant, Michael D. Weiden
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Low FEV
In T2DM requiring insulin initiation, icodec titrated with an app safely reduced HbA<sub>1c</sub> vs. daily basal insulin analogues at 52 wk
Authors: Aris Liakos, Thomas Karagiannis, Apostolos Tsapas
Journal: Annals of Internal Medicine (2024)

Bajaj HS, Aberle J, Davies M, et al.
Development and Validation of a Protein Risk Score for Mortality in Heart Failure
Authors: Kayode O. Kuku, Joseph J. Shearer, Maryam Hashemian, Rebecca Oyetoro, Hoyoung Park, Brittany Dulek, Suzette J. Bielinski, Nicholas B. Larson, Peter Ganz, Daniel Levy, Bruce M. Psaty, Jungnam Joo, Véronique L. Roger
Journal: Annals of Internal Medicine (2024)

Heart failure (HF) is a complex clinical syndrome with high mortality. Current risk stratification approaches lack precision. High-throughput proteomics could improve risk prediction. Its use in clinical practice to guide the management of patients with HF depends on validation and evidence of clinical benefit. To develop and validate a protein risk score for mortality in patients with HF. Community-based cohort. Southeast Minnesota. Patients with HF enrolled between 2003 and 2012 and followed through 2021. A total of 7289 plasma proteins in 1351 patients with HF were measured using the SomaScan Assay (SomaLogic). A protein risk score was derived using least absolute shrinkage and selection operator regression and temporal validation in patients enrolled between 2003 and 2007 (development cohort) and 2008 and 2012 (validation cohort). Multivariable Cox regression was used to examine the association between the protein risk score and mortality. The performance of the protein risk score to predict 5-year mortality risk was assessed using calibration plots, decision curves, and relative utility analyses and compared with a clinical model, including the Meta-Analysis Global Group in Chronic Heart Failure mortality risk score and N-terminal pro-B-type natriuretic peptide. The development (n = 855; median age, 78 years; 50% women; 29% with ejection fraction <40%) and validation cohorts (n = 496; median age, 76 years; 45% women; 33% with ejection fraction <40%) were mostly similar. In the development cohort, 38 unique proteins were selected for the protein risk score. Independent of ejection fraction, the protein risk score demonstrated good calibration, reclassified mortality risk particularly at the extremes of the risk distribution, and showed greater clinical utility compared with the clinical model. Participants were predominantly of European ancestry, potentially limiting the generalizability of the findings to different patient populations. Validation of the protein risk score demonstrated good calibration and evidence of predicted benefits to stratify the risk for death in HF superior to that of clinical methods. Further studies are needed to prospectively evaluate the score's performance in diverse populations and determine risk thresholds for interventions. Division of Intramural Research at the National Heart, Lung, and Blood Institute of the National Institutes of Health.