tbuckley/cabot-search huggingface dataset:
Venetoclax-Based Combination Regimens in Acute Myeloid Leukemia
Authors: Hannah Goulart, Hagop Kantarjian, Naveen Pemmaraju, Naval Daver, Courtney D. DiNardo, Caitlin R. Rausch, Farhad Ravandi, Tapan M. Kadia
Journal: Blood Cancer Discovery (2024)

Abstract Incorporation of the B-cell lymphoma 2 inhibitor venetoclax into the treatment of acute myeloid leukemia (AML) has been transformative. Initially studied in combination with low-intensity therapy in older adults and those ineligible for intensive therapy, venetoclax has proven to be efficacious and tolerable in this setting. Recently, venetoclax has been investigated in combination with more intensive regimens. However, these approaches come with a myriad of dosing strategies and questions surrounding the practicality of venetoclax administration. In this study, we provide an overview of the incorporation of venetoclax into AML treatment and a discussion of practical considerations and areas of unmet need. Significance: In recent years, there has been tremendous interest surrounding the integration of venetoclax into both non-intensive and intensive chemotherapy regimens for AML. However, with this increasing utilization of venetoclax, considerable questions surrounding key issues such as dosing strategies and the practicality of venetoclax administration have arisen. This review highlights the evolution of venetoclax-based regimens in AML and provides a commentary on notable practical considerations when utilizing this agent.
Antibiotic Treatment for 7 versus 14 Days in Patients with Bloodstream Infections
Authors: Nick Daneman, Asgar Rishu, Ruxandra Pinto, Benajmin A Rogers, Yahya Shehabi, Rachael Parke, Deborah Cook, Yaseen Arabi, John Muscedere, Steven Reynolds, Richard Hall, Dhiraj B Dwivedi, Colin McArthur, Shay McGuinness, Dafna Yahav, Bryan Coburn, Anna Geagea, Pavani Das, Phillip Shin, Michael Detsky, Andrew Morris, Michael Fralick, Jeff E Powis, Christopher Kandel, Wendy Sligl, Sean M Bagshaw, Nishma Singhal, Emilie Belley-Cote, Richard Whitlock, Kosar Khwaja, Susan Morpeth, Alex Kazemi, Anthony Williams, Derek R MacFadden, Lauralyn McIntyre, Jennifer Tsang, Francois Lamontagne, Alex Carignan, John Marshall, Jan O Friedrich, Robert Cirone, Mark Downing, Christopher Graham, Joshua Davis, Erick Duan, John Neary, Gerald Evans, Basem Alraddadi, Sameera Al Johani, Claudio Martin, Sameer Elsayed, Ian Ball, Francois Lauzier, Alexis Turgeon, Henry T Stelfox, John Conly, Emily G McDonald, Todd C Lee, Richard Sullivan, Jennifer Grant, Ilya Kagan, Paul Young, Cassie Lawrence, Kevin O'Callaghan, Matthew Eustace, Keat Choong, Pierre Aslanian, Ulrike Buehner, Tom Havey, Alexandra Binnie, Josef Prazak, Brenda Reeve, Edward Litton, Sylvain Lother, Anand Kumar, Ryan Zarychanski, Tomer Hoffman, David Paterson, Peter Daley, Robert J Commons, Emmanuel Charbonney, Jean-Francois Naud, Sally Roberts, Ravindranath Tiruvoipati, Sachin Gupta, Gordon Wood, Omar Shum, Spiros Miyakis, Peter Dodek, Clement Kwok, Robert A Fowler
Journal: New England Journal of Medicine (2024)

Bloodstream infections are associated with substantial morbidity and mortality. Early, appropriate antibiotic therapy is important, but the duration of treatment is uncertain.
Gut microbiota in health and disease: advances and future prospects
Authors: Yusheng Zhang, Hong Wang, Yiwei Sang, Mei Liu, Qing Wang, Hongjun Yang, Xianyu Li
Journal: MedComm (2024)

Abstract The gut microbiota plays a critical role in maintaining human health, influencing a wide range of physiological processes, including immune regulation, metabolism, and neurological function. Recent studies have shown that imbalances in gut microbiota composition can contribute to the onset and progression of various diseases, such as metabolic disorders (e.g., obesity and diabetes) and neurodegenerative conditions (e.g., Alzheimer's and Parkinson's). These conditions are often accompanied by chronic inflammation and dysregulated immune responses, which are closely linked to specific forms of cell death, including pyroptosis and ferroptosis. Pathogenic bacteria in the gut can trigger these cell death pathways through toxin release, while probiotics have been found to mitigate these effects by modulating immune responses. Despite these insights, the precise mechanisms through which the gut microbiota influences these diseases remain insufficiently understood. This review consolidates recent findings on the impact of gut microbiota in these immune‐mediated and inflammation‐associated conditions. It also identifies gaps in current research and explores the potential of advanced technologies, such as organ‐on‐chip models and the microbiome–gut–organ axis, for deepening our understanding. Emerging tools, including single‐bacterium omics and spatial metabolomics, are discussed for their promise in elucidating the microbiota's role in disease development.
Ferroptosis: mechanisms and therapeutic targets
Authors: Qian Zhou, Yu Meng, Jiayuan Le, Yuming Sun, Yating Dian, Lei Yao, Yixiao Xiong, Furong Zeng, Xiang Chen, Guangtong Deng
Journal: MedComm (2024)

Ferroptosis is a nonapoptotic form of cell death characterized by iron-dependent lipid peroxidation in membrane phospholipids. Since its identification in 2012, extensive research has unveiled its involvement in the pathophysiology of numerous diseases, including cancers, neurodegenerative disorders, organ injuries, infectious diseases, autoimmune conditions, metabolic disorders, and skin diseases. Oxidizable lipids, overload iron, and compromised antioxidant systems are known as critical prerequisites for driving overwhelming lipid peroxidation, ultimately leading to plasma membrane rupture and ferroptotic cell death. However, the precise regulatory networks governing ferroptosis and ferroptosis-targeted therapy in these diseases remain largely undefined, hindering the development of pharmacological agonists and antagonists. In this review, we first elucidate core mechanisms of ferroptosis and summarize its epigenetic modifications (e.g., histone modifications, DNA methylation, noncoding RNAs, and N6-methyladenosine modification) and nonepigenetic modifications (e.g., genetic mutations, transcriptional regulation, and posttranslational modifications). We then discuss the association between ferroptosis and disease pathogenesis and explore therapeutic approaches for targeting ferroptosis. We also introduce potential clinical monitoring strategies for ferroptosis. Finally, we put forward several unresolved issues in which progress is needed to better understand ferroptosis. We hope this review will offer promise for the clinical application of ferroptosis-targeted therapies in the context of human health and disease.
Bortezomib before and after high‐dose therapy in transplant‐eligible patients with newly diagnosed multiple myeloma: Long‐term overall survival after more than 10 years of follow‐up from the phase III HOVON‐65/GMMG‐HD4 trial
Authors: Elias K. Mai, Axel Nogai, Henk M. Lokhorst, Bronno van der Holt, Sonja Zweegman, Katja C. Weisel, Sandra Croockewit, Anna Jauch, Jens Hillengass, Marian Stevens‐Kroef, Marc S. Raab, Annemiek Broijl, Gerard M. J. Bos, Peter Brossart, Paula Ypma, Christine Hanoun, Uta Bertsch, Thomas Hielscher, Hans J. Salwender, Christoph Scheid, Hartmut Goldschmidt, Pieter Sonneveld
Journal: HemaSphere (2024)
Effect of voxelotor on cerebral perfusion and cerebral oxygen metabolism and cardiac stress in adult patients with sickle cell disease
Authors: Kadère Konté, Liza Afzali‐Hashemi, Koen P. A. Baas, Anouk Schrantee, John C. Wood, Erfan Nur, Aart J. Nederveen, Bart J. Biemond
Journal: American Journal of Hematology (2024)

Sickle cell disease (SCD) is complicated by silent cerebral infarcts (SCIs), for which anemia is an important risk factor. Despite normal oxygen delivery (OD), cerebral vascular reserve (CVR), and cerebral metabolic rate of oxygen (CMRO
Corrigendum to “CD248 induces a maladaptive unfolded protein response in diabetic kidney disease.” Kidney International 2023;103:304–319
Authors: Shruthi Krishnan, Jayakumar Manoharan, Hongjie Wang, Dheerendra Gupta, Sameen Fatima, Yanfei Yu, Akash Mathew, Zhen Li, Shrey Kohli, Constantin Schwab, Antje Körner, Peter R Mertens, Peter Nawroth, Khurrum Shahzad, Michael Naumann, Berend Isermann, Ronald Biemann
Journal: Kidney International (2024)
UBXN9 governs GLUT4-mediated spatial confinement of RIG-I-like receptors and signaling
Authors: Andrew G. Harrison, Duomeng Yang, Jason G. Cahoon, Tingting Geng, Ziming Cao, Timofey A. Karginov, Youjia Hu, Xin Li, Conner C. Chiari, Yibing Qyang, Anthony T. Vella, Zhichao Fan, Sivapriya Kailasan Vanaja, Vijay A. Rathinam, Carol A. Witczak, Jonathan S. Bogan, Penghua Wang
Journal: Nature Immunology (2024)
Clinical validation of a wearable ultrasound sensor of blood pressure
Authors: Sai Zhou, Geonho Park, Katherine Longardner, Muyang Lin, Baiyan Qi, Xinyi Yang, Xiaoxiang Gao, Hao Huang, Xiangjun Chen, Yizhou Bian, Hongjie Hu, Ray S. Wu, Wentong Yue, Mohan Li, Chengchangfeng Lu, Ruotao Wang, Siyu Qin, Esra Tasali, Theodore Karrison, Isac Thomas, Benjamin Smarr, Erik B. Kistler, Belal Al Khiami, Irene Litvan, Sheng Xu
Journal: Nature Biomedical Engineering (2024)
Corrigendum to “Long-term impact of immediate versus deferred antiretroviral therapy on kidney health in people with HIV.” Kidney International 2024;106:136–144
Authors: Annegret Pelchen-Matthews, Amanda Mocroft, Lene Ryom, Michael J Ross, Shweta Sharma, Steven Coca, Amit Achhra, Elaine Cornell, Russell Tracy, Andrew Phillips, Marta Montero Alonso, Giota Toulomi, Brian K Agan, Nicholas Medland, Christina M Wyatt
Journal: Kidney International (2024)
Navigating toward standardization: a systematic review mapping outcome measures in masculinizing genital gender affirming surgery
Authors: Philippine J. Roijer, Marleen S. Vallinga, Melle M. F. Jorna, Thomas E. Pidgeon, Johannes C. F. Ket, Mark-Bram Bouman, Margriet G. Mullender
Journal: International Journal of Transgender Health (2024)
Blood Plasma Methylated <scp>DNA</scp> Markers in the Detection of Lymphoma: Discovery, Validation, and Clinical Pilot
Authors: Thomas E. Witzig, William R. Taylor, Douglas W. Mahoney, William R. Bamlet, Patrick H. Foote, Kelli N. Burger, Karen A. Doering, Mary E. Devens, Jacquelyn R. Arndt, Maria C. O'Connell, Calise K. Berger, Anne J. Novak, James R. Cerhan, Jacquelyn Hennek, Slava Katerov, Hatim T. Allawi, Dragan Jevremovic, Linda N. Dao, Rondell P. Graham, John B. Kisiel
Journal: American Journal of Hematology (2024)

Lymphoma is one of the leading causes of cancer and cancer deaths and yet has not been amenable to population screening. The role of methylated DNA markers (MDMs) in the detection of lymphoma has not been extensively studied. We aimed to discover, validate, and test tissue-derived MDMs of lymphoma in archival plasma specimens. Reduced representation bisulfite sequencing (RRBS) was performed on a discovery set of frozen tissues. MDMs identified were converted to methylation-specific PCR assays and validated on independent formalin-fixed, paraffin-embedded (FFPE) tissues. Target enrichment long-probe quantitative-amplified signal (TELQAS) assays were developed and assayed in plasma-extracted, bisulfite-converted DNA from independent treatment-naïve lymphoma patients and healthy controls. Prediction of cancer status was modeled using random forest model with in silico cross-validation. After discovery and validation in tissue, 16 TELQAS assays (ZNF503, VWA5B1, HOXA9, GABRG3, ITGA5, MAX.chr17.7190, BNC1, CDK20, MAX.chr4.4069, TPBG, DNAH14, SYT6, CACNG8, FAM110B, ADRA1D, and NRN1) were selected for testing in plasma. These detected 78% (95% CI, 74%-82%) of lymphoma cases at 90% specificity. Excluding marginal zone and T-cell lymphomas, sensitivity increased to 84% (80%-88%). MDMs in plasma show promise to detect lymphoma and are candidates for inclusion in multi-cancer detection studies.
Different impacts of granulocyte colony‐stimulating factor administration on allogeneic hematopoietic cell transplant outcomes for adult acute myeloid leukemia according to graft type
Authors: Takaaki Konuma, Kazuaki Kameda, Kaoru Morita, Tadakazu Kondo, Fumihiko Kimura, Hideki Nakasone, Fumihiko Ouchi, Naoyuki Uchida, Masatsugu Tanaka, Tetsuya Nishida, Takahiro Fukuda, Yuta Hasegawa, Mamiko Sakata‐Yanagimoto, Makoto Onizuka, Masashi Sawa, Shuichi Ota, Noboru Asada, Shin‐Ichiro Fujiwara, Satoshi Yoshihara, Fumihiko Ishimaru, Makoto Yoshimitsu, Yoshinobu Kanda, Marie Ohbiki, Yoshiko Atsuta, Masamitsu Yanada
Journal: American Journal of Hematology (2024)

We retrospectively evaluated the impacts of using granulocyte colony-stimulating factor (G-CSF) and its timing on posttransplant outcomes for 9766 adults with acute myeloid leukemia (AML) between 2013 and 2022 using a Japanese database. We separately evaluated three distinct cohorts based on graft type: 3248 received bone marrow transplantation (BMT), 3066 received peripheral blood stem cell transplantation (PBSCT), and 3452 received single-unit cord blood transplantation (CBT). Multivariate analysis showed that G-CSF administration significantly accelerated neutrophil recovery after BMT, PBSCT, and CBT. However, it was associated with a higher risk of grades II-IV acute graft-versus-host disease (GVHD) across all graft types. Moreover, an increased incidence of overall chronic GVHD was observed with G-CSF administration in BMT and CBT patients, but not in PBSCT patients. G-CSF administration significantly improved overall survival (OS) and leukemia-free survival (LFS) only following CBT. Regarding the timing of G-CSF, in comparison with late initiation of G-CSF (Days 5-10), early initiation (Days 0-4) did not provide benefits for hematopoietic recovery regardless of graft type. In contrast, late initiation was significantly associated with a lower risk of grades II-IV acute GVHD and better OS and LFS in CBT patients. These data demonstrated that G-CSF administration accelerated neutrophil recovery and increased the risk of grades II-IV acute GVHD across all graft types, but significantly improved survival outcomes but only following CBT. Therefore, routine use of G-CSF should be considered for CBT in adult patients with AML.
Evaluating the effects of the World Health Organization's online intervention ‘iSupport’ to reduce depression and distress in dementia carers: a multi-centre six-month randomised controlled trial in the UK
Authors: Gill Windle, Greg Flynn, Zoe Hoare, Nia Goulden, Rhiannon Tudor Edwards, Bethany Anthony, Patricia Masterson Algar, Suman Kurana, Aimee Spector, Gwenllian Hughes, Ryan Innes, John Connaghan, Danielle Proctor, Fatene Abakar Ismail, Kiara Jackson, Kieren Egan, Joshua Stott
Journal: The Lancet Regional Health - Europe (2024)
Cellular senescence in Alzheimer’s disease: from physiology to pathology
Authors: Jing Zhu, Chongyun Wu, Luodan Yang
Journal: Translational Neurodegeneration (2024)

Abstract Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders, characterized by the accumulation of Aβ and abnormal tau hyperphosphorylation. Despite substantial efforts in development of drugs targeting Aβ and tau pathologies, effective therapeutic strategies for AD remain elusive. Recent attention has been paid to the significant role of cellular senescence in AD progression. Mounting evidence suggests that interventions targeting cellular senescence hold promise in improving cognitive function and ameliorating hallmark pathologies in AD. This narrative review provides a comprehensive summary and discussion of the physiological roles, characteristics, biomarkers, and commonly employed in vivo and in vitro models of cellular senescence, with a particular focus on various cell types in the brain, including astrocytes, microglia, oligodendrocyte precursor cells, neurons, and endothelial cells. The review further delves into factors influencing cellular senescence in AD and emphasizes the significance of targeting cellular senescence as a promising approach for AD treatment, which includes the utilization of senolytics and senomorphics.
Prognostic factors in localized pancreatic ductal adenocarcinoma after neoadjuvant therapy and resection: a systematic review and Meta-Analysis
Authors: Ammar A Javed, Alyssar Habib, Omar Mahmud, Asad Saulat Fatimi, Mahip Grewal, Nabiha Mughal, Jin He, Christopher L Wolfgang, Lois Daamen, Marc G Besselink
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Introduction Prognostic markers for overall survival (OS) in resected pancreatic ductal adenocarcinoma (PDAC) are well-established but remain unclear following neoadjuvant therapy (NAT). This systematic review and meta-analysis aimed to determine factors associated with OS following NAT in resected PDAC. Methods The PubMed, Embase, Scopus, Web of Science, and Cochrane CENTRAL databases were systematically searched from inception till May 2024. Studies that reported univariable and multivariable hazard ratios (HRs) were included if patients underwent NAT and resection for localized PDAC. Study quality assessment was performed using the Newcastle-Ottawa scale. Meta-analysis was performed using generic inverse-variance random-effects models. Results Among 2,208 unique articles identified by the search, 92 were included in the meta-analysis. Eighty-five of these were of 'good' and 7 of 'poor' quality. The NAT regimen was described in 84 studies, of which 62 included patients treated with FOLFIRINOX (FFX). Margin status, nodal disease, AJCC T-stage, and normalization of CA19-9 after NAT were prognostic for OS, while age, sex, perineural invasion, baseline tumor size, and baseline CA19-9 were not. The test for subgroup differences between ypN-substages was not significant in the multivariable model. Neoadjuvant FFX was associated with better survival than other regimens. Conclusions This meta-analysis identified margin status, nodal disease, AJCC T-stage, and normalization of CA19-9 after NAT as prognostic factors for OS in patients with resected localized PDAC following NAT.
Venetoclax combined with three-day multi-frequency decitabine (DEC3-VEN) in elder or intensive chemotherapy ineligible patients with newly diagnosed acute myeloid leukemia
Authors: Xiaohui Suo, Xiaojun Ma, Fang Zheng, Dongmei Wang, Guanchen Bai, Liyun Zhao, Zhongjing Han, Xin Lv, Congcong Zhang, Ju Wang, Kangxin Tuo, Zhen Meng, Shan Liu, Sifeng Gao, Jilei Zhang, Zongjiu Jiao, Jiaojie Song, Ling Li, Xinxiao Lu, Linyu Yuan, Kaiqi Liu, Xingli Zhao, Yingchang Mi
Journal: Blood Cancer Journal (2024)
Global patterns of leukemia by subtype, age, and sex in 185 countries in 2022
Authors: Dagrun S. Daltveit, Eileen Morgan, Murielle Colombet, Eva Steliarova-Foucher, Karima Bendahhou, Rafael Marcos-Gragera, Zheng Rongshou, Alexandra Smith, Hui Wei, Isabelle Soerjomataram
Journal: Leukemia (2024)
Impact of Respiratory Syncytial Virus (RSV) on adult haematology oncology patients
Authors: F Farina, D Sannipoli, E Diral, S Mastaglio, C Oltolini, R Dell'Acqua, M Marcatti, V Ferla, L Canziani, E Xue, D Clerici, A Bruno, S Marktel, M G Carrabba, M Bernardi, A Carmagnola, V Spagnuolo, P Scarpellini, M Moro, J Peccatori, R Greco, F Ciceri, C Corti, M T Lupo-Stanghellini
Journal: Journal of Infection (2024)
Hypertensive pregnancy disorder, an under‐recognized women specific risk factor for heart failure?
Authors: Chahinda Ghossein‐Doha, Basky Thilaganathan, Arthur Jason Vaught, Joan E. Briller, Jolien W. Roos‐Hesselink
Journal: European Journal of Heart Failure (2024)

Abstract During pregnancy, the maternal cardiovascular (CV) system undergoes major haemodynamic alterations ensuring adequate placental perfusion and a healthy pregnancy course. Hypertensive disorders of pregnancy (HDP) occur in almost 10% of gestations and preeclampsia, a more severe form, in 3–4%. Women with HDP demonstrated impaired myocardial function, biventricular chamber dysfunction and adverse biventricular remodelling. Shortly after delivery, women who experienced HDP express increased risk of classic CV risk factors such as hypertension, renal disease, abnormal lipid profile, and diabetes. Within the first two decades following a HDP, women experience increased rates of heart failure, chronic hypertension, ischaemic heart and cerebral disease. The mechanism underlying the relationship between HDP in younger women and CV disease later in life could be explained by sharing pre‐pregnancy CV risk factors or due to a direct impact of HDP on the maternal CV system conferring a state of increased susceptibility to future metabolic or haemodynamic insults. Racial disparities in CV risk and social determinants of health also play an important role in their remote CV risk. Although there is general agreement that women who suffered from HDP should undertake early CV screening to allow appropriate prevention and timely treatment, a screening and intervention protocol has not been standardized due to limited available evidence. In this review, we discuss why women with hypertensive pregnancy may be disproportionately affected by heart failure with preserved ejection fraction and how cardiac remodelling during or after pregnancy may influence its development.
Knowledge and application of <scp>ESC</scp>/<scp>HFA</scp> guidelines in the management of advanced heart failure
Authors: Guillaume Baudry, Nicolas Girerd, Maja Cikes, Maria Generosa Crespo‐Leiro, Kevin Damman, Clément Delmas, Stamatis Adamopoulos, Sanem Nalbantgil, Hoong Sern Lim, Frank Ruschitzka, Marco Metra, Finn Gustafsson
Journal: European Journal of Heart Failure (2024)

Aims Management of advanced heart failure (HF) remains challenging despite specific sections in the 2021 European Society of Cardiology/Heart Failure Association (ESC/HFA) guidelines, with delays in referrals exacerbating the issue. This study aimed to evaluate the awareness and implementation of these guidelines among cardiologists and identify barriers to effective referral. Methods and results From June to October 2023, an online survey was disseminated through the ESC mailing list, targeting cardiologists across Europe. The survey investigated four areas: guideline awareness, healthcare network organization, clinical case management, and perceptions of mechanical circulatory support (MCS) outcomes. Respondents were categorized into heart failure cardiologists (HFCs), general cardiologists (GCs), and other participants (OPs). Among 497 respondents, 25% were heart HFCs, 40% were GCs, and 35% were OPs. A total of 84% of HFCs reported a high level of guideline knowledge, compared to 57% of GCs and 62% of OPs ( p &lt; 0.001). Additionally, 76% of HFCs ‘regularly or always’ used ESC/HFA criteria to identify advanced HF, compared to 44% of GCs and 48% of OPs ( p &lt; 0.001). Correct responses regarding the recommendation class for heart transplantation were 84%, 55%, and 60% ( p &lt; 0.0001), and for MCS as a bridge to transplantation, 69%, 65%, and 55% ( p = 0.018) among HFCs, GCs, and OPs, respectively. Referring patients with severe HF to a tertiary centre team was found to be ‘very difficult’ or ‘difficult’ by 8.4% of HFCs, 19.6% of GCs, and 18.2% of OPs ( p = 0.0005). Conclusion The study highlights significant disparities in knowledge and application of advanced HF guidelines among cardiologists, revealing an opportunity for educational initiatives. The difficulty in referring patients to tertiary centres underscores the need to improve the referral pathway for advanced HF patients.
Effects of sacubitril/valsartan according to background beta‐blocker therapy in patients with heart failure and reduced ejection fraction: Insights from <scp>PARADIGM</scp>‐<scp>HF</scp>
Authors: Sharmistha Datta Gupta, Jawad H. Butt, Eoghan G.M. McMurray, Atefeh Talebi, Shingo Matsumoto, Adel R. Rizkala, Alasdair D. Henderson, Akshay S. Desai, Martin Lefkowitz, Milton Packer, Jean L. Rouleau, Scott D. Solomon, Karl Swedberg, Michael R. Zile, Pardeep S. Jhund, John J.V. McMurray
Journal: European Journal of Heart Failure (2024)