tbuckley/cabot-search huggingface dataset:
Vertical Integration and the Transformation of American Medicine
Authors: Dhruv Khullar, Lawrence P Casalino, Amelia M Bond
Journal: New England Journal of Medicine (2024)

Audio Interview Interview with Dhruv Khullar on the trend of hospital acquisition of physician practices in the United States. 8m 57s Download AbstractHospital acquisition of physician practices has become a dominant trend in American medicine. The FTC and the DOJ recently issued guidelines that could strengthen their approach to vertical integration in health care.
Genetic variation drives differences in obesity-related gene regulation
Authors: Minna U. Kaikkonen
Journal: Trends in Genetics (2024)

Heikkinen and colleagues recently demonstrated that genetic variation, rather than dietary changes, governs gene regulation in liver. This finding highlights the impact of noncoding variants on chromatin accessibility, histone modifications, transcription factor binding, and gene expression and has implications for future research directions in understanding the genetic basis of disease.
The latest insights into rare blood disorders: Diagnosis and treatment strategies
Authors: David J. Kuter, Spero R. Cataland, Catherine M. Broome, Cindy Neunert
Journal: American Journal of Hematology (2024)

Please visit https://bit.ly/AJHpodcast to complete the accredited learning activity and receive CME credit or NCPD contact hours. Because immune-mediated rare blood disorders are uncommon, healthcare providers often lack the knowledge and experience necessary to identify, diagnose, and treat them in accordance with best practices. As a result, there are significant gaps in care, including delays in diagnosis and suboptimal treatment. To ensure that more patients with these rare disorders are offered quality, evidence-based care, it is essential that healthcare providers possess up-to-date information about best practices and new developments in this area of medicine. In this activity, composed of three podcasts, an expert moderator will interview three expert faculty members about evidence-based guidelines for the diagnosis and treatment of acquired thrombotic thrombocytopenic purpura; developments in the diagnosis and treatment of cold agglutinin disease; and the challenges of achieving enduring remission in patients with immune thrombocytopenia.
Self-adaptive pyroptosis-responsive nanoliposomes block pyroptosis in autoimmune inflammatory diseases
Authors: Kaiwang Xu, Huang Yang, Jinghua Fang, Kaijie Qiu, Haotian Shen, Guanrui Huang, Qiangqiang Zheng, Canlong Wang, Tengjing Xu, Xinning Yu, Jiajie Wang, Yunting Lin, Jiacheng Dai, Yuting Zhong, Hongyun Song, Sunan Zhu, Siheng Wang, Zhuxing Zhou, Guang Yang, Zhengwei Mao, Zongyou Pan, Xuesong Dai
Journal: Bioactive Materials (2024)

Nanoliposomes have a broad range of applications in the treatment of autoimmune inflammatory diseases because of their ability to considerably enhance drug transport. For their clinical application, nanoliposomes must be able to realize on-demand release of drugs at disease sites to maximize drug-delivery efficacy and minimize side effects. Therefore, responsive drug-release strategies for inflammation treatment have been explored; however, no specific design has been realized for a responsive drug-delivery system based on pyroptosis-related inflammation. Herein, we report a pioneering strategy for self-adaptive pyroptosis-responsive liposomes (R8-cardiolipin-containing nanoliposomes encapsulating dimethyl fumarate, RC-NL@DMF) that precisely release encapsulated anti-pyroptotic drugs into pyroptotic cells. The activated key pyroptotic protein, the
Do the associations of daily steps with mortality and incident cardiovascular disease differ by sedentary time levels? A device-based cohort study
Authors: Matthew N Ahmadi, Leandro F M Rezende, Gerson Ferrari, Borja Del Pozo Cruz, I-Min Lee, Emmanuel Stamatakis
Journal: British Journal of Sports Medicine (2024)

Objectives This study aims to examine the associations of daily step count with all-cause mortality and incident cardiovascular disease (CVD) by sedentary time levels and to determine if the minimal and optimal number of daily steps is modified by high sedentary time. Methods Using data from the UK Biobank, this was a prospective dose–response analysis of total daily steps across low (&lt;10.5 hours/day) and high (≥10.5 hours/day) sedentary time (as defined by the inflection point of the adjusted absolute risk of sedentary time with the two outcomes). Mortality and incident CVD was ascertained through 31 October 2021. Results Among 72 174 participants (age=61.1±7.8 years), 1633 deaths and 6190 CVD events occurred over 6.9 (±0.8) years of follow-up. Compared with the referent 2200 steps/day (5th percentile), the optimal dose (nadir of the curve) for all-cause mortality ranged between 9000 and 10 500 steps/day for high (HR (95% CI)=0.61 (0.51 to 0.73)) and low (0.69 (0.52 to 0.92)) sedentary time. For incident CVD, there was a subtle gradient of association by sedentary time level with the lowest risk observed at approximately 9700 steps/day for high (0.79 (0.72 to 0.86)) and low (0.71 (0.61 to 0.83)) sedentary time. The minimal dose (steps/day associated with 50% of the optimal dose) of daily steps was between 4000 and 4500 steps/day across sedentary time groups for all-cause mortality and incident CVD. Conclusions Any amount of daily steps above the referent 2200 steps/day was associated with lower mortality and incident CVD risk, for low and high sedentary time. Accruing 9000–10 500 steps/day was associated with the lowest mortality risk independent of sedentary time. For a roughly equivalent number of steps/day, the risk of incident CVD was lower for low sedentary time compared with high sedentary time.
Predictive Performance of an Updated Polygenic Risk Score for Age-Related Macular Degeneration
Authors: Chenglong Yu, Liubov Robman, Weixiong He, Robyn L. Woods, Le Thi Phuong Thao, Rory Wolfe, James Phung, Galina A. Makeyeva, Lauren A.B. Hodgson, John J. McNeil, Robyn H. Guymer, Stuart MacGregor, Paul Lacaze
Journal: Ophthalmology (2024)
Epigenetic control over the cell-intrinsic immune response antagonizes self-renewal in acute myeloid leukemia
Authors: Eloísa Felipe Fumero, Carolin Walter, Joris Maximillian Frenz, Franca Seifert, Vijay Alla, Thorben Hennig, Linus Angenendt, Wolfgang Hartmann, Sebastian Wolf, Hubert Serve, Thomas Oellerich, Georg Lenz, Carsten Müller-Tidow, Christoph Schliemann, Otmar Huber, Martin Dugas, Matthias Mann, Ashok Kumar Jayavelu, Jan-Henrik Mikesch, Maria Francisca Arteaga
Journal: Blood (2024)

Abstract Epigenetic modulation of the cell-intrinsic immune response holds promise as a therapeutic approach for leukemia. However, current strategies designed for transcriptional activation of endogenous transposons and subsequent interferon type-I (IFN-I) response, show limited clinical efficacy. Histone lysine methylation is an epigenetic signature in IFN-I response associated with suppression of IFN-I and IFN-stimulated genes, suggesting histone demethylation as key mechanism of reactivation. In this study, we unveil the histone demethylase PHF8 as a direct initiator and regulator of cell-intrinsic immune response in acute myeloid leukemia (AML). Site-specific phosphorylation of PHF8 orchestrates epigenetic changes that upregulate cytosolic RNA sensors, particularly the TRIM25-RIG-I-IFIT5 axis, thereby triggering the cellular IFN-I response-differentiation-apoptosis network. This signaling cascade largely counteracts differentiation block and growth of human AML cells across various disease subtypes in vitro and in vivo. Through proteome analysis of over 200 primary AML bone marrow samples, we identify a distinct PHF8/IFN-I signature in half of the patient population, without significant associations with known clinically or genetically defined AML subgroups. This profile was absent in healthy CD34+ hematopoietic progenitor cells, suggesting therapeutic applicability in a large fraction of patients with AML. Pharmacological support of PHF8 phosphorylation significantly impairs the growth in samples from patients with primary AML. These findings provide novel opportunities for harnessing the cell-intrinsic immune response in the development of immunotherapeutic strategies against AML.
Impact of risk-based therapy on late morbidity and mortality in neuroblastoma survivors: a report from the Childhood Cancer Survivor Study
Authors: Danielle Novetsky Friedman, Pamela J Goodman, Wendy M Leisenring, Lisa R Diller, Susan L Cohn, Rebecca M Howell, Susan A Smith, Emily S Tonorezos, Suzanne L Wolden, Joseph P Neglia, Kirsten K Ness, Todd M Gibson, Paul C Nathan, Lucie M Turcotte, Brent R Weil, Leslie L Robison, Kevin C Oeffinger, Gregory T Armstrong, Charles A Sklar, Tara O Henderson
Journal: JNCI Journal of the National Cancer Institute (2024)

Early efforts at risk-adapted therapy for neuroblastoma are predicted to result in differential late effects; the magnitude of these differences has not been well described.
New treatment options for critically important WHO fungal priority pathogens
Authors: Lisa Kriegl, Matthias Egger, Johannes Boyer, Martin Hoenigl, Robert Krause
Journal: Clinical Microbiology and Infection (2024)

BackgroundYet often overlooked in public health discourse, fungal infections pose a crucialglobal disease burden associated with annual mortality rates approximately equal to tuberculosis and HIV. In response, the World Health Organization (WHO) published its first global priority list of fungal pathogens in 2022 assigning Aspergillus fumigatus, Candida albicans, Candida auris, and Cryptococcus neoformans to the critical group.ObjectivesThis review provides succinct insights on novel antifungals in development, aiming to contribute valuable information and perspectives with focus on recent clinical findings and new treatment approaches for critical members of the WHO fungal pathogen priority list.SourcesPubMed literature search using "Aspergillus fumigatus," "Cryptococcus neoformans," "Candida auris," and "Candida albicans," along with the names of novel antifungal substances, including "fosmanogepix", "ibrexafungerp", "opelconazole", "oteseconazole", "MAT2203", "olorofim", and "rezafungin" was conducted.ContentForeach critical pathogen, current issues and global clinical data from recent trials are covered. The remarkable development of three new antifungal therapeutics recently receiving Food and Drug Administration (FDA) approval (ibrexafungerp -June 2021, oteseconazole -April 2022, rezafungin -March 2023) is outlined, with two more exciting new antifungal substances, namely olorofim and fosmanogepix expecting approval within the next years. Ibrexafungerp, fosmanogepix and rezafungin have additionally been granted orphan drug status by the European Medicines Agency (EMA) in Europe (ibrexafungerp -November 2021, fosmanogepix -July 2022, rezafungin -January 2024).ImplicationsWhile the limited number of targets and the emergence of resistance have posed challenges to antifungal treatment, new drugs such as ibrexafungerp, rezafungin, fosmanogepix, or olorofim have shown promising clinical efficacy. These drugs not only provide alternative options for invasive fungal infections but also alleviate treatment in outpatient settings. More clinical data, implementation of stewardship programs, and surveillance, including utilization of drugs in agriculture are necessary to prevent resistance development and ensure the safety and efficacy of these new agents.
Diagnostic tests for human Schistosoma mansoni and Schistosoma haematobium infection: a systematic review and meta-analysis
Authors: Michel T Vaillant, Fred Philippy, Anouk Neven, Jessica Barré, Dmitry Bulaev, Piero L Olliaro, Jürg Utzinger, Jennifer Keiser, Amadou T Garba
Journal: The Lancet Microbe (2024)
Long-Term Effectiveness and Durability of COVID-19 Vaccination Among Patients With Inflammatory Bowel Disease
Authors: Erica J. Brenner, Kimberly N. Weaver, Xian Zhang, Arthur J. Kastl, Jennifer A. Strople, Jeremy Adler, Marla C. Dubinsky, Athos Bousvaros, Runa Watkins, Xiangfeng Dai, Wenli Chen, Raymond K. Cross, Peter D.R. Higgins, Ryan C. Ungaro, Meenakshi Bewtra, Emanuelle A. Bellaguarda, Francis A. Farraye, Kelly Y. Chun, Michael Zikry, Monique Bastidas, Ann Firestine, Riley G. Craig, Margie E. Boccieri, Millie D. Long, Michael D. Kappelman
Journal: Clinical Gastroenterology and Hepatology (2024)
<i>Myb</i> overexpression synergizes with the loss of <i>Pten</i> and is a dependency factor and therapeutic target in T‐cell lymphoblastic leukemia
Authors: André Almeida, Sara T'Sas, Luca Pagliaro, Igor Fijalkowski, Wouter Sleeckx, Hannah Van Steenberge, Raffaella Zamponi, Béatrice Lintermans, Wouter Van Loocke, Bruno Palhais, Alexandra Reekmans, Valentina Bardelli, Lisa Demoen, Lindy Reunes, Dieter Deforce, Filip Van Nieuwerburgh, Alex Kentsis, Panagiotis Ntziachristos, Nadine Van Roy, Barbara De Moerloose, Cristina Mecucci, Roberta La Starza, Giovanni Roti, Steven Goossens, Pieter Van Vlierberghe, Tim Pieters
Journal: HemaSphere (2024)

T-lineage acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy that accounts for 10%-15% of pediatric and 25% of adult ALL cases. Although the prognosis of T-ALL has improved over time, the outcome of T-ALL patients with primary resistant or relapsed leukemia remains poor. Therefore, further progress in the treatment of T-ALL requires a better understanding of its biology and the development of more effective precision oncologic therapies. The proto-oncogene
Comprehensive analysis of <i>MYB/MYBL1</i>-altered pediatric-type diffuse low-grade glioma
Authors: Daniel C Moreira, Ibrahim Qaddoumi, Susan Spiller, Thomas W Bouldin, Alan Davidson, Nasjla Saba-Silva, Daniel V Sullivan, Ryuma Tanaka, Aaron S Wagner, Matthew Wood, Paul Klimo, Godwin Job, Meenakshi Devidas, Xiaoyu Li, Amar Gajjar, Giles W Robinson, Jason Chiang
Journal: Neuro-Oncology (2024)

Abstract Background Pediatric-type diffuse low-grade gliomas (pLGG) harboring recurrent genetic alterations involving MYB or MYBL1 are closely related tumors. Detailed treatment and outcome data of large cohorts are still limited. This study aimed to comprehensively evaluate pLGG with these alterations to define optimal therapeutic strategies. Methods We retrospectively reviewed details of pLGG with MYB or MYBL1 alterations from patients treated or referred for pathologic review at St. Jude Children’s Research Hospital. Tumor specimens were centrally reviewed, and clinical data were collated. Results Thirty-three patients (18 male; median age, 5 years) were identified. Two tumors had MYBL1 alterations; 31 had MYB alterations, MYB::QKI fusion being the most common (n = 10, 30%). Most tumors were in the cerebral hemispheres (n = 22, 67%). Two patients (6%) had metastasis at diagnosis. The median follow-up was 6.1 years. The 5-year event-free survival (EFS) rate was 81.3% ± 8.3%; the 5-year overall survival (OS) rate was 96.4% ± 4.1%. Patients receiving a near-total or gross-total resection had a 5-year EFS of 100%; those receiving a biopsy or subtotal resection had a 5-year EFS rate of 56.6% ± 15.2% (P &amp;lt; .01). No difference in EFS was observed based on location, histology, or molecular alterations. However, the tumors that progressed or metastasized may have distinct methylation profiles with evidence of activation of the MAPK and PI3K/AKT/mTOR pathways. Conclusions pLGG with MYB/MYBL1 alterations have good outcomes. Our findings suggest that surgical resectability is a crucial determinant of EFS. Further characterization is required to identify optimal treatment strategies for progressive tumors.
Challenges, limitations, and pitfalls of PET and advanced MRI in patients with brain tumors: A report of the PET/RANO group
Authors: Norbert Galldiks, Timothy J Kaufmann, Philipp Vollmuth, Philipp Lohmann, Marion Smits, Michael C Veronesi, Karl-Josef Langen, Roberta Rudà, Nathalie L Albert, Elke Hattingen, Ian Law, Markus Hutterer, Riccardo Soffietti, Michael A Vogelbaum, Patrick Y Wen, Michael Weller, Joerg-Christian Tonn
Journal: Neuro-Oncology (2024)

Abstract Brain tumor diagnostics have significantly evolved with the use of positron emission tomography (PET) and advanced magnetic resonance imaging (MRI) techniques. In addition to anatomical MRI, these modalities may provide valuable information for several clinical applications such as differential diagnosis, delineation of tumor extent, prognostication, differentiation between tumor relapse and treatment-related changes, and the evaluation of response to anticancer therapy. In particular, joint recommendations of the Response Assessment in Neuro-Oncology (RANO) Group, the European Association of Neuro-oncology, and major European and American Nuclear Medicine societies highlighted that the additional clinical value of radiolabeled amino acids compared to anatomical MRI alone is outstanding and that its widespread clinical use should be supported. For advanced MRI and its steadily increasing use in clinical practice, the Standardization Subcommittee of the Jumpstarting Brain Tumor Drug Development Coalition provided more recently an updated acquisition protocol for the widely used dynamic susceptibility contrast perfusion MRI. Besides amino acid PET and perfusion MRI, other PET tracers and advanced MRI techniques (e.g. MR spectroscopy) are of considerable clinical interest and are increasingly integrated into everyday clinical practice. Nevertheless, these modalities have shortcomings which should be considered in clinical routine. This comprehensive review provides an overview of potential challenges, limitations, and pitfalls associated with PET imaging and advanced MRI techniques in patients with gliomas or brain metastases. Despite these issues, PET imaging and advanced MRI techniques continue to play an indispensable role in brain tumor management. Acknowledging and mitigating these challenges through interdisciplinary collaboration, standardized protocols, and continuous innovation will further enhance the utility of these modalities in guiding optimal patient care.
Frameshift mutations in peripheral blood as a biomarker for surveillance of Lynch syndrome
Authors: Yurong Song, Holli Loomans-Kropp, Ryan N Baugher, Brandon Somerville, Shaneen S Baxter, Travis D Kerr, Teri M Plona, Stephanie D Mellott, Todd B Young, Heidi E Lawhorn, Lei Wei, Qiang Hu, Song Liu, Alan Hutson, Ligia Pinto, John D Potter, Shizuko Sei, Ozkan Gelincik, Steven M Lipkin, Johannes Gebert, Matthias Kloor, Robert H Shoemaker
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background Lynch syndrome is a hereditary cancer predisposition syndrome caused by germline mutations in DNA mismatch repair genes, which lead to high microsatellite instability and frameshift mutations at coding mononucleotide repeats in the genome. Recurrent frameshift mutations in these regions are thought to play a central role in the increased risk of various cancers, but no biomarkers are currently available for the surveillance of high microsatellite instability-associated cancers. Methods A frameshift mutation-based biomarker panel was developed and validated by targeted next-generation sequencing of supernatant DNA from cultured high microsatellite instability colorectal cancer cells. This panel supported selection of 122 frameshift mutation targets as potential biomarkers. This biomarker panel was then tested using matched tumor, adjacent normal tissue, and buffy coat samples (53 samples) and blood-derived cell-free DNA (cfDNA) (38 samples) obtained from 45 high microsatellite instability and mismatch repair-deficient patients. We also sequenced cfDNA from 84 healthy participants to assess background noise. Results Recurrent frameshift mutations at coding mononucleotide repeats were detectable not only in tumors but also in cfDNA from high microsatellite instability and mismatch repair-deficient patients, including a Lynch syndrome carrier, with a varying range of target detection (up to 85.2%), whereas they were virtually undetectable in healthy participants. Receiver operating characteristic curve analysis showed high sensitivity and specificity (area under the curve = 0.94) of the investigated panel. Conclusions We demonstrated that frameshift mutations can be detected in cfDNA from high microsatellite instability and mismatch repair-deficient patients and asymptomatic carriers. The 122-target frameshift mutation panel described here has promise as a tool for improved surveillance of high microsatellite instability and mismatch repair-deficient patients, with the potential to reduce the frequency of invasive screening methods for this high-cancer-risk cohort.
Very long-term outcomes of pediatric patients treated for optic pathway gliomas: A longitudinal cohort study
Authors: Alice Morin, Rodrigue Allodji, Dulanjalee Kariyawasam, Philippe Touraine, Stéphanie Puget, Kevin Beccaria, Emilie De Carli, Virginie Kieffer, Sophie Rivollet, Samuel Abbou, Chiraz Fayech, Vincent Souchard, Christelle Dufour, Florent De Vathaire, Stéphanie Bolle, Jacques Grill, Brice Fresneau
Journal: Neuro-Oncology (2024)

Optic pathway gliomas (OPGs) represent 5% of childhood brain tumors. Successive relapses lead to multiple treatments exposing to late complications.
Tracing the origin of SARS-CoV-2 omicron-like spike sequences detected in an urban sewershed: a targeted, longitudinal surveillance study of a cryptic wastewater lineage
Authors: Martin M Shafer, Max J Bobholz, William C Vuyk, Devon A Gregory, Adelaide Roguet, Luis A Haddock Soto, Clayton Rushford, Kayley H Janssen, Isla E Emmen, Hunter J Ries, Hannah E Pilch, Paige A Mullen, Rebecca B Fahney, Wanting Wei, Matthew Lambert, Jeff Wenzel, Peter Halfmann, Yoshihiro Kawaoka, Nancy A Wilson, Thomas C Friedrich, Ian W Pray, Ryan Westergaard, David H O'Connor, Marc C Johnson
Journal: The Lancet Microbe (2024)
SCancerRNA: Expression at the Single Cell Level and Interaction Resource of Non-coding RNA Biomarkers for Cancers
Authors: Hongzhe Guo, Liyuan Zhang, Xinran Cui, Liang Cheng, Tianyi Zhao, Yadong Wang
Journal: Genomics Proteomics & Bioinformatics (2024)

Abstract Non-coding RNAs (ncRNAs) participate in multiple biological processes associated with cancers as tumor suppressors or oncogenic drivers. Due to their high stability in plasma, urine, and many other fluids, ncRNAs have the potential to serve as key biomarkers for early diagnosis and screening of cancers. During cancer progression, tumor heterogeneity plays a crucial role, and it is particularly important to understand the gene expression patterns of individual cells. With the development of single-cell RNA sequencing (scRNA-seq) technologies, uncovering gene expression in different cell types for human cancers has become feasible by profiling transcriptomes at the cellular level. However, a well-organized and comprehensive online resource that provides access to the expression of genes corresponding to ncRNA biomarkers in different cell types at the single-cell level is not available yet. Therefore, we developed the SCancerRNA database to summarize experimentally supported data on long ncRNA, microRNA, PIWI-interacting RNA, small nucleolar RNA, and circular RNA biomarkers, as well as data on their differential expression at the cellular level. Furthermore, we collected biological functions and clinical applications of biomarkers to facilitate the application of ncRNA biomarkers to cancer diagnosis, as well as the monitoring of progression and targeted therapies. SCancerRNA also allows users to explore interaction networks of different types of ncRNAs, and build computational models in the future. SCancerRNA is freely accessible at http://www.scancerrna.com/BioMarker.