tbuckley/cabot-search huggingface dataset:
Retraction Notice to: Inhibition of Multiple Protective Signaling Pathways and Ad.5/3 Delivery Enhances mda-7/IL-24 Therapy of Malignant Glioma
Authors: Hossein A. Hamed, Adly Yacoub, Margaret A. Park, Patrick J. Eulitt, Rupesh Dash, Devanand Sarkar, Igor P. Dmitriev, Maciej S. Lesniak, Khalid Shah, Steven Grant, David T. Curiel, Paul B. Fisher, Paul Dent
Journal: Molecular Therapy (2024)
Thrombosis, brain metastasis formation, and the perivascular metastatic niche—novel insights from the tumor microvascular circulation
Authors: Christopher Alvarez-Breckenridge, Priscilla K Brastianos, Daniel P Cahill
Journal: Neuro-Oncology (2024)

Journal Article Accepted manuscript Thrombosis, brain metastasis formation, and the perivascular metastatic niche—novel insights from the tumor microvascular circulation Get access Christopher Alvarez-Breckenridge, Christopher Alvarez-Breckenridge Department of Neurosurgery, University of Texas MD Anderson Cancer Center, Houston, Texas, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Priscilla Brastianos, Priscilla Brastianos Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USACancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Daniel Cahill Daniel Cahill Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA Correspondence should be addressed: 55 Fruit Street, Yawkey 9E, Boston, MA 02114, cahill@mgh.harvard.edu Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, noae168, https://doi.org/10.1093/neuonc/noae168 Published: 29 August 2024 Article history Received: 20 August 2024 Published: 29 August 2024
Haemodynamic significance of extrinsic outflow graft stenoses during HeartMate 3™ therapy
Authors: Linus Ohlsson, Mårten Sandstedt, Joanna-Maria Papageorgiou, Anders Svensson, Ann Bolger, Éva Tamás, Hans Granfeldt, Tino Ebbers, Jonas Lantz
Journal:  (2024)

The HeartMate 3 (HM3) implantable left ventricular assist device connects the left ventricle apex to the aorta via an outflow graft. Extrinsic obstruction of the graft (eOGO) is associated with serious morbidity and mortality and recently led to a Food and Drug Administration Class 1 device recall of HM3. This study aimed to provide a better understanding of the haemodynamic impact of extrinsic stenoses.
A targetable type III immune response with increase of IL-17A expressing CD4+ T cells is associated with immunotherapy-induced toxicity in melanoma
Authors: Florentia Dimitriou, Phil F. Cheng, Annalisa Saltari, Katrin Schaper-Gerhardt, Ramon Staeger, Veronika Haunerdinger, Federica Sella, Aizhan Tastanova, Christian Urban, Susanne Dettwiler, Daniela Mihic-Probst, Christian M. Matter, Olivier Michielin, Ralf Gutzmer, Georgina V. Long, Burkhard Becher, Mitchell P. Levesque, Reinhard Dummer
Journal: Nature Cancer (2024)

Immune checkpoint inhibitors are standard-of-care for the treatment of advanced melanoma, but their use is limited by immune-related adverse events. Proteomic analyses and multiplex cytokine and chemokine assays from serum at baseline and at the adverse event onset indicated aberrant T cell activity with differential expression of type I and III immune signatures. This was in line with the finding of an increase in the proportion of CD4+ T cells with IL-17A expression at the adverse event onset in the peripheral blood using flow cytometry. Multiplex immunohistochemistry and spatial transcriptomics on immunotherapy-induced skin rash and colitis showed an increase in the proportion of CD4+ T cells with IL-17A expression. Anti-IL-17A was administered in two patients with mild myocarditis, colitis and skin rash with resolution of the adverse events. This study highlights the potential role of type III CD4+ T cells in adverse event development and provides proof-of-principle evidence for a clinical trial using anti-IL-17A for treating adverse events. Dimitriou et al. perform multiomic profiling of patients with melanoma experiencing immunotherapy-associated toxicity and identify a targetable role for type III-associated immune responses with an increase in CD4+ T cells expressing IL-17A.
Global 13C tracing and metabolic flux analysis of intact human liver tissue ex vivo
Authors: Nina Grankvist, Cecilia Jönsson, Karin Hedin, Nicolas Sundqvist, Per Sandström, Bergthor Björnsson, Arjana Begzati, Evgeniya Mickols, Per Artursson, Mohit Jain, Gunnar Cedersund, Roland Nilsson
Journal: Nature Metabolism (2024)

Abstract Liver metabolism is central to human physiology and influences the pathogenesis of common metabolic diseases. Yet, our understanding of human liver metabolism remains incomplete, with much of current knowledge based on animal or cell culture models that do not fully recapitulate human physiology. Here, we perform in-depth measurement of metabolism in intact human liver tissue ex vivo using global 13 C tracing, non-targeted mass spectrometry and model-based metabolic flux analysis. Isotope tracing allowed qualitative assessment of a wide range of metabolic pathways within a single experiment, confirming well-known features of liver metabolism but also revealing unexpected metabolic activities such as de novo creatine synthesis and branched-chain amino acid transamination, where human liver appears to differ from rodent models. Glucose production ex vivo correlated with donor plasma glucose, suggesting that cultured liver tissue retains individual metabolic phenotypes, and could be suppressed by postprandial levels of nutrients and insulin, and also by pharmacological inhibition of glycogen utilization. Isotope tracing ex vivo allows measuring human liver metabolism with great depth and resolution in an experimentally tractable system.
MIDAS: a new platform for quality-graded health data for AI-enabled healthcare in India
Authors: Dibyajyoti Maity, Rohit Satish, Dushyantsinh Anupsinh Jadeja, Raghu Dharmaraju, Vijay Chandru, Rajesh Sundaresan, Harpreet Singh, Debnath Pal
Journal: Nature Medicine (2024)
Rare coding variant analysis for human diseases across biobanks and ancestries
Authors: Sean J. Jurgens, Xin Wang, Seung Hoan Choi, Lu-Chen Weng, Satoshi Koyama, James P. Pirruccello, Trang Nguyen, Patrick Smadbeck, Dongkeun Jang, Mark Chaffin, Roddy Walsh, Carolina Roselli, Amanda L. Elliott, Leonoor F. J. M. Wijdeveld, Kiran J. Biddinger, Shinwan Kany, Joel T. Rämö, Pradeep Natarajan, Krishna G. Aragam, Jason Flannick, Noël P. Burtt, Connie R. Bezzina, Steven A. Lubitz, Kathryn L. Lunetta, Patrick T. Ellinor
Journal: Nature Genetics (2024)
Genetics and precision genomics approaches to pulmonary hypertension
Authors: Eric D. Austin, Micheala A. Aldred, Mona Alotaibi, Stefan Gräf, William C. Nichols, Richard C. Trembath, Wendy K. Chung
Journal: European Respiratory Journal (2024)

Considerable progress has been made in the genomics of pulmonary arterial hypertension (PAH) since the 6th World Symposium on Pulmonary Hypertension, with the identification of rare variants in several novel genes, as well as common variants that confer a modest increase in PAH risk. Gene and variant curation by an expert panel now provides a robust framework for knowing which genes to test and how to interpret variants in clinical practice. We recommend that genetic testing be offered to specific subgroups of symptomatic patients with PAH, and to children with certain types of group 3 pulmonary hypertension (PH). Testing of asymptomatic family members and the use of genetics in reproductive decision-making require the involvement of genetics experts. Large cohorts of PAH patients with biospecimens now exist and extension to non-group 1 PH has begun. However, these cohorts are largely of European origin; greater diversity will be essential to characterise the full extent of genomic variation contributing to PH risk and treatment responses. Other types of omics data are also being incorporated. Furthermore, to advance gene- and pathway-specific care and targeted therapies, gene-specific registries will be essential to support patients and their families and to lay the foundation for genetically informed clinical trials. This will require international outreach and collaboration between patients/families, clinicians and researchers. Ultimately, harmonisation of patient-derived biospecimens, clinical and omic information, and analytic approaches will advance the field.
Geriatric assessment for the practicing clinician: The why, what, and how
Authors: Allison Magnuson, Kah Poh Loh, Fiona Stauffer, William Dale, Nikesha Gilmore, Sindhuja Kadambi, Heidi D. Klepin, Kaitlin Kyi, Lisa M. Lowenstein, Tanyanika Phillips, Erika Ramsdale, Melody K. Schiaffino, John F. Simmons, Grant R. Williams, Jason Zittel, Supriya Mohile
Journal: CA A Cancer Journal for Clinicians (2024)

Abstract Older adults with cancer heterogeneously experience health care, treatment, and symptoms. Geriatric assessment (GA) offers a comprehensive evaluation of an older individual's health status and can predict cancer‐related outcomes in individuals with solid tumors and those with hematologic malignancies. In the last decade, randomized controlled trials have demonstrated the benefits of GA and GA management (GAM), which uses GA information to provide tailored intervention strategies to address GA impairments (e.g., implementing physical therapy for impaired physical function). Multiple phase 3 clinical trials in older adults with solid tumors and hematologic malignancies have demonstrated that GAM improves treatment completion, quality of life, communication, and advance care planning while reducing treatment‐related toxicity, falls, and polypharmacy. Nonetheless, implementation and uptake of GAM remain challenging. Various strategies have been proposed, including the use of GA screening tools, to identify patients most likely to benefit from GAM, the systematic engagement of the oncology workforce in the delivery of GAM, and the integration of technologies like telemedicine and mobile health to enhance the availability of GA and GAM interventions. Health inequities in minoritized groups persist, and systematic GA implementation has the potential to capture social determinants of health that are relevant to equitable care. Caregivers play an important role in cancer care and experience burden themselves. GA can guide dyadic supportive care interventions, ultimately helping both patients and caregivers achieve optimal health.
The Development of Lung Tissue Engineering: From Biomaterials to Multicellular Systems
Authors: Jingge Ma, Chengtie Wu, Jinfu Xu
Journal: Advanced Healthcare Materials (2024)

The challenge of the treatment of end-stage lung disease poses an urgent clinical demand for lung tissue engineering. Over the past few years, various lung tissue-engineered constructs are developed for lung tissue regeneration and respiratory pathology study. In this review, an overview of recent achievements in the field of lung tissue engineering is proposed. The introduction of lung structure and lung injury are stated briefly at first. After that, the lung tissue-engineered constructs are categorized into three types: acellular, monocellular, and multicellular systems. The different bioengineered constructs included in each system that can be applied to the reconstruction of the trachea, airway epithelium, alveoli, and even whole lung are described in detail, followed by the highlight of relevant representative research. Finally, the challenges and future directions of biomaterials, manufacturing technologies, and cells involved in lung tissue engineering are discussed. Overall, this review can provide referable ideas for the realization of functional lung regeneration and permanent lung substitution.
Clinical trial design, end-points, and emerging therapies in pulmonary arterial hypertension
Authors: Jason Weatherald, Thomas R. Fleming, Martin R. Wilkins, Thomas M. Cascino, Mitchell A. Psotka, Roham Zamanian, Werner Seeger, Nazzareno Galiè, Mardi Gomberg-Maitland
Journal: European Respiratory Journal (2024)

Clinical trials in pulmonary arterial hypertension (PAH) have led to the approval of several effective treatments that improve symptoms, exercise capacity and clinical outcomes. In phase 3 clinical trials, primary end-points must reflect how a patient "feels, functions or survives". In a rare disease like PAH, with an ever-growing number of treatment options and numerous candidate therapies being studied, future clinical trials are now faced with challenges related to sample size requirements, efficiency and demonstration of incremental benefit on traditional end-points in patients receiving background therapy with multiple drugs. Novel clinical trial end-points, innovative trial designs and statistical approaches and new technologies may be potential solutions to tackle the challenges facing future PAH trials, but these must be acceptable to patients and regulatory bodies while preserving methodological rigour. In this World Symposium on Pulmonary Hypertension task force article, we address emerging trial end-points and designs, biomarkers and surrogate end-point validation, the concept of disease modification, challenges and opportunities to address diversity and representativeness, and the use of new technologies such as artificial intelligence in PAH clinical trials.
Emerging multimodality imaging techniques for the pulmonary circulation
Authors: Sudarshan Rajagopal, Harm J. Bogaard, Mohammed S.M. Elbaz, Benjamin H. Freed, Martine Remy-Jardin, Edwin J.R. van Beek, Deepa Gopalan, David G. Kiely
Journal: European Respiratory Journal (2024)

Pulmonary hypertension (PH) remains a challenging condition to diagnose, classify and treat. Current approaches to the assessment of PH include echocardiography, ventilation/perfusion scintigraphy, cross-sectional imaging using computed tomography and magnetic resonance imaging, and right heart catheterisation. However, these approaches only provide an indirect readout of the primary pathology of the disease: abnormal vascular remodelling in the pulmonary circulation. With the advent of newer imaging techniques, there is a shift toward increased utilisation of noninvasive high-resolution modalities that offer a more comprehensive cardiopulmonary assessment and improved visualisation of the different components of the pulmonary circulation. In this review, we explore advances in imaging of the pulmonary vasculature and their potential clinical translation. These include advances in diagnosis and assessing treatment response, as well as strategies that allow reduced radiation exposure and implementation of artificial intelligence technology. These emerging modalities hold the promise of developing a deeper understanding of pulmonary vascular disease and the impact of comorbidities. They also have the potential to improve patient outcomes by reducing time to diagnosis, refining classification, monitoring treatment response and improving our understanding of disease mechanisms.
Low-cost and scalable projected light-sheet microscopy for the high-resolution imaging of cleared tissue and living samples
Authors: Yannan Chen, Shradha Chauhan, Cheng Gong, Hannah Dayton, Cong Xu, Estanislao Daniel De La Cruz, Yu-Young Wesley Tsai, Malika S. Datta, Gorazd B. Rosoklija, Andrew J. Dwork, J. John Mann, Maura Boldrini, Kam W. Leong, Lars E. P. Dietrich, Raju Tomer
Journal: Nature Biomedical Engineering (2024)
Pathophysiology of the right ventricle and its pulmonary vascular interaction
Authors: Anna R. Hemnes, David S. Celermajer, Michele D'Alto, Francois Haddad, Paul M. Hassoun, Kurt W. Prins, Robert Naeije, Anton Vonk Noordegraaf
Journal: European Respiratory Journal (2024)

The right ventricle and its stress response is perhaps the most important arbiter of survival in patients with pulmonary hypertension of many causes. The physiology of the cardiopulmonary unit and definition of right heart failure proposed in the 2018 World Symposium on Pulmonary Hypertension have proven useful constructs in subsequent years. Here, we review updated knowledge of basic mechanisms that drive right ventricular function in health and disease, and which may be useful for therapeutic intervention in the future. We further contextualise new knowledge on assessment of right ventricular function with a focus on metrics readily available to clinicians and updated understanding of the roles of the right atrium and tricuspid regurgitation. Typical right ventricular phenotypes in relevant forms of pulmonary vascular disease are reviewed and recent studies of pharmacological interventions on chronic right ventricular failure are discussed. Finally, unanswered questions and future directions are proposed.
Identification of a specific APOE transcript and functional elements associated with Alzheimer’s disease
Authors: Qiang Chen, Luis Aguirre, Guoming Liang, Huanhuan Zhao, Tao Dong, Felix Borrego, Itziar de Rojas, Qichan Hu, Christopher Reyes, Ling-Yan Su, Bao Zhang, James D. Lechleiter, Harald H. H. Göring, Philip L. De Jager, Joel E. Kleinman, Thomas M. Hyde, Pan P. Li, Agustín Ruiz, Daniel R. Weinberger, Sudha Seshadri, Liang Ma
Journal: Molecular Neurodegeneration (2024)

The APOE gene is the strongest genetic risk factor for late-onset Alzheimer's Disease (LOAD). However, the gene regulatory mechanisms at this locus remain incompletely characterized.
Exploiting WEE1 kinase activity as FUS::DDIT3-dependent therapeutic vulnerability in myxoid liposarcoma
Authors: Lorena Heinst, Kwang Seok Lee, Ruth Berthold, Ilka Isfort, Svenja Wosnig, Anna Kuntze, Susanne Hafner, Bianca Altvater, Claudia Rossig, Pierre Åman, Eva Wardelmann, Claudia Scholl, Wolfgang Hartmann, Stefan Fröhling, Marcel Trautmann
Journal: Clinical Cancer Research (2024)

Abstract Purpose: The pathognomonic FUS::DDIT3 fusion protein drives myxoid liposarcoma (MLS) tumorigenesis via aberrant transcriptional activation of oncogenic signaling. As FUS::DDIT3 has so far not been pharmacologically tractable to selectively target MLS cells, this study investigated the functional role of the cell cycle regulator WEE1 as novel FUS::DDIT3-dependent therapeutic vulnerability in MLS. Experimental Design: Immunohistochemical evaluation of the cell cycle regulator WEE1 was performed in a large cohort of MLS specimens. FUS::DDIT3 dependency and biological function of the G1/S cell cycle checkpoint were analyzed in a mesenchymal stem cell model and liposarcoma cell lines in vitro. WEE1 activity was modulated by RNAi-mediated knockdown and the small molecule inhibitor MK-1775 (adavosertib). An established MLS cell line–based chicken chorioallantoic membrane model was employed for in vivo confirmation. Results: We demonstrate that enhanced WEE1 pathway activity represents a hallmark of FUS::DDIT3-expressing cell lines as well as MLS tissue specimens and that WEE1 is required for MLS cellular survival in vitro and in vivo. Pharmacologic inhibition of WEE1 activity results in DNA damage accumulation and cell cycle progression forcing cells to undergo apoptotic cell death. In addition, our results uncover FUS::DDIT3-dependent WEE1 expression as an oncogenic survival mechanism to tolerate high proliferation and resulting replication stress in MLS. Fusion protein–driven G1/S cell cycle checkpoint deregulation via overactive Cyclin E/CDK2 complexes thereby contributes to enhanced WEE1 inhibitor sensitivity in MLS. Conclusions: Our preclinical study identifies WEE1-mediated replication stress tolerance as molecular vulnerability in FUS::DDIT3-driven MLS tumorigenesis that could represent a novel target for therapeutic intervention.
Characteristics of blood–brain barrier heterogeneity between brain regions revealed by profiling vascular and perivascular cells
Authors: Sarah J. Pfau, Urs H. Langen, Theodore M. Fisher, Indumathi Prakash, Faheem Nagpurwala, Ricardo A. Lozoya, Wei-Chung Allen Lee, Zhuhao Wu, Chenghua Gu
Journal: Nature Neuroscience (2024)

Abstract The blood–brain barrier (BBB) protects the brain and maintains neuronal homeostasis. BBB properties can vary between brain regions to support regional functions, yet how BBB heterogeneity occurs is poorly understood. Here, we used single-cell and spatial transcriptomics to compare the mouse median eminence, one of the circumventricular organs that has naturally leaky blood vessels, with the cortex. We identified hundreds of molecular differences in endothelial cells (ECs) and perivascular cells, including astrocytes, pericytes and fibroblasts. Using electron microscopy and an aqueous-based tissue-clearing method, we revealed distinct anatomical specializations and interaction patterns of ECs and perivascular cells in these regions. Finally, we identified candidate regionally enriched EC–perivascular cell ligand–receptor pairs. Our results indicate that both molecular specializations in ECs and unique EC–perivascular cell interactions contribute to BBB functional heterogeneity. This platform can be used to investigate BBB heterogeneity in other regions and may facilitate the development of central nervous system region-specific therapeutics.
YY1-controlled regulatory connectivity and transcription are influenced by the cell cycle
Authors: Jessica C. Lam, Nicholas G. Aboreden, Susannah C. Midla, Siqing Wang, Anran Huang, Cheryl A. Keller, Belinda Giardine, Kate A. Henderson, Ross C. Hardison, Haoyue Zhang, Gerd A. Blobel
Journal: Nature Genetics (2024)
Transplantation, bridging, and support technologies in pulmonary hypertension
Authors: Laurent Savale, Alberto Benazzo, Paul Corris, Shaf Keshavjee, Deborah Jo Levine, Olaf Mercier, R. Duane Davis, John T. Granton
Journal: European Respiratory Journal (2024)

Despite the progress made in medical therapies for treating pulmonary hypertension (PH), a subset of patients remain susceptible to developing a maladaptive right ventricular phenotype. The effective management of end-stage PH presents substantial challenges, necessitating a multidisciplinary approach and early identification of patients prone to acute decompensation. Identifying potential transplant candidates and assessing the feasibility of such a procedure are pivotal tasks that should be undertaken early in the treatment algorithm. Inclusion on the transplant list is contingent upon a comprehensive risk assessment, also considering the specific type of PH and various factors affecting waiting times, all of which should inform the decision-making process. While bilateral lung transplantation is the preferred option, it demands expert intra- and post-operative management to mitigate the heightened risks of pulmonary oedema and primary graft dysfunction in PH patients. Despite the availability of risk assessment tools, the occurrence of acute PH decompensation episodes can be unpredictable, potentially leading to refractory right ventricular failure even with optimal medical intervention, necessitating the use of rescue therapies. Advancements in right ventricular assist techniques and adjustments to graft allocation protocols for the most critically ill patients have significantly enhanced the survival in intensive care, affording the opportunity to endure while awaiting an urgent transplant. Given the breadth of therapeutic options available, specialised centres capable of delivering comprehensive care have become indispensable for optimising patient outcomes. These centres are instrumental in providing holistic support and management tailored to the complex needs of PH patients, ultimately enhancing their chances of a successful transplant and improved long-term prognosis.
ImAge quantitates aging and rejuvenation
Authors: Martin Alvarez-Kuglen, Kenta Ninomiya, Haodong Qin, Delany Rodriguez, Lorenzo Fiengo, Chen Farhy, Wei-Mien Hsu, Brian Kirk, Aaron Havas, Gen-Sheng Feng, Amanda J. Roberts, Rozalyn M. Anderson, Manuel Serrano, Peter D. Adams, Tatyana O. Sharpee, Alexey V. Terskikh
Journal: Nature Aging (2024)