tbuckley/cabot-search huggingface dataset:
Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype
Authors: Mate Maus, Vanessa López-Polo, Lidia Mateo, Miguel Lafarga, Mònica Aguilera, Eugenia De Lama, Kathleen Meyer, Anna Sola, Cecilia Lopez-Martinez, Ines López-Alonso, Marc Guasch-Piqueras, Fernanda Hernandez-Gonzalez, Selim Chaib, Miguel Rovira, Mayka Sanchez, Rosa Faner, Alvar Agusti, Rodrigo Diéguez-Hurtado, Sagrario Ortega, Anna Manonelles, Stefan Engelhardt, Freddy Monteiro, Camille Stephan-Otto Attolini, Neus Prats, Guillermo Albaiceta, Josep M. Cruzado, Manuel Serrano
Journal: Nature Metabolism (2023)

Abstract Fibrogenesis is part of a normal protective response to tissue injury that can become irreversible and progressive, leading to fatal diseases. Senescent cells are a main driver of fibrotic diseases through their secretome, known as senescence-associated secretory phenotype (SASP). Here, we report that cellular senescence, and multiple types of fibrotic diseases in mice and humans are characterized by the accumulation of iron. We show that vascular and hemolytic injuries are efficient in triggering iron accumulation, which in turn can cause senescence and promote fibrosis. Notably, we find that senescent cells persistently accumulate iron, even when the surge of extracellular iron has subdued. Indeed, under normal conditions of extracellular iron, cells exposed to different types of senescence-inducing insults accumulate abundant ferritin-bound iron, mostly within lysosomes, and present high levels of labile iron, which fuels the generation of reactive oxygen species and the SASP. Finally, we demonstrate that detection of iron by magnetic resonance imaging might allow non-invasive assessment of fibrotic burden in the kidneys of mice and in patients with renal fibrosis. Our findings suggest that iron accumulation plays a central role in senescence and fibrosis, even when the initiating events may be independent of iron, and identify iron metabolism as a potential therapeutic target for senescence-associated diseases.
Restoration of sensory feedback from the foot and reduction of phantom limb pain via closed-loop spinal cord stimulation
Authors: Ameya C. Nanivadekar, Rohit Bose, Bailey A. Petersen, Elizaveta V. Okorokova, Devapratim Sarma, Tyler J. Madonna, Beatrice Barra, Juhi Farooqui, Ashley N. Dalrymple, Isaiah Levy, Eric R. Helm, Vincent J. Miele, Michael L. Boninger, Marco Capogrosso, Sliman J. Bensmaia, Douglas J. Weber, Lee E. Fisher
Journal: Nature Biomedical Engineering (2023)
Immunoglobulin light chain amyloidosis: 2024 update on diagnosis, prognosis, and treatment
Authors: Morie A. Gertz
Journal: American Journal of Hematology (2023)

Abstract Disease Overview Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include heart failure with preserved ejection fraction, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and “atypical smoldering multiple myeloma or MGUS.” Diagnosis Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple‐green birefringence is required for the diagnosis of AL amyloidosis. Organ biopsy is not required in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. The gold standard is laser capture mass spectroscopy. Prognosis N‐terminal pro–brain natriuretic peptide (NT‐proBNP or BNP), serum troponin T(or I), and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four stages; 5‐year survivals are 82%, 62%, 34%, and 20%, respectively. Therapy All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. Current first‐line therapy with the best outcome is daratumumab, bortezomib, cyclophosphamide, and dexamethasone. The goal of therapy is a ≥VGPR. In patients failing to achieve this depth of response options for consolidation include pomalidomide, stem cell transplantation, venetoclax, and bendamustine. Future Challenges Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end‐stage organ failure. Trials of antibodies to deplete deposited fibrils are underway.
Occupational anaphylaxis—Data from the anaphylaxis registry
Authors: Margitta Worm, Veronika Höfer, Sabine Dölle‐Bierke, Maria Beatrice Bilo, Karin Hartmann, Dominique Sabouraud‐Leclerc, Regina Treudler
Journal: Allergy (2023)

Abstract Background Epidemiologic data on occupational anaphylaxis is scarce, and there is a need of more knowledge about work‐related anaphylactic episodes. Methods Based on the data of the Anaphylaxis Registry, we identified cases related to occupational exposure and analyzed the elicitors, demographics, severity of clinical reaction and management. Results Since 2017, 5851 cases with an information about the occupational relation of the anaphylactic episode were registered whereby 225 (3.8%) were assigned to be caused by an occupational allergen. The vast majority of these occupational anaphylaxis cases were caused by insects ( n = 186, 82.7%) followed by food ( n = 27, 12.0%) and drugs ( n = 8, 3.6%). Latex elicited occupational anaphylaxis in only two cases. Beekeepers, gardeners, farmers, and individuals working in professions associated with food handling, for example, employees in restaurants, bakery, pastry, and cooks were most frequently affected. The comparison of the occupational insect venom‐induced anaphylaxis to a group of non‐occupational insect anaphylaxis in adults ( n = 1842) revealed a significant younger age in occupational anaphylaxis (46 vs. 53 years), a predominance of bee‐induced cases (38% vs. 17%), and a higher rate of venom immunotherapy in a primary care setting (3.3% vs. 1.3%, p = .044). In the occupational‐ versus non‐occupational adults with food‐induced anaphylaxis atopic dermatitis as concomitant atopic disease was observed more frequently ( n = 486; 20% vs. 10%), although this was not significant. Conclusion Our data demonstrate the impact of venom allergy in work‐related anaphylaxis. Foods and drugs are less frequently elicitors, and latex‐induced occupational anaphylaxis was rare. More data are needed to determine risk factors associated with occupational anaphylaxis.
Clinical and Molecular Characteristics of Gonadotroph Pituitary Tumors According to the WHO Classification
Authors: Francesca Carbonara, Tiziana Feola, Francesca Gianno, Michela Anna Polidoro, Rosa Maria Di Crescenzo, Antonietta Arcella, Michelangelo De Angelis, Roberta Morace, Dario de Alcubierre, Vincenzo Esposito, Felice Giangaspero, Marie-Lise Jaffrain-Rea
Journal: Endocrine Pathology (2023)

Abstract Since 2017, hormone-negative pituitary neuroendocrine tumors expressing the steroidogenic factor SF1 have been recognized as gonadotroph tumors (GnPT) but have been poorly studied. To further characterize their bio-clinical spectrum, 54 GnPT defined by immunostaining for FSH and/or LH (group 1, n = 41) or SF1 only (group 2, n = 13) were compared and studied for SF1 , βFSH , βLH , CCNA2 , CCNB1 , CCND1 , caspase 3 , D2R , and AIP gene expression by qRT-PCR. Immunohistochemistry for AIP and/or D2R was performed in representative cases. Overall, patients were significantly younger in group 1 ( P = 0.040 vs group 2), with a similar trend excluding recurrent cases ( P = 0.078), and no significant difference in gender, tumor size, invasion or Ki67. SF1 expression was similar in both groups but negatively correlated with the patient’s age ( P = 0.013) and positively correlated with βLH ( P &lt; 0.001) expression. Beta-FSH and AIP were significantly higher in group 1 ( P = 0.042 and P = 0.024, respectively). Ki67 was unrelated to gonadotroph markers but positively correlated with CCNB1 ( P = 0.001) and negatively correlated with CCND1 ( P = 0.008). D2R and AIP were strongly correlated with each other ( P &lt; 0.001), and both positively correlated with SF1 , βFSH , βLH , and CCND1 . AIP immunopositivity was frequently observed in both groups, with a similar median score, and unrelated to Ki67. D2R immunostaining was best detected with a polyclonal antibody and mostly cytoplasmic. This study indicates that hormone-negative GnPT tend to occur in older patients but do not significantly differ from other GnPT in terms of invasion or proliferation. It also points out the current limits of D2R immunostaining in such tumors.
Reply: Simplifying pharmacotherapy for patients with COPD: a viewpoint
Authors: Bartolome Celli, Jørgen Vestbo
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>There are evidence-based arguments showing that it is possible to provide precision pharmacological treatment for COPD patients, using current clinical, physiological and biological markers available to most healthcare providers</b>https://bit.ly/4a4mus7
Role of the immune system in liver transplantation and its implications for therapeutic interventions
Authors: Guanrong Chen, Xin Hu, Yingchen Huang, Xiaonan Xiang, Sheng Pan, Ronggao Chen, Xiao Xu
Journal: MedComm (2023)

Abstract Liver transplantation (LT) stands as the gold standard for treating end‐stage liver disease and hepatocellular carcinoma, yet postoperative complications continue to impact survival rates. The liver's unique immune system, governed by a microenvironment of diverse immune cells, is disrupted during processes like ischemia–reperfusion injury posttransplantation, leading to immune imbalance, inflammation, and subsequent complications. In the posttransplantation period, immune cells within the liver collaboratively foster a tolerant environment, crucial for immune tolerance and liver regeneration. While clinical trials exploring cell therapy for LT complications exist, a comprehensive summary is lacking. This review provides an insight into the intricacies of the liver's immune microenvironment, with a specific focus on macrophages and T cells as primary immune players. Delving into the immunological dynamics at different stages of LT, we explore the disruptions after LT and subsequent immune responses. Focusing on immune cell targeting for treating liver transplant complications, we provide a comprehensive summary of ongoing clinical trials in this domain, especially cell therapies. Furthermore, we offer innovative treatment strategies that leverage the opportunities and prospects identified in the therapeutic landscape. This review seeks to advance our understanding of LT immunology and steer the development of precise therapies for postoperative complications.
Clinical remission with biologic therapies in severe asthma: a matter of definition
Authors: Richard Beasley, Jonathan Noble, Mark Weatherall
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>Biologic agents have transformed the treatment of severe asthma; however, whether they can induce remission remains to be determined. A crucial early step will be to define the specific criteria of disease remission, on which their effects can be measured.</b> https://bit.ly/3u0vjTa
BDH1‐mediated LRRC31 regulation dependent on histone lysine β‐hydroxybutyrylation to promote lung adenocarcinoma progression
Authors: Jingjing Huang, Lu Liang, Shiyao Jiang, Yueying Liu, Hua He, Xiaoyan Sun, Yi Li, Li Xie, Yongguang Tao, Li Cong, Yiqun Jiang
Journal: MedComm (2023)

Abstract Lung adenocarcinoma (LUAD) is the most common form of lung cancer, with a consistently low 5‐year survival rate. Therefore, we aim to identify key genes involved in LUAD progression to pave the way for targeted therapies in the future. BDH1 plays a critical role in the conversion between acetoacetate and β‐hydroxybutyrate. The presence of β‐hydroxybutyrate is essential for initiating lysine β‐hydroxybutyrylation (Kbhb) modifications. Histone Kbhb at the H3K9 site is attributed to transcriptional activation. We unveiled that β‐hydroxybutyrate dehydrogenase 1 (BDH1) is not only conspicuously overexpressed in LUAD, but it also modulates the overall intracellular Kbhb modification levels. The RNA sequencing analysis revealed leucine‐rich repeat‐containing protein 31 (LRRC31) as a downstream target gene regulated by BDH1. Ecologically expressed BDH1 hinders the accumulation of H3K9bhb in the transcription start site of LRRC31, consequently repressing the transcriptional expression of LRRC31. Furthermore, we identified potential BDH1 inhibitors, namely pimozide and crizotinib, which exhibit a synergistic inhibitory effect on the proliferation of LUAD cells exhibiting high expression of BDH1. In summary, this study elucidates the molecular mechanism by which BDH1 mediates LUAD progression through the H3K9bhb/LRRC31 axis and proposes a therapeutic strategy targeting BDH1‐high‐expressing LUAD, providing a fresh perspective for LUAD treatment.
An osteosarcoma-on-a-chip model for studying osteosarcoma matrix-cell interactions and drug responses
Authors: Zuyan Lu, XiangWan Miao, Chenyu Zhang, Binbin Sun, Aleksander Skardal, Anthony Atala, Songtao Ai, JiaNing Gong, Yongqiang Hao, Jie Zhao, Kerong Dai
Journal: Bioactive Materials (2023)

Marrow niches in osteosarcoma (OS) are a specialized microenvironment that is essential for the maintenance and regulation of OS cells. However, existing animal xenograft models are plagued by variability, complexity, and high cost. Herein, we used a decellularized osteosarcoma extracellular matrix (dOsEM) loaded with extracellular vesicles from human bone marrow-derived stem cells (hBMSC-EVs) and OS cells as a bioink to construct a micro-osteosarcoma (micro-OS) through 3D printing. The micro-OS was further combined with a microfluidic system to develop into an OS-on-a-chip (OOC) with a built-in recirculating perfusion system. The OOC system successfully integrated bone marrow niches, cell‒cell and cell-matrix crosstalk, and circulation, allowing a more accurate representation of OS characteristics
The intrinsic defects of T cells impact the efficacy of CAR-T therapy in patients with diffuse large B-cell lymphoma
Authors: Jinrong Zhao, Chong Wei, Shuqing Wang, Yan Zhang, Wei Wang, Danqing Zhao, Zi Wang, Zhipeng Zhou, Jing Bai, Wei Zhang, Daobin Zhou
Journal: Blood Cancer Journal (2023)

Abstract CAR-T cell therapy did not achieve the desired efficacy in some patients with diffuse large B-cell lymphoma (DLBCL). We conducted single-cell RNA and TCR sequencing as well as methylation chip profiling of peripheral blood samples in DLBCL patients. Patients who achieved complete remission (CR) showed an upward trend in T-cell levels, especially CD8-effector T cells. The responders exhibited T-cell clone expansion, more active T-cell transformation, and frequent cell communication. Highly expressed genes in the CR group were enriched in functions like leukocyte-mediated cytotoxicity and activation of immune response, while the non-CR group was enriched in pathways related to DNA damage and P53-mediated intrinsic apoptotic. More differentially methylated probes (DMPs) were identified in the baseline of the non-CR group (779 vs 350). GSEA analysis revealed that the genes annotated by DMPs were associated with cellular immune functions in T cells, including the generation of chemokines, leukocyte-mediated cytotoxicity, and cell-killing functions. The genes with low expression in the non-CR group exhibited a high methylation status. There is heterogeneity in the cellular, molecular, and epigenetic characteristics of host T cells in patients with different clinical outcomes. Intrinsic defects in T cells are important factors leading to poor efficacy of CAR-T therapy.
Glatiramer acetate induces mast cell degranulation via MRGPRX2, implications for local and systemic adverse reactions
Authors: Shaswati Chaki, Aetas Amponnawarat, Brett Levenstein, Yvonne Hui, Carole Oskeritzian, Hydar Ali
Journal: Allergy (2023)

Data sharing is not applicable to this article as no new data were created or analyzed in this study. Data S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Typhoid fever
Authors: James E. Meiring, Farhana Khanam, Buddha Basnyat, Richelle C. Charles, John A. Crump, Frederic Debellut, Kathryn E. Holt, Samuel Kariuki, Emmanuel Mugisha, Kathleen M. Neuzil, Christopher M. Parry, Virginia E. Pitzer, Andrew J. Pollard, Firdausi Qadri, Melita A. Gordon
Journal: Nature Reviews Disease Primers (2023)
Predicting Acute Changes in Suicidal Ideation and Planning: A Longitudinal Study of Symptom Mediators and the Role of the Menstrual Cycle in Female Psychiatric Outpatients With Suicidality
Authors: Jaclyn M. Ross, Jordan C. Barone, Hafsah Tauseef, Katja M. Schmalenberger, Anisha Nagpal, Natania A. Crane, Tory A. Eisenlohr-Moul
Journal: American Journal of Psychiatry (2023)

Cross-sectional and preliminary longitudinal findings suggest that cyclical ovarian hormone fluctuations influence acute suicide risk. The authors provide the first analyses in females with suicidality to investigate which daily symptoms covary with suicidal ideation and planning thoughts, the role of the menstrual cycle in daily symptom variation, how daily fluctuations in symptoms mediate the menstrual cycle-suicidality relationship, and how these associations vary across individuals.
Current Status and Principles for the Treatment and Prevention of Diabetic Foot Ulcers in the Cardiovascular Patient Population: A Scientific Statement From the American Heart Association
Authors: Katherine A. Gallagher, Joseph L. Mills, David G. Armstrong, Michael S. Conte, Robert S. Kirsner, Samantha D. Minc, Jorge Plutzky, Kevin W. Southerland, Marjana Tomic-Canic
Journal: Circulation (2023)

Despite the known higher risk of cardiovascular disease in individuals with type 2 diabetes, the pathophysiology and optimal management of diabetic foot ulcers (DFUs), a leading complication associated with diabetes, is complex and continues to evolve. Complications of type 2 diabetes, such as DFUs, are a major cause of morbidity and mortality and the leading cause of major lower extremity amputation in the United States. There has recently been a strong focus on the prevention and early treatment of DFUs, leading to the development of multidisciplinary diabetic wound and amputation prevention clinics across the country. Mounting evidence has shown that, despite these efforts, amputations associated with DFUs continue to increase. Furthermore, due to increasing patient complexity of management secondary to comorbid conditions, such as cardiovascular disease, the management of peripheral artery disease associated with DFUs has become increasingly difficult, and care delivery is often episodic and fragmented. Although structured, process-specific approaches exist at individual institutions for the management of DFUs in the cardiovascular patient population, there is insufficient awareness of these principles in the general medicine communities. Furthermore, there is growing interest in better understanding the mechanistic underpinnings of DFUs to better define personalized medicine to improve outcomes. The goals of this scientific statement are to provide salient background information on the complex pathogenesis and current management of DFUs in cardiovascular patients, to guide therapeutic and preventive strategies and future research directions, and to inform public policy makers on health disparities and other barriers to improving and advancing care in this expanding patient population.
Author Correction: Consensus Statement on the definition and classification of metabolic hyperferritinaemia
Authors: Luca Valenti, Elena Corradini, Leon A. Adams, Elmar Aigner, Saleh Alqahtani, Marco Arrese, Edouard Bardou-Jacquet, Elisabetta Bugianesi, Jose-Manuel Fernandez-Real, Domenico Girelli, Hannes Hagström, Benjamin Henninger, Kris Kowdley, Guido Ligabue, Donald McClain, Fabrice Lainé, Koji Miyanishi, Martina U. Muckenthaler, Alessia Pagani, Patrizia Pedrotti, Antonello Pietrangelo, Daniele Prati, John D. Ryan, Laura Silvestri, C. Wendy Spearman, Per Stål, Emmanuel A. Tsochatzis, Francesca Vinchi, Ming-Hua Zheng, Heinz Zoller
Journal: Nature Reviews Endocrinology (2023)
The Role of <i>MAPRE2</i> and Microtubules in Maintaining Normal Ventricular Conduction
Authors: David Y. Chiang, Arie O. Verkerk, Rachelle Victorio, Boris I. Shneyer, Babet van der Vaart, Mariam Jouni, Nakul Narendran, Ashmita Kc, James R. Sampognaro, Franki Vetrano-Olsen, John S. Oh, Eva Buys, Berend de Jonge, Disheet A. Shah, Tuomas Kiviniemi, Paul W. Burridge, Connie R. Bezzina, Anna Akhmanova, Calum A. MacRae
Journal: Circulation Research (2023)

Brugada syndrome is associated with loss-of-function
Troponin I Tyrosine Phosphorylation Beneficially Accelerates Diastolic Function
Authors: Lorien G. Salyer, Hussam E. Salhi, Elizabeth A. Brundage, Vikram Shettigar, Sarah L. Sturgill, Helena Zanella, Benjamin Templeton, Eaman Abay, Kathryn M. Emmer, Jeovanna Lowe, Jill A. Rafael-Fortney, Narasimham Parinandi, D. Brian Foster, Timothy A. McKinsey, Kathleen C. Woulfe, Mark T. Ziolo, Brandon J. Biesiadecki
Journal: Circulation Research (2023)

A healthy heart is able to modify its function and increase relaxation through post-translational modifications of myofilament proteins. While there are known examples of serine/threonine kinases directly phosphorylating myofilament proteins to modify heart function, the roles of tyrosine (Y) phosphorylation to directly modify heart function have not been demonstrated. The myofilament protein TnI (troponin I) is the inhibitory subunit of the troponin complex and is a key regulator of cardiac contraction and relaxation. We previously demonstrated that TnI-Y26 phosphorylation decreases calcium-sensitive force development and accelerates calcium dissociation, suggesting a novel role for tyrosine kinase-mediated TnI-Y26 phosphorylation to regulate cardiac relaxation. Therefore, we hypothesize that increasing TnI-Y26 phosphorylation will increase cardiac relaxation in vivo and be beneficial during pathological diastolic dysfunction.
Gynecological primary care of trans men and transmasculine non-binary individuals, a French descriptive study
Authors: Juliette Cuq, Lucie Jurek, Nicolas Morel-Journel, Séverine Oriol, Paul Neuville
Journal: International Journal of Transgender Health (2023)

Gynecological primary care is a public health issue, however, there is no French data on the transmasculine population, despite identified needs and a low coverage rate described in the international literature. The objective was to analyze the access of the French transmasculine population to gynecological primary care.
The locus coeruleus as a global model failure system
Authors: Rebecca Jordan
Journal: Trends in Neurosciences (2023)

Predictive processing models posit that brains constantly attempt to predict their sensory inputs. Prediction errors signal when these predictions are incorrect and are thought to be instructive signals that drive corrective plasticity. Recent findings support the idea that the locus coeruleus (LC) - a brain-wide neuromodulatory system - signals several types of prediction error. I discuss how these findings support models proposing that the LC signals global model failures: instances where predictions about the world are strongly violated. Focusing on the cortex, I explore the utility of this signal in learning rate control, how the LC circuit may compute the signal, and how this view may aid our understanding of neurodivergence.