tbuckley/cabot-search huggingface dataset:
Immune Dysfunction in Schizophrenia Spectrum Disorders
Authors: S.S. Gangadin, A.D. Enthoven, N.J.M. van Beveren, J.D. Laman, I.E.C. Sommer
Journal: Annual Review of Clinical Psychology (2024)

Evidence from epidemiological, clinical, and biological research resulted in the immune hypothesis: the hypothesis that immune system dysfunction is involved in the pathophysiology of schizophrenia spectrum disorders (SSD). The promising implication of this hypothesis is the potential to use existing immunomodulatory treatment for innovative interventions for SSD. Here, we provide a selective historical review of important discoveries that have shaped our understanding of immune dysfunction in SSD. We first explain the basic principles of immune dysfunction, after which we travel more than a century back in time. Starting our journey with neurosyphilis-associated psychosis in the nineteenth century, we continue by evaluating the role of infections and autoimmunity in SSD and findings from assessment of immune function using new techniques, such as cytokine levels, microglia density, neuroimaging, and gene expression. Drawing from these findings, we discuss anti-inflammatory interventions for SSD, and we conclude with a look into the future.
Targeting CERS6-AS1/FGFR1 axis as synthetic vulnerability to constrain stromal cells supported proliferation in Mantle cell lymphoma
Authors: Udita Jindal, Mukesh Mamgain, Uttam Kumar Nath, Isha Sharma, Bhaskar Pant, Ankita Sharma, Archita Gupta, Khaliqur Rahman, Sunil Yadav, Manish Pratap Singh, Shaktiprasad Mishra, Chandra Praksah Chaturvedi, Jose Courty, Navin Singh, Seema Gupta, Sanjeev Kumar, Shailendra Prasad Verma, Saumyaranjan Mallick, Ajay Gogia, Sunil Raghav, Jayanta Sarkar, Kinshuk Raj Srivastava, Dipak Datta, Neeraj Jain
Journal: Leukemia (2024)
Untargeted faecal metabolomics for the discovery of biomarkers and treatment targets for inflammatory bowel diseases
Authors: Arnau Vich Vila, Jingwan Zhang, Moting Liu, Klaas Nico Faber, Rinse K Weersma
Journal: Gut (2024)

The gut microbiome has been recognised as a key component in the pathogenesis of inflammatory bowel diseases (IBD), and the wide range of metabolites produced by gut bacteria are an important mechanism by which the human microbiome interacts with host immunity or host metabolism. High-throughput metabolomic profiling and novel computational approaches now allow for comprehensive assessment of thousands of metabolites in diverse biomaterials, including faecal samples. Several groups of metabolites, including short-chain fatty acids, tryptophan metabolites and bile acids, have been associated with IBD. In this
Prevalence of cancer survivors in the United States
Authors: Emily Tonorezos, Theresa Devasia, Angela B Mariotto, Michelle A Mollica, Lisa Gallicchio, Paige Green, Michelle Doose, Rachelle Brick, Brennan Streck, Crystal Reed, Janet S de Moor
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background With aging of the population and improvements in diagnosis, treatment, and supportive care, the number of cancer survivors in the United States has increased; updated prevalence estimates are needed. Methods Cancer prevalence on January 1, 2022, was estimated using the Prevalence Incidence Approach Model, utilizing incidence, survival, and mortality. Prevalence by age decade, sex, and time from diagnosis was calculated. The percentage of cancer survivors in the projected US population by age and sex was calculated as the ratio of the sex-specific projected prevalence to the sex-specific projected US population. Results There were an estimated 18.1 million US cancer survivors as of January 1, 2022. From 2022 to 2030, the number of US cancer survivors is projected to increase to 21.6 million; by 2040, the number is projected to be 26 million. Long-term survivors are highly prevalent; in 2022, 70% of cancer survivors had lived 5 years or more after diagnosis, and 11% of cancer survivors had lived 25 years or more after diagnosis. Among all US females aged 40-54 years, 3.6% were cancer survivors; among females aged 65-74 years, 14.5% were cancer survivors; among females aged 85 years and older, 36.4% were cancer survivors. Among all US males aged 40-54 years, 2.1% were cancer survivors; among males aged 65-74 years, 16% were cancer survivors; and among those aged 85 years and older, 48.3% were cancer survivors. Conclusions Cancer survivors are growing in number. In the United States, most cancer survivors are long-term and very long-term survivors, representing a substantial proportion of the US population.
Genetic deletion or pharmacologic inhibition of HDAC6 protects the heart against ischemia/reperfusion injury by limiting TNFα-induced mitochondrial injury in experimental diabetes
Authors: Shelley L Baumgardt, Juan Fang, Xuebin Fu, Yanan Liu, Zhengyuan Xia, Ming Zhao, Ling Chen, Rachana Mishra, Muthukumar Gunasekaran, Progyaparamita Saha, Joseph M Forbess, Zeljko J Bosnjak, Amadou K S Camara, Judy R Kersten, Edward B Thorp, Sunjay Kaushal, Zhi-Dong Ge
Journal: Cardiovascular Research (2024)

Abstract Aims The histone deacetylase 6 (HDAC6) inhibitor, tubastatin A (TubA), reduces myocardial ischaemia/reperfusion injury (MIRI) in type 1 diabetic rats. It remains unclear whether HDAC6 regulates MIRI in type 2 diabetic animals. Diabetes augments the activity of HDAC6 and the generation of tumour necrosis factor alpha (TNF-α) and impairs mitochondrial complex I (mCI). Here, we examined how HDAC6 regulates TNF-α production, mCI activity, mitochondria, and cardiac function in type 1 and type 2 diabetic mice undergoing MIRI. Methods and results HDAC6 knockout, streptozotocin-induced type 1 diabetic, and obese type 2 diabetic db/db mice underwent MIRI in vivo or ex vivo in a Langendorff-perfused system. We found that MIRI and diabetes additively augmented myocardial HDAC6 activity and generation of TNF-α, along with cardiac mitochondrial fission, low bioactivity of mCI, and low production of adenosine triphosphate. Importantly, genetic disruption of HDAC6 or TubA decreased TNF-α levels, mitochondrial fission, and myocardial mitochondrial nicotinamide adenine dinucleotide levels in ischaemic/reperfused diabetic mice, concomitant with augmented mCI activity, decreased infarct size, and improved cardiac function. Moreover, HDAC6 knockout or TubA treatment decreased left ventricular dilation and improved cardiac systolic function 28 days after MIRI. H9c2 cardiomyocytes with and without HDAC6 knockdown were subjected to hypoxia/reoxygenation injury in the presence of high glucose. Hypoxia/reoxygenation augmented HDAC6 activity and TNF-α levels and decreased mCI activity. These negative effects were blocked by HDAC6 knockdown. Conclusion HDAC6 is an essential negative regulator of MIRI in diabetes. Genetic deletion or pharmacologic inhibition of HDAC6 protects the heart from MIRI by limiting TNF-α–induced mitochondrial injury in experimental diabetes.
Long-term prognostic impact of fasting plasma glucose and myocardial flow reserve beyond other risk factors and heart disease phenotypes
Authors: Elena Filidei, Chiara Caselli, Luca Menichetti, Michela Poli, Debora Petroni, Letizia Guiducci, Oreste Sorace, Patrizia Pisani, Silvia Pardini, Danilo Bonora, Assuero Giorgetti, Alessia Gimelli, Danilo Neglia
Journal:  (2024)

Cardiometabolic risk factors, including high fasting plasma glucose (hFPG), are emerging prognostic determinants in patients with coronary artery disease (CAD) or heart failure (HF). Coronary microvascular dysfunction might be a comprehensive risk predictor in these patients. The purpose of this study was to assess whether hFPG and global myocardial blood flow (MBF) reserve measured by positron emission tomography (PET), expressing global coronary function, predict long-term prognosis beyond other risk factors and presence of obstructive CAD or left ventricular (LV) dysfunction associated with HF. We retrospectively collected long-term follow-up data in 103 patients (mean age 61 ± 10 years, 74 males) with stable chest pain or dyspnoea who underwent cardiac PET/computerized tomography and coronary angiography. Disease phenotypes included obstructive CAD (35%), LV dysfunction without obstructive CAD (43%), or none (22%). At multivariable logistic regression analysis, MBF reserve lower than the median value (OR 1.8, 95% CI 1.5-2.2) was significantly associated with male gender (OR 3.45, 95% CI 1.21-9.83) and hFPG (OR 3.87, 95% CI 1.17-12.84) among all risk factors. In a median follow-up of 10.9 years (interquartile range 7.8-13.9), 39 patients (37.8%) died (13.6% cardiac death). At multivariable Cox analyses including all risk factors and disease phenotypes, age (HR 1.07, 95% CI 1.02-1.12), hFPG (HR 2.18, 95% CI 1.02-4.63), and depressed MBF reserve (HR 4.47, 95% CI 1.96-10.18) were independent predictors of death (global
Necrotizing Soft-Tissue and Retropharyngeal Space Infections and Mediastinitis
Authors: Martin A Gomez, Beatriz Mejia
Journal: New England Journal of Medicine (2024)

A 50-year-old man presented with a 3-day history of jaw pain, fever, and shortness of breath. CT showed severe dental disease with gas formation in the retropharyngeal space, chest wall, and mediastinum.
Copper‐Based Composites Nanoparticles Improve Triple‐Negative Breast Cancer Treatment with Induction of Apoptosis‐Cuproptosis and Immune Activation
Authors: Ning Wang, Yichao Liu, Dezhou Peng, Qiyu Zhang, Zhibo Zhang, Lina Xu, Lianhong Yin, Xuerong Zhao, Zhi Lu, Jinyong Peng
Journal: Advanced Healthcare Materials (2024)

The synergistic effect of apoptosis and cuproptosis, along with the activation of the immune system, presents a promising approach to enhance the efficacy against triple-negative breast cancer (TNBC). Here, two prodrugs are synthesized: a reactive oxygen species (ROS)-responsive prodrug PEG-TK-DOX and a glutathione (GSH)-responsive prodrug PEG-DTPA-SS-CPT. These prodrugs are self-assembled and chelated Cu2+ to prepare nanoparticle PCD@Cu that simultaneously loaded doxorubicin (DOX), camptothecin (CPT), and Cu2+. The elevated levels of ROS and GSH in TNBC cells disrupted the PCD@Cu structure, leading to the release of Cu+, DOX, and CPT and the depletion of GSH. DOX and CPT triggered apoptosis with immunogenic cell death (ICD) in TNBC cells. Simultaneously, PCD@Cu downregulated the expression of copper transporting ATPase 2 (ATP7B), causing a significant accumulation of copper ions in TNBC cells. This further induced the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT) and downregulation of iron-sulfur (Fe-S) cluster proteins, ultimately leading to cuproptosis and ICD in TNBC. In vitro and in vivo experiments confirmed that PCD@Cu induced apoptosis and cuproptosis in TNBC and activated the immune system, demonstrating strong anti-tumor capabilities. Moreover, PCD@Cu exhibited an excellent biosafety profile. Overall, this study provides a promising strategy for effective TNBC therapy.
Hypoxic–Normoxic Crosstalk Activates Pro‐Inflammatory Signaling in Human Cardiac Fibroblasts and Myocytes in a Post‐Infarct Myocardium on a Chip
Authors: Natalie N. Khalil, Megan L. Rexius‐Hall, Divya Gupta, Liam McCarthy, Riya Verma, Austin C. Kellogg, Kaelyn Takamoto, Maryann Xu, Tiana Nejatpoor, Sarah J. Parker, Megan L. McCain
Journal: Advanced Healthcare Materials (2024)

Myocardial infarctions locally deprive myocardium of oxygenated blood and cause immediate cardiac myocyte necrosis. Irreparable myocardium is then replaced with a scar through a dynamic repair process that is an interplay between hypoxic cells of the infarct zone and normoxic cells of adjacent healthy myocardium. In many cases, unresolved inflammation or fibrosis occurs for reasons that are incompletely understood, increasing the risk of heart failure. Crosstalk between hypoxic and normoxic cardiac cells is hypothesized to regulate mechanisms of repair after a myocardial infarction. To test this hypothesis, microfluidic devices are fabricated on 3D printed templates for co-culturing hypoxic and normoxic cardiac cells. This system demonstrates that hypoxia drives human cardiac fibroblasts toward glycolysis and a pro-fibrotic phenotype, similar to the anti-inflammatory phase of wound healing. Co-culture with normoxic fibroblasts uniquely upregulates pro-inflammatory signaling in hypoxic fibroblasts, including increased secretion of tumor necrosis factor alpha (TNF-α). In co-culture with hypoxic fibroblasts, normoxic human induced pluripotent stem cell (hiPSC)-derived cardiac myocytes also increase pro-inflammatory signaling, including upregulation of interleukin 6 (IL-6) family signaling pathway and increased expression of IL-6 receptor. Together, these data suggest that crosstalk between hypoxic fibroblasts and normoxic cardiac cells uniquely activates phenotypes that resemble the initial pro-inflammatory phase of post-infarct wound healing.
Liquid–liquid phase separation in diseases
Authors: Xinyue Zhang, Lin Yuan, Wanlu Zhang, Yi Zhang, Qun Wu, Chunting Li, Min Wu, Yongye Huang
Journal: MedComm (2024)

Liquid-liquid phase separation (LLPS), an emerging biophysical phenomenon, can sequester molecules to implement physiological and pathological functions. LLPS implements the assembly of numerous membraneless chambers, including stress granules and P-bodies, containing RNA and protein. RNA-RNA and RNA-protein interactions play a critical role in LLPS. Scaffolding proteins, through multivalent interactions and external factors, support protein-RNA interaction networks to form condensates involved in a variety of diseases, particularly neurodegenerative diseases and cancer. Modulating LLPS phenomenon in multiple pathogenic proteins for the treatment of neurodegenerative diseases and cancer could present a promising direction, though recent advances in this area are limited. Here, we summarize in detail the complexity of LLPS in constructing signaling pathways and highlight the role of LLPS in neurodegenerative diseases and cancers. We also explore RNA modifications on LLPS to alter diseases progression because these modifications can influence LLPS of certain proteins or the formation of stress granules, and discuss the possibility of proper manipulation of LLPS process to restore cellular homeostasis or develop therapeutic drugs for the eradication of diseases. This review attempts to discuss potential therapeutic opportunities by elaborating on the connection between LLPS, RNA modification, and their roles in diseases.
Virus as the cause of type 1 diabetes
Authors: Knut Dahl-Jørgensen
Journal: Trends in Molecular Medicine (2024)

Type 1 diabetes (T1D), a severe disease requiring intensive insulin treatment, carries an increased risk for complications and reduced lifespan. Certain viruses have been implicated in T1D's etiology, with 'live', replicating enteroviruses (EVs) recently found in the pancreas at diagnosis. This discovery prompted a trial to slow down disease progression using antiviral drugs. A 6-month treatment combining pleconaril and ribavirin in new-onset T1D patients preserved residual insulin production after 1 year, unlike placebo. The results support the theory that viruses may cause T1D in genetically susceptible individuals. A low-grade, persistent viral infection may initiate a cascade of pathogenic mechanisms initially involving the innate immune system, inducing β-cell stress and neoantigen release, leading to autoimmunity, and eventually the destruction of insulin-producing β-cells.
Life histories are not just fast or slow
Authors: Iain Stott, Roberto Salguero-Gómez, Owen R. Jones, Thomas H.G. Ezard, Marlène Gamelon, Shelly Lachish, Jean-Dominique Lebreton, Emily G. Simmonds, Jean-Michel Gaillard, Dave J. Hodgson
Journal: Trends in Ecology & Evolution (2024)

HighlightsLife history studies support the fast–slow continuum as the dominant but not unique axis structuring life history variation.Other important axes of life history variation associated with development and reproductive tactics exist, and exploration of further axes, clusters, and boundaries of life history variation is needed.Existing life history analyses are venturing far from theory and could benefit from a stronger focus on hypothesis testing rather than exploration.We make recommendations to identify the structuring axes of life history variation through data choices and analytical methods of dimensionality reduction with recourse to a comprehensive model of life history.AbstractLife history strategies, which combine schedules of survival, development, and reproduction, shape how natural selection acts on species' heritable traits and organismal fitness. Comparative analyses have historically ranked life histories along a fast–slow continuum, describing a negative association between time allocation to reproduction and development versus survival. However, higher-quality, more representative data and analyses have revealed that life history variation cannot be fully accounted for by this single continuum. Moreover, studies often do not test predictions from existing theories and instead operate as exploratory exercises. To move forward, we offer three recommendations for future investigations: standardizing life history traits, overcoming taxonomic siloes, and using theory to move from describing to understanding life history variation across the Tree of Life.
Cellular senescence and metabolic reprogramming: Unraveling the intricate crosstalk in the immunosuppressive tumor microenvironment
Authors: Fusheng Zhang, Junchen Guo, Shengmiao Yu, Youwei Zheng, Meiqi Duan, Liang Zhao, Yihan Wang, Zhi Yang, Xiaofeng Jiang
Journal: Cancer Communications (2024)

Abstract The intrinsic oncogenic mechanisms and properties of the tumor microenvironment (TME) have been extensively investigated. Primary features of the TME include metabolic reprogramming, hypoxia, chronic inflammation, and tumor immunosuppression. Previous studies suggest that senescence‐associated secretory phenotypes that mediate intercellular information exchange play a role in the dynamic evolution of the TME. Specifically, hypoxic adaptation, metabolic dysregulation, and phenotypic shifts in immune cells regulated by cellular senescence synergistically contribute to the development of an immunosuppressive microenvironment and chronic inflammation, thereby promoting the progression of tumor events. This review provides a comprehensive summary of the processes by which cellular senescence regulates the dynamic evolution of the tumor‐adapted TME, with focus on the complex mechanisms underlying the relationship between senescence and changes in the biological functions of tumor cells. The available findings suggest that components of the TME collectively contribute to the progression of tumor events. The potential applications and challenges of targeted cellular senescence‐based and combination therapies in clinical settings are further discussed within the context of advancing cellular senescence‐related research.
Fluconazole-resistant Candida parapsilosis: fast detection of the Y132F ERG11p substitution, and a proposed microsatellite genotyping scheme
Authors: Jesús Guinea, Eva Alcoceba, Eduardo Padilla, Aída Ramírez, Elena De Carolis, Maurizio Sanguinetti, María Muñoz-Algarra, Teresa Durán-Valle, Inmaculada Quiles-Melero, Paloma Merino, Fernando González-Romo, Aída Sánchez-García, Elia Gómez-García-de-la-Pedrosa, Ana Pérez-Ayala, María Ángeles Mantecón-Vallejo, Javier Pemán, María Soledad Cuétara, Nelly Daniela Zurita, Coral García-Esteban, María Del Carmen Martínez-Jiménez, Miguel Ángel Sánchez Castellano, Elena Reigadas, Patricia Muñoz, Pilar Escribano
Journal: Clinical Microbiology and Infection (2024)
Elevated WTAP promotes hyperinflammation by increasing m6A modification in inflammatory disease models
Authors: Yong Ge, Rong Chen, Tao Ling, Biaodi Liu, Jingrong Huang, Youxiang Cheng, Yi Lin, Hongxuan Chen, Xiongmei Xie, Guomeng Xia, Guanzheng Luo, Shaochun Yuan, Anlong Xu
Journal: Journal of Clinical Investigation (2024)

Emerging evidence has linked the dysregulation of N6-methyladenosine (m6A) modification to inflammation and inflammatory diseases, but the underlying mechanism still needs investigation. Here, we found that high levels of m6A modification in a variety of hyperinflammatory states are p65-dependent because Wilms tumor 1–associated protein (WTAP), a key component of the "writer" complex, is transcriptionally regulated by p65, and its overexpression can lead to increased levels of m6A modification. Mechanistically, upregulated WTAP is more prone to phase separation to facilitate the aggregation of the writer complex to nuclear speckles and the deposition of m6A marks on transcriptionally active inflammatory transcripts, thereby accelerating the proinflammatory response. Further, a myeloid deficiency in WTAP attenuates the severity of LPS-induced sepsis and DSS-induced IBD. Thus, the proinflammatory effect of WTAP is a general risk-increasing mechanism, and interrupting the assembly of the m6A writer complex to reduce the global m6A levels by targeting the phase separation of WTAP may be a potential and promising therapeutic strategy for alleviating hyperinflammation.
Patient-Reported Quality of Life at Diagnosis in Adolescent and Young Adults With Cancer
Authors: Goldy C. George, Clark Andersen, Xiaohui Tang, Elizabeth Rodriguez, Midhat Jafry, Maria C. Swartz, Sairah Ahmed, Carlos H. Barcenas, J. Andrew Livingston, Michael E. Roth, Michelle A.T. Hildebrandt
Journal: Journal of the National Comprehensive Cancer Network (2024)

Background: The overall landscape of health-related quality of life (HRQoL) has not been thoroughly investigated in adolescents and young adults (AYAs) with cancer. Data are also lacking on how well HRQoL at the time of cancer diagnosis can prognosticate long-term survival in AYA survivors. Patients and Methods: We included 3,497 survivors of AYA cancer (age 15–39 years at diagnosis) who completed the Short-Form 12 Health Survey (SF-12) HRQoL questionnaire at diagnosis. Physical component summary (PCS) and mental component summary (MCS) scores were generated, with scores &lt;50 representing poor HRQoL. Differences in HRQoL by patient characteristics and tumor type were investigated using violin plots and t tests/analysis of variance. The effect of HRQoL on overall survival was assessed using Kaplan-Meier plots and Cox proportional hazards models. Results: Overall mean PCS and MCS scores in this racially/ethnically diverse cohort (64% White, 19% Hispanic, 10% Black, and 7% other race/ethnicity) were 43.6 and 46.7, respectively. Women with breast cancer reported the most favorable PCS (50.8), and those with cervical cancer reported the lowest MCS (42.8). Age at diagnosis was associated positively with PCS ( P &lt;.001) and inversely with MCS ( P &lt;.001). Females had higher PCS yet lower MCS than males (both P &lt;.001). Marginalized racial and ethnic populations reported lower PCS than White patients ( P &lt;.001). Physical and mental HRQoL were prognostic and associated with increased risk of poor survival (hazard ratio, 1.95; 95% CI, 1.72–2.21 for physical HRQoL, and 1.26; 95% CI, 1.13–1.40 for mental HRQoL). Conclusions: Physical and mental HRQoL at diagnosis vary across patient characteristics in AYA cancer survivors. Poor HRQoL at diagnosis may be a prognosticator of diminished overall survival among AYA cancer survivors.
Establishing Minimal Clinically Important Differences (MCIDs) for the Pemphigus Disease Area Index (PDAI)
Authors: Henry Tseng, Corey Stone, Boaz Shulruf, Dédée F Murrell
Journal: British Journal of Dermatology (2024)

Pemphigus is a rare autoimmune blistering disease with potentially life-threatening consequences. Establishing minimal clinically important differences (MCIDs) for disease severity scores like the Pemphigus Disease Area Index (PDAI) is crucial for assessing treatment efficacy.