tbuckley/cabot-search huggingface dataset:
The Risk of Lung Cancer in Rheumatoid Arthritis and Rheumatoid Arthritis‐Associated Interstitial Lung Disease
Authors: Rebecca T. Brooks, Brent Luedders, Austin Wheeler, Tate M. Johnson, Yangyuna Yang, Punyasha Roul, Apar Kishor Ganti, Namrata Singh, Brian C. Sauer, Grant W. Cannon, Joshua F. Baker, Ted R. Mikuls, Bryant R. England
Journal: Arthritis & Rheumatology (2024)

Objective We aimed to evaluate lung cancer risk in patients with rheumatoid arthritis (RA) and RA‐interstitial lung disease (ILD). Methods We performed a retrospective, matched cohort study of RA and RA‐ILD within the Veterans Health Administration (VA) between 2000 and 2019. Patients with RA and RA‐ILD were identified with validated administrative‐based algorithms, then matched (up to 1:10) on age, gender, and VA enrollment year to individuals without RA. Lung cancers were identified from a VA oncology database and the National Death Index. Conditional Cox regression models assessed lung cancer risk adjusting for race, ethnicity, smoking status, Agent Orange exposure, and comorbidity burden among matched individuals. Several sensitivity analyses were performed. Results We matched 72,795 patients with RA with 633,937 patients without RA (mean age 63 years; 88% male). Over 4,481,323 patient‐years, 17,099 incident lung cancers occurred. RA was independently associated with an increased lung cancer risk (adjusted hazard ratio [aHR] 1.58 [95% confidence interval (CI) 1.52–1.64]), which persisted in never smokers (aHR 1.65 [95% CI 1.22–2.24]) and in those with incident RA (aHR 1.54 [95% CI 1.44–1.65]). Compared to non‐RA controls, prevalent RA‐ILD (n = 757) was more strongly associated with lung cancer risk (aHR 3.25 [95% CI 2.13–4.95]) than RA without ILD (aHR 1.57 [95% CI 1.51–1.64]). Analyses of both prevalent and incident RA‐ILD produced similar results (RA‐ILD vs non‐RA aHR 2.88 [95% CI 2.45–3.40]). Conclusion RA was associated with a &gt;50% increased risk of lung cancer, and those with RA‐ILD represented a particularly high‐risk group with an approximate three‐fold increased risk. Increased lung cancer surveillance in RA, and especially RA‐ILD, may be a useful strategy for reducing the burden posed by the leading cause of cancer death.
Harnessing Dual Phototherapy and Immune Activation for Cancer Treatment: The Development and Application of BODIPY@F127 Nanoparticles
Authors: Yang Peng, Chenyan Hu, Ludan Zhang, Fan Dong, Ruwan Li, Huihui Liang, Hao Dai, Won Jun Jang, Hong‐Bo Cheng, Liming Zhou, Yuguang Wang, Juyoung Yoon
Journal: Advanced Healthcare Materials (2024)

Conventional phototherapeutic agents are typically used in either photodynamic therapy (PDT) or photothermal therapy (PTT). However, efficacy is often hindered by hypoxia and elevated levels of heat shock proteins in the tumor microenvironment (TME). To address these limitations, a formylated, near-infrared (NIR)-absorbing and heavy-atom-free Aza-BODIPY dye is presented that exhibits both type-I and type-II PDT actions with a high yield of reactive oxygen species (ROS) and manifests efficient photothermal conversion by precise adjustments to the conjugate structure and electron distribution, leading to a large amount of ROS production even under severe hypoxia. To improve biosafety and water solubility, the dye with an amphiphilic triblock copolymer (Pluronic F-127), yielding BDP-6@F127 nanoparticles (NPs) is coated. Furthermore, inspired by the fact that phototherapy triggers the release of tumor-associated antigens, a strategy that leverages potential immune activation by combining PDT/PTT with immune checkpoint blockade (ICB) therapy to amplify the systemic immune response and achieve the much-desired abscopal effect is developed. In conclusion, this study presents a promising molecular design strategy that integrates multimodal therapeutics for a precise and effective approach to cancer therapy.
Unleashing Novel Therapeutic Strategies for Dry Eye: Targeting ROS and the cGAS‐STING Signaling Pathway with Tetrahedral Framework Nucleic Acids
Authors: Dan Yan, Caihong Huang, Weijie Ouyang, Jiaoyue Hu, Zuguo Liu
Journal: Advanced Healthcare Materials (2024)

Abstract Dry eye affects majority of the global population, causing significant discomfort or even visual impairment, of which inflammation plays a crucial role in the deterioration process. This highlights the need for effective and safe anti‐inflammatory treatments to achieve satisfactory therapeutic outcomes. This study focuses on the potential of tetrahedral framework nucleic acids (tFNA), a self‐assembled nucleic acid material, as a simple and rapid treatment for oxidative stress and inflammation‐induced disorders associated with dry eye. Mechanistically, tFNA is found to effectively alleviate dry eye damage by promoting corneal epithelial healing, restoring goblet cell function, and facilitating tear secretion recovery. Through RNA‐seq analysis, it is observed that tFNA treatment normalizes the expression levels of most genes. Further exploration of the mechanism reveals that tFNA reduces excessive production of reactive oxygen species and modulates the inflammatory microenvironment, especially through cGAS‐STING pathway thereby levels of inflammatory cytokines, including MMP9 and IL‐6, are reduced. Additionally, tFNA demonstrates excellent safety performance without causing damage to the eye. Importantly, this study represents a successful application of nanophase materials with nucleic acid biological features for the effective treatment of dry eye, highlighting the potential clinical use of tFNA in the treatment of dry eye.
Enhancing adherence for total body skin examination in post-surgical veterans: an interventional study at an urban Veterans Affairs center
Authors: Vignesh Ramachandran, Efe Kakpovbia, Michelle C. Juarez, Neil Jairath, Andjela Nemcevic, Christine C. Akoh, Ian M. Ahearn, Ian W. Tattersall, Nayoung Lee, Jo-Ann M. Latkowski, John G. Zampella
Journal: Military Medical Research (2024)
<scp>IL</scp>‐10‐modulated dendritic cells from birch pollen‐ and hazelnut‐allergic patients facilitate Treg‐mediated allergen‐specific and cross‐reactive tolerance
Authors: Patricia Vanessa Heinl, Edith Graulich, Benno Weigmann, Andrea Wangorsch, Robert Ose, Iris Bellinghausen, Rahul Khatri, Verena K. Raker, Stephan Scheurer, Stefan Vieths, Joachim Saloga, Kerstin Steinbrink
Journal: Allergy (2024)

Abstract Background Approximately 70% of individuals allergic to birch pollen (Bet v 1.01 [Bet]) develop a secondary food allergy (e.g., hazelnut: Cor a 1.04 [Cor]), due to allergen cross‐reactivity. However, standard immunotherapy for type I allergies often does not improve the food allergy sufficiently. We analyzed the allergen‐specific and cross‐reactive suppressive capacity of primary human regulatory T cells (Treg) induced by autologous IL‐10‐modulated dendritic cells (IL‐10 DC) in vitro and in vivo. Methods CD4 + T cells of patients with birch pollen and associated hazelnut allergies were differentiated into Bet‐specific or non‐specific induced Treg (iTreg). After Bet‐ or Cor‐specific restimulation the phenotype, proliferation, and suppressive capacity of iTreg subsets were analyzed. iTreg function was further investigated in humanized mouse models of airway and intestinal allergy, generated by engraftment of peripheral blood mononuclear cells from allergic donors into immunodeficient animals. Results After IL‐10 DC priming and allergen‐specific restimulation (Bet or Cor), non‐specific control iTreg remained anergic, whereas Bet‐specific iTreg proliferated extensively and exhibited a regulatory phenotype (enhanced expression of CTLA‐4, PD‐1, TNFR2, IL‐10). Accordingly, activated Bet‐specific iTreg displayed a high capacity to suppress Bet‐ and Cor‐induced responder Th2 cell responses in vitro, indicating induction of both allergen‐specific (birch) and cross‐reactive tolerance (hazelnut). In vivo, the beneficial effect of Bet‐specific iTreg was verified in humanized mouse models of allergic airway and intestinal inflammation, resulting in reduced allergen‐induced clinical symptoms, and immune responses. Conclusion Human IL‐10 DC‐induced iTreg facilitate allergen‐specific and cross‐reactive tolerance. Therefore, they are potential candidates for regulatory cell therapy in allergic and autoimmune diseases.
Advances and clinical applications of immune checkpoint inhibitors in hematological malignancies
Authors: Wenyue Sun, Shunfeng Hu, Xin Wang
Journal: Cancer Communications (2024)

Abstract Immune checkpoints are differentially expressed on various immune cells to regulate immune responses in tumor microenvironment. Tumor cells can activate the immune checkpoint pathway to establish an immunosuppressive tumor microenvironment and inhibit the anti‐tumor immune response, which may lead to tumor progression by evading immune surveillance. Interrupting co‐inhibitory signaling pathways with immune checkpoint inhibitors (ICIs) could reinvigorate the anti‐tumor immune response and promote immune‐mediated eradication of tumor cells. As a milestone in tumor treatment, ICIs have been firstly used in solid tumors and subsequently expanded to hematological malignancies, which are in their infancy. Currently, immune checkpoints have been investigated as promising biomarkers and therapeutic targets in hematological malignancies, and novel immune checkpoints, such as signal regulatory protein α (SIRPα) and tumor necrosis factor‐alpha‐inducible protein 8‐like 2 (TIPE2), are constantly being discovered. Numerous ICIs have received clinical approval for clinical application in the treatment of hematological malignancies, especially when used in combination with other strategies, including oncolytic viruses (OVs), neoantigen vaccines, bispecific antibodies (bsAb), bio‐nanomaterials, tumor vaccines, and cytokine‐induced killer (CIK) cells. Moreover, the proportion of individuals with hematological malignancies benefiting from ICIs remains lower than expected due to multiple mechanisms of drug resistance and immune‐related adverse events (irAEs). Close monitoring and appropriate intervention are needed to mitigate irAEs while using ICIs. This review provided a comprehensive overview of immune checkpoints on different immune cells, the latest advances of ICIs and highlighted the clinical applications of immune checkpoints in hematological malignancies, including biomarkers, targets, combination of ICIs with other therapies, mechanisms of resistance to ICIs, and irAEs, which can provide novel insight into the future exploration of ICIs in tumor treatment.
Galectin 3‐binding protein (LGALS3BP) depletion attenuates hepatic fibrosis by reducing transforming growth factor‐β1 (TGF‐β1) availability and inhibits hepatocarcinogenesis
Authors: Dae‐Hwan Kim, Minjeong Sung, Myong‐Suk Park, Eun‐Gene Sun, Sumin Yoon, Kyung Hyun Yoo, Kamalakannan Radhakrishnan, Sung Yun Jung, Woo‐Kyun Bae, Sang‐Hee Cho, Ik‐Joo Chung
Journal: Cancer Communications (2024)

Abstract Background Increased Galectin 3‐binding protein (LGALS3BP) serum levels have been used to assess hepatic fibrosis stages and the severity of hepatocellular carcinoma (HCC). Considering the crucial role of transforming growth factor‐β1 (TGF‐β1) in the emergence of these diseases, the present study tested the hypothesis that LGALS3BP regulates the TGF‐β1 signaling pathway. Methods The expression levels of LGALS3BP and TGFB1 were analyzed in patients with metabolic dysfunction‐associated steatohepatitis (MASH) and HCC. Multiple omics techniques, such as RNA‐sequencing, transposase‐accessible chromatin‐sequencing assay, and liquid chromatography‐tandem mass spectrometry proteomics, were used to identify the regulatory mechanisms for the LGALS3BP‐TGF‐β1 axis. The effects of altered TGF‐β1 signaling by LGALS3BP were investigated in conditional LGALS3BP ‐knockin and LGALS3BP ‐knockout mice. Results In patients with MASH and HCC, the levels of LGALS3BP and TGFB1 exhibited positive correlations. Stimulation of LGALS3BP by the inflammatory cytokine interferon α in HCC cells or ectopic overexpression of LGALS3BP in hepatocytes promoted the expression levels of TGFB1. Aggravated fibrosis was observed in the livers of hepatocyte‐specific LGALS3BP ‐knockin mice, with increased TGFB1 levels. LGALS3BP directly bound to and assembled integrin αV, an integral mediator required for releasing active TGF‐β1 from extracellular latent complex with the rearranged F‐actin cytoskeleton. The released TGF‐β1 activated JunB transcription factor, which in turn promoted the TGF‐β1 positive feedback loop. LGALS3BP deletion in the hepatocytes downregulated TGF‐β1 signaling and CCl 4 induced fibrosis. Moreover, LGALS3BP depletion hindered hepatocarcinogenesis by limiting the availability of fibrogenic TGF‐β1. Conclusion LGALS3BP plays a crucial role in hepatic fibrosis and carcinogenesis by controlling the TGF‐β1 signaling pathway, making it a promising therapeutic target in TGF‐β1‐related diseases.
Noninvasive ventilation on reintubation in patients with obesity and hypoxemic respiratory failure following abdominal surgery: a post hoc analysis of a randomized clinical trial
Authors: Samir Jaber, Joris Pensier, Emmanuel Futier, Catherine Paugam-Burtz, Philippe Seguin, Martine Ferrandiere, Sigismond Lasocki, Julien Pottecher, Paër-Sélim Abback, Beatrice Riu, Fouad Belafia, Jean-Michel Constantin, Daniel Verzilli, Gérald Chanques, Audrey De Jong, Nicolas Molinari
Journal: Intensive Care Medicine (2024)
Identification of a novel DEC-205 binding peptide to develop dendritic cell-targeting nanovaccine for cancer immunotherapy
Authors: Jie Zheng, Mingshuang Wang, Liwei Pang, Shuai Wang, Yanan Kong, Xueqin Zhu, Xiuman Zhou, Xiaoxi Wang, Chunxia Chen, Haoming Ning, Wenshan Zhao, Wenjie Zhai, Yuanming Qi, Yahong Wu, Yanfeng Gao
Journal: Journal of Controlled Release (2024)
Parallel evolution at the regulatory base-pair level contributes to mammalian inter-specific differences in polygenic traits
Authors: Alexander S Okamoto, Terence D Capellini
Journal: Molecular Biology and Evolution (2024)

Parallel evolution occurs when distinct lineages with similar ancestral states converge on a new phenotype. Parallel evolution has been well documented at the organ, gene pathway, and amino acid sequence level but in theory, it can also occur at individual nucleotides within noncoding regions. To examine the role of parallel evolution in shaping the biology of mammalian complex traits, we used data on single-nucleotide polymorphisms (SNPs) influencing human intraspecific variation to predict trait values in other species for 11 complex traits. We found that the alleles at SNP positions associated with human intraspecific height and red blood cell (RBC) count variation are associated with interspecific variation in the corresponding traits across mammals. These associations hold for deeper branches of mammalian evolution as well as between strains of collaborative cross mice. While variation in RBC count between primates uses both ancient and more recently evolved genomic regions, we found that only primate-specific elements were correlated with primate body size. We show that the SNP positions driving these signals are flanked by conserved sequences, maintain synteny with target genes, and overlap transcription factor binding sites. This work highlights the potential of conserved but tunable regulatory elements to be reused in parallel to facilitate evolutionary adaptation in mammals.
GWAS breakthroughs: mapping the journey from one locus to 393 significant coronary artery disease associations
Authors: Rédouane Aherrahrou, Tobias Reinberger, Satwat Hashmi, Jeanette Erdmann
Journal: Cardiovascular Research (2024)

Abstract Coronary artery disease (CAD) poses a substantial threat to global health, leading to significant morbidity and mortality worldwide. It has a significant genetic component that has been studied through genome-wide association studies (GWAS) over the past 17 years. These studies have made progress with larger sample sizes, diverse ancestral backgrounds, and the discovery of multiple genomic regions related to CAD risk. In this review, we provide a comprehensive overview of CAD GWAS, including information about the genetic makeup of the disease and the importance of ethnic diversity in these studies. We also discuss challenges of identifying causal genes and variants within GWAS loci with a focus on non-coding regions. Additionally, we highlight tissues and cell types relevant to CAD, and discuss clinical implications of GWAS findings including polygenic risk scores, sex-specific differences in CAD genetics, ethnical aspects of personalized interventions, and GWAS guided drug development.
TDP-43 proteinopathy in frontotemporal lobar degeneration and amyotrophic lateral sclerosis: From pathomechanisms to therapeutic strategies
Authors: Pei-Chuan Ho, Tsung-Chi Hsieh, Kuen-Jer Tsai
Journal: Ageing Research Reviews (2024)

Proteostasis failure is a common pathological characteristic in neurodegenerative diseases. Revitalizing clearance systems could effectively mitigate these diseases. The transactivation response (TAR) DNA-binding protein 43 (TDP-43) plays a critical role as an RNA/DNA-binding protein in RNA metabolism and synaptic function. Accumulation of TDP-43 aggregates in the central nervous system is a hallmark of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Autophagy, a major and highly conserved degradation pathway, holds the potential for degrading aggregated TDP-43 and alleviating FTLD/ALS. This review explores the causes of TDP-43 aggregation, FTLD/ALS-related genes, key autophagy factors, and autophagy-based therapeutic strategies targeting TDP-43 proteinopathy. Understanding the underlying pathological mechanisms of TDP-43 proteinopathy can facilitate therapeutic interventions.
SNO-EANO-EURACAN consensus on management of pineal parenchymal tumors
Authors: Anthony P Y Liu, Bryan K Li, Alexandre Vasiljevic, Michael C Dewan, Benita Tamrazi, Birgit Ertl-Wagner, Jordan R Hansford, Elke Pfaff, Martin Mynarek, Ho-Keung Ng, Derek S Tsang, Nicholas G Gottardo, Amar Gajjar, Eric Bouffet, Christelle Dufour, Barry Pizer, David Schiff, Michael D Jenkinson, Giuseppe Lombardi, Patrick Y Wen, Martin J van den Bent, Annie Huang
Journal: Neuro-Oncology (2024)

Pineal parenchymal tumors are rare neoplasms for which evidence-based treatment recommendations are lacking. These tumors vary in biology, clinical characteristics, and prognosis, requiring treatment that ranges from surgical resection alone to intensive multimodal antineoplastic therapy. Recently, international collaborative studies have shed light on the genomic landscape of these tumors, leading to refinement in molecular-based disease classification in the 5th edition of the World Health Organization (WHO) classification of tumors of the central nervous system. In this review, we summarize the literature on diagnostic and therapeutic approaches, and suggest pragmatic recommendations for the clinical management of patients presenting with intrinsic pineal region masses including parenchymal tumors (pineocytoma, pineal parenchymal tumor of intermediate differentiation, and pineoblastoma), pineal cyst, and papillary tumors of the pineal region.
Beneath the surface: a case of subcutaneous human dirofilariasis
Authors: Bhukampa Acharya, Anubha Dev, Anindita Sinha, Parmod Kumar, Dipankar De, Rahul Mahajan
Journal: British Journal of Dermatology (2024)

A woman in her sixties, from Kerala, India, presented with a painless cystic swelling of the left infraorbital area for 15 days, with a preceding history of an insect bite.
Remodeling the hepatic immune microenvironment and demolishing T cell traps to enhance immunotherapy efficacy in liver metastasis
Authors: Zhenyu Luo, Mengshi Jiang, Ningtao Cheng, Xiaoqi Zhao, Huihui Liu, Sijie Wang, Qing Lin, Jiaxin Huang, Xuemeng Guo, Xu Liu, Xinyu Shan, Yichao Lu, Yingying Shi, Lihua Luo, Jian You
Journal: Journal of Controlled Release (2024)
Neutrophil Extracellular Traps‐Inspired Bismuth‐Based Polypeptide Nanonets for Synergetic Treatment of Bacterial Infections
Authors: Jiang Xiao, Zengchao Guo, Gang Lv, Zhihong Yan, Tengfei Liu, Yihan Wang, Hao Liu, Jesús Martínez, Lihong Yin, Xiaohui Liu, Hui Jiang, Yossi Weizmann, Xuemei Wang
Journal: Advanced Healthcare Materials (2024)

Abstract Excessive use of antibiotics and the formation of bacterial biofilms can lead to persistent infections caused by drug‐resistant bacteria, rendering ineffective immune responses and even life‐threatening. There is an urgent need to explore synergistic antibacterial therapies across all stages of infection. Drawing inspiration from the antibacterial properties of neutrophil extracellular traps (NETs) and integrating the bacterial biofilm dispersal mechanism involving boronic acid–catechol interaction, the multifunctional bismuth‐based polypeptide nanonets (PLBA‐Bi‐Fe‐TA) are developed. These nanonets are designed to capture bacteria through a coordination complex involving cationic polypeptides (PLBA) with boronic acid‐functionalized side chains, alongside metal ions (bismuth (Bi) and iron (Fe)), and tannic acid (TA). Leveraging the nanoconfinement‐enhanced high‐contact network‐driven multiple efficiency, PLBA‐Bi‐Fe‐TA demonstrates the excellent ability to swiftly capture bacteria and their extracellular polysaccharides. This interaction culminates in the formation of a highly hydrophilic complex, effectively enabling the rapid inhibition and dispersion of antibiotic‐resistant bacterial biofilms, while Fe‐TA shows mild photothermal ability to further assist fluffy mature biofilm. In addition, Bi is beneficial to regulate the polarization of macrophages to pro‐inflammatory phenotype to further kill escaping biofilm bacteria. In summary, this novel approach offers a promising bionic optimization strategy for treating bacterial‐associated infections at all stages through synergetic treatment.
Definition and assessment of psychological frailty in older adults: A scoping review
Authors: Joanes Lameirinhas, Arantxa Gorostiaga, Igone Etxeberria
Journal: Ageing Research Reviews (2024)

The confusion surrounding psychological frailty and its components prompts the need for a standardized conceptual definition. To address this, we aimed to (1) identify the psychological variables included in multicomponent frailty assessment instruments used with older adults and examine their operationalization; and (2) formulate a thorough conceptualization of psychological frailty based on the variables identified.
Viral hepatitis elimination — time to act
Journal: Nature Reviews Gastroenterology & Hepatology (2024)

Viral hepatitis elimination -time to actThe countdown to the 2030 viral hepatitis elimination goal continues, but time is running out and progress is not keeping pace.Viral hepatitis remains a major public health challenge; we need to take action now to mobilize resources and focus efforts.Check for updates "equitable access is paramount to ensure that interventions are available"