tbuckley/cabot-search huggingface dataset:
Rare Presentations of Differentiated Thyroid Cancer Exposing Dr Jekyll and Mr Hyde Nature of an Otherwise Indolent Disease
Authors: Priyanka Verma, Gaurav Malhotra, Ramesh D. Rao, Sunita Sonavane, Ritesh Agrawal
Journal: Clinical Nuclear Medicine (2024)

Abstract Differentiated thyroid carcinoma (DTC) usually manifests as an indolent cancer with good prognosis. However, rarely uncommon sites of metastatic involvement can worsen the prognosis and require aggressive therapeutic approach. Here in, we describe 5 patients (3 women and 2 men) harboring rare sites of metastatic involvement from DTC including the adrenals, colon, kidneys, urinary bladder, brachial plexus, and superior vena cava with contiguous right atrial involvement. The awareness of such rare sites of involvement from DTC is imperative for treating clinicians to plan individualistic approach in management including multiprong therapies for better patient care.
“Three‐in‐one”: A Photoactivable Nanoplatform Evokes Anti‐Immune Response by Inhibiting BRD4‐cMYC‐PDL1 Axis to Intensify Photo‐Immunotherapy
Authors: Ayeskanta Mohanty, Mingyu Lee, Adityanarayan Mohapatra, Hwangjae Lee, Arathy Vasukutty, Seonguk Baek, Jae Young Lee, In‐Kyu Park
Journal: Advanced Healthcare Materials (2024)

Abstract Combinatorial immuno‐cancer therapy is recognized as a promising approach for efficiently treating malignant tumors. Yet, the development of multifunctional nanomedicine capable of precise tumor targeting, remote activation, and immune‐regulating drug delivery remains a significant challenge. In this study, nanoparticles loaded with an immune checkpoint inhibitor (JQ‐1) using polypyrrole/hyaluronic acid (PPyHA/JQ‐1) are developed. These nanoparticles offer active tumor targeting, photothermal tumor ablation using near‐infrared light, and laser‐controlled JQ‐1 release for efficient breast cancer treatment. When the molecular weight of HA varies (from 6.8 kDa to 3 MDa) in the PPyHA nanoparticles, it is found that the nanoparticles synthesized using 1 MDa HA, referred to as PPyHA (1 m ), show the most suitable properties, including small hydrodynamic size, high surface HA contents, and colloidal stability. Upon 808 nm laser irradiation, PPyHA/JQ‐1 elevates the temperature above 55 °C, which is sufficient for thermal ablation and active release of JQ‐1 in the tumor microenvironment (TME). Notably, the controlled release of JQ‐1 substantially inhibits the expression of cancer‐promoting genes. Furthermore, PPyHA/JQ‐1 effectively suppresses the expression of programmed cell death ligand 1 (PD‐L1) and prolongs dendritic cell maturation and CD8+ T cell activation against the tumor both in vitro and in vivo. PPyHA/JQ‐1 treatment simultaneously provides a significant tumor regression through photothermal therapy and immune checkpoint blockade, leading to a durable antitumor‐immune response. Overall, “Three‐in‐one” immunotherapeutic photo‐activable nanoparticles have the potential to be beneficial for a targeted combinatorial treatment approach for TNBC.
Blood-based biomarkers of cerebral small vessel disease
Authors: Liu-Yun Wu, Yuek Ling Chai, Irwin K. Cheah, Rachel S.L. Chia, Saima Hilal, Thiruma V. Arumugam, Christopher P. Chen, Mitchell K.P. Lai
Journal: Ageing Research Reviews (2024)

Age-associated cerebral small vessel disease (CSVD) represents a clinically heterogenous condition, arising from diverse microvascular mechanisms. These lead to chronic cerebrovascular dysfunction and carry a substantial risk of subsequent stroke and vascular cognitive impairment in aging populations. Owing to advances in neuroimaging, in vivo visualization of cerebral vasculature abnormities and detection of CSVD, including lacunes, microinfarcts, microbleeds and white matter lesions, is now possible, but remains a resource-, skills- and time-intensive approach. As a result, there has been a recent proliferation of blood-based biomarker studies for CSVD aimed at developing accessible screening tools for early detection and risk stratification. However, a good understanding of the pathophysiological processes underpinning CSVD is needed to identify and assess clinically useful biomarkers. Here, we provide an overview of processes associated with CSVD pathogenesis, including endothelial injury and dysfunction, neuroinflammation, oxidative stress, perivascular neuronal damage as well as cardiovascular dysfunction. Then, we review clinical studies of the key biomolecules involved in the aforementioned processes. Lastly, we outline future trends and directions for CSVD biomarker discovery and clinical validation.
Inhibition of Gpx4-mediated ferroptosis alleviates cisplatin-induced hearing loss in C57BL/6 mice
Authors: Ziyi Liu, Hanbing Zhang, Guodong Hong, Xiuli Bi, Jun Hu, Tiancheng Zhang, Yachun An, Na Guo, Fengyue Dong, Yu Xiao, Wen Li, Xiaoxu Zhao, Bo Chu, Siwei Guo, Xiaohan Zhang, Renjie Chai, Xiaolong Fu
Journal: Molecular Therapy (2024)
SMART-lipid nanoparticles enabled mRNA vaccine elicits cross-reactive humoral responses against the omicron sub-variants
Authors: Gokulnath Mahalingam, Hari Krishnareddy Rachamalla, Porkizhi Arjunan, Karthik V. Karuppusamy, Yogapriya Periyasami, Aruna Mohan, Kanimozhi Subramaniyam, Salma M, Vigneshwar Rajendran, Mahesh Moorthy, George M. Varghese, Kumarasamypet M. Mohankumar, Saravanabhavan Thangavel, Alok Srivastava, Srujan Marepally
Journal: Molecular Therapy (2024)
Activation of the YAP/KLF5 transcriptional cascade in renal tubular cells aggravates kidney injury
Authors: Yang Liu, Yu Wang, Chunhua Xu, Yu Zhang, Yang Wang, Jinzhong Qin, Hui-Yao Lan, Li Wang, Yu Huang, Kingston Kinglun Mak, Zhihua Zheng, Yin Xia
Journal: Molecular Therapy (2024)
Paraspeckle protein NONO attenuates vascular calcification by inhibiting bone morphogenetic protein 2 transcription
Authors: Yue Lu, Linlin Meng, Ruiqing Ren, Xinlu Wang, Wenhai Sui, Fei Xue, Lin Xie, Ang Chen, Yuxia Zhao, Jianmin Yang, Wencheng Zhang, Xiao Yu, Bo Xi, Feng Xu, Meng Zhang, Yun Zhang, Cheng Zhang
Journal: Kidney International (2024)
Correction: The major TMEM106B dementia risk allele affects TMEM106B protein levels, fibril formation, and myelin lipid homeostasis in the ageing human hippocampus
Authors: Jun Yup Lee, Dylan J. Harney, Jonathan D. Teo, John B. Kwok, Greg T. Sutherland, Mark Larance, Anthony S. Don
Journal: Molecular Neurodegeneration (2024)
Clinical characteristics, molecular aberrations, treatments, and outcomes of malignant histiocytosis
Authors: Gordon J. Ruan, Saurabh Zanwar, Aishwarya Ravindran, Susan Schram, Jithma P. Abeykoon, Antonious Hazim, Jason R. Young, Mithun V. Shah, N. Nora Bennani, Liuyan Jiang, Diana Morlote, Karen L. Rech, Gaurav Goyal, Ronald S. Go
Journal: American Journal of Hematology (2024)

Malignant histiocytosis (MH) is an extremely rare neoplasm of the macrophage-dendritic cell lineage. We report the clinical characteristics, molecular aberrations, treatments, and outcomes of patients with MH seen at two referral centers from January 2000 to May 2023. We identified 43 patients with MH, of which 26 had histiocytic sarcoma (MH-H), 9 interdigitating dendritic cell sarcoma (MH-IDC), and 8 Langerhans cell sarcoma (MH-LC). The median age at diagnosis was 61 years (range, 3-83). Thirty-three patients (77%) had multifocal disease, while 10 had unifocal involvement. Tumor specimens from 22 patients (51%) underwent targeted next generation sequencing, and 19 of 22 (86%) had at least one pathogenic mutation, including mutations in MAPK pathway genes (73%). The median overall survival (OS) among the entire cohort was 16 months (95% CI: 8-50). The outcomes of those with multifocal disease were significantly shorter than their unifocal counterpart: median OS of 10 months versus 50 months (p = .07). Patients with risk organ involvement (bone marrow, spleen, or liver) had significantly inferior outcomes. Chemotherapy and surgery were the most common first-line treatments for multifocal and unifocal disease, respectively. While the outcome for patients with multifocal disease was poor, there was a subset of patients who had durable responses to treatment. Our study highlights that MH has heterogeneous clinical presentation, frequent oncogenic mutations, and prognosis, which is strongly tied to disease extent and type of organ involvement.
Ondansetron and the Risk of Sudden Cardiac Death among Individuals Receiving Maintenance Hemodialysis
Authors: Sherin Ismail, Michele Jonsson Funk, Jennifer E. Flythe
Journal: Journal of the American Society of Nephrology (2024)

Key Points In hemodialysis, ondansetron initiation versus initiation of lesser QT-prolonging antiemetics associated with higher 10-day sudden cardiac death risk. Analyses considering additional cardiac outcomes had consistent findings. Background Individuals receiving hemodialysis have a high incidence of sudden cardiac death and are susceptible to QT interval–prolonging medication–related cardiac complications. Ondansetron, an antiemetic with known QT-prolonging potential, is associated with fatal arrhythmias in the general population when administered intravenously. The cardiac safety of ondansetron in the hemodialysis population is unknown. Methods We conducted a new-user, active-comparator, cohort study using United States Renal Data System data (2012–2019) to examine the association between the initiation of oral ondansetron versus antiemetics with lesser QT-prolonging potential (promethazine, metoclopramide, or prochlorperazine) and the 10-day risk of sudden cardiac death among individuals receiving hemodialysis. We used inverse probability of treatment-weighted survival models to estimate adjusted hazard ratios, risk differences, and 95% confidence intervals (CIs). We used an intention-to-treat approach in which non-sudden cardiac death was considered a competing event. We examined additional cardiac outcomes in secondary analyses. Results Of 119,254 study patients, 64,978 (55%) initiated ondansetron and 54,276 (45%) initiated a comparator antiemetic. Initiation of ondansetron versus a comparator antiemetic was associated with higher relative and absolute 10-day risks of sudden cardiac death (adjusted hazard ratio, 1.44 [95% CI, 1.08 to 1.93]; adjusted risk difference, 0.06% [95% CI, 0.01% to 0.11%]). The number needed to harm was 1688. Analyses of additional cardiac outcomes yielded similar findings. Conclusions Compared with initiation of antiemetics with lesser QT-prolonging potential, initiation of ondansetron was associated with higher short-term cardiac risks among people receiving hemodialysis.
PET/CT in a 65-Year-Old Woman With Epstein-Barr Virus–Associated Smooth Muscle Tumor After Chemotherapy for Follicular Lymphoma
Authors: Chia-Shang Wu, Yu-Ching Wen, Wei-Yu Chen, Tzeon-Jye Chiou
Journal: Clinical Nuclear Medicine (2024)

Abstract The Epstein-Barr virus–associated smooth muscle tumor (SMT) is an uncommon neoplasm. It arises mainly in 3 immunosuppression settings: HIV-associated SMT; drug-related immunosuppression in transplant recipients; and congenital immunodeficiency disorder–associated SMT. We present 18 F-FDG PET/CT findings of an adrenal Epstein-Barr virus–associated SMT in a 65-year-old woman with a history of follicular lymphoma after chemotherapy.
Ureter Metastasis From Colorectal Cancer Revealed on 18F-FDG PET/CT
Authors: JiaNing Zhang, Lan Yang, LingGe Wei, ZiYu Guo, Peng Xie
Journal: Clinical Nuclear Medicine (2024)

Abstract The involvement of the ureter as a site of metastasis of colorectal cancer is quite rare. Here we present FDG PET/CT findings of the right ureter metastasis from colon cancer in a patient after colectomy 6 years ago. 18 F-FDG PET/CT showed increased 18 F-FDG uptake in the right ureter with SUV max of 4.3. The pathology and immunohistochemistry confirmed the diagnosis of ureter metastasis from colon cancer.
Correction: Comprehensive review of CRISPR‑based gene editing: mechanisms, challenges, and applications in cancer therapy
Authors: Mohammad Chehelgerdi, Matin Chehelgerdi, Milad Khorramian‑Ghahfarokhi, Marjan Shafieizadeh, Esmaeil Mahmoudi, Fatemeh Eskandari, Mohsen Rashidi, Asghar Arshi, Abbas Mokhtari‑Farsani
Journal: Molecular Cancer (2024)

s attention that this article cites their work in an incorrect fashion and at least the related part of the paper raises some concern about the integrity of the reported information.In Table 3 on clinical trials of CRISPR-based therapy of the manuscript, the authors cite our study (Ref
A Genetically Engineered “Reinforced Concrete” Scaffold Regulates the N2 Neutrophil Innate Immune Cascade to Repair Bone Defects
Authors: Wenxiao Shi, Yu Feng, Jincheng Tang, Yichang Xu, Wei Wang, Lichen Zhang, Xinzhao Jiang, Zhouye Ding, Kun Xi, Liang Chen, Yong Gu
Journal: Advanced Healthcare Materials (2024)

The innate immune response is crucial to inflammation, but how neutrophils and macrophages act in bone repair and tissue engineering treatment strategies await clarification. In this study, it is found that N2 neutrophils release stronger "eat me" signals to induce macrophage phagocytosis and polarize into the M2 anti-inflammatory phenotype. Guided by this biological mechanism, a mesoporous bioactive glass scaffold (MBG) is filled with hyaluronic acid methacryloyl (HAMA) hydrogel loaded with Transforming growth factor-β1 (TGFβ1) adenovirus (Ad@H), constructing a genetically engineered composite scaffold (Ad@H/M). The scaffold not only has good hydrophilicity and biocompatibility, but also provides mechanical stress support for bone repair. Adenovirus infection quickly induces N2 neutrophils, upregulating NF-κB and MAPK signaling pathways through Toll-like receptor 4 (TLR4) to promote the inflammatory response and macrophage phagocytosis. Macrophages perform phagocytosis and polarize towards the M2 phenotype, mediating the inflammatory response by inhibiting the PI3K-AKT-NF-κB pathway, maintaining homeostasis of the osteogenic microenvironment. The role of the Ad@H/M scaffold in regulating early inflammation and promoting long-term bone regeneration is further validated in vivo. In brief, this study focuses on the cascade of reactions between neutrophils and macrophage subtypes, and reports a composite scaffold that coordinates the innate immune response to promote bone repair.
Report of <scp><i>IRF2BP1</i></scp> as a novel partner of <scp><i>RARA</i></scp> in variant acute promyelocytic leukemia
Authors: Mei Jiang, Xuemei Wang, Min Yu, Shuling Jiang, Miao Hong, Yuru Zhou, Fei Li, Hongxing Liu, Zhanglin Zhang
Journal: American Journal of Hematology (2024)

IRF2BP1 breaked in the middle of exon 1 at the c.322 position and fused with RARA intron 2 which is located at 3717 bp upstream of its exon 3. The fusion produced a new intron by forming a paired splicing donor GT at 9 bp downstream of RARA breakpoint and acceptor AG at the 5' end of RARA exon 3. The IRF2BP1::RARA fusion gene leads a fusion transcript involving IRF2BP1 exon 1 and RARA exon 3, linked by a 9-bp fragment derived from RARA intron 2. The patient with IRF2BP1::RARA has same clinical features of APL.
BANKSY unifies cell typing and tissue domain segmentation for scalable spatial omics data analysis
Authors: Vipul Singhal, Nigel Chou, Joseph Lee, Yifei Yue, Jinyue Liu, Wan Kee Chock, Li Lin, Yun-Ching Chang, Erica Mei Ling Teo, Jonathan Aow, Hwee Kuan Lee, Kok Hao Chen, Shyam Prabhakar
Journal: Nature Genetics (2024)

Spatial omics data are clustered to define both cell types and tissue domains. We present Building Aggregates with a Neighborhood Kernel and Spatial Yardstick (BANKSY), an algorithm that unifies these two spatial clustering problems by embedding cells in a product space of their own and the local neighborhood transcriptome, representing cell state and microenvironment, respectively. BANKSY's spatial feature augmentation strategy improved performance on both tasks when tested on diverse RNA (imaging, sequencing) and protein (imaging) datasets. BANKSY revealed unexpected niche-dependent cell states in the mouse brain and outperformed competing methods on domain segmentation and cell typing benchmarks. BANKSY can also be used for quality control of spatial transcriptomics data and for spatially aware batch effect correction. Importantly, it is substantially faster and more scalable than existing methods, enabling the processing of millions of cell datasets. In summary, BANKSY provides an accurate, biologically motivated, scalable and versatile framework for analyzing spatially resolved omics data.
Intranasal Epitope‐Polymer Vaccine Lodges Resident Memory T Cells Protecting Against Influenza Virus
Authors: Ziyang Liu, Md. Tanvir Kabir, Shuxiong Chen, Heran Zhang, Linda M. Wakim, Bernd H. A. Rehm
Journal: Advanced Healthcare Materials (2024)

Intranasal vaccines, unlike injectable vaccines, boost immunity along the respiratory tract; this can significantly limit respiratory virus replication and shedding. There remains a need to develop mucosal adjuvants and vaccine delivery systems that are both safe and effective following intranasal administration. Here, biopolymer particles (BP) densely coated with repeats of MHC class I restricted immunodominant epitopes derived from influenza A virus namely NP
Apoptotic Vesicles Modulate Endothelial Metabolism and Ameliorate Ischemic Retinopathy via PD1/PDL1 Axis
Authors: Yutong Jing, Wanmin Zhao, Ziyi Zhou, Wenzhe Wang, Yali Niu, Xiaoning He, Tianfang Chang, Changmei Guo, Bei Li, Guorui Dou
Journal: Advanced Healthcare Materials (2024)

Pathological angiogenesis with subsequent disturbed microvascular remodeling is a major cause of irreversible blindness in a number of ischemic retinal diseases. The current anti-vascular endothelial growth factor therapy can effectively inhibit angiogenesis, but it also brings significant side effects. The emergence of stem cell derived extracellular vesicles provides a new underlining strategy for ischemic retinopathy. Apoptotic vesicles (apoVs) are extracted from stem cells from human exfoliated deciduous teeth (SHED). SHED-apoVs are delivered into the eyeballs of oxygen-induced retinopathy (a most common model of angiogenic retinal dieseases) mice through intravitreal injection. The retinal neovascularization and nonperfusion area, vascular structure, and density changes are observed during the neovascularization phase (P17) and vascular remodeling phase (P21), and visual function is measured. The expression of extracellular acidification rate and lactic acid testing are used to detect endothelial cells (ECs) glycolytic activity. Furthermore, lentivirus and neutralizing antibody are used to block PD1-PDL1 axis, investigating the effects of SHED-apoVs on glycolysis and angiogenic activities. This work shows that SHED-apoVs are taken up by ECs and modulate the ECs glycolysis, leading to the decrease of abnormal neovessels and vascular remodeling. Furthermore, it is found that, at the molecular level, apoVs-carried PD1 interacts with PDL1 on hypoxic ECs to regulate the angiogenic activation. SHED-apoVs inhibit pathological angiogenesis and promote vascular remodeling in ischemic retinopathy partially by modulating ECs glycolysis through PD1/PDL1 axis. This study provides a new potential strategy for the clinical treatment of pathological retinal neovascularization.
The role of viruses in oral mucosal lesions
Authors: Henrik Dommisch, Andrea Maria Schmidt‐Westhausen
Journal: Periodontology 2000 (2024)

Abstract The mucosa of the oral cavity is exposed to a large number of different microorganisms such as archaea, bacteria, fungi, parasites, and viruses. Among those, viruses cause specific infections, which can easily be transmitted from one person to another. The infectious route may not only include patients and their relatives but also the dental professional team. Thus, a wide knowledge regarding specific viral infections is crucial for the daily routine. Signs and symptoms of oral viral infections can be completely absent or develop into a pronounced clinical picture, so that early detection and information determine the further course of the infection and its influence on other inflammatory diseases, such as periodontitis, as well as the safety of family members and the social environment. As the clinical manifestation of viral infections may be highly variable leading to heterogenous mucosal lesions it is, in most cases, mandatory to differentiate them by specific microbiological tests in addition to clinical examination procedures. This article will give an overview of the role of viruses infecting the oral mucosa, and in addition, describe their clinical manifestation and management.
Anti‐Wound Dehiscence and Antibacterial Dressing with Highly Efficient Self‐Healing Feature for Guided Bone Regeneration Wound Closure
Authors: Shenghao Xue, Ning Tang, Cheng Zhou, Shuobo Fang, Hossam Haick, Jiao Sun, Xueying Wu
Journal: Advanced Healthcare Materials (2024)

Guided bone regeneration (GBR) is a well-established technique for preserving and enhancing alveolar ridge structures. Success in GBR relies on fulfilling the Primary wound closure, Angiogenesis, Space maintenance, and Stability (PASS) principles. Conventional methods, involving titanium meshes and sutures, have drawbacks, including the need for secondary removal and customization challenges. To address these issues, an innovative multifunctional GBR dressing (MGD) based on self-healing elastomer (PUIDS) is introduced. MGD provides sutureless wound closure, prevents food particle accumulation, and maintains a stable environment for bone growth. It offers biocompatibility, bactericidal properties, and effectiveness in an oral GBR model. In summary, MGD provides a reliable, stable osteogenic environment for GBR, aligning with PASS principles and promoting superior post-surgery bone regeneration.
A qualitative exploration of the motivations and implications of chest binding practices for transmasculine Australians
Authors: Serena G. Pehlivanidis, Joel R. Anderson
Journal: International Journal of Transgender Health (2024)

Introduction Trans and gender diverse individuals experience heightened levels of poor mental health outcomes compared to cisgender people. For transmasculine people, a contributor to this disparity can be chest dysphoria, which can be addressed through the masculinization of one's physique in a practice known as chest binding. Current research is limited in its breadth and depth, with there being a scarcity of literature on chest binding motivations and subsequent implications. Addressing this gap, this study aimed to qualitatively explore the chest binding motivations and implications experienced by transmasculine Australians.
E-cadherin loss drives diffuse-type gastric tumorigenesis via EZH2-mediated reprogramming
Authors: Gengyi Zou, Yuanjian Huang, Shengzhe Zhang, Kyung-Pil Ko, Bongjun Kim, Jie Zhang, Vishwa Venkatesan, Melissa P. Pizzi, Yibo Fan, Sohee Jun, Na Niu, Huamin Wang, Shumei Song, Jaffer A. Ajani, Jae-Il Park
Journal: The Journal of Experimental Medicine (2024)

Diffuse-type gastric adenocarcinoma (DGAC) is a deadly cancer often diagnosed late and resistant to treatment. While hereditary DGAC is linked to CDH1 mutations, the role of CDH1/E-cadherin inactivation in sporadic DGAC tumorigenesis remains elusive. We discovered CDH1 inactivation in a subset of DGAC patient tumors. Analyzing single-cell transcriptomes in malignant ascites, we identified two DGAC subtypes: DGAC1 (CDH1 loss) and DGAC2 (lacking immune response). DGAC1 displayed distinct molecular signatures, activated DGAC-related pathways, and an abundance of exhausted T cells in ascites. Genetically engineered murine gastric organoids showed that Cdh1 knock-out (KO), KrasG12D, Trp53 KO (EKP) accelerates tumorigenesis with immune evasion compared with KrasG12D, Trp53 KO (KP). We also identified EZH2 as a key mediator promoting CDH1 loss-associated DGAC tumorigenesis. These findings highlight DGAC's molecular diversity and potential for personalized treatment in CDH1-inactivated patients.