tbuckley/cabot-search huggingface dataset:
Advances in the Model Structure of In Vitro Vascularized Organ-on-a-Chip
Authors: Hongze Yin, Yue Wang, Na Liu, Songyi Zhong, Long Li, Quan Zhang, Zeyang Liu, Tao Yue
Journal: Cyborg and Bionic Systems (2024)

Microvasculature plays a crucial role in human physiology and is closely related to various human diseases. Building in vitro vascular networks is essential for studying vascular tissue behavior with repeatable morphology and signaling conditions. Engineered 3D microvascular network models, developed through advanced microfluidic-based techniques, provide accurate and reproducible platforms for studying the microvasculature in vitro, an essential component for designing organ-on-chips to achieve greater biological relevance. By optimizing the microstructure of microfluidic devices to closely mimic the in vivo microenvironment, organ-specific models with healthy and pathological microvascular tissues can be created. This review summarizes recent advancements in in vitro strategies for constructing microvascular tissue and microfluidic devices. It discusses the static vascularization chips’ classification, structural characteristics, and the various techniques used to build them: growing blood vessels on chips can be either static or dynamic, and in vitro blood vessels can be grown in microchannels, elastic membranes, and hydrogels. Finally, the paper discusses the application scenarios and key technical issues of existing vascularization chips. It also explores the potential for a novel organoid chip vascularization approach that combines organoids and organ chips to generate better vascularization chips.
Beyond T cell exhaustion: TIM-3 regulation of myeloid cells
Authors: Karen O. Dixon, Gonzalo Fernandez Lahore, Vijay K. Kuchroo
Journal: Science Immunology (2024)

T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) is an important immune checkpoint molecule initially identified as a marker of IFN-γ–producing CD4 + and CD8 + T cells. Since then, our understanding of its role in immune responses has significantly expanded. Here, we review emerging evidence demonstrating unexpected roles for TIM-3 as a key regulator of myeloid cell function, in addition to recent work establishing TIM-3 as a delineator of terminal T cell exhaustion, thereby positioning TIM-3 at the interface between fatigued immune responses and reinvigoration. We share our perspective on the antagonism between TIM-3 and T cell stemness, discussing both cell-intrinsic and cell-extrinsic mechanisms underlying this relationship. Looking forward, we discuss approaches to decipher the underlying mechanisms by which TIM-3 regulates stemness, which has remarkable potential for the treatment of cancer, autoimmunity, and autoinflammation.
Subcapsular sinus macrophages maximize germinal center development in non-draining lymph nodes during blood-borne viral infection
Authors: Cynthia C. Aguilar, Anurag Kalia, Morgan E. Brisse, Kimberly A. Dowd, Olivia Wise-Dent, Katherine E. Burgomaster, Joanna Droppo, Theodore C. Pierson, Heather D. Hickman
Journal: Science Immunology (2024)

Lymph node (LN) germinal centers (GCs) are critical sites for B cell activation and differentiation. GCs develop after specialized CD169 + macrophages residing in LN sinuses filter antigens (Ags) from the lymph and relay these Ags into proximal B cell follicles. Many viruses, however, first reach LNs through the blood during viremia (virus in the blood), rather than through lymph drainage from infected tissue. How LNs capture viral Ag from the blood to allow GC development is not known. Here, we followed Zika virus (ZIKV) dissemination in mice and subsequent GC formation in both infected tissue–draining and non-draining LNs. From the footpad, ZIKV initially disseminated through two LN chains, infecting LN macrophages and leading to GC formation. Despite rapid ZIKV viremia, non-draining LNs were not infected for several days. Non-draining LN infection correlated with virus-induced vascular leakage and neutralization of permeability reduced LN macrophage attrition. Depletion of non-draining LN macrophages significantly decreased GC B cells in these nodes. Thus, although LNs inefficiently captured viral Ag directly from the blood, GC formation in non-draining LNs proceeded similarly to draining LNs through LN sinus CD169 + macrophages. Together, our findings reveal a conserved pathway allowing LN macrophages to activate antiviral B cells in LNs distal from infected tissue after blood-borne viral infection.
Rare case of beet juice mimicking gastrointestinal bleeding: diagnostic implication
Authors: Byung Chul Jin, Seung Young Seo, Sang-Wook Kim
Journal: Endoscopy (2024)

Lower gastrointestinal hemorrhage has demonstrated an increasing trend in morbidity and mortality, classifying it as a potential cause of life-threatening events [1]. In cases of acute intestinal bleeding in the large intestine, a colonoscopy should be performed when the patient is stable to identify the cause. This case highlights the importance of comprehensive patient interviews before diagnostic procedures.
Common bile duct polyp: an infrequent cause of jaundice and biliary obstruction
Authors: Gerly E. Guzmán-Calderon, Carlos Huaraca, Brandon Bravo, Joseph Arzapalo
Journal: Endoscopy (2024)

The most common etiology of common bile duct (CBD) obstruction is bile duct stones; less common causes include biliary polyps and intraductal papillary neoplasm of the bile duct (IPNB). Initially described by Nakamura et al. [1] in 2010, IPNB is defined as a pedunculated mass with intraluminal growth exhibiting significant malignant potential that can subsequently lead to cholangiocarcinoma.
<i>IDH</i>-mutant myeloid neoplasms are associated with seronegative rheumatoid arthritis and innate immune activation
Authors: Lih En Hong, Mihir D. Wechalekar, Monika Kutyna, Annabelle Small, Kelly Lim, Chloe Thompson-Peach, Joule J. Li, Rakchha Chhetri, Hamish S. Scott, Anna Brown, Christopher N. Hahn, David T. Yeung, Salvia Sajid, Nirmal Robinson, Ranjeny Thomas, Susan Branford, Richard J. D’Andrea, Saumya E. Samaraweera, Mrinal Patnaik, Susanna Proudman, Daniel Thomas, Chung Hoow Kok, Mithun V. Shah, Devendra K. Hiwase
Journal: Blood (2024)

High prevalence of IDH mutations in seronegative rheumatoid arthritis (RA) with myeloid neoplasm, elevated 2-hydroxyglutarate, dysregulated innate immunity, and proinflammatory microenvironment suggests causative association between IDH mutations and seronegative RA. Our findings merit investigation of IDH inhibitors as therapeutics for seronegative IDH-mutated RA.
Evaluation of Major Pathologic Response and Pathologic Complete Response as Surrogate End Points for Survival in Randomized Controlled Trials of Neoadjuvant Immune Checkpoint Blockade in Resectable in NSCLC
Authors: Jacobi B. Hines, Robert B. Cameron, Alessandra Esposito, Leeseul Kim, Luca Porcu, Antonio Nuccio, Giuseppe Viscardi, Roberto Ferrara, Giulia Veronesi, Patrick M. Forde, Janis Taube, Everett Vokes, Christine M. Bestvina, James M. Dolezal, Matteo Sacco, Marta Monteforte, Tina Cascone, Marina C. Garassino, Valter Torri
Journal: Journal of Thoracic Oncology (2024)

IntroductionControversy remains as to whether pathologic complete response (pCR) and major pathologic response (MPR) represent surrogate end points for event-free survival (EFS) and overall survival (OS) in neoadjuvant trials for resectable NSCLC.MethodsA search of PubMed and archives of international conference abstracts was performed from June 2017 through October 31, 2023. Studies incorporating a neoadjuvant arm with immune checkpoint blockade alone or in combination with chemotherapy were included. Those not providing information regarding pCR, MPR, EFS, or OS were excluded. For trial-level surrogacy, log ORs for pCR and MPR and log hazard ratios for EFS and OS were analyzed using a linear regression model weighted by sample size. The regression coefficient and R2 with 95% confidence interval were calculated by the bootstrapping approach.ResultsSeven randomized clinical trials were identified for a total of 2385 patients. At the patient level, the R2 of pCR and MPR with 2-year EFS were 0.82 (0.66–0.94) and 0.81 (0.63–0.93), respectively. The OR of 2-year EFS rates by response status was 0.12 (0.07–0.19) and 0.11 (0.05–0.22), respectively. For the 2-year OS, the R2 of pCR and MPR were 0.55 (0.09–0.98) and 0.52 (0.10–0.96), respectively. At the trial level, the R2 for the association of OR for response and HR for EFS was 0.58 (0.00–0.97) and 0.61 (0.00–0.97), respectively.ConclusionsOur analyses reveal a robust correlation between pCR and MPR with 2-year EFS but not OS. Trial-level surrogacy was moderate but imprecise. More mature follow-up and data to assess the impact of study crossover are needed.
Reply to Akoumianaki <i>et al</i>.: Studying Diaphragm Activity During Expiration in Mechanically Ventilated Patients – Expiratory Asynchrony Is Important
Authors: Heder Jonathan de Vries, Leo Heunks
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Reply to Akoumianaki et al.: Diaphragm Activity During Expiration in Ventilated Critically Ill Patients – Expiratory Asynchrony Is Important." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Uplifting Antitumor Immunotherapy with Lymph‐Node‐Targeted and Ratio‐Controlled Codelivery of Tumor Cell Lysate and Adjuvant
Authors: Guanhong Cui, Yinping Sun, Liping Qu, Cui Shen, Yu Sun, Fenghua Meng, Yiran Zheng, Zhiyuan Zhong
Journal: Advanced Healthcare Materials (2024)

Cancer vaccines provide a potential strategy to cure patients. Their clinical utilization and efficacy is, however, limited by incomplete coverage of tumor neoantigens and unspecific and restricted activation of dendritic cells (DCs). Tumor cell lysates (TCLs) containing a broad spectrum of neoantigens, while are considered ideal in formulating personalized vaccines, induce generally poor antigen presentation and transient antitumor immune response. Here, intelligent polymersomal nanovaccines (PNVs) that quantitatively coload, efficiently codeliver, and responsively corelease TCL and CpG adjuvant to lymph node (LN) DCs are developed to boost antigen presentation and to induce specific and robust antitumor immunity. PNVs carrying CpG and ovalbumin (OVA) markedly enhance the maturation, antigen presentation, and downstream T cell activation ability of bone-marrow-derived dendritic cells and induce strong systemic immune response after tail base injection. Remarkably, PNVs carrying CpG and TCL cure 85% of B16-F10 melanoma-bearing mice and generate long-lasting anticancer immune memory at a low dose, protecting all cured mice from tumor rechallenge. These LN-directed PNVs being highly versatile and straightforward opens a new door for personalized cancer vaccines.
Triboelectric‐Responsive Drug Delivery Hydrogel for Accelerating Infected Wound Healing
Authors: Xuan Qin, Haoliang Shi, Zhen Wen, Binbin Chu, Hongyang Li, Houyu Wang, Yao He, Xuhui Sun
Journal: Advanced Healthcare Materials (2024)

Abstract Electrotherapy is of great interest in the field of tissue repair as an effective, well‐tolerated, and noninvasive treatment. Triboelectric nanogenerator (TENG) has shown advantages in promoting wound healing due to its peak output characteristic and low Joule heating effect. However, it is limited in infected wound healing due to poor antimicrobial capacity. Here, a wearable triboelectric stimulator (WTS) is developed that consists of a flexible TENG (F‐TENG) and a triboelectric‐responsive drug delivery hydrogel (TR‐DDH) for healing of bacterium‐infected wounds. F‐TENG can generate pulsed current to wounds by converting mechanical energy from body movements. Polypyrrole is prone to reduction and volume contraction under electrical stimulation, resulting in desorption of curcumin nanoparticles (CUR NPs) from the polypyrrole in TR‐DDH. Therefore, the highly efficient and controllable release of CUR NPs can be achieved by triboelectric stimulation. According to the in vitro and in vivo experiments, WTS has the greatest antimicrobial effect and the fastest promotion of infected wound healing compared to treatment with electrical stimulation or curcumin. Finally, the safety assessment demonstrates that the WTS has excellent tissue safety for chronic wound healing. Synergistic therapy with WTS provides an efficient strategy for chronic wound healing and smart‐responsive drug delivery systems.
Cancer Death Rates By State
Journal: JNCI Journal of the National Cancer Institute (2024)

Cancer Death Rates By StateAge-adjusted cancer death rates are for all cancer sites combined for the years 2016-2020, all races (includes Hispanics), both sexes, all ages.Death rates (deaths per 100,000 population per year) are age-adjusted to the 2000 US standard population (19 age groups: <1, 1-4, 5-9, . .., 80-84, 85þ).Source: Cancer death data were provided by the National Vital Statistics System, population counts for the denominators are based on census population as modified
Consensus definitions in imported human schistosomiasis: a GeoSentinel and TropNet Delphi study
Authors: Francesca Tamarozzi, Cristina Mazzi, Spinello Antinori, Marta Arsuaga, Sören L Becker, Emmanuel Bottieau, Daniel Camprubi-Ferrer, Eric Caumes, Alexandre Duvignaud, Martin P Grobusch, Stephane Jaureguiberry, Sabine Jordan, Andreas Mueller, Andreas Neumayr, Jose A Perez-Molina, Joaquin Salas-Coronas, Fernando Salvador, Lina R Tomasoni, Jaap J van Hellemond, Stephen D Vaughan, Linda J Wammes, Lorenzo Zammarchi, Dora Buonfrate, Ralph Huits, Lisette van Lieshout, Federico Gobbi
Journal: The Lancet Infectious Diseases (2024)
Enhanced osteochondral regeneration with a 3D-Printed biomimetic scaffold featuring a calcified interfacial layer
Authors: Di Wu, Kaiwen Zheng, Wenjing Yin, Bin Hu, Mingzhao Yu, Qingxiao Yu, Xiaojuan Wei, Jue Deng, Changqing Zhang
Journal: Bioactive Materials (2024)

The integrative regeneration of both articular cartilage and subchondral bone remains an unmet clinical need due to the difficulties of mimicking spatial complexity in native osteochondral tissues for artificial implants. Layer-by-layer fabrication strategies, such as 3D printing, have emerged as a promising technology replicating the stratified zonal architecture and varying microstructures and mechanical properties. However, the dynamic and circulating physiological environments, such as mass transportation or cell migration, usually distort the pre-confined biological properties in the layered implants, leading to undistinguished spatial variations and subsequently inefficient regenerations. This study introduced a biomimetic calcified interfacial layer into the scaffold as a compact barrier between a cartilage layer and a subchondral bone layer to facilitate osteogenic–chondrogenic repair. The calcified interfacial layer consisting of compact polycaprolactone (PCL), nano-hydroxyapatite, and tasquinimod (TA) can physically and biologically separate the cartilage layer (TA-mixed, chondrocytes-load gelatin methacrylate) from the subchondral bond layer (porous PCL). This introduction preserved the as-designed independent biological environment in each layer for both cartilage and bone regeneration, successfully inhibiting vascular invasion into the cartilage layer and preventing hyaluronic cartilage calcification owing to devascularization of TA. The improved integrative regeneration of cartilage and subchondral bone was validated through gross examination, micro-computed tomography (micro-CT), and histological and immunohistochemical analyses based on an in vivo rat model. Moreover, gene and protein expression studies identified a key role of Caveolin (CAV-1) in promoting angiogenesis through the Wnt/β-catenin pathway and indicated that TA in the calcified layer blocked angiogenesis by inhibiting CAV-1.
Fibroblast function recovery through rejuvenation effect of nanovesicles extracted from human adipose-derived stem cells irradiated with red light
Authors: Jiyu Hyun, Jiin Eom, Jisoo Im, Yu-Jin Kim, Inwoo Seo, Sung-Won Kim, Gwang-Bum Im, Yeong Hwan Kim, Dong-Hyun Lee, Hyun Su Park, Dae Won Yun, Dong-Ik Kim, Jeong-Kee Yoon, Soong Ho Um, Dae Hyeok Yang, Suk Ho Bhang
Journal: Journal of Controlled Release (2024)
Placenta-anchored tadalafil liposomes rescues intrauterine growth restriction through continuous placental blood perfusion improvement
Authors: Miao Tang, Yu Xin, Yunchun Zhao, Xiao Zhang, Meng Zhang, Dongli Sun, Xiaojun Zhu, Yao Yao, Weidong Fei, Caihong Zheng
Journal: Journal of Controlled Release (2024)
3D volume growth rate evaluation in the EORTC-BTG-1320 clinical trial for recurrent WHO grade 2 and 3 meningiomas
Authors: Emeline Tabouret, Julia Furtner, Thomas Graillon, Antonio Silvani, Emilie Le Rhun, Riccardo Soffietti, Giuseppe Lombardi, Juan Manuel Sepúlveda-Sánchez, Petter Brandal, Martin Bendszus, Vassilis Golfinopoulos, Thierry Gorlia, Michael Weller, Felix Sahm, Wolfgang Wick, Matthias Preusser
Journal: Neuro-Oncology (2024)

We previously reported that tumor 3D volume growth rate (3DVGR) classification could help in the assessment of drug activity in patients with meningioma using 3 main classes and a total of 5 subclasses: class 1: decrease; 2: stabilization or severe slowdown; 3: progression. The EORTC-BTG-1320 clinical trial was a randomized phase II trial evaluating the efficacy of trabectedin for recurrent WHO 2 or 3 meningioma. Our objective was to evaluate the discriminative value of 3DVGR classification in the EORTC-BTG-1320.
ANKRD22 promotes resolution of psoriasiform skin inflammation by antagonizing NIK-mediated IL-23 production
Authors: Xichun Xia, Leqing Zhu, Miaomiao Xu, Zhiwei Lei, Hai Yu, Guangqiang Li, Xiao Wang, Hongling Jia, Zhinan Yin, Fang Huang, Yunfei Gao
Journal: Molecular Therapy (2024)
Spatial intratumor heterogeneity of programmed death-ligand 1 expression predicts poor prognosis in resected non–small cell lung cancer
Authors: Yusuke Nagasaki, Tetsuro Taki, Kotaro Nomura, Kenta Tane, Tomohiro Miyoshi, Joji Samejima, Keiju Aokage, Seiyu Jeong-Yoo Ohtani-Kim, Motohiro Kojima, Shingo Sakashita, Naoya Sakamoto, Shumpei Ishikawa, Kenji Suzuki, Masahiro Tsuboi, Genichiro Ishii
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background We quantified the pathological spatial intratumor heterogeneity of programmed death-ligand 1 (PD-L1) expression and investigated its relevance to patient outcomes in surgically resected non–small cell lung carcinoma (NSCLC). Methods This study enrolled 239 consecutive surgically resected NSCLC specimens of pathological stage IIA-IIIB. To characterize the spatial intratumor heterogeneity of PD-L1 expression in NSCLC tissues, we developed a mathematical model based on texture image analysis and determined the spatial heterogeneity index of PD-L1 for each tumor. The correlation between the spatial heterogeneity index of PD-L1 values and clinicopathological characteristics, including prognosis, was analyzed. Furthermore, an independent cohort of 70 cases was analyzed for model validation. Results Clinicopathological analysis showed correlations between high spatial heterogeneity index of PD-L1 values and histological subtype (squamous cell carcinoma; P &amp;lt; .001) and vascular invasion (P = .004). Survival analysis revealed that patients with high spatial heterogeneity index of PD-L1 values presented a significantly worse recurrence-free rate than those with low spatial heterogeneity index of PD-L1 values (5-year recurrence-free survival [RFS] = 26.3% vs 47.1%, P &amp;lt; .005). The impact of spatial heterogeneity index of PD-L1 on cancer survival rates was verified through validation in an independent cohort. Additionally, high spatial heterogeneity index of PD-L1 values were associated with tumor recurrence in squamous cell carcinoma (5-year RFS = 29.2% vs 52.8%, P &amp;lt; .05) and adenocarcinoma (5-year RFS = 19.6% vs 43.0%, P &amp;lt; .01). Moreover, we demonstrated that a high spatial heterogeneity index of PD-L1 value was an independent risk factor for tumor recurrence. Conclusions We presented an image analysis model to quantify the spatial intratumor heterogeneity of protein expression in tumor tissues. This model demonstrated that the spatial intratumor heterogeneity of PD-L1 expression in surgically resected NSCLC predicts poor patient outcomes.
Modeling of intravenous caspofungin administration using an intestine-on-chip reveals altered Candida albicans microcolonies and pathogenicity
Authors: Tim Kaden, Raquel Alonso-Roman, Parastoo Akbarimoghaddam, Alexander S. Mosig, Katja Graf, Martin Raasch, Bianca Hoffmann, Marc T. Figge, Bernhard Hube, Mark S. Gresnigt
Journal: Biomaterials (2024)

Candida albicans is a commensal yeast of the human intestinal microbiota that, under predisposing conditions, can become pathogenic and cause life-threatening systemic infections (candidiasis). Fungal-host interactions during candidiasis are commonly studied using conventional 2D in vitro models, which have provided critical insights into the pathogenicity. However, microphysiological models with a higher biological complexity may be more suitable to mimic in vivo-like infection processes and antifungal drug efficacy. Therefore, a 3D intestine-on-chip model was used to investigate fungal-host interactions during the onset of invasive candidiasis and evaluate antifungal treatment under clinically relevant conditions. By combining microbiological and image-based analyses we quantified infection processes such as invasiveness and fungal translocation across the epithelial barrier. Additionally, we obtained novel insights into fungal microcolony morphology and association with the tissue. Our results demonstrate that C. albicans microcolonies induce injury to the epithelial tissue by disrupting apical cell-cell contacts and causing inflammation. Caspofungin treatment effectively reduced the fungal biomass and induced substantial alterations in microcolony morphology during infection with a wild-type strain. However, caspofungin showed limited effects after infection with an echinocandin-resistant clinical isolate. Collectively, this organ-on-chip model can be leveraged for in-depth characterization of pathogen-host interactions and alterations due to antimicrobial treatment.
Redefining high risk multiple myeloma with an APOBEC/Inflammation-based classifier
Authors: Sarah Grasedieck, Afsaneh Panahi, Matthew C. Jarvis, Faezeh Borzooee, Reuben S. Harris, Mani Larijani, Hervé Avet-Loiseau, Mehmet Samur, Nikhil Munshi, Kevin Song, Arefeh Rouhi, Florian Kuchenbauer
Journal: Leukemia (2024)

Graphical Abstract
Effectiveness of Endoscopic Screening on Esophageal Cancer Incidence and Mortality: A 9-Year Report of the Endoscopic Screening for Esophageal Cancer in China (ESECC) Randomized Trial
Authors: Mengfei Liu, Wenlei Yang, Chuanhai Guo, Zhen Liu, Fenglei Li, Anxiang Liu, Haijun Yang, Lin Shen, Qi Wu, Liping Duan, Hui Wang, Hongrui Tian, Chao Shi, Yaqi Pan, Ying Liu, Fangfang Liu, Noel S. Weiss, Hong Cai, Zhonghu He, Yang Ke
Journal: Journal of Clinical Oncology (2024)

To evaluate the effectiveness of endoscopic screening against incidence of and mortality from esophageal squamous cell carcinoma (ESCC).
Using Tumor Marker Gene Variants to Improve the Diagnostic Accuracy of DUPAN-2 and Carbohydrate Antigen 19-9 for Pancreatic Cancer
Authors: Yohei Ando, Mohamad Dbouk, Takeichi Yoshida, Helena Saba, Elizabeth Abou Diwan, Kanako Yoshida, Ali Dbouk, Amanda L. Blackford, Ming-Tseh Lin, Anne Marie Lennon, Richard A. Burkhart, Jin He, Lori Sokoll, James R. Eshleman, Marcia Irene Canto, Michael Goggins
Journal: Journal of Clinical Oncology (2024)

Circulating carbohydrate antigen 19-9 (CA19-9) levels reflect FUT3 and FUT2 fucosyltransferase activity. Measuring the related glycan, DUPAN-2, can be useful in individuals unable to synthesize CA19-9. We hypothesized that similar to CA19-9, FUT functional groups determined by variants in
T-cell help in the tumor microenvironment enhances rituximab-mediated NK-cell ADCC
Authors: Jyoti Arora, Sabarish Ayyappan, Chaobo Yin, Brian J. Smith, Caitlin D. Lemke-Miltner, Zhaoming Wang, Umar Farooq, George J. Weiner
Journal: Blood (2024)