tbuckley/cabot-search huggingface dataset:
Phenotype and severity of asthma determines bronchial epithelial immune responses to a viral mimic
Authors: Celeste Porsbjerg, Juan Jose Nieto-Fontarigo, Samuel Cerps, Sangheeta Ramu, Mandy Menzel, Morten Hvidtfeldt, Alexander Silberbrandt, Laurits Frøssing, Ditte Klein, Asger Sverrild, Lena Uller
Journal: European Respiratory Journal (2021)

Asthma is characterised by an aggravated immune response to respiratory viral infections. This phenomenon is a clinically well-recognised driver of acute exacerbations, but how different phenotypes of asthma respond immunologically to viruses is unclear.To describe the association between different phenotypes and severity of asthma and bronchial epithelial immune responses to viral stimulation.In the Immunoreact study, healthy subjects (n=10) and 50 patients with asthma were included; 30 (60%) were atopic, and 34 (68%) were eosinophilic; 14 (28%) had severe asthma. All participants underwent bronchoscopy with collection of bronchial brushings. Bronchial epithelial cells (BECs) were expanded and stimulated with the viral replication mimic poly (I:C) (Toll-like receptor (TLR)3 agonist) in vitro. The expression of TLR3-induced pro-inflammatory and antiviral responses of BECs were analysed using reverse transcriptase quantitative PCR and multiplex ELISA and compared across asthma phenotypes and severity of disease.Patients with atopic asthma had increased induction of interleukin (IL)-4, interferon (IFN)-β, IL-6, tumour necrosis factor-α, and IL-1β after poly (I:C) stimulation compared to non-atopic patients, whereas in patients with eosinophilic asthma only IL-6 and IL-8 induction was higher than in non-eosinophilic asthma. Patients with severe asthma displayed a decreased antiviral IFN-β, and increased expression of IL-8, most pronounced in atopic and eosinophilic asthmatics. Furthermore, induction of IL-33 in response to poly (I:C) was increased in severe atopic and in severe eosinophilic asthma, but thymic stromal lymphopoietin only in severe eosinophilic asthma.The bronchial epithelial immune response to a viral mimic stimulation differs between asthma phenotypes and severities, which may be important to consider when targeting novel asthma treatments.
181P Poor response to PD-1 inhibitors in metastatic non-small cell lung cancer (mNSCLC) patients with liver metastases may be mediated by myeloid populations
Authors: M. Makarem, S.C. Lau, M.J. Elliott, A. Rabinovitch, S. Kuang, S. Schmid, M.S. Tsao, T. McGaha, P. Ohashi, F.A. Shepherd, P. Bradbury, G. Liu, N.B. Leighl, A. Sacher
Journal: Annals of Oncology (2021)
Difficulties in Diagnosing Shin Bone Formations in a Child with Primary Oxaluria (Clinical Case)
Authors: N. A. Sholokhova, E. B. Ol’khova, E. A. Grik
Journal: Radiology - Practice (2021)

Diagnosis of bone mineral disorders (MCI) is an urgent task in pediatrics. Of particular importance is the timely visualization of destructive changes in bone tissue, leading to significant deformations and impairment of the quality of life of patients. At the moment, there are no unified algorithms for radiological examination of children with chronic kidney disease (CKD), allowing early detection of disorders of mineral and bone metabolism. This clinical example demonstrates the difficulties of diagnosing a brown tumor in a child with primary type I hyperoxaluria. Along with this, the effectiveness of methods of radiation diagnostics in the protocol of dynamic observation of patients with the syndrome of mineral and bone disorders in chronic kidney disease (MCD-CKD) is presented.
Long-term ecological assessment of intracranial electrophysiology synchronized to behavioral markers in obsessive-compulsive disorder
Authors: Nicole R. Provenza, Sameer A. Sheth, Evan M. Dastin-van Rijn, Raissa K. Mathura, Yaohan Ding, Gregory S. Vogt, Michelle Avendano-Ortega, Nithya Ramakrishnan, Noam Peled, Luiz Fernando Fracassi Gelin, David Xing, Laszlo A. Jeni, Itir Onal Ertugrul, Adriel Barrios-Anderson, Evan Matteson, Andrew D. Wiese, Junqian Xu, Ashwin Viswanathan, Matthew T. Harrison, Kelly R. Bijanki, Eric A. Storch, Jeffrey F. Cohn, Wayne K. Goodman, David A. Borton
Journal: Nature Medicine (2021)
Btm-3566, a Novel Activator of the Mitochondrial Stress Response Promotes Robust Therapeutic Responses <i>in Vitro</i> and <i>In Vivo</i> in Diffuse Large B-Cell Lymphoma
Authors: Adrian Schwarzer, Matheus Oliveira, Marc-Jens Kleppa, Andy Anantha, Alan Cooper, Mark Hannink, Todd Hembrough, Jedd Levine, Michael Luther, Michael Stocum, Marc Liesa-Roig, Matthew Kostura
Journal: Blood (2021)
Hard to Swallow
Authors: Michael J. Litt, Mary W. Montgomery, Kirstin M. Small, Amy L. Miller, Joseph Loscalzo
Journal: New England Journal of Medicine (2021)

A previously healthy 20-year-old college student presented before the Covid-19 pandemic with a 3-day history of throat pain, malaise, cough, and chills. She had no congestion or rhinorrhea.
Immunotherapy First for <i>BRAF</i>-Mutant Melanoma
Journal: Cancer Discovery (2021)

More people with newly diagnosed BRAFV600-mutant metastatic melanoma survive at least 2 years when they begin treatment with a combination of immunotherapies-the PD-1 inhibitor nivolumab and the CTLA4 inhibitor ipilimumab-instead of a combination of targeted therapies-the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib. Researchers say the findings point to a new standard for first-line treatment.
Hybrid argon plasma coagulation-assisted endoscopic mucosal resection for large sessile colon polyps to reduce local recurrence: a prospective pilot study
Authors: Victoria L. Motz, Courtney Lester, Matthew T. Moyer, Jennifer L. Maranki, John M. Levenick
Journal: Endoscopy (2021)

Abstract Background Endoscopic mucosal resection (EMR) of large, sessile colon polyps often results in incomplete resection with subsequent recurrence. The aim of this prospective pilot study was to evaluate the efficacy and safety of a novel technique, hybrid argon plasma coagulation-assisted EMR (hAPC-EMR), to remove large, sessile polyps. Methods 40 eligible patients underwent hAPC-EMR for the removal of one or more nonpedunculated colon polyps ≥ 20 mm. Participants were contacted 30 days post-procedure to assess for adverse events and were recommended to return for a surveillance colonoscopy at 6 months to assess for local recurrence. Results At the time writing, 32 patients with 35 polyps (median size 27 mm; interquartile range 14.5 mm) resected by hAPC-EMR had undergone the 6-month follow-up colonoscopy. Recurrence rate was 0 % (95 % confidence interval [CI] 0–0) at follow-up. Post-polypectomy bleeding was experienced by three patients (7.5 %; 95 %CI 0.00–0.15), and no patients developed post-polypectomy syndrome. Conclusion These preliminary results showed 0 % local recurrence rate at 6 months and demonstrated the safety profile of hAPC-EMR. A large, randomized, controlled trial is required to confirm these results.
A Versatile Calcium Phosphate Nanogenerator for Tumor Microenvironment‐activated Cancer Synergistic Therapy (Adv. Healthcare Mater. 23/2021)
Authors: Lian‐Hua Fu, Chunying Li, Weimin Yin, Yan‐Ru Hu, Tuanwei Sun, Yilin Wan, Jing Lin, Zhiming Li, Peng Huang
Journal: Advanced Healthcare Materials (2021)

Calcium Phosphate In article number 2101563, Zhiming Li, Peng Huang, and co-workers develop a tumor targeting and tumor microenvironment (TME)-activated calcium phosphate nanotheranostic system for effective synergistic cancer starvation/gas therapy. This system not only exhausts the glucose nutrients in tumors by glucose oxidase-triggered glucose oxidation, the generated H2O2 can oxidize L-Arg into NO under acidic TME for enhanced gas therapy.
Mapping the conformational epitope of a therapeutic monoclonal antibody against HBsAg by in vivo selection of HBV escape variants
Authors: Chang‐Ru Wu, Hyun‐Jin Kim, Cheng‐Pu Sun, Chen‐Yen Chung, You‐Yu Lin, Mi‐Hua Tao, Jung‐Hwan Kim, Ding‐Shinn Chen, Pei‐Jer Chen
Journal: Hepatology (2021)

Abstract Background and Aims Hepatitis B immunoglobulin (HBIG) has been routinely applied in the liver transplantation setting to block HBV reinfection of grafts. However, new monoclonal anti‐HBV surface antibodies have been developed to replace HBIG. The epitopes of such monoclonal antibodies may affect the emergence of escape variants and deserve study. Approach and Results The conformational epitope of sLenvervimab, a surrogate form of Lenvervimab, which is a monoclonal anti‐HBsAg antibody currently under phase 3 trial, was investigated by selecting escape mutants from a human liver chimeric mouse. HBV‐infected chimeric mice treated with sLenvervimab monotherapy showed an initial decline in circulating HBsAg levels, followed by a quick rebound in 1 month. Sequencing of circulating or liver HBV DNA revealed emerging variants, with replacement of amino acid E164 or T140, two residues widely separated in HBsAg. E164 HBV variants strongly resisted sLenvervimab neutralization in cell culture infection, and the T140 variant moderately resisted sLenvervimab neutralization. Natural HBV variants with amino‐acid replacements adjacent to E164 were constructed and examined for sLenvervimab neutralization effects. Variants with K160 replacement also resisted neutralization. These data revealed the conformational epitope of sLenvervimab. Conclusions Selection of antibody‐escape HBV variants in human chimeric mice works efficiently. Analysis of such emerging variants helps to identify anchor amino‐acid residues of the conformational epitope that are difficult to discover by conventional approaches.
Template‐Enabled Biofabrication of Thick 3D Tissues with Patterned Perfusable Macrochannels
Authors: Elham Davoodi, Hossein Montazerian, Masoud Zhianmanesh, Reza Abbasgholizadeh, Reihaneh Haghniaz, Avijit Baidya, Homeyra Pourmohammadali, Nasim Annabi, Paul S. Weiss, Ehsan Toyserkani, Ali Khademhosseini
Journal: Advanced Healthcare Materials (2021)

Interconnected pathways in 3D bioartificial organs are essential to retaining cell activity in thick functional 3D tissues. 3D bioprinting methods have been widely explored in biofabrication of functionally patterned tissues; however, these methods are costly and confined to thin tissue layers due to poor control of low-viscosity bioinks. Here, cell-laden hydrogels that could be precisely patterned via water-soluble gelatin templates are constructed by economical extrusion 3D printed plastic templates. Tortuous co-continuous plastic networks, designed based on triply periodic minimal surfaces (TPMS), serve as a sacrificial pattern to shape the secondary sacrificial gelatin templates. These templates are eventually used to form cell-encapsulated gelatin methacryloyl (GelMA) hydrogel scaffolds patterned with the complex interconnected pathways. The proposed fabrication process is compatible with photo-crosslinkable hydrogels wherein prepolymer casting enables incorporation of high cell populations with high viability. The cell-laden hydrogel constructs are characterized by robust mechanical behavior. In vivo studies demonstrate a superior cell ingrowth into the highly permeable constructs compared to the bulk hydrogels. Perfusable complex interconnected networks within cell-encapsulated hydrogels may assist in engineering thick and functional tissue constructs through the permeable internal channels for efficient cellular activities in vivo.
W-Net: Dense and diagnostic semantic segmentation of subcutaneous and breast tissue in ultrasound images by incorporating ultrasound RF waveform data
Authors: Gautam Rajendrakumar Gare, Jiayuan Li, Rohan Joshi, Rishikesh Magar, Mrunal Prashant Vaze, Michael Yousefpour, Ricardo Luis Rodriguez, John Michael Galeotti
Journal: Medical Image Analysis (2021)

We study the use of raw ultrasound waveforms, often referred to as the "Radio Frequency" (RF) data, for the semantic segmentation of ultrasound scans to carry out dense and diagnostic labeling. We present W-Net, a novel Convolution Neural Network (CNN) framework that employs the raw ultrasound waveforms in addition to the grey ultrasound image to semantically segment and label tissues for anatomical, pathological, or other diagnostic purposes. To the best of our knowledge, this is also the first deep-learning or CNN approach for segmentation that analyzes ultrasound raw RF data along with the grey image. We chose subcutaneous tissue (SubQ) segmentation as our initial clinical goal for dense segmentation since it has diverse intermixed tissues, is challenging to segment, and is an underrepresented research area. SubQ potential applications include plastic surgery, adipose stem-cell harvesting, lymphatic monitoring, and possibly detection/treatment of certain types of tumors. Unlike prior work, we seek to label every pixel in the image, without the use of a background class. A custom dataset consisting of hand-labeled images by an expert clinician and trainees are used for the experimentation, currently labeled into the following categories: skin, fat, fat fascia/stroma, muscle, and muscle fascia. We compared W-Net and attention variant of W-Net (AW-Net) with U-Net and Attention U-Net (AU-Net). Our novel W-Net's RF-Waveform encoding architecture outperformed regular U-Net and AU-Net, achieving the best mIoU accuracy (averaged across all tissue classes). We study the impact of RF data on dense labeling of the SubQ region, which is followed by the analyses of the generalization capability of the networks to patients and analysis on the SubQ tissue classes, determining that fascia tissues, especially muscle fascia in particular, are the most difficult anatomic class to recognize for both humans and AI algorithms. We present diagnostic semantic segmentation, which is semantic segmentation carried out for the purposes of direct diagnostic pixel labeling, and apply it to breast tumor detection task on a publicly available dataset to segment pixels into malignant tumor, benign tumor, and background tissue class. Using the segmented image we diagnose the patient by classifying the breast lesion as either benign or malignant. We demonstrate the diagnostic capability of RF data with the use of W-Net, which achieves the best segmentation scores across all classes.
PRDM16 Is a Compact Myocardium-Enriched Transcription Factor Required to Maintain Compact Myocardial Cardiomyocyte Identity in Left Ventricle
Authors: Tongbin Wu, Zhengyu Liang, Zengming Zhang, Canzhao Liu, Lunfeng Zhang, Yusu Gu, Kirk L. Peterson, Sylvia M. Evans, Xiang-Dong Fu, Ju Chen
Journal: Circulation (2021)

Left ventricular noncompaction cardiomyopathy (LVNC) was discovered half a century ago as a cardiomyopathy with excessive trabeculation and a thin ventricular wall. In the decades since, numerous studies have demonstrated that LVNC primarily has an effect on left ventricles (LVs) and is often associated with LV dilation and dysfunction. However, in part because of the lack of suitable mouse models that faithfully mirror the selective LV vulnerability in patients, mechanisms underlying the susceptibility of LVs to dilation and dysfunction in LVNC remain unknown. Genetic studies have revealed that deletions and mutations in
Interleukin-10 receptor signaling promotes the maintenance of a PD-1int TCF-1+ CD8+ T cell population that sustains anti-tumor immunity
Authors: Bola S Hanna, Laura Llaó-Cid, Murat Iskar, Philipp M Roessner, Lara C Klett, John K L Wong, Yashna Paul, Nikolaos Ioannou, Selcen Öztürk, Norman Mack, Verena Kalter, Dolors Colomer, Elías Campo, Johannes Bloehdorn, Stephan Stilgenbauer, Sascha Dietrich, Manfred Schmidt, Richard Gabriel, Karsten Rippe, Markus Feuerer, Alan G Ramsay, Peter Lichter, Marc Zapatka, Martina Seiffert
Journal: Immunity (2021)
Association of Health-Care System and Survival in African American and Non-Hispanic White Patients With Bladder Cancer
Authors: Nikhil V Kotha, Abhishek Kumar, Edmund M Qiao, Alex S Qian, Rohith S Voora, Vinit Nalawade, A Karim Kader, Rana R McKay, Tyler F Stewart, Brent S Rose
Journal: JNCI Journal of the National Cancer Institute (2021)

African American patients with bladder cancer have inferior outcomes compared with non-Hispanic White (White) patients. We hypothesize that access to health care is a primary determinant of this disparity. We compared outcomes by race for patients with bladder cancer receiving care within the predominant hybrid-payer health-care model of the United States captured in the Surveillance, Epidemiology, and End Results (SEER) database with those receiving care within the equal-access model of the Veterans' Health Administration (VHA).African American and White patients diagnosed with bladder cancer were identified in SEER and VHA. Stage at presentation, bladder cancer-specific mortality (BCM), and overall survival (OS) were compared by race within each health-care system.The SEER cohort included 122 449 patients (93.7% White, 6.3% African American). The VHA cohort included 36 322 patients (91.0% White, 9.0% African American). In both cohorts, African American patients were more likely to present with muscle-invasive disease and metastases, but the differences between races were statistically significantly smaller in VHA. In SEER multivariable models, African American patients had worse BCM (hazard ratio [HR] = 1.22, 95% confidence interval [CI] = 1.15 to 1.29) and OS (HR = 1.26, 95% CI = 1.20 to 1.31). In contrast within the VHA, African American patients had similar BCM (HR = 0.97, 95% CI = 0.88 to 1.07) and OS (HR = 0.99, 95% CI = 0.93 to 1.05).In this study of contrasting health-care models, receiving medical care in an equal-access system was associated with reduced differences in stage at presentation and eliminated disparities in survival outcomes for African American patients with bladder cancer. Our findings highlight the importance of reducing financial barriers to care to notably improve health equity and oncologic outcomes for African American patients.
Digital technologies: a new determinant of health
Authors: None The Lancet Digital Health
Journal: The Lancet Digital Health (2021)

The Lancet and Financial Times have published a Commission with recommendations for successful integration of digital technologies in health. The bottom line of the Commission is that weak governance of digital technologies is causing health inequities and compromising human rights. This finding is compounded by the fact that many companies are expanding their reach into the health sector, collating and analysing health and personal data. The future governance of digital technologies in health care "must be driven by public purpose, not private profit".
ATRX loss promotes immunosuppressive mechanisms in IDH1 mutant glioma
Authors: Chengchen Hu, Kimberly Wang, Ceylan Damon, Yi Fu, Tengjiao Ma, Lisa Kratz, Bachchu Lal, Mingyao Ying, Shuli Xia, Daniel P Cahill, Christopher M Jackson, Michael Lim, John Laterra, Yunqing Li
Journal: Neuro-Oncology (2021)

ATRX inactivation occurs with IDH1R132H and p53 mutations in over 80% of Grades II/III astrocytomas. It is believed that ATRX loss contributes to oncogenesis by dysregulating epigenetic and telomere mechanisms but effects on anti-glioma immunity have not been explored. This paper examines how ATRX loss contributes to the malignant and immunosuppressive phenotypes of IDH1R132H/p53mut glioma cells and xenografts.Isogenic astrocytoma cells (+/-IDH1R132H/+/-ATRXloss) were established in p53mut astrocytoma cell lines using lentivirus encoding doxycycline-inducible IDH1R132H, ATRX shRNA, or Lenti-CRISPR/Cas9 ATRX. Effects of IDH1R132H+/-ATRXloss on cell migration, growth, DNA repair, and tumorigenicity were evaluated by clonal growth, transwell and scratch assays, MTT, immunofluorence and immunoblotting assays, and xenograft growth. Effects on the expression and function of modulators of the immune microenvironment were quantified by qRT-PCR, immunoblot, T-cell function, macrophage polarization, and flow cytometry assays. Pharmacologic inhibitors were used to examine epigenetic drivers of the immunosuppressive transcriptome of IDH1R132H/p53mut/ATRXloss cells.Adding ATRX loss to the IDH1R132H/p53mut background promoted astrocytoma cell aggressiveness, induced expression of BET proteins BRD3/4 and an immune-suppressive transcriptome consisting of up-regulated immune checkpoints (e.g., PD-L1, PD-L2) and altered cytokine/chemokine profiles (e.g., IL33, CXCL8, CSF2, IL6, CXCL9). ATRX loss enhanced the capacity of IDH1R132H/p53mut cells to induce T-cell apoptosis, tumorigenic/anti-inflammatory macrophage polarization and Treg infiltration. The transcriptional and biological immune-suppressive responses to ATRX loss were enhanced by temozolomide and radiation and abrogated by pharmacologic BET inhibition.ATRX loss activates a BRD-dependent immune-suppressive transcriptome and immune escape mechanism in IDH1R132H/p53mut astrocytoma cells.
Nintedanib enhances the efficacy of PD-L1 blockade by upregulating MHC-I and PD-L1 expression in tumor cells
Authors: Jingyao Tu, Haoran Xu, Li Ma, Chunya Li, Wan Qin, Xinyi Chen, Ming Yi, Li Sun, Bo Liu, Xianglin Yuan
Journal: Theranostics (2021)

Background: Immune checkpoint inhibitors (ICIs), such as programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), have been widely applied in clinical and scientific research. Despite their effective antitumor effects in clinical tumor therapy, most tumors are still resistant to ICIs and long-term benefits are lacking. In addition, tumor patients complicated with interstitial lung disease limit the application of ICI therapy. Therefore, for these cases, there is an urgent need to develop new methods to relieve lung complications and enhance the efficacy of ICI therapy. Nintedanib, a potent triple angiokinase inhibitor approved for the treatment of progressive fibrotic interstitial lung disease. However, its immunotherapy synergy properties and mechanism are still pending further exploration. Methods: To explore the therapeutic potential of nintedanib and αPD-L1 combination therapy, MC38, LLC, and 4T1 tumor models were used to investigate antitumor and antimetastatic activities in vivo. An idiopathic pulmonary fibrosis-tumor bearing model was used to evaluate the effect of the synergy therapy on tumor model complicated with lung disease. Moreover, RNA-seq, immunohistochemistry, and flow cytometry were utilized to analyze the effect of combination treatment on the tumor microenvironment. The bioactivity following different treatments was determined by western blotting, CCK-8, and flow cytometry. Results: In this study, nintedanib and αPD-L1 synergy therapy exhibited significant antitumor, antimetastatic and anti-pulmonary fibrosis effects. Both in vitro and in vivo experiments revealed that these effects included promoting vessel normalization, increasing infiltration and activation of immune cells in tumors, enhancing the response of interferon-gamma, and activating the MHC class I-mediated antigen presentation process. Moreover, our results showed an increased expression of PD-L1 and promoted phosphorylation of STAT3 after nintedanib (1 µM) treatment. Conclusion: The combination of nintedanib and αPD-L1 increased ICI therapy responses, relieved lung complications and further activated the tumor immune microenvironment; thus, exhibiting a notable antitumor effect. Accordingly, the nintedanib synergy strategy is expected to be a promising candidate therapy for tumor patients complicated with interstitial lung disease in clinical practice.
The Impact of Genetic Ancestry on the Biology and Prognosis of Childhood Acute Lymphoblastic Leukemia
Authors: Shawn Lee, Federico Antillón, Deqing Pei, Wenjian Yang, Kathryn G Roberts, Zhenhua Li, Meenakshi Devidas, Wentao Yang, Cesar Najera, Hai Peng Lin, Ah Moy Tan, Hany Ariffin, Cheng Cheng, William E. Evans, Stephen P Hunger, Sima Jeha, Charles G. Mullighan, Mignon L. Loh, Allen Eng Juh Yeoh, Ching-Hon Pui, Jun J. Yang
Journal: Blood (2021)
Rational administration sequencing of immunochemotherapy elicits powerful anti-tumor effect
Authors: Chunqi Zhu, Yingying Shi, Qingpo Li, Lihua Luo, Xiang Li, Zhenyu Luo, Yichao Lu, Junlei Zhang, Mengshi Jiang, Bing Qin, Weigen Qiu, Zhaolei Jin, Xindong Jiang, Jiandong Xiao, Jian You
Journal: Journal of Controlled Release (2021)