tbuckley/cabot-search huggingface dataset:
Functions and clinical significance of mechanical tumor microenvironment: cancer cell sensing, mechanobiology and metastasis
Authors: Hanying Zhou, Meng Wang, Yixi Zhang, Qingqing Su, Zhengxin Xie, Xiangyan Chen, Ran Yan, Ping Li, Tingting Li, Xiang Qin, Hong Yang, Chunhui Wu, Fengming You, Shun Li, Yiyao Liu
Journal: Cancer Communications (2022)

Dynamic and heterogeneous interaction between tumor cells and the surrounding microenvironment fuels the occurrence, progression, invasion, and metastasis of solid tumors. In this process, the tumor microenvironment (TME) fractures cellular and matrix architecture normality through biochemical and mechanical means, abetting tumorigenesis and treatment resistance. Tumor cells sense and respond to the strength, direction, and duration of mechanical cues in the TME by various mechanotransduction pathways. However, far less understood is the comprehensive perspective of the functions and mechanisms of mechanotransduction. Due to the great therapeutic difficulties brought by the mechanical changes in the TME, emerging studies have focused on targeting the adverse mechanical factors in the TME to attenuate disease rather than conventionally targeting tumor cells themselves, which has been proven to be a potential therapeutic approach. In this review, we discussed the origins and roles of mechanical factors in the TME, cell sensing, mechano-biological coupling and signal transduction, in vitro construction of the tumor mechanical microenvironment, applications and clinical significance in the TME.
Ominous Electrocardiographic Abnormalities in a Patient With Hepatocellular Carcinoma
Authors: Yu Xu, Lili Hong, Tong Liu
Journal: JAMA Internal Medicine (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
A novel unbiased method reveals progressive podocyte globotriaosylceramide accumulation and loss with age in females with Fabry disease
Authors: Behzad Najafian, Aurelio Silvestroni, Alexey Sokolovskiy, Camilla Tøndel, Einar Svarstad, Bogdan Obrisca, Gener Ismail, Myrl D. Holida, Michael Mauer
Journal: Kidney International (2022)
Do the Youngest Drivers Crash the Most?
Authors: Federico E. Vaca, Kaigang Li
Journal: JAMA Network Open (2022)

Elizabeth A. Walshe, PhD; Daniel Romer, PhD; Abraham J. Wyner, PhD; Shukai Cheng, MS; Michael R. Elliott, PhD; Robert Zhang, BA; Alexander K. Gonzalez, MS; Natalie Oppenheimer, BA; Flaura K. Winston, MD, PhD
An ACE2-blocking antibody confers broad neutralization and protection against Omicron and other SARS-CoV-2 variants of concern
Authors: Wenjuan Du, Daniel L. Hurdiss, Dubravka Drabek, Anna Z. Mykytyn, Franziska K. Kaiser, Mariana González-Hernández, Diego Muñoz-Santos, Mart M. Lamers, Rien van Haperen, Wentao Li, Ieva Drulyte, Chunyan Wang, Isabel Sola, Federico Armando, Georg Beythien, Malgorzata Ciurkiewicz, Wolfgang Baumgärtner, Kate Guilfoyle, Tony Smits, Joline van der Lee, Frank J. M. van Kuppeveld, Geert van Amerongen, Bart L. Haagmans, Luis Enjuanes, Albert D. M. E. Osterhaus, Frank Grosveld, Berend-Jan Bosch
Journal: Science Immunology (2022)

The ongoing evolution of SARS-CoV-2 has resulted in the emergence of Omicron, which displays notable immune escape potential through mutations at key antigenic sites on the spike protein. Many of these mutations localize to the spike protein ACE2 receptor binding domain, annulling the neutralizing activity of therapeutic antibodies that were effective against other variants of concern (VOCs) earlier in the pandemic. Here, we identified a receptor-blocking human monoclonal antibody, 87G7, that retained potent in vitro neutralizing activity against SARS-CoV-2 variants including the Alpha, Beta, Gamma, Delta, and Omicron (BA.1/BA.2) VOCs. Using cryo–electron microscopy and site-directed mutagenesis experiments, we showed that 87G7 targets a patch of hydrophobic residues in the ACE2-binding site that are highly conserved in SARS-CoV-2 variants, explaining its broad neutralization capacity. 87G7 protected mice and hamsters prophylactically against challenge with all current SARS-CoV-2 VOCs and showed therapeutic activity against SARS-CoV-2 challenge in both animal models. Our findings demonstrate that 87G7 holds promise as a prophylactic or therapeutic agent for COVID-19 that is more resilient to SARS-CoV-2 antigenic diversity.
Proctitis and prostatitis by Neisseria meningitidis among MSM: A case series
Authors: Elena Bruzzesi, Angelo Roberto Raccagni, Diana Canetti, Laura Galli, Flavia Badalucco, Giovanni Mori, Matteo Chiurlo, Monica Guffanti, Antonella Castagna, Silvia Nozza
Journal: Journal of Infection (2022)
Ecoresponsible actions in operating rooms: A health ecological and economic evaluation
Authors: N. Rouvière, S. Chkair, F. Auger, C. Alovisetti, MJ. Bernard, P. Cuvillon, J-M. Kinowski, G. Leguelinel-Blache, V. Chasseigne
Journal: International Journal of Surgery (2022)

In the current context of climate change, actions must be taken to improve the hospital's ecological footprint, particularly in the operating room, which is a major consumer of medical devices.This prospective pilot study assessed the ecological and economic impacts of sustainable actions targeting medical devices designed by a multidisciplinary working group and implemented in the 24 operating rooms of a University Hospital over one year. The ecological analysis was based on the life cycle assessment method and categorized in seven impacts. The economic impact was assessed by a micro-costing analysis and divided in four main expense items: human and material resources, logistics, and waste management.In total, 13 actions were implemented with the aim of reducing waste volume, improving waste sorting, and increasing eco-responsible purchases. In one year, these 13 actions allowed avoiding the emission of 203 tons eq CO2. The environmental and human toxicity benefits were 707.8 and 156.2 tons of 1.4 dichlorobenzene, respectively. Concerning non-renewable resources, these actions avoided the extraction of 9 tons of oil (petroleum) and 610 kg of copper per year. These actions led to a land occupation reduction of 1071.3 m2year and to water saving of 552 m3. From the economic side, the implementation of these actions brought a gain of €3747.9 for the first year and of €5188.2 for the following years.The integration of sustainable measures in operating rooms leads to important ecological benefits and also generating savings. This more eco-responsible approach should be considered in all healthcare establishments that generate a significant annual volume of waste.
Injectable remote magnetic nanofiber/hydrogel multiscale scaffold for functional anisotropic skeletal muscle regeneration
Authors: Ling Wang, Ting Li, Zihan Wang, Juedong Hou, Sitian Liu, Qiao Yang, Liu Yu, Weihong Guo, Yongjie Wang, Baolin Guo, Wenhua Huang, Yaobin Wu
Journal: Biomaterials (2022)
Clinical advances in oncolytic virotherapy for pediatric brain tumors
Authors: Gelare Ghajar-Rahimi, Kyung-Don Kang, Stacie K. Totsch, Sam Gary, Abbey Rocco, Sarah Blitz, Kara Kachurak, M.R. Chambers, Rong Li, Elizabeth A. Beierle, Asim Bag, James M. Johnston, James M. Markert, Joshua D. Bernstock, Gregory K. Friedman
Journal: Pharmacology & Therapeutics (2022)
Ontology-aware deep learning enables ultrafast and interpretable source tracking among sub-million microbial community samples from hundreds of niches
Authors: Yuguo Zha, Hui Chong, Hao Qiu, Kai Kang, Yuzheng Dun, Zhixue Chen, Xuefeng Cui, Kang Ning
Journal: Genome Medicine (2022)

Abstract The taxonomic structure of microbial community sample is highly habitat-specific, making source tracking possible, allowing identification of the niches where samples originate. However, current methods face challenges when source tracking is scaled up. Here, we introduce a deep learning method based on the Ontology-aware Neural Network approach, ONN4MST, for large-scale source tracking. ONN4MST outperformed other methods with near-optimal accuracy when source tracking among 125,823 samples from 114 niches. ONN4MST also has a broad spectrum of applications. Overall, this study represents the first model-based method for source tracking among sub-million microbial community samples from hundreds of niches, with superior speed, accuracy, and interpretability. ONN4MST is available at https://github.com/HUST-NingKang-Lab/ONN4MST .
NR2F1 Is a Barrier to Dissemination of Early-Stage Breast Cancer Cells
Authors: Carolina Rodriguez-Tirado, Nupura Kale, Maria J. Carlini, Nitisha Shrivastava, Alcina A. Rodrigues, Bassem D. Khalil, Jose Javier Bravo-Cordero, Yan Hong, Melissa Alexander, Jiayi Ji, Fariba Behbod, Maria Soledad Sosa
Journal: Cancer Research (2022)

Cancer cells can disseminate during very early and sometimes asymptomatic stages of tumor progression. Though biological barriers to tumorigenesis have been identified and characterized, the mechanisms that limit early dissemination remain largely unknown. We report here that the orphan nuclear receptor nuclear receptor subfamily 2, group F, member 1 (NR2F1)/COUP-TF1 serves as a barrier to early dissemination. NR2F1 expression was decreased in patient ductal carcinoma in situ (DCIS) samples. High-resolution intravital imaging of HER2+ early-stage cancer cells revealed that loss of function of NR2F1 increased in vivo dissemination and was accompanied by decreased E-cadherin expression, activation of wingless-type MMTV integration site family, member 1 (WNT)-dependent β-catenin signaling, disorganized laminin 5 deposition, and increased expression of epithelial-mesenchymal transition (EMT) genes such as twist basic helix-loop-helix transcription factor 1 (TWIST1), zinc finger E-box binding homeobox 1 (ZEB1), and paired related homeobox 1 (PRRX1). Furthermore, downregulation of NR2F1 promoted a hybrid luminal/basal phenotype. NR2F1 expression was positively regulated by p38α signaling and repressed by HER2 and WNT4 pathways. Finally, early cancer cells with NR2F1LOW/PRRX1HIGH staining were observed in DCIS samples. Together, these findings reveal the existence of an inhibitory mechanism of dissemination regulated by NR2F1 in early-stage breast cancer cells.
A new diagnosis of monoclonal B‐cell lymphocytosis with cytoplasmic inclusions in a patient with <scp>COVID</scp>‐19
Authors: Lorella Lanza, Brisejda Koroveshi, Francesca Barducchi, Angela Lorenzo, Ezio Venturino, Enrico Cappelli, Flavia Lillo, Barbara J. Bain
Journal: American Journal of Hematology (2022)

A 75-year-old man with a history of chronic ischemic heart disease with a previously normal blood count, presented to the emergency room with fever and tachycardia. There was no hepatosplenomegaly or lymphadenopathy. An electrocardiogram showed a left bundle branch block. Oxygen saturation was 95%. Because of the fever, the patient was tested for SARS-CoV-2; the reverse transcriptase-polymerase chain reaction was positive. A diagnosis of COVID-19 was made. The patient's blood count showed a white blood cell count (WBC) of 10.46 × 109/L, lymphocytes 4.51 × 109/L, hemoglobin 129 g/L, and platelet count 233 × 109/L. D-dimer was 659 μg/L (normal range < 500) and interleukin 6 was 76.3 pg/ml (normal range < 6.4). A computed tomography scan of the chest showed bilateral interstitial infiltrates associated with multiple enlarged mediastinal lymph nodes. Following a rapid and unexpected increase of the WBC to 17.49 × 109/L and of the lymphocyte count to 8.37 × 109/L over the next 48 h, a blood film and immunophenotyping were performed. The film showed small and medium-sized lymphocytes, with a variable N:C ratio and moderately basophilic cytoplasm. Smear cells were present. A quarter of the lymphocytes showed the negative images of one to three rod-shaped crystals (average two per cell). There were some immature monocytes and some neutrophils showed mild toxic granulation or abnormal nuclear shapes, consistent with COVID-19. Flow cytometric immunophenotyping showed an increased number of circulating B cells (93% of lymphocytes, 7.78 × 109/L) with lambda light chain restriction and expressing CD19, CD5, CD23, weak CD20, CD43, and CD200; the cells were negative for CD10, CD79b, CD81, FMC7, and CD38. The matutes score was 5/5. At this stage, the condition could not be distinguished from chronic lymphocytic leukemia (CLL). Two months later the WBC and lymphocyte count had returned to normal and repeated immunophenotyping showed only 0.63 × 109/L CD5-positive clonal B cells. However, lymphocytes with cytoplasmic crystals were still present. A diagnosis of monoclonal B-cell lymphocytosis (MBCL) was made. Patients with CLL in whom COVID-19 led to a marked but transient increase in the lymphocyte count have been reported. In this case, COVID-19 in a patient with MBCL led to an increase in the lymphocyte count to a level simulating CLL with follow-up indicating the correct diagnosis. In addition, we report here the observation of the negative images of crystals, attributable to crystallization of immunoglobulin, in MCBL. This phenomenon has previously been reported in CLL. The authors declare no conflict of interest. Data sharing is not applicable to this article as no new data were created or analyzed in this study.
Minimally Invasive Surfactant Therapy vs Sham Treatment and Death or Bronchopulmonary Dysplasia in Preterm Infants With Respiratory Distress Syndrome
Authors: Pengxiang Zhou, Tongyan Han
Journal: JAMA (2022)

To the Editor We have several concerns about the sham intervention and the control of factors related to bronchopulmonary dysplasia in the recent study1 of minimally invasive surfactant therapy vs sham treatment in preterm infants with respiratory distress syndrome.
Cancer Care During COVID-19—A Shock to the System
Authors: Joseph M. Unger
Journal: JAMA Network Open (2022)

Meghan J. Walker, PhD; Jonathan Wang, MASc; Joshua Mazuryk, BSc; Siew-Mei Skinner, BMRSc; Olivia Meggetto, MSc; Eta Ashu, PhD; Steven Habbous, PhD; Narges Nazeri Rad, PhD; Gabriela Espino-Hernández, MSc; Ryan Wood, MHS; Munaza Chaudhry, PhD; Saba Vahid, PhD; Julia Gao, MSc; Daniela Gallo-Hershberg, BScPhm, PharmD; Eric Gutierrez, BSc; Claudia Zanchetta, MN(ACNP); Deanna Langer, PhD; Victoria Zwicker, MPH; Michelle Rey, PhD; Martin C. Tammemägi, PhD; Jill Tinmouth, MD, PhD; Rachel Kupets, MD, MSc; Anna M. Chiarelli, PhD; Simron Singh, MD, MPH; Padraig Warde, MD; Leta Forbes, MD; Julian Dobranowski, MD; Jonathan Irish, MD, MSc; Linda Rabeneck, MD, MPH; Cancer Care Ontario COVID-19 Impact Working Group; Chamila Adhihetty; Jaclyn Beca; Diane Burns; Catherine Chan; Kelvin KW Chan; Lauren Chun; Melissa Coulson; Gail E Darling; Prithwish De; Steven Dong; Catherine Dubé; Maria Eberg; Samantha Fienberg; Colleen Fox; Sophie Foxcroft; Ron Fung; Scott Gavura; Natasha Gray; Sherrie Hertz; Brian Ho; Claire M Holloway; Amber Hunter; Nathaniel Jembere; Tina Karapetyan; Shivali Kaushal; Mary J King; Ordeena Linton; Aisha K Lofters; Andrea Mackesy; Faisal Majeed; Jessica Mann; Pamela MacCrostie; Garth Matheson; Bronwen R McCurdy; Elaine Meertens; Reeza Menalo; Lisa Milgram; Nicole Moleschi; Elena Mow; K Joan Murphy; Rohini Naipaul; Karen Nguyen; Diane O'Grady; Aaron Pollett; Elizabeth Quilliam; Dimpho Radebe; Jocelyn E Sacco; Nancy Shukla; Vicky Simanovski; Steve Scott; Xiaochen Tai; Cristina Tassone; Arany Theivendram; Rebecca Truscott; Christa Wang; Audrey Wong; Lyndee Yeung; Marta Yurcan
Pediatric Hospital Admission and Role of Clinical Practice Guidelines
Authors: Shabih Manzar
Journal: JAMA Pediatrics (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Error in Methods
Journal: JAMA Network Open (2022)

there was an error in the wording used to describe the study sample in the Methods section.The correct description of the sample is, "We examined each identified case where more than one person was intentionally shot in a school building during a school day or a person arrived at school with the intent of firing indiscriminately (133 total cases) from 1980 to 2019 as reported by the public K-12 School Shooting Database."This article has been corrected.
Cell type and gene expression deconvolution with BayesPrism enables Bayesian integrative analysis across bulk and single-cell RNA sequencing in oncology
Authors: Tinyi Chu, Zhong Wang, Dana Pe’er, Charles G. Danko
Journal: Nature Cancer (2022)

Inferring single-cell compositions and their contributions to global gene expression changes from bulk RNA sequencing (RNA-seq) datasets is a major challenge in oncology. Here we develop Bayesian cell proportion reconstruction inferred using statistical marginalization (BayesPrism), a Bayesian method to predict cellular composition and gene expression in individual cell types from bulk RNA-seq, using patient-derived, scRNA-seq as prior information. We conduct integrative analyses in primary glioblastoma, head and neck squamous cell carcinoma and skin cutaneous melanoma to correlate cell type composition with clinical outcomes across tumor types, and explore spatial heterogeneity in malignant and nonmalignant cell states. We refine current cancer subtypes using gene expression annotation after exclusion of confounding nonmalignant cells. Finally, we identify genes whose expression in malignant cells correlates with macrophage infiltration, T cells, fibroblasts and endothelial cells across multiple tumor types. Our work introduces a new lens to accurately infer cellular composition and expression in large cohorts of bulk RNA-seq data.
Blocking ribosomal protein S6 phosphorylation inhibits podocyte hypertrophy and focal segmental glomerulosclerosis
Authors: Fang Li, Yili Fang, Qiyuan Zhuang, Meichu Cheng, Desmond Moronge, Hao Jue, Oded Meyuhas, Xiaoqiang Ding, Zhigang Zhang, Jian-Kang Chen, Huijuan Wu
Journal: Kidney International (2022)

Ribosomal protein S6 (rpS6) phosphorylation mediates the hypertrophic growth of kidney proximal tubule cells. However, the role of rpS6 phosphorylation in podocyte hypertrophy and podocyte loss during the pathogenesis of focal segmental glomerulosclerosis (FSGS) remains undefined. Here, we examined rpS6 phosphorylation levels in kidney biopsy specimens from patients with FSGS and in podocytes from mouse kidneys with Adriamycin-induced FSGS. Using genetic and pharmacologic approaches in the mouse model of FSGS, we investigated the role of rpS6 phosphorylation in podocyte hypertrophy and loss during development and progression of FSGS. Phosphorylated rpS6 was found to be markedly increased in the podocytes of patients with FSGS and Adriamycin-induced FSGS mice. Genetic deletion of the Tuberous sclerosis 1 gene in kidney glomerular podocytes activated mammalian target of rapamycin complex 1 signaling to rpS6 phosphorylation, resulting in podocyte hypertrophy and pathologic features similar to those of patients with FSGS including podocyte loss, leading to segmental glomerulosclerosis. Since protein phosphatase 1 is known to negatively regulate rpS6 phosphorylation, treatment with an inhibitor increased phospho-rpS6 levels, promoted podocyte hypertrophy and exacerbated formation of FSGS lesions. Importantly, blocking rpS6 phosphorylation (either by generating congenic rpS6 knock-in mice expressing non-phosphorylatable rpS6 or by inhibiting ribosomal protein S6 kinase 1-mediated rpS6 phosphorylation with an inhibitor) significantly blunted podocyte hypertrophy, inhibited podocyte loss, and attenuated formation of FSGS lesions. Thus, our study provides genetic and pharmacologic evidence indicating that specifically targeting rpS6 phosphorylation can attenuate the development of FSGS lesions by inhibiting podocyte hypertrophy and associated podocyte depletion.
Proton pump inhibition for secondary hemochromatosis in hereditary anemia: a phase <scp>III</scp> placebo‐controlled randomized cross‐over clinical trial
Authors: Annelies van Vuren, Jean Louis Kerkhoffs, Saskia Schols, Anita Rijneveld, Erfan Nur, Dore Peereboom, Yves Gandon, Paco Welsing, Richard van Wijk, Roger Schutgens, Wouter van Solinge, Joannes Marx, Tim Leiner, Bart Biemond, Eduard van Beers
Journal: American Journal of Hematology (2022)

Abstract Iron overload is a severe general complication of hereditary anemias. Treatment with iron chelators is hampered by important side‐effects, high costs, and the lack of availability in many countries with a high prevalence of hereditary anemias. In this phase III randomized placebo‐controlled trial, we assigned adults with non‐transfusion‐dependent hereditary anemias with mild‐to‐moderate iron overload to receive esomeprazole (at a dose of 40 mg twice daily) or placebo for 12 months in a cross‐over design. The primary end point was change of liver iron content measured by MRI. A total of 30 participants were enrolled in the trial. Treatment with esomeprazole resulted in a statistically significant reduction in liver iron content that was 0.55 mg Fe/g dw larger than after treatment with placebo (95%CI [0.05 to 1.06]; p = 0.03). Median baseline liver iron content at the start of esomeprazole was 4.99 versus 4.49 mg Fe/g dw at start of placebo. Mean delta liver iron content after esomeprazole treatment was −0.57 (SD 1.20) versus −0.11 mg Fe/g dw (SD 0.75) after placebo treatment. Esomeprazole was well tolerated, reported adverse events were mild and none of the patients withdrew from the study due to side effects. In summary, esomeprazole resulted in a significant reduction in liver iron content when compared to placebo in a heterogeneous group of patients with non‐transfusion‐dependent hereditary anemias. From an international perspective this result can have major implications given the fact that proton pump inhibitors may frequently be the only realistic therapy for many patients without access to or not tolerating iron chelators.