tbuckley/cabot-search huggingface dataset:
Chromosome 3p25.3 Gain Is Associated With Cisplatin Resistance and Is an Independent Predictor of Poor Outcome in Male Malignant Germ Cell Tumors
Authors: Dennis M. Timmerman, Thomas F. Eleveld, Sruthi Sriram, Lambert C.J. Dorssers, Ad J.M. Gillis, Silvia Schmidtova, Katarina Kalavska, Harmen J.G. van de Werken, Christoph Oing, Friedemann Honecker, Michal Mego, Leendert H.J. Looijenga
Journal: Journal of Clinical Oncology (2022)

Cisplatin is the main systemic treatment modality for male type II germ cell tumors (GCTs). Although generally very effective, 5%-10% of patients suffer from cisplatin-resistant disease. Identification of the driving mechanisms of resistance will enable improved risk stratification and development of alternative treatments.
CDK6-PI3K signaling axis is an efficient target for attenuating ABCB1/P-gp mediated multi-drug resistance (MDR) in cancer cells
Authors: Lei Zhang, Yidong Li, Chaohua Hu, Yangmin Chen, Zhuo Chen, Zhe-Sheng Chen, Jian-Ye Zhang, Shuo Fang
Journal: Molecular Cancer (2022)

Multidrug resistance (MDR) mediated by ATP binding cassette subfamily B member 1 (ABCB1/P-gp) is a major cause of cancer chemotherapy failure, but the regulation mechanisms are largely unknown.Based on single gene knockout, we studied the regulation of CDK6-PI3K axis on ABCB1-mediated MDR in human cancer cells. CRISPR/Cas9 technique was performed in KB-C2 cells to knockout cdk6 or cdk4 gene. Western blot, RT-PCR and transcriptome analysis were performed to investigate target gene deletion and expression of critical signaling factors. The effect of cdk4 or cdk6 deficiency on cell apoptosis and the cell cycle was analyzed using flow cytometry. In vivo studies were performed to study the sensitivity of KB-C2 tumors to doxorubicin, tumor growth and metastasis.Deficiency of cdk6 led to remarkable downregulation of ABCB1 expression and reversal of ABCB1-mediated MDR. Transcriptomic analysis revealed that CDK6 knockout regulated a series of signaling factors, among them, PI3K 110α and 110β, KRAS and MAPK10 were downregulated, and FOS-promoting cell autophagy and CXCL1-regulating multiple factors were upregulated. Notably, PI3K 110α/110β deficiency in-return downregulated CDK6 and the CDK6-PI3K axis synergizes in regulating ABCB1 expression, which strengthened the regulation of ABCB1 over single regulation by either CDK6 or PI3K 110α/110β. High frequency of alternative splicing (AS) of premature ABCB1 mRNA induced by CDK6, CDK4 or PI3K 110α/110β level change was confirmed to alter the ABCB1 level, among them 10 common skipped exon (SE) events were found. In vivo experiments demonstrated that loss of cdk6 remarkably increased the sensitivity of KB-C2 tumors to doxorubicin by increasing drug accumulation of the tumors, resulting in remarkable inhibition of tumor growth and metastasis, as well as KB-C2 survival in the nude mice.CDK6-PI3K as a new target signaling axis to reverse ABCB1-mediated MDR is reported for the first time in cancers. Pathways leading to inhibition of cancer cell proliferation were revealed to be accompanied by CDK6 deficiency.
Methodological considerations in D-health cancer mortality results – Authors' reply
Authors: Rachel E Neale, Briony Duarte Romero, Donald S A McLeod, Dallas R English, Gunter Hartel, Jolieke C van der Pols, Alison J Venn, Penelope M Webb, David C Whiteman, Mary Waterhouse
Journal: The Lancet Diabetes & Endocrinology (2022)
Multilayered omics reveal sex- and depot-dependent adipose progenitor cell heterogeneity
Authors: Bo Shan, Clive S. Barker, Mengle Shao, Qianbin Zhang, Rana K. Gupta, Yibo Wu
Journal: Cell Metabolism (2022)

Single-cell RNA sequencing (scRNA-seq) has revealed that adult white adipose tissue (WAT) harbors functionally diverse subpopulations of mesenchymal stromal cells that differentially impact tissue plasticity. To date, the molecular basis of this cellular heterogeneity has not been fully defined. Here, we describe a multilayered omics approach to dissect adipose progenitor cell heterogeneity in three dimensions: progenitor subpopulation, sex, and anatomical localization. We applied state-of-the-art mass spectrometry methods to quantify 4,870 proteins in eight different stromal cell populations from perigonadal and inguinal WAT of male and female mice and acquired transcript expression levels of 15,477 genes using RNA-seq. Our data unveil molecular signatures defining sex differences in preadipocyte differentiation and identify regulatory pathways that functionally distinguish adipose progenitor subpopulations. This multilayered omics analysis, freely accessible at http://preadprofiler.net/, provides unprecedented insights into adipose stromal cell heterogeneity and highlights the benefit of complementary proteomics to support findings from scRNA-seq studies.
An Airway-Centric View of Idiopathic Pulmonary Fibrosis
Authors: Ian T. Stancil, Jacob E. Michalski, David A. Schwartz
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"An Airway-Centric View of Idiopathic Pulmonary Fibrosis." American Journal of Respiratory and Critical Care Medicine, 206(4), pp. 410–416
Novel treatments in B cell non-Hodgkin’s lymphomas
Authors: Yazeed Sawalha, Kami Maddocks
Journal: BMJ (2022)

ABSTRACT The improved understanding of lymphoma biology and recent advances in the field of cancer immunology have paved the way for the development of many effective small molecule inhibitors and immunotherapies in B cell non-Hodgkin’s lymphomas. This article reviews novel treatments that have been approved recently by the US Food and Drug Administration and are now routinely used in clinical practice. It discusses their mechanisms of action, efficacy and safety, current therapeutic roles, and future directions in the treatment paradigm of different types of B cell non-Hodgkin’s lymphoma. It also reviews other exciting novel treatments that are not yet approved but have unique mechanisms of action and have shown encouraging early results.
18F-FDG PET/CT Appearance of Radiation-Induced Delayed Transverse Myelitis
Authors: Sayak Choudhury, Nilendu Purandare, Sneha Shah, Archi Agrawal, Venkatesh Rangarajan
Journal: Clinical Nuclear Medicine (2022)

Delayed-onset radiation-induced myelitis is a rare but serious complication of radiation exposure to the spinal cord. In this report, we describe the 18 F-FDG PET/CT findings of radiation-induced myelitis in a patient with carcinoma of buccal mucosa treated with external beam radiotherapy.
Dermatopathologist Perceptions of Overdiagnosis of Melanocytic Skin Lesions and Association With Diagnostic Behaviors
Authors: Kathleen F. Kerr, Megan M. Eguchi, Michael W. Piepkorn, Andrea C. Radick, Lisa M. Reisch, Hannah L. Shucard, Stevan R. Knezevich, Raymond L. Barnhill, David E. Elder, Joann G. Elmore
Journal: JAMA Dermatology (2022)

Despite evidence of overdiagnosis of in situ and invasive melanoma, neither the perceptions of practicing dermatopathologists about overdiagnosis nor possible associations between perceptions of overdiagnosis and diagnostic practices have been studied.
Infectious complications of targeted drugs and biotherapies in acute leukemia. Clinical practice guidelines by the European Conference on Infections in Leukemia (ECIL), a joint venture of the European Group for Blood and Marrow Transplantation (EBMT), the European Organization for Research and Treatment of Cancer (EORTC), the International Immunocompromised Host Society (ICHS) and the European Leukemia Net (ELN)
Authors: Georg Maschmeyer, Lars Bullinger, Carolina Garcia-Vidal, Raoul Herbrecht, Johan Maertens, Pierantonio Menna, Livio Pagano, Anne Thiebaut-Bertrand, Thierry Calandra
Journal: Leukemia (2022)

Abstract The 9th web-based European Conference on Infections in Leukemia (ECIL-9), held September 16-17, 2021, reviewed the risk of infections and febrile neutropenia associated with more recently approved immunotherapeutic agents and molecular targeted drugs for the treatment of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Novel antibody based treatment approaches (inotuzumab ozogamicin, gemtuzumab ozogamicin, flotetuzumab), isocitrate dehydrogenases inhibitors (ivosidenib, enasidenib, olutasidenib), FLT3 kinase inhibitors (gilteritinib, midostaurin, quizartinib), a hedgehog inhibitor (glasdegib) as well as a BCL2 inhibitor (venetoclax) were reviewed with respect to their mode of action, their immunosuppressive potential, their current approval and the infectious complications and febrile neutropenia reported from clinical studies. Evidence-based recommendations for prevention and management of infectious complications and specific alerts regarding the potential for drug-drug interactions were developed and discussed in a plenary session with the panel of experts until consensus was reached. The set of recommendations was posted on the ECIL website for a month for comments from members of EBMT, EORTC, ICHS and ELN before final approval by the panelists. While a majority of these agents are not associated with a significantly increased risk when used as monotherapy, caution is required with combination therapy such as venetoclax plus hypomethylating agents, gemtuzumab ozogamicin plus cytotoxic drugs or midostaurin added to conventional AML chemotherapy.
Assessment of T-cell Reactivity to the SARS-CoV-2 Omicron Variant by Immunized Individuals
Authors: Lorenzo De Marco, Silvia D’Orso, Marta Pirronello, Alice Verdiani, Andrea Termine, Carlo Fabrizio, Alessia Capone, Andrea Sabatini, Gisella Guerrera, Roberta Placido, Manolo Sambucci, Daniela F. Angelini, Flavia Giannessi, Mario Picozza, Carlo Caltagirone, Antonino Salvia, Elisabetta Volpe, Maria Pia Balice, Angelo Rossini, Olaf Rötzschke, Emiliano Giardina, Luca Battistini, Giovanna Borsellino
Journal: JAMA Network Open (2022)

The emergence of the highly contagious Omicron variant of SARS-CoV-2 and the findings of a significantly reduced neutralizing potency of sera from individuals with previous SARS-CoV-2 infection or vaccination highlights the importance of studying cellular immunity to estimate the degree of immune protection to the new SARS-CoV-2 variant.To determine T-cell reactivity to the Omicron variant in individuals with established (natural and/or vaccine-induced) immunity to SARS-CoV-2.This was a cohort study conducted between December 20 and 21, 2021, at the Santa Lucia Foundation Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy, among health care worker and scientist volunteers. Lymphocytes from freshly drawn blood samples were isolated and immediately tested for reactivity to the spike protein of SARS-CoV-2.The main outcomes were the measurement of T-cell reactivity to the mutated regions of the spike protein of the Omicron BA.1 SARS-CoV-2 variant and the assessment of remaining T-cell immunity to the spike protein by stimulation with peptide libraries.A total of 61 volunteers (mean (range) age, 41.62 (21-62) years; 38 women [62%]) with different vaccination and SARS-CoV-2 infection backgrounds were enrolled. The median (range) frequency of CD4+ T cells reactive to peptides covering the mutated regions in the Omicron variant was 0.039% (0%-2.356%), a decrease of 64% compared with the frequency of CD4+ cells specific for the same regions of the ancestral strain (0.109% [0%-2.376%]). Within CD8+ T cells, a median (range) of 0.02% (0%-0.689%) of cells recognized the mutated spike regions, while 0.039% (0%-3.57%) of cells were reactive to the equivalent unmutated regions, a reduction of 49%. However, overall reactivity to the peptide library of the full-length protein was largely maintained (estimated 87%). No significant differences in loss of immune recognition were identified between groups of participants with different vaccination or infection histories.This cohort study of immunized adults in Italy found that despite the mutations in the spike protein, the SARS-CoV-2 Omicron variant was recognized by the cellular component of the immune system. It is reasonable to assume that protection from hospitalization and severe disease will be maintained.
Rapid Plastic Deformation of Cancer Cells Correlates with High Metastatic Potential (Adv. Healthcare Mater. 8/2022)
Authors: Zishen Yan, Xingyu Xia, William C. Cho, Dennis W. Au, Xueying Shao, Chao Fang, Ye Tian, Yuan Lin
Journal: Advanced Healthcare Materials (2022)

Cell Plasticity During metastasis, cancer cells must severely deform themselves to squeeze through tight spaces in the surrounding tissue or junctions between capillary endothelial cells. Therefore, the capability of tumor cells to undergo plastic deformations could greatly facilitate their metastasis. Using a novel microfluidic setup, the study in article number 2101657 by William C. Cho, Yuan Lin, and co-workers, shows that the invasiveness of cancer cells is indeed correlated with their plastic response.
A third dose of the BNT162b2 mRNA vaccine significantly improves immune responses among liver transplant recipients
Authors: Yana Davidov, Victoria Indenbaum, Keren Tsaraf, Oranit Cohen-Ezra, Mariya Likhter, Gil Ben Yakov, Rebecca Halperin, Itzchak Levy, Orna Mor, Nancy Agmon-Levin, Arnon Afek, Galia Rahav, Yaniv Lustig, Ziv Ben Ari
Journal: Journal of Hepatology (2022)
Central memory T cells are the most effective precursors of resident memory T cells in human skin
Authors: Tiago R. Matos, Ahmed Gehad, Jessica E. Teague, Beatrice Dyring-Andersen, Theresa Benezeder, Mitra Dowlatshahi, Jack Crouch, Yoshinori Watanabe, John T. O’Malley, Thomas S. Kupper, Chao Yang, Rei Watanabe, Rachael A. Clark
Journal: Science Immunology (2022)

The circulating precursor cells that give rise to human resident memory T cells (T RM ) are poorly characterized. We used an in vitro differentiation system and human skin–grafted mice to study T RM generation from circulating human memory T cell subsets. In vitro T RM differentiation was associated with functional changes, including enhanced IL-17A production and FOXP3 expression in CD4 + T cells and granzyme B production in CD8 + T cells, changes that mirrored the phenotype of T cells in healthy human skin. Effector memory T cells (T EM ) had the highest conversion rate to T RM in vitro and in vivo, but central memory T cells (T CM ) persisted longer in the circulation, entered the skin in larger numbers, and generated increased numbers of T RM . In summary, T CM are highly efficient precursors of human skin T RM , a feature that may underlie their known association with effective long-term immunity.
Computational drug repurposing in the age of COVID-19: mixing antiviral cocktails in silico
Authors: James A. Diao, Marium M. Raza, Kaushik P. Venkatesh, Joseph C. Kvedar
Journal: npj Digital Medicine (2022)

As clinicians and scientists gather more data on the clinical trajectory of COVID-19 and the biology of its causative agent, the SARS-CoV-2 virus, novel strategies are needed to integrate these data to inform new therapies. A recent study by Howell et al. introduces a network model of viral-host interactions to produce explainable and testable predictions for treatment effects. Their model was consistent with experimental data and recommended treatments, and one of its predicted drug combinations was validated through in vitro assays. These findings support the utility of computational strategies for leveraging the vast literature on COVID-19 to generate insights for drug repurposing.
Rechallenge With Additional Doses of 177Lu-DOTATOC After Failure of Maintenance Therapy With Cold Somatostatin Analogs
Authors: Alexander Weich, Rudolf A. Werner, Sebastian E. Serfling, Lilja B. Solnes, Martin G. Pomper, Andreas K. Buck, Takahiro Higuchi, Steven P. Rowe
Journal: Clinical Nuclear Medicine (2022)

Abstract Here, we report a case of a 52-year-old woman with a well-differentiated, metastasized neuroendocrine tumor (NET G1) of the duodenum. Initial imaging with 68 Ga-DOTATOC revealed multiple sites of disease with intense uptake. Peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATOC induced partial remission. Treatment was then switched to cold somatostatin analog as a maintenance therapy. After 2 years of follow-up, progressive disease with multiple lesions in the skeleton was noted. Given the initial response to PRRT, a rechallenge with another 2 cycles of PRRT were given, and the patient had an excellent response to treatment, in particular in the skeleton.
Sphingosine-1-phosphate hinders the osteogenic differentiation of dental pulp stem cells in association with AKT signaling pathways
Authors: Bongkun Choi, Ji-Eun Kim, Si-On Park, Eun-Young Kim, Soyoon Oh, Hyuksu Choi, Dohee Yoon, Hyo-Jin Min, Hyung-Ryong Kim, Eun-Ju Chang
Journal: International Journal of Oral Science (2022)

Abstract Sphingosine-1-phosphate (S1P) is an important lipid mediator that regulates a diverse range of intracellular cell signaling pathways that are relevant to tissue engineering and regenerative medicine. However, the precise function of S1P in dental pulp stem cells (DPSCs) and its osteogenic differentiation remains unclear. We here investigated the function of S1P/S1P receptor (S1PR)-mediated cellular signaling in the osteogenic differentiation of DPSCs and clarified the fundamental signaling pathway. Our results showed that S1P-treated DPSCs exhibited a low rate of differentiation toward the osteogenic phenotype in association with a marked reduction in osteogenesis-related gene expression and AKT activation. Of note, both S1PR1/S1PR3 and S1PR2 agonists significantly downregulated the expression of osteogenic genes and suppressed AKT activation, resulting in an attenuated osteogenic capacity of DPSCs. Most importantly, an AKT activator completely abrogated the S1P-mediated downregulation of osteoblastic markers and partially prevented S1P-mediated attenuation effects during osteogenesis. Intriguingly, the pro-inflammatory TNF-α cytokine promoted the infiltration of macrophages toward DPSCs and induced S1P production in both DPSCs and macrophages. Our findings indicate that the elevation of S1P under inflammatory conditions suppresses the osteogenic capacity of the DPSCs responsible for regenerative endodontics.
Selected Bibliography of Recent Research in COVID-19
Authors: Benjamin D. Singer, Sanjay H. Chotirmall, Lindsay M. Leither, Oliver W. Meldrum, Anthony M. Joudi, Nitin Seam, Samuel M. Brown, Başak Çoruh
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

This article has been removed from the AJRCCM website, as it may be revised in the near future.
Treatment With Tumor Necrosis Factor Inhibitors Is Associated With a <scp>Time‐Shifted</scp> Retardation of Radiographic Sacroiliitis Progression in Patients With Axial Spondyloarthritis: <scp>10‐Year</scp> Results From the German Spondyloarthritis Inception Cohort
Authors: Murat Torgutalp, Valeria Rios Rodriguez, Fabian Proft, Mikhail Protopopov, Maryna Verba, Judith Rademacher, Hildrun Haibel, Joachim Sieper, Martin Rudwaleit, Denis Poddubnyy
Journal: Arthritis & Rheumatology (2022)

To investigate the longitudinal association between radiographic sacroiliitis progression and treatment with tumor necrosis factor inhibitors (TNFi) in patients with early axial spondyloarthritis (SpA) in a long-term inception cohort.We included patients from the German Spondyloarthritis Inception Cohort who underwent radiographic assessment of the sacroiliac joints at baseline and at least once more during the 10-year follow-up. Two central readers scored the radiographs according to the modified New York criteria for ankylosing spondylitis. The sacroiliac sum score was calculated as a mean of the scores determined by both readers. TNFi use was assessed according to exposure in the current and/or previous 2-year radiographic interval. The association between TNFi use and radiographic sacroiliitis progression was examined by longitudinal generalized estimating equation analysis with adjustment for potential confounders.In this long-term inception cohort, 10-year follow-up data on 737 radiographic intervals assessed in 301 patients with axial SpA (166 patients with nonradiographic axial SpA and 135 patients with radiographic axial SpA) were obtained. Having received ≥12 months of treatment with TNFi in the previous 2-year radiographic interval was associated with a significant decrease in the sacroiliitis sum score (β = -0.09 [95% confidence interval (95% CI) -0.18, -0.003]; analyses adjusted for age, sex, symptom duration, HLA-B27 status, Bath Ankylosing Spondylitis Disease Activity Index score, C-reactive protein, and nonsteroidal antiinflammatory drug intake). In contrast, among patients receiving TNFi in the current radiographic interval, there was no significant association with change in the sacroiliitis sum score (β = 0.05 [95% CI -0.05, 0.14]). This effect of having received ≥12 months of treatment with TNFi in the previous 2-year radiographic interval was stronger in patients with nonradiographic axial SpA as compared to patients with radiographic axial SpA (β = -0.16 [95% CI -0.28, -0.03] versus β = -0.04 [95% CI -0.15, 0.07]).Treatment with TNFi was associated with the reduction in radiographic sacroiliitis progression in patients with axial SpA. This effect became evident between 2 and 4 years after treatment was initiated.
Author Correction: Effectiveness of mRNA-1273 against SARS-CoV-2 Omicron and Delta variants
Authors: Hung Fu Tseng, Bradley K. Ackerson, Yi Luo, Lina S. Sy, Carla A. Talarico, Yun Tian, Katia J. Bruxvoort, Julia E. Tubert, Ana Florea, Jennifer H. Ku, Gina S. Lee, Soon Kyu Choi, Harpreet S. Takhar, Michael Aragones, Lei Qian
Journal: Nature Medicine (2022)

In the version of this article initially published, there were errors in the inset graph to Fig. 2a, where the inset had the graph lines and symbols for the 0.3 mg kg -1 and the 0.6 mg kg -1 switched, and the wrong data were shown for the 0.6 mg kg -1 in the inset.The labels and plots have been corrected in the HTML and PDF versions of the article.The original and corrected Fig 2a graphs are shown below.
Quenching Epigenetic Drug Resistance Using Antihypoxic Microparticles in Glioblastoma Patient‐Derived Chips (Adv. Healthcare Mater. 8/2022)
Authors: Sewoom Baek, Seung Eun Yu, Yu‐Heng Deng, Yong‐Jae Lee, Dong Gue Lee, Surim Kim, Seonjin Yoon, Hye‐Seon Kim, Jeongeun Park, Chan Hee Lee, Jung Bok Lee, Hyun Joon Kong, Seok‐Gu Kang, Young Min Shin, Hak‐Joon Sung
Journal: Advanced Healthcare Materials (2022)

Epigenetic Alterations In article number 2102226, Young Min Shin, Hak-Joon Sung, and co-workers demonstrate that loading anti-hypoxic microparticles onto glioblastoma (GBM) masses reduces epigenetic drug resistance and suppresses subsequent cell invasiveness. The results are verified using a 3D GBM chip with cell spheres in vitro under media perfusion and in vivo through chip implantation into mouse ischemic hind limbs.