tbuckley/cabot-search huggingface dataset:
Lenalidomide and Rituximab (ReRi) As Front-Line Chemo-Free Therapy for Elderly Frail Patients with Diffuse Large B-Cell Lymphoma. a Phase II Study of the Fondazione Italiana Linfomi (FIL)
Authors: Guido Gini, Monica Tani, Renato Bassan, Alessandra Tucci, Filippo Ballerini, Michela Sampaolo, Francesco Merli, Francesca Re, Attilio Olivieri, Mauro Petrini, Ombretta Annibali, Anna Marina Liberati, Carlo Visco, Annalisa Arcari, Sergio Storti, Alberto Fabbri, Gerardo Musuraca, Vittorio Ruggero Zilioli, M. Christina Cox, Stefano Luminari
Journal: Blood (2021)
Medical imaging of pulmonary disease in SARS-CoV-2-exposed non-human primates
Authors: Marieke A. Stammes, Ji Hyun Lee, Lisette Meijer, Thibaut Naninck, Lara A. Doyle-Meyers, Alexander G. White, H. Jacob Borish, Amy L. Hartman, Xavier Alvarez, Shashank Ganatra, Deepak Kaushal, Rudolf P. Bohm, Roger le Grand, Charles A. Scanga, Jan A.M. Langermans, Ronald E. Bontrop, Courtney L. Finch, JoAnne L. Flynn, Claudia Calcagno, Ian Crozier, Jens H. Kuhn
Journal: Trends in Molecular Medicine (2021)

Chest X-ray (CXR), computed tomography (CT), and positron emission tomography-computed tomography (PET-CT) are noninvasive imaging techniques widely used in human and veterinary pulmonary research and medicine. These techniques have recently been applied in studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-exposed non-human primates (NHPs) to complement virological assessments with meaningful translational readouts of lung disease. Our review of the literature indicates that medical imaging of SARS-CoV-2-exposed NHPs enables high-resolution qualitative and quantitative characterization of disease otherwise clinically invisible and potentially provides user-independent and unbiased evaluation of medical countermeasures (MCMs). However, we also found high variability in image acquisition and analysis protocols among studies. These findings uncover an urgent need to improve standardization and ensure direct comparability across studies.
Temporal single-cell tracing reveals clonal revival and expansion of precursor exhausted T cells during anti-PD-1 therapy in lung cancer
Authors: Baolin Liu, Xueda Hu, Kaichao Feng, Ranran Gao, Zhiqiang Xue, Sujie Zhang, Yuanyuan Zhang, Emily Corse, Yi Hu, Weidong Han, Zemin Zhang
Journal: Nature Cancer (2021)

Abstract Anti-PD-1 treatment has shown unprecedented clinical success in the treatment of non-small-cell lung cancer (NSCLC), but the underlying mechanisms remain incompletely understood. Here, we performed temporal single-cell RNA and paired T-cell receptor sequencing on 47 tumor biopsies from 36 patients with NSCLC following PD-1-based therapies. We observed increased levels of precursor exhausted T (Texp) cells in responsive tumors after treatment, characterized by low expression of coinhibitory molecules and high expression of GZMK . By contrast, nonresponsive tumors failed to accumulate Texp cells. Our data suggested that Texp cells were unlikely to be derived from the reinvigoration of terminally exhausted cells; instead, they were accumulated by (1) local expansion and (2) replenishment by peripheral T cells with both new and pre-existing clonotypes, a phenomenon we named clonal revival. Our study provides insights into mechanisms underlying PD-1-based therapies, implicating clonal revival and expansion of Texp cells as steps to improve NSCLC treatment.
OCEAN (OP-103): Melflufen/Dexamethasone Compared with Pomalidomide/Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma-Age Subgroup Analysis of Older Patients
Authors: Maria-Victoria Mateos, Pawel J. Robak, Laura Rosiñol, Argiris Symeonidis, Pieter Sonneveld, Marcus Thuresson, Catriona Byrne, Johan Harmenberg, Roman Hájek
Journal: Blood (2021)
ASO-Based PKM Splice-Switching Therapy Inhibits Hepatocellular Carcinoma Growth
Authors: Wai Kit Ma, Dillon M. Voss, Juergen Scharner, Ana S.H. Costa, Kuan-Ting Lin, Hyun Yong Jeon, John E. Wilkinson, Michaela Jackson, Frank Rigo, C. Frank Bennett, Adrian R. Krainer
Journal: Cancer Research (2021)

Abstract The M2 pyruvate kinase (PKM2) isoform is upregulated in most cancers and plays a crucial role in regulation of the Warburg effect, which is characterized by the preference for aerobic glycolysis over oxidative phosphorylation for energy metabolism. PKM2 is an alternative-splice isoform of the PKM gene and is a potential therapeutic target. Antisense oligonucleotides (ASO) that switch PKM splicing from the cancer-associated PKM2 to the PKM1 isoform have been shown to induce apoptosis in cultured glioblastoma cells when delivered by lipofection. Here, we explore the potential of ASO-based PKM splice switching as a targeted therapy for liver cancer. A more potent lead constrained-ethyl (cEt)/DNA ASO induced PKM splice switching and inhibited the growth of cultured hepatocellular carcinoma (HCC) cells. This PKM isoform switch increased pyruvate-kinase activity and altered glucose metabolism. In an orthotopic HCC xenograft mouse model, the lead ASO and a second ASO targeting a nonoverlapping site inhibited tumor growth. Finally, in a genetic HCC mouse model, a surrogate mouse-specific ASO induced Pkm splice switching and inhibited tumorigenesis, without observable toxicity. These results lay the groundwork for a potential ASO-based splicing therapy for HCC. Significance: Antisense oligonucleotides are used to induce a change in PKM isoform usage in hepatocellular carcinoma, reversing the Warburg effect and inhibiting tumorigenesis.
Improvement of Mortality Prognostication in Patients With Epidermal Necrolysis
Authors: Hui Kai Koh, Stephanie M. C. Fook-Chong, Haur Yueh Lee
Journal: JAMA Dermatology (2021)

Epidermal necrolysis is a severe cutaneous adverse reaction in which severe systemic inflammation results in extensive epithelial keratinocyte necrosis. The most commonly used prognostic score in epidermal necrolysis, the Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN), was recently found to overestimate mortality in contemporary cohorts. Identification of independent prognostic markers may help to stratify risk more accurately.This study evaluates the association between novel inflammatory markers and in-hospital mortality in patients with epidermal necrolysis to study the incremental prognostic value of these markers in combination with SCORTEN.A retrospective cohort study was conducted over a 17-year period from 2003 to 2019. Patients were enrolled from Singapore General Hospital, the national referral center for epidermal necrolysis. A total of 196 patients with epidermal necrolysis were recruited, 4 (2%) of whom were excluded owing to incomplete data.The main outcome assessed was the in-hospital mortality rate. Discrimination and calibration of risk scores were assessed using the area under the receiver operating characteristic curve (AUC) and calibration plot, respectively. Evaluation of the incremental prognostic value of these markers was done by comparing the AUC between the old and new risk score, and the use of net reclassification improvement (NRI) and integrated discrimination improvement (IDI).Among 192 total patients (median [IQR] age 56 [42-70] years; 114 [59.4%] women), there were 43 (22.4%) who did not survive to discharge. Of the novel inflammatory markers, only red cell distribution width to hemoglobin ratio was significant in predicting in-hospital mortality (odds ratio [OR] 3.55; 95% CI, 1.76-7.16; P < .001) after adjusting for SCORTEN. The RDW/Hb as applied in 4 risk groups showed similar discrimination to SCORTEN (AUC [95% CI]: RDW/Hb in 4 groups, 0.76 [0.69-0.84], vs SCORTEN, 0.78 [0.70-0.85], P = .89). When RDW/Hb was added to SCORTEN, the composite score Re-SCORTEN showed significantly better discrimination than SCORTEN alone (AUC [95% CI]: Re-SCORTEN, 0.83 [0.77-0.89], vs SCORTEN, 0.78 [0.70-0.85], P = .02). The overall NRI was 0.94 (95% CI, 0.68-1.20), P < .001. The IDI was 0.06 (95% CI 0.03-0.08), P < .001. Re-SCORTEN showed good calibration based on the calibration plot.In this cohort of patients, RDW/Hb, an inexpensive and readily available marker, showed similar predictive accuracy with SCORTEN. Furthermore, when used in combination with SCORTEN, it also helped augment prognostic ability.
Epidemiological trends of severely immunosuppressed people living with HIV at time of starting antiretroviral treatment in China during 2005–2018
Authors: Yuying Hou, Jiaye Liu, Yan Zhao, Yasong Wu, Ye Ma, Decai Zhao, Zhihui Dou, Zhongfu Liu, Ming Shi, Yanmei Jiao, Huihuang Huang, Zunyou Wu, Lifeng Wang, Mengjie Han, Fu-Sheng Wang
Journal: Journal of Infection (2021)
Paclitaxel derivative-based liposomal nanoplatform for potentiated chemo-immunotherapy
Authors: Yingli Wang, Jiang Yu, Dan Li, Liwen Zhao, Bingjun Sun, Jiamei Wang, Zhenjie Wang, Shuang Zhou, Menglin Wang, Yinxian Yang, Hongzhuo Liu, Haotian Zhang, Qingzhi Lv, Qikun Jiang, Zhonggui He, Yongjun Wang
Journal: Journal of Controlled Release (2021)
SARS-CoV-2 vaccine boosters: The time to act is now
Authors: Maya Petersen, Joshua Schwab, Diane V. Havlir
Journal: PLoS Medicine (2021)

We have a new and unprecedented opportunity to mitigate the suffering, death and inequities of COVID-19 in the United States with vaccine boosters-if we deploy them effectively, rapidly, and widely with simplified messaging to all eligible adults.
General Anesthesia and Postoperative Neurocognitive Outcomes
Authors: Michael S. Avidan, Elizabeth L. Whitlock, George A. Mashour
Journal: JAMA (2021)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Immune Responsiveness to LPS Determines Risk of Childhood Wheeze and Asthma in 17q21 Risk Allele Carriers
Authors: Sabina Illi, Martin Depner, Petra Ina Pfefferle, Harald Renz, Caroline Roduit, Diana Hazard Taft, Karen M. Kalanetra, David A. Mills, Freda M. Farquharson, Petra Louis, Elisabeth Schmausser-Hechfellner, Amandine Divaret-Chauveau, Roger Lauener, Anne M. Karvonen, Juha Pekkanen, Pirkka V. Kirjavainen, Marjut Roponen, Josef Riedler, Michael Kabesch, Bianca Schaub, Erika von Mutius, Andreas Böck, Markus J. Ege, Remo Frei, Jon Genuneit, Lucie Laurent, Sonali Pechlivanis, Martin Täubel, Johanna Theodorou
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: In murine models, microbial exposures induce protection from experimental allergic asthma through innate immunity. Objectives: Our aim was to assess the association of early life innate immunity with the development of asthma in children at risk. Methods: In the PASTURE farm birth cohort, innate T-helper cell type 2 (Th2), Th1, and Th17 cytokine expression at age 1 year was measured after stimulation of peripheral blood mononuclear cells with LPS in n = 445 children. Children at risk of asthma were defined based on single-nucleotide polymorphisms at the 17q21 asthma gene locus. Specifically, we used the SNP rs7216389 in the GSDMB gene. Wheeze in the first year of life was assessed by weekly diaries and asthma by questionnaire at age 6 years. Measurements and Main Results: Not all cytokines were detectable in all children after LPS stimulation. When classifying detectability of cytokines by latent class analysis, carrying the 17q21 risk allele rs7216389 was associated with risk of wheeze only in the class with the lowest level of LPS-induced activation: odds ratio (OR), 1.89; 95% confidence interval [CI], 1.13–3.16; P = 0.015. In contrast, in children with high cytokine activation after LPS stimulation, no association of the 17q21 risk allele with wheeze (OR, 0.63; 95% CI, 0.29–1.40; P = 0.258, P = 0.034 for interaction) or school-age asthma was observed. In these children, consumption of unprocessed cow’s milk was associated with higher cytokine activation (OR, 3.37; 95% CI, 1.56–7.30; P = 0.002), which was in part mediated by the gut microbiome. Conclusions: These findings suggest that within the 17q21 genotype, asthma risk can be mitigated by activated immune responses after innate stimulation, which is partly mediated by a gut–immune axis.
Assessment of Venous Thromboembolism Risk Based on the Khorana Predictive Model and Compliance with Prophylactic Anticoagulation at a Regional Cancer Center- a Quality Improvement Study
Authors: Noman Ahmed Jang Khan, Hassaan Yasin, Kemnasom Nwanwene, Mahmoud Abdallah, Todd Gress, Maria Tirona
Journal: Blood (2021)
DNA-PKcs: A Targetable Protumorigenic Protein Kinase
Authors: Emanuela Dylgjeri, Karen E. Knudsen
Journal: Cancer Research (2021)

Abstract DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a pleiotropic protein kinase that plays critical roles in cellular processes fundamental to cancer. DNA-PKcs expression and activity are frequently deregulated in multiple hematologic and solid tumors and have been tightly linked to poor outcome. Given the potentially influential role of DNA-PKcs in cancer development and progression, therapeutic targeting of this kinase is being tested in preclinical and clinical settings. This review summarizes the latest advances in the field, providing a comprehensive discussion of DNA-PKcs functions in cancer and an update on the clinical assessment of DNA-PK inhibitors in cancer therapy.
Prognostic Impact of Minimal Residual Disease Assessment in Elderly Patients with Secondary Acute Myeloid Leukemia. a Comparison between CPX-351 and Intensified Fludarabine-Based Regimens
Authors: Fabio Guolo, Paola Minetto, Marino Clavio, Maurizio Miglino, Riccardo Marcolin, Monica Passannante, Carola Riva, Michela Frello, Chiara Vernarecci, Elisabetta Tedone, Nicoletta Colombo, Enrico Carminati, Girolamo Pugliese, Clara Nurra, Antonia Cagnetta, Michele Cea, Marco Gobbi, Roberto M. Lemoli
Journal: Blood (2021)
A Phase 1/2 Trial of Cladribine, High-Dose Cytarabine, G-CSF, and Dose-Escalated Mitoxantrone (CLAG-M) Plus Gemtuzumab Ozogamicin in Adults with Newly-Diagnosed Acute Myeloid Leukemia (AML) or Other High-Grade Myeloid Neoplasm
Authors: Colin D. Godwin, Megan Othus, Mary-Elizabeth M. Percival, Paul C. Hendrie, Bart L. Scott, Jacob S. Appelbaum, Anna B. Halpern, Vivian G. Oehler, Johnnie J. Orozco, Sioban B. Keel, Janis L. Abkowitz, Jason P. Cooper, Ryan D. Cassaday, Kaysey F. Orlowski, Anise J. Marshall, Clarisa N. Brown, Elihu H. Estey, Roland B. Walter
Journal: Blood (2021)
Definitive Chemoradiotherapy for Older Patients With Esophageal Cancer
Authors: Masato Hayashi, Naohiro Okano, Tomonori Mizutani
Journal: JAMA Oncology (2021)

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 Oncology 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 Oncology journal
A structurally engineered fatty acid, icosabutate, suppresses liver inflammation and fibrosis in NASH
Authors: David A. Fraser, Xiaoyu Wang, Jenny Lund, Nataša Nikolić, Marta Iruarrizaga-Lejarreta, Tore Skjaeret, Cristina Alonso, John J.P. Kastelein, Arild C. Rustan, Yong Ook Kim, Detlef Schuppan
Journal: Journal of Hepatology (2021)
Incorrect Patient Data Reported
Authors: Neale Mahoney, Francis Wong, Wesley Yin
Journal: JAMA (2021)

data furnishers or processors and that our data are insufficiently granular to assess the accuracy of classification.Section 623 of the Fair Credit Report Act 2 requires accurate classification of medical debt, and most furnishers report debt using a standardized data format.Given this standardization and legal obligation to accurately report debt to credit bureaus, there is little reason to believe that misclassification of debt meaningfully affected our results.Also, despite nominal access restrictions, the Consumer Data Industry Association Credit Reporting Resource Guide containing industry guidelines can be readily found via an internet search.Nevertheless, in the Limitations section of our article, 1 we noted that our data did not include unreported medical debts.Third, Uppal and colleagues note that the downtrends in medical debt coincided with the Medical Debt Responsibility Act, which required national credit reporting agencies to remove paid medical collections from credit reports.As described in the Methods section, 1 we excluded from our analysis accounts that were paid, so the policy change referred to by Uppal and colleagues had no bearing on our results.Fourth, as acknowledged in the Limitations section of our article, 1 we agree with Uppal and colleagues that some medical debt may be captured as nonmedical debt because it may be paid with other loans.Given the lack of systematic data, we do not feel comfortable speculating on the dollar amount of medical debt that falls into this category.Uppal and colleagues cite survey evidence that 62% of patients "reported increasing their credit card debt, taking out other loans, or borrowing from payday lenders."This evidence does not allow us to estimate the dollar value of medical bills or collections paid with such loans or to speculate on how such payments have changed over time or evolved differentially across geographies or income deciles.Although we share the desire to quantify the dollar value of medical bills paid with other loans, we are not aware of currently available systematic data that allow us to determine this amount and quantify its importance.
Silicon‐Phosphorus‐Nanosheets‐Integrated 3D‐Printable Hydrogel as a Bioactive and Biodegradable Scaffold for Vascularized Bone Regeneration
Authors: Chao Xu, Yukai Chang, Yan Xu, Ping Wu, Congpu Mu, Anmin Nie, Yanzhen Qu, Deyu Duan, Xiaodong Guo, Zhongyuan Liu, Jianglin Wang, Zhiqiang Luo
Journal: Advanced Healthcare Materials (2021)

Natural bone is a highly vascularized tissue that relies on the vasculature for blood and nutrients supply to maintain skeletal integrity. Bioactive nanomaterials with the capability of improving vascularized bone regeneration are highly demanded for bone tissue engineering. In this work, 2D silicon phosphorus (SiP) is explored as a new kind of bioactive and biodegradable nanomaterial with excellent angiogenesis and osteogenesis, and a 3D printed biohybrid hydrogel of GelMA-PEGDA incorporated with photocrosslinkable SiP-nanosheet (GelMA-PEGDA/SiPAC) is developed to apply on bone tissue engineering. Findings show that the GelMA-PEGDA/SiPAC possessess excellent biocompatibility and biodegradability, and can sustainably release Si and P elements. Compared with the biohybrid hydrogel scaffolds incorporated with black phosphorus nanosheets, the GelMA-PEGDA/SiPAC can further enhance the osteogenesis of mesenchymal stem cells, and tubular networking of human umbilical vascular endothelial cells. In a rat calvarial bone defect model, the superior angiogenesis and osteogenesis induced by GelMA-PEGDA/SiPAC have been confirmed in vivo. The current strategy paves a new way to design a multifunctional SiP nanocomposite scaffold on mediating the osteogenesis and angiogenesis in one system, and provides a bioactive and biodegradable alternative nanomaterial for tissue engineering and regenerative medicine.
The biological basis of disease recurrence in psoriasis: a historical perspective and current models
Authors: Lluís Puig, Antonio Costanzo, Ernesto J. Muñoz‐Elías, Maria Jazra, Sven Wegner, Carle F. Paul, Curdin Conrad
Journal: British Journal of Dermatology (2021)

A key challenge in psoriasis therapy is the tendency for lesions to recur in previously affected anatomical locations after treatment discontinuation following lesion resolution. Available evidence supports the concept of a localized immunological 'memory' that persists in resolved skin after complete disappearance of visible inflammation, as well as the role of a specific subpopulation of T cells characterized by the dermotropic CCR4+ phenotype and forming a local memory. Increasing knowledge of the interleukin (IL)-23/T helper 17 (Th17) cell pathway in psoriasis immunopathology is pointing away from the historical classification of psoriasis as primarily a Th1-type disease. Research undertaken from the 1990s to the mid-2000s provided evidence for the existence of a large population of CD8+ and CD4+ tissue-resident memory T cells in resolved skin, which can initiate and perpetuate immune responses of psoriasis in the absence of T-cell recruitment from the blood. Dendritic cells (DCs) are antigen-presenting cells that contribute to psoriasis pathology via the secretion of IL-23, the upstream regulator of Th17 cells, while plasmacytoid DCs are involved via IL-36 signalling and type I interferon activation. Overall, the evidence discussed in this review indicates that IL-23-driven/IL-17-producing T cells play a critical role in psoriasis pathology and recurrence, making these cytokines logical therapeutic targets. The review also explains the clinical efficacy of IL-17 and IL-23 receptor blockers in the treatment of psoriasis.
Beyondcell: targeting cancer therapeutic heterogeneity in single-cell RNA-seq data
Authors: Coral Fustero-Torre, María José Jiménez-Santos, Santiago García-Martín, Carlos Carretero-Puche, Luis García-Jimeno, Vadym Ivanchuk, Tomás Di Domenico, Gonzalo Gómez-López, Fátima Al-Shahrour
Journal: Genome Medicine (2021)

Abstract We present Beyondcell, a computational methodology for identifying tumour cell subpopulations with distinct drug responses in single-cell RNA-seq data and proposing cancer-specific treatments. Our method calculates an enrichment score in a collection of drug signatures, delineating therapeutic clusters (TCs) within cellular populations. Additionally, Beyondcell determines the therapeutic differences among cell populations and generates a prioritised sensitivity-based ranking in order to guide drug selection. We performed Beyondcell analysis in five single-cell datasets and demonstrated that TCs can be exploited to target malignant cells both in cancer cell lines and tumour patients. Beyondcell is available at: https://gitlab.com/bu_cnio/beyondcell .