tbuckley/cabot-search huggingface dataset:
MLKL: Functions beyond serving as the Executioner of Necroptosis
Authors: Chaoning Zhan, Minchun Huang, Xiaojun Yang, Jin Hou
Journal: Theranostics (2021)

Recently, necroptosis, as a programmed cell death pathway, has drawn much attention as it has been implicated in multiple pathologies, especially in the field of inflammatory diseases. Pseudokinase mixed lineage kinase domain-like protein (MLKL) serves as a terminal-known obligate effector in the process of necroptosis. To date, the majority of research on MLKL has focused on its role in necroptosis, and the prevailing view has been that the sole function of MLKL is to mediate necroptosis. However, increasing evidence indicates that MLKL can serve as a regulator of many diseases via its non-necroptotic functions. These functions of MLKL shed light on its functional complexity and diversity. In this review, we briefly introduce the current state of knowledge regarding the structure of MLKL, necroptosis signaling, as well as cross-linkages among necroptosis and other regulated cell death pathways, and we particularly highlight recent progress related to newly identified functions and inhibitors of MLKL. These discussions promote a better understanding of the role of MLKL in diseases, which will foster efforts to pharmacologically target this molecule in clinical treatments.
P86.18 Prevalence, Clinical Characteristics and Survival of Patients with KRAS Mutant Lung Cancer in Argentina.
Authors: J. Blaquier, M. Cerini, V. Denninghoff, F. Jauk, V. Wainsztein, L. Basbus, L. Dalurzo, V. Romano, L. Lupinacci, G. Recondo, H. Garcia Rivello, J. Minatta, G. Recondo
Journal: Journal of Thoracic Oncology (2021)
Covid-19: AstraZeneca vaccine is not linked to increased risk of blood clots, finds European Medicine Agency
Authors: Elisabeth Mahase
Journal: BMJ (2021)

The Oxford-AstraZeneca covid-19 vaccine is not linked to an increased risk of blood clots and is both safe and effective, an investigation by the European Medicine Agency (EMA) has concluded.1

The in-depth analysis of evidence—including laboratory results, clinical reports, autopsies, and clinical trial data—was carried out after a small number of blood clot cases (37) were reported in people who had received the vaccine. This led to 16 EU countries halting their vaccine rollout.2

“The committee has come to a clear scientific conclusion. This is a safe and effective vaccine,” said Emer Cooke, EMA executive director, at a press conference on 18 March. “Its benefits in protecting people from covid-19 with the associated risks of death and hospitalisation outweigh the possible risks. The committee also concluded that the vaccine is not associated with an increase in the overall risk of thromboembolic events or blood clots.”

Sabine Straus, chair of the Pharmacovigilance Risk …
Covid-19: Government’s failure to share data and face scrutiny have undermined response, say MPs
Authors: Elisabeth Mahase
Journal: BMJ (2021)

A coagulation screen is an important screening test when investigating a child who presents with easy bruising or bleeding. Interpretation of a coagulation screen can be challenging for clinicians. Evolution of the haemostasis system during childhood means normal ranges vary with age and needs to be interpreted alongside the clinical information. It is essential to consider preanalytical variables when interpreting a coagulation screen, and the reason for the investigation must always be considered. It is important that the sample is taken under optimal conditions, including sample technique, use of the correct bottle and prompt transport to the laboratory. An abnormal coagulation screen may indicate an underlying congenital bleeding disorder or an acquired bleeding disorder, or may be due to sampling error. Limitations of the coagulation screen are essential to be aware of, as some children with normal coagulation screen results may have bleeding disorders. Conversely, an abnormal coagulation screen does not always indicate a bleeding disorder.
Biomineralization Directed by Prenucleated Calcium and Phosphorus Nanoclusters Improving Mechanical Properties and Osteogenic Potential of <i>Antheraea pernyi</i> Silk Fibroin‐Based Artificial Periosteum
Authors: Yajun Shuai, Huan Lu, Ruyin Lv, Jie Wang, Quan Wan, Chuanbin Mao, Mingying Yang
Journal: Advanced Healthcare Materials (2021)

Abstract The use of biomacromolecules as templates to control the nucleation and growth of hydroxyapatite crystals to prepare bioactive materials is a valuable approach in bone tissue engineering. Here, an artificial periosteum is prepared by biomineralizing Antheraea pernyi fibroin ( AF ) membrane with prenucleated nanoclusters, which can promote the osteogenic differentiation of mesenchymal stem cells (MSCs) and induce the formation of bone matrix protein in vivo. To achieve this, a biologically inspired prenucleated calcium and phosphorus nanocluster mineralization system is designed to nucleate and generate hydroxyapatite crystals on the surface of the AF membrane. This biomineralization process provides AF membranes with improved elastic modulus and tensile strength. Subsequently, cell viability assay, hemolysis test, and H&amp;E staining show that the mineralized AF ( MAF ) membranes has good cytocompatibility, hemocompatibility, and histocompatibility in vitro and in vivo. Additionally, the MAF membranes significantly promote osteogenic differentiation of MSCs in the absence of osteogenic inducer in vitro. Experiments in vivo demonstrate that bone‐related matrix proteins are highly expressed in MAF groups with or without MSCs seeded. Therefore, the use of bioinspired prenucleated nanoclusters to prepare artificial periosteum based on biomineralized AF membrane is a promising strategy in the field of bone tissue engineering.
Tipifarnib in Head and Neck Squamous Cell Carcinoma With<i>HRAS</i>Mutations
Authors: Alan L. Ho, Irene Brana, Robert Haddad, Jessica Bauman, Keith Bible, Sjoukje Oosting, Deborah J. Wong, Myung-Ju Ahn, Valentina Boni, Caroline Even, Jerome Fayette, Maria José Flor, Kevin Harrington, David S. Hong, Sung-Bae Kim, Lisa Licitra, Ioanna Nixon, Nabil F. Saba, Stephan Hackenberg, Pol Specenier, Francis Worden, Binaifer Balsara, Mollie Leoni, Bridget Martell, Catherine Scholz, Antonio Gualberto
Journal: Journal of Clinical Oncology (2021)

Mutations in the HRAS (mHRAS) proto-oncogene occur in 4%-8% of patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Tipifarnib is a farnesyltransferase inhibitor that disrupts HRAS function. We evaluated the efficacy of tipifarnib in patients with R/M mHRAS HNSCC.We enrolled 30 patients with R/M HNSCC in a single-arm, open-label phase II trial of tipifarnib for mHRAS malignancies; one additional patient was treated on an expanded access program. After an ad hoc analysis of the first 16 patients with HNSCC with mHRAS variant allele frequency (VAF) data, enrollment was limited to those with a mHRAS VAF of ≥ 20% (high VAF). The primary end point was objective response rate. Secondary end points included assessing safety and tolerability. Patients received tipifarnib 600 or 900 mg orally twice daily on days 1-7 and 15-21 of 28-day cycles.Of the 22 patients with HNSCC with high VAF, 20 were evaluable for response at the time of data cutoff. Objective response rate for evaluable patients with high-VAF HNSCC was 55% (95% CI, 31.5 to 76.9). Median progression-free survival on tipifarnib was 5.6 months (95% CI, 3.6 to 16.4) versus 3.6 months (95% CI, 1.3 to 5.2) on last prior therapy. Median overall survival was 15.4 months (95% CI, 7.0 to 29.7). The most frequent treatment-emergent adverse events among the 30 patients with HNSCC were anemia (37%) and lymphopenia (13%).Tipifarnib demonstrated encouraging efficacy in patients with R/M HNSCC with HRAS mutations for whom limited therapeutic options exist (NCT02383927).
P76.42 OsimertinibTreatment in Non-Small Cell Lung Cancer (NSCLC) EGFR-T790M+. Activity in Patients with CNS Metastases. OSIREX
Authors: J. Terrasa, P. Garrido, R. Garcia Campelo, F. Aparisi, P. Diz, D. Aguiar, C. Garcia Giron, J. Hidalgo, C. Aguado De La Rosa, J.J. Garcia Gonzalez, E. Esteban, L. Gómez Aldavari, T. Moran, O. Juan, L.E. Chara, J.L. Martí, R. Lopez Castro, A.L. Ortega Granados, N. Martinez Moreno, J. Coves, A.M. Sánchez Peña, J. Bosch-Barrera, M. Provencio
Journal: Journal of Thoracic Oncology (2021)
BPI21-007: Physician Adherence to Treatment Guidelines Based on Priority Groups for Breast Cancer Patients During the COVID-19 Pandemic
Authors: Courtney Elisabeth Pisano, Janice A. Lyons, Gino Cioffi, Jill S. Barnholtz-Sloan, Joy Knight, Steven Maximuk, Megan E. Miller, Alberto J. Montero, Hannah Gilmore, Eleanor E. Harris
Journal: Journal of the National Comprehensive Cancer Network (2021)

"BPI21-007: Physician Adherence to Treatment Guidelines Based on Priority Groups for Breast Cancer Patients During the COVID-19 Pandemic" published on 17 Mar 2021 by National Comprehensive Cancer Network.
Fc-Optimized Anti-CCR8 Antibody Depletes Regulatory T Cells in Human Tumor Models
Authors: Joseph R. Campbell, Bryan R. McDonald, Paul B. Mesko, Nathan O. Siemers, Priti B. Singh, Mark Selby, Tim W. Sproul, Alan J. Korman, Logan M. Vlach, Jeff Houser, Sharmila Sambanthamoorthy, Kai Lu, Sandra V. Hatcher, Jack Lohre, Renu Jain, Ruth Y. Lan
Journal: Cancer Research (2021)

FOXP3+ regulatory T cells (Treg) play a critical role in mediating tolerance to self-antigens and can repress antitumor immunity through multiple mechanisms. Therefore, targeted depletion of tumor-resident Tregs is warranted to promote effective antitumor immunity while preserving peripheral homeostasis. Here, we propose the chemokine receptor CCR8 as one such optimal tumor Treg target. CCR8 was expressed by Tregs in both murine and human tumors, and unlike CCR4, a Treg depletion target in the clinic, CCR8 was selectively expressed on suppressive tumor Tregs and minimally expressed on proinflammatory effector T cells (Teff). Preclinical mouse tumor modeling showed that depletion of CCR8+ Tregs through an FcyR-engaging anti-CCR8 antibody, but not blockade, enabled dose-dependent, effective, and long-lasting antitumor immunity that synergized with PD-1 blockade. This depletion was tumor Treg-restricted, sparing CCR8+ T cells in the spleen, thymus, and skin of mice. Importantly, Fc-optimized, nonfucosylated (nf) anti-human CCR8 antibodies specifically depleted Tregs and not Teffs in ex vivo tumor cultures from primary human specimens. These findings suggest that anti-CCR8-nf antibodies may deliver optimal tumor-targeted Treg depletion in the clinic, providing long-term antitumor memory responses while limiting peripheral toxicities. SIGNIFICANCE: These findings show that selective depletion of regulatory T cells with an anti-CCR8 antibody can improve antitumor immune responses as a monotherapy or in combination with other immunotherapies. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/11/2983/F1.large.jpg.
Deep sequencing of sncRNAs reveals hallmarks and regulatory modules of the transcriptome during Parkinson’s disease progression
Authors: Fabian Kern, Tobias Fehlmann, Ivo Violich, Eric Alsop, Elizabeth Hutchins, Mustafa Kahraman, Nadja L. Grammes, Pedro Guimarães, Christina Backes, Kathleen L. Poston, Bradford Casey, Rudi Balling, Lars Geffers, Rejko Krüger, Douglas Galasko, Brit Mollenhauer, Eckart Meese, Tony Wyss-Coray, David W. Craig, Kendall Van Keuren-Jensen, Andreas Keller
Journal: Nature Aging (2021)
MA03.04 A Gender-Specific Radiomics Models for Predicting Recurrence in Early Stage (Stage I, II) Non-Small Cell Lung Cancer (ES-NSCLC) Patients
Authors: P. Vaidya, K. Bera, P. Patil, A. Gupta, P. Fu, P. Velu, H. Choi, V. Velcheti, A. Madabhushi
Journal: Journal of Thoracic Oncology (2021)
Transillumination breast spectroscopy (TiBS) as biomarker for breast cancer risk assessment.
Authors: Samantha Dick, Sally Hanna, Kristina Blackmore, Julia Knight, Supriya Kulkarni, Susan Done, David McCready, Wei-Liang Leong, Fei-Fei Liu, Lothar Lilge
Journal: Cancer Research (2008)

1607  The amount of x-ray derived breast density is highly correlated with breast cancer risk, providing an odds ratio (OR) of 4 - 6 when comparing high versus low breast tissue density. Transillumination breast spectroscopy (TiBS) is a safe method that uses non-ionizing, visible near-infrared light to provide compositional and physiologic information of the breast. A study on 300 women with radiologically normal mammograms showed TiBS, as an intermediate biomarker for breast cancer risk, can identify women with high parenchymal density. Correlation between transillumination spectra and mammographic parenchymal density showed a sensitivity and specificity of classifying high versus low breast tissue density of 0.97. TiBS offers an alternative method to assess breast cancer risk.  Interim analysis presented here of an ongoing study aims to determine the direct association between TiBS and the incidence of breast cancer. Subjects (mean age 53.4 y, age range 32 - 70 y) comprise women with confirmed unilateral breast cancer, ductal or loblar carcinoma in situ (DCIS or LCIS) (cases, n = 50), high- and low- risk benign conditions (e.g. atypical hyperplasia and dysplasia respectively, n = 85) and case-matched controls (n = 59). Case-control matching is based on age (+/- 2.5 years), date of screening mammogram (+/- up to 3 months), and screening center. Study data comprises of TiBS spectral data, anthropometric, risk factor, radiologic, pathologic and demographic information. For spectral collection, visible near infrared light (spectral range 576 - 1061 nm) from a 50W lamp is delivered to the breast tissue. Four quadrants per breast in the cranial-caudal axis are measured. A total of 8 measurements per subject are collected (a total of 4 for post-biopsy measurements). Light is detected on the opposite side of the breast in tissue up to 10 cm thick. No plate compression is required.  Principal component analysis (PCA) was used to reduce mean-centered spectral data and generate principal components (px), which is representative of physiologic and morphologic tissue states, and their associated scalar coefficients (or t scores, tx). 5 principal components (p1 to p5) were identified accounting for 99.99% of the spectral variance seen in the dataset. Each subject has 5 t scores (t1 - t5) for each quadrant of the breast. Differences in t scores between malignant/pre-malignant cases and controls were detected for t4, t5 (p
Differential regulation of survivin gene expression and cell death by sequence dependent DNA-binding drugs
Authors: Jianguo Wu, Pasha Apontes, Lei Song, Ping Liang, Terry Beerman, Fengzhi Li
Journal: Cancer Research (2004)

1449  Expression of the anti-apoptotic protein survivin has been demonstrated to be associated with cancer cell viability. Thus, control of its expression in cancer cells is important for targeted cancer therapeutics. Here, we report that data from Northern, Western and luciferase reporter assays revealed that Hoechst 33342, a drug that binds A/T rich regions within the DNA minor groove, upregulated survivin expression in HeLa and HCT116 cells while Hedamycin, a drug that binds G/C rich regions within the major groove, downregulated its expression. Consistent with the opposite effects of these drugs on survivin expression, HeLa and HCT116 cells are resistant to Hoechst 33342 treatment but sensitive to treatment of Hedamycin. Using a series of oriented nest-deleted survivin promoter-luciferase constructs, we identified an A/T rich region (-1342 to –1050) that mediates the major effects of Hoechst 33342 on upregulation of survivin transcription, and the G/C rich core promoter region (-269 to -39) that mediates the effects of Hedamycin on downregulation of survivin promoter activity. Computer analysis of the functionally identified A/T rich region revealed two A/T rich DNA elements (-1176 to -1141 and -1096 to -1048) that potentially interact with several transcription activators. Gel shift (EMSA) assays using these two cis-acting DNA elements as probes indicated that protein binding was elevated using nuclear extracts isolated from Hoechst 33342 treated HeLa cells relative to untreated controls. In contrast, Hedamycin treatments decreased protein binding to two potential Hedamycin-interacting DNA elements located in the survivin core promoter region. Together, these data suggest that alteration of DNA sequence-specific protein binding by these drugs to DNA targets within the survivin promoter region may contribute to their opposite effects on survivin transcription. Utilization of sequence-dependent DNA-binding drugs as probes to investigate survivin transcription may lead to novel approaches to control survivin expression for treatment of cancer.
Addressing Unmet Adaptive Equipment Needs Through Primary Care
Authors: Brian E. McGarry, Jason R. Falvey
Journal: JAMA Internal Medicine (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 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
P33.04 Programmed Death-Ligand 1 (PD-L1) Changes in Non-Small-Cell Lung Cancer (NSCLC): Clinical, Pathologic, and Genomic Correlates
Authors: S. Alden, B. Ricciuti, L. Spurr, H. Gupta, G. Lamberti, Y. Li, L. Sholl, A. Cherniack, M. Awad
Journal: Journal of Thoracic Oncology (2021)
P38.02 Reproducibility and Accuracy of Intra-Operative Assessment on Tumor Spread Through Air Spaces in Stage 1 Lung Adenocarcinomas
Authors: J. Villalba, T. Sayo, A. Shih, Y. Hung, A. Ly, M. Kem, L. Hariri, M. Mino-Kenudson
Journal: Journal of Thoracic Oncology (2021)
Experimental Resurrection of Ancestral Mammalian CPEB3 Ribozymes Reveals Deep Functional Conservation
Authors: Devin P. Bendixsen, Tanner B. Pollock, Gianluca Peri, Eric J. Hayden
Journal: Molecular Biology and Evolution (2021)

Self-cleaving ribozymes are genetic elements found in all domains of life, but their evolution remains poorly understood. A ribozyme located in the second intron of the cytoplasmic polyadenylation binding protein 3 gene (CPEB3) shows high sequence conservation in mammals, but little is known about the functional conservation of self-cleaving ribozyme activity across the mammalian tree of life or during the course of mammalian evolution. Here, we use a phylogenetic approach to design a mutational library and a deep sequencing assay to evaluate the in vitro self-cleavage activity of numerous extant and resurrected CPEB3 ribozymes that span over 100 My of mammalian evolution. We found that the predicted sequence at the divergence of placentals and marsupials is highly active, and this activity has been conserved in most lineages. A reduction in ribozyme activity appears to have occurred multiple different times throughout the mammalian tree of life. The in vitro activity data allow an evaluation of the predicted mutational pathways leading to extant ribozyme as well as the mutational landscape surrounding these ribozymes. The results demonstrate that in addition to sequence conservation, the self-cleavage activity of the CPEB3 ribozyme has persisted over millions of years of mammalian evolution.
Omega-3 Fatty Acids and Atrial Fibrillation
Authors: Gregory Curfman
Journal: JAMA (2021)

Christine M. Albert, MD, MPH; Nancy R. Cook, ScD; Julie Pester, BA; M. Vinayaga Moorthy, PhD; Claire Ridge, MPH; Jacqueline S. Danik, MD, DrPH; Baris Gencer, MD; Hasan K. Siddiqi, MD, MSCR; Chee Ng, MD; Heike Gibson, PhD; Samia Mora, MD, MHS; Julie E. Buring, ScD; JoAnn E. Manson, MD, DrPH
Abstract 16009: Effects of Cognitive Behavioral and Psycho-Educational Therapy in Patients With Implantable Cardioverter Defibrillators: Systematic Review and Meta-Analysis of Randomized and Quasi-Experimental Trials
Authors: Zahra Azizi, Hadi Tohidi, Pouria Alipour, Meysam Pirbaglou, Chris Ardern, Michael Rotondi, Paul Ritvo, Atul Verma, Yaariv Khaykin
Journal: Circulation (2019)

Introduction: Shocks delivered by Implantable cardioverter defibrillators (ICD), while life-saving, can affect patients’ quality of life. Psychoeducational and Cognitive behavioral therapy (CBT) ha...
Relieving lipid accumulation through UCP1 suppresses the progression of acute kidney injury by promoting the AMPK/ULK1/autophagy pathway
Authors: Wei Xiong, Zhiyong Xiong, Anni Song, Chuntao Lei, Chen Ye, Chun Zhang
Journal: Theranostics (2021)

Rationale: Acute kidney injury (AKI) is a serious clinical emergency with an acute onset, rapid progression, and poor prognosis. Recent evidence suggests that AKI is accompanied by significant metabolic abnormalities, including alterations in lipid metabolism. However, the specific changes in lipids in AKI, and their role and regulation mechanisms are currently unclear. Methods: Quantitative metabolomics was performed in AKI models to reveal the differences of lipid metabolism-related products. Regulated pathway was detected by western blot, qRT-PCR, immunoblot analysis and immunohistochemistry. Results: The present study systematically analyzes the changes in lipid composition in AKI for the first time and find that the degree of lipid accumulation was highly correlated with uncoupling protein 1 (UCP1). Importantly, relieving lipid accumulation in AKI by upregulating UCP1 can significantly inhibit the progression of AKI through promoting AMPK/ULK1/autophagy pathway. Conclusions: The present findings suggest that lipid accumulation in AKI is directly regulated by UCP1, which can activate cell autophagy and thus significantly inhibit disease progression. It will provide new ideas and targets for the treatment of AKI.
The Good Doctor — Jack Geiger, Social Justice, and U.S. Health Policy
Authors: Sara Rosenbaum, Daniel R. Hawkins
Journal: New England Journal of Medicine (2021)

H. Jack Geiger, who died in December, left an indelible imprint on health equity and social justice as paramount elements of a national health policy. Above all, this imprint is found in the community health centers program, where medicine is an entry point into health.
P76.64 Alternating Osimertinib and Gefitinib as Second-Line Treatment for EGFR-Mutated NSCLC Harbouring a T790M Resistance Mutation (OSCILLATE)
Authors: B. Solomon, A. Mersiades, C. Brown, S. Dawson, S. Wong, L. Tan, S. Yip, Y. Cheung, H. Jurkovic, M. Walker, S. Kao, C.K. Lee, G. Newnham, K. O'Byrne, S. Parakh, K. Jasas, V. Bray, M. Stockler, T. John, N. Pavlakis
Journal: Journal of Thoracic Oncology (2021)