tbuckley/cabot-search huggingface dataset:
Abstract P101: The Double Burden Of Malnutrition Among Women And Preschool Children In Low- And Middle-income Countries: A Scoping Review And Thematic Analysis Of The Literature
Authors: Jason M Were, Saverio Stranges, Ishor Sharma, Juan Camilo Vargas-Gonzalez, M. K Campbell
Journal: Circulation (2022)

Background: The double burden of malnutrition (DBM), the simultaneous existence of both underweight and overweight sequelae, is an emerging public health concern in low- and middle-income countries (LMICs). Women of child-bearing age (15-49 years) and preschool children (under 5 years) are among the most vulnerable groups to be affected by the DBM. However, the DBM phenomenon among these population subgroups is understudied. Objectives: We explored the following objectives: 1) To determine which nutrition indicators have been used to define the DBM among women of child-bearing age and preschool children; 2) To establish the plausible explanations for the identified DBM phenotypes women of child-bearing age and preschool children; and 3) To identify the risk factors for the DBM women of child-bearing age and preschool children. Methods: We systematically searched for literature from the following databases: EMBASE, CINAHL, MEDLINE, LILACS, Scopus and ProQuest Dissertations &amp; Thesis Global. Studies discussing the DBM phenomenon in LMICs were included. Thematic analysis was conducted on extracted information from the literature to reveal emerging themes from included studies. The findings were reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Results: Preliminary findings indicate that frequently used indicators for defining DBM across all levels of operationalization were anthropometric indices and micronutrients measurements (e.g., overweight/obesity and anemia) for women and anthropometric indices (e.g., overweight/obesity and stunting) for preschool children. The following themes emerged as plausible explanations for the DBM phenotypes: Food insecurity; diet behavior; breastfeeding; illness and metabolic programming. Age, child sex, household wealth, women’s education, occupation and urbanization were frequently occurring DBM risk factors. Of note was the use of the term ‘double burden’ as a buzz word in substantial number of studies without a proper definition or discussion of the DBM concept. Conclusion: The DBM phenomenon is loosely understood due to the varying operational definitions of the DBM construct. Emerging themes and common risk factors may provide target areas for public health interventions. Studies with robust designs are needed to succinctly understand the DBM phenomenon.
Recurrence of a Pheochromocytoma With TNEM127 Mutation Negative on 18F-FDOPA and 18F-FDG but Positive on 123I-MIBG and 68Ga-DOTATOC Imaging
Authors: Anne-Ségolène Cottereau, Cyril Garcia, Bertrand Dousset, Rossella Libe, Florence Tenenbaum
Journal: Clinical Nuclear Medicine (2021)

Abstract We report the case of a 75-year-old woman with liver metastasis as a recurrence of a pheochromocytoma resected 10 years ago, with a rare germline mutation in transmembrane protein 127, falsely negative on 18 F-FDOPA and 18 F-FDG PET/CT scans but strongly positive on 123 I-MIBG scintigraphy and on 68 Ga-DOTATOC PET/CT. Functional imaging has a key role in diagnosis of pheochromocytoma and paraganglioma, especially 18 F-FDOPA shows very high sensitivity and specificity. However, 18 F-FDOPA might be falsely negative in some of these tumors, depending on specific mutations, and thus MIBG or 68 Ga-DOTATOC imaging could be an alternative.
Functional theories can describe many features of conscious phenomenology but cannot account for its existence
Authors: Max Velmans
Journal: Behavioral and Brain Sciences (2022)

Abstract Merker, Williford, and Rudrauf argue persuasively that integrated information is not identical to or sufficient for consciousness, and that projective geometries more closely formalize the spatial features of conscious phenomenology. However, these too are not identical to or sufficient for consciousness. Although such third-person specifiable functional theories can describe the many forms of consciousness, they cannot account for its existence .
Management of Chronic Low Back Pain
Authors: Thiru M. Annaswamy, Michael Hatzakis, Andre Panagos
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
Anatomical, physiological, and psychophysical data show that the nature of conscious perception is incompatible with the integrated information theory (IIT)
Authors: Moshe Gur
Journal: Behavioral and Brain Sciences (2022)

Abstract The integrated information theory (IIT) equates levels of consciousness with the amount of information integrated over the elements that constitute a system. Conscious visual perception provides two observations that contradict the IIT. First, objects are accurately perceived when presented for ≪100 ms during which time no neural integration is possible. Second, an object is seen as an integrated whole and, concurrently, all constituent elements are evident. Because integration destroys information about details, IIT cannot account for perceptual detail preservation.
Phase II Study of Nivolumab and Salvage Nivolumab/Ipilimumab in Treatment-Naive Patients With Advanced Clear Cell Renal Cell Carcinoma (HCRN GU16-260-Cohort A)
Authors: Michael B. Atkins, Opeyemi A. Jegede, Naomi B. Haas, David F. McDermott, Mehmet A. Bilen, Mark Stein, Jeffrey A. Sosman, Robert Alter, Elizabeth R. Plimack, Moshe Ornstein, Michael Hurwitz, David J. Peace, Sabina Signoretti, Thomas Denize, Alessia Cimadamore, Catherine J. Wu, David Braun, David Einstein, Paul J. Catalano, Hans Hammers
Journal: Journal of Clinical Oncology (2022)

To determine the value of tumor cell programmed death-ligand 1 (PD-L1) expression as a predictive biomarker of nivolumab monotherapy efficacy in treatment-naive patients with clear cell renal cell carcinoma (ccRCC) and the efficacy of salvage nivolumab/ipilimumab in patients with tumors unresponsive to nivolumab monotherapy.
68P Clinical implications of cardiotoxicity and pharmacokinetics of alectinib in patients (pts) with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC)
Authors: M. Pruis, M.G.D. Veerman, C. Hassing, D. Lanser, M.S. Paats, R.H. Mathijssen, O. Manintveld, A-M.C. Dingemans
Journal: Annals of Oncology (2022)
Trivalent nucleoside-modified mRNA vaccine yields durable memory B cell protection against genital herpes in preclinical models
Authors: Sita Awasthi, James J. Knox, Angela Desmond, Mohamad-Gabriel Alameh, Brian T. Gaudette, John M. Lubinski, Alexis Naughton, Lauren M. Hook, Kevin P. Egan, Ying K. Tam, Norbert Pardi, David Allman, Eline T. Luning Prak, Michael P. Cancro, Drew Weissman, Gary H. Cohen, Harvey M. Friedman
Journal: Journal of Clinical Investigation (2021)

Nucleoside-modified mRNA vaccines have gained global attention because of COVID-19. We evaluated a similar vaccine approach for preventing a chronic, latent genital infection rather than an acute respiratory infection. We used animal models to compare an HSV-2 trivalent nucleoside-modified mRNA vaccine with the same antigens prepared as proteins, with an emphasis on antigen-specific memory B cell responses and immune correlates of protection. In guinea pigs, serum neutralizing-antibody titers were higher at 1 month and declined far less by 8 months in mRNA- compared with protein-immunized animals. Both vaccines protected against death and genital lesions when infected 1 month after immunization; however, protection was more durable in the mRNA group compared with the protein group when infected after 8 months, an interval representing greater than 15% of the animal's lifespan. Serum and vaginal neutralizing-antibody titers correlated with protection against infection, as measured by genital lesions and vaginal virus titers 2 days after infection. In mice, the mRNA vaccine generated more antigen-specific memory B cells than the protein vaccine at early times after immunization that persisted for up to 1 year. High neutralizing titers and robust B cell immune memory likely explain the more durable protection by the HSV-2 mRNA vaccine.
The Role of high-resolution Magnetic Resonance Imaging at Different Stages of Subchondral Insufficiency Fracture in the Knee
Authors: A. P. Ivankov, P. V. Seliverstov
Journal: Radiology - Practice (2021)

The history of subchondral insufficiency fracture of knee is closely related to a pre-existing diagnosis of spontaneous osteonecrosis (SONK). Previously, it was believed that subchondral linear or lunate pathological changes on magnetic resonance imaging in elderly patients with osteoporosis are the result of spontaneous osteonecrosis that has occurred, but it was later found that a small proportion of patients with osteonecrosis of the femoral head initially have a failure fracture, then complicated by secondary osteonecrosis. The main methods for diagnosing subchondral insufficiency fracture are radiography and magnetic resonance imaging. Magnetic resonance imaging has demonstrated high information content in subchondral insufficiency fracture of knee.
Abstract EP34: Association Of Aortic Valve Calcification And High Levels Of Lipoprotein (a) . A Meta-analysis
Authors: Karam R. Motawea, Hager Fathy, Dina M. Awad, Mohamed Mohamed Belal, Sarya Swed, Merna Aboelenein, Nesreen Elsayed Talat, Samah S. Rozan, Nancy Ibrahim, Bisher Sawaf, Hani Aiash
Journal: Circulation (2022)

Background: Some studies reported a positive link between high levels of lipoprotein (a) and aortic valve calcification. The aim of this study is to perform a meta-analysis to find whether aortic valve calcification has a significant association with high levels of lipoprotein (a). Methods: We searched PUBMED, WOS and OVID databases. We included cohort studies or clinical trials that measured lipoprotein (a) levels in patients with aortic valve calcium and controls without aortic valve calcium. Case reports, editorials and animal studies were excluded. RevMan software (5.4) was used to perform the meta-analysis. Levels of lipoprotein (a) and number of patients with increased levels of lipoprotein (a) outcomes were presented as standardized mean difference (SMD) and Odds ratio (OR) with 95% confidence interval (CI). Results: After complete screening, 7 studies were included with a total number of 446179 patients included in the analysis. The pooled analysis showed a statistically significant association between incidence of aortic valve calcium and increased levels of lipoprotein (a) compared with controls (SMD = 1.71, 95% CI = 1.04 to 2.38, p-value &lt; 0.00001). The pooled analysis showed a statistically significant association between incidence of aortic valve calcium and increased number of patients with high levels of lipoprotein (a) compared with controls (OR = 2.21, 95% CI = 1.26 to 3.87, p-value = 0.006). We observed a significant heterogeneity in both outcomes ( P &lt; 0.00001) that was not solved by subgroup analysis or leave-one out test. Conclusion: This meta-analysis showed a statistically significant association between incidence of aortic valve calcium and increased levels of lipoprotein (a) compared with controls. Patients with high levels of lipoprotein (a) are at increased risk of developing aortic valve calcification. Medications targeting lipoprotein (a) in future clinical trials may be useful in primary prevention of aortic valve calcification in high risk patients.
On CRDPs and CRPD: why the rights of people with disabilities are crucial for understanding climate-resilient development pathways
Authors: Siri H Eriksen, Robyn Grøndahl, Ann-Marit Sæbønes
Journal: The Lancet Planetary Health (2021)

In this Personal View, we examine how the Convention on the Rights of Persons with Disabilities and lived experiences of disability can deepen understanding of four key features of climate-resilient development: social justice and equity as normative goals; the ethical underpinnings of social choices; the inequitable relations that drive marginalisation; and the ways in which society navigates uncertainty through inclusive and contestatory politics. A disability lens not only helps to understand how marginalisation generates vulnerability; it also helps to elaborate the ethic of solidarity as underpinning social choices and steering development towards climate-resilient pathways. Social justice concerns non-discrimination and equitable participation in everyday informal arenas, as well as formal decision making processes. The resilience knowledges of disabled people help to rethink sustainable development by expounding human interdependence and everyday problem solving in the face of uncertainties. They also contribute to opening up climate change decision making and knowledge processes in ways crucial to engendering transformative change. Embracing human diversity by recognising dignity and capacity is required to counter othering and marginalisation, ensure human wellbeing and planetary health, and achieve socially just development. As such, solidarity is not just a normative goal, but also a means of building climate-resilient development.
Phosphorylation and Stabilization of PD-L1 by CK2 Suppresses Dendritic Cell Function
Authors: Xixi Zhao, Yongkun Wei, Yu-Yi Chu, Yintao Li, Jung-Mao Hsu, Zhou Jiang, Chunxiao Liu, Jennifer L. Hsu, Wei-Chao Chang, Riyao Yang, Li-Chuan Chan, Jingkun Qu, Shuqun Zhang, Haoqiang Ying, Dihua Yu, Mien-Chie Hung
Journal: Cancer Research (2022)

Targeting immune checkpoints such as programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) has transformed cancer treatment, with durable clinical responses across a wide range of tumor types. However, a high percentage of patients fail to respond to anti-PD-1/PD-L1 treatment. A greater understanding of PD-L1 regulation is critical to improving the clinical response rate of PD-1/PD-L1 blockade. Here, we demonstrate that PD-L1 is phosphorylated and stabilized by casein kinase 2 (CK2) in cancer and dendritic cells (DC). Phosphorylation of PD-L1 at Thr285 and Thr290 by CK2 disrupted PD-L1 binding with speckle-type POZ protein, an adaptor protein of the cullin 3 (CUL3) ubiquitin E3 ligase complex, protecting PD-L1 from CUL3-mediated proteasomal degradation. Inhibition of CK2 decreased PD-L1 protein levels by promoting its degradation and resulted in the release of CD80 from DC to reactivate T-cell function. In a syngeneic mouse model, combined treatment with a CK2 inhibitor and an antibody against T-cell immunoglobulin mucin-3 (Tim-3) suppressed tumor growth and prolonged survival. These findings uncover a mechanism by which PD-L1 is regulated and suggest a potential antitumor treatment option to activate DC function by blocking the CK2-PD-L1 pathway and inhibiting Tim-3.This work identifies a role for CK2 in immunosuppression by phosphorylation and stabilization of PD-L1, identifying CK2 inhibition as an immunotherapeutic approach for treating cancer.
Functional Analysis of <i>MET</i> Exon 14 Skipping Alteration in Cancer Invasion and Metastatic Dissemination
Authors: Feng Wang, Yang Liu, Wanglong Qiu, Elaine Shum, Monica Feng, Dejian Zhao, Deyou Zheng, Alain Borczuk, Haiying Cheng, Balazs Halmos
Journal: Cancer Research (2022)

MET exon 14 skipping alteration (METΔ14Ex) is an actionable oncogenic driver that occurs in 2% to 4% of non-small cell lung cancer (NSCLC) cases. The precise role of METΔ14Ex in tumor progression of NSCLC is poorly understood. Using multiple isogenic METΔ14Ex cell models established with CRISPR editing, we demonstrate that METΔ14Ex expression increases receptor kinase activity and downstream signaling by impairing receptor internalization and endocytic degradation, significantly boosting cell scatter, migration, and invasion capacity in vitro as well as metastasis in vivo. RNA sequencing analysis revealed that METΔ14Ex preferentially activates biological processes associated with cell movement, providing novel insights into its unique molecular mechanism of action. Activation of PI3K/Akt/Rac1 signaling and upregulation of multiple matrix metallopeptidases (MMP) by METΔ14Ex induced cytoskeleton remodeling and extracellular matrix disassembly, which are critical functional pathways that facilitate cell invasion and metastasis. Therapeutically, MET inhibitors dramatically repressed METΔ14Ex-mediated tumor growth and metastasis in vivo, indicating potential therapeutic options for METΔ14Ex-altered NSCLC patients. These mechanistic insights into METΔ14Ex-mediated invasion and metastasis provide a deeper understanding of the role of METΔ14Ex in NSCLC.These findings reveal the mechanistic function of METΔ14Ex alteration in driving metastasis and define novel metastasis-related pathways that could be targeted for more effective treatment of lung cancer with METΔ14Ex alterations.
35P Real-world treatment outcomes of amivantamab in pre-approval access (PAA) participants with advanced non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations (ex20ins)
Authors: T.M. Kim, S-H. Lee, G-C. Chang, J-Y. Shih, M.J. Hochmair, J.K. Sabari, A.I. Spira, C.A. Schioppa, J.B. Rose, M. Chioda, A. Panaccione, P. Mahadevia, B.C. Cho
Journal: Annals of Oncology (2022)
Neoadjuvant FOLFIRINOX Therapy Is Associated with Increased Effector T Cells and Reduced Suppressor Cells in Patients with Pancreatic Cancer
Authors: Hui Peng, C. Alston James, Darren R. Cullinan, Graham D. Hogg, Jacqueline L. Mudd, Chong Zuo, Rony Takchi, Katharine E. Caldwell, Jingxia Liu, David G. DeNardo, Ryan C. Fields, William E. Gillanders, S. Peter Goedegebuure, William G. Hawkins
Journal: Clinical Cancer Research (2021)

Abstract Purpose: FOLFIRINOX has demonstrated promising results for patients with pancreatic ductal adenocarcinoma (PDAC). Chemotherapy-induced immunogenic cell death can prime antitumor immune responses. We therefore performed high-dimensional profiling of immune cell subsets in peripheral blood to evaluate the impact of FOLFIRINOX on the immune system. Experimental Design: Peripheral blood mononuclear cells (PBMC) were obtained from treatment-naïve (n = 20) and FOLFIRINOX-treated patients (n = 19) with primary PDAC tumors at the time of resection. PBMCs were characterized by 36 markers using mass cytometry by time of flight (CyTOF). Results: Compared with treatment-naïve patients, FOLFIRINOX-treated patients showed distinct immune profiles, including significantly decreased inflammatory monocytes and regulatory T cells (Treg), increased Th1 cells, and decreased Th2 cells. Notably, both monocytes and Treg expressed high levels of immune suppression-associated CD39, and the total CD39+ cell population was significantly lower in FOLFIRINOX-treated patients compared with untreated patients. Cellular alterations observed in responders to FOLFIRINOX included a significantly decreased frequency of Treg, an increased frequency of total CD8 T cells, and an increased frequency of CD27−Tbet+ effector/effector memory subsets of CD4 and CD8 T cells. Conclusions: Our study reveals that neoadjuvant chemotherapy with FOLFIRINOX enhances effector T cells and downregulates suppressor cells. These data indicate that FOLFIRINOX neoadjuvant therapy may improve immune therapy and clinical outcome in patients with PDAC.
<i>In vivo</i> outer hair cell gene editing ameliorates progressive hearing loss in dominant-negative <i>Kcnq4</i> murine model
Authors: Byunghwa Noh, John Hoon Rim, Ramu Gopalappa, Haiyue Lin, Kyu Min Kim, Min Jin Kang, Heon Yung Gee, Jae Young Choi, Hyongbum Henry Kim, Jinsei Jung
Journal: Theranostics (2022)

Outer hair cell (OHC) degeneration is a major cause of progressive hearing loss and presbycusis.Despite the high prevalence of these disorders, targeted therapy is currently not available.Methods: We generated a mouse model harboring Kcnq4 W276S/+ to recapitulate DFNA2, a common genetic form of progressive hearing loss accompanied by OHC degeneration.After comprehensive optimization of guide RNAs, Cas9s, vehicles, and delivery routes, we applied in vivo gene editing strategy to disrupt the dominant-negative allele in Kcnq4 and prevent progressive hearing loss.Results: In vivo gene editing using a dual adeno-associated virus package targeting OHCs significantly improved auditory thresholds in auditory brainstem response and distortion-product otoacoustic emission.In addition, we developed a new live-cell imaging technique using thallium ions to investigate the membrane potential of OHCs and successfully demonstrated that mutant allele disruption resulted in more hyperpolarized OHCs, indicating elevated KCNQ4 channel activity.Conclusion: These findings can facilitate the development of targeted therapies for DFNA2 and support the use of CRISPR-based gene therapy to rectify defects in OHCs.
Microglial Phagocytosis of Newborn Cells Is Induced by Endocannabinoids and Sculpts Sex Differences in Juvenile Rat Social Play
Authors: Jonathan W. VanRyzin, Ashley E. Marquardt, Kathryn J. Argue, Haley A. Vecchiarelli, Sydney E. Ashton, Sheryl E. Arambula, Matthew N. Hill, Margaret M. McCarthy
Journal: Neuron (2022)