tbuckley/cabot-search huggingface dataset:
New Drug for Sleeplessness
Authors: Jane E. Henney
Journal: JAMA (1999)

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
11P BioItaLEE: Comparative biomarker analysis of liquid biopsies and paired tissue samples of patients treated with ribociclib and letrozole as first-line therapy for advanced breast cancer (aBC)
Authors: G. Bianchini, M. De Laurentiis, G. Arpino, A. Zambelli, F. Puglisi, L. Del Mastro, M.A. Colleoni, F. Montemurro, G.V. Bianchi, I. Paris, G. Allegrini, L. Amaducci, M.E. Cazzaniga, M. Orditura, C. Zamagni, S. Bianchetti, D. Castelletti, M. Benelli, M. Callari, L. Malorni
Journal: Annals of Oncology (2020)
Emerging role of RNA methyltransferase METTL3 in gastrointestinal cancer
Authors: Qiang Wang, Wei Geng, Huimin Guo, Zhangding Wang, Kaiyue Xu, Chen Chen, Shouyu Wang
Journal: Journal of Hematology & Oncology (2020)

Abstract Gastrointestinal cancer, the most common solid tumor, has a poor prognosis. With the development of high-throughput sequencing and detection technology, recent studies have suggested that many chemical modifications of human RNA are involved in the development of human diseases, including cancer. m 6 A, the most abundant modification, was revealed to participate in a series of aspects of cancer progression. Recent evidence has shown that methyltransferase-like 3 (METTL3), the first identified and a critical methyltransferase, catalyzes m 6 A methylation on mRNA or non-coding RNA in mammals, affecting RNA metabolism. Abnormal m 6 A levels caused by METTL3 have been reported to be involved in different aspects of cancer development, including proliferation, apoptosis, and metastasis. In this review, we will shed light on recent findings regarding the biological function of METTL3 in gastrointestinal cancer and discuss future research directions and potential clinical applications of METTL3 for gastrointestinal cancer.
Bioactive poly (methyl methacrylate) bone cement for the treatment of osteoporotic vertebral compression fractures
Authors: Jinjin Zhu, Shuhui Yang, Kaiwen Cai, Shuo Wang, Zhiye Qiu, Junfei Huang, Guoqiang Jiang, Xiumei Wang, Xiangqian Fang
Journal: Theranostics (2020)

Rationale: Poly (methyl methacrylate) (PMMA) bone cement is one of the most commonly used biomaterials for augmenting/stabilizing osteoporosis-induced vertebral compression fractures (OVCFs), such as percutaneous vertebroplasty (PVP) and balloon kyphoplasty (BKP).However, its clinical applications are limited by its poor performance in high compressive modulus and weak bonding to bone.To address these issues, a bioactive composite bone cement was developed for the treatment of osteoporotic vertebral compression fractures, in which mineralized collagen (MC) was incorporated into the PMMA bone cement (MC-PMMA).Methods: The in vitro properties of PMMA and MC-PMMA composite bone cement were determined, including setting time, compressive modulus, adherence, proliferation, and osteogenic differentiation of rat bone mesenchymal stem cells.The in vivo properties of both cements were evaluated in an animal study (36 osteoporotic New Zealand female rabbits divided equally between the two bone cement groups; PVP at L5) and a small-scale and short-term clinical study (12 patients in each of the two bone cement groups; follow-up: 2 years).Results: In terms of value for PMMA bone cement, the handling properties of MC-PMMA bone cement were not significantly different.However, both compressive strength and compressive modulus were found to be significantly lower.In the rabbit model study, at 8 and 12 weeks post-surgery, bone regeneration was more significant in MC-PMMA bone cement (cortical bone thickness, osteoblast area, new bone area, and bone ingrowth %; each significantly higher).In the clinical study, at a follow-up of 2 years, both the Visual Analogue Score and Oswestry Disability Index were significantly reduced when MC-PMMA cement was used.Conclusions: MC-PMMA bone cement demonstrated good adaptive mechanical properties and biocompatibility and may be a promising alternative to commercial PMMA bone cements for the treatment of osteoporotic vertebral fractures in clinical settings.While the present results for MC-PMMA bone cement are encouraging, further study of this cement is needed to explore its viability as an ideal alternative for use in PVP and BKP.
Statin Use Is Prospectively Associated With New-Onset Diabetes After Transplantation in Renal Transplant Recipients
Authors: Tamas Szili-Torok, Stephan J.L. Bakker, Uwe J.F. Tietge
Journal: Diabetes Care (2020)

OBJECTIVE New-onset diabetes after transplantation (NODAT) is frequent and worsens graft and patient outcomes in renal transplant recipients (RTRs). In the general population, statins are diabetogenic. This study investigated whether statins also increase NODAT risk in RTRs. RESEARCH DESIGN AND METHODS From a prospective longitudinal study of 606 RTRs (functioning allograft &amp;gt;1 year, single academic center, follow-up: median 9.6 [range, 6.6–10.2] years), 95 patients using statins were age- and sex-matched to RTRs not on statins (all diabetes-free at inclusion). RESULTS NODAT incidence was 7.2% (73.3% of these on statins). In Kaplan-Meier (log-rank test, P = 0.017) and Cox regression analyses (HR 3.86 [95% CI 1.21–12.27]; P = 0.022), statins were prospectively associated with incident NODAT, even independent of several relevant confounders including immunosuppressive medication and biomarkers of glucose homeostasis. CONCLUSIONS This study demonstrates that statin use is prospectively associated with the development of NODAT in RTRs independent of other recognized risk factors.
Insights gained from a comprehensive all-against-all transcription factor binding motif benchmarking study
Authors: Giovanna Ambrosini, Ilya Vorontsov, Dmitry Penzar, Romain Groux, Oriol Fornes, Daria D. Nikolaeva, Benoit Ballester, Jan Grau, Ivo Grosse, Vsevolod Makeev, Ivan Kulakovskiy, Philipp Bucher
Journal: Genome biology (2020)

Abstract Background Positional weight matrix (PWM) is a de facto standard model to describe transcription factor (TF) DNA binding specificities. PWMs inferred from in vivo or in vitro data are stored in many databases and used in a plethora of biological applications. This calls for comprehensive benchmarking of public PWM models with large experimental reference sets. Results Here we report results from all-against-all benchmarking of PWM models for DNA binding sites of human TFs on a large compilation of in vitro (HT-SELEX, PBM) and in vivo (ChIP-seq) binding data. We observe that the best performing PWM for a given TF often belongs to another TF, usually from the same family. Occasionally, binding specificity is correlated with the structural class of the DNA binding domain, indicated by good cross-family performance measures. Benchmarking-based selection of family-representative motifs is more effective than motif clustering-based approaches. Overall, there is good agreement between in vitro and in vivo performance measures. However, for some in vivo experiments, the best performing PWM is assigned to an unrelated TF, indicating a binding mode involving protein-protein cooperativity. Conclusions In an all-against-all setting, we compute more than 18 million performance measure values for different PWM-experiment combinations and offer these results as a public resource to the research community. The benchmarking protocols are provided via a web interface and as docker images. The methods and results from this study may help others make better use of public TF specificity models, as well as public TF binding data sets.
Chromosomal Damage in LSD Users
Authors: Jose Egozcue
Journal: JAMA (1968)

An increase of chromosomal abnormalities was found in leukocytes of LSD users compared to drug-free controls. Elevated breakage rates were also found in children exposed to the drug in utero. The data showed no correlation between amount of drug per dose, number of doses, or total dosage and frequency of chromosomal breaks.
Comparative study of preclinical mouse models of high-grade glioma for nanomedicine research: the importance of reproducing blood-brain barrier heterogeneity
Authors: Caterina Brighi, Lee Reid, Laura A Genovesi, Marija Kojic, Amanda Millar, Zara Bruce, Alison L White, Bryan W Day, Stephen Rose, Andrew K Whittaker, Simon Puttick
Journal: Theranostics (2020)

The clinical translation of new nanoparticle-based therapies for high-grade glioma (HGG) remains extremely poor. This has partly been due to the lack of suitable preclinical mouse models capable of replicating the complex characteristics of recurrent HGG (rHGG), namely the heterogeneous structural and functional characteristics of the blood-brain barrier (BBB). The goal of this study is to compare the characteristics of the tumor BBB of rHGG with two different mouse models of HGG, the ubiquitously used U87 cell line xenograft model and a patient-derived cell line WK1 xenograft model, in order to assess their suitability for nanomedicine research. Method: Structural MRI was used to assess the extent of BBB opening in mouse models with a fully developed tumor, and dynamic contrast enhanced MRI was used to obtain values of BBB permeability in contrast enhancing tumor. H&E and immunofluorescence staining were used to validate results obtained from the in vivo imaging studies. Results: The extent of BBB disruption and permeability in the contrast enhancing tumor was significantly higher in the U87 model than in rHGG. These values in the WK1 model are similar to those of rHGG. The U87 model is not infiltrative, has an entirely abnormal and leaky vasculature and it is not of glial origin. The WK1 model infiltrates into the non-neoplastic brain parenchyma, it has both regions with intact BBB and regions with leaky BBB and remains of glial origin. Conclusion: The WK1 mouse model more accurately reproduces the extent of BBB disruption, the level of BBB permeability and the histopathological characteristics found in rHGG patients than the U87 mouse model, and is therefore a more clinically relevant model for preclinical evaluations of emerging nanoparticle-based therapies for HGG.
<i>F</i><sub>ENO</sub>as a biomarker guide for inhaled corticosteroid step down in patients with mild-to-moderate well-controlled asthma
Authors: Anh Tuan Dinh-Xuan, Guy Brusselle
Journal: European Respiratory Journal (2020)

<b>Reducing inhaled corticosteroid dose can be considered when <i>F</i><sub>ENO</sub> is less than 50 ppb in patients with well-controlled mild-to-moderate asthma. However, larger studies with longer follow-up are required in order to validate these preliminary data.</b>https://bit.ly/2SckpnE
Egested Feces Revealed Massive Protein Loss in 99mTc-HSA-D Scintigraphy
Authors: Yohji Matsusaka, Tadaki Nakahara, Yu Iwabuchi, Yoshiki Owaki, Hidetoshi Narimatsu, Masahiro Jinzaki
Journal: Clinical Nuclear Medicine (2020)

Abstract A 66-year-old man with severe diarrhea and severe hypoproteinemia was referred for 99m Tc-DTPA-human serum albumin (HSA-D) scintigraphy. The scintigraphy at 24 hours postinjection showed strong accumulation of 99m Tc-HSA-D in not only the colon but also all his diapers containing his egested feces. The ratio of the diapers counts to the total counts was 17.0%, and a considerable amount of protein loss was confirmed. 99m Tc-HSA-D scintigraphy has an important role in diagnosing protein-losing enteropathy, but the abdomen is the only routinely scanned area. Additional scanning of egested radiotracer and the whole body can be useful for evaluating the disease severity.
Towards multi-center glaucoma OCT image screening with semi-supervised joint structure and function multi-task learning
Authors: Xi Wang, Hao Chen, An-Ran Ran, Luyang Luo, Poemen P. Chan, Clement C. Tham, Robert T. Chang, Suria S. Mannil, Carol Y. Cheung, Pheng-Ann Heng
Journal: Medical Image Analysis (2020)
The infection rate of intralesional triamcinolone and the safety of compounding in dermatology for intradermal and subcutaneous injection: A retrospective medical record review
Authors: Chelsea A. Luther, James L. Griffith, Elena Kurland, Reem Al Shabeeb, Misty Eleryan, Kelley Redbord, David M. Ozog
Journal: Journal of the American Academy of Dermatology (2020)
Coexistent COVID-19 pneumonia and pulmonary embolism: challenges in identifying dual pathology
Authors: Katrina Abernethy, Parthipan Sivakumar, Tanya Patrick, Hasti Robbie, Jimstan Periselneris
Journal: Thorax (2020)

In early March 2020, a 53-year-old man was admitted to King’s College Hospital (KCH). He presented with a 2-week history of a dry cough, followed by fevers. He had a long flight 9 weeks prior to admission. His presentation to the emergency department was prompted by feeling increasingly breathless; his cough was occasionally productive of yellow sputum with streaks of haemoptysis. He had no medical history. His temperature was 38°C with peripheral oxygen saturation level of 92% on room air, respiratory rate was 28 breaths per minute but he was haemodynamically stable with blood pressure 128/75 mm Hg and heart rate 98 beats per minute.

A chest X-ray on arrival showed bilateral infiltrates with denser consolidation in the right lower and upper zone. An arterial blood gas showed type 1 respiratory failure with pH 7.52, PaCO2 3.87 kPA, PaO2 8.45 kPa and lymphopenia 0.86×109/L. ECG demonstrated sinus rhythm.

The patient was suspected to have viral pneumonia—likely COVID-19. He was given oxygen to target saturations 94%–98%, covered for bacterial infection as per local community-acquired pneumonia protocol and given venous thromboembolism (VTE) prophylaxis in the form of enoxaparin 40 mg once daily. Viral RT-PCR (reverse transcription polymerase chain reaction) for COVID-19 from naso-oropharyngeal and oropharyngeal swabs on both day 1 and day 2 of admission were negative. Urinary pneumococcal and legionella antigens were also negative. His D dimer was 2560 ng/mL (normal <500 ng/mL) and serial troponin Ts were 3 and 7 ng/L …
CD8+ T-cell–Mediated Immunoediting Influences Genomic Evolution and Immune Evasion in Murine Gliomas
Authors: Joshua R. Kane, Junfei Zhao, Takashi Tsujiuchi, Brice Laffleur, Víctor A. Arrieta, Aayushi Mahajan, Ganesh Rao, Angeliki Mela, Crismita Dmello, Li Chen, Daniel Y. Zhang, Edgar González-Buendia, Catalina Lee-Chang, Ting Xiao, Gerson Rothschild, Uttiya Basu, Craig Horbinski, Maciej S. Lesniak, Amy B. Heimberger, Raul Rabadan, Peter Canoll, Adam M. Sonabend
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Cancer immunoediting shapes tumor progression by the selection of tumor cell variants that can evade immune recognition. Given the immune evasion and intratumor heterogeneity characteristic of gliomas, we hypothesized that CD8+ T cells mediate immunoediting in these tumors. Experimental Design: We developed retrovirus-induced PDGF+Pten−/− murine gliomas and evaluated glioma progression and tumor immunogenicity in the absence of CD8+ T cells by depleting this immune cell population. Furthermore, we characterized the genomic alterations present in gliomas that developed in the presence and absence of CD8+ T cells. Results: Upon transplantation, gliomas that developed in the absence of CD8+ T cells engrafted poorly in recipients with intact immunity but engrafted well in those with CD8+ T-cell depletion. In contrast, gliomas that developed under pressure from CD8+ T cells were able to fully engraft in both CD8+ T-cell–depleted mice and immunocompetent mice. Remarkably, gliomas developed in the absence of CD8+ T cells exhibited increased aneuploidy, MAPK pathway signaling, gene fusions, and macrophage/microglial infiltration, and showed a proinflammatory phenotype. MAPK activation correlated with macrophage/microglia recruitment in this model and in the human disease. Conclusions: Our studies indicate that, in these tumor models, CD8+ T cells influence glioma oncogenic pathways, tumor genotype, and immunogenicity. This suggests immunoediting of immunogenic tumor clones through their negative selection by CD8+ T cells during glioma formation.
Success (but Unfinished) Story of Metabolic Surgery
Authors: Ali Aminian, Steven E. Nissen
Journal: Diabetes Care (2020)

In patients with type 2 diabetes (T2D), evidence has evolved rapidly in recent years demonstrating major benefits of metabolic surgery on control of blood glucose (1–3) and a wide range of cardiovascular (CV) and renal outcomes (4–6). Historically, the relative risks versus benefits of surgical treatment of obesity remained controversial for two principal reasons: the complicated nature of the surgery and the absence of compelling evidence for meaningful clinical benefits. Both of these concerns have now been substantially clarified, but there remains considerable scientific work to be done.

Surgical treatment of obesity started more than half a century ago with complicated operations such as intestinal rerouting procedures (e.g., jejunoileal bypass). Severe adverse outcomes from these procedures, including malnutrition and liver failure, seemed to outweigh the benefits. Over the years, surgical innovations have resulted in the development of less complicated and less invasive, but metabolically effective, alternative procedures targeting the stomach (e.g., gastric bypass). In parallel, the growing epidemics of obesity and T2D and absence of effective and durable pharmacotherapy for severe obesity have resulted in increased demand for more effective treatments, which has fueled surgical innovations.

The increased acceptance of metabolic surgery has been enhanced by many advancements in minimally invasive surgical techniques, formal training of bariatric surgeons, a rigorous accreditation process for recognition of bariatric surgeons and bariatric centers, and emergence of less invasive procedures (e.g., sleeve gastrectomy). Evidence generated through collaboration between the medical and surgical communities has strongly suggested that the metabolic and CV benefits of surgical procedures extend beyond the effects of weight loss alone (7,8). As …
Sleep disturbances in bereavement: A systematic review
Authors: Marike Lancel, Margaret Stroebe, Maarten C. Eisma
Journal: Sleep Medicine Reviews (2020)

Severe, persistent and disabling grief occurs among a sizable minority experiencing bereavement, with diagnostic manuals newly including complicated grief (CG) disorders. Sleep disturbances/disorders have been established as worsening affective and stress-related conditions. However, the role of sleep difficulties in bereavement and CG has not received similar scientific attention. We therefore conducted a systematic review with narrative syntheses on this topic to clarify the role of sleep in bereavement (PROSPERO: CRD42018093145). We searched PubMed, Web of Science and PsychInfo for peer-reviewed English-language articles including (at least one) bereaved sample and sleep disturbance measure. We identified 85 articles on 12.294 participants. We answered seven pre-defined research questions demonstrating: high prevalence of sleep disturbances in bereavement; positive associations of grief intensity with sleep difficulties; preliminary indications of risk factors of post-loss sleep disturbance; higher prevalence of sleep disturbances in CG, enhanced by psychiatric comorbidity (i.e., depression); and initial evidence of causal relationships between (complicated) grief and sleep. Grief therapy partly improves sleep difficulties, yet no intervention studies have specifically targeted sleep problems in bereaved persons. Causal relationships between sleep and grief require further examination in intensive longitudinal investigations, including randomized trials, thereby clarifying whether treating sleep problems enhances CG treatment effects.
An Unsuccessful Randomized Trial of Percutaneous vs Endoscopic Drainage of Suspected Malignant Hilar Obstruction
Authors: B. Joseph Elmunzer, Zachary L. Smith, Paul Tarnasky, Andrew Y. Wang, Patrick Yachimski, Filip Banovac, Jonathan M. Buscaglia, James Buxbaum, Amitabh Chak, Bradford Chong, Gregory A. Coté, Peter V. Draganov, Kulwinder Dua, Valerie Durkalski, Brian S. Geller, Laith H. Jamil, Rajesh N. Keswani, Mouen A. Khashab, Ryan Law, Simon K. Lo, Sean McCarthy, J. Bayne Selby, Vikesh K. Singh, Jason R. Taylor, Field F. Willingham, Rebecca L. Spitzer, Lydia D. Foster
Journal: Clinical Gastroenterology and Hepatology (2020)
Talin1 controls dendritic cell activation by regulating TLR complex assembly and signaling
Authors: Thomas Jun Feng Lim, Maegan Bunjamin, Christiane Ruedl, I-hsin Su
Journal: The Journal of Experimental Medicine (2020)

Talin critically controls integrin-dependent cell migration, but its regulatory role in skin dendritic cells (DCs) during inflammatory responses has not been investigated. Here, we show that talin1 regulates not only integrin-dependent Langerhans cell (LC) migration, but also MyD88-dependent Toll-like receptor (TLR)-stimulated DC activation. Talin1-deficient LCs failed to exit the epidermis, resulting in reduced LC migration to skin-draining lymph nodes (sdLNs) and defective skin tolerance induction, while talin1-deficient dermal DCs unexpectedly accumulated in the dermis despite their actomyosin-dependent migratory capabilities. Furthermore, talin1-deficient DCs exhibited compromised chemotaxis, NFκB activation, and proinflammatory cytokine production. Mechanistically, talin1 was required for the formation of preassembled TLR complexes in DCs at steady state via direct interaction with MyD88 and PIP5K. Local production of PIP2 by PIP5K then recruited TIRAP to the preassembled complexes, which were required for TLR signalosome assembly during DC activation. Thus, talin1 regulates MyD88-dependent TLR signaling pathways in DCs through a novel mechanism with implications for antimicrobial and inflammatory immune responses.