tbuckley/cabot-search huggingface dataset:
Effects of incorporating multidomain interventions into integrated primary care on quality of life: a randomised controlled trial
Authors: Wei-Ju Lee, Li-Ning Peng, Chi-Hung Lin, Ran-Chou Chen, Shinn-Zong Lin, Ching-Hui Loh, Sheng-Lun Kao, Tzu-Shing Hung, Chia-Yun Chang, Chun-Feng Huang, Ting-Ching Tang, Shih-Tsung Huang, Yu-Wen Wen, Fei-Yuan Hsiao, Liang-Kung Chen, Hui-Ping Lin, Ming-Hsien Lin, Ming-Yueh Chou, Chih-Kuang Liang, Chu-Sheng Lin, Li-Kuo Liu, An-Chun Hwang
Journal: The Lancet Healthy Longevity (2021)

Integrating primary prevention into care pathways for older adults is a core strategy of healthy ageing, but evidence remains limited. We aimed to determine whether incorporating a multidomain intervention into primary health care could improve standard value-based health outcomes and quality of life.For this Taiwan Integrated Geriatric Care (TIGER) study, a pragmatic randomised controlled trial, we recruited community-dwelling outpatients aged 65 years or older with at least three chronic medical conditions. We excluded people with malignancies undergoing chemotherapy, people with a life expectancy of less than 12 months, or people who were insufficiently able to communicate with study staff. Participants were randomly assigned (1:1) to usual care or to the integrated multidomain intervention using block randomisation. The integrated multidomain intervention entailed 16 2-h sessions per year, comprising communal physical exercise, cognitive training, nutrition and disease education, plus individualised treatment by specialists in integrated geriatric care. The primary outcome was changes from baseline quality of life, based on 36-item Short Form Health Survey (SF-36) scores, at 3, 6, 9, and 12 months. Intervention effects were analysed per protocol using a generalised linear mixed model. This trial is registered with ClinicalTrials.gov, NCT03528005.Between June 25, 2018, and Feb 15, 2019, 628 participants were screened, of whom 398 were assigned to the integrated multidomain intervention (n=199) or to usual care (n=199). 335 (84%) participants completed the 12-month follow-up. Compared with the usual care group, the integrated multidomain intervention group had significantly higher mean SF-36 physical component scores across all timepoints (overall difference 0·8, 95% CI 0·2-1·5; p=0·010), but differences at 3, 6, 9, and 12 months did not reach statistical significance. The SF-36 mental component scores did not differ significantly overall, but were significantly higher in the integrated multidomain intervention group at the 12-month follow-up (55·3 [SD 7·6] vs 57·2 [7·0]; p=0·019). No serious adverse events occurred.Incorporating multidomain interventions into integrated health care improved quality of life. Our standardised protocol is amenable to inclusion in policies to promote value-based care and healthy ageing.National Health Research Institutes, Taiwan, and Ministry of Science and Technology, Taiwan.
Metastable attractors explain the variable timing of stable behavioral action sequences
Authors: Stefano Recanatesi, Ulises Pereira-Obilinovic, Masayoshi Murakami, Zachary Mainen, Luca Mazzucato
Journal: Neuron (2021)

The timing of self-initiated actions shows large variability even when they are executed in stable, well-learned sequences. Could this mix of reliability and stochasticity arise within the same neural circuit? We trained rats to perform a stereotyped sequence of self-initiated actions and recorded neural ensemble activity in secondary motor cortex (M2), which is known to reflect trial-by-trial action-timing fluctuations. Using hidden Markov models, we established a dictionary between activity patterns and actions. We then showed that metastable attractors, representing activity patterns with a reliable sequential structure and large transition timing variability, could be produced by reciprocally coupling a high-dimensional recurrent network and a low-dimensional feedforward one. Transitions between attractors relied on correlated variability in this mesoscale feedback loop, predicting a specific structure of low-dimensional correlations that were empirically verified in M2 recordings. Our results suggest a novel mesoscale network motif based on correlated variability supporting naturalistic animal behavior.
A synaptic learning rule for exploiting nonlinear dendritic computation
Authors: Brendan A. Bicknell, Michael Häusser
Journal: Neuron (2021)

Information processing in the brain depends on the integration of synaptic input distributed throughout neuronal dendrites. Dendritic integration is a hierarchical process, proposed to be equivalent to integration by a multilayer network, potentially endowing single neurons with substantial computational power. However, whether neurons can learn to harness dendritic properties to realize this potential is unknown. Here, we develop a learning rule from dendritic cable theory and use it to investigate the processing capacity of a detailed pyramidal neuron model. We show that computations using spatial or temporal features of synaptic input patterns can be learned, and even synergistically combined, to solve a canonical nonlinear feature-binding problem. The voltage dependence of the learning rule drives coactive synapses to engage dendritic nonlinearities, whereas spike-timing dependence shapes the time course of subthreshold potentials. Dendritic input-output relationships can therefore be flexibly tuned through synaptic plasticity, allowing optimal implementation of nonlinear functions by single neurons.
TCT-241 Pericoronary Adipose Tissue Is a Predictor of In-Stent Restenosis and Stent Failure in Patients Undergoing Coronary Artery Stent Insertion
Authors: Jason Nogic, Jiwon Kim, Jamie Layland, Jasmine Chan, Kevin Cheng, Dennis Wong, Adam Brown
Journal: Journal of the American College of Cardiology (2021)
TCT-373 Balloon-Expandable Transcatheter Heart Valve Geometry in Low-Risk Bicuspid Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Giorgio Medranda, Toby Rogers, Brian Case, Syed Ali, Corey Shea, Cheng Zhang, Federico Asch, Gaby Weissman, Christian Shults, Hector Garcia-Garcia, Itsik Ben-Dor, Lowell Satler, Ron Waksman
Journal: Journal of the American College of Cardiology (2021)
Inherited Autoinflammatory Syndromes
Authors: Julia E. Rood, Edward M. Behrens
Journal: Annual Review of Pathology Mechanisms of Disease (2021)

Autoinflammation describes a collection of diverse diseases caused by indiscriminate activation of the immune system in an antigen-independent manner. The rapid advancement of genetic diagnostics has allowed for the identification of a wide array of monogenic causes of autoinflammation. While the clinical picture of these syndromes is diverse, it is possible to thematically group many of these diseases under broad categories that provide insight into the mechanisms of disease and therapeutic possibilities. This review covers archetypical examples of inherited autoinflammatory diseases in five major categories: inflammasomopathy, interferonopathy, unfolded protein/cellular stress response, relopathy, and uncategorized. This framework can suggest where future work is needed to identify other genetic causes of autoinflammation, what types of diagnostics need to be developed to care for this patient population, and which options might be considered for novel therapeutic targeting.
Lipoprotein-biomimetic nanostructure enables tumor-targeted penetration delivery for enhanced photo-gene therapy towards glioma
Authors: Ruoning Wang, Xiaohong Wang, Junsong Li, Liuqing Di, Jianping Zhou, Yang Ding
Journal: Bioactive Materials (2021)

Glioma is one of the most malignant primary tumors affecting the brain. The efficacy of therapeutics for glioma is seriously compromised by the restriction of blood-brain barrier (BBB), interstitial tumor pressure of resistance to chemotherapy/radiation, and the inevitable damage to normal brain tissues. Inspired by the natural structure and properties of high-density lipoprotein (HDL), a tumor-penetrating lipoprotein was prepared by the fusion tLyP-1 to apolipoprotein A-I-mimicking peptides (D4F), together with indocyanine green (ICG) incorporation and lipophilic small interfering RNA targeted HIF-1α (siHIF) surface anchor for site-specific photo-gene therapy. tLyP-1 peptide is fused to HDL-surface to facilitate BBB permeability, tumor-homing capacity and -site accumulation of photosensitizer and siRNA. Upon NIR light irradiation, ICG not only served as real-time targeted imaging agent, but also provided toxic reactive oxygen species and local hyperthermia for glioma phototherapy. The HIF-1α siRNA in this nanoplatform downregulated the hypoxia-induced HIF-1α level in tumor microenvironment and enhanced the photodynamic therapy against glioma. These studies demonstrated that the nanoparticles could not only efficiently across BBB and carry the payloads to orthotopic glioma, but also modulate tumor microenvironment, thereby inhibiting tumor growth with biosafety. Overall, this study develops a new multifunctional drug delivery system for glioma theranostic, providing deeper insights into orthotopic brain tumor imaging and treatment.
Auditory stimulation during sleep suppresses spike activity in benign epilepsy with centrotemporal spikes
Authors: Jens G. Klinzing, Lilian Tashiro, Susanne Ruf, Markus Wolff, Jan Born, Hong-Viet V. Ngo
Journal: Cell Reports Medicine (2021)

Benign epilepsy with centrotemporal spikes (BECTS) is a common form of childhood epilepsy linked to diverse cognitive abnormalities. The electroencephalogram of patients shows focal interictal epileptic spikes, particularly during non-rapid eye movement (NonREM) sleep. Spike formation involves thalamocortical networks, which also contribute to the generation of sleep slow oscillations (SOs) and spindles. Motivated by evidence that SO-spindle activity can be controlled through closed-loop auditory stimulation, here, we show in seven patients that auditory stimulation also reduces spike rates in BECTS. Stimulation during NonREM sleep decreases spike rates, with most robust reductions when tones are presented 1.5 to 3.5 s after spikes. Stimulation further reduces the amplitude of spikes closely following tones. Sleep spindles are negatively correlated with spike rates, suggesting that tone-evoked spindle activity mediates the spike suppression. We hypothesize spindle-related refractoriness in thalamocortical circuits as a potential mechanism. Our results open an avenue for the non-pharmacological treatment of BECTS.
A Phase II Study to Assess the Safety and Efficacy of the Dual mTORC1/2 and PI3K Inhibitor Bimiralisib (PQR309) in Relapsed, Refractory Lymphoma
Authors: Graham P. Collins, Toby A. Eyre, Debora Schmitz-Rohmer, William Townsend, Rakesh Popat, Lisa Giulino-Roth, Paul A. Fields, Fatime Krasniqi, Carole Soussain, Anastasios Stathis, Nebojsa Andjelkovic, David Cunningham, Danijela Mandic, Sinisa Radulovic, Ivan Tijanic, Netanel A. Horowitz, Sabira Kurtovic, Elisabeth Schorb, Christian Schmidt, Saša Dimitrijević, Martin Dreyling
Journal: HemaSphere (2021)

Bimiralisib is an orally bioavailable pan-phosphatidylinositol 3-kinase and mammalian target of rapamycin inhibitor which has shown activity against lymphoma in preclinical models. This phase I/II study evaluated the response rate to bimiralisib at 2 continuous dose levels (60 mg and 80 mg) in patients with relapsed/refractory lymphoma. Fifty patients were enrolled and started treatment. The most common histologies were diffuse large B-cell lymphoma (n = 17), follicular lymphoma (n = 9), T-cell lymphoma (n = 8), and others (mostly indolent). Patients had been treated with a median of 5 prior lines of treatment and 44% were considered refractory to their last treatment. Mean duration of treatment (and standard deviations) with 60 mg once daily (o.d.) was 1.3 ± 1.2 months, and with 80 mg o.d. 3.7 ± 3.9 months. On an intention to treat analysis, the overall response rate was 14% with 10% achieving a partial response and 4% a complete response. Thirty-six percent of patients were reported as having stable disease. No dose-limiting toxicities were observed during the phase I portion of the study. Overall, 70% of patients had a grade 3 treatment emergent adverse events (TEAE) and 34% had a grade 4 TEAE; 28% of patients discontinued treatment due to toxicity. The most frequent TEAEs grade ≥3 was hyperglycemia (24%), neutropenia (20%), thrombocytopenia (22%), and diarrhea (12%). Per protocol, hyperglycemia required treatment with oral antihyperglycemic agents in 28% and with insulin in 14%. At 60 mg or 80 mg continuous dosing, bimiralisib showed modest efficacy with significant toxicity in heavily pretreated patients with various histological subtypes of lymphoma.
幼児(RSV GOLD)における全体的な呼吸器合胞体ウイルス関連死亡率:遡及的症例シリーズ【Powered by NICT】
Authors: Scheltema Nienke M, Gentile Angela, Lucion Florencia, Nokes D James, Munywoki Patrick K, Madhi Shabir A, Groome Michelle J, Cohen Cheryl, Moyes Jocelyn, Thorburn Kentigern, Thamthitiwat Somsak, Oshitani Hitoshi, Lupisan Socorro P, Gordon Aubree, Sanchez Jose F, O’Brien Katherine L, Gessner Bradford D, Sutanto Agustinus, Mejias Asuncion, Ramilo Octavio, Khuri-Bulos Najwa, Halasa Natasha, de-Paris Fernanda, Pires Marcia Rosane, Spaeder Michael C, Paes Bosco A, Simoees Eric A F, Leung Ting F, da Costa Oliveira Maria Tereza, de Freitas Lazaro Emediato Carla Cecilia, Bassat Quique, Butt Warwick, Chi Hsin, Aamir Uzma Bashir, Ali Asad, Lucero Marilla G, Fasce Rodrigo A, Lopez Olga, Rath Barbara A, Polack Fernando P, Papenburg Jesse, Roglic Srdan, Ito Hisato, Goka Edward A, Grobbee Diederick E, Nair Harish, Bont Louis J
Journal: The Lancet Global Health (2017)
Association of Endotoxemia with AKI in Critically Ill Patients with SARS-CoV-2 Infection
Authors: Sobia N. Khan, Olena Bolotova, Chris R. Gordon, Sandeep K. Mallipattu
Journal: Journal of the American Society of Nephrology (2021)

Background: AKI is frequently complicated by sepsis. Endotoxin (lipopolysaccharide), a component of the outer wall of gram-negative bacteria, has been investigated and acknowledged as one of the triggers of lethal shock during sepsis and drivers of cytokine storm. In studies, septic shock was present in 6.4% patients with severe COVID-19, but blood cultures and respiratory cultures were negative in 76%. Initial cohort study of COVID-19 patients from China showed 4.5% developed AKI, subsequent reports showed higher prevalence. While these data suggest that patients with COVID-19 are at risk for septic shock and AKI, mechanisms mediating these processes in the setting of severe coronavirus 2 (SARS-CoV-2) infection remain unclear. Methods: We conducted a single-center, cross-sectional study in critically ill patients with COVID-19 to test the prevalence of endotoxemia and whether endotoxemia is associated with the development of AKI. Patients were recruited using criteria: Age ≥ 18yr, MODS ≥ 9, sepsis and intensive care unit admission, excluded if pregnant, requiring chronic dialysis or chronic immunosuppressive medications. Blood endotoxin activity (EA) measured in patients who met the criteria using the FDA-approved Endotoxin Activity Assay (EAA). EAA is a chemiluminescent bio-assay based on the oxidative burst reaction of activated neutrophils to complement coated LPS-IgM immune complexes. Patients divided into low (0.0 -0.39 EA units), intermediate (0.40 -0.59 EA units), high (≥ 0.60 EA units), and non-responder (NR) (patients whose neutrophils do not have the ability to respond to preformed immune complexes in the EAA) group based on measurements from the EAA. Results: In this study, endotoxemia observed in 24/32 (75%) of our critically ill patients with COVID-19, despite only 2 patients having positive blood cultures for gramnegative organisms. The incidence of AKI was higher in the high EA group (7/14, 50%) as compared to intermediate EA group (1/10, 10%), p=0.01. The need for renal replacement therapy (RRT) was higher in the elevated EA group (4/14, 29%), with none of the patients in the intermediate group requiring RRT, p=0.008. Conclusions: This study demonstrates the high prevalence of endotoxemia in critically ill patients with COVID-19, regardless of presence of bacteremia. We also observed that high EA was associated with AKI and the need for RRT.
Phase 3 Trial of mRNA-1273 during the Delta-Variant Surge
Authors: Lindsey R Baden, Hana M El Sahly, Brandon Essink, Dean Follmann, Kathleen M Neuzil, Allison August, Heather Clouting, Gabrielle Fortier, Weiping Deng, Shu Han, Xiaoping Zhao, Brett Leav, Carla Talarico, Bethany Girard, Yamuna D Paila, Joanne E Tomassini, Florian Schödel, Rolando Pajon, Honghong Zhou, Rituparna Das, Jacqueline Miller
Journal: New England Journal of Medicine (2021)

mRNA-1273 Vaccine Efficacy against the Delta Variant Participants who had received placebo in a previous phase of this trial were offered the mRNA-1273 vaccine in the open-label phase. The incidenc...
Abstract 16200: Fetal Double Outlet Right Ventricle: Diagnostic Spectrum, Associated Extracardiac Pathology and Clinical Outcomes
Authors: Aisling A Young, Kim Haberer, Oana Caluseriu, Timothy Colen, Luke Eckersley, Angela McBrien, Lisa K Hornberger
Journal: Circulation (2018)

Introduction: Double outlet right ventricle (DORV) is a heterogenous group of congenital heart defects (CHD) that is increasingly diagnosed prenatally. There is a paucity of data from the recent er...
Human skin mast cells express photoreceptors, and blue light inhibits their degranulation
Authors: H. Siiskonen, J.S. Fok, S. Buscone, I. Castellano Pellicena, N. Uzunbajakava, N. Botchkareva, Marcus Maurer, J. Scheffel
Journal: Allergy (2020)

Background: Allergic skin reactions are driven by dermal mast cells (MCs) and exhibit circadian differences. In human skin, circadian rhythms may be regulated by cryptochromes (CRYs) and opsins (OPNs), photoreceptors (PRs), which were recently identified to be expressed in a number of human cutaneous cell types. Whether human skin MCs express these receptors is currently unknown Method: We obtained MCs from human skin (breast, foreskin, eyelids) and used also cultured CD34‐positive peripheral blood stem cell‐derived MCs (PSCMCs) and LAD2‐MCs. MCs were analyzed for the expression of CRY1 and OPN 1‐3 by qRT‐PCR and Western Blot as well as for the effects of irradiation with blue light on activation via IgE/anti‐IgE or cortistatin, a MRGPRX2 agonist. Results: We found expression of the blue light sensitive CRY1, OPN1 MW (medium‐wave‐length), OPN2 and OPN3 in LAD2‐MCs, cultured MCs from breast skin and foreskin as well as freshly isolated MCs from breast skin and eyelids, with the exception of OPN2 in eyelid MCs. CRY1 expression was the highest overall, and its presence was confirmed at protein level in cultured as well as freshly isolated MCs from breast skin and foreskin. PSCMCs, however, did not show expression of any of the investigated PRs. Importantly, fresh and cultured skin MCs were sensitive to blue light irradiation (at 453 nm) showing a dose‐dependent reduction in their degranulation after exposure to 2 or 30 J/cm2 blue light as measured by β‐hexosaminidase release. Conclusion: Our results demonstrate, for the first time, that human skin MCs express photoreceptors, i.e. CRY1 and OPN1‐3, and blue light, which activates these receptors, inhibits MC degranulation. These findings may explain, at least in part, circadian differences in allergic skin reactions and may be relevant for the development of photoreceptor‐targeted treatments for patients with MC‐driven skin diseases such as chronic spontaneous or inducible urticaria.
Addressing the Lack of Clarity About Administering Surfactant in Preterm Infants With Respiratory Distress Syndrome Treated With Noninvasive Respiratory Support
Authors: Viraraghavan Vadakkencherry Ramaswamy, Thangaraj Abiramalatha, Charles Christoph Roehr
Journal: JAMA Pediatrics (2021)

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線維細胞と心筋細胞の間での断続的ストレッチ刺激により誘導されたギャップ結合形成による円形状の人工心筋組織(EHT)における非同期収縮の改善
Authors: Ando M, Katare Rg, Kakinuma Y, Yamasaki F, Sato T
Journal: Circulation (2006)
A Review of General Health Checks in Adult Primary Care
Authors: Jeremy S. Faust
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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
炎症誘発性骨髄性細胞受容体TREM-1は,Kupffer細胞の活性化および原発性肝細胞癌の発達を制御する
Authors: Wu Juan, LI Jiaqi, Salcedo Rosalba, F Mivechi Nahid, Trinchieri Giorgio, Horuzsko Anatolij
Journal: Cancer Research (2012)
PD-L2 glycosylation promotes immune evasion and predicts anti-EGFR efficacy
Authors: Yiqi Xu, Zhenyue Gao, Ruxin Hu, Yuqing Wang, Yuhong Wang, Zheng Su, Xiaoyue Zhang, Jingxuan Yang, Mei Mei, Yu Ren, Min Li, Xuan Zhou
Journal: Journal for ImmunoTherapy of Cancer (2021)

Combination therapy has been explored for advanced head and neck squamous cell carcinoma (HNSCC) owing to the limited efficacy of anti-epidermal growth factor receptor (EGFR) therapy. Increased expression and glycosylation of immune checkpoint molecules in tumors are responsible for cetuximab therapy refractoriness. The role of programmed death ligand 2 (PD-L2), a ligand of PD-1, in the immune function is unclear. Here, we examined the regulatory mechanism of PD-L2 glycosylation and its role in antitumor immunity and cetuximab therapy.Single-cell RNA sequencing and immunohistochemical staining were used to investigate PD-L2 expression in cetuximab-resistant/sensitive HNSCC tissues. The mechanism of PD-L2 glycosylation regulation was explored in vitro. The effects of PD-L2 glycosylation on immune evasion and cetuximab efficacy were verified in vitro and using mice bearing orthotopic SCC7 tumors.The PD-L2 levels were elevated and N-glycosylated in patients with cetuximab-resistant HNSCC. Glycosylated PD-L2 formed a complex with EGFR, which resulted in the activation of EGFR/signal transducer and activator of transcription 3 (STAT3) signaling and decreased the cetuximab binding affinity to EGFR. The N-glycosyltransferase fucosyltransferase (FUT8), a transcriptional target of STAT3, was required for PD-L2 glycosylation. Moreover, glycosylation modification stabilized PD-L2 by blocking ubiquitin-dependent lysosomal degradation, which consequently promoted its binding to PD-1 and immune evasion. Inhibition of PD-L2 glycosylation using Stattic, a specific STAT3 inhibitor, or PD-L2 mutation blocking its binding to FUT8, increased cytotoxic T lymphocyte activity and augmented response to cetuximab.Increased expression and glycosylation of PD-L2 in tumors are an important mechanism for cetuximab therapy refractoriness. Thus, the combination of PD-L2 glycosylation inhibition and cetuximab is a potential therapeutic strategy for cancer.