251 research outputs found

    Catch and Contain Novel Pathogens Early!—Assessing U.S. Medical Isolation Laws as Applied to a Future Pandemic Detection and Prevention Model

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    As of July 2, 2021, there have been 196,553,009 confirmed cases of the Coronavirus Disease (COVID-19), including 4,200,412 deaths, globally. Unfortunately, infectious diseases have been an “unavoidable fact of life” throughout history. While the global community looks forward to a gradual return to normalcy from COVID-19 with an increasing number of individuals getting vaccinated on a daily basis, the COVID-19 public health crisis has exposed significant inadequacies in many countries’ pandemic responses—the United States included. Governing authorities must actively consider more effective solutions to quickly detect and prevent the spread of future pandemics. One proposed model that offers promising potential, but is not yet developed in greater detail, is a future pandemic detection and monitoring architecture. This Comment will refer to this architecture as the “test-and-isolate model.” In his May 2020 Scientific American article, biochemist Dr. David J. Ecker recommends strategically placing modern high-speed metagenomic sequencing technology in urban hospitals across the United States to flag previously-unknown pathogens before the infectious agents have the opportunity to spread widely and pose threats of a new pandemic. Under this model, during a time period without any apparent pandemics (peacetime), the 200 biggest metropolitan hospitals in the U.S. would automatically run diagnostic tests upfront for novel causative agents for patients who visit the emergency room with severe respiratory symptoms that are possibly infectious. If such a system detects a sufficiently serious pathogen, public health agencies would send out diagnostic tests to all residents in the affected geographical area(s) within weeks and isolate those who test positive. This system could be integrated with contact tracing and more standard outbreak response

    Information Privacy: Current and future research directions

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    As more and more data is collected, concerns about information privacy become more and more salient. Information privacy is an inter- and multi-disciplinary subject relevant to researchers throughout the iSchools community. This full-day workshop will bring researchers together to discuss current and future research directions in information privacy and how iSchools can respond to the forthcoming National Privacy Research Strategy. Through a keynote presentation, plenary speakers, position papers, and group discussion, participants will explore current privacy research issues and their relevance to information research conducted by the iSchools community. Privacy scholars may submit position papers on their research projects and future directions to the workshop website for selection for presentation during the afternoon of the workshop. In addition to discussions of the presentations, during breakout sessions the workshop participants will seek to define new information privacy research questions for future work by iSchools scholars.Ope

    Photoacoustic imaging as a potential tool for clinical evaluation of Inflammatory arthritis

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    Presenting highly sensitive and clinically relevant functional information from soft tissues in and around the joint with spatial resolution comparable to ultrasound (US) imaging, photoacoustic (PA) imaging may shed new light on early diagnosis and treatment evaluation of human inflammatory arthritis. In this study on severe arthritis patients and healthy control subjects, we explored the potential contribution of PA imaging to rheumatology clinic. The feasibility of a point-of-care device built on a LED based PA imaging system for evaluating human finger joints was also studied. By performing imaging at a single laser wavelength, the spatially distributed hemoglobin content reflecting the hyperemia in synovial tissue in the finger joints of arthritis patients were imaged. By performing imaging at two laser wavelengths, the spatially distributed hemoglobin oxygenation reflecting the hypoxia in the finger joints of arthritis patients were also imaged. The measurements from the arthritis patients and the healthy controls were statistically analyzed by using two-tailed student t-tests. Please click Additional Files below to see the full abstract

    Applying latent tree analysis to classify Traditional Chinese Medicine syndromes (Zheng) in patients with psoriasis vulgari

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    OBJECTIVE To treat patients with psoriasis vulgaris using Traditional Chinese Medicine (TCM), one must stratify patients into subtypes (known as TCM syndromes or Zheng) and apply appropriate TCM treatments to different subtypes. However, no unified symptom-based classification scheme of subtypes (Zheng) exists for psoriasis vulgaris. The present paper aims to classify patients with psoriasis vulgaris into different subtypes via the analysis of clinical TCM symptom and sign data. METHODS A cross-sectional survey was carried out in Beijing from 2005-2008, collecting clinical TCM symptom and sign data from 2764 patients with psoriasis vulgaris. Roughly 108 symptoms and signs were initially analyzed using latent tree analysis, with a selection of the resulting latent variables then used as features to cluster patients into subtypes. RESULTS The initial latent tree analysis yielded a model with 43 latent variables. The second phase of the analysis divided patients into three subtype groups with clear TCM Zheng connotations: 'blood deficiency and wind dryness'; 'blood heat'; and 'blood stasis'. CONCLUSIONS Via two-phase analysis of clinic symptom and sign data, three different Zheng subtypes were identified for psoriasis vulgaris. Statistical characteristics of the three subtypes are presented. This constitutes an evidence-based solution to the syndromedifferentiation problem that exists with psoriasis vulgaris

    YAP/TAZ Activation Drives Uveal Melanoma Initiation and Progression

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    Uveal melanoma (UM), the most common ocular malignancy, is characterized by GNAQ/11 mutations. Hippo/YAP and Ras/mitogen-activated protein kinase (MAPK) emerge as two important signaling pathways downstream of G protein alpha subunits of the Q class (GalphaQ/11)-mediated transformation, although whether and how they contribute to UM genesis in vivo remain unclear. Here, we adapt an adeno-associated virus (AAV)-based ocular injection method to directly deliver Cre recombinase into the mouse uveal tract and demonstrate that Lats1/2 kinases suppress UM formation specifically in uveal melanocytes. We find that genetic activation of YAP, but not Kras, is sufficient to initiate UM. We show that YAP/TAZ activation induced by Lats1/2 deletion cooperates with Kras to promote UM progression via downstream transcriptional reinforcement. Furthermore, dual inhibition of YAP/TAZ and Ras/MAPK synergizes to suppress oncogenic growth of human UM cells. Our data highlight the functional significance of Lats-YAP/TAZ in UM initiation and progression in vivo and suggest combination inhibition of YAP/TAZ and Ras/MAPK as a new therapeutic strategy for UM

    Additive effect of cerebral atrophy on cognition in dementia-free elderly with cerebrovascular disease

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    Objective: To explore the additive effect of neurodegenerative diseases, measured by atrophy, on neurocognitive function in Asian dementia-free elderly with cerebrovascular disease (CeVD). Methods: The present study employed a cross-sectional design and was conducted between 2010 and 2015 among community-dwelling elderly participants recruited into the study. Eligible participants were evaluated with an extensive neuropsychological battery and neuroimaging. The weighted CeVD burden scale comprising markers of both small- and large-vessel diseases was applied, with a score of ≥2, indicating significant CeVD burden. Cortical atrophy (CA) and medial temporal atrophy (MTA) were graded using the global cortical atrophy scale and Schelten's scale, respectively. Global and domain-specific (attention, executive function, language, visuomotor speed, visuoconstruction, visual memory, and verbal memory) neurocognitive performance was measured using a locally validated neuropsychological battery (Vascular Dementia Battery, VDB). Results: A total of 819 dementia-free participants were included in the analysis. Among none-mild CeVD subjects, there was no significant difference in the global cognitive performance across atrophy groups (no atrophy, CA, and CA+MTA). However, in moderate-severe CeVD subjects, CA+MTA showed significantly worse global cognitive performance compared with those with CA alone (mean difference=-0.35, 95% CI -0.60 to -0.11, p=0.002) and those without atrophy (mean difference=-0.46, 95% CI -0.74 to -0.19, p<0.001, p<0.001). In domain-specific cognitive performance, subjects with CA+MTA performed worse than other groups in visual memory (p=0.005), executive function (p=0.001) and visuomotor speed (p<0.001) in moderate-severe CeVD but not in none-mild CeVD. Conclusions and relevance: Atrophy and moderate-severe CeVD burden showed an additive effect on global and domain-specific cognitive performance. This study highlights the importance of investigating the mechanisms of clinico-pathological interactions between neurodegenerative processes and vascular damage, particularly in the pre-dementia stage

    Safety of Ixekizumab Treatment for up to 5 Years in Adult Patients with Moderate-to-Severe Psoriasis : Results from Greater Than 17,000 Patient-Years of Exposure

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    Altres ajuts: The studies described herein and the Rapid Service Fee were funded by Eli Lilly and Company.Long-term safety data are critical for evaluating therapies for psoriasis. Ixekizumab has demonstrated efficacy and is well tolerated for the treatment of moderate-to-severe plaque psoriasis. We examined the safety and tolerability of up to 5 years of ixekizumab therapy in patients with psoriasis. Integrated safety data were analyzed from 13 ixekizumab clinical studies. Rates of treatment-emergent adverse events (TEAEs), serious AEs (SAEs) and AEs of special interest were analyzed for the 12-week induction period in the combined pivotal studies, and for all pooled studies by year(s) of therapy and overall, reported as exposure-adjusted incidence rates (IRs) per 100 patient-years (p-y) and/or frequencies. Total ixekizumab exposure was 17,003.4 p-y (N = 5898); 2749 patients had ≥ 4 years of exposure. When compared across years of exposure, rates for AEs remained largely stable or declined, including TEAEs leading to discontinuation (3.8/100 p-y in year 1, declining to 2.0/100 p-y in year 5); SAEs (range 6.2-7.0/100 p-y); serious infections (range 1.3-1.7/100 p-y); nonmelanoma skin cancer (ranging from 0.5/100 p-y in year 1 to 0.2/100 p-y in years 4-5); other malignancies (range 0.4-0.6/100 p-y); inflammatory bowel disease including ulcerative colitis and Crohn's disease (IR 0.2/100 p-y); and major adverse cardiovascular events (MACE) (range 0.3-0.7/100 p-y). Candidiasis was reported in 327 patients (IR 1.9/100 p-y), with the majority identified as mucocutaneous. The rate of injection site reactions was 15.5/100 p-y during year 1 and 2.0-2.3/100 p-y by years 3-5. The decrease in rates of TEAEs and the stable rates of SAEs, other malignancies and MACE during up to 5 years of ixekizumab dosing are consistent with previous reports describing a favorable safety profile of ixekizumab following shorter durations of exposure. Eli Lilly and Company

    XPO1 expression worsens the prognosis of unfavorable DLBCL that can be effectively targeted by selinexor in the absence of mutant p53

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    Additional file 1. Table S1: Clinicopathologic and molecular characteristics of DLBCL patients with high or low XPO1 expression. Table S2: Significantly differentially expressed genes between XPO1high and XPO1low DLBCL patients with concurrent TP53 mutation and high MYC expression. Figure S1: Biomarker study for XPO1 and selinexor. (A–B) XPO1high expression showed significant adverse prognostic impact in the ABC subtype but not the GCB subtype of DLBCL. (C) XPO1high expression showed a trend of unfavorable prognostic effect on PFS in MYC-rearranged (MYC-R+) DLBCL. (D) XPO1high expression was associated with significantly poorer survival in DLBCL patients with wild type (Wt) TP53. (E) ABC-DLBCL and GCB-DLBCL cells showed similar sensitivity to the cytotoxicity of selinexor. (F) TP53 mutation (Mut-TP53) significantly reduced the anti-lymphoma efficacy of selinexor in HGBCL-DH cells. IC50 values were calculated by GraphPad Prism 8 based on the cell viability data after 72-hour treatment
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