Activation of nuclear factor (NF)-κB, one of the most investigated transcription factors, has been found to control multiple cellular processes in cancer including inflammation, transformation, ...proliferation, angiogenesis, invasion, metastasis, chemoresistance and radioresistance. NF-κB is constitutively active in most tumor cells, and its suppression inhibits the growth of tumor cells, leading to the concept of 'NF-κB addiction' in cancer cells. Why NF-κB is constitutively and persistently active in cancer cells is not fully understood, but multiple mechanisms have been delineated including agents that activate NF-κB (such as viruses, viral proteins, bacteria and cytokines), signaling intermediates (such as mutant receptors, overexpression of kinases, mutant oncoproteins, degradation of IκBα, histone deacetylase, overexpression of transglutaminase and iNOS) and cross talk between NF-κB and other transcription factors (such as STAT3, HIF-1α, AP1, SP, p53, PPARγ, β-catenin, AR, GR and ER). As NF-κB is 'pre-active' in cancer cells through unrelated mechanisms, classic inhibitors of NF-κB (for example, bortezomib) are unlikely to mediate their anticancer effects through suppression of NF-κB. This review discusses multiple mechanisms of NF-κB activation and their regulation by multitargeted agents in contrast to monotargeted agents, thus 'one size does not fit all' cancers.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Human activity recognition is an important area of computer vision research. Its applications include surveillance systems, patient monitoring systems, and a variety of systems that involve ...interactions between persons and electronic devices such as human-computer interfaces. Most of these applications require an automated recognition of high-level activities, composed of multiple simple (or atomic) actions of persons. This article provides a detailed overview of various state-of-the-art research papers on human activity recognition. We discuss both the methodologies developed for simple human actions and those for high-level activities. An approach-based taxonomy is chosen that compares the advantages and limitations of each approach.
Recognition methodologies for an analysis of the simple actions of a single person are first presented in the article. Space-time volume approaches and sequential approaches that represent and recognize activities directly from input images are discussed. Next, hierarchical recognition methodologies for high-level activities are presented and compared. Statistical approaches, syntactic approaches, and description-based approaches for hierarchical recognition are discussed in the article. In addition, we further discuss the papers on the recognition of human-object interactions and group activities. Public datasets designed for the evaluation of the recognition methodologies are illustrated in our article as well, comparing the methodologies' performances. This review will provide the impetus for future research in more productive areas.
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IZUM, KILJ, NUK, PILJ, SAZU, UL, UM, UPUK
Precision medicine methodologies and approaches have advanced our understanding of the clinical presentation, development, progression, and management of Alzheimer's disease (AD) dementia. However, ...sex and gender have not yet been adequately integrated into many of these approaches.
The Society for Women's Health Research Interdisciplinary Network on AD, comprised of an expert panel of scientists and clinicians, reviewed ongoing and published research related to sex and gender differences in AD.
The current review is a result of this Network's efforts and aims to: (1) highlight the current state-of-the-science in the AD field on sex and gender differences; (2) address knowledge gaps in assessing sex and gender differences; and (3) discuss 12 priority areas that merit further research.
The exclusion of sex and gender has impeded faster advancement in the detection, treatment, and care of AD across the clinical spectrum. Greater attention to these differences will improve outcomes for both sexes.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
BACKGROUND Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is superior to conventional transbronchial needle aspiration (cTBNA) in the staging of lung cancer. However, ...its efficiency in diagnosis of sarcoidosis when combined with endobronchial biopsy (EBB) and transbronchial lung biopsy (TBLB) has not been studied. This randomized controlled trial compares diagnostic yield of EBUS-TBNA vs cTBNA in combination with EBB and TBLB. METHODS Patients with clinical diagnosis of sarcoidosis were randomized 1:1 to EBUS-TBNA or cTBNA. All patients underwent TBLB and EBB. The primary outcome was detection of granulomas. The secondary end points were the individual and cumulative yields of various procedures, serious adverse events, and procedure time. RESULTS Of the 130 patients, sarcoidosis was diagnosed in 117 (62 cTBNA, 55 EBUS-TBNA). The two groups were similar at baseline. Granulomas were demonstrated in 104 (53 cTBNA, 51 EBUS-TBNA) patients and were similar in two groups (85.5% vs 92.7%, P = .34). Individually, EBUS-TBNA had the highest yield (41 of 55, 74.5%), which was better than cTBNA (30 of 62, 48.4%, P = .004) or EBB (40 of 111, 36.3%, P < .0001) but not TBLB (78 of 112, 69.6%, P = .54). Adding EBB/TBLB to cTBNA led to an increase in granuloma detection, whereas the addition of TBLB (but not EBB) significantly enhanced the yield of EBUS-TBNA. The procedure time was significantly longer with EBUS-TBNA. No major adverse events occurred. CONCLUSIONS Individually, EBUS-TBNA has the highest diagnostic yield in sarcoidosis, but it should be combined with TBLB for the optimal yield. The diagnostic yield of cTBNA (plus EBB and TBLB) is similar to EBUS-TBNA plus TBLB. TRIAL REGISTRY ClinicalTrials.gov ; No.: NCT01908868; URL: www.clinicaltrials.gov
To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups.
Candidate variables were assembled from published ...criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology and paediatric clinics worldwide. Several statistical methods were used to derive the classification criteria.
Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cut-off of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) 'probable IIM', had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to 'definite IIM'. A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of ≥50 to <55% as 'possible IIM'.
The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology and paediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of 'definite', 'probable' and 'possible' IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.
Arthritis, an inflammation of the joints, is usually a chronic disease that results from dysregulation of pro-inflammatory cytokines (e.g. tumour necrosis factor and interleukin-1β) and ...pro-inflammatory enzymes that mediate the production of prostaglandins (e.g. cyclooxygenase-2) and leukotrienes (e.g. lipooxygenase), together with the expression of adhesion molecules and matrix metalloproteinases, and hyperproliferation of synovial fibroblasts. All of these factors are regulated by the activation of the transcription factor nuclear factor-κB. Thus, agents that suppress the expression of tumour necrosis factor-α, interleukin-1β, cyclooxygenase-2, lipooxygenase, matrix metalloproteinases or adhesion molecules, or suppress the activation of NF-κB, all have potential for the treatment of arthritis. Numerous agents derived from plants can suppress these cell signaling intermediates, including curcumin (from turmeric), resveratrol (red grapes, cranberries and peanuts), tea polyphenols, genistein (soy), quercetin (onions), silymarin (artichoke), guggulsterone (guggul), boswellic acid (salai guggul) and withanolides (ashwagandha). Indeed, several preclinical and clinical studies suggest that these agents have potential for arthritis treatment. Although gold compounds are no longer employed for the treatment of arthritis, the large number of inexpensive natural products that can modulate inflammatory responses, but lack side effects, constitute ‘goldmines’ for the treatment of arthritis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective The differential diagnosis of sarcoidosis and tuberculosis is difficult, especially in countries with a high tuberculosis burden. We hypothesized that sonographic features on endobronchial ...ultrasonography (EBUS) would help in differentiating tuberculosis from sarcoidosis. In this study, the endosonographic features of tuberculosis and sarcoidosis are compared. Methods This was a retrospective analysis of prospectively collected data of patients with intrathoracic lymphadenopathy who underwent EBUS-guided transbronchial needle aspiration (TBNA), and were finally diagnosed with sarcoidosis or tuberculosis. Sonographic features such as size, shape (round or oval), margin (distinct or indistinct), echogenicity (heterogeneous or homogeneous), presence or absence of a central hilar structure, and coagulation necrosis sign were recorded and compared in the 2 groups. Results During the study period, 249 EBUS-guided TBNA procedures were performed and a diagnosis of sarcoidosis (n = 118) or tuberculosis (n = 47) was made in 165 patients. A total of 358 lymph node stations were examined. Heterogeneous echotexture (53.4% vs 12.6%, P < .001) and coagulation necrosis (26.1% vs 3.3%; P < .001) were significantly higher in tuberculous lymph nodes. A combination of a positive tuberculin skin test (TST) and either heterogeneous echotexture or coagulation necrosis sign had specificity of 98% and positive predictive value of 91% for a diagnosis of tuberculosis. Conclusions Sonographic features of heterogeneous echotexture or coagulation necrosis in the lymph nodes on EBUS are fairly specific for tuberculosis. Along with a positive TST, these features strongly favor a diagnosis of tuberculosis over sarcoidosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This paper is motivated by the question: how does governance emerge within social-ecological systems (SESs)? Addressing this question is critical for fostering sustainable transformations because it ...directs attention to the context specific and process intensive nature of governance as arising from the internal dynamics (i.e., interplay of feedbacks and interdependencies between the components) of SESs. This contrasts with the commonly held view of governance as an external intervention applied to a system. To systematically examine the recurrent patterns in how the internal dynamics promote/detract from the emergence of different types of governance, we applied archetype analysis to 60 selected cases of irrigation systems from Asia. Drawing inspiration from grid-group typology of cultural theory, we developed four specific archetypes: egalitarian, individualist, hierarchical, and fatalist. To build these archetypes, we applied a robustness framework and several other theories/perspectives to identify the different social-ecological and infrastructural attributes of irrigation SESs, and their interdependencies and feedback structures. We then used these attributes, identified through our theoretical review, to deductively code our selected cases and classify them into the different archetypes. The results show the different configurations of attributes that co-occur in each archetype, and how together these attributes and their inter-relationships lead to specific types of governance. Our archetype analysis also provides several interesting examples of fine-tuning between different SES attributes and how this fine-tuning is being threatened by various social and environmental changes. Through a systematic exploration of recurrent patterns using archetype analysis, our work builds on past efforts to apply ideas from complexity theory-specifically emergence-to unpack the complexities of SESs and offer practical guidance for fostering sustainability.
Abstract Background Platelet inhibitory effects induced by oral P2Y12 receptor antagonists are delayed in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary ...percutaneous coronary intervention (PPCI), which may be attributed to impaired absorption affecting drug pharmacokinetics (PK) and pharmacodynamics (PD). Crushing tablets has been suggested to lead to more favorable PK/PD profiles. To date, no studies have investigated the PK/PD effects of crushing prasugrel. Objectives This study sought to determine whether crushing prasugrel is associated with more favorable drug bioavailability and platelet inhibitory effects compared with whole tablets in STEMI patients undergoing PPCI. Methods Our prospective, randomized, open-label study assessed STEMI patients undergoing PPCI (n = 52) who were treated with a prasugrel 60-mg loading dose (LD) either as whole or crushed tablets. PK/PD analyses were performed at 7 time points. PD effects were measured as P2Y12 reaction units and platelet reactivity index, and PK by plasma levels of prasugrel’s active metabolite. Results Compared with whole tablets, crushed prasugrel led to reduced P2Y12 reaction units by 30 min post-LD, which persisted at 1, 2 (164 vs. 95; least square mean difference = 68; 95% confidence interval: 10 to 126; primary endpoint), and 4 h post-LD. Significant differences were no longer present at 6 h post-LD. Parallel findings were shown with platelet reactivity index. Accordingly, high on-treatment platelet reactivity rates were reduced with crushed prasugrel. PK analyses showed a >3-fold faster absorption with crushed compared with whole prasugrel. Conclusions In STEMI patients undergoing PPCI, crushed prasugrel leads to faster drug absorption, and consequently, more prompt and potent antiplatelet effects compared with whole tablet ingestion. (Pharmacological Effects of Crushing Prasugrel in STEMI Patients; NCT02212028 )
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A photochemical method for converting aliphatic alcohols into boronic esters is described. Preactivation of the alcohol as a 2‐iodophenyl‐thionocarbonate enables a novel Barton–McCombie‐type radical ...deoxygenation that proceeds efficiently with visible light irradiation and without the requirement for a photocatalyst, a radical initiator, or tin or silicon hydrides. The resultant alkyl radical is intercepted by bis(catecholato)diboron, furnishing boronic esters from a diverse range of structurally complex alcohols.
Visible light irradiation of 2‐iodophenyl‐thionocarbonates enabled Barton–McCombie‐type radical deoxygenations to proceed in the absence of a photocatalyst, a radical initiator, or tin or silicon hydrides. Applying this strategy to deoxygenative borylation reactions allowed a wide range of structurally diverse aliphatic alcohols to be transformed into synthetically valuable boronic esters.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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