Chulalongkorn University

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is thatthere is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the completeprocess including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increasedautophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in manycases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as forreviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multipleassays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagyrelated protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

Rhinosinusitis is a significant and increasing health problem which results in a large financial burden on society. This evidence based position paper describes what is known about rhinosinusitis and nasal polyps, offers evidence based recommendations on diagnosis and treatment, and considers how we can make progress with research in this area. Rhinitis and sinusitis usually coexist and are concurrent in most individuals; thus, the correct terminology is now rhinosinusitis. Rhinosinusitis (including nasal polyps) is defined as inflammation of the nose and the paranasal sinuses characterised by two or more symptoms, one of which should be either nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior nasal drip), +/- facial pain/pressure, +/- reduction or loss of smell; and either endoscopic signs of polyps and/or mucopurulent discharge primarily from middle meatus and/or; oedema/mucosal obstruction primarily in middle meatus, and/or CT changes showing mucosal changes within the ostiomeatal complex and/or sinuses. The paper gives different definitions for epidemiology, first line and second line treatment and for research. Furthermore the paper describes the anatomy and (patho)physiology, epidemiology and predisposing factors, inflammatory mechanisms, evidence based diagnosis, medical and surgical treatment in acute and chronic rhinosinusitis and nasal polyposis in adults and children. Evidence based schemes for diagnosis and treatment are given for the first and second line clinicians. Moreover attention is given to complications and socio-economic cost of chronic rhinosinusitis and nasal polyps. Last but not least the relation to the lower airways is discussed.

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Advances in processor, memory, and radio technology enable small and cheap nodes capable of sensing, communication, and computation. Networks of such nodes can coordinate to perform distributed sensing of environmental phenomena. We explore the directed diffusion paradigm for such coordination. Directed diffusion is data-centric in that all communication is for named data. All nodes in a directed-diffusion-based network are application aware. This enables diffusion to achieve energy savings by selecting empirically good paths and by caching and processing data in-network (e.g., data aggregation). We explore and evaluate the use of directed diffusion for a simple remote-surveillance sensor network analytically and experimentally. Our evaluation indicates that directed diffusion can achieve significant energy savings and can outperform idealized traditional schemes (e.g., omniscient multicast) under the investigated scenarios.

This review article examines the current state of understanding in how metal halide perovskite solar cells can degrade when exposed to moisture, oxygen, heat, light, mechanical stress, and reverse bias. It also highlights strategies for improving stability, such as tuning the composition of the perovskite, introducing hydrophobic coatings, replacing metal electrodes with carbon or transparent conducting oxides, and packaging. The article concludes with recommendations on how accelerated testing should be performed to rapidly develop solar cells that are both extraordinarily efficient and stable.

Abstract Improving the long-term stability of perovskite solar cells is critical to the deployment of this technology. Despite the great emphasis laid on stability-related investigations, publications lack consistency in experimental procedures and parameters reported. It is therefore challenging to reproduce and compare results and thereby develop a deep understanding of degradation mechanisms. Here, we report a consensus between researchers in the field on procedures for testing perovskite solar cell stability, which are based on the International Summit on Organic Photovoltaic Stability (ISOS) protocols. We propose additional procedures to account for properties specific to PSCs such as ion redistribution under electric fields, reversible degradation and to distinguish ambient-induced degradation from other stress factors. These protocols are not intended as a replacement of the existing qualification standards, but rather they aim to unify the stability assessment and to understand failure modes. Finally, we identify key procedural information which we suggest reporting in publications to improve reproducibility and enable large data set analysis.

As the world is witnessing the epidemic of COVID-19, a disease caused by a novel coronavirus, SARS-CoV-2, emerging genetics and clinical evidences suggest a similar path to those of SARS and MERS. The rapid genomic sequencing and open access data, together with advanced vaccine technology, are expected to give us more knowledge on the pathogen itself, including the host immune response as well as the plan for therapeutic vaccines in the near future. This review aims to provide a comparative view among SARS-CoV, MERS-CoV and the newly epidemic SARS-CoV-2, in the hope to gain a better understanding of the host-pathogen interaction, host immune responses, and the pathogen immune evasion strategies. This predictive view may help in designing an immune intervention or preventive vaccine for COVID-19 in the near future.

Infection and inflammation induce the acute-phase response (APR), leading to multiple alterations in lipid and lipoprotein metabolism. Plasma triglyceride levels increase from increased VLDL secretion as a result of adipose tissue lipolysis, increased de novo hepatic fatty acid synthesis, and suppression of fatty acid oxidation. With more severe infection, VLDL clearance decreases secondary to decreased lipoprotein lipase and apolipoprotein E in VLDL. In rodents, hypercholesterolemia occurs attributable to increased hepatic cholesterol synthesis and decreased LDL clearance, conversion of cholesterol to bile acids, and secretion of cholesterol into the bile. Marked alterations in proteins important in HDL metabolism lead to decreased reverse cholesterol transport and increased cholesterol delivery to immune cells. Oxidation of LDL and VLDL increases, whereas HDL becomes a proinflammatory molecule. Lipoproteins become enriched in ceramide, glucosylceramide, and sphingomyelin, enhancing uptake by macrophages. Thus, many of the changes in lipoproteins are proatherogenic. The molecular mechanisms underlying the decrease in many of the proteins during the APR involve coordinated decreases in several nuclear hormone receptors, including peroxisome proliferator-activated receptor, liver X receptor, farnesoid X receptor, and retinoid X receptor. APR-induced alterations initially protect the host from the harmful effects of bacteria, viruses, and parasites. However, if prolonged, these changes in the structure and function of lipoproteins will contribute to atherogenesis.

BACKGROUND AND OBJECTIVES: The burden of AKI around the globe has not been systematically examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A systematic review (2004-2012) of large cohort studies was conducted to estimate the world incidence of AKI and its stages of severity and associated mortality, and to describe geographic variations according to countries, regions, and their economies. AKI definitions were reclassified according to the Kidney Disease Improving Global Outcomes (KDIGO) staging system. Random-effects model meta-analyses and meta-regressions were used to generate summary estimates and explore sources of heterogeneity. RESULTS: There were 312 studies identified (n=49,147,878) , primarily in hospital settings. Most studies originated from North America, Northern Europe, and Eastern Asia, from high-income countries, and from nations that spent ≥5% of the gross domestic product on total health expenditure. Among the 154 studies (n=3,585,911) that adopted a KDIGO-equivalent AKI definition, the pooled incidence rates of AKI were 21.6% in adults (95% confidence interval [95% CI], 19.3 to 24.1) and 33.7% in children (95% CI, 26.9 to 41.3). The pooled AKI-associated mortality rates were 23.9% in adults (95% CI, 22.1 to 25.7) and 13.8% in children (95% CI, 8.8 to 21.0). The AKI-associated mortality rate declined over time, and was inversely related to income of countries and percentage of gross domestic product spent on total health expenditure. CONCLUSIONS: Using the KDIGO definition, 1 in 5 adults and 1 in 3 children worldwide experience AKI during a hospital episode of care. This analysis provides a platform to raise awareness of AKI with the public, government officials, and health care professionals.

Objective To conduct a systematic review and meta‐analysis of studies that measured cytokine and chemokine levels in individuals with major depressive disorder ( MDD ) compared to healthy controls ( HC s). Method The PubMed/MEDLINE, EMBASE , and PsycINFO databases were searched up until May 30, 2016. Effect sizes were estimated with random‐effects models. Result Eighty‐two studies comprising 3212 participants with MDD and 2798 HC s met inclusion criteria. Peripheral levels of interleukin‐6 ( IL ‐6), tumor necrosis factor ( TNF )‐alpha, IL ‐10, the soluble IL ‐2 receptor, C‐C chemokine ligand 2, IL ‐13, IL ‐18, IL ‐12, the IL ‐1 receptor antagonist, and the soluble TNF receptor 2 were elevated in patients with MDD compared to HC s, whereas interferon‐gamma levels were lower in MDD (Hedge's g = −0.477, P = 0.043). Levels of IL ‐1β, IL ‐2, IL ‐4, IL ‐8, the soluble IL ‐6 receptor ( sIL ‐6R), IL ‐5, CCL ‐3, IL ‐17, and transforming growth factor‐beta 1 were not significantly altered in individuals with MDD compared to HC s. Heterogeneity was large ( I 2 : 51.6–97.7%), and sources of heterogeneity were explored (e.g., age, smoking status, and body mass index). Conclusion Our results further characterize a cytokine/chemokine profile associated with MDD . Future studies are warranted to further elucidate sources of heterogeneity, as well as biosignature cytokines secreted by other immune cells.

BACKGROUND: We now know that depression is associated with a chronic, low-grade inflammatory response and activation of cell-mediated immunity, as well as activation of the compensatory anti-inflammatory reflex system. It is similarly accompanied by increased oxidative and nitrosative stress (O&NS), which contribute to neuroprogression in the disorder. The obvious question this poses is 'what is the source of this chronic low-grade inflammation?' DISCUSSION: This review explores the role of inflammation and oxidative and nitrosative stress as possible mediators of known environmental risk factors in depression, and discusses potential implications of these findings. A range of factors appear to increase the risk for the development of depression, and seem to be associated with systemic inflammation; these include psychosocial stressors, poor diet, physical inactivity, obesity, smoking, altered gut permeability, atopy, dental cares, sleep and vitamin D deficiency. SUMMARY: The identification of known sources of inflammation provides support for inflammation as a mediating pathway to both risk and neuroprogression in depression. Critically, most of these factors are plastic, and potentially amenable to therapeutic and preventative interventions. Most, but not all, of the above mentioned sources of inflammation may play a role in other psychiatric disorders, such as bipolar disorder, schizophrenia, autism and post-traumatic stress disorder.

EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists. no immunosuppressants IV D no nasal saline irrigation Ib, no data in single use D yes for symptomatic relief topical antibiotics no data D no anti-IL-5 no data D unclear phytotherapy no data D no decongestant topical / oral no data in single use D no mucolytics no data D no oral antihistamine in allergic patients no data D no antimycotics -topical Ia (-) ** A(-) no antimycotics -systemic Ib (-)# A(-) $ no anti leukotrienes Ib (-) A(-) no anti-IgE Ib (-) A(-) no * Some of these studies also included patients with CRS with nasal polyps. % short term antibiotics shows one positive and one negative study. Therefore recommendation C. oral antibiotic short term <4 weeks Ib(-) # A(-)* no intravenous antibiotics III(-) ## C(-) ** no # Ib (-): Ib study with a negative outcome.

A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4ℓ decay channels. The results are obtained from a simultaneous fit to the reconstructed invariant mass peaks in the two channels and for the two experiments. The measured masses from the individual channels and the two experiments are found to be consistent among themselves. The combined measured mass of the Higgs boson is m_{H}=125.09±0.21 (stat)±0.11 (syst) GeV.

Pain sensitivity varies substantially among humans. A significant part of the human population develops chronic pain conditions that are characterized by heightened pain sensitivity. We identified three genetic variants (haplotypes) of the gene encoding catecholamine-O-methyltransferase (COMT) that we designated as low pain sensitivity (LPS), average pain sensitivity (APS) and high pain sensitivity (HPS). We show that these haplotypes encompass 96% of the human population, and five combinations of these haplotypes are strongly associated (P=0.0004) with variation in the sensitivity to experimental pain. The presence of even a single LPS haplotype diminishes, by as much as 2.3 times, the risk of developing myogenous temporomandibular joint disorder (TMD), a common musculoskeletal pain condition. The LPS haplotype produces much higher levels of COMT enzymatic activity when compared with the APS or HPS haplotypes. Inhibition of COMT in the rat results in a profound increase in pain sensitivity. Thus, COMT activity substantially influences pain sensitivity, and the three major haplotypes determine COMT activity in humans that inversely correlates with pain sensitivity and the risk of developing TMD.

We report the first demonstration of electrochemical detection for paper-based microfluidic devices. Photolithography was used to make microfluidic channels on filter paper, and screen-printing technology was used to fabricate electrodes on the paper-based microfluidic devices. Screen-printed electrodes on paper were characterized using cyclic voltammetry to demonstrate the basic electrochemical performance of the system. The utility of our devices was then demonstrated with the determination of glucose, lactate, and uric acid in biological samples using oxidase enzyme (glucose oxidase, lactate oxidase, and uricase, respectively) reactions. Oxidase enzyme reactions produce H2O2 while decomposing their respective substrates, and therefore a single electrode type is needed for detection of multiple species. Selectivity of the working electrode for H2O2 was improved using Prussian Blue as a redox mediator. The determination of glucose, lactate, and uric acid in control serum samples was performed using chronoamperometry at the optimal detection potential for H2O2 (0 V versus the on-chip Ag/AgCl reference electrode). Levels of glucose and lactate in control serum samples measured using the paper devices were 4.9 +/- 0.6 and 1.2 +/- 0.2 mM (level I control sample), and 16.3 +/- 0.7 and 3.2 +/- 0.3 mM (level II control sample), respectively, and were within error of the values measured using traditional tests. This study shows the successful integration of paper-based microfluidics and electrochemical detection as an easy-to-use, inexpensive, and portable alternative for point of care monitoring.

BACKGROUND: Patients with advanced biliary tract cancer have a poor prognosis, and first-line standard of care (gemcitabine plus cisplatin) has remained unchanged for more than 10 years. The TOPAZ-1 trial evaluated durvalumab plus chemotherapy for patients with advanced biliary tract cancer. METHODS: In this double-blind, placebo-controlled, phase 3 study, we randomly assigned patients with previously untreated unresectable or metastatic biliary tract cancer or with recurrent disease 1:1 to receive durvalumab or placebo in combination with gemcitabine plus cisplatin for up to eight cycles, followed by durvalumab or placebo monotherapy until disease progression or unacceptable toxicity. The primary objective was to assess overall survival. Secondary end points included progression-free survival, objective response rate, and safety. RESULTS: Overall, 685 patients were randomly assigned to durvalumab (n=341) or placebo (n=344) with chemotherapy. As of data cutoff, 198 patients (58.1%) in the durvalumab group and 226 patients (65.7%) in the placebo group had died. The hazard ratio for overall survival was 0.80 (95% confidence interval [CI], 0.66 to 0.97; P=0.021). The estimated 24-month overall survival rate was 24.9% (95% CI, 17.9 to 32.5) for durvalumab and 10.4% (95% CI, 4.7 to 18.8) for placebo. The hazard ratio for progression-free survival was 0.75 (95% CI, 0.63 to 0.89; P=0.001). Objective response rates were 26.7% with durvalumab and 18.7% with placebo. The incidences of grade 3 or 4 adverse events were 75.7% and 77.8% with durvalumab and placebo, respectively. CONCLUSIONS: Durvalumab plus chemotherapy significantly improved overall survival versus placebo plus chemotherapy and showed improvements versus placebo plus chemotherapy in prespecified secondary end points including progression-free survival and objective response rate. The safety profiles of the two treatment groups were similar. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT03875235.)

BACKGROUND: Chronic human immunodeficiency virus (HIV) infection is associated with intestinal permeability and microbial translocation that contributes to systemic immune activation, which is an independent predictor of HIV disease progression. The association of microbial translocation with clinical outcome remains unknown. METHODS: This nested case-control study included 74 subjects who died, 120 of whom developed cardiovascular disease and 81 of whom developed AIDS during the Strategies for Management of Anti-Retroviral Therapy (SMART) study with matched control subjects. Intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), soluble CD14 (sCD14), endotoxin core antibody (EndoCAb), and 16S ribosomal DNA (rDNA) were measured in baseline plasma samples. RESULTS: Subjects with the highest quartile of sCD14 levels had a 6-fold higher risk of death than did those in the lowest quartile (95% confidence interval, 2.2-16.1; P<.001), with minimal change after adjustment for inflammatory markers, CD4(+) T cell count, and HIV RNA level. No other marker was significantly associated with clinical outcomes. I-FABP, LPS, and sCD14 were increased and EndoCAb was decreased in study subjects, compared with healthy volunteers. sCD14 level correlated with levels of IL-6, C-reactive protein, serum amyloid A and D-dimer. CONCLUSIONS: sCD14, a marker of monocyte response to LPS, is an independent predictor of mortality in HIV infection. Therapeutic attenuation of innate immune activation may improve survival in patients with HIV infection.

Combined ATLAS and CMS measurements of the Higgs boson production and decay rates, as well as constraints on its couplings to vector bosons and fermions, are presented. The combination is based on the analysis of five production processes, namely gluon fusion, vector boson fusion, and associated production with a W or a Z boson or a pair of top quarks, and of the six decay modes H → ZZ, W W , γγ, ττ, bb, and μμ. All results are reported assuming a value of 125.09 GeV for the Higgs boson mass, the result of the combined measurement by the ATLAS and CMS experiments. The analysis uses the CERN LHC proton-proton collision data recorded by the ATLAS and CMS experiments in 2011 and 2012, corresponding to integrated luminosities per experiment of approximately 5 fb$^{−1}$ at $\sqrt{s}$=7 TeV and 20 fb−1 at $\sqrt{s}$=8 TeV. The Higgs boson production and decay rates measured by the two experiments are combined within the context of three generic parameterisations: two based on cross sections and branching fractions, and one on ratios of coupling modifiers. Several interpretations of the measurements with more model-dependent parameterisations are also given. The combined signal yield relative to the Standard Model prediction is measured to be 1.09 ± 0.11. The combined measurements lead to observed significances for the vector boson fusion production process and for the H → ττ decay of 5.4 and 5.5 standard deviations, respectively. The data are consistent with the Standard Model predictions for all parameterisations considered.

Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high-resolution manometry (HRM). Fifty-two diverse international experts separated into seven working subgroups utilized formal validated methodologies over two-years to develop CCv4.0. Key updates in CCv.4.0 consist of a more rigorous and expansive HRM protocol that incorporates supine and upright test positions as well as provocative testing, a refined definition of esophagogastric junction (EGJ) outflow obstruction (EGJOO), more stringent diagnostic criteria for ineffective esophageal motility and description of baseline EGJ metrics. Further, the CCv4.0 sought to define motility disorder diagnoses as conclusive and inconclusive based on associated symptoms, and findings on provocative testing as well as supportive testing with barium esophagram with tablet and/or functional lumen imaging probe. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification and provide more standardized and rigorous criteria for patterns of disorders of peristalsis and obstruction at the EGJ.

Recently, nanocellulose and its applications gain high attraction in both research and industrial areas due to its attractive properties such as excellent mechanical properties, high surface area, rich hydroxyl groups for modification, and natural properties with 100% environmental friendliness. In this review, the background of nanocellulose originated from lignocellulosic biomass and the typical extraction methods and general applications are summarized, in which the nanocellulose extraction methods related to ball milling are mainly introduced. Also, an outlook on its future is given. It is expected to provide guidance on the effective extraction of nanocellulose from biomass and its most possible applications in the future.