Showing papers by "Flinders University published in 2021"
Daniel J. Klionsky1, Amal Kamal Abdel-Aziz2, Sara Abdelfatah3, Mahmoud Abdellatif4 +2980 more•Institutions (777)
TL;DR: In this article, the authors present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes.
Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide 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.
1,129 citations
TL;DR: The InvaCost database has enabled the generation of a reliable, comprehensive, standardized and easily updatable synthesis of the monetary costs of biological invasions worldwide as mentioned in this paper, with the total reported costs reaching a minimum of US$1288 trillion (2017 US dollars).
Abstract: Biological invasions are responsible for substantial biodiversity declines as well as high economic losses to society and monetary expenditures associated with the management of these invasions1,2 The InvaCost database has enabled the generation of a reliable, comprehensive, standardized and easily updatable synthesis of the monetary costs of biological invasions worldwide3 Here we found that the total reported costs of invasions reached a minimum of US$1288 trillion (2017 US dollars) over the past few decades (1970-2017), with an annual mean cost of US$268 billion Moreover, we estimate that the annual mean cost could reach US$1627 billion in 2017 These costs remain strongly underestimated and do not show any sign of slowing down, exhibiting a consistent threefold increase per decade We show that the documented costs are widely distributed and have strong gaps at regional and taxonomic scales, with damage costs being an order of magnitude higher than management expenditures Research approaches that document the costs of biological invasions need to be further improved Nonetheless, our findings call for the implementation of consistent management actions and international policy agreements that aim to reduce the burden of invasive alien species
396 citations
TL;DR: Paremoer et al. as discussed by the authors called for action to create a fairer and more sustainable post-covid world, and proposed a sustainable postcovidian world.
Abstract: Lauren Paremoer and colleagues call for action to create a fairer and more sustainable post-covid world
333 citations
University of California, San Diego1, Northwestern University2, University of Zurich3, University of Amsterdam4, Washington University in St. Louis5, Claude Bernard University Lyon 16, University of Colorado Denver7, United States Department of Veterans Affairs8, Katholieke Universiteit Leuven9, University of Padua10, Queen Mary University of London11, Vanderbilt University12, University of Bordeaux13, Ege University14, University of Michigan15, Universidad del Desarrollo16, Flinders University17, University of Pisa18, University of Chile19, Case Western Reserve University20, Sanjay Gandhi Post Graduate Institute of Medical Sciences21, Chulalongkorn University22, University of Melbourne23, University of Ulsan24, Cornell University25, Mayo Clinic26, New York University27, Monash University28, University of Alberta29, University of Bern30, Kosin University31, University of Milan32, University of South Florida33, Autonomous University of Barcelona34, University College Hospital35, University of Washington36, National University of Singapore37, The Chinese University of Hong Kong38, Sun Yat-sen University39
TL;DR: The Chicago Classification v4.4.0 as discussed by the authors is the most recent version of the Chicago Classification, which uses high-resolution manometry (HRM) for motility disorders.
Abstract: 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.
306 citations
TL;DR: In this paper, the authors show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19.
Abstract: The durability of infection-induced SARS-CoV-2 immunity has major implications for reinfection and vaccine development. Here, we show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19. Binding and neutralising antibody responses, together with individual serum clonotypes, decay over the first 4 months post-infection. A similar decline in Spike-specific CD4+ and circulating T follicular helper frequencies occurs. By contrast, S-specific IgG+ memory B cells consistently accumulate over time, eventually comprising a substantial fraction of circulating the memory B cell pool. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent participants to 74 days, although there is probably additive protection from B cell and T cell immunity. This study indicates that SARS-CoV-2 immunity after infection might be transiently protective at a population level. Therefore, SARS-CoV-2 vaccines might require greater immunogenicity and durability than natural infection to drive long-term protection.
273 citations
TL;DR: The worldwide prevalence of gaming disorder appears to be comparable to obsessive-compulsive disorder and some substance-related addictions, but lower than compulsive buying and higher than problem gambling.
Abstract: Background:Gaming disorder was included in the latest revision of the International Classification of Diseases (11th ed.). Worldwide, prevalence estimates of gaming disorder are considerably hetero...
255 citations
TL;DR: In this paper, a sample of online participants (N = 1,040), in five western countries, were asked to indicate the COVID-19 events they had been directly exposed to, events they anticipated would happen in the future, and other forms of indirect exposure such as through media coverage.
Abstract: The COVID-19 pandemic does not fit into prevailing Post-traumatic Stress Disorder (PTSD) models, or diagnostic criteria, yet emerging research shows traumatic stress symptoms as a result of this ongoing global stressor. Current pathogenic event models focus on past, and largely direct, trauma exposure to certain kinds of life-threatening events. Yet, traumatic stress reactions to future, indirect trauma exposure, and non-Criterion A events exist, suggesting COVID-19 is also a traumatic stressor which could lead to PTSD symptomology. To examine this idea, we asked a sample of online participants (N = 1,040), in five western countries, to indicate the COVID-19 events they had been directly exposed to, events they anticipated would happen in the future, and other forms of indirect exposure such as through media coverage. We then asked participants to complete the Posttraumatic Stress Disorder Checklist-5, adapted to measure pre/peri/post-traumatic reactions in relation to COVID-19. We also measured general emotional reactions (e.g., angry, anxious, helpless), well-being, psychosocial functioning, and depression, anxiety, and stress symptoms. We found participants had PTSD-like symptoms for events that had not happened and when participants had been directly (e.g., contact with virus) or indirectly exposed to COVID-19 (e.g., via media). Moreover, 13.2% of our sample were likely PTSD-positive, despite types of COVID-19 "exposure" (e.g., lockdown) not fitting DSM-5 criteria. The emotional impact of "worst" experienced/anticipated events best predicted PTSD-like symptoms. Taken together, our findings support emerging research that COVID-19 can be understood as a traumatic stressor event capable of eliciting PTSD-like responses and exacerbating other related mental health problems (e.g., anxiety, depression, psychosocial functioning, etc.). Our findings add to existing literature supporting a pathogenic event memory model of traumatic stress.
226 citations
Memorial Sloan Kettering Cancer Center1, Medical College of Wisconsin2, University of Western Australia3, Ohio State University4, University of California, San Francisco5, University of Oxford6, Columbia University7, Sarah Cannon Research Institute8, University of Miami9, University of Texas MD Anderson Cancer Center10, University of North Carolina at Chapel Hill11, University of Pennsylvania12, Vita-Salute San Raffaele University13, University of Nantes14, Roswell Park Cancer Institute15, Emory University16, Royal Melbourne Hospital17, Flinders University18, Harvard University19
TL;DR: Pirtobrutinib was shown to be safe and effective in multiple B-cell malignancies, including patients previously treated with covalent BTK inhibitors as mentioned in this paper.
189 citations
TL;DR: The 2018 IFSO Survey as mentioned in this paper focused on similarities and disparities in the number and types of surgical and endoluminal interventions among the IGS chapters occurred in the last decade.
Abstract: The 2018 IFSO Survey focused on similarities and disparities in the number and types of surgical and endoluminal interventions among the IFSO chapters occurred in the last decade. All IFSO Societies were asked to fill in the IFSO survey form on how many and which surgical and endoluminal interventions have been performed in the 2018. A special section was added, asking about the existence of national guidelines for bariatric and metabolic surgery, national recommendations for preoperative gastroscopy, type of reimbursement for bariatric/metabolic surgery, including for patients with BMI < 35 kg/m2. The trend analyses from 2008 to 2018 were also performed. Fifty-seven/65 (87.7%) IFSO Societies submitted completed forms. The American Society for Metabolic and Bariatric Surgery did not fill the IFSO survey form but provided an official report on the performed interventions. The total number of surgical and endoluminal procedures performed in 2018 in the world was 696,191. Sleeve gastrectomy (SG) remained the most commonly performed bariatric procedure (N = 386,096; 55.4%). Among the total reported bariatric/metabolic interventions, 604,223 (86.8%) were primary surgical and 29,167 (4.2%) primary endoluminal operations; 62,801 (9%) were revisional procedures. There was only a slight increase (10.317 procedures) in the total number of the reported bariatric interventions compared to the last IFSO survey. SG continues to be the most commonly performed operation since 2014. The one anastomosis gastric bypass (OAGB), currently the third most performed procedure after SG and Roux-en-Y gastric bypass (RYGB), continues to rise in popularity worldwide.
187 citations
Ohio State University1, Los Angeles Biomedical Research Institute2, University of Leicester3, French Institute of Health and Medical Research4, Salem Hospital5, University of Hong Kong6, Imperial College London7, Mayo Clinic8, University of North Carolina at Chapel Hill9, University of California, Los Angeles10, University of Cambridge11, The George Institute for Global Health12, Mount Elizabeth Novena Hospital13, Nanjing University14, University of Iowa15, Columbia University Medical Center16, University of Toronto17, University of Groningen18, Juntendo University19, Charles University in Prague20, Radboud University Nijmegen21, McMaster University22, Flinders University23, University of Sydney24, University of Calgary25, RWTH Aachen University26
TL;DR: The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Glomerular Diseases is an update to the KDIGO 2012 guideline.
180 citations
Flinders University1, Australian Research Council2, Stanford University3, Macquarie University4, National Autonomous University of Mexico5, Virginia Tech6, University of California, Berkeley7, Rocky Mountain Biological Laboratory8, Missouri Botanical Garden9, Oregon State University10, University of California, Los Angeles11
TL;DR: The scale of the threats to the biosphere and all its lifeforms is in fact so great that it is difficult to grasp for even well-informed experts as mentioned in this paper, and this dire situation places an extraordinary responsibility on scientists to speak out candidly and accurately when engaging with government, business, and the public.
Abstract: We report three major and confronting environmental issues that have received little attention and require urgent action. First, we review the evidence that future environmental conditions will be far more dangerous than currently believed. The scale of the threats to the biosphere and all its lifeforms — including humanity — is in fact so great that it is difficult to grasp for even well-informed experts. Second, we ask what political or economic system, or leadership, is prepared to handle the predicted disasters, or even capable of such action. Third, this dire situation places an extraordinary responsibility on scientists to speak out candidly and accurately when engaging with government, business, and the public. We especially draw attention to the lack of appreciation of the enormous challenges to creating a sustainable future. The added stresses to human health, wealth, and well-being will perversely diminish our political capacity to mitigate the erosion of ecosystem services on which society depends. The science underlying these issues is strong, but awareness is weak. Without fully appreciating and broadcasting the scale of the problems and the enormity of the solutions required, society will fail to achieve even modest sustainability goals.
University of Utah1, Stanford University2, University of Tennessee Health Science Center3, Children's Hospital of Philadelphia4, University of Pennsylvania5, Southern Medical University6, University of California, San Diego7, Veterans Health Administration8, Ottawa Hospital Research Institute9, University of Alabama at Birmingham10, Pontifícia Universidade Católica do Paraná11, Tufts Medical Center12, University of Toronto13, Northern Ontario School of Medicine14, Freeman Hospital15, McMaster University16, Cochrane Collaboration17, Flinders University18, University of Sydney19, University of Calgary20, University of Erlangen-Nuremberg21
TL;DR: A systolic blood pressure target of less than 120 mm Hg is proposed using standardized office reading for most people with chronic kidney disease (CKD) not receiving dialysis, the exception being children and kidney transplant recipients.
TL;DR: In this article, a review of ensemble learning methodologies in various areas of hydrology for simulation and prediction purposes has been presented, and the general findings demonstrate the absolute superiority of using ensemble strategies over the regular (individual) model learning in hydrology.
TL;DR: In this article, the authors demonstrate that a healthy Mediterranean-style dietary pattern is associated with specific functional and taxonomic components of the gut microbiome, and that its protective associations with cardiometabolic health vary depending on microbial composition.
Abstract: To address how the microbiome might modify the interaction between diet and cardiometabolic health, we analyzed longitudinal microbiome data from 307 male participants in the Health Professionals Follow-Up Study, together with long-term dietary information and measurements of biomarkers of glucose homeostasis, lipid metabolism and inflammation from blood samples. Here, we demonstrate that a healthy Mediterranean-style dietary pattern is associated with specific functional and taxonomic components of the gut microbiome, and that its protective associations with cardiometabolic health vary depending on microbial composition. In particular, the protective association between adherence to the Mediterranean diet and cardiometabolic disease risk was significantly stronger among participants with decreased abundance of Prevotella copri. Our findings advance the concept of precision nutrition and have the potential to inform more effective and precise dietary approaches for the prevention of cardiometabolic disease mediated through alterations in the gut microbiome. The beneficial effects of a Mediterranean diet on cardiometabolic health are associated with specific changes in the gut microbiome, suggesting a personalized approach towards cardiometabolic disease prevention.
TL;DR: An update is provided regarding the emerging cellular and molecular mechanisms involved in the onset and progression of idiopathic pulmonary fibrosis.
Abstract: Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia, is a progressive, irreversible, and typically lethal disease characterized by an abnormal fibrotic response involving vast areas of the lungs. Given the poor knowledge of the mechanisms underpinning IPF onset and progression, a better understanding of the cellular processes and molecular pathways involved is essential for the development of effective therapies, currently lacking. Besides a number of established IPF-associated risk factors, such as cigarette smoking, environmental factors, comorbidities, and viral infections, several other processes have been linked with this devastating disease. Apoptosis, senescence, epithelial-mesenchymal transition, endothelial-mesenchymal transition, and epithelial cell migration have been shown to play a key role in IPF-associated tissue remodeling. Moreover, molecules, such as chemokines, cytokines, growth factors, adenosine, glycosaminoglycans, non-coding RNAs, and cellular processes including oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, hypoxia, and alternative polyadenylation have been linked with IPF development. Importantly, strategies targeting these processes have been investigated to modulate abnormal cellular phenotypes and maintain tissue homeostasis in the lung. This review provides an update regarding the emerging cellular and molecular mechanisms involved in the onset and progression of IPF.
TL;DR: In this article, the authors examined the efficacy of distinct types of psychological interventions, irrespective of their theoretical underpinning, and the impact of various moderators, in a unified systematic review and meta-analysis.
Abstract: Our current understanding of the efficacy of psychological interventions in improving mental states of wellbeing is incomplete. This study aimed to overcome limitations of previous reviews by examining the efficacy of distinct types of psychological interventions, irrespective of their theoretical underpinning, and the impact of various moderators, in a unified systematic review and meta-analysis. Four-hundred-and-nineteen randomized controlled trials from clinical and non-clinical populations (n = 53,288) were identified for inclusion. Mindfulness-based and multi-component positive psychological interventions demonstrated the greatest efficacy in both clinical and non-clinical populations. Meta-analyses also found that singular positive psychological interventions, cognitive and behavioural therapy-based, acceptance and commitment therapy-based, and reminiscence interventions were impactful. Effect sizes were moderate at best, but differed according to target population and moderator, most notably intervention intensity. The evidence quality was generally low to moderate. While the evidence requires further advancement, the review provides insight into how psychological interventions can be designed to improve mental wellbeing. This meta-analysis of 419 randomized controlled trials found that various types of psychological interventions could improve mental wellbeing in clinical and non-clinical populations. Effect sizes tended to be small to moderate and were influenced by various moderators.
TL;DR: In this article, a systematic literature search was conducted to identify studies reporting on prevalence, hospitalisations, and deaths from COVID-19 by race groups between 1 January 2020 - 15 April 2021.
Abstract: Background: People from racial minority groups in western countries experience disproportionate socioeconomic and structural determinants of health disadvantages. These disadvantages have led to inequalities and inequities in health care access and poorer health outcomes. We report disproportionate disparities in prevalence, hospitalisation, and deaths from COVID-19 by racial minority populations. Methods: We conducted a systematic literature search of relevant databases to identify studies reporting on prevalence, hospitalisations, and deaths from COVID-19 by race groups between 01 January 2020 - 15 April 2021. We grouped race categories into Blacks, Hispanics, Whites and Others. Random effects model using the method of DerSimonian and Laird were fitted, and forest plot with respective ratio estimates and 95% confidence interval (CI) for each race category, and subgroup meta-regression analyses and the overall pooled ratio estimates for prevalence, hospitalisation and mortality rate were presented. Results: Blacks experienced significantly higher burden of COVID-19: prevalence ratio 1.79 (95% confidence interval (CI) = 1.59-1.99), hospitalisation ratio 1.87 (95% CI = 1.69-2.04), mortality ratio 1.68 (95% CI = 1.52-1.83), compared to Whites: prevalence ratio 0.70 (95% CI = 0.0.64-0.77), hospitalisation ratio 0.74 (95% CI = 0.65-0.82), mortality ratio 0.82 (95% CI = 0.78-0.87). Also, Hispanics experienced a higher burden: prevalence ratio 1.78 (95% CI = 1.63-1.94), hospitalisation ratio 1.32 (95% CI = 1.08-1.55), mortality ratio 0.94 (95% CI = 0.84-1.04) compared to Whites. A higher burden was also observed for Other race groups: prevalence ratio 1.43 (95% CI = 1.19-1.67), hospitalisation ratio 1.12 (95% CI = 0.89-1.35), mortality ratio 1.06 (95% CI = 0.89-1.23) compared to Whites. The disproportionate burden among Blacks and Hispanics remained following correction for publication bias. Conclusions: Blacks and Hispanics have been disproportionately affected by COVID-19. This is deeply concerning and highlights the systemically entrenched disadvantages (social, economic, and political) experienced by racial minorities in western countries; and this study underscores the need to address inequities in these communities to improve overall health outcomes.
TL;DR: In this article, the causal effects of online education on student exam performance using administrative data from Chinese middle schools were estimated. But not all online education was equal: students who were given recorded online lessons from external higher-quality teachers had higher exam scores than those whose lessons were recorded by teachers from their own school.
TL;DR: This review comprehensively highlights the potentiality of various nanocarriers and nanomedicines for multifaceted applications in diagnostics and drug delivery, especially the potentialities of polymeric nanoparticle, nanoemulsion, solid-lipid nanoparticles, nanostructured lipid carrier, self-micellizing anticancer lipids, dendrimer, nanocapsule and nanosponge-based therapeutic approaches in the field of cancer.
Michael E. DeBakey Veterans Affairs Medical Center in Houston1, Monash University2, University of Minnesota3, The Chinese University of Hong Kong4, University Medical Center Groningen5, Mount Elizabeth Novena Hospital6, Johns Hopkins University School of Medicine7, Obafemi Awolowo University8, All India Institute of Medical Sciences9, University of Washington10, University of Würzburg11, Northwest Kidney Centers12, McMaster University13, Flinders University14, University of Sydney15, University of Calgary16, University of Copenhagen17, Leicester General Hospital18
TL;DR: The guideline includes 12 recommendations and 48 practice points for clinicians caring for patients with diabetes and CKD, and focuses on the key recommendations pertinent to the following issues: comprehensive care needs, glycemic monitoring and targets, lifestyle interventions, antihyperglycemic therapies, and educational and integrated care approaches.
Abstract: Description The Kidney Disease: Improving Global Outcomes (KDIGO) organization developed a clinical practice guideline in 2020 for the management of patients with diabetes and chronic kidney disease (CKD). Methods The KDIGO Work Group (WG) was tasked with developing the guideline for diabetes management in CKD. It defined the scope of the guideline, gathered evidence, determined systematic review topics, and graded evidence that had been summarized by an evidence review team. The English-language literature searches, which were initially done through October 2018, were updated in February 2020. The WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of the recommendations. Expert judgment was used to develop consensus practice points supplementary to the evidence-based graded recommendations. The guideline document underwent open public review. Comments from various stakeholders, subject matter experts, and industry and national organizations were considered before the document was finalized. Recommendations The guideline includes 12 recommendations and 48 practice points for clinicians caring for patients with diabetes and CKD. This synopsis focuses on the key recommendations pertinent to the following issues: comprehensive care needs, glycemic monitoring and targets, lifestyle interventions, antihyperglycemic therapies, and educational and integrated care approaches.
TL;DR: In this paper, the authors conducted qualitative research among healthcare professionals of different hospitals and clinics in Khulna and Dhaka city of Bangladesh from May 2020 to August 2020 and conducted 15 in-depth telephone interviews using a snowball sampling technique.
Abstract: Background: The coronavirus disease 2019 (COVID-19) pandemic has caused increasing challenges for healthcare professionals globally. However, there is a dearth of information about these challenges in many developing countries, including Bangladesh. This study aims to explore the challenges faced by healthcare professionals (doctors and nurses) during COVID-19 in Bangladesh. Methods: We conducted qualitative research among healthcare professionals of different hospitals and clinics in Khulna and Dhaka city of Bangladesh from May 2020 to August 2020. We conducted 15 in-depth telephone interviews using a snowball sampling technique. We used an in-depth interview guide as data were collected, audiotaped, and transcribed. The data were analyzed both manually and using QDA Miner software as we used thematic analysis for this study. Results: Seven themes emerged from the study. Participants experienced higher workload, psychological distress, shortage of quality personal protective equipment (PPE), social exclusion/stigmatization, lack of incentives, absence of coordination, and proper management during their service. These healthcare professionals faced difficulty coping with these challenges due to situational and organizational factors. They reported of faith in God and mutual support to be the keys to adapt to adversities. Adequate support to address the difficulties faced by healthcare professionals is necessary for an overall improved health outcome during the pandemic. Conclusion: The findings highlight the common challenges faced by healthcare professionals during the COVID-19 outbreak. This implies the need to support adequate safety kits, protocols, and support for both physical and mental health of the healthcare professionals.
TL;DR: TDM has been proven to be feasible for individualised dosing of abiraterone, everolimus, imatinib, pazopanib, sunitinib and tamoxifen in prospective studies and is a powerful tool to individualise drug dosing, ensure drug concentrations within the therapeutic window and increase treatment success rates.
Abstract: This review provides an overview of the current challenges in oral targeted antineoplastic drug (OAD) dosing and outlines the unexploited value of therapeutic drug monitoring (TDM). Factors influencing the pharmacokinetic exposure in OAD therapy are depicted together with an overview of different TDM approaches. Finally, current evidence for TDM for all approved OADs is reviewed. A comprehensive literature search (covering literature published until April 2020), including primary and secondary scientific literature on pharmacokinetics and dose individualisation strategies for OADs, together with US FDA Clinical Pharmacology and Biopharmaceutics Reviews and the Committee for Medicinal Products for Human Use European Public Assessment Reports was conducted. OADs are highly potent drugs, which have substantially changed treatment options for cancer patients. Nevertheless, high pharmacokinetic variability and low treatment adherence are risk factors for treatment failure. TDM is a powerful tool to individualise drug dosing, ensure drug concentrations within the therapeutic window and increase treatment success rates. After reviewing the literature for 71 approved OADs, we show that exposure-response and/or exposure-toxicity relationships have been established for the majority. Moreover, TDM has been proven to be feasible for individualised dosing of abiraterone, everolimus, imatinib, pazopanib, sunitinib and tamoxifen in prospective studies. There is a lack of experience in how to best implement TDM as part of clinical routine in OAD cancer therapy. Sub-therapeutic concentrations and severe adverse events are current challenges in OAD treatment, which can both be addressed by the application of TDM-guided dosing, ensuring concentrations within the therapeutic window.
TL;DR: In this article, the authors used real-time measurements of enteroendocrine cells (EECs) and found that the bacteria Edwardsiella tarda activate EECs through the receptor transient receptor potential ankyrin A1 (Trpa1) and increase intestinal motility.
TL;DR: The role of the androgen receptor (AR) in estrogen receptor (ER)-α-positive breast cancer is controversial, constraining implementation of AR-directed therapies as discussed by the authors, using a diverse, clinically relevant panel of cell-line and patient-derived models, demonstrating that AR activation, not suppression, exerts potent antitumor activity in multiple disease contexts, including resistance to standard-of-care ER and CDK4/6 inhibitors.
Abstract: The role of the androgen receptor (AR) in estrogen receptor (ER)-α-positive breast cancer is controversial, constraining implementation of AR-directed therapies. Using a diverse, clinically relevant panel of cell-line and patient-derived models, we demonstrate that AR activation, not suppression, exerts potent antitumor activity in multiple disease contexts, including resistance to standard-of-care ER and CDK4/6 inhibitors. Notably, AR agonists combined with standard-of-care agents enhanced therapeutic responses. Mechanistically, agonist activation of AR altered the genomic distribution of ER and essential co-activators (p300, SRC-3), resulting in repression of ER-regulated cell cycle genes and upregulation of AR target genes, including known tumor suppressors. A gene signature of AR activity positively predicted disease survival in multiple clinical ER-positive breast cancer cohorts. These findings provide unambiguous evidence that AR has a tumor suppressor role in ER-positive breast cancer and support AR agonism as the optimal AR-directed treatment strategy, revealing a rational therapeutic opportunity. Functional interplay of sex hormones in estrogen receptor–positive breast cancer unveils the therapeutic potential of androgen receptor agonists.
University of Valencia1, Flinders University2, University of Cape Town3, University of Duisburg-Essen4, University of Southampton5, Southern Health NHS Foundation Trust6, Eötvös Loránd University7, Hertfordshire Partnership University NHS Foundation Trust8, University of Hertfordshire9, University of Cambridge10, Monash University11, Geneva College12, All India Institute of Medical Sciences13, Ministry of Health (Malaysia)14, University of Sydney15, University College London16, Ramon Llull University17, St. John's University18, Kaohsiung Medical University19, Cliniques Universitaires Saint-Luc20, Université du Québec à Montréal21, Catholic University of Korea22, Carlos III Health Institute23, Bellvitge University Hospital24, Nottingham Trent University25, Shanghai Jiao Tong University26, Université catholique de Louvain27, Hannover Medical School28, University of Florence29, Yale University30, Tehran University of Medical Sciences31, University of Queensland32, Kore University of Enna33, University of Indonesia34, Universidade Federal do Rio Grande do Sul35, Ariel University36, University of Mainz37, University of Luxembourg38, University of Lausanne39
TL;DR: In this article, the authors employed the Delphi expert consensus method to obtain expert agreement on the diagnostic validity, clinical utility and prognostic value of the DSM-5 criteria and ICD-11 clinical guidelines for gaming disorder.
Abstract: Background and aims: Following the recognition of ‘internet gaming disorder’ (IGD) as a condition requiring further study by the DSM-5, ‘gaming disorder’ (GD) was officially included as a diagnostic entity by the World Health Organization (WHO) in the 11th revision of the International Classification of Diseases (ICD-11). However, the proposed diagnostic criteria for gaming disorder remain the subject of debate, and there has been no systematic attempt to integrate the views of different groups of experts. To achieve a more systematic agreement on this new disorder, this study employed the Delphi expert consensus method to obtain expert agreement on the diagnostic validity, clinical utility and prognostic value of the DSM-5 criteria and ICD-11 clinical guidelines for GD. Methods: A total of 29 international experts with clinical and/or research experience in GD completed three iterative rounds of a Delphi survey. Experts rated proposed criteria in progressive rounds until a pre-determined level of agreement was achieved. Results: For DSM-5 IGD criteria, there was an agreement both that a subset had high diagnostic validity, clinical utility and prognostic value and that some (e.g. tolerance, deception) had low diagnostic validity, clinical utility and prognostic value. Crucially, some DSM-5 criteria (e.g. escapism/mood regulation, tolerance) were regarded as incapable of distinguishing between problematic and non-problematic gaming. In contrast, ICD-11 diagnostic guidelines for GD (except for the criterion relating to diminished non-gaming interests) were judged as presenting high diagnostic validity, clinical utility and prognostic value. Conclusions: This Delphi survey provides a foundation for identifying the most diagnostically valid and clinically useful criteria for GD. There was expert agreement that some DSM-5 criteria were not clinically relevant and may pathologize non-problematic patterns of gaming, whereas ICD-11 diagnostic guidelines are likely to diagnose GD adequately and avoid pathologizing.
TL;DR: This review helps in better understanding of the behavior of FA-based concrete as a sustainable and eco-friendly material used in construction and building industries.
Abstract: Development of sustainable concrete as an alternative to conventional concrete helps in reducing carbon dioxide footprint associated with the use of cement and disposal of waste materials in landfill. One way to achieve that is the use of fly ash (FA) as an alternative to ordinary Portland cement (OPC) because FA is a pozzolanic material and has a high amount of alumina and silica content. Because of its excellent mechanical properties, several studies have been conducted to investigate the use of alkali-activated FA-based concrete as an alternative to conventional concrete. FA, as an industrial by-product, occupies land, thereby causing environmental pollution and health problems. FA-based concrete has numerous advantages, such as it has early strength gaining, it uses low natural resources, and it can be configurated into different structural elements. This study initially presents a review of the classifications, sources, chemical composition, curing regimes and clean production of FA. Then, physical, fresh, and mechanical properties of FA-based concretes are studied. This review helps in better understanding of the behavior of FA-based concrete as a sustainable and eco-friendly material used in construction and building industries.
Maria Lc Iurilli1, Bin Zhou1, James E. Bennett1, Rodrigo M. Carrillo-Larco1 +1399 more•Institutions (374)
TL;DR: In this article, the authors investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants.
Abstract: From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
University of Texas MD Anderson Cancer Center1, Cornell University2, City of Hope National Medical Center3, University of California, San Diego4, Monash University, Clayton campus5, Ministry of Health (New South Wales)6, Flinders University7, Middlemore Hospital8, Autonomous University of Barcelona9, Sarah Cannon Research Institute10, Vita-Salute San Raffaele University11, University of Melbourne12
TL;DR: PURPOSECAPTIVATE (NCT02910583), a randomized phase II study, evaluates minimal residual disease (MRD)-guided treatment discontinuation following completion of first-line ibrutinib plus venetoclax t...
Abstract: PURPOSECAPTIVATE (NCT02910583), a randomized phase II study, evaluates minimal residual disease (MRD)-guided treatment discontinuation following completion of first-line ibrutinib plus venetoclax t...
TL;DR: A review of state-of-the-art progress in the BCI field over the last decades and highlights critical challenges can be found in this paper, where the authors highlight the challenges of time-variant psycho-neurophysiological fluctuations and their impact on brain signals.
Abstract: Brain computer interfaces (BCI) provide a direct communication link between the brain and a computer or other external devices. They offer an extended degree of freedom either by strengthening or by substituting human peripheral working capacity and have potential applications in various fields such as rehabilitation, affective computing, robotics, gaming, and neuroscience. Significant research efforts on a global scale have delivered common platforms for technology standardization and help tackle highly complex and non-linear brain dynamics and related feature extraction and classification challenges. Time-variant psycho-neurophysiological fluctuations and their impact on brain signals impose another challenge for BCI researchers to transform the technology from laboratory experiments to plug-and-play daily life. This review summarizes state-of-the-art progress in the BCI field over the last decades and highlights critical challenges.
TL;DR: In this paper, the authors synthesize this evidence, discuss the immunological mechanisms that potentially mediate these effects and consider the potential of microbiota-targeted interventions to optimize vaccine effectiveness.
Abstract: The need for highly effective vaccines that induce robust and long-lasting immunity has never been more apparent. However, for reasons that are still poorly understood, immune responses to vaccination are highly variable between different individuals and different populations. Furthermore, vaccine immunogenicity is frequently suboptimal in the very populations who are at most risk from infectious disease, including infants, the elderly, and those living in low-income and middle-income countries. Although many factors have the potential to influence vaccine immunogenicity and therefore vaccine effectiveness, increasing evidence from clinical studies and animal models now suggests that the composition and function of the gut microbiota are crucial factors modulating immune responses to vaccination. In this Review, we synthesize this evidence, discuss the immunological mechanisms that potentially mediate these effects and consider the potential of microbiota-targeted interventions to optimize vaccine effectiveness.