Comparing quality of life and treatment satisfaction between patients on warfarin and direct oral anticoagulants : a cross-sectional study

Introduction and aim: Patient quality of life (QOL) while on long-term oral anticoagulant therapy has been receiving greater attention in recent years due to the increase in life expectancy brought about by advances in medical care. This study aimed to compare the QOL, treatment satisfaction, hospitalization and bleeding rate in patients on long-term warfarin versus direct oral anticoagulants (DOAC). Methods: This was a cross-sectional study of patients with non-valvular atrial fibrillation (NVAF) or venous thromboembolism (VTE) on long-term anticoagulant therapy attending the cardiology clinic and anticoagulation clinic of the University Malaya Medical Centre from July 1, 2016, to June 30, 2018. Patient QOL was assessed by using the Short Form 12 Health Survey (SF12), while treatment satisfaction was assessed by using the Perception of Anticoagulation Treatment Questionnaire 2 (PACT-Q2). Results: A total of 208 patients were recruited; 52.4% received warfarin and 47.6% received DOAC. There was no significant difference in QOL between warfarin and DOAC based on SF12 (physical QOL, P=0.083; mental QOL, P=0.665). Nevertheless, patients in the DOAC group were significantly more satisfied with their treatment compared to the warfarin group based on PACT-Q2 (P=0.004). The hospitalisation rate was significantly higher in the warfarin group than the DOAC group (15.6% versus 3.0%, P=0.002). Clinically relevant minor bleeds and severe bleeding events were non-significantly higher in the warfarin group than the DOAC group (66.7% versus 40.0%, P=0.069). Conclusion: Compared to warfarin, treatment of NVAF and VTE with DOAC showed comparable QOL, higher treatment satisfaction, lesser hospitalization, and a non-significant trend toward fewer bleeding episodes

Passive Picoinjection Enables Controlled Crystallization in a Droplet Microfluidic Device

Segmented flow microfluidic devices offer an attractive means of studying crystallization processes. However, while they are widely employed for protein crystallization, there are few examples of their use for sparingly soluble compounds due to problems with rapid device fouling and irreproducibility over longer run‐times. This article presents a microfluidic device which overcomes these issues, as this is constructed around a novel design of “picoinjector” that facilitates direct injection into flowing droplets. Exploiting a Venturi junction to reduce the pressure within the droplet, it is shown that passive injection of solution from a side‐capillary can be achieved in the absence of an applied electric field. The operation of this device is demonstrated for calcium carbonate, where highly reproducible results are obtained over long run‐times at high supersaturations. This compares with conventional devices that use a Y‐junction to achieve solution loading, where in‐channel precipitation of calcium carbonate occurs even at low supersaturations. This work not only opens the door to the use of microfluidics to study the crystallization of low solubility compounds, but the simple design of a passive picoinjector will find wide utility in areas including multistep reactions and investigation of reaction dynamics

A review of thermal management for Li-ion batteries: Prospects, challenges, and issues

Li-ion batteries are essential component in the current generation of electric vehicles. However, further pushing electric vehicles are concerned with battery life. Since the temperature dictates battery lifetime, it is crucial to manage the heat and keep the temperature at an acceptable range within the battery pack. The benefit of a cooling system is to prevent the premature degradation of battery life. This paper provides a critical review of the so far thermal management strategy dealing with temperature within the cells, module, and packs. This paper reviews the advantages and disadvantages of state of the art (traditional) thermal cooling system. In this paper, we have reviewed separately cell, module, and pack level cooling system. The battery thermal modeling techniques and cooling system design challenges are also reviewed. This paper also reviews the future cooling system for future vehicles with rising fast charge rate and these techniques can improve the limitations of the traditional cooling system. This paper also suggests the best suitable and economically viable technology for the upcoming EVs issues

Observation of the electromagnetic doubly OZI-suppressed decay J/ψ→ϕπ0J/\psi \rightarrow \phi \pi^{0}

Using a sample of $1.31$ billion $J/\psi$ events accumulated with the BESIII detector at the BEPCII collider, we report the observation of the decay $J/\psi \rightarrow \phi\pi^{0}$, which is the first evidence for a doubly Okubo-Zweig-Iizuka suppressed electromagnetic $J/\psi$ decay. A clear structure is observed in the $K^{+} K^{-}$ mass spectrum around 1.02 GeV/$c^2$, which can be attributed to interference between $J/\psi \rightarrow \phi\pi^{0}$ and $J/\psi \rightarrow K^{+}K^{-}\pi^{0}$ decays. Due to this interference, two possible solutions are found. The corresponding measured values of the branching fraction of $J/\psi \to \phi\pi^{0}$ are $[2.94 \pm 0.16\text{(stat.)} \pm 0.16\text{(syst.)}] \times 10^{-6}$ and $[1.24 \pm 0.33\text{(stat.)} \pm 0.30\text{(syst.)}] \times 10^{-7}$.Comment: 7 pages, 4 figures, published in Phys. Rev.

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

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

Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin

Recent genomic analyses of pathologically-defined tumor types identify “within-a-tissue” disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head & neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multi-platform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All datasets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies