Fiber Optical Tweezers for Applying and Measuring Forces in a 3D Solid Compartment

We developed an inclined dual fiber optical tweezers (DFOTs) for simultaneous force application and measurements in a 3D hydrogel matrix. The inclined DFOTs provide a potential solution for cell mechanics study in a three-dimensional matrix

Covid-19 vaccines production and societal immunization under the serendipity-mindsponge-3D knowledge management theory and conceptual framework

Since the outbreak of the Coronavirus disease 2019 (Covid-19), tremendous efforts have been made by scientists, health professionals, business people, politicians, and laypeople around the world. Covid-19 vaccines are one of the most crucial innovations that help fight against the virus. This paper attempts to revisit the Covid-19 vaccines production process by employing the serendipity-mindsponge-3D creativity management theory. Vaccine production can be considered an information process and classified into three main stages. The first stage involved the processes of absorbing information (e.g., digital data and open science) and rejecting unhelpful information (e.g., misinformation and fake news) for effectively acquiring useful insights. Useful insights were later employed by experts, enterprises, governments, and international organizations through interdisciplinary coordinated efforts for developing vaccines within a short period. Finally, the appearance of multiple types of vaccines enabled more strategic options for vaccine distribution and administration. Findings from this vaccine creativity management process could be used as critical lessons for further improvements of vaccination programs

Mechanobiology as a tool for addressing the genotype-to- phenotype problem in microbiology

The central hypothesis of the genotype–phenotype relationship is that the phenotype of a developing organism (i.e., its set of observable attributes) depends on its genome and the environment. However, as we learn more about the genetics and biochemistry of living systems, our understanding does not fully extend to the complex multiscale nature of how cells move, interact, and organize; this gap in understanding is referred to as the genotype-to-phenotype problem. The physics of soft matter sets the background on which living organisms evolved, and the cell environment is a strong determinant of cell phenotype. This inevitably leads to challenges as the full function of many genes, and the diversity of cellular behaviors cannot be assessed without wide screens of environmental conditions. Cellular mechanobiology is an emerging field that provides methodologies to understand how cells integrate chemical and physical environmental stress and signals, and how they are transduced to control cell function. Biofilm forming bacteria represent an attractive model because they are fast growing, genetically malleable and can display sophisticated self-organizing developmental behaviors similar to those found in higher organisms. Here, we propose mechanobiology as a new area of study in prokaryotic systems and describe its potential for unveiling new links between an organism\u27s genome and phenome

Effect of calcium chloride treatment by vacuum infiltration method on texture and shelf life of black cherry tomatoes (Solanum lycopersicum cv. OG)

The use of vacuum infiltration in the food industry has several advantages, such as improving the quality, eliminating chemical treatment requirements, stabilizing products, and retaining nutrients during storage and processing. This study was performed to optimize the vacuum level (516-684 mmHg), treatment time (10-20 min), and calcium chloride (CaCl2) concentration (0.58- 1.42%) using the Response Surface Methodology (RSM). The firmness of black cherry tomatoes (Solanum lycopersicum cv. OG) reached an optimum value (1477.81 g/cm2) when fruits were treated at a vacuum level of 637 mmHg with a concentration of CaCl2 1.09% for 17 min. Meanwhile, the firmness was 746 g/cm2 for the control sample, which was dipped in 1.42% CaCl2 solution for 20 min at the atmospheric condition. The scanning electron microscope (SEM) images of stomata of two samples with/without vacuum treatment were also significantly different. The sample after vacuum treatment at optimum parameters was put into PE and PP bags for storage at 10-12°C. Vacuum-infiltrated tomatoes contained in PE and PP bags had a corresponding storage time of 30 and 28 days. The control samples were maintained for shorter periods, only 22 and 20 days, respectively

A Multinational Data Set of Game Players' Behaviors in a Virtual World and Environmental Perceptions

Video gaming has been rising rapidly to become one of the primary entertainment media, especially during the COVID-19 pandemic. Playing video games has been reported to associate with many psychological and behavioral traits. However, little is known about the connections between game players' behaviors in the virtual environment and environmental perceptions. Thus, the current data set offers valuable resources regarding environmental worldviews and behaviors in the virtual world of 640 Animal Crossing: New Horizons (ACNH) game players from 29 countries around the globe. The data set consists of six major categories: 1) socio-demographic profile, 2) COVID-19 concern, 3) environmental perception, 4) game-playing habit, 5) in-game behavior, and 6) game-playing feeling. By making this data set open, we aim to provide policymakers, game producers, and researchers with valuable resources for understanding the interactions between behaviors in the virtual world and environmental perceptions, which could help produce video games in compliance with the United Nations (UN) Sustainable Development Goals

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Effects of cancerous mutations on mechanosensing of cells

The ability of cells to sense mechanical cues is essential for normal cell function, tissue development, and wound healing. Aberrant sensitivity to mechanical cues from the extracellular environment has been observed in cancer cells and many other types of diseases. Abnormal activities/expression of several proteins have been identified as hallmarks of cancer. Understanding how these proteins regulate the mechanosensing ability of cells would further explore the potential usage of these proteins as targets for cancer therapeutics. In this study, we characterized the effects of three prominent cancer markers used in pharmacology–vimentin, PTEN and KRAS–on cells’ mechanosensing behavior. We observed that lowering the level of vimentin expression in fibroblasts reduces the cell traction force but does not affect mechanosensing ability. These results suggest that the function of vimentin in mechanosensing is facilitating the force transmission inside cells. By studying the effects of knocking out PTEN and overexpressing KRAS in MCF-10A breast epithelial cells, we investigated the impacts of cancer-associated pathways PI3K/AKT and Ras/MAPK on mechanosensing. Knocking out PTEN abolished mechanosensing ability and inhibited the formation of stress fibers–bundles of actin filaments –which is critical for force transmission and hence mechanosensing. Overexpressing KRAS promotes stress fiber formation but did not significantly affect the mechanosensing of MCF-10A. Furthermore, KRAS overexpression overturns the effects of PTEN knockout on stress fiber and rescues the mechanosensing ability of PTEN knockout cells. Our results suggest that both the PI3K/AKT pathway (upregulated via PTEN loss) and the KRAS/MAPK pathway (upregulated via KRAS overexpression) impact mechanosensing through their effects on the actin cytoskeleton. More importantly, we unveiled that the crosstalk of these two pathways co-modulates mechanosensing and cell migration

Monte Carlo characterization of the AAPM Task Group 43 Dosimetry Parameters for the M-15 high dose rate Iridium-192 brachytherapy source

The Source Production & Equipment Co. (SPEC) Model M-15 Iridium Brachytherapy is intended for use as a temporary High Dose Rate (HDR) Brachytherapy source. The clinical dosimetry parameters of this source was calculated using the MCNP Monte Carlo analysis program (MCNP6; Los Alamos National Laboratory) in accordance to the updated AAPM Task Group Report No.43 (TG43U1). All TG43U1 dosimetry parameters and their respective statistical uncertainty are presented in the reports