Miracle-dz/UniFAR-FTUs huggingface dataset:
Are Japanese older adults rejuvenating? Changes in health-related measures among older community dwellers in the last decade.

During the last three decades, Japan has become one of the world's top countries for longevity, and the increase in average life expectancy is accompanied by a sharp rise in older population aged 65 years and above to approximately 28%. This study aimed to examine the changes in major health-related measures including physical constitution, physical function, and functional capacity of community-dwelling Japanese older people in the last decade. From the data of 13 longitudinal cohort studies on aging conducted in Japan with a total of 13,441 older subjects, the present study analyzed the changes in six indices that are related to health and functioning of the older people; height, weight, BMI, walking speed, grip strength, and instrumental ADL, between 2007 (± 2 years) and 2017 (± 2 years). Comparison of data for the two periods between subjects matched for age group and gender evidently showed better health status and a slower decline in most of the health-related measures in 2017 compared to a decade ago. The results of the present study indicate that the phenomenon of "rejuvenation" is occurring among the new generation of Japanese older adults, and the importance of this older population as a social resource in the super-aged society should be re-acknowledged.
Influence of type of dairy matrix micro- and macrostructure on in vitro lipid digestion.

Recent research indicates that the food matrix can influence digestion kinetics and uptake of nutrients, thus affecting human health. The aim of this study was to obtain knowledge on how variations in microstructure and texture of foods represented by four dairy products; (i) cheddar cheese, (ii) a homogenized cheddar cheese, (iii) a micellar casein and cream drink or (iv) a micellar casein and cream gel, all of identical nutrient ratios of protein : fat and calcium : fat, affect the in vitro digestibility kinetics of lipids. Rheology of the four dairy structures was measured at 10 °C and 37 °C before digestion, and during the gastric phase of in vitro digestion. During digestion cheddar cheese was most resistant to enzymatic and mechanical disintegration, followed by homogenized cheese, while both the drink and gel had low resistance and dissolved in the gastric juice. Particle size, fat droplet size and microstructure were assessed by light scattering and confocal microscopy during digestion. Significantly larger fat droplets were observed during digestion of the cheddar cheese sample. The release of free fatty acids during the initial intestinal digestion showed cheddar cheese to provide a significantly lower release than homogenized cheese, whereas the drink and gel both had significantly higher free fatty acid release. The results suggest that the cheese matrix resistance to degradation and its large fat droplets were responsible for a slower fat digestion.
Impact of Microbiome on Hepatic Metabolizing Enzymes and Transporters in Mice during Pregnancy

The microbiome and pregnancy are known to alter drug disposition, yet the interplay of the two physiologic factors on the expression and/or activity of drug metabolizing enzymes and transporters (DMETs) is unknown. This study investigated the effects of microbiome on host hepatic DMETs in mice during pregnancy by comparing four groups of conventional (CV) and germ-free (GF) female mice and pregnancy status, namely, CV nonpregnant, GF non-pregnant, CV pregnant, and GF pregnant mice. Transcriptomic and targeted proteomics of hepatic DMETs were profiled by using multiomics. Plasma bile acid and steroid hormone levels were quantified by liquid chromatography tandem mass spectrometry. CYP3A activities were measured by mouse liver microsome incubations. The trend of pregnancy-induced changes in the expression or activity of hepatic DMETs in CV and GF mice was similar; however, the magnitude of change was noticeably different. For certain DMETs, pregnancy status had paradoxical effects on mRNA and protein expression in both CV and GF mice. For instance, the mRNA levels of Cyp3a11, the murine homolog of human CYP3A4, were decreased by 1.7-fold and 3.3-fold by pregnancy in CV and GF mice, respectively; however, the protein levels of CYP3A11 were increased similarly ∼twofold by pregnancy in both CV and GF mice. Microsome incubations revealed a marked induction of CYP3A activity by pregnancy that was 10-fold greater in CV mice than that in GF mice. This is the first study to show that the microbiome can alter the expression and/or activity of hepatic DMETs in pregnancy. SIGNIFICANCE STATEMENT We demonstrated for the first time that microbiome and pregnancy can interplay to alter the expression and/or activity of hepatic drug metabolizing enzymes and transporters. Though the trend of pregnancy-induced changes in the expression or activity of hepatic drug metabolizing enzymes and transporters in conventional and germ-free mice was similar, the magnitude of change was noticeably different.
Engineering the specificity of Streptococcus pyogenes sortase A by loop grafting

Sortases are a group of enzymes displayed on the cell‐wall of Gram‐positive bacteria. They are responsible for the attachment of virulence factors onto the peptidoglycan in a transpeptidation reaction through recognition of a pentapeptide substrate. Most housekeeping sortases recognize one specific pentapeptide motif; however, Streptococcus pyogenes sortase A (SpSrtA WT) recognizes LPETG, LPETA and LPKLG motifs. Here, we examined SpSrtA's flexible substrate specificity by investigating the role of the β7/β8 loop in determining substrate specificity. We exchanged the β7/β8 loop in SpSrtA with corresponding β7/β8 loops from Staphylococcus aureus (SaSrtA WT) and Bacillus anthracis (BaSrtA WT). While the BaSrtA‐derived variant showed no enzymatic activity toward either LPETG or LPETA substrates, the activity of the SaSrtA‐derived mutant toward the LPETA substrate was completely abolished. Instead, the mutant had an improved activity toward LPETG, the preferred substrate of SaSrtA WT.
The effect of low-volume high-intensity interval training on cardiometabolic health and psychological responses in overweight/obese middle-aged men

ABSTRACT High-intensity interval training (HIIT) has been proposed as a time-efficient exercise protocol to improve metabolic health, but direct comparisons with higher-volume moderate-intensity continuous training (MICT) under unsupervised settings are limited. This study compared low-volume HIIT and higher-volume MICT interventions on cardiometabolic and psychological responses in overweight/obese middle-aged men. Twenty-four participants (age: 48.1±5.2yr; BMI: 25.8±2.3kg·m−2) were randomly assigned to undertake either HIIT (10 X 1-min bouts of running at 80–90% HRmax separated by 1-min active recovery) or MICT (50-min continuous jogging/brisk walking at 65–70% HRmax) for 3 sessions/week for 8 weeks (2-week supervised + 6-week unsupervised training). Both groups showed similar cardiovascular fitness (VO2max) improvement (HIIT: 32.5±5.6 to 36.0±6.2; MICT: 34.3±6.0 to 38.2±5.1mL kg−1 min−1, p < 0.05) and %fat loss (HIIT: 24.5±3.4 to 23.2±3.5%; MICT: 23.0±4.3 to 21.5±4.1%, p< 0.05) over the 8-week intervention. Compared to baseline, MICT significantly decreased weight and waist circumference. No significant group differences were observed for blood pressure and cardiometabolic blood markers such as lipid profiles, fasting glucose and glycated haemoglobin. Both groups showed similar enjoyment levels and high unsupervised adherence rates (>90%). Our findings suggest that low-volume HIIT can elicit a similar improvement of cardiovascular fitness as traditional higher-volume MICT in overweight/obese middle-aged men.
Image-based Malware Family Detection: An Assessment between Feature Extraction and Classification Techniques

: The increasing number of malware in mobile environment follows the continuous growth of the app stores, which required constant research in new malware detection approaches, considering also the weaknesses of signature-based anti-malware software. Fortunately, most of the malware are composed of well-known pieces of code, thus can be grouped into families sharing the same malicious behaviour. One interesting approach, which makes use of Image Classiﬁcation techniques, proposes to convert the malware binaries to images, extract feature vectors and classifying them with supervised machine learning models. Realizing that re-searchers usually evaluate their solutions on private datasets, it is difﬁcult to establish whether a model can be generalized on another dataset, making it difﬁcult to compare the performance of the various models. This paper presents a comparison between different combination of feature vector extraction methods and machine learning models. The methodology aimed to evaluate feature extractors and supervised machine learning al-gorithms, and it was tested on more than 20 thousand images of malware, grouped into 10 different malware families. The best classiﬁer, a combination of GIST descriptors and Random Forest classiﬁers, achieved an accuracy of 0.97 on average.
Succinate Uptake by Free-living and Bacteroid Forms of Rhizobium leguminosarum

Free-living cells of Rhizobium leguminosarum possess a constitutive succinate uptake system. Bacteroids isolated from nodules of Pisum sativum also showed immediate uptake of succinate. In both cases the uptake of [14C] succinate appeared to be dependent on an energized membrane. Fumarate, malate and several succinate analogues were also transported via the succinate system. One or both of the carboxyl groups of the succinate molecule must be free in order to be recognized by the carrier. Glucose had effects on the uptake or metabolism of succinate.
Technologies for Opioid Use Disorder Management: Mobile App Search and Scoping Review

Background Advances in technology engender the investigation of technological solutions to opioid use disorder (OUD). However, in comparison to chronic disease management, the application of mobile health (mHealth) to OUD has been limited. Objective The overarching aim of our research was to design OUD management technologies that utilize wearable sensors to provide continuous monitoring capabilities. The objectives of this study were to (1) document the currently available opioid-related mHealth apps, (2) review past and existing technology solutions that address OUD, and (3) discuss opportunities for technological withdrawal management solutions. Methods We used a two-phase parallel search approach: (1) an app search to determine the availability of opioid-related mHealth apps and (2) a scoping review of relevant literature to identify relevant technologies and mHealth apps used to address OUD. Results The app search revealed a steady rise in app development, with most apps being clinician-facing. Most of the apps were designed to aid in opioid dose conversion. Despite the availability of these apps, the scoping review found no study that investigated the efficacy of mHealth apps to address OUD. Conclusions Our findings highlight a general gap in technological solutions of OUD management and the potential for mHealth apps and wearable sensors to address OUD.
Immediate targets of ETTIN suggest a key role for pectin methylesterase inhibitors in the control of Arabidopsis gynecium development

ABSTRACT The control of gynecium development in Arabidopsis thaliana by the auxin response factor ETTIN (ETT) correlates with a reduction in the methylesterification of cell-wall pectins and a decrease in cell-wall stiffness in the valve tissues of the ovary. Here, we determine the list of genes rapidly regulated following the in-vivo activation of an ETT fusion protein, and show these to be significantly enriched in genes encoding cell-wall proteins, including several pectin methylesterases (PMEs) and pectin methylesterase inhibitors (PMEIs). We also perform a genome-wide scan for potential ETT-binding sites, and incorporate the results of this procedure into a comparison of datasets, derived using four distinct methods, to identify genes regulated directly or indirectly by ETT. We conclude from our combined analyses that PMEIs are likely to be key actors that mediate the regulation of gynecium development by ETT, while ETT may simultaneously regulate PMEs to prevent exaggerated developmental effects from the regulation of PMEIs. We also postulate the existence of one or more rapidly-acting intermediate factors in the transcriptional regulation of PMEs and PMEIs by ETT.
Twelve Weeks of Whole Body Vibration Training Improve Regucalcin, Body Composition and Physical Fitness in Postmenopausal Women: A Pilot Study

(1) Background: Regucalcin or senescence marker protein 30 (SMP30) is a Ca2+ binding protein discovered in 1978 with multiple functions reported in the literature. However, the impact of exercise training on SMP30 in humans has not been analyzed. Aging is associated with many detrimental physiological changes that affect body composition, functional capacity, and balance. The present study aims to investigate the effects of whole body vibration (WBV) in postmenopausal women. (2) Methods: A total of 13 women (aged 54.3 ± 3.4 years) participated in the study. SMP30, body composition (fat mass, lean mass, and bone mass) and physical fitness (balance, time up and go (TUG) and 6-min walk test (6MWT)) were measured before and after the 12 weeks of WBV training. (3) Results: The WBV training program elicited a significant increase in SPM30 measured in plasma (27.7%, p = 0.004) and also in 6MWT (12.5%, p < 0.001). The WBV training also significantly reduced SPM30 measured in platelets (38.7%, p = 0.014), TUG (23.1%, p < 0.001) and total body fat mass (4.4%, p = 0.02). (4) Conclusions: There were no significant differences in balance, lean mass or bone mass. The present study suggests that 12 weeks of WBV has the potential to improve SPM30, fat mass, TUG and 6MWT in postmenopausal women.
Cerebral vasomotor reactivity in migraine: effect of patent foramen ovale and aerogenic microembolism

ABSTRACT Objective The first data on the effect of presence of patent foramen ovale (PFO) with high-volume right-to-left shunt (RLS) on cerebral vasomotor reactivity (CVMR) in migraineurs are herein presented. In addition, the immediate effect of air microbubbles on CVMR has been determined. Methods Breath-holding index (BHI) and percent velocity decrease during hyperventilation (HPV) tests were performed before and after agitated saline injections in bilateral middle and posterior cerebral arteries (MCA and PCA) in 38 migraineurs (19 with aura) and 18 control subjects. Results Presence of PFO correlated with a significant decrease of MCA BHI (1.43 ± 0.39 vs 1.04 ± 0.67, p = 0.032) and marginal reduction of PCA BHI (1.25 ± 0.46 vs. 1.01 ± 0.39, p = 0.090) in migraineurs. After agitated saline injection, PCA BHI significantly decreased from 1.03 to 0.78 (p = 0.007) in patients with PFO, from 1.15 to 0.91 (p = 0.014) in those without PFO, and from 1.01 to 0.76 (p = 0.023) in subjects with migraine and PFO. No significant MCA BHI difference was noted soon after bubble injection. Conclusions The presence of high grade RLS is associated with reduced vasodilatory CVMR in migraineurs. Further decrease of CVMR of PCA upon aerogenic microemboli passage may support the mechanism of ‘facilitation with subclinical cerebral ischemia caused by microembolism’, hypothesis explaining the onset of migraine. Abbreviations BHI: Breath-holding index; BHT: Breath Holding Test; CVMR: Cerebral vasomotor reactivity; EDV: End-diastolic velocity; HIT-6: Headache Impact Test; HPV: Hyperventilation; MCA: Middle cerebral artery; MIDAS: migraine disability Assessment score; PCA: Posterior cerebral artery; PFO: Patent foramen ovale; PI: Pulsatility index; PSV: Peak systolic velocity; RLS: Right-to-left shunt; TCD: Transcranial Doppler; Vmean: Mean velocity.
Can Psychopathy Be Adaptive at Work? Development and Application of a Work Focused Self- and Other-Report Measure of the Triarchic Psychopathy Model

Psychopathy may have both adaptive and maladaptive effects at work but research into workplace psychopathy is constrained by the lack of short, work-relevant measures that can be used for both self- and other-report. We adapt the Triarchic Psychopathy Measure (TriPM) for this purpose and distinguish the (mal)adaptive effects of psychopathy at work in two time-lagged survey samples. Sample 1 consisted of managers reporting their psychopathic traits and work outcomes (well-being, engagement, burnout and job performance). Sample 2 reported on their managers’ psychopathic traits and leadership styles (servant and abusive supervision) and their own work outcomes. The TriPM (Work) is a reliable, valid, 21-item measure of triarchic psychopathy at work with self- and other-report forms. Using this measure, we demonstrate that the triarchic model’s boldness trait is related to servant leadership and predicts improved well-being and performance while meanness and disinhibition are related to abusive supervision and predict increased burnout.
Blockchain-based Traceability of Carbon Footprint: A Solidity Smart Contract for Ethereum

In recent decades there has been an increasing concern about climate change. Every person is increasingly concerned about global warming and, as a consumer, with their own individual contribute to that issue, wich may be measured by each one’s carbon footprint. In this sense, it is only natural that each person wants to consume products with a lower carbon footprint, meaning with a lower environmental impact. For this, however, consumers need to be able to know the carbon footprint of the products they are buying. This is only possible by having every company tracking and sharing their own products carbon footprint. The blockchain is a distributed technology that allows for registering and sharing information between those companies and the final consumers. The blockchain is being used in many areas as a distributed database, and has some strong points like trust, transparency, security, immutability, durability, disintermediation and others. In this paper the blockchain technology is being used to track and trace back the carbon footprint of products and organizations. More exactly, this paper proposes a smart contract-based platform for the traceability of the carbon footprint of products and organizations.
Lenalidomide before and after autologous stem cell transplantation for transplant-eligible patients of all ages in the randomized, phase III, Myeloma XI trial

The optimal way to use immunomodulatory drugs as components of induction and maintenance therapy for multiple myeloma is unresolved. We addressed this question in a large phase III randomized trial, Myeloma XI. Patients with newly diagnosed multiple myeloma (n=2,042) were randomized to induction therapy with cyclophosphamide, thalidomide, and dexamethasone (CTD) or cyclophosphamide, lenalidomide, and dexamethasone (CRD). Additional intensification therapy with cyclophosphamide, bortezomib, and dexamethasone (CVD) was administered before autologous stem-cell transplantation to patients with a suboptimal response to induction therapy using a response-adapted approach. After receiving high-dose melphalan with autologous stem cell transplantation, eligible patients were further randomized to receive either lenalidomide alone or observation alone. Co-primary endpoints were progression-free survival (PFS) and overall survival (OS). The CRD regimen was associated with significantly longer PFS (median: 36 vs. 33 months; hazard ratio [HR], 0.85; 95% confidence interval [CI]: 0.75-0.96; P=0.0116) and OS (3-year OS: 82.9% vs. 77.0%; HR, 0.77; 95% CI: 0.63-0.93; P=0.0072) compared with CTD. The PFS and OS results favored CRD over CTD across all subgroups, including patients with International Staging System stage III disease (HR for PFS, 0.73; 95% CI: 0.58-0.93; HR for OS, 0.78; 95% CI: 0.56-1.09), high-risk cytogenetics (HR for PFS, 0.60; 95% CI: 0.43-0.84; HR for OS, 0.70; 95% CI: 0.42-1.15) and ultra-high-risk cytogenetics (HR for PFS, 0.67; 95% CI: 0.41-1.11; HR for OS, 0.65; 95% CI: 0.34-1.25). Among patients randomized to lenalidomide maintenance (n=451) or observation (n=377), maintenance therapy improved PFS (median: 50 vs. 28 months; HR, 0.47; 95% CI: 0.37-0.60; P<0.0001). Optimal results for PFS and OS were achieved in the patients who received CRD induction and lenalidomide maintenance. The trial was registered with the EU Clinical Trials Register (EudraCT 2009-010956-93) and ISRCTN49407852.
Anti-hepatoma effect of taccalonolide A through suppression of sonic hedgehog pathway

Abstract Taccalonolide A has been reported to have anti-tumour efficiency. However, the underlying mechanism for taccalonolides A therapy of hepatocellular carcinoma (HCC) is still obscure. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. Apoptosis was determined by flow cytometry. Protein expression of B cell lymphoma (Bcl-2), Bcl-2 associated X (Bax), sonic hedgehog (Shh), Smoothened (Smo) and Gli family zinc finger 1 (Gli1) was analyzed by western blot. The expression of Shh, Smo and Gli1 mRNA was determined using quantitative real-time polymerase chain reaction (qRT-PCR). Results showed that taccalonolide A inhibited cell proliferation, induced apoptosis and cell cycle arrest at the G0/G1 phase, and improved the cytotoxicity of sorafenib in HCC cells. The expressions of Shh, Smo, Gli1 mRNA and protein were decreased after taccalonolide A treatment. More importantly, activation of the Shh pathway attenuated taccalonolide A-induced inhibition on cell viability and promotion on apoptosis and cell cycle arrest in HCC. Also, activation of the Shh pathway neutralized the effect of taccalonolide A on sorafenib cytotoxicity in HCC. We clarified that taccalonolide A suppressed cell viability facilitated apoptosis, and improved the cytotoxicity of sorafenib in HCC by inhibition of the activation of the Shh pathway, providing alternative treatments for HCC.
Investigating Phishing on Demand

Gathering protected information by disguising an attacker as a trustworthy contact in electronic communication, also known as “phishing,” is the primary technique attackers use to steal sensitive data. Phishing websites are mainly static and barely synchronize with the original website. We investigate “Phishing on Demand”, a technique to dynamically replicate any website for phishing purposes. The replicas are available with a few clicks and are always in sync with the original web pages. Our studies with a proof of concept show that this phishing technique is highly effective. For instance, we could successfully run phishing campaigns against major Swiss e-banking websites with two-factor authentication. With this thesis, we show that there is a demand for more robust visual similarity algorithms for websites that are able to track changes applied to original sites such as insertions of banners, rewritings of text, or alterations to graphics.