Miracle-dz/UniFAR-FTUs huggingface dataset:
pH-Sensitive Mixed Micelles Assembled from PDEAEMA-PPEGMA and PCL-PPEGMA for Doxorubicin Delivery: Experimental and DPD Simulations Study

To decrease critical micelle concentration (CMC), improve stability, and keep high drug-loading capacity, three pH-sensitive mixed micelles applied for anticancer drug controlled delivery were prepared by the mixture of polymers poly (N,N-diethylaminoethyl methacrylate)-b-poly(poly(ethylene glycol) methyl ether methacrylate) (PDEAEMA-PPEGMA) and polycaprolactone-b-poly (poly(ethylene glycol) methyl ether methacrylate) (PCL-PPEGMA), which were synthesized and confirmed by 1H NMR and gel permeation chromatographic (GPC). The critical micelle concentration (CMC) values of the prepared mixed micelles were low, and the micellar sizes and zeta potentials of the blank mixed micelles demonstrated good pH-responsive behavior. Combined experimental techniques with dissipative particle dynamics (DPD) simulation, the particle sizes, zeta potentials, drug loading content (LC), encapsulation efficiency (EE), aggregation morphologies, and doxorubicin (DOX) distribution of the mixed micelles were investigated, and the high DOX-loading capacity of the mixed micelles was found. Both in vitro DOX release profiles and DPD simulations of the DOX dynamics release process exhibited less leakage and good stability in neutral conditions and accelerated drug release behavior with a little initial burst in slightly acidic conditions. Cytotoxicity tests showed that the polymer PDEAEMA-PPEGMA and the blank mixed micelles had good biocompatibility, and DOX-loaded mixed micelles revealed certain cytotoxicity. These results suggest that the drug-loaded mixed micelles that consisted of the two polymers PDEAEMA-PPEGMA and PCL-PPEGMA can be new types of pH-responsive well-controlled release anticancer drug delivery mixed micelles.
INCIDENCE AND OUTCOME OF NEUROLOGICAL SEQUELAE IN SURVIVORS OF CEREBRAL MALARIA

: This hospital based study was carried out on 185 adult patients of cerebral malaria. Out of 185 patients, 62 (33.5%) died and 123 (66.5%) survived. Neurological sequelae were present in 13 (10.5%) of 123 survivors at the time of discharge (i.e. 10-15 days after recovery from coma) from the hospital. These were in form of psychosis in 5 patients (4%), cerebellar ataxia in 4 patients (3.2%), extrapyramidal rigidity in 2 patients (1.62%) and hemiplegia in 2 patients (1.62%).
Vitamin E does not prevent Western diet-induced NASH progression and increases metabolic flux dysregulation in mice

Fatty liver involves ectopic lipid accumulation and dysregulated hepatic oxidative metabolism, which can progress to a state of elevated inflammation and fibrosis referred to as nonalcoholic steatohepatitis (NASH). The factors that control progression from simple steatosis to NASH are not fully known. Here, we tested the hypothesis that dietary vitamin E (VitE) supplementation would prevent NASH progression and associated metabolic alterations induced by a Western diet (WD). Hyperphagic melanocortin-4 receptor-deficient (MC4R−/−) mice were fed chow, chow+VitE, WD, or WD+VitE starting at 8 or 20 weeks of age. All groups exhibited extensive hepatic steatosis by the end of the study (28 weeks of age). WD feeding exacerbated liver disease severity without inducing proportional changes in liver triglycerides. Eight weeks of WD accelerated liver pyruvate cycling, and 20 weeks of WD extensively upregulated liver glucose and oxidative metabolism assessed by 2H/13C flux analysis. VitE supplementation failed to reduce the histological features of NASH. Rather, WD+VitE increased the abundance and saturation of liver ceramides and accelerated metabolic flux dysregulation compared with 8 weeks of WD alone. In summary, VitE did not limit NASH pathogenesis in genetically obese mice, but instead increased some indicators of metabolic dysfunction.
Nutrigenomics and Breast Cancer: State-of-Art, Future Perspectives and Insights for Prevention

Proper nutrition plays a major role in preventing diseases and, therefore, nutritional interventions constitute crucial strategies in the field of Public Health. Nutrigenomics and nutriproteomics are arising from the integration of nutritional, genomics and proteomics specialties in the era of postgenomics medicine. In particular, nutrigenomics and nutriproteomics focus on the interaction between nutrients and the human genome and proteome, respectively, providing insights into the role of diet in carcinogenesis. Further omics disciplines, like metabonomics, interactomics and microbiomics, are expected to provide a better understanding of nutrition and its underlying factors. These fields represent an unprecedented opportunity for the development of personalized diets in women at risk of developing breast cancer.
RABL6A Is an Essential Driver of MPNSTs that Negatively Regulates the RB1 Pathway and Sensitizes Tumor Cells to CDK4/6 Inhibitors

Purpose: Malignant peripheral nerve sheath tumors (MPNST) are deadly sarcomas that lack effective therapies. In most MPNSTs, the retinoblastoma (RB1) tumor suppressor is disabled by hyperactivation of cyclin-dependent kinases (CDK), commonly through loss of CDK-inhibitory proteins such as p27(Kip1). RABL6A is an inhibitor of RB1 whose role in MPNSTs is unknown. To gain insight into MPNST development and establish new treatment options, we investigated RABL6A-RB1 signaling and CDK inhibitor–based therapy in MPNSTs. Experimental Design: We examined patient-matched MPNSTs and precursor lesions by RNA sequencing (RNA-Seq) and IHC. Molecular and biological effects of silencing RABL6A and/or p27 in MPNST lines and normal human Schwann cells were determined. Tumor-suppressive effects of CDK inhibitors were measured in MPNST cells and orthotopic tumors. Results: RABL6A was dramatically upregulated in human MPNSTs compared with precursor lesions, which correlated inversely with p27 levels. Silencing RABL6A caused MPNST cell death and G1 arrest that coincided with p27 upregulation, CDK downregulation, and RB1 activation. The growth-suppressive effects of RABL6A loss, and its regulation of RB1, were largely rescued by p27 depletion. Importantly, reactivation of RB1 using a CDK4/6 inhibitor (palbociclib) killed MPNST cells in vitro in an RABL6A-dependent manner and suppressed MPNST growth in vivo. Low-dose combination of drugs targeting multiple RB1 kinases (CDK4/6, CDK2) had enhanced antitumorigenic activity associated with potential MPNST cell redifferentiation. Conclusions: RABL6A is a new driver of MPNST pathogenesis that acts in part through p27-RB1 inactivation. Our results suggest RB1 targeted therapy with multiple pathway drugs may effectively treat MPNSTs.
A unique feature of swine ANP32A provides susceptibility to avian influenza virus infection in pigs

Both the replication and transcription of the influenza virus are catalyzed by the viral polymerase complex. The polymerases of most avian influenza A viruses have poor performance in mammalian cells, which is considered to be one of the important species barriers. Pigs have been long considered as important intermediate hosts for interspecies transmission of the avian influenza virus, because of their susceptibility to infection with both avian and mammalian influenza viruses. However, the molecular basis of influenza polymerase adaptation in pigs remains largely unknown. ANP32A and ANP32B proteins have been identified as playing fundamental roles in influenza virus replication and host range determination. In this study, we found that swine ANP32A (swANP32A), unlike swine ANP32B or other mammalian ANP32A or B, shows stronger supporting activity to avian viral polymerase. Knockout of ANP32A in pig cells PK15 dramatically reduced avian influenza polymerase activity and viral infectivity, suggesting a unique feature of swANP32A in supporting avian influenza viral polymerase. This species-specific activity is mapped to two key sites, 106V and 156S, in swANP32A. Interestingly, the amino acid 106V is unique to pigs among all the vertebrate species studied, and when combined with 156S, exhibits positive epistasis in pigs. Mutation of 106V and 156S to the signature found in ANP32As from other mammalian species weakened the interaction between swANP32A and chicken viral polymerase, and reduced polymerase activity. Understanding the molecular basis of ANP32 proteins may help to discover new antiviral targets and design avian influenza resistant genome edited pigs.
Adherence to Timely Vaccinations in the United States

Using the 2014 NIS, we estimated the association between recommended and nonrecommended vaccination patterns and up-to-date status of early childhood immunizations. OBJECTIVES: To estimate (1) the proportion of children not adhering to the Advisory Committee on Immunization Practices (ACIP) recommended early childhood immunization schedule and (2) associations between schedule adherence, sociodemographic characteristics, and up-to-date immunization status by 19 to 35 months of age. METHODS: We used 2014 National Immunization Survey provider-verified vaccination data to classify vaccination patterns as “recommended” (ie, in line with ACIP dose- and age-specific recommendations), “alternate” (ie, in line with either limiting the number of shots per visit or skipping at least 1 vaccine series), or “unknown or unclassifiable” (ie, not in line with ACIP recommendations or clearly limiting shots per visit or vaccine series). We evaluated the association between vaccination patterns and up-to-date status for all ACIP-recommended vaccinations (including rotavirus and hepatitis A vaccines) using Poisson regression. RESULTS: The majority of children’s patterns were classified as “recommended” (63%), with 23% and 14% following alternate or unknown or unclassifiable patterns, respectively; 58% of children were up-to-date with all ACIP-recommended immunizations by 19 to 35 months. Not being up-to-date was associated with alternate (prevalence ratio = 4.2, 95% confidence interval: 3.9–4.5) and unknown or unclassifiable (prevalence ratio = 2.4, 95% confidence interval: 2.2–2.7) patterns. CONCLUSIONS: High vaccine coverage by 19 to 35 months of age may miss nonadherence to the recommended immunization schedule in the first 18 months of life, leaving children vulnerable to preventable diseases. With more than one-third of US children not following the ACIP schedule, targeted interventions are needed to minimize vaccine delays and disease susceptibility.
Drivers of global Scolytinae invasion patterns.

Biological invasions are affected by characteristics of invading species, strength of pathway connectivity among world regions and habitat characteristics of invaded regions. These factors may interact in complex ways to drive geographical variation in numbers of invasions among world regions. Understanding the role of these drivers provides information that is crucial to the development of effective biosecurity policies. Here we assemble for the first time a global database of historical invasions of Scolytinae species and explore factors explaining geographical variation in numbers of species invading different regions. This insect group includes several pest species with massive economic and ecological impacts and these beetles are known to be accidentally moved with wood packaging in global trade. Candidate explanatory characteristics included in this analysis are cumulative trade among world regions, size of source species pools, forest area and climatic similarity of the invaded region with source regions. Species capable of sib-mating comprised the highest proportion on non-native Scolytines, and these species colonized a higher number of regions than outbreeders. The size of source species pools offered little power in explaining variation in numbers of invasions among world regions nor did climate or forest area. In contrast, cumulative trade had a strong and consistent positive relationship with numbers of Scolytinae species moving from one region to another, and this effect was highest for bark beetles, followed by ambrosia beetles, and was low for seed and twig feeders. We conclude that global variation in Scolytine invasions is primarily driven by variation in trade levels among world regions. Results stress the importance of global trade as the primary driver of historical Scolytinae invasions and we anticipate other hitchhiking species would exhibit similar patterns. One implication of these results is that invasions between certain world regions may be historically low because of past low levels of trade but future economic shifts could result in large numbers of new invasions as a result of increased trade among previously isolated portions of the world. With changing global flow of goods among world regions, it is crucial that biosecurity efforts keep pace to minimize future invasions and their impacts.
Mechanism of Action of Botulinum Toxin A in Treatment of Functional Urological Disorders

Intravesical botulinum toxin (BoNT) injection is effective in reducing urgency and urinary incontinence. It temporarily inhibits the detrusor muscle contraction by blocking the release of acetylcholine (Ach) from the preganglionic and postganglionic nerves in the efferent nerves. BoNT-A also blocks ATP release from purinergic efferent nerves in the detrusor muscle. In afferent nerves, BoNT-A injection markedly reduces the urothelial ATP release and increases nitric oxide (NO) release from the urothelium. BoNT-A injection in the urethra or bladder has been developed in the past few decades as the treatment method for detrusor sphincter dyssyndergia, incontinence due to neurogenic or idiopathic detrusor overactivity, sensory disorders, including bladder hypersensitivity, overactive bladder, and interstitial cystitis/chronic pelvic pain syndrome. Although the FDA only approved BoNT-A injection treatment for neurogenic detrusor overactivity and for refractory overactive bladder, emerging clinical trials have demonstrated the benefits of BoNT-A treatment in functional urological disorders. Cautious selection of patients and urodynamic evaluation for confirmation of diagnosis are crucial to maximize the successful outcomes of BoNT-A treatment.
Vertical Profiles of Pollution Particle Concentrations in the Boundary Layer above Paris (France) from the Optical Aerosol Counter LOAC Onboard a Touristic Balloon

Atmospheric pollution by particulate matter represents a significant health risk and needs continuous monitoring by air quality networks that provide mass concentrations for PM10 and PM2.5 (particles with diameter smaller than 10 μm and 2.5 μm, respectively). We present here a new approach to monitor the urban particles content, using six years of aerosols number concentration measurements for particles in the 0.2−50 μm size range. These measurements are performed by the Light Optical Aerosols Counter (LOAC) instrument onboard the tethered touristic balloon “Ballon de Paris Generali”, in Paris, France. Such measurements have allowed us first to detect at ground a seasonal variability in the particulate matter content, due to the origin of the particles (anthropogenic pollution, pollens), and secondly, to retrieve the mean evolution of particles concentrations with height above ground up to 150 m. Measurements were also conducted up to 300 m above ground during major pollution events. The vertical evolution of concentrations varies from one event to another, depending on the origin of the pollution and on the meteorological conditions. These measurements have shown the interest of performing particle number concentrations measurements for the air pollution monitoring in complement with regulatory mass concentrations measurement, to better evaluate the intensity of the pollution event and to better consider the effect of smallest particles, which are more dangerous for human health.
Posttraumatic Stress Disorder Symptoms and Reckless Behaviors: A Network Analysis Approach.

Existing literature indicates a theoretical and empirical relation between engagement in reckless behaviors and posttraumatic stress disorder (PTSD). Thus, the DSM-5 revision of the PTSD nosology added a new "reckless or self-destructive behavior" (RSDB) symptom (Criterion E2). The current study applied a network analytic approach to examine the item-level relations among a range of reckless behaviors and PTSD symptom clusters. Participants were recruited from Amazon's Mechanical Turk (N = 417), and network analysis was conducted with 20 variables: six PTSD symptom clusters, corresponding to the hybrid model of PTSD (Armour et al., 2015) and excluding the externalizing behavior cluster (Community 1), and 14 items related to reckless behavior (Community 2). The results showed that the network associations were strongest within each construct (i.e., within PTSD and within reckless behaviors), although several bridge connections (i.e., between PTSD clusters and reckless behaviors) were identified. Most reckless behavior items had direct associations with one or more PTSD symptom clusters. The present findings support the existence of close relations between a variety of reckless behaviors and PTSD symptom clusters beyond their relations with DSM Criterion E2. The results provide testable hypotheses about the associations between specific reckless behaviors and PTSD symptom clusters, which may inform future research.
Tapping on the Black Box: How Is the Scoring Power of a Machine-Learning Scoring Function Dependent on the Training Set?

In recent years, protein-ligand interaction scoring functions derived through machine-learning are repeatedly reported to outperform conventional scoring functions. However, several published studies have questioned that the superior performance of machine-learning scoring functions is dependent on the overlap between the training set and the test set. In order to examine the true power of machine-learning algorithms in scoring function formulation, we have conducted a systematic study of six off-the-shelf machine-learning algorithms, including Bayesian Ridge Regression (BRR), Decision Tree (DT), K-Nearest Neighbors (KNN), Multi-layer Perceptron (MLP), Linear Support Vector Regression (L-SVR) and Random Forest (RF). Model scoring functions were derived with these machine-learning algorithms on various training sets selected from over 3700 protein-ligand complexes in the PDBbind refined set (version 2016). All resulting scoring functions were then applied to the CASF-2016 test set to validate their scoring power. In our first series of trial, the size of the training set was fixed; while the overall similarity between the training set and the test set was varied systematically. In our second series of trial, the overall similarity between the training set and the test set was fixed; while the size of the training set was varied. Our results indicate that the performance of those machine-learning models are more or less dependent on the contents or the size of the training set, where the RF model demonstrates the best learning capability. In contrast, the performance of three conventional scoring functions (i.e. ChemScore, ASP, and X-Score) is basically insensitive to the use of different training sets. Therefore, one has to consider not only "hard overlap" but also "soft overlap" between the training set and the test set in order to evaluate machine-learning scoring functions. In this spirit, we have complied data sets based on the PDBbind refined set by removing redundant samples under several similarity thresholds. Scoring functions developers are encouraged to employ them as standard training sets if they want to evaluate their new models on the CASF-2016 benchmark. Those standard data sets are listed in the Supporting Information of this article.
Hypoxia-Dependent Expression of TG2 Isoforms in Neuroblastoma Cells as Consequence of Different MYCN Amplification Status

Transglutaminase 2 (TG2) is a multifunctional enzyme and two isoforms, TG2-L and TG2-S, exerting opposite effects in the regulation of cell death and survival, have been revealed in cancer tissues. Notably, in cancer cells a hypoxic environment may stimulate tumor growth, invasion and metastasis. Here we aimed to characterize the role of TG2 isoforms in neuroblastoma cell fate under hypoxic conditions. The mRNA levels of TG2 isoforms, hypoxia-inducible factor (HIF)-1α, p16, cyclin D1 and B1, as well as markers of cell proliferation/death, DNA damage, and cell cycle were examined in SH-SY5Y (non-MYCN-amplified) and IMR-32 (MYCN-amplified) neuroblastoma cells in hypoxia/reoxygenation conditions. The exposure to hypoxia induced the up-regulation of HIF-1α in both cell lines. Hypoxic conditions caused the up-regulation of TG2-S and the reduction of cell viability/proliferation associated with DNA damage in SH-SY5Y cells, while in IMR-32 did not produce DNA damage, and increased the levels of both TG2 isoforms and proliferation markers. Different cell response to hypoxia can be mediated by TG2 isoforms in function of MYCN amplification status. A better understanding of the role of TG2 isoforms in neuroblastoma may open new venues in a diagnostic and therapeutic perspective.
A Novel Method of Human Joint Prediction in an Occlusion Scene by Using Low-Cost Motion Capture Technique

Microsoft Kinect, a low-cost motion capture device, has huge potential in applications that require machine vision, such as human-robot interactions, home-based rehabilitation and clinical assessments. The Kinect sensor can track 25 key three-dimensional (3D) “skeleton” joints on the human body at 30 frames per second, and the skeleton data often have acceptable accuracy. However, the skeleton data obtained from the sensor sometimes exhibit a high level of jitter due to noise and estimation error. This jitter is worse when there is occlusion or a subject moves slightly out of the field of view of the sensor for a short period of time. Therefore, this paper proposed a novel approach to simultaneously handle the noise and error in the skeleton data derived from Kinect. Initially, we adopted classification processing to divide the skeleton data into noise data and erroneous data. Furthermore, we used a Kalman filter to smooth the noise data and correct erroneous data. We performed an occlusion experiment to prove the effectiveness of our algorithm. The proposed method outperforms existing techniques, such as the moving mean filter and traditional Kalman filter. The experimental results show an improvement of accuracy of at least 58.7%, 47.5% and 22.5% compared to the original Kinect data, moving mean filter and traditional Kalman filter, respectively. Our method provides a new perspective for Kinect data processing and a solid data foundation for subsequent research that utilizes Kinect.