Miracle-dz/UniFAR-FTUs huggingface dataset:
Hot-Melt Extrusion as an Advantageous Technology to Obtain Effervescent Drug Products

Here, we assessed the feasibility of hot-melt extrusion (HME) to obtain effervescent drug products for the first time. For this, a combined mixture design was employed using paracetamol as a model drug. Extrudates were obtained under reduced torque (up to 0.3 Nm) at 100 °C to preserve the stability of the effervescent salts. Formulations showed vigorous and rapid effervescent disintegration (<3 min), adequate flow characteristics, and complete solubilization of paracetamol instantly after the effervescent reaction. Formulations containing PVPVA in the concentration range of 15–20% m/m were demonstrated to be sensitive to accelerated aging conditions, undergoing marked microstructural changes, since the capture of water led to the agglomeration and loss of their functional characteristics. HPMC matrices, in contrast, proved to be resistant to storage conditions in high relative humidity, showing superior performance to controls, including the commercial product. Moreover, the combined mixture design allowed us to identify significant interactions between the polymeric materials and the disintegrating agents, showing the formulation regions in which the responses are kept within the required levels. In conclusion, this study demonstrates that HME can bring important benefits to the elaboration of effervescent drug products, simplifying the production process and obtaining formulations with improved characteristics, such as faster disintegration, higher drug solubilization, and better stability.
Applications of Photoinduced Phenomena in Supramolecularly Arranged Phthalocyanine Derivatives: A Perspective

This review focuses on the description of several examples of supramolecular assemblies of phthalocyanine derivatives differently functionalized and interfaced with diverse kinds of chemical species for photo-induced phenomena applications. In fact, the role of different substituents was investigated in order to tune peculiar aggregates formation as well as, with the same aim, the possibility to interface these derivatives with other molecular species, as electron donor and acceptor, carbon allotropes, cyclodextrins, protein cages, drugs. Phthalocyanine photo-physical features are indeed really interesting and appealing but need to be preserved and optimized. Here, we highlight that the supramolecular approach is a versatile method to build up very complex and functional architectures. Further, the possibility to minimize the organization energy and to facilitate the spontaneous assembly of the molecules, in numerous examples, has been demonstrated to be more useful and performing than the covalent approach.
Autophagy Dances with Phytohormones upon Multiple Stresses

Autophagy is an evolutionarily conserved process for turning over unwanted cellular components, thus promoting nutrient recycling and maintaining cellular homeostasis, which eventually enables plants to survive unfavorable growth conditions. In addition to plant growth and development, previous studies have demonstrated that autophagy is involved in the responses to various environmental challenges through interplaying with multiple phytohormones, including abscisic acid (ABA), jasmonic acid (JA), and salicylic acid (SA). In this review, we summarize the advances made in their synergistic interactions in response to multiple abiotic and biotic stresses; we also discuss the remaining issues and perspectives regarding their crosstalk.
Temporal and micro-spatial heterogeneity in transmission dynamics of co-endemic Plasmodium vivax and Plasmodium falciparum in two rural cohort populations in the Peruvian Amazon.

BACKGROUND Malaria is highly heterogeneous; its changing malaria micro-epidemiology needs to be addressed to support malaria elimination efforts at the regional level. METHODS A three-year, population-based cohort study in two settings in the Peruvian Amazon (Lupuna, Cahuide) followed participants by passive and active case detection from January 2013 to December 2015. Incidence and prevalence rates were estimated using microscopy and PCR. RESULTS Lupuna registered 1,828 infections (1,708 P. vivax, 120 P. falciparum; incidence was 80.7 infections/100 person-years (95%CI [77.1-84.5]). Cahuide detected 1,046 infections (1,024 P. vivax, 20 P. falciparum, two mixed); incidence was 40.2 infections/100 person-years (95%CI [37.9-42.7]). Recurrent P. vivax infections predominated onwards from 2013. According to PCR data, submicroscopic predominated over microscopic infections, especially in periods of low transmission. The integration of parasitological, entomological and environmental observations evidenced an intense and seasonal transmission resilient to standard control measures in Lupuna, and a persistent residual transmission after severe outbreaks were intensively handled in Cahuide. CONCLUSIONS In two exemplars of complex local malaria transmission, standard control strategies failed to eliminate submicroscopic and hypnozoite reservoirs, enabling persistent transmission.
Influence of Iron on the Gut Microbiota in Colorectal Cancer

Perturbations of the colonic microbiota can contribute to the initiation and progression of colorectal cancer, leading to an increase in pathogenic bacteria at the expense of protective bacteria. This can contribute to disease through increasing carcinogenic metabolite/toxin production, inducing inflammation, and activating oncogenic signaling. To limit disease progression, external factors that may influence the colonic microbiota need to be considered in patients with colorectal cancer. One major factor that can influence the colonic microbiota is iron. Iron is an essential micronutrient that is required by both prokaryotes and eukaryotes for cellular function. Most pathogenic bacteria have heightened iron acquisition mechanisms and therefore tend to outcompete protective bacteria for free iron. Colorectal cancer patients often present with anemia due to iron deficiency, and thus they require iron therapy. Depending upon the route of administration, iron therapy has the potential to contribute to a procarciongenic microbiota. Orally administered iron is the common treatment for anemia in these patients but can lead to an increased gut iron concentration. This suggests the need to reassess the route of iron therapy in these patients. Currently, this has only been assessed in murine studies, with human trials being necessary to unravel the potential microbial outcomes of iron therapy.
Critical Elements of Community Engagement to Address Disparities and Related Social Determinants of Health: The Centers of Disease Control and Prevention Community Approaches to Reducing Sexually Transmitted Disease Initiative

A study of 8 CARS sites identified 12 elements of community engagement that provide guidance for the development and implementation of strategies to reduce sexually transmitted disease disparities. Background Community Approaches to Reducing Sexually Transmitted Disease (CARS), a unique initiative of the US Centers for Disease Control and Prevention, promotes the use of community engagement to increase sexually transmitted disease (STD) prevention, screening, and treatment and to address locally prioritized STD-related social determinants of health within communities experiencing STD disparities, including youth, persons of color, and sexual and gender minorities. We sought to identify elements of community engagement as applied within CARS. Methods and Materials Between 2011 and 2018, we collected and analyzed archival and in-depth interview data to identify and explore community engagement across 8 CARS sites. Five to 13 interview participants (mean, 7) at each site were interviewed annually. Participants included project staff and leadership, community members, and representatives from local community organizations (e.g., health departments; lesbian, gay, bisexual, transgender, and queer–serving organizations; faith organizations; businesses; and HIV-service organizations) and universities. Data were analyzed using constant comparison, an approach to grounded theory development. Results Twelve critical elements of community engagement emerged, including commitment to engagement, partner flexibility, talented and trusted leadership, participation of diverse sectors, establishment of vision and mission, open communication, reducing power differentials, working through conflict, identifying and leveraging resources, and building a shared history. Conclusions This study expands the community engagement literature within STD prevention, screening, and treatment by elucidating some of the critical elements of the approach and provides guidance for practitioners, researchers, and their partners as they develop, implement, and evaluate strategies to reduce STD disparities.
Antiviral Properties of Flavonoids and Delivery Strategies

This review summarizes the latest advancements in phytochemicals as functional antiviral agents. We focused on flavonoids, like apigenin, vitexin, quercetin, rutin and naringenin, which have shown a wide range of biological effects including antiviral activities. The molecular mechanisms of their antiviral effects mainly consist in the inhibition of viral neuraminidase, proteases and DNA/RNA polymerases, as well as in the modification of various viral proteins. Mixtures of different flavonoids or combination of flavonoids with antiviral synthetic drugs provide an enhancement of their antiviral effects. Recent strategies in drug delivery significantly contribute to overcoming the low bioavailability of flavonoids. Frequent viral infections worldwide have led to the need for new effective antiviral agents, which can be identified among the various phytochemicals. In this light, screening the antiviral activities of a cocktail of flavonoids would be advantageous in order to prevent viral infections and improve current antiviral therapies.
ERK1/2 has Divergent Roles in LPS-Induced Microvascular Endothelial Cell Cytokine Production and Permeability.

Endothelial cells play a major role in inflammatory responses to infection and sterile injury. Endothelial cells express Toll-like receptor 4 (TLR4) and are activated by LPS to express inflammatory cytokines/chemokines, and to undergo functional changes, including increased permeability. The extracellular signal-regulated kinase 1/2 (ERK1/2) mediates pro-inflammatory signaling in monocytes and macrophages, but the role of ERK1/2 in LPS-induced activation of microvascular endothelial cells has not been defined. We therefore studied the role of ERK1/2 in LPS-induced inflammatory activation and permeability of primary human lung microvascular endothelial cells (HMVEC). Inhibition of ERK1/2 augmented LPS-induced IL-6 and vascular cell adhesion protein (VCAM-1) production by HMVEC. ERK1/2 siRNA knockdown also augmented IL-6 production by LPS-treated HMVEC. Conversely, ERK1/2 inhibition abrogated permeability and restored cell-cell junctions of LPS-treated HMVEC. Consistent with the previously described pro-inflammatory role for ERK1/2 in leukocytes, inhibition of ERK1/2 reduced LPS-induced cytokine/chemokine production by primary human monocytes. Our study identifies a complex role for ERK1/2 in TLR4-activation of HMVEC, independent of myeloid differentiation primary response gene (MyD88) and TIR domain-containing adaptor inducing IFN-β (TRIF) signaling pathways. The activation of ERK1/2 limits LPS-induced IL-6 production by HMVEC, while at the same time promoting HMVEC permeability. Conversely, ERK1/2 activation promotes IL-6 production by human monocytes. Our results suggest that ERK1/2 may play an important role in the nuanced regulation of endothelial cell inflammation and vascular permeability in sepsis and injury.
The Diversity of Muscles and Their Regenerative Potential across Animals

Cells with contractile functions are present in almost all metazoans, and so are the related processes of muscle homeostasis and regeneration. Regeneration itself is a complex process unevenly spread across metazoans that ranges from full-body regeneration to partial reconstruction of damaged organs or body tissues, including muscles. The cellular and molecular mechanisms involved in regenerative processes can be homologous, co-opted, and/or evolved independently. By comparing the mechanisms of muscle homeostasis and regeneration throughout the diversity of animal body-plans and life cycles, it is possible to identify conserved and divergent cellular and molecular mechanisms underlying muscle plasticity. In this review we aim at providing an overview of muscle regeneration studies in metazoans, highlighting the major regenerative strategies and molecular pathways involved. By gathering these findings, we wish to advocate a comparative and evolutionary approach to prompt a wider use of “non-canonical” animal models for molecular and even pharmacological studies in the field of muscle regeneration.
GNSS/IMU/ODO/LiDAR-SLAM Integrated Navigation System Using IMU/ODO Pre-Integration

In this paper, we proposed a multi-sensor integrated navigation system composed of GNSS (global navigation satellite system), IMU (inertial measurement unit), odometer (ODO), and LiDAR (light detection and ranging)-SLAM (simultaneous localization and mapping). The dead reckoning results were obtained using IMU/ODO in the front-end. The graph optimization was used to fuse the GNSS position, IMU/ODO pre-integration results, and the relative position and relative attitude from LiDAR-SLAM to obtain the final navigation results in the back-end. The odometer information is introduced in the pre-integration algorithm to mitigate the large drift rate of the IMU. The sliding window method was also adopted to avoid the increasing parameter numbers of the graph optimization. Land vehicle tests were conducted in both open-sky areas and tunnel cases. The tests showed that the proposed navigation system can effectually improve accuracy and robustness of navigation. During the navigation drift evaluation of the mimic two-minute GNSS outages, compared to the conventional GNSS/INS (inertial navigation system)/ODO integration, the root mean square (RMS) of the maximum position drift errors during outages in the proposed navigation system were reduced by 62.8%, 72.3%, and 52.1%, along the north, east, and height, respectively. Moreover, the yaw error was reduced by 62.1%. Furthermore, compared to the GNSS/IMU/LiDAR-SLAM integration navigation system, the assistance of the odometer and non-holonomic constraint reduced vertical error by 72.3%. The test in the real tunnel case shows that in weak environmental feature areas where the LiDAR-SLAM can barely work, the assistance of the odometer in the pre-integration is critical and can effectually reduce the positioning drift along the forward direction and maintain the SLAM in the short-term. Therefore, the proposed GNSS/IMU/ODO/LiDAR-SLAM integrated navigation system can effectually fuse the information from multiple sources to maintain the SLAM process and significantly mitigate navigation error, especially in harsh areas where the GNSS signal is severely degraded and environmental features are insufficient for LiDAR-SLAM.
The relationship between body mass index and poor self-rated health in the South Korean population

Objective This study aimed to examine the association between body mass index (BMI) and self-rated health (SRH) in Korean adults. Methods The study included 214,997 adults who participated in the 2016 Korean Community Health Survey. Participants were categorized into four groups according to WHO Asian classification based on their BMI: underweight (<18.5 kg/m2), normal-weight (18.5–22.9 kg/m2), overweight (23.0‒24.9 kg/m2), obese (25.0‒29.9 kg/m2), and severely obese (≥30.0 kg/m2). Multivariate Poisson regression analysis with sampling weights and robust variance estimators was performed to evaluate the relationship between BMI categories and poor SRH. Results A J-shaped association was observed between BMI and poor SRH in both sexes. Compared to normal-weight subjects, the age, lifestyle, and comorbidities adjusted prevalence rate ratios (PRRs) in men for poor SRH were 1.73 (95% confidence interval [CI], 1.60–1.88) for underweight, 0.87 (95% CI, 0.83–0.92) for overweight, 0.98 (95% CI, 0.93–1.03) for obese, and 1.79 (95% CI, 1.63–1.97) for severely obese. In women, compared to normal-weight subjects, the age, lifestyle, and comorbidities adjusted PRRs for poor SRH were 1.33 (95% CI, 1.26–1.41) for underweight, 1.02 (95% CI, 0.98–1.06) for overweight, 1.15 (95% CI, 1.10–1.19) for obese, and 1.42 (95% CI, 1.31–1.53) for severely obese. Associations between underweight and SRH were stronger at older ages than at younger ages, whereas those between high BMI and SRH were stronger at younger ages than at older ages. Conclusions This cross-sectional study using a nationally representative survey observed a J-shaped relationship between BMI and poor SRH. This association differed depending on age and presence or absence of comorbidities.
Oxidative Stress and Vascular Dysfunction in the Retina: Therapeutic Strategies

Many retinal diseases, such as diabetic retinopathy, glaucoma, and age-related macular (AMD) degeneration, are associated with elevated reactive oxygen species (ROS) levels. ROS are important intracellular signaling molecules that regulate numerous physiological actions, including vascular reactivity and neuron function. However, excessive ROS formation has been linked to vascular endothelial dysfunction, neuron degeneration, and inflammation in the retina. ROS can directly modify cellular molecules and impair their function. Moreover, ROS can stimulate the production of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) causing inflammation and cell death. However, there are various compounds with direct or indirect antioxidant activity that have been used to reduce ROS accumulation in animal models and humans. In this review, we report on the physiological and pathophysiological role of ROS in the retina with a special focus on the vascular system. Moreover, we present therapeutic approaches for individual retinal diseases targeting retinal signaling pathways involving ROS.
Impact of phytoplankton size and physiology on particulate optical properties determined with scanning flow cytometry

Layers and patches of phytoplankton at sub-meter scales in the vertical dimension and kilometer scales in horizontal dimensions are common features in the coastal ocean. These heterogeneous distributions of cells are fundamental to their population dynamics and the function of pelagic ecosystems. To better understand biological processes at these small scales, methods were developed to assess phytoplankton community composition and physiological characteristics based on high-resolution, in situ optical measurements. Scanning flow cytometry of discrete samples was used to determine the effects of phytoplankton and non-algal particle abundance, size, and pigment content on the spectral shape and relative magnitude of particulate attenuation, absorption, scatter, and backscatter coefficients. The slope of particulate attenuation varied with phytoplankton size and morphology, the slope of particulate absorption and the ratio of scatter to absorption varied primarily with cellular pigment content, and the backscatter ratio varied primarily with the relative abundance of non-algal particles. Determination of particle and phytoplankton characteristics from optical measurements over small spatial and temporal scales was tested with 2 independent high-resolution data sets collected from an in situ autonomous profiling system. Comparison of these high-resolution optical data with flow cytometric sample analyses generally agreed with the previously determined relationships but suggest that complex morpho logy of large colonial diatoms may result in higher than expected particulate attenuation slopes. High-resolution data revealed variations in community size structure and physiology that would be difficult to visualize with discrete samples or measures of total chlorophyll concentration.
Comprehensive Serum Glycopeptide Spectra Analysis Combined with Artificial Intelligence (CSGSA-AI) to Diagnose Early-Stage Ovarian Cancer

Ovarian cancer is a leading cause of deaths among gynecological cancers, and a method to detect early-stage epithelial ovarian cancer (EOC) is urgently needed. We aimed to develop an artificial intelligence (AI)-based comprehensive serum glycopeptide spectra analysis (CSGSA-AI) method in combination with convolutional neural network (CNN) to detect aberrant glycans in serum samples of patients with EOC. We converted serum glycopeptide expression patterns into two-dimensional (2D) barcodes to let CNN learn and distinguish between EOC and non-EOC. CNN was trained using 60% samples and validated using 40% samples. We observed that principal component analysis-based alignment of glycopeptides to generate 2D barcodes significantly increased the diagnostic accuracy (88%) of the method. When CNN was trained with 2D barcodes colored on the basis of serum levels of CA125 and HE4, a diagnostic accuracy of 95% was achieved. We believe that this simple and low-cost method will increase the detection of EOC.
Stemness Potency of Human Gingival Cells—Application in Anticancer Therapies and Clinical Trials

Gingivae, as the part of periodontium, are involved in tooth support and possess the ability to heal rapidly, without scar formation. Recently, dental tissues have been identified as a potential source of mesenchymal stem cells (MSCs) and several populations of MSCs were isolated from the orofacial region, including gingival mesenchymal stem cells (GMSCs). GMSCs exhibit robust immunomodulatory and differentiation potential and are easily obtainable, which make them promising candidates for cellular therapies. Apart from being tested for application in immunologic- and inflammatory-related disorders and various tissue regeneration, GMSCs promise to be a valuable tool in cancer treatment, especially in tongue squamous cell carcinoma (TSCC) with the use of targeted therapy, since GMSCs are able to selectively migrate towards the cancerous cells both in vitro and in vivo. In addition to their ability to uptake and release anti-neoplastic drugs, GMSCs may be transduced with apoptosis-inducing factors and used for cancer growth inhibition. Moreover, GMSCs, as most mammalian cells, secrete exosomes, which are a subset of extracellular vesicles with a diameter of 40–160 nm, containing DNA, RNA, lipids, metabolites, and proteins. Such GMSCs-derived exosomes may be useful therapeutic tool in cell-free therapy, as well as their culture medium. GMSCs exhibit molecular and stem-cell properties that make them well suited in preclinical and clinical studies.
KCND3-Related Neurological Disorders: From Old to Emerging Clinical Phenotypes

KCND3 encodes the voltage-gated potassium ion channel subfamily D member 3, a six trans-membrane protein (Kv4.3), involved in the transient outward K+ current. KCND3 defect causes both cardiological and neurological syndromes. From a neurological perspective, Kv4.3 defect has been associated to SCA type 19/22, a complex neurological disorder encompassing a wide spectrum of clinical features beside ataxia. To better define the phenotypic spectrum and course of KCND3-related neurological disorder, we review the clinical presentation and evolution in 68 reported cases. We delineated two main clinical phenotypes according to the age of onset. Neurodevelopmental disorder with epilepsy and/or movement disorders with ataxia later in the disease course characterized the early onset forms, while a prominent ataxic syndrome with possible cognitive decline, movement disorders, and peripheral neuropathy were observed in the late onset forms. Furthermore, we described a 37-year-old patient with a de novo KCND3 variant [c.901T>C (p.Ser301Pro)], previously reported in dbSNP as rs79821338, and a clinical phenotype paradigmatic of the early onset forms with neurodevelopmental disorder, epilepsy, parkinsonism-dystonia, and ataxia in adulthood, further expanding the clinical spectrum of this condition.