Miracle-dz/UniFAR-FTUs huggingface dataset:
Preparation and in-vitro, in-vivo characterisation of pioglitazone loaded chitosan/PEG blended PLGA biocompatible nanoparticles

Abstract The purpose of this research was to formulate Polymeric (Chitosan/PEG blended PLGA) nanoparticles containing Pioglitazone as a model drug using the solvent evaporation method. The resultant nanoparticles were characterized by dynamic laser spectroscopy, transmission electron microscopy, atomic force microscopy, and X-ray diffraction. The nanoparticles had a spherical shape with a mean particle diameter of 323 ± 1.15 nm. Furthermore, data from differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) research revealed no drug-polymer interaction. The efficiency of drug encapsulation was determined to be 61.7 ± 2.91%. The formulated nanoparticles also showed improved drug bioavailability in an in vivo system. When compared to the native drug-treated group, blood glucose levels in Pioglitazone-loaded nanoparticle treated streptozotocin caused diabetic rats were reduced dramatically (up to 7 days) to normal levels (up to 6 h). In albino rats, the nanoparticles' in vivo toxicity investigation revealed no significant changes in behavioral, biochemical, or hematological exams. As a result, the developed system may be useful in achieving a controlled release of the drug, which may help decrease dose frequency and increase patient compliance with pioglitazone for the treatment of type 2 diabetes mellitus.
GDF15 Suppresses Lymphoproliferation and Humoral Autoimmunity in a Murine Model of Systemic Lupus Erythematosus

Growth and differentiation factor 15 (GDF15), a divergent member of the transforming growth factor-β superfamily, has been associated with acute and chronic inflammatory conditions including autoimmune disease, i.e., type I diabetes and rheumatoid arthritis. Still, its role in systemic autoimmune disease remains elusive. Thus, we studied GDF15-deficient animals in Fas-receptor intact (C57BL/6) or deficient (C57BL/6lpr/lpr) backgrounds. Further, lupus nephritis (LN) microdissected kidney biopsy specimens were analyzed to assess the involvement of GDF15 in human disease. GDF15-deficiency in lupus-prone mice promoted lymphoproliferation, T-, B- and plasma cell-expansion, a type I interferon signature, and increased serum levels of anti-DNA autoantibodies. Accelerated systemic inflammation was found in association with a relatively mild renal phenotype. Splenocytes of phenotypically overall-normal Gdf15−/− C57BL/6 and lupus-prone C57BL/6lpr/lpr mice displayed increased in vitro lymphoproliferative responses or interferon-dependent transcription factor induction in response to the toll-like-receptor (TLR)-9 ligand CpG, or the TLR-7 ligand Imiquimod, respectively. In human LN, GDF15 expression was downregulated whereas type I interferon expression was upregulated in glomerular- and tubular-compartments versus living donor controls. These findings demonstrate that GDF15 regulates lupus-like autoimmunity by suppressing lymphocyte-proliferation and -activation. Further, the data indicate a negative regulatory role for GDF15 on TLR-7 and -9 driven type I interferon signaling in effector cells of the innate immune system.
Host transmission dynamics of first- and third-stage Angiostrongylus cantonensis larvae in Bullastra lessoni

Abstract Abstract Given the importance of angiostrongyliasis as an emerging infectious disease of humans, companion animals, and wildlife, the current study focused on the transmission dynamics of first- and third-stage larvae of the parasitic nematode, Angiostrongylus cantonensis. The migration of infective larvae and their subsequent distribution within the Lymnaeidae snail, Bullastra lessoni, were investigated over time using microscopic examination of histological sections and fresh tissue. Snails were divided into four anatomical regions: (i) anterior and (ii) posterior cephalopedal masses, (iii) mantle skirt and (iv) visceral mass. The viability of free-swimming third-stage larvae, after their release from snail tissues, was evaluated in vitro by propidium iodide staining and infectivity by in vivo infection of Wistar rats. Snails were sequentially dissected over time to assess the number and anatomical distribution of larvae within each snail and hence infer their migration pathway. Herein, ongoing larval migratory activity was detected over 28 days post-infection. A comparison of infection rates and the larval distribution within the four designated snail regions demonstrated a significant relationship between anatomical region and density of infective larvae, with larvae mostly distributed in the anterior cephalopedal mass (43.6 ± 10.8%) and the mantle skirt (33.0 ± 8.8%). Propidium iodide staining showed that free-swimming third-stage larvae retained viability for between 4 and 8 weeks when stored under laboratory conditions. In contrast to viability, larval infectivity in rats remained for up to 2 weeks only. Knowledge gained from the current work could provide information on the development of new approaches to controlling the transmission of this parasite.
Advances in infrared spectroscopy and hyperspectral imaging combined with artificial intelligence for the detection of cereals quality

Abstract Cereals provide humans with essential nutrients, and its quality assessment has attracted widespread attention. Infrared (IR) spectroscopy (IRS) and hyperspectral imaging (HSI), as powerful nondestructive testing technologies, are widely used in the quality monitoring of food and agricultural products. Artificial intelligence (AI) plays a crucial role in data mining, especially in recent years, a new generation of AI represented by deep learning (DL) has made breakthroughs in analyzing spectral data of food and agricultural products. The combination of IRS/HSI and AI further promotes the development of quality evaluation of cereals. This paper comprehensively reviews the advances of IRS and HSI combined with AI in the detection of cereals quality. The aim is to present a complete review topic as it touches the background knowledge, instrumentation, spectral data processing (including preprocessing, feature extraction and modeling), spectral interpretation, etc. To suit this goal, principles of IRS and HSI, as well as basic concepts related to AI are first introduced, followed by a critical evaluation of representative reports integrating IRS and HSI with AI. Finally, the advantages, challenges and future trends of IRS and HSI combined with AI are further discussed, so as to provide constructive suggestions and guidance for researchers.
Speech Recognition in Noise Performance Measured Remotely Versus In-Laboratory From Older and Younger Listeners.

PURPOSE This study examined the performance difference between remote and in-laboratory test modalities with a speech recognition in noise task in older and younger adults. METHOD Four groups of participants (younger remote, younger in-laboratory, older remote, and older in-laboratory) were tested on a speech recognition in noise protocol with 72 sentences. RESULTS While the younger remote group performed more poorly than the younger in-laboratory group, older participants' performance was comparable between the two modality groups, particularly in the easy to moderately difficult conditions. These results persisted after controlling for demographic variables (e.g., age, gender, and education). CONCLUSION While these findings generally support the feasibility of remote data collection with older participants for research on speech perception, they also suggest that technological proficiency is an important factor that affects performance on remote testing in the aging population.
Follow-up after gestational diabetes: a qualitative study of perspectives from general practices

Background Women whose pregnancies are complicated by gestational diabetes mellitus (GDM) are approximately eight times more likely to develop type 2 diabetes mellitus (T2DM). Although regular participation in follow-up screening increases the chance of early detection of diabetes, participation rates are often suboptimal. A better understanding of general practice as a key contextual setting for screening could help inform the development and adoption of, for example, electronic reminder interventions to support women’s participation. Aim To explore the perspectives of GPs and relevant staff members engaged in early detection of diabetes after gestational diabetes in order to identify barriers to and facilitators of follow-up screening. Design & setting A qualitative interview study undertaken in general practices in the North Denmark Region. Method Based on a purposive sample strategy, 18 semi-structured interviews of 12 GPs and six staff members, who were either nurses or midwives, were analysed using a reflexive thematic analytical approach. Results The following three main themes were formulated: (1) challenges of addressing women’s risk; (2) prioritisation of early detection of diabetes; and (3) system influence on clinical procedures. Conclusion Follow-up screening was facilitated by knowledge of guidelines. Professional collaboration and adaptation support were found to lead to successful implementation of guidelines in general practice. Supporting GPs and their staff’s reflection and discussion of ways to engage in communication and decisionmaking processes with women is, however, important; it was found to create an important barrier to follow-up screening. Overall, the findings can help inform the future development of interventions to increase uptake.
Impact of Fluoride on Associations between Free Sugars Intake and Dental Caries in US Children

Objective: Dental caries is the most prevalent chronic disease in US children, with the highest burden among Black and Hispanic youth. Sugars are a primary risk factor, but few studies have specifically measured intakes of free sugars and related this to dental caries or explored the extent to which water fluoride mitigates the cariogenicity of free sugars. Furthermore, the cariogenicity of certain free sugars sources, such as extruded fruit and vegetable products, is unclear. Methods: Using cross-sectional data on 4,906 children aged 2 to 19 y in the US National Health and Nutrition Examination Survey 2013–2016, we examined associations of free sugars intake with counts of decayed or filled primary tooth surfaces (dfs) and decayed, missing, or filled permanent surfaces (DMFS) in negative binomial regressions. Stratified models examined these associations in children with home water fluoride above or below the Centers for Disease Control and Prevention (CDC)–recommended level of 0.7 ppm. Results: Free sugars accounted for 16.4% of energy, primarily contributed by added sugars. In adjusted models, a doubling in the percentage of energy from free sugars was associated with 22% (95% confidence interval [CI], 1%–47%) greater dfs among children aged 2 to 8. A doubling in energy from added sugars was associated with 20% (95% CI, 1%–42%) greater dfs and 10% (95% CI, 2%–20%) greater DMFS in children aged 6 to 19 y. Beverages were the most important source of added sugars associated with increased caries. Other free sugars were not associated with dfs or DMFS. Associations between free sugars and caries were diminished among children with home water fluoride of 0.7 ppm or greater. Conclusions: Free sugars intake, especially in the form of added sugars and specifically in sweetened beverages, was associated with higher dental caries. Water fluoride exposures modify these associations, reducing caries risk in the primary dentition of children whose home water meets recommended fluoride levels. Knowledge Transfer Statement: Intake of free sugars, especially in the form of added sugars and specifically in beverages, was associated with higher dental caries in US children in this study. Water fluoride exposure at CDC-recommended levels protected against caries, especially in the primary dentition. These findings suggest that household water fluoridation at CDC-recommended levels protects against the cariogenic potential of free and added sugars during childhood.
Resuscitative endovascular balloon occlusion of the aorta for life-threatening postpartum hemorrhage: A nationwide observational study in Japan

This study focused 143 patients with life-threatening postpartum hemorrhage who underwent resuscitative endovascular balloon occlusion of the aorta (REBOA). The maternal mortality was 7.0% and the prevalence of hysterectomy was 16.1%. BACKGROUND Resuscitative endovascular balloon occlusion of the aorta (REBOA) is used for postpartum hemorrhage (PPH), which is one of the leading causes of maternal mortality worldwide; however, its utility in the obstetrics setting remains unclear. Thus, this study aimed to describe the characteristics, demographics, and mortality of patients with PPH who underwent REBOA. METHODS We used the Japanese Diagnosis Procedure Combination inpatient database to identify patients with PPH who underwent REBOA from April 2012 to March 2020. We examined the patients' characteristics, interventions administered, and in-hospital mortality. RESULTS We identified 143 patients with PPH who underwent REBOA. The most common cause of PPH was atonic postpartum hemorrhage (52.4%), followed by disseminated intravascular coagulation (29.4%) and amniotic fluid embolism documented (11.2%). Among patients who delivered at hospitals in which REBOA was performed (n = 55), 38.2% of patients experienced preterm births, and 70.9% delivered via cesarean delivery. The proportion of patients who underwent transcatheter arterial embolization and hysterectomy was 53.8% and 16.1%, respectively. In-hospital mortality was 7.0%. CONCLUSION The results of the present study could be helpful in clinical decision making and providing patients and families with additional treatment options for PPH. LEVEL OF EVIDENCE Therapeutic/Care Management; Level IV.
Determination of degradative gene frequencies : applications in polycyclic aromatic hydrocarbon contaminated sediments.

DETERMINATION OF DEGRADATIVE GENE FREQUENCIES: APPLICATIONS IN POLYCYCLIC AROMATIC HYDROCARBON CONTAMINATED SEDIMENTS By Karen L. Mumy Aerobic polycyclic aromatic hydrocarbon (PAH) degradative pathways have been described in a wide variety of bacteria, fungi and algae. The occurrence and role of these pathways and their corresponding genes in natural attenuation in environmental systems remain poorly understood. The primary goal of this dissertation research was to determine the concentration and frequency of five degradative genes within natural microbial communities exposed to ambient, low and high levels of PAHs using a quantitative-competitive PCR approach adapted for microbial ecology use. PAH concentrations, total microbial biomass and microbial community structure for sediment samples were also determined using a coupled biochemical approach. Community structure analysis indicated that microeukaryotes may be indirectly responding to the contamination, suggesting the development of a PAH-based food web within the microbial communities. Gene frequencies and concentrations reflected increases with elevated levels of contamination. However, the measured frequencies for most genes indicated that only 0.1% or less of the microbial community had the genetic capacity to degrade the contaminants using described aerobic pathways and their corresponding genes and suggested these sequences are rare in these environmental samples. Metabolic assays indicated that the detected genetic capacity was sufficient to account for the overall biodegradative potential observed within the entire sediment microbial community. These data support that, although the reported frequencies were lower than those others have described, the determined frequencies are indicative of the genetic capacity of natural populations in these sediments. While it is likely that additional unidentified degradative pathways and genes exist and are operating in the environment, the data presented in this dissertation support that many of the well understood enzymes and pathways, while primarily studied and defined within laboratory settings, catalyze the majority of the metabolic activity observed in this environmental setting. DETERMINATION OF DEGRADATIVE GENE FREQUENCIES: APPLICATIONS IN POLYCYCLIC AROMATIC HYDROCARBON CONTAMINATED SEDIMENTS
Pathogen exposure leads to a transcriptional downregulation of core cellular functions that may dampen the immune response in a macroalga

Diseases in marine eukaryotic organisms caused by opportunistic pathogens represent a serious threat to our oceans with potential downstream consequences for ecosystem functioning. Disease outbreaks affecting macroalgae are of particular concern due to their critical role as habitat‐forming organisms. However, there is limited understanding of the molecular strategies used by macroalgae to respond to opportunistic pathogens. In this study, we used mRNA‐sequencing analysis to investigate the early antipathogen response of the model macroalga Delisea pulchra (Rhodophyta) under the environmental conditions that are known to promote the onset of disease. Using de novo assembly methods, 27,586 unique transcripts belonging to D. pulchra were identified that were mostly affiliated with stress response and signal transduction processes. Differential gene expression analysis between a treatment with the known opportunistic pathogen, Aquimarina sp. AD1 (Bacteroidota), and a closely related benign strain (Aquimarina sp. AD10) revealed a downregulation of genes coding for predicted protein metabolism, stress response, energy generation and photosynthesis functions. The rapid repression of genes coding for core cellular processes is likely to interfere with the macroalgal antipathogen response, later leading to infection, tissue damage and bleaching symptoms. Overall, this study provides valuable insight into the genetic features of D. pulchra, highlighting potential antipathogen response mechanisms of macroalgae and contributing to an improved understanding of host–pathogen interactions in a changing environment.
Assessment of porphyrogenicity of drugs and chemicals in selected hepatic cell culture models through a fluorescence‐based screening assay

Compounds that induce 5‐aminolevulinic acid [ALA] synthase‐1 and/or cytochromes P‐450 may induce acute porphyric attacks in patients with the acute hepatic porphyrias [AHPs]. Currently, there is no simple, robust model used to assess and predict the porphyrogenicity of drugs and chemicals. Our aim was to develop a fluorescence‐based in vitro assay for this purpose. We studied four different hepatic cell culture models: HepG2 cells, LMH cells, 3D HepG2 organoids, and 3D organoids of primary liver cells from people without known disease [normal human controls]. We took advantage of the fluorescent properties of protoporphyrin IX [PP], the last intermediate of the heme biosynthesis pathway, performing fluorescence spectrometry to measure the intensity of fluorescence emitted by these cells treated with selected compounds of importance to patients with AHPs. Among the four cell culture models, the LMH cells produced the highest fluorescence readings, suggesting that these cells retain more robust heme biosynthesis enzymes or that the other cell models may have lost their inducibility of ALA synthase‐1 [ALAS‐1]. Allyl isopropyl acetamide [AIA], a known potent porphyrogen and inducer of ALAS‐1, was used as a positive control to help predict porphyrogenicity for tested compounds. Among the tested compounds (acetaminophen, acetylsalicylic acid, β‐estradiol, hydroxychloroquine sulfate, alpha‐methyldopa, D (‐) norgestrel, phenobarbital, phenytoin, sulfamethoxazole, sulfisoxazole, sodium valproate, and valsartan), concentrations greater than 0.314 mM for norgestrel, phenobarbital, phenytoin, and sodium valproate produced fluorescence readings higher than the reading produced by the positive AIA control. Porphyrin accumulation was also measured by HPLC to confirm the validity of the assay. We conclude that LMH cell cultures in multi‐well plates are an inexpensive, robust, and simple system to predict the porphyrogenicity of existing or novel compounds that may exacerbate the AHPs.
Immunogenicity assessment of bispecific antibody-based immunotherapy in oncology

With increasing numbers of bispecific antibodies (BsAbs) and multispecific products entering the clinic, recent data highlight immunogenicity as an emerging challenge in the development of such novel biologics. This review focuses on the immunogenicity risk assessment (IgRA) of BsAb-based immunotherapies for cancer, highlighting several risk factors that need to be considered. These include the novel scaffolds consisting of bioengineered sequences, the potentially synergistic immunomodulating mechanisms of action (MOAs) from different domains of the BsAb, as well as several other product-related and patient-related factors. In addition, the clinical relevance of anti-drug antibodies (ADAs) against selected BsAbs developed as anticancer agents is reviewed and the advances in our knowledge of tools and strategies for immunogenicity prediction, monitoring, and mitigation are discussed. It is critical to implement a drug-specific IgRA during the early development stage to guide ADA monitoring and risk management strategies. This IgRA may include a combination of several assessment tools to identify drug-specific risks as well as a proactive risk mitigation approach for candidate or format selection during the preclinical stage. The IgRA is an on-going process throughout clinical development. IgRA during the clinical stage may bridge the gap between preclinical immunogenicity prediction and clinical immunogenicity, and retrospectively guide optimization efforts for next-generation BsAbs. This iterative process throughout development may improve the reliability of the IgRA and enable the implementation of effective risk mitigation strategies, laying the foundation for improved clinical success.
MECHANICAL AND STRAIN BEHAVIOUR OF HUMAN ACHILLES TENDON DURING IN VITRO TESTING TO FAILURE

The Achilles tendon is the strongest tendon in the human body but its mechanical behaviour during failure has been little studied and the basis of its high tensile strength has not been elucidated in detail. In the present study, healthy, human, Achilles tendons were loaded to failure in an anatomically authentic fashion while the local deformation and strains were studied in real time, with very high precision, using digital image correlation (DIC). The values determined for the strength of the Achilles tendon were at the high end of those reported in the literature, consistent with the absence of a pre-existing tendinopathy in the samples, as determined by careful gross inspection and histology. Early in the loading cycle, the proximal region of the tendon accumulated high lateral strains while longitudinal strains remained low. However, immediately before rupture, the mid-substance of the Achilles tendon, its weakest part, started to show high longitudinal strains. These new insights advance the understanding of the mechanical behaviour of tendons as they are stretched to failure.