Miracle-dz/UniFAR-FTUs huggingface dataset:
Parametric Study of Residence Time Distributions and Granulation Kinetics as a Basis for Process Modeling of Twin-Screw Wet Granulation

Twin-screw wet granulation is a crucial unit operation in shifting from pharmaceutical batch to continuous processes, but granulation kinetics as well as residence times are yet poorly understood. Experimental findings are highly dependent on screw configuration as well as formulation, and thus have limited universal validity. In this study, an experimental design with a repetitive screw setup was conducted to measure the effect of specific feed load (SFL), liquid-to-solid ratio (L/S), and inclusion of a distributive feed screw on particle size distribution (PSD) and shape as well as residence time distribution of a hydrophilic lactose/microcrystalline cellulose based formulation. An intermediate sampling point was obtained by changing inlet ports along the screw axis. Camera-based particle size analysis (QICPIC) indicated no significant change of PSD between the first and second kneading section, except for low L/S and low SFL where fines increase. Mean residence time was approximated as a bilinear fit of L/S and SFL. Moreover, large mass flow pulsations were observed by continuous camera measurements of residence time distribution and correlated to hold-up of the twin-screw granulator. These findings indicate fast granulation kinetics and process instabilities for high mean residence times, questioning current standards of two kneading compartments for wet granulation. The present study further underlines the necessity of developing a multiscale simulation approach including particle dynamics in the future.
Epidemiology of Meropenem/Vaborbactam Resistance in KPC-Producing Klebsiella pneumoniae Causing Bloodstream Infections in Northern Italy, 2018

Meropenem/Vaborbactam (MEM-VAB) is a novel carbapenem- β-lactamase inhibitor active against KPC-producing Enterobacteria. Herein, we evaluate the incidence of meropenem/vaborbactam-resistance among KPC-producing K. pneumoniae (KPC-Kp) bloodstream infection in a large Italian hospital. Meropenem/vaborbactam-resistance was found in 8% (n = 5) KPC-Kp, while 5% (n = 3) strains exhibited cross-resistance to ceftazidime/avibactam (CAZ-AVI). Genomic analysis revealed that meropenem/vaborbactam-resistance was associated with truncated OmpK35 and insertion of glycine and aspartic acid within OmpK36 at position 134–135 (GD134–135). Notably, no specific mutation was associated to cross-resistance. No specific antimicrobial treatment was related to favorable clinical outcomes, while cross-resistance was not associated to higher clinical and/or microbiological failures. Our study indicated that resistance to meropenem/vaborbactam was due to porins mutations and is associated with reduced susceptibility to both ceftazidime/avibactam and carbapenems.
Investigation by Synchrotron Radiation Circular Dichroism of the Secondary Structure Evolution of Pepsin under Oxidative Environment

Food processing affects the structure and chemical state of proteins. In particular, protein oxidation occurs and may impair protein properties. These chemical reactions initiated during processing can develop during digestion. Indeed, the physicochemical conditions of the stomach (oxygen pressure, low pH) favor oxidation. In that respect, digestive proteases may be affected as well. Yet, very little is known about the link between endogenous oxidation of digestive enzymes, their potential denaturation, and, therefore, food protein digestibility. Thus, the objective of this study is to understand how oxidative chemical processes will impact the pepsin secondary structure and its hydrolytic activity. The folding and unfolding kinetics of pepsin under oxidative conditions was determined using Synchrotron Radiation Circular Dichroism. SRCD gave us the possibility to monitor the rapid kinetics of protein folding and unfolding in real-time, giving highly resolved spectral data. The proteolytic activity of control and oxidized pepsin was investigated by MALDI-TOF mass spectrometry on a meat protein model, the creatine kinase. MALDI-TOF MS allowed a rapid evaluation of the proteolytic activity through peptide fingerprint. This study opens up new perspectives by shifting the digestion paradigm taking into account the gastric digestive enzyme and its substrate.
Use of Recombinant Escherichia coli Strains in Immunofluorescence Assays for Melioidosis Diagnosis

Burkholderia pseudomallei is a Gram-negative bacterium and the causative agent of melioidosis in humans and animals in the tropics. The clinical manifestations of melioidosis are diverse, ranging from localized infections to whole-body sepsis. The effective serological method is crucial for the point-of-care diagnosis of melioidosis. The aim of this study was to develop indirect immunofluorescence assay (IFA)-based methods for detecting immunoglobulin G (IgG) antibodies in melioidosis patients. These methods use whole-cell antigens made from recombinant E. coli strains that express major B. pseudomallei antigens, including TssM, OmpH, AhpC, BimA, and Hcp1. A total of 271 serum samples from culture-confirmed melioidosis patients (n = 81), patients with other known infections (n = 70), and healthy donors (n = 120) were tested. Our study showed that the recombinant TssM strain had the highest performance, with 92.6% sensitivity, 100% specificity, 100% positive predictive value, 96.9% negative predictive value, 97.8% efficiency, 97.0% accuracy, and no cross-reactivity. The method agreement analysis based on k efficiency calculations showed that all five IFA methods perfectly agreed with the standard culturing method, while the traditional indirect hemagglutination (IHA) method moderately agreed with the culture. In summary, our investigations showed that the TssM-IFA method could be used for melioidosis diagnosis.
Research Advances on Tilapia Streptococcosis

Streptococcus agalactiae, often referred to as group B streptococci (GBS), is a severe pathogen that can infect humans as well as other animals, including tilapia, which is extremely popular in commercial aquaculture. This pathogen causes enormous pecuniary loss, and typical symptoms of streptococcosis—the disease caused by S. agalactiae—include abnormal behavior, exophthalmos, and meningitis, among others. Multiple studies have examined virulence factors associated with S. agalactiae infection, and vaccines were explored, including studies of subunit vaccines. Known virulence factors include capsular polysaccharide (CPS), hemolysin, Christie-Atkins-Munch-Peterson (CAMP) factor, hyaluronidase (HAase), superoxide dismutase (SOD), and serine-threonine protein kinase (STPK), and effective vaccine antigens reported to date include GapA, Sip, OCT, PGK, FbsA, and EF-Tu. In this review, I summarize findings from several studies about the etiology, pathology, virulence factors, and vaccine prospects for S. agalactiae. I end by considering which research areas are likely to yield success in the prevention and treatment of tilapia streptococcosis.
The Effect of Antimicrobial Treatment upon the Gill Bacteriome of Atlantic Salmon (Salmo salar L.) and Progression of Amoebic Gill Disease (AGD) In Vivo

Branchial surfaces of finfish species contain a microbial layer rich in commensal bacteria which can provide protection through competitive colonization and production of antimicrobial products. Upon disturbance or compromise, pathogenic microbiota may opportunistically infiltrate this protective barrier and initiate disease. Amoebic gill disease (AGD) is a globally significant health condition affecting salmonid mariculture. The current study examined whether altering the diversity and/or abundance of branchial bacteria could influence the development of experimentally induced AGD. Here, we challenged Atlantic salmon (Salmo salar) with Neoparamoeba perurans in a number of scenarios where the bacterial community on the gill was altered or in a state of instability. Administration of oxytetracycline (in-feed) and chloramine-T (immersion bath) significantly altered the bacterial load and diversity of bacterial taxa upon the gill surface, and shifted the community profile appreciably. AGD severity was marginally higher in fish previously subjected to chloramine-T treatment following 21 days post-challenge. This research suggests that AGD progression and severity was not clearly linked to specific bacterial taxa present in these systems. However, we identified AGD associated taxa including known pathogenic genus (Aliivibrio, Tenacibaculum and Pseudomonas) which increased in abundance as AGD progressed. Elucidation of a potential role for these bacterial taxa in AGD development is warranted.
Dietary Selenium Regulates microRNAs in Metabolic Disease: Recent Progress

Selenium (Se) is an essential element for the maintenance of a healthy physiological state. However, due to environmental and dietary factors and the narrow safety range of Se, diseases caused by Se deficiency or excess have gained considerable traction in recent years. In particular, links have been identified between low Se status, cognitive decline, immune disorders, and increased mortality, whereas excess Se increases metabolic risk. Considerable evidence has suggested microRNAs (miRNAs) regulate interactions between the environment (including the diet) and genes, and play important roles in several diseases, including cancer. MiRNAs target messenger RNAs to induce changes in proteins including selenoprotein expression, ultimately generating disease. While a plethora of data exists on the epigenetic regulation of other dietary factors, nutrient Se epigenetics and especially miRNA regulated mechanisms remain unclear. Thus, this review mainly focuses on Se metabolism, pathogenic mechanisms, and miRNAs as key regulatory factors in Se-related diseases. Finally, we attempt to clarify the regulatory mechanisms underpinning Se, miRNAs, selenoproteins, and Se-related diseases.
An Association Rule Mining Analysis of Lifestyle Behavioral Risk Factors in Cancer Survivors with High Cardiovascular Disease Risk

We aimed to assess which lifestyle risk behaviors have the greatest influence on the risk of cardiovascular disease in cancer survivors and which of these behaviors are most prominently clustered in cancer survivors, using logistic regression and association rule mining (ARM). We analyzed a consecutive series of 897 cancer survivors from the Korean National Health and Nutritional Exam Survey (2012–2016). Cardiovascular disease risks were assessed using the atherosclerotic cardiovascular disease score (ASCVDs). We classified participants as being in a low-risk group if their calculated ASCVDs was less than 10% and as being in a high-risk group if their score was 10% or higher. We used association rule mining to analyze patterns of lifestyle risk behaviors by ASCVDs risk group, based upon public health recommendations described in the Alameda 7 health behaviors (current smoking, heavy drinking, physical inactivity, obesity, breakfast skipping, frequent snacking, and suboptimal sleep duration). Forty-two percent of cancer survivors had a high ASCVD. Current smoking (common odds ratio, 11.19; 95% confidence interval, 3.66–34.20, p < 0.001) and obesity (common odds ratio, 2.67; 95% confidence interval, 1.40–5.08, p < 0.001) were significant predictors of high ASCVD in cancer survivors within a multivariate model. In ARM analysis, current smoking and obesity were identified as important lifestyle risk behaviors in cancer survivors. In addition, various lifestyle risk behaviors co-occurred with smoking in male cancer survivors.
The Ubiquitin Proteasome System as a Double Agent in Plant-Virus Interactions

The ubiquitin proteasome is a rapid, adaptive mechanism for selective protein degradation, crucial for proper plant growth and development. The ubiquitin proteasome system (UPS) has also been shown to be an integral part of plant responses to stresses, including plant defence against pathogens. Recently, significant progress has been made in the understanding of the involvement of the UPS in the signalling and regulation of the interaction between plants and viruses. This review aims to discuss the current knowledge about the response of plant viral infection by the UPS and how the viruses counteract this system, or even use it for their own benefit.
PHYTOREMEDIATION OF POLLUTED SOILS : RECENT PROGRESS AND DEVELOPMENTS Physiological and biochemical responses of Dolichos lablab L . to cadmium support its potential as a cadmium phytoremediator

Purpose This study aims to investigate the response of a high biomass producer non-hyperaccumulator legume plant species, Dolichos lablab L. , to cadmium (Cd) stress for phytoremediation process. Materials and methods Three individual experiments were carried out to assess physiological and biochemical parameters to support the use of this plant species as a phytoremediator. The first experiment was carried out in Cdcontaminated soil while the second and third experiments were conducted in sand in which Cd was applied to study biochemical responses. Analysis of mineral nutrition, phytoremediation parameters, antioxidant response, and protein identification by gel-based proteomics were performed. Results and discussion Good tolerance to Cd under moderate level of contamination was observed. Mineral nutrition was little affected, and phytoremediation index was satisfactory. Additionally, biochemical responses based on antioxidant enzyme analysis were well responsive in roots, reflecting the capacity of Cd stress attenuation in this organ. A proteomic analysis revealed positive regulation of root proteins involved in carbohydrate, amino acids, nitrogen metabolism, and abiotic/biotic stress response, which together may contribute to create a scenario to overcome Cd-induced stress. Conclusions Based on the physiological and biochemical results, we concluded that D. lablab L. is suitable for phytoremediation/phytostabilization purposes.
Genetic Confirmation and Identification of Novel Variants for Glanzmann Thrombasthenia and Other Inherited Platelet Function Disorders: A Study by the Korean Pediatric Hematology Oncology Group (KPHOG)

The diagnosis of inherited platelet function disorders (IPFDs) is challenging owing to the unavailability of essential testing methods, including light transmission aggregometry and flow cytometry, in several medical centers in Korea. This study, conducted by the Korean Pediatric Hematology Oncology Group from March 2017 to December 2020, aimed to identify the causative genetic variants of IPFDs in Korean patients using next-generation sequencing (NGS). Targeted exome sequencing, followed by whole-genome sequencing, was performed for diagnosing IPFDs. Of the 11 unrelated patients with suspected IPFDs enrolled in this study, 10 patients and 2 of their family members were diagnosed with Glanzmann thrombasthenia (GT). The variant c.1913+5G>T of ITGB3 was the most common, followed by c.2333A>C (p.Gln778Pro) of ITGB2B. Known variants of GT, including c.917A>C (p.His306Pro) of ITGB3 and c.2975del (p.Glu992Glyfs*), c.257T>C (p.Leu86Pro), and c.1750C>T (p.Arg584*) of ITGA2B, were identified. Four novel variants of GT, c.1451G>T (p.Gly484Val) and c.1595G>T (p.Cys532Phe) of ITGB3 and c.1184G>T (p.Gly395Val) and c.2390del (p.Gly797Valfs*29) of ITGA2B, were revealed. The remaining patient was diagnosed with platelet type bleeding disorder 18 and harbored two novel RASGRP2 variants, c.1479dup (p.Arg494Alafs*54) and c.813+1G>A. We demonstrated the successful application of NGS for the accurate and differential diagnosis of heterogeneous IPFDs.
Synthesis and Antibacterial Activity of 3‐(Substituted arylmethyl)‐4‐acylaminomethyloxazolidin‐2‐ones and Derivatization to Symmetrical Twin‐Drug Type Molecules

In connection with our studies on antibacterial active compounds in the class of new oxazolidinones against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) strains, some molecular modifications were attempted. In this study, molecular modifications of 4-aminomethyloxazolidin-2-ones (3a) to the corresponding 4-acylaminomethyloxazolidin-2-one derivatives (3c–d) and preparations of the represented twin-drug type molecules (10–14) were investigated. Some additional 4-dialkylaminomethyloxazolidin-2-ones (2) were also synthesized. The synthesized compounds were evaluated for antibacterial activity with Gram-positive (S. aureus) and Gram-negative (E. coli) strains.
CMV-Specific Cell-Mediated Immunity in Immunocompetent Adults with Primary CMV Infection: A Case Series and Review of the Literature

Cytomegalovirus-specific cell-mediated immunity (CMV-CMI) in actively infected healthy immunocompetent hosts has been poorly investigated. Conversely, correlates of maternal protective immunity for the fetus after primary infection in pregnancy continue to be studied. The kinetics and magnitude of CMV-specific CMI in immunocompetent primary CMV-infected adults are described. A literature review on CMV-CMI in primarily infected pregnant women and its correlation to the risk of vertical virus transmission is included. Immunological measurements after infection were performed by enzyme-linked ImmunoSPOT assay enumerating IFN-γ secreting CMV-specific T cells, at a single cell level, upon in vitro stimulation with viral antigens. Simultaneously, serological and virological profiles of infected patients were investigated. Patients displayed mild-to-moderate clinical and laboratory profiles for infection, and all showed positive EliSpot results in the early stage of infection (<20 days after onset). The virus-CMI was strong in the majority of patients (58.8%) in which the lowest CMV-DNAemia levels (<300 copies/mL) were detected. Significantly higher viral loads were observed in patients with weak CMV-CMI at the same time-point post-infection (up to 15,104 copies/mL; p < 0.001). T cell response magnitudes to IE-1 and pp65-UL83 peptides were overlapping and stable over time. In these case series, the early presence of CMV-CMI was probably pivotal in controlling viral replication and led to spontaneous viral clearance.
Role of Transportin-SR2 in HIV-1 Nuclear Import

The HIV replication cycle depends on the interaction of viral proteins with proteins of the host. Unraveling host–pathogen interactions during the infection is of great importance for understanding the pathogenesis and the development of antiviral therapies. To date HIV uncoating and nuclear import are the most debated steps of the HIV-1 replication cycle. Despite numerous studies during past decades, there is still much controversy with respect to the identity and the role of viral and host factors involved in these processes. In this review, we provide a comprehensive overview on the role of transportin-SR2 as a host cell factor during active nuclear transport.
Immunotoxicity of Per- and Polyfluoroalkyl Substances: Insights into Short-Chain PFAS Exposure

Novel per- and polyfluoroalkyl substances (PFAS) were recently identified in drinking water sources throughout North Carolina. These include the perfluoroether acids (PFEAs) perfluoro-2-methoxyacetic acid (PFMOAA), perfluoro-2-methoxypropanoic acid (PFMOPrA), and perfluoro-4-methoxybutanioc acid (PFMOBA). Little toxicological data exist for these PFEAs. Therefore, the present study described signs of toxicity and immunotoxicity following oral exposure. Adult male and female C57BL/6 mice were exposed once/day for 30 days to PFMOAA (0, 0.00025, 0.025, or 2.5 mg/kg), PFMOPrA, or PFMOBA (0, 0.5, 5, or 50 mg/kg). A dose of 7.5 mg/kg of perfluorooctanoic acid (PFOA) was used as a positive control. Terminal body weights, and absolute liver, spleen, or thymus weights did not differ by dose for any compound; exposure to 50 mg/kg of PFMOBA increased relative liver weights in males. Changes in splenic cellularity were observed in males exposed to PFMOPrA and decreased numbers of B and natural killer (NK) cells were observed in males and females exposed to PFMOBA. Exposure did not alter NK cell cytotoxicity or T cell-dependent antibody responses at doses administered. Our results indicate that these “understudied” PFAS have toxicological potential but require additional investigation across endpoints and species, including humans, to understand health effects via drinking water exposure.
Automated Sequential Analysis of Hydrophilic and Lipophilic Fractions of Biological Samples: Increasing Single-Injection Chemical Coverage in Untargeted Metabolomics

In order to increase metabolite coverage in LC–MS-based untargeted metabolomics, HILIC- and RPLC-mode separations are often combined. Unfortunately, these two techniques pose opposite requirements on sample composition, necessitating either dual sample preparations, increasing needed sample volume, or manipulation of the samples after the first analysis, potentially leading to loss of analytes. When sample material is precious, the number of analyses that can be performed is limited. To that end, an automated single-injection LC–MS method for sequential analysis of both the hydrophilic and lipophilic fractions of biological samples is described. Early eluting compounds in a HILIC separation are collected on a trap column and subsequently analyzed in the RPLC mode. The instrument configuration, composed of commercially available components, allows easy modulation of the dilution ratio of the collected effluent, with sufficient dilution to obtain peak compression in the RPLC column. Furthermore, the method is validated and shown to be fit for purpose for application in untargeted metabolomics. Repeatability in both retention times and peak areas was excellent across over 140 injections of protein-precipitated blood plasma. Finally, the method has been applied to the analysis of real perilymph samples collected in a guinea pig model. The QC sample injections clustered tightly in the PCA scores plot and showed a high repeatability in both retention times and peak areas for selected compounds.
Geminivirus–Host Interactions: Action and Reaction in Receptor-Mediated Antiviral Immunity

In plant−virus interactions, the plant immune system and virulence strategies are under constant pressure for dominance, and the balance of these opposing selection pressures can result in disease or resistance. The naturally evolving plant antiviral immune defense consists of a multilayered perception system represented by pattern recognition receptors (PRR) and resistance (R) proteins similarly to the nonviral pathogen innate defenses. Another layer of antiviral immunity, signaling via a cell surface receptor-like kinase to inhibit host and viral mRNA translation, has been identified as a virulence target of the geminivirus nuclear shuttle protein. The Geminiviridae family comprises broad-host range viruses that cause devastating plant diseases in a large variety of relevant crops and vegetables and hence have evolved a repertoire of immune-suppressing functions. In this review, we discuss the primary layers of the receptor-mediated antiviral immune system, focusing on the mechanisms developed by geminiviruses to overcome plant immunity.