Astragalus plants belong to the legume family and have obvious rhizosphere effect. The northwestern area of Yunnan China is the main distribution region of Astragalus plants with high application value, but low recognition and resource reserves. The aim of this research is to explore the species diversity of cultivable rhizosphere fungi derived from A. acaulis, A. forrestii, and A. ernestii growing in special high-cold environment of northwest Yunnan, and discover anti-infective components from these fungi. A total of 93 fungal strains belonging to 38 species in 18 genera were isolated and identified. Antibacterial and antimalarial screening yielded 10 target strains. Among them, the ethyl acetate crude extract of the fungus Aspergillus calidoustus AA12 from A. acaulis fermentation substance showed a broad antibacterial spectrum and the best antimalarial activity. Further chemical investigation led to the first discovery of seven compounds from the species of A. calidoustus, including a sesterterpine 6-epi-ophiobolin G (1), two sesquiterpenes penicisochroman A (2), pergillin (3) and 7-methyl-2-(1-methylethylethlidene)-furo[3,2-H]isoquinoline-3-one (4), and three polyketides trypacidin (5), 1,2-seco-trypacidin (6) and questin (7). Compound 1 exhibited moderate to strong antibacterial activity against six Gram-positive pathogens with the minimum inhibitory concentration (MIC) ranging from 25 to 6.25 μg/mL, and prominent inhibitory effect on the biofilm of Streptococcus agalactiae at MIC value of 3.125 μg/mL. This compound also displayed potent antimalarial activity against Plasmodium falciparum strains 3D7 and chloroquine-resistant Dd2 at the half maximal inhibitory concentration (IC50) values of 3.319 and 4.340 µmol/L at 72 h, respectively. This study contributed to our understanding of the cultivable rhizosphere fungi Astragalus-derived in special high-cold environment and further increased the library of fungi available for natural anti-infectious products screening.

Marine microalgae are a rich reservoir of natural compounds, including bioactives. Nonetheless, these organisms remain fairly unexplored despite their potential biotechnological applications. Culture collections with diverse taxonomic groups and lifestyles are a good source to unlock this potential and discover new molecules for multiple applications such as the treatment of human pathologies or the production of aquaculture species. In the present work extracts from 33 strains (including 20 dinoflagellates, 4 diatoms and 9 strains from other 7 algal classes), cultivated under identical conditions were examined for antiviral, antibacterial, anti-inflammatory and anti-cancer activities. Among these, antiviral and anti-inflammatory activities were detected in a few strains while antibacterial tests showed positive results in most assays. In turn, most trials did not show any anti-cancer activity. Wide differences were observed between species within the same class, in particular dinoflagellates which were better represented in this study. These preliminary findings pave the way for in-depth characterization of extracts with highest signals in each test, identification of compounds responsible of the biological activities found, and a further screening of the CCVIEO culture collection.

Bartonella species, intracellular parasitic zoonotic pathogens, has drawn increasing attention for their diverse host range and associated human diseases. This study investigates Bartonella infection in small mammals in Yunnan Province, China, focusing on tissue tropism. 333 small mammals were sampled from 13 species, 3 orders, 4 families, and 4 genera in Heqing and Gongshan Counties. Conventional PCR and real-time quantitative PCR (qPCR) were utilized for detection and quantification, followed by bioinformatic analysis of obtained DNA sequences. Results show a 31.5% detection rate, varying across species. Notably, Apodemus chevrieri, Eothenomys eleusis, Niviventer fulvescens, Rattus tanezumi, Episoriculus leucops, Anourosorex squamipes, and Ochotona Thibetana exhibited infection rates of 44.4%, 27.7%, 100.0%, 6.3%, 60.0%, 23.5%, and 22.2%, respectively. Genetic analysis identified 30, 10, and 5 strains based on ssrA, rpoB, and gltA genes, with nucleotide identities ranging from 92.1% to 100.0%. Bartonella strains were assigned to B. grahamii, B. rochalimae, B. sendai, B. koshimizu, B. phoceensis, B. taylorii, and a new species identified in the Episoriculus leucops (GS136). Tissue distribution analysis revealed varied copy numbers across different tissues, with the highest load in spleen. These findings underscore Bartonella's diverse species and host range in Yunnan Province, highlighting its broad tissue tropism in small mammals.

Genetically diverse influenza A viruses (IAV) circulates in wild aquatic birds with relatively frequent spillover (cases of single infections) to other mammals, but only a small proportion of outbreaks. The spillover of IAV to marine mammals such as seals have been reported throughout the last 45 years. Majority of these viruses when reached seals population cased pneumonia and death of infected animals. Until 2016, all avian influenza viruses found in seals were of low pathotype (LP) IAV. The H5Nx clade 2.4.4.4b highly pathogenic avian influenza viruses (HPAIV) were found in seals for the first time in 2016/2017. Our review highlights 45 years of AIV history in seals population, showing interesting features of different AIV subtypes and emphasis on avian-to-mammals transmission. Furthermore, we also included phylogenetic characterisation of the representative seal isolates.

Lower cutoff levels in screening programs have led to an increase in the proportion of detected cases with transient hypothyroidism, leading to increase of the overall incidence of primary congenital hypothyroidism (CH) in several countries. We have performed retrospective evaluation on the data from 251,008 (96.72%) neonates screened for thyroid-stimulating hormone (TSH) level in dried blood spot specimens taken 48 hours after birth, between 2002 and 2015, using DELFIA method. A TSH value of 15 mIU/L was used as the cutoff point until 2010 and 10 mIU/L thereafter. Primary CH was detected in 127 newborns (1/1976) of which 81.1% had permanent and 18.9% had transient CH. The incidence of primary CH was increased from 1/2489 until to 2010 to 1/1585 thereafter (p=0.131). However, the incidence of permanent CH was slightly increased (p=0.922), while the transient CH incidence had 8-fold increasing after lowering the TSH cutoff level (p<0.001). In cases with permanent CH, we observed lower frequency for thyroid dysgenesis (82.7 vs. 66.7%) and higher frequency for normal in-situ thyroid gland (17.3 vs. 33.3%), for the period with reduced TSH cutoff value. Our findings support the impact of lower TSH cutoff on the increasing incidence of congenital hypothyroidism.

Newborn screening (NBS) is hailed as a public health success, but little is known about long-term outcomes following a positive newborn screen. There has been difficulty gathering long-term follow-up (LTFU) data consistently, reliably, and with minimal effort. Six programs developed and tested a core set of minimal LTFU data elements. After an iterative data collection process and the development of a data collection tool, the group agreed on minimal LTFU data elements. The denominator captured all infants with an NBS diagnosis, accounting for children who moved or died prior to the follow-up year. They also agreed on three LTFU outcomes: if the child was still alive, had contact with a specialist, and received appropriate care specific to their diagnosis within the year. The six programs representing NBS public health programs, clinical providers, and research programs provided data across multiple NBS disorders. In 2022, 83.8% (563/672) of the children identified by the LTFU programs were alive and living in the jurisdiction; of those, 92.0% (518/563) saw a specialist, and 87.7% (494/563) received appropriate care. The core LTFU data elements can be applied as a foundation to address the impact of early diagnosis by NBS within and across jurisdictions.

Mammalian species possess sophisticated innate immune mechanisms that collectively combat a wide array of viral pathogens. Among these, the well-characterized interferon (IFN) response has been extensively researched; however, the role of antiviral RNA interference (RNAi) in mammals is emerging as an area of significant interest. Previous research has noted that Dicer, an enzyme crucial for processing double-stranded RNA (dsRNA), exhibits reduced activity in vitro, and that the IFN response may overshadow or inhibit the antiviral functions of RNAi in mammalian cells. Consequently, the functional relevance of RNAi in antiviral defense within mammalian somatic cells remains an open question. The evolution of antiviral systems in human populations reflects their substantial advantages, paralleling the evolutionary pressure on genomes encoding such defense mechanisms. While the well-studied protein-guided immune responses in mammals are essential for survival in viral environments, small RNA-mediated antiviral systems, which utilize complementary base pairing to silence non self-genetic material, also play a crucial role. In mammals, evidence suggests that microRNAs (miRNAs) regulate genes integral to antiviral responses, and emerging data indicate that small interfering RNAs (siRNAs), PIWI-interacting RNAs (piRNAs), and transfer RNAs (tRNAs) can directly target virus-derived nucleic acids. This review aims to highlight some of the recent progress in understanding mammalian antiviral RNAi mechanisms.

Medicinal plants are being tested as options to prevent infectious diseases in many countries. Baccharis crispa Spreng. (Asteraceae), is a native medicinal species widely used throughout South America. Our objective was to evaluate the antiviral activity of four wild populations of B. crispa from the province of Córdoba (Argentina) and determine if there is variability between them. The cytotoxicity of the extracts (chlorofom, ethanol and aquose) was evaluated by the neutral red uptake method. Using the plaque-forming unit reduction assay, virucidal and antiviral activity against Herpes Simplex type 1 and Chikungunya viruses were tested. Phytochemical screening of each extract was also performed. Puesto Pedernera (PP) population showed the best antiviral and virucidal effect, standing out the ethanolic extract as the least toxic and with the best inhibitory activity against both viral models. Villa del Parque (VP) population was inactive, regardless of the extract and the virus tested. The results revealed that extracts bioactivities vary significantly depending on the geographic area of collection, with PP and VP populations showing the most significant variability, not only in activity but also in chemical composition. These findings support the potential use of extracts as a source of therapeutic agents against different viruses.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes severe disease in humans with case fatality rates of approximately 30%. There are few treatment options for SFTSV infection. SFTSV RNA synthesis is conducted using a virus-encoded complex with RNA-dependent RNA polymerase activity that is required for viral propagation. This complex and its activities are, therefore, potential antiviral targets. A library of small molecule compounds was screened using a high-throughput screening (HTS) based on an SFTSV minigenome assay (MGA) in a 96-well microplate format to identify potential lead inhibitors of SFTSV RNA synthesis. The assay confirmed inhibitory activities of previously reported SFTSV inhibitors, favipiravir, and ribavirin. A small-scale screening using MGA identified four candidate inhibitors that inhibited SFTSV minigenome activity by more than 80% while exhibiting less than 20% cell cytotoxicity with selectivity index (SI) values of more than 100. These included mycophenolate mofetil, methotrexate, clofarabine, and bleomycin. Overall, these data demonstrate that the SFTSV MGA is useful for anti-SFTSV drug development research.

Antiviral peptides (AVPs) represent a promising strategy for addressing the global challenge of viral infections and their growing resistance to traditional drugs. Lab-based AVP discovery methods are resource-intensive, highlighting the need for efficient computational alternatives. In this study, we developed five non-trained but supervised Multi-Query Similarity Search Models (MQSSMs) integrated into the StarPep toolbox. Rigorous testing and validation across diverse AVP datasets confirmed the models' robustness and reliability. The top-performing model, M13+, demonstrated impressive results with an accuracy of 0.969 and a Matthew’s correlation coeffi-cient of 0.71. To assess their competitiveness, the top five models were benchmarked against 14 publicly available machine learning and deep learning AVP predictors. The MQSSMs outper-formed these predictors, highlighting their efficiency in terms of resource demand and public ac-cessibility. Another significant achievement of this study is the creation of the most comprehensive dataset of antiviral sequences to date.

The oral mucosa represents a defense between the external environment and the rest of the body and encompasses several antimicrobial and antiviral mechanisms. Oral mucosal cells are constantly bathed in hypotonic saliva (normally one-third tonicity compared to plasma) and are repeatedly exposed to environmental stresses of tonicity, temperature and pH by the drinks we imbibe (e.g. hypotonic: water, tea, coffee; hypertonic: assorted fruit juices, red wines), as well as of diverse microbial and viral flora. In the mouth, the broad-spectrum antiviral mediator MxA (a dynamin-family large GTPase) is constitutively expressed in healthy periodontal tissues, and also induced by Type III interferons (e.g. IFN-λ1). Endogenously induced human MxA and exogenously expressed human GFP-MxA formed membraneless biomolecular condensates in the cytoplasm of oral carcinoma cells (OECM1 cell line). These condensates likely represent storage granules in equilibrium with antivirally active dispersed MxA. Remarkably, cytoplasmic MxA condensates were exquisitely sensitive sensors of hypotonicity – the condensates in oral epithelium disassembled within 1-2 min of exposure of cells to saliva-like one-third hypotonicity, and spontaneously reassembled in the next 4-7 min. OECM1 cells preloaded with calcein-AM (a reporter of cytosolic “macromolecular crowding”) confirmed unquenching and then requenching of calcein fluorescence during this process. Hypertonicity had little effect on MxA condensates. The spontaneous reassembly of GFP-MxA condensates in oral epithelial cells even under continuous saliva-like hypotonicity was slowed by the protein phosphatase inhibitor cyclosporin A (CsA) and by the K-channel blocker tetraethylammonium chloride (TEA) suggestive of the involvement of the volume-sensitive WNK kinase-protein phosphatase (PTP)-K-Cl cotransporter (KCC) pathway in the regulated volume decrease (RVD) during condensate reassembly in oral cells. Thus, physiologically, hypotonic drinks (water, tea, coffee) trigger a rapid deployment of antiviral MxA throughout the cytoplasm of oral epithelial cells, with subsequent salvage of MxA back into storage granules/condensates.

Glioblastoma (GBM) is the most common malignant brain tumor in adults. Despite advancements in treatment, the prognosis for patients with GBM remains poor due to its aggressive nature and resistance to therapy. CRISPR-based genetic screening has emerged as a powerful tool for identifying genes crucial for tumor progression and treatment resistance, offering promising targets for tumor therapy. In this review, we provide an overview of the recent advancements in CRISPR-based genetic screening approaches and their applications in GBM. We highlight how these approaches have been used to uncover genetic determinants of GBM progression and susceptibility to various therapies. Furthermore, we discuss ongoing challenges and future directions of CRISPR-based screening methods in advancing GBM research.

Abstract: The SARS-CoV-2 pandemic has reemphasized the urgent need for broad-spectrum antiviral therapies. We developed a computational workflow using scRNA-Seq data to assess cellular metabolism during viral infection. With this workflow we predicted the capacity of cells to sustain SARS-CoV-2 virion production in patients and found a tissue-wide induction of metabolic pathways that support viral replication. Expanding our analysis to influenza A and dengue viruses, we identified metabolic targets and inhibitors for potential broad-45 spectrum antiviral treatment. These targets were highly enriched for known interaction partners of all analyzed viruses. Indeed, phenformin, an NADH:ubiquinone oxidoreductase inhibitor, suppressed SARS-CoV-2 and dengue virus replication. Atpenin A5, blocking succinate dehydrogenase, inhibited SARS-CoV-2, dengue virus, respiratory syncytial virus, and influenza A with high selectivity indices. In vivo, phenformin showed antiviral activity against SARS-CoV-2 in a Syrian hamster model. Our work establishes host metabolism as druggable for broad-spectrum antiviral strategies, providing invaluable tools for pandemic preparedness.

Systematic reviews represent a powerful instrument to summarize the existing evidence in medical literature. However, articles for a systematic review are hard to identify, and mostly require a structured search of the literature through a number of databases, using keyword-based search strategies, followed by the painstaking manual selection of pieces of evidence that are pertinent to the query. A.I. algorithms may offer solutions to reduce the workload on investigators. We applied BERTopic, a newer and much-recognized transformer-based topic-modeling algorithm, to two datasets of 6137 and 5309 articles of newly published systematic reviews in the area of peri-implantitis and bone regeneration in implant dentistry. In the two datasets, BERTopic identified 14 and 22 clusters, respectively, and it automatically created labels describing the nature of the topics for each individual cluster based on semantic interpretation of their titles. Most themes regarded the query theme, but in both conditions, BERTopic also uncovered articles related to off-themes, which composed around 30% of the dataset—with sensitivity up to 0.79 and specificities of at least 0.99. Our results suggest that adding a topic-modeling step to the screening process could potentially save working hours for researchers involved in systematic reviews of the literature.

Breast cancer remains a major public health concern, and early detection can result in more treatment options, which are crucial for improving survival rates. Metabolomics offers the potential to develop blood-based screening and diagnostics tools that are less invasive and more cost-effective. However, the inherent complexity of metabolomic datasets makes identifying the most diagnostically relevant biomarkers a difficult task, with multiple studies demonstrating lim-ited agreement on the specific metabolites and pathways involved. This study aims to identify a set of biomarkers for early diagnosis of breast cancer using metabolomics data. Plasma samples from 185 breast cancer patients and 53 controls (CHTN) were analyzed. We utilized univariate Naïve Bayes, L2-regularized Support Vector Machines, and Principal Component Analysis (PCA), along with feature engineering techniques, to select the most informative features. Multiple ma-chine learning models, including Support Vector Machines, Multidimensional Scaling, Logistic Regression, and Ensemble Learning were utilized for classification. The best-performing feature set comprised 4 biomarkers and 2 demographic variables, achieving an accuracy of 98%, demon-strating the potential for a robust, cost-effective, non-invasive breast cancer screening and diagnostic tool.

Thromboembolic conditions, such as stroke and myocardial infarction [MI], are the primary causes of mortality globally. High efficiency was demonstrated by fibrinolytic enzymes isolated from microbial sources in dissolving various blood clots. The study aimed to investigate and produce bacterial fibrinolytic enzymes from various Egyptian soil conditions using recombinant DNA technology. Fifty soil samples were examined to determine the production of fibrinolytic enzymes. The plasmin plate technique assessed the thrombolytic activities of the strong fibrinolytic enzyme-producing bacterial isolates. In addition to determining the molecular mass using a mass spectrometer and the western blot method, the activity and thermostability of the enzymes were characterized. An affinity chromatography approach was used to purify the fibrinolytic enzymes. However, bacterial recombinant DNA technology produced the pure bacterial fibrinolytic enzyme. Several dosage formulations for the formulation of fibrinolytic enzymes were tested. By using affinity chromatography and the SDS-PAGE test, the isolated bacterial fibrinolytic enzyme in this investigation was almost 83% pure. Bacillus cereus ATCC 4342 was identified as the predominant bacterial isolate secreting fibrinolytic enzymes. It was discovered that the fibrinolytic enzyme activity of fifty soil samples ranged from 0.167 U/ml to 1.853 U/ml. The extracellular enzyme extracted from Bacillus cereus culture supernatant demonstrated a relatively stable fibrinolytic activity over 18 hours at a pH range of 7.4–10, as well as stability with maximum productivity at 43℃ for over 60 minutes. In this investigation, the enzyme was referred to as Fibrin-proteinase[ FP]. The fibrin clots were directly thrombolyzed by the FP. The calculated values for the specific activity and molecular mass of the FP were approximately 40.71 units/mg of protein and approximately 30 KDa, respectively. It was observed that the presence of Fe+3 marginally boosted protease activity, but the presence of EDTA decreased it. On the other hand, adding monovalent cations like K+1 and Na+1 significantly increased the fibrinolytic activity of FP. The enzyme exhibited activity throughout the temperature range of 20 to 65℃, peaking at 55℃. The ideal range for the generation of protease was 35–43℃ and 8.0–10. The thermostable fibrinolytic enzyme FP, which was isolated from Bacillus cereus ATCC 4342 in various soil environments in Egypt during the current study, was a promising fibrinolytic enzyme because it demonstrated a more extensive and effective fibrinolytic activity and fewer side effects than the fibrinolytic enzymes that are currently available worldwide. It is advised that further research be done on optimizing the right formulation of bacterial fibrinolytic enzymes in the future to help dissolve different types of blood clots and, as a result, lower the high death rate that exists worldwide.

New antiviral agents are essential to improving treatment and control of SARS-CoV-2 infections that can lead to the disease COVID-19. Antimicrobial peptoids are sequence-specific oligo-N-substituted glycine peptidomimetics that emulate the structure and function of natural antimicrobial peptides but are resistant to proteases. We demonstrate antiviral activity of a new peptoid (TM9) against the coronavirus, murine hepatitis virus (MHV), as a closely related model for the structure and antiviral susceptibility profile of SARS-CoV-2. This peptoid mimics the human cathelicidin LL-37, which has also been shown to have antimicrobial and antiviral activity. In this study TM9 was effective against three murine coronavirus strains, demonstrating the therapeutic window is large enough to allow use of TM9 for treatment. All three isolates of MHV generated infection in mice after 15 min of exposure by aerosol using the Madison aerosol chamber and all three viral strains could be isolated from the lungs throughout the 5-day observation period post-infection, with the peak titers on day 2. MHV-A59 and MHV-A59-GFP were also isolated from liver, heart, spleen, olfactory bulbs, and brain. These data demonstrate that MHV serves as a valuable natural murine model of coronavirus pathogenesis in multiple organs, including the brain.

BACKGROUND: Thromboembolic disorders including Myocardial infarction[ MI] and stroke represent the leading causes of death worldwide. Fibrinolytic enzymes extracted from microbial sources showed high efficacy in the dissolution of different blood clots. AIM OF THE STUDY: Screening and the bacterial recombinant DNA manufacture of bacterial fibrinolytic enzymes from different soil environments in Egypt. METHODOLOGY: A total of 50 soil samples were screened for their fibrinolytic enzyme production. The potent fibrinolytic enzyme-producing bacterial isolates were evaluated for their thrombolytic activities using the plasma plate method. The characterization of the enzyme activity and thermostability were carried out; also, the determination of molecular mass using a mass spectrometer and western blot technique was performed. The purification of the fibrinolytic enzymes was done through the affinity chromatography technique. On the other hand, the production of the purified bacterial fibrinolytic enzyme was achieved via bacterial recombinant DNA technology. Formulation of fibrinolytic enzymes in different dosage forms was tried. RESULTS: In the present study, the purified bacterial fibrinolytic enzyme was approximately 83% pure through affinity chromatography and SDS-PAGE assay. The predominating bacterial isolate secreting fibrinolytic enzymes was found to be Bacillus cereus. The fibrinolytic enzyme activities of 50 soil samples were found to be in the range of 0.167-1.853 U/ ml. The fibrinolytic activity of the extracellular enzyme refined from the culture supernatant of Bacillus cereus was relatively stable over the PH range from 7.4-10 for 18 hours and also it showed stability with the highest productivity at a temperature of 43 0C for nearly 60 minutes. The enzyme was called fibrin-proteinase[ FP] in the present study. The FP degraded the fibrin clots via direct thrombolysis. The specific activity and the molecular mass of the FP were estimated to be nearly 40.71 Units/ mg protein and nearly 30 KDa respectively. Protease activity was noticed to be slightly increased in the presence of Fe+3; While it was inhibited in the presence of EDTA. On the other hand, the FP fibrinolytic activity was enhanced greatly after the addition of monovalent cations such as K+1 and Na +1. The enzyme was also active over the temperature range of 20- 65 0C with the highest activity at 55 0C. The optimum temperature and PH of protease production was at 35-43 0C and PH 8.0-10. Conclusion: During the present study, the thermostable fibrinolytic enzyme FP purified from Bacillus cereus in different soil environments in Egypt was a promising fibrinolytic enzyme because it showed a broader efficacious fibrinolytic activity as well as less adverse effects than the current fibrinolytic enzymes globally. It is recommended in the future advanced exploration of the optimization of suitable formulation of bacterial fibrinolytic enzymes to aid in the dissolution of various blood clots and as a consequence overcoming the high rate of mortality globally.

Objectives: Evaluate the performance of diagnostic measures (sensitivity and specificity) of the intrinsic capacity (IC) construct recommended by the WHO ICOPE guidelines by domain and by age group. Study design: This cross-sectional study included 164 community-dwelling elderly (95 women and 69 men). The participants completed the assessment of the 5 domains of IC (cognition, psychological, vitality, locomotion and sensory). In addition, they were assessed for activities of daily living (ADL), instrumental activities of daily living (IADL), frailty and urinary incontinence. Main outcomes measures: Descriptive statistics were used to summarize the intrinsic capacity and identify which domains were compromised. Comparisons between three or more samples were made by 1-way ANOVA with Bonferroni post-test and those with two samples by the t-test or Mann-Whitney test for quantitative variables. Chi-square test was used for qualitative variables. The sensitivity and specificity of each domain and each domain by age group were evaluated using the ROC curve. Results: Participants with a decline in IC were older, worse ADL, IADL and mental function, low gait speed, and higher depression scores. In addition, people with a decline in IC had frailty, urinary incontinence. Other issues related to the decline in CI were self-reported non-practice of physical activities and level of schooling.The evaluation of each domain did not prove to be a good screening tool (sensitivity or specificity &lt; 80%, but both values &gt; 50%). When the analyses were separated by domain and age group, good performance was found in the psychological (69-69 years and ≥80 years), vitality (≥80 years) and sensory (≥80 years) domains. Conclusions: The ICOPE screening tool performed well in terms of diagnostic measures when applied by domain and age group.

In this review article will be described the (wide) variety of approaches that I envisaged to develop a specific therapy of viral infections: (i) interferon and its inducers, (ii) HSV, VZV and CMV inhibitors, (iii) NRTIs (nucleoside reverse transcriptase inhibitors), NtRTIs (nucleotide reverse transcriptase inhibitors) and NNRTIs (non-nucleoside reverse transcriptase inhibitors) as HIV inhibitors, (iv) NtRTIs as HBV inhibitors and finally, (v) the transition of an HIV inhibitor to a stem cell mobilizer, as exemplified by AMD-3100 (Mozobil®).

Influenza viruses cause acute respiratory infections responsible for significant mortality and morbidity around the world. Various factors, such as antigenic drift, allow influenza strains to avoid being fully suppressed by seasonal vaccines. This has led to the increased scrutiny of antivirals as treatment and prophylaxis options for seasonal outbreaks and potential pandemics. Unfortunately, many influenza antivirals suffer from a lack of adequate clinical trials, as well as a lack of toxicity data. This is especially true of umifenovir (arbidol), a drug popularly used for the prevention and treatment of influenza strains in China and Russia. Neuraminidase inhibitors, though widely prescribed, display a potential for future resistance. Adamantanes, while proven to be effective in treating influenza A, are already encountering rapid and widespread cross-resistance and are effectively obsolete. Baloxavir marboxil, a newer antiviral, shows promise in treating acute uncomplicated influenza and may avoid the development of resistance when co-administered with other antiviral drugs. Indeed, the low genetic barrier to resistance associated with influenza antivirals could potentially be overcome by co-administration with other antivirals. This review explores the most widely prescribed antivirals for influenza treatment, their mechanisms of action, and the data currently available about their susceptibility to resistance and efficacy.

Bacterial infections have attracted the attention of researchers in recent decades, especially due to the special problems they have faced, such as their increasing diversity and resistance to antibiotic treatment. The emergence and development of the SARS-CoV-2 infection stimulated even more research, to find new structures with antimicrobial and antiviral properties. Among the heterocyclic compounds with remarkable therapeutic properties, benzimidazoles and triazoles stand out, possessing antimicrobial, antiviral, antitumor, anti-Alzheimer, anti-inflammatory, analgesic, antidiabetic, or anti-ulcer activities. In addition, the literature of the last decade reports benzimidazole-triazole hybrids with improved biological properties compared to the properties of simple mono-heterocyclic compounds. This review aims to provide an update on the synthesis methods of these hybrids, along with their antimicrobial and antiviral activities, as well as the structure–activity relationship reported in literature.

(1) Background: The prediction of cervical lesions evolution is a challenge for clinicians. The prospective study aimed to determine and compare the predictive accuracy of cytology, HPV genotyping, and p16/Ki67 dual staining alone or in combination with personal risk factors for the prediction of progression, regression or persistence of cervical lesions in human papillomavirus (HPV)-infected patients; (2) Methods: This prospective study included HPV-positive patients with or without cervical lesions that underwent follow-up. Descriptive statistics and sensitivity analysis for individual or combined index tests were used for data analysis; (3) Results: The highest predictive performance for the progression of cervical lesions was achieved by a model that comprised a Pap smear suggestive of high-grade squamous intraepithelial lesion (HSIL), the presence of 16/18 HPV strains, a positive p16/Ki67 dual staining result along with the presence of at least 3 clinical risk factors, which had a sensitivity (Se) of 74.42%, a specificity of 97.92%, an area under the receiver operating curve (AUC) of 0.961, and an accuracy of 90.65%. The prediction of cervical lesions regression or persistence was modest; (4) Conclusions: Multiple testing or new biomarkers should be used to improve HPV-positive patient surveillance, especially for cervical lesion regression or persistence prediction.

An influenza A virus (H3N2) with an envelope with the same structure as COVID-19 was used for antiviral testing of material surfaces, in comparison with some results of feline calicivirus. The evaluation method used was the film adhesion method, in which the virus solution is placed on the material and adhered to it using a film. The evaluation method was based on the film adhesion method, in which the virus solution is placed on the material and adhered with a film, and the plaque method, in which the cell virus is allowed to infect the material and form plaques, but the appropriate virus concentration must be adjusted to observe the plaques. When not under that restriction, the plaques are often incomplete; this is observed. For this reason, this study applied an area measurement method that can reflect viral activity even when plaques are not obtained. This study revealed that different types of metallic materials have different antiviral properties. Specifically, the antiviral activity of iron, carbon steel, and nickel was relatively high, while that of stainless steel and titanium was relatively low. The order of antiviral activity was as follows: Fe, SS400, Ni, SUS316L, SUS304, and Ti.

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium that remains a prevalent clinical and environmental challenge. Quorum sensing (QS) molecules are effective biomarkers in pinpointing the presence of P. aeruginosa. This study aimed to develop a convenient-to-use whole-cell biosensor using P. aeruginosa reporters individually encapsulated within alginate-poly-L-lysine (alginate-PLL) microbeads to specifically detect the presence of bacterial autoinducers. The PLL-reinforced microbeads were prepared using a two-step method involving ionic crosslinking and subsequent coating with thin layers of PLL. The alginate-PLL beads showed good stability in the presence of a known cation scavenger (sodium citrate), which typically limits the widespread applications of calcium alginate. In media containing synthetic autoinducers, such as N-(3-oxo dodecanoyl) homoserine lactone (3-oxo-C12-HSL) and N-butanoyl-L-homoserine lactone (C4-HSL) or cell-free supernatants of planktonic or flow cell biofilm effluent of wild P. aeruginosa (PAO1), the encapsulated bacteria enabled a dose-dependent detection of the presence of these QS molecules. The prepared bioreporter beads remained stable during prolonged storage at 4 and -80 °C and were ready for on-the-spot sensing without the need for recovery. This whole-cell biosensor demonstrates the practicality of the encapsulated bioreporter for bacterial detection based on specific QS molecules.

As the number of publications is quickly growing in any area of science, the need to efficiently find relevant information amidst a large number of similarly themed articles becomes very important. Semantic searching through text documents has the potential to overcome the limits of keyword-based searches, especially since the introduction of attention-based transformers, which can capture contextual nuances of meaning in single words, sentences or whole documents. The deployment of these computational tools has been made simpler and accessible to investigators in every field of research thanks to a growing number of dedicated libraries, but a knowledge of how meaning representation strategies work is crucial to make the most out of these instruments. The present work aims at introducing the technical evolution of the meaning representation systems, from vectors to embeddings and transformers tailored to life science investigators with no previous knowledge of natural language processing.

Sarcopenia is associated with clinical complications, which increase mortality. Effective sarcopenia risk screening in the elderly should be grounded in a comprehensive assessment, encompassing both nutritional status and medication use. Current screening tools, while emphasizing muscular per-formance, exhibit limited sensitivity in identifying elderly individuals at risk of sarcopenia. This cross-sectional study aimed to develop a sarcopenia risk screening tool, named Sarc-Global, with enhanced sensitivity, incorporating factors pertinent to the overall health of the elderly. Utilizing the criteria established by EWGSOP2 for diagnosing sarcopenia, we evaluated 395 communi-ty-dwelling elderly individuals. This evaluation served as a reference for assessing the efficacy of two validated questionnaires, Sarc-F and Sarc-CalF, and our newly developed Sarc-Global. Con-structed through multiple logistic regression, Sarc-Global integrates variables such as sex, age, medication use, body mass index, arm circumference, and handgrip strength – all significantly associated with sarcopenia (p

The influenza virus has been the primary cause of the pandemic, posing a constant threat to human society. Due to its genetic evolution and continuous outbreak, antiviral research currently focuses on exploring a novel lead agent. A comprehensive antiviral screening discovered a marine bacterium whose extract exerted excellent efficacy against influenza viruses. Parerythrobacter sp. M20A3S10, a novel strain under the family Erythrobacteraceae, could produce carotenoids exhibiting antiviral and anticancer activity by enhancing the cellular immune system. Post-treatment of M20A3S10 extract showed outstanding therapeutic indexes: against influenza virus A/PR8 (H1N1) [selectivity index (SI) = 24.0], A/Wisconsin/15/2009 (H3N2) (SI = 30.1) and B/Florida/78/2015 (SI = 38.2). Comparably, the effectiveness was demonstrated against Zika virus (ZIKV) and dengue virus type 2 (DENV2) with an SI of 22.5 and 24.1, respectively, namely broad-spectrum activity. Of note, the antiviral responses resulted from the common replication mechanism between IAV, ZIKV, and DENV2. The stimulation of apoptosis-mediated cellular immunity prevented the viral release and protected the host, suggesting that switching from necroptosis to apoptosis is a novel antiviral target. Although the specific compound affecting the antiviral activity was not identified, its promising efficacy with broad activity will contribute to developing a strategy for preventing future pandemics.

From 2008 to 2024, the Newborn Screening Translational Research Network (NBSTRN), part of the National Institute of Child Health and Human Development (NICHD) Hunter Kelly Newborn Screening Program, served as a robust infrastructure to facilitate groundbreaking research in newborn screening (NBS), rare disease, and genomics. Over fifteen years, NBSTRN developed into a significant international network, supporting innovative research on novel technologies to screen, diagnose, treat, manage, and understand the natural history of more than 280 rare diseases. A key component of these efforts has been the development of resources and expertise for the newborn screening community in ethical, legal, and social issues (ELSI). This paper presents findings from a survey conducted by the NBSTRN team with input from one of theNBSTRN's expert workgroups, the Bioethics and Legal Workgroup. With responses from 88 members of the NBS community including researchers and state NBS programs, the survey found that individuals rely on internal and collegial ELSI resources and highlighted a substantial demand for structured, accessible training and resources. The survey’s insights emphasize the importance of privacy and informed consent in NBS research, and suggested a need for improved collaborative tools and educational programs focused on ELSI for the NBS community. The survey results may inform future efforts in ELSI and NBS research including the development of expanded ELSI tools that leverage digital platforms and consultative services.

Malnutrition is a serious problem with negative impact on the quality of life and the evolution of our patients, contributing to an increase in morbidity, hospital stay, mortality and health spending. Early identification is fundamental to implement the necessary therapeutic actions involving adequate nutritional support to prevent or reverse malnutrition. This review presents two complementary methods of fighting malnutrition: nutritional screening and nutritional assessment. Nutritional risk screening is conducted using simple, quick-to-perform tools and is the first line of action in detecting at-risk patients. It should be implemented systematically and periodically on admission to hospital or residential care, as well as on an outpatient basis for patients with chronic conditions. Once patients with a nutritional risk have been detected they should undergo a more detailed nutritional assessment to identify and quantify the type and degree of malnutrition. This should include health history and clinical examination, dietary history, anthropometric measurements, evaluation of the degree of aggression determined by the disease, functional assessment and, whenever possible, some method of measuring body composition.

The results of the most recent investigation of triterpenoid-based antiviral agents effective namely in the HIV-1 and HSV-1 treatment were reviewed and summarized. Several key historical achievements are included to stress consequences and continuity in this research. Most of the agents studied belong into a series of compound derived from betulin or betulinic acid, and their synthetic derivative called bevirimat. A termination of clinical trials of bevirimat in the Phase IIb initiated a search for more successful compounds partly derived from bevirimat or designed independently of bevirimat structure. Surprisingly, a majority of bevirimat mimics are derivatives of betulinic acid, while other plant triterpenoids, such as ursolic acid, oleanolic acid, glycyrrhetinic acid or other miscellaneous triterpenoids, are relatively rarely involved in a search for novel antiviral agent. Therefore, this review article is divided into three parts based on the leading triterpenoid core structure.

Flaviviruses cause a significant amount of mortality and morbidity, especially in the area where they are endemic. A recent example is the outbreak of Zika virus though out the world. Development of antiviral drugs against different viral targets is as important as development of vaccine. During viral replication, the flavivirus genome is translated as a single polyprotein precursor, which must be cleaved into individual proteins by a complex of the viral protease, NS3, and its cofactor, NS2B. Flavivirus protease is the most attractive target for development of therapeutic antivirals because it is essential for processing of viral polyprotein precursor and generation of functional viral proteins. In this review, we have summarized recent development in drug discovery targeting NS3-NS2B protease of flaviviruses, especially Zika, dengue and West Nile virus.

Viral diseases represent a major public health concern and an ever-present risk for developing into a future pandemic. Antiviral antibody therapeutics, either alone or in combination with other therapies, have emerged as valuable preventative and treatment options, including during a global emergency. Here we will discuss polyclonal and monoclonal antiviral antibody therapies, focusing on the unique biochemical and physiological properties that make them well suited as therapeutic agents. We will describe the methods of antibody characterization and potency assessment throughout development, highlighting similarities and differences between polyclonal and monoclonal products as appropriate. In addition, we will consider the benefits and challenges of antiviral antibodies when used in combination with other antibodies or other types of antiviral therapeutics. Lastly, we will discuss novel approaches to the characterization and development of antiviral antibodies and identify areas that would benefit from additional research.

Rapid advances in the screening, diagnosis, and treatment of genetic disorders has increased the number of conditions that could be detected through universal newborn screening (NBS). However, addition of conditions to the Recommended Uniform Screening Panel (RUSP) and implementation of nationwide screening has been a slow process taking several years to accomplish for individual conditions. Here we describe web-based tools and resources developed and implemented by the newborn screening translational research network (NBSTRN) to advance newborn screening research and support NBS stakeholders. NBSTRN’s tools include the Longitudinal Pediatric Data Resource (LPDR), the NBS Condition Resource (NBS-CR), the NBS Virtual Repository (NBS-VR), and the Ethical, Legal, and Social Issues (ELSI) Advantage. Research programs including the Inborn Errors of Metabolism Information System (IBEM-IS), BabySeq, EarlyCheck, and Family Narratives Use Cases have utilized NBSTRN’s tools, and in turn contributed research data to further expand and refine these this resource. Additionally, we discuss ongoing tool development to facilitate expansion of genetic disease screening in increasingly diverse populations. In conclusion, NBSTRN’s tools and resources provide a trusted platform to enable NBS stakeholders to advance NBS research and improve clinical care for patients and their families.

New dimers of selected dipyridothiazines with an m-xylene linker have been designed, synthesized and characterized. Their structure was identified using 1H and 13C NMR as well as 2D NMR techniques (COSY, ROESY, HSQC and HMBC experiments) and HR MS spectrometry. The compounds were subjected to preliminary in silico biological profile tests using the Way2Drug server and analysis of the probable cytotoxic effect on various cancer cell lines. Preliminary in vitro cytotoxicity tests were performed against normal cell lines (HaCaT) and five cancer cell lines (SW480, SW620, MDA-MB-231, A-549, LN-229) showing moderate activity. An analysis of the structure-activity relationship was performed.

Background: Across the world, antibiotic resistance is a grave problem. To address this issue, it is necessary to investigate new antibiotic sources. Aim of the study: Egypt's diverse soil habitats were used to produce bacterial Myxopyronin B, which was then tested for antimicrobial activity in preclinical animal studies and randomized human clinical trials stages 1/2. Type of the study: Screening experimental study. Methodology: Egypt's various soil conditions were examined for the development of bacterial isolates that produced the antibiotic compound Myxopyronin B. Reversed phase HPLC was used to purify Myxopyronin B. To determine the test antibiotic's minimum inhibitory concentration( MIC) and invitro antibacterial activity, the Broth microdilution method and the Paper disc diffusion assay were utilized. Moreover, in vivo antibacterial spectrum, adverse medication responses, and pharmacokinetics were found in preclinical animal testing stages and phases 1/2 of randomized clinical studies involving volunteer humans. Results: Myxopyronin B was generated from the culture supernatant of Myxococcus SDU36, the main soil bacterial isolate cultured on a Casein yeast peptone plate. With MICs less than 100 mcg/ml, the test antibiotic prevented the growth of several Gram +ve bacteria, whereas, at MICs higher than 100 mcg/ml, it inhibited the development of a small number of Gram -ve bacteria, including Escherichia coli. However, eukaryotic cells—such as those found in fungi and humans—were unaffected. The test antibiotic was seen to inhibit prokaryotic DNA-dependent RNA polymerase( RNLP), indicating its bactericidal activity. Mean Cmax was 9-10 mcg/ ml at mean Tmax 1 hour when 600 mg dose was orally administered in randomized human clinical trials phases 1/2, and T1/2 reached 2.25 hours following first-order kinetics of elimination. Duration of its action was nearly 8 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and GI upset in less than 7 % of experimental candidates. It exhibited approximately 90% plasma protein binding, especially with albumin which resulted in prolonged therapeutic action. It showed a concentration dependant antibiotic killing effect. With the concentration-dependent killing pattern, the higher the drug concentration relative to the pathogen minimum inhibitory concentration( MIC), the greater the rate and extent of antimicrobial activity. Conclusion: The present study was promising due to the production of the bactericidal antibiotic Myxopyronin B from Myxococcus sp. SDU36 isolated from different soil environments in Egypt.

Structures inevitably suffer damages after an earthquake, with their severity ranging from minimal damages to non-structural elements to partial or even total collapse, possibly with loss of human lives. Thus, it is essential for engineers to understand the crucial factors that drive a structure towards suffering higher degrees of damage, so that preventative measures can be taken. In the present study, we focus on three well-known damage thresholds, namely Collapse Limit State, Ultimate Limit State and Serviceability Limit State and analyze which of the features obtained via Rapid Visual Screening, determine whether or not a given structure will cross that threshold. To this end, we use Machine Learning to perform binary classification for each damage threshold, as well as Explainability via SHAP values (acronym for SHapley Additive exPlanations) to quantify the effect of each parameter. The quantitative results obtained demonstrate the potential applicability of ML methods to re-calibrate the computation of structural vulnerability indices using data from recent earthquakes.

The role of innate immunity in neutralization of viral infections (including COVID-19) and forming long-lasting and specific immune memory is considered. It is assumed that antiviral protection is generated by the mechanism of RNA interference (RNAi) and is based on the presence of specific viral patterns in the DNA library of the host cells.

Viruses are the major causes of acute and chronic infectious diseases in the world. According to the World Health Organization, there is an urgent need for better control of viral diseases. Re-purposing existing antiviral agents from one viral disease to another could play a pivotal role in this process. Here we identified novel activities of obatoclax and emetine against herpes simplex virus type 2 (HSV-2), human immunodeficiency virus 1 (HIV-1), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures. Moreover, we demonstrated novel activities of emetine against influenza A virus (FluAV), niclosamide against HSV-2, brequinar against HIV-1, and homoharringtonine against EV1. Our findings may expand the spectrum of indications of these safe-in-man agents and reinforce the arsenal of available antiviral therapeutics pending the results of further in vivo tests.

In this study, we investigate different control scenarios through theoretical analysis and numerical simulations. To account for two important types of control for an early ascending stage of an outbreak, social distancing and treatment with antiviral medications, a compartmental model is considered with one control, $u_1(t)$, aimed to lower the disease transmission rate and the other control, $u_2(t)$, aimed to lower the period of infectiousness. In all experiments, the implementation of control strategies reduces the daily cumulative number of cases and successfully "flattens the curve". The reduction in the cumulative cases is achieved by eliminating or delaying new cases. This delay is incredibly valuable as it provides public health organizations with more time to advance antiviral treatments and devise alternative preventive measures. The main theoretical result of the paper, Theorem 3.1, concludes that the optimal control functions, $u_i(t)$, $i=1,2,$ may be increasing until some moment $\tau \in [0, T)$. However, for all $t \in [\tau, T]$, both controls, $u_i(t)$, decline as $t$ approaches $T$ (possibly causing the number of newly infected people to grow). Numerical simulations presented in Section 4 confirm theoretical findings, which indicates that, ideally, around the time $t=\tau$, the control strategy has to be upgraded and a vaccination campaign needs to start to ensure the epidemic wave does not rebound.

Infection with Ebola virus (EBOV) is responsible for haemorrhagic fever in humans with a high mortality rate. Combined efforts of prevention and therapeutic intervention are required to tackle highly variable RNA viruses, whose infections often lead to outbreaks. Here, we have screened the 2P2I3D chemical library using a nanoluc-based protein complementation assay (NPCA) and isolated two compounds disrupting the interaction of the EBOV protein fragment VP35IID with the N terminus of the dsRNA-binding proteins PKR and PACT, involved in IFN response and/or intrinsic immunity, respectively. The two compounds inhibited EBOV infection in cell culture as well as infection by measles virus (MV) independently of IFN induction. Consequently, we propose the compounds are antiviral by restoring intrinsic immunity driven by PACT. Given that PACT is highly conserved across mammals, we support further testing of the compounds in other species, as well as against further negative sense RNA viruses.

Background: Antibiotic resistance is an overwhelming serious difficulty globally. This necessitates the exploration of novel sources of antibiotics to overcome this challenge. Aim of the study: Bacterial Myxopyronin A production from various soil environments Egypt; as well as testing its antimicrobial activity in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Different soil environments in Egypt were screened for the growth of bacterial isolates producing Myxopyronin A as an antimicrobial agent. Purification of Myxopyronin A was performed via reversed-phase HPLC. Paper disc diffusion assay, as well as broth dilution technique, were exploited to assess the invitro antimicrobial and minimum inhibitory concentration( MIC) of the test antibiotic. Furthermore, in vivo antimicrobial spectrum, adverse drug reactions, and pharmacokinetics were detected during animal model testing stages and human randomized clinical trials phases 1/2. Results: From the culture supernatant of the Myxobacterium Myxococcus fulvus 124B02 which was the predominant soil bacterial isolate grown on the Casein yeast peptone plate, Myxopyronin A was produced. The test antibiotic blocked the growth of many Gram +ve bacteria with MICs less than 100 mcg/ ml; whereas it inhibited the growth of a few Gram -ve bacteria such as Escherichia coli at MICs greater than 100 mcg/ ml. On the other hand, Eukaryotic cells such as fungal and human cells were not affected. Prokaryotic DNA-dependant-RNA polymerase( RNLP) was noticed to be inhibited via the test antibiotic suggesting its bactericidal action. Cmax was 7-8 mcg/ ml at Tmax 2 hours when 600 mg dose was orally administered in randomized human clinical trials phases 1/2; as well as T1/2 reached 2.5 hours following first-order kinetics of elimination. The duration of its action was nearly 12 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and cholestatic jaundice in less than 5 % of experimental candidates. Conclusion: The present study was promising due to the production of the bactericidal antibiotic Myxopyronin A from Myxococcus fulvus 124B02 isolated from different soil environments in Egypt.

Bat feces were reported in ancient Chinese medicine books to have the effect of reducing heat and improving eyesight, but the mechanism of vision improvement still needs further research. To this end, we used 2,2-diphenyl-1-picrylhydrazyl (DPPH) and liquid chromatography/tandem mass spectrometry (LC/MS/MS) to analyze the antioxidant capacity of and the types of vitamins in bat feces. We hoped to screen the pharmacological components of bat feces, and to explain the role that these components may play in the treatment of visual deterioration. Our results found that bat feces had a good antioxidant capacity and mainly contain vitamins B1 (thiamine), B2 (riboflavin), B3 (nicotinamide), B3 (nicotinic acid), and B5 (pantothenic acid). Although these vitamins may help maintain the health of the optic nerve and cornea, the vitamin content of bat feces is low, but the heavy metal content is high, as shown using inductively coupled plasma mass spectrometry (ICP-MS) analysis. Therefore, we suggest that the use of bat feces as traditional Chinese medicine to improve vision should be strictly restricted.

Recently the number of studies investigating triterpenoid saponins has drastically increased due to their diverse and potentially attractive biological activities. Currently the literature contains chemical structures of few hundreds of triterpenoid saponins of plant and animal origin. Triterpenoid saponins consist of a triterpene aglycone with one or more sugar moieties attached to it. However, due to similar physico-chemical properties, isolation and identification of a large diversity of triterpenoid saponins remain challenging. This study demonstrates a methodology to screen saponins using hyphenated analytical platforms, GC-MS, LC-MS/MS, and LC-SPE-NMR/MS, in the example of two different phenotypes of the model plant Barbarea vulgaris (winter cress), glabrous (G) and pubescent (P) type that are known to differ by their insect resistance. The proposed methodology allows for detailed comparison of saponin profiles from intact plant extracts as well as saponin aglycone profiles from hydrolysed samples. Continuously measured 1D proton NMR data during LC separation along with mass spectrometry data revealed significant differences, including contents of saponins, types of aglycones and numbers of sugar moieties attached to the aglycone. A total of 49 peaks were tentatively identified as saponins from both plants; they are derived from eight types of aglycones and with 2–5 sugar moieties. Identification of two previously known insect-deterrent saponins, hederagenin cellobioside and oleanolic acid cellobioside, demonstrated the applicability of the methodology for relatively rapid screening of bioactive compounds.

Gestational diabetes mellitus (GDM) pathophysiology comprises clinical and genetic factors. In fact, GDM has been associated with several single nucleotide polymorphisms (SNPs). This study aimed to build a prediction model of GDM combining clinical and genetic risk factors. A total of 1588 pregnant women from the San Carlos Cohort participated in the present study, 1069 (67.3%) Caucasian (CAU) and 519 (32.7%) Latin American (LAT), 255 (16.1%) with GDM. The incidence of GDM was similar in both groups (16.1% CAU and 16.0% LAT). Genotyping was performed by IPLEX Mass ARRAY PCR selecting 110 SNPs based on literature references. The SNPs showing the strongest likelihood of GDM development were the rs10830963, rs7651090 and rs1371614 in CAU and rs1387153 and the rs9368222 in LAT. Clinical variables including age, pre-pregnancy body mass index and fasting plasma glucose (FPG) at 12 gestational weeks predicted the risk of GDM (AUC 0.648, 95%CI 0.601-0.695 in CAU; AUC 0.688, 95%CI 0.628-9.748 in LAT) and adding the SNPs modestly improved prediction (AUC 0.722, 95%CI 0.680-0.764 in CAU; AUC 0.769, 95%CI 0.711-0.826 in LAT). In conclusion, adding genetic variants enhanced the prediction model of GDM risk in CAU and LAT pregnant women. An RCT is underway to demonstrate its usefulness

Congenital heart disease (CHD) is a prevalent congenital disorder diagnosed with high frequency, affecting approximately 0.8% to 1.2% of all live births. Research has demonstrated that the use of pulse oximetry and clinical examination as a screening tool for CHD diagnosis has proven extremely valuable. We conducted a retrospective longitudinal study over a 3-year period that involved screening 1188 newborns admitted to the NICU during the first 72 hours of life within this timeframe. 201 newborns were diagnosed with CHD. Almost all (n=198) had a positive screening test during the 72-hour period, while 3 had a negative screening test, but were later diagnosed using echocardiography. The prevalence rate was 16.67%. A confusion matrix was constructed with 198 true positives (TP), 3 false negatives (FN), no false positives (FP), and 987 true negatives (TN). The sensitivity of the screening test was 98.51%, while the specificity 100%, with no false positives. In our study, a total of 9 deaths occurred. Using the Kaplan-Meier method, the survival probability appeared to be slightly above 0.9 (95.5%), indicating that almost all patients survived past 72 hours after being diagnosed with CHD. Pulse oximetry is an effective, low cost and easy-to-use method and a useful tool to assess and lead to the diagnosis of CHD.

Type I (IFN-α/β) and Type III (IFN-λ) interferon-inducible myxovirus resistance (Mx) proteins have long been recognized to inhibit a broad spectrum of RNA- and DNA-containing viruses (1-5). Mx proteins are dynamin-family GTPases of size 60-70 kDa (1-3) with different subcellular localization and antiviral activities. In the last 5 years there has been a paradigm shift in our understanding of the structures formed by human and murine Mx proteins in the cytoplasm and nucleus. We now recognize that the major human MxA protein forms structures in the cytoplasm and the major murine Mx1 forms structure in the nucleus which comprise liquid-liquid phase separated (LLPS) biomolecular condensates [membraneless organelles (MLOs)] with a gel-like internal consistency. The second human Mx protein, MxB, which had been previously observed to associate with the cytoplasmic face of nuclear pores, was also recently confirmed to represent cytoplasmic biomolecular condensates. Our overall focus now is to understand the formation, dynamics and antiviral function of biomolecular condensates of different Mx proteins in the cytoplasm and nucleus in cells of different species. We highlight the metastability and rapidly reversible hypotonicity sensing properties of MxA condensates in human cells, especially as applicable to environmental stress inflicted on the oral mucosa.

Influenza is an acute respiratory illness caused by influenza virus infection, which is managed using vaccines and antiviral drugs. Recently, the antiviral effects of plants and foods have gained attention. This review summarizes the therapeutic properties of Euglena against influenza from a functional food viewpoint. While it has been reported that Euglena contributes to suppressing blood sugar levels and ameliorates symptoms caused by stress by acting on the autonomic nervous system, the immunostimulatory and antiviral activities of Euglena have also been reported. In this review, I focused on the immunostimulation of antiviral activity via the intestinal environment and the suppression of viral replication in infected cells. The functions of specific components of Euglena, which also serve as a source of a wide range of nutrients such as vitamins, minerals, amino acids, unsaturated fatty acids, and β-1,3-glucan (paramylon), are also reviewed. Euglena has animal and plant properties and natural compounds with a wide range of functions, providing crucial information for improved antiviral strategies.

Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of general population from emerging and re-emerging viral diseases reinforcing the arsenal of available antiviral options. Here, we reviewed discovery and development of BSAAs and summarized the information on 120 safe-in-man agents in freely accessible database (https://drugvirus.info/). Future and ongoing pre-clinical and clinical studies will increase the number of BSAAs, expand spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections as well as co-infections.

The epitranscriptomic modification m6A is a prevalent RNA modification that plays a crucial role in the regulation of various aspects of RNA metabolism. It has been found to be involved in a wide range of physiological processes and disease states. Of particular interest is the role of m6A machinery and modifications in viral infections, serving as an evolutionary marker for distinguishing between self and non-self entities. In this review article, we present a comprehensive overview of the epitranscriptomic modification m6A and its implications in the interplay between viruses and their host, focusing on immune responses and viral replication. We outline future research directions that highlight the role of m6A in viral nucleic acid recognition, initiation of antiviral immune responses, and modulation of antiviral signaling pathways. Additionally, we discuss the potential of m6A as a prognostic biomarker and a target for therapeutic interventions in viral infections.

Background: The coexistence of HIV infection and latent tuberculosis infection (LTBI) presents a significant public health concern due to the increased risk of tuberculosis (TB) reactivation and progression to active disease. The multicenter observational cohort study, TUBHIVIT, conducted in Italy from 2017 to 2023, aimed to assess the prevalence of LTBI among people living with HIV (PLHIV) and their outcomes following LTBI screening and therapy initiation. Methods: We performed a prospective study in 5 referral centers for HIV care in Italy. PLHIV who consented to participate underwent QuantiFERON-TB Gold Plus and clinical, microbiological, and radiological assessments to exclude subclinical tuberculosis, as opportune. PLHIV diagnosed with LTBI that started chemoprophylaxis were followed until the ending of therapy. Results: A total of 1105 PLHIV were screened for LTBI using the QuantiFERON-TB Gold Plus test, revealing a prevalence of 3.4% of positive results (38/1105). Non-Italy-born individuals exhibited a significantly higher likelihood of testing positive. Thirty-one were diagnosed with LTBI, 1 showed active subclinical TB, 6 were lost to follow-up before discriminating between latent and active TB. Among PLHIV diagnosed with LTBI, 83.9% (26/31) started chemoprophylaxis. Most individuals received 6-9 months of isoniazid-based therapy. Of the 26 PLHIV commencing chemoprophylaxis, 18 (69.2%) completed the therapy, while 3 discontinued it and 5 were still on treatment at the time of the analysis. Adverse events were observed in two cases, while in one case the patient refused to continue the treatment.

Objective. The present study examined the potential use of computed tomography panoramic mandibular indices on cone beam CT (CBCT) for the assessment of bone density in postmenopausal women with low bone mass. Study design. We enrolled 104 postmenopausal women who performed dual energy X-ray absorptiometry (DXA) using a DXA scanner and mental foramen region CBCT using NewTom VGi EVO Cone Beam 3D system. We assessed the relationship between DXA parameters: lumbar, femoral neck and total hip T score, bone mineral density (BMD), and lumbar trabecular bone score (TBS) and the panoramic mandibular indices: computed tomography mandibular index superior (CTI(S)), computed tomography mandibular index inferior (CTI(I)) and computed tomography mental index (CTMI). Results. We found important correlations between the CTI(I), CTI(S) and CTMI and bone mass, quantitative evaluated as BMD and T-score and also quality using TBS score. Conclusion. CBCT measured indices CTI(S), CTI(I), CTMI are useful in assessing patients with low bone mass.

Throughout the Covid19 period, families were forced to stay indoors, adapting to online school-ing, remote work, and virtual social engagements, inevitably altering the dynamics within households. There is a notable increase in mental health challenges in terms of anxiety and de-pression in children and adolescents. This study intends to explore the psychosocial effects of the Covid-19 pandemic in Italian families adopting self- and proxy-report questionnaires on anxiety, anger, and health-related quality of life. The results showed that approximately 20% obtained a clinical anxiety score and only 10% obtained a clinical anger score. There was found a difference in the perception of the quality of life reported by the child and that perceived by the parent. The stepwise regression model showed that total anxiety scores were predicted by sex, quality of life scores from the parents' self-report version and total anger score. Another stepwise regression model identified physiological and social anxiety as the best predictors that impact the quality of life. Parental well-being actively influences the well-being of children, so it is fundamental to implement preventive programmes and promote child well-being providing parents the most adequate support possible.

The collection of forty-nine 8-hydroxyquinoline derivatives, substituted at C5, C6 or C7, was designed and studied by computational methods of modified POM analysis, using SwissADME, Osiris and Molinspiration tool. POM analysis (Petra/Osiris/Molinspiration) and its modified version using SwissADME instead of Petra software are indisputably tools of modern chemoinformatics, often published in the professional literature as well as in the field of research of new antibacterial active compounds, developed to replace existing antibiotics that fail due to increased resistance of bacteria. NitroxolineTM and the group of 8-hydroxyquinoline derivatives with their broad antibacterial effect and the possibility of extensive derivatization of the skeleton, represent a promising direction in the research of new antibacterial active substances. Twenty 8-hydroxyquinoline derivatives were also evaluated on their antibacterial activity against eight selected G+ and G- bacterial strains with a defined resistance mechanism. All structures were in accordance with Lipinski's criteria, twenty-one structures were interesting from the point of view of individual or average value of the bioactivity prediction score and fourteen structures showed one or more mechanisms of toxicity prediction. Furthermore, eleven structures showed a low rate of GI absorption or the inability to cross the BBB barrier, fourteen substances showed a BRENK or PAIN warning, eleven substances are an undesirable substrate of P-glycoprotein and all structures predicted the same level of bioavailability and a relatively low rate of metabolism in the liver. Five structures were selected by the intersection of the POM criteria. The virtual structures 17, 25, 35 and 43 can be favored for the continuity of next study. The resulting scores of bioactivity can indicate the potential of studied structures to be used for the design and development of new active antibacterial agents.

In most industrialized countries, screening programs for cervical cancer have shifted from cytology (Pap smear or ThinPrep) alone on clinician-obtained samples to the addition of screening for human papillomavirus (HPV), its main causative agent. For HPV testing, self-sampling instead of clinician-sampling has proven to be equally accurate, in particular for assays that use nucleic acid amplification techniques. In addition, HPV testing of self-collected samples in combination with a follow-up Pap smear in case of a positive result is more effective in detecting precancerous lesions than a Pap smear alone. Self-sampling for HPV testing has already been adopted by some countries, while others have started trials to evaluate its incorporation into national cervical cancer screening programs. Self-sampling may result in more individuals willing to participate in cervical cancer screening, because it removes many of the barriers that prevent women, especially those in low socioeconomic and minority populations, from participating in regular screening programs. Several studies have shown that the majority of women who have been underscreened but who tested HPV-positive in a self-obtained sample, will visit a clinic for follow-up diagnosis and management. Additionally, a self-collected sample can also be used for vaginal microbiome analysis, which can provide additional information about HPV infection persistence as well as vaginal health in general.

Background: Breast cancer and other neoplasms like acute lymphocytic leukemia pose a serious threat to public health worldwide. Treatment for malignancies including acute lymphocytic leukemia and breast cancer requires enzymes that break down L-glutamine. An amidohydrolase called L-glutaminase can be an effective chemotherapeutic tool for treating various cancers. Methods: On mineral L-glutamine agar selective medium (MGA), a few bacterial isolates were examined in the current investigation to see if they produced L-glutaminase. However, the most effective positive bacterial isolates generating L-glutaminase were identified using morphological and biochemical testing. Molecular detection using the direct Southern blotting approach was also used to determine the main positive isolate that produces L-glutaminase. L-glutaminase synthesis by bacteria was evaluated for its characteristics. Using an MTT test, the anticancer activity was evaluated. Results: exclusive bacterial isolates that used L-glutamine as their sole source of metabolic nitrogen exhibited favorable growth on MGA. PH 7.4 and a temperature of 37 0C were the ideal environmental and physiological conditions for developing positive bacterial isolates. From the soil samples taken from various soil conditions in Egypt, the morphological and biochemical analyses showed that Bacillus cereus 14579 was the main positive bacterial generating L-glutaminase isolate. At a pH of 7.4 and a temperature of 37 °C, the following activators—KCL, ZnSO4, FeSO4, K2HPO4, and MgSO4—provided the high-grade circumstances for characterizing L-glutaminase synthesis. Bacillus cereus-produced L-glutaminase has shown excellent bioavailability and effectiveness as an anticancer therapy. The yield [productivity] was 5.2 U/ml during the original manufacture from MGA, but it increased to 42.96 U/ ml by bacterial recombinant DNA manufacturing. The molecular mass of L-glutaminase was roughly 37 KDa. L-glutaminase was purified, yielding final enzyme recovery of 55 1.23%, total activity 12,990± 19.76 ( U), specific activity 384.66± 8.92( U/ mg of protein), and purification fold 2± 2.99. Furthermore, the L-glutaminase activity was raised by 19%, 23%, 15%, and 9%, respectively, by the enzymatic activators Mn2+, K+, Na+, and Fe3+. It demonstrated strong DPPH scavenging activity (IC50 = 61 μg/ mL) and anticancer activity( IC50 = 40.72, 9.7, 7.39, 20.61, 51.28, and 11.55 μg/ mL, respectively) against human liver (HepG-2), colon ( HCT-116), breast ( MCF-7), lung( A-549), lymphocytic( CCL-120), and cervical( Hela) cancer cell lines. A stronger affinity for its substrate was shown by the kinetic parameters of Km and Vmax, which were 13.2 10-5 M and 119.86 μmol/ ml/ min, respectively. Conclusion: Acute lymphocytic leukemia and breast cancer are examples of auxotrophic malignancies for which L-glutamine serves as the only metabolic source, and L-glutaminase generated by Bacillus cereus was an appropriate enzyme in the therapy of these diseases.

Dengue (DENV) and Zika (ZIKV) virus continue to pose significant challenges globally due to their widespread prevalence and severe health implications. Given the absence of effective vaccines and specific therapeutics, targeting of the highly conserved NS5 RNA-dependent RNA polymerase (RdRp) domain has emerged as a promising strategy. However, limited efforts have been made to develop inhibitors for this crucial target. In this study, we employed an integrated in silico approach utilizing combinatorial chemistry, docking, molecular dynamics simulations, MM/GBSA, and ADMET studies to target the allosteric N-pocket of DENV3-RdRp and ZIKV-RdRp. Using this methodology, we designed lycorine analogs with natural S-enantiomers (LYCS) and R-enantiomers (LYCR) as potential inhibitors of non-structural protein 5 (NS5) in DENV3 and ZIKV. Notably, 12 lycorine analogs displayed a robust binding free energy (&lt;-9.00 kcal/mol), surpassing that of RdRp-Ribavirin (&lt;-7.00 kcal/mol) along with promising ADMET score predictions (&lt;4.00), of which (LYCR728-210, LYCS728-210, LYCR728-212, LYCS505-214) displayed binding properties to both DENV3 and ZIKV targets. This study highlights the potential of non-nucleoside lycorine-based analogs with different enantiomers that may present different or even completely opposite metabolic, toxicological, and pharmacological profiles as promising candidates for inhibiting NS5-RdRp in ZIKV and DENV3, paving the way for further exploration for the development of effective antiviral agents.

Viral pathogens pose a substantial threat to public health and necessitate the development of effective remediation and antiviral strategies. This short communication aimed to investigate the antiviral efficacy of disinfectants on the surface proteins of human pathogenic viruses. Using in silico modeling, ligand binding energies (LBEs) of selected disinfectants were predicted and combined with their environmental impacts and costs through eco-pharmaco-economic analysis (EPEA). Results revealed the binding affinities of chemical disinfectants to viral proteins varied significantly (p

Dengue is the most prevalent arthropod-borne disease globally and affects approximately 2.5 billion people living in over 100 countries. The increasing geographic expansion of Aedes aegypti mosquitoes which transmit the virus has made dengue fever a global health concern. There are currently no approved antivirals available to treat dengue, and the only approved vaccine used in some countries is limited to seropositive patients. Treatment of dengue therefore remains largely supportive to date; hence research efforts are being intensified for the development of antivirals against dengue. The NS3 and NS5 nonstructural proteins have been the major targets for dengue antiviral development due to their indispensable enzymatic and biological functions in the viral replication process. NS5 is the largest and most conserved nonstructural protein encoded by flaviviruses including dengue. Its multifunctionality makes it an attractive target for antiviral development against dengue, but research efforts are hindered due to its limited structural characterization compared to the NS5 of other flaviviruses like the Zika virus. Increase in structural insights into the dengue NS5 protein will accelerate drug discovery efforts focused on NS5 as an antiviral target. In this review, we will give an overview of the current state of therapeutic development against dengue.

Monoclonal antibody (mAb) therapy has revolutionized the treatment of various diseases, including cancer and autoimmune disorders. However, the emergence of SARS-CoV-2 variants, as well as other pathogenic variants, poses challenges in maintaining the therapeutic efficacy of mAbs. In this mini review article, we aim to explore the strategies to overcome variants resistance in mAb therapy against viral infections. Firstly, we discuss the mechanisms through which variants can evade the neutralizing effects of mAbs. Understanding these mechanisms is crucial in developing targeted approaches to combat resistance. Next, we delve into the strategies being pursued to address variants resistance. These include developing new mAbs or antibody cocktails that target multiple epitopes, engineering mAbs with improved binding affinities or enhanced neutralizing capabilities, and exploring alternative therapeutic modalities such as bispecific antibodies or antibody-drug conjugates. Furthermore, we highlight the role of computational modeling and artificial intelligence in predicting variant escape mutations and aiding in the design of more effective mAbs. Additionally, we examine the importance of continuous surveillance and monitoring of emerging variants to inform treatment strategies. This article emphasizes the urgent need for proactive approaches to tackle variants resistance in mAb therapy. By combining innovative design strategies, computational modeling, and vigilant surveillance, we can maintain the therapeutic effectiveness of mAbs and stay ahead in the battle against evolving pathogens and viral infections.

Viral infection activates the transcription factors IRF3 and NF-κB, which synergistically induce type I interferons (IFNs). Here, we identify the E3 ubiquitin ligase RNF138 as an important negative regulator of virus-triggered IRF3 activation and IFN-β induction. Overexpression of RNF138 inhibited virus-induced activation of IRF3 and transcription of the IFNB1 gene, whereas knockout of RNF138 promoted virus-induced activation of IRF3, and transcription of the IFNB1 gene. We further found that RNF138 promotes ubiquitination of PTEN and subsequently inhibits PTEN interactions with IRF3, which is essential for PTEN-mediated nuclear translocation of IRF3, thereby inhibiting IRF3 import into the nucleus. Our findings suggest that RNF138 negatively regulates virus-triggered signaling by inhibiting the interaction of PTEN with IRF3, and these data provide new insights into the molecular mechanisms of cellular antiviral responses.

The present study aims to evaluate the antibacterial activity of five commercially available essential oils (EOs): Lavender (LEO), Clove (CEO), Oregano (OEO), Eucalyptus (EEO), and Peppermint (PEO) against the most-known MDR Gram-positive and Gram-negative bacteria - Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853) - alone and in various combinations. Gas Chromatography-Mass Spectrometry (GC-MS) analysis established their complex composition. Then, the antibacterial activity was investigated in vitro by diffusimetric antibiogram method, using sterile cellulose discs with Ø 6 mm impregnated with 10 µl of sample and sterile borosilicate glass cylinders loaded with 100 µl of sample; MIC (µg/mL) for each EO was calculated from IZD values (mm) measured after 24 hours. The following EO combinations were evaluated: OEO+CEO, CEO+EEO, CEO+PEO, LEO+EEO, and EEO+PEO. Then, the influence of each dual combination on 3 conventional antibacterial drugs – Neomycin (NEO), Tetracycline (TET), and Bacitracin (BAC) - activity was investigated. The most active EOs against S. aureus and E. coli were LEO and OEO (IZD = 40 mm). They were followed by the CEO and EEO (IZD = 20-27 mm); PEO exhibited the lowest antibacterial activity (IZD = 15-20 mm). EEO alone showed the highest inhibitory activity on P. aeruginosa (IZD = 25-35 mm). It was followed by the CEO, LEO, and EEO (IZD = 7-11 mm), while PEO proved no antibacterial action against it (IZD = 0 mm). Only one synergic action was recorded (OEO+CEO against P. aeruginosa); EEO+PEO revealed partial synergism against S. aureus and CEO+PEO additive behavior against E. coli. Two triple associations with TET showed partial synergism against E. coli, and the other 2 ones (with NEO and TET) evidenced the same behavior against S. aureus; all contained EEO+PEO or CEO+PEO. Most combinations reported indifference. However, numerous cases were of antagonism between constituents included in double and triple combinations, and EOs with the strongest antibacterial activities belong to the highest antagonistic combinations. A consistent statistical analysis supports our results, showing that EOs with moderate antibacterial activities could generate combinations with higher inhibitory effects based on synergistic or additive interactions.

Dengue virus is a global health problem most prevalent in tropical and subtropical regions. However, after the approval of two vaccines, Dengvaxia, TV003/TV005 of Takeda, for its prevention, problems were reported, like enhanced risks of infection or less efficiency of protection. Since then, more struggles have been in demand for the development of better vaccines. Here, we conducted a new design through an in-silico strategy. Initially, epitopes were chosen based on their antigenicity, immunogenicity, and binding affinity with MHC molecule, while excluded with allergenicity, toxicity and potential risk of antibody dependent enhancement. Subsequently, a core antigen was constructed with selected epitopes and linked with distinct adjuvant proteins to achieve three candidate vaccines, PSDV-1~3. PSDV-2 was chosen for further validation based on their advantage in physicochemical and structural properties. With a panel of simulations, this artificial protein showed tight binding with pattern recognition receptors, good stability, robust immune induction, and ultimately was confirmed as a high quality vaccine candidate. The plasmid for its recombinant expression was then designed accordingly. With our new design, one more choice was obtained for the effective protection from Dengue virus. Further experimental validations are still require to confirm it protection capacity and safety.

(1) Background: Sudden Infant Death Syndrome (SIDS) represents unexplained and sudden deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for prolonged QTc or Long QT Syndrome (LQTS) should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiogram (ECG) could identify congenital heart defects (CHD) early, especially those not detected at birth. Infants with prolonged QT intervals typically undergo genetic analysis for Long QT Syndrome; (2) Methods: The study involved infants aged 20-40 days, born clinically healthy, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHD identified immediately after birth, as well as those who underwent ECG or echocardiogram for other clinical or historical indications, were excluded from the study. The data were analyzed using SPSS version 22.0; (3) Results: Of the 42,200 infants involved, 2,245 were enrolled, with 39.9% being males. Subsequently, 164 children (37.8% males) with prolonged QT intervals underwent further diagnostic investigations. Genetic mutations were identified in 11 out of 18 tested children. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Medications used included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%; (4) Conclusions: The screening has proven effective in early diagnosing Long QT Syndrome and other cardiac rhythm anomalies, with additional benefits in detecting mutations and/or QTc prolongations in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening.

Background/Objectives Gastroparesis, a chronic digestive disorder characterized by delayed gastric emptying, often results from diabetes, post-surgical complications, autoimmune diseases, and neurological disorders. In approximately 50% of cases, the cause is idiopathic gastroparesis (IGD). Recent studies suggest a link between chronic enteroviral infections and persistent gas-trointestinal symptoms, including delayed gastric emptying. This study investigates the effects of a silydianin-rich extract from Silybum marianum seeds on enteroviral infections in vitro and the mitigation of delayed gastric emptying in mice. Silydianin, a key bioactive compound known for its liver-protective and antioxidant properties, has not been extensively studied for its impact on enteroviral infections and gastroparesis; Methods NMR spectroscopy (¹H, ¹³C, and DEPT) identi-fied silydianin as the primary compound, with minor flavonolignans and trace amounts of an oxidation product. The study assessed the cytotoxicity and antiviral activity of the extract at various stages of the viral life cycle, including virucidal activity, cell protection, and post-infection effects, using neutral red assays in RD cells, with results confirmed by real-time PCR. The viruses studied included Coxsackievirus B2, Coxsackievirus A10, Poliovirus SL-1, and Enterovirus EV71. The impact on delayed gastric emptying was evaluated in a mouse model of gastroparesis using doses of 100 and 200 mg/kg compared to a control; Results: The silydianin-rich extract exhibited con-sistent antiviral activity, with the highest selectivity index (SI) for EV71 (4.08) during virucidal activity. It provided moderate cell protection, with EC50 values ranging from 120.88 to 186.10 µg/mL and SI values from 2.20 to 3.39. Post-infection treatment showed varying efficacy, with Coxsackie A10 demonstrating the highest SI (3.90). In vivo, the extract at 200 mg/kg significantly improved gastric emptying to 96.47% and slightly increased gastrointestinal transit from 50.33% to 61.46%; Conclusions These results suggest that silydianin may be effective in treating enteroviral infections and enhancing intestinal function, making it a promising candidate for gastroparesis treatment and warranting further research.

The blood counts of α thalassemia carriers (α-thal) are similar to those of β thalassemia carriers, except for Hgb A2 that is not elevated. The objective of this study was to determine whether mathematical formulas are effective for detecting suspected α-thal. The data were obtained from the database of the prevention program for detecting couples at risk for having a child with hemoglobinopathy. RBC indices were analyzed using mathematical formulas and the sensitivity and negative predictive value (NPV) calculated. Among 1334 blood counts suspected α-thal analyzed, only the Shine&Lal and the Support Vector Machine formulas revealed high sensitivity and NPV. Sensitivity was 85.54 and 99.33% and NPV 98.93 and 99.93%, respectively. Molecular defects were found in 291, 81 had normal α genes. Molecular analysis was not performed in 962. Based on these results, mathematical formulas incorporating one of these reliable formulas for detecting suspected α or β thalassemia carriers in the program of the automatic analyzers can flag these results and increase the awareness of the primary physicians about the carrier risk and send an alert with a recommendation for further testing.

We analyze a time-delayed SIQR model that considers the transportation-related infections and entry-exit screening. This model aims to determine the measures for preventing and controlling major emergent infectious diseases and the associated costs. We calculate the basic reproduction number (R0), apply the linearization method, and construct an appropriate Lyapunov function to determine the stability of the disease-free equilibrium in the local and global. We collect COVID-19 infection data from two regions in the United States in 2020 for data fitting, obtain a set of optimal parameter values, and show that the model is suitable for simulating the outbreak and spread of emerging infectious diseases. We find that transportation-related infections increase the basic reproduction number, enhancing the impact on disease spread. Entry-exit screening effectively suppress the spread of disease by reducing the basic reproduction number. Furthermore, we investigate the influence of the incubation period on disease and find that a shorter incubation period results in a shorter duration but a larger scale of infection, and the peaks are reduced. We conduct a sensitivity analysis of the R0 and propose three measures to prevent the spread of new infectious diseases based on the most sensitive parameters: wearing masks, implementing urban closures, and administering medication to sick but not yet hospitalized patients promptly. In the case of COVID-19, we use Pontryagin’s minimum principle to get time-varying control measures to control the spread of the outbreak. Optimal control effectively controls the development and deterioration of the disease. Finally, several control measures are compared through cost-effectiveness analysis, and the results show that wearing masks is the most cost-effective measure. Our study provides some practical guidance for controlling the spread of major emerging infectious diseases.

Early childhood may be a stressful period for families with a significant impact on parents’ mental health and the child’s healthy development. The goal of the SKKIPPI cohort study was to assess the occurrence and determinants of psychosocial stress and mental health disorders in parents as well as in their offspring in early childhood in three German regions. Based on random samples from three residents' registration offices, parents with infants up to 12 months of age at the time of sampling, were invited to participate in the study. A screening online questionnaire was newly developed, available in four languages, to assess common psy-chosocial stressors and mental health problems of parents with small children. The study enrolled 4,984 mothers and 962 fathers. The most common potential psychosocial stressors at baseline were professional problems (mothers 22%, fathers 33%), lack of social sup-port (20%, 14%), and severe, negative experiences in childhood (22%, 16%). Obses-sive-compulsive thoughts (21%, 16%), depressive (9%, 9%) and anxiety symptoms (11%, 7%) were the most frequently reported mental health problems by both parents. Regulatory prob-lems of the child were reported by between 1.5% and 5.1% of parents. The SKKIPPI study showed that a substantial proportion of parents are burdened by psychoso-cial problems and suffer from mental health problems in the first years after birth. Early pre-ventive and low-threshold support measures should be available in the health and social care system. The newly developed questionnaire can be used to screen in the relevant populations in order to avoid disturbances in the mother-child attachment.

Background: Reliable HPV testing and genotyping are essential for quality assurance in HPV-based primary screening, disease management and for monitoring the impact of HPV vaccination. The clinical validation of HPV molecular diagnostic assays has significantly contributed to these objectives, however little emphasis has been placed in assuring sample quality. This study aims to assess the accuracy of sample cellularity assessment using C-C Motif Chemokine Receptor 5 (CCR5) gene target as a marker of sample adequacy in molecular diagnostics. Methods: Jurkat cell line samples were counted both using Thoma cell-counting chamber and Fluorescent-Activated Cell Sorting (FACS). Jurkat cell line samples at three different concentrations were subsequently evaluated using the OncoPredict HPV Quality Control (QC) real-time PCR assay, employing CCR5 for molecular cellularity quantification. Results: Cellularity values obtained were comparable across the 3 different methods for all dilutions of the cell line tested. Conclusions: The results obtained from this study show that CCR5 represents a promising molecular marker for the accurate quantification of sample cellularity, confirming its use as a reliable sample adequacy control, thus reducing the risk of “false negative” results.

The development of potent antiviral agents is of utmost importance to combat the global burden of viral infections. Traditional antiviral drug development involves targeting specific viral proteins, which may lead to the emergence of resistant strains. To explore alternative strategies, we investigated the antiviral potential of antimicrobial peptidomimetic compounds. In this study, we evaluated the antiviral potential of short anthranilamide-based peptidomimetic compounds 1-17 against two viruses: Murine Hepatitis Virus 1 (MHV-1-single stranded RNA virus) which is a surrogate of human coronaviruses and Herpes Simplex Virus 1 (HSV-1-double stranded DNA virus). The half-maximal inhibitory concentration (IC50) values of these compounds were determined in vitro to assess their potency as antiviral agents. Compounds 11 and 14 displayed the most potent inhibitory effect with IC50 values of 2.38μM, and 6.3μM against MHV-1 while compounds 9 and 14 showed IC50 values of 14.8μM and 13μM, against HSV-1. Multiple antiviral assessments and microscopic images obtained through transmission electron microscopy (TEM) collectively demonstrated that these compounds exert a direct influence on the viral envelope. Based on this outcome, it can be concluded that peptidomimetic compounds could offer a new approach for the development of potent antiviral agents.

Piceatannol is a naturally occurring polyphenolic compound that is widely found in grapes, blueberries, mushrooms, passion fruit and other edible fruits and vegetables. It has a variety of biological activities and pharmacological effects, including anti-inflammatory, antioxidation, antiaging, antiviral, antitumor, anticancer, antiatherosclerosis, antiparasitic, immunoregulatory, and cardiovascular protection effects. The aim of this study was to investigate the antiherpesvirus effects of piceatannol. Pseudorabies virus (PRV) belongs to the family Herpesviridae. PRV has a wide host range and can cause cytopathic effects (CPEs) in PK-15 cells. Therefore, PRV was used as a model to study the antiherpesvirus effect of piceatannol. In this study, we evaluated the antiviral activity of piceatannol against PRV in vitro and in vivo. The results showed that piceatannol could reatrain PRV multiplication in PK-15 cells in a dose-dependent manner. The 50% inhibitory concentration (IC50) was 0.0307 mg/mL, the IC50 was 0.0307 mg/mL, and the selectivity index (SI, CC50/IC50) was 3.68. The addition of piceatannol at different stages of PRV infection inhibited the viral adsorption and intracellular replication phases of PRV. Piceatannol significantly reduced the expression levels of the IE180, EP0, UL29, UL44, US6 and UL27 genes of PRV within 48 h, significantly reduced the expression levels of the PRV gB and gD proteins, and reduced PRV-induced apoptosis. Molecular docking showed that piceatannol had good binding activity with the PRV gB and gD proteins. The results of animal experiments in vitro indicated that piceatannol could delay the onset of disease, improve the survival rate of the mice (14.3%), reduce the viral load in the brain and kidney of the mice, alleviate the pathological changes in the mouse tissues and organs, and increase the levels of TNF-α, IEN-γ and IL-4 in the serum of the mice. These data indicate that piceatannol has good anti-PRV activity in vitro and in vivo, indicating that it could be a novel antiherpesvirus infection agent in the future.

Viral infections, such as those caused by Herpes Simplex Virus-1 (HSV-1) and SARS-CoV-2, affect millions of people each year. However, there are few antiviral drugs that can effectively treat these infections. The standard approach in the development of antiviral drugs involves the identification of a unique viral target, followed by the design of an agent that addresses that target. Antimicrobial peptides (AMPs) represent a novel source of potential antiviral drugs. AMPs have been shown to inactivate numerous different enveloped viruses through the disruption of their viral envelopes. However, the clinical development of AMPs as antimicrobial therapeutics has been hampered by a number of factors, especially their structure as peptides. We have examined the antiviral potential of peptoid mimics of AMPs (sequence-specific N-substituted glycine oligomers). These peptoids have the distinct advantage of being insensitive to proteases, and also exhibit increased bioavailability and stability. Our results demonstrate that several peptoids exhibit potent in vitro antiviral activity against both HSV-1 and SARS-CoV-2 when incubated prior to infection. Visualization by cryo-EM shows viral envelope disruption similar to what has been observed with AMP activity against other viruses. This suggests a common or biomimetic mechanism, possibly due to the differences between the phospholipid head group makeup of viral envelopes and host cell membranes. Furthermore, we observed no cytotoxicity against primary cultures of oral epithelial cells, thus underscoring the potential of this class of molecules as safe and effective broad-spectrum antiviral agents.

There are dozens of approved, investigational and experimental antiviral agents. Many of these agents cause serious side effects, which can be revealed only after drug administration. Identification of the side effects prior to drug administration is challenging. Here we describe an ex vivo approach for studying immuno- and neuro-modulatory properties of antiviral agents, which could be associated with potential side effects of these therapeutics. The approach combines drug toxicity/efficacy tests and transcriptomics, which is followed by cytokine and metabolite profiling. We demonstrated the utility of this approach with several examples of antiviral agents. We also showed that the approach can utilize different immune stimuli and cell types. It can also include other omics techniques, such as genomics and epigenomics, to allow identification of individual markers associated with adverse reactions to antivirals with immuno- and neuro-modulatory properties.

Background: Diabetes is a common non-communicable disease that is responsible for about 9% of all deaths and 25% reduction in life expectancy and nearly half of the diabetic patients are not aware of their disease. In this regard, diabetes screening to identify un-known diabetic patients is of great importance. Aims: The aims of this study were first to evaluate the performance of two commonly used diabetes screening tests that are currently recommended by the Iranian national screening program for diabetes (NSPD). Methods: The validities of the two diabetes screening tests were measured among 1057 participants older than 30 years. The studied screening tests included Capillary fasting blood glucose (CBG) and glycated hemoglobin (HbA1c). The golden standard for measuring the validity of the tests was venous fasting plasma glucose (VPG). Results: According to the results, the sensitivity of CBG and HbA1c tests were 69.01% and 84.5% and the specificity of the tests were 95.7% and 79.3% respectively. Positive and negative predictive values were 53.84% and 97.72% for CBG and 22.72% and 98.61% for HbA1c respectively. The recommended cut-points for CBG and HbA1c were 116.5 mg/dl and 7.15% respectively. Using these values as the new cut-points, sensitivity and specificity of CBG and HbA1c changed to 80.30% and 89.10%, and 77.50% and 94.20% respectively. Conclusions: Compared to several other countries, the performance of NSPD is relatively higher in Iran. ROC analysis suggested new cut-points for significantly better performance of NSPD.

We assessed the impact of social determinants of health (SDOH) and psychosocial factors on screening behavior in a nationally representative sample of women in the US. A retrospective population-level cross-sectional sample was extracted from the 2022 Health Information National Trends Survey. Descriptive statistics were conducted for demographic characteristics and covariates. Population-based estimates with 95% confidence intervals (95% CI) were produced for Pap testing behaviors across study years. We used logistic regression models to assess Pap testing differences based on SDOH and psychosocial factors, adjusting for covariates, with a significance level of 0.05 for hypothesis testing. Women (n=2,224) with a mean age of 46.96 participated in the study. Our study found that 90% of women were interested in cervical cancer screening, with an 80% actual screening rate. Screening rates differed by age group and rurality. SDOH and psychosocial factors were associated with participants’ interest in screening and in actual screening behavior. The impacts of SDOH and psychosocial factors on screening behavior were 3% and 1%, respectively. The SDOH and psychosocial factors are associated with the uptake of cervical cancer screening among women in the United States. Policies must be directed at bridging the gap created by these SDOHs.

Abstract: Background: Patients with diabetes are particularly susceptible to COVID-19 infection, which can result in severe respiratory illness. Methods: This study conducted a comparative as-sessment of the impact of antiviral therapy using molnupiravir and favipiravir in COVID-19 pa-tients with underlying diabetes. A cohort of one hundred individuals infected with SARS-CoV-2, diagnosed with diabetes, and consecutively admitted, was included in the present study. These patients were treated with antivirals according to local guidelines: Group F (51 cases) was treated with favipiravir – 10 days and Group M (49 cases) was treated with molnupiravir – 5 days. Re-sults: In Group F, the average hospitalization was higher than in Group M (11.29±2.27 vs. 7.14±3.16, p

Coxsackievirus B3 (CVB3) is one of the most common pathogens that cause myocarditis in humans. However, a sufficient therapeutic drug was not developed yet. Caboxamycin, a benzoxazole antibiotic, isolated from the culture broth of the marine strain Streptomyces sp., SC0774, displayed an antiviral effect in the CVB3-infected HeLa cells and CVB3-induced myocarditis mouse model. Caboxamycin significantly inhibited CVB3 VP1 production and cleavage of translation factor eIF4G1 from CVB3-infected HeLa cells at a 100 μg/ml concentration. Moreover, virus RNA amplification was dramatically reduced by caboxamycin treatment in HeLa cells. The caboxamycin cardiac protective effect was observed on the CVB3-mediated myocarditis mice model. The caboxamycin-treated mice survival was significantly increased compared to untreated mice (treated vs untreated, 100 vs 45 %). Heart histologic findings showed that myocardium damage and inflammation were significantly decreased by caboxamycin treatment. Caboxamycin directly inhibited caspase3 activity and cardiac myocytes apoptosis. These results suggested that caboxamycin strongly suppressed cardiac myocyte apoptosis and effectively inhibited the proliferation of CVB3 from in vitro and in vivo conditions. Furthermore, this study proposed that caboxamycin could potentially be applied in developing a new antiviral drug for CVB3-induced myocarditis.

Viral infections inflict many serious human diseases, being responsible for remarkably high mortality rates. In this sense, both the academy and the pharmaceutical industry are continuously searching for new compounds with antiviral activity, and in addition, face the challenge of developing greener and more efficient methods to synthesize these compounds. This becomes even more important with drugs possessing stereogenic centers as highly enantioselective processes are required. In this minireview, the advances achieved to improve synthetic routes efficiency and sustainability of important commercially antiviral chiral drugs are discussed, highlighting the use of organocatalytic methods.

Human papillomavirus (HPV) is a well-known cause of cervical cancer, with HIV infection exacerbating the prevalence of high-risk HPV (HR-HPV) and cervical intraepithelial neoplasia (CIN). ART has been shown to reduce the likelihood of developing squamous intraepithelial lesions (SILs) and HR-HPV prevalence, although its impact on invasive cervical cancer remains inconclusive. In a study in Accra, 250 sexually active HIV-positive women exhibited a high HPV prevalence, emphasising the need for regular screening. HPV testing, visual inspection with acetic acid (VIA), and cytology-based tests are primary screening methods, each with specific advantages and limitations. Cervical cancer rates in sub-Saharan Africa are alarmingly high, necessitating targeted vaccination and prevention strategies.

Since the onset of coronavirus disease 2019 (COVID-19) pandemic, the virus kept developing and mutating into different variants over time that also gained increased transmissibility and spread in populations at a higher pace, culminating in successive waves of COVID-19 cases. The scientific community has developed vaccines and antiviral agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease. Realizing that growing SARS-CoV-2 variations significantly impact the efficacy of antiviral therapies and vaccines, we have summarized the appearance and attributes of SARS-CoV-2 variants for future perspectives in drug design, bringing up-to-date hints for developing therapeutic agents targeting the variants. The Omicron variant is among the most mutated form; its strong transmissibility and immune resistance capacity have prompted international worry. Most mutation sites currently being studied are located in the BCOV_S1_CTD of the S protein. Despite this, several hurdles remain, such as developing vaccination and pharmacological treatment efficacies for emerging mutants of SARS-CoV-2 strains. In this review, we present an updated viewpoint on the current issues faced by the emergence of various SARS-CoV-2 variants. Furthermore, we discuss the clinical studies conducted to assist the development and dissemination of vaccines, small molecule therapeutics, and therapeutic antibodies having broad-spectrum action against SARS-CoV-2 strains.

Cervical cancer (CC) is the most common cancer in women worldwide and is almost always associated with repeated infections by human papillomavirus (HPV). Screening by traditional tests combined with biomarker identification techniques for low- or high-grade injuries, are becoming increasingly important in diagnosis and prognosis, avoiding countless deaths. This article explores existing literature on the main serum biomarkers and the identification of biomarkers associated with the oncogenesis of HPV expression in the identification of pre-cancerous lesions and of CC for an effective treatment, with reduction of recurrence, as well as we explain strategies for the development of biomarkers based on DNA, proteins and other markers. We also describe how markers of chromosomal instability host DNA, promoting hypo- or hypermethylation of DNA, as well as polymorphisms and epigenetic events in the p53 gene. Finally, we discuss changes in gene expression using cDNA microarray techniques and changes in the expression of proteins and markers identified through mass spectrometry.

Human Papillomavirus (HPV) self-sampling has the potential to increase cervical cancer screening (CCS) and reduce the cervical cancer burden in Medically Underserved Women (MUW). However, interventions promoting self-sampling are limited. We examined the effectiveness of an intervention study in increasing CCS among MUW. We conducted a quasi-experimental intervention study. Face-to-face verbal approach was to recruit MUW (n=85, mean age 48.57±11.02) living in a small city in the US. Behavioral intervention based on reframing, reprioritizing, and reforming (3R model) was used to educate the women about CCS in a group format. The women completed pre-and post-intervention assessments and followed-up interviews. The primary outcome was CCS uptake. Mixed methods analyses were conducted using a t-test for the primary outcome, PROCESS for mediation analysis, and NVivo for interview data. Majority of women (75%) completed self-testing. High-risk HPV prevalent among the women was 11%, and of those, 57% followed-up with physicians for care. We found that the significant increase in the women’s post-intervention screening behaviors was mediated by the increase in knowledge (Indirect Effect [IE] = .1314; 95% CI, .0104, .4079) and attitude (IE = .2167; 95% CI, .0291, .6050) scores, (p&lt;0.001). Interview analyses offered further explanations (see the explanations in parenthesis) why MUW found the intervention messages acceptable (encourages proactive behavior), feasible (simple and easy to understand), and appropriate (helpful and informative). Barriers including lack of trust and fear of results were identified. The findings suggest that an intervention that combines the 3R model and self-sampling may increase CCS among MUW.

A variety of myricetin derivatives bearing ferulic acid amide scaffolds were designed and synthesized. The structures of all title compounds were determined by 1 H NMR, 13 C NMR, 19 F NMR and HRMS. Preliminary bioassays suggested that some of the target compounds exhibited remarkable antiviral activities. In particular, compound 4l possessed significant protection activity against tobacco mosaic virus (TMV), with an half maximal effective concentration (EC50) value of 196.11 μg/mL, which was better than commercial agent ningnamycin (447.92 μg/mL). Meanwhile, microscale thermophoresis (MST) indicated that compound 4l have strong binding capability to tobacco mosaic virus coat protein (TMV-CP) with dissociation constant (Kd) values of 0.34 μmol/L, which was better than ningnamycin (0.52 μmol/L). These results suggest that novel myricetin derivatives bearing ferulic acid amide scaffolds may be considered as an activator for antiviral agents.

A two-stage pilot plant study has been completed that evaluated the performance of a reverse osmosis (RO) membrane process for the treatment of a feedwater that consisted of a blend of nanofiltration (NF) concentrate and brackish groundwater. Membrane performance was assessed by monitoring the process operation, collecting water quality data, and documenting the blended feedwater’s impact on fouling due to a combination of, or solely caused by, plugging, scaling, microbiological, or organic means. Fluorescence and biological activity reaction tests were used to identify the types of organics and microorganisms present in the blended feedwater. Additionally, scanning electron microscopy (SEM) and energy dispersive x-ray spectroscopy (EDS) were used to analyze suspended matter that collected on the surfaces of cartridge filters used in the pilot’s pretreatment system. SEM and EDS were also used to evaluate solids collected on the surfaces of 0.45-µm silver filter pads after filtering known volumes of NF concentrate and RO feedwater blends. Water quality analyses confirmed that the blended feedwater contained little to no dissolved oxygen, and the blended feedwater was absent of a significant amount of particulate matter as defined by silt density index and turbidity measurements. However, water quality results suggested that the presence of sulfate, sulfide, iron, anaerobic bacteria, and humic acid organics likely contributed to the formation of pyrite observed on some of the membrane surfaces autopsied at the conclusion of pilot operations. It was determined that first-stage membrane productivity was impacted by the location of cartridge filter pretreatment; however, second-stage productivity was maintained with no observed flux decline during the entire pilot operation’s timeline. Study results indicated that the operation of an RO process treating a blend of NF concentrate and brackish groundwater could maintain a sustainable and productive operation that provided a practical zero-discharge process operation while the dilution of RO feedwater salinity would lower overall production costs.

The burden of hypertension remains unacceptably high globally, particularly in low- and middle-income countries (LMICs). Workplace offer enormous potential as an idea setting for early detection and treatment of hypertension among the working class. Analysis of such a Workplace Screening Programme can reveal information about its potential impact. Machine learning techniques such as k-Means Clustering are untapped tools for such analyses. We set out to deploy this tool for the analysis of our university annual medical screening of workforce for hypertension. An anonymized dataset containing the demography and blood pressure measurements values obtained from staffs of different departments/units in an academic institution was obtained. The total number of samples or data points are 1, 723 in which the input dataset contains six features, including year category (2018, 2019, 2021,2022), Department/Unit (academic and non-academic), gender (male and female), while the target output is the blood pressure status (low, normal and high) respectively. Analysis of the dataset was carried out using machine learning techniques. In this retrospective analysis, it was observed that the mean age for this working class is 42 years old. Similarly, it was discovered that hypertension was prevalent among members of staff above the age of 40 irrespective of their gender or professional category (academic or non-academic). The analysis also revealed that there was a steady decline in the prevalence of hypertension from 2018 to 2022. From the research, it is evident that the adoption of machine learning techniques for periodic analyses of workplace health status screening initiative (especially for hypertension) is effective, feasible, and sustainable to diagnose and control hypertension among the working class.

Background/Objectives: Malnutrition is a common issue among cancer patients, leading to adverse outcomes and reduced survival rates; therefore, nutritional screening and assessment are essential. Our study aims to evaluate the diagnostic efficacy of the GLIM criteria to assess malnutrition and to compare the performance of various nutritional screening tests in evaluating nutritional risk. Methods: A cross-sectional observational study was conducted on outpatient oncologic patients. Malnutrition was assessed using PG-SGA and GLIM criteria. Nutritional screening was performed using NRS-2002, MUST, MST, and NUTRISCORE. Anthropometric measurements, handgrip strength, cancer medical records and descriptive data were collected and analyzed. Results: A total of 396 patients were involved. Malnutrition was diagnosed in 37.4% according to GLIM criteria and in 25.8% according to PG-SGA (p<0.001). The agreement between GLIM criteria and PG-SGA was substantial (ƙ= 0.63). The diagnostic performance of PG-SGA showed a sensitivity of 93% and a specificity of 96.3%, whereas the GLIM criteria demonstrated a sensitivity of 81.3% and a specificity of 91.2%. Both tools had a significant association with low dynamometry and low BMI (p<0.001). Nutritional risk was identified in 22.7% of the patients using NRS-2002, 25.8% with MUST, 26.5% with MST, and 12.9% with NUTRISCORE. The highest agreement among the nutritional screening tests was observed between MUST and PG-SGA (ƙ =0.64). Conclusions: GLIM criteria detected a higher prevalence of malnutrition compared to PG-SGA; however, PG-SGA demonstrated higher sensitivity and specificity. Both significantly agree with low dynamometry and low BMI. Among the nutritional screening tests, MUST and PG-SGA showed the highest agreement.

Virtual screening - predicting which compounds within a specified compound library bind to a target molecule, typically a protein - is a fundamental task in the field of drug discovery. Doing virtual screening well provides tangible practical benefits, including reduced drug development costs, faster time to therapeutic viability, and fewer unforeseen side effects. As with most applied computational tasks, the algorithms currently used to perform virtual screening feature inherent tradeoffs between speed and accuracy. Furthermore, even theoretically rigorous, computationally intensive methods may fail to account for important effects relevant to whether a given compound will ultimately be usable as a drug. Here we investigate the virtual screening performance of the recently released Gnina molecular docking software, which uses deep convolutional networks to score protein-ligand structures. We find, on average, that Gnina outperforms conventional empirical scoring. The default scoring in Gnina outperforms the empirical AutoDock Vina scoring function on 89 of the 117 targets of the DUD-E and LIT-PCBA virtual screening benchmarks with a median 1% early enrichment factor that is more than twice that of Vina. However, we also find that issues of bias linger in these sets, even when not used directly to train models, and this bias obfuscates to what extent machine learning models are achieving their performance through a sophisticated interpretation of molecular interactions versus fitting to non-informative simplistic property distributions.

Cytomegalovirus (CMV) is the leading infectious cause of brain defects and neurological dysfunctions, including sensorineural hearing loss (SNHL). A targeted screening in neonates failing the hearing screen is currently recommended in Italy according to national guidelines. However, SNHL may not be present at birth; also, congenital CMV (cCMV) may manifest with subtle signs other than SNHL. Therefore, inclusion of additional criteria for cCMV screening appears clinically valuable. Starting January 2021, we have implemented an expanded targeted cCMV screening at our center, with testing in case of maternal CMV infection during pregnancy, inadequate antenatal care, maternal HIV infection or immunosuppression, birthweight and/or head circumference.

Bone Morphogenetic Proteins (BMPs) are a group of structurally and functionally related signaling molecules that comprise a subfamily, belonging to the TGF-β superfamily. Most BMPs play roles in the regulation of embryonic development, stem cell differentiation, tumor growth and some cardiovascular and cerebrovascular diseases. Although evidences are emerging for the antiviral immunity of a few BMPs, more BMPs are needed to determine whether this function is universal. Here we identified the zebrafish bmp4 ortholog, whose expression is up-regulated by challenge with virus or its mimic poly(I:C). Overexpression of bmp4 in EPC cells significantly decreased the viral titer of GCRV-infected cells. Moreover, compared to wild type zebrafish, viral load and mortality were significantly increased in both larvae and adults of bmp4-/- mutant zebrafish infected with GCRV virus. We further demonstrated that Bmp4 promotes the phosphorylation of Tbk1 and Irf3 through p38 MAPK pathway, thereby inducing the production of type I IFNs in response to virus infection. These data suggest that Bmp4 runs an important role in the host defense against virus infection. Our study expands the understanding of BMP protein functions and opens up new targets for the control of viral infection.

The prevalence of antiviral drugs (AVTs) has seen a substantial increase in response to the COVID-19 pandemic, leading to heightened concentrations of these pharmaceuticals in wastewater systems. The hydrophilic nature of AVTs has been identified as a significant factor contributing to the low degradation efficiency observed in wastewater treatment plants. This characteristic often necessitates the implementation of additional treatment steps to achieve complete degradation of AVTs. Semiconductor-based photocatalysis has garnered considerable attention due to its promising potential in achieving efficient degradation rates and subsequent mineralization of pollutants, leveraging the inexhaustible energy of sunlight. However, in recent years, there have been few comprehensive reports that have thoroughly summarized and analyzed the application of photocatalysis for the removal of AVTs. This review commences by summarizing the types and occurrence of AVTs. Furthermore, it places a significant emphasis on delivering a comprehensive summary and analysis of the characteristics pertaining to the photocatalytic elimination of AVTs. Ultimately, the review sheds light on the identified research gaps and key concerns, offering invaluable insights to steer future investigations in this field.

Mammalian seminal plasma contains a multitude of bioactive components, including lipids, glucose, mineral elements, metabolites, proteins, cytokines and growth factors, with various functions during insemination and fertilization. The seminal plasma protein PDC-109 is one of the major soluble components of the bovine ejaculate and is crucially important for sperm motility, capacitation and acrosome reaction. A hitherto underappreciated function of seminal plasma is its anti-microbial and anti-viral activity, which may limit sexual transmission of infectious diseases during intercourse. We have recently discovered that PDC-109 inhibits the membrane fusion activity of influenza virus particles and significantly impairs viral infections at micromolar concentrations. Here we investigated whether the antiviral activity of PDC-109 is restricted to Influenza or if other mammalian viruses are similarly affected. We focused on Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the etiological agent of the Coronavirus Disease 19 (COVID-19), thoroughly assessing PDC-109 inhibition with SARS-CoV-2 Spike (S)-pseudotyped reporter virus particles, but also live-virus infections. Consistent with our previous publications we found significant virus inhibition, albeit accompanied by substantial cytotoxicity. Using time-of-addition experiments however, we discovered treatment regimen that enable virus suppression without affecting cell viability. We furthermore demonstrated that PDC-109 is also able to impair infections mediated by the VSV glycoprotein (VSVg) thus indicating a broad pan-antiviral activity against multiple virus species and families.

Plants have had historical significance in medicine since the beginning of civilization. The oldest medical pharmacopeias of the African, Arabian, and Asian countries solely utilize plants and herbs to treat pain, oral diseases, skin diseases, microbial infections, multiple types of cancers, reproductive disorders among a myriad of other ailments. The World Health Organization (WHO) estimates that over 65% of the world population solely utilize botanical preparations as medicine. Due to the abundance of plants, plant-derived medicines are more readily accessible, affordable, convenient, and have safer side-effect profiles than synthetic drugs. Plant-based decoctions have been a significant part of Jamaican traditional folklore medicine. Jamaica is of particular interest because it has approximately 52% of the established medicinal plants that exist on earth. This makes the island particularly welcoming for rigorous scientific research on the medicinal value of plants and the development of phytomedicine thereof. Viral infections like human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2), hepatitis virus B and C, influenza A virus, the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) have significant global burden. This is a review of some important Jamaican medicinal plants, with particular reference to their antiviral activity.

Seed longevity is a crucial trait for the seed industry and genetic resource preservation. To develop excellent cultivars with extended seed lifespans, it is important to understand the mechanism of keeping seed germinability long-term and to find useful genetic resources as prospective breeding materials. This study was conducted to identify the best cultivars with a high and stable seed longevity trait in the germplasm of rice (Oryza sativa L.) and to analyse the correlation between seed longevity and embryonic RNA integrity. Seeds from 69 cultivars of the world rice core collection selected by the NIAS in Japan were harvested in different years and subjected to long-term storage or controlled deterioration treatment (CDT). The long-term storage (4 °C, RH under 35%, 10 years) was performed on seeds harvested in 2010 and 2013. The seeds harvested in 2016 and 2019 were used for CDT (36 °C, RH of 80%, 40 days). Seed longevity and embryonic RNA integrity were estimated by a decrease in germination rate and RNA integrity number (RIN) after long-term storage, or CDT. The RIN value was obtained by electrophoresis of total RNA extracted from seed embryos. Seeds of ‘Vandaran (Indica)’, ‘Tupa 729 (Japonica)’, and ‘Badari Dhan (Indica)’ consistently showed higher seed longevity and embryonic RNA integrity both under long-term storage and CDT conditions, regardless of the harvest year. A strong correlation (R2 = 0.93) was observed between germination rates and RIN values of the seeds after long-term storage or CDT among nine cultivars selected based on differences in their seed longevity. The study findings revealed the relationship between rice seed longevity and embryo RNA stability and suggested potential breeding materials, including both Japonica and Indica cultivars, for improving rice seed longevity.

Developing recombinant Saccharomyces cerevisiae strains capable of transporting and fermenting cellobiose directly is a promising strategy for second-generation ethanol production from lignocellulosic biomass. In this study we cloned and expressed in the CEN.PK2-1C strain an intracellular βglucosidase (SpBGL7) from Spathaspora passalidarum, and co-expressed the cellobiose transporter SiHXT2.4 from Scheffersomyces illinoinensis, and two putative transporters from Candida tropicalis (CtCBT1) and Meyerozyma guilliermondii (MgCBT2). While all three transporters allowed cell growth on cellobiose, only the MgCBT2 permease allowed cellobiose fermentation, although cellobiose consumption was stuck (incomplete). The analysis of the βglucosidase and transport activities revealed that the cells stopped to consume cellobiose due to a drop in the transport activity. Since ubiquitinylation of lysine residues at the N- or C-terminal domains of the permease are involved in the endocytosis and degradation of sugar transporters, we constructed truncated versions of the permease lacking lysine residues at the C-terminal domain (MgCBT2ΔC), and at both the C- and N-terminal domain (MgCBT2ΔNΔC), and co-expressed these permeases with the SpBGL7 βglucosidase in an industrial strain. While the strain harboring the MgCBT2ΔC transporter continued to produce stuck cellobiose fermentations as the wild-type MgCBT2 permease, the strain with the MgCBT2ΔNΔC permease was able to consume and ferment all the cellobiose present in the medium. Thus, our results highlight the importance of expressing cellobiose transporters lacking lysine at the N- and C-terminal domains for efficient cellobiose fermentation by recombinant S. cerevisiae.

Background: Screening for postpartum depression can lower prevalence and ensure that mothers get adequate treatment and support. Yet, few practitioners screen.The present article is a brief review on barriers to screening and two screening scales that are validated for perinatal women. Findings: Despite recommendations from health organizations, most new mothers are not screened for depression. Providers cite lack of time, opening “Pandora’s box,” and lack of resources for mothers who screen positive as reasons for why they do not screen. The Edinburgh Postnatal Depression Scale and the Patient Health Questionnaires are brief screening scales that have been validated for new mothers and are widely available.Conclusions: Screening is the necessary first step to identifying new mothers who are depressed. Practitioners who screen need a clear plan, and to know how to access available community resources, so they will know what to do when a mother screens positive.

Some preterm and sick neonates have altered biochemical profiles and follow-up newborn screening (NBS) collections are recommended. The Victorian NBS program historically recommended recollections for babies with birth weight &lt;1500g (managed by the maternity service provider) and 3 weeks post-transfusion (managed by the laboratory). We aimed to determine adherence to current guidelines and review the guidelines to improve NBS performance. To do this we audited data from 348,584 babies between January 2018 and June 2022. Babies with a recorded birth weight of &lt;1500g were filtered for inclusion. For the overall review and visualization of the protocol, we sourced information from the literature, our professional society and tertiary hospital services. A total of 2647 babies had a birth weight recorded between 200 and 1499g. Of these 2036 (77%) had a second sample collected, indicating that &gt;1 in 5 babies were not receiving a follow-up collection. Our timing of recollections for transfused babies, requiring a 3-week follow-up collection, was longer than in other Australasian jurisdictions. A new combined “sick-prem-protocol” was launched to support recollections and after a one-year review achieve 95% compliance. We recommend NBS laboratories audit preterm and sick neonate recollections to ensure appropriate follow-up. This should be supported with a visual process map to aid education and compliance.

Cotton (Gossypium spp.) is the most important fibre crop worldwide. Black root rot and Fusarium wilt are two major diseases of cotton caused by soil-borne Berkeleyomyces rouxiae and Fusarium oxysporum f. sp. vasinfectum (Fov), respectively. Phenotyping plant symptoms caused by soil-borne pathogens has always been a challenge. To increase the uniformity of infection, we adapted a seedling screening method that directly uses liquid cultures to inoculate the plant roots and the soil. Four isolates each of B. rouxiae and Fov were collected from cotton fields in Australia and were characterised for virulence on cotton under controlled plant growth conditions. While the identity of all four B. rouxiae isolates were confirmed by multi-loci sequencing, only two of them were found to be pathogenic on cotton, suggesting variability in the ability of isolates of this species to cause disease. The four Fov isolates were phylogenetically clustered together with the other Australian Fov isolates and displayed both external and internal symptoms characteristic of Fusarium wilt on cotton plants. Furthermore, the isolates appeared to induce varied levels of plant disease severity indicating differences in their virulence on cotton. To contrast the virulence of the Fov isolates, four putatively non-pathogenic Fusarium oxysporum (Fo) isolates collected from cotton seedlings exhibiting atypical wilt symptoms were assessed for their ability to colonise cotton host. Despite the absence of Secreted In Xylem genes (SIX6, SIX11, SIX13 and SIX14) characteristic of Fov, all four Fo isolates retained the ability to colonise cotton and induce wilt symptoms. This suggests that slightly virulent strains of Fo may contribute to the overall occurrence of Fusarium wilt in cotton fields. Findings from this study will allow better distinction to be made between plant pathogens and endophytes and allow fungal effectors underpinning pathogenicity to be explored.

Commiphora molmol myrrh resin extracts, which have different physical properties such as polarity and dielectric constant, were prepared by immersion in extraction solvents (hot water, DMSO, hexane, ethanol, and methanol). Methanolic myrrh resin extracts showed broad antibacterial activity against isolated airborne bacteria. Furanoeudesma-1,3-diene and curzerene, as the main terpenoids in the methanolic myrrh resin extract, were analyzed using GC-MS, and the methanolic myrrh resin extracts were found to have antiviral activity (81.2% viral RNA inhibition) against H1N1 influenza virus. Biochars (wood powder-and rice husk-derived) coated with myrrh resin extracts also showed antiviral activity (22.6% and 24.3% viral RNA inhibition), due to the adsorption of terpenoids onto biochar. Myrrh resin extract using methanol as the extraction solvent is a promising agent with antibacterial and antiviral efficacy, and it can be utilized as a novel material via adsorption onto biochar for air filtration processes, cosmetics, fertilizers, drug delivery, and corrosion inhibition.

Abstract: Background: The optimal strategy for the microelimination of HCV within community settings remains ambiguous. We evaluated the percentage of participants who achieved linkage to care (LTC) following the conclusion of the screening campaign, and examined the diverse factors influencing LTC among these individuals. The effectiveness of recall intervention for the non-LTC population and its barriers were analyzed. Methods: We initiated an HCV patients recall program to identify the HCV participants who might not be treated after the HCV screening campaign. A program staff recalled HCV participants who lost to follow-up through the telephone from March 2019 to June 2019. They were informed of HCV treatment's importance, efficacy, availability, and safety. Result: Among 185 HCV-infected participants, 109 (58.9%) HCV-infected participants had obtained LTC. Compared with those who had LTC, those without LTC were older, lower education levels, were less aware of their HCV infection, less frequently lived in urban areas, and had less health insurance. At the end of the recall program, 125 (67.6 %) persons had liked to care. The proportion of LTC increased by 8.7 %. 119 persons had an HCV RNA test, and 82 (68.9%) had viremia. Of 82 patients with viremia, 78 (95.1%) received antiviral therapy. 76 (97.4 %) of them achieved a sustained virological response. Conclusion: After a community screening campaign, 59 % of participants with anti-HCV positive had LTC. The recall program can increase by 9 %. However, there were still 32% of HCV participants who couldn't be linked to care. Outreach care for non-LTC patients is a way worth trying to achieve micro-elimination of HCV in the rural community.

: Since the COVID-19 pandemic, people have become aware that materials (products) can transmit infection and have begun to focus on questions such as how bacteria and germs, the sources of in-fection, maintain their infectivity on material surfaces, and the extent to which materials can or cannot prevent this. and to what extent materials can and cannot prevent it. The SIAA, a non-profit organization of many Japanese companies, had created an entirely separate interna-tional standard for materials' antibacterial, antiviral, and antibiofilm properties (products). The authors have studied the academic basis for the operation of the standards and were deeply in-volved as researchers in establishing one of the standards. This paper describes the interna-tional standards and some representative examples of the authors' actual use of these standards and explains the current status and future problems.