bluuebunny/crossref_metadata_2025 huggingface dataset:
Nucleoside Analogues for Chagas Disease and Leishmaniasis Therapy: Current Status and Future Perspectives
Authors: Nwoke Emmanuel Awucha , Lowe Silvester , Aldabbagh Fawaz , Kalesh Karunakaran , Kadri Hachemi
Published: November 2024

Chagas disease and leishmaniasis are two neglected tropical diseases that affect millions of people in low- and middle-income tropical countries. These diseases caused by protozoan parasites pose significant global health challenges, which have been exacerbated by the recent COVID-19 pandemic. There is an urgent need for novel therapeutics as current treatments are limited by toxicity and drug resistance. Nucleoside analogues, which have been extensively studied and successfully applied in antiviral and antitumor therapies, hold potential that has yet to be fully explored for treating these neglected diseases. In this review, we discuss the use of nucleoside analogues as promising therapeutic agents for Chagas disease and leishmaniasis. After briefly examining the pathology, progression, and current treatment options for these diseases, we provide a comprehensive analysis of the status of nucleoside analogues and explore their prospects. By outlining the current landscape and future directions, this review aims to guide research and development efforts towards more effective nucleoside-based treatments for Chagas disease and leishmaniasis.
Construction and Application of Au NRs/4-MBA/PAM Ratiometric Surface-Enhanced Raman Scattering Substrate for Fish Veterinary Drug Residue Detection
Authors: Yu Jianxing , Fu Huiping , Gu Qing
Published: November 2024

Surface-enhanced Raman scattering (SERS) is widely used for trace detection of substances, and the key to this technology lies in the preparation of the substrate material. In this study, a composite SERS material of Au NRs/4-MBA/PAM was constructed and characterized to better immobilize the reference molecule 4-mercaptobenzoic acid (4-MBA). Electron transmission microscopy results demonstrated that the PAM film helps Au NRs to pack closely, enhancing the stability of the material structure and reducing the interference of external environmental factors on the response of 4-MBA, thus improving the accuracy of quantitative determination. Comparative experimental results with the Au NRs/4-MBA substrate showed that the relative standard deviations (RSDs) of the detection results for MG on different batches of Au NRs/4-MBA/PAM were less than 8.0%, and the RSDs of different points on the same material were less than 10.0%, indicating that the Au NRs/4-MBA/PAM has higher uniformity, better reproducibility, and higher sensitivity in detecting malachite green (MG). Applying this material in the recovery determination of fish extract showed that the recovery rates of MG were between 75.60% and 83.24%. Therefore, the Au NRs/4-MBA/PAM substrate can accurately detect and quantify veterinary drug residue in complex matrices such as food tissue.
Improved Pyroelectric Nanogenerator Performance of P(VDF-TrFE)/rGO Thin Film by Optimized rGO Reduction
Authors: Yaseen Hafiz Muhammad Abid , Park Sangkwon
Published: November 2024

The pyroelectric nanogenerator (PyNG) has gained increasing attention due to its capability of converting ambient or waste thermal energy into electrical energy. In recent years, nanocomposite films of poly(vinylidene fluoride-co-trifluoro ethylene) (P(VDF-TrFE)) and nanofillers such as reduced graphene oxide (rGO) have been employed due to their high flexibility, good dielectric properties, and high charge mobility for the application of wearable devices. This work investigated the effect of rGO reduction on pyroelectric nanogenerator performance. To prepare rGO, GO was reduced with different reducing agents at various conditions. The resulting rGO samples were characterized by XPS, FT-IR, XRD, and electrical conductivity measurements to obtain quantitative and qualitative information on the change in surface functionalities. Molecularly thin nanocomposite films of P(VDF-TrFE)/rGO were deposited on an ITO-glass substrate by the Langmuir–Schaefer (LS) technique. A PyNG sandwich-like structure was fabricated by arranging the thin films facing each other, and it was subjected to the pyroelectric current test. For various PyNGs of the thin films containing rGO prepared by different methods, the average pyroelectric peak-to-peak current (APC) and the pyroelectric coefficient (p) values were measured. It was found that a more reduced rGO resulted in higher electrical conductivity, and the thin films containing rGO of higher conductivity yielded higher APC and p values and, thus, better energy-harvesting performance. However, the thin films having rGO of too high conductivity produced slightly reduced performance. The Maxwell–Wagner effect in the two-phase system successfully explained these optimization results. In addition, the APC and p values for the thin film with the best performance increased with increasing temperature range. The current PyNG’s performance with an energy density of 3.85 mW/cm2 and a p value of 334 μC/(m2∙K) for ΔT = 20 °C was found to be superior to that reported in other studies in the literature. Since the present PyNG showed excellent performance, it is expected to be promising for the application to microelectronics including wearable devices.
A Facile Microwave-Promoted Formation of Highly Photoresponsive Au-Decorated TiO2 Nanorods for the Enhanced Photo-Degradation of Methylene Blue
Authors: Bondarev Andreea , Mihai Sonia , Usman Abubakar Katsina , Cursaru Diana Luciana , Matei Dănuţa , Sătulu Veronica , Gheorghe Cătălina , Brănoiu Gheorghe , Şomoghi Raluca
Published: November 2024

The integration of noble metal nanoparticles (NPs) effectively modifies the electronic properties of semiconductor photocatalysts, leading to improved charge separation and enhanced photocatalytic performance. TiO2 nanorods decorated with Au NPs were successfully synthesized using a cost-effective, rapid microwave-assisted method in H2O2 and HF media for methylene blue (MB) degradation under visible light illumination. X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), N2 physisorption, and UV–vis spectroscopy were employed to characterize the structures, morphologies, compositions, and photoelectronic properties of the as-synthesized materials. The fusing of Au NPs effectively alters the electronic structure of TiO2, enhancing the charge separation efficiency and improved electrical conductivity. The HF treatment promotes the exposure of the highly reactive (001) and (101) crystalline facets. The improved photocatalytic activity of Au/TiO2, achieving 97% efficiency, is attributed to the surface plasmon resonance (SPR) effect of the Au NPs and the presence of oxygen vacancies. The photodegradation of MB using the TiO2/Au photocatalysts follows pseudo-first-order kinetics, highlighting the enhanced catalytic efficiency of the synthesized nanostructures. The exceptional properties of the binary Au/TiO2 photocatalysts, including the SPR effect, exposed crystallographic faces, and efficient charge carrier separation through a decrease in the recombination of electrons and holes, contribute to the photocatalytic degradation of MB.
Extracellular Vesicle lncRNAs as Key Biomolecules for Cell-to-Cell Communication and Circulating Cancer Biomarkers
Authors: Papoutsoglou Panagiotis , Morillon Antonin
Published: November 2024

Extracellular vesicles (EVs) are secreted by almost every cell type and are considered carriers of active biomolecules, such as nucleic acids, proteins, and lipids. Their content can be uptaken and released into the cytoplasm of recipient cells, thereby inducing gene reprogramming and phenotypic changes in the acceptor cells. Whether the effects of EVs on the physiology of recipient cells are mediated by individual biomolecules or the collective outcome of the total transferred EV content is still under debate. The EV RNA content consists of several types of RNA, such as messenger RNA (mRNA), microRNA (miRNA), and long non-coding RNA (lncRNA), the latter defined as transcripts longer than 200 nucleotides that do not code for proteins but have important established biological functions. This review aims to update our insights on the functional roles of EV and their cargo non-coding RNA during cancer progression, to highlight the utility of EV RNA as novel diagnostic or prognostic biomarkers in cancer, and to tackle the technological advances and limitations for EV RNA identification, integrity assessment, and preservation of its functionality.
Can Phonemic Verbal Fluency Be Used to Predict Alzheimer’s Disease?
Authors: García-González Sara
Published: November 2024

Background: Among the cognitive markers, the deterioration of semantic and phonemic verbal fluency seems to be an early indicator of Alzheimer’s disease (AD). The aims of this study are (1) to evaluate both types of verbal fluency in the early stages of AD in order to know which of them deteriorates earlier and (2) to investigate if verbal fluency tasks can help to differentiate between patients with Mild Cognitive Impairment (MCI) who will progress to AD two years later (progress) and those who will not (non-progress). Method: A verbal fluency task was administered to 25 patients with MCI and their respective control subjects. All patients underwent a neuropsychological evaluation twice in order for us to follow up on their global cognitive status. The second time, eight of them converted to AD. Results: On the one hand, phonemic verbal fluency deteriorates earlier than semantic verbal fluency in MCI patients; on the other hand, although we found statistically significant differences between patients with MCI and AD in both types of fluency tasks, none were found when comparing the performance of progress and non-progress. Conclusions: These results point to a greater impairment in phonemic verbal fluency in MCI patients and its potential capacity to predict conversion to AD.
Limited Potential of Repetitive Transcranial Magnetic Stimulation for Treatment of Essential Tremor: A Systematic Review
Authors: Bishay Andrew A. E. D. , Guo Anton , Desai Rhea , Mushinski Samuel , Au Andy , Swenson Andrew J. , Iacoboni Marco , Bystritsky Alexander , Spivak Norman M.
Published: November 2024

Essential tremor (ET) is a prevalent movement disorder characterized by action tremors, predominantly affecting the upper limbs. While various pharmacological and non-pharmacological interventions have shown efficacy in managing ET, the therapeutic role of repetitive transcranial magnetic stimulation (rTMS) remains uncertain. This systematic review synthesizes evidence from clinical trials investigating rTMS as a treatment for ET. Despite some open-label trials reporting reductions in tremor severity, double-blinded studies revealed no significant difference between active and sham rTMS, suggesting a strong placebo effect. The findings indicate that while rTMS can reduce tremor scores, its therapeutic efficacy in ET remains unproven. Future research should focus on improving sham designs and conducting larger, rigorously controlled trials to clarify rTMS’s role in ET management. Current evidence supports considering alternative treatments, such as deep brain stimulation, over rTMS for ET.
Effect of Nitrogen and Sulphur Fertilization on Winter Oilseed Rape Yield
Authors: Jarecki Wacław , Korczyk-Szabó Joanna , Macák Milan
Published: November 2024

Oilseed rape is one of many crops with high nutritional requirements, particularly for nitrogen (N) and sulphur (S). Both macronutrients affect important physiological plant functions and are essential for the proper growth and development of oilseed rape. The objective of the experiment was to investigate the impact of nitrogen and sulphur fertilization on the yield of the winter oilseed rape cultivar LG Absolut. The experiment was conducted during the 2019/2020, 2020/2021, and 2022/2023 growing seasons on Haplic Cambisol soil formed from loess, with medium levels of mineral nitrogen and sulphur. In the experiment, two nitrogen fertilization treatments (150 and 200 kg ha−1) were compared in combination with three additional sulphur fertilization rates (20, 40, and 60 kg ha−1). The results demonstrated that the effectiveness of N and S fertilization varied between individual years. On average, the highest seed yields were obtained with the application of 200 kg N ha−1 combined with sulphur, regardless of the rate. This was attributed to a significant increase in soil–plant analysis development (SPAD) values, the number of pods per plant, and the thousand-seed weight. The increase in seed yield with the higher nitrogen rate without sulphur ranged from 0.36 to 0.57 t ha−1 compared to the lower rate (control 150 N kg ha−1). Supplementary sulphur fertilization increased seed yield ranging from 0.22 to 0.76 t ha−1. The protein content in the seeds increased, while the fat content decreased, following the application of the higher nitrogen rate. The decrease in fat content was mitigated by higher rates of sulphur. The application of 60 kg S ha−1 yielded similar results of the tested parameters to the lower rates. Therefore, for soils with moderate levels of mineral nitrogen and sulphur, it is recommended to fertilize winter oilseed rape with 200 kg N ha−1 combined with 20 or 40 kg S ha−1.
Correction: Al Dhaheri et al. The Effect of Therapeutic Doses of Culinary Spices in Metabolic Syndrome: A Randomized Controlled Trial. Nutrients 2024, 16, 1685
Authors: Al Dhaheri Ayesha S. , Alkhatib Dana Hasan , Feehan Jack , Cheikh Ismail Leila , Apostolopoulos Vasso , Stojanovska Lily
Published: November 2024

In the original publication [...]
Erythrocyte Selenium as a Potential Key Indicator for Selenium Supplementation in Low-Selenium Populations: A Selenium Supplementation Study Based on Wistar Rats
Authors: Lv Cunqi , Wang Ruixiang , Zeng Qingyu , Feng Chen , Li Guijin , Hao Shuxiu , Li Jiacheng , Wang Cheng , Sun Huixin , Du Linlin , Zhang Yu , Wang Xinshu , Wang Tong , Li Qi
Published: November 2024

Background: Selenium (Se) is an essential trace element for maintaining human health, with significant antioxidant and immunoregulatory functions. Inadequate Se intake may be associated with Keshan disease, Kashin–Beck disease, and hypothyroidism. However, effective indicators for scientifically guiding Se supplementation in Se-deficient populations are still lacking. Objectives: This study aims to explore the dynamic distribution of Se across various nutritional biomarkers and major organs in rats through a Se supplementation experiment, as well as the pairwise correlations between them, in order to identify reliable nutritional indicators for evaluating Se levels in the body. Methods: Se levels in hair, blood, and major tissues and organs were determined by atomic fluorescence spectrometry, and glutathione peroxidase (GSH-Px) levels were measured using an ELISA. Results: Se supplementation significantly increased Se levels in rat blood, hair, and major organs, as well as GSH-Px levels in blood. Se primarily accumulated in the liver and kidneys, followed by myocardium, spleen, and muscles. Serum and plasma Se were found to be the best indicators of short-term Se intake, while erythrocyte Se levels showed a stronger correlation with Se levels in tissues and organs, making it a better marker for assessing long-term Se nutritional status compared to hair Se. Conclusions: This study demonstrates the potential of erythrocyte Se levels as an indicator for evaluating long-term Se nutritional status, providing scientific evidence for Se nutritional assessments.
Consumption of a Branched-Chain Amino Acids-Containing Sports Beverage During 21 km of Running Reduces Dehydration, Lowers Muscle Damage, and Prevents a Decline in Lower Limb Strength
Authors: Liang Zhuoying , Liang Yiheng , Zhang Chengnan , Zhao Xueyuan , Qiu Junqiang
Published: November 2024

Objectives: The purpose of this study was to examine the acute effects of branched-chain amino acids (BCAAs)-containing electrolyte beverage (AE) on water–electrolyte balance, muscle damage, time to finish the final 5 km, and muscle strength compared to a standard commercially available carbohydrate–electrolyte sports beverage (CE), pure water (W), and no rehydration (N). Methods: Fourteen trained male participants (20 ± 2 years old) completed four randomized 21 km running trials. The participants were instructed to consume their drink (150 mL W, 150 mL CE, or 150 mL AE) or no rehydration (N) at 5 km, 10 km, and 15 km. Body mass and muscle strength were assessed, and blood samples were collected before and after exercise. Perceptual scales were administered during and after running. Blood electrolyte levels (sodium, potassium, and chloride) and creatine kinase (CK) concentration were analyzed. Results: The change in plasma volume with AE was significantly smaller than that with N (p < 0.05). Consuming AE maintained the best potassium balance (p < 0.05). Twenty-four hours after exercise, serum CK concentrations significantly elevated in N, W, and CE (p < 0.05), but did not reach statistical significance in the AE group (p > 0.05). Compared to N, consuming AE resulted in significantly less soreness 24 h after exercise (p < 0.05). There was no difference in time to finish the final 5 km (p > 0.05). Maximal voluntary isometric force output was significantly lower after exercise with N and W (p < 0.05) but not with CE or AE (p > 0.05). Conclusions: Consuming a BCAAs-containing sports beverage during a 21 km run can help reduce dehydration, maintain potassium balance, lower muscle damage, and prevent the decline in lower limb strength after 21 km running.
Organizational Rigidity and Demands: A Qualitative Study on Nursing Work in Complex Organizations
Authors: van Kraaij Julia , van Merode Frits , Lenssen Emma , Vermeulen Hester , van Oostveen Catharina ,   RN2Blend Consortium
Published: November 2024

Background/Objectives: The nursing work environment is a critical element in healthcare delivery and a strong predictor of both patient and nurse outcomes. Understanding the complexity and multifaceted nature of this environment is essential for improving nursing practices and optimizing healthcare systems. This study aimed to gain insights into the perceived characteristics of the nursing work environment, considering it as a complex and multifaceted system. Methods: A qualitative research approach was employed, involving 42 semi-structured interviews with 43 nurses and managers from academic, teaching, and general hospitals in The Netherlands. Data were collected between July 2020 and August 2021 through convenience sampling. Thematic coding was conducted to identify key patterns and themes. Results: The findings revealed that nurses demonstrated flexibility and a strong commitment to high-quality care, despite grappling with rigorous organizational tasks and processes. Four key themes emerged: (1) direct patient care as a standard feature of nursing work; (2) nurses’ flexibility for hospital productivity; (3) interdependencies, which decrease autonomous nursing practices; and (4) organizational structures that determine how nurses can shape their work. Nurses found it difficult to balance direct care with broader tasks due to organizational rigidity, revealing a gap between ideal nursing practices and daily reality. Conclusions: This study highlighted the challenges within the nursing work environment, particularly in balancing direct care with organizational demands. Addressing this gap between ideal nursing practice and reality requires a systems approach. This includes autonomous practices, supportive management, and flexible structures, allowing nurses to shape their work and enhance job satisfaction and care quality.
Characterizing the Tropical Cyclones Activity over Arabian Sea (1982–2021)
Authors: Labban Abdulhaleem H. , Hasanean H. M. , Almahri Ali , Al-Sakkaf Ali Salem , Hussein Mahmoud A. A.
Published: November 2024

The current study looks at how the characteristics of Arabian Sea tropical cyclones (TCs) change over time. The results show that in the pre-monsoon (April–June) and the post-monsoon (October–December), the activity of TCs > 34 knots, including cyclonic storm (CS), severe cyclonic storm (SCS), very severe cyclonic storm (VSCS), extreme severe cyclonic storm (ESCS), and super cyclonic storm (Sup. CS), has significantly increased, while the tendency of TCs < 34 knots, depressions and deep depressions (Ds) over the Arabian Sea has only slightly increased. Most of the TC activity in the first two decades (1982–2001) over the Arabian Sea activated on the eastern side, while in the last two decades (2002–2021), there was an expansion toward the southwest region of the Arabian Sea, especially in the post-monsoon season. The composite analysis of environmental parameters over the Arabian Sea reveals that the negative anomalies of outgoing longwave radiation (OLR) and the positive anomalies of relative humidity at 500 hPa (RH–500 hPa) in the first decade (1982–1991) and the second decade (1992–2001) are more concentrated on the eastern side of the Arabian Sea, leading to increased activity for TCs. Decades three (2002–2011) and four (2012–2021) demonstrated a wide distribution of weak vertical wind shear (VWS) and strong convection (OLR and RH–500 hPa) over the Arabian Sea basin. This led to TCs occurring more frequently and stronger, especially in the post-monsoon season. SST over the Arabian Sea was sufficient for tropical storm activity (≥26.5 °C) for both typical seasons.
The Impact of Perfluorooctanoic Acid (PFOA) on the Mussel Mytilus galloprovincialis: A Multi-Biomarker Evaluation
Authors: Copeto Sandra , Ganço Sara , Ferreira Inês João , Sanchez Didier , Nunes Maria João , Motta Carla , Silva Marco , Diniz Mário
Published: November 2024

Perfluorooctanoic acid (PFOA) has been widely studied due to its environmental persistence and bioaccumulation potential, raising concerns about its effects on aquatic life. This research evaluates the impact of PFOA on the antioxidant defenses and stress response systems of the mussel Mytilus galloprovincialis. Mussels were exposed to three concentrations of PFOA (1, 10, and 100 µg·L−1) over 28 days. Several biomarkers, including glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (LPO), total antioxidant capacity (TAC), vitellogenin (VTG), ubiquitin (UBI), and caspase-3 (CASP) were analyzed. The results suggest stress responses, particularly in animals exposed to higher concentrations, as shown by GST and SOD activities which increased according to PFOA concentrations. Additionally, oxidative stress markers such as MDA and CAT showed variable responses depending on the exposure concentration tested. This study underscores the need for further investigation into the effects of PFOA on mollusks but also the need to unveil gender-specific responses in aquatic organisms exposed to this contaminant. The concentrations of PFOA used in our research are lower than those examined in previous studies, providing crucial insights into the impacts of even minimal exposure levels. It highlights the potential of M. galloprovincialis as a bioindicator in environmental monitoring programs, providing crucial insights for environmental management and policymaking regarding regulating and monitoring PFOA in marine settings. Consequently, in a country where seafood consumption is the second largest in Europe, implementing environmental policies and regulatory measures to manage and monitor PFOA levels in marine environments is crucial.
Marine-Derived Therapeutics for the Management of Glioblastoma: A Case Series and Comprehensive Review of the Literature
Authors: Karbhari Nishika , Khagi Simon
Published: November 2024

Introduction: Glioblastoma is a fatal intracranial neoplasm that is refractory to treatment, with inevitable disease recurrence and progression to death. Marine-derived compounds, including those found in nutraceutical products, may provide therapeutic benefit in the setting of glioblastoma. We present two patient cases whose courses demonstrate a compelling role for marine-derived products in the management of glioblastoma. Cases: Case 1 describes a patient with MGMT promoter unmethylated glioblastoma who went on to complete standard of care chemoradiation along with concurrent use of a majority sea cucumber (MSC) blend known as SeaCare® (SeaCare, Torrington, CT, USA). Her survival of over 2 years significantly exceeds the recognized median survival time of glioblastoma. Case 2 describes a patient with a complicated course who experienced dramatic improvement after the initiation of the MSC blend, with an exceptional survival time of over 4 years post-diagnosis. Discussion: The mechanisms of marine-derived products that underlie these dramatic clinical effects are likely multifaceted but may hinge on the modification of the tumor immune microenvironment and suppression of tumorigenic effects. Specifically, the change in tumor-associated macrophages (TAMs) within the tumor microenvironment is central to this complex interplay. Conclusions: Ultimately, the use of marine products in the treatment of glioblastoma may present a novel and promising therapeutic strategy that warrants further investigation.
A Probe into the Evolution of Primordial Perturbations in the f(T) Gravity Framework with Chaplygin Gas
Authors: Sultana Sanjeeda , Chattopadhyay Surajit , Pasqua Antonio
Published: November 2024

This work is focused on studying the cosmology of variable modified Chaplygin gas (VMCG) in the framework of exponential and logarithmic f(T) theory. The equation of state (EoS) for VMCG in exponential and logarithmic f(T) gravity shows quintom behavior. Primordial perturbations were studied for VMCG in both exponential and logarithmic f(T) gravity, and it was observed that the potential increases with cosmic time t, and the scalar field decreases toward the minimum value of the potential. The squared speed of sound was positive, meaning that VMCG in both exponential and logarithmic f(T) gravity shows stability against small gravitational perturbations.
Longitudinal Fecal Microbiota Profiles in A Cohort of Non-Hospitalized Adolescents and Young Adults with COVID-19: Associations with SARS-CoV-2 Status and Long-Term Fatigue
Authors: Olbjørn Christine , Hagen Milada , Moen Aina Elisabeth Fossum , Havdal Lise Beier , Sommen Silke Lauren , Berven Lise Lund , Thiis-Evensen Espen , Stiansen-Sonerud Tonje , Selvakumar Joel , Wyller Vegard Bruun Bratholm
Published: November 2024

Adolescents most often experience mild acute COVID-19, but may still face fatigue and persistent symptoms such as post-COVID-19 condition (PCC) and post-infective fatigue syndrome (PIFS). We explored the fecal microbiota of SARS-CoV-2 positive and negative non-hospitalized adolescents and young adults (12–25 years of age) in the “Long-Term Effects of COVID-19 in Adolescents” (LoTECA) project, a longitudinal observational cohort study. With a targeted qPCR approach, the quantities of 100 fecal bacterial taxa were measured at baseline (early convalescent stage) in 145 SARS-CoV-2-positive and 32 SARS-CoV-2 negative participants and after six months in 107 of the SARS-CoV-2-positive and 19 of the SARS-CoV-2 negative participants. Results: Faecalibacterium prausnitzii M21.2 and Gemmiger formicilis (both p < 0.001) were enriched in the SARS-CoV-2-positive participants compared to negative controls at baseline. In SARS-CoV-2-positive participants, lower baseline abundance of Faecalibacterium prausnitzii M21/2 (p = 0.013) and higher abundance of Clostridium spiroforme (p = 0.006), Sutterella wadsworthensis (p < 0.001), and Streptococcus thermophilus (p = 0.039) were associated with six-month fatigue. Sutterella wadsworthensis and Streptococcus thermophilus enrichment was additionally associated with PCC in the SARS-CoV-2-positive group (p < 0.001 and 0.042 respectively). Conclusions: Adolescents and young adults with mild acute COVID-19 infection had increased fecal abundance of the beneficial Faecalibacterium prausnitzii M21/2 and Gemmiger formicilis compared to SARS-CoV-2 negative controls in the early convalescent stage. Additionally, the abundance of both known (Faecalibacterium prausnitzii, Streptococcus thermophilus) and new (Clostridium spiroforme, Sutterella wadsworthensis) bacteria were associated with persistent symptoms such as fatigue in the COVID-19 infected group, warranting further exploration of the role of these bacteria in COVID-19 disease and PCC pathophysiology.
Biofilm Production in Intensive Care Units: Challenges and Implications
Authors: Taner Ferdiye , Baddal Buket , Theodoridis Liana , Petrovski Steve
Published: November 2024

The prevalence of infections amongst intensive care unit (ICU) patients is inevitably high, and the ICU is considered the epicenter for the spread of multidrug-resistant bacteria. Multiple studies have focused on the microbial diversity largely inhabiting ICUs that continues to flourish despite treatment with various antibiotics, investigating the factors that influence the spread of these pathogens, with the aim of implementing sufficient monitoring and infection control methods. Despite joint efforts from healthcare providers and policymakers, ICUs remain a hub for healthcare-associated infections. While persistence is a unique strategy used by these pathogens, multiple other factors can lead to persistent infections and antimicrobial tolerance in the ICU. Despite the recognition of the detrimental effects biofilm-producing pathogens have on ICU patients, overcoming biofilm formation in ICUs continues to be a challenge. This review focuses on various facets of ICUs that may contribute to and/or enhance biofilm production. A comprehensive survey of the literature reveals the apparent need for additional molecular studies to assist in understanding the relationship between biofilm regulation and the adaptive behavior of pathogens in the ICU environment. A better understanding of the interplay between biofilm production and antibiotic resistance within the environmental cues exhibited particularly by the ICU may also reveal ways to limit biofilm production and indivertibly control the spread of antibiotic-resistant pathogens in ICUs.
Clinical Snapshot of Group A Streptococcal Isolates from an Australian Tertiary Hospital
Authors: Shaw Phoebe K. , Hayes Andrew J. , Langton Maree , Berkhout Angela , Grimwood Keith , Davies Mark R. , Walker Mark J. , Brouwer Stephan
Published: November 2024

Streptococcus pyogenes (Group A Streptococcus, GAS) is a human-restricted pathogen that causes a wide range of diseases from pharyngitis and scarlet fever to more severe, invasive infections such as necrotising fasciitis and streptococcal toxic shock syndrome. There has been a global increase in both scarlet fever and invasive infections during the COVID-19 post-pandemic period. The aim of this study was the molecular characterisation of 17 invasive and non-invasive clinical non-emm1 GAS isolates from an Australian tertiary hospital collected between 2021 and 2022. Whole genome sequencing revealed a total of nine different GAS emm types with the most prevalent being emm22, emm12 and emm3 (each 3/17, 18%). Most isolates (14/17, 82%) carried at least one superantigen gene associated with contemporary scarlet fever outbreaks, and the carriage of these toxin genes was non-emm type specific. Several mutations within key regulatory genes were identified across the different GAS isolates, which may be linked to an increased expression of several virulence factors. This study from a single Australian centre provides a snapshot of non-emm1 GAS clinical isolates that are multiclonal and linked with distinct epidemiological markers commonly observed in high-income settings. These findings highlight the need for continual surveillance to monitor genetic markers that may drive future outbreaks.
Methylene Blue Has Strong Extracellular Virucidal Activity Against a SARS-CoV-2-Related Pangolin Coronavirus with No Intracellular or In Vivo Efficacy
Authors: Wei Lai , Ma Yuezhen , Ren Yuhao , Lu Shanshan , Xiao Xiumei , Luo Shengdong , An Xiaoping , Li Erguang , Fan Huahao , Song Lihua
Published: November 2024

Studies have demonstrated that methylene blue exhibits significant antiviral activity against SARS-CoV-2 or related coronaviruses at the cellular level, suggesting its potential as an anti-SARS-CoV-2 drug. Herein, we report that methylene blue does not exhibit noticeable antiviral activity in a lethal model involving SARS-CoV-2-related pangolin coronavirus GX_P2V (short_3UTR) infection in CAG-hACE2 transgenic mice. We employed plaque reduction assays and cell infection experiments to compare the extracellular virucidal activity of the compound and its ability to inhibit viral replication in cells to those of nirmatrelvir. Methylene blue demonstrated strong virucidal activity but did not inhibit viral replication in cells. The control compound nirmatrelvir lacked virucidal activity but exhibited strong abilities to inhibit viral replication. The virucidal activity of methylene blue was further tested in mouse plasma. Incubation in mouse plasma increased the virucidal EC50 value of methylene blue, indicating that mouse plasma can affect the stability of the compound, although mouse plasma has some extent of natural virucidal activity. These findings elucidate why methylene blue lacks antiviral efficacy in vivo and provide insights for the development of antiviral drugs.
An Overview of a Re-Emerging Disease in Italy: Bovine Tuberculosis Outbreaks in Cattle from MTBC-Free Territories
Authors: Giusti Alice , Carbonetta Lorenzo , Fratini Filippo , Spatola Gabriele , Panerai Fiorenza , Pardini Stefano , Cianti Luca , Armani Andrea
Published: November 2024

Bovine tuberculosis (bTB) is a zoonotic disease with consequences for public health as well as the economy. In the EU, compulsory eradication programmes have been applied, and most territories in Italy have been reported as disease-free (FTs). However, outbreaks (OBs), i.e., an officially confirmed occurrence of bTB in one or more animals in an establishment, have continued to be reported. In this study we provide an overview of bTB in terms of OB numbers in cattle from Italian FTs. Legislative sources were collected to find the FTs, the relevant declaration of free status year (FSY), and regional control and surveillance plans. Then, descriptive and statistical analyses were applied to the collected OBs. A total of 12 regions and 19 provinces were declared FTs in the 20 years from 2003 to 2023. Differences in regional plans were observed with respect to the percentages of herds that were annually controlled (control frequency). Overall, 370 OBs were recorded. A non-statistically significant decrease in the OB incidence rate after the FSY was declared. However, a notable increase in OBs detected at slaughterhouses after the FSY suggests that control systems (serological tests) at the herd level are not completely effective. Differences in the herds’ control frequencies among FTs seem to not have had a significant influence on the observed OB number. The Tuscany region was the most affected FT based on the OB numbers after the FSY (especially in the last year). Epidemiologically relevant primary determinants seem to be the farming system (semi-extensive and adjacent herds) and the cattle movements from positive incidence areas (trade and animal fairs). The role of wild boars in the disease maintenance cannot be excluded. The results of this study stress the need to revise bTB eradication and surveillance plans based on risk analysis.
Vancomycin-Resistant Enterococci: Current Understandings of Resistance in Relation to Transmission and Preventive Strategies
Authors: Mareković Ivana , Markanović Manda , Lešin Joško , Ćorić Mario
Published: November 2024

Due to the limited treatment options and increased mortality rates, infection prevention and control strategies have been implemented for many years to mitigate dissemination of vancomycin-resistant enterococci (VRE) within healthcare settings. The overview provides an insight into the most recent research, particularly the pathogen’s resilience in the healthcare environment, and the critical need for infection control strategies, which are currently being scrutinized by some researchers. The notable resilience of enterococci to various environmental conditions highlights the necessity for investigations into innovative technologies capable of effectively targeting the biofilm produced by enterococci on hospital surfaces. A critical approach to traditional infection control strategies is becoming more accepted worldwide, taking into account the epidemiological situation in the given healthcare setting as well as specific characteristics of a patient. For certain high-risk patient populations, traditional infection control strategies including CP and screening should not be omitted. Additionally, further investigation into the resistance mechanisms of available antimicrobial agents is essential, as is research into their potential association with specific successful clones through WGS genotyping, to pre-emptively mitigate their spread before it escalates.
IGFBP-2 in Critical Illness: A Prognostic Marker in the Growth Hormone/Insulin-like Growth Factor Axis
Authors: Savvidis Christos , Kouroglou Eleni , Kallistrou Efthymia , Ragia Dimitra , Dionysopoulou Sofia , Gavriiloglou Georgios , Tsiama Vasiliki , Proikaki Stella , Belis Konstantinos , Ilias Ioannis
Published: November 2024

Critical illness (CI) triggers complex disruptions in the growth hormone (GH)/insulin-like growth factor (IGF) axis, significantly affecting the dynamics of insulin-like growth-factor-binding proteins (IGFBPs). Among these, IGFBP-2 shows a sustained elevation during CI, which inversely correlates with serum levels of IGF-1, IGFBP-3, and the acid-labile subunit (ALS). Although IGFBP-2 does not directly interact with ALS, it may influence the availability of IGFs by competing with other IGFBPs for binding to IGF-1 and IGF-2. Research suggests that this persistent elevation of IGFBP-2 is largely driven by cytokine activity during CI, reflecting an adaptive response rather than a direct result of GH/IGF axis dysregulation. The clinical importance of IGFBP-2 is emphasized by its correlation with disease severity in conditions like sepsis and coronavirus disease 2019 (COVID-19), where its levels are markedly elevated compared to healthy controls and are similar to those observed in sepsis from various causes. Beyond its role in endocrine regulation, IGFBP-2 appears to play a part in metabolic and inflammatory pathways. Elevated IGFBP-2 levels have been linked to increased mortality and longer hospital stays, indicating its potential utility as a prognostic marker. Furthermore, measuring plasma IGFBP-2 may have other diagnostic applications, aiding in the assessment of CI when traditional biomarkers are inconclusive.
Trace Lithium for Suicide Prevention and Dementia Prevention: A Qualitative Review
Authors: Terao Takeshi , Hirakawa Hirofumi , Muronaga Masaaki , Izumi Toshihiko , Kohno Kentaro
Published: November 2024

Background: Anti-manic effects of lithium and the nature of trace element in lithium were first observed in 1949. In this review, we explore the potential effects of trace lithium in the prevention of suicide and dementia. Methods: This is a qualitative and non-systematic review. Results: While most studies to date have been cross-sectional, limiting the establishment of causal relationships, the potential benefits of trace lithium for suicide prevention and dementia prevention are notable, especially in the absence of radical treatments for suicide and dementia. Furthermore, trace lithium appears to lack many of the adverse effects associated with so-called therapeutic lithium levels. Conclusions: The present findings suggest that trace lithium may be associated with lower suicide rates and reduced dementia rates. Probably, trace lithium may inhibit testosterone and thereby mitigate aggression and impulsivity and decrease suicide. Also, trace lithium may inhibit GSK-3β and thereby lower amyloid β and tau hyperphosphorylation and inhibit pro-inflammatory cytokines such as IL 6 and IL 8 and thereby mitigate inflammation, whereas trace lithium may promote BDNF and neurogenesis in the general population.
Manipulation of Lipid Nanocapsules as an Efficient Intranasal Platform for Brain Deposition of Clozapine as an Antipsychotic Drug
Authors: Katamesh Ahmed A. , Abdel-Bar Hend Mohamed , Break Mohammed Khaled Bin , Hassoun Shimaa M. , Subaiea Gehad , Radwan Amr , Abo El-Enin Hadel A.
Published: November 2024

Background/objectives: The blood–brain barrier (BBB) significantly limits the treatment of central nervous system disorders, such as schizophrenia, by restricting drug delivery to the brain. This study explores the potential of intranasal clozapine-loaded lipid nanocapsules (IN LNCsClo) as a targeted and effective delivery system to the brain. Methods: LNCsClo were prepared using the phase inversion technique and characterized in terms of size, zeta potential, entrapment efficiency (EE%), and in vitro drug release. The pharmacokinetic, safety, and pharmacodynamic effects of LNCsClo were then evaluated in a rat model through intranasal (IN) administration and compared with those of oral and intravenous (IV) Clo solutions. Results: LNCsClo were prepared using a phase inversion technique, resulting in a nanocarrier with a particle size of 28.6 ± 3.6 nm, homogenous dispersion, and high EE% (84.66 ± 5.66%). Pharmacokinetic analysis demonstrated that IN LNCsClo provided enhanced Clo brain bioavailability, rapid CNS targeting, and prolonged drug retention compared to oral and intravenous routes. Notably, the area under the curve (AUC) for brain concentration showed more than two-fold and eight-fold increases with LNCsClo, compared to IV and oral solutions, respectively, indicating improved brain-targeting efficiency. Safety assessments indicated that LNCsClo administration mitigated Clo-associated metabolic side effects, such as hyperglycemia, insulin imbalance, and liver enzyme alterations. Additionally, pharmacodynamic studies showed that LNCsClo significantly improved antipsychotic efficacy and reduced schizophrenia-induced hyperactivity, while preserving motor function. Conclusions: These results highlight the potential of IN LNCsClo as a novel drug delivery system, offering improved therapeutic efficacy, reduced systemic side effects, and better patient compliance in the treatment of schizophrenia and potentially other CNS disorders.
From Chaos to the Absurd: Existentialism for the 21st Century
Authors: Aberšek Boris
Published: November 2024

As Sartre pointed out, philosophical questions are questions that each generation must ask themselves because only this promotes the feeling of being alive, which is especially true for existential questions closely related to time–space, the moment, and our society. Sartre placed his philosophy of existentialism in wartime and the social conditions of the time at the beginning of the 20th century. We can equate these conditions with today’s conditions; we are once again facing threats of war, and once again, we are facing chaotic conditions that increasingly lead to absurdity but are also entirely different. Today, at the beginning of the 21st century, the clarity and disambiguation of the 20th century no longer exist, as the relationships between beings and the world have drastically changed. We can observe that (1) the world is not one; there are two worlds, the physical and the cyber world and (2) being is not one; there are two beings (entities), human and AI-based forms of artificial life (ALF), between which there is a permanent tension. We advocate the thesis that in the society of the future, man must still play a master role; he must still be the being who will guide this society. Also, as Sartre claimed, each era must create its philosophy and consider real time–space. Responses to changes in this time–space also relate to existentialism in the 21st century. In this context, it is necessary to redefine the view of the future and the guidelines for the development of future society.
Threshold Gain Reduction in Tandem Semiconductor Nano-Lasers
Authors: Fan Yuanlong , Zhang Jing , Shore K. Alan
Published: November 2024

It is shown that a significant reduction in the threshold gain of electrically pumped semiconductor nano-lasers may be achieved in bridge-connected tandem semiconductor nano-lasers. Optimization of the design is achieved by exploring the impact of bridge length and width on the threshold gain. In addition, a detailed examination is also made of the emission patterns of the structure. It is found that a trade-off emerges between threshold gain and beam quality where multi-lobed far field emission may be associated with the lowest threshold gains.
Antifungal Properties of Sargassum cinereum and Padina boergesenii Extracts Against Fungi Associated with Strawberry Fruits Concerning Mycotoxin Production
Authors: El-Shahir Amany A. , Alzamel Nurah M. , Abuzaid Amani Omar , Loutfy Naglaa , Alwaleed Eman A.
Published: November 2024

Strawberries are susceptible to decay and destruction while being harvested and stored. This study had the following objectives: (1) the documentation of fungi and mycotoxin production associated with infected strawberry fruits; (2) the evaluation of the primary phytochemicals of Sargassum cinereum and Padina boergesenii by gas chromatography–mass spectrometry (GC–MS) and Fourier transform infrared (FT-IR) analysis to identify the active chemical composition of the seaweed extracts; and (3) the assessment of the antifungal activity of five extracts from brown seaweeds both in vitro and in vivo against fungal infections on fresh fruit under post-harvest conditions. The most common fungi were Aspergillus niger 14.36%, Botrytis cinerea 38.29%, and Mucor irregularis 16.88%. Padina boergesenii acetone extract had the highest in vitro antifungal activity. The methanol extracts of both S. cinereum and P. boergesenii were effective against the pathogenicity and aggressiveness (in vivo) on post-harvest strawberry fruits. B. cinerea could produce botrydial and dihydrobotrydial toxins with concentrations of 8.14 µg/mL and 4.26 µg/mL, respectively. A. niger could produce ochratoxin A with a concentration of 10.05 µg/mL. The present study demonstrates that the extracts of macroalgae S. cinereum and P. boergesenii contain secondary metabolites and antioxidants, indicating their potential utilization in antifungal applications.
Heat Shock Factor HSFA6b Mediates Mitochondrial Unfolded Protein Response in Arabidopsis thaliana
Authors: Yu Guolong , Huang Zhuoran , Guo Chaocheng , Li Jiahao , Wang Xinyuan , Wang Yudong , Wang Xu
Published: November 2024

Mitochondria are important organelles in eukaryotes and are involved in various metabolic processes. Mitochondrial proteotoxic stress triggers the mitochondrial unfolded protein response (UPRmt) to restore mitochondrial protein homeostasis and maintain normal life activities. However, the regulatory mechanism of plant UPRmt remains to be revealed in Arabidopsis. Based on the fact that UPRmt activates heat shock protein (HSP) genes, we identified the heat shock transcription factor HSFA6b as a key regulator mediating UPRmt through reverse genetics. HSFA6b responded to mitochondrial proteotoxic stress and regulated mitochondrial heat shock proteins’ genes’ (mtHSPs) expression. HSFA6b translocated to the nuclear after treatment with doxycycline (Dox)—a mitochondrial ribosome translation inhibitor. HSFA6b binds to the mtHSPs promoters and activates mtHSPs expression. The HSFA6b mutation blocked the UPRmt signals to promote root growth under mitochondrial proteotoxic stress and accelerated leaf senescence during development. Our study reveals a novel signal-regulating mechanism in the UPRmt pathways and provides new insights regarding the regulation of plant growth and development and stress resistance by the UPRmt pathways.