Chlamydial infections and diseases caused by filarial nematodes are global health concerns. However, treatment presents challenges due to treatment failures potentially caused by persisting Chlamydia and long regimens against filarial infections accompanied by low compliance. A new treatment strategy could be the targeting of the reduced peptidoglycan structures involved in cell division in the obligate intracellular bacteria Chlamydia and Wolbachia, the latter being obligate endosymbionts supporting filarial development, growth, and survival. Here, cell culture experiments with C. trachomatis and Wolbachia showed that the nucleoside antibiotics muraymycin and carbacaprazamycin interfere with bacterial cell division and induce enlarged, aberrant cells resembling the penicillin-induced persistence phenotype in Chlamydia. Enzymatic inhibition experiments with purified C. pneumoniae MraY revealed that muraymycin derivatives abolish the synthesis of the peptidoglycan precursor lipid I. Comparative in silico analyses of chlamydial and wolbachial MraY with the corresponding well-characterized enzyme in Aquifex aeolicus revealed a high degree of conservation, providing evidence for a similar mode of inhibition. Muraymycin D2 treatment eradicated persisting non-dividing C. trachomatis cells from an established penicillin-induced persistent infection. This finding indicates that nucleoside antibiotics may have additional properties that can break bacterial persistence. Full article

(1) Background: International students with sufficient health literacy are better equipped to respond to public health emergencies and reduce any unintentional harm that may occur during such events. This study aims to assess the current status of health literacy among international students and investigate the factors that influence health literacy. (2) Methods: A cross-sectional study was conducted in Tokyo on international university students using a questionnaire consisting of the Communicative and Critical Health Literacy and eHealth Literacy Scales. The study analyzed 205 valid responses. Descriptive statistics were utilized to assess the level of health literacy, and linear regression was used to identify the association of socio-demographic characteristics and disease status with health and e-health literacy. (3) Results: Health literacy and e-health literacy were low in 48.29% and 47.29% of international students, respectively. The mean scores of CCHL items ranged from 3.13 to 3.26, while the mean scores of eHEALS items ranged from 3.33 to 3.49. Both health literacy and e-health literacy were better with unmarried status (p = 0.015), and e-health literacy was worse with higher age (p = 0.007). (4) Conclusions: Overall, international students’ health literacy and e-health literacy were at intermediate levels, with considerable room for improvement, and affected by certain student attributes. Full article

Cardiac arrest survivors suffer the repercussions of anoxic brain injury, a critical factor influencing long-term prognosis. This injury is characterised by profound and enduring metabolic impairment. Ketone bodies, an alternative energetic resource in physiological states such as exercise, fasting, and extended starvation, are avidly taken up and used by the brain. Both the ketogenic diet and exogenous ketone supplementation have been associated with neuroprotective effects across a spectrum of conditions. These include refractory epilepsy, neurodegenerative disorders, cognitive impairment, focal cerebral ischemia, and traumatic brain injuries. Beyond this, ketone bodies possess a plethora of attributes that appear to be particularly favourable after cardiac arrest. These encompass anti-inflammatory effects, the attenuation of oxidative stress, the improvement of mitochondrial function, a glucose-sparing effect, and the enhancement of cardiac function. The aim of this manuscript is to appraise pertinent scientific literature on the topic through a narrative review. We aim to encapsulate the existing evidence and underscore the potential therapeutic value of ketone bodies in the context of cardiac arrest to provide a rationale for their use in forthcoming translational research efforts. Full article

Osteoporosis (OP), a prevalent skeletal disorder characterized by compromised bone strength and increased susceptibility to fractures, poses a significant public health concern. This review aims to provide a comprehensive analysis of the current state of research in the field, focusing on the application of proteomic techniques to elucidate diagnostic markers and therapeutic targets for OP. The integration of cutting-edge proteomic technologies has enabled the identification and quantification of proteins associated with bone metabolism, leading to a deeper understanding of the molecular mechanisms underlying OP. In this review, we systematically examine recent advancements in proteomic studies related to OP, emphasizing the identification of potential biomarkers for OP diagnosis and the discovery of novel therapeutic targets. Additionally, we discuss the challenges and future directions in the field, highlighting the potential impact of proteomic research in transforming the landscape of OP diagnosis and treatment. Full article

Obstructive sleep apnea is a common type of sleep-disordered breathing associated with multiple comorbidities. Nearly a billion people are estimated to have obstructive sleep apnea, which carries a substantial economic burden, but under-diagnosis is still a problem. Continuous positive airway pressure (CPAP) is the first-line treatment for OSAS. Telemedicine-based interventions (TM) have been evaluated to improve access to diagnosis, increase CPAP adherence, and contribute to easing the follow-up process, allowing healthcare facilities to provide patient-centered care. This narrative review summarizes the evidence available regarding the potential future of telemedicine in the management pathway of OSA. The potential of home sleep studies to improve OSA diagnosis and the importance of remote monitoring for tracking treatment adherence and failure and to contribute to developing patient engagement tools will be presented. Further studies are needed to explore the impact of shifting from teleconsultations to collaborative care models where patients are placed at the center of their care. Full article

Immune checkpoint blockade (ICB) therapy is used to treat a wide range of cancers; however, some patients are at risk of developing treatment resistance and/or immune-related adverse events (irAEs). Thus, there is a great need for the identification of reliable predictive biomarkers for response and toxicity. The cytokine MIF (macrophage migration inhibitory factor) and its cognate receptor CD74 are intimately connected with cancer progression and have previously been proposed as prognostic biomarkers for patient outcome in various cancers, including solid tumors such as malignant melanoma. Here, we assess their potential as predictive biomarkers for response to ICB therapy and irAE development. We provide a brief overview of their function and roles in the context of cancer and autoimmune disease. We also review the evidence showing that MIF and CD74 may be of use as predictive biomarkers of patient response to ICB therapy and irAE development. We also highlight that careful consideration is required when assessing the potential of serum MIF levels as a biomarker due to its reported circadian expression in human plasma. Finally, we suggest future directions for the establishment of MIF and CD74 as predictive biomarkers for ICB therapy and irAE development to guide further research in this field. Full article

Stance information has a significant influence on market strategy, government policy, and public opinion. Users differ not only in their polarity but also in the degree to which they take a stand. The traditional classification of stances is quite simple and cannot fully depict the diversity of stances. At the same time, traditional approaches ignore user sentiment features when expressing their stances. As a result, this paper develops a multi-stance detection model by fusing sentiment features. First, a five-category stance indicator system is built based on the LDA model, then sentiment features are extracted from the reviews using the sentiment lexicon, and finally, stance detection is implemented using a hybrid neural network model. The experiment shows that the proposed method can classify stances into five categories and perform stance detection more accurately. Full article

Liver cancer is one of the leading causes of cancer-related mortality. Hepatocellular carcinoma and cholangiocarcinoma are the most common types, and despite numerous advances, therapeutic options still remain poor for these cancer patients. Tumor development and progression strictly depend on a supportive tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are the most abundant immune cells population within a tumorigenic liver; they sustain cancer cells’ growth and invasiveness, and their presence is correlated with a poor prognosis. Furthermore, TAM cross-talk with cells and components of the TME promotes immunosuppression, a desmoplastic response, and angiogenesis. In this review, we summarize the latest advances in understanding TAM heterogeneity and function, with a particular focus on TAM modulation of the TME. We also discuss the potential of targeting macrophage subpopulations and how this is now being exploited in current clinical trials for the treatment of liver cancer. Full article

Upon a variety of environmental stresses, eukaryotic cells usually recruit translational stalled mRNAs and RNA-binding proteins to form cytoplasmic condensates known as stress granules (SGs), which minimize stress-induced damage and promote stress adaptation and cell survival. SGs are hijacked by cancer cells to promote cell survival and are consequently involved in the development of anticancer drug resistance. However, the design and application of chemical compounds targeting SGs to improve anticancer drug efficacy have rarely been studied. Here, we developed two types of SG inhibitory peptides (SIPs) derived from SG core proteins Caprin1 and USP10 and fused with cell-penetrating peptides to generate TAT-SIP-C1/2 and SIP-U1-Antp, respectively. We obtained 11 SG-inducing anticancer compounds from cell-based screens and explored the potential application of SIPs in overcoming resistance to the SG-inducing anticancer drug sorafenib. We found that SIPs increased the sensitivity of HeLa cells to sorafenib via the disruption of SGs. Therefore, anticancer drugs which are competent to induce SGs could be combined with SIPs to sensitize cancer cells, which might provide a novel therapeutic strategy to alleviate anticancer drug resistance. Full article

In this critical narrative essay, titled A Genealogy Toward Methodic Doubts, I ask readers not only how and why educational leadership research(ers) detoured from the rigorous pursuits of truths, but also how and why I had missed the signposts which might have alerted me and others that our continuing practices, even with recognizing methodological limitations, were flawed. The empirical examples presented here come mostly from US policies, Western theories, and traditional methods, but likely apply to other contexts worldwide. Full article

The use of probiotic lactobacilli has been proposed as a strategy to mitigate damage associated with exposure to toxic metals. Their protective effect against cationic metal ions, such as those of mercury or lead, is believed to stem from their chelating and accumulating potential. However, their retention of anionic toxic metalloids, such as inorganic arsenic, is generally low. Through the construction of mutants in phosphate transporter genes (pst) in Lactiplantibacillus plantarum and Lacticaseibacillus paracasei strains, coupled with arsenate [As(V)] uptake and toxicity assays, we determined that the incorporation of As(V), which structurally resembles phosphate, is likely facilitated by phosphate transporters. Surprisingly, inactivation in Lc. paracasei of PhoP, the transcriptional regulator of the two-component system PhoPR, a signal transducer involved in phosphate sensing, led to an increased resistance to arsenite [As(III)]. In comparison to the wild type, the phoP strain exhibited no differences in the ability to retain As(III), and there were no observed changes in the oxidation of As(III) to the less toxic As(V). These results reinforce the idea that specific transport, and not unspecific cell retention, plays a role in As(V) biosorption by lactobacilli, while they reveal an unexpected phenotype for the lack of the pleiotropic regulator PhoP. Full article

The mental health of medical students is a growing concern worldwide, with studies indicating high levels of stress, anxiety, and depression among this population. In a South African context, this review aims to review the existing literature on mental health needs and challenges among medical students in South Africa. The rationale for this review is crucial to identify gaps, understand unique contextual factors, and inform the development of targeted interventions and support tailored to the specific needs of South African medical students. This review followed a scoping review framework by Arksey and O’Malley which consists of five stages. The review was initiated in December 2023. The search process was conducted on the following electronic databases: PubMed, Psych-info, Scopus, Google Scholar, and Science Direct. The search terms of this review were “Medical students” OR “Mental health”, OR “Challenges”, OR “South Africa”, OR “Universities” OR “Needs”, OR “Support systems”, OR “Mental health interventions”. This study included articles published in English between 2010 and 2023. After a thorough review of the literature, only eight articles met the inclusion criteria. This study excluded articles that were not published in English, articles published before 2010, full-text articles that could not be retrieved, and studies that did not address the mental health needs and challenges faced by medical students and risk factors contributing to mental issues among South African medical students. The review yielded only three themes utilizing Creswell’s Tesch method of data analysis. (1) Prevalence of mental health disorders, (2) risk factors contributing to poor mental health, and (3) available university support systems and interventions. Therefore, the unique aspect of our review lies in shedding light on the underexplored intersections between mental health and the unique context of medical education in South Africa. This includes examining the impact of historical, cultural, and institutional factors on the mental health and well-being of medical students, which has not been comprehensively addressed in previous literature in terms of the South African context. The findings of this review highlight the importance of implementing comprehensive mental health support programs within medical education institutions to address the needs of students and promote their well-being. Full article

Weed control in cutting propagation is limited to manual hand weeding, which is time-consuming and labor-intensive. Preemergence herbicides and mulches may be viable weed control methods for cutting propagation, but crop safety and weed control efficacy must be better understood. Four preemergence herbicides (indaziflam, isoxaben, isoxaben + dithiopyr, and oxyfluorfen + oxadiazon) and two mulches (pine pellets and rice hulls) were assessed in cutting propagation for their impact on rooting and subsequent liner growth (butterfly bush [Buddleja davidii Franch.] and crape myrtle [Lagerstroemia indica L.]) and control of four common weed species. Butterfly bush cuttings had lower rooting percentage and root dry weight with isoxaben and isoxaben + dithiopyr, but no damage was observed for all other treatments during propagation or after transplant. Crape myrtle cutting root development and liner growth were statistically similar for all treatments compared to the non-treated control. Isoxaben, isoxaben + dithiopyr, oxyfluorfen + oxadiazon, and pine pellets provided excellent control (87 to 100%) of all four weed species tested. Overall, several preemergence herbicides and mulches were safe for use in cutting propagation and effective weed control varied by product and weed species. Full article

The purpose of this study was to compare the change of Body Composition (BC) (height, weight, body fat percentage and muscle mass) as a function of the trimester and category in a sample of young soccer players. Data collection was performed in five consecutive seasons (2016–2021). The sample consisted of 741 young male football players of different categories (Under 14 year old (U14), U15, U16, U17 and U18) belonging to a high-performance football academy. Considering the trimestral change of all the raw anthropometrics variables a set of new variables called the trimestral change in percentage (TC) of each raw variable was computed. Two-way repeated measures ANOVA (including the raw anthropometric variables as dependent and trimester and the age-category as independent) revealed differences for the anthropometric variables (p value < 0.001 in all cases), concluding that the effect of trimester reaches conventional levels of statistical significance. The trimester by age in contrast was significant (p < 0.05) in all raw variables except for the height. Considering the TC variables, the variable height-TC showed an increase (p value < 0.05) while the variable muscle mass-TC was near the significative value (p = 0.09). In this case the interaction trimester by age category was not significative (p > 0.05 in all cases). It seems that height suffers more changes in the first trimester but the weight, body fat percentage and muscle mass changes more in the second and third trimester. It is important to modulate the training load according to the trimester-specific response, although these improvements may vary according to factors such as genetics, diet, sleep and the specific training. Full article

The formulation of novel delivery protocols for the targeted delivery of genes into hepatocytes by receptor mediation is important for the treatment of liver-specific disorders, including cancer. Non-viral delivery methods have been extensively studied for gene therapy. Gold nanoparticles (AuNPs) have gained attention in nanomedicine due to their biocompatibility. In this study, AuNPs were synthesized and coated with polymers: chitosan (CS), and polyethylene glycol (PEG). The targeting moiety, lactobionic acid (LA), was added for hepatocyte-specific delivery. Physicochemical characterization revealed that all nano-formulations were spherical and monodispersed, with hydrodynamic sizes between 70 and 250 nm. Nanocomplexes with pCMV-Luc DNA (pDNA) confirmed that the NPs could bind, compact, and protect the pDNA from nuclease degradation. Cytotoxicity studies revealed that the AuNPs were well tolerated (cell viabilities > 70%) in human hepatocellular carcinoma (HepG2), embryonic kidney (HEK293), and colorectal adenocarcinoma (Caco-2) cells, with enhanced transgene activity in all cells. The inclusion of LA in the NP formulation was notable in the HepG2 cells, which overexpress the asialoglycoprotein receptor on their cell surface. A five-fold increase in luciferase gene expression was evident for the LA-targeted AuNPs compared to the non-targeted AuNPs. These AuNPs have shown potential as safe and suitable targeted delivery vehicles for liver-directed gene therapy. Full article

Performing a minimally invasive surgery comes with a significant advantage regarding rehabilitating the patient after the operation. But it also causes difficulties, mainly for the surgeon or expert who performs the surgical intervention, since only visual information is available and they cannot use their tactile senses during keyhole surgeries. This is the case with laparoscopic hysterectomy since some organs are also difficult to distinguish based on visual information, making laparoscope-based hysterectomy challenging. In this paper, we propose a solution based on semantic segmentation, which can create pixel-accurate predictions of surgical images and differentiate the uterine arteries, ureters, and nerves. We trained three binary semantic segmentation models based on the U-Net architecture with the EfficientNet-b3 encoder; then, we developed two ensemble techniques that enhanced the segmentation performance. Our pixel-wise ensemble examines the segmentation map of the binary networks on the lowest level of pixels. The other algorithm developed is a region-based ensemble technique that takes this examination to a higher level and makes the ensemble based on every connected component detected by the binary segmentation networks. We also introduced and trained a classic multi-class semantic segmentation model as a reference and compared it to the ensemble-based approaches. We used 586 manually annotated images from 38 surgical videos for this research and published this dataset. Full article

Background: Preterm birth impacts 60% of twin pregnancies, with the subsequent risk of complications in both newborns secondary to the immaturity of organs. This study aims to assess the utility of the sFlt-1/PlGF ratio throughout pregnancy in predicting late preterm birth and adverse perinatal outcomes related to prematurity in twin pregnancies. Methods: This is a prospective cohort study developed at a tertiary hospital. All pregnant women with a twin pregnancy who signed the informed consent were included. The sFlt-1/PlGF ratio was measured at 12, 24, and 32 weeks’ gestation. Results: Seventy patients were included, from which 54.3% suffered late preterm birth. Results revealed a significant difference in sFlt-1/PlGF ratio at week 32 between term and preterm groups, with a one-unit increase associated with a 1.11-fold increase in the probability of preterm birth. The sFlt-1/PlGF ratio at week 32 alone presented considerable predictive capacities (sensitivity of 71%, specificity of 72%, a PPV of 75%, and an NPV of 68%. Similarly, at week 24, a one-unit increase in sFlt-1/PlGF ratio was associated with a 1.24-fold increase in the probability of adverse perinatal events due to prematurity. Combining parity, maternal age, conception method, BMI, and chorionicity, the model yielded better predictive capacities (sensitivity of 82%, specificity of 80%, PPV of 58%, NPV of 93%). Conclusions: The potential of the sFlt-1/PlGF ratio as a predictive tool for preterm birth and adverse perinatal outcomes secondary to prematurity in twin pregnancies is underscored. Full article

Gerty T. and Carl F. Cori discovered, during research on the metabolism of sugars in organisms, the important role of the phosphate ester of a simple sugar. Glucose molecules are released from glycogen—the glucose stored in the liver—in the presence of phosphates and enter the blood as α-D-glucose-1-phosphate (Glc-1PH₂). Currently, the crystal structure of three phosphates, Glc-1PNa₂·3.5·H₂O, Glc-1PK₂·2H₂O, and Glc-1PHK, is known. Research has shown that reactions of Glc-1PH₂ with carbonates produce new complexes with ammonium ions [Glc-1P(NH₄)₂·3H₂O] and mixed complexes: potassium–sodium and ammonium–sodium [Glc-1P(X)_1.5Na_0.5·4H₂O; X = K or NH₄]. The crystallization of dicationic complexes has been carried out in aqueous systems containing equimolar amounts of cations (1:1; X–Na). It was found that the first fractions of crystalline complexes always had cations in the ratio 3/2:1/2. The second batch of crystals obtained from the remaining mother liquid consisted either of the previously studied Na+, K+ or NH₄+ complexes, or it was a new sodium hydrate—Glc-1PNa₂·5·H₂O. The isolated ammonium–potassium complex shows an isomorphic cation substitution and a completely unique composition: Glc-1PH(NH₄)_xK_1−x (x = 0.67). The Glc-1P²⁻ ligand has chelating fragments and/or bridging atoms, and complexes containing one type of cation show different modes of coordinating oxygen atoms with cations. However, in the case of the potassium–sodium and ammonium–sodium structures, high structural similarities are observed. The 1D and 2D NMR spectra showed that the conformation of Glc-1P²⁻ is rigid in solution as in the solid state, where only rotations of the phosphate group around the C-O-P bonds are observed. Full article

MicroRNAs (miRNAs) are a class of small non-coding RNAs that may function as tumor suppressors or oncogenes. Alteration of their expression levels has been linked to a range of human malignancies, including cancer. The objective of this investigation is to assess the relative expression levels of certain miRNAs to distinguish between prostate cancer (PCa) from benign prostatic hyperplasia (BPH). Blood plasma was collected from 66 patients diagnosed with BPH and 58 patients with PCa. Real-time PCR technology was used to evaluate the relative expression among the two groups for miR-106a-5p and miR-148a-3p. The significant downregulation of both miRNAs in plasma from PCa versus BPH patients suggests their potential utility as diagnostic biomarkers for distinguishing between these conditions. The concurrent utilization of these two miRNAs slightly enhanced the sensitivity for discrimination among the two analyzed groups, as shown in ROC curve analysis. Further validation of these miRNAs in larger patient cohorts and across different stages of PCa may strengthen their candidacy as clinically relevant biomarkers for diagnosis and prognosis. Full article

This Editorial precedes the Special Issue entitled “Novel Challenges and Therapeutic Options for Liver Diseases”. Following a historical outline of the roots of hepatology, we provide a brief insight into our colleagues’ contributions in this issue on the current developments in this discipline related to the prevention of liver diseases, the metabolic dysfunction-associated steatotic liver disease (or non-alcoholic fatty liver disease, respectively), liver cirrhosis, chronic viral hepatitides, acute-on-chronic liver failure, liver transplantation, the liver–microbiome axis and microbiome transplantation, and telemedicine. We further add some topics not covered by the contributions herein that will likely impact future hepatology. Clinically, these comprise the predictive potential of organokine crosstalk and treatment options for liver fibrosis. With regard to promising developments in basic research, some current findings on the genetic basis of metabolism-associated chronic liver diseases, chronobiology, metabolic zonation of the liver, aspects of the aging liver against the background of demography, and liver regeneration will be presented. We expect machine learning to thrive as an overarching topic throughout hepatology. The largest study to date on the early detection of liver damage—which has been kicked off on 1 March 2024—is highlighted, too. Full article

This paper deals with the phenomenon of torsion oscillations in railway vehicle drive systems. The main goal is to reduce the risk of presence of torsional oscillations in wheelset drive, eventually to propose systems to effectively identify and eliminate torsional oscillations of wheelsets. Therefore, a simulation wheelset drive model including a detailed model of the asynchronous traction motor control was built. The results of computer simulations show that the torsional oscillations can be effectively eliminated by avoiding the resonance states between the excitation frequencies given by pulse width modulation of the inverter and the eigenfrequencies of the mechanical part of the drive. Furthermore, it was found that the presence of torsional oscillations of the wheels can be detected based on the traction motor current ripple. The wheelset drive model was subsequently implemented in a simulation model of a four-axle locomotive. A new algorithm of an anti-slip protection system that utilizes motor currents was implemented in the model. Simulations show that such an anti-slip protection system can prevent the occurrence of undesired large amplitude of wheelset torsional oscillations. The models and simulation results are presented in detail in the paper. Full article

This review discusses the scientific evidence that supports the nutritional value of mare milk and how its properties are essentially achieved when mares are managed under grazing conditions. Mare milk’s similarity with the chemical composition of human milk makes this food and its derived products not only suitable for human consumption but also an interesting food regarding human health. The contribution of horse breeding under grazing management to other socio-ecological benefits generated by equine farms is also highlighted. Both the high added value of mare milk and the socio-ecological benefits derived from pasture-based systems could be explored to improve the performance of equine farms located in arid and semi-arid areas or in regions with moderately harsh environmental conditions as equids have a strong adaptation capacity. Full article