The roots and rhizomes of Rubia tinctorum L. have been widely used both for industrial and medicinal purposes for centuries. The primary biologically active substances from Rubia tinctorum L. roots and rhizomes are anthraquinone derivatives such as ruberythric acid and lucidin-3-primeveroside. Their identification and quantification are carried out by various analytical methods, requiring a complicated sample preparation as well as special reagents and reference samples. However, NMR spectroscopy has no limitations of this kind. In this work, we have developed and validated a new express and standard-free method for the qualitative and quantitative analysis of ruberythric acid and lucidin-3-primeveroside by ¹H NMR spectroscopy in the extracts from the roots and rhizomes of Rubia tinctorum L. In this work, we have optimized the conditions of the sample preparation and registration of ¹H NMR spectra, determined the optimal solvent and reference compound and confirmed the obtained results by HPLC-UV-MS. Full article

Large-scale genomic studies have significantly increased our knowledge of genetic variability across populations. Regional genetic profiling is essential for distinguishing common benign variants from disease-causing ones. To this end, we conducted a comprehensive characterization of exonic variants in the population of Navarre (Spain), utilizing whole genome sequencing data from 358 unrelated individuals of Spanish origin. Our analysis revealed 61,410 biallelic single nucleotide variants (SNV) within the Navarrese cohort, with 35% classified as common (MAF > 1%). By comparing allele frequency data from 1000 Genome Project (excluding the Iberian cohort of Spain, IBS), Genome Aggregation Database, and a Spanish cohort (including IBS individuals and data from Medical Genome Project), we identified 1069 SNVs common in Navarre but rare (MAF ≤ 1%) in all other populations. We further corroborated this observation with a second regional cohort of 239 unrelated exomes, which confirmed 676 of the 1069 SNVs as common in Navarre. In conclusion, this study highlights the importance of population-specific characterization of genetic variation to improve allele frequency filtering in sequencing data analysis to identify disease-causing variants. Full article

Because of the high prevalence of bone destruction in patients with multiple myeloma (MM), physical exercise is oftentimes discouraged by healthcare providers. The goal of this prospective trial was to investigate the feasibility of two six-month exercise interventions in patients with MM (N = 42): a remotely prompted home-based walking intervention or a supervised strength training intervention. Physical function and pain were assessed with the Activity Measure for Post-Acute Care (AM-PAC) Basic Mobility Short Form raw score, a six-minute walk test (6 MWT), a 30-second sit-to-stand test (30 SST), a timed up-and-go (TUG) test, a visual analog scale (VAS) for pain, handheld dynamometer tests, heart rate at rest, blood oxygen saturation at rest, and body mass index. No intervention-related serious adverse events were observed. Adverse events mostly affected the musculoskeletal system. In the resistance training group (n = 24), patients showed significant improvements in AM-PAC, TUG, 6 MWT, and 30 SST, with all effects but the 6 MWT sustained six months after the intervention. The walking group (n = 18) saw improvements in the AM-PAC, TUG, 6 MWT, and 30 SST, with a sustained change in the AM-PAC and TUG. This trial shows the feasibility of both exercise interventions with a sustained beneficial effect on the physical functioning of a six-month strength training intervention and, to a lesser extent, a six-month unsupervised walking intervention. A larger study building on these findings is currently underway. Full article

A distributed state observer is designed for state estimation and tracking of mobile robots amidst dynamic environments and occlusions within distributed LiDAR sensor networks. The proposed novel framework enhances three-dimensional bounding box detection and tracking utilizing a consensus-based information filter and a region of interest for state estimation of mobile robots. The framework enables the identification of the input to the dynamic process using remote sensing, enhancing the state prediction accuracy for low-visibility and occlusion scenarios in dynamic scenes. Experimental evaluations in indoor settings confirm the effectiveness of the framework in terms of accuracy and computational efficiency. These results highlight the benefit of integrating stationary LiDAR sensors’ state estimates into a switching consensus information filter to enhance the reliability of tracking and to reduce estimation error in the sense of mean square and covariance. Full article

In this study, we developed a XGBoost-based algorithm to downscale 2 km-resolution land surface temperature (LST) data from the GOES satellite to a finer 70 m resolution, using ancillary variables including NDVI, NDBI, and DEM. This method demonstrated a superior performance over the conventional TsHARP technique, achieving a reduced RMSE of 1.90 °C, compared to 2.51 °C with TsHARP. Our approach utilizes the geostationary GOES satellite data alongside high-resolution ECOSTRESS data, enabling hourly LST downscaling to 70 m—a significant advancement over previous methodologies that typically measure LST only once daily. Applying these high-resolution LST data, we examined the hottest days in Chicago and their correlation with ethnic inequality. Our analysis indicated that Hispanic/Latino communities endure the highest LSTs, with a maximum LST that is 1.5 °C higher in blocks predominantly inhabited by Hispanic/Latino residents compared to those predominantly occupied by White residents. This study highlights the intersection of urban development, ethnic inequality, and environmental inequities, emphasizing the need for targeted urban planning to mitigate these disparities. The enhanced spatial and temporal resolution of our LST data provides deeper insights into diurnal temperature variations, crucial for understanding and addressing the urban heat distribution and its impact on vulnerable communities. Full article

During deep-sea mining, heavy metal pollutants can cause contamination in the marine environment. In this paper, the multiphasic coupling model is established to describe the heavy metal migration process during deep-sea mining, which takes the effects of the convection–diffusion, adsorption–desorption, and sedimentation–resuspension of heavy metals in the aquatic environment into full consideration. Due to the advantages of the Lattice Boltzmann method, it is adopted to numerically solve the multiphasic coupling model and achieve the simulation of the heavy metal migration process during deep-sea mining. In addition, taking cadmium as an example, the concentration variations are discussed and analyzed in detail. Based on the established model and Lattice Boltzmann method, the concentration distribution of heavy metals can be accurately described to provide the reasonable bases for the evaluation of marine environmental protection. Full article

The COVID-19 pandemic produced acute effects on health inequities, yet more enduring impacts in vulnerable populations in rural Appalachia are understudied. This qualitative study included three focus groups with thirty-nine adults (74% female, mean age 52.7 years) to obtain perspectives on the impact of the COVID-19 pandemic on well-being in Martin County, Kentucky, in fall 2022. Grounded Theory was employed using an iterative inductive-deductive approach to capture the lasting effects of the COVID-19 pandemic on health practices and status. Three prominent themes emerged: (1) increased social isolation; (2) household cost of living strains caused by inflation; and (3) higher food prices and diminished food availability causing shifts in food purchasing and consumption. Participants noted that the rising cost of living resulted in residents having to “choose between medication, food and utilities”. Increased food prices resulted in residents “stretching” their food, modifying how they grocery shopped, and limiting meat consumption. Persistent food shortages were exacerbated by there being few grocery stores in the county. Lastly, increased social isolation was profoundly articulated as widely impacting mental health, especially among youth. Our findings underscore the ongoing deleterious effects of inflation and food supply chain disruptions in this rural, geographically isolated community, which resulted in difficult spending choices for residents. Full article

Hulls and shells are an abundant by-product from almond production with potential as an organic matter amendment (OMA). A combination of incubation study and field research was conducted in 2019–2021 to evaluate the impacts of three practices in combination on orchard soils’ C and N cycling, including a 210-day period of laboratory incubation with hulls and shells, and field sampling of orchard soils with and without historic applications of green waste compost as an OMA; with hulls and shells and with and without off-ground harvest where orchard soils remain undisturbed year round. Hulls and shells increased microbial biomass carbon in the field study by 248 μg g⁻¹ dry soil after one year (p < 0.001) and during incubation, and increased cumulative respiration in soils with and without historic OMA (p < 0.001). Historic OMA resulted in double the total soil organic carbon (SOC) and total nitrogen (TN) compared to soil without resulting in significantly higher respiration and N mineralization when amended with hulls and shells. The decomposition of hull and shell biomass following surface application progressed at similar rates in the laboratory and field (1.7 g kg⁻¹ d⁻¹ during incubation (R² = 0.84) and 1.3 g kg⁻¹ d⁻¹ in the field trial (R² = 0.91). Our results highlight the suitability of hulls and shells as a by-product source of OMA for improving soil health in orchards with historic OMA and transitioning to organic matter management. Full article

Soft rocks are prone to softening upon contact with water, and their rapid deterioration in mechanical properties is a significant cause of instability and failure soft rock masses. Besides, the macroscopic mechanical response of rocks is closely related to the mineral composition and microstructure. The purpose of this research is to consider the heterogeneity factors and softening effects, and systematically investigate the influence of confining pressure and softening time on the damage and failure characteristics of soft rocks. The Voronoi polygons generated using a built-in Voronoi diagram algorithm and contact elements (the substances with cementing capacity) of UDEC discrete element method are employed to represent the clastic grains and interfacial cemented bonding (ICB) structures in soft rock. Based on the Voronoi probabilistic method, the grain-based discrete element model (GB-DEM) considering the softening effect is established by introducing a meso-scale softening damage factor, along with a detailed calibration method for meso-scale parameters. The damage parameters such as the crack initiation threshold, the crack damage threshold, the damage degree, and the tensile and shear crack ratio are then analyzed. The study results indicate that the simulated strengths of the heterogeneous models under different water immersion time are in good agreement with the experimental results. The thresholds for crack initiation and damage, the proportions of tensile and shear cracks, and the degree of damage are positively correlated with the confining pressure. The attenuation patterns of the crack initiation threshold and damage threshold in the heterogeneous models with water immersion time are highly consistent with the meso-scale softening damage factor. The damage parameters show a trend of increasing first and then decreasing with the extension of water immersion time. The cement–cement contact elements are the main locations for crack initiation and propagation. The research outcomes have significant theoretical and practical implications for understanding and predicting the mechanical behavior of soft rocks under a water–rock interaction. Full article

The disruption of the blood–brain barrier (BBB) in Alzheimer’s Disease (AD) is largely influenced by amyloid beta (Aβ). In this study, we developed a high-throughput microfluidic BBB model devoid of a physical membrane, featuring endothelial cells interacting with an extracellular matrix (ECM). This paper focuses on the impact of varying concentrations of Aβ_1–42 oligomers on BBB dysfunction by treating them in the luminal. Our findings reveal a pronounced accumulation of Aβ_1–42 oligomers at the BBB, resulting in the disruption of tight junctions and subsequent leakage evidenced by a barrier integrity assay. Additionally, cytotoxicity assessments indicate a concentration-dependent increase in cell death in response to Aβ_1–42 oligomers (LC50 ~ 1 µM). This study underscores the utility of our membrane-free vascular chip in elucidating the dysfunction induced by Aβ with respect to the BBB. Full article

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