Quasi-solid composited electrolytes were produced by LiFSI initiated polymerized poly-(Dioxolane) (PDOL) with garnet-LLZO (Li7La2Zr3O12) nanofibers and used in lithium-metal batteries. Linear sweep voltammetry shows that the initial oxidation voltage of 4.6 V for Gel-10% (G10, 10% wt. LLZO in PDOL) vs Li/Li+. EIS test of stainless steel// stainless steel symmetric cells for Gel-1% (G1), Gel-5% (G5) and Gel-10% (G10) show ion conductivity (5*10-5 S/cm). Li/G10/Li symmetric cells have stable stripping-plating cycling performance over 1300 hours continuously with the current density of 0.1 mA/cm2 at 25 oC, indicating a good interface contact and stable lithium-ion transport pathway through the composite electrolytes. LFP/G10/Li batteries have stable charge-discharge plateau, low polarization voltage of 0.07-volt, energy efficiency of 95% and coulombic efficiency of ~99% at current density of 26.3 mA/g at 25 oC for over 100 cycles.

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

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

Earthquake is among the most devastating natural disasters causing severe economic, environmental, and social destruction. Earthquake safety assessment and building hazard monitoring can highly contribute to urban sustainable development through identification and insight into optimum materials and structures. While the vulnerability of structures mainly depends on the structural resistance, the safety assessment of buildings can be highly challenging. In this paper, we consider Rapid Visual Screening (RVS) method which is a qualitative procedure for estimating structural scores for buildings suitable for medium- to high-seismic cases. This paper presents an overview of the common RVS methods, i.e., FEMA P-154, IITK-GGSDMA, and EMPI. To examine the accuracy and validation, a practical comparison is performed between their assessment and observed damage of reinforced concrete buildings from a street survey in the Bingöl region, Turkey, after the 11 May 2003 earthquake. The results demonstrate that the application of RVS methods for preliminary damage estimation is a vital tool. Furthermore, the comparative analysis showed that FEMA P-154 creates an assessment that overestimates damage states and is not economically viable while EMPI and IITK-GGSDMA provide for more accurate and practical estimation, respectively.

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

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

Effective and rapid mixing is essential for various chemical and biological assays. The present work reports a simple and low-cost micromixer based on magnetofluidic actuation. The device takes advantage of magnetoconvective secondary flow, a bulk flow induced by an external magnetic field, for mixing. A paramagnetic stream of diluted ferrofluid and a non-magnetic stream are introduced to a straight microchannel. A permanent magnet placed next to the microchannel induced a non-uniform magnetic field. The magnetic field gradient and the mismatch in magnetic susceptibility between the two streams create a body force, which leads to rapid and efficient mixing. The micromixer reported here could achieve a high throughput and a high mixing efficiency of 90 % in a relatively short microchannel.

Bisphenol A diglycidyl ether (BADGE) is widely existed in the inner coating of canned foods. It migrates into food and generate various derivatives in the process of storage, such as Bisphenol A (2, 3-dihydroxypropyl) glycidyl ether (BADGE·H2O), Bisphenol A (3-chloro-2-hydroxypropyl) glycidyl ether (BADGE·HCl) and Bisphenol A (3-chloro-2-hydroxypropyl) (2, 3-dihydroxypropyl) glycidyl ether (BADGE·HCl·H2O), which have negative effects on human health. A gold nanoparticle-based immu-nochromatographic assay for simultaneous detection of BADGE and its derivatives was developed by using a broad-spectrum polyclonal antibody, and the detection can be finished in 15 min. The visuali-zation of results was processed by Adobe Photoshop CC software to achieve quantitative analysis and the detection limit (IC15) is 0.97ng/mL. The recoveries of BADGE and its derivatives at various spiking levels in canned food samples ranged from 79.86% to 93.81%. The detection results of the proposed immu-nochromatographic assay were also validated by HPLC analysis, and got good consistency (R2=0.9580).

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

Viral infections have long been the biggest threat to human survival, and from a medical perspective, the development of noninvasive high-throughput screening methods that target the incubation period to either treat diseases or limit viral spread would be strikingly effective. Using this technology to target viral incubation periods would also be inexpensive to perform. The current study proposes to transform pulse signals into a rapid diagnostic test using “coincidence analysis” in the hope of preventing or reducing the symptoms of viral infections. The heart plays a critical role in calculating and supplying the needs of all tissues of the body. Pulse waves are pressurized signals in response to heart’s calculations and include all phases of the cardiac cycle, which maintains life and provides energy needed to perform tasks. Any small movement gives a corresponding signal to pulse waves. The current study investigated conclusive data on self-limiting infections, such as common cold. We used pulse wave, coincidence analysis technology to capture signals from individuals with common cold during the incubation period and investigated if particular characteristic signals could be applied to influenza during the incubation period. Preliminary work demonstrated that pulse waves could generate signals using this technology that would be worthwhile for future research. A small amount of analytical data from common cold existed previously. The data structure is based on the idea that a single pulse wave at differing physiological conditions would have slight modifications that would be amplified and presented by various geometrical shapes after extensive data are accumulated. These geometric shapes can then be sliced vertically or horizontally to extract data during different illness stages. The significance of these findings are impressive; from a personal or a public hygiene perspective, this analytical technology provides many benefits, such as rapid and precise decision-making that can be directly visualized or can be analyzed using software programs. Also, this technology also uses futuristic wearable technology that brings practical problem solving to physiology.

Background: Study to assess glucose levels of people with type 1 diabetes (T1D) overnight based on insulin type and timing. Methods: Real-world, retrospective study in T1D using multiple daily insulin injections. Contin-uous glucose monitoring and insulin injections data were collected for ten hours after dinner us-ing the Insulclock® connected cap. Meal events were identified using ROC detection methodology. The timing of rapid insulin, second injections, and the type of insulin analogs used were evaluat-ed. Results: Nocturnal profiles (n=775, 49 subjects) were analyzed. Higher glucose AUC over 180mg/dL was observed in delayed injections (number; %; mg/dL x h): -45-15min (n=136; 17.5%, 175.9 ±271.0); -15-0min (n= 231; 29.8%, 164.0 ±237.1); 0+45min (n= 408; 52.6%, 203.6 ±260.9), (p 0.049). The use of ultrarapid (FiAsp®) (URI) vs rapid insulin analogs (RI) was associated with less hypoglycemia events (7.1 vs 13.6%; p 0.005) and TBR70 (1.7 +6.9 vs 4.6 +13.9%; p 0.003). Us-ers of glargine U300 vs degludec had higher TIR (70.7 vs 58.5 %) (Adjusted R-squared: 0.22, p < 0.001). The use of a correction injection (n= 144, 18.6%) was associated with higher hypoglycemia events (18.1 vs 9.5%; p 0.003), TBR70 (5.5 +14.2 vs 3.0 +11.1%; p 0.003), glucose AUC over 180 mg/dL (226.1 +257.8 vs 178.0 +255.3 mg/dL x h; p 0.001), and lower TIR (56.0 +27.4 vs 62.7 +29.6 mg/dL x h; p 0.004). Conclusions: Dinner rapid insulin timing, insulin types and correction injections affect nocturnal glucose profile in T1D.

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

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

Rapid and accurate detection of road cracks is of great significance for road health monitoring, but currently this work is mainly completed through manual site surveys. Low-altitude UAV remote sensing can obtain images with centimeter or even subcentimeter ground resolution, which provides a new efficient and economical approach for rapid crack detection. Nevertheless, crack detection networks face challenges such as edge blurring and misidentification due to the heterogeneity of road cracks and the complexity of the background. To address these issues, we propose a real-time edge reconstruction crack detection network (ERNet) which adopts multi-level information aggregation to reconstruct crack edges and improve the accuracy of segmentation between the target and background. To capture global dependencies across spatial and channel levels, we propose an efficient bilateral decomposed convolutional attention module (BDAM) that combines depth separable convolution and dilated convolution to capture global dependencies across spatial and channel levels. To enhance the accuracy of crack detection, we use a coordinate-based fusion module that integrates spatial, semantic, and edge reconstruction information. In addition, we propose an automatic measurement of crack information for extracting the crack trunk and its corresponding length and width. Experimental results demonstrate that our network achieves the best balance between accuracy and inference speed.

Meat serves as a vital component of the human diet, offering a rich source of protein and essential trace elements. China stands as both a significant producer and consumer of meat on a global scale, leading the world in terms of total meat production and consumption. As the standard of living within the country continues to rise, there is a growing emphasis on the nutritional value and safety of meat consumption. The tenderness of meat is a critical factor influencing its overall quality. Traditionally, tenderness has been assessed through shear force testing, a method that is inherently destructive, inefficient, and results in considerable sample wastage. In light of these drawbacks, non-destructive testing techniques have emerged as a preferred alternative, promising greater accuracy, efficiency, and convenience without compromising the integrity of the samples. This paper delves into the application of five advanced non-destructive testing technologies in the realm of meat tenderness assessment. These include near-infrared spectroscopy, hyperspectral imaging, Raman spectroscopy, airflow optical fusion detection, and nuclear magnetic resonance detection. Each technology is scrutinized for its respective strengths and limitations, providing a comprehensive overview of their current utility and potential for future development. Moreover, the integration of these techniques with the latest advancements in artificial intelligence (AI) technology is explored. The fusion of AI with non-destructive testing offers a promising avenue for the development of more sophisticated, rapid, and intelligent systems for meat tenderness evaluation. This integration is anticipated to significantly enhance the efficiency and accuracy of quality assessment in the meat industry, ensuring a higher standard of safety and nutritional value for consumers. The paper concludes with a set of technical recommendations aimed at guiding the future direction of non-destructive, AI-enhanced meat tenderness detection, thereby contributing to the ongoing improvement of the meat industry in China and beyond.

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

Detecting cracks in structural health monitoring is crucial for ensuring infrastructure safety and longevity. Using drones to obtain crack images and automate processing can improve the efficiency of crack detection. To address the challenges posed by the limited computing resources of edge devices in practical applications, we propose CrackScopeNet, a lightweight segmentation network model that simultaneously considers local and global crack features, suitable for deployment on drone platforms with limited computational power and memory. CrackScopeNet features a multi-scale branch to improve sensitivity to cracks of varying sizes without substantial computational overhead and a stripe-wise context attention mechanism to enhance the capture of long-range contextual information, mitigating the interference from complex backgrounds. Experimental results on CrackSeg9k dataset demonstrate that CrackScopeNet leads to a significant improvement in prediction performance, with the highest mean intersection over union (mIoU) scores reaching 82.12%, while maintaining a lightweight architecture with only 1.05M parameters and 1.58G floating point operations (FLOPs). Besides, CrackScopeNet excels in inference speed on edge devices without GPU because of its low FLOPs. CrackScopeNet contributes to the development of efficient and effective crack segmentation networks, suitable for practical structural health monitoring applications using drone platforms.

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

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

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

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

In the context of rapid urbanization, the spatiotemporal patterns of socio-economic exposed to high seismic hazard in large cities lacks quantitative assessment, thus, it is difficult to understand the evolution of earthquake catastrophe risk there. In this paper, exposure change rate, and absolute and relatively exposure indices were proposed to quantitatively study the changes of spatiotemporal exposure to high seismic hazard in urban areas of large cities (i.e., permanent residents in urban areas more than 1 million) in Chinese mainland, using a set of multi-temporal population, GDP, and built-up datasets and a seismic hazard zoning map. The results show that, 64 out of 78 large cities are entirely or partially located in high seismically hazardous zones. Although the urban areas of large cities in high seismically hazardous zones (HSHUAs) cover only 1.73% (167177 km²) of mainland China, their share of population, GDP, and built-up land amounted to 18.14%, 30.24% and 24.55%, respectively, in 2015. Unprecedented urbanization has led to a dramatic exposure growth in HSHUAs between 1990 and 2015. The population, GDP, and built-up land in HSHUAs increased by 110 million people (with an average annual growth rate of 2.37%), 273.71 trillion USD(average annual growth rate of 11.15%), and 10593 km2 (average annual growth rate of 2.02%), respectively. HSHUAs experienced much faster population and GDP growth than the whole country, while relatively slower growth in built-up land. Exposure growth in HSHUAs also was varied for different types of large cities. Megacities had a higher proportion of increased GDP and population in HSHUAs, induced by industry and population agglomeration. Whereas, Type II large cities had a higher proportion of increased built-up land in HSHUAs, driven mainly by urban sprawl. Our analysis indicates that, for large cities under rapid urbanization, it is an urgent need to strengthen resilient urban planning, renewal and construction.

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

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

Scedosporium species are human pathogenic fungi, responsible for chronic, localised, and life-threatening disseminated infections in both immunocompetent and immunocompromised individuals. Diagnosis of Scedosporium infections currently relies on non-specific CT, lengthy and insensitive culture from invasive biopsy, and time-consuming histopathology of tissue samples. At present, there are no rapid antigen tests that detect Scedosporium-specific biomarkers. Here we report the development of a rapid (30 min) and sensitive (pmol/L sensitivity) lateral-flow device (LFD) test, incorporating a Scedosporium-specific IgG1 monoclonal antibody (mAb), HG12, which binds to extracellular polysaccharide (EPS) antigens of between ~15 kDa and 250 kDa secreted during hyphal growth of the pathogens. The test is compatible with human serum, and allows the detection of the Scedosporium species most-frequently reported as agents of human disease (Scedosporium apiospermum, Scedosporium aurantiacum, and Scedosporium boydii), with limits of detection (LOD) of the EPS biomarkers in human serum of ~0.81 ng/mL (S. apiospermum), ~0.94 ng/mL (S. aurantiacum), and ~1.95 ng/mL (S. boydii). The Scedosporium-specific LFD (ScedLFD) test therefore provides a potential novel opportunity for the detection of infections caused by different Scedosporium species.

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

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

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

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

Preschoolers with disabilities and their caregivers have been neglected in health and social service provision in most low-income countries and arguably too in low resourced areas of more affluent nations. Yet as this rapid review of published literature identifies, there are low-cost, evidence-based strategies to address their needs that can be implemented in communities by local people. Five key features of the necessary supports are examined. First the leadership functions required to create and implement the support services. Second, the family-centred, home-based support provided to caregivers and the personnel undertaking this form of support. Third, providing opportunities for peer support to flourish and encouraging the formation of advocacy groups across families. Fourth, mobilizing the support of significant groups within the community; notably traditional healers and leaders; health services and poverty alleviation initiatives. Fifth, devising ways in which preschool educational opportunities can be offered to children as a prelude to their inclusion in primary schools. The review serves a further purpose. It provides an example of how public health researchers and academics could achieve more rapid implementation of evidence-based knowledge into existing and new support services through dissemination to community practitioners.

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

It is an utmost importance to characterize drug candidates as early in the development pipeline as possible. Appropriate application of the emerging high throughput analytical techniques unlocks the opportunities to obtain experimental data for in vitro absorption, distribution, metabolism and elimination (ADME) profiling of large compound libraries which is crucial for selection of lead compounds. In an usual scenario, only one drug candidate will be selected from thousands of early compounds based on several stability and screening results. A high to medium throughput screening approaches could significantly accelerates the subsequent research and production phases. Traditionally, the analysis of metabolic stability assays heavily relies on high throughput LC-MS/MS techniques to meet with the lead profiling demands. In this study presented an innovative experimental approach that can offer a refreshing alternative. Laser Assisted Rapid Evaporative Ionization Mass Spectrometry (LA-REIMS) is a quick and efficient method for characterizing complex biological samples without laborious sample preparation and chemical separation. Therefore, using an automated LA-REIMS well plate reader as fast as 8 seconds per sample, we assessed the oxidative metabolic stability of active agents using biomimetic metalloporphyrin-based oxidative model reactions at various pH for commercially available drug substances and compared stability measurements with traditional HPLC-DAD-MS results.

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

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

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

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

Dysregulation of cartilage homeostasis and the changes in the density and the architecture of the subchondral bone were postulated as a potent mechanically pathological activity contributing to osteoarthritis (OA) pathogenesis. Extracorporeal shockwave therapy (ESWT) is a new, none invasive and effective method in the treatment of animal OA model. In the current study, we demonstrated that shockwave induced the expression of protein-disulfide isomerase-associated 3 (Pdia-3) which is a multifunctional protein hypothesized to be a significant mediator for 1α,25-Dihydroxyvitamin D3 (1α,25(OH)₂D₃) signaling pathway using two-dimensional electrophoresis. Histological analysis and quantitative polymerase chain reaction (qPCR) were verified and observed that the expression of Pdia-3 at 2 weeks was significantly higher than that of any other group at 4 weeks, 8 weeks, and 12 weeks post-shockwave treatment in early OA knee of rat. The other factors of the 1α,25(OH)₂D₃ rapid membrane signaling pathway including extracellular signal-regulated protein kinases 1 (ERK1), osteopontin (OPG), alkaline phosphatase (ALP), and matrix metallopeptidase 13 (MMP13) were measured and significantly increased by qPCR at 2 weeks post-shockwave treatment in early OA knee. Our proteomic data revealed significant Pdia-3 expression in microenvironments of joint tissue that could be actively responded to ESWT, which may potentially regulate biological function of chondrocytes and osteoblasts in the treatment of OA knee.

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

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

The development of new turbomachinery designs requires numerous time-consuming and computationally intensive computational fluid dynamics (CFD) calculations. However, most of the generated high spatial resolution data remains unused at later development steps. That is also the case with automated optimization processes that use only a few integral values to determine objectives and constraints. Therefore the development of a data-driven AI model was initiated to ensure the potential of further use of the CFD data which is also used to train the AI model. The presented method subsequently provides a fast approximation of the 3D flow for new designs. In this paper, the structure of the developed AI model is presented and the approximation quality is analysed using a complex, state-of-the-art compressor test case. It is shown that the AI model can reproduce many characteristics of the 3D flow of new designs, and performance measures such as efficiency can be derived from these flow predictions. In addition, the complex test case revealed that greater design variation reduces the AI approximation quality which can lead to undesirable exploratory behaviour in an optimisation setup. Overall, the test case has shown promising results and has provided hints for further improvements of the AI model.

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

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

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

The adulteration of goat milk powder occurs frequently, cattle-derived and soybean-derived ingredients are common adulterants in goat milk powder. However, simultaneously and rapidly detecting cattle-derived and soybean-derived components is still a challenge. high throughput and efficient screening method for adulteration detection is need. In this study, a rapid method was developed to detect the adulteration of common cattle-derived and soybean-derived components simultaneously in goat milk powder by combining the CRISPR/ Cas12a system with recombinant polymerase amplification (RPA). A dual DNA extraction method was employed, primers and crRNA for dual detection were designed and screened, and a series of condition optimizations were carried out in this experiment. The optimized assay can rapidly detect cattle-derived and soybean-derived components in 40 min. The detection limits of both cattle-derived and soybean-derived components were 1% (w/w) for the mixed adulteration models. The established method was applied into a blind survey of 55 commercially available goat milk powder products. The results showed that 36.36% of the samples contained cattle-derived or soybean-derived ingredients, which revealed the noticeable adulteration situation in the goat milk powder market. This study realizes a fast flow of dual extraction, dual amplification and dual detection of cattle-derived and soybean-derived components in goat milk powder for the first time. It can be used for high-throughput and high-efficiency on-site primary screening of goat milk powder adulterants, and provide a technical reference for combating with food adulteration.

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

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

Current antibiograms cannot discern the particular effect of a specific antibiotic when the bacteria are incubated with a mixture of antibiotics. To prove that this task is achievable, Escherichia coli strains were treated with ciprofloxacin for 45 min, immobilized on a slide and stained with SYBR Gold. In susceptible strains, the nucleoid relative surface started to decrease near the MIC, being progressively condensed as dose increased. The shrinkage level correlated with the DNA fragmentation degree. Ciprofloxacin-resistant bacilli showed no change. Additionally, E. coli strains were incubated with ampicillin for 45 min and processed similarly. The ampicillin-susceptible strain revealed intercellular DNA fragments that increased with dose, unlike the resistant strain. Co-incubation with both antibiotics revealed that ampicillin did not modify the nucleoid condensation effect of ciprofloxacin, whereas the quinolone partially decreased the background of DNA fragments induced by ampicillin. Sixty clinical isolates, with different combinations of susceptibility-resistance to each antibiotic, were co-incubated with the EUCAST breakpoints of susceptibility of ciprofloxacin and ampicillin. The morphological assay correctly categorized all the strains for each antibiotic in 60 min, demonstrating the feasible independent evaluation of a mixture of quinolone and beta-lactam. The rapid phenotypic assay may shorten the incubation times and necessary microbial mass currently required for evaluation.

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

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

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

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

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

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

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

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

Sepsis is a life-threatening syndrome triggered by infection and accompanied by high mortality, with antimicrobial resistances (AMRs) further escalating clinical challenges. Rapid and reliable detection of causative pathogens and AMRs are key factors for fast and appropriate treatment, in order to improve outcome in septic patients. However, current sepsis diagnostics based on blood culture is limited by low sensitivity and specificity while current molecular approaches fail to enter clinical routine. Therefore, we developed a Suppression PCR-based selective enrichment sequencing approach (SUPSETS), providing a molecular method combining multiplex suppression PCR with Nanopore sequencing to identify most common sepsis-causative pathogens and AMRs using plasma cell-free DNA. Applying only 1 mL of plasma, we target eight pathogens across three kingdoms and ten AMRs in a proof-of-concept study. SUPSETS was successfully tested on first ten clinical samples and revealed comparable results to clinical metagenomics while clearly outperforming blood culture. Several clinically relevant AMRs could be detected additionally. Furthermore, SUPSETS provided first pathogen and AMR-specific sequencing reads within minutes of starting sequencing, thereby potentially decreasing time to results to 11 - 13 hours and suggesting diagnostic potential in sepsis.

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

The importance of sleep for healthy brain function is widely acknowledged. However, it remains unclear how the internal generation of dreams might facilitate cognitive processes. In this perspective we review a computational approach inspired by artificial intelligence that proposes a framework for how dreams occurring during rapid-eye-movement (REM) sleep can contribute to learning and creativity. In this framework, REM dreams are characterized by an adversarial process that, against the dream reality, tell a discriminator network to classify the internally created sensory activity as real. Such an adversarial dreaming process is shown to facilitate the emergence of real-world semantic representations in higher cortical areas. We further discuss the potential contributions of adversarial dreaming beyond learning, such as balancing fantastic and realistic dream elements, and facilitating the occurrence of creative insights. We characterize non-REM (NREM) dreams, where a single hippocampal memory is replayed at a time, as serving a complementary role of improving the robustness of cortical representations to environmental perturbations. We finally explain how subjects can become aware of the adversarial REM dreams, but less of the NREM dreams, and how the awareness phenomenon of wake, dream and lucid dreaming may appear.

The electrical motor design requires a lot of work and resources. In the field, motor designers need to decide on competitive motor sizing quickly to compete with other motor suppliers. Generally, it requires expensive FEM S/W to get accurate motor sizing results, but buying and maintaining many licenses is costly. Moreover, it needs some patience to get the result from FEM analysis. In this paper, the motor sizing technique using an existing production motor is presented to respond to urgent requests from customers without using FEM analysis. In order to enhance the fidelity of the result, magnetic flux loss by magnet coating and non-linear characteristics are considered during the motor sizing process. The proposed sizing method was verified by comparison to the FEM analysis and test result and showed reasonable confidence in them. Also, this method has the substantial advantage of outputting accurate results instantly without taking any time. It helps with the modification design of electrical motors without using expensive FEM S/W and a certain level of skill or experience.

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

2019-n-CoV is the seventh coronavirus known to infect humans and cause serious illness, and due to its lethality there was a worldwide mobilization for the development of new drugs and new vaccines for Covid-19. Therefore, the present work aims to carry out a virtual screening of terpenes with potential anti SARS-CoV-2 activity. To perform the ligand-based virtual, a model was constructed regarding the compounds which already showed inhibitory activity of the SARS-CoV-2. The test series corresponded to terpenes isolated in the Fabaceae Family. The compounds that were most likely to activity were subjected to Molecular Docking and the best poses obtained were subjected to Molecular Dynamics (MD) simulations carried. The molecules under study were submitted to in vitro evaluation to assess inhibitory activity of compounds against SARS-CoV-2 in a phenotypic screening model of the virus. The compounds selected by in silico screening corresponded to triterpenoids from the lupane series. In the in vitro test, both demonstrated activity against the SARS-CoV-2 virus. The virtual screening performed managed to identify the compounds with the highest probability of activity, as well as the most stable compounds, and the method used was validated by the in vitro study carried out.

To date, various chimeric lysins have been developed as efficacious antibiotics against multidrug-resistant bacteria, but direct comparisons of their antibacterial activities have been difficult due to the preparation of multiple recombinant chimeric lysins. Previously, we reported an E. coli cell-free expression method to screen better chimeric lysins against Staphylococcus aureus, but we still needed to increase the amounts of expressed proteins enough to be able to detect them non-isotopically for quantity comparisons. In this study, we improved the previous cell-free expression system by adding a previously reported artificial T7 terminator and reversing the different nucleotides between the T7 promoter and start codon to those of the T7 phage. The new method increased the expressed amount of chimeric lysins enough for us to detect them using Western blotting. Therefore, the qualitative comparison of activity between different chimeric lysins has become possible via the adjustment of the amount variables between samples without protein purification. We applied it to select more active chimeric lysins derived from our previously reported chimeric lysin (ALS2). Finally, we compared the antibacterial activities of our selected chimeric lysins with reported chimeric lysins (ClyC and ClyO) and lysostaphin, and determined the rank orders of antibacterial activities on different S. aureus strains in our experimental conditions.

In this contribution we present work on rapid thermal annealing of as-electrodeposited thin films of Cu2ZnSnS4. The treatment was carried out in cold wall tubular reactor in dynamic conditions with variations of temperature, speed and time of the specific elements of the process. The effect of annealing was investigated by X-ray diffractometry, Raman scattering and Scanning Electron Microscopy (SEM). The phase composition of the films in dependence on conditions of treatment was analysed and have been shown that in slow and prolonged high-temperature process the low temperature binaries react completely and only Kesterite and ZnS is left. In addition, structural investigations by XRD have shown gradual decrease of crystallite sizes when the temperature level and duration of the high-temperature segment increases and respectively increase in the strain, due to formation of the phases in non-equilibrium conditions. In opposite, when the speed of dynamic segments in the process decreases the both crystallite size and strain of the Kesterite decreases non-monotonically. The grain sizes of Kesterite, presented by SEM investigations, have shown increase when the temperature and the duration increase, respectively the speed decreases with exemption at higher temperature near 750 C. The set of experiments gave idea by scrupulous analysis of Raman data to elucidate the track for fine manipulating of the defects in the structure of CZTS thin films having in mind the dependences of the ratios of Q = I287/I303 and Q’= I338/(I366+I374) on the process variables.

Road segment can be estimated from GPS trajectories by averaging. However, most existing averaging strategies suffer from high complexity or poor accuracy. For example, finding the optimal mean for a set of sequences is known to be NP-hard, while using Medoid compromises the quality. In this paper, we introduce three extremely fast and practical methods for solving the problem. The methods first analyze three descriptors and then use either a simple linear model or a more complex curvy model depending on an angle criterion. The results outperform Medoid and provide equal or better accuracy than the best existing methods while being very fast, and therefore suitable for real-time processing.

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

World health is increasingly threatened by the growing number of spice-related food hazards. Further development of reliable methods for rapid, non-targeted identification of counterfeit ingredients within the supply chain is needed. ENEA has developed a portable, user-friendly photoacoustic laser system for food fraud detection, based on a quantum cascade laser and multivariate calibration. Following a study on the authenticity of saffron, the instrument was challenged with a more elusive adulterant, olive leaves in oregano. The results show that the reported method of laser sensing and chemometric analysis was able to detect adulterants at mass ratios of at least 20% in less than five minutes.

Real estate has the dual characteristics of consumption and investment. Under the inherent concept of "where there is land, there is wealth", real estate has become the investment target of the main asset. In addition to the supply and demand of the market will affect the price of real estate, many general economic factors will also have a certain impact on the price of real estate. This paper pays a special focus on the effects of MRT on housing prices, finding the closer a house is to an MRT station, the higher its price. In addition, convenience stores are very popularized, and this research report is also interested in whether the number of convenience stores within walking distance will affect the house price. In a word, these two factors do affect housing prices significantly.

Tandem mass spectrometry (MS/MS) for diagnosing inborn errors of metabolism (IEM) is recognized as an ethical, safe, simple, and reliable screening test. Presented bibliometric analysis aims to describe the network structure of the scientific community in the study area at the level of countries, institutions, authors, papers, keywords, and sources; scientific productivity, directions, and collaboration efforts in a considered period (1991–2023.) Using the PRISMA method, we conducted a systematic search for articles reporting using MS/MS to screen for inherited metabolic disorders and inborn errors of metabolism collected from the Web of Science Core Collection (WOSCC.) A total of 451 articles out of 546, by 2,682 authors, published in 190 journals, with 15,440 citations in 8,181 citing articles, with an average citation of 34.24 per article, and an H-index of 64 were retrieved from the WOSCC. The research status of MS/MS in IEM screening was identified. The most relevant current research directions and future areas of interest were revealed: "selective screening for IEM," "new treatments for IEM," "new disorders considered for MS/MS testing," "ethical issues associated with newborn screening," "new technologies that may be used for newborn screening," "use of a combination of MS/MS and gene sequencing," etc.

GS provides exciting opportunities to rapidly identify a diagnosis in critically ill newborns and children with rare genetic conditions. But there are good reasons to remain cautious about the broad implementation of these strategies in babies and children. At best, rapid GS leads to diagnoses in many infants in highly selected populations. It sometimes leads to beneficial and changes in management. Parents and physicians both often find these results useful. We don’t know how useful such testing will be in the general population. It is almost inevitable that genetic counseling will be more challenging in a more general population. We don’t know how often GS helps improve outcome and survival or reduce symptoms in babies who receive a molecular diagnosis. We don’t know the relative cost-effectiveness of whole genome, whole exome, or targeted panels in different populations. We don’t know the relative contribution of a molecular diagnosis to the decision to withdraw life support. Each of these concerns will require careful study of both the technology and the ethical issues to allow us to harness the potential of these new technologies while avoiding foreseeable problems. Studies are underway to see how the tests are used in general populations. These studies should generate important information to guide clinicians and policymakers. In the meantime, parents should know that genetic results sometimes confirm an already suspected dismal prognosis and sometimes yield only ambiguous findings. Anticipatory discussions should try to give parents a realistic understanding of the likely impact of a genetic diagnosis. Both doctors and parents should recognize that the clinical usefulness of diagnostic genomic testing in newborns is a work in progress. We are only a decade into the age of true genomic medicine. We still have much to learn.

Klebsiella pneumoniae (KP) is an important gram-negative zoonotic conditional pathogen. It can infect humans and a variety of farm animals, leading to infections such as pneumonia, meningitis and even sepsis. thereby posing a significant threat to public health. OmpX acts as a virulence protein that can participate in bacterial pathogenesis, mediates bacterial adhesion to and invasion of epithelial cells, and is involved in bacterial adaptation to the osmotic pressure of the external environment. In this study, MBs-SELEX was used as the main strategy for screening aptamers. Omp X was used as the target protein and Omp A as the counter-screening target. qPCR and flow cytometry were used to determine the nature and specificity of the obtained aptamers for the Omp X protein. The analysis showed that among the obtained aptamers, three aptamers, Apt-1, Apt-2 and Apt-3, were selected with Kd values of 62.50 nM, 22.05 nM and 7.9 nM, respectively. In addition, total internal reflection fluorescence microscopy (TIRFM) was used for the characterization of KP in complex with specific FITC-labeled aptamers (FITC-Apt-3) and AuNCs. The complexes were characterized by observing blue fluorescent dots from AuNCs and green fluorescent dots from FITC-labeled aptamers overlapping with bacterial presence. These results suggest that AuNCs and aptamers can specifically bind to target bacteria, forming complexes. Furthermore, in vitro results demonstrated that Apt-1, Apt-2 and Apt-3 inhibited bacterial growth, with Apt-3 having the most significant inhibitory effect. The results suggest that aptamers can selectively recognize membrane proteins, thereby disrupting bacterial cell membrane formation and effectively inhibiting bacterial growth. Aptamers have a potential mechanism to inhibit bacterial growth.

Dermatoses are essentially due to infectious or free radical aggression, immunoallergic disor-ders, or can be secondary to general diseases. To investigate new antimicrobial sources against dermatoses, Opilia amentacea crude ethanol extracts and fractions were subjected to phytochemical screening and tested for antioxidant and antimicrobial activities on Gram-positive cocci, Gram negative bacilli and fungi. Phytochemical screening revealed secondary metabolites such as sterols, triterpenes, flavonoids and tannins. Leaves and stem bark of Opilia amentacea exhibited the highest total phenolic contain (65,92 ± 0,93 and 65,71 ± 0,57 mg GAE/g DW respectivily) and flavonoids (38,8 ± 1,05 and 26,81 ± 0,19mg QE/g DW respectively). Dichloromethane fractions of leaves (FDFe) and stem bark (FDET) exhibited the best antioxidant activity with FRAP values of 741,15 and 662,84 mMol AAE/g and IC50 values of ABTS of 88,40 and 36,85 µg/mL respectively. These fractions were also the most active on Gram positive bacilli while Hexane leaves (FHFe) and hexane root bark (FHER) fractions exhibited the best antifungal activity against Candida tropicalis at MIC values of 0.23 mg/mL and 0.43 mg/mL respectively. Gram-negative bacteria were particularly resistant. This study constitutes a solid scientific basis that could justify the traditional uses of Opilia amen-tacea as an antidermatosis plant.

Background: As noninvasive prenatal screening usage grows in the general obstetrics setting, proper patient education on the screen’s benefits and limitations is needed. Objective: Describe the use of a technology platform designed for large-scale dissemination of noninvasive prenatal screening information and results. Study Design: The technology platform functioned as follows: Patients were emailed a link to an noninvasive prenatal screening general-education video upon laboratory receipt of a test requisition. Providers were then notified upon availability of patients’ results. If noninvasive prenatal screening results were negative, the patient was sent an automated email with instructions to access results through a secure portal where she could watch tailored informational videos, request “on-demand” or scheduled genetic counseling, or decline any further services. If genetic counseling was elected, a summary of the session was sent to the ordering provider and patient upon completion. If noninvasive prenatal screening results were positive, either the ordering provider or a board-certified genetic counselor contacted the patient directly to communicate test results and provide counseling. The number and type of results issued through the platform, the number and type of genetic counseling consultations completed, and factors associated with requesting laboratory-delivered genetic counseling were tracked and analyzed for a 39-month period. Results: Over the study period, 67,122 noninvasive prenatal screening results were issued through the platform, and 4,673 patients elected genetic counseling consultations; 95.2% (n=4,450) of consultations were for patients receiving negative results. Over 70% (n= 3,370) of consultations were on-demand rather than scheduled. Median consultation time was 14 minutes for positive results and six minutes for negative results. A positive screen, advanced maternal age, family history, previous history of a pregnancy with a chromosomal abnormality, and other high-risk pregnancy were associated with the greatest odds of electing laboratory-delivered genetic counseling. Conclusions: By combining web education, automated notifications, and genetic counseling, we implemented a service that effectively facilitates results disclosure for ordering providers. These data demonstrate the capability to deliver noninvasive prenatal screening results, education, and counseling—congruent with management guidelines—to a large population, which is imperative to quality care as uptake increases.

Embryonic and larval Danio rerio is increasingly used as a toxicological model to conduct rapid in vivo tests and developmental toxicity assays; the zebrafish features as high genetic homology to mammals; robust phenotypes; and its value in high-throughput genetic and chemical screening have made it a powerful tool to evaluate in vivo toxicity. New methodologies of genome editing as CRISPR/Cas9; ZFN or Talen make it a suitable model to perform studies to pair human genetic diseases as well. This review surveys recent studies; employing zebrafish as experimental model; comparing it with other in vivo and in vitro models; presenting zebrafish as a potent vertebrate tool to evaluate drug toxicity to facilitate more extensive; easy and comprehensive knowledge of new generation drugs.

The consumption of dairy products and the dairy industry is one of the main global agro-food sectors for size, economic importance and level of technology. Microbiological quality of pasteurized milk or other milk products is dependent on microbiological quality of raw milk. A variety of microbiological count methods is available for monitoring the hygienic quality of raw milk. Among them, the pour plate method is the official essay for counting the number of colony forming units in milk samples according to ISO 4833-1:2013. The aim of the present study is the validation of the Micro Biological Survey (MBS) method, against the reference plate count method, for the assessment of the microbiological quality of raw milk. This comparative study, performed in collaboration with the “Istituto Zooprofilattico Sperimentale del Lazio e della Toscana M. Aleandri” (IZSLT), demonstrates the accuracy of this alternative method for the determination of total viable bacterial count in cow’s raw milk. The results obtained with the MBS method highlighting its potential as a valid tool for reliable microbiological analysis in dairy industries.

We report the detection of live Escherichia coli (E. coli) in liquid samples using a biosensor based on a field effect transistor (FET) biosensor with B/N co-coped graphene oxide (GO) gel (BN-GO) as the transducer material. The FET was functionalized with antibodies to detect E. coli K12 O-antigens in phosphate-buffered saline (PBS). The biosensor detected the presence of planktonic E. coli bacterial cells within a mere 2 minutes. The biosensor exhibited a limit of detection (LOD) of 10 cells per sample, which can be extrapolated to a limit of detection at the level of a single cell per sample and a detection range of at least 10– 108 CFU/mL. The selectivity of the biosensor for E. coli was demonstrated using Bacillus thuringiensis (B. thuringiensis) as a sample contaminant. We also present a comparison of our functionalized BN-GO FET biosensor with established detection methods of E. coli k12 bacteria, as well as with state-of-the-art detection mechanisms.

In this paper, PEN3 electronic nose was used to detect and recognize fresh and moldy apples (inoculated with Penicillium expansum and Aspergillusniger) taken Golden Delicious apples as model subject. Firstly, the apples were divided into two groups: apples only inoculated with different molds (Group A) and mixed apples of inoculated apples with fresh apples (Group B). Then the characteristic gas sensors of the PEN3 electronic nose that were most closely correlated with the flavor information of the moldy apples were optimized and determined, which can simplify the analysis process and improve the accuracy of results. Four pattern recognition methods, including linear discriminant analysis (LDA), backpropagation neural network (BPNN), support vector machines (SVM) and radial basis function neural network (RBFNN), were then applied to analyze the data obtained from the characteristic sensors, respectively, aiming at establishing the prediction model of flavor information and fresh/moldy apples. The results showed that only the gas sensors of W1S, W2S, W5S, W1W and W2W in the PEN3 electronic nose exhibited strong signal response to the flavor information, indicating were most closely correlated with the characteristic flavor of apples and thus the data obtained from these characteristic sensors was used for modeling. The results of the four pattern recognition methods showed that BPNN presented the best prediction performance for the training and validation sets for both the Group A and Group B, with prediction accuracies of 96.29% and 90.00% (Group A), 77.70% and 72.00% (Group B), respectively. Therefore, it first demonstrated that PEN3 electronic nose can not only effectively detect and recognize the fresh and moldy apples, but also can distinguish apples inoculated with different molds.

(1) Background: Hepatitis C virus (HCV) screening mostly uses a one-assay anti-HCV testing approach, which has a higher probability of false-positive results in populations with low HCV prevalence. (2) Methods: In this investigation, 17,926 participants, were screened for HCV, and the reactives were tested using a two-assay anti-HCV approach: Elecsys ElectroChemiLuminescence (ECL) and a ChemiLuminescence ImmunoAssay (CLIA), respectively. A recombinant immunoblot assay (RIBA) was performed to confirm anti-HCV positivity. Statistical analysis was performed. (3) Results: A total of 350 specimens resulted reactive in the ECL screening, of which CLIA retesting showed that 292 (83.4%) were anti-HCV reactive (283 positive, 9 indeterminate, none negative by RIBA), but 58 (16.6%) were not anti-HCV reactive (15 positive, 12 indeterminate, 31 negative by RIBA). The two-assay strategy significantly improved the positive predictive value (PPV: 95.00%) with χ2: 7.59(p&lt;0.01) then the PPV assessed by one assay (PPV: 90.6%) with χ2: 34.51 (p&lt; 0.001). The ROC curve defined a sensibility and specificity for the dual approach of: 99.66% and 100.00%. (4) Conclusions: Compared with a one-assay testing strategy, the two-assay testing strategy may significantly reduce false positives in anti-HCV testing and identify inactive HCV infection in low seroprevalence populations.

Introduction: The combination of Virtual Screening (VS) techniques with in vivo screening in the zebrafish model is currently being used in tandem for drug development in a faster and more efficient way. Areas covered: We review the different virtual screening techniques, the use of zebrafish as a vertebrate model for drug discovery and the synergy that exists between them. Expert opinion: We highlight the advantages of combining virtual and zebrafish larvae screening for drug discovery. On the one hand, VS is a faster and cheaper tool for searching active compounds and possible candidates for therapy than in vivo screening when processing large compound libraries. On the other hand, zebrafish larvae form a vertebrate model which allows in vivo screening of large amounts of the compounds. Importantly physiology and chemical response are mostly conserved between zebrafish and mammals. The availability of the transgenic and mutant zebrafish lines allows an analysis of a specific phenotype upon treatment along with toxicity, off-target effect, side effects, and dosage. Advantages of VS, in vivo whole animal approach screening, and the screening combinations are also reviewed.

The up-and-coming microfluidic technology is the most promising platform for designing anti-cancer drugs and new point-of-care diagnostics. Compared to conventional drug screening methods based on Petri dishes and animal studies, drug delivery in microfluidic systems has many advantages. For instance, these platforms offer high throughput drug screening, require a small amount of samples, provide an in vivo-like microenvironment for cells, and eliminate ethical issues associated with animal studies. Multiple cell cultures in microfluidic chips could better mimic the 3D tumor environment using low reagents consumption. The clinical experiments have shown that combinatorial drug treatments have a better therapeutic effect than monodrug therapy. So many attempts were performed in this field in the last decade. This review highlights the applications of microfluidic chips in anti-cancer drug screening and systematically categorizes these systems as a function of sample size and combination of drug screening. Finally, it provides a perspective on the future of the clinical applications of microfluidic systems for anti-cancer drug development.

The coronavirus disease (COVID-19) is a respiratory tract infection caused by the new virus SARS-CoV-2. In March 2020, the World Health Organization (WHO) declared a worldwide COVID-19 pandemic. Since then, there has been a rush to find preventative or curative treatment. This arrived with the appearance of the COVID-19 vaccine, months after the declaration of the pandemic. In the setting of global COVID-19 immunization, there have been reports of rare skin immune-mediated diseases (IMD) after COVID-19 vaccination, particularly systemic sclerosis. Systemic sclerosis (SSc) is the most reported new onset IMD following messenger RNA (mRNA) COVID-19 vaccination. The pathogenesis of SSc is not fully understood, and the diagnosis is based on clinical symptoms. We report a 54-year-old male, with no prior history of autoimmune disorder, with rapid and progressive skin thickening (Modified Rodnan skin score 30/51), weeks after his mRNA COVID-19 vaccination. Antinuclear antibodies (ANA) showed a strongly positive nuclear fine-speckled pattern, but no SSc autoantibodies were found. The patient was diagnosed with SSc based on the persistence of autoantibodies and the clinical criteria according to the 2013 American College of Rheumatology/European League Against Rheumatism classification. Due to the proximity of the two events, we hypothesized a cross-reaction between COVID-19 vaccination and, in genetically predisposed patients, an emergence of systemic sclerosis. Our case suggests a potential relationship between the mRNA COVID-19 vaccine and new-onset autoimmune diseases. Physicians should be aware of this possible association.

The importance of detecting bacteria in various food products is ever-increasing, due to recent food trends that lend themselves to food contamination. Additionally, the detection of probiotics in food products is of increasing importance to consumers, who realize the benefits of probiotics on one’s diet. Existing technologies for detection of bacteria in food are accurate, but most are slow, increasingly costly and unsuitable for applications outside of research laboratories. Optic approaches have recently emerged as an alternative, allowing rapid detection of bacterial presence. This study employs a portable kinetics fluorometer, fabricated in-house, in conjunction with NADH sensitive fluorescence reporter for analysis of various food products. The presence of bacteria is detected in 5 minutes. Both pathogenic and probiotic bacteria were detected in food products, such as raw chicken and beef, spoiled lettuce and contaminated water, yogurt, and kombucha tea. The cellular activity of two probiotic pills was also verified. All samples displayed varying levels of bacterial activity. The study indicates the viability of biosensors being used as an alternate method to detect bacteria in food products – and the viability of a fluorescence-based biosensor to detect viable bacteria. The approach is suitable for both laboratory and field determinations.

Purpose: Expanded carrier screening (ECS) informs couples of their risk of having offspring affected by certain genetic conditions. Limited data exists assessing the actions and reproductive outcomes of at-risk couples (ARCs). We describe the impact of ECS on planned and actual pregnancy management in the largest sample of ARCs studied to date. Methods: Couples who elected ECS and were found to be at high risk of having a pregnancy affected by at least one of 176 genetic conditions were invited to complete a survey about their actions and pregnancy management. Results: Three hundred ninety-one ARCs completed the survey. Among those screened before becoming pregnant, 77% planned or pursued actions to avoid having affected offspring. Among those screened during pregnancy, 37% elected prenatal diagnostic testing (PNDx) for that pregnancy. In subsequent pregnancies that occurred in both the preconception and prenatal screening groups, PNDx was pursued in 29%. The decision to decline PNDx was most frequently based on the fear of procedure-related miscarriage, as well as the belief that termination would not be pursued in the event of a positive diagnosis. Conclusions: ECS results impacted couples’ reproductive decision-making and led to altered pregnancy management that effectively eliminates the risk of having affected offspring.

We aimed to directly compare the cost-effectiveness of the NELSON and NLST screening protocols, two trials influencing lung cancer screening implementation internationally. A decision-analytic model analyzing the cost-effectiveness of the NELSON protocols was manipulated to reflect the protocols of the NLST, while maintaining features specific to the Hungarian healthcare setting. In the NELSON protocol, there are three possible outcomes to the initial round of screening: positive, negative, or indeterminate, indicating an uncertain degree of suspicion for lung cancer. This pro-tocol differs from the NLST protocol, in which the only possible screening outcomes are positive or negative, with no indeterminate option. The NLST pathway for smokers aged 55-74 resulted in a 43 € increase in total average lifetime costs compared to the Hungarian screening pathway and re-sulted in a lifetime gain of 0.006 QALYs. The incremental costs and QALYs yield an ICER of 7875 €/QALY. Our results demonstrate that assigning any suspicious LDCT screen as a positive result (NLST protocol) rather than indeterminate (NELSON protocol) can yield a slight QALY gain that is worth the additional use of resources according to Hungary’s willingness to pay threshold. Our study provides insight on the cost-effectiveness, advantages, and disadvantages of various LDCT screening protocols for lung cancer and can assist other countries as they implement their screening programs.

The moisture content of maize seed is an important indicator for evaluating seed quality and a fundamental item in grain testing. The experiment used direct drying method to measure the moisture content of 80 different varieties of maize samples, and captured their images using a hyperspectral imaging (HSI) system in the spectral range of 1100~2498nm. By comparing seven spectral preprocessing methods, the PLSR model established after Normalize pretreatment had the best effect. The characteristic wavelengths were selected by Successive Projections Algorithm (SPA), Competitive Adaptive Reweighted Sampling (CARS) and Uninformative Variable Elimination (UVE). Twelve prediction models were established for full band spectra and characteristic wavelengths based on PLSR, PCR and SVM. By comparing the performance of the prediction models, it was found the Normalize-SPA-PLSR algorithm was optimized. The values of RC2 and RP2 in the model were higher, which were 0.9936 and 0.9933, respectively, while the values of RMSEP and RMSECV were lower, which were 0.0357 and 0.0380, respectively. The Normalize-SPA-PLSR model was used as a visual prediction model for moisture content of maize seed, the 20 maize varieties in the prediction set were visualized to obtain visualized color images of moisture content. The color differences between different moisture content images were significant. The result indicated that hyperspectral imaging could accurately, rapidly, and non-destructive predict moisture content of maize seed, which provided technical support for moisture content detection in the process of maize harvest, storage and processing.

Positive Health (PH) has been described as a promising transformative innovation to address the challenges of promoting well-being and reducing the burden of disease. The aim of this study is to review the current state of knowledge about PH as introduced by Huber et al. (2016) within the available scientific literature. A rapid review of the literature following the Cochrane Rapid Review recommendations. Three databases were searched (PubMed, Google Scholar, and CINAHL). Data were extracted and synthesized using a narrative approach. A total of 55 articles were included. Initial evaluation studies reveal promising results both at individual and collective levels. However, a need is expressed in several articles for further refinement of the conceptualization of PH and ways to make the effects of the PH approach more measurable. Professionals also expressed a desire for a more informed application and elaboration of the PH method across various settings and populations to enhance its effectiveness in practice. This rapid review highlights the transformative potential of PH in shifting from a disease-focused to a health-oriented paradigm of healthcare. It underscores the need for continued research regarding further development of the concept and its practical method, along with the necessity for methodological innovation.

Despite the increasing popularity of liquid chromatography-mass spectrometry (LC-MS)-based lipidomics, there is a lack of accepted and validated method for lipid extract quality and quantity assessment prior to LC-MS. Fourier-Transform Infrared Spectroscopy (FTIR) has been reported for quantification of pure lipids, however, the sample complexity and purity complex lipid extract quantification in lipidomics experiments could be impact quantification accuracy. Here, we report comprehensive assessment of the sample matrix on the accuracy of lipid quantification using Attenuated Total Reflectance Fourier-Transform Infrared Spectroscopy (ATR-FTIR). Pure lipids are characterized by CH-and C=O-stretching vibrations on FTIR, with quantitative range of 40–3000 ng and a limit of detection of 12 ng. Sample extraction method and local baseline subtraction during FTIR spectral processing significantly impact lipid quantification by CH-stretching. To facilitate sample quality screening, we developed the Lipid Quality (LiQ) score from a spectral library of common contaminants, using a ratio of peak heights between CH-stretching vibrations maxima and the collective vibrations from amide/amine, CH-stretching minima and sugar moieties. We evaluated LiQ score as a rapid sample quality control method by comparing to total LC-MS intensity of targeted lipidomics of 107 human plasma lipid extracts. Exclusion of poor-quality samples based on LiQ score improved the correlation between FTIR and LC-MS quantification. Finally, the uncertainty of absolute quantification by FTIR was estimated using a 795 ng SPLASH LipidoMix standard to be &lt;10%. In summary, this study identified key parameters for accurate FTIR-based quantification of complex lipid mixture, and developed a rapid workflow requiring only 1 µL of MS-ready sample and &lt; 5 minutes for routine lipidomics sample quality and quantity assessment.

Biosensors have shown great potential in realizing rapid, low cost and portable on-site detection for diseases. This work reports the development of a new bioelectronic sensor called AC electrokinetics-based capacitive (ABC) biosensor, for the detection of genomic DNA (gDNA) of methicillin-resistant Staphylococcus aureus (MRSA). The ABC sensor is based on interdigitated microelectrodes biofunctionalized with oligonucleotide probes. It uses a special AC signal for direct capacitive monitoring of topological change on nanostructured sensor surface, which simultaneously induce dieletrophoretic enrichment of target gDNAs. As a result, rapid and specific detection of gDNA/probe hybridization can be realized with high sensitivity. It requires no signal amplification such as labelling, hybridization chain reaction, or nucleic acid sequence-based amplification. This method involves only simple sample preparation. After optimization of nano-structured sensor surface and signal processing, the ABC sensor demonstrated fast turnaround of results (~10 s detection), excellent sensitivity (a detection limit of 4.7 DNA copies /µL MRSA gDNA) and high specificity, suitable for point of care diagnosis. As a bioelectronic sensor, the developed ABC sensors can be easily adapted for detection of other infectious agents.

Since the UK commenced newborn screening for isovaleric acidemia in 2015, changes in prescribing have increased the incidence of false positive (FP) results due to pivaloylcarnitine. A review of screening results between 2015-22 identified 24 true positive (TP) and 84 FP cases, with pivalate interference confirmed in 76/84. Initial C5 carnitine (C5C) did not discriminate between FP and TP with median (range) C5C of 2.9 (2.0 - 9.6) and 4.0 (1.8 - &gt;70) µmol/L respectively and neither did Precision Newborn Screening via Collaborative Laboratory Integrated Reports (CLIR), which identified only 1/47 FP cases. However, among the TP cases, disease severity showed a correlation with initial C5C, in ‘asymptomatic’ individuals (n=17), demonstrating a median (range) C5C of 3.0 (1.8 – 7.1) whilst ‘clinically affected’ patients (n=7), showed a median (range) C5C of 13.9 (7.7 - &gt; 70) µmol/L. These findings allowed the introduction of dual cut-off values into the screening algorithm to reduce the incidence of FPs, with initial C5C results ≥ 5 µmol/L triggering urgent referral, and those &gt; 2.0 and &lt; 5.0 µmol/L prompting 2nd tier C5-isobar testing. This will avoid delayed referral in babies at particular risk whilst reducing the FP rate for the remainder.

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

To screen and validate immunosuppressive factors in luminal- and basal-like breast cancer cell lines and tissue samples associated with malignant phenotypes. The mRNA microarray datasets, GSE40057 and GSE1561, were downloaded and remodelled. Differentially expressed genes (DEGs) were identified. Enrichment analyses performed and the online resources, GOBO and Kaplan-Meier Plotter, were employed to screen for immunosuppressive factors associated with breast cancer malignant phenotypes. qRT-PCR and western blot were used to validate the expression of CD274 and IL8 in cell lines and immunohistochemical detected the MIF and VEGFA on tissue microarrays. The results showed that CD274 and IL8 were both upregulated in basal-like cell lines. That MIF expression was dramatically increased in patients with breast cancer metastases (p<0.05) and that VEGFA expression positively correlates with breast cancer pathologic grade (p<0.05).During the formation and development of breast cancer, immune-related genes are always activated, and immunosuppressive factors CD274, IL8, MIF and VEGFA are upregulated. Such molecules could be used as biomarkers for breast cancer prognosis. However, because individual immune-related factors can play several biological roles, the mechanistic relationship between immunosuppressive factors and breast cancer malignant phenotypes and the feasibility of their application as drug targets require further investigation.

The successful advancement of xenotransplantation has led to the development of highly sensitive detection systems for the screening for potentially zoonotic viruses in donor pigs and preventing their transmission to the recipient. To validate these methods, genetically modified pigs generated for xenotransplantation, numerous minipig and other pig breeds have been tested, thereby increasing our knowledge concerning the pig virome and the distribution of pig viruses. Of particular importance are the porcine cytomegalovirus, a porcine roseolovirus (PCMV/PRV) and the hepatitis E virus genotype 3 (HEV3). PCMV/PRV has been shown to reduce the survival time of pig transplants in non-human primates and was also transmitted in the first pig heart transplantation to a human patient. Here, we determined the sensitivities of our methods to detect PCMV/PRV, HEV3, porcine lymphotropic herpesvirus - 1 (PLHV-1), PLHV-2, PLHV-3, porcine circovirus 2 (PCV2), PCV3, PCV4 and porcine parvovirus 1 (PPV1) efficiently and used the methods to screen indigenous Greek black pigs. Since porcine endogenous retroviruses (PERVs) of type A and B are integrated in the genome of all pigs, but PERV-C is not, the animals were screened for PERV-C and PERV-A/C. Our detection methods were sensitive and detected PCMV/PRV, PLHV-1, PLHV-1, PLHV-3, PVC3 and PERV-C in most animals. PPV1, HEV3, PCV4 and PERV-A/C were not detected. These data are of great interest since the animals are healthy and very resistant to diseases.

The present investigation has been conducted on one hundred tissue fragments of breast cancer, collected and immediately cryopreserved following the surgical resection. The fragments were selected from patients with invasive ductal carcinoma of the breast, the most common and potentially aggressive type of mammary cancer, with the objective to increase the knowledge of breast cancer molecular markers, useful for diagnostic and prognostic categorization of patients, in assessing post-surgical therapeutic regimes. The proteomic screening, by 2D-IPG and mass spectrometry, allowed us to identify two main classes of protein clusters: proteins expressed ubiquitously at high levels in all patients, and proteins expressed sporadically among the same patients. Within the group of ubiquitous proteins, glycolytic enzymes and proteins with anti-apoptotic activity were predominant. Among the sporadic ones, proteins involved in cell motility, molecular chaperones and proteins involved in the detoxification appeared prevalent. The data of the present study indicates that the primary tumor growth is generally supported by two concurrent pathways: the inhibition of apoptosis and the stimulation of cellular proliferation. The second phase of the evolution of the tumor can be prematurely scheduled by the occasional presence of proteins involved in cell motility and in the defenses of the oxidative stress. To our knowledge this report on large-scales proteomics of breast cancer is currently a unique approach in the literature that offers the opportunity to evaluate the presence and recurrence of proteins to be used as prognostic indicators and susceptibility to metastasis in patients operated on for invasive ductal carcinoma of the breast.

Understanding and preventing the “great obstetrical syndromes” has been the focus of pregnancy research for decades. The combined global impact from these syndromes on maternal and perinatal morbidity and mortality is compounded by increased long-term risk of adverse health effects following pregnancy. Accumulating evidence indicates that conditions such as pre-eclampsia, fetal growth restriction, spontaneous preterm labour, and stillbirth, are syndromes with etiologic heterogeneity that share common pathophysiologic pathways involving placental dysfunction. Recently, the importance of the interaction between fetal and maternal genomes has been extended to include the epigenetic impact of pre-existing maternal pathophysiology on placental development and highlights the importance of nutritional and environmental factors in altered placentation. Validated first-trimester screening algorithms for preeclampsia can identify high-risk women and prophylactic treatment with low-dose aspirin can be initiated. High-risk women can be monitored during the second trimester using clinical assessment, ultrasound, and biochemical markers, that are able to predict complications prior to the development of clinical signs and symptoms. The integration of lifestyle interventions, pregnancy screening, and medical management represents a conceptual advance in pregnancy care. This approach has the potential to significantly reduce pregnancy complications, maternal and perinatal morbidity and mortality, adverse health outcomes later in life, and health-care costs.

Drug discovery utilizes high-throughput screening (HTS) methods applying target and cell-based assays. This review discusses the challenges and benefits associated with these assays in HTS. Discussed the strategies that can be applied for the development of screening assays through primary and secondary screens for target identification. Further discussion on identify-ing the most efficacious drugs following these approaches in cancer. Even though various drugs have been identified to treat cancer, there is high demand of more relevant phenotypic assays to produce desired diseased phenotype to only highlighting the specific targets instead of off-targets. Hopefully, the new developing strategies could provide innovative drugs to treat cancer patients to reduce mortality rate.

This article presents research on selected materials with the aim of determining their rare earth element (REE) content and attempting to intensify it. The test material was coal slurry, which is a waste product from the operation of a preparation plant of a closed coal mine. Research on REE concentration intensification tests was carried out using magnetic separation. Laboratory analyses determining the REE content in the samples obtained, were carried out using the inductively coupled plasma ionisation mass spectrometry (ICP-MS) technique. Carrying out this research by the KOMAG Institute of Mining Technology, is a continuation of work related to making mining waste economically useful and determining a new source of REE recovery. Previous research and development work showed REE content (scandium 40.49 ppm) in the coal slurries studied. The result of the work carried out is the determination of the economic utility of REE recovery from the studied waste.

This article aims to review the screening and diagnostic tools for eating disorders (ED). Eating disorders represent a complex pathology defined by an imbalance between hunger and satiety, installed in an emotional, traumatic, or conflictive context. Recently, the emphasis regarding ED is focused on the link between genetics, mental pathology, and the somatic and metabolic phenotype and early detection. Early detection and intervention can assure a better recovery and can improve a lot the quality of life of these patients. Methods: We selected ten articles of central importance on the topic in a systematic search on eight databases, articles selected on the type of scales, and size of the study. Results: We identified eight questionnaire scales used in large trials in ED disorders in the scanned literature, choose because we consider it the most accurate and the ones that evaluate best the pathology and the elements that are important as specific traits in ED. There are interview-type scales and self-administered scales. Interview scales are characterized by assessments of symptoms and diagnosis, while self-administered assess particular traits and the possibility of further development of eating disorders. The majority of the scales evaluated were described and used in adult populations. From all the scales assessed and analyzed, only three are described at the child population – it is EAT-26 (> 16 years), EDI-3 (>13 years), and ANSOCQ (> 13 years). Conclusions: It is essential to develop specific scales for people under 18 years of age, given the increasing incidence of ED among children and the need for early detection and appropriate intervention. Early detection of ED in children implies a simple and accurate evaluation at the primary care level or in schools, as the course of the disease can be subclinical for several years. Moreover, the need for accurate scales and telemedicine testing and diagnosis is of high importance during the COVID-19 pandemic as youth are at particular risk being psychologically affected due to disrupted education and social interactions - at a critical time.

Leaves of Citrus aurantifolia, Citrus hystrix and Citrus microcarpa collected from Mersing, Johor were selected for this research. The extraction of these samples were carried out using three different polarities of solvents (hexane, ethyl acetate, and methanol). Phytochemical screening were done with various test for each of crude extracts. The results showed that C. aurantifolia gave positive result for alkaloids, saponins, reducing sugar and carbohydrates in hexane and ethyl acetate extracts. In contrast to C. hystrix where the presence of alkaloids, steroids, reducing sugar and carbohydrates were proven in all crude extracts. Lastly, C. microcarpa showed positive result for alkaloids, triterpenoids, saponins, flavonoids, reducing sugar, carbohydrates, phenolic content, glycosides and tannins for hexane and ethyl acetate crude extracts. Through antioxidant assays measured at wavelength 234 nm, C. aurantifoliaa has the highest AOA which was 10. The scavenging effect on DPPH radical was done at the wavelength of 517 nm and C. microcarpa has the highest percentage of scavenging effect with 96.41%. Next, the non-enzymatic antioxidant assays on the determination of α-tocopherol and carotenoids showed that C. hystrix has the highest concentration of α-tocopherol (2.30 ± 0.026), while C. microcarpa has the highest concentration of carotenoids (18.40 ± 2.83).

G protein-coupled receptor 15 (GPR15, also known as BOB) is an extensively studied orphan GPCR involving HIV infection, colonic inflammation and smoking-related diseases. Recently, GPR15 was deorphanized and its corresponding natural ligand demonstrated an ability of inhibiting cancer cell growth. However, no study reported the potential role of GPR15 in a pan-cancer manner. Using large-scale publicly available data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases, we found that GPR15 expression is significantly lower in colon adenocarcinoma (COAD) than in normal tissues. And among 33 cancer types, GPR15 expression is significantly correlated with the prognoses of COAD, neck squamous carcinoma (HNSC), lung adenocarcinoma (LUAD) positively and stomach adenocarcinoma (STAD) negatively. This study also revealed that commonly upregulated gene set in the high GPR15 expression group (stratified via median) of COAD, HNSC, LUAD and STAD are enriched in immune systems, indicating that GPR15 might be considered as a potential target for cancer immunotherapy. Furthermore, we modelled the 3D structure of GPR15 and conducted the structure-based virtual screening. The top 8 hits compounds were screened and then subjected to molecular dynamics (MD) simulation for stability analysis. Our study provided novel insights into the role of GPR15 in a pan-cancer manner and discovered a potential hit compound for GPR15 antagonists.

Background: First-line biological diagnosis of malaria in Mali is based on the use of rapid diagnostic tests (RDT), which detect in the blood the Histidin Rich Protein 2 antigen, specific to Plasmodium falciparum. Our study, based on a real-time polymerase chain reaction (qPCR) gold-standard diagnosis, aims to evaluate the performance of RDTs used in Mali and to describe the distribution of Plasmodium species in each administrative regions of Mali; Methods: We collected RDT cassettes in 47 sites of the nine regions of Mali. We randomly selected 150 malaria-negative and up to 30 malaria-positive RDTs from each regions. DNA was extracted from the RDTs’ nitrocellulose strip and then assayed with a pan-Plasmodium qPCR. Positive samples were then analyzed with qPCRs specific for P. falciparum, P. malariae, P. vivax, and P. ovale; Results: Of the 1,389 tested by qPCR RDTs, 258 (18.6%) were positive for Plasmodium spp. P.falciparum was the most predominant (97.3%). However, the prevalence of P.vivax reach 21.1% in the Ménaka region in the north; Conclusion: Overall, RDT diagnostic indices are adequate for the biological diagnosis of malaria in Mali. Our finding support the adjustment of RDTs to the local epidemiology.

This study reports the design of a dielectric resonator (DR) metasurface-based terahertz biosensor for rapid and accurate detection of different kinds of viruses (H1N1, SARA-COV-2, etc.). The characterization of the sensor is done by analyzing its absorbance properties with and without the presence of the H1N1 virus layer of different concentrations and electrical properties in the frequency range of 2.4 THz to 3 THz. A full-wave EM model of the sensor is designed using CST MWS software. The geometrical parameters of the proposed biosensor, as well as its dielectric constant of the virus swab, are varied to achieve good performance with an absorption level close to 1 (100%). A significant change in the resonating pick-up frequency owing to the variation in the effective refractive index of the realized sensor ensures the detection and classification of the different concentrations of the same or different viruses. The presented design could be used for the rapid detection of viruses with the added advantages of contactless, label-free, and accurate identification of different concentrations of viruses.