Cardiomyopathies are diseases of heart muscle, a significant percentage of which are genetic in origin. Cardiomyopathies can be classified as dilated, hypertrophic, restrictive, arrhythmogenic right ventricular or left ventricular non-compaction, although mixed morphologies are possible. A subset of neuromuscular disorders, notably Duchenne and Becker muscular dystrophies, are also characterized by cardiomyopathy aside from skeletal myopathy. The global burden of cardiomyopathies is certainly high, necessitating further research and novel therapies. Genome editing tools, which include zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR) systems have emerged as increasingly important technologies in studying this group of cardiovascular disorders. In this review, we discuss the applications of genome editing in the understanding and treatment of cardiomyopathy. We also describe recent advances in genome editing that may help improve these applications, and some future prospects for genome editing in cardiomyopathy treatment.

Thalassemia is genetic blood disease cause by absence or decrease of one or more of the globin chain synthesis. Beta thalassemia is characterized by one or more mutations in beta globin gene. Absence or reduced amount the of beta globin chains cause ineffective erythropoiesis which leads to anemia. Beta thalassemia has been further divided into three main forms: Thalassemia minor/silent carrier, major and intermedia. More severe form is thalassemia major in which patients depend upon blood transfusion for survival and high level of iron occur as a consequence of consistent blood transfusion. Over loaded iron invokes the synthesis of reactive oxygen species that are toxic in redundancy and triggering the impairment to vascular, endocrine and hepatic system. Thalassemia can be diagnosed and detected through various laboratory tests such as blood smear, prenatal testing (genetic testing of amniotic fluid), DNA analysis (genetic testing) and complete blood count. Treatment of thalassemia intermedia is symptomatic but it can also be managed by splenectomy and folic supplementation. While thalassemia major can be treated by transplantation of bone marrow, regular transfusion of blood and iron chelation treatment, stimulation of fetal hemoglobin production, hematopoietic stem cell transplantation and gene therapy.

Objectives: To compare the effects of high-velocity resistance training to slow-velocity re-sistance training on neuromuscular and functional parameters and to analyze the relationship between changes in walking speed and improvements in neuromuscular parameters following intervetions. Methods: 40 participants were randomly assigned to either a high-speed resistance training group (GHS, n = 18; age = 80.41 ± 10.12 years; BMI = 23.81 ± 3.45 kg/m²) or a low-speed resistance training group (GLS, n = 22; age = 82.89 ± 5.32 years; BMI = 23.81 ± 3.45 kg/m²). Before and after the interventions, gait speed (m/s) was assessed using a 10-minute walking test, and relative maximal force (Relative F max, N/kg) was evaluated during maximal voluntary isometric con-traction of the plantar flexors. From the force-time curve, early (0 – 50 ms) and late (100 – 200 ms) rates of force development (RFD) were extracted from the linear slopes (Δ force / Δ time). Results: Gait speed significantly improved in both groups (p < 0.05). However, the improvement was more pronounced in the GHS compared to the GLS (p < 0.05). Relative Fmax showed a more significant increase in the GLS than in the GHS (p < 0.05). Moreover, a significant 10% increase in early RFD in the GLS and a 20.1% increase in the GHS were observed (p < 0.05). The improvement in early RFD was greater in the GHS (p < 0.05). Additionally, late RFD improved significantly only in the GHS (+20.4%, p < 0.05). Conclusion: High-velocity resistance training appears particularly effective in improving the ability to rapidly generate force, which is essential for many daily activities re-quiring explosive movements and quick responses.

Background: The increase in the prevalence of obesity in South Africa is a problem and weight management play an important role in the treatment of the high prevalence. For this purpose, a quantitative study was carried out using a structured questionnaire to assess predictors of attempt and failure to lose weight. Methods: One thousand and fifty adults were enrolled in the study and 54% (n=562) were overweight and obese (BMI &gt;/25kg/m2). Descriptive statistics were analysed. Inferential statistical tests (chi-square tests, logistic regression, and Pearson’s correlation coefficients) were used to determine the relationship between variables. Results: The results revealed that age, sex, marital status, educational level, employment status, income level, area of residence, ethnic groups, and self-perceived BMI (normal weight, overweight, and obese) were predictors of attempt and failure to lose weight. There was a positive correlation between self-perceived BMI and the attempt and failure to lose weight. Conclusion: Weight management is important in the realm of public health and can be regarded as an investment in the population, as it leads people toward weight control strategies grounded in empirical evidence. Additionally, the findings can inform public health policies and interventions to improve weight management strategies at the population level.

Allergic reactions are the most frequent adverse effects of blood transfusion, and anaphylactic shock, although less frequent, is systemic and serious. The causes of allergic reactions to blood transfusions are largely unknown, but deficiencies in serum proteins such as haptoglobin (Hp) can lead to anaphylactic shock. A complete deletion of the haptoglobin gene (HPdel) was first identified in families with anomalous inheritance and then verified as a genetic variant that can cause anaphylactic shock because homozygotes of HPdel have an Hp deficiency. Thereby, they may produce antibodies against Hp from blood transfusions. HPdel is found in East and Southeast Asian populations, but not in other populations, with a frequency of approximately 0.9% to 4%. Diagnosis of Hp deficiency due to HPdel prior to transfusion is desirable because severe adverse reactions can be prevented by washing the red blood cells and/or platelets with saline or by administrating plasma products obtained from an Hp deficient donor pool. This review outlines the background of the identification of HPdel and several genetic and immunological methods developed for diagnosing Hp deficiency caused by HPdel.

More than one million curable sexually transmitted infections occur every day. Trichomonas vaginalis is one of the main responsible for these epidemiological data, however, the diagnosis of this protozoan is still mainly based on microscopic and culture identification. The commerciali-zation of immunological tests and the development of molecular techniques have improved the sensitivity of classical methods. Nevertheless, the fact that trichomoniasis is a neglected parasitic infection, hinders the development of novel techniques and their implementation in routine di-agnosis. This review article shows the different methods developed to identify T. vaginalis in population and the difficulties to diagnose male and asymptomatic patients. The importance of including this parasite in routine gynecological screening, especially in pregnant women, and the importance of considering T. vaginalis as an indicator of high-risk sexual behavior is also discussed.

To enhance the overall reliability of the power system, engineers have redirected their focus toward health monitoring and early detection of faults in transformers. Among these faults, transformer core defects demand particular attention. While fault simulation using software has traditionally been the preferred approach, these methods suffer from data inaccuracies in real-world conditions. Consequently, conducting actual experimental setups with induced faults is imperative to investigate core issues. This study uses Hilbert Transform (HT) as a signal processing technique to extract crucial data characteristics, thereby enhancing the performance of the classifier model. The research involves analyzing electric current signals from a single-phase 1kVA transformer. A comparative assessment of our proposed model was conducted using raw data and Fast Fourier Transform (FFT), evaluating accuracy, precision, recall, F1-score, and computational time. The results demonstrate a significant improvement in all metrics for the classifier models, particularly the k-nearest neighbor (KNN) algorithm, which exhibited values of 83.89%, 84.39%, 83.89%, 83.79%, and 0.0156 seconds, respectively. Future work aims to extend this analysis under different loading conditions.

Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a predominant cause of mortality, especially in low- and middle-income nations. Recently antimicrobial peptides were discovered that at low concentrations could stimulate the growth of M. tuberculosis (hormetic response). In this study, such a peptide was used to investigate the effects on the time to positivity (TTP). A systematic substitution analysis of peptide 14D was synthesized using Spot synthesis technology, resulting in 171 novel peptides. Our findings revealed a spectrum of interactions, with some peptides accelerating M. tuberculosis growth, potentially aiding in faster diagnostics, while others exhibited inhibitory effects. Notably, peptide NH2-wkivfiwrr-CONH2 significantly reduced the TTP by 25 hours compared to the wild-type peptide 14D, highlighting its potential in improving TB diagnostics by culture. Several peptides demonstrated potent antimycobacterial activity, with a minimum inhibitory concentration (MIC) of 20 µg/mL against H37Rv and a multidrug-resistant M. tuberculosis strain. Additionally, a reduction in the formation of cord-like structures was observed, which is indicative of reduced virulence and transmission potential. This study underscores the multifaceted roles of antimicrobial peptides in TB management, from enhancing diagnostic efficiency to offering therapeutic avenues against M. tuberculosis.

Radiator reliability is crucial in environments characterized by high temperatures and friction, where prompt interventions are often required to prevent system failures. This study introduces a proactive approach to radiator fault diagnosis, leveraging the integration of Gaussian Mixture Model (GMM) and Long-Short Term Memory (LSTM) autoencoders. Vibration signals from radiators were systematically collected through randomized durability vibration bench tests, resulting in four operating states—two normal, one unknown, and one faulty. Time-domain statistical features of these signals were extracted and subjected to Principal Component Analysis (PCA) to facilitate efficient data interpretation. Subsequently, this study discusses the comparative effectiveness of GMM and LSTM in fault detection. GMMs are deployed for initial fault classification, leveraging their clustering capabilities, while LSTM autoencoders excel in capturing time-dependent sequences, facilitating advanced anomaly detection for previously unencountered faults. This alignment offers a potent and adaptable solution for radiator fault diagnosis, particularly in challenging high-temperature or high-friction environments. Consequently, the proposed methodology not only provides a robust framework for early-stage fault diagnosis but also effectively balances diagnostic capabilities during operation. Additionally, this study presents the foundation for advancing reliability life assessment in accelerated life testing, achieved through dynamic threshold adjustments using both the absolute log-likelihood distribution of the GMM and the reconstruction error distribution of the LSTM autoencoder model.

Advanced heart failure (AHF) presents a complex landscape with challenges spanning diagnosis, management, and patient outcomes. In response, the integration of multimodality imaging techniques has emerged as a pivotal approach. This comprehensive review delves into the profound significance of these imaging strategies within AHF scenarios. Multimodality imaging, encompassing echocardiography, cardiac magnetic resonance imaging (CMR), and cardiac computed tomography (CCT), stands as a cornerstone in the care of patients with both short- and long-term mechanical support devices. These techniques facilitate precise device selection, placement, and vigilant monitoring, ensuring patient safety and optimal device functionality. In the context of orthotopic cardiac transplant (OTC), the role of multimodality imaging remains indispensable. Echocardiography offers invaluable insights into allograft function and potential complications. Advanced methods, like speckle tracking echocardiography (STE), empower the detection of acute cell rejection. CMR and CCT further enhance diagnostic precision, especially concerning allograft rejection and cardiac allograft vasculopathy. This comprehensive imaging approach goes beyond diagnosis, shaping treatment strategies and risk assessment. By harmonizing diverse imaging modalities, clinicians gain a panoramic understanding of each patient's unique condition, facilitating well-informed decisions. Thus, this review underscores the irreplaceable role of multimodality imaging in elevating patient outcomes, refining treatment precision, and propelling advancements in the evolving landscape of advanced heart failure management.

We present a case of a combination of two rare hereditary disorders: Аdrenal insufficiency, obesity, and red hair syndrome (OBAIRH) and Duchenne muscular dystrophy (DMD) in a boy. Both diseases were diagnosed during the first year of life. OBAIRH was suggested based on the ethnicity and family history of the patient, while DMD – based on an extreme increase in transaminase and CK levels during biochemical analysis of his blood.

In a complex working environment, the fault signal of the gearbox is greatly affected by the outside world, and fault feature recognition is difficult, so the fault diagnosis accuracy is difficult to meet the expected requirements. To solve this problem, this paper proposes a gearbox fault diagnosis method based on an optimized stacked denoising auto encoder (SDAE) and kernel extreme learning machine (KELM). Firstly, the Particle Swarm Optimization algorithm in Adaptive Weight (SAPSO) was adopted to optimize the SDAE network structure, and the number of hidden layer nodes, learning rate, noise addition ratio and iteration times were adaptively obtained to make SDAE obtain the best network structure. Then, the best SDAE network structure was used to extract the deep feature information of weak faults in the original signal. Finally, the extracted fault features are fed into KELM for fault classification. Experimental results show that, compared with existing commonly used methods of fault diagnosis, the fault diagnosis model proposed in this paper can reduce the influence of noise in the original signal can better learn the deep-level features in the original signal and has higher diagnosis accuracy, faster diagnosis speed and good generalization in fault diagnosis.

Improvements in the treatment of childhood cancer have considerably enhanced survival rates over the last decades, to over 80% as per today. However, this great achievement has been accompanied by the occurrence of several early and long-term treatment-related complications major of which is the cardiotoxicity. The chemotherapeutic agents that have been implicated as a cause of cardiotoxicity, are mostly anthracyclines and mitoxantrone, alkylating agents, proteasome inhibitors and to a lesser extent anti-microtubule agents, cisplatin, monoclonal antibodies, small molecular tyrosine kinase inhibitors, and nucleotide synthesis inhibitors. Routine diagnosis and monitoring of cardiotoxicity rely on electrocardiography and echocardiography. For the early detection of cardiotoxicity, in recent years, major studies have been conducted using biomarkers such as troponin, N-terminal pro b-natriuretic peptide, etc. Despite refinements in diagnostics still severe limitations exist, due to the increase of the above-mentioned biomarkers, only after significant cardiac damage has occurred. Lately, research has been expanded by introducing new technologies and finding new markers by omics approach. These new markers could be used not only for early detection, but also for early prevention of cardiotoxicity. The omics science, which includes genomics, transcriptomics, proteomics, and metabolomics, offers new opportunities for biomarker discovery in cardiotoxicity and may provide understanding of mechanisms of cardiotoxicity, beyond traditional technologies. This article reviews the contemporary definition of cardiotoxicity, older and newer chemotherapeutic agents mainly involved in cardiotoxicity and the methods of early and preventive diagnosis, using omics technology.

Background: This paper examined the gap between obesity and its diagnosis for cohorts of patients with overweight, obesity, and morbid obesity in the Veterans Administration (VA) population. Using the risk adjustment models, it also identified factors associated with the underdiagnosis of obesity. Methods: Analysis was performed on a VA data set. We identified diagnosed patients and undiag-nosed patients (identified through BMI but not diagnosed by ICD-10 codes). The groups’ de-mographics were compared using nonparametric chi-square tests. We used logistic regression analysis to predict the likelihood of the omission of diagnosis. Results: Of the 2,900,067 veterans with excess weight, 46% were overweight, 46% had obesity, and 8% of them had morbid obesity. The overweight patients were the most underdiagnosed (96%), followed by the obese (75%) and morbidly obese cohorts (69%). Older, male, and White patients were more likely to be undiagnosed as overweight and obese; younger males were more likely to be undiagnosed as morbidly obese. (p<.05) Comorbidities significantly contributed to diagnosis. Conclusion: Underdiagnosis of obesity continues to be a significant problem despite its prevalence. Diagnosing obesity accurately is necessary to provide effective management and treatment.

Background: Idiopathic normal pressure hydrocephalus is a syndrome with neuroradiological findings and clinical pattern characteristic but not specific for the pathology. Since the prevalence is growing due to the rapidly aging society, standardized and validated protocol for diagnosis is needed, also because this condition may mimic other disorders among elderly such as Parkinson's and Alzheimer's disease. Material and methods: We analysed data from 44 patients with suspect diagnosis of idiopathic normal pressure hydrocephalus with age > 60 years, clinical triad and neuroradiological pattern examined in our ward from November 2018 to November 2022. Neu-ropsychological assessment includes Mini Mental State Examination and Mental Deterioration Battery. Motor scores were collected from gait and balance tests. The evaluation was performed before and after an extended lumbar drainage last 48h. Patients who has scores improvement after the extended lumbar drainage, undergo ventriculoperitoneal shunt with a programmable valve. Results: All patients undergo neuropsychological assessment and motor tests, only 2 patients were unable to perform motor tests because bedridden. 16 patients showed no benefit from the tests, in 2 cases even a worsening of cognitive performance. 28 patients showed an improvement in their performances, but in most cases the improvement involved only the neuropsychological as-sessment. All patients underwent ventriculoperitoneal shunt have had a typical answers pattern in Mental Deterioration Battery test. We performed 9 ventriculoperitoneal shunt and 1 ventricu-lo-atrial shunt. Conclusions: Qualitative neurocognitive tests come out to be more sensitive compared to quantitative neurocognitive tests in identifying patients with suspected idiopathic normal pressure hydrocephalus benefiting from extended lumbar drainage test and then un-derwent surgical treatment. This could be considered a valid screening in elderly patients with suspected idiopathic normal pressure hydrocephalus in order to minimize the number of invasive procedures. More studies are necessary to validate this tool.

Objective: Radiomics and deep transfer learning are two popular technologies used to develop computer-aided detection and diadnosis (CAD) schemes of medical images. This study aims to investigate and compare advantages and potential limitations of applying these two technologies in developing CAD schemes. Methods: A relatively large and diverse retrospective dataset including 3,000 digital mammograms is assembled in which 1,496 images depict malignant lesions and 1,054 images depict benign lesions. Two CAD schemes are developed to classify breast lesions. The first scheme is developed using four steps namely, applying an adaptive multi-layer topographic region growing algorithm to segment lesions, computing initial radiomics features, applying a principal component algorithm to generate an optimal feature vector, and building a support vector machine classifier. The second CAD scheme is built based a pre-trained residual net architecture (ResNet50) as a transfer learning model to classify breast lesions. Both CAD schemes are trained and tested using a 10-fold cross-validation method. Several score fusion methods are also investigated to classify breast lesions. CAD classification performance is evaluated by the area under ROC curve (AUC). Results: ResNet50 model-based CAD scheme yields AUC = 0.85±0.02, which is significantly higher than radiomics feature-based CAD scheme with AUC = 0.77±0.02 (p < 0.01). Additionally, fusion of classification scores generated by two CAD schemes does not further improve classification performance. Conclusion: This study indicates that using deep transfer learning is more efficient to develop CAD schemes and enables to yield higher lesion classification performance than CAD schemes developed using radiomics-based technology.

At present, there are no hardware or biochemical systems allow to assess the severity of post-COVID syndrome in vivo. The hardware of the proposed biotechnical system is based on routine transthoracic electrical impedance rheography, which makes it possible to register the frequency characteristics of the patient's bioimpedance response to controlled stress stimulation, thereby simultaneously fixing the characteristics of his productive heart, the state of the hemomicrocirculatory bed, the efficiency of the gas transport function of his blood, and also reliably assess personal reactivity and adaptive potential. Subsequent mathematical approximation of the obtained biometric data by an original neural network makes it possible to rank the results obtained and automatically generate a program of medical rehabilitation for a particular patient, depending on the severity of his post-COVID syndrome. The study results proved two reliable physiological signs confirming the presence of latent post-COVID complications: a decrease in the base impedance value for light exercise and an increase in the length of the systolic arc of the rheocardiogram.

A developed six-port reflectometry (SPR) system was integrated to measure the relative permittivity of tumor and normal breast tissue for medical diagnostic purpose. In order to obtain an accurate and precise measurement, the calibration process was done to the SPR using the well-known three-standard technique. Next, the studied dielectric probe was connected to the calibrated measurement-port of the SPR. The open end of the probe aperture was dibbed into the normal and tumor synthetic breast tissue samples to measure the synthetic breast tissues dielectric constant, ɛrʹ, and loss factor, ɛrʺ in the frequency range of 1.5 GHz to 3.3 GHz. Finally, the comparative studies were conducted between commercial VNA with Keysight 85070E dielectric probe and the studied SPR-probe system based on the measured magnitude of the reflection coefficient, phase shift, dielectric constant, and loss factor of the synthetic breast samples. The maximum absolute errors of the measured reflection coefficient magnitude, phase shift, dielectric constant, and loss factor were found to be 0.01, 1.07°, 1.12, and 0.75, respectively. It was ascertained that the predicted dielectric constant, ɛrʹ, is able to differentiate between normal, (ɛrʹ &lt; 50) and tumor, (ɛrʹ &gt; 50) breast tissues.

Nitric oxide (NO) is a key molecule in cardiovascular homeostasis and its abnormal delivery is highly associated with the occurrence and development of cardiovascular disease (CVD). The assessment and manipulation of NO delivery is crucial to the diagnosis and therapy of CVD, such as endothelial dysfunction, atherosclerotic progression, pulmonary hypertension, and cardiovascular manifestations of Coronavirus (COVID-19). However, due to the low concentration and fast reaction characteristics of NO in cardiovascular system, the clinical applications centered on the NO delivery are challenging. In this tutorial review, we first summarized the methods to estimate the in vivo NO delivery process based on the clinical images and mathematical modeling to assess the endothelial function and vulnerability of atherosclerotic plaque. Then, the emerging bioimaging technologies that have the potential to directly measure the arterial NO concentration were discussed, including the Raman spectroscopy and electrochemical sensor. Aside from the diagnostic methods, therapies aimed at controlling NO delivery to regulate CVD were reviewed, including the inhaled NO therapy to treat the pulmonary hypertension and COVID-19, stem cell therapy and NO-releasing platform to treat endothelial dysfunction and atherosclerosis.

Background Reliable and field-applicable diagnosis of schistosome infections in non-human animals is important for surveillance, control, and verification of interruption of human schistosomiasis transmission. This study aimed to summarize uses of available diagnostic techniques through a systematic review and meta-analysis. Methods and principal findings We systematically searched the literature and reports comparing two or more diagnostic tests in non-human animals for schistosome infection. Out of 4,909 articles and reports screened, 18 met our inclusion criteria, four of which were considered in the meta-analysis. A total of 14 techniques (parasitologic, immunologic, and molecular) and nine types of non-human animals were involved in the studies. Notably, four studies compared parasitologic tests (miracidium hatching test (MHT), Kato-Katz (KK), the Danish Bilharziasis Laboratory technique (DBL), and formalin-ethyl acetate sedimentation-digestion (FED-SD)) with quantitative polymerase chain reaction (qPCR), and sensitivity estimates (using qPCR as the reference) were extracted and included in the meta-analyses, showing significant heterogeneity across studies and animals hosts. The pooled estimate of sensitivity was 0.21 (95% confidence interval (CI): 0.03 – 0.48) with FED-SD showing highest sensitivity (0.89, 95% CI: 0.65 – 1.00). Conclusions and significance Our findings suggest that the parasitologic technique FEA-SD and the molecular technique, qPCR, are the most promising field-applicable techniques for schistosome diagnosis in non-human animal hosts. Future studies are needed for validation and standardization of the techniques for real-world field applications.

Esophageal adenocarcinoma (EAC) detection relies on endoscopy-biopsy diagnosis, with routine endoscopic surveillance recommended for Barrett’s esophagus (BE) patients. Here, we examine the utility of blood biomarkers in patient risk stratification by translating the EAC blood biomarker Jacalin lectin binding complement C9 (JAC-C9) into a novel microfluidic immunoassay, the EndoScreen Chip. Cohort evaluation (n=46) showed elevated serum total C9 and JAC-C9 in EAC. Logistic regression modeling demonstrated that addition of C9 and JAC-C9 to patient risk factors (age, body mass index and heartburn/reflux history) improved EAC prediction from AUROC of 0.838 to 0.931. Serum JAC-C9 strongly predicted EAC (vs BE OR= 4.6, 95% CI: 1.6-15.6, p = 0.014; vs Healthy OR=4.1, 95% CI:1.2-13.7, p = 0.024) while total C9 was moderately predictive for BE (vs EAC OR=1.4; 95% CI: 1.0-1.8, p = 0.032; vs Healthy OR=0.8; 95% CI: 0.6-1.0, p = 0.039). This translational study demonstrates the potential utility of blood biomarkers in improving triaging for diagnostic endoscopy.

(1) Background: Children with autism spectrum disorder (ASD) show certain characteristics in visual attention which generate difficulties in the integration of relevant social information to set the basis of communication. Gaze following and pupil dilation could be used to identify signs for the early detection of ASD. Eye-tracking methodology allows objective measurement of these anomalies in visual attention. The aim is to determine whether measurements of gaze following and pupillary dilation in a linguistic interaction task, captured using eye-tracking methodology, are objective for early diagnosis of ASD. (2) Methods: 20 children between 17 and 24 months of age, made up of 10 neurotypical children and 10 children with ASD were paired together according to chronological age. A human face on a monitor pronounced pseudowords associated with pseudo-objects. Gaze following and pupil dilation was registered during the task. (3) Results: Significant statistical differences were found in the time of gaze fixation on the human face and on the object, as well as in the number of gazes. Also, there were significant differences in the maximum peak of pupil dilation, this being found in the neurotypical group at the moment of processing of the pseudoword, and in the ASD group in the baseline prior to the task (4) Conclusions: The registration and the duration of gaze, and the measurement of pupil dilation with ‘eye-tracker’ are objective measures for early detection of ASD.

Background: A new coronavirus (SARS-CoV-2) that emerged from Wuhan, Hubei Province, China, has spread throughout the world and is declared a pandemic by the World Health Organization (WHO). A lot remains to be understood of SARS-CoV-2 and the disease (COVID-19). SARS-CoV-2 has until recently been identified as responsible for both asymptomatic and serious life-threatening infections. The unavailability of specific therapeutic agents is a major hurdle in the treatment and management of COVID-19 patients. The present review attempts to evaluate the immunobiochemical aspects of the pathogenesis, diagnosis, and management of SARS-CoV-2 infection. Main Body: This review is a comprehensive evaluation of the data collected through various sources, including Google Scholar, PubMed, and Scopus. The articles were searched and selected using key words such as “Coronavirus disease (COVID-19)”, “Diagnosis of COVID-19”, Pathogenesis of Covid-19”, “management of COVID-19”, “Immunology of COVID-19”, and “Complications of COVID-19”. The study noted that the novel Coronavirus infection could result in an exaggerated immune response, causing a cytokine storm and damaging several organs of the body. The infected patients develop several complications, including immunological, hematological, and biochemical alterations. Consequently, COVID-19 patients may develop cardiovascular, liver, renal, and neurological complications, among others. Conclusion: An increased understanding of the immunobiochemical aspects of the disease may contribute to better management of SARS-CoV-2-infected persons, as evidenced from the available literature. A holistic approach to the management of COVID-19 patients taking into consideration the effect of COVID-19 infection on various organs of the body assumes increased significance in patient management.

MicroRNAs are used as biomarkers for classification of cancer subtypes since certain miRNAs are differentially expressed in normal and patient samples. Moreover, miRNAs target mRNAs and can heavily influence Gene Expressions. Thus, deregulation of miRNAs is linked to various disorders. Thus, miRNAs can be used for prognosis and developing personalized health solutions for patients. Given the importance of miRNAs, there has been substantial work done in the field. In this paper, recent works in the field of using miRNAs expressions of patients were considered. A total of 20 papers were surveyed which utilized feature selection ensembles, fuzzy logic as well as deep learning. 10 papers have been reported which offer insight into how miRNAs can be utilized for subtype-specific or generalized cancer diagnosis.

Diesel engines, as power equipment, are widely used in the fields of automobile industry, ship and power equipment. Due to wear or faulty adjustment, the valve train clearance abnormal fault is a typical failure of diesel engines, which may result in the performance degradation, even valve fracture and cylinder hit fault. However, the failure mechanism features mainly in time domain and angular domain, on which the current diagnosis methods based, are easily affected by working conditions or hard to extract accurate enough, as the diesel engine keeps running in transient and non-stationary process. This work arms at diagnosing this fault mainly based on frequency band features which would change when the valve clearance fault occurs. For the purpose of extracting a series of frequency band features adaptively，a decomposition technique based on improved variational mode decomposition is investigated in this work. As the connection between the features and the fault is fuzzy, the random forest algorithm is used to analyze the correspondence between features and faults. In addition, the feature dimension is reduced to improve the operation efficiency according to importance score. The experimental results under variable speed condition show that the method based on variational mode decomposition and random forest is capable to detect valve clearance fault effectively.

Introduction and importance: Congenital bicuspid aortic valve (BAV) is a common cardiac malformation predisposing individuals to aortic stenosis, regurgitation, and aortopathy. This risk persists even after aortic valve replacement (AVR). Case presentation: We report a case of a male in his 60s with a history of BAV who underwent bioprosthetic aortic valve replacement (BVR) and ascending aorta/root repair in 2014. The patient was noncompliant with follow-up and presented nine years later with severe bioprosthetic aortic stenosis and an 8.0 cm ascending aortic aneurysm with no symptoms. Emergent redo BVR and aneurysm repair were successful. Clinical discussion: It should be emphasized that successful outcomes for BAV patients require a lifelong commitment to surveillance, even after surgical intervention. Noncompliance can lead to life-threatening consequences like bioprosthetic valve deterioration or progressive aortic dilation. Conclusion: This case highlights the importance of early BAV diagnosis for ongoing monitoring, accessible follow-up care after complex cardiac procedures, and addressing patient barriers to treatment adherence.

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.

Globally increasing antibiotic resistance has been connected to the use of antibiotics in medical, veterinary, and agricultural medicine, contributing to the burden of antibiotic resistance in Asia and Europe. The main objective of this study was to correlations of antimicrobial-resistant of various pathogens in three compartments: humans, animals and the environment in India and Germany. A systematic search was carried out in Medline via PubMed, Google Scholar, and science direct, including studies published in 2022. Out of 532 papers, 24 were considered for meta-analysis. This study reveals that in India, β-lactam is highly resistant in animals. Quinolone, on the other hand, was highly resistant in humans. Furthermore, in the environment and integrated studies, aminoglycosides and β-lactams is resistant. While in Germany, a high rate of AMR resistance in all three sectors was reported in β-lactam. However, E. coli was the most frequent pathogen in both countries and is highly resistant to β-lactam, followed by cephalosporin in all the compartments. Monitoring and evaluating antibiotic-sensitivity patterns and developing proper antibiotic regimens may lead to improved outcomes for inhibiting and controlling E. coli infections in various parts of the world.

Until recently, no disease-specific health-related quality of life (HRQoL) instrument existed for pediatric traumatic brain injury (TBI). In this revalidation study, the psychometric properties and the validity of the final German version of the 35-item QOLIBRI-KID/ADO questionnaire were examined in 300 children and adolescents. It is the first self-reported TBI-specific instrument for measuring pediatric HRQoL in individuals aged 8–17 years. The six-factor model fits the data adequately. Internal consistencies were excellent for the total score and satisfactory to excellent for the scale scores. Intraclass correlations indicated good test-retest reliability. Construct validity was supported by overlaps between the QOLBRI-KID/ADO and the PedsQL, which measures generic HRQoL. Discriminant validity indicated that HRQoL was significantly lower in older children and girls, and in those with anxiety, depression, and post-concussion symptoms than in comparison groups, replicating the results of the questionnaire’s first development study. Our results suggest that the QOLIBRI-KID/ADO is a valid and reliable multidimensional instrument for assessing disease-specific HRQoL after pediatric TBI in clinical and research settings, which can additionally be used across the lifespan in combination with the adult version. This may help to improve care, treatment, daily functioning and HRQoL after TBI.

Viral hepatitis caused by hepatitis B virus (HBV) and hepatitis C virus (HCV) pose a significant global health challenge, with an increasing number of deaths and a substantial burden on healthcare systems, among prisoners in particular. Nigeria ranks fifth in Africa for prison population, with 98.2% being males and are more likely than females to have higher rates of viral hepatitis and other risky behaviours. This literature review explores the impact of social determinants of health (SDoH) on the prevalence and outcomes of HBV and HCV infections among male prison inmates in Nigeria, by examining factors such as overcrowding, inadequate healthcare access, and food insecurity. This review reports the updated data on HBV and HCV infection rates among inmates in different regions in Nigeria, with a special focus on related risk factors, highlighting how these determinants contribute to the high rates of hepatitis infections in this category. The review underscores the urgent need for a multifaceted approach involving policy changes, improved healthcare access, and enhanced preventive measures to address these health disparities. The findings aim to inform public health strategies and interventions to reduce the transmission and impact of viral hepatitis in prison settings, aligning with global health goals and promoting health equity among this population group.

Critically the paper argues that a truly people-centered technology supported chronic care system can only be designed by understanding and responding to the needs, attributes and capabilities of the most vulnerable in society. The paper suggests innovative ways of supporting interactions with these ‘end-users’ and highlights how reflection on these approaches can contribute to emancipating both the health system to move towards more socially inclusive e-health solutions.

The present study examined the volatile composition and antimicrobial and gastrointestinal activity of the essential oils of Elettaria cardamomum (L.) Maton harvested in India (EC-I) and Guatemala (EC-G). Monoterpene were present in higher concentration in EC-I (83.24%) than in EC-G (73.03%), whereas sesquiterpenes were present in higher concentration in EC-G (18.35%) than in EC-I (9.27%). Minimum inhibitory concentrations (MICs) of 0.5 and 0.1 mg/mL were demonstrated against Pseudomonas aeruginosa in EC-I and EC-G, respectively, whereas MICs of 0.125 and 1 mg/mL were demonstrated against Escherichia coli in EC-I and EC-G, respectively. The treatment with control had the highest kill-time potential, whereas the treatment with oils had shorter kill-time. EC-I was found to be more potent in the castor oil-induced diarrhoea model than EC-G. At 100 and 200 mg/kg, EC-I exhibited 40% and 80% protection, respectively, and EC-G exhibited 20% and 60% protection, respectively, in mice, whereas loperamide (positive control) exhibited 100% protection. In the in vitro experiments, EC-I inhibited both carbachol (CCh, 1 µM) and high K+ (80 mM)-induced contractions at significantly lower concentrations than EC-G. Thus, EC-I significantly inhibited P. aeruginosa and E. coli and exhibited more potent antidiarrheal and antispasmodic effects than EC-G.

Usage of novel non-tobacco oral nicotine delivery products (ONDP) has been increasing among adolescents in the United States. It is presumed that they are less toxic than their tobacco containing counterparts, but that has not been examined in controlled studies. Most of the studies have focused on non-renal manifestations of tobacco consumption via different means. The renal manifestations of non-tobacco ONDPs are not very well known, especially in immunocompromised patients. Here, we describe a 19-year-old adolescent with kidney transplant who sustained acute tubular necrosis leading to advanced chronic disease apparently following the usage of non-tobacco ONDP. Further larger studies are needed to study the renal manifestations of these next generation products to raise awareness among public.

Cranioplasty (CP) is the main surgical procedure aimed at reproducing a structural or morphological defect of the skull. It has been shown that cranioplasty can be useful for patients with traumatic brain injury (TBI) to achieve functional cognitive and motor improvements. Here, we describe a patient with long-term severe TBI who recovered consciousness following delayed CP. We found that a delayed CP may result in a meaningful functional recovery with emergence from a minimally conscious state and recovery of functional communication, even more than a year after decompressive craniectomy. Delayed intervention is equally successful in promoting functional recovery in long-term TBI patients, as early CP has already shown.

Alcohol abuse can lead to alcoholic liver disease, becoming a major global burden. Hovenia dulcis fruit peduncle polysaccharides (HDPs) has the potential to alleviate alcoholic liver injury may play essential roles in treating for alcohol-exposed liver disease, however, the hepatoprotective effects and mechanisms remain unclear. In this study, the hepatoprotective effects of HDPs and its potential mechanisms were investigated in alcohol-exposed mice by liver metabolomics and gut microbiome. The results found that HDPs reduced medium-dose alcohol-caused dyslipidemia (significantly elevated T-CHO, TG, LDL-C), elevated liver glycogen levels and inhibited intestinal-hepatic inflammation (significantly decreased IL-4, IFN-γ and TNF-α), consequently reversing hepatic pathological changes. By applying gut microbiome analysis, HDPs showed significant decreases in Proteobacteria while significant increases in Firmicutes at the phylum level, and increased Lactobacillus abundance while decreased Enterobacteria abundance, maintaining the composition of gut microbiota. Further hepatic metabolomics analysis revealed that HDPs had a regulatory effect on hepatic fatty acid metabolism, by increasing the major metabolic pathways including arachidonic acid metabolism and glycerophospholipid metabolism and identified two important metabolites C00157 and C04230 involved in the above metabolism. Overall, HDPs reduced intestinal dysbiosis and hepatic fatty acid metabolism disorders in alcohol-exposed mice, suggesting that HDPs has a beneficial effect on alleviating alcohol-induced hepatic metabolic disorders.

Research conducted on individuals with depression reveals that major depressive disorders (MDDs) coincide with diminished levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the brain, as well as modifications in the subunit composition of the primary receptors (GABAA receptors) responsible for mediating GABAergic inhibition. Furthermore, there is substantial evidence supporting the significant role of GABA in regulating stress within the brain, which is a pivotal vulnerability factor in mood disorders. Although there is substantial evidence indicating that GABA may be affecting GABA receptors in peripheral tissues, there is comparatively less evidence supporting its direct action within the brain. Emerging evidence highlights that GABA may exert beneficial effects on the brain and psyche through the gut-brain axis. GABA is readily available and approved as a food supplement in many countries. While GABA enjoys wide consumer acceptance in Eastern Asian markets, with many consumers reporting favorable effects on stress regulation, mood, and sleep, rigorous independent research is still largely lacking. Basic research, coupled with initial clinical findings, makes GABA an intriguing neuro-nutritional compound deserving of clinical studies in individuals with depression and other psychological problems.

Identifying a vestibular source of pathology in patients complaining of post-traumatic brain injury (TBI) dizziness can be difficult. We describe a possible new method utilizing the reduction of post-TBI symptom (including dizziness) with the use of a noise cancellation device (NCD). This retrospective case series included patients with TBI and dizziness presenting to a binocular vision specialty clinic, who were diagnosed with a vertical heterophoria (VH). If they did not respond adequately to microprism lenses and/or if they experienced hyperacusis, they were evaluated with an NCD. If there was marked reduction of TBI symptoms (including dizziness), the patients were referred to a neuro-otologist for vestibular diagnostic evaluation and treatment. Fourteen patients were identified and found to have abnormalities on vestibular testing consistent with Third Mobile Window Disorder (TMWD). All were treated with a 6-week medical protocol (diuretics, no straining, low sodium/no caffeine diet). Five responded positively, requiring no further treatment. Nine required surgical intervention and responded positively. In conclusion, 14 patients with post-concussive dizziness and VH, a positive response to NCD was associated with abnormal vestibular testing, a diagnosis of TMWD, and symptom reduction/resolution with a medical or surgical approach. The removal of sound resulting in reduction or resolution of vestibular symptoms represents an Inverse Tullio Phenomena.

AbstractIn the evolving modern era of neuromodulation for movement disorders in adults and children, much progress has been made recently characterizing the human motor network (MN) with potentially important treatment implications. Herein is a focused review of relevant resting state fMRI functional and effective connectivity of the human motor network across the lifespan in health and disease. The goal is to examine how the transition from static functional to dynamic effective connectivity may be especially informative of network-targeted movement disorder therapies, with hopeful implications for children.Impact StatementWhile functional connectivity has elucidated much MN properties with relation to age, disease, and behavior, effective connectivity has been shown to be useful in MN-informed therapies in adults. Thus, effective connectivity may have potential to impact childhood movement disorder therapies, given the lower to no patient demand.

Background: There is a strong comorbidity between mood disorders and metabolic syndrome (MetS). Increased levels of reactive oxygen and nitrogen species (RONS) and nitro-oxidative stress toxicity (NOSTOX) partially underpin this comorbidity.Aims: To examine the associations of RONS/NOSTOX biomarkers with MetS after adjusting for the significant effects of mood disorders (major depression, and bipolar type 1 and 2), generalized anxiety disorder (GAD), tobacco use disorder (TUD), and male sex.Methods: The study included subjects with (n=65) and without (n=107) MetS and measured levels of superoxide dismutase 1 (SOD1), lipid hydroperoxides (LOOH), nitric oxide metabolites (NOx), malondialdehyde (MDA), and advanced oxidation protein products (AOPP) and computed z unit-weighted composite scores which reflect RONS/NOSTOX. The study included 105 patients with mood disorders, 46 with GAD, and 95 with TUD.Results: MetS was associated with increased levels of MDA and AOPP, independently from mood disorders, TUD, sex and GAD. Atherogenicity and insulin resistance (IR) were significantly associated with a NOSTOX composite score. Mood disorders, TUD, GAD, male sex and MetS independently contribute to increased RONS/NOSTOX. The RONS/NOSTOX profile of MetS was different from that of GAD, which showed increased SOD1 and NOx levels. TUD was accompanied by increased SOD1, LOOH and MDA, and male sex by increased LOOH and AOPP.Conclusions: MetS is characterized by increased lipid peroxidation with aldehyde formation and chlorinative stress, and atherogenicity and IR are strongly mediated by RONS/NOSTOX. Partially shared RONS/NOSTOX pathways underpin the comorbidity of MetS with mood disorders, GAD, and TUD.

Taking due account of users' perspectives is crucial for improving the quality of healthcare services. This study aimed to analyse the representations and evaluation criteria that users of a public health agency express towards care and treatment services and to explore whether and how the content and meaning of their communications varied according to pre-pandemic, pandemic or post-pandemic periods. 501 communications (73.4% complaints, 16% appreciations, 10.6% enquiries) sent to the public relations office of an Italian health agency were collected. An automatic content analysis procedure (ACASM) was applied to the textual corpus. Four main thematic cores were identified concerning the request for care and respect, the value of the doctor-patient relationship and the difficulties in contacting services and accessing care. Two main latent dimensions of meaning were identified, which capture the dialectic between the demand for relationships and the demand for access to care, and between attention to the relational competence of health workers and attention to the needs and rights of users. Communications collected during the pre-pandemic and post-pandemic periods mainly concern the difficulty of access to care; those collected during the pandemic period mainly concern the doctor-patient relationship. Interpersonal aspects and timely access to care appear to be crucial in users' assessment of the quality of care.

The keratinocyte carcinomas, basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), are the most common cancers in humans. Recently, an increasing body of literature has investigated the role of miRNAs in keratinocyte carcinoma pathogenesis, progression and their use as therapeutic agents and targets, or biomarkers. However, there is very little consistency in the literature regarding the identity of and/or role of individual miRNAs in cSCC (and to a lesser extent BCC) biology. miRNA analyses that combine clinical evidence with experimental elucidation of targets and functional impact provide far more compelling evidence than studies purely based on clinical findings or bioinformatic analyses. In this study, we review the clinical evidence associated with miRNA dysregulation in KCs assessing the quality of validation evidence provided, identify gaps, and provide recommendations for future studies based on relevant studies that investigated miRNA levels in human cSCC and BCC. Furthermore, we demonstrate how miRNAs contribute to the regulation of a diverse network of cellular functions, and that large-scale changes in tumor cell biology can be attributed to miRNA dysregulation. We highlight the need for further studies investigating the role of miRNAs as communicators between different cell types in the tumor microenvironment. Finally, we explore the clinical benefits of miRNAs as biomarkers of keratinocyte carcinoma prognosis and treatment.

Postprandial glucose levels between 4 and 7.9 hours (PPG4–7.9h) correlate with mortality from various diseases including hypertension, diabetes, cardiovascular disease, and cancer. This study aimed to assess if predicted PPG4–7.9h could diagnose diabetes. Two groups of participants were involved: Group 1 (4420 participants) had actual PPG4–7.9h, while Group 2 (8422 participants) lacked this measure but had all the diabetes diagnostic measures. Group 1 underwent multiple linear regression to predict PPG4–7.9h using 30 predictors, achieving accuracy within 11.1 mg/dL in 80% of the participants. Group 2 had PPG4–7.9h predicted using this model. Receiver operating characteristic curve analysis showed that predicted PPG4–7.9h could diagnose diabetes with an accuracy of 87.3% in Group 2, with a sensitivity of 75.1% and specificity of 84.1% at the optimal cutoff of 102.5 mg/dL. Simulation on 10,000 random samples from Group 2 revealed that 175 participants may be needed to investigate PPG4–7.9h as a diabetes diagnostic marker with a power of at least 80%. In conclusion, predicted PPG4–7.9h appears to be a promising diagnostic indicator for diabetes. Future studies seeking to ascertain its definitive diagnostic value might require a minimum sample size of 175 participants.

A previous report showed that the urine output of HPLBII-P in patients with diabetes mellitus and SARS-Cov-2 infection was increased as a sign of glomerular dysfunction. . The aim of this report was to investigate the relation of urine output of HPLBII-P to diabetes mellitus in two large community-based elderly populations i.e. the ULSAM and PIVUS cohorts. Methods HPLBII-P was measured by ELISA in the urine of a community-based cohort of 839 men (ULSAM) collected at 77 years of age and in urine of a community-based cohort of 75-year-old men, n=387, and women, n=401 (PIVUS). KIM-1, NGAL and Albumin were measured in urine and Cathepsin S and Cystatin C in serum. Results HPLBII-P was significantly raised among males with diabetes in the ULSAM (p

5-(4-aminophenyl )-2-amino -1,3,4-thiadiazole was prepared by reaction of Thiosemicarbazide with 4-amino benzoic acid under reflux condition for 7 hours. The compound which has been synthesized successfully was subjected to addition reaction with 4-(Dimethylamino) benzaldehyde under reflux condition for 6 hours to synthesize Schiff bases. These compounds was characterized by using FTIR) and evaluated for their anticancer activity. The effect of (1, 3, 4-thiadiazole derivative) on the activity of malignant cells was studied by using different types of cell lines [Breast cancer, and human prostate cancer]. And was used the Electron microscope to show that the effect of the derivative on the cancer cells before and after 3 days of the injection time. It was found that the Schiff base of thiadiazole-1,3,4-(Dimethylamino)benzylidineamino]- [4-2-phenyl]amino was effective in reducing the size and density of malignant cells. That of 46.7 while in breast ) 145(DUprostate for growth inhibition produce of equal 85.9 µg/ml.

Currently, the primary strategy for addressing polycystic ovarian syndrome (PCOS) involves lifestyle modifications, with a focus on weight loss. The purpose of this meta-analysis was to assess the impact of weight loss through dietary interventions on inflammatory status and hyperandrogenism in PCOS women. A comprehensive search was conducted to identify randomised controlled trials (RCTs) and cohort studies assessing the impact of diet-induced weight loss on circulating inflammatory markers (CRP, IL-6, IL-1β, TNF-α), androgens (testosterone, SHBG, androstenedione) and luteinising hormone (LH) in PCOS women. The quality and risk of bias of the included studies were assessed using the Cochrane Collaboration's tool for RCTs and the Newcastle–Ottawa Scale for cohort studies. Data were entered into RevMan software v5.9 for the calculation of standard mean difference (SMD) and 95% confidence interval (95%CI) of circulating inflammatory markers, androgens and LH between baseline and post-weight loss values. Eleven studies (n=323) were eligible for the systematic review, of which nine (n=286) were included in the meta-analysis. Pooled analysis of data revealed a statistically significant decrease in circulating CRP (SMD 0.39, 95%CI 0.22, 0.56; 9 studies, n=286), IL-6 (SMD 0.37, 95%Cl, 0.12, 0.61; 3 Studies, n=140), TNF- α (SMD 0.30, 95%Cl, 0.07, 0.53; 4 Studies, n=162), androstenedione (SMD 0.36, 95%Cl, 0.13, 0.60; 4 studies, n=147) and LH (SMD 0.30, 95% Cl, 0.09, 0.51; 5 studies, n=197) after weight loss compared to baseline levels among PCOS women. Meta-analysis of five studies (n=173) showed a statistically significant increase in circulating SHBG after weight loss compared to baseline levels (SMD -0.43, 95%Cl, -0.65, -0.21). These findings suggest that weight loss induced by dietary interventions seems to improve PCOS-related chronic inflammation and hyperandrogenism. The possible causative relationship between the improvement in inflammation and hyperandrogenism remains to be determined.

Overconsumption of an unbalanced diet and overweight, leading to insulin resistance, dyslipidemia, hepatic steatosis, cardiovascular diseases and obesity, is nowadays a worldwide health issue, with different patterns of metabolic disturbances in the young and adult popula-tions, in both gender. Preclinical models that closely mimic the gradual weight gain that occurs in humans upon consumption of a “western-type” diet (WD) are of great interest. In particular, the diet-induced obesity (DIO) model in the C57BL/6J mouse sub-strain is often used in biomed-ical research, considering that it is prone to metabolic disorders and obesity, and is widely used to generate genetically modified mice. This study aimed to phenotypically characterize the C57BL/6J mouse strain fed a WD-like diet, using high-frequency ultrasound imaging (HFUS) as a complementary tool to longitudinally monitor morphofunctional changes in the liver, heart and kidney associated with DIO. Long term WD feeding increased mice body weight (BW), liver/BW ratio and body condition score (BCS), serum transaminases, glucose and insulin, as well as Homeostasis model assessment (HOMA) indexes, and caused dyslipidemia and insulin resistance. According to the 3Rs, ultrasound imaging has enabled a comprehensive study of metabolic syndrome in mice, in vivo and non-invasive, improving the identification of early stages of diseases.

The operation of transformers suffers from natural or man-made disasters, subjecting the equipment to prolonged exposure to temperature, lightning strikes, transient over-voltages, and over-current, gradually producing insulation aging phenomenon, which results in partial discharges within the transformer. Without dealing with it beforehand properly, it may lead to insulation breakdown. Nowadays, with the mature development of microchip control technology and wireless communication technology, which is helpful for realizing the research for online real-time and long-term monitoring capabilities for power equipment. A transformer operating condition monitoring and diagnostic system that can rapidly and effectively prevent the breakdown of transformer insulation, which can impact the overall power supply system is developed in this paper. The system is divided into two parts based on its function. The first part is the operating condition monitoring and real-time alert unit for the transformer, primarily composed of an embedded computing module, a sensor module, and a transmission module. Its work content is to capture real-time online partial discharge ultrasonic signals and high frequency current comparator pulse signals, and analyze and determine the condition of the internal insulation and operational status whether it is fault or not. The second part is the central control unit, consisting mainly of an industrial computer and a transmission module. Its work content is to store the ultrasonic and high frequency current comparator pulse signals from the transformer operation monitoring and real-time alert unit. It uses the software to eliminate signal noise and interference, and then utilizes artificial neural networks to identify the type of fault. In this paper, the research for the phenomenon of insulation degradation in transformer equipment aims to establish aging trend profiles through the dual malfunctioning alert and aging process analysis, as well as the long-term measurement of ultrasonic signals from partial discharges and high-frequency current comparator pulse signals. This approach provides crucial reference data and a foundation for disposable on-site measurement, assessing the phenomenon of insulation aging stages, defects and damage of the transformers effectively. It allows for timely replacement or maintenance in advance, achieving the prevention of malfunctioning and predictive diagnosis of aging.

Cardiovascular and cerebrovascular disease incidence has risen mainly due to poor control of preventable risk factors and still constitutes a significant financial and health burden worldwide. ChatGPT is an artificial intelligence language-based model developed by OpenAI. Due to the model’s unique cognitive capabilities beyond data processing and the production of high-quality text, there has been a surge of research interest concerning its role in the scientific community and contemporary clinical practice. To fully exploit ChatGPT's potential benefits and reduce its possi-ble misuse, extreme caution must be taken to ensure its implications ethically and equitably. In this article, we explore the language model's possible applications and limitations while empha-sizing its potential value for diagnosing, managing, and prognosis cardiovascular and cerebro-vascular disease.

Background: Smad4, a critical tumor suppressor gene, plays a significant role in pancreatic biology and tumorigenesis. Genetic background and sex are known to influence phenotypic outcomes, but their impact on pancreatic weight in Smad4-deficient mice remains unclear. This study investigates the impact of Smad4 deficiency on pancreatic weight in F1 mice from diverse Collaborative Cross (CC) lines, focusing on the influence of genetic background and sex. Methods: F1 mice were generated by crossbreeding female CC mice with C57BL/6J-Smad4tm1Mak males. Genotyping confirmed the presence of Smad4 knockout alleles. Mice were housed under standard conditions, euthanized at 80 weeks, and their pancreatic weights were measured, adjusted for body weight, and analyzed for effects of Smad4 deficiency, sex, and genetic background. Results: The overall population of F1 mice showed a slight but non-significant increase in adjusted pancreatic weights in heterozygous knockout mice compared to wild-type mice. Sex-specific analysis revealed no significant difference in males but a significant increase in adjusted pancreatic weights in heterozygous knockout females. Genetic background analysis showed that lines CC018 and CC025 substantially increased adjusted pancreatic weights in heterozygous knockout mice. In contrast, other lines showed no significant difference or varied non-significant changes. The interplay between genetic background and sex further influenced these outcomes. Conclusion: Smad4 deficiency affects pancreatic weight in a manner significantly modulated by genetic background and sex. This study highlights the necessity of considering these factors in genetic research and therapeutic development, demonstrating the value of the Collaborative cross-mouse population in dissecting complex genetic interactions.

Zinc (Zn) is the second most abundant metal in the human body, and is essential for the function of 10% of all proteins. As metals cannot be synthesized or degraded, they must be assimilated from diet by specialized transport proteins, which unfortunately also provide an entry route for the toxic metal pollutant cadmium (Cd). The intestinal absorption of Zn depends on the composition of food that is consumed, firstly the amount of Zn itself, and then the quantity of other food constituents such as phytate, protein and calcium (Ca). In cells, Zn is involved in regulation of intermediary metabolism, gene expression, cell growth, differentiation, apoptosis, and antioxidant defense mechanisms. Cellular influx, efflux, subcellular compartmentalization, and trafficking of Zn are coordinated by transporter proteins, the Solute-Linked Carrier 30A and 39A (SLC30A and SLC39A), known as the ZnT and the Zrt-/Irt-like protein (ZIP). Because of its chemical similarity with Zn and Ca, Cd disrupts the physiological functions of both. The concurrent induction of a Zn efflux transporter ZnT1 (SLC30A1) and metallothionein by Cd disrupts the homeostasis and reduces the bioavailability of Zn. The present review highlights the increased mortality and the severity of various diseases, including those induced by COVID-19 infections, among Cd-exposed persons and the roles of Zn and other transport proteins in the manifestation of Cd cytotoxicity. Special emphasis is given to the potential protective effects of Zn against bone, lung and heart diseases associated with Cd exposure. The difficult challenge of determining a permissible intake level of Cd is discussed in relation to the recommended dietary Zn intake levels.

Walking School Buses (WSBs) provide a safe alternative to being driven to school. Children benefit from the contribution the exercise provides towards their daily exercise target, it gives children practical experience with respect to road safety and helps to relieve traffic congestion around the entrance to their school. Walking routes are designed largely based in road safety considerations, catchment need and the availability of parent support. However, little attention is given to the air pollution exposure experienced by children during their journey to school, despite the commuting microenvironment being an important contributor to a child’s daily air pollution exposure. This study aims to quantify the air pollution exposure experienced by children walking to school and those being driven by car. A school was chosen in Bradford, UK. Three adult participants carried out the journey to and from school each carrying a P-Trak ultrafine particle (UFP) count monitor. One participant travelled the journey to school by car while the other two walked, each on opposite sides of the road for the majority of the journey. Data collection was carried out over a period of two weeks, for a total of five journeys to school in the morning and five on the way home at the end of the school day. Results of the study suggest that car commuters experience lower levels of air pollution dose due to lower exposures and reduced commute times. The largest reductions in exposure for pedestrians can be achieved by avoiding close proximity to traffic queuing up to intersections, and, where possible, walking on the side of the road opposite the traffic, especially during the morning commuting period. Major intersections should also be avoided as they were associated with peak exposures. Steps to ensure that the phasing of lights is optimized to minimize pedestrian waiting time would also help reduce exposures. If possible, busy roads should be avoided altogether. By the careful design of WSB routes, taking into account air pollution, children will be able to experience the benefits that walking to school brings while minimizing their air pollution exposure during their commute to and from school.

The study addresses the challenge of efficiently peeling pineapples, which have a distinct elliptical form, thick skin, and small eyes that are difficult to detect with conventional automated methods. This results in significant flesh waste. To improve the process, the researchers developed an integrated system combining an enhanced BlendMask method, termed SAAF-BlendMask, and a PCP method. SAAF-BlendMask improves the detection of small pineapple eyes, while PCP ensures accurate posture adjustment for precise path planning. The system uses 3D vision and deep learning technologies, achieving an average precision (AP) of 73.04% and a small object precision (APs) of 62.54% in eye detection, with a path planning success rate reaching 99%. The fully automated electromechanical system was tested on 110 real pineapples, demonstrating a reduction in flesh waste by 11.7% compared to traditional methods. This study highlights the potential of advanced machine vision and robotics in enhancing the efficiency and precision of food processing.

This study provides a methodology for optimizing oil production and CO2 sequestration using an integrated asset model of the Farnsworth Unit field, incorporating extensive geological, geophysical, and engineering data. Sensitivity analysis identified critical parameters impacting oil recovery and CO2 storage, leading to the construction of a proxy model using polynomial regression and radial basis function neural networks, with the latter proving more effective for "What-if" analysis. The sensitivity analysis indicated that the Corey parameters impact cumulative oil produced the most. Comprehensive history matching validated the model against historical production data, ensuring reliability for forecasting and optimization. Two scenarios, "Do-Nothing" and development strategy, were forecasted over 15 years (2020-2035). The "Do-Nothing" scenario resulted in 9.57 MMSTB of oil recovery and 2,822.70 MMlbs of CO2 storage. The development strategy case improved outcomes with 13.95 MMSTB of oil recovery and 5,061.68 MMlbs of CO2 stored, and was selected for optimization using particle swarm optimization. The optimized strategy achieved 14,043,372 STB of cumulative oil and 4,832.18 MMlbs of CO2 stored, and increased the field NPV by 25.84% to $114,871,730. This study underscores the significance of integrated asset modeling in enhancing oil recovery and optimizing CO2-EOR processes, providing valuable insights into operational conditions and constraints.

This research paper investigates ultra-wideband (UWB) localization systems by focusing on the use of average filter (AVG), Kalman filter (KF), and extended Kalman filter (EKF) algorithms, as well as a novel integrated filtering method that incorporates low-pass filter (LPF) into AVG, KF, and EKF. The study aims to improve localization loss in indoor environments using a TurtleBot robot equipped with a camera to observe ground truth positions. To evaluate the effectiveness of the proposed algorithms, a comprehensive comparison of the raw and filtered data with the camera-based ground truth observations is performed. Quantitative analyses of the results, including max, min, max-min, and mean error, are performed to evaluate the localization performance of the algorithms and the integrated filtering method. The results reveal that the integrated filtering method has performed better accuracy in comparison with existing methods.

The prevalence of chronic diseases is dramatically increasing demand for emergency healthcare. Existing systems rely on patients self-identifying symptoms, causing dangerous delays. This study develops an AI and IoT-powered “digital twin” solution to enable continuous real-time monitoring and timely prediction of diverse medical emergencies. A digital twin is a virtual representation of an individual, modeled using multidimensional physiological data from wearable sensors. Machine learning techniques analyze patterns in this data to identify anomalies and predict emergencies like heart attacks or falls. A key contribution is an optimized ensemble algorithm combining gradient boosted trees, neural networks, and other techniques to accurately detect emergency events. Evaluation on a dataset of 9158 samples shows the digital twin identifies key emergencies with over 90% recall, enabling prevention and rapid response. It allows risk stratification and personalized interventions based on early warnings, circumventing over 2 million avoidable emergency room visits annually. This study demonstrates the feasibility of an integrated, predictive, patient-centric emergency response system enabled by digital twin technology.

Microlens arrays (MLAs) which are increasingly popular micro-optical elements in compact integrated optical systems were fabricated by femtosecond direct laser write (fs-DLW) technique in the low-shrinkage SZ2080TM photoresist. High fidelity definition of 3D surfaces on IR transparent CaF2 substrates allowed to achieve ∼ 50% transmittance at chemical fingerprinting spectral region 2-5 μm wavelengths since MLAs were only ∼ 10 μm high corresponding to the numerical aperture of 0.3 (the lens height is comparable with the IR wavelength). To combine diffractive and refractive capabilities in miniaturised optical setup, a graphene oxide (GO) grating acting as a linear polariser was also fabricated by fs-DLW by ablation of a 1 μm-thick GO thin film. Such an ultra-thin GO polariser can be integrated with the fabricated MLA to add dispersion control at the focal plane. Pairs of MLAs and GO polarisers were characterised throughout visible-IR spectral window and numerical modeling was used to simulate their performance. Good match between experimental results of MLA focusing and simulations was achieved.

In the present study, piecewise integrated composite (PIC) bumper beam for passenger cars was proposed and design optimisation process for composite bumper beam against IIHS test was carried out with the help of machine learning. Several elements in IIHS bumper FE model have been assigned to be references, in order to collect training data which, allow the machine learning model to study the method of predicting loading types of each finite element. 2-D and 3-D implementations were provided by machine learning models, which determined stacking sequences of each finite element in PIC bumper beam. It was found that the PIC bumper beam, which was designed by machine learning model has direct impact on reducing the possibility of failure as well as increasing bending strength effectively than conventional composite bumper beam. Moreover, 3-D implementation produced better results compared with 2-D implementation since it was preferable to choose loading type information which was achieved from surroundings when the target elements were located either at corner or junction of planes instead of using information came from the same plane of target.

Single-layer core corrugated sandwich panels generally consist of a corrugated core and two layers of panels, while multi-layer core corrugated sandwich panels are formed by stacking multiple layers of panels with multiple layers of core layers. In this study, integrated multilayer core corrugated sandwich panels with different shapes of corrugated cores (triangular, trapezoidal, and rectangular) and the different number of core layers were fabricated using 3D printing technology, and the mechanical behavior of such multilayer core corrugated sandwich panels under quasi-static three-point bending was investigated using experiments and numerical simulations. The effects of core shape and number of core layers on the bending deformation process, damage mode, load carrying capacity, and bending energy dissipation capacity of multilayer core sandwich panels are discussed. Parametric design of multilayer triangular core corrugated sandwich panels was also carried out by finite element software ABAQUS. It was found that a new multilayer corrugated sandwich panel with a multi-layer core is better than the single core shape multilayer corrugated sandwich panel in terms of bending load capacity, energy dissipation capacity and deformation capacity can be obtained through the combination design of different core shapes.

Groundwater degradation is a global problem linked to irrigation agriculture and aggravated by climate change. In drylands, where aquifer recharge is low, irrigation has emerged as an engine of economic growth. This problem falls under the paradigm of desertification, as it fits the definition of this complex problem in that the degradation of drylands is due to climatic variations and inappropriate human activities. Land Degradation Neutrality (LDN), the response of the United Nations Convention to Combat Desertification to the lack of progress in tackling desertification, is integrated into Sustainable Development Goal 15.3 and provides the adequate framework for implementing effective solutions. LDN prioritizes prevention strategies, and early warning systems coupled to integrated simulation models is a sound approach. We analyze the dynamics of a coastal aquifer in southern Spain, a “desertification landscape” according to the Spanish National Action Plan to Combat Desertification. For this purpose, we have (i) adapted a generic desertification model that considers socio-ecological systems as a particular case of predator-prey systems; and (ii) coupled to this model a risk analysis to calculate the probabilities of groundwater salinization under the current scenario of water resources use, driven by the expansion of greenhouse agriculture supported by external water transfer. The risk of desertification is close to 100%: groundwater salinity is 40 dS m-1 (well above tomato tolerance, 3.5 dS m-1), and 2.4 Mm3 yr–1 water transfer is needed to support the 631 ha of greenhouses. This worrying result suggests that complimentary solutions should be promoted to deactivate the ongoing process of desertification. Among them, we propose reclaimed water, diversifying the economy, or promoting crops adapted to aridity. This simulation framework shows how to explore the future of a socio-ecosystem under current scenarios and others that consider climate change, the energy crisis, or the impact of alternative solutions.

We investigated layered titanium nitride (TiN) and aluminum nitride (AlN) for color glasses in Building Integrated Photovoltaic (BIPV) systems. AlN and TiN are among suitable and cost-effective optical materials to be used as thin multilayer films, owing to the significant difference in their refractive index. To fabricate the structure, we used radio frequency magnetron deposition method to achieve the target thickness uniformly. A simple, fast, and cheap fabrication method is achieved by depositing the multilayer films in a single sputtering chamber. It is demonstrated that a multilayer stack that allows light to move from a low refractive index layer to a high refractive index layer or vice-versa can effectively create various distinct color reflections for different film thicknesses and multilayer structures. It is investigated from simulation based on wave optics that, TiN/AlN multilayer offers better color design freedom and cheaper fabrication process as compared to AlN/TiN multilayer films. Blue, green, and yellow color glasses with optical transmittance of more than 80% was achieved by ITO coated glass/TiN/AlN multilayer films. This technology exhibits good potential in commercial BIPV system applications.

Statistical management policy and system plays significant role in development of any nation as it guides the planner to analyze the gaps, design programs and allocate budget in efficient manner. Globally, design and usage of statistical management system varies relying on country specific ability and resources availability. Government of Nepal has been managing database in individual as well as thematic manner. Policy wise, thematic database is in operation based on Statistics Act 1958 and individual database is in operation based on Birth, Death and Other Personal Related Events Registration Act 1976. Though civil registration related policies have been either updated or newly formed, sectoral statistic management related policy has not been updated since its first promulgation period (1958). With no policy supporting the consolidated statistical management system, government as well as non-government agencies has been investing millions of dollars annually to collect, compile and analyze individual related data and fulfill their respective objectives. It has forced the government services and performance to be paper-based, time-consuming and tedious thus creating dis-trust among citizen each passing day. Though, formulation of legal instrument promoted digital movement and mandated shift towards e-government modality, the process has been low. Theoretically, Technology Acceptance Model (TAM) state the need of having advanced and efficient technology to be in place in current setting to improve governance, efficiency, accountability, transparency and trust. Also, the same theory state the requirement of strong willingness and motivation from the users (government, non-government and citizen) to adopt the technology based policy and system. As the integrated statistical management policy emphasizes on technology-based system or digital system, the perspectives of Technology Acceptance Model also termed as Information System Theory aid in understanding the context, conceptualizing and addressing the needs with an establishment and implementation of digital system or technology based system. This policy paper applied the Technology Acceptance Model (TAP) to examine the underlying opportunities and challenges associated with an integrated statistical management policy. With existing gaps in existing policy, system and practice alongside an overview of opportunities and challenges, this paper recommends the need of stand-alone integrated statistical management policy to consolidate sectoral as well as civil related information through single system based on recommended policy.

We theoretically investigate integrated photonic resonators formed by two mutually coupled Sagnac loop reflectors (MC-SLRs). Mode interference in the MC-SLR resonators is tailored to achieve versatile filter shapes with high performance, which enable flexible spectral engineering for diverse applications. By adjusting the reflectivity of the Sagnac loop reflectors (SLRs) as well as the coupling strength between different SLRs, we achieve optical analogues of Fano resonance with ultrahigh spectral slope rates, wavelength interleaving / non-blocking switching functions with significantly enhanced filtering flatness, and compact bandpass filters with improved roll-off. In our designs the requirements for practical applications are considered, together with detailed analyses of the impact of structural parameters and fabrication tolerances. These results highlight the strong potential of MC-SLR resonators as advanced multi-functional integrated photonic filters for flexible spectral engineering in optical communications systems.

Increased smart devices in various industries is creating numerous sensors in each of the equipment prompting the need for methods and models for sensor data. Current research proposes a systematic approach to analyze the data generated from sensors attached to industrial equipment. The methodology involves data cleaning, preprocessing, basics statistics, outlier, and anomaly detection. Present study presents the prediction of RUL by using various Machine Learning models like Regression, Polynomial Regression, Random Forest, Decision Tree, XG Boost. Hyper Parameter Optimization is performed to find the optimal parameters for each variable. In each of the model for RUL prediction RMSE, MAE are compared. Outcome of the RUL prediction should be useful for decision maker to drive the business decision; hence Binary classification is performed, and business case analysis is performed. Business case analysis includes the cost of maintenance and cost of non-maintaining a particular asset. Current research is aimed at integrating the machine intelligence and business intelligence so that the industrial operations optimized both in resource and profit.

Ninety percent of the people added to the planet over the next 30 years will live in African and Asian cities, and a large portion of these populations will reside in deprived neighborhoods defined by slum conditions, informal settlement, or inadequate housing. The four current approaches to neighborhood deprivation mapping are largely silo-ed, and each fall short of producing accurate, timely, comparable maps that reflect local contexts. The first approach, classifying “slum households” in census and survey data and aggregating to administrative areas, reflects household-level rather than neighborhood-level deprivation. The second approach, field-based mapping, can produce the most accurate and context-relevant maps for a given neighborhood, however it requires substantial resources, preventing up-scaling. The third and fourth approaches, human interpretation and machine classification of satellite, aerial, or drone imagery, both overemphasize informal settlements, and fail to represent key social characteristics of deprived areas such as lack of tenure, exposure to pollution, and lack of basic public services. The latter, machine classification of imagery, can be automated and extended to incorporate new and multiple sources of data. This diverse collection of authors represent experts from these four approaches to neighborhood deprivation mapping. We summarize common areas of understanding, and present a set of requirements to produce maps of deprived urban areas that can be used by local-to-international stakeholders for advocacy, planning, and decision-making.

We have conducted a comprehensive year-long sampling campaign for particulate matter (PM) pollutants at a site near a major highway, following standard protocols. Total mass, and elemental and chemical composition of the fine fractions (PM2.5) of traffic-related pollutants are determined utilizing several complementary techniques. These complementary techniques included gravimetric analysis, X-ray fluorescence (XRF), scanning electron microscopy and energy dispersive spectroscopy, X-ray diffraction (XRD) and black carbon multi-wavelength absorption. The results show that the PM2.5 mass concentrations are within or slightly above international standards and include natural dust and anthropogenic pollutants such as black carbon, sulfates and other traffic-related elements. Anthropogenic sources include the secondary pollutants Mascagnite and Koktaite, traffic emissions such as exhaust emissions and tires, brakes and road erosions. It was found that the sulfates are the highest contributors to PM2.5 (~40%), as evident from XRD results and the S content in the XRF analysis.

Integrated ultra-low-loss waveguides are highly desired for integrated photonics to enable applications that require long delay lines, high-Q resonators, narrow filters, etc. Here we present an ultra-low-loss silicon waveguide on 500 nm thick SOI platform. Meter-scale delay lines, million-Q resonators and tens of picometer bandwidth grating filters are experimentally demonstrated. We design a low-loss low-reflection taper to seamlessly integrate the ultra-low-loss waveguide with standard heterogeneous Si/III-V integrated photonics platform to allow realization of high-performance photonic devices such as ultra-low-noise lasers and optical gyroscopes.

Logistics Engineering has transcended over the decades into an approach for competitive benefits in organisational performance and logistics efficiency. Most industries are recognising that significant savings are available to companies that are able to ordinate and improve within their logistics operations. Companies today face great challenges because the successful supply of many products and services needs to the effective integration of logistics activities across a prolongation supply chain and an increasing geographical separation. Moreover, logistics integration approach involves both internal integration for an ordinated, unified process as well as relationships to react flexibly, changeability, and responsibility to customer's demands. In this study, by using of Fuzzy Vikor (F-Vikor), the best combination of RIR was selected and RIR Locating was done. The main aim of this paper is survey and design of the integrated operational logistics network (IOLN) and also, a proposed IOLN to integration of the Iran Khodro Co Supply Network.

In this paper, a two-stage stochastic programming modelling is proposed to design a multi-period, multistage, and single-commodity integrated forward/reverse logistics network design problem under uncertainty. The problem involves both strategic and tactical decision levels. The first stage deals with strategic decisions, which are the number, capacity, and location of forward and reverse facilities. At the second stage tactical decisions such as base stock level as an inventory policy is determined. The generic introduced model consists of suppliers, manufactures, and distribution centers in forward logistic and collection centers, remanufactures, redistribution, and disposal centers in reverse logistic. The strength of proposed model is its applicability to various industries. The problem is formulated as a mixed-integer linear programming model and is solved by using Benders’ Decomposition (BD) approach. In order to accelerate the Benders’ decomposition, a number of valid inequalities are added to the master problem. The proposed accelerated BD is evaluated through small-, medium-, and large-sized test problems. Numerical results reveal that proposed solution algorithm increases convergence of lower bound and upper bound of BD and is able to reach an acceptable optimality gap in a convenient CPU time.

The oral health of older individuals can be negatively impacted by various systemic health factors, leading to rapid oral health deterioration. Older people are at risk of experiencing adverse reactions to medications due to multimorbidity, polypharmacy, and changes in pharmacokinetics and pharmacodynamics. Hyposalivation, a significant side effect of some medications, can be induced by both the type and number of medications used. Frailty, disability, sarcopenia, care dependency, and limited access to professional oral healthcare can also compromise the oral health of older people. To prevent rapid oral health deterioration, a comprehensive approach is required that involves effective communication between oral healthcare providers, other healthcare providers, and informal carers. Regardless of their health status, it is crucial to prioritize the well-being of older people. Oral healthcare providers have a responsibility to advocate for the importance of maintaining adequate oral health and to raise awareness of the serious consequences of weakened oral health. By doing so, we can prevent weakened oral health from becoming a geriatric syndrome.

Cardiovascular disease (CVD) is the primary cause of mortality globally with a multifactorial etiology that involves epigenetics. Chromobox 3 (CBX3), the major isoform of heterochromatin protein 1, is involved in intricate epigenetic mechanisms affecting congestive heart failure. In patients with CVD affected by lung cancer risk, CBX3 exerts a sophisticated mechanism of action, suppressing the proliferation, migration, and formation of neointima in vascular smooth muscle cells (VSMCs) by affecting the Notch3 pathway, indicating a potential protective function against vascular remodeling and atherosclerosis. However, the broader impact of CBX3 on endothelial function, as well as its effects on monocyte/macrophage and lymphocyte infiltration and function within the arterial wall, remain poorly understood. Since very little is known so far, more definite research would be needed to reveal the fine mechanisms of CBX3 action, along with its relationship in molecular processes and prospects as a biomarker. Specifically, CBX3 biological features could be examined to gain a greater insight into CVD risks. This review outlines the role of CBX3 in mechanisms associated with CVD and feasibility for optimizing pre-existing therapy and developing new therapeutic strategies based on personalized medi-cine.

Introduction: Signet-ring cells are typically associated with mucin-secreting epithelium thus most commonly found in a gastrointestinal tract, however not exclusively. Primary signet ring cell carcinoma of the prostate is a rare and poorly differentiated, aggressive acinar adenocarcinoma variant with a grim prognosis. Clinical case: In June of 2023 a 54-year-old Caucasian male came to the hospital complaining of lower urinary tract obstructive symptoms with occasional macrohematuria, non-specific body aches, and shortness of breath. A prostate specimen obtained in transurethral resection of the prostate was sent for histopathological examination. After a series of extraprostatic diagnostic workups including fibrogastroduodenoscopy, colonoscopy computed tomography imaging, and immunohistochemical studies, the patient was diagnosed with primary prostatic signet-ring cell adenocarcinoma st. IV. Unfortunately, the patient with the disease this advanced, PE, and third-degree thrombocytopenia was not a candidate for chemotherapy and died of cardiopulmonary insufficiency later that week. Discussion: Prostatic signet-ring cell carcinoma accounts for 0.02% of all prostate adenocarcinoma cases. Due to its nature and epidemiology, a diligent extraprostatic investigation has to be carried out. The disease often presents with unremarkable clinical symptoms and variable serum prostate-specific antigen results which may contribute to its late diagnosis which together with inconsistent immunohistochemical findings and unpredictable response to hormonal treatment pose both diagnostic and therapeutic challenges that negatively affect the prognosis. Conclusion: The study highlights the importance of a multidisciplinary approach and the need for diagnostic and therapeutic consensus within the research community in search of the primary site of the disease which may positively influence the prognosis.

Preventing the rebound of black and odorous water bodies is critical for improving the ecological environment of water bodies. This study investigated the effect and mechanism of in-situ improvement of sediment microenvironment by nitrate in tailwater of wastewater treatment plants combined with aerobic denitrifying bacteria under low-DO regulation (TailN+CFM+LDO). On the 60th day of remediation, the dissolved oxygen and oxidation-reduction potential in the overlying water increased to 5.6 mg/L and 300 mV, respectively, the acid volatile sulfide in the sediment decreased by 70.4%, and the organic matter in the sediment was reduced by 62.7%, in which the HFOM was degraded from 105 g/kg to 56 g/kg, and the potential risk of water reverting to black and odorous conditions significantly decreased. Amplicon sequencing analysis revealed that the relative abundance of electroactive bacteria Thiobacillus and Pseudomonas with denitrification capacity was found to be significantly higher in the TailN+CFM+LDO group than in the other remediation groups. Functional prediction of 16S sequencing results indicated that both the quantity and activity of critical microbial enzymes involved in nitrification and denitrification processes could enhance in the TailN+CFM+LDO group. These results improved our understanding of the improvement of the sediment microenvironment and could thus facilitate its application.

Dynamical manipulation of plasmon-induced transparency (PIT) in graphene metasurfaces is promising for optoelectronic devices such as optical switching and modulating, however, previous design approaches are limited within one or two bright/dark modes, and the realization of dual PIT windows through triple bright modes in graphene metasurfaces is rare and urgently needed. Here we demonstrate that dual PIT can be realized through a symmetry-engineered graphene metasurface, which consists the graphene central cross (GCC) and graphene rectangular ring (GRR) arrays. The GCC supports a bright mode from electric dipole (ED), the GRR supports two nondegenerate bright modes from ED and electric quadrupole (EQ) due to the C2v symmetry breaking, and the resonant coupling of these three bright modes induces the dual PIT windows. A triple coupled-oscillator model (TCM) is proposed to evaluate the transmission performances of the dual PIT phenomenon, and the results are in good agreement with the finite-difference time-domain (FDTD) method. In addition, the dual PIT windows are robust to the variation of the structural parameters of the graphene metasurface except the y-directioned length of the GRR. By changing the carrier mobility of graphene, the amplitudes of the two PIT windows can be effectively tuned. The alteration of the Fermi level of graphene enables the dynamic modulation of the dual PIT with good performances for both modulation degree (MD) and insertion loss (IL).

The dual leucine zipper kinase (DLK) alias mitogen-activated protein 3 kinase 12 (MAP3K12) has gained much attention in recent years. DLK belongs to the mixed lineage kinases, characterized by homology to serine/threonine and tyrosine kinase but exerts serine/threonine kinase activity. DLK has been implicated in many diseases including several neurodegenerative diseases, glaucoma, and diabetes mellitus. As a MAP3K, it is generally assumed that DLK becomes phosphorylated and activated by upstream signals and phosphorylates and activates itself, the downstream serine/threonine MAP2K, and ultimately MAPK. In addition, other mechanisms such as protein-protein interactions, proteasomal degradation, dephosphorylation by various phosphatases, palmitoylation, and subcellular localization have been shown to be involved in the regulation of DLK activity or its fine-tuning. In the present review, the diverse mechanisms regulating DLK activity will be summarized to provide a better insight into DLK action and possibly new targets to modulate DLK function.

Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, is a disease of chronic inflammatory conditions of the intestinal tract due to disturbance of the inflammation and immune system. Symptoms of IBD include abdominal pain, diarrhea, bleeding, reduced weight, and fatigue. In IBD, the immune system attacks the intestinal tract's inner wall, causing chronic inflammation and tissue damage. In particular, IL-6 and IL-17 act on immune cells, including T cells and macrophages, to amplify the immune responses so that tissue damage and morphological changes occur. Of note, excessive calorie intake and obesity also affect the immune system due to inflammation caused by lipotoxicity and changes in lipids supply. Similarly, individuals with IBD have alterations in liver function after sustained high-fat diet feeding. In addition, excess dietary fat intake, along with alterations in primary and secondary bile acids in the colon, can affect the onset and progression of IBD because inflammatory cytokines contribute to insulin resistance; the factors include the release of inflammatory cytokines, oxidative stress, and changes in intestinal microflora, which may also contribute to the disease progression. However, interfering with de novo fatty acid synthase by deleting the enzyme acetyl-CoA-carboxylase 1 in intestinal epithelial cells leads to the deficiency of epithelial crypt structures and tissue regeneration, which seems to be due to Lgr5+ intestinal stem cell function. Thus, conflicting reports exist regarding high-fat diet effects on IBD animal models. This review will focus on the pathological basis of the link between dietary lipids intake and IBD and cover currently available pharmacological approaches.

The COVID-19 pandemic has emphasized the crucial role of ventilation systems in mitigating cross-infections, especially in infectious disease hospitals. This study introduces a dual-design operation ventilation system that can operate under two sets of ventilation conditions for normal and epidemic times. A challenge is optimizing duct diameters for required airflow while maintaining hydraulic balance. We design a genetic algorithm with adaptive penalty factor, the velocity constraint and the improved crossover and mutation probability. The improved genetic algorithm is suitable for ventilation system networks, which can find a better air duct diameters combination to improve the hydraulic balance rate, and reduce the usage of air valves, resulting in efficient hydraulic balancing commissioning. Compared with the traditional genetic algorithm, it has a faster search speed and a better global search ability, which is effective for the optimal design of ventilation system networks.

In response to injury, vascular smooth muscle cells (VSMCs) of the arterial wall dedifferentiate into a proliferative and migratory phenotype, leading to intimal hyperplasia. The ERK1/2 pathway participates in cellular proliferation and migration while dual-specificity phosphatase 6 (DUSP6, also named MKP3) can dephosphorylate activated ERK1/2. We showed that DUSP6 was expressed in low baseline levels in normal arteries; however, arterial injury significantly increased DUSP6 levels in the vessel wall. Compared with wild-type mice, Dusp6-deficient mice had smaller neointima. In vitro, IL-1β induced DUSP6 expression and increased VSMC proliferation and migration. Lack of DUSP6 diminished IL-1β-induced VSMC proliferation and migration. DUSP6 deficiency did not affect IL-1β-stimulated ERK1/2 activation. Instead, ERK1/2 inhibitor U0126 prevented DUSP6 induction by IL-1beta, indicating that ERK1/2 functions upstream of DUSP6 to regulate DUSP6 expression in VSMCs rather than downstream as a DUSP6 substrate. IL-1β decreased levels of cell cycle inhibitor p27 and cell-cell adhesion molecule N-cadherin in VSMCs whereas lack of DUSP6 prevented their downregulation, revealing novel functions of DUSP6 in regulating these two molecules. Taken together, our results indicate that lack of DUSP6 attenuated neointima formation following arterial injury by reducing VSMC proliferation and migration, which were likely mediated via maintaining p27 and N-cadherin levels.

In this paper we demonstrate first ever dual-period diffraction gratings that do not require electrical tuning to obtain the effect of period change. Our method allows for multiplication of the base period by proper modification of the subsequent slits of the grating. The proposed elements are fabricated by selective photopolymerization of a composite based on nematic liquid crystal. The gratings are formed by polymer stabilization of liquid crystal in different orientations of the molecules in selected grating slits to allow for period manipulation. The operating principle is based on changing the phase delay introduced by the slits depending on polarization direction of incident light with respect to the director in each type of slit, which allows to change the grating’s period. The proposed technique was successfully utilized to obtain diffraction gratings with either doubling or tripling of the period.

Side-scan sonar (SSS) detection is a key method in applications such as underwater environmental security and subsea resource development. The use of acoustic images for seabed target detection has gradually become a mainstream underwater detection method. However, many existing detection approaches primarily concentrate on tracking the evolution path of optical image object detection tasks, resulting in complex structures and limited versatility. To tackle this issue, we introduce a pioneering Dual-Domain Multi-Frequency Network (D2MFNet) meticulously crafted to harness the distinct characteristics of SSS image detection. In D2MFNet, aiming at the underwater detection requirements of small scenes, we introduce a novel method for optimize and improve the detection sensitivity of different frequency ranges and propose a Multi-Frequency Combined Attention Mechanism (MFCAM). This mechanism amplifies the relevance of dual-domain features across different channels and space. Moreover, recognizing that SSS images can provide richer insights after frequency domain conversion, we introduce a Dual-Domain Feature Pyramid Network (D2FPN). By incorporating frequency domain information representation, D2FPN significantly augments the depth and breadth of feature information in underwater small datasets. Our methods are seamlessly designed for integration into existing networks, offering plug-and-play functionality with substantial performance enhancements. We have conducted extensive experiments to validate the efficacy of our proposed techniques, and the results showcase their state-of-the-art performance. MFCAM improves the mAP by 16.9% in the KLSG dataset and 15.5% in the SCTD dataset. The mAP of D2FPN was improved by 8.4% in the KLSG dataset and by 9.8% in the SCTD dataset. We will make our code and models publicly available at https://dagshub.com/estrellaww00/D2MFNet.

Duchenne muscular dystrophy (DMD) is a yet incurable rare genetic disease that affects the skeletal and cardiac muscles, leading to progressive muscle wasting and premature death. DMD is caused by the lack of dystrophin, a muscle protein essential for the biochemical support and integrity of muscle fibers. Gene replacement strategies for Duchenne muscular dystrophy (DMD) employing the adeno-associated virus (AAV) face the challenge imposed by the limited packaging capacity of AAV, only allowing the accommodation of a short version of dystrophin (µDys) that is still far removed from correcting human disease. The need to develop strategies leading to the expression of a best performing dystrophin variant led to only few studies reporting on the use of dual vectors, but none reported on a method to assess in vivo transgene reconstitution efficiency, the degree of which directly affects the use of safe AAV dosing. We report here on the generation of a dual AAV vector approach for the expression of a larger dystrophin version (quasidystrophin) based on homologous recombination, and the development of a methodology employing a strategic droplet digital PCR design, to determine the recombination efficiency as well as the occurrence of unwanted concatemerization events or aberrant expression from the single vectors. We demonstrated that, upon systemic delivery in the dystrophic DBA2mdx mice, our dual AAV approach led to high transgene reconstitution efficiency and negligible ITR-dependent concatemerization, with consequent remarkable protein restoration in muscles and improvement of muscle pathology. This evidence supports the suitability of our system for gene therapy application and the potential of this methodology to assess and improve the feasibility for therapeutic translation of multiple vector approaches

The study presents the synthesis and characterization of dual-layer sulfonated polyphenylenesulfone (SPPSu) nanocomposite hollow fiber nanofiltration membranes incorporating titanium dioxide (TiO2) nanoparticles using the phase inversion technique. The newly developed membranes were systematically characterized using advanced tools and methods to evaluate their properties and performance. The study focused on investigating the effects of TiO2 addition in the SPPSu inner layer on pure water permeability, and salt rejection. The nanocomposite hollow fiber nanofiltration membranes exhibited a significant enhancement in pure water permeability, with a three-fold increase compared to the pristine membranes, achieving a flux of 5.4 L/m2h.bar. The addition of TiO2 also led to an improvement in the mechanical properties of the membranes, as evidenced by the increase in the expected tensile strength from 2.4 to 3.9 MPa. To evaluate the salt rejection performance, rejection tests were conducted using a laboratory-scale filtration setup in recycle mode. Aqueous solutions containing different divalent ions, specifically magnesium sulfate (Mg2SO4) and sodium sulfate (Na2SO4) at a concentration of 500 ppm, were used as the feed solution. The modified dual-layer hollow fiber nanocomposite membranes exhibited a maximal rejection of 95% for Mg2SO4, demonstrating their effective separation capabilities for divalent ions. The findings of this study highlight the successful synthesis and characterization of dual-layer SPPSu nanocomposite hollow fiber nanofiltration membranes incorporating TiO2 nanoparticles. The incorporation of TiO2 resulted in improved pure water flux, mechanical strength, and salt rejection performance. These enhanced properties make the developed nanocomposite membranes promising candidates for applications in nanofiltration processes, particularly for the selective separation of divalent ions from aqueous solutions.

Optical tweezers, as a kind of ultra-sensitive acceleration sensing platform, show a minimum measurable value inversely proportional to the square of the diameter of the levitated spherical particle. However, the coupling of the displacement measurement between axes becomes notable, along with the increasing of the diameter. This paper analyzes the source of coupling in a forward scattering far-field detection regime and proposes a novel method of suppression. We theoretically and experimentally demonstrated that when three variable irises added into detection optics, without changing other parts of optical structures, the decoupling of triaxial displacement signals mixed with each other show significant improvement. The detection coupling ratio reduction of 49.1 dB and 22.9dB has been realized in radial and axial direction respectively, which is principally in accord with simulations. This low cost and robust approach makes it possible to accurately measure three-dimensional mechanical quantities simultaneously and even go further such as active cooling the particle to quantum ground state.

Dual-method use is the most reliable form of protection against unintended pregnancies and HIV/STIs. Although dual-method use remains uncommon among women in stable relationships, some women do practice it. In this study, we explored the barriers that make dual-method use rare and the behaviors of women who practice dual-method use using a positive deviance framework in Uganda. We screened 150 women using highly effective contraceptives at five health facilities. We identified nine women who practiced dual-method use and 141 women who did not. In a qualitative study, we conducted in-depth interviews with all nine women practicing dual-method use and 10 women randomly selected out of the 141 who did not. We performed a thematic analysis using the positive deviance framework. Regardless of practicing dual-method use or not, women faced perceived barriers against dual-method use, such as partner’s objection, distrust, shyness about introducing condoms into marital relationships, and limited access to condoms. However, women practicing dual-method use had higher levels of risk perception about unintended pregnancies and HIV/STIs. They also engaged in unique behaviors, such as influencing their partners’ condom use by initiating discussions, educating their partners on sexual risks and condom use, and obtaining condoms by themselves. These findings will be useful in developing effective community-led and peer-based interventions promoting dual-method use to reduce the dual burden of unintended pregnancies and HIV/STIs among women in Uganda.

Background: Dual function tail tubular proteins (TTP) belonging to the lytic bacteriophages are the interesting group of biologically active enzymes. Surprisingly, apart from their structural function, they are also polysaccharide hydrolyzes destroying bacterial extracellular components. One of the representatives of this group is TTPB from Klebsiella pneumoniae phage – KP32. TTPB hydrolyzes exopolysaccharide (EPS) of Klebsiella pneumoniae and Enterococcus faecalis strain. This depolymerizing feature was associated with the activity to prevent bacterial biofilm formation. TTPB can inhibit biofilm formation by K. pneumoniae, Enterobacter cloacae, Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa strains. Moreover, synergistic activity with antibiotic action has been observed, most likely due to depolymerases’ facilitation of contact of antibiotic with bacterial cells. Methods: TTPB was overexpressed in E coli system, purified and tested towards the bacterial strains using agar overlay method. The hydrolytic activity of TTPB was performed using EPSs of K. pneumoniae PCM2713 and E. cloacae ATCC 13047 as the substrates. Next, we determined the reducing sugar (RS) levels in the TTPB/EPS mixtures, regarding the RS amount obtained after acidic hydrolysis. The antibiofilm activity of TTPB has been set down on bacterial biofilm using a biochemical method. Finally, we have demonstrated the synergistic activity of TTPB with kanamycin. Results: For the first time, the hydrolytic activity of TTPB towards bacterial EPSs has been shown. TTPB releases about a half of the whole RS amount of EPSs belonging to K. pneumoniae PCM 2713 and E. cloacae ATCC 13047 strains. 1.12 µM of the phage protein reduces biofilm of both strains by over 60%. Destroying the bacterial biofilm the phage protein improves the antibiotic action increasing kanamycin effectiveness up to four times.

Semantic image segmentation has recently witnessed considerable progress by training deep convolutional neural networks (CNNs). The core issue of this technique is the limited capacity of CNNs to depict visual objects. Existing approaches tend to utilize approximate inference in a discrete domain or additional aides and do not have a global optimum guarantee. We propose the use of the multi-label manifold ranking (MR) method in solving the linear objective energy function in a continuous domain to delineate visual objects and solve these problems. We present a novel embedded single stream optimization method based on the manifold ranking (MR) model to avoid approximations without sacrificing expressive power. In addition, we propose a novel network, which we refer to as dual multi-scale manifold ranking (\textbf{DMSMR}) network, that combines the dilated, multi-scale strategies with the single stream MR optimization method in the deep learning architecture to further improve the performance. Experiments on high resolution images, including close-range and remote sensing datasets, demonstrate that the proposed approach can achieve competitive accuracy without additional aides in an end-to-end manner.

Aim: the main aim of this study is to compare the onset of effectiveness of mental nerve block with lingual infiltration and inferior alveolar nerve block on patients visiting dental hospital for extraction of mandibular anterior teeth. Materials and methods: The study was set in a clinical setting. This was a randomized controlled double-blind cross study, where 25 subjects received two treatments at an interval of at least 1 week in a within a dental hospital.Inferior alveolar nerve block and lingual nerve block injection is given with 2mL lignocaine 2% with 1:2,00,000 epinephrine was administered for the right side. Mental nerve block along with lingual infiltration of the corresponding tooth was given with 2mL lignocaine 2% with 1:2,00,000 epinephrine was administered on the left side.Visual analogue scale (VAS) was used in this study, which consists of a scale with range of 0-10 pain severity on which 0 indicated absence of pain and 10 the worst pain possible. The patients were asked to give scores corresponding to his/her pain, after IANB, mental nerve block and lingual infiltration and these scores were recorde.Results: From the results we can see that patients gave scores between 3-4, stating that they had moderate pain during extraction after administration of IANB (54%) (graph 2) and VAS scores of 0-1 were given by patients, which is suggestive of no pain during extraction after administration of Mental nerve block and lingual nerve infiltration (62%)Conclusion: Within the limits of the study we can conclude that mental nerve block along with lingual infiltration is an effective way to completely and quickly anaesthetise the central incisor to the 1st premolar region.

Abstract Antibacterial activities can be improved using mixed ligands. Mixed ligands involved in this research are sodium sulfadiazine (Na-sfz) and dithiocarbamate (ai-dtc). One-pot synthesis was used to synthesize ligand of aniline dithiocarbamate (ai-dtc) and the corresponding coordination compounds of [VO(sfz)(ai-dtc)] and [Zn(sfz)(ai-dtc)]. Crystals of ai-dtc, which grew from the solution when refrigerated after five days, were diffracted with technique of single crystal x-ray crystallography to reveal the structure. Other characterization techniques involving physicochemical parameters, FT-IR, UV-Vis and NMR (1H NMR and 13C NMR) were carried out on ligands of ai-dtc, sfz and corresponding coordination compounds. Differences in results of FT-IR, UV-Vis and NMR between ligands and their respective metal ions confirmed the coordination. The in vitro antibacterial studies showed that the ligands (not the metal complexes) had modest activity against Gram negative bacteria: Staphylococcus aureus, whereas, the coordination compounds had modest activities against the Gram negative bacteria: Escherichia coli and Pseudomonas aeruginosa.

Background: Burns are a common and severe medical emergency requiring immediate specialized care to minimize damage and prevent complications. Burn severity depends on depth, extent, and location, with more complex care needed for burns on critical areas or extensive burns. Nursing is essential in burn management, providing immediate care, adapting treatments, managing pain, preventing infections, and offering emotional support for recovery. Methods: Retrospective, observational study that analyzed burn cases treated at the Hospital Complex of Cáceres (Spain) 2018-2022. Inclusion criteria were based on ICD-10 codes for burns, excluding severe cases not treated in this service. Data were analyzed using descriptive statistics, Student's t-tests, Chi-square tests, and ANOVA. Results: 220 patients, with a mean age of 47 years and 60.9% male. Most burns (95.5%) affected the external body surface, with a mean hospital stay of 7.86 days. Medical treatment was provided to 75.5% of patients, and 24.5% required surgical intervention. Significant differences in treatment procedures were observed according to age, skin thickness, and burn degree. Older patients had more procedures and longer hospital stays. Excision and transfer procedures were more common in full-thickness and severe burns. Conclusions: The findings align with previous research on burn demographics and treatment approaches. Treatment differences by age and burn severity highlight the need for tailored interventions. The study underscores the importance of comprehensive burn management, including psychological support for improved long-term outcomes. Further research could explore the impact of socio-economic factors on burn incidence and treatment.

This study investigated the efficacy and safety of a propolis mangosteen extract complex (PMEC) on gingival health in patients with gingivitis and incipient periodontitis. A multi-centered randomized, double-blind, placebo-controlled trial involving 104 subjects receiving either PMEC or placebo for eight weeks was conducted. The primary focus was on changes in inflammatory biomarkers from gingival crevicular fluid (GCF), with clinical parameters as secondary outcomes. Results revealed that the PMEC group showed significantly reduced expression of all measured GCF biomarkers compared to the placebo group (p&lt;0.0001) at 8 weeks, including substantial reductions in IL-1β, PGE2, MMP-8, and MMP-9 levels compared to baseline. While clinical parameters trended towards improvement in both groups, inter-group differences were not statistically significant. No significant adverse events were reported, indicating a favorable safety profile. These findings suggest that PMEC consumption can attenuate gingival inflammation and mitigate periodontal tissue destruction by modulating key inflammatory mediators in gingival tissue. Although PMEC shows promise as a potential adjunctive therapy for supporting gingival health, the discrepancy between biomarker improvements and clinical outcomes warrants further investigation to fully elucidate its therapeutic potential in periodontal health management.

Respiratory syncytial virus (RSV) infection is a major cause of severe respiratory disease in infants and young children worldwide. Two vaccines targeting the elderly and pregnant women have been recently approved employing the prefusion form of the RSV-fusion protein (F). However, there are currently no vaccines for infants. Studies have shown a fusion-inactive prefusogenic F form is significantly more immunogenic and produces higher antibody titers to both the prefusion and postfusion structures of the F protein. Here we have developed RSV virus-like particles (RSV-VLPs) consisting of prefusogenic F, RSV glycoprotein and matrix proteins, produced them using the baculovirus expression system, and studied their protective efficacy in Balb/c mice. Morphology and successful assembly of VLPs were confirmed by transmission electron microscopy and western blot. Mice immunized with VLPs developed high levels of serum IgG and neutralizing antibodies as compared with mice immunized with inactivated virus. The VLP vaccine also induced higher levels of IFNγ and IL4, elicited limited proliferation of CD4+ and CD8+ T cells but higher cytotoxic-T-lymphocyte responses. VLP immunization abolished lung pathology in the mice after RSV challenge. Overall, our results indicate that RSV-VLPs consisting of prefusogenic F, glycoprotein and matrix proteins are a potential vaccine candidate against RSV.

The problem can be stated as over 3 billion choices to improve 14 disease states with 9 optimization goals (some of the optimization goals are diametrically opposed) to improve dyspnea, shortness of breath, fatigability, exercise intolerance, edema, swelling, fluid retention, and arrhythmias. The goal is to increase Left Ventricular Outflow Integral, reduce mitral regurgitation, increase longitudinal conduction velocities and restore synchrony of the septum to the ventricle that needs it the most. A method to accomplish this task for the spectrum of cardiac disease is presented.

We show the tensor properties of joint probabilities on a Riemannian parametric manifold. Initially we develop a binary data matrix for parameter measurements of a large number of particles confining in a closed system in order to retrieve the joint probability densities of related parameters. By introducing a new generalized inner product as a multilinear operation on dual basis of parametric space, we extract the set of joint probabilities and prove them to meet contravariant tensor properties in a general Riemannian parametric space. We show these contravariant tensors reduce to classical ordinary partial derivatives definition in ordinary Euclidean parametric space. Finally we prove by a theorem that symmetrized iterative contravariant derivative of cumulative probability function on Riemannian manifold gives the set of joint probabilities in those manifold. We bring some examples for compatibility with physical tensors.

Obesity and environmental toxins are risk factors for breast cancer, however there is limited knowledge on how these risk factors interact to promote breast cancer. Acrylamide, a probable carcinogen and obesogen, is a biproduct in foods prevalent in the obesity-inducing Western diet. Acrylamide is metabolized by cytochrome P450 2E1 (CYP2E1) to the genotoxic epoxide, glycidamide, and is associated with increased risk for breast cancer. To investigate how acrylamide and obesity interact to increase breast cancer risk, female mice were fed a low-fat (LFD) or high-fat diet (HFD) and 0.7mM acrylamide-supplemented water or control water. While HFD significantly enhanced weight gain in mice, the addition of acrylamide did not significantly alter body weights compared to respective controls. Mammary epithelial cells from obese, acrylamide-treated mice had increased DNA strand breaks and oxidative DNA damage compared to all other groups. In vitro, glycidamide-treated COMMA-D cells showed significantly increased DNA strand breaks while acrylamide-treated cells demonstrated significantly higher levels of intracellular reactive oxygen species. Knockdown of CYP2E1 rescued the acrylamide-induced oxidative stress. These studies suggest that long-term acrylamide exposure through foods common in the Western diet may enhance DNA damage and CYP2E1-induced generation of oxidative stress in mammary epithelial cells, potentially enhancing obesity-induced breast cancer risk.

The growing demand in industrial and biotechnological settings for more efficient enzymes with enhanced biochemical features, particularly thermostability and thermotolerance, necessitates a timely response. Renowned for their versatility, thermostable enzymes, offer significant promise across a range of applications, including agricultural, medicinal, and biotechnological domains. This comprehensive review summarizes the structural attributes, catalytic mechanisms, and the relationships between structure and function of two major classes of thermostable enzymes: α-amylases and laccases. These enzymes serve as valuable models for understanding the structural basis of protein thermostability. Commercial significance of these enzymes and researchers' interest in further optimization and innovation, this article can greatly contribute to ongoing research on thermostable enzymes and aiding industries in optimizing production processes. It also give insights to the exploration of suitable strategies and factors for enhancing thermostability, resulting in heightened multipronged stability and notable enhancements in the enzymes’ industrial applicability.

Glioblastoma (GBL) is one of the more malignant primary brain tumors, currently treated by a multimodality strategy including surgery, radio- and chemotherapy, mainly consisting of Temozolomide(TMZ)-based chemotherapy. Tumor relapse often occurs due to the establishment of TMZ resistance, with a patient median survival <2 years. The identification of natural molecules having strong anti-tumor activity, led to combine these compounds with conventional chemotherapeutic agents, developing protocols of integrated anticancer therapies. Curcumin (CUR), Resveratrol (RES), and its glucoside Polydatin (PLD) are widely employed in the pharmaceutical and nutraceutical fields, and several studies demonstrated that the combination of these natural products was more cytotoxic than the single compound alone in different cancers. Some of us recently demonstrated the synergistic efficacy of the sublingual administration of a new nutraceutical formulation of CUR+PLD in reducing tumor size and improving GBL patient survival. To deepen some mechanistic aspects of these results, we investigated if the pretreatment with a combination of CUR+PLD, can improve TMZ cytotoxicity on GBL cells, by analyzing the effects on cell cycle, viability and morphology, on proteins related to cell proliferation, differentiation, apoptosis or autophagy, and on actin network. Cell viability was assessed by MTT or by the cell counter CytoSmart. CalcuSyn software was used to study the CUR+PLD synergism. Morphology was evaluated by optical and scanning electron microscopy, and protein expression was analyzed by Western Blot. Flow cytometry was used for cell cycle, autophagic flux, and apoptosis analyses. The results obtained provide evidence that CUR and PLD, acting in synergy with each other, strongly improve the efficacy of alkylating antitumor agents such as TMZ, also in drug-resistant GBL cells, through their abilities to affect survival, differentiation, and tumor invasiveness.

Scale drop disease virus (SDDV), a double-stranded DNA virus in the family Iridoviridae, has been reported widely in southeast Asian countries as a causative agent of scale drop syndrome (SDS) in Asian seabass. SDS have resulted in high mortality and significant economic losses to the aquaculture industry. This study demonstrated the use of metagenomic methods to investigate bacterial and viral communities present in infected fish tissues and recovering a complete genome of the causative agent named SDDV TH7_2019. Characterization of the TH7_2019 genome revealed a genome size of 131 kb with 134 putative ORFs encoding viral proteins potentially associated with host apoptosis manipulation. A comparative genome analysis showed a high degree of amino acid identity across SDDV strains, with variations in number of repeat sequences and mutations within core genes. Phylogenetic analyses indicate a close relationship among SDDV genomes. This research enhances our understanding of the genetic diversity and evolutionary relationship of SDDV, contributing valuable insights for further development of effective control strategies of SDDV.

Epidemic diseases that arise from infectious RNA viruses, particularly influenza viruses, pose a constant threat to the global economy and public health. Viral evolution has undermined the efficacy of acquired immunity from vaccines and the antiviral effects of FDA-approved drugs. As such, there is an urgent need to develop new antiviral lead agents. Natural compounds, owing to their historical validation of application and safety, have become a promising solution. In this light, a novel marine bacterium, Pseudomonas sp. M20A4R8, has been found to exhibit significant antiviral activity [half maximal inhibitory concentration (IC50) = 1.3 µg/mL, selectivity index (SI) = 919.4] against influenza virus A/Puerto Rico/8/34, surpassing the activity of chloroquine. The antiviral response by M20A4R8 extract was induced during post-entry stages of the influenza virus, indicating suitability for post-application after the establishment of viral infection. Furthermore, post-treatment with M20A4R8 extract protected the host from virus-induced apoptosis, suggesting its potential use in acute respiratory disease complexes resulting from immune effectors' overstimulation and autophagy-mediated self-apoptosis. The extract demonstrated an outstanding therapeutic index against influenza virus A/Wisconsin/15/2009 (IC50 = 8.1 µg/mL, SI = 146.2) and B/Florida/78/2015 Victoria lineage (IC50 = 3.5 µg/mL, SI = 343.8), indicating a broad anti-influenza virus activity with guaranteed safety and effectiveness. This study provides a new perspective on mechanisms for preventing a broad spectrum of viral infections through antiviral agents from novel and natural origins. Future studies on a single or combined compound from the extract hold promise, encouraging its use in preclinical challenge tests with various influenza virus strains.

Colonoscopy, essential for diagnosing and treating colorectal cancer, relies on effective bowel preparation to inspect the colonic mucosa fully. Traditional education methods include printed instructions and verbal explanations, but these may not ensure clear patient understanding. Poor bowel preparation can obscure mucosal visibility, delaying cancer diagnosis and treatment. Using the outpatient’s Android mobile device, the mobile health care model is provided as a nursing guide to assist in bowel preparation for colonoscopy. This single-blinded, randomized trial en-rolled patients for colonoscopy at a Northern Taiwan gastroenterology center. Eligible patients were physically and mentally healthy and could communicate in Chinese. The study tested the ColonClean app during bowel preparation. After the procedure, endoscopists rated the prepara-tion quality using the Aronchick Scale. Data analysis with SPSS software (version 25.0) evaluated if the app significantly improved bowel preparation compared to those who did not use it. Forty patients were recruited for both the control (conventional method) and experimental (conven-tional method plus ColonClean app) groups. In the experimental group, endoscopists assessed bowel preparation quality; all achieved at least "Fair," with 75% receiving "Excellent" or "Good" ratings. The ColonClean App enhanced bowel preparation quality more effectively than tradi-tional nursing guidance.

Issues presented by the application of monoclonal antibodies in diagnostic assays and as curative agents can make the use of such molecules cost-prohibitive and sometimes even unsafe. This has warranted the development of short single-stranded oligonucleotides known as Aptamers. The structural malleability of these short DNA or RNA nucleotide segments allows them to exist in distinct conformations. SELEX (Systematic Evolution of Ligands by Exponential Enrichment) is a multi-step process for synthesis of aptamers. Each step of this procedure is governed by a diverse set of factors that influence production efficiency, binding affinity, and specificity of the oligonucleotides. Headway in aptamer research has been made in recent years by the introduction of newer iterations of the SELEX process. A greater number of studies are now being carried out to incorporate aptamers into existing disease detection tools and therapies. An overview has been given first on the key aptamer properties and the process of their production (with its newer iterations), contrasting each of them with that of monoclonal antibodies. Possible manifold applications afforded due to unique aptamer characteristics are also discussed. A keen review is further provided on the design, development and use of fluorescent aptamers in bioimaging, sequencing or profiling, and treatment of pathogenic bacteria and tumor cells.

Post-operative chemotherapy is still required for the treatment of glioblastoma (GBM), and nanocarrier-based drug delivery has been identified as one of the most effective methods. However, the blood-brain barrier (BBB) and non-specific delivery to non-tumor tissues can significantly limit drug accumulation in tumor tissues and cause damage to nearby normal tissues. This study describes a targeted cancer therapy approach that uses AS1411 aptamer-conjugated nanospheres, 100-300 nm in size, loaded with doxorubicin (Dox) to selectively identify tumor cells overexpressing nucleolin (NCL) proteins. The study demonstrates that the active target model, which employs aptamer-mediated drug delivery, is more effective than nonspecific enhanced permeability and maintenance (EPR)-mediated delivery and passive drug delivery in improving drug penetration and maintenance in tumor cells. Additionally, the study shows the potential for anticancer effects through 3D spheroidal and in vivo GBM xenograft models. The DNA-protein hybrid nanospheres utilized in this study offer numerous benefits, such as efficient synthesis, structural stability, high drug loading, dye labelling, biocompatibility, and biodegradability. When combined with nanospheres, the 1411 aptamer has been shown to be an effective drug delivery carrier for precisely targeting tumors. This combination has the potential to produce anti-tumor effects in active targeted therapy of GBM.