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Multiple myeloma (MM) is an incurable malignancy of plasma cells. Epidemiological studies indicate a substantial heritable component, but the underlying mechanisms remain unclear. Here, in a genome-wide association study totaling 10,906 cases and 366,221 controls, we identify 35 MM risk loci, 12 of which are novel. Through functional fine-mapping and Mendelian randomization, we uncover two causal mechanisms for inherited MM risk: longer telomeres; and elevated levels of B-cell maturation antigen (BCMA) and interleukin-5 receptor alpha (IL5RA) in plasma. The largest increase in BCMA and IL5RA levels is mediated by the risk variant rs34562254-A at TNFRSF13B. While individuals with loss-of-function variants in TNFRSF13B develop B-cell immunodeficiency, rs34562254-A exerts a gain-of-function effect, increasing MM risk through amplified B-cell responses. Our results represent an analysis of genetic MM predisposition, highlighting causal mechanisms contributing to MM development.
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Antígeno de Maduración de Linfocitos B , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Mieloma Múltiple , Polimorfismo de Nucleótido Simple , Mieloma Múltiple/genética , Humanos , Antígeno de Maduración de Linfocitos B/genética , Análisis de la Aleatorización Mendeliana , Linfocitos B/inmunología , Linfocitos B/metabolismo , Estudios de Casos y Controles , Proteína Activadora Transmembrana y Interactiva del CAML/genética , Masculino , Telómero/genéticaRESUMEN
Coronary artery disease (CAD) is a major cause of morbidity and mortality in the United States, and as strides have been made in its management, outcomes have continued to improve. Management has evolved from expectant management to coronary artery bypass graft surgery and thrombolysis, to more recently percutaneous intervention with stenting and medical management in select cases. Here, we describe a case of a complex patient with severe triple-vessel disease who was deemed a poor surgical candidate for coronary artery bypass graft surgery and would instead undergo high-risk percutaneous intervention with the placement of nine drug-eluting stents.
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This study aimed to characterize interactions within colloidal silica particles in their concentrated suspensions, using rheo-confocal measurements and imaging, followed by image analysis. We studied the effect of shear rate (0-500 s-1) and solution pH (6, 10) on the dispersion degree of colloidal silica particles via the determination and comparison of interparticle distances and their modeling. Images corresponding to different shear rates were analyzed to identify the coordinates of the particles. These coordinates were further analyzed to calculate the distance among the particles and then their surface-to-surface distance normalized by the particle diameter (H/D). It was found that the population of the particles per unit area of the image and H/D varied with increasing shear rate. The comparison between experimentally measured and theoretically calculated H/D identified that for some particles, the former was shorter than the latter, indicating the unexpected attractions among them against the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. Then, the modification of previously reported equations for H/D was suggested and confirmed its validity. Assuming pair potential interaction and hydrodynamic interaction were the main non-DLVO interactions, their magnitudes were calculated and confirmed the significance of pH and shear application strength on particle dispersion/coagulation.
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Coloides , Tamaño de la Partícula , Dióxido de Silicio , Suspensiones , Dióxido de Silicio/química , Coloides/química , Suspensiones/química , Hidrodinámica , Concentración de Iones de Hidrógeno , Reología/métodosRESUMEN
First-degree atrioventricular block (1-AVB), characterized by a PR interval exceeding 200 milliseconds, has traditionally been perceived as a benign cardiac condition. Recently, this perception has been challenged by investigations that indicate a potential association between PR prolongation and an elevated risk of atrial fibrillation (AF). To consolidate these findings, we performed a comprehensive review to assess the available evidence indicating a relationship between these two conditions. We searched MEDLINE and EMBASE databases as well as manually searched references of retrieved articles. We selected 18 cohort studies/meta-analyses involving general and special populations. Consistent findings across expansive cohort studies reveal that incremental increases in the PR interval may serve as an independent risk factor for AF. However, our analyses underscore the need for further research into the association between 1-AVB, defined by a specified PR interval cutoff, and the risk of AF.
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Fibrilación Atrial , Cardiopatías , Humanos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Factores de RiesgoRESUMEN
Petrochemical-based synthetic plastics poses a threat to humans, wildlife, marine life and the environment. Given the magnitude of eventual depletion of petrochemical sources and global environmental pollution caused by the manufacturing of synthetic plastics such as polyethylene (PET) and polypropylene (PP), it is essential to develop and adopt biopolymers as an environment friendly and cost-effective alternative to synthetic plastics. Research into bioplastics has been gaining traction as a way to create a more sustainable and eco-friendlier environment with a reduced environmental impact. Biodegradable bioplastics can have the same characteristics as traditional plastics while also offering additional benefits due to their low carbon footprint. Therefore, using organic waste from biological origin for bioplastic production not only reduces our reliance on edible feedstock but can also effectively assist with solid waste management. This review aims at providing an in-depth overview on recent developments in bioplastic-producing microorganisms, production procedures from various organic wastes using either pure or mixed microbial cultures (MMCs), microalgae, and chemical extraction methods. Low production yield and production costs are still the major bottlenecks to their deployment at industrial and commercial scale. However, their production and commercialization pose a significant challenge despite such potential. The major constraints are their production in small quantity, poor mechanical strength, lack of facilities and costly feed for industrial-scale production. This review further explores several methods for producing bioplastics with the aim of encouraging researchers and investors to explore ways to utilize these renewable resources in order to commercialize degradable bioplastics. Challenges, future prospects and Life cycle assessment of bioplastics are also highlighted. Utilizing a variety of bioplastics obtained from renewable and cost-effective sources (e.g., organic waste, agro-industrial waste, or microalgae) and determining the pertinent end-of-life option (e.g., composting or anaerobic digestion) may lead towards the right direction that assures the sustainable production of bioplastics.
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Compostaje , Plásticos , Humanos , Biopolímeros/química , Tecnología , Residuos IndustrialesRESUMEN
BACKGROUND: Advancements in nanoscience have led to a profound paradigm shift in the therapeutic applications of medicinally important natural drugs. The goal of this research is to develop a nano-natural product for efficient cancer treatment. METHODS AND RESULTS: For this purpose, mesoporous silica nanoparticles (MSNPs) were formulated, characterized, and loaded with caffeine to develop a targeted drug delivery system, i.e., caffeine-coated nanoparticles (CcNPs). In silico docking studies were conducted to examine the binding efficiency of the CcNPs with different apoptotic targets followed by in vitro and in vivo bioassays in respective animal models. Caffeine, administered both as a free drug and in nanomedicine form, along with doxorubicin, was delivered intravenously to a benzene-induced AML model. The anti-leukemic potential was assessed through hematological profiling, enzymatic biomarker analysis, and RT-PCR examination of genetic alterations in leukemia markers. Docking studies show strong inter-molecular interactions between CcNPs and apoptotic markers. In vitro analysis exhibits statistically significant antioxidant activity, whereas in vivo analysis exhibits normalization of the genetic expression of leukemia biomarkers STMN1 and S1009A, accompanied by the restoration of the hematological and morphological traits of leukemic blood cells in nanomedicine-treated rats. Likewise, a substantial improvement in hepatic and renal biomarkers is also observed. In addition to these findings, the nanomedicine successfully normalizes the elevated expression of GAPDH and mTOR induced by exposure to benzene. Further, the nanomedicine downregulates pro-survival components of the NF-kappa B pathway and upregulated P53 expression. Additionally, in the TRAIL pathway, it enhances the expression of pro-apoptotic players TRAIL and DR5 and downregulates the anti-apoptotic protein cFLIP. CONCLUSIONS: Our data suggest that MSNPs loaded with caffeine, i.e., CcNP/nanomedicine, can potentially inhibit transformed cell proliferation and induce pro-apoptotic TRAIL machinery to counter benzene-induced leukemia. These results render our nanomedicine as a potentially excellent therapeutic agent against AML.
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Novel hardware architectures for dynamic reconfigurable implementation of 64-bit MISTY1 and KASUMI block ciphers are proposed to enhance the performance of cryptographic chips for secure IoT applications. The SRL32 primitive (Reconfigurable Look up Tables-RLUTs) and DPR (Dynamic Partial Reconfiguration) are employed to reconfigure single round MISTY1 / KASUMI algorithms on the run-time. The RLUT based architecture attains dynamic logic functionality without extra hardware resources by internally modifying the LUT contents. The proposed adaptive reconfiguration can be adopted as a productive countermeasure against malicious attacks with the added advantage of less reconfiguration time (RT). On the other hand, the block architecture reconfigures the core hardware by externally uploading the partial bit stream and has significant advantages in terms of low area implementation and power reduction. Implementation was carried out on FPGA, Xilinx Virtex 7. The results showed remarkable results with very low area of 668 / 514 CLB slices consuming 460 / 354 mW for RLUT and DPR architectures respectively. Moreover, the throughput obtained for RLUT architecture was found as 364 Mbps with very less RT of 445 nsec while DPR architecture achieved speed of 176 Mbps with RT of 1.1 msec. The novel architectures outperform the stand-alone existing hardware designs of MISTY1 and KASUMI implementations by adding the dynamic reconfigurability while at the same achieving high performance in terms of area and throughput. Design details of proposed unified architectures and comprehensive analysis is described.
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Motivation: AliGater is an open-source framework to accelerate the development of bioinformatic pipelines for the analysis of large-scale, high-dimensional flow cytometry data. AliGater provides a Python package for automatic feature extraction workflows, as well as building blocks to construct analysis pipelines. Results: We illustrate the use of AliGater in a high-resolution flow cytometry-based genome-wide association study on 46 immune cell populations in 14 288 individuals. Availability and implementation: Source code and documentation at https://github.com/LudvigEk/aligater and https://aligater.readthedocs.io.
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Cutaneous Leishmaniasis (CL) affects millions of people globally and has a significant impact on morbidity and mortality. Innate immune mediators are likely to influence the clinical phenotype of CL through primary responses that restrict or facilitate parasite spread. The aim of this preliminary study was to bring to attention the significance of microbiota in the development of CL and emphasized the necessity of including the role of microbiota in CL while promoting a One Health approach for managing diseases. To achieve this, we used 16S amplicon metagenome sequencing and QIIME2 pipeline to analyze the microbiome composition of CL-infected patients compared to non-infected, healthy subjects. 16S sequencing analysis showed serum microbiome was dominated by Firmicutes, Proteobacteria, Bacteroidota, and Actinobacteria. CL-infected individuals, Proteobacteria were the most prevalent (27.63 ± 9.79), with the relative abundance (10.73 ± 5.33) of Proteobacteria in control. Bacilli class was found to be the most prevalent in healthy controls (30.71 ± 8.44) while (20.57 ± 9.51) in CL-infected individuals. The class Alphaproteobacteria was found to be more in CL-infected individuals (5.47 ± 2.07) as compared to healthy controls (1.85 ± 0.39). The CL-infected individuals had a significantly lower relative abundance of the Clostridia class (p < 0.0001). An altered serum microbiome of CL infection and higher microbial abundance in the serum of healthy individuals was observed.
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Leishmaniasis Cutánea , Microbiota , Humanos , Microbiota/genética , Bacterias/genética , Metagenoma , Proteobacteria/genética , Inflamación/genética , ARN Ribosómico 16S/genéticaRESUMEN
Granulomatosis with polyangiitis (GPA) is a rare, immunologically mediated systemic vasculitis that presents as an aseptic necrotizing granulomatous inflammation of the small and medium vessels. Case presentation: The authors report the case of a 47-year-old Syrian female smoker who was admitted to the hospital due to painless palpable masses in her left cheek and left upper lip. Her medical and family histories were unremarkable. Physical examination demonstrated facial asymmetry and bulging in the left cheek and left suborbital region, with marked limitation of the mouth opening and notable oozing from the maxillary sinus seen within the area of the extracted second premolar, in addition to swelling in the parotid gland region, which caused facial nerve weakness. Lab findings were significant for an elevated neutrophil count (16 400/mm3) and positivity of Cytoplasmic- Antineutrophil Cytoplasmic Autoantibody (c-ANCA). Microscopic examination revealed noncaseating necrotizing granulomas surrounded by histocytes and multinucleated giant cells. The disease kept its local invasion going despite the treatment with cyclophosphamide. Thus, surgical debridement was considered a notable improvement. Discussion: GPA is a systemic disease that usually affects multiple organs, especially the kidneys and the upper and lower respiratory tracts. The diagnosis of GPA is made based on a biopsy and the presence of c-ANCA. The treatment of GPA is patient-adjusted, and it usually consists of two major phases: induction and maintenance. However, surgery is preferred for patients who do not respond to pharmacotherapy. Conclusion: This article demonstrates a rare case of GPA in the head and neck region; that highlights the significant role of c-ANCA and histological exam in confirming the diagnosis as well as the importance of surgery when the disease is intractable.
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BACKGROUND: Surface-enhanced Raman spectroscopy (SERS) is an efficient technique which has been used for the analysis of filtrate portions of serum samples of Hepatitis B (HBV) and Hepatitis C (HCV) virus. OBJECTIVES: The main reason for this study is to differentiate and compare HBV and HCV serum samples for disease diagnosis through SERS. Hepatitis B and hepatitis C disease biomarkers are more predictable in their centrifuged form as compared in their uncentrifuged form. For differentiation of SERS spectral data sets of hepatitis B, hepatitis C and healthy person principal component analysis (PCA) proved to be a helpful. Centrifugally filtered serum samples of hepatitis B and hepatitis C are clearly differentiated from centrifugally filtered serum samples of healthy individuals by using partial least square discriminant analysis (PLS-DA). METHODOLOGY: Serum sample of HBV, HCV and healthy patients were centrifugally filtered to separate filtrate portion for studying biochemical changes in serum sample. The SERS of these samples is performed using silver nanoparticles as substrates to identify specific spectral features of both viral diseases which can be used for the diagnosis and differentiation of these diseases. The purpose of centrifugal filtration of the serum samples of HBV and HCV positive and control samples by using filter membranes of 50 KDa size is to eliminate the proteins bigger than 50 KDa so that their contribution in the SERS spectrum is removed and disease related smaller proteins may be observed. Principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA) are statistical tools which were used for the further validation of SERS. RESULTS: HBV and HCV centrifugally filtered serum sample were compared and biomarkers including (uracil, phenylalanine, methionine, adenine, phosphodiester, proline, tyrosine, tryptophan, amino acid, thymine, fatty acid, nucleic acid, triglyceride, guanine and hydroxyproline) were identified through PCA and PLS-DA. Principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA) were used as a multivariate data analysis tool for the diagnosis of the characteristic SERS spectral features associated with both types of viral diseases. For the classification and differentiation of centrifugally filtered HBV, HCV, and control serum samples, Principal component analysis is found helpful. Moreover, PLS-DA can classify these two distinct sets of SERS spectral data with 0.90 percent specificity, 0.85 percent precision, and 0.83 percent accuracy. CONCLUSIONS: Surface enhanced Raman spectroscopy along with chemometric analysis like PCA and PLS-DA have been successfully differentiated HBV and HCV and healthy individuals' serum samples.
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Hepatitis B , Hepatitis C , Nanopartículas del Metal , Fotoquimioterapia , Humanos , Nanopartículas del Metal/química , Plata/química , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes , Análisis Discriminante , Hepatitis C/diagnóstico , Espectrometría Raman/métodos , Hepatitis B/diagnóstico , Análisis de Componente PrincipalRESUMEN
Blood serum contains essential biochemical information which are used for early disease diagnosis. Blood serum consisted of higher molecular weight fractions (HMWF) and lower molecular weight fractions (LMWF). The disease biomarkers are lower molecular weight fraction proteins, and their contribution to disease diagnosis is suppressed due to higher molecular weight fraction proteins. To diagnose diabetes in early stages are difficult because of the presence of huge amount of these HMWF. In the current study, surface-enhanced Raman spectroscopy (SERS) are employed to diagnose diabetes after centrifugation of serum samples using Amicon ultra filter devices of 50 kDa which produced two fractions of whole blood serum of filtrate, low molecular weight fraction, and residue, high molecular weight fraction. Furthermore SERS is employed to study the LMW fractions of healthy and diseased samples. Some prominent SERS bands are observed at 725 cm-1, 842 cm-1, 1025 cm-1, 959 cm-1, and 1447 cm-1 due to small molecular weight proteins, and these biomarkers helped to diagnose the disease early stage. Moreover, chemometric techniques such as principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA) are employed to check the potential of surface-enhanced Raman spectroscopy for the differentiation and classifications of the blood serum samples. SERS can be employed for the early diagnosis and screening of biochemical changes during type II diabetes.
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Diabetes Mellitus Tipo 2 , Suero , Humanos , Espectrometría Raman/métodos , Análisis Discriminante , Biomarcadores , Análisis de Componente PrincipalRESUMEN
Background: Neurodevelopmental disorders are characterized by different combinations of intellectual disability (ID), communication and social skills deficits, and delays in achieving motor or language milestones. SLITRK2 is a postsynaptic cell-adhesion molecule that promotes neurite outgrowth and excitatory synapse development. Methods and Results: In the present study, we investigated a single patient segregating Neurodevelopmental disorder. SLITRK2 associated significant neuropsychological issues inherited in a rare X-linked fashion have recently been reported. Whole-exome sequencing and data analysis revealed a novel nonsense variant [c.789T>A; p.(Cys263*); NM_032539.5; NP_115928.1] in exon 5 of the SLITRK2 gene (MIM# 300561). Three-dimensional protein modeling revealed substantial changes in the mutated SLITRK2 protein, which might lead to nonsense-medicated decay. Conclusion: This study confirms the role of SLITRK2 in neuronal development and highlights the importance of including the SLITRK2 gene in the screening of individuals presenting neurodevelopmental disorders.
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Schistosomiasis is a neglected tropical disease that continues to be a leading cause of illness and mortality around the globe. The causing parasites are affixed to the skin through defiled water and enter the human body. Failure to diagnose Schistosomiasis can result in various medical complications, such as ascites, portal hypertension, esophageal varices, splenomegaly, and growth retardation. Early prediction and identification of risk factors may aid in treating disease before it becomes incurable. We aimed to create a framework by incorporating the most significant features to predict Schistosomiasis using machine learning techniques. A dataset of advanced Schistosomiasis has been employed containing recovery and death cases. A total data of 4316 individuals containing recovery and death cases were included in this research. The dataset contains demographics, socioeconomic, and clinical factors with lab reports. Data preprocessing techniques (missing values imputation, outlier removal, data normalisation, and data transformation) have also been employed for better results. Feature selection techniques, including correlation-based feature selection, Information gain, gain ratio, ReliefF, and OneR, have been utilised to minimise a large number of features. Data resampling algorithms, including Random undersampling, Random oversampling, Cluster Centroid, Near miss, and SMOTE, are applied to address the data imbalance problem. We applied four machine learning algorithms to construct the model: Gradient Boosting, Light Gradient Boosting, Extreme Gradient Boosting and CatBoost. The performance of the proposed framework has been evaluated based on Accuracy, Precision, Recall and F1-Score. The results of our proposed framework stated that the CatBoost model showed the best performance with the highest accuracy of (87.1%) compared with Gradient Boosting (86%), Light Gradient Boosting (86.7%) and Extreme Gradient Boosting (86.9%). Our proposed framework will assist doctors and healthcare professionals in the early diagnosis of Schistosomiasis.
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BACKGROUND: Surface-enhanced Raman spectroscopy (SERS) is explored to design a rapid screening method for the characterization and diagnosis of typhoid fever by employing filtrate fractions of blood serum samples obtained by centrifugal filtration with 50 KDa filters. OBJECTIVES: The purpose of this study, to separate the filtrate portions of blood serum samples in this way contain proteins smaller than 50 kDa and removal of bigger size protein which allows to acquire the SERS spectral features of smaller proteins more effectively which are probably associated with typhoid disease. Disease caused by Salmonella typhi diagnose more effectively by using surface-enhanced Raman spectroscopy (SERS) and multivariate data analysis tools. METHODS: SERS was used as a diagnostic tool for typhoid fever by comparison between healthy and diseased samples. For this purpose, all the samples were analyzed by comparing their SERS spectral features. Over the spectral range of 400-1800cm-1, multivariate data analysis techniques such as Principal Component Analysis (PCA) and Partial Least Squares-Discriminant Analysis (PLS-DA) are applied to diagnose and differentiate different filtrate fractions of blood serum samples of patients of typhoid fever and healthy ones. RESULTS: By comparing SERS spectra of healthy filtrate with that of filtrate of typhoid sample, the SERS spectral features associated with disease development are identified including PCA is found to be efficient for the qualitative differentiation of all of the samples analyzed. Moreover, PLS-DA successfully identified and classified healthy and typhoid positive blood serum samples with 97 % accuracy, 99 % specificity, 91 % sensitivity and 0.78 area under the receiver operating characteristic (AUROC) curve. CONCLUSIONS: Surface enhanced Raman spectroscopy using silver nanoparticles SERS substrate, is found to be useful technique for the quick identification and evaluation of filtrate fractions of the blood serum samples of healthy and typhoid samples for disease diagnosis.
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Nanopartículas del Metal , Fotoquimioterapia , Fiebre Tifoidea , Humanos , Espectrometría Raman/métodos , Nanopartículas del Metal/química , Plata/química , Fiebre Tifoidea/diagnóstico , Suero , Fotoquimioterapia/métodos , Análisis de Componente PrincipalRESUMEN
INTRODUCTION: Talar neck fractures are injuries which frequently result in adverse outcomes or impairment of functional activity. Four groups were identified according to Hawkins classification and Canale modification. We present a female patient with a fractured neck of the talus associated with talonavicular dislocation, but intact tibiotalar and subtalar joints; an injury pattern not fulfilling the criteria described in the Hawkins classification. PATIENT CONCERNS: A 46-year-old woman missed a step and fell down stairs with an immediate painful right ankle and inability to bear weight. DIAGNOSIS: Talar neck fracture with an unusual isolated talonavicular dislocation. INTERVENTIONS: Temporary closed reduction followed by open reduction and internal fixation were performed. OUTCOMES: The patient had excellent functional and radiological outcomes following surgical management. CONCLUSION: We discuss the management of this rare case in addition to a review of the current literature to provide the best evidence-based recommendations for this injury pattern.
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Fracturas Óseas , Luxaciones Articulares , Traumatismos del Cuello , Fracturas de la Columna Vertebral , Astrágalo , Femenino , Humanos , Persona de Mediana Edad , Astrágalo/diagnóstico por imagen , Astrágalo/cirugía , Astrágalo/lesiones , Fracturas Óseas/cirugía , Fijación Interna de Fracturas , Luxaciones Articulares/diagnóstico por imagen , Luxaciones Articulares/cirugía , Luxaciones Articulares/complicaciones , Reducción Abierta , Fracturas de la Columna Vertebral/complicaciones , Traumatismos del Cuello/complicacionesRESUMEN
BACKGROUND: Surface-enhanced Raman spectroscopy (SERS) is an effective tool for identifying biofilm forming bacterial strains. Biofilm forming bacteria are considered a major issue in the health sector because they have strong resistance against antibiotics. Staphylococcus epidermidis is commonly present on intravascular devices and prosthetic joints, catheters and wounds. OBJECTIVES: To identify and characterize biofilm forming and non-biofilm forming bacterial strains, surface- enhanced Raman spectroscopy with principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA) were used. METHODS: Surface-enhanced Raman spectroscopy (SERS) with silver nanoparticles were employed for the analysis and characterization of biofilm forming bacterial strains. SERS is used to differentiate between non biofilm forming (five samples), medium biofilm forming (five samples) and strong biofilm forming (five samples) bacterial strains by applying silver nanoparticles (AgNPs) as SERS substrate. Principal component analysis (PCA) and Partial least square discriminant analysis (PLS-DA) were used to discriminate between non, medium and strong biofilm ability of bacterial strains. RESULTS: Principal component analysis (PCA) and Partial least square discriminant analysis (PLS-DA) have been used to identify the biochemical differences in the form of SERS features which can be used to differentiate between biofilm forming and non-biofilm forming bacterial strains. PLS-DA provides successful differentiation and classification of these different strains with 94.5% specificity, 96% sensitivity and 89% area under the curve (AUC). CONCLUSIONS: Surface-enhanced Raman spectroscopy can be utilized to differentiate between non, medium and strong biofilm forming bacterial strains.