High resolution information on nucleotide arrangement in the genome of any or-ganism is critical to understand its genetic makeup, function, and evolutionary his-tory. For years, DNA sequencing has provided crucial breakthroughs in the field of genomics and molecular biology. With the advent of technology, Next Generation Sequencing has now transformed the whole genome sequencing prospects, thus unveiling the novel and interesting features of an organism genome that can behold. Next generation sequencing platforms offer realistic approach to identify and anal-yses whole genome with high throughput, accuracy, scalability in a very short time span. Information obtained can be further used in improving our existing healthcare systems, designing novel and personalized therapeutic modules, making the envi-ronment sustainable and proactively preparing ourselves for future pandemics and outbreaks. This article discusses the various NGS technologies and approaches, their advantages, drawbacks, and futuristic usage in different fields. Though still in nascent stages and marred with flaws, with ongoing advancement, NGS will indeed have promising impacts in the future.

Multiple myeloma (MM) is an incurable, diverse cancer in which abnormal plasma cells produce and release monoclonal immunoglobulin (Ig), also known as monoclonal protein or M protein. MM is always preceded by monoclonal gammaglobulinemia of unknown significance (MGUS) and smoldering multiple myeloma (SMM). Diagnosis of MM is made from a bone marrow sample, which involves analysis of the appearance of plasma cells. Quantification of CD138+ plasma cells in core biopsies is performed using techniques such as immunohistochemistry, flow cytometry, fluorescence in situ hybridization (FISH) and conventional cytogenetics. Urinalysis includes total protein by immunofixation and 24-hour urine by serum protein electrophoresis. FISH probes should detect the presence of at least del 13, del 17p, t(4;14), t(11;14), t(14;16), and 1q21 amplifications. Indeed, next-generation sequencing (NGS) has become an increasingly important tool in the diagnosis and treatment of MM. It can be used to identify genetic mutations, copy number changes, and clonal structures to help determine disease prognosis and treatment strategies. NGS can identify subclonal populations of cancer cells that are resistant to therapy and may lead to disease relapse, and can be used to identify potential targets for personalized therapy. For example, NGS can identify mutations in genes involved in drug resistance, enabling the selection of drugs that may be more effective in treating a patient's cancer. This systematic review analyzes 182 papers to determine the position and role of NGS in the diagnosis of MM. We first analyze the platforms and sample types used in the selected studies, and then start discussing the results.

Background: The microbiome of the ocular surface has been characterised, but only limited in-formation is available on a possible silent intraocular microbial colonisation in normal eyes. Therefore, we performed next generation sequencing (NGS) of 16S rDNA genes in aqueous hu-mor. Methods: Aqueous humor was sampled from three patients during cataract surgery. Air swabs, patient’s and healthy donor conjunctival swab served as controls. Following DNA extraction, the V3 and V4 hypervariable regions of the 16S rDNA gene were amplified and sequenced fol-lowed by denoising. The resulting Amplicon Sequence Variants were matched to a subset of the Ribosomal Database Project 16S database. The deduced bacterial community was then statis-tically analysed. Results: DNA content in all samples was low (0-1.49 ng/µl) but sufficient for analysis. Main phyla in all samples were Acinetobacteria (48%), Proteobacteria (26%), Firmicutes (14%), Acidobac-teria (8%) and Bacteroidetes (2%). Patients conjunctival control samples and anterior chamber fluid showed similar patterns of bacterial species containing many waterborne species. Non-disinfected samples showed a different bacterial spectrum than the air swab sample. Conclusions: The data confirm the existence of an ocular surface microbiome. A distinct intraoc-ular microbiome was not discernable from the background, suggesting the absence of an intra-ocular microbiome in normal eyes.

Understanding microbial composition in upper respiratory infections (URIs) is critical for effective diagnosis and treatment. Precision Metagenomic next-generation sequencing p(mNGS) can provide a comprehensive yet clinically relevant profile of respiratory infection. The hybridization capture-based targeted sequencing generated a precision metagenomics profile of 29 patients with acute URIs. Nasopharyngeal samples were collected from the subjects suspected of respiratory infection, and p(mNGS) was performed using the Illumina®/IDbyDNA Respiratory Pathogen ID/AMR Panel (RPIP). The dataset obtained from the mNGS analysis contains a wealth of information on the composition of acute URI microbiota, including the relative abundance of known pathogens and potential clinical implications. The dataset represents a valuable resource for future research endeavors in respiratory medicine, infectious disease epidemiology, and therapeutic interventions. In addition, the dataset offers significant potential for reuse and integration with other omics datasets. The comprehensive nature of the mNGS data allows the exploration of associations between the respiratory microbiota and host factors such as clinical outcomes, immune responses, or genetic predisposition. Combining this dataset with other relevant datasets, such as transcriptomics or metabolomics, could provide a deeper understanding of the complex interactions between the microbiota and the host in acute URIs.

BACKGROUND: Glioblastoma (GBM) is driven by various genomic alterations. Next generation sequencing (NGS) could yield targetable alterations that may impact outcomes. The goal of this study was to describe how NGS can inform targeted therapy (TT) in this patient population. METHODS: The medical records of patients (pts) with a diagnosis of GBM from 2017-2019 were reviewed. Records of patients with recurrent GBM and genomic alterations were evaluated. Objective response rates and disease control rates were deter-mined. RESULTS: A total of 87 pts with GBM underwent NGS. Forty percent (n = 35) were considered to have actionable alterations. Of the 35, 40% (n=14) pts had their treatment changed due to an alteration. The objective response rate (ORR) of this population was 43%. The disease control rate (DCR) was 100%. The absolute mean decrease in contrast enhancing disease was 50.7% (95% CI 34.8 – 66.6). CONCLUSION: NGS for GBM, particularly in the recurrent setting, yields a high rate of actionable alterations. We observed a high ORR and DCR, reflecting the value of NGS in deciding on TT to match alterations that are likely to respond. In conclusion, patient selection and availability of NGS may impact outcomes in select pts with recurrent GBM.

A sufficient amount of tissue sample is required to perform next-generation sequencing (NGS) with a high success rate, but the majority of patients with advanced non-small-cell lung cancer (NSCLC) are diagnosed with small biopsy specimens. Biopsy samples were collected from 184 patients with bronchoscopically diagnosed NSCLC. The tissue surface area, tumor cell count, and tumor content rate of each biopsy sample were evaluated. The impact of the cut-off criteria for the tissue surface area (≥ 1 mm2) and tumor content rate (≥ 30%) on the success rate of Oncomine Dx Target Test (ODxTT) was evaluated. The mean tissue surface area of the transbronchial biopsies was 1.23 ± 0.85 mm2 when small endobronchial ultrasonography with a guide sheath (EBUS-GS) was used, 2.16 ± 1.49 mm2 with large EBUS-GS, and 1.81 ± 0.75 mm2 with endobronchial biopsy (EBB). The proportion of samples with a tissue surface area of ≥ 1 mm2 was 48.8% for small EBUS-GS, 79.2% for large EBUS-GS, and 78.6% for EBB. Sixty-nine patients underwent ODxTT. The success rate of DNA sequencing was 84.1% and that of RNA sequencing was 92.7% over all patients. The success rate of DNA (RNA) sequencing was 57.1% (71.4%) for small EBUS-GS (n = 14), 93.4% (96.9%) for large EBUS-GS (n = 32), 62.5% (100%) for EBB (n = 8), and 100% (100%) for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) (n = 15). Regardless of the device used, a tissue surface area of ≥ 1 mm2 is adequate for samples to be tested with NGS.

In the last decade, we have witnessed an upsurge in nuclei-based studies, particularly coupled with next-generation sequencing. Such studies aim at understanding the molecular states that exist in heterogeneous cell populations by applying increasingly more affordable sequencing approaches, in addition to optimized methodologies developed to isolate and select nuclei. Although these powerful new methods promise unprecedented insights, it is important to understand and critically consider the associated challenges. Here, we provide a comprehensive overview of the rise of nuclei-based studies and elaborate on their advantages and disadvantages. Improved designs and appropriate use of the various experimental strategies will result in acquiring biologically accurate and meaningful information.

Understanding ecological interactions is a key in managing phytopathology. Although entomologists rely mostly on both traditional molecular methods and morphological characteristics to identify pests, next-generation sequencing is becoming the go-to avenue for scientists studying fungal and oomycete phytopathogens. These organisms sometimes infect plants together with insects. There are many relationships yet to be discovered and much to learn about how these organisms interact with one another. Considering the growing number of exotic insect introductions in Canada, a high-throughput strategy for screening those insects is already implemented by the Canadian Food Inspection Agency (CFIA). However, no plan is deployed to investigate the phytopathogenic fungal and oomycete species interacting with insects. Metagenomics analysis was performed on the preservation fluids from CFIA’s insect traps across Canada. Using the Ion Torrent PGM technology and fusion primers for multiplexing and indexing, community profiling was conducted on the different semiochemicals used in the insect traps and the various areas where these traps were placed. Internal transcribed spacer 1 (fungi and oomycetes) and adenosine triphosphate synthase subunit 9-nicotinamide adenine dinucleotide dehydrogenase subunit 9 spacer amplicons were generated. Although direct links between organisms could not be established, moderately phytopathogenic fungi (e.g., Leptographium spp. and Meria laricis) and oomycetes (mainly Peronospora spp. and Pythium spp.) unique to every type of semiochemical were discovered. The entomopathogenic yeast Candida michaelii was also detected. This project demonstrated our ability to screen for unwanted species faster and at a higher scale and throughput than traditional pathogen diagnostic techniques. Additionally, minimal modifications to this approach would allow it to be used in other phytopathology fields.

After human genome sequencing and rapid changes in genome sequencing methods, we have entered in the era of rapidly accumulating genome-sequencing data. This has poses development of several types of methods for representing results of genome sequencing data. Circular genome visualizations tools are also critical in this area as they provide rapid interpretation and simple visualization of overall data. In the last 15 years, we have seen rapid changes in circular visualization tools after the development of the circos tool with 1–2 tools published per year. Herein we have summarized and revisited all these tools until the third quarter of 2018.

The rapid and accurate detection of viruses and the discovery of single nucleotide polymorphisms (SNPs) are crucial for disease management and understanding viral evolution. In this study, a pipeline for virus detection, validation, and SNP discovery from next-generation sequencing (NGS) data is presented. By integrating state-of-the-art bioinformatics tools with artificial intelligence, the pipeline processes raw sequencing data to identify viral sequences with high accuracy and sensitivity. Before aligning the reads to the reference genomes, quality control measures and adapter trimming are performed to ensure the integrity of the data. Unmapped reads are subjected to de novo assembly to reveal novel viral sequences and genetic elements. The effectiveness of the pipeline is demonstrated by the identification of virus sequences, illustrating its potential for the detection of known and emerging pathogens. SNP discovery is performed using a custom Python script that compares the entire population of sequenced viral reads to a reference genome. This approach provides a comprehensive overview of viral genetic diversity and identifies dominant variants and a spectrum of genetic variations. The robustness of the pipeline is confirmed by the recovery of complete viral sequences, which improves our understanding of viral genomics. This study highlights the synergy between traditional bioinformatics techniques and modern approaches, providing a robust tool for analyzing viral genomes and contributing to the broader field of viral genomics.

Crop output is directly impacted by plant infections (with fungi as the major pathogen), making accurate diagnosis of these threats crucial. Developing technology and multidisciplinary approaches are turning to genomic analyses in addition to traditional culture methods in diagnosing fungal plant diseases. The metagenomic next-generation sequencing (mNGS) method is preferred for genotyping identification of organisms, identification at the species level, illumination of metabolic pathways, and determination of microbiota. Moreover, the data obtained so far show that this new approach shows promise as an emerging new trend in fungal disease detection. Another approach covered by mNGS technologies, known as metabarcoding, enables use of specific markers specific to a genetic region and allows for genotypic identification by facilitating the sequencing of certain regions. Although the core concept of mNGS remains constant across applications, the specific sequencing methods and bioinformatics tools used to analyze the data do differ. In this review, we focus on how mNGS technology, including metabarcoding, is applied in fungal pathogenesis and its promising developments for the future.

Precision medicine seeks to use genomic data to help provide the right treatment to the right patient at the right time. Next-generation sequencing technology allows for the rapid and accurate sequencing of many genes at once. This technology is becoming more common in oncology, though the clinical benefit of incorporating it into precision medicine strategies remains under significant debate. In this manuscript, we discuss the early findings of the impact of next-generation sequencing on cancer patient outcomes. We investigate why not all patients with genomic variants linked to a specific therapy receive that therapy and describe current barriers. Finally, we explore the current state of health insurance coverage for individual genome sequencing and targeted therapies for cancer. Based on our analysis, we recommend increased transparency around the determination of “actionable mutations” and a heightened focus on investigating the variations in health insurance coverage across patients receiving sequencing-matched therapies.

The efficacy and cost-effectivness of Multigene Panel Next-Generation Sequencing (NGS) in directing patients towards genomically matched therapies remains uncertain. This study investigated metastatic colorectal cancer (mCRC) patients who underwent NGS analysis on formalin-fixed paraffin-embedded tumor samples. Data from 179 patients were analyzed, revealing no mutations in 39 patients (21.8%), one mutation in 83 patients (46.4%), and two or more mutations in 57 patients (31.8%). KRAS mutations were found in 87 patients (48.6%), including KRAS G12C mutations in 5 patients (2.8%), PIK3CA mutations in 40 patients (22.4%), BRAF mutations in 26 patients (14.5%). Less common mutations were identified: ERBB2 in 5 patients (2.8%) and SMO in 4 patients (2.2%). Additionally, MAP2K1, CTNNB1, and MYC were mutated in 3 patients (2.4%). Two mutations (1.1%) were observed in ERBB3, RAF1, MTOR, JAK1, and FGFR2. No significant survival differences were observed based on mutation numbers. 40% of patients had druggable molecular alterations, but only 1.1% received genomically guided treatment, suggesting limited application in standard practice. Despite this, expanded gene panel testing can identify actionable mutations, aiding personalized treatment strategies in metastatic CRC, although current eligibility for biomarker-guided trials remains limited.

Transposable elements (TEs) are mobile genetic elements capable of rapidly altering the genome through their movements. The importance of TE activity has been documented in many biological processes, such as introducing genetic instability, altering patterns of gene expression, and accelerating genome evolution. Increasing appreciation of TEs results in the growing number of bioinformatics software to identify insertion events. However, the application of existing TE finding tools is limited by either narrow-focused design of the package, too many dependencies on other tools, or prior knowledge required as input files that may not be readily available to all users. Here, we report a simple pipeline, TEfinder, developed for the detection of new TE insertions with minimal software dependencies using four inputs that can be easily generated with popular variant calling pipelines. The external software requirements are BEDTools, SAMtools, and Picard. Necessary inputs include TEs present in the reference genome, binary paired-end alignment, reference genome index, and a list of TE names. We tested TEfinder pipeline among several evolving populations of Fusarium oxysporum generated through a short-term adaptation study. Our results demonstrate that this easy-to-use tool can effectively detect new TE insertion events, making it accessible and practical for TE analysis.

Bread wheat (Triticum aestivum L.) is one of the most important cereal crops for food security. Of all the stresses that curtail wheat productivity, drought has the most detrimental effects. Especially terminal drought stress i.e. at the time of flowering imposes a big challenge to sustain grain production. In the current study, 339 pre-breeding lines derived from three-way crosses of exotics x elite lines were evaluated in the irrigated and drought stress environments at Obregon, Mexico for the year 2016 and 2018. Drought significantly reduced yield (Y), spike length (SL), number of grains per spikes (NGS) and thousand kernel weight (TKW) by 46.4, 19.2, 23.5 and 25.9%, respectively in comparison to irrigated conditions. Kernel abortion (KA), highly correlated with Y, increased significantly (11.6%) under drought stress environment. Population structure analysis in this panel revealed three sub-populations and a genome wide linkage disequilibrium (LD) decay was at 2.5 cM. Single marker and haplotypes-based genome wide association study (GWAS) revealed significant associations on three chromosomes; 4A (HB10.7), 2D (HB6.10) and 3B (HB8.12) with Y, SL and TKW, respectively. Likewise, associations on chromosomes 6B (HB17.1) and 3A (HB7.11) were identified for NGS and on 3A (HB7.12) for KA. Five traits i.e. normalized difference vegetation index (NDVI), canopy temperature depression (CTD) days to heading (DTH), NGS, KA were associated at chromosome 3A both under irrigated and drought conditions however, different haplotypes were estimated. Twenty-six SNPs were part of 10 haplotype blocks associated with Y, SL, TKW, NGS and KA. In silico analysis of the associated SNPs/haplotypes showed hits with candidate genes known to confer abiotic stress resistance in model species and crops. Potential candidate genes include those coding for sulfite exporter TauE/SafE family in Arabidopsis thaliana, TBC domain containing protein in Oryza sativa subsp. Japonica and heat shock proteins in Aegilops tauschii subsp. tauschii were revealed. The SNPs linked to the promising genes identified in the study can be used for marker-assisted selection.

The study of the currently known >3,000 species of snakes can provide valuable insights into the evolution of their genomes. Deinagkistrodon acutus, also known as Sharp-nosed Pit Viper, one hundred-pacer viper or five-pacer viper, is a venomous snake with significant economic, medicinal and scientific importance. Widely distributed in southeastern China and South-East Asia, D. acutus has been primarily studied for its venom. Here, we employed next-generation sequencing to assemble and annotate a highly continuous genome of D. acutus. The genome size is 1.46 Gb; its scaffold N50 length is 6.21 Mb, the repeat content is 42.81%, and 24,402 functional genes were annotated. This study helps to further understand and utilize D. acutus and its venom at the genetic level.

Forest health is dependent on the variability of microorganisms interacting with the host tree/holobiont. Symbiotic microbiota and pathogens engage in a permanent interplay, which influences the host. Thanks to the development of NGS technologies, a vast amount of genetic information on the virosphere of temperate forests has been gained the last seven years. To estimate the qualitative/quantitative impact of NGS in forest virology, we have summarized viruses affecting major tree/shrub species and their fungal associates, including fungal plant pathogens, mutualists and saprotrophs. The contribution of NGS methods is extremely significant for forest virology. Reviewed data about viral presence in holobionts, allowed us to address the role of the virome in the holobionts. Genetic variation is a crucial aspect in hologenome, significantly reinforced by horizontal gene transfer among all interacting actors. Through virus-virus interplays synergistic or antagonistic relations may evolve, which may drastically affect the health of the holobiont. Novel insights of these interplays may allow practical applications for forest plant protection based on endophytes and mycovirus biocontrol agents. The current analysis is conceived in light of the prospect that novel viruses may initiate an emergent infectious disease and that measures for avoidance of future outbreaks in forests should be considered.

Keywords: Cystic fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator gene, CFTR, Next Generation Sequencing, Cystic fibrosis carriers

SARS-CoV-2 is a novel betacoronavirus and the aetiological agent of the current COVID-19 outbreak that originated in Hubei Province, China. While polymerase chain reaction is the front-line tool for SARS-CoV-2 surveillance, application of amplification-free and culture-free methods for isolation of SARS-CoV-2 RNA, partnered with next-generation sequencing, would provide a useful tool for both surveillance and research of SARS-CoV-2. We here release into the public domain a set of bait capture hybridization probe sequences for enrichment of SARS-CoV-2 RNA from complex biological samples. These probe sequences have been designed using rigorous bioinformatics methods to provide sensitivity, accuracy, and minimal off-target hybridization. Probe design was based on existing, validated approaches for detecting antimicrobial resistance genes in complex samples and it is our hope that this SARS-CoV-2 bait capture platform, once validated by those with samples in hand, will be of aid in combating the current outbreak.

Coal gasification with carbon dioxide is a process for generating clean gaseous fuels and relieving greenhouse effect. Zhundong coal has high alkali and alkali earth metals (AAEMs) content, medium volatile and low ash in nature. Isothermal CO₂ gasification of char derived from Zhundong coal (R-char) and char from acid washing R-char (AR-char) are performed in thermo-gravimetric analyzer (TGA). The effect of AAEMs is investigated on the gasification behavior in the range of temperatures 1073 K to 1273 K. The carbon conversion increases rapidly with increasing reaction temperature and CO₂ concentration. R-char has high gasification rate and carbon conversion compared with AR-char. The accuracy of the free-model approach for calculating activation energy at different conversions is validated by compared with different kinetic models (volume reaction model, distributed activation energy model). Moreover, R-char gasification with CO₂ shows a compensation effect as the Arrhenius parameters (EA and k0) increase or decrease simultaneously.

The accurate virus detection, strain discrimination, and source attribution of contaminated food items remains a persistent challenge because of the high mutation rates anticipated to occur in foodborne RNA viruses, such as Hepatitis A virus (HAV). This has led to predictions of the existence of more than one sequence variant between the hosts (inter-host) or within an individual host (intra-host). However, there have been no reports of intra-host variants from an infected single individual, and little is known about the accuracy of the single nucleotide variations (SNVs) calling with various methods. In this study, the presence and identity of viral SNVs, either between HAV clinical specimens or among a series of samples derived from HAV clone1-infected FRhK4 cells, were determined following analyses of nucleotide sequences generated using next-generation sequencing (NGS) and pyrosequencing methods. The results demonstrate the co-existence of inter- and intra-host variants both in the clinical specimens and the cultured samples. The discovery and confirmation of multi-viral RNAs in an infected individual is dependent on the strain discrimination at the SNV level, and critical for successful outbreak traceback and source attribution investigations. The detection of SNVs in a time series of HAV infected FRhK4 cells improved our understanding on the mutation dynamics determined probably by different selective pressures. Additionally, it demonstrated that NGS could potentially provide a valuable investigative approach toward SNV detection and identification for other RNA viruses.

In recent years, the focus of disease resistance and susceptibility studies in cattle have been on determining patterns in the innate immune response of key proteins, such as Toll-like receptors (TLR). In the bovine genome, there are 10 TLR family members and, of these, TLR2, TLR4 and TLR6 are specialized in recognition of bacterial ligands. Indigenous cattle breeds of Anatolia have been reported to show fewer signs of clinical bacterial infections, such as bovine tuberculosis and mastitis, and it is hypothesized that this might be due to a less stringent genetic selection during breeding. In contrast, Holstein-Friesian cattle have been under strong selection for milk production, which may have resulted in greater susceptibility to diseases. To test this hypothesis, we have compared the TLR2, TLR4 and TLR6 genes of Anatolian Black (AB), East Anatolian Red (EAR), South Anatolian Red (SAR), Turkish Grey (TG), and Holstein (HOL) cattle using Next Generation Sequencing. The SAR breed had the most variations overall, followed by EAR, AB, TG and HOL. TG had the most variations for TLR2 whereas SAR had the most variations in TLR4 and TLR6. We compared these variants with those associated with disease and susceptibility traits. We used exon variants to construct haplotypes, investigated shared haplotypes within breeds and determined candidate haplotypes for disease resistance phenotype in Anatolian cattle breeds.

Experiential learning in the field is an opportunity for students to enter the heart of a scientific discipline. Through such experience, they can extract conceptual clues and discover motivational stepping stones that will potentially influence the rest of their education and career choice. Unfortunately, in Biology, the inescapable topic of Next-Generation Sequencing represents a challenge when it comes to create an educational curriculum that aims to provide students with hands-on experience on sequencers. It is an even more difficult task to accomplish if one’s purpose was to set such curriculum in a field situation. However, in recent years, educators have seen possibility to bring Next-Generation Sequencing to the reach of students more easily, with the Oxford Nanopore MinION, a low-budget, user-friendly, hand-held sequencer. Academic researchers have illustrated the performances of this device in the field and are inspirational for curricula aiming to take the next generation of scientists in the outdoors. We designed a modular 5-day workshop, with nanopore sequencing to be performed in field conditions. Here we describe the material and methods that lead the students and instructors from sample collection, DNA extraction and preparation for nanopore sequencing with MinION to real-time analysis of the data collected. This curriculum was implemented for the first-time aboard Research Vessel Sikuliaq during a transit organized by the STEMSEAS program at Columbia University in collaboration with the University of Alaska BLaST program. The line of investigation formulated for the workshop was an open-ended question that led the students to establish a proof of concept in terms of technology deployment at sea: what will show metagenomic results from DNA obtained from sea water and sequenced with Oxford Nanopore MinION? The workshop took place in October 2018 while Research Vessel Sikuliaq sailed the Alaskans seas for 7 days. Students successfully used nanopore sequencing for multiple metagenomic seawater samples. Their introductory analysis was consistent with environmental conditions and they were able to present their results by the end of the workshop.

In this report, we describe the course and successful treatment of complicated infective endocarditis (IE). A patient presented with a high-grade irregular fever with chills lasting at least 2 months, dyspnoea, chest pain, fatigue, weight loss, and night sweats during the previous 3 months. Above cardiac congenital disorders, he was found to have Granulicatella adiacens infective aortic valve endocarditis, presumably transmitted from the oral cavity niche. Validated metagenomic 16S rDNA next generation sequencing was used to perform taxonomic identification, allowing for specific adequate antibiotic therapy instead of empiric therapy. This paper highlights the critical role of rapid taxonomic identification of nutritionally variant streptococci crucial and the benefit of proper IE treatment to avoid relapses or fatal complications.

Three kinds of inorganic alkali are introduced into tetraethylenepentamine (TPEA) and polyethyleneimine (PEI) modified MCM-41 as the CO2 adsorbents. FT-IR and TGA are used to characterize the surface groups and the thermal stability of adsorbents. Chemical titration method is used to measure the alkali amounts of adsorbents. Thermo-gravimetric analysis with 10%CO2/N2 as the simulated flue gas is used to test the CO2 adsorption performance of adsorbents. The results show that all three kinds of inorganic alkali containing adsorbents exhibit promoted CO2 adsorption capability than traditional TPEA and PEI modified samples. Ca(OH)2 and PEI modified samples exhibit the highest adsorption capacity and stable regeneration property. The introduction of inorganic alkali changes the chemical adsorption mechanism between CO2 and increases the effective alkali amounts due to its hydroxyl groups. The CO2 adsorption capacities have a linear dependence relation with the alkali amounts of adsorbents, indicating that alkali amount is a critical factor for novel adsorbents exploring.

A bacterium known as Akkermansia muciniphila (AkkermansiaA. muciniphila) was detected in human feces in 2004. It is defined as a gram-negative, anaerobic, and mucin-degrading microbe belonging to the Verrucomicrobia species. Although the majority of A. muciniphila is found in the human intestinal tract playing a role in the gut microbiome, there are also smaller levels detected in breast milk and oral cavities as well as in the pancreas and appendix.Evidence suggests that having A. muciniphila present in the gut microbiome has positive effects on human health. As a result, A. muciniphila has been shown to have health benefits when taken as a dietary supplementation where it is considered a promising next-generation probiotic. However, the large-scale production of A. muciniphila remains a challenge due to its need for a stable environment. While culturing A. muciniphila in a mucin-based medium is one option, other strategies that use plate-based mediums have also been explored. Currently, both live and pasteurized forms of A. muciniphila are available on the market and shown to have promising outcomes in animal models. Additionally, researchers are investigating various prebiotics to increase the abundance of A. muciniphila in the human gut. This article presents a detailed summary of the phenotypic characteristics of A. muciniphila and its associations with various human health condition illnesses. Finally, the paper explores A. muciniphila's potential as an effective next-generation probiotic.

Blackcurrant leaf chlorosis associated virus (BCLCaV) was detected recently by next-generation sequencing (NGS) and proposed as a new and distinct species in the genus Idaeovirus. Genomic components of BCLCaV that were detected and confirmed include: 1) RNA-1 that is monocistronic and encodes the replicase complex; 2) a bicistronic RNA-2 that encodes a movement protein (MP) and the coat protein (CP) of the virus, with open reading frames (ORF) that overlap by a single adenine (A) nucleotide (nt) representing the third position of an opal stop codon of the MP ORF2a and the first position of the start codon of the CP ORF2b; 3) a subgenomic form of RNA-2 (RNA-3) that contains ORF2b; and 4) a concatenated form of RNA-2 that consists of a complementary and inverted RNA-3 conjoined to the full-length RNA-2. Analysis of NGS-derived paired-end reads revealed the existence of bridge reads encompassing the 3’-terminus and 5’-terminus of RNA-2 or RNA-3 of BCLCaV. The full RNA-2 or RNA-3 could be amplified using outward facing or abutting primers; also RNA-2/RNA-3 could be detected even after three consecutive RNase R enzyme treatments with denaturation at 95 ^oC preceding each digestion. Evidence was obtained indicating that there are circular forms of BCLCaV RNA-2 and RNA-3.

Monoclonal antibodies (mAbs) are an important treatment option for COVID-19 caused by SARS-CoV-2, especially in immunosuppressed patients. However, this treatment option can become ineffective due to mutations in the SARS-CoV-2 genome, mainly in the receptor binding domain (RBD) of the spike (S) protein. In the present study 7950 SARS-CoV-2 positive samples from the Uppsala and Örebro regions of central Sweden collected between March 2022 and May 2023 were whole-genome sequenced using next-generation sequencing, mainly with the Nanopore sequencing method. Pango lineages were determined and all single nucleotide polymorphism (SNP) mutations that occurred in these samples were identified. The dominant sublineages changed over time and mutations conferring resistance to currently available mAbs became common. Notable ones are R346T and K444T mutations in the RBD that confer significant resistance against tixagevimab and cilgavimab mAbs. Further, mutations conferring a high-fold resistance to bebtelovimab, such as the K444T and V445P mutations, were also observed in the samples. This study highlights that resistance mutations have over time rendered currently available mAbs ineffective against SARS-CoV-2 in most patients. Therefore, there is a need for continued surveillance of resistance mutations and the development of new mAbs that target more conserved regions of the RBD.

The biological heterogeneity of glioblastoma (GBM), the most aggressive type of brain cancer, is a critical hallmark, caused by changes in the genomic mutational asset and influencing the clinical progression over the time. The understanding and monitoring of the mutational profile is important not only to reveal novel therapeutic targets in this set of patients, but also to ameliorate the clinical stratification of subjects and the prognostic significance. As neurosurgery represents the primary technique to manage GBM, it is of outmost importance to optimize alternative and less invasive methods to monitor the dynamic mutation profile of these patients. Extracellular vesicles (EV) are included in the liquid biopsy analysis and have emerged as the biological mirror of escaping and surviving mechanisms by many tumors as well as glioblastoma. Very few studies have investigated the technical feasibility to detect and analyze the genomic profile by Next Generation Sequencing (NGS) in circulating EV of patients with grade IV glioblastoma. Here, we attempted to characterize and to compare with the corresponding matched tissue samples, potential variants with pathogenic significance of the DNA contained in peripheral blood derived EV. The NGS analysis has revealed that patients with grade IV glioblastoma, exhibited lesser DNA content in EV than controls and that both in EV and matched cancer tissues, the NF1 gene was consistently mutated in all patients with the c.2568C>G as the most common pathogenic variant expressed. This study supports the clinical utility of the circulating EV in glioblastoma and as eligible tool for personalized medicine.

Storage, transmission and processing of data become a significant problem when large digital data files or databases are involved, as in the case of decentralized online global databases such as blockchain. Here we propose a novel method that allows the scalability of digital assets, including blockchain databases in the download, validation and confidentiality process, by developing a lightweight blockchain technology called Entropic Blockchain. This is a computer-implemented mathematical method to generate an information-entropic numerical representation of a digital asset, which can be utilized on its own, or as an optically machine-readable entropic barcode, for data secure transmission, processing, labelling, identification, one-way encryption and compression, validation, and digital tamper-proof check.

In this article, we discuss problems that exist in modern SCADA systems and present a Controls-kt (formerly DataForge-controls) software development kit, that allows both to create a control system from scratch and provide integration with existing systems via Magix specification and connector.

With the inclusion of snakebite envenoming on the World Health Organisation’s list of Neglected Tropical Diseases, an incentive has been established to promote research and development effort in novel snakebite antivenom therapies. Different technological approaches are being pursued by different research groups, including the use of small molecule inhibitors against enzymatic toxins, as well as peptide and oligonucleotide-based aptamers and antibody-based biotherapeutics against both enzymatic and non-enzymatic toxins. In this article, the most recent advances in these fields are presented, and the advantages, disadvantages, and feasibility of using different toxin-neutralizing molecules are reviewed. Particular focus within small molecules is directed towards the inhibitors, varespladib, batimastat, and marimastat, while in the field of antibody-based therapies, novel recombinant polyclonal plantivenom technology is discussed.

MCPH1, otherwise known as the microcephalin gene (*607117) and protein, is a basic regulator of chromosome condensation (BCRT-BRCA1 C-terminus). The Microcephalin protein is made up of three BCRT domains and conserved tandem repeats of interacting phospho-peptide. There is a strong connection between mutations of the MCPH1 and reduced brain growth. Specifically, individuals with such mutations have underdeveloped brains which means smaller size, varying levels of mental retardation, delayed speech and poor language skills, individuals with mild microcephaly and normal intelligence notwithstanding. In this case, a fetus with novel homozygous mutation of the MCPH1 gene ((c.348del)), whose parents were recessive heterozygous for (c.348del), displayed severe microcephaly at 22 weeks of gestation. Due to the effect on splice sites in introns, this mutation causes forming of dysfunctional proteins which lack crucial domains of the C-terminus. Our findings portray an association between the new MCPH1 mutation ((c.348del)) and the clinical features of autosomal recessive primary microcephaly (MCPH) contributing to a broader spectrum related to these pathologies.

Tsunami modeling and simulation has changed in the past few years more than it had in decades, especially so with respect to coastal inundation. Among other things, this change is supported by the approaching era of exa-scale computing, whether via GPU or more likely forms of hybrid computing whose presence is growing across the geosciences. For reasons identified across this review, exa-scale computing efforts will impact the on-shore, highly turbulent r\'egime to higher degree than the 2D shallow water equations used to model tsunami propagation in the open ocean. This short review describes the different approaches to tsunami modeling from generation to impact and underlines the limits of each model based on the flow r\'egime. Moreover, from the perspective of a future comprehensive multi-scale modeling infrastructure to simulate a full tsunami, we underline the current challenges associated with this approach and review the few efforts that are currently underway to achieve this goal. A table of existing tsunami software packages is provided along with an open Github repository to allow developers and model users to update the table with additional models as they are published and help with model discoverability.

Transportation is the primary consumer of oil, accounting for a significant portion of global energy consumption (34%) and CO2 emissions (40%). Electrifying road transportation is crucial to mitigate the effects of global warming. The abundant potential of renewable energy sources like solar and wind is hindered by their intermittent nature and incongruity with peak energy demands. This calls for the development of sophisticated energy storage solutions. Metal-air batteries (MABs), emerging as viable alternatives to lithium-ion batteries (LIBs), have attracted considerable attention due to their promising applications in the transportation sector. Despite substantial progress in MAB development over the past two decades, overcoming critical challenges such as electrolyte decomposition, carbon cathode degradation, anodic dendrite growth, and air impurities remains essential for their commercial viability. This mini-review provides a comprehensive overview of MAB fundamentals and the challenges associated with their development. The insights presented in this review serve to illuminate the current landscape and future prospects of MABs in the transportation sector.

This paper presents ROSGPT, an innovative concept that harnesses the capabilities of large language models (LLMs) to significantly advance human-robot interaction. We develop ROSGPT as a ROS2 package that seamlessly integrates ChatGPT with ROS2-based robotic systems. The core idea is to leverage prompt engineering with LLMs, specifically ChatGPT, utilizing its unique properties such as ability eliciting, chain-of-thought, and instruction tuning. The concept employs ontology development to convert unstructured natural language commands into structured robotic instructions specific to the application context through prompt engineering. We capitalize on LLMs' zero-shots and few-shots learning capabilities by eliciting \textit{structured} robotic commands from \textit{unstructured} human language inputs. To demonstrate the feasibility of this concept, we implemented a proof-of-concept that integrates ChatGPT with ROS2, showcasing the transformation of human language instructions into spatial navigation commands for a ROS2-enabled robot. This versatile concept can be easily adapted to various other robotic missions. ROSGPT serves as a new stride towards Artificial General Intelligence (AGI) and paves the way for the robotics and natural language processing communities to collaborate in creating novel, intuitive human-robot interactions. The open-source implementation of ROSGPT on ROS 2 is available on GitHub.

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

Although effective in term of chance of future live birth, the current methods for fertility preservation such as oocytes, embryo or ovarian tissue cryopreservation cannot be offered to all cancer patients and in all clinical contexts. Expanding options for fertility preservation is crucial to address the need to encompass all situations. One emerging strategy is pharmacoprotection, which is non-invasive and has the potential to fill existing gaps in fertility preservation. Besides the identification of the most efficient therapeutic agent itself, the potential off-target effect re-mains one of the main limitation of this strategy for clinical application, particularly when healthy ovarian tissue is targeted. This review focuses on the advances in pharmacoprotective approaches and the challenge of targeting the ovaries to deliver these agents. The unique properties of gold nanoparticles (AuNPs) make them an attractive candidate for this purpose. We discuss how AuNPs meet many of the requirements for an ideal drug delivery system, as well as the existing limitations that have hindering the progression of AuNPs research into more clinical trials. Additionally, the review highlights microRNA (miRNA) therapy as a next-generation approach to address the issues of fertility preservation and discusses the obstacles that currently impede its clinical availability.

Specialized, reductionist, and linear approaches are applied in clinical research; they are based on linear logic and used towards therapeutic molecule-based targets. However, those approaches do not consider a systemic vision that describes the remote cause of the pathogenic activation. We propose new theoretical and practical methods for the next drug generation development. Self-organization, network structure, hierarchical organization, non-linearity, feedback circuits, reactions to information, and the view of drugs as information clarify the existing pharmacological methods. We suggest a perspective and hierarchical vision of the human organism based on six levels (mechanic and structural; metabolic; bodily dynamic; emotional, cognitive, spiritual). The therapy should restore the self-organization of every level using the “intelligent” modulation of the network responses. Multi-targeted drugs should act on the remote cause of the pathogenic cascade and be administered based on personal variability and networks. This approach may help the development of individualized, precise, and integrated medicine.

Biological control is widely successful for controlling pests, but effective biocontrol agents are now more difficult to obtain due to more restrictive international trade laws. Coupled with increasing demand, the efficacy of existing and new biocontrol agents needs to be improved with genetic and genomic approaches. Although they have been underutilised in the past, applying genetic and genomic techniques is becoming more feasible from both technological and economic perspectives. We review current methods and provide a framework for using them, incorporating evolutionary and ecological principles. First, it is necessary to identify which biocontrol trait to select and in what direction. Next, the genes or markers linked to these traits need be determined to better target their selection, followed by how to implement this information into a breeding program. Choosing a trait can be assisted by modelling to account for the proper agro-ecological context, and by knowing which traits have sufficiently high heritability values. We provide guidelines for designing genomic strategies in biocontrol programs, which depends on the organism, budget, and desired objective. Genomic approaches start with genome sequencing and assembly. We provide a guide for deciding the most successful sequencing strategy for biocontrol agents. Gene discovery involves quantitative trait loci (QTL) analyses, transcriptomic and proteomic studies, and gene editing. Improving biocontrol practices include marker-assisted selection, genomic selection and microbiome manipulation of biocontrol agents, and monitoring for genetic variation during rearing and post-release. We conclude by identifying the most promising applications of genetic and genomic methods to improve biological control efficacy.

Understanding the evolution patterns in patients diagnosed with acute myeloid leukemia (AML) after therapy is relevant due to the dismal outcome still present in refractory or relapsed AML patients. We performed a retrospective, single-center study to evaluate the mutation profile in paired samples obtained at the time of diagnosis and at the onset of progressive or refractory disease in patients diagnosed with AML through a commercial next-generation sequencing (NGS) panel. In total, 62 patients were analyzed. Of these, 28 patients received ICT, and 34 patients underwent low-intensity treatments. In LIT patients, there were emergent mutations at progressive disease in a 64% (22/34) of the patients. Emergent mutations in the RAS-MAPK signaling pathway were observed in 35.9% (12/34) , corresponding to 54.5% of all patients with emergent mutations (12/22). These were found in 12/22 patients that received venetoclax in combination with hypomethylating agents. Six presented mutations in genes related to the RAS-MAPK pathway. Emerging mutations are frequently observed at progressive AML disease after therapy. In patients treated with LIT, mutations in RAS-MAPK signaling pathway might have a key role on the secondary clinical resistance, not only if they are present at diagnosis, becoming a potential target for the development of new drugs.

Chronic Myeloid Leukemia, resulting due to chromosomal aberration t(9;22) through formation of oncogenic BCR-ABL fusion oncogene. Modern BCR-ABL inhibitors, called TKIs, have revolutionized CML treatment. CML has three stages: chronic, accelerated, and blast crisis. TKIs work well in CP-CML, where patients survive as long as the normal population, but they don't work in AP- and BC-CML. Even with advances in treatment, BC-CML has an average overall survival of less than a year, giving oncologists little time to clinically intervene. Oncologists can delay or prevent CML advancement by detecting patients at risk of disease progression early and making timely treatment decisions, especially with third and fourth generation TKIs. However, no universal molecular biomarkers exist to diagnose CML patient groups at risk of disease progression. A recent study found that all BC-CML patients have mutant FANCD2. Our study was designed to detect mutant FANCD2 in AP-CML (early progression phase) to investigate its potential as a novel biomarker of early CML progression from chronic phase to accelerated phase due to the urgent need for such a biomarker. Our study comprised of 123 CP-CML (control group) and 60 AP-CML patients (as experimental group) from Hayatabad Medical Complex, Peshawar, Pakistan, from Jan 2020 to July 2023. DNA was extracted from the patients and FANCD2 gene was sequenced using Illumina next generation sequencer (NGS) Illumina MiSeq sequencer. NGS analysis revealed a unique splice site mutation in FANCD2 gene (c. 2022-5C>T). This mutation was detected in all CP-CML patients but in none of CP-CML. The mutation was confirmed by Sanger sequencing. FANCD2 is member of Fanconi anemia (FA-) pathway gene involved in DNA repair and genomic instability. Therefore, our studies show that FANCD2 (c. 2022-5C>T) mutation as a very specific molecular biomarker for early CML progression. We recommend to clinical validate this biomarker is prospective clinical trials.

Resistance to therapy and disease progression are the main causes of mortality in most cancers. In particular, the development of resistance is an important limitation affecting the efficacy of therapeutic alternatives for cancer, including chemotherapy, radiotherapy, and immunotherapy. Signaling pathways are largely responsible for the mechanisms of resistance to cancer treatment and progression, and multiple myeloma is no exception. p38 mitogen-activated protein kinase (p38) is downstream of several signaling pathways specific to treatment resistance and progression. Therefore, in recent years, developing therapeutic alternatives directed at p38 MAPK has been of great interest, in order to reverse chemotherapy resistance and prevent progression. In this review, we discuss recent findings on the role of p38, including recent advances in our understanding of its expression and activity as well as its isoforms, and its possible clinical role based on the mechanisms of resistance and progression in multiple myeloma.

In order to provide high capacity and universal access of telecommunication networks, this paper reviews and prospects the advanced multiplexing technology, physical layer digital signal processing technology, infrastructure sharing technology, security protection technology, intelligent control management and other key technologies for beyond 100G next generation passive optical network (NG-PON).

Increasing clinical and preclinical evidences implicate gut microbiome (GM) dysbiosis as a key susceptibility factor for neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s diseases (PD). In recent years, neurodegenerative diseases have not been viewed as driven solely by defects in brain, and the role of GM in modulating the central nervous system function via gut-brain axis has attracted considerable interest. Encouraged by GM researches, the next-generation probiotics may lead to tangible impacts on the treatment of neurodegenerative disorders. This review summarizes the current understandings of GM composition and characteristics associated with neurodegenerative diseases, and the demonstrations of molecules from GM affecting neurodegeneration. Particularly, applications of next-generation probiotics such as Clostridium butyricum, Akkermansia muciniphila, Faecalibacterium prausnitzii, and Bacteroides fragilis for remediation of neurodegenerative diseases are discussed.

Abstract Purpose of review: RNA therapeutics are a new and rapidly expanding class of drugs to prevent or treat a wide spectrum of diseases. We discuss the defining characteristics of the diverse family of molecules under the RNA therapeutics umbrella. Recent findings:RNA therapeutics are designed to regulate gene expression in a transient manner. For example, depending upon the strategy employed, RNA therapies offer the versatility to replace, supplement, correct, suppress, or eliminate the expression of a targeted gene. RNA therapies include antisense nucleotides, microRNAs and small interfering RNAs, RNA aptamers, and messenger RNAs. Further, we discuss the mechanism(s) by which different RNA therapies either reduce or increase the expression of their targets. Summary: We review the RNA therapeutics approved (and those in trials) to treat cardiovascular indications. RNA-based therapeutics are a new, rapidly growing class of drugs that will offer new alternatives for an increasing array of cardiovascular conditions.

ABSTRACT Surfactants are a broad category of tensio-active biomolecules with multifunctional properties applications in diverse industrial sectors and processes. Surfactants are produced synthetically and biologically. The biologically derived surfactants (biosurfactants) are produced from microorganisms with Pseudomonas aeruginosa, Bacillus subtilis Candida albicans and Acinetobacter calcoaceticus as dominant species. Rhamnolipids, sophorolipids, mannosylerithritol lipids, surfactin, and emulsan are well known in terms of their biotechnological applications. Biosurfactants can compete with the synthetic surfactants in terms of performance with established advantages over the synthetic ones including eco-friendliness, biodegradability, low toxicity, and stability over a wide variability of environmental factors. However, at present, the synthetic surfactants are a preferred option in different industrial applications, because of their availability in commercial quantities, unlike the biosurfactants. Usage of synthetic surfactants introduce new species of recalcitrant pollutants to the environment and lead to undesired results where a wrong selection of surfactants is made. Substituting synthetic surfactants with biosurfactants resolves these drawbacks, thus, interest has been intensified in biosurfactant applications in a wide range of industries hitherto considered as experimental fields. This review, therefore, intends to offer an overview of diverse applications where biosurfactants have found useful, with emphases in petroleum biotechnology, environmental remediation and in the agriculture sector. Application of biosurfactant in these settings would lead to industrial growth and environmental sustainability.

The explosive emergence of wireless technologies and standards, covering licensed and unlicensed spectrum bands has triggered the appearance of a huge amount of wireless technologies, with many of them coexisting in the same band. Unfortunately, the wireless spectrum is a scarce resource, and the available frequency bands will not scale with the foreseen demand for new capacity. Certain parts of the spectrum, in particular the license-free ISM bands, are overcrowded, while other parts, mostly licensed bands, may be significantly underutilized. As such, there is a need to introduce more advanced techniques to access and share the wireless medium, either to improve the coordination within a given band, or to explore the possibilities of intelligently using unused spectrum in underutilized (e.g., licensed) bands. Therefore, in this paper, we present an open source SDR-based framework that can be employed to devise disruptive techniques to optimize the sub-optimal use of radio spectrum that exists today. Additionally, we describe three use cases where the proposed framework can be employed along with intelligent algorithms to achieve improved spectrum utilization.

A fully automated bacteria whole genome sequencing (WGS) assay was evaluated to characterize Mycobacterium tuberculosis (MTB) and non-tuberculosis Mycobacterium (NTM) clinical isolates. Results generated were highly reproducible with 100% concordance in species and sub-lineage classification, and 92% concordance between antimicrobial resistance (AMR) genotypic and phenotypic profiles. These findings demonstrate that a fully automated WGS assay, with a short turnaround time of 24.5 hours, provides timely and valuable insights into MTB outbreak investigation while providing reliable genotypic AMR profiling consistent with traditional antimicrobial susceptibility tests (AST). This study establishes a favorable proposition in the adoption of an end-to-end fully automated WGS solutions for decentralized TB diagnostics, thereby aiding in WHO’s vision of tuberculosis eradication.

Coronary artery disease is the most prevalent cardiovascular disease, claiming millions of lives annually around the world. The current treatment includes surgically inserting a tubular construct called as a stent inside arteries to restore blood flow. However, due to lack of patient-specific design, the commercial products cannot be used with different vessel anatomies. In this review, we have summarized the drawbacks in existing commercial metal stents which face problems of restenosis and inflammatory responses, owing to the development of neointimal hyperplasia. Further, we have highlighted the fabrication of stents using biodegradable polymers, which can circumvent most of the existing limitations. In this regard, we elaborated on utilization of new fabrication methodologies based on additive manufacturing such as three-dimensional printing to design patient-specific stents. Finally, we have discussed on the functionalization of these stent surfaces with suitable bioactive molecules which can prove to enhance their properties in preventing thrombosis and better healing of injured blood vessel lining.

Inflammatory diseases are common pathological processes caused by various acute and chronic factors and some of them are autoimmune diseases. Exosomes are fundamental extracellular vesicles secreted by almost all cells, which contain a series of constituents, i.e. cytoskeletal and cytosolic proteins (actin, tubulin, histones), nucleic acids (mRNA, miRNA, DNA), lipids (diacylglycerophosphates, cholesterol, sphingomyelin, ceramide), and other bioactive components (cytokines, signal transduction proteins, enzymes, antigen presentation and membrane transport/fusion molecules, adhesion molecules). This review would be a synopsis of the actual knowledge on the contribution of exosomes from different cell sources as possible therapeutic agents against inflammation, focusing on several inflammatory diseases, neurological diseases, rheumatoid arthritis and osteoarthritis, intestinal bowel disease, asthma, liver and kidney injuries. Current knowledge indicates that the role of exosomes in therapy of inflammation and in inflammatory diseases could be distinctive. Main limitations to their clinical translation are still production, isolation, and storage. Additionally, there is an urgent need to personalize the treatments in terms of selection of exosomes, their dosages and routes of administration, and a deeper knowledge about their biodistribution, type and incidence of adverse events and long-term effects of exosomes. In conclusion, exosomes can very promising next generation therapeutic option, superior to synthetic nanocarriers and cell therapy, and can represent a new strategy of effective, safe, versatile and selective delivery systems in the future.

Self-healing is the capability of materials to repair themselves after damage has occurred, usually by interaction between molecules or chains. Physical and chemical processes are applied for the preparation of self-healing systems. There are different approaches for these systems such as heterogeneous systems, shape memory effects, hydrogen bonding or covalent-bond interaction, diffusion and flow dynamics. Self-healing mechanisms can occur in particular by heat and light exposure or by reconnection without direct effect. The applications of these systems display an increasing trend in both R&D and industry sectors. Moreover, self-healing systems and their energy storage applications are currently getting great importance. This review aims to provide general information on recent developments in self-healing materials and their energy applications in view of the critical importance of self-healing systems for lithium-ion batteries (LIBs). In the first part of the review, an introduction about self-healing mechanisms and design strategies of self-healing materials is given. Then, selected important healing materials in the literature for the anodes of LIBs are mentioned in the second part. The results and future perspectives are stated in the conclusion section.

It has been widely established that the characterization of extracellular vesicles (EVs), particularly small EVs (sEVs), shed by different cell types into biofluids, helps identify biomarkers and therapeutic targets in neurological and neurodegenerative diseases. Recent studies are also exploring the efficacy of mesenchymal stem cell-derived extracellular vesicles naturally enriched with therapeutic microRNAs and proteins for treating various diseases. Besides, EVs released by various neural cells play a crucial function in the modulation of signal transmission in the brain in physiological conditions. However, in pathological conditions, such EVs can facilitate the spread of pathological proteins from one brain region to the other. On the other hand, analysis of EVs in biofluids can identify sensitive biomarkers for diagnosis, prognosis, and disease progression. This review discusses the potential therapeutic use of stem cell-derived EVs in several central nervous system diseases. It lists their differences and similarities and confers various studies exploring EVs as biomarkers. Further advances in EV research in the coming years will likely lead to the routine use of EVs in therapeutic settings.

Plant viral diseases constitute a major contributor to agricultural production losses, significantly impacting the economies of exporting countries by more than $30 billion annually. Understanding and researching the biology and genomics of viruses is crucial for developing virus-resistant, genetically edited or genetically modified plants. Genetic modifications can be targeted to specific regions within genes of target plants which are important or essential for the virus to establish a systemic infection, thus fostering resistance or enabling plants to effectively respond to invading agents while preserving their yield. This review provides an overview of viral incidence and diversity in tropical fruit crops and aims to examine the current state of the knowledge on recent research efforts aimed at reducing or eliminating the damage caused by viral diseases, with emphasis on genetically edited products that have reached the market in recent years.

The utilisation of the industrial residual products to develop new value-added materials and to reduce footprint is one of the critical challenges of science and industry. Development of the new multifunctional and bio-based composites materials is an excellent opportunity for the effective utilisation of industrial residual products. Keeping the different issues in mind, in this work, we describe the manufacturing and characterisation of the three-phases bio-based composites. The key components are bio-based binder made of peat, devulcanised crumb rubber (DCR) from used tires and part of the fly ash, i.e. the cenosphere (CS). The three-phase composite prepared in the form of a block were investigated for their mechanical properties and density. The three-phase composite was prepared in the form a) of a block were investigated for their mechanical properties, and density and b) a form of granules for determination of the water and oil products sorption were investigated. We have also investigated the dependence of the properties on the DCR and CS fraction. It has been found, that maximum compression strength (in block form) observed for composition without CS and DCR addition was- 79.3 MPa, while the second-highest value of compression strength is 11.2 MPa for composition with 27.3 wt% of CS. For compositions with bio binder content from 17.4 to 55.8 wt% and with DCR contents in range from 11.0 to 62.0 wt%, the compression strength is in the range from 1.1 to 2.0 MPa. Liquid sorption analysis (water and diesel) showed that the maximum saturation of liquids in both cases is set after 35 minutes and ranges from 1.05 to 1.4 g·g -1 for water and 0.77 to 1.25 g·g-1 for diesel. It was noted that 90% of the maximum saturation with diesel fuel comes after 10 minutes and for water after 35 minutes.

Small modular reactors (SMR) (<300 MW) offer a potentially attractive nuclear energy option for the middle-east region (MER). Currently, the MER uses a significant amount of fossil fuel to process heat applications such as water desalination and in petroleum refineries and chemical plants, besides generating electricity. SMR technologies represent an opportunity to meet future energy demand in the MER. This paper discusses issues related to the future development and use of SMR technology in nuclear-renewable hybrid energy systems for application in the middle east. SMRs have also been examined as part of a resilient hybrid energy system that combines nuclear energy with renewable energy and traditional fossil energy to produce chemicals, fuels, and electricity. This paper presents the results of a techno-economic analysis of a Nuclear-Renewable-Conventional Hybrid Energy System. The paper concludes that SMR technology will be an essential feature of future hybrid energy systems for the MER.

Protein tyrosine sulfation (PTS), a vital post-translational modification, facilitates protein–protein interactions and regulates many physiological and pathological responses. Monitoring PTS has been difficult owing to the instability of sulfated proteins and the lack of a suitable method for detecting the protein sulfate ester. In this study, we combined an in situ PTS system with an ultra-high-sensitivity polysilicon nanowire field-effect transistor (pSNWFET)-based sensor to directly monitor PTS formation. A peptide containing the tyrosine sulfation site of P-selectin glycoprotein ligand (PSGL)-1 was immobilized onto the surface of the pSNWFET by using 3-aminopropyltriethoxysilane and glutaraldehyde as linker molecules. A coupled enzyme sulfation system consisting of tyrosylprotein sulfotransferase and phenol sulfotransferase was used to catalyze PTS of the immobilized PSGL-1 peptide. Enzyme-catalyzed sulfation of the immobilized peptide was readily observed through the shift of the drain current–gate voltage curves of the pSNWFET before and after PTS. To the best of our knowledge, this is the first study to describe in situ PTS and its direct observation by using semiconductor devices. We expect that this approach can be developed as a next generation biochip for biomedical research and industries.

Atopic dermatitis (AD) is a chronic skin disease marked by inflammation, erythema, dryness and pruritic lesions. Due to the intermittent nature of the disease, management strategies for AD focus on flare prevention following remission. A 24-year-old patient with mild-to-moderate AD lesions, previously non-responsive to topical corticosteroids (TCS), was treated with pimecrolimus for 12 days and emollient plus cream (EC) every day. After the initial 12-day treatment course, the patient was advised to use pimecrolimus if his symptoms reoccured. AD symptoms improved substantially between Weeks 0 and 12 with daily use of EC. However, by Week 12, his symptoms had relapsed, necessitating retreatment with pimecrolimus. Overall, the patient experienced flare-free periods between Weeks 3 and 12 and between Weeks 13 and 16. No tolerability issues were reported. This case report demonstrates the use of a complementary approach of daily administration of maintenance EC and intermittent application of pimecrolimus for flare management, which was effective for treating a patient with mild-to-moderate AD resistant to TCS.

The integration of Wireless Power Transfer (WPT) technologies with Artificial Intelligence (AI) is poised to revolutionize multiple industries, including consumer electronics and industrial applications. This study delves into the latest advancements in WPT, with a focus on AI-enhanced efficiency, range, and reliability. AI-driven algorithms optimize power transfer, improve device alignment, and predict maintenance needs, leading to smarter and more sustainable power solutions. Machine learning and computer vision are employed to achieve precise alignment, while predictive maintenance minimizes downtime and costs. Additionally, AI-powered power management systems adapt to varying demands, optimizing energy usage. This research highlights the transformative potential of AI in enhancing WPT technologies, with significant implications for next-generation applications. The findings emphasize the importance of ongoing research in this interdisciplinary field to address existing challenges and unlock new opportunities for innovation.

This literature review offers a comprehensive analysis of antenna designs tailored for 6G applications and THz communications. Various antenna types, including elliptical lens, WHEMS, grid array, CP horn, Quasi Yagi-Uda, patch, transmit array, Vivaldi patch, SRR slotted waveguide array, RCA, and Cassegrain antennas, are scrutinized in terms of their dimensions, characteristics, frequency ranges, and materials. The study highlights existing works on antenna design for 6G applications, exploring different fabrication techniques like PCB technology, LCP technology, Topas fabrication, Wire-cutting EDM, 3D Printing, Laser-drilling processes, and CNC machining. Notably, PCB technology exhibited promise with antennas such as WHEMS, patch, and Vivaldi patch, achieving significant bandwidth and gain. However, gaps remain in research, urging further exploration into additional fabrication methods and antenna designs to meet the demands of 6G networks. The study underlines the need for advanced, intelligent antennas capable of higher bandwidth and better performance in view of future wireless communications technologies such as 6G.

The HER2-targeted antibody-drug conjugates (ADCs) trastuzumab emtansine (T-DM1) and Trastuzumab deruxtecan (T-DXd) improved outcomes in breast cancer. Novel combinations and sequential approaches are under investigation to overcome resistance to T-DM1 and T-DXd. Furthermore, the landscape of HER2-targeted therapy is rapidly advancing with the development of ADCs designed to attack cancer cells with greater precision and reduced toxicity. Disitamab Vedotin (RC48) incorporates a HER2 antibody with unique binding epitope and a potent microtubule inhibitor as its cytotoxic moiety. ARX-788 comprises a non-cleavable linker and a novel maytansinoid derivative as the cytotoxic drug, engineered for increased stability and a higher drug-to-antibody ratio. SYD985, a duocarmycin-based ADC, is designed to be activated only in the acidic environment of the tumor, thus reducing off-target effects. BL-M0701 targets a different epitope on the HER2 protein, which might be beneficial in circumventing resistance that affects the binding of other ADCs and incorporate a camptothecin derivative as its payload. Zanidatamab zovodotin (ZW25) is an ADC that binds to two different HER2 epitopes simultaneously, enhancing the internalization and delivery of its cytotoxic payload. These and other ADCs in phase I trials hold the potential to improve outcomes for HER2-positive and HER2-Low breast cancer and possibly other solid tumors.

Microbial biofilms cause several environmental and industrial issues, even on the human health. Although they have represented a threaten due to their resistance to antibiotics, there are currently no approved antibiofilm agents for clinical treatments. The multi-functionality of antimicrobial peptides (AMPs) including the antibiofilm activity and their potentialities to target multiple mi-crobes motivated the synthesis of AMP relatives for developing antibiofilm agents for clinical purposes. Antibiofilm peptides (ABFPs) have been organized in databases that allowed the building of prediction tools which have assisted in the discovery/design of new antibiofilm agents. However, the complex network approach has been explored yet as an assistant tool for this aim. Herein, a kind of similarity networks, called the Half-Space Proximal Network (HSPN) is applied to represent/analyse the chemical space of the ABFPs aimed to identify promising scaf-folds for the development of next generation antimicrobials, able to target both planktonic and biofilm microbial forms. Such analyses also considered the metadata associated to the ABFPs such as origin, other activities, targets, etc. in which the relationships were projected by multilayer networks called metadata networks (METNs). From the complex networks mining, a reduced but informative set of 66 ABFPs representing the original antibiofilm space was extracted. This subset retained from the most central to atypical ABFPs, having some of them, desired properties for developing next generation antimicrobials. So, this subset is advisable for assisting the search/design both new antibiofilm/antimicrobial agents. The provided ABFP motifs list, dis-covered within the HSPN communities, is also useful for the same purpose.

Many types of banana (Musa spp.)—one of the most economically important horticultural crops—exist, and their ploidy (diploid, triploid, and tetraploid, usually) and genome types (containing A or/and B genome in most cases) differ. At present, observation and genome type detection are commonly used to identify banana germplasm resources. However, the former is tedious, while the latter cannot distinguish categories below genome types. It is therefore urgent that a simple and effective method for identifying banana germplasm resources is established. We sequenced and analyzed the ribosomal DNA internal transcribed spacer (ITS) sequences of 62 banana germplasm and found that the sequencing peaks, especially the 20 bp region near the 420 bp position (referred to as the “420 bp region”), exhibited relatively recognizable and repeatable polymorphism characteristics. Using the “420 bp region” as a marker, we were able to quickly distinguish bananas belonging to different genome type groups (comprising the AA, AB, AAA, ABB, AAB, ABBB, AAAB, and AAAA groups) or different subgroups in the same genome type group (for example, the Cavendish, Gros Michel, Red, Lakatan, and Ibota Bota subgroups in the AAA group; and the Pisang Raja, Plantain, Pome and Silk subgroups in the AAB group). Moreover, it appeared that Sanger sequencing of ITS could be used for identifying banana hybrid offspring. These results demonstrated that the banana ITS region contains rich genetic information that is useful for genotyping. In general, ITS sequencing simplifies the classification of banana germplasm resources and has potential application in several areas of Musa improvement.

Transparent materials used for facial protection equipment provide protection against microbial infections caused by viruses and bacteria, including multidrug-resistant strains. However, transparent materials used for this type of application are made of materials that do not possess antimicrobial activity. They just avoid direct contact between the person and the biological agent. Therefore, healthy people can get infected through contact of the contaminated material surfaces and this equipment constitute an increasing source of infectious biological waste. Furthermore, infected people can transmit microbial infections easily because the protective equipment do not inactivate the microbial load generated while breathing, sneezing, or coughing. In this regard, the goal of this work consisted of fabricating a transparent face shield with intrinsic antimicrobial activity that could provide extra-protection against infectious agents and reduce the generation of infectious waste. Thus, a single-use transparent antimicrobial face shield composed of polyethylene terephthalate and an antimicrobial coating of benzalkonium chloride has been developed for the next generation of facial protective equipment. The antimicrobial coating was analyzed by atomic force microscopy and field emission scanning electron microscopy with elemental analysis. This is the first facial transparent protective material capable of inactivating enveloped viruses such as SARS-CoV-2 in less than one minute of contact, and the methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. Bacterial infections contribute to severe pneumonia associated with the SARS-CoV-2 infection, and their resistance to antibiotics is increasing. Our extra protective broad-spectrum antimicrobial composite material could also be applied for the fabrication of other facial protective tools such as such as goggles, helmets, plastic masks and space separation screens used for counters or vehicles. This low-cost technology would be very useful to combat the current COVID-19 pandemic and protect health care workers from multidrug-resistant infections in developed and underdeveloped countries.

Among all economically important plant species in the world, grapevine (Vitis vinifera L.) is the most cultivated fruit plant. It has a significant impact on the economies of many countries through wine and fresh and dried fruit production. In recent years, the grape and wine industry has been facing outbreaks of known and emerging viral diseases across the world. Although high-throughput sequencing (HTS) has been used extensively in grapevine virology, the application and potential of third-generation sequencing have not been explored in understanding grapevine viruses and their impact on the grapevine. Nanopore sequencing, a third-generation technology, can be used for direct sequencing of both RNA and DNA with minimal infrastructure. Compared to other HTS methods, the MinION nanopore platform is faster and more cost-effective and allows for long-read sequencing. Due to the size of the MinION device, it can be easily carried for field viral disease surveillance. This review article discusses grapevine viruses and their diagnostic methods, the principle of nanopore sequencing technology and its application in grapevine virus detection, virus–plant interactions, as well as the characterization of viral RNA modifications.

Recently, considerable work has been directed at development of a ultra-compact X-ray free-electron laser based on emerging techniques in high field cryogenic acceleration, with attendant dramatic improvements in electron beam brightness, and state-of-the-art concepts in beam dynamics, magnetic undulators, and X-ray optics. A full conceptual design of a 1 nm XFEL with a length and cost over an order of magnitude below current XFELs has resulted from this effort. This instrument has been developed with an emphasis on permitting exploratory scientific research in a wide variety of fields in a university setting. Concurrently, compact FELs are being urgently developed for use as an instrument to enable next generation chip manufacturing through use as a high flux, few-nm lithography source. This new role suggests consideration of XFELs to addressed urgently emerging demands in this sector, as identified by recent national need studies, for new radiation sources aimed at chip manufacturing: a coherent hard X-ray source which enables frontier metrology methods. Indeed, it has been shown that one may use coherent X-rays to perform 10 nm-class resolution surveys of macroscopic, cm-scale structures such as chips, using ptychographic laminography. As the XFEL is a very promising candidate for realizing such methods, we present here an analysis of the issues and likely solutions associated with extending the UCXFEL to harder X-rays (above 7 keV), much higher fluxes and levels of coherence, and methods of applying such a source for ptychographic laminography to micro-electronic device measurements. We discuss the development path to move the concept to rapid realization of a transformative FEL-based application, outlining FEL and metrology system challenges.

The National Agrobiodiversity Center under the Rural Development Administration (RDA) in Jeonju, Republic of Korea, is the largest international genebank of Korea. The National Agrobi-odiversity Center has continuously been making efforts to introduce overseas genetic resources to its collection and has currently grown into a world-class PGR holding genebank. Currently, several steps are undertaken to, improve the accessibility of the collection to national as well as international researchers, improve data available on the resources and amend the passport in-formation of the accessions. With the implementation of the Nagoya Protocol, the origin of ge-netic resources is being highlighted as an important input in the passport information of germplasms. The RDA-Genebank actively responds to the Nagoya Protocol by supplementing passport data of resources lacking information on the origin of germplasm. In addition, a large number of conserved resources are continuously multiplied, and agronomic traits are investi-gated concurrently. With the traditional methods of characterization of the germplasm requiring a significant amount of time and effort, we have intiated high-throughput phenotyping using digital techniques to improve our germplasm data. Primarily, we have started adding seed phenotype information followed by measuring root phenotypes which are stored under agro-nomic traits. This may be the initial step for a germplasm center to use large-scale high-throughput techniques for their collection. In this shortcommunication, we aim to provide an introduction to the RDA- Genebank, adopted international standards, and establishment of high throughput phenotyping techniques for improvement of passport information.

Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold certain promise for regenerative medicine. This paper is intended to clarify and facilitate the understanding, development and adoption of regenerative medicine in general and specifically of therapies based on unmodified, autologous adipose-derived regenerative cells (UA-ADRCs). To this end, results of landmark experiments on stem cells and stem cell therapy performed in the labs of the authors are summarized, the most intriguing of which are the following: (i) vascular associated mesenchymal stem cells (MSCs) can be isolated from different organs (adipose tissue, heart, skin, bone marrow and skeletal muscle) and differentiated into ectoderm, mesoderm and endoderm, providing significant support for the hypothesis of the existence of a small, ubiquitously distributed, universal vascular associated stem cell with full pluripotency; (ii) the orientation and differentiation of MSCs are driven by signals of the respective microenvironment; and (iii) these stem cells irrespective of the tissue origin exhibit full pluripotent differentiation potential without any prior genetic modification or the need for culturing. They can be obtained from a small amount of adipose tissue when using the appropriate technology for isolating the cells, and can be harvested from and re-applied to the same patient at the point of care without the need for complicated processing, manipulation, culturing, expensive equipment, or repeat interventions. These findings demonstrate the potential of UA-ADRCs for triggering the development of an entire new generation of medicine for the benefit of patients and of healthcare systems.

The interest in flying wings dates as far the early years of the aviation age. Over the 20th century, numerous attempts were made to investigate the feasibility of the concept, which demonstrated numerous early benefits: increased aerodynamic efficiency, reduced fuel consumption and lower noise and pollutant emissions compared to conventional tube and wing aircraft. However, major technical challenges prevented that type of design from entering mass production, especially with regards to structural design and manufacturing, stability and control and ride quality. In the 1990’s, a new concept, the blended wing body (BWB), was created to alleviate some of the concerns of flying wings while maintaining increased efficiency. Despite the promise, technical hurdles once again proved to be a deal breaker, and as of 2024, the only flying wing to enter serial production is the B-2 Spirit, an extremely complex and expensive aircraft. Thirty years later, as the world is quickly transitioning towards cleaner energy, the interest in the blended wing body has been renewed. The latest technological advancements in the aerospace industry should make the development of the BWB more plausible, however passenger comfort issues remain. Surprisingly, the BWB development may come from an unexpected application: as a tanker aircraft. As the U.S. Air Force is seeking a replacement to hundreds of aging tankers, a startup company was recently funded to develop the concept and build a prototype. In this study, we explore the history of blended designs from its early days, highlighting its opportunities and challenges – and why the design is an intriguing fit for application as a tanker aircraft.

Background and aim We investigated the clinical outcomes of patients with hepatocellular carcinoma (HCC) who underwent next-generation microwave thermosphere ablation (MTA). Methods A total of 429 patients with 607 HCCs (maximum tumor diameter ≤40 mm) were included. Results The primary etiologies of HCC were hepatitis-related: 259 (60.4%) cases of HCV, 31 (7.3%) cases of HBV, and two instances of both. Median maximum tumor diameter was 15.0 (interquartile range, 10.0–21.0) mm. There were 86 tumors in areas of the liver where MTA is difficult. The most common area was near the primary and secondary branches of the intrahepatic portal vein (26 nodules). The cumulative local tumor recurrence rates at 1, 2, and 3 years were 4.4%, 8.0%, and 8.5%, respectively. The cumulative local tumor recurrence rate differed significantly by tumor size group: ≤20 mm group (n=483), 20–30 mm group (n=107), and ≥30 mm group (n=17) (p<0.001). The cumulative local tumor recurrence rate was similar by difficult-to-treat status (p=0.169). In the multivariable analysis, tumor size (per 1 mm) (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.03–1.11; p<0.001) and ablative margin (per 1 mm) (HR, 0.81; 95% CI, 0.70–0.92; p=0.002) were significantly associated with local tumor recurrence. Only tumor size (per 1 mm) (odds ratio, 1.08; 95% CI, 1.02–1.15; p=0.015) was significantly associated with complications. Conclusions MTA is a safe and effective local ablation therapy for HCC, even for tumors located in areas of the liver where local ablation therapy is difficult.

The traditional practice of harvesting and processing raw date palm sap is not only culturally significant but also an essential nutritional source in South Asia. Yet, the potential for bacterial or viral contamination from animals and environmental sources during its collection remains a real and insufficiently studied risk. Implementing improved food safety measures and collection techniques could mitigate the risk of these infections. Additionally, the adoption of advanced food analytical methods has the potential to identify pathogens and uncover the natural bacterial diversity of these products. The advancement of NGS technologies, particularly nanopore sequencing, offers rapid and highly mobile capabilities. In this study, we employed nanopore sequencing for bacterial metabarcoding of a set of raw date palm sap samples collected without protective coverage against animals in Bangladesh in 2021. We identified several bacterial species with importance in the natural fermentation of the product and demonstrated the feasibility of this NGS method in the surveillance of raw palm sap products. We revealed two fermentation directions dominated by either Leuconostoc species or Lactococcus species in these products at the first 6 hours from harvest along with opportunistic human pathogens in the background, represented with low abundance. Plant pathogens, bacteria with the potential for opportunistic human infections and the sequences of the Exiguobacterium genus were also described and their potential role is discussed.

This study aimed to determine shifts in microbial populations regarding richness and diversity from the daily use of a popular over-the-counter nasal spray. In addition, the finding of nasal commensal bacterial species that overlap with the oral microbiome may prove to be potential probiotics for the “gateway microbiomes.” Nasal swab samples were obtained before and after using the most popular over-the-counter (OTC) nasal spray in 10 participants aged 18–48. All participants were healthy volunteers with no significant medical histories. The participants were randomly assigned a number by randomizing software and consisted of five men and five women. The sampling consisted of placing a nasal swab atraumatically into the nasal cavity. The samples were preserved and sent to Northwestern University Sequencing Center for whole-genome deep sequencing. After 21 days of OTC nasal spray use twice daily, the participants returned for further nasal microbiome sampling. The microbial analysis included all bacteria, archaea, viruses, molds, and yeasts via deep sequencing for species analysis. The Northwestern University Sequencing Center utilized artificial intelligence analysis to determine shifts in species and strains following nasal spray use that resulted in changes in diversity and richness.

This review explores the potential of Intelligent Reflecting Surfaces (IRS) to address limitations of traditional antennas and empower next-generation wireless networks. IRS technology offers a paradigm shift by passively manipulating radio waves, enhancing signal coverage, network capacity, and energy efficiency. IRS technology utilizes flat surfaces equipped with tiny, adjustable reflectors. Unlike traditional antennas that actively send and receive radio waves, IRS passively manipulates incoming signals by reflecting them in specific directions with controlled adjustments. This approach significantly improves signal coverage and strength, particularly in areas with poor reception. The review reveals the IRS technology offers significant advantages over traditional antennas. It can enhance signal coverage by reflecting radio waves, boost network capacity which allows networks to handle a larger number of users simultaneously, promote lower energy consumption compare, and unlock potential of 6G Networks and beyond. Additionally, IRS enables functionalities such as enhanced localization and ultra-fast data transfer. Integrating IRS with next-generation antennas unlocks new possibilities. This includes reconfigurable antennas that dynamically adjust radiation patterns, compact and low-profile designs, and multi-functional antennas that support various services simultaneously. In conclusion, this paves the way for a new generation of robust and sustainable wireless communication systems.

Cardiomyopathy is the leading cause of morbidity and mortality among all complications of type 2 diabetes (T2D) and obese patients. Diabetic cardiomyopathy (DC) is characterized by changes in cardiac morphology with declines in both systolic and diastolic functions. No rodent models fully captured phenotypes of DC. The ZDSD rat, a new generation of T2D rat model with intact leptin signaling features with slow onset of diabetes and obesity, which closely mimics the development of the disease in patients. Age-matched male ZDSD and SD rats were monitored for blood pressure, glucose and cardiac function using echocardiography. Animals were also challenged with 1 mg/kg dobutamine for the assessment of cardiac reserve. ZDSD rats developed hypertension from age of 18 weeks with blood pressure significantly higher than controls. At resting state, ZDSD rats showed biphasic changes in left ventricular posterior wall thickness and cavity volume. Concomitantly, both ejection fraction (EF) and transmitral E/A ratio of LV declined at 34 weeks old. Upon treatment with dobutamine, ZDSD lost cardiac contractility. Therefore, ZDSD rats may serve as a suitable preclinical model to study potential therapeutic approaches to treat cardiomyopathy with presence of metabolic syndromes.

: Tunnel instability and lining integrity are intimately tied to the creep properties of the surrounding rock. The acquisition of rock mass creep parameters is critical in ascertaining the appropriate timing for lining construction. Nevertheless, creep tests on rock specimens conducted in a controlled setting cannot be straightforwardly extrapolated to rock mass creep analysis. This study performs laboratory-based creep tests on mudstone samples and establishes the corresponding creep constitutive model. Integration of a Mohr-Coulomb element with the Burgers model in series serves to characterise the yield creep behaviour of the rock mass. Additionally, the research outlines a series of 100 orthogonal experiments utilising randomised creep parameters, and formulates a GA-BP neural network inversion model. Employing long-term deformation measurements from the crown and sidewalls of the project site, this study deduces the creep parameters of the mudstone in the investigated tunnel section and examines the prolonged deformation traits of the surrounding rock. Drawing on the deformation traits of the surrounding rock and the forces impacting the primary support and lining structures, this paper evaluates the earliest and latest viable lining casting periods and pinpoints an optimal timing interval for lining implementation. The methodologies employed herein can serve as a benchmark for analogous endeavors internationally.

The purpose of this paper is to explore the implementation of Retrieval-Augmented Gen- 14 eration (RAG) technology with open-source Large Language Models (LLMs). For this purpose, a 15 web-based application named PaSSER that integrates RAG with three models - Mistral:7b, 16 Llama2:7b: Orca2:7b, is developed. In its development various technologies are used, including 17 Blockchain for managing and storing assessment results of built-in testing modules. PaSSER em- 18 ploys a set of evaluation metrics for LLMs’ performance - METEOR, ROUGE, BLEU, Perplexity, 19 Cosine similarity, Pearson correlation, and F1 score. The specialized knowledge base is in the smart 20 agriculture domain. As an illustration, the paper presents results and analysis of two tests. First one 21 is assessing the performance of LLMs across different hardware configurations, the other is deter- 22 mining the model that delivers most accurate and contextually relevant responses within the RAG. 23 The paper also discusses the integration of blockchain technology with LLMs to manage and store 24 assessment results within a blockchain environment. The tests revealed that Mistral:7b demon- 25 strates the best results across most of the evaluated metrics. The discussion section comments on 26 technical and hardware considerations that affect the performance of LLMs. Future development 27 will focus in leveraging new larger pre-trained open-source LLMs, exploring different finetuning 28 approaches, and further integration with Blockchain and IPFS.

Migraine is a neurovascular disorder that can be debilitating for individuals and society. Current research focuses on finding effective analgesics and management strategies for migraines by targeting specific receptors and neuropeptides. Nevertheless, the responder rates of recently approved calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and receptor inhibitors remain around 50 percent. To address the need for novel therapeutic targets, researchers are exploring the potential of another secretin family peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), as a ground-breaking treatment avenue for migraine. Preclinical models have revealed how PACAP affects the trigeminal system, which is implicated in headache disorders. Clinical studies have demonstrated the significance of PACAP in migraine pathophysiology; however, a few clinical trials remain inconclusive: the pituitary adenylate cyclase-activating peptide 1 receptor mAb, AMG 301 showed no benefit for migraine prevention, while the PACAP ligand mAb, Lu AG09222 significantly reduced the number of monthly migraine days over placebo in a phase 2 clinical trial. Meanwhile, another secretin family peptide vasoactive intestinal peptide (VIP) is gaining interest as a potential new target. In light of recent advances in PACAP research, we emphasize the potential of PACAP as a promising target for migraine treatment, highlighting the significance of exploring PACAP as a member of the antimigraine armamentarium, especially for patients who do not respond to or contraindicated to anti-CGRP therapies. By updating our knowledge on PACAP and its unique contribution to migraine pathophysiology, we can pave the way for reinforcing PACAP and other secretin peptides, including VIP, as a novel treatment option for migraines.

This paper performs a comprehensive analysis of the wind energy potential of onshore regions in Greece with emphasis on quantifying the volume risk and the spatial covariance structure. Optimization techniques are employed to derive efficient wind capacity allocation plans (also known as generation portfolios) incorporating different yield aspirations. The generation profile of minimum variance and other optimal portfolios along the efficient frontier are subject to rigorous evaluation using a fusion of descriptive and statistical methods. In particular, principal component analysis is employed to estimate factor models and investigate the spatiotemporal properties of wind power generation, providing valuable insights into the persistence of volume risk. The overarching goal of the study is to employ a set of statistical and mathematical programming tools guiding investors, aggregators and policy makers in their selection of wind energy generating assets. The findings of this research challenge the effectiveness of current policies and industry practices, offering a new perspective on wind energy harvesting with a focus on the management of volume risk.

The classic, chronic Philadelphia chromosome-negative (Ph-) myeloproliferative neoplasms (MPN)- mainly essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF)— represent a heterogeneous group of stem cell disorders characterized by clonal proliferation of one or more hematopoietic cell lineages with organomegaly and constitutional symptoms. Several studies have shown that the presence of chronic inflammation and a dysregulated immune system play indisputable roles in the pathogenesis of these diseases. Lately, the treatment of cancer including hematological malignancy has progressed on the agents targeting the immune system, cytokine milieu, immunomodulatory agents, and targeted immune therapy. Immune checkpoints are the molecules that regulate T cells function in the tumor microenvironment (TME). The fully unraveled primary immune checkpoints are programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte antigen-4 (CTLA-4). Immune checkpoint inhibitor therapy (ICIT) is based on blocking the inhibitory pathways in T cells to promote anti-tumor immune responses and has revolutionized cancer treatment paradigms. Despite the impressive clinical success of ICIT, tumor intrinsic resistance remains a daunting challenge for oncologists leading to a low response rate in solid tumors and hematological malignancies. A phase II trial on Nivolumab for patients with Primary Myelofibrosis, post-Essential thrombocythemia myelofibrosis, or post- Polycythemia myelofibrosis has been performed (ClinicalTrials.gov Identifier: NCT02421354). This clinical trial, on the efficacy of PD-1 blockade using the monoclonal antibody Nivolumab, was prematurely terminated due to a lack of efficacy and adverse events. A multicenter, open-label, phase 2, single-arm study was conducted including pembrolizumab in patients with Dynamic International Prognostic Scoring System category of intermediate-2 or greater primary, post-essential thrombocythemia or post-polycythemia vera myelofibrosis that were ineligible for or were previously treated with Ruxolitinib. Pembrolizumab treatment was well tolerated, but there were no objective clinical responses, so the study closed after the first stage was completed. To permit more patients to benefit from immunotherapy, the focus has changed to targeting alternative novel immune checkpoints in the tumor microenvironment such as lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin, and mucin domain 3 (TIM-3), V-domain immunoglobulin-containing suppressor of T-cell activation (VISTA), T cell immunoglobulin and ITIM domain (TIGIT) and human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) forming the basis of next-generation ICIT. Our article aims at emphasizing and discovering the role of next-generation ICIT in MPN as targeted immunotherapy involving monoclonal antibodies, checkpoint inhibitors, or therapeutic vaccines against selected MPN epitopes that could further enhance tumor-specific immune responses. Immunotherapeutic approaches are expanding and hopefully will extend the therapeutic armamentarium in patients with myeloproliferative neoplasms. Preliminary studies from our laboratory showed over-expressed MDSC and over-expressed VISTA in MDSC, and in progenitor and immune cells directing the need for more clinical trials using next-generation ICI in the treatment of MPN.

Radiolabelled tracers targeting the prostate-specific membrane antigen (PSMA) have become important radiopharmaceuticals for the PET-imaging of prostate cancer. In this connection we recently developed the fluorine-18 labelled PSMA-ligand [¹⁸F]PSMA-1007 as next generation radiofluorinated Glu-ureido PSMA inhibitor after [¹⁸F]DCFPyL and [¹⁸F]DCFBC. Since radiosynthesis so far was suffering for rather poor yields novel procedures for the automated radiosyntheses of [¹⁸F]PSMA-1007 have been developed. We herein report on both the two-step and the novel one-step procedures, which have been performed on different commonly used radiosynthesisers. Using the novel one-step procedure the [¹⁸F]PSMA-1007 was produced in good radiochemical yields ranging from 30-70 % and synthesis times less than 55 minutes. Furthermore, upscaling to product activities up to 50 GBq per batch was successfully conducted. All batches passed quality control according to European Pharmacopoeia standards. Therefore, we were able to disclose a new, simple and at the same time high yielding production pathway for the next generation PSMA radioligand [¹⁸F]PSMA-1007. Actually it turned out that the radiosynthesis is as easily realised as the well-known [¹⁸F]FDG synthesis and thus transferable onto all currently available radiosynthesisers. Using the new procedures, clinical daily routine can be sustainably supported in-house even in larger hospitals by a single production batch.

This paper introduces an innovative energy circuit that challenges conventional understandings of energy conservation, marking a significant departure from traditional frameworks. Seeking to enhance energy generation within existing paradigms, this innovation holds promise for addressing pressing global issues such as the energy crisis and environmental sustainability, while also stimulating scientific inquiry. In contrast to prevalent misconceptions rooted in philosophical and scientific constraints, this study refutes the notion of generating energy from nothing and questions the viability of perpetual motion machines as conceptual models. Instead, it proposes a novel circuit design derived from an unconventional electrical short circuit, which is shown to disrupt the established principles of energy conservation. This circuit offers a transformative approach with diverse applications, including self-recharging capabilities for electric vehicles, bolstering microgrid infrastructure, and facilitating the integration of renewable energy sources. Transcending conventional scientific boundaries, this paper prompts philosophical reflections on the evolving nature of scientific exploration. Ultimately, the energy circuit represents a pivotal step towards mitigating the global energy crisis by reducing reliance on finite resources and fostering sustainability. The paper concludes by illustrating the circuit's potential to revolutionize energy systems and contribute to a more resilient and sustainable future.

DNA sequencing methods were first developed more than 20 years ago with the publication of two approaches to sequencing methodology that became known as Sanger sequencing (1), based on enzymatic synthesis from a single-stranded DNA template with chain termination using dideoxynucleotides (ddNTPs) and Maxim-Gilbert sequencing (2),which involved chemical degradation ofend-radio-labeled DNA fragments. Both methods relied on four-lane,high resolution polyacrylamide gel electrophoresis to separate the labeled fragment and allow the base sequence to be read in a staggered ladder-like fashion. Sanger sequencing was technically easier and faster, and thus became the main DNA sequencing method for the vast majority of applications.

Marburg virus disease (MVD) is a hemorrhagic fever and cause death up to 88% of people and is the same as Ebola virus, It is transmitted through skin contact or mucous membrane in the eyes, nose or mouth with blood or body fluids like urine, saliva sweat, feces and by object contaminated with body fluids. Despite these facts, yet there is no approved vaccine have been developed for the eradication of Marburg virus infections. Therefore, this study described a multi epitope-based peptide vaccine against Marburg virus viral protein 35, using several immunoinformatics tools combined with molecular docking studies. Utilizing Vaxijen 2.0 server, the V35 protein revealed to be antigenic with a score of 0.4316. Prediction of the T-cell and B-cell epitopes was then conducted. RTFDAFLGV epitope was found to be the most promising one with binding affinity to the highest numbers of MHC I alleles, a positive score in the Class I immunogenicity study and non-allergen. These results were further confirmed by the good interaction of RTFDAFLGV to the groove of HLA-A*02:01 with binding energy of -8.1 kcal/mole. Finally, the vaccine was cloned in silico to ensure its validity and efficiency of expression. To ensure its safety and immunogenic profile, in-vitro and in-vivo bioassays are recommended to confirm these findings.

This study considers an application of the first-order Grey Markov Model to foresee the values of Italian power generation in relation to the available energy sources. The model is used to fit data from the Italian energy system from 2000 to 2022. The integration of Markovian error introduces a random element to the model, which is able now to capture inherent uncertainties and misalignments between the Grey model predictions and the real data. This application provides valuable insights for strategic planning in the energy sector and future developments. The results show good accuracy of the predictions, which provides powerful information for the effective implementation of energy policies concerning the evolution of energy demand in the country. Despite advancements, Italy’s 2032 energy mix will still significantly rely on fossil fuels, emphasizing the need for sustained efforts beyond 2032 to enhance sustainability.

Dynamic optical structural color is always desired in various display applications and usually involves active materials. Full-color generation, especially bi-directional full-color generation in both reflective and transmissive modes, without any active materials included has been rarely investigated. Herein, we demonstrate a scheme of bi-directional full-color generation based on a plasmonic metasurface modulated by rotation of the polarization angle of the incident light without varying the geometry and the optical properties of the materials and the environment where the metasurface resides. The metasurface unit cell consists of plasmonic modules aligning in three directions and is patterned in a square array. The metasurface structural color device generates full colors in both reflection and transmission. Based on the proposed polarization-dependent structural color, information encoding of three multiplexed animal images and quick-responsive (QR) codes is demonstrated to verify the efficient information encoding and decoding of the proposed scheme. The animals can be seen under different polarization incidence and the QR codes can be successfully decoded by the polarization rotation in transmission. The proposed bi-directional full-color generation metasurface has great potential in applications such as kaleidoscope generation, anti-counterfeiting, dynamic color display, and optical information encoding.

In this research, catalytic steam reforming acetic acid derived from the aqueous portion of bio-oil for hydrogen production was investigated by using different Ni/ATC (Attapulgite Clay) catalysts prepared by precipitation, impregnation and mechanical blending methods. The fresh and reduced catalysts were characterized by XRD, N₂ adsorption-desorption, TEM and H₂-TPR. The comprehensive results demonstrated that the interaction between active metallic Ni and ATC carrier was significantly improved in Ni/ATC catalyst prepared by precipitation method, and in which the mean Ni particle size was the smallest (~13 nm) resulted in the highest metal dispersion (7.5%). The catalytic performance of the three catalysts was evaluated through the process of steam reforming of acetic acid in a fixed-bed reactor under atmospheric pressure at two different temperatures, such as 550 ℃ and 650 ℃. Results showed that the Ni/ATC (PM-N/ATC) prepared by precipitation method, achieved the highest H₂ yield of ~82% and little lower acetic acid conversion efficiency of ~85% than that (~95%) of Ni/ATC (IM-NATC) prepared by impregnation method. In addition, the deactivation catalysts after reaction for 4 h were analyzed by XRD, TGA-DTG and TEM, which demonstrated that the catalyst deactivation was not caused by the amount of carbon deposition, but owed to the significant agglomeration and sintering of Ni particles in the carrier.

Fluorinated compounds and co-enzymes are being widely researched and employed throughout research community because of their versatile physical, chemical and biological properties. In this work, we synthesized NiS-NiO/S-g-C3N4, a highly effective photocatalyst for C(sp3)-F bond activation and the regeneration of coenzyme (1,4-NADH) employing a new and ecologically acceptable route. The obtained photocatalyst exhibited important photocatalytic properties, such as good solar light harvesting ability, suitability of the optical band-gap, and facilitating efficient charge migrations. As a result, the newly designed NiS-NiO/S-g-C3N4 photocatalyst shows the excellent yield for regenerations of 1,4-NADH (51%). Further, a method of combining C(sp3)-F bond activation with photocatalysis has been demonstrated that represents a very powerful and sustainable approach, that can be a major breakthrough for the field of pharmaceutical.

In this work, satellite data from the Clouds and Earth’s Radiant Energy System (CERES) and Moderate Resolution Imaging Spectroradiometer (MODIS) instruments is analyzed to determine how the global absorbed sunlight and global entropy generation rate have changed during the time period from 2002 to 2023. The data is used to test hypotheses derived from the Maximum Power Principle (MPP) and Maximum Entropy Production Principle (MEP) about the evolution of earth’s surface and atmosphere. The results indicate that the amount of absorbed sunlight has increased over the last 20 years but rising surface temperatures have caused the entropy generation rate to remain approximately constant despite that decrease in albedo. The results are simpler to explain using the MPP but do not completely rule out the MEP. Given the acceptance of the MPP or MEP, some extensions and nuances are discussed.

Canonical quantization is a wonderful procedure for selected problems, but there are many problems for which it fails. Affine quantization is a different procedure that has shown that it can solve many problems that canonical quantization cannot. Here, words like succeed and fail refer to whether the quantization results are correct or incorrect. This paper offers two simple examples that serve to introduce affine quantization, and compare studies of two different quantization procedures. Brief comments about field theory and gravity problems undergoing quantization by affine procedures completes the paper.

Latin binomials, popularised in the eighteenth century by the Swedish naturalist Linnaeus, have stood the test of time in providing a stable, clear and memorable system of nomenclature across biology. However, relentless and ever-deeper exploration and analysis of the microbial world has created an urgent unmet need for huge numbers of new names for Archaea and Bacteria. Manual creation of such names remains difficult and slow and typically relies on expert-driven nomenclatural quality control. Keen to ensure the legacy of Linnaeus lives on in the age of microbial genomics and metagenomics, we propose an automated approach, employing combinatorial concatenation of roots from Latin and Greek to create linguistically correct names for genera and species that can be used off the shelf as needed. As proof of principle, we document over a million new names for Bacteria and Archaea. We are confident that our approach provides a road map for how to create new names for decades to come.

The development of a highly specific drug delivery system (DDS) for anti-cancer therapeutics is an area of intense research focus. Chemical engineering of a “smart” DDS to specifically target tumor cells has gained interest, designed for safer, more efficient, and effective use of chemotherapeutics for the treatment of cancer. However, the selective targeting and choosing the critical cancer surface biomarker are essential for targeted treatments to work. The folic acid receptor alpha (FRalpha) has gained popularity as a potential target in triple-negative breast cancer (TNBC). We have previously reported on a functionalized folic acid (FA)-conjugated amphiphilic alternating copolymer poly(styrene-alt-maleic anhydride) (FA-DABA-SMA) via a biodegradable linker 2,4-diaminobutyric acid (DABA) that has the essential features for efficient “smart” DDS. This biocompatible DDS self-assembles in a pH-dependent manner, providing stimuli-responsive, active targeting, extended-release of hydrophobic chemotherapeutic agents, and can effectively penetrate the inner core of 3-dimensional cancer spheroid models. The empty FA-DABA-SMA decreased spheroid volume, revealing a previously unknown mechanism of action. Upon further investigation, a size- and shape-dependent interaction FA-DABA-SMA with FR reduced the expression of p53, the product of the highly mutated TP53 gene, and additional oncogenic c-Myc and STAT3 proteins. Here, we investigated how this copolymer influences FR behavior and disrupting the receptor’s functions. Results indicate that FA-DABA-SMA increases FR expression levels in breast MDA MB-231 cancer cells and disrupting FR signaling by the reduction in HES1 and NOTCH1 protein expression levels. Also, FA-DABA-SMA induces apoptosis and further causes a change in the morphology of the MDA MB-231 cells, as well as significantly reduces their ability to migrate in a Scratch wound assay. Collectively, these findings provide a novel insight into the functionalized FA-DABA-SMA copolymer. The 350 kDa and 20 kDa copolymers actively target FRα to initialize internationalization. However, only the large size and sheet-shaped 350 kDa copolymers disrupt FRα signaling. The significance of these novel findings reveals the intracellular activity of the copolymer that is critically dependent on the size and structural shape. This report offers novel therapeutic insight into a dual mechanism of FA-DABA-SMA copolymer for its therapeutic potential for the treatment of cancer.

Electricity consumption is often the hotspot of life cycle assessment (LCA) of products, industrial activities, or services. The objective of this paper is to provide a consistent, scientific, region-specific electricity-supply-based inventory of electricity generation technology for national and regional power grids. Marginal electricity generation technology is pivotal in assessing impacts related to additional consumption of electricity. China covers a large geographical area with regional supply grids; these are arguably equally or less integrated. Meanwhile, it is also a country with internal imbalances in regional energy supply and demand. Therefore, we suggest an approach to achieve a geographical subdivision of the Chinese electricity grid, corresponding to the interprovincial regional power grids, namely the North, the Northeast, the East, the Central, the Northwest, and the Southwest China Grids, and the China Southern Power Grid. The approach combines information from the Chinese national plans on for capacity changes in both production and distribution grids, and knowledge of resource availability. The results show that nationally, marginal technology is coal-fired electricity generation, which is the same scenario in the North and Northwest China Grid. In the Northeast, East, and Central China Grid, nuclear power gradually replaces coal-fired electricity and becomes the marginal technology. In the Southwest China Grid and the China Southern Power Grid, the marginal electricity is hydropower towards 2030.

Acute lymphoblastic leukemia (ALL) is a blood cancer that primarily affects children but also adults. It is due to the malignant proliferation of lymphoid precursor cells that invade the bone marrow and can spread to extramedullary sites. ALL is divided into B cell (85%) and T cell lineages (10 to 15%); rare cases are associated with the natural killer (NK) cell lineage (<1%). To date, the survival rate in children with ALL is excellent while in adults continues to be poor. Despite the therapeutic progress, there are subsets of patients that still have high relapse rates after chemotherapy or hematopoietic stem cell transplantation (HSCT) and an unsatisfactory cure rate. Hence, the identification of more effective and safer therapy choices represents a primary issue. In this review, we will discuss novel therapeutic options including bispecific antibodies, antibody-drug conjugates,chimeric antigen receptor (CAR)-based therapies, and other promising treatments for both pediatric and adult patients.

Recently concluded, large-scale cancer genomics studies involving multiregion sequencing of primary tumors and paired metastases appear to indicate that many or most cancer patients have one or more “clonal" mutations in their tumors. Clonal mutations are those that are present in all of a patient’s cancer cells. Achilles Therapeutics is currently the only company specifically targeting clonal mutations. However, they are doing so with tumor-derived T cells. To address the potential limitations of immunotherapy, I have devised another approach for exploiting clonal mutations, which I call “Oncolytic Vector Efficient Replication Contingent on Omnipresent Mutation Engagement” (OVERCOME). The ideal version of OVERCOME would likely employ a bioengineered facultative intracellular bacterium. The bacterium would initially be attenuated, but (transiently) reverse its attenuation upon clonal mutation detection.

The ability to read and quantify nucleic acids such as DNA and RNA using sequencing technologies has revolutionized our understanding of life. With the emergence of synthetic biology, these tools are now being put to work in new ways - enabling de novo biological design. Here, we show how sequencing is supporting the creation of a new wave of biological parts and systems, as well as providing the vast data sets needed for the machine learning of design rules for predictive bioengineering. However, we believe this is only the tip of the iceberg and end by providing an outlook on recent advances that will likely broaden the role of sequencing in synthetic biology and its deployment in real-world environments.

This paper proposes a novel single-stage buck-boost three-Level neutral-point-clamped (NPC) inverter with two independent dc sources coupled for the grid-tied photovoltaic (PV) application, which can effectively solve the unbalanced operational conditions generally appeared between two coupled independent PV sources induced by the unequal irradiation and temperature distribution. The proposed control scheme can simultaneously guarantee the maximum power point (MPP) operation of both PV sources and maintain the output waveform quality. Compared to the traditional two-stage PV inverter, the proposed NPC inverter could reduce the PV array voltage requirement and dc-link capacitors’ voltage rating, meanwhile show the advantage in operational efficiency. MATLAB simulations and the captured experimental results are presented to show the performance of the proposed three-level inverter.

The numerical simulation of entropy generation at mixed natural free and forced convection flow in a square lid-driven cavity filled with an eletrically conducting binary fluids saturated porous media in the presence of a magnetic field is performed in this investigation. Both the top and bottom horizontal walls of the cavity are kept at constant and different temperatures while the left and right vertical walls are adiabatic and insulated. The magnetic field is applied in normal direction to the cavity. The Darcy model, including Brinkman term relative to viscous effects and Forchheimer term due to inertial forces, is used for the momentum equations, and the SIMPLER algorithm, based on the control volume finite-element method approach is used to solve the pressure –velocity coupling. The flow pattern and the heat transfer characteristics inside the cavity are presented in the form of isotherms, streamlines and isentropic lines and average Nusselt number trend. The entropy generation rate is determined for various values of Darcy number (10^-3 ≤ Da ≤ 1) and for a range of Hartmann number (0 ≤ Ha ≤ 10²). This study is limited to Pr = 7 which corresponds to water. It is observed that entropy generation is very affected by the variations of dimensionless control parameters considered.

During the last few years, advancement in the area of biochemistry, science of the material world, engineering and computer-aided testing has directed towards advancement of high-throughput tools for the sake of profiling information encoded in a gene. Single-cell RNA-sequencing (scRNA-seq) tools capable to examine the sequence data from each individual cells and it shows within population variety and permit exploring of cell conditions and transformation by extreme resolution, possibly give out cell sub-types or gene expression fluctuations that are shaded in mass sequencing processes, which shows population-averaged evaluations. Yet, the major disadvantage for this tool is the lack of success to pick out location related details of the RNA transcriptome, as this needs tissue detachment and cell isolation. Location based transcript determination is among the advancements in the area of medical biotechnology as this can find out the molecules like RNA dataset in their intact physical placement in tissue segment with spatial context at the scale of a single-cell, which is very advantageous as compare to single-cell sequencing techniques. These approaches give key observation in the areas of biomedical field sub-disciplines like neurology, embryology, carcinoma study, immune cell investigation and histological activities. Generally, this review mainly focused towards single-cell sequencing methods, technology development, its challenges observed, different expression data analysis mechanisms and their applications in different areas, such as in cancer research, microbes, central nervous system, sex organs and immune-biology, intensifying the essentiality of sequencing tools at single-cell level for the characterization of extremely dynamic individual cells.

The psychedelic renaissance has reignited interest in the therapeutic potential of psychedelics for mental health and well-being. An emerging area of interest is the potential modulation of psychedelic effects by the gut microbiome - the ecosystem of microorganisms residing in our digestive tract. This review explores the intersection of the gut microbiome and psychedelic therapy, underlining potential implications for personalized medicine and mental health. We delve into the current understanding of the gut-brain axis, its influence on mood, cognition, and behavior, and how the microbiome may affect the metabolism and bioavailability of psychedelic substances. We also discuss the role of microbiome variations in shaping individual responses to psychedelics, along with potential risks and benefits. Moreover, we consider the prospect of microbiome-targeted interventions as a fresh approach to boost or modulate psychedelic therapy's effectiveness. By synthesizing insights from the fields of psychopharmacology, microbiology, and neuroscience, our objective is to advance knowledge about the intricate relationship between the microbiome and psychedelic substances, thereby paving the way for novel strategies to optimize mental health outcomes amid the ongoing psychedelic renaissance.

Alfalfa is an important forage crop around the world. LncRNAs are considered to be a class of functional biomacromolecules, while little is known about lncRNAs in alfalfa. In this study, RNAs from different tissues of alfalfa were sequenced and anlyzed with full-length transcriptome sequencing technology, yielding the full-length transcripts dataset of alfalfa. Based on sequencing and public RNA-seq data, lncRNAs of alfalfa were predicted genome-wide by CPC2 and PLEK. The results showed most lncRNAs shared low sequence conservation with those in other plant species, part of which seems originate from plastid genome. We also identified 88563 lncRNAs, approximately 99.8% of total lncRNAs, with possibility of coding small ORFs using two prediction tools. Our research generated the biggest sequence set of alfalfa lncRNAs, and revealed some plastid originated lncRNAs with high sequence conservation.