Strategies for translating proteomics discoveries into drug discovery for dementia

Tauopathies,diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of fro ntotemporal dementia,make up the vast majority of dementia cases.Although there have been recent developments in tauopathy biomarkers and disease-modifying treatments,ongoing progress is required to ensure these are effective,economical,and accessible for the globally ageing population.As such,continued identification of new potential drug targets and biomarkers is critical."Big data"studies,such as proteomics,can generate information on thousands of possible new targets for dementia diagnostics and therapeutics,but currently remain underutilized due to the lack of a clear process by which targets are selected for future drug development.In this review,we discuss current tauopathy biomarkers and therapeutics,and highlight areas in need of improvement,particularly when addressing the needs of frail,comorbid and cognitively impaired populations.We highlight biomarkers which have been developed from proteomic data,and outline possible future directions in this field.We propose new criteria by which potential targets in proteomics studies can be objectively ranked as favorable for drug development,and demonstrate its application to our group's recent tau interactome dataset as an example.

A Study on the Acceptance of the English Translation of Romance of the Three Kingdoms by Overseas Readers Based on Python Data Analysis Technology

Paperless reading has become a prevalent trend among global readers,leading to the accumulation of vast amounts of reading data on numerous book websites.This offers new perspectives for studying translated works.This paper utilizes Python-based data processing technology to collect and analyze reader reviews of Romance of the Three Kingdoms on Amazon and Goodreads,presenting trends in review volume,word cloud maps,and readers’emotional attitudes in a quantitative manner.The findings indicate that overseas readers generally exhibit a positive emotional tendency towards Romance of the Three Kingdoms and recognize its cultural value.However,negative opinions do exist,focusing on aspects of the book’s quality,such as printing quality and proofreading.These results provide valuable insights for the foreign translation of canonical texts.

Use of the “Veda-Lab Easy Reader+” for the Determination of T3, T4 and TSH Hormones in the Mountainous Population of Benin: Case of Natitingou

The thyroid, an endocrine gland located at the base of the neck, produces thyroid hormones (triiodothyronine (T3) and thyroxine (T4)). The production of these hormones is possible by iodine and other nutrients such as selenium and certain vitamins. To assess the thyroid disturbances in the mountain population of Benin, a survey was conducted in Natitingou, a mountain town located in the department of Atacora, in the northwest of Benin, on a sample of thirty (30) adults (15 men and 15 women), most of whom are educated. The results of the questionnaire revealed that 43% of the surveyed population acknowledged having knowledge on the mentioned subject and have dietary habits based on the consumption of seafood, and also legumes (20%). The examination of the serum results of the dosage of T3, T4 and TSH hormones revealed cases of thyroid disturbances in the region (36.32% in men and 44.98% in women). The analysis of a comparative table including the “VEDALAB Easy Reader+” and five (05) other readers, presents the performance, reading techniques, principles, advantages and disadvantages of each device. Pending further studies, some recommendations were made at the end of this study to the academic authorities regarding probable cases of dysthyroidism for which additional examinations are required and an awareness for the improvement of dietary habits.

Floating Waste Discovery by Request via Object-Centric Learning

Discovering floating wastes,especially bottles on water,is a crucial research problem in environmental hygiene.Nevertheless,real-world applications often face challenges such as interference from irrelevant objects and the high cost associated with data collection.Consequently,devising algorithms capable of accurately localizing specific objects within a scene in scenarios where annotated data is limited remains a formidable challenge.To solve this problem,this paper proposes an object discovery by request problem setting and a corresponding algorithmic framework.The proposed problem setting aims to identify specified objects in scenes,and the associated algorithmic framework comprises pseudo data generation and object discovery by request network.Pseudo-data generation generates images resembling natural scenes through various data augmentation rules,using a small number of object samples and scene images.The network structure of object discovery by request utilizes the pre-trained Vision Transformer(ViT)model as the backbone,employs object-centric methods to learn the latent representations of foreground objects,and applies patch-level reconstruction constraints to the model.During the validation phase,we use the generated pseudo datasets as training sets and evaluate the performance of our model on the original test sets.Experiments have proved that our method achieves state-of-the-art performance on Unmanned Aerial Vehicles-Bottle Detection(UAV-BD)dataset and self-constructed dataset Bottle,especially in multi-object scenarios.

Towards cultivar-oriented gene discovery for better crops

The continued expansion of the world population,increasingly inconsistent climate and shrinking agricultural resources present major challenges to crop breeding.Fortunately,the increasing ability to discover and manipulate genes creates new opportunities to develop more productive and resilient cultivars.Many genes have been described in papers as being beneficial for yield increase.However,few of them have been translated into increased yield on farms.In contrast,commercial breeders are facing gene decidophobia,i.e.,puzzled about which gene to choose for breeding among the many identified,a huge chasm between gene discovery and cultivar innovation.The purpose of this paper is to draw attention to the shortfalls in current gene discovery research and to emphasise the need to align with cultivar innovation.The methodology dictates that genetic studies not only focus on gene discovery but also pay good attention to the genetic backgrounds,experimental validation in relevant environments,appropriate crop management,and data reusability.The close of the gaps should accelerate the application of molecular study in breeding and contribute to future global food security.

Identification of partial differential equations from noisy data with integrated knowledge discovery and embedding using evolutionary neural networks

Identification of underlying partial differential equations(PDEs)for complex systems remains a formidable challenge.In the present study,a robust PDE identification method is proposed,demonstrating the ability to extract accurate governing equations under noisy conditions without prior knowledge.Specifically,the proposed method combines gene expression programming,one type of evolutionary algorithm capable of generating unseen terms based solely on basic operators and functional terms,with symbolic regression neural networks.These networks are designed to represent explicit functional expressions and optimize them with data gradients.In particular,the specifically designed neural networks can be easily transformed to physical constraints for the training data,embedding the discovered PDEs to further optimize the metadata used for iterative PDE identification.The proposed method has been tested in four canonical PDE cases,validating its effectiveness without preliminary information and confirming its suitability for practical applications across various noise levels.

A Multi-Token Sector Antenna Neighbor Discovery Protocol for Directional Ad Hoc Networks

In this paper,we propose a Multi-token Sector Antenna Neighbor Discovery(M-SAND)protocol to enhance the efficiency of neighbor discovery in asynchronous directional ad hoc networks.The central concept of our work involves maintaining multiple tokens across the network.To prevent mutual interference among multi-token holders,we introduce the time and space non-interference theorems.Furthermore,we propose a master-slave strategy between tokens.When the master token holder(MTH)performs the neighbor discovery,it decides which 1-hop neighbor is the next MTH and which 2-hop neighbors can be the new slave token holders(STHs).Using this approach,the MTH and multiple STHs can simultaneously discover their neighbors without causing interference with each other.Building on this foundation,we provide a comprehensive procedure for the M-SAND protocol.We also conduct theoretical analyses on the maximum number of STHs and the lower bound of multi-token generation probability.Finally,simulation results demonstrate the time efficiency of the M-SAND protocol.When compared to the QSAND protocol,which uses only one token,the total neighbor discovery time is reduced by 28% when 6beams and 112 nodes are employed.

Recent Advances of Bioactive Marine Natural Products in Drug Discovery

Marine natural products(MNPs)are valuable resources for drug development.To date,17 drugs from marine sources are in clinical use,and 33 pharmaceutical compounds are in clinical trials.Presently the success of drug development from the marine resources is higher than the industry average.It is a feasible strategy to conduct the discovery of druglead compounds based on marine chemical ecology by fully exploiting the pharmacological potential of marine chemical defense matters.In the search for bioactive MNPs,our group has constructed a biological resources library including more than 1500 strains of fungi.Focusing on the strategy of Blue Drug Library,we have discovered a series of novel MNPs with abundant biological functions.Highly efficient and scalable total synthesis of(+)-aniduquinolone A(44)and pesimquinolone I(48)have been completed,which will facilitate access to sufficient quantities of candidates for in vivo pharmacological and toxicological studies.As a nucleoprotein(NP)inhibitor,QLA(75)possesses significant anti-influenza A virus(IAV)activities both in vitro and in vivo.CHNQD-00803(76)is a potent and selective AMP-activated kinase(AMPK)activator that can effectively inhibit metabolic disorders and metabolic dysfunction-associated steatohepatitis(MASH)progression.Moreover,we identified two new candidate molecules with potent anti-hepatocellular carcinoma effects.Particularly,as a natural guanine-nucleotide exchange factors for ADP-ribosylation factor GTPases(Arf-GEFs)inhibitor prodrug,CHNQD-01255(78)is qualified to be developed as a targeted candidate anticancer drug,which may be promising to apply for cancer immunotherapy.Hence,it is evident that MNPs play an important role in drug development.

Artificial intelligence as a tool in drug discovery and development

The rapidly advancing field of artificial intelligence(AI)has garnered substantial attention for its potential application in drug discovery and development.This opinion review critically examined the feasibility and prospects of integrating AI as a transformative tool in the pharmaceutical industry.AI,encompassing machine learning algorithms,deep learning,and data analytics,offers unprecedented opportunities to streamline and enhance various stages of drug development.This opinion review delved into the current landscape of AI-driven approaches,discussing their utilization in target identification,lead optimization,and predictive modeling of pharmacokinetics and toxicity.We aimed to scrutinize the integration of large-scale omics data,electronic health records,and chemical informatics,highlighting the power of AI in uncovering novel therapeutic targets and accelerating drug repurposing strategies.Despite the considerable potential of AI,the review also addressed inherent challenges,including data privacy concerns,interpretability of AI models,and the need for robust validation in realworld clinical settings.Additionally,we explored ethical considerations surrounding AI-driven decision-making in drug development.This opinion review provided a nuanced perspective on the transformative role of AI in drug discovery by discussing the existing literature and emerging trends,presenting critical insights and addressing potential hurdles.In conclusion,this study aimed to stimulate discourse within the scientific community and guide future endeavors to harness the full potential of AI in drug development.

Sensing and Communication Integrated Fast Neighbor Discovery for UAV Networks

In unmanned aerial vehicle(UAV)networks,the high mobility of nodes leads to frequent changes in network topology,which brings challenges to the neighbor discovery(ND)for UAV networks.Integrated sensing and communication(ISAC),as an emerging technology in 6G mobile networks,has shown great potential in improving communication performance with the assistance of sensing information.ISAC obtains the prior information about node distribution,reducing the ND time.However,the prior information obtained through ISAC may be imperfect.Hence,an ND algorithm based on reinforcement learning is proposed.The learning automaton(LA)is applied to interact with the environment and continuously adjust the probability of selecting beams to accelerate the convergence speed of ND algorithms.Besides,an efficient ND algorithm in the neighbor maintenance phase is designed,which applies the Kalman filter to predict node movement.Simulation results show that the LA-based ND algorithm reduces the ND time by up to 32%compared with the Scan-Based Algorithm(SBA),which proves the efficiency of the proposed ND algorithms.

Analysis and Design of a Quadrature Down-Conversion Mixer for UHF RFID Readers

A quadrature mixer with a shared transconductor stage is analyzed,including voltage conversion gain, linearity, noise figure, and image rejection. The analysis indicates it has better performance than a conventional Gilbert mixer pair in commutating mode. A quadrature down-conversion mixer based on this topology is designed and optimized for an ultra high frequency RFID reader. Operating in the 915MHz ISM band, the presented quadrature mixer measures a conversion gain of 12.5dB,an IIP3 of 10dBm, an IIP2 of 58dBm, and an SSB noise figure of 17.6riB. The chip was fabricated in a 0. 18μm 1P6M RF CMOS process and consumes only 3mA of current from a 1.8V power supply.

Rediscovering Don Swanson:The Past,Present and Future of Literature-based Discovery

Purpose： The late Don R. Swanson was well appreciated during his lifetime as Dean of the Graduate Library School at University of Chicago, as winner of the American Society for Information Science Award of Merit for 2000, and as author of many seminal articles. In this informal essay, I will give my personal perspective on Don＇s contributions to science, and outline some current and future directions in literature-based discovery that are rooted in concepts that he developed.Design/methodology/approach： Personal recollections and literature review. Findings： The Swanson A-B-C model of literature-based discovery has been successfully used by laboratory investigators analyzing their findings and hypotheses. It continues to be a fertile area of research in a wide range of application areas including text mining, drug repurposing, studies of scientific innovation, knowledge discovery in databases, and bioinformatics. Recently, additional modes of discovery that do not follow the A-B-C model have also been proposed and explored （e.g. so-called storytelling, gaps, analogies, link prediction, negative consensus, outliers, and revival of neglected or discarded research questions）. Research limitations： This paper reflects the opinions of the author and is not a comprehensive nor technically based review of literature-based discovery. Practical implications： The general scientific public is still not aware of the availability of tools for literature-based discovery. Our Arrowsmith project site maintains a suite of discovery tools that are free and open to the public （http：//arrowsmith.psych.uic.edu）, as does BITOLA which is maintained by Dmitar Hristovski （http：// http：//ibmi.mf.uni-lj.si/bitola）, and Epiphanet which is maintained by Trevor Cohen （http：//epiphanet.uth.tme.edu/）. Bringing user-friendly tools to the public should be a high priority, since even more than advancing basic research in informatics, it is vital that we ensure that scientists actually use discovery tools and that these are actually able to help them make experimental discoveries in the lab and in the clinic. Originality/value： This paper discusses problems and issues which were inherent in Don＇s thoughts during his life, including those which have not yet been fully taken up and studied systematically.

Sensitivity and inter-observer variability for capsule endoscopy image analysis in a cohort of novice readers

AIM： To determine the performance of novice readers （4^th year medical students） for detecting capsule endoscopy findings. METHODS： Ten capsule endoscopy cases of small bowel lesions were administered to the readers. Gold standard findings were pre-defined by gastroenterologists. Ten gold standard ＂targets＂ were identified among the 10 cases. Readers were given a 30-min overview of Rapid Reader software and instructed to mark any potential areas of abnormalities. A software program was developed using SAS to analyze the thumbnailed findings. RESULTS： The overall sensitivity for detecting the gold standard findings was 80%. As a group, at least 5 out of 10 readers detected each gold standard finding per recording. All the gold standard targets were identified when the readers＇ results were combined. Incidental finding/false positive rate ranged between 8.2-59.8 per reader. CONCLUSION： A panel of medical students with minimal endoscopic experience can achieve high sensitivity in detecting lesions on capsule endoscopy. A group of novice readers can pre-screen recordings to thumbnail potential areas of small bowel lesions for further review. These thumbnails must be reviewed to determine the clinical relevance. Further studies are ongoing to assess other cohorts.

What are the Differences between Good and Poor Readers?

Reading is a very essential skill in the process of knowledge aqusition,while,effective reading ability is the outcome of the good combination of both time and skills.The differences between good readers and poor reader will be studied in terms of comparisons towards their reading speed,efficiency and reasons behind in the domain of psychological perspectives.

An Analysis of the Readers' Roles in the Construction of Meaning in John Donne's The Flea under Reader-Oriented Theory

Among the sundry studies in China on John Donne's The Flea,there has been none done from the perspective of Reader-Oriented Theory to probe into the readers' roles in the construction of meaning.The present article under Wolfgang Iser's theories,in a further pursuit of the expansion of the gestalt of such studies on the poem,aims at exploring the readers' active roles in complementing,completing and recreating the textual meaning,and differentiating the implied reader and the actual reader through the poem as well as attempting to fulfill the construction of the reading cognitive model through the interpretation of the conceit the flea.

To our readers: Important questions from the editors/editorial board

This letter proposes updating the World Journal of Gastroenterology(WJG) with several new items and subsections and seeks the readers' input for these suggested changes. In order to further enhance the scope of the WJG, to make it more interactive, and to accommodate our readers' interest, the editors ask the readers for their input regarding potential new proposed changes and new subsections listed below:(1) new subsection-selected highlights from other related Baishideng Publishing Group world series journals;(2) new subsection-challenging images of the week-a quiz with an answer and references on another page;(3) to re-introduce or restore for some issues the cover page on which selected illustration;(4) new subsection-new hypotheses, new concepts and revisiting old concepts in a short, commentary format;(5) preview of the forthcoming issue articles(title and authors);(6) suggestions submitted by the readers-new topics and initiatives; and(7) additional topic area-molecular basis of gastric/liver diseases as an additional area for articles submitted to the journal.

Metabolomics in drug discovery: Restoring antibiotic pipeline

Metabolomics has emerged as a valuable tool in drug discovery and development,providing new insights into the mechanisms of action and toxicity of potential therapeutic agents.Metabolomics focuses on the comprehensive analysis of primary as well as secondary metabolites,within biological systems.Metabolomics provides a comprehensive understanding of the metabolic changes that occur within microbial pathogens when exposed to therapeutic agents,thus allowing for the identification of unique metabolic targets that can be exploited for therapeutic intervention.This approach can also uncover key metabolic pathways essential for survival,which can serve as potential targets for novel antibiotics.By analyzing the metabolites produced by diverse microbial communities,metabolomics can guide the discovery of previously unexplored sources of antibiotics.This review explores some examples that enable medicinal chemists to optimize drug structure,enhancing efficacy and minimizing toxicity via metabolomic approaches.

How Does Headlines Capture Readers——An Analysis of Characteristics of English News Report Headlines

Since the emergence of newspaper,the headline has been the necessity of a news report.The Newspaper headline which takes the crucial part in a news report has been given the responsibility to capture readers,especially in the environment of highly intense competition of this industry.Even with the application of high technology in the news industry,the significance of the headline is enormously strengthened rather than weakened.On the one hand,the mission of the headline determines its significance.And on the other,its characteristics help to achieve the responsibility.Therefore the particular language adopted in the headline,namely "headlinese",must contain certain features which could appeal readers' attention.This paper will focus on the characteristics of the English newspaper headline and find out how it captures readers.

Information for Readers

Aims and Scope World Journal of Emergency Medicine(ISSN 1920-8642,CN 33-1408/R),a quarterly journal,publishes peer-reviewed original research articles,review articles including systematic review and meta-analysis,editorials,commentaries,etc in different fields of emergency medicine.The content of articles could be varied in medical,surgical,radiological,pathological,biochemical,physiological and pharmaceutical aspects of the subject areas.The journal also deals with basic sciences and experimental work.

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Hepatobiliary & Pancreatic Diseases International(HBPD INT)Copyright 2013, Hepatobiliary & Pancreatic Diseases International. All rights reserved. www.hbpdint.com