The big data challenge-and how polypharmacology supports the translation from pre-clinical research into clinical use against neurodegenerative diseases and beyond

Introductory comments:The identification and validation of disease-modifying proteins are fundamental aspects in drug development.However,the m ultifactority of n eurodegen era tive diseases poses a real challenge for targeted therapies.Furthermore,the behavior of individually(over-)expressed to rget proteins in vitro is likely to differ from their actual functional behavior when embedded in cascades and pathways in vivo.

Commentary on"Speed and surface steepness affect internal tibial loading during running"

It is a pleasure to write a commentary on the work of Dr.Hannah Rice and colleagues,l who have advanced our understanding of how the mechanical loading environment of the tibia changes as a function of running grade and speed.It is important that we understand how the tibia is loaded during conditions that an individual is likely to encounter when running as it is these internal loads which we believe are responsible for the development of bone-stress injuries.

Germline Gene-Editing Creates Enhanced Livestock-Technical and Especially Ethical Issues Challenge Its Use in Humans

Using clustered regularly interspaced short palindromic repeats(CRISPR)-based molecular tools,scientists are engineering-as they are also doing with plants.-animals with advantageous traits,like disease resistance and improved food yield.While these innovative techniques could one day be applied in humans,technical hurdles and ethical concerns likely place this possibility far in the future,The enhancements rely on germline gene editing,which alters the genes in a way that passes the changes on to offspring.Ger m-line gene editing differs from the somatic cell gene editing used in the highly promising new treatment recently approved for the human disease sickle cell anemia.

Trends in mortality among the geriatric population undergoing Surgical aortic valve replacement (SAVR) and potential racial disparities: a 20-year perspective via the National (Nationwide) Inpatient Sample

Background Racial disparities in cardiovascular conditions are well documented.Whether similar race-based discrepancies in health outcomes also exist among elderly patients undergoing surgical aortic valve replacement(SAVR) for aortic stenosis remains understudied.Methods We abstracted data from the National(Nationwide) Inpatient Sample over a 20-year period from 2001 to 2020 using specific ICD-9 and ICD-10 codes.We included patients aged ≥ 60 and ≤ 80 years with races recorded as White,African American,or Hispanic at the time of their hospitalization for surgery.We analyzed and reported the baseline characteristics,risk-adjusted inhospital mortality,and complications stratified by race.Results Of 420,181 patients studied,90.0% identified as White,4.0% as African American and 6.0% as Hispanic.Despite a decrease in overall in-hospital mortality rates from 3.8% between 2001-2005 to 1.8% between 2016-2020,African Americans had higher odds of all-cause in-hospital deaths compared to Whites(a OR = 1.390,P < 0.001).Additionally,they were more likely to experience cardiogenic shock(a OR = 1.241,P < 0.001) and acute kidney injury(a OR = 1.314,P < 0.001) as well as more likely to require organ support such as IABP use(a OR = 1.336,P < 0.001) or invasive mechanical ventilation(a OR = 1.342,P < 0.001).Interestingly,African Americans were less likely to report events of acute ischemic stroke compared to Whites(a OR = 0.852,P < 0.001).Conclusions Despite a reassuring reduction in overall in-hospital mortality rates of geriatric patients undergoing SAVR for aortic stenosis,racial disparities in health outcomes remain pervasive with minorities more likely to report higher in-hospital morbidity and mortality.

Understanding intrarenal backflow: Intrarenal pressure during ureteroscopy and beyond

The number of ureterorenoscopic procedures for upper urinary tract stone management has increased dramatically during recent years worldwide[1].Developments in flexible ureteroscope and laser technology have made it possible to successfully address larger and more complex stone scenarios retrogradely.On the other hand,this means that more and more patients are exposed to the potential adverse effects of ureteroscopy[2].In general,ureteroscopy is considered a safe procedure.However,serious complications and even deaths do occur,and these events are most likely underreported[3,4].

Developments in the U.S.Republican Party Since the 2020 Election

On November 8,2023,the Republican Party of the United States hosted its third televised debate for the presidential nomination primary in Miami,Florida.Former President Donald Trump,though absent once again,still maintains a lead in all polls and is even considered highly likely to win the Republican nomination for the third time,to fight Biden again and compete for the White House throne.In fact,over the three years since Trump left office,and Biden came to power,the Republican Party did not get rid of the influence of the political philosophy represented by Trump,and the party’s political ecology and policy agenda inevitably by Trump’s personal influence,presenting a subtle and complex political phenomenon as Trump has never left.

Embracing the Year of the Dragon

The Lunar New Year has increasingly become a common festival of people throughout the world.CHINESE people,and people throughout the world,are looking forward to welcoming the Year of the Dragon,which falls on February 10,2024.The Dragon is considered the most auspicious of the 12 signs in the Chinese zodiac and this year is specifically the Year of the Wood Dragon,the first since 1964.According to Lifestyle Asia,“Wood Dragons enjoy fulfilling careers.They’re likely to materialize all their ambitions into actions,coming up with truly revolutionary ideas.”

马尔代夫泛在化教育的演变:实践、挑战和问题

Learning and teaching have been undergoing transformational changes in the past 100 years,each change promising a richer and more meaningful interaction of learners and instructors. Beginning from the limitations of correspondence courses and distance education, remote learning has trended through computerassisted instruction(CAI), e-learning, m-learning, and now ubiquitous or u-learning. Some forms of this type of education have been renamed or repackaged in multiple forms of instruction including hybrid and flexible learning. More recently, u-learning or ubiquitous learning has been gaining currency and approbation.This article outlines the development of education other than face-to-face learning and teaching in the context of the Maldives to disentangle its practices, challenges, and issues. Some of these issues are likely to impact u-learning and its descendent and off-shoot modes.

Medals for Merchants Yiwu’s small commodities shine on the Olympic playground

If there’s one place outside of France where the Olympic buzz is equally palpable,it’s likely to be Yiwu,Zhejiang Province,in east China.Known as the global capital of small commodities,Yiwu has become a main supplier of many of the items at major sports events worldwide.In Yiwu’s markets,astute merchants,keenly attuned to the rhythms of global mega sports events,spring into action well ahead of time,ready to meet the soaring demand for everything from sportswear and souvenirs to the disposable cups used in stadiums.

为什么思考会让我们感到疲惫?

Have you ever wondered why thinking too much makes you tired? A new study has found out some answers to this question.Researchers from the Paris Brain Institute looked at why mental^(1) effort makes us tired.They found that when people think a lot,the brain releases a chemical called glutamate^(2).Too much glutamate upsets the brain's functions.It means the brain tells the body it is tired and that it must rest.People who spend more than six hours working on a task that requires a lot of thought are more likely to feel tired.A period of rest allows the brain to return to normal.This explains why a power nap^(3) is good for us.

7th CIIE likely to prove solid growth platform for many companies

The robust demand of the Chinese market and the improving business environment in the country make China a big growth opportunity for companies wishing to further expand their operations,said corporates that have registered to participate at this year's China International Import Expo.The 7th edition of the annual CIIE,to be held in Shanghai from Nov 5 to 10,started its 100-day countdown on Saturday.

2050年的世界将是什么样子

主题语境:科技与未来篇幅:371词建议用时:6分钟。Below are eight things that will have happened by the mid‑point of this century—both for good and bad.Right now,people are focused on AI potentially causing job losses,but the reality could be far worse.George Stakhov said,“By 2050,AI will have profoundly reshaped the world.It is very likely that there is a dark AI future where those who control AI will gain huge power,while 99 percent of the population will be disenfranchised.

Leggings: The new fashion staple

Leggings have been a staple in the fashion industry for decades,consistently remaining one of the most popular and versatile items of clothing.They have achieved viral status and continue to be a highly sought-after fashion item,transcending age and cultural barriers.The body-hugging style of leggings has remained in vogue,attracting young people of all ages and backgrounds.With their enduring popularity,it’s likely that leggings will remain a fashion staple for years to come.

如何扩大积极词汇量

对于英语学习者来说,词汇学习历来都是一个十分重要的环节。正如高楼大厦的建设需要建筑材料一样,英语学习要求学习者具有一定的词汇量。英语学习者要想学好英语,要想不断提高英语水平,就必须在词汇学习上下一定的功夫。然而,一个学习者词汇量的大小不仅仅取决于绝对词汇数量的多少,更重要的是要看他所掌握并能熟练运用的词汇的多寡。所以,在一个人的词汇量中。

Ligand Based Virtual Screening of Molecular Compounds in Drug Discovery Using GCAN Fingerprint and Ensemble Machine Learning Algorithm

The drug development process takes a long time since it requires sorting through a large number of inactive compounds from a large collection of compounds chosen for study and choosing just the most pertinent compounds that can bind to a disease protein.The use of virtual screening in pharmaceutical research is growing in popularity.During the early phases of medication research and development,it is crucial.Chemical compound searches are nowmore narrowly targeted.Because the databases containmore andmore ligands,thismethod needs to be quick and exact.Neural network fingerprints were created more effectively than the well-known Extended Connectivity Fingerprint(ECFP).Only the largest sub-graph is taken into consideration to learn the representation,despite the fact that the conventional graph network generates a better-encoded fingerprint.When using the average or maximum pooling layer,it also contains unrelated data.This article suggested the Graph Convolutional Attention Network(GCAN),a graph neural network with an attention mechanism,to address these problems.Additionally,it makes the nodes or sub-graphs that are used to create the molecular fingerprint more significant.The generated fingerprint is used to classify drugs using ensemble learning.As base classifiers,ensemble stacking is applied to Support Vector Machines(SVM),Random Forest,Nave Bayes,Decision Trees,AdaBoost,and Gradient Boosting.When compared to existing models,the proposed GCAN fingerprint with an ensemble model achieves relatively high accuracy,sensitivity,specificity,and area under the curve.Additionally,it is revealed that our ensemble learning with generated molecular fingerprint yields 91%accuracy,outperforming earlier approaches.

关于“意象造型”(英文)

The imagery mould-making is a sort of concept of modeling betweenthe above two.which neither completely imitate the formal truthfulness of theobjective reality.

Biometric Analysis on Genetic Divergence between Parental and Regenerated Accessions in Tall Coconut Palms (Cocos nucifera L.) from International Genebank for Africa and the Indian Ocean

This study endeavour assesses agromorphological likeness between initial introductions and regenerated accessions at the International Coconut Genebank for Africa and the Indian Ocean (ICG-AIO) based in C?te d’Ivoire. Ten couples of parental (G0) and regenerated (G1) accessions of Tall coconut palms were analyzed using Principal Component Analysis (PCA) and Multiple Analysis of Variance (MANOVA) from 26 agromorphological characters. The main results showed a relative decrease in the expression of the phenotypical traits concerning the component of the fruit, height and vigor of the stem and yield of bunches and fruits after one regeneration cycle. But, a high proportion (69%) of studied characters from leaf, inflorescence and nut components showed likeness between G0 and G1 accessions. After one regeneration cycle, the controlled pollination method guarantees significant conservation of the expression of the majority of agromorphological traits. Consequently, regenerated accessions of Tall coconut palms can be used to pursue research and development programs in C?te d’Ivoire.

阅读理解三则(英文)

Americans and Their Cars美国人喜欢汽车胜过任何别的东西。美国的儿童从小就想拥有一部自己的汽车。在很多青年人看来,一纸驾照就是他们成人的象征。

英语专业本科毕业综合模拟试题(中)

Ⅲ.Reading Comprehension 20%Questions 1 -4 are based on the following passage.Are you a team person? Are you at your best as part of a small tightly united group of dedicated workers? If so, the future may hold more for you than you think.