Insights from an academic endeavor into central nervous system drug discovery

Historically,"big pharma"did most central nervous system drug discovery R&D in-house.Yet,in modern times their"management reductionism"resulted in disappointing pipelines and pharma resided to(late)development,regulatory approval,and marketing(Thong,2015).This had significant consequences for financing and executing research,resulting in a larger role for funding by governments and patient-organizations and a shift of research to academia(Mazzucato,2013).

Extended Lorenz majorization and frequencies of distances in an undirected network

Purpose:To contribute to the study of networks and graphs.Design/methodology/approach:We apply standard mathematical thinking.Findings:We show that the distance distribution in an undirected network Lorenz majorizes the one of a chain.As a consequence,the average and median distances in any such network are smaller than or equal to those of a chain.Research limitations:We restricted our investigations to undirected,unweighted networks.Practical implications:We are convinced that these results are useful in the study of small worlds and the so-called six degrees of separation property.Originality/value:To the best of our knowledge our research contains new network results,especially those related to frequencies of distances.

Lithium-Metal-Free Sulfur Batteries with Biochar and Steam-Activated Biochar-Based Anodes from Spent Common Ivy

Lithium-sulfur batteries are emerging as sustainable replacements for current lithium-ion batteries.The commercial viability of this novel type of battery is still under debate due to the extensive use of highly reactive lithium-metal anodes and the complex electrochemistry of the sulfur cathode.In this research,a novel sulfur-based battery has been proposed that eliminates the need for metallic lithium anodes and other critical raw materials like cobalt and graphite,replacing them with biomass-derived materials.This approach presents numerous benefits,encompassing ample availability,cost-effectiveness,safety,and environmental friendliness.In particular,two types of biochar-based anode electrodes(non-activated and activated biochar)derived from spent common ivy have been investigated as alternatives to metallic lithium.We compared their structural and electrochemical properties,both of which exhibited good compatibility with the typical electrolytes used in sulfur batteries.Surprisingly,while steam activation results in an increased specific surface area,the non-activated ivy biochar demonstrates better performance than the activated biochar,achieving a stable capacity of 400 mA h g^(−1)at 0.1 A g^(−1)and a long lifespan(>400 cycles at 0.5 A g^(−1)).Our results demonstrate that the presence of heteroatoms,such as oxygen and nitrogen positively affects the capacity and cycling performance of the electrodes.This led to increased d-spacing in the graphitic layer,a strong interaction with the solid electrolyte interphase layer,and improved ion transportation.Finally,the non-activated biochar was successfully coupled with a sulfur cathode to fabricate lithium-metal-free sulfur batteries,delivering a specific energy density of~600 Wh kg^(−1).

An Optimization Approach of IoD Deployment for Optimal Coverage Based on Radio Frequency Model

Recently,Internet of Drones(IoD)has garnered significant attention due to its widespread applications.However,deploying IoD for area coverage poses numerous limitations and challenges.These include interference between neighboring drones,the need for directional antennas,and altitude restrictions for drones.These challenges necessitate the development of efficient solutions.This research paper presents a cooperative decision-making approach for an efficient IoDdeployment to address these challenges effectively.The primary objective of this study is to achieve an efficient IoDdeployment strategy thatmaximizes the coverage regionwhile minimizing interference between neighboring drones.In deployment problem,the interference increases as the number of deployed drones increases,resulting in bad quality of communication.On the other hand,deploying a few drones cannot satisfy the coverage demand.To accomplish this,an enhanced version of a concise population-based meta-heuristic algorithm,namely Improved Particle SwarmOptimization(IPSO),is applied.The objective function of IPSO is defined based on the coverage probability,which is primarily influenced by the characteristics of the antennas and drone altitude.A radio frequency(RF)model is derived to evaluate the coverage quality,considering both Line of Sight(LOS)and Non-Line of Sight(NLOS)down-link coverage probabilities for ground communication.It is assumed that each drone is equipped with a directional antenna to optimize coverage in a given region.Extensive simulations are conducted to assess the effectiveness of the proposed approach.Results demonstrate that the proposed method achieves maximum coverage with minimum transmission power.Furthermore,a comparison is made against Collaborative Visual Area Coverage Approach(CVACA),and a game-based approach in terms of coverage quality and convergence speed.The simulation results reveal that our approach outperforms both CVACA and the gamebased schemes in terms of coverage and convergence speed.Comparisons validate the superiority of our approach over existing methods.To assess the robustness of the proposed RFmodel,we have considered two distinct ranges of noise:range1 spanning from−120 to−90 dBm,and range2 spanning from−90 to−70 dBmfor different numbers of UAVs.In summary,this research presents a cooperative decision-making approach for efficient IoD deployment to address the challenges associatedwith area coverage and achieves an optimal coveragewithminimal interference.

Oncostatin M:a love-hate relationship in neuroinflammation

Oncostatin M and multiple sclerosis:Every 5minutes,someone in the world is diagnosed with multiple sclerosis(MS),a chronic inflammatory and degenerative disease of the central nervous system(CNS).MS appears in unpredictable episodes of symptoms,which are highly patient-dependent,but often include visual impairment,muscle weakness/spasms,fatigue,cognitive difficulties,and bladder.bowel.or sexual dysfunction.

Novel insights in phosphodiesterase 4 subtype inhibition to target neuroinflammation and stimulate remyelination

In neurodegenerative and classically demyelinating disorders such as multiple sclerosis(MS),spinal cord injury(SCI),stroke,and Charcot-Marie-Tooth disease,glial functioning is compromised and nervous tissue integrity is lost.Recently,primary neurodegenerative disorders such as Alzheimer’s disease,amyotrophic lateral sclerosis(ALS),and Parkinson’s disease(PD)are increasingly linked to impaired oligodendroglia functioning upon neurodegeneration.Due to the destructive micro-environment created by nervous tissue damage,the progressive cellular loss in these disorders,and the amitotic nature of neurons,spontaneous endogenous repair process are limited in nature.Hence,there is a medical need for efficient therapeutic strategies capable of supporting neuro-reparative processes to occur,likely supported by improved oligodendroglia cell functioning.

A Lightweight Intrusion Detection System Using Convolutional Neural Network and Long Short-Term Memory in Fog Computing

The Internet of Things(IoT)links various devices to digital services and significantly improves the quality of our lives.However,as IoT connectivity is growing rapidly,so do the risks of network vulnerabilities and threats.Many interesting Intrusion Detection Systems(IDSs)are presented based on machine learning(ML)techniques to overcome this problem.Given the resource limitations of fog computing environments,a lightweight IDS is essential.This paper introduces a hybrid deep learning(DL)method that combines convolutional neural networks(CNN)and long short-term memory(LSTM)to build an energy-aware,anomaly-based IDS.We test this system on a recent dataset,focusing on reducing overhead while maintaining high accuracy and a low false alarm rate.We compare CICIoT2023,KDD-99 and NSL-KDD datasets to evaluate the performance of the proposed IDS model based on key metrics,including latency,energy consumption,false alarm rate and detection rate metrics.Our findings show an accuracy rate over 92%and a false alarm rate below 0.38%.These results demonstrate that our system provides strong security without excessive resource use.The practicality of deploying IDS with limited resources is demonstrated by the successful implementation of IDS functionality on a Raspberry Pi acting as a Fog node.The proposed lightweight model,with a maximum power consumption of 6.12 W,demonstrates its potential to operate effectively on energy-limited devices such as low-power fog nodes or edge devices.We prioritize energy efficiency whilemaintaining high accuracy,distinguishing our scheme fromexisting approaches.Extensive experiments demonstrate a significant reduction in false positives,ensuring accurate identification of genuine security threats while minimizing unnecessary alerts.

我国制造业能源消耗强度变化的因素分解——基于结构份额和效率份额视角

在借鉴已有研究成果基础上,将能源消耗强度分解为结构份额和效率份额两个因素,并测算了1994-2006年我国制造业中能源消耗强度中两个因素的变化情况,分析了制造业产业结构调整和能源效率提高对能源消耗强度的影响。研究结果表明:我国制造业能源消耗强度在不断下降,原因是产业结构调整和能源使用效率提高的综合影响。两者对降低能源消耗强度都有正面作用,同时,能源使用效率提高作用略大于产业结构调整作用。

AP-TPR-MS法考察六枝煤固定床热解过程中的硫变迁行为

实验选取六枝(LZ)原煤及其在固定床热解所得半焦,采用常压程序升温还原-质谱法(AP-TPR-MS)与化学法相结合考察温度和气氛对固定床热解过程中硫变迁行为的影响。对于LZ煤而言,经氮气气氛500℃热解后,只能使煤中部分不稳定有机硫分解,黄铁矿硫却不能分解;而经氮气气氛700℃热解后可以使不稳定有机硫和黄铁矿硫全部分解。合成气气氛在500℃以前煤中的不稳定有机硫和黄铁矿硫就能全部分解,且随着温度的升高,合成气表现出与氢气相近的脱硫活性。1.0%O2-N2对于六枝煤并没有明显的脱硫效果,这与氮气气氛相差不大。

Pathophysiology of colorectal peritoneal carcinomatosis: Role of the peritoneum

Colorectal cancer(CRC) is the third most common cancer and the fourth most common cause of cancerrelated death worldwide. Besides the lymphatic and haematogenous routes of dissemination,CRC frequently gives rise to transcoelomic spread of tumor cells in the peritoneal cavity,which ultimately leads to peritoneal carcinomatosis(PC). PC is associated with a poor prognosis and bad quality of life for these patients in their terminal stages of disease. A loco-regional treatment modality for PC combining cytoreductive surgery and hyperthermic intraperitoneal peroperative chemotherapy has resulted in promising clinical results. However,this novel approach is associated with significant morbidity and mortality. A comprehensive understanding of the molecular events involved in peritoneal disease spread is paramount in avoiding unnecessary toxicity. The emergence of PC is the result of a molecular crosstalk between cancer cells and host elements,involving several well-defined steps,together known as the peritoneal metastatic cascade. Individual or clumps of tumor cells detach from the primary tumor,gain access to the peritoneal cavity and become susceptible to the regular peritoneal transport. They attach to the distant peritoneum,subsequently invade the subperitoneal space,where angiogenesis sustains proliferation and enables further metastatic growth. These molecular events are not isolated events but rather a continuous and interdependent process. In this manuscript,we review current data regarding the molecular mechanisms underlying the development of colorectal PC,with a special focus on the peritoneum and the role of the surgeon in peritoneal disease spread.

Sensory innervation around immediately vs. delayed loaded implants: a pilot study

Although neurophysiological and psychophysical proof of osseoperception is accumulating, histomorphometric evidence for the neural mechanisms of functional compensation following immediate and delayed implant loading is still lacking. For this randomized split-mouth study, six mongrel dogs randomly received one of four treatment protocols at 36 implant-recipient sites over 16 weeks （third maxillary incisor, third and fourth mandibular premolar）： immediate implant placement and immediate loading （liP＋ IL）; delayed implant placement and delayed loading （DIP＋DL）; delayed implant placement and immediate loading （DIP＋IL）; and natural extraction socket healing （control）. Histomorphometry was performed in the peri-implant bone and soft tissues within 300 pm around the implants. Immunocytochemistry and transmission electron microscopy were used to confirm the presence of neural structures and to reveal their ultrastructural characteristics, respectively. Myelinated nerve fibres densely populated the peri-implant crestal gingival and apical regions, although they were also identified in the woven bone and in the osteons near the implant threads. Compared with the control group in the mandible, the group that received IIP＋IL showed a higher innervation （in N.mm^-2, 5.94±1.12 vs. 3.15±0.63, P〈0.001） and smaller fibre diameter （in pm, 1.37±0.05 vs. 1.64±0.13, P=0.016）, smaller axon diameter （in pm, 0.89±0.05 vs. 1.24±0,10, P=0.009） and g-ratio （0.64±0.04 vs. 0.76±0.05, P〈0.001） in the middle region around the implants. Compared with DIP＋IL in the mandible, IIP＋IL had a higher nerve density （in N.mm^-2, 13.23±2.54 vs. 9.64±1.86, P=0.027）, greater fibre diameter （in pm, 1.32±0.02 vs. 1.20±0.04, P=0.021）, greater axon diameter （in μm, 0.92±0.01 vs. 0.89±0.03, P=-0.035） and lower g-ratio （0.69±0.01 vs. 0.74±0.01, P=-0.033） in the apical region around the implants. It may be assumed that the treatment protocol with liP＋ IL is the preferred method to allow optimized peri-implant re-innervation, but further functional measurements are still required.

结合功能测试与模拟驾驶的老年人驾驶适性评估

为应对老年驾驶人驾驶能力下降带来的交通安全问题并降低与其相关的事故风险,建立了可有效替代道路驾驶测试的老年人驾驶适性评估方法.对92名老年驾驶人进行了功能测试、模拟驾驶测试与道路驾驶测试,通过独立样本T检验与分层逐步Logistic回归确定评价指标体系,分别建立并比选了决策树、随机森林和支持向量机3种评估模型.结果表明,以对比敏感度、功能性伸展、交通标志理解以及合流变道距离等作为评价指标的支持向量机模型对驾驶适性的评估效果最好,准确率高达84.6%.该方法可以有效替代道路测试评估老年人的驾驶适性,能为其停止驾驶、调整驾驶行为、训练提升驾驶能力、使用辅助驾驶技术等提供参考.

Photocatalytic and Electrocatalytic Generation of Hydrogen Peroxide: Principles, Catalyst Design and Performance

Hydrogen peroxide(H_(2)O_(2)) is a high-demand organic chemical reagent and has been widely used in various modern industrial applications. Currently,the prominent method for the preparation of H_(2)O_(2) is the anthraquinone oxidation.Unfortunately, it is not conducive to economic and sustainable development since it is a complex process and involves unfriendly environment and potential hazards. In this context, numerous approaches have been developed to synthesize H_(2)O_(2). Among them, photo/electro-catalytic ones are considered as two of the most promising manners for on-site synthesis of H_(2)O_(2). These alternatives are sustainable in that only water or O_(2) is required. Namely, water oxidation(WOR) or oxygen reduction(ORR)reactions can be further coupled with clean and sustainable energy. For photo/electro-catalytic reactions for H_(2)O_(2) generation, the design of the catalysts is extremely important and has been extensively conducted with an aim to obtain ultimate catalytic performance. This article overviews the basic principles of WOR and ORR,followed by the summary of recent progresses and achievements on the design and performance of various photo/electro-catalysts for H_(2)O_(2) generation. The related mechanisms for these approaches are highlighted from theoretical and experimental aspects. Scientific challenges and opportunities of engineering photo/electro-catalysts for H_(2)O_(2) generation are also outlined and discussed.

Platelet-rich plasma for regeneration of neural feedback pathways around dental implants: a concise review and outlook on future possibilities

Along with the development of new materials, advanced medical imaging and surgical techniques, osseointegrated dental implants are considered a successful and constantly evolving treatment modality for the replacement of missing teeth in patients with complete or partial edentulism. The importance of restoring the peripheral neural feedback pathway and thus repairing the lack of periodontal rnechanoreceptors after tooth extraction has been highlighted in the literature. Nevertheless, regenerating the nerve fibers and reconstructing the neural feedback pathways around osseointegrated implants remain a challenge. Recent studies have provided evidence that platelet-rich plasma （PRP） therapy is a promising treatment for musculoskeletal injuries. Because of its high biological safety, convenience and usability, PRP therapy has gradually gained popularity in the clinical field Although much remains to be learned, the growth factors from PRP might play key roles in peripheral nerve repair mechanisms. This review presents known growth factors contributing to the biological efficacy of PRP and illustrates basic and （pre-）clinical evidence regarding the use of PRP and its relevant products in peripheral nerve regeneration. In addition, the potential of local application of PRP for structural and functional recovery of iniured peripheral nerves around dental implants is discussed.

型煤中硫的还原热解MS和GC/MS分析(英文)

以煤和生物质为主要原料的商用型煤为研究对象,采用还原热解(AP-TPR)在线质谱(M S)联用,以及离线色谱/质谱(GC/M S)分析法,定性和定量研究了家用型煤释放的含硫化合物。不同组成的型煤表现出各自不同的硫释放特性。对于生物型煤来说,仅检测到少量二烷基硫醚和脂肪硫醇的存在。褐煤型煤检测到种类最多的有机硫化物。在高阶煤制成的型煤中没有检测到氧化态的硫化物,其典型特征是存在一些噻吩类硫化物。

Acute heart failure in elderly patients:a review of invasive and non-invasive management

Acute heart failure(AHF)is a major cause of unplanned hospitalisations in the elderly and is associated with high mortality.Its prevalence has grown in the last years due to population aging and longer life expectancy of chronic heart failure patients.Although international societies have provided guidelines for the management of AHF in the general population,scientific evidence for geriatric patients is often lacking,as these are underrepresented in clinical trials.Elderly have a different risk profile with more comorbidities,disability,and frailty,leading to increased morbidity,longer recovery time,higher readmission rates,and higher mortality.Furthermore,therapeutic options are often limited,due to unfeasibility of invasive strategies,mechanical circulatory support and cardiac transplantation.Thus,the in-hospital management of AHF should be tailored to each patient's clinical situation,cardiopulmonary condition and geriatric assessment.Palliative care should be considered in some cases,in order to avoid unnecessary diagnostics and/or treatments.After discharge,a strict follow-up through outpatient clinic or telemedicine is can improve quality of life and reduce rehospitalisation rates.The aim of this review is to offer an insight on current literature and provide a clinically oriented,patient-tailored approach regarding assessment,treatment and follow-up of elderly patients admitted for AHF.

Energy-Efficient UAVs Coverage Path Planning Approach

Unmanned aerial vehicles(UAVs),commonly known as drones,have drawn significant consideration thanks to their agility,mobility,and flexibility features.They play a crucial role in modern reconnaissance,inspection,intelligence,and surveillance missions.Coverage path planning(CPP)which is one of the crucial aspects that determines an intelligent system’s quality seeks an optimal trajectory to fully cover the region of interest(ROI).However,the flight time of the UAV is limited due to a battery limitation and may not cover the whole region,especially in large region.Therefore,energy consumption is one of the most challenging issues that need to be optimized.In this paper,we propose an energy-efficient coverage path planning algorithm to solve the CPP problem.The objective is to generate a collision-free coverage path that minimizes the overall energy consumption and guarantees covering the whole region.To do so,the flight path is optimized and the number of turns is reduced to minimize the energy consumption.The proposed approach first decomposes the ROI into a set of cells depending on a UAV camera footprint.Then,the coverage path planning problem is formulated,where the exact solution is determined using the CPLEX solver.For small-scale problems,the CPLEX shows a better solution in a reasonable time.However,the CPLEX solver fails to generate the solution within a reasonable time for large-scale problems.Thus,to solve the model for large-scale problems,simulated annealing forCPP is developed.The results show that heuristic approaches yield a better solution for large-scale problems within amuch shorter execution time than the CPLEX solver.Finally,we compare the simulated annealing against the greedy algorithm.The results show that simulated annealing outperforms the greedy algorithm in generating better solution quality.

Detecting Man-in-the-Middle Attack in Fog Computing for Social Media

Fog computing(FC)is a networking paradigm where wireless devices known as fog nodes are placed at the edge of the network(close to the Internet of Things(IoT)devices).Fog nodes provide services in lieu of the cloud.Thus,improving the performance of the network and making it attractive to social media-based systems.Security issues are one of the most challenges encountered in FC.In this paper,we propose an anomalybased Intrusion Detection and Prevention System(IDPS)against Man-in-theMiddle(MITM)attack in the fog layer.The system uses special nodes known as Intrusion Detection System(IDS)nodes to detect intrusion in the network.They periodically monitor the behavior of the fog nodes in the network.Any deviation from normal network activity is categorized as malicious,and the suspected node is isolated.ExponentiallyWeighted Moving Average(EWMA)is added to the system to smooth out the noise that is typically found in social media communications.Our results(with 95%confidence)show that the accuracy of the proposed system increases from 80%to 95%after EWMA is added.Also,with EWMA,the proposed system can detect the intrusion from 0.25–0.5 s seconds faster than that without EWMA.However,it affects the latency of services provided by the fog nodes by at least 0.75–1.3 s.Finally,EWMA has not increased the energy overhead of the system,due to its lightweight.

Eligibility of persons who inject drugs for treatment of hepatitis C virus infection

In this decade, an increase is expected in end-stageliver disease and hepatocellular carcinoma, most commonly caused by hepatitis C virus(HCV) infection.Although people who inject drugs(PWID) are the ma-jor source for HCV infection, they were excluded fromantiviral treatments until recently. Nowadays there isincontrovertible evidence in favor of treating these patients, and substitution therapy and active substanceuse are no longer contraindications for antiviral treatment. The viral clearance in PWID after HCV antiviraltreatment with interferon or pegylated interferon combined with ribavirin is comparable to the viral clearancein non-substance users. Furthermore, multidisciplinary approaches to delivering treatment to PWID are advised, and their treatment should be considered on anindividualized basis. To prevent the spread of HCV inthe PWID community, recent active PWID are eligiblefor treatment in combination with needle exchange programs and substitution therapy. As the rate of HCV reinfection is low after HCV antiviral treatment, there is no need to withhold HCV treatment due to concerns about reinfection alone. Despite the advances in treatment efficacies and data supporting their success, HCV assessment of PWID and initiation of antiviral treatment remains low. However, the proportion of PWID assessed and treated for HCV is increasing, which can be further enhanced by understanding the barriers to and facilitators of HCV care. Removing stigmatization and implementing peer support and group treatment strategies, in conjunction with greater involvement by nurse educators/practitioners, will promote greater treatment seeking and adherence by PWID. Moreover, screening can be facilitated by noninvasive methods for detecting HCV antibodies and assessing liver fibrosis stages. Recently, HCV clearance has become a major endpoint in the war against drugs for the Global Commission on Drug Policy. This review highlights the most recent evidence concerning HCV infection and treatment strategies in PWID.

网络信息检索中利用the Staceys测度方法提高逻辑运算效率的思考

网络信息检索中，逻辑运算符AND连接检索词的顺序很大程度上会影响检索效率。论文首先分析、介绍了the Staceys测度方法在改善AND检索效率中发挥的作用，并在此基础上提出简化了的测度算法，最后通过实例说明其实现步骤。