Carbon Quantum Dots (CQDs) have emerged as promising nanomaterials for enhancing the performance of supercapacitors, offering unique advantages such as high surface area, excellent electrical conductivity, and tunable surface chemistry. This review provides a comprehensive overview of recent advancements in the synthesis, characterization, and integration of CQDs into supercapacitor devices. Various synthesis methods, including chemical oxidation, hydrothermal/solvothermal methods, microwave-assisted synthesis, and pyrolysis, are discussed, highlighting their impact on the structural and electrochemical properties of CQDs. Characterization techniques such as transmission electron microscopy (TEM), X-ray diffraction (XRD), Raman spectroscopy, and photoluminescence (PL) spectroscopy are elucidated for assessing the morphology, crystallinity, and optical properties of CQDs. The integration of CQDs into supercapacitors, including their utilization in composite electrodes, binder-free electrodes, and doping strategies, is explored to enhance specific capacitance, energy density, power density, and cycle stability of the devices. Challenges and future perspectives in the field are outlined, emphasizing the need for scalable synthesis methods, enhanced electrochemical performance, and sustainable device engineering to realize the full potential of CQD-based supercapacitors for various energy storage applications. This review aims to provide insights into the current state of research and guide future endeavors towards developing high-performance and environmentally sustainable energy storage technologies.

Solar energy has emerged as a promising alternative to traditional fossil fuels due to its abundant availability and sustainability. Solar cells, the fundamental units of solar energy conversion, have undergone significant advancements in fabrication techniques to enhance their efficiency, durability, and cost-effectiveness. This review aims to provide a comprehensive overview of various methods employed in the preparation of solar cells, including thin-film, crystalline silicon, organic, and perovskite-based technologies. By analyzing recent research developments, challenges, and future prospects, this article sheds light on the evolving landscape of solar cell fabrication, contributing to the ongoing efforts in achieving widespread adoption of solar energy.

This comprehensive review explores the multifaceted landscape of supercapacitors, highlighting their pivotal role in meeting the global demand for efficient energy storage solutions. Supercapacitors, with their high power density, rapid charge-discharge cycles, and extended cycle life, offer a compelling alternative to conventional batteries and capacitors. The review delves into the fundamental mechanisms of energy storage in supercapacitors, categorizing them into Electrochemical Double-Layer Capacitors (EDLCs), pseudocapacitors, and hybrid capacitors. It discusses significant advancements in supercapacitor technology, including nanostructured materials, flexible and wearable supercapacitors, solid-state supercapacitors, and hybrid supercapacitors, highlighting their potential applications across industries such as transportation, renewable energy, consumer electronics, and industrial power management. Through continued research and development, supercapacitors are poised to play a pivotal role in driving the transition towards a greener and more efficient future.

The escalating global demand for clean water has propelled research into sustainable and cost-effective purification methods. Activated carbon (AC) derived from biowaste materials presents an environmentally friendly and economically viable solution for water treatment. This review article provides an extensive overview of the synthesis techniques, characterization methods, and applications of biowaste activated carbon (BAC) for water purification. It discusses the diverse sources of biowaste, such as agricultural residues, food waste, and biomass, and explores various activation methods including physical, chemical, and biological processes. Furthermore, the article examines the adsorption mechanisms, performance factors, regeneration strategies, and emerging trends in BAC synthesis and application. Insights from this review can guide future research endeavors and facilitate the development of sustainable water purification technologies.

The timely and accurate detection of HIV infection is pivotal in stemming the tide of this global pandemic and facilitating early treatment initiation. This review offers a comprehensive examination of the diverse array of methods employed for HIV detection, spanning traditional serological assays to cutting-edge technologies such as nucleic acid amplification, biosensor innovations, and artificial intelligence-driven diagnostics. Each method is scrutinized in terms of its principles, applications, strengths, and limitations. By integrating these complementary approaches and fostering collaboration across disciplines, researchers and clinicians gain a multifaceted understanding of HIV infection, enabling them to navigate the complexities of the virus with precision and insight. Through a multidisciplinary lens, encompassing immunology, molecular biology, engineering, and public health, this review aims to inform future directions in HIV detection, ultimately guiding efforts towards personalized, precise, and accessible diagnostics for all individuals affected by the HIV/AIDS epidemic.

Medicinal plants have been a cornerstone of traditional medicine systems for centuries, offering a vast array of bioactive compounds with therapeutic potential. However, the identification, characterization, and elucidation of the pharmacological properties of these plants have often been challenging due to their complex chemical composition and diverse biological activities. Bioinformatics, with its interdisciplinary approach combining biology, computer science, and information technology, presents a powerful toolkit for the systematic study of medicinal plants. This review provides an overview of bioinformatics methodologies and resources that can facilitate the identification, phytochemical analysis, pharmacological investigation, and conservation of medicinal plants. It highlights the integration of omics technologies, computational algorithms, database resources, and molecular modeling techniques in advancing our understanding of medicinal plants' therapeutic potential and their applications in drug discovery and development.

Prestressed concrete sleepers (or railroad ties) are principally designed in order to carry wheel loads from the rails to the ground of railway tracks. Their design takes into account static and dynamic loading conditions. In spite of the most common use of the prestressed concrete crossties in railway tracks, there have always been many demands from rail engineers to improve serviceability and functionality of concrete crossties. For example, signaling, fiber optic, equipment cables are often damaged either by ballast corners or by tamping machine. There has been a need to re-design concrete crosstie to cater cables internally so that they would not experience detrimental or harsh environments. Also, many concrete crossties need a retrofit for automatic train control device and similar signaling equipment. In contrast, the effects of holes and web openings on structural capacity of concrete crossties have not been thoroughly investigated. This paper accordingly highlights the effect of holes and web openings on the toughness and ductility of concrete crossties. The outcome of this research enables better decision making process for retrofiting prestressed concrete crossties with holes and web opening in practice.

Blood cancers, including leukemia, lymphoma, and myeloma, pose significant diagnostic challenges due to their diverse and complex nature. Detecting these cancers early and accurately is crucial for timely intervention and improved patient outcomes. This review explores current and emerging detection methods for human blood cancers, focusing on their principles, advantages, limitations, and potential clinical applications.

Graphene quantum dots (GQDs) have garnered significant attention in recent years due to their unique properties and promising applications in various fields such as electronics, optoelectronics, bioimaging, and sensing. The synthesis of GQDs is a critical step in harnessing their potential, and numerous methods have been developed to produce GQDs with specific properties. This review provides an overview of the different techniques employed for synthesizing GQDs, including top-down and bottom-up approaches. Furthermore, it discusses the advantages, limitations, and potential applications of each method, offering insights into the future direction of GQD synthesis research.

HIV early detection (CD4 counts ≥350 cells/μL) is correlated with higher life expectancy among people living with HIV (PLHIV). Several factors including physical, cultural, structural, and financial barriers have contributed to HIV late detection. This is the first-of-its-kind study on the regional differences in early detection of HIV within Tajikistan and any country in the Central Asia region. Utilizing Tajikistan Ministry of Health's national HIV data (N=10,700) spanning 2010 to 2023, we developed median regression models with median CD4 cell count as the outcome and as predictors: time (years), region, age, gender, and area (urban/rural status). Individuals younger than 19 years old are more likely to be detected early for HIV, whereas those older than 39 years are more prone to late detection. Given their active engagement in age-related and sexual activities, those older than 39 years face a higher risk of HIV transmission to others if diagnosed late. Therefore, they require further attention and targeted interventions. Females are detected earlier compared to their male counterparts, regardless of region of residence. Rural populations are detected earlier in most years compared to their urban counterparts. The COVID-19 pandemic accelerated HIV early detection in 2021 but most regions have returned to near pre-pandemic levels of detection in 2022 and 2023. These fluctuations in early detection may signify a shift in attention and resource allocation, potentially affecting efforts to address access gaps during the initial year of the COVID-19 pandemic. There are significant health inequities among different demographic and geographic groups which warrant further attention.

We presented unusual case of double left ventricular false aneurysm complicating late presentation AMI successfully treated with the combination of urgent surgical drainage of tamponade, staged PCI of non-culprit lesion, preventive implantation of ICD-DR, guideline directed heart failure medical therapy and delayed but effective reconstructive operation.

The nucleus has been studied for well over 100 years, and chromatin has been the intense focus of experiments for decades. In this review, we focus on an understudied aspect of chromatin biology, namely the chromatin fiber polymer's mechanical properties. In recent years, innovative work deploying interdisciplinary approaches including computational modeling, in vitro manipulations of purified and native chromatin have resulted in deep mechanistic insights into how the mechanics of chromatin might contribute to its function. The picture that emerges is one of a nucleus that is shaped as much by external forces pressing down upon it, as internal forces pushing outwards from the chromatin. These properties may have evolved to afford the cell a dynamic and reversible force-induced communication highway which allows rapid coordination between external cues and internal genomic function.

Actuators are essential components for intelligent machines that can fulfill certain tasks in response to environmental stimuli. In recent years, actuators that can transform from a 2D ribbon shape to a 3D helical configuration under certain external stimuli have attracted significant attention due to the potential applications of the targeted helical structures in springs, propulsion generation, and artificial muscles. Inspired by the chiral opening of Bauhinia variegate‘s seedpods and the coiling of the Towel Gourd tendril with perversions, researchers have made significant breakthroughs in synthesizing state-of-the-art actuators capable of mimicking helical transformations. In this review, we give a brief overview of the shape evolution mechanisms of these two plant structures and then review recent progress in the fabrication of biomimetic helical actuators. These structures are categorized by the stimuli-responsive materials involved, including hydrogels, liquid crystal networks/elastomers, shape memory polymers, and multiwall carbon nanotubes. By providing this survey on important recent advances along with our perspectives, we hope to solicit new inspirations and insights on the development and fabrication of smart actuators, as well as the future development of interdisciplinary research at the interface of physics, engineering, and biology.

Despite the expansion of financial institutions and proliferation of mobile financial services, reaching the unbanked and bringing them under formal financial services has become a policy concern in many developing countries. Due to the lack of financial accounts, unbanked people prefer informal, risky, and inconvenient mechanisms for receiving, sending and transferring money. Previous studies rely much on common intervention like no account maintenance and opening fees, easy documentation processes and money subsidies for opening financial accounts. This study aims to examine the impact of the motivational workshop on opening savings accounts through causality among the unbanked people in a setting where the respondents are unbanked despite having all the requirements and many institutional offers for opening savings accounts. We encouraged the unbanked people through a one-hour-long motivational workshop to open saving account. Based on our cross-sectional data and randomized controlled trial experiment among 505 unbanked Village Defense Party (VDP) members at Dhubil Union under Sirajganj in Bangladesh, we have the evidence that motivational workshop positively impacts opening ac-counts by 32.33 percent. However, the account opening rate differs in terms of respondent’s pref-erence for financial institutions. Our study also finds that unbanked people have the highest pref-erence for mobile financial services for opening accounts resulting in 15.33 percent. The result of the study has some policy implications for adopting effective strategies of financial access in many developing countries.

This research review explores the synthesis of graphene quantum dots (GQDs) from biowaste for supercapacitor applications, driven by the need for sustainable and efficient energy storage technologies. GQDs, with their unique properties like high surface area and excellent conductivity, hold promise for enhancing supercapacitor performance. Various synthesis methods, including hydrothermal/solvothermal processes, chemical exfoliation, carbonization/pyrolysis, and microwave-assisted synthesis, are discussed alongside characterization techniques to evaluate GQD properties. Biowaste-derived GQDs demonstrate significant potential by improving specific capacitance and cycling stability in supercapacitor electrodes. Challenges such as scalability and material purity are identified, with future directions focusing on enhancing energy density, cycle life, and cost-effectiveness to propel the adoption of biowaste-derived GQDs in commercial energy storage applications.

Graphene, a single layer of carbon atoms arranged in a two-dimensional honeycomb lattice, has attracted tremendous attention due to its exceptional properties and diverse applications. Synthesis methods play a crucial role in tailoring graphene's properties for specific applications. This review provides a comprehensive overview of recent advances in graphene synthesis techniques, including chemical vapor deposition (CVD), exfoliation, epitaxial growth, and chemical reduction. We discuss the principles, advantages, challenges, and applications associated with each method. Furthermore, emerging trends and future prospects in graphene synthesis are explored, with a focus on scalability, cost-effectiveness, and environmental sustainability.

Machine learning (ML) has emerged as a critical tool for making sense of the growing amount of genetic and genomic data available because of its ability to find complex patterns in high dimensional and heterogeneous data. While the complexity of ML models is what makes them powerful, it also makes them difficult to interpret. Fortunately, recent efforts to develop approaches that make the inner workings of ML models understandable to humans have improved our ability to make novel biological insights using ML. Here we discuss the importance of interpretable ML, different strategies for interpreting ML models, and examples of how these strategies have been applied. Finally, we identify challenges and promising future directions for interpretable ML in genetics and genomics.

The issue of when and how to return to business following COVID-19 lockdown is occupying the minds of policymakers, C-Suite executives and managers the world over. We are concerned by the extent to which it appears that these decisions are being taken on a wing and a prayer, while being pitched to the public as though they shouldn’t be questioned. In this paper, we compare the likely impact of COVID-19 infections from travellers coming from the main countries that visit Greece, to the revenues they generate for the Greek economy. We find that arrivals from some countries should be excluded but aren't, while arrivals from other countries that are excluded perhaps shouldn't be. We show that a rational choice around limitations on the reopening of tourist markets depends on the demand for travel to Greece. We conclude that the current policy is largely economically rational, with some exceptions, but also speculate that Greece may not be ready to handle the resulting infection load.

Evaluating genetic diversity in walnut (Juglans regia L.) populations is a rapid approach used by walnut breeding programs to distinguish superior genotypes. The present study identified the Hamedan province walnut population as one of the richest, most genetically diverse regions in Iran during 2019-2020. After initial screening, 47 genotypes were selected for further evaluation of pomological and phenological traits based on International Plant Genetic Resources Institute (IPGRI) descriptors. Nut and kernel weights among the selected genotypes ranged between 7.15-21.05 g and 3.0-10.8 g, respectively. Principal component analysis (PCA) categorized genotypes into three distinct groups while cluster analysis (CA) further categorized genotypes into one of four groups. Spearman correlation analysis showed a positive correlation (P <0.01) between nut weight (NWT), nut size, and kernel weight (KW) while a negative correlation (P <0.01) between shell thickness (STH) and packing tissue thickness (PTT) with kernel percentage (KP) was observed. Lastly, 10 of 47 genotypes (TAL8, TAL9, TAL10, TAL14, TAL19, TAL22, TB2, TB4, TB6, and RDGH5) were considered superior. Superior genotypes were late-leafing (25-40 days after the standard) and displayed a lateral bearing (LB) habit with heavy nuts (12.52–16.82 g) and kernels (6.53–8.15 g), thin-shells (1.06–1.25 mm), and lightly-colored kernels. Cuttings of superior genotypes were then grafted in the orchard. Detecting superior and late-leafing genotypes in this investigation suggests cultivars resistant to late-spring frost may soon be isolated.

Background: Infantile tibia vara (ITV) is a rare proximal tibia deformity in infancy, leading to progressive knee varus. High tibial osteotomy is commonly practiced but has high recurrence rates. This study analyzed factors affecting treatment failure and recurrence in children undergoing opening-wedge high tibial osteotomy (OWHTO) for ITV. Methods: We retrospectively studied children with ITV who had OWHTO with press-fit cancellous bone allograft between 2000 and 2020, with ≥2-year follow-up. Outcomes included recurrence (knee varus with tibiofemoral angle >10°), complications, and reintervention. Results: We analyzed 39 knees in 29 patients (mean age: 4.8 ± 1.9 years; median follow-up: 7.4 years). Recurrence occurred in 22 cases (56%). Age at surgery significantly influenced recurrence, with rates of 16% before age 5 versus 95% later (hazard ratio: 12.0, p = 0.001). Langenskiöld stage also affected recurrence (β-coefficient: 2.7, 95% C.I. 1.0–4.5, p = 0.002; pseudo-R-squared: 0.50, p = 0.001), with recurrence in all stage III IV or higher cases. Conclusions: Early diagnosis and treatment before age 45, ideally with Langenskiöld stage III or lower, are crucial for stable correction with OWHTO alone. Late, high-grade ITV may require combined, acute or gradual, and/or staged correction. Further evidence is needed for optimal management.

The growing concerns about floods have highlighted the need for accurate and detailed precipitation data as extreme precipitation occurrences can lead to catastrophic floods, resulting in significant economic losses and casualties. Integrated Multi-satellitE Retrievals for the Global Precipitation Measurement (GPM-IMERG) is a commonly used high-resolution gridded precipitation dataset and is recognized as trustworthy alternative sources of precipitation data. The aim of this study is to comprehensively evaluate the performance of GPM IMERG Early (IMERG-E), Late (IMERG-L), and Run Final (IMERG-F) in precipitation estimation and their capability in detecting extreme rainfall indices over southwestern Iran during 2001-2020. The Asfezari gridded precipitation data which are developed using a dense of ground-based observation were utilized as the reference dataset. The findings indicate that the IMERG-F performs reasonably well in capturing many extreme precipitation events (defined by various indices). All the three products showed a better performance in capturing fixed and non-threshold precipitation indices across the study region. The findings also revealed that both IMERG-E and IMERG-L have problems in rainfall estimation over elevated areas showing values of overestimations. Examining the effect of land cover type on the accuracy of the precipitation products suggest that both IMERG-E and IMERG-L show large and highly unrealistic overestimations over inland water bodies and permanent wetlands. The results of the current study highlight the potential of IMERG-F as a valuable source of data for precipitation monitoring in the region.

The experimental results of forces and efforts derived from the opening of incisions in the orbital cavity in a pig’s head are presented in this article. The different areas of the incision openings are related to the needs at the incision procedure for a dacryocystorhinostomy. In terms of the experimental procedure, an origin and a plane are defined so as to allow the location of the opening of the incision. The incisions are retracted along an axis of said origin. This procedure has been based on the mathematical model developed for this work, which consists of a procedure for determining the behavior of an incision when a force is applied to retract the skin. The experimental data obtained, suggests the existence of an almost linear relationship between the increment of resistance in relation to the time obtained for each opening, the same of which is deemed to be consistent with the behavior of an elastic material.

Frontotemporal lobar degeneration (FTLD) belongs to a heterogeneous group of highly complex neurodegenerative diseases and represents the second cause of presenile dementia in individuals under 65. Frontotemporal-TDP is a subgroup of frontotemporal dementia characterized by the aggregation of abnormal protein deposits, predominantly transactive response DNA-binding protein 43 (TDP-43), in the frontal and temporal brain regions. These deposits lead to progressive degeneration of neurons resulting in cognitive and behavioral impairments. Limbic age-related encephalopathy (LATE) pertains to age-related cognitive decline primarily affecting the limbic system which is crucial for memory, emotions, and learning. Though distinct, emerging research suggests a potential overlap in pathogenic processes, with some cases of limbic encephalopathy displaying TDP-43 pathology. Genetic factors play a pivotal role in both disorders. Mutations in various genes, such as progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72), have been identified as causative in frontotemporal-TDP. Similarly, specific genetic variants have been associated with an increased risk of developing LATE. Understanding these genetic links provides crucial insights into disease mechanisms and the potential for targeted therapies.

The article contains the results of experimental studies for a multi-opening orifice with substitute constriction factor of β = 0.5 (m = 0.25), mounted in a DN50 hydraulic measuring flume. Flow measurements were taken for a progressing turbulent flow within Reynolds numbers (Re = 4700...19500). Based on experimental data, flow characteristics as well as discharge coefficient C characteristics were determined. Relative expanded uncertainty of determining a discharge coefficient C was estimated within the changes of volume flow qv from 0.35 dm3/s to 0.68 dm3/s. The value does not exceed 1.25% within the changes of Reynolds numbers 9800 ≤ Re ≤ 19500.

In C. elegans, gap junctions couple cells of the somatic gonad with the germline to support germ cell proliferation and gametogenesis. We previously characterized a strong loss-of-function mutation (T239I) affecting the second extracellular loop (EL2) of the somatic INX-8 hemichannel subunit. These mutant hemichannels form non-functional gap junctions with germline-expressed innexins. Here we describe the characterization of mutations that restore germ cell proliferation in the T239I EL2 mutant background. We recovered seven intragenic mutations located in diverse domains of INX-8 but not the EL domains. These second-site mutations compensate for the original channel defect to varying degrees, from nearly complete wild-type rescue, to partial rescue of germline proliferation. One suppressor mutation (E350K) supports the innexin cryo-EM structural model that the channel pore opening is surrounded by a cytoplasmic dome. Two suppressor mutations (S9L and I36N) may form leaky hemichannels that support germline proliferation but cause the demise of somatic sheath cells. Phenotypic analyses of three other suppressors reveal an equivalency in the rescue of germline proliferation and comparable delays in gametogenesis but a graded rescue of fertility. These latter mutations may be useful to probe interactions with the biochemical pathways that produce the molecules transiting through soma-germline gap junctions.

Background and Objectives: Uveitis, a prevalent eye disorder characterized by inflammatory processes, often leads to cataract formation and significant visual impairment. This study aimed to evaluate preoperative conditions and postoperative outcomes following cataract surgery in uveitis patients. Materials and Methods: A retrospective study was conducted at the University Hospital Center Rebro Zagreb, Croatia, involving uveitis patients who underwent cataract surgery between 2013 and 2022. Eligible patients had uveitic cataracts affecting visual acuity or posterior segment visualization in a "quiet eye" and were disease-inactive for at least three months. Patients with certain preexisting ocular conditions were excluded. Data collected included patient demographics, uveitis type, preoperative therapy, preexisting lesions, and postoperative outcomes such as visual acuity, intraocular pressure, central macular thickness, and complications. Statistical analysis was performed to identify risk factors associated with complications. Results: The study included 105 patients. After cataract surgery, there was a significant improvement in visual acuity at various time points, with 90% of eyes showing improvement. Intraocular pressure decreased over time. Central macular thickness increased at three months post-surgery but remained stable thereafter. Early and late complications were observed in 52.4% and 63.8% of eyes, respectively. The most common complications were posterior capsular opacification, macular edema, and epiretinal membrane. Factors associated with complications varied between early and late stages but included age, age at onset of uveitis, and uveitis type. Conclusion: Cataract surgery in uveitis patients presents challenges but can lead to significant visual improvement. This study highlights the importance of careful patient selection, preoperative and postoperative inflammation management, and precise surgical techniques. Although complications were common, they were manageable, and most patients experienced improved vision, emphasizing the benefits of cataract surgery in this population. However, future investigations should address the study's limitations and further refine perioperative strategies.

There is limited data on pregnancy outcomes in Pompe Disease (PD) resulting from deficiency of the lysosomal enzyme acid alpha-glucosidase. Late-onset PD is characterized by progressive proximal muscle weakness and decline of respiratory function secondary to the involvement of the respiratory muscles. In a cohort of twenty-five females, the effects of both PD on the course of pregnancy and the effects of pregnancy on PD were investigated. Reproductive history, course of pregnancy, use of Enzyme replacement therapy (ERT), PD symptoms, and outcomes of each pregnancy were obtained through a questionnaire. Among 20 subjects that reported one or more pregnancies, one subject conceived while on ERT and continued therapy through two normal pregnancies with worsening of weakness during pregnancy and improvement postpartum. While fertility was not affected, pregnancy may worsen symptoms, or cause initial symptoms to arise. Complications with pregnancy or birth were not higher, except for an increase in the rate of stillbirths (3.8% compared to the national average of 0.2-0.7%). Given small sample size and possible bias of respondents being only women who have been pregnant, further data may be needed to better analyze the effects of pregnancy on PD, and the effects of ERT on pregnancy outcomes.

In this review, we explore a broad-based view of technologies for supporting human activities on the Moon. Primarily, we assess the state of life support systems technology beginning with physicochemical processes, waste processing, bioregenerative methods, food production systems and the robotics and advanced biological technologies that support the latter. We observe that the Moon possesses in-situ resources but that these resources are of limited value in CELSS – indeed, CELSS technology is most mature in recycling water and oxygen, the two resources that are abundant on the Moon. This places a premium on developing CELSS that recycles other elements that are rarified on the Moon including C and N in particular but also other elements such as P, S and K which might be challenging to extract from local resources. Although we focus on closed loop ecological life support systems, we also consider related technologies that involve the application of biological organisms to bioregenerative medical technologies and bioregenerative approaches to industrial activity on the Moon as potential future developments.

Background: The practices of various health-care professionals have been improvised to accommodate the on-going covid-19 pandemic situation. Different guidelines have been set in place to ease the process of re-opening of non-elective healthcare services like out-patient physiotherapy clinics. Although the measures taken should be guided by evidence based information, major consensus amongst practicing therapists needs to guide the India physiotherapy clinics. Objective: To identify and present the opinions of different physiotherapists about the various strategies for re-opening the out-patient physiotherapy clinics. Methods: An online cross-sectional survey was conducted. Over 169 participants were selected to participate in the survey according to the pre-decided inclusion and exclusion criteria. The data was collected and saved via google forms. Result and conclusion: A majority of respondents had a consensus over different strategies for re-opening the physiotherapy OPDs. These were regarding different measures to be adapted including modifications in the clinic infrastructure and the practice pattern. This would help in smoothly re-instating the physiotherapy services post the covid-19 lockdown.

Opening gated-communities (GCs) has been widely discussed for urban inclusion and revitalization. With the policies of opening GCs being promoted in China, quantitative and comprehensive evaluation of the potential benefits is heavily needed. Taking Shanghai as an example, this study quantifies and analyzes the accessibility benefits and risks of opening GCs with factors including GC types, opening levels, travel modes, and travel destinations considered. We found that (1) opening GCs can bring 50m+ accessibility gains to 17% and 52% of the residents in Moderately Opening (MO) and Completely Opening (CO) scenarios, respectively. (2) Cycling benefits more than walking in all cases and scenarios. (3) For different GCs, conventional GCs have fewer benefits in MO but more in CO than the newly-established one. For different facilities, trips to bus stations demonstrate the largest accessibility gains. (4) The accessibility benefit of a residential building is highly determined by its closeness to the gates and relative location in the block. (5) Only 1% and 5-7% of external trips may penetrate the opened communities in MO and CO scenarios, respectively, which are far less than both expectation and the benefits. These findings precipitate at least two policy implications in China.

This article focuses on the description of the other view of Valencia in the fifteenth century, that of social marginalization, which could be manifested by the fact of exercising various trades considered immoral. In the following pages, a description is offered of two female collectives that are particularly treated as vile and despicable: that of healers, sorceresses and witches, whose strength was considered to stem from a demonic origin, and that of prostitutes, dedicated to covering a "lesser evil" in society but seen as unworthy by society because of the practical exercise of their trade.

We measure the accelerated cosmic expansion rate of the late-time Universe and derive constraints on cosmological parameters from the final baryon acoustic oscillation (BAO) uncorrelated measurements of different surveys after two decades of dedicated spectroscopic observation combined with the Pantheon sample of Type Ia supernovae, the Hubble diagram of gamma-ray bursts &amp; quasars data, the Cosmic Chronometers data, and the recent Hubble constant value measurement from the Hubble Space Telescope and the SH0ES Team as an additional prior. In Λ cold dark matter (ΛCDM) scenario, the model fit yields Ωm=0.313±0.034 and ΩΛ=0.672±0.025. Combining BAO with CC+Pantheon+QSR+GRB data sets we get H0=69.21±1.22 km s−1 Mpc−1, rd=133.46±2.49 Mpc. For the a flat wCDM model, we get w=−1.111±0.030. For a dynamical evolution of dark energy in a flat w0waCDM cosmology, we get wa=−0.292±0.167. We apply the Akaike information criteria probe to compare the three models, and see that all models are favored and cannot be discarded from the current data.

Using a joint statistical analysis, we test a four-dimensional FLWR model embedded in a five-dimensional bulk based on the Nash-Greene embedding theorem. Performing a Markov Chain Monte Carlo (MCMC) modelling, we combine observational data sets as those of the recent Pantheon type Ia supernovae, Baryon Acoustic Oscillations (BAO) and the angular acoustic scale of the Cosmic Microwave Background (CMB) to impose restrictions on the model and correlating the model parameters to mimick an equation of state. From statistical classifiers as the Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC), we use the Jeffreys' scale and find a strong evidence favoring a statistically consistence with a dynamical Dark energy (CPL parameterization) and a relative consistence with both ΛCDM and ωCDM models. Moreover, we find that the transition redshift used as a cosmic discriminator with the best fit z_t=0.634 ± 0.014 at 1-σ C.L. with a range scenario for late time sharp transitions.

Paracetamol, also known as acetaminophen, is one of the most widely used over-the-counter analgesics and antipyretics globally. While generally considered safe when used as directed, excessive or prolonged use of paracetamol can lead to adverse effects on various organ systems within the human body. This comprehensive review explores the physiological mechanisms underlying paracetamol toxicity, its effects on different organs, risk factors for overdose, diagnostic methods, and potential management strategies.

Background: Meniere disease (MD) is an inner ear disorder associated with comorbidities such as autoimmune diseases or migraine. This study describes clinical and cytokine profile in MD according to the age of onset of the condition. Methods: A cross-sectional study including 83 MD patients: 44 with early onset MD (EOMD, <35 years old), and 39 with late onset MD (LOMD, > 50 years old), 64 patients with migraine and 55 controls was carried out. Clinical variables and cytokines levels of CCL3, CCL4, CCL18, CCL22, CXCL1 and IL-1β were compared among the different groups. Results: CCL18 levels were higher in patients with migraine or MD than in controls. Elevated levels of IL-1β were observed in 11.4% EOMD and in 10.3% LOMD patients and these levels were not dependent on the age of individuals. EOMD had a longer duration of the disease (p=0.004) and a higher prevalence of migraine than LOMD (p=0.045). Conclusions: Patients with EOMD have a higher prevalence of migraine than LOMD, but migraine is not associated with any cytokine profile in patients with MD. The levels of CCL18, CCL3 and CXCL4 were different between patients with MD or migraine and controls.

We investigate the evolution of gravitational waves through discontinuous evolution (transition) of the Hubble expansion rate H(z) at a sudden cosmological singularity which may be due to a transition of the value of the gravitational constant. We find the evolution of the scale factor and the gravitational wave waveform through the singularity by imposing the proper boundary conditions. We also use existing cosmological data and mock data of future gravitational wave experiments (the ET) to impose current and anticipated constraints on the magnitude of such a transition. We show that mock data of the Einstein Telescope can reduce the uncertainties by up to a factor of 3 depending on the cosmological parameter considered.

Introduction: Third molar surgery can cause post-operative complications to the patient due to the presence of wound from the incision. The study aimed to compare marginal flap with para-marginal flap on postoperative complications by the measurements on pre and post-surgical plaque index (PI), bleeding on probing (BoP), maximum opening of the mouth (MOM), pain perception (PP) and post-surgical tumefaction (PT). Methods: In this double-blind randomized clinical trial, 40 patients were recruited and randomly allocated in two groups. In Group 1, third molar extraction was carried out after a marginal flap design was performed, while in group 2 a para-marginal flap was per-formed. Plaque Index, Bleeding on Probing, Maximum Mouth Opening, and Distal Probing were assessed right before and one week after surgery, while Post-operative Pain Perception and Post-operative Swelling were accounted one week following sur-gery. Results: Statistically significant difference are reported between treatment groups, as the para-marginal flap led to better outcomes for all the measured indexes. Conclusion: The para-marginal flap design may decrease the occurrence of post-operative compli-cations and discomforts after mandibular third molar surgery, compared to marginal flap design.

Cardiovascular diseases (CVDs) remain the leading cause of mortality. Traditional approaches to diagnosing and treating CVDs often involve interpretation, which can lead to errors. The emergence of Artificial Intelligence (AI) and Machine Learning aids the management of CVDs. AI examines amounts of data and identifies patterns offering solutions for disease detection, risk prediction, and patient care. The American Heart Association's 2023 Scientific Sessions (AHA23) showcased studies that highlight AIs potential to revolutionize cardiac healthcare. This article presents a review of these cutting-edge studies exploring how AI is applied in health, the outcomes of these applications, and their implications for clinical practice. The insights gained from this review will contribute to the discussion on AI's role in healthcare and its capacity to enhance outcomes.

Sepsis is a life-threatening condition with high hospital mortality. Elevated mortality has also been observed in patients after hospital discharge due to post-sepsis syndrome (PSS). The etiology of PSS is still not entirely known, but it involves inflammation. Plasma extracellular vesicles (EVs) are recognized as a unique mechanism of intercellular communication in inflammatory processes. It has been reported that EV microRNA (miRNA) production during the acute sepsis phase may persist until after disease resolution and is associated with PSS. We employed mass spectrometry and qPCR analysis to determine the protein and miRNA composition of plasma-derived EVs of 36 patients during sepsis-related hospitalization, immediately after ICU discharge (post-sepsis), and three, six, twelve, and up to 36 months post-sepsis. We determined that patients’ immune system cells were the primary EV source. Fifteen differentially expressed EV miRNAs (DEmiRs) were identified in samples from septic patients compared to the control group. Predictive analyses revealed that these DEmiRs could influence inflammation by modulating pathways mediated by NF-κB, STAT3, and TLR4 signaling activation. Thirteen miRNAs (-15b-5p,-16-5p,-20a-5p,-25-3p,-27a-3p,-29a-3p,-30d-5p,-93-5p,-146a-5p,-148a-3p,-191-5p,-195-5p,-223-3p) were downregulated in the death group compared to the survivor group, making them candidate prognostic markers of ICU survival. One year after ICU discharge, the expression of miR-21-5p and miR-195-5p were decreased in the survivor group. The miRNAs identified in the present study represent potential biomarkers for the survival prognosis of post-sepsis patients.

Alzheimer’s disease (AD) predominantly occurs as a late-onset form (LOAD), involving neurodegeneration and cognitive decline with progressive memory loss. Over time, risk factors and aging promote accumulation of well-known AD pathologies in oxidative stress, amyloid-beta and tau protein pathology, as well as inflammation. Homeostatic glial functions regulate and suppress these AD pathologies; however, other glial states involve increased pro-inflammatory cytokine release and further pathology accumulation. Different stresses can additionally induce cellular senescence, or an irreversible differentiation process resulting in decreased supportive functions and increased, pro-inflammatory cytokine release. While these pathophysiological underpinnings all contribute to LOAD, they require temporal and mechanistic integration. This perspective hypothesizes that when individuals have threshold senescent glia accumulation, they transition from healthy cognition into mild cognitive impairment and LOAD diagnosis. Particularly, senescent microglia are predicted to represent a final threshold required for the tau pathology burden and spreading that corresponds to sustained neurodegeneration and dementia severity. We first explore age-related decline in glia that promote increases in AD pathologies, and then discuss emerging evidence linking oxidative stress, neurons containing tau pathology, and amyloid-beta to microglia, oligodendrocyte progenitor cell, and astrocyte senescence. Our hypothesis proposes that senescent astrocytes and oligodendrocyte progenitors pressure microglia to phagocytose neurons containing tau pathology. The resulting senescent microglia would form neuritic plaques and induce paracrine senescence transitioning into a progressive clinical dementia presentation. This predictive hypothesis can potentially account for why medications used to treat LOAD fail, as previous treatments have not reduced senescent glial burden. It is also coherent with the predominant hypotheses surrounding LOAD, generates testable hypotheses about LOAD, and increases rationale in testing senolytics as targeted treatments for LOAD arrest and reversal.

We show that the accelerating expansion phase of the universe can emerge from the group field theory formalism, a candidate theory of quantum gravity. The cosmological evolution can be extracted from condensate states using mean field approximation, in a form of modified FLRW equations. By introducing an effective equation of state w, we can reveal the relevant features of the evolution, and show that with proper choice of parameters, w will approach to −1, corresponds to the behaviour of cosmological constant, results in a late time acceleration and leads to de Sitter spacetime asymptotically.

This article presents a narrative review of neonatal and paediatric complications in post-dated pregnancy and covers scientific views on the aetiology, pathology, risk factors, symptoms and complications of post-dated pregnancy. A pregnancy extending beyond 42 weeks of gestation is termed as a post term pregnancy. There are multiple complications that can occur in the perinatal period, some of the most common ones are stillbirth, asphyxia, meconium aspiration syndrome, fetal distress syndrome, etc which are found to be greater in post-dated pregnancy and hence ultimately leads to increased mortality and morbidity of the new born. Studies have shown that post-term pregnancy also causes increased risk of developing behavioural and emotional problems in children of paediatric age group. It is surprising not much importance has been given to the maternal and neonatal consequences of post- term pregnancies. It is not well understood why some women experience post-dated pregnancies. It is found that factors such as hormones and genetic build up, are responsible for causing post-term pregnancy in an obese female. The treatment and management of a post-term pregnancy still poses a challenge to clinicians in determining the right choice and right time for a particular intervention so that both mother and fetus can be prevented from having complications.

(1) Background: Although resistance to pathogens and pests has been researched in many potato cultivars and breeding lines with DNA markers, there is scarce evidence as to the efficiency of the marker-assisted selection (MAS) for these traits when applied at the early stages of breeding. A goal of this study was to estimate the potential of affordable DNA markers to track Rpi disease resistance genes, that are effective against the pathogen Phytophthora infestans, as a practical breeding tool on a progeny of 68 clones derived from a cross between the cultivar Sudarynya and 13/11-09. (2) Methods: this population was studied for four years to elucidate the distribution of LB resistance and other agronomical desirable or simple to phenotype traits such as tuber and flower pigmentation, capacity and structure of yield. LB resistance was phenotypically determined through natural and artificial infection and the presence/absence of nine Rpi genes was assessed via 11 sequence-characterized amplified region (SCAR) markers. To aid this analysis, the profile of Rpi genes in the 13/11-09 parent was established using diagnostic resistance gene enrichment sequencing (dRenSeq) as a gold standard. (3) Results: at the early stages of a breeding program, MAS can halve the workload when screening the segregation of F1 offspring and selected SCAR markers for Rpi-genes provide useful tools.

One of the challenges in Content-Based Image Retrieval (CBIR) is to reduce the semantic gaps between low-level features and high-level semantic concepts. In CBIR, the images are represented in the feature space and the performance of CBIR depends on the type of selected feature representation. Late fusion also known as visual words integration is applied to enhance the performance of image retrieval. The recent advances in image retrieval diverted the focus of research towards the use of binary descriptors as they are reported computationally efficient. In this paper, we aim to investigate the late fusion of Fast Retina Keypoint (FREAK) and Scale Invariant Feature Transform (SIFT). The late fusion of binary and local descriptor is selected because among binary descriptors, FREAK has shown good results in classification-based problems while SIFT is robust to translation, scaling, rotation and small distortions. The late fusion of FREAK and SIFT integrates the performance of both feature descriptors for an effective image retrieval. Experimental results and comparisons show that the proposed late fusion enhances the performances of image retrieval.

Anderson – Fabry disease (AFD) is a rare, X-linked lysosomal storage disorder caused by a mutation in the α-Galactosidase A gene resulting in α-Galactosidase A enzyme (α-Gal A) deficiency. The metabolic defect leads to progressive accumulation of glycosphingolipids and structural and functional impairment of affected organs. Due to the inheritance pattern, male patients are hemizygous with more severe manifestations of the disease as compared to females who in most cases are heterozygous with delayed and variable clinical presentation caused by uneven X – chromosome inactivation. Fabry disease cases are often identified by targeted screening programs in high-risk groups, such as in patients with end-stage renal disease, premature stroke or unexplained cardiomyopathy. Here we describe a unique case of homozygous female patient identified by a nationwide screening program in hypertrophic cardiomyopathy patients. Before the systematic screening, the patient had a diagnosis of hypertrophic obstructive cardiomyopathy and was treated accordingly including alcohol septal ablation to reduce the obstructive gradient. The confirmation of Fabry disease has led to discovery of the same variant in several members of her family. The identified variant was c.644A>G, p.Asn215Ser (N2015S) known to cause predominant cardiac involvement with late onset of the disease. The variant is amenable for an oral therapy by the small molecular chaperone migalastat which was started, then interrupted for recurrence of patient´s migraine and then re-initiated again after two years. During this period the patient received enzyme replacement therapy by agalsidase beta but developed a progressively worsening venous access. Our case illustrates the importance of systematic screening of patients with clinical evidence of hypertrophic cardiomyopathy in whom routine diagnostic process fails to discover Fabry disease, in particular variants with late onset cardiac manifestations. Many of the late onset variants are amenable for orally active therapy by migalastat which significantly improves the comfort of the treatment. Its long term results are analysed by a large international “Follow-me” registry which was designed to verify the validity of pivotal trials with migalastat in Fabry disease.

Ebstein anomaly, a congenital heart condition, can manifest across a broad age spectrum, including adulthood. We present a unique case of a 67-year-old woman with no significant medical history who sought medical attention for severe headaches, vomiting, and respiratory distress, accompanied by elevated blood pressure and rapid pulse. Initial investigations, including troponin T levels, yielded unremarkable results. However, an electrocardiogram unveiled a right bundle branch block (RBBB) pattern, prompting further assessment. A subsequent chest X-ray disclosed an enlarged heart, indicating cardiomegaly, prompting echocardiography. The echocardiogram confirmed the diagnosis of Ebstein anomaly, revealing a 26 mm apical displacement of the tricuspid valve (TV). The patient was managed conservatively with supplemental oxygen and exhibited gradual improvement. This case underscores the infrequent occurrence of Ebstein anomaly in adulthood and underscores the necessity for thorough evaluation in cases of unexplained cardiopulmonary symptoms.

The aim of this study was to determine the potential of early inflammatory markers to diagnose late-onset neonatal sepsis - procalcitonin (PCT), interleukin 6 (IL-6), interleukin 8 (IL-8) and endocan (ESM-1), and to compare them with routinely used markers. A prospective (January, 2022 – January, 2023) clinical-epidemiological study was conducted in a third level NICU in Pleven, Bulgaria. Patients with suspected nosocomial infection and healthy controls were tested. A sandwich ELISA method was used to measure the serum concentrations. Sixty newborns with an average gestational age of 29.75 ± 3.61 gestational weeks were included, of which 35 % were symptomatic and infected, 33.3 % were symptomatic but uninfected, and 31.7 % were asymptomatic controls. The mean values of PCT, IL-6, I:T index and PLT differ significantly in the three groups. For ESM-1, IL-8 and CRP, the difference was statistically insignificant. The best sensitivity (78%) and negative predictive value (84%) was found for IL-6. The combination of PCT + IL-6 + I:T+ PLT demonstrated high precision (78%) and best sensitivity (94%) and negative predictive value (95%). The introduction into routine practice of indicators such as PCT and IL-6 may provide an opportunity to promptly optimize the diagnostic and therapeutic approach to LOS.

Cell death by apoptosis is a major cellular response, in the control of tissue homeostasis and as a defense mechanism in case of cellular aggression like an infection. Cell self-destruction is part of antiviral responses, aimed at limiting the spread of a virus. Although it may contribute to the deleterious effects in infectious pathology, apoptosis remains a key mechanism for viral clearance and resolution of infection. The control mechanisms of cell death processes by viruses have been extensively studied. Apoptosis can be triggered by different viral determinants, through different pathways, as a result of virally induced cell stresses and innate immune responses. Zika virus (ZIKV) induces Zika disease in humans which has caused severe neurological forms, birth defects and microcephaly in newborns during the last epidemics. ZIKV also surprised by revealing an ability to persist in the genital tract and in semen, thus being sexually transmitted. Mechanisms of diverting antiviral responses such as the interferon response, the role of cytopathic effects and apoptosis in the etiology of the disease have been widely studied and debated. In this review, we examined the interplay between ZIKV infection of different cell types and apoptosis and how the virus deals with this cellular response. We illustrate a duality in the effects of ZIKV-controlled apoptosis, depending on whether it occurs too early or too late, respectively in neuropathogenesis, or in long-term viral persistence. We further discuss a prospective role for apoptosis in ZIKV-related therapies, and the use of ZIKV as an oncolytic agent.

The Hubble parameter H(z), as a function of redshift, is modified by the presence of a new term originated from the extrinsic curvature in an embedded space-time. Assuming an asymptotic expansion factor $a\sim 0$ or, equivalently $z\rightarrow \infty$, it is obtained a nearly resemblance of the present model ($\beta$-model) with quintessence $w$CDM model with $H(z)\sim H_{wCDM}(z)$ at background level. In conjunction with $\Lambda$CDM, we test the models using a pack of recent datasets like that of the ``Gold 2018'' growth data, the best-fit Planck2018/$\Lambda$CDM parameters on the Cosmic Microwave Background (CMB), the Baryon Acoustic Oscillations (BAO) measurements, the Pantheon Supernovae type Ia and the Hubble parameter data with redshift ranging from $0.01 < z < 2.3$. Performing the Akaike Information Criterion (AIC) to ascertain the statistical viability of the model from Jeffreys' scale, we apply a joint likelihood analysis to the data with the Markov Chain Monte Carlo (MCMC) method. We find that the present model is in very good agreement with observations with a close statistical equivalence with the $\Lambda$CDM and $w$CDM cosmologies at 1-$\sigma$ level. We also show that a mild alleviation of the $\sigma$ tension between the growth amplitude factor and the matter content $(\sigma_8$-$\Omega_m)$ of the observations from CMB and Large Scale Structure (LSS) probes. A comparison of the aforementioned full pack of data in MCMC chains is made with the resulting MCMC from Pantheon SNIa+$H(z)$ in order to analyse the sensitivity of the models and how they respond to a cosmography analysis on the evolution of $H(z)$ and the deceleration parameter $q(z)$. In this sense, we find that only the $\beta$-model can be unaffected to the variations of the previous datasets due to its several minima in the likelihood (degeneracies) of the related parameters with an overall percentage relative difference only up to 4$\%$.

We report an unusual transformation where a transient formation of a nitrene moiety initiates a sequence of steps where leading to a remote oxidative C-H functionalization (R-CH3 to R-CH2OC(O)R’) and concomitant reduction of the nitrene into an amino group. No external oxi-dants or reductants are needed for this formal molecular com-proportionation. Detected and iso-lated intermediates and computational analysis suggest that the process occurs with pyrazole ring opening and recyclization.

Genotype imputation is widely used to enrich genetic datasets. The operation relies of panels of known reference haplotypes with typically whole-genome sequencing data. How to choose a reference panel has been widely studied and it is essential to have a panel that is well matched to the individuals who require imputation of missing genotypes. However, it is broadly accepted that such an imputation panel will have an enhanced performance with the inclusion of diversity; haplotypes from many different populations. We investigate this observation in this work by examining in fine detail exactly which reference haplotypes are contributing at different regions of the genome. This is achieved using a novel method of inserting synthetic genetic variation into the reference panel in order to track the performance of leading imputation algorithms. We show that while diversity may globally improve imputation accuracy, there can be occasions where incorrect genotypes are imputed following the inclusion of more diverse haplotypes in the reference panel. We however demonstrate a technique for retaining and benefitting from the diversity in the reference panel whilst avoiding the occasional adverse effects on imputation accuracy. What is more, our results elucidate more clearly the role of the diversity in a reference panel than has been shown in previous studies.

The issue of women’s participation in top management and boardroom positions has received increasing attention in the academic literature and the press. However, the pace of advancement for women managers and directors continues to be slow and uneven. The novel framework of this study organizes the factors at the individual, organizational and public policy level that affect both career persistence and the advancement of women in top management positions; namely, factors affecting 1) career persistence (staying at the organization) and 2) career advancement or mobility (getting promoted within the organization). In the study location, Chile, only 32 percent of women “persist”, or have a career without interruptions, mainly due to issues with work–family integration and organizational environments with opaque and challenging working conditions. Women who “advanced” in their professional careers represent 30 percent of high management positions in the public sector and 18 percent in the private sector. Only 3 percent of general managers in Chile are women. Women in Chile have limited access and are still not integrated into business power networks. Our findings will enlighten business leaders and public policy-makers interested in designing organizations that retain and promote talented women in top positions.

This study evaluated the exogenous application of PGRs substitute chemical fertilization without compromising the growth and yield of tomato in fluctuated day-night temperature and humidity stressed late winter. Two-factor experiment comprising chemical fertilizers at 100, 110, 90 and 80 % of recommended doses besides control and PGRs of GA3; NAA, 4-CPA and SA @ 50 ppm including control was conducted where treatments were assigned in triplicates. Results revealed no significant variation among the fertilizer doses (80% to 110% of recommendation) regarding growth and yield contributing traits while among the PGRs, GA3 @ 50 ppm produced maximum number of flower clusters plant-1 (16.85), flowers (8.80) and fruits (5.79) cluster-1, single fruit weight (67.83 g) and fruit yield (6.61 kg plant-1) of tomato that was statistically identical with the findings of SA. But significant reduction in yield was noted in NAA and 4-CPA (1.20 kg and 1.21 kg plant-1, respectively). Interestingly, GA3 and SA in combination with any doses of the studied fertilizers maximize the tomato morphological and reproductive traits while fertilizer plus NAA and 4-CPA interaction gave the inferior results. Further, correlation matrix and PCA findings revealed that five fertilizer doses have no distinctiveness whereas GA3 and SA has distinct position than other PGRs with the maximum dependent variables those were contributed positively in the total variations. The study findings suggested that 20% fertilizer requirement could be reduced with the substitution of GA3 and SA @ 50 ppm for successful cultivation of tomato in late winter having the extreme environmental issues.

Over the last decade, advances in our understanding about the genetic architecture of complex traits and common diseases, have increased our ability to perform susceptibility genetic testing for diseases in asymptomatic individuals. These technological developments raise complex ethical, legal and social considerations. Here we discuss a series of ethical issues associated with susceptibility genetic testing for Alzheimer's and Parkinson's disease. These include, amongst others, informed consent, disclosure of results and unexpected findings, mandatory screening, privacy and confidentiality, and stigma and genetic discrimination. As knowledge of the genetic basis of these diseases continues growing, and as genetic testing becomes more widespread, we anticipate that it will become increasingly important for scientists and clinicians to engage in the conversation about the ethical, social and policy implications of these technologies.

Age-related diseases place an intense and growing stress on healthcare systems. Numerous theories of ageing exist. Yet prediction, prevention and treatment limitations of age-related disease persist because we lack a complete aetiological understanding of their origins. Here we propose a new theory that aims to provide a blueprint-type understanding of ageing and disease aetiology, working across multiple scientific disciplines. Supported by specific examples, we demonstrate that the primary driver of much of age-related diseases is the futile triggering of specific molecular pathways in a pathological manner, which we term patho-pathways. Patho-pathways induce pathological cell, tissue and system changes in the form of hyperactivity (undesirable increased and new biological activities that are typical of age related disease). As part of patho-pathways, all wild-type (normal) genes have the potential to contribute to age-related diseases (though specific risk varies and can be formularised). In a domino-style effect, one patho-pathway typically triggers others, resulting in complex, but traceable, cascades. Utility, in terms of changing clinical and scientific practice, is derived from mapping these cascades to create Blueprint Maps that allow identification of biomarkers and therapeutic targets far upstream in the causal chain of events. Finally, our theory provides testable hypotheses concerning predictions of links between otherwise seemingly disparate diseases as well as new interventions into ageing.

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. In late-stage AMD, geographic atrophy (GA) of dry AMD or choroidal neovascularization (CNV) of neovascular AMD results in macular atrophy (MA), leading to significant visual loss. Despite the development of innovative therapies, there are currently no established effective treatments for MA. As a result, early detection of MA is critical in identifying later central macular involvement throughout time. Accurate and early diagnosis is achieved through a combination of clinical examination and imaging techniques. Our review of the literature depicted advances in retinal imaging to identify biomarkers of progression and risk factors for late AMD. Imaging methods like fundus autofluorescence (FAF), near-infrared reflectance (NIR), widefield imaging, optical coherence tomography (OCT), multicolor confocal scanning laser ophthalmoscopy (cSLO), and optical coherence tomography angiography (OCTA) can be used to detect and monitor the progression of retinal atrophy. Multifocal electroretinogram (ERG) and microperimetry are methods for quantifying visual function to map disease progression. The evolving diverse imaging modalities optimize detection of pathology anatomy and measurement of visual function; they may also contribute to the understanding of the underlying mechanistic pathways, particularly the underlying MA changes in late AMD.

Tomato is the highest-value fruit/vegetable crop worldwide. However, the quality and yield of tomatoes are severely affected by late blight. MicroRNA482s (miR482s) are involved in plant immune system. In this study, miR482c was transiently and stably overexpressed in tomatoes in transgenic plants to explore its mechanism in tomato resistance against late blight. Tomato in transgenic plants transiently overexpressed miR482c displayed larger lesion area than the control plants upon infection. Furthermore, compared with the WT tomato plants, the transgenic tomato plants stably overexpressing miR482c displayed decreased expression of target genes accompanied by lower POD, SOD, and PAL activity activities and higher MDA content, thereby leading to a decline in the ROS scavenging ability and aggravating the damage of lipid peroxidation product accumulation on the cell membrane, eventually enhancing plant susceptibility. This finding indicates that miR482c may act as a negative regulator in tomato resistance by regulating NBS-LRR expression levels and ROS levels.

War dominated the royal policies in late Medieval Europe, yet recent historiography has shifted focus to the conflict resolution strategies employed by nonsovereign powers. This essay delves into the escalation of confrontations at sea, distinguishing between legal acts of privateering and criminal acts of piracy. It further compares the conflict mitigation policies of the town ports of Northern Iberia and the duchy of Brittany, highlighting the role of an international arbitration court, the Guild of the Contractation. The analysis concludes that attempts to diminish maritime violence through shortlived bilateral peace agreements were largely unsuccessful, with the more stringent policies of monarchical states taking precedence. Despite this, trade and maritime transport remained crucial for the inhabitants of both regions, who endeavored to surmount the perils of the sea by fostering networks of trust, bolstered by shared institutions for risk management. Nevertheless, these efforts were ultimately eclipsed by the royal policies aimed at extending state jurisdiction over the seas, through the criminalization of certain sea activities, thereby reinforcing the state's control over maritime commerce. The essay underscores the complex interplay between local interests and royal ambitions, illustrating how the latter often subsumed the former in the quest for greater control over maritime resources and trade routes.

Hungary's first national park was created in 1973 in the Hortobágy area to protect Europe's largest contiguous steppe area with its flora and fauna. The Hortobágy National Park - the Puszta was inscribed on the UNESCO World Heritage List as a cultural landscape in 1999. The park's outstanding importance is due to the predominantly non-arboreal steppe vegetation, home to a unique bird fauna, and the alkaline and chernozem soils with a complex, mosaic-like spatial structure. In addition, the landscape of the Hortobágy has a pastoral history stretching back thousands of years. Several hypotheses have been put forward, which suggest that the alkaline soils and the habitats that cover them were formed as a result of human activities related to river regulation that began in the second half of the 19th century. However, palaeoecological and palaeobiological studies over the last 30-40 years have pointed to the natural origin of the alkaline steppes, dating back to the end of the Ice Age. For thousands of years human activities, in particular grazing by domestic animals, hardly influenced the natural evolution of the area. Drainage of marshy and flooded areas began in the 19th century, and the introduction of more and more intensive agriculture, had a significant impact on the landscape. This paper aims to describe the past natural development of this special alkaline steppe ecosystem, with particular reference to the impacts of past and present human activities, including conservation measures.

The craft guilds have been at the core of important historiographical debates on the economic, social and political history of medieval cities for twenty years. The aim of this article is to examine the seamen’s guilds in the town ports of Northern Peninsula in the late Middle Ages. This study analyzes fundamental aspects of the social assistance, labour organization and social identity of the town ports, located on the maritime border of the Kingdom of Castile. In contrast to the more classical view of the craft guilds as protectionist institutions, which only served the interests of a privileged group of masters, this analysis highlights the contribution of the seamen craft guilds to the organization of labor at sea, the training of sea workers, the ability to negotiate with merchants and avoid labor exploitation, the provision of social assistance to the most vulnerable population, and the ability to lead the social protest for the guilders’ representation in the urban government. In summary, it is concluded that the seafarers’ guilds were constituted as networks of mutual help between individuals in the labor, welfare and political spheres of the population of the town ports of Northern Iberia in the late Middle Ages.

Therapeutic antibodies targeting immune checkpoints have shown limited efficacy in clinical trials in glioblastoma (GBM) patients. Ultrasound-mediated blood-brain barrier opening (UMBO) using low-intensity pulsed ultrasound improved drug delivery to the brain. We explored the safety and the efficacy of UMBO plus immune checkpoint inhibitors in preclinical models of GBM. A Blood-brain barrier (BBB) opening was performed using a 1 MHz preclinical ultrasound system in combination with 10µl/g microbubbles. Brain penetration of immune checkpoint inhibitors was determined, and immune cell populations were evaluated using flow cytometry. The impact of repeated treatments on survival was determined. In syngeneic GL261-bearing immunocompetent mice, we showed that UMBO safely and repeatedly open the BBB. BBB opening was confirmed visually and microscopically using Evans’s blue dye and magnetic resonance imaging. UMBO plus anti-PDL-1 was associated with a significant improvement of the overall survival compared to anti-PD-L1 alone. Using mass spectroscopy, we showed that the penetration of therapeutic antibodies can be increased when delivered intravenously compared to non-sonicated brains. Furthermore, we observed an enhancement of activated microglia percentage when combined with anti-PD-L1. Here, we report that the combination of UMBO and anti-PD-L1 dramatically increases GL261-bearing mice's survival compared to their counterparts treated with anti-PD-L1 alone. Our study highlights the BBB as a limitation to overcome to increase the efficacy of anti-PD-L1 in GBM and supports clinical trials combining UMBO and in GBM patients.

The breeding of stress-tolerant cultivated plants that would allow for a reduction in harvest losses and undesirable decrease in quality attributes requires a new quality of knowledge on molecular markers associated with relevant agronomic traits, on quantitative metabolic responses of plants on stress challenges, and on the mechanisms controlling the biosynthesis of these molecules. By combining metabolomics with genomics, transcriptomics and proteomics datasets a more comprehensive knowledge of the composition of crop plants used for food or animal feed is possible. In order to optimize crop trait developments, to enhance crop yields and quality, as well as to guarantee nutritional and health factors, that provides the possibility to create functional food or feedstuffs, the knowledge about the plants’ metabolome is crucial. Next to classical metabolomics studies, this review focusses on several metabolomics based working techniques, such as sensomics, lipidomics, hormonomics and phytometabolomics, which were used to characterize metabolome alterations during abiotic and biotic stress, to find resistant food crops with a preferred quality or at least to produce functional food crops are highlighted.

The physiological process of iodine uptake in the thyroid is used for 131I treatment of thyroid diseases. Children are more sensitive to radiation compared to adults and may react differently to 131I exposure. The aims of this study were to evaluate the effects on thyroid protein expression in young and adult rats one year after 131I injection, and identify potential biomarkers related to 131I exposure, absorbed dose, and age. Twelve Sprague Dawley Rats (young and adults) were i.v. injected with 50 kBq or 500 kBq 131I and were killed twelve months later. Twelve untreated rats were used as age-matched controls. Quantitative proteomics, statistical analysis and evaluation of biological effects was performed. The effects of irradiation were most prominent in young rats. Protein biomarker candidates were proposed related to age, absorbed dose, thyroid function and cancer and a panel was proposed for 131I exposure. In conclusion, the proteome of rat thyroid was differentially regulated twelve months after low-intermediate dose exposure to 131I in both young and adult rats. Several biomarker candidates are proposed for 131I exposure, age, and many of them are known to be related to thyroid function or thyroid cancer. Further research on human samples are needed for validation.

This study aimed to investigate the effects of lupin flake supplementation on the growth, plasma parameters, carcass characteristics, and meat composition of late-fattening Hanwoo steers. The steers (n = 40) were randomly divided into the four groups with 10 steers each: LP0 (Lupin flake 0%), LP3 (lupin flake 3%), LP6 (Lupin flake 6%), and LP9 (lupin flake 9%). The total digestible nutriant intake increased as the concentration of lupin increased (linear and quadratic effects; P &lt; 0.05). The thiobarbituric acid-reactive substance content in the strip loins decreased as lupin flake supplementation levels increased (linear and quadratic effects; P &lt; 0.05), while carnosine levels increased linearly (P &lt; 0.05). As the lupin flake supplementation level increased, anserine and creatinine contents increased linearly and quadratically (P &lt; 0.05). Similarly, adenosine triphosphate (ATP) and adenosine monophosphate (AMP) contents increased with increasing lupin flake supplementation levels in linear and quadratic effects (P &lt; 0.001). Palmitoleic acid content increased significantly with increasing lupin flake supplementation level (linear and quadratic effects; P &lt; 0.05). The content of oleic acid in the strip loin was not significant, but the unsaturated fatty acid (UFA) (P &lt; 0.05) and n-6/n-3 ratio (P &lt; 0.05) increased. The results of this study indicated that although lupin flake supplementation did not markedly affect the growth, carcass characteristics, or meat composition of late-fattening Hanwoo steers, it exerted a positive effect on the flavor, taste profiles (anserine, creatinine, ATP, and AMP), hypotonicity(TBARS), and healthy meat production (UFA and n-6/n-3 ratio) related to beef.

In this work, we propose an approach for the autonomous navigation of mobile robots using fusion of sensor data by a Double Deep Q-Network with collision avoidance by detecting moving people via computer vision techniques. We evaluate two data fusion methods for the proposed autonomous navigation approach: Interactive and Late fusion strategy. Both are used to integrate mobile robot sensors through the following sensors: GPS, IMU and, an RGB-D camera. The proposed collision avoidance module is implemented along with the sensor fusion architecture in order to prevent the autonomous mobile robot from colliding with moving people. The simulation results indicate a significant impact on the success of completing the proposed mission by the mobile robot with the fusion of sensors, indicating a performance increase (success rate) of 27% in relation to navigation without sensor fusion. With the addition of moving people in the environment, deploying the people detection and collision avoidance security module has improved about 14% the success rate when compared to that of the autonomous navigation approach without the security module. Video was developed with robot navigation using the DDQN-Late Fusion https://www.loom.com/share/684afa6a5b0148afadc9a200ab9f3483.

Feline immunodeficiency virus (FIV) is a lentivirus in the family Retroviridae that infects domestic cats resulting in an immunodeficiency disease featuring a progressive and profound decline in multiple sets of peripheral lymphocytes. Despite compelling evidence of FIV-associated immunopathology, there are conflicting data concerning the clinical effects of FIV infection on host morbidity and mortality. To explore FIV-associated immunopathogenesis and clinical disease, we experimentally inoculated a cohort of 4 specific pathogen free kittens with a biological isolate of FIV clade C and continuously monitored these animals along with 2 uninfected control animals for more than 13 years, from the time of inoculation to the humane euthanasia endpoint. Here we report the results obtained during the late asymptomatic and terminal phases of FIV infection in this group of experimentally FIV-infected cats.

Background: There are anecdotal reports on reversible QTc prolongation during therapeutic hypothermia (TH) for moderate to severe neonatal encephalopathy after asphyxia. As the QTc interval is a relevant biomarker to assess safety during medication development, a structured search and review on published neonatal QTc values to generate reference values is warranted to facilate medication development in this specific population. Methods: A structured search and literature assessment (PubMed, Embase, Google Scholar) with ‘Newborn/Infant, QT and hypothermia’ was conducted (October 2021). Retrieved individual values were converted to QTc (Bazett) over postnatal age (day 1-7). Results: We retrieved 94 QTc intervals [during TH (n=50, until day 3) or subsequent normothermia (n=44, day 4-7)] in 33 neonates from 6 publications. The median (range) of QTc intervals during TH was 508 (430-678), and 410 (317-540) ms afterwards (difference 98 ms, or +28 ms/°C decrease). Four additional cohorts (without individual QTc intervals) confirmed the pattern and magnitude of the effect of body temperature on the QTc interval. Conclusions: We added a relevant non-maturational covariate (TH, °C dependent) and generated reference values for the QTc interval in this specific neonatal subpopulation. This knowledge on QTc during TH should be considered and integrated in neonatal medication development.

Late onset Pompe disease is a recessive lysosomal storage disease. Clinical features include skeletal muscles deficiency and diaphragm weakness. Clinical management relies on supportive treatment and mechanical ventilation in patents with chronic respiratory failure. M mode ultrasound and tissue Doppler imaging can be used to assess and to follow up diaphragm function.

We present a novel method for online measurement of multi-point opening distances of midpalatal suture during rapid palatal expansion (RPE) using fiber optic Fabry-Perot (F-P) sensors. The sensor consists of an optical fiber with a cut flat end face and an optical reflector, which are implanted into the palatal base structure of an expander and is capable of measuring the precise distance between two optical reflective surfaces. As a demonstration, a 3D printed skull model containing the maxilla and zygomaticomaxillary complex (ZMC) was produced and a miniscrew-assisted rapid palatal expander (MARPE) with two guide rods was used to generate the midpalatal suture expansion. The reflected spectrums of the sensors were used to dynamically extract cavity length information for full process monitoring of expansion. The dynamic opening of the midpalatal suture during the gradual activation of the expander was measured, and a displacement resolution of 2.5 μm was demonstrated. The angle of expansion was derived and the results suggested that the midpalatal suture was opened with a slightly V type expansion of 0.03 rad at the first loading and subsequently expanded in parallel. This finding might be useful for understanding the mechanical mechanisms that lead to different types of expansion. The use of a fiber-optic sensor for mounting the rapid palatal expander facilitates biomechanical studies and experimental and clinical evaluation of the effects of RPE.

The coastal Peru, one of the driest deserts in the world, has recently experienced dramatic landscape changes and asset destruction during precipitation events due to El Niño. Nevertheless, catastrophic explanations for landscape variations and human responses to the so-called "Super" or "Mega" El Niños are recurrent in pre-Hispanic time, even if alternative hypotheses were provided in literature. A deeper understanding of the geological and archaeological record can improve the knowledge on the relationship between such a coupled atmosphere-ocean phenomenon and landscape processes. The bibliographic sources required for this purpose are scattered throughout various disciplines ranging from physical to human sciences, thus comprehensive databases were used to identify and screen the relevant studies. The results provide knowledge synthesis in order to identify critical gaps and suggest specific research goals. Inferred episodes of landscape change due to severe precipitations in late pre-Hispanic time are discussed and consistencies and inconsistencies exposed. Examples of variation in landscape response due to extensive human intervention are reported.

Diagnosis of neonatal sepsis is difficult as signs and symptoms are nonspecific. Interleukin-6 (IL-6) is a promising marker for neonatal sepsis. We aimed to test the accuracy of IL-6 in term and preterm infants after 72 hours of life (late-onset sepsis-LOS). We searched for IL-6 diagnostic accuracy studies between 1990 and 2020 using the PubMed database. Study selection was performed. The range of reported IL-6 sensitivities and specificities was 68% to 100% and 28% to 100%, respectively, the median values were 85.7% and 82% from 15 studies including 1306 infants. Subgroup analysis was performed. Sensitivity (87% vs 82%), but not specificity (both 86%), was better in preterm infants than in preterm and term infants. Early sample collection had the highest sensitivity (84%), but the lowest specificity (86%). To assess quality we used a STARD checklist adapted for septic neonates. Limitation of this review include the heterogeneous group of studies on the one side and the small number of studies on the other side that analyzed different combinations of biomarker. We concluded that IL-6 had a good performance especially in the preterm infant population and best results are achieved by measurements at the time of LOS suspicion.

Acute encephalopathy with biphasic seizures and reduced diffusion (AESD) is characterized by biphasic seizures following febrile viral infections and delayed reduced diffusion of the cerebral white matter on magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) (bright tree appearance, BTA). However, hypoxic encephalopathy with biphasic seizures and AESD-mimicking imaging findings has not been reported. Herein, we report an case of hypoxic encephalopathy due to suffocation with concomitant biphasic seizures and BTA, mimicking AESD. On day 1, a 5-month-old female was found face down with breathing cessation and deteriorating consciousness level. The electroencephalography (EEG) revealed periodic epileptic discharges, suggesting possible nonconvulsive status epilepticus. Despite the improvements in consciousness level and EEG abnormalities on day 2, her consciousness level deteriorated again with generalized tonic-clonic seizures on day 3, and head MRI-DWI revealed restricted diffusion predominantly in the subcortical areas, suggesting BTA. Treatment for acute encephalopathy resolved clinical sei-zures and EEG abnormalities. The persistence of abnormal EEG, reflecting abnormal excitation and accumulation of neurotoxic substances caused by hypoxia, may have contributed to the devel-opment of AESD-like findings. As hypoxic encephalopathy causes AESD-like biphasic seizures, monitoring the consciousness level, seizure occurrence, and EEG abnormalities even after acute symptoms have temporarily improved following hypoxia is essential.

Mastitis-causing bacteria can establish persistent infections in the mammary gland of commercially important dairy animals despite the presence of strong specific humoral and cellular immune mechanisms. The aim of this study was to encapsulate vitamin D3 by complex coacervation with sulfur-saturated bovine lactoferrin-alginate using microbial transglutaminase-catalyzed crosslinking and investigate the oral administration of encapsulated vitamin D3 in blood serum biomarkers of the immune response in late-lactating dairy goats. Dairy goats (n = 18) in late lactation were randomly assigned to three experimental groups (n = 6), after balancing weight. Dairy goats were orally administered with 0.35 mg vitamin D3/day in the unencapsulated form and 0.35 mg vitamin D3/day in the encapsulated powder form. Another group received the basal diet. The experimental period lasted 6 weeks. The blood serum concentrations of 25-hydroxyvitamin D3 [25-(OH)-D3], lactoferrin, immunoglobulin A (IgA), and interferon-gamma (INF-γ) were measured. The delivery of vitamin D3 to dairy goats resulted in a marked increase of 25-(OH)-D3 concentration in serum while the serum level of lactoferrin also increased. Alternatively, the serum levels of IgA and the immunomodulatory cytokine INF-γ were elevated following supplementation with the encapsulated vitamin D3. Overall, the capsules in the powder form used in this study kept vitamin D3 highly bioavailable.

This paper focuses on the paradigm that explains the link between energy transitions and financial transformations. In particular, it attempts to shed some light on the following question: How did the transition from wood to coal affect financial development in late 18^th and early 19^th century Britain? The results demonstrate that the energy transition in Britain during the 1^st Industrial Revolution constituted an important moment in the country's financial development and can be used as an example of how an energy innovation can foster the financial development of particular countries or regions.

The objective of this study was aimed to study the sensory processes of the “human-computer interaction” model when classifying visual images with an incomplete set of signs based on the analysis of early, middle, late and slow components of event-related potentials (ERPs). 26 healthy subjects (men) aged 20-22 years were investigated. ERPs in 19 monopolar sites according to the 10/20 system were recorded. Discriminant and factor analysis were applied. The component N450 is the most specialized indicator of the perception of unrecognizable (oddball) visual images. The amplitude of the ultra-late components N750 and N900 is also higher under conditions of presentation of the oddball image, regardless of the location of the registration points. The results of the study are discussed in the light of the paradigm of the P300 wave application in brain-computer interface systems, as well as with the peculiarities in brain pathology. Promising directions for the development of studies of the “Brain Computer Interface” (BCI) P300 systems are to increase the throughput of information flows. To extend the application of the P300 ERPs to multiple modalities, the underlying physiological mechanisms and responses of the brain for a particular sensory system and mental function must be carefully examined.

Reelin depletion and stress seem to affect similar pathways including GABAergic and glutamatergic signaling and both are implicated in psychiatric disorders in late adolescence/early adulthood. The interaction between reelin depletion and stress, however, remains unclear. To investigate this, male and female heterozygous reelin mice (HRM) and wildtype (WT) controls were treated with the stress hormone, corticosterone (CORT), during late adolescence to simulate chronic stress. Glucocorticoid receptors (GR), N-methyl-D-aspartate receptor (NMDAr) subunits, glutamic acid decarboxylase (GAD67) and parvalbumin (PV) were measured in the hippocampus and the prefrontal cortex (PFC) in adulthood. While no changes were seen in male mice, female HRM showed a significant reduction in GR expression in the dorsal hippocampus. In addition, CORT reduced GR levels as well as GluN2B and GluN2C subunits of NMDAr in the dorsal hippocampus in female mice only. CORT furthermore reduced GluN1 levels in the PFC of female mice. The combined effect of HRM and CORT treatment appeared to be additive in terms of GR expression in the dorsal hippocampus. Female-specific CORT-induced changes were associated with overall higher circulating CORT levels in female compared to male mice. This study shows differential effects of reelin depletion and CORT treatment on GR and NMDAr protein expression in male and female mice, suggesting that females are more susceptible to reelin haploinsufficiency as well as late-adolescent stress. These findings shed more light on female-specific vulnerability to stress and have implications for stress-associated mental illnesses with a female bias including anxiety and major depression.

Global temperature rise due to hydrocarbon gases emission that are produced by generating the electrical power has a great attention by the researchers to reduce it till zero emission is successfully achieved. Sustainable energy source such as solar energy, wind, hydro-energy and sea wave energy are focal areas to replace the fossil fuel by clean energy. In this article, daylight is used to minimize the power consumption that required for indoor lighting using electric roller blind. Smart controller is designed to adjust the position of the roller blind stepper motor, and hence, adjust the roller blind opening, based on the preset light intensity, to achieve precise utilization of daylight inside the room. If the desired Lux is not achieved for any reason, the smart controller adjusts the LED circuit current to boost the light intensity to achieve precisely the desired Lux. Comprehensive test cases using MATLAB-Simulink is carried out to verify the performance of the proposed smart controller. Techno-economic analysis is introduced to evaluate the benefits of installing the controller. Summary and recommendation are given at the end.

A silicified, thick-shelled, smooth-surfaced nuculanoid bivalve has been recovered by acid maceration of the Late Triassic (Carnian-Norian) strata of the Luning Formation, Nevada. Comparable modern nuculanoid clams inhabit water depths from 525-2,562 meters, and the living clam (an undescribed species of Pseudoneilonella from Caleta Sierra, Coquimbo, Chile) most similar to the fossil lives at 878-933 m. The Triassic nuculanoid clam (possibly a neilonellid) is inferred here to have inhabited marine waters at approximately 1000 m deep during deposition of the Shaly Limestone Member of the Luning Formation. This new fossil discovery falsifies hypotheses that the ichthyosaurs (Shonisaurus popularis) of Berlin-Ichthyosaur State Park, Nevada, USA, were deposited, respectively, in either shoreline deposits or in strata that accumulated above storm wave base.

Background: Surgical parameters of phacoemulsification can have a significant impact on behavior of anterior hyaloid membrane (AHM). Methods: In a prospective study using anterior segment optical coherence tomograph the attachment or detachment of AHM of 82 eyes were examined after uneventful phacoemulsification preoperatively and postoperatively over a 1-year period. The impact of capsulorhexis size, number of hydrodissections, difficulty of nucleus rotation, nuclear sclerosis grade, cumulative dissipated energy (CDE), ultrasonic time, total surgical time, difficulty of irrigation/aspiration, intensity of capsular polish, weakness of zonular fibers, presence of lens materials in Berger's space (LM-BS), and fluid usage were investigated related to the behavior of AHM. Results: In presence of zonular weakness and high CDE, a significant linear trend was observed regarding anterior vitreous detachment (AVD) at all postoperative times. Similarly, AVD is observed at 1-month, 3-month, and 1-year follow-up in cases of high nuclear sclerosis grade and high fluid usage. A significant linear trend was observed in the case of zonular weakness, hard nucleus and extensive capsular polish with LM-BS, while CDE, total surgical time, and fluid usage were significantly higher in these cases. Conclusions: Zonular weakness, high CDE, hard nucleus and high fluid usage are risk factors of postoperative AVD.

DNA methylation and other epigenetic factors are important in the pathogenesis of late-onset Alzheimer’s disease (LOAD). Methylenetetrahydrofolate reductase (MTHFR) gene mutations occur in most elderly patients with memory loss. MTHFR is critical for production of S-adenosyl-L-methionine (SAM), the principal methyl donor. A common mutation (1364T/T) of the cystathionine-γ-lyase (CTH) gene affects the enzyme that converts cystathionine to cysteine in the trans-sulfuration pathway causing plasma elevation of total homocysteine (tHcy) or hyperhomocysteinemia – a strong and independent risk factor for cognitive loss and AD. Other causes of hyperhomocysteinemia include aging, nutritional factors, and deficiencies of B vitamins. We emphasize the importance of supplementing vitamin B₁₂ (methylcobalamin), vitamin B₉ (folic acid), vitamin B₆ (pyridoxine), and SAM to patients in early stages of LOAD.

Thrombosis after severe acute respiratory syndrome coronavirus 2 vaccination is a serious complication in patients who have a thrombophilic predisposition. In this case, a female patient with no family history of thrombophilia who had pediatric antiphospholipid syndrome (APS) developed deep vein thrombosis (DVT) when she was 6 years old; 6 months after receiving a second dose of the BNT162b2 vaccine, DVT reoccurred. The original thrombi were found in the right common iliac vein and the inferior vena cava, with concomitant left pulmonary infarction. The patient was treated with anticoagulants for 6 years after DVT onset, with subsequent treatment cessation for 5 years without recurrence. She received the BNT162b2 vaccine at 17 years of age, 1 week before a routine outpatient visit. Platelet factor 4 elevation was detected 14 days after the first vaccination, persisting for 5 months without thrombotic symptoms. Six months after the second vaccine dose, the DVT recurred and was treated with a direct oral anticoagulant. The vaccine exacerbated the patient’s APS by activating coagulation, causing thrombosis recurrence. Platelet factor 4 levels may indicate coagulation status. When patients predisposed to thrombosis are vaccinated, coagulation status and platelet activation markers should be monitored to prevent DVT development.

Telomeres are structures at the ends of eukaryotic chromosomes that help maintain genomic stability. During aging, telomere length gradually shortens, producing short telomeres, which are considered markers of premature cellular senescence. This is believed to contribute to age-related diseases, including Alzheimer's disease (AD) and based on this, several studies have hypothesized that telomere shortening may characterize AD. Current research, however, has been inconclusive regarding the direction of the association between leukocyte telomere length (LTL) and disease risk. We assessed the association between LTL and AD in a retrospective case-control study of a sample of 255 unrelated patients with late-onset AD (LOAD), including 120 sporadic cases and 135 with positive family history for LOAD, and a group of 279 cognitively healthy unrelated controls, which were all from Calabria, a region from south Italy. Following regression analysis, telomeres were found to be significantly shorter in LOAD cases than in controls (p<0.001 for both sporadic and familial cases). Interestingly, LTL were associated to disease risk independently of the presence of conventional risk factors (e.g., age, sex, MMSE scores, presence of the APOE-ε4 allele). Altogether, our findings lend support to the notion that LTL shortening may be an indicator of the patho-genesis of LOAD.

Presentation of case: A 20 year old men from Simanjiro district in northern Tanzania presented with a 3 year history of splenomegaly, fatigue, cachexia, skin maculae and recent onset of watery diarrhea at Kilimanjaro Christian Medical Centre (KCMC) in Northern Tanzania. Due to laboratory findings of pancytopenia, diagnostic workup included bone marrow aspiration cytology and biopsy. Although the rapid test (IT LEISH, rK39 RDT) was negative, blood smear showed amastigote forms of Leishmaniasis in macrophages. Repeat bone marrow aspiration and PCR eventually confirmed VL. The patient denied travel to known endemic areas of visceral leishmaniasis (VL). Treatment was initiated with Amphotericin B, but the patient died on the fourth day of treatment from respiratory insufficiency. An autopsy revealed massive organ manifestations of VL. Case discussion: This is the first reported autochthonous case of VL in Tanzania. Clark et al. detected the vector Phlebotomous martini in Northern Tanzania in 2013, in a region boardering the district of our patient. The negative rapid test draws attention to the fact that sensitivity and specificity was found to be low in East African VL patients as displayed earlier by a Kenyan study. Therefore, tissue samples (spleen or bone marrow) remain necessary for diagnosis. The variety of symptoms in this presented case was remarkable, including the occurrence of Post Kala Azar Dermal Leishmaniasis (PKDL) and VL at the same time. This has been described in East African VL cases before as well as the occurrence of chronic diarrhea. An elongated undiagnosed period likely led to a mixed clinical picture that included: hepato-splenomegaly, PKDL, cachexia, and diarrhea.

Type 2 diabetes mellitus (T2DM) and late-onset Alzheimer’s disease-dementia (LOAD) are increasing in global prevalence and current predictions indicate they will only increase over the coming decades. These increases may be a result of the concurrent increases of obesity and aging. T2DM is associated with cognitive impairments associated with metabolic factors and increases the cellular vulnerability to develop the age-related increased risk of LOAD. This review addresses possible mechanisms due to obesity, aging, multiple intersections between T2DM and LOAD and mechanisms for the continuum of progression. Multiple ultrastructural images in female diabetic db/db models are utilized to demonstrate marked cellular remodeling changes of mural and glia cells and provide for the discussion of functional changes in T2DM. Throughout this review multiple endeavors to demonstrate how T2DM increases the vulnerability of the brain’s neurovascular unit (NVU), neuroglia and neurons are presented. Five major intersecting links are considered: i. aging (chronic age-related diseases); ii. metabolic (hyperglycemia - advanced glycation end-products and its receptor (AGE/RAGE) interactions and hyperinsulinemia – insulin resistance (a linking linchpin); iii. oxidative stress (reactive oxygen-nitrogen species); iv. inflammation (peripheral macrophage and central brain microglia); v. vascular (macrovascular accelerated atherosclerosis - vascular stiffening and microvascular NVU/neuroglial remodeling) with resulting impaired cerebral blood flow.

There is little information about moisture changes in different altitudinal belts in mountainous regions of the Southern Russian Far East. We present ecological-taxonomic composition of the diatom flora, the botanical composition of peat of small mountain lake/mire complexes located in the Central Sikhote-Alin within large landslides on the paleovolcano slopes are identified. Frequent changes in diatom assemblages and peat-forming plants indicate unstable hydroclimatic conditions with varying degrees of watering and dry condition up to complete overgrowth of the lakes. Frequent change of sphagnum mosses with different trophic preferences was established. The chronology is based on 11 radiocarbon dates. Accumulation rates reached up to 1.9 mm/year, the temporal resolution for the reconstructions is up to 30–40 years. The tendencies of lake evolution depended on different-scale hydroclimatic changes for the last 4400 yr. The most detailed data for the last 2600 yr were obtained from the Nizhnee Lake sequence, more sensitive to climatic changes. The main reason for the change in the hydrological regime of the lakes was variations in precipitation during short-term climatic changes. The sediment record moisture fluctuations are relatively well correlated with regional patterns reflecting summer monsoon intensity and cyclogenesis activity.

Introduction: Spinal epidural arteriovenous fistulas (SEDAVFs) are extremely rare and the pathological process still remains unclear. Nevertheless, neurofibromatosis, surgery, as well as trauma have been implicated as causes. Nevertheless, long standing chronic vertebral compression fractures (VCFs) as a cause of SEDAVFs has not been reported in literature. Case Presentation: Our cases comprised of a male and female with ages 67 and 62 year respectively. They presented with weakness of bilateral lower extremities and back pain. Their symptoms deteriorated into mild recto-bladder dysfunction as well as hypoesthesia of lower limbs. They both had history of road traffic accidents (RTAs) prior to their symptomatology. In both cases, Magnetic resonance imaging (MRI) revealed VCFs prior to the above symptomatology. Spinal digital subtraction angiography (DSA) was used to confirm SEDAVFs in both cases. We utilized the trans-arterial route with Onyx embolization agent to obliterate both fistulae and their symptom resolved after the embolization. Two-years follow-ups revealed no recurrence of their fistulae. Conclusion: The initial long standing VCFs caused by trauma resulted in perforation of the dorsal somatic branches of the radicular artery leading to the occurrences of SEDAVFs in our cases.

This paper is an extension to previous work that introduced successful classical-control for indoor lighting system that simultaneously control LED system and roller curtain to achieve accurate light intensity for indoor lighting applications. In this paper, Multi Input Multi Output Fuzzy Logic Controller (MIMO FLC) is proposed to replace the classical-controller. Detailed method is provided to illustrate the steps to design the required MIMO FLC that has two fuzzy input, two fuzzy output and forty-five fuzzy rules with mamdani fuzzy engine. The proposed MIMO FLC is simulated in Matlab using Simulink tools. The results are illustrated, analyzed and compared with the classical-control. The response showed very close performance to the classical-controller. The maximum average error and the maximum error with respect to “Desired Lux” inside the room is -6% and -10% respectively.

Abstract: Background and Objectives: Holter-based late potentials (LPs) are useful for predicting lethal arrhythmias in organic cardiac diseases. Although Holter-based LPs exhibit diurnal varia-tion, no studies have evaluated the optimal timing of LP measurement over 24 h for predicting lethal arrhythmia that leads to sudden cardiac death. Thus, this study aimed to validate the most effective timing for Holter-based LP testing and to explore factors influencing diurnal variability of LP parameters. Materials and Methods: We retrospectively analyzed 126 patients with post-myocardial infarction (MI) status and 60 control participants who underwent high-resolution Holter electrocardiography. Among the 126 post-MI patients, 23 developed sustained ventricular tachycardia (VT) (the MI-VT group), while 103 did not (the MI-non-VT group) during the obser-vation period. Holter-based LPs were measured at 0:00, 4:00, 8:00, 12:00, 16:00, and 20:00, and heart rate variability analysis was simultaneously performed to investigate factors influencing diurnal variability of LP parameters. Results: Holter-based LP parameters showed diurnal variation with significant deterioration at night and improvement during the day. Assessment at the time with the longest duration of low-amplitude signals <40 μV in the filtered QRS complex terminus (LAS40) gave the highest receiver operating characteristics curve (area under the curve, 0.659) and the highest odds ratio (3.75; 95% confidence interval, 1.45–9.71; p=0.006) for predicting VT. In the multiple regression analysis, heart rate and noise were significant factors affecting LP parameters in the MI-VT and control groups. In the non-VT group, LP parameters were significantly influenced by noise and parasympathetic heart rate variability parameters such as logPNN50. Conclusions: For Holter-based LP measurements, test accuracy was higher when LP was measured at the time of the highest or worst value of LAS40. Changes in autonomic nervous system activity, including heart rate and noise levels, were factors influencing diurnal variability.

In 1998, the Lisbon Universal Exhibition – Expo'98 – led to an urban regeneration process on Lisbon’s waterfront. Following other cities, this event was a pretext to replace a depressed area and to re-connect it with the river, through the creation of a set of new spaces for common use along the water. For them, it was promoted a public art program, which can be considered quite innovative in the Portuguese context, and that resulted in a monumentalisation of Lisbon’s eastern riverfront, later extended to other areas. Behind this framework, this article aims to debate the relations between public art and the dynamics of urban regeneration at the end of the 20th century. For that, it will analyse: 1) the Expo'98’s public art program, comparing its initial assumptions with the final results; 2) the impact of this program, through the identification of public art’s placements before (1974-1998) and after (1999-2009) the event. As a result, it is possible to find that the placement of public art reveals the spaces that were "conquered" to the port system, and a dialectic between functional/economic and leisure/symbolic values. It is concluded that public art had a significant role in the urban processes of the late 20th century, which is quite evident in a discourse that considers it as a qualifying factor of urban space and a mean of economic and social development.

In this work, we show that a late fusion approach to multi-modality in sign language recognition improves the overall ability of the model in comparison to the singular approaches of Computer Vision (88.14%) and Leap Motion data classification (72.73%). With a large synchronous dataset of 18 BSL gestures collected from multiple subjects, two deep neural networks are benchmarked and compared to derive a best topology for each. The Vision model is implemented by a CNN and optimised MLP and the Leap Motion model is implemented by an evolutionary optimised deep MLP topology search. Next, the two best networks are fused for synchronised processing which results in a better overall result (94.44%) since complementary features are learnt in addition to the original task. The hypothesis is further supported by application of the three models to a set of completely unseen data where a multi-modality approach achieves the best results relative to the single sensor method. When transfer learning with the weights trained via BSL, all three models outperform standard random weight distribution when classifying ASL, and the best model overall for ASL classification was the transfer learning multi-modality approach which scored 82.55% accuracy.

To analyze the predictive ability and incremental value of left ventricular longitudinal axis strain (LAS) and late gadolinium enhancement (LGE) using standard cardiovascular magnetic resonance (CMR) imaging for the diagnosis and prognosis of severe aortic stenosis (AS) in patients with an indication for aortic valve replacement. We conducted a prospective study on 128 patients with severe AS and 52 volunteers. The evaluation protocol included standard biochemistry tests, novel biomarkers of myocardial fibrosis, 12-lead electrocardiograms and 24-hour Holter, the 6-minute walk test and extensive echocardiographic and CMR imaging studies. Outcomes were defined as the composite of major cardiovascular events (MACEs). Among AS patients, most (n = 17, 77.2%) of those who exhibited LGE at CMR imaging had MACEs during follow-up. Kaplan-Meier curves for event-free survival showed a significantly higher rate of MACEs in patients with LGE (p < 0.01) and decreased LAS (p < 0.001). In Cox regression analysis, only reduced LAS [hazard ratio 1.33, 95%CI (1.01 to 1.74), p < 0.01] and the presence of LGE [hazard ratio 11.3, 95%CI (1.82 to 70.0), p < 0.01] were independent predictors for MACEs. The predictive value increased if both LGE and reduced LAS were added to LVEF. None of the biomarkers of increased collagen turnover exhibited any predictive value for MACEs. LAS by CMR is an independent predictor of outcomes in patients with AS and provides incremental value beyond the assessment of LVEF and the presence of LGE.

Purpose: The aim of present study was to compare the treatment results of daily cisplatin (CDDP), weekly docetaxel (DOC) intra-arterial infusion chemotherapy combined with radiotherapy (DIACRT) regimen and weekly CDDP intra-arterial infusion chemotherapy combined with radiotherapy (WIACRT) for patients with tongue cancer. Materials and Methods: Between January 2007 and December 2016, a total of 11 patients treated with WIACRT and 45 patients treated with DIACRT were enrolled in present study. In DIACRT group, 25 patients had T2, 20 patients had T3. A total of 9 patients had T2 and 2 had T3 in WIACRT (p = NS). In DIACRT, the treatment schedule consisted of intra-arterial chemotherapy (DOC, total 60 mg/m²; CDDP, total 150 mg/m²) and daily concurrent radiotherapy (RT) (total, 60 Gy). In WIACRT, the treatment schedule consisted of intra-arterial chemotherapy (CDDP, total 360 mg/m²) and daily concurrent RT (total, 60 Gy). Results: The median follow-up periods for DIACRT and WIACRT were 61 and 66 months respectively. The 5-year local control (LC) and overall survival (OS) rate were 94.5% and 89.6% for DIACRT group, 60.6% and 63.6% for WIACRT group respectively. The LC rate and OS of DIACRT group were significantly higher than that of WIACRT group. As regards toxicities, no treatment-related deaths were observed during the follow-up periods both in two groups. Conclusions: DIACRT was found to be feasible and effective for patients with tongue cancer and could become a new treatment modality.

Background: Risk of metastatic recurrence of breast cancer after initial diagnosis and treatment depends on the presence of a number of risk factors. Although most univariate risk factors have been identified using classical methods, machine-learning methods are also being conducted to tease out non-obvious contributors to a patient’s individual risk of developing late distant metastasis. Bayesian-network algorithms may predict not only risk factors but also interactions among these risks, which consequently lead to metastatic breast cancer. We proposed to apply a previously developed machine-learning method to predict risk factors of 5-, 10- and 15-year metastasis. Methods: We applied a previously validated algorithm named the Markov Blanket and Interactive risk factor Learner (MBIL) on the electronic health record (EHR)-based Lynn Sage database (LSDB) from the Lynn Sage Comprehensive Breast Cancer at Northwestern Memorial Hospital. This algorithm provided an output of both single and interactive risk factors of 5-, 10-, and 15-year metastasis from LSDB. We individually examined and interpreted the clinical relevance of these interactions based on years to metastasis and the reliance on interactivity between risk factors. Results: We found that with lower alpha values (low interactivity score), the prevalence of variables with an independent influence on long term metastasis was higher (i.e., HER2, TNEG). As the value of alpha increased to 480, stronger interactions were needed to define clusters of factors that increased the risk of metastasis (i.e., ER, smoking, race, alcohol usage). Conclusion: MBIL identified single and interacting risk factors of metastatic breast cancer, many of which were supported by clinical evidence. These results strongly recommend the development of further large data studies with different databases to validate the degree to which some of these variables impact metastatic breast cancer in the long term.

A long-standing problem in the understanding of deep-water turbidite reservoirs relates to how the three-dimensional evolution of deep-water channel systems evolve in response to channel filling on spatio-temporal scales, and how depositional environments affect channel architecture. The 3-D structure and temporal evolution of late Miocene deep-water channel complexes in the southern Taranaki Basin, New Zealand is investigated, and the geometry, distribution and stacking patterns of the channel complexes are analyzed. Two recently acquired 3-D seismic datasets, the Pipeline-3D (proximal) and Hector-3D (distal) are analyzed. These surveys provide detailed imaging of late Miocene deep-water channel systems, allowing for the assessment of the intricate geometry and seismic geomorphology of the systems. Seismic attributes resolve the channel bodies and the associated architectural elements. Spectral decomposition, amplitude curvature, and coherence attributes reveal NW-trending straight to low-sinuosity channels and less prominent NE-trending high-sinuosity feeder channels. Stratal slices across the seismic datasets better characterize the architectural elements. The mapped turbidite systems transition from low-sinuosity to meandering high-sinuosity patterns, likely caused by a change in the shelf-slope gradient due to localized structural relief. Stacking facies patterns within the channel systems reveal the temporal variation from a depositional environment characterized by sediment bypass to vertically aggrading channel systems.

Adolescents experience rapid physical, cognitive, and psychosocial growth with different factors that contribute to health and well-being. In this view, an important role is played by body weight and its perception. The aim of this study was to determine, in a sample of Italian late adolescents, whether health related quality of life (HRQoL) is associated with the different weight status categories (underweight, normal weight, overweight, obese), even considering sex differences. Data were collected from 1826 adolescents (n=735 males). HRQOL was analyzed using the Italian version of KIDSCREEN-52. Overweight adolescents showed a reduced psychological well-being (p<0.05) and self-perception (p<0.05), then other BMI categories. Subjects with obesity reported an increased bullying victimisation (p<0.05), reduced self-perception and eating disorders (p<0.001), while underweight were characterised by an altered adherence to the Mediterranean diet (p<0.001), eating disorders (p<0.001), and problematic use of social media (p<0.05). No sex differences were found, except for socio-economic status perception, where underweight girls reported a higher economic well-being than boys (p<0.05). Our results may suggest that there is an association between weight status categories and HRQoL, more pronounced in underweight and overweight adolescents. The association between BMI categories and psychosocial dimensions opens the need to define specific domains on which such preventive interventions should focus, always through a personalized perspective.

Precise determination of the tectonothermal events at the Qinling-Qilian junction is extremely significant for understanding the tectonic evolution of the eastern branch of the Paleo-Tethys. The Banpo porphyry outcrops in the northern margin of the North Qinling were chosen as the research subject, and its formation and tectonic environment were analyzed using Zircon U-Pb age estimation and geochemical studies. The results indicated the final stage of the Triassic orogeny and the closure phase of the Paleo-Tethys. The weighted average values of 206Pb/238U ages of samples from 3 sites of the Banpo porphyry corresponded to 213.4 ±2.1 Ma (MSWD = 0.56), 213.0 ±1.6 Ma (MSWD = 0.92), and 213.2 ±4.4 Ma (MSWD = 1.6). This study revealed that the Banpo porphyry was formed during the Late Triassic (Norian). The porphyry with high SiO2 and high alkali is typical A-type granite, which belongs to the weak peraluminous shoshonite series. All the samples are rich in low rare earth elements. However, the heavy rare earth elements are low, especially Eu, which exhibits a seagull-type right-leaning partitioning curve. In addition, based on the regional geological data, it can be concluded that the Banpo porphyry was formed during the transition period from a post-orogenic environment to a non-orogenic environment. This study indicated the closure of the Paleo-Tethys-Mianxian-Lveyang Ocean by the Late Triassic as well as the completion of the collision between the North China and Yangtze Blocks along the Qinling orogenic belt.

(1) Background: There is a need of a novel surrogate marker to ease decision making when facing ascending aortic dilatation. In this article we study the ratio between ascending and descending aorta diameters as a potential one; (2) Methods: Retrospective observational cohort study, including all the patients who have undergone surgery for aTAAD between January 2014 and September 2020 at our center. A total of 50 patients were included. Clinical and demographic data was collected. Anatomical measurements were made including orthogonal maximal diameters of the ascending and descending aorta, post-dissection whole circumference length (post-wCL), post-dissection true lumen circumference length (post-tCL), surface and sphericity index of the ascending and descending aorta. Pre-dissection ascending aorta diameter (pre-AAD) and pre-dissection descending aorta diameter (pre-DAD) were calculated as well as the ratio between them and compared with reference values; (3) Results: 96% of the patients pre-AAD was smaller than the recommended 55mm. The ratio between the descending and ascending aorta pre-dissection diameters was significantly smaller compared to the reference value (0.657±0.125 versus 0.745± 0.016 with a mean difference of -0.088 and a p&lt;0.001); (4) Conclusions: The 55mm threshold for aorta maximal diameter is an insufficient criterion when assessing the risk of dissection. The ratio between DAD and AAD is a parameter worthy of analysis as a tool to stratify the risk of dissection.

Inadequate protein intake can impair protein balance and lead to skeletal muscle atrophy, impaired body growth, and functional decline. Foods provide both non-essential (NEAAs) and essential amino acids (EAAs) that may convey different metabolic stimuli to specific organs and tissues. In this study, we sought to evaluate the impact of six diets with various EAA/NEAA blends on body composition and the risk of developing tissue wasting in late middle-aged male mice. Mice consuming NEAA-based diets, although showing increased food and calorie intake, suffered the most severe weight loss. Interestingly, even moderate NEAAs prevalence was able to induce inflammatory catabolic stimuli, generalized body wasting and systemic metabolic alterations. Complete depletion of retroperitoneal white adipose tissue and a severe loss (>75%) of brown adipose tissue were observed together with muscle wasting. Conversely, EAA-based diets induced significant decreases in weight by reducing primarily fat reserves, but improved clinical parameters. Tissue wasting was caused by altered AA quality, independent of reduced nitrogen or caloric intake. Our results indicate that an optimized balance of AA composition is necessary for preserving overall bodily energy status. These findings are particularly relevant in the context of aging and may be exploited for contrasting its negative correlates including body wasting.

Fossil body parts of the two cold-adapted ground beetle species, Elaphrus lapponicus and Diacheila polita, were found from a deposit dated in the late Last Glacial period in Hokkaido, Japan. The paleoenvironment was estimated from their modern distribution and habitat, along with the results of the paleobotanical studies at the site. The temperature was at least 6 degrees lower than modern in summer, and the area around the site was mostly covered with forest tundra, which can currently be seen in areas further north of Hokkaido.

Acanthamoeba keratitis (AK) is a blinding corneal infection caused by the protozoan Acanthamoeba. The long-term course of AK suggests the host immunity could not kill Acanthamoeba rapidly. The immune status is still unclear in the late stage of AK. The comparative transcriptome analysis was made based on the bulk RNA sequencing of cornea tissues from AK patients and donors. Differentially expressed genes and enriched signaling pathways were calculated. CIBERSORT algorithm was used for Immune infiltration analysis of cornea tissue between AK and normal controls. A total of 2668 differentially expressed genes, including 1477 upregulated genes and 1191 downregulated genes, were detected. Gene Ontology analysis revealed that the pathways were significantly enriched in leukocyte migration, regulation of T cell activation, the external side of plasma membrane, collagen-containing extracellular matrix, immune receptor activity and cytokine binding. KEGG pathway analysis showed that the pathways were significantly enriched in the cytokine-cytokine receptor interaction, hematopoietic cell lineage and Staphylococcus aureus infection pathway. The immune infiltration profiles varied little between AK and normal controls. Compared with normal tissue, cornea tissue of AK contained a higher proportion of M0 macrophages and CD8 T cells, while resting memory CD4 T cells contributed to a relatively lower portion (P &lt; 0.05). Finally, the expression levels of cell markers and SLAMF7/STAT6 pathway were confirmed by histopathology examinations, RT-qPCR and western blot.