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Acute disseminated encephalomyelitis (ADEM) is an immune demyelinating central nervous system (CNS) disorder, characterized by monophasic new onset neurological symptoms including encephalopathy, combined with neuroradiological evidence of multifocal demyelination. ADEM is extremely rarely diagnosed and is much more common in children and adolescents than in adults. The aim of this study is to present an extremely rare case of ADEM in a heroin-addicted patient with a very difficult diagnostic course. The results of the magnetic resonance imaging (MRI) examination in this patient were inconclusive. Fungal abscesses or inflammatory lesions of an unclear nature were suspected especially in a patient with impaired immunodeficiency. In view of the constantly deteriorating condition of the patient with disturbed consciousness and the unclear aetiology, the lack of effective treatment, a decision was made to perform a bilateral stereotactic biopsy and aspiration of brain abnormalities in order to obtain a neuropathological specimen and begin with the causal treatment. Neuropathological examination revealed the presence of Creutzfeldt-Peters cells characteristic of ADEM. Treatment with methylprednisolone significantly improved the patient’s general and neurological condition. To our knowledge, the above case is the first in the world literature in which ADEM has been confirmed by bilateral stereotaxic aspiration for the treatment of symptoms of increased intracranial pressure as a lifesaving procedure. Neuropathological confirmation allowed for the implementation of appropriate treatment, which resulted in complete recovery. Moreover, this case is interesting because ADEM was diagnosed in a patient addicted to heroin, where opportunistic inflammation of a fungal aetiology was considered in the first place.

Abstract Photovoltaic‐powered electric transportation systems are gaining global momentum owing to their superior enactment and zero carbon emissions. With a growing number of electric vehicles (EVs) on the road, implementation of efficient and well‐organised charging stations is extremely indispensable. The authors investigate the feasibility of creating a charging station for plug‐in‐hybrid EVs at an educational institution, E.G.S. Pillay Engineering College, Nagapattinam, Tamil Nadu, India (10°48.2′N, 79°50.1′E). The statistics related to the solar radiations of the Nagapattinam region are employed to find out the energy availability for the EV charging station (EVCS) and the requirement for grid connection. The authors use a hybrid optimisation model for an electric renewable (HOMER) simulator to determine the optimum specification of the proposed EVCS. Also, the authors carry out a techno‐economic study against the specified load requirement to evaluate the potential of the charging station. The solar irradiance data obtained from NASA ground climatology and the solar power dataset of the designated site are used to realise the precise fallouts. The optimisation results provide minimum annual system cost and reliable power to the EVs. Based on these results, an EVCS is erected in the college campus to charge plug‐in hybrid electric vehicles. The established EVCS contains 3 kW EV charger operating as a microgrid and includes nine solar panels with 335 W each, 48 V, 150 Ah specification. The authors use solar photovoltaic (PV) panels using Copper Indium Selenide‐Zinc sulfide (CISZS) quantum dots for maximising energy yield from the EVCS. The authors consider that eight different charging profiles for different months are employed for estimating the solar irradiance probability density in the designated site. From this study, the authors can conclude that Gaussian mixer model (G4) profile is optimum for the Nagapattinam region to install a potential and reliable EVCS.

Abstract There is an ongoing debate on the implementation of the COVID-19 passport throughout Europe. We sought to build and test a feasible prevention strategy to ensure low SARS-CoV transmission risk in public events. We conducted a non-randomised controlled study. The intervention group obtained a confidential digital certificate of very low capacity for transmitting SARS-CoV-2 and attended socio-cultural events in Girona (Spain) between 1 April and 21 May 2021. The primary care services and a network of pharmacies cooperated in providing the certification. A group of non-attendees was randomly selected from pseudonymised health records as controls. We estimated the incidences of SARS-CoV-2 infection and recorded the challenges in the process. Follow-up was complete for 1351 participants, who were matched with 4050 controls. Mean age of the study population was 31.1 years, and 53% of participants were women. Incidence rates of SARS-CoV infection at 14 days in the group of attendees and non-attendees were 15.9 and 17.7 per 100,000 person-days, respectively; the difference between incidences was − 1.8 (95% CI − 22.8, 19.3). Implementation problems were minor, and 89.2% of respondents to a survey were satisfied with the process. The incidence rate of SARS-CoV-2 infection was not different in the intervention and control groups. These results are in favour of establishing a COVID-19 certificate to attend public events, and connote feasibility of implementation at a population level.

Transactive response DNA binding protein of 43 kDa (TDP-43) is considered to play an essential role in the pathogenesis of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Growing body of evidence indicate that pathological TDP-43 inclusions frequently occur in the context of other distinctive hallmark pathologies, referred to as secondary TDP-43 proteinopathies. Comorbid TDP-43 pathology is well-documented in several neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, multiple system atrophy, or progressive supranuclear palsy. It may also appear as a consequence of less obvious disease etiologies, i.e. post-traumatic (chronic traumatic encephalopathy), neoplastic (pilocytic astrocytoma), or post-infectious (post-encephalitic parkinsonism). The aim of the present review was to evaluate the incidence, morphology, and role of TDP-43 pathology in the secondary TDP-43 proteinopathies. This article (Part 1) discussed TDP-43 pathology in more common neurodegenerative diseases, including Alzheimer’s disease, Lewy body disease, Huntington’s disease, multiple system atrophy, corticobasal degeneration, and progressive supranuclear palsy. A follow-up article (Part 2) will describe abnormal TDP-43 changes in rare neurodegenerative diseases or neurological diseases with nondegenerative etiology.

ABSTRACTPlantain is one of the major staples contributing to food security and income generation in West and Central Africa. Local cultivars in Cameroon are susceptible to pests and diseases causing severe losses in plantain production. This study aimed at evaluating the agronomic performance and producer’s perception of plantain hybrids in the humid forest of Cameroon. Field trials were established in a completely randomized block design with eight genotypes and three replicates. Data on pest and disease as well as farmer perception were collected over two growing cycles. These genotypes included seven improved and one local genotype (check). Improved genotypes were highly tolerant to the Black Sigatoka disease compared to local plantain. While root necrosis index was above 50% in local varieties, indices below 25% were recorded in hybrids. Weevil severity in local was higher (55.0 ± 5.2%) compared to 21.0 ± 4.6% to 28.5 ± 3.2% in improved plantains. Average bunch weight was higher for FHIA 21 with 17.9 ± 0.7 kg in the first and 19.7 ± 0.3 kg for the second cycle, while those of the local Ebang were 9.6 ± 0.5 kg and 12.8 ± 0.9 kg, respectively. FHIA 21 and CRBP 568 were the preferred varieties by farmers (68.8% and 56.3% acceptance) from an agronomic perspective. The consumers’ preferences for all the genotypes varied with types of cooking. The implications of these findings for adoption by farmers and consumers as well as for the promotion of the plantain sector in central Africa are discussed.

Ensuring respect for human rights is an imperative for societies that strive for well-being, peace and the strengthening of the rule of law. The Republic of Moldova has shown interest in fundamental human rights values when it ratified most international treaties in the field. In this scientific approach, it is proposed the scientific approach of the institute of detention regulated by the national contravention and criminal procedure law, by identifying the particularities and notion of contravention detention and criminal procedural detention, assessing the moment from which the person considers himself/herself to be detained, which in itself represents this measure, By whom and under what conditions it can be applied, as well as the brief analysis of the legal framework and the case-law of the ECtHR regarding the specificity of the application of the given measure in case of a contravention process and in case of a criminal trial.

Indisputably the right to a fair trial is one of the basic rights enjoyed by any person involved in a contravention process. Even if it is not directly enshrined in the contravention law, it is still found in the content of the law, its application being an obligation of the state authorities involved in carrying out the contravention process. Both the national jurisprudence and the ECtHR jurisprudence denote the role that this principle has in the administration of justice, its non-compliance having the consequence of harming the principles and fundamental rights guaranteed. Although the contravention presents a social danger that is reduced in relation to the crime, that fact must not influence the smooth progress of the contravention process, so that the investigating agent ignores the observance of all the principles established by law in the process of examining the contravention.

Analizar el cine de animación experimental realizado por mujeres en España a lo largo de la última década es el motivo principal de este artículo. Esclarecer la idiosincrasia de un conjunto de realizaciones creadas por cineastas femeninas que trabajan en la actualidad, dentro del panorama nacional, es el objetivo prioritario de una investigación inevitablemente parcial. En ella se establece un primer apartado que debate el concepto de “animación experimental” vinculado con la perspectiva de género y la cuestión identitaria. Describiendo tres procedimientos prácticos asociados a la experimentación fílmica, se estudia el trabajo de seis realizadoras audiovisuales de trayectoria consolidada. De este modo se indaga sobre los procesos de creación que se esconden en sus piezas, enfatizando su valor artístico y la reflexión teórica que desencadenan.

Abstract Access to public transport increases vulnerable people's social mobility, facilitates economic integration and improves general well‐being. This is possible given the low vehicular acquisition and low cost required to enjoy public transport services. Unfortunately, the discourse on the responsiveness of public transport services to the disability community in the Global South has been viewed from users' perspectives, leaving out key stakeholders whose actions impact persons with disability (PWDs') mobility needs. This study seeks to fill the gap by exploring stakeholders' responses to the travel needs of commuters with disability in the Accra Metropolitan Assembly. Employing an exploratory research design, this study purposively engaged five national stakeholders on transport and disability issues. All interviews and transcripts were transcribed using MaxQDA. The qualitative data analysis was iterative as the study adopted a thematic analytical approach to explore participants' opinions. From the data, all stakeholders did not have a disability‐inclined transport agenda or policy despite making various attempts to meet the travel needs of PWDs. Some attempts include the reliance on one's discretion as seen in the case of transport operators, while other stakeholders appeared to offer little support due to financial and administrative bottlenecks. Transport‐oriented stakeholders cared little about PWD while disability‐oriented stakeholders cared little about transport issues. This study recommends a consultative action framework to guide all stakeholders in ensuring the delivery of barrier‐free transport services to the disability community.

Abstract In this paper, we report on a wind observation method based on the movement of hot‐air balloons (HABs). A quality assessment was carried out by comparing against wind observations at the meteorological tower of Cabauw in the Netherlands during May–September 2018, and the obtained standard deviations in error were σu=0.65ms−1 and σv=0.69ms−1 for the measured zonal and meridional wind components, respectively. Subsequent comparison against short‐term forecasts of the HARMONIE‐AROME model showed a standard deviation of 2.5 ms−1 for the wind vector difference. From the HAB observation set, a case was selected with a rapidly changing wind field belonging to a small intensifying depression. The HAB wind observation was applied in data assimilation as a proof of principle for a single‐observation experiment. It is shown that in a complex baroclinic situation, the model state is slightly improved.

Abstract This article describes the electromagnetic analysis of high efficient hybrid motor, which comprises the salient features of switched reluctance motor (SRM) and spoke‐type brushless DC motor. The main objective is to develop a motor with a high‐power density and winding faulty capability. Furthermore, this research article extends in the manner to increase the power density of the motor through the sensitivity analysis on rotor geometry by replacing the rotating part of SRM and adopting the rotor of spoke type brushless DC motor, originating the hybrid motor with the high‐power density and enhanced efficiency. To ensure the winding fault capability, a SRM‐based stator winding is adopted. Then, the modelling process for hybrid motor 48 V, 1500 RPM, 2 kW, and 12.7 Nm are detail in both analytical and finite element methods. The electromagnetic analysis is carried out to estimate the torque characteristics and flux pattern of the proposed motor. Furthermore, the proposed motor is analysed with the selection of laminating core material among M 27 24 Ga, 36F155, 46F165, 47F165, M 420 50D, and arnon 7. This infers 36F155 material assists proposed motor has high‐performance characteristics. The vibration frequencies are investigated in modal aspects to estimate the natural frequencies of vibrations. These analyses are validated among analytical and finite element results under no‐load conditions.

Background Baseline stroke severity is probably partly responsible for poor stroke outcomes in sub‐Saharan Africa. However, there is a paucity of information on determinants of stroke severity among indigenous Africans. We sought to identify the factors associated with stroke severity among West Africans in the SIREN (Stroke Investigative Research and Educational Networks) study. Methods and Results Stroke was diagnosed clinically and confirmed with brain neuroimaging. Severe stroke was defined as a Stroke Levity Scale score of ≤5. A multivariate logistic regression model was constructed to identify factors associated with stroke severity at 95% CI and a nominal cutoff of 5% type 1 error. A total of 3660 stroke cases were included. Overall, 50.7%% had severe stroke, including 47.6% of all ischemic strokes and 56.1% of intracerebral hemorrhage. Factors independently associated with severe stroke were meat consumption (adjusted odds ratio [aOR], 1.97 [95% CI, 1.43–2.73]), low vegetable consumption (aOR, 2.45 [95% CI, 1.93–3.12]), and lesion volume, with an aOR of 1.67 (95% CI, 1.03–2.72) for lesion volume of 10 to 30 cm3 and aOR of 3.88 (95% CI, 1.93–7.81) for lesion volume >30 cm3. Severe ischemic stroke was independently associated with total anterior circulation infarction (aOR, 3.1 [95% CI, 1.5–6.9]), posterior circulation infarction (aOR, 2.2 [95% CI, 1.1–4.2]), and partial anterior circulation infarction (aOR, 2.0 [95% CI, 1.2–3.3]) compared with lacunar stroke. Increasing age (aOR, 2.6 [95% CI, 1.3–5.2]) and lesion volume >30 cm3 (aOR, 6.2 [95% CI, 2.0–19.3]) were independently associated with severe intracerebral hemorrhage. Conclusions Severe stroke is common among indigenous West Africans, where modifiable dietary factors are independently associated with it. These factors could be targeted to reduce the burden of severe stroke.

Cannabis sativa, also known as “hemp” or “weed,” is a versatile plant with various uses in medicine, agriculture, food, and cosmetics. This review attempts to evaluate the available literature on the ecology, chemical composition, phytochemistry, pharmacology, traditional uses, industrial uses, and toxicology of Cannabis sativa. So far, 566 chemical compounds have been isolated from Cannabis, including 125 cannabinoids and 198 non-cannabinoids. The psychoactive and physiologically active part of the plant is a cannabinoid, mostly found in the flowers, but also present in smaller amounts in the leaves, stems, and seeds. Of all phytochemicals, terpenes form the largest composition in the plant. Pharmacological evidence reveals that the plants contain cannabinoids which exhibit potential as antioxidants, antibacterial agents, anticancer agents, and anti-inflammatory agents. Furthermore, the compounds in the plants have reported applications in the food and cosmetic industries. Significantly, Cannabis cultivation has a minimal negative impact on the environment in terms of cultivation. Most of the studies focused on the chemical make-up, phytochemistry, and pharmacological effects, but not much is known about the toxic effects. Overall, the Cannabis plant has enormous potential for biological and industrial uses, as well as traditional and other medicinal uses. However, further research is necessary to fully understand and explore the uses and beneficial properties of Cannabis sativa.

The improvement of human living conditions has led to an increase in average life expectancy, creating a new social and medical problem—aging, which diminishes the overall quality of human life. The aging process of the body begins with the activation of effector signaling pathways of aging in cells, resulting in the loss of their normal functions and deleterious effects on the microenvironment. This, in turn, leads to chronic inflammation and similar transformations in neighboring cells. The cumulative retention of these senescent cells over a prolonged period results in the deterioration of tissues and organs, ultimately leading to a reduced quality of life and an elevated risk of mortality. Among the most promising methods for addressing aging and age-related illnesses are pharmacological, genetic, and cellular therapies. Elevating the activity of aging-suppressing genes, employing specific groups of native and genetically modified cells, and utilizing senolytic medications may offer the potential to delay aging and age-related ailments over the long term. This review explores strategies and advancements in the field of anti-aging therapies currently under investigation, with a particular emphasis on gene therapy involving adeno-associated vectors and cell-based therapeutic approaches.

Development challenges in the domain of superconducting magnets are concentrated on technical problems in the current literature. Organizational, domain-specific challenges are often seen as secondary but must be considered with new holistic development approaches like Model-Based Systems Engineering (MBSE) becoming more popular. This work quantifies the domain challenges and gives the foundation to derive success criteria for design support in the future. A systematic literature review has been conducted to identify the overall domain challenges, and extensive interviews in the CERN technology department have been carried out to identify the development challenges on a practical level. Problems in knowledge management have been identified as a major challenge in the development process and the general literature. The paper concludes by picking up the most important challenges from the interviews and literature and puts them into the context of the authors’ knowledge of electrical magnet design.

Despite the large impact chronic obstructive pulmonary disease (COPD) that has on the population, the implementation of new technologies for diagnosis and treatment remains limited. Current practices in ambulatory oxygen therapy used in COPD rely on fixed doses overlooking the diverse activities which patients engage in. To address this challenge, we propose a software architecture aimed at delivering patient-personalized edge-based artificial intelligence (AI)-assisted models that are built upon data collected from patients’ previous experiences along with an evaluation function. The main objectives reside in proactively administering precise oxygen dosages in real time to the patient (the edge), leveraging individual patient data, previous experiences, and actual activity levels, thereby representing a substantial advancement over conventional oxygen dosing. Through a pilot test using vital sign data from a cohort of five patients, the limitations of a one-size-fits-all approach are demonstrated, thus highlighting the need for personalized treatment strategies. This study underscores the importance of adopting advanced technological approaches for ambulatory oxygen therapy.

The work readiness of property graduates is the subject of global discourse and is an increasingly critical gap as employers demand professionals with competencies in their fundamental roles and digital technologies. Although these issues have been explored from the perspectives of students, graduates, and employers, the insights of property academics remain unexplored. As such, this study delved into the challenges encountered by property academics in Australia concerning the training of property graduates for the digital age, as well as the efficacy of strategies used to achieve this. The opinions of 22 property academics were gathered through an online questionnaire survey and analysed through mean scores, relative importance index (RII), and exploratory factor analysis (EFA). The profile of respondents suggests that approximately half of them have no more than five years of industry experience, and only 54.5% currently engage with the industry. The most significant challenges include limited funding to procure bespoke software and insufficient time to achieve digital competency. Furthermore, academics cited limited support from the universities as a key challenge, but rated curriculum rigidity as non-pertinent. Regarding strategies, retraining academics for digital proficiency, increased technical support from universities, adopting active learning, and revising curricula to incorporate digital technology are critical. Collaboration with industry partners and increased funding for software procurement also emerged as key external factors. Variations in these perceptions also suggest that older academics are less receptive towards retraining, academics with more industry experience believe that a restructuring of the curricula is required, and smaller institutions require more funding and industry support. The core themes of the proposed strategies also indicate that holistic curricula integration is required to incorporate the perspectives of all stakeholders. Practically, these findings underscore the pivotal role of academics in bridging the skills gap and the interconnected roles of graduates, universities, and industry partners.

Racial-ethnic minority populations in the US are disproportionately exposed to airborne fine particulate matter (PM _2.5 ), but few national studies have focused individually on the sources that contribute to these disparities. We address this gap by conducting a comprehensive analysis of PM _2.5 exposure disparities by race-ethnicity in the US, focusing on three source-categories: mobile-sources, cooking, and all other sources combined. Our approach is based on high-resolution, national land-use regression estimates of source-resolved PM _2.5 components, derived from high-resolution aerosol mass spectrometer measurements. We find that each of these sources contributes approximately one-third of the overall PM _2.5 exposure disparities by race-ethnicity. While the importance of mobile-source tailpipe emissions is well recognized, our study underscores the significance of cooking emissions in creating PM _2.5 exposure disparities. This finding represents a potentially significant opportunity to reduce these disparities, as cooking emissions are currently largely unregulated. It has important implications for policymakers and public health advocates aiming to address the persistent issue of racial-ethnic disparities in air pollution.

Modular precast construction is a methodological approach to reduce environmental impacts and increase productivity when building with concrete. Constructions are segmented into similar precast concrete elements, prefabricated with integrated quality control, and assembled just-in-sequence on site. Due to the automatised prefabrication, inaccuracies are minimised and the use of high-performance materials is enabled. As a result, the construction process is accelerated, and the modules can be designed to be lightweight and resource-efficient. This contribution presents the fundamentals of modular constructions made from precast concrete components. Then, to elaborate the requirements of a contemporary modular precast construction, the historic developments are described. Further, concepts and technical processes–comprehensible to non-expert readers–are introduced to formalise the discussion about the current state-of-the-art methods. Three case studies treating ongoing research are introduced and related to the conceptual fundamentals. The research is evaluated with regard to current barriers and future directions. In conclusion, modular precast construction is able to reduce emissions and increase productivity in the sector if researchers and firms coordinate the development of suitable technologies that bring value to critical stakeholders.

Background: Serum glycoproteins, which are made up of various monosaccharides, are altered in malignancy, a disorder of cellular conduct. L-fucose, a methyl pentose that serves as the last sugar in the majority of plasma glycoproteins, is one of the monosaccharides. Numerous illness conditions and cancers have been linked to increased levels of protein-bound fucose. Materials and Methods: In the current study, the serum fucose levels of patients with oral squamous cell carcinoma (OSCC) and healthy individuals were assessed and compared. The present study included a total of 30 OSCC patients and 30 healthy controls. The Winzler method was used to estimate the serum L-fucose levels using a spectrophotometer (Spectronic 20, Thermo Fisher Scientific, USA). Results: Age and sex had no effect on serum fucose levels. In contrast to healthy individuals, OSCC patients' mean serum fucose levels significantly increased. In conclusion, patients with OSCC can benefit from the use of serum fucose as an investigative biomarker.

Abstract There is definitive evidence that microplastics, defined as plastic particles less than 5 mm in size, are ubiquitous in the environment and can cause harm to aquatic organisms. These findings have prompted legislators and environmental regulators to seek out strategies for managing risk. However, microplastics are also an incredibly diverse contaminant suite, comprising a complex mixture of physical and chemical characteristics (e.g., sizes, morphologies, polymer types, chemical additives, sorbed chemicals, and impurities), making it challenging to identify which particle characteristics might influence the associated hazards to aquatic life. In addition, there is a lack of consensus on how microplastic concentrations should be reported. This not only makes it difficult to compare concentrations across studies, but it also begs the question as to which concentration metric may be most informative for hazard characterization. Thus, an international panel of experts was convened to identify 1) which concentration metrics (e.g., mass or count per unit of volume or mass) are most informative for the development of health-based thresholds and risk assessment and 2) which microplastic characteristics best inform toxicological concerns. Based on existing knowledge, it is recommended that microplastic concentrations in toxicity tests are calculated from both mass and count at minimum, though ideally researchers should report additional metrics, such as volume and surface area, which may be more informative for specific toxicity mechanisms. Regarding particle characteristics, there is sufficient evidence to conclude that particle size is a critical determinant of toxicological outcomes, particularly for the mechanisms of food dilution and tissue translocation .

Abstract Posttraumatic stress disorder (PTSD) is a significant public health issue. Yet, there are limited treatment options and no data to suggest which treatment will work for whom. We tested the efficacy of virtual reality exposure (VRE) or prolonged imaginal exposure (PE), augmented with D-cycloserine (DCS) for combat-related PTSD. As an exploratory aim, we examined whether brain-derived neurotrophic factor (BDNF) and fatty acid amide hydrolase (FAAH) moderated treatment response. Military personnel with PTSD (n = 192) were recruited into a multisite double-blind randomized controlled trial to receive nine weeks of VRE or PE, with DCS or placebo. Primary outcome was the improvement in symptom severity. Randomization was stratified by comorbid depression (MDD) and site. Participants in both VRE and PE showed similar meaningful clinical improvement with no difference between the treatment groups. A significant interaction (p = 0.45) suggested VRE was more effective for depressed participants (CAPS difference M = 3.51 [95% CI 1.17–5.86], p = 0.004, ES = 0.14) while PE was more effective for nondepressed participants (M = −8.87 [95% CI −11.33 to −6.40], p

Abstract Aerosols and clouds greatly affect the Earth’s radiation budget and global climate. Light detection and ranging (lidar) has been recognized as a promising active remote sensing technique for the vertical observations of aerosols and clouds. China launched its first space-borne aerosol-cloud high-spectral-resolution lidar (ACHSRL) on April 16, 2022, which is capable for high accuracy profiling of aerosols and clouds around the globe. This study presents a retrieval algorithm for aerosol and cloud optical properties from ACHSRL which were compared with the end-to-end Monte-Carlo simulations and validated with the data from an airborne flight with the ACHSRL prototype (A2P) instrument. Using imaging denoising, threshold discrimination, and iterative reconstruction methods, this algorithm was developed for calibration, feature detection, and extinction coefficient (EC) retrievals. The simulation results show that 95.4% of the backscatter coefficient (BSC) have an error less than 12% while 95.4% of EC have an error less than 24%. Cirrus and marine and urban aerosols were identified based on the airborne measurements over different surface types. Then, comparisons were made with U.S. Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) profiles, Moderate-resolution Imaging Spectroradiometer (MODIS), and the ground-based sun photometers. High correlations (R > 0.79) were found between BSC (EC) profiles of A2P and CALIOP over forest and town cover, while the correlation coefficients are 0.57 for BSC and 0.58 for EC over ocean cover; the aerosol optical depth retrievals have correlation coefficient of 0.71 with MODIS data and show spatial variations consistent with those from the sun photometers. The algorithm developed for ACHSRL in this study can be directly employed for future space-borne high-spectral-resolution lidar (HSRL) and its data products will also supplement CALIOP data coverage for global observations of aerosol and cloud properties.

Abstract Assessing microplastics risk to aquatic ecosystems has been limited by lack of holistic exposure data and poor understanding of biological response thresholds. Here we take advantage of two recent advances, a toxicological meta-analysis that produced biotic response thresholds and a method to quantitatively correct exposure data for sampling methodology biases, to assess microplastic exposure risk in San Francisco Bay, California, USA. Using compartment-specific particle size abundance data, we rescaled empirical surface water monitoring data obtained from manta trawls (> 333 μm) to a broader size (1 to 5000 μm) range, corrected for biases in fiber undercounting and spectroscopic subsampling, and assessed the introduced uncertainty using probabilistic methods. We then compared these rescaled concentrations to four risk thresholds developed to inform risk management for California for each of two effect categories/mechanisms - tissue translocation-mediated effects and food dilution - each aligned to ecologically relevant dose metrics of surface area and volume, respectively. More than three-quarters of samples exceeded the most conservative food dilution threshold, which rose to 85% when considering just the Central Bay. Within the Central Bay, 38% of the samples exceeded a higher threshold associated with management planning, which was statistically significant at the 95% confidence interval. For tissue translocation-mediated effects, no samples exceeded any threshold with statistical significance. The risk associated with food dilution is higher than that found in other systems, which likely reflects this study having been conducted for an enclosed water body. A sensitivity analysis indicated that the largest contributor to assessment variability was associated with estimation of ambient concentration exposure due to correcting for fiber undercounting. Even after compensating for biases associated with fibers and other small particles, concentrations from the trawl samples were still significantly lower than the 1-L grab samples taken at the same time, suggesting our SFB risk estimates are an underestimate. We chose to rely on the trawl data because the 1-L grab sample volume was too small to provide accurate spatial representation, but future risk characterization studies would be improved by using in-line filtration pumps that sample larger volumes while capturing a fuller range of particle size than a towed net.

Second-order macroscopic traffic models are characterized by a continuity equation and an acceleration equation. Convection, anticipation, relaxation, diffusion, and viscosity are the predominant features of the different classes of the acceleration equation. As a unique approach, this paper presents a new macro-model that accounts for all these dynamic speed quantities. This is done to determine the collective role of these traffic quantities in macroscopic modeling. The proposed model is solved numerically to explain some phenomena of a multilane traffic flow. It also includes a linear stability analysis. Furthermore, the evolution of speed and density wave profiles are presented under the perturbation of some parameters.

Abstract Microplastic particles (MPs) are ubiquitous across a wide range of aquatic habitats but determining an appropriate level of risk management is hindered by a poor understanding of environmental risk. Here, we introduce a risk management framework for aquatic ecosystems that identifies four critical management thresholds, ranging from low regulatory concern to the highest level of concern where pollution control measures could be introduced to mitigate environmental emissions. The four thresholds were derived using a species sensitivity distribution (SSD) approach and the best available data from the peer-reviewed literature. This included a total of 290 data points extracted from 21 peer-reviewed microplastic toxicity studies meeting a minimal set of pre-defined quality criteria. The meta-analysis resulted in the development of critical thresholds for two effects mechanisms: food dilution with thresholds ranging from ~ 0.5 to 35 particles/L, and tissue translocation with thresholds ranging from ~ 60 to 4100 particles/L. This project was completed within an expert working group, which assigned high confidence to the management framework and associated analytical approach for developing thresholds, and very low to high confidence in the numerical thresholds. Consequently, several research recommendations are presented, which would strengthen confidence in quantifying threshold values for use in risk assessment and management. These recommendations include a need for high quality toxicity tests, and for an improved understanding of the mechanisms of action to better establish links to ecologically relevant adverse effects.

Gene expression patterns have been associated with functional activity patterns in the brain. Here the authors determine how gene expression patterns in the human brain supports brain phenotypes obtained from resting state fMRI imaging, identifying brain regions and genes relevant to autism.

Glioblastoma (GBM) is the most malignant type of glial tumor associated with a very unfavorable prognosis. Typical radiological features of GBM include the presence of a tumor with irregular contrast-enhancing margins and central necrosis surrounded by a wide area of vasogenic edema. Here, we presented an atypical clinical presentation of GBM mimicking autoimmune meningitis. A 69-years-old previously healthy male was admitted to the emergency room due to signs of increasing cognitive impairment, weight loss, changes in behavior, difficulty in walking, and prolonged episodes of nausea over the past month. An magnetic resonance imaging (MRI) brain scan revealed hyperintense changes of the periventricular area surrounding brain ventricles in T2 and FLAIR, and post-contrast leptomeningeal enhancement and thickening of meninges involving cerebellar sulci. An additional MRI scan of the cervical spine showed an in-core contrastenhancing lesion on the C7-Th1 level as well as leptomeningeal thickening and post-contrast-enhancement around the spinal cord. Various laboratory tests and two stereotactic biopsies were performed with no essential to diagnosis clinical findings. A couple of months after first hospital admission, the patient died. Post-mortem examination of the brain revealed numerous foci of abnormal tissue inside the subarachnoid space, lateral ventricles, and cerebral aqueduct. Histological examination showed diffuse malignant astroglial neoplasm, and diagnosis of glioblastoma NOS WHO G IV was established. Even though the appearance of usual GBM is widely recognizable, one must bear in mind the possibility of unusual presentation. The presented case highlights the diagnostic difficulties of diffuse glioblastoma with atypical clinical presentation.

Background: It is estimated that about 13 million artisanal and small-scale miners carry out their activities under harsh, precarious, unfriendly, and risky conditions. Yet, our understanding of the extent to which these workers use personal protective equipment (PPE) and navigate through the various risks and hazards they face is still limited. This article has two main objectives. First, it explores the extent of usage of PPE among artisanal and small-scale miners for the prevention of hazards and risks. Second, it examines the coping strategies used by these miners as a response to experiences of occupational injuries and risks Methods: A cross-sectional survey of small-scale miners was conducted in six communities across three districts in Ghana, West Africa. The mixed methods approach was adopted. A total of 148 small-scale miners participated in the study. Six focus group discussions (FGDs) were held across the six communities. The data were analysed using descriptive statistics. Chi-square tests were used to analyse the relationship between some socio-demographic characteristics (sex, age, and educational background) and the usage of PPE. Open-ended questions and responses from FGDs were analysed based on the content and verbatim quotations from miners. Results: Findings suggest that 78% of the miners interviewed do not use the appropriate PPE citing reasons such as cost, and their personal discomfort associated with use of PPE. There was no significant relationship between socio-demographic characteristics (i.e., sex, age, education and major mining activity) and the usage of PPE. The study further revealed four main coping strategies used by miners to handle the risks. These are rest, taking unprescribed medication and hard drugs, registration with health insurance scheme and savings and investments. Conclusion: This study shows that very few artisanal miners use PPE despite the significant hazards and risks to which they are exposed. The study recommends to the government to put in place measures to ensure that miners adhere to health and safety regulations before undertaking mining activities. This means that health and safety plans and use of PPE should be linked to the license acquisition process for miners.

Omega-O-acyl ceramides such as 32-linoleoyloxydotriacontanoyl sphingosine (Cer[EOS]) are essential components of the lipid skin barrier, which protects our body from excessive water loss and the penetration of unwanted substances. These ceramides drive the lipid assembly to epidermal-specific long periodicity phase (LPP), structurally much different than conventional lipid bilayers. Here, we synthesized Cer[EOS] with selectively deuterated segments of the ultralong N-acyl chain or deuterated or 13C-labeled linoleic acid and studied their molecular behavior in a skin lipid model. Solid-state 2H NMR data revealed surprising molecular dynamics for the ultralong N-acyl chain of Cer[EOS] with increased isotropic motion toward the isotropic ester-bound linoleate. The sphingosine moiety of Cer[EOS] is also highly mobile at skin temperature, in stark contrast to the other LPP components, N-lignoceroyl sphingosine acyl, lignoceric acid, and cholesterol, which are predominantly rigid. The dynamics of the linoleic chain is quantitatively described by distributions of correlation times and using dynamic detector analysis. These NMR results along with neutron diffraction data suggest an LPP structure with alternating fluid (sphingosine chain-rich), rigid (acyl chain-rich), isotropic (linoleate-rich), rigid (acyl-chain rich), and fluid layers (sphingosine chain-rich). Such an arrangement of the skin barrier lipids with rigid layers separated with two different dynamic “fillings” i) agrees well with ultrastructural data, ii) satisfies the need for simultaneous rigidity (to ensure low permeability) and fluidity (to ensure elasticity, accommodate enzymes, or antimicrobial peptides), and iii) offers a straightforward way to remodel the lamellar body lipids into the final lipid barrier.

Abstract Background and Aim The COVID‐19 booster dose has been cited as an important supplement for the control of the COVID‐19 pandemic due to reports of waning immunity among fully vaccinated persons. Determining factors that would affect its acceptability is necessary for initiating successful vaccination programs. In this study, we aimed to evaluate the factors associated with the acceptability of the COVID‐19 booster dose in Ghana. Methods We conducted an online cross‐sectional survey among the public. A self‐administered questionnaire was used to collect information on demographic characteristics, willingness to vaccinate, perceptions toward COVID‐19 vaccines, and trust in the government. Participants provided reasons and sources of advice that may affect their willingness to accept a booster dose. Using IBM SPSS and R Statistic; descriptive, univariate, and multivariate analyses were performed. Results Out of 812 respondents, 375 (46.2%) intended to accept the booster dose. Individuals who were males (adjusted odds ratio [aOR] 1.63, 95% confidence interval [CI] 1.07−2.48), had previously received other forms of vaccination twice (aOR 1.96, 95% CI 1.07−3.57) or in most years (aOR 2.51, 95% CI 1.38−4.57), tested positive for COVID‐19 (aOR 3.46, 95% CI 1.23−10.52), have high trust in government (aOR=1.77, 95% CI: 1.15‐2.74) and had positive perceptions regarding COVID‐19 vaccines (OR = 14.24, 95% CI: 9.28−22.44) were more likely to accept a booster dose. Experiencing side effects from the primer dose (aOR 0.12, 95% CI 0.08−0.18) was associated with reduced acceptance. Concerns about vaccine safety and efficacy were the common reasons impeding willingness, while advice from health professionals would be the most considered. Conclusion Low intention to accept the booster dose which is associated with a range of factors including the perception of vaccines and trust in the government, is a cause for concern. Thus, more effort would have to be taken through education and policy interventions to increase booster vaccine acceptability.

Summary: Background: Identification of convulsive epilepsy in sub-Saharan Africa relies on access to resources that are often unavailable. Infrastructure and resource requirements can further complicate case verification. Using machine-learning techniques, we have developed and tested a region-specific questionnaire panel and predictive model to identify people who have had a convulsive seizure. These findings have been implemented into a free app for health-care workers in Kenya, Uganda, Ghana, Tanzania, and South Africa. Methods: In this retrospective case-control study, we used data from the Studies of the Epidemiology of Epilepsy in Demographic Sites in Kenya, Uganda, Ghana, Tanzania, and South Africa. We randomly split these individuals using a 7:3 ratio into a training dataset and a validation dataset. We used information gain and correlation-based feature selection to identify eight binary features to predict convulsive seizures. We then assessed several machine-learning algorithms to create a multivariate prediction model. We validated the best-performing model with the internal dataset and a prospectively collected external-validation dataset. We additionally evaluated a leave-one-site-out model (LOSO), in which the model was trained on data from all sites except one that, in turn, formed the validation dataset. We used these features to develop a questionnaire-based predictive panel that we implemented into a multilingual app (the Epilepsy Diagnostic Companion) for health-care workers in each geographical region. Findings: We analysed epilepsy-specific data from 4097 people, of whom 1985 (48·5%) had convulsive epilepsy, and 2112 were controls. From 170 clinical variables, we initially identified 20 candidate predictor features. Eight features were removed, six because of negligible information gain and two following review by a panel of qualified neurologists. Correlation-based feature selection identified eight variables that demonstrated predictive value; all were associated with an increased risk of an epileptic convulsion except one. The logistic regression, support vector, and naive Bayes models performed similarly, outperforming the decision-tree model. We chose the logistic regression model for its interpretability and implementability. The area under the receiver operator curve (AUC) was 0·92 (95% CI 0·91–0·94, sensitivity 85·0%, specificity 93·7%) in the internal-validation dataset and 0·95 (0·92–0·98, sensitivity 97·5%, specificity 82·4%) in the external-validation dataset. Similar results were observed for the LOSO model (AUC 0·94, 0·93–0·96, sensitivity 88·2%, specificity 95·3%). Interpretation: On the basis of these findings, we developed the Epilepsy Diagnostic Companion as a predictive model and app offering a validated culture-specific and region-specific solution to confirm the diagnosis of a convulsive epileptic seizure in people with suspected epilepsy. The questionnaire panel is simple and accessible for health-care workers without specialist knowledge to administer. This tool can be iteratively updated and could lead to earlier, more accurate diagnosis of seizures and improve care for people with epilepsy. Funding: The Wellcome Trust, the UK National Institute of Health Research, and the Oxford NIHR Biomedical Research Centre.

Periodontal Ehlers-Danlos syndrome (pEDS) is an autosomal dominant disorder characterized by early-onset periodontitis leading to premature loss of teeth, lack of attached gingiva and thin and fragile gums leading to gingival recession. Connective tissue abnormalities of pEDS typically include easy bruising, pretibial plaques, distal joint hypermobility, hoarse voice, and less commonly manifestations such as organ or vessel rupture. pEDS is caused by heterozygous missense mutations in C1R and C1S genes of the classical complement C1 complex. Previously we showed that pEDS pathogenic variants trigger intracellular activation of C1r and/or C1s, leading to extracellular presence of activated C1s. However, the molecular link relating activated C1r and C1s proteases to the dysregulated connective tissue homeostasis in pEDS is unknown. Using cell- and molecular-biological assays, we identified activated C1s (aC1s) as an enzyme which degrades collagen I in cell culture and in in vitro assays. Matrix collagen turnover in cell culture was assessed using labelled hybridizing peptides, which revealed fast and comprehensive collagen protein remodeling in patient fibroblasts. Furthermore, collagen I was completely degraded by aC1s when assays were performed at 40°C, indicating that even moderate elevated temperature has a tremendous impact on collagen I integrity. This high turnover is expected to interfere with the formation of a stable ECM and result in tissues with loose compaction a hallmark of the EDS phenotype. Our results indicate that pathogenesis in pEDS is not solely mediated by activation of the complement cascade but by inadequate C1s-mediated degradation of matrix proteins, confirming pEDS as a primary connective tissue disorder.

Environmental sanitation policy implementation is a vital factor that ensures that citizens are kept healthy and productive. The study sought to assess key factors impeding the implementation of environmental sanitation policy in Ghana. Using an explanatory design, a sample of 384 respondents was selected from the population of Accra through a simple random sampling technique. The questionnaire was the main instrument used to collect the data. The Partial Least Square-Structural Equation Modeling (PLS-SEM) technique was used to analyse the hypothesised path models. Based on the results, government approach, community representation, and lack of citizens' commitment were found to be statistically significant. The study also revealed that the government approach partially mediated the relationship between community representation and environmental sanitation policy implementation, and lack of citizens’ commitment and environmental sanitation policy implementation. The study has contributed to knowledge in the research endeavour by demonstrating that the implementation of public policy can easily be realised when the government uses the right approach in involving its citizens in policy decision-making and enhance their commitment to policy implementation.

ABSTRACT Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) is a proteomic technique with proven efficiency in the identification of microorganisms, such as bacteria, fungi, and parasites. The present study aimed to evaluate the usefulness of MALDI-TOF MS for the characterization of Leishmania species circulating in Bolivia using hsp70 gene sequencing as a reference technique. 55 Leishmania strains that were isolated from patients with tegumentary leishmaniasis were analyzed. MALDI-TOF MS identified two species of the L. braziliensis complex (L. braziliensis, n = 26; L. braziliensis outlier, n = 18), one species of the L. guyanensis complex (L. guyanensis, n = 1), one species of the L. lainsoni complex (L. lainsoni, n = 2), and two species of the L. mexicana complex (L. amazonensis, n = 5; and L. garnhami, n = 3). All of the strains were correctly identified at the subgenus, genus, and complex level, but 10 of them (18%) were misidentified as other species within the same complex by the hsp70 gene sequencing, with 7 of these corresponding to possible hybrids. Thus, one L. braziliensis corresponded to L. peruviana, two L. braziliensis corresponded to L. braziliensis/L. peruviana possible hybrids, two L. amazonensis corresponded to L. mexicana, and three L. garnhami and two L. amazonensis corresponded to L. mexicana/L. amazonensis possible hybrids. Accordingly, MALDI-TOF MS could be used as an alternative to molecular techniques for the identification of Leishmania spp., as it is low cost, simple to apply, and able to quickly produce results. In Bolivia, its application would allow for the improvement of the management of patient follow-ups, the updating of the epidemiological data of the Leishmania species, and a contribution to the control of tegumentary leishmaniasis. IMPORTANCE The objective of the study was to evaluate the usefulness of MALDI-TOF MS for the characterization of Leishmania species circulating in Bolivia, in comparison with the sequencing of the hsp70 gene. In our study, all of the isolates could be identified, and no misidentifications were observed at the complex level. Although the equipment implies a high initial investment in our context, MALDI-TOF MS can be used in different areas of microbiology and significantly reduces the cost of testing. Once the parasite culture is obtained, the technique quickly yields information by accessing a free database that is available online. This would allow for the improvement of the management of patients and follow-ups, the updating of the epidemiological data of the species, and a contribution to the control of tegumentary leishmaniasis in Bolivia. Likewise, it can be used to determine a specific treatment to be given, according to the causal species of Leishmania, when there are protocols in this regard in the area.

Konstruksi ramping telah diterapkan banyak proyek, artinya dalam masa perencanaan proyek telah meminimalisir waste dengan efektif dan efisien. Tujuan penelitian ini untuk mengidentifikasi variabel penyebab waste yang paling dominan pada proyek dan mengetahui penerapan Konstruksi Ramping pada proyek. Dalam mencapai tujuan tersebut maka digunakan metode Teorema Bayes untuk menentukan probabilitas dari waste 5M ruang lingkup manajemen. Hasil dari analisis probabilitas waste bahwa variabel-variabel yang menyebabkan waste adalah tenaga kerja sulit untuk bekerja sama dalam satu tim kerja (18,18%), material datang ke lokasi terlalu cepat (20,00%), alat berat terlambat sampai di lapangan (15,69%), denda karena keterlambatan proyek (34,88%) dan kesalahan dalam pemilihan jenis objek struktur (19.35%). Kemudian hasil dari analisis pengisian kuesioner penerapan konstruksi ramping dan observasi di lapangan bahwa proyek ini telah menerapkan konstruksi ramping sebesar 94,44%.

Abstract Microplastics have been documented in drinking water, but their effects on human health from ingestion, or the concentrations at which those effects begin to manifest, are not established. Here, we report on the outcome of a virtual expert workshop conducted between October 2020 and October 2021 in which a comprehensive review of mammalian hazard studies was conducted. A key objective of this assessment was to evaluate the feasibility and confidence in deriving a human health-based threshold value to inform development of the State of California’s monitoring and management strategy for microplastics in drinking water. A tiered approach was adopted to evaluate the quality and reliability of studies identified from a review of the peer-reviewed scientific literature. A total of 41 in vitro and 31 in vivo studies using mammals were identified and subjected to a Tier 1 screening and prioritization exercise, which was based on an evaluation of how each of the studies addressed various quality criteria. Prioritized studies were identified largely based on their application and reporting of dose–response relationships. Given that methods for extrapolating between in vitro and in vivo systems are currently lacking, only oral exposure in vivo studies were identified as fit-for-purpose within the context of this workshop. Twelve mammalian toxicity studies were prioritized and subjected to a Tier 2 qualitative evaluation by external experts. Of the 12 studies, 7 report adverse effects on male and female reproductive systems, while 5 reported effects on various other physiological endpoints. It is notable that the majority of studies (83%) subjected to Tier 2 evaluation report results from exposure to a single polymer type (polystyrene spheres), representing a size range of 0.040 to 20 µm. No single study met all desired quality criteria, but collectively toxicological effects with respect to biomarkers of inflammation and oxidative stress represented a consistent trend. While it was possible to derive a conservative screening level to inform monitoring activities, it was not possible to extrapolate a human–health-based threshold value for microplastics, which is largely due to concerns regarding the relative quality and reliability of current data, but also due to the inability to extrapolate data from studies using monodisperse plastic particles, such as polystyrene spheres to an environmentally relevant exposure of microplastics. Nevertheless, a conservative screening level value was used to estimate a volume of drinking water (1000 L) that could be used to support monitoring activities and improve our overall understanding of exposure in California’s drinking water. In order to increase confidence in our ability to derive a human–health-based threshold value in the future, several research recommendations are provided, with an emphasis towards strengthening how toxicity studies should be conducted in the future and an improved understanding of human exposure to microplastics, insights critically important to better inform future risk assessments. Graphical abstract

Abstract Throughout the past decade, many studies have reported adverse effects in biota following microplastic exposure. Yet, the field is still emerging as the current understanding of microplastic toxicity is limited. At the same time, recent legislative mandates have required environmental regulators to devise strategies to mitigate microplastic pollution and develop health-based thresholds for the protection of human and ecosystem health. The current publication rate also presents a unique challenge as scientists, environmental managers, and other communities may find it difficult to keep up with microplastic research as it rapidly evolves. At present, there is no tool that compiles and synthesizes the data from these studies to allow for visualization, interpretation, or analysis. Here, we present the Toxicity of Microplastics Explorer (ToMEx), an open access database and open source accompanying R Shiny web application that enables users to upload, search, visualize, and analyze microplastic toxicity data. Though ToMEx was originally created to facilitate the development of health-based thresholds to support California legislations, maintaining the database by the greater scientific community will be invaluable to furthering research and informing policies globally. The database and web applications may be accessed at https://microplastics.sccwrp.org/ . Graphical Abstract

Abstract Background Integration of medicinal chemistry data from numerous public resources is an increasingly important part of academic drug discovery and translational research because it can bring a wealth of important knowledge related to compounds in one place. However, different data sources can report the same or related compounds in various forms (e.g., tautomers, racemates, etc.), thus highlighting the need of organising related compounds in hierarchies that alert the user on important bioactivity data that may be relevant. To generate these compound hierarchies, we have developed and implemented canSARchem, a new compound registration and standardization pipeline as part of the canSAR public knowledgebase. canSARchem builds on previously developed ChEMBL and PubChem pipelines and is developed using KNIME. We describe the pipeline which we make publicly available, and we provide examples on the strengths and limitations of the use of hierarchies for bioactivity data exploration. Finally, we identify canonicalization enrichment in FDA-approved drugs, illustrating the benefits of our approach. Results We created a chemical registration and standardization pipeline in KNIME and made it freely available to the research community. The pipeline consists of five steps to register the compounds and create the compounds’ hierarchy: 1. Structure checker, 2. Standardization, 3. Generation of canonical tautomers and representative structures, 4. Salt strip, and 5. Generation of abstract structure to generate the compound hierarchy. Unlike ChEMBL’s RDKit pipeline, we carry out compound canonicalization ahead of getting the parent structure, similar to PubChem’s OpenEye pipeline. canSARchem has a lower rejection rate compared to both PubChem and ChEMBL. We use our pipeline to assess the impact of grouping the compounds in hierarchies for bioactivity data exploration. We find that FDA-approved drugs show statistically significant sensitivity to canonicalization compared to the majority of bioactive compounds which demonstrates the importance of this step. Conclusions We use canSARchem to standardize all the compounds uploaded in canSAR (> 3 million) enabling efficient data integration and the rapid identification of alternative compound forms with useful bioactivity data. Comparison with PubChem and ChEMBL pipelines evidenced comparable performances in compound standardization, but only PubChem and canSAR canonicalize tautomers and canSAR has a slightly lower rejection rate. Our results highlight the importance of compound hierarchies for bioactivity data exploration. We make canSARchem available under a Creative Commons Attribution-ShareAlike 4.0 International License (CC BY-SA 4.0) at https://gitlab.icr.ac.uk/cansar-public/compound-registration-pipeline .

Abstract Ixodes ricinus ticks (Acari: Ixodidae) are the most important vector for Lyme borreliosis in Europe. As climate change might affect their distributions and activities, this study aimed to determine the effects of environmental factors, i.e., meteorological, bioclimatic, and habitat characteristics on host-seeking (questing) activity of I. ricinus nymphs, an important stage in disease transmissions, across diverse climatic types in France over 8 years. Questing activity was observed using a repeated removal sampling with a cloth-dragging technique in 11 sampling sites from 7 tick observatories from 2014 to 2021 at approximately 1-month intervals, involving 631 sampling campaigns. Three phenological patterns were observed, potentially following a climatic gradient. The mixed-effects negative binomial regression revealed that observed nymph counts were driven by different interval-average meteorological variables, including 1-month moving average temperature, previous 3-to-6-month moving average temperature, and 6-month moving average minimum relative humidity. The interaction effects indicated that the phenology in colder climates peaked differently from that of warmer climates. Also, land cover characteristics that support the highest baseline abundance were moderate forest fragmentation with transition borders with agricultural areas. Finally, our model could potentially be used to predict seasonal human-tick exposure risks in France that could contribute to mitigating Lyme borreliosis risk.

We present a comprehensive checklist of scleractinian (hard) corals for the Mersing Islands, Malaysia based on surveys conducted at 24 reefs across protected and unprotected marine areas. A total of 261 species of corals from 16 families and one incertae sedis (Pachyseris spp.) were recorded, along with ten records that are new for the east coast of Peninsular Malaysia. Compared against the IUCN Red List, 46.7% of coral species found in the Mersing Islands were of Least Concern (LC), 29.5% as Near Threatened (NT) and 16.4% Vulnerable (V). Only one recorded species, Pectinia maxima (Moll & Best, 1984), was listed as Endangered (EN). Baseline species diversity data are essential for the monitoring and management of marine biodiversity, especially within marine protected areas. With both protected and unprotected coral reef areas in the vicinity of the widely scattered Mersing Islands, the diversity and distribution of coral species can be used as the basis for area-based conservation and management strategies. The diversity and abundance of scleractinian corals of each island or area should be surveyed periodically to ensure the appropriate level of protection is afforded to retain scleractinian biodiversity in this region.

Abstract Background Neuronal uptake and subsequent spread of proteopathic seeds, such as αS (alpha-synuclein), Tau, and TDP-43, contribute to neurodegeneration. The cellular machinery participating in this process is poorly understood. One proteinopathy called multisystem proteinopathy (MSP) is associated with dominant mutations in Valosin Containing Protein (VCP). MSP patients have muscle and neuronal degeneration characterized by aggregate pathology that can include αS, Tau and TDP-43. Methods We performed a fluorescent cell sorting based genome-wide CRISPR-Cas9 screen in αS biosensors. αS and TDP-43 seeding activity under varied conditions was assessed using FRET/Flow biosensor cells or immunofluorescence for phosphorylated αS or TDP-43 in primary cultured neurons. We analyzed in vivo seeding activity by immunostaining for phosphorylated αS following intrastriatal injection of αS seeds in control or VCP disease mutation carrying mice. Results One hundred fifty-four genes were identified as suppressors of αS seeding. One suppressor, VCP when chemically or genetically inhibited increased αS seeding in cells and neurons. This was not due to an increase in αS uptake or αS protein levels. MSP-VCP mutation expression increased αS seeding in cells and neurons. Intrastriatal injection of αS preformed fibrils (PFF) into VCP-MSP mutation carrying mice increased phospho αS expression as compared to control mice. Cells stably expressing fluorescently tagged TDP-43 C-terminal fragment FRET pairs (TDP-43 biosensors) generate FRET when seeded with TDP-43 PFF but not monomeric TDP-43. VCP inhibition or MSP-VCP mutant expression increases TDP-43 seeding in TDP-43 biosensors. Similarly, treatment of neurons with TDP-43 PFFs generates high molecular weight insoluble phosphorylated TDP-43 after 5 days. This TDP-43 seed dependent increase in phosphorlyated TDP-43 is further augmented in MSP-VCP mutant expressing neurons. Conclusion Using an unbiased screen, we identified the multifunctional AAA ATPase VCP as a suppressor of αS and TDP-43 aggregate seeding in cells and neurons. VCP facilitates the clearance of damaged lysosomes via lysophagy. We propose that VCP’s surveillance of permeabilized endosomes may protect against the proteopathic spread of pathogenic protein aggregates. The spread of distinct aggregate species may dictate the pleiotropic phenotypes and pathologies in VCP associated MSP.

Typha lepechinii, a new species from European Russia, is described. In terms of the external morphology, it is similar to T. shuttleworthii but differs from the latter by the shape of female inflorescence, wider leaf blades and geographical distribution. Like T. shuttleworthii, T. lepechinii is clearly distinct from all other cattails of T. sect. Ebracteolatae due to its short male inflorescence that is 2–4 times shorter than the contiguous female inflorescence. The spatial disjunction of this new species from the main distribution range of predominantly European T. shuttleworthii is significant: T. lepechinii is an endemic of the outmost East of the Russian Plain, in particular, the regions of Middle and Southern Cis-Ural region (basin of the Middle and Lower Kama). In terms of the political administrative borders, this new cattail was found in the Udmurt Republic, the Republics of Tatarstan and Bashkortostan, the parts of the Russian Federation. From the elementary comparative molecular standpoint, T. lepechinii is different from its sister T. shuttleworthii due to four single nucleotide positions and two indels of the rpl32 gene and rpl32-trnL intergenic spacer (cpDNA). The new cattail is named after I. I. Lepechin (1737–1802)—a Russian scientist-encyclopedist whose primary botanical interest focused on the regions of Ural and Siberia.

Purpose – This study aimed to determine the prevalence and risk factors of hepatitis B virus (HBV) infection among medical laboratory science students (MLSSs) in the University of Health and Allied Sciences (UHAS), Ghana. Design/methodology/approach – A cross-sectional study design was employed to recruit a total of 178 students into the study. A self-administered questionnaire was used to gather relevant information on risk factors, and a hepatitis B diagnostic test kit was used to test for HBV infection. Descriptive, chi-square test, bivariate and multiple logistic regression statistical analysis were computed. Significance was observed at p < 0.05. Findings – The prevalence of HBV infection among MLSSs was 6.7%. Torn gloves and splash of blood and body fluids contributed to 43.0% and 28.0% of all the risk factors of HBV infection, respectively. Also, 43.3% of students had received at least one dose of the hepatitis B vaccination. Sharp object-related injury and torn gloves increased the odds of HBV infection, while vaccination decreased the odds of HBV infection. Originality/value – This study reveals the prevalence of HBV among MLSSs, who are recognized as being among the high-risk student populations aside from student nurses.

Introduction Heterotopic ossification (HO), also known as myositis ossification, paraosteoarthropathy, or heterotopic calcification, among others, is a common pathological condition that refers to ectopic bone formation in soft tissues. Although the molecular mechanism of HO is not fully understood, it is believed that signaling of bone morphogenetic proteins (BMPs) plays a key role in the overall process of HO. Today, recombinant human BMP-2 (rhBMP-2) and recombinant human BMP-7 (rhBMP-7) have been already actively used in clinical practice in the treatment of bone defects. However, despite the positive sides of using rhBMPs, there are a number of side effects, one of which is HO. Purpose In this study, we demonstrate cases of HO following the use of rhBMPs in both clinical and preclinical studies and make an attempt to explain the relationship between the signaling pathways of BMPs and the HO process, as well as the possibilities of preventing and treating the HO process. Materials and methods PubMed, Embase, the Cochrane Database, and Google Scholar were comprehensively searched for original articles, literature reviews, case reports, and meta-analyses demonstrating a causal relationship between therapeutic rhBMPs and HO as a complication. Results This review analyzes the potential for therapeutic use of rhBMPs in neurosurgery and traumatology and orthopedics, demonstrated by both clinical and preclinical studies. In particular, the studies confirm that ectopic bone formation is one of the side effects following administration of rhBMPs. Moreover, the molecular mechanisms of the HO process were highlighted, and the possibilities of modern methods of prevention and treatment of HO were discussed. Conclusion According to the FDA safety database for rhBMPs, the rates of adverse effects related to HO range from 1 % to 10 %. However, to date, the clinical use of rhBMPs is justified, especially when there are no alternative substitutes for bone grafting.

Abstract Across neurodegenerative diseases, common mechanisms may reveal novel therapeutic targets based on neuronal protection, repair, or regeneration, independent of etiology or site of disease pathology. To address these mechanisms and discuss emerging treatments, in April, 2021, Glaucoma Research Foundation, BrightFocus Foundation, and the Melza M. and Frank Theodore Barr Foundation collaborated to bring together key opinion leaders and experts in the field of neurodegenerative disease for a virtual meeting titled “Solving Neurodegeneration”. This “think-tank” style meeting focused on uncovering common mechanistic roots of neurodegenerative disease and promising targets for new treatments, catalyzed by the goal of finding new treatments for glaucoma, the world’s leading cause of irreversible blindness and the common interest of the three hosting foundations. Glaucoma, which causes vision loss through degeneration of the optic nerve, likely shares early cellular and molecular events with other neurodegenerative diseases of the central nervous system. Here we discuss major areas of mechanistic overlap between neurodegenerative diseases of the central nervous system: neuroinflammation, bioenergetics and metabolism, genetic contributions, and neurovascular interactions. We summarize important discussion points with emphasis on the research areas that are most innovative and promising in the treatment of neurodegeneration yet require further development. The research that is highlighted provides unique opportunities for collaboration that will lead to efforts in preventing neurodegeneration and ultimately vision loss.