bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple and multidrug resistance in Botrytis cinerea: molecular mechanisms of MLR/MDR strains in Greece and effects of co-existence of different resistance mechanisms on fungicide sensitivity
Authors: Sofianos Georgios , Samaras Anastasios , Karaoglanidis Georgios
Published: October 2023

Botrytis cinerea is a high-risk pathogen for fungicide resistance development. Within the fungal populations, strains have developed multiple mutations in different target genes leading to multiple resistance (MLR) or mutations associated with overexpression of efflux transporters leading to multidrug resistance (MDR). These types of resistance are a major threat, and their successful management is a major challenge. The current study was initiated to a) determine frequencies of MLR/MDR strains in populations originating from several crops, b) identify the types of MDR that occur in Greece, and c) determine interactions between MLR and MDR at the level of sensitivity to botryticides. The frequencies of MLR/MDR phenotypes were determined in 515 isolates subjected to bioassays using discriminatory concentrations of thiophanate-methyl, iprodione, cyprodinil, fenhexamid, boscalid, fluopyram, fludioxonil, pyraclostrobin, and tolnaftate. Interestingly, 7.8% and 31.3% of isolates from strawberry and rootstock seedlings were resistant to every single fungicide class, while MDR phenotypes from strawberries, rootstocks, and tomatoes accounted for 26%, 87%, and 13.4%, respectively. The MLR and MDR isolates were further molecularly analyzed regarding genes erg27, sdhB, Bcpos5, and Mrr1, responsible for resistance to fenhexamid, boscalid and fluopyram, cyprodinil, and MDR, respectively. The different mutations’ presence was determined along with a new mutation in Mrr1 leading to MDR. MDR isolates were characterized as MDR1 or MDR1h based on the presence of a 3-bp deletion in Mrr1. MDR1h was predominant in isolates from rootstocks and MDR1 from tomatoes and strawberries, whereas the most frequent target-site mutations were F412S (erg27), H272R (sdhB), and L412F (Bcpos5). To determine whether the accumulation of target-site mutations along with MDR mutations exhibits an additive effect concerning fungicide resistance, the sensitivity of isolates possessing the predominant target-site mutations was calculated in both the presence and the absence of MDR-associated mutations. EC50 in cyprodinil and boscalid increased to about twofold in the presence of MDR mutations, while there was no difference for fenhexamid. In conclusion, MLR/MDR frequencies are notably high in heavily treated crops in Greece, and the combination of MLR and MDR mutations leads to even higher fungicide resistance levels, highlighting the importance of resistance management.
The effect of acute exercise on objectively measured sleep and cognition in older adults
Authors: Sewell Kelsey R. , Smith Nathan D. W. , Rainey-Smith Stephanie R. , Peiffer Jeremiah , Sohrabi Hamid R. , Erickson Kirk I. , Brown Belinda M.
Published: October 2023

Background

Exercise can improve cognition in aging, however it is unclear how exercise influences cognition, and sleep may partially explain this association. The current study aimed to investigate whether objectively measured sleep mediates the effect of an acute exercise intervention on cognition in older adults.

Methods

Participants were 30 cognitively unimpaired, physically active older adults (69.2 ± 4.3 years) with poor sleep (determined via self-report). After a triple baseline cognitive assessment to account for any natural fluctuation in cognitive performance, participants completed either a single bout of 20-minutes of high intensity exercise on a cycle ergometer, or a control condition, in a cross-over trial design. Cognition was measured immediately post-intervention and the following day, and sleep (total sleep time, sleep onset latency, sleep efficiency, % of rapid eye movement sleep, light sleep and deep sleep) was characterized using WatchPAT™ at baseline (5 nights) and measured for one night after both exercise and control conditions.

Results

Results showed no effect of the exercise intervention on cognition immediately post-intervention, nor an effect of acute exercise on any sleep variable. There was no mediating effect of sleep on associations between exercise and cognition. However, a change from baseline to post-intervention in light sleep and deep sleep did predict change in episodic memory at the ~24 h post-intervention cognitive assessment, regardless of intervention condition.

Discussion

There was no effect of acute high intensity exercise on sleep or cognition in the current study. However, results suggest that associations between sleep and cognition may exist independently of exercise in our sample. Further research is required, and such studies may aid in informing the most effective lifestyle interventions for cognitive health.
Diagnostic assessment of autism in adults – current considerations in neurodevelopmentally informed professional learning with reference to ADOS-2
Authors: Curnow Eleanor , Utley Izy , Rutherford Marion , Johnston Lorna , Maciver Donald
Published: October 2023

Services for the assessment and diagnosis of autism in adults have been widely criticized and there is an identified need for further research in this field. There is a call for diagnostic services to become more accessible, person-centered, neurodiversity affirming, and respectful. There is a need for workforce development which will increase capacity for diagnostic assessment and support for adults. ADOS-2 is a gold-standard diagnostic assessment tool for autism recommended in clinical guidelines. However, diagnostic procedures such as the ADOS-2 are rooted in the medical model and do not always sit comfortably alongside the neurodiversity paradigm or preferences of the autistic community. Training and educational materials need to account for the differences between these approaches and support clinicians to provide services which meet the needs of the adults they serve. The National Autism Implementation Team worked alongside ADOS-2 training providers to support clinicians in Scotland, to provide effective and respectful diagnostic assessment. The team engaged with clinicians who had attended ADOS training to identify areas of uncertainty or concern. Training materials were developed to support ADOS assessors to incorporate key principles including “nothing about us without us”; “difference not deficit”; “environment first”; “diagnosis matters,” “language and mindsets matter”; and “a neurodevelopmental lens,” to support the provision of neurodiversity affirming assessment practice. The National Autism Implementation Team also provided examples of actions which can be undertaken by clinicians to improve the assessment experience for those seeking a diagnosis. Training materials are based on research evidence, clinical experience, and the needs and wishes of autistic people.
Livelihood risks impact livestock reduction behavior of herders: evidence from Inner Mongolia, China
Authors: Dong Haibin , Jimoh Saheed Olaide , Jiang Qishen , Liu Sibo , Yin Yanting , Hou Xiangyang
Published: October 2023

We analyzed the primary livelihood risks faced by livestock-herding households across six counties and three grassland types in Inner Mongolia. The major livelihood risks were natural, market, financial, and policy. These risks are influenced by changes in stocking rate (SR), which are critical for controlling livestock numbers and averting risks associated with overgrazing in natural grasslands. We propose a correction method for SR based on hay purchase from a survey of 450 herders. We compared the distribution of households’ SR after the correction and used a multiple linear regression model to empirically test the effect of livelihood risks on SR. The empirical model passed robustness test and the regression results of variables were robust. SR declined across grassland types after hay purchases. The SR of the meadow steppe was reduced by 35%, typical steppe by 23%, and desert steppe by 32%. Various factors affected changes in SR, including ecological subsidies to household income, timely access to market information, and annual livestock losses. We discuss implications of our findings for policy, market transactions, livestock insurance, social security, and formal credit systems in pastoral areas.
Putting food in the driver’s seat: aligning food-systems policy to advance sustainability, health, and security
Authors: Andrews Elisabeth , Sanderson Bellamy Angelina ,   Food Policy Alliance Cymru
Published: October 2023

Food is a basic need, but seldom a basic policy area. Food systems are widely governed by disconnected policies distributed across a range of sectors including agriculture, education, health, environment, economy, and security. Failure to align food system strategies often results in these disparate policies operating at cross-purposes. Conventional food production and consumption practices contribute to biodiversity decline and climate change, cause diet-related health problems, are associated with worker exploitation, and create national security risks. Drawing on agroecology for cohesive national food strategies can provide benefits across all these sectors: supporting public health, environmental sustainability, economic stability, social cohesion, and national security and sovereignty.
Farmed fish welfare during slaughter in Italy: survey on stunning and killing methods and indicators of unconsciousness
Authors: Clemente Gianfilippo Alessio , Tolini Clara , Boscarino Andrea , Lorenzi Valentina , Dal Lago Tania Lidia , Benedetti Daniele , Bellucci Fabio , Manfrin Amedeo , Trocino Angela , Rota Nodari Sara
Published: October 2023

Information on slaughter procedures for farmed fish in aquaculture is limited, both in Europe and in Italy, due to a general lack of field data. The aim of this study was to gather information on the procedures used to slaughter fish in Italy and to discuss them considering the WOAH and EFSA recommendations on fish welfare. Using a questionnaire survey, data were collected by official veterinarians in 64 slaughtering facilities where 20 different species of fish were slaughtered. The main species slaughtered were rainbow trout (Oncorhynchus mykiss; 29/64), followed by European sea bass (Dicentrarchus labrax; 21/64), sea bream (Sparus aurata; 21/64), Arctic char (Salvelinus alpinus; 14/64), European eel (Anguilla anguilla; 11/64), sturgeon (Acipenser spp; 11/64), common carp (Cyprinus carpio; 6/64), and brown trout (Salmo trutta fario L.; 5/64). The most applied stunning/killing methods were “asphyxia in ice/thermal shock” and “electric in water bath,” followed by “percussion,” “asphyxia in air,” and “electric dry system.” After the application of the method, the assessment of the fish level of unconsciousness was practiced in 72% of the facilities using more than one indicator, with “breathing” and “coordinated movements” the most practiced. The collected data showed a discrepancy between the available recommendations about the welfare of fish at slaughter and what is practiced in many production sites, but for many species precise recommendations are still not available.
Leverage of Essential Oils on Faeces-Based Methane and Biogas Production in Dairy Cows
Authors: Mazurkiewicz Jakub , Sidoruk Pola , Dach Jacek , Szumacher-Strabel Malgorzata , Lechniak Dorota , Galama Paul , Kuipers Abele , Antkowiak Ireneusz R. , Cieslak Adam
Published: October 2023

Currently, there is an ongoing intensive search for solutions that would effectively reduce greenhouse gas emissions (mainly methane) into the environment. From a practical point of view, it is important to reduce methane emissions from cows in such a way as to simultaneously trim emissions from the digestive system and increase its potential production from feces, which is intended as a substrate used in biogas plants. Such a solution would not only lower animal-based methane emissions but would also enable the production of fuel (in chemical form) with a high yield of methane from biogas, which would boost the economic benefits and reduce the use of fossil fuels. We tested the effect of administering an essential oil blend consisting of 5.5% oils and fats on methane and biogas production from dairy cow feces during fermentation. Three subsequent series (control and experimental) were conducted in dairy cows fed a total mixed ration (TMR) rich in brewer’s cereals and beet pulp, with 20% dry matter (DM) of the total diet. Cows from the experimental group received 20 g/cow/day of essential oil blend, namely a commercial additive (CA). The study showed that CA can increase the production of methane and biogas from dairy cow feces. It can be concluded that in the experimental groups, approx. 15.2% and 14.4% on a fresh matter basis and 11.7% and 10.9% on a dry matter basis more methane and biogas were generated compared to the control group, respectively. Therefore, it can be assumed that the use of CA in cow nutrition improved dietary digestibility, which increased the efficiency of the use of feces organic matter for biogas production.
Studying the Effect of Dense Planting on the Mechanism of Flower Abscission in Soybean through Combined Transcriptome-Metabolome Analysis
Authors: Wang Nan , He Dexin , Sun Hexiang , Yao Xingdong , Xie Futi
Published: October 2023

A high pod abscission rate in soybean plants results in a significant decrease in the yield per plant. Under dense planting conditions, dense tolerant soybean cultivars had a relatively low rate of pod abscission, thereby facilitating higher yield. In this experiment, two planting densities were used to analyze the differentially expressed genes and metabolites between the abscised and non-abscised flowers of two soybean cultivars on the basis of transcriptomic and metabolomic techniques. The flower abscission rate of LD32 was significantly lower than that of SND28. Both cultivars were enriched in the photosynthesis, sugar, and starch metabolism; MAPK signaling; and phenylalanine metabolism pathways at different planting densities. However, under dense planting, the trend of differential gene changes in the density-tolerant CV LD32 was opposite to that of the conventional CV SND28. The results of the joint analysis indicated that the co-regulation of cytokinin dehydrogenase 6 (CKX6) and cis-zeatin riboside monophosphate (CZRM) in the zeatin biosynthesis pathway of LD32 under dense planting conditions was the main factor for the relatively low rate of pod abscission under dense planting conditions.
Assessing the Effects of Dietary Cadmium Exposure on the Gastrointestinal Tract of Beef Cattle via Microbiota and Transcriptome Profile
Authors: Xu Xinxin , Xu Zebang , Yang Bin , Yi Kangle , He Fang , Sun Ao , Li Jianbo , Luo Yang , Wang Jiakun
Published: October 2023

Cadmium (Cd) is an environmental pollutant, widely existing in soil, and can be absorbed and accumulated by plants. Hunan Province exhibits the worst cadmium contamination of farmland in China. Ruminants possess an abundant microbial population in the rumen, which enables them to tolerate various poisonous plants. To investigate whether the rumen microbiota could respond to Cd and mitigate the toxicity of Cd-accumulated maize to ruminants, 6-month-old cattle were fed with 85.82% (fresh basis) normal whole-plant maize silage diet (CON, n = 10) or Cd-accumulated whole-plant maize silage diet (CAM, n = 10) for 107 days. When compared to the CON cattle, CAM cattle showed significantly higher gain-to-feed ratio and an increased total bacterial population in the rumen, but a decreased total bacterial population in the colon. CAM cattle had higher relative abundance of Prevotella and Lachnospiraceae ND3007 group in the rumen, and Lachnospiraceae NK4A136 group and Clostridia vadinBB60 group in the colon. Notably, microbial correlations were enhanced in all segments of CAM cattle, especially Peptostreptococcaceae in the jejunum. Transcriptome analysis revealed down-regulation of several immune-related genes in the rumen of CAM cattle, and differentially expressed genes in the rumen were mostly involved in immune regulation. These findings indicated that feeding Cd-accumulated maize diet with a Cd concentration of 6.74 mg/kg dry matter (DM) could stimulate SCFA-related bacteria in the rumen, induce hormesis to promote weight gain, and improve energy utilization of cattle.
Characterization of Bioactive Compounds and Antioxidant Activity of Plants—Editorial Comments and Summary
Authors: Kashchenko Nina I.
Published: October 2023

The biological potential of plant objects depends on the active compounds they contain [...]
Special Issue on Industrial Applications of Computational Fluid Dynamics
Authors: Lisowski Edward , Filo Grzegorz
Published: October 2023

The CFD (Computational Fluid Dynamics) method can be used in various areas that concern almost every field of technology, including water bodies, air spaces, as well as technical devices and machines [...]
Gait Recognition Based on Gait Optical Flow Network with Inherent Feature Pyramid
Authors: Ye Hongyi , Sun Tanfeng , Xu Ke
Published: October 2023

Gait is a kind of biological behavioral characteristic which can be recognized from a distance and has gained an increased interest nowadays. Many existing silhouette-based methods ignore the instantaneous motion of gait, which is an important factor in distinguishing people with similar shapes. To further emphasize the instantaneous motion factor in human gait, the Gait Optical Flow Image (GOFI) is proposed to add the instantaneous motion direction and intensity to original gait silhouettes. The GOFI also helps to leverage both the temporal and spatial condition noises. Then, the gait features are extracted by the Gait Optical Flow Network (GOFN), which contains a Set Transition (ST) architecture to aggregate the image-level features to the set-level features and an Inherent Feature Pyramid (IFP) to exploit the multi-scaled partial features. The combined loss function is used to evaluate the similarity between different gaits. Experiments are conducted on two widely used gait datasets, the CASIA-B and the CASIA-C. The experiments show that the GOFN performs better on both datasets, which shows the effectiveness of the GOFN.
Viscoelastic Strains of Palaeozoic Shales under the Burger’s Model Description
Authors: Wilczynski Przemyslaw Michal , Cieslik Jerzy , Domonik Andrzej , Lukaszewski Pawel
Published: October 2023

This article presents the results of creep studies of Palaeozoic shales from the Baltic Basin in which the exploitation of shale gas in Poland was planned. Knowledge of instantaneous and long-term properties investigated in triaxial stress conditions is important from the point of view of exploitation techniques related to hydraulic fracturing. Rheological phenomena also play an important role in the analysis of the initial stress in shales, the knowledge of which is indispensable in the hydraulic fracturing process. The tests were carried out on samples representing four siltstone–claystone lithostratigraphic units occurring in the Baltic Basin. The studies and analyses were aimed at determining the character of creep in shales, selection of the appropriate rheological model for the analyzed rocks, and determination of the threshold of the linear creep under triaxial compression conditions. An original approach together with analysis results are presented here, which enable the separation and monitoring of shear and volume creep effects, and on this basis, the determination of the significance of the contribution of volume creep in the entire creep process. A relatively simple methodology for determination of the parameters of the Burgers model using this division is presented. The original value of the article is also due to the test results themselves and the parameter values of the analyzed model for triaxial creep of shales, which are not numerous in the literature. The investigations were performed at various loading levels in relation to the triaxial strength of the shales. Depending on the load, at its low values up to 0.7 (σ1 − σ3)max, creep had a determined character and did not show features of progressive creep. The linear creep threshold was also analyzed in this range. The loading level of 0.7 (σ1 − σ3)max was the limit of linear creep. Exceeding this load resulted in the loss of the linear character of creep, which in consequence lead to the subsequent third creep phase ending with rock damage. Parameters of the Burger’s model for gas shales from the Baltic Basin (northern Poland) were identified. There are significant differences in the behavior of shales depending on the lithostratigraphic unit from which the samples were collected. The mineral composition of the shales also influenced their behavior.
Generalized, Complete and Accurate Modeling of Non-Ideal Push–Pull Converters for Power System Analysis and Control
Authors: Vivas Francisco José , Segura Francisca , Andújar José Manuel
Published: October 2023

Power converters are a basic element for the control and design of any power electronic system. Among the many available topologies, the push–pull converter is widely used due to its versatility, safety and efficiency. For its correct analysis, sizing, simulation and control, models that meet the characteristics of generality, accuracy and simplicity are required, especially if its control is to be optimized by means of some analytical technique. This requires models that consider the practical non-idealities intrinsic to the converter, as well as being intuitive and easy to handle analytically in a control loop. In general, the models reviewed in the scientific literature adopt simplifications in their definition that are detrimental to their accuracy. In response to the posed problem, this work presents a generalized, complete, accurate and versatile model of real (non-ideal) push–pull converters, ideal for the analysis, simulation, and control of power systems. Following the premise of general and complete converters, the proposed model includes all the practical non-idealities of the converter elements, and it is accurate because it faithfully reflects its dynamics. Furthermore, the model is versatile, as its state space formulation allows for its easy adaptability to the converter operating conditions (voltage, current and temperature) for each sampling time. Also, the model is excellent for use in model-based control techniques, as well as for making very accurate simulators. The behavior of the developed model has been contrasted with a real push–pull converter, as well as with reference models present in the scientific literature for both dynamic and steady-state response tests. The results show excellent performance in all the studied cases, with behavior faithful to the real converter and with relative errors that are much lower than those obtained for the reference models. It follows that the model behaves like a digital twin of a real push–pull converter.
Motion, Static Force, and Efficiency Analysis of Planetary Gear Transmission Based on Graph Theory
Authors: Xue Huiling , Li Lijian
Published: October 2023

This paper employs graph theory to analyze kinematic relationships, static force, and power flow for planetary gear systems. We start from the graphs of these trains to determine all the structurally distinct kinematic inversions. We then obtain all the constructive solutions resulting from every possible combination of gear configuration. Based on the kinematic and static force analysis model, related matrices are acquired. Hence, a kinematic and static force analysis of the planetary gear mechanism is achieved. The link power can be determined by the link speed and torque. Power flow diagrams of each gear are acquired. The efficiency is calculated by the transmission ratio method. This analysis is useful in the design of power transmission applications. A planetary gear system of a 6HP26 automatic transmission is further illustrated for the motion, static force, and efficiency calculations by using graph theory technique and matrix equations. This paper provides a guide for engineers in gear transmission fields to easily finish mechanical transmission design.
Biogeographic Analysis Suggests Two Types of Planktonic Prokaryote Communities in the Barents Sea
Authors: Namsaraev Zorigto , Kozlova Aleksandra , Tuzov Fedor , Krylova Anastasia , Izotova Anna , Makarov Ivan , Bezgreshnov Andrei , Melnikova Anna , Trofimova Anna , Kuzmin Denis , Patrushev Maksim , Toshchakov Stepan
Published: October 2023

The Barents Sea is one of the most rapidly changing Arctic regions, with an unprecedented sea ice decline and increase in water temperature and salinity. We have studied the diversity of prokaryotic communities using 16S metabarcoding in the western and northeastern parts of the Barents Sea along the Kola Section and the section from Novaya Zemlya to Franz Joseph Land. The hypothesis-independent clustering method revealed the existence of two distinct types of communities. The most common prokaryotic taxa were shared between two types of communities, but their relative abundance was different. It was found that the geographic location of the sampling sites explained more than 30% of the difference between communities, while no statistically significant correlation between environmental parameters and community composition was found. The representatives of the Psychrobacter, Sulfitobacter and Polaribacter genera were dominant in samples from both types of communities. The first type of community was also dominated by members of Halomonas, Pseudoalteromonas, Planococcaceae and an unclassified representative of the Alteromonadaceae family. The second type of community also had a significant proportion of Nitrincolaceae, SAR92, SAR11 Clade I, NS9, Cryomorphaceae and SUP05 representatives. The origin of these communities can be explained by the influence of environmental factors or by the different origins of water masses. This research highlights the importance of studying biogeographic patterns in the Barents Sea in comparison with those in the North Atlantic and Arctic Ocean prokaryote communities.
Mitochondrial Dysfunction-Associated Mechanisms in the Development of Chronic Liver Diseases
Authors: Arumugam Madan Kumar , Gopal Thiyagarajan , Kalari Kandy Rakhee Rathnam , Boopathy Lokesh Kumar , Perumal Sathish Kumar , Ganesan Murali , Rasineni Karuna , Donohue Terrence M. , Osna Natalia A. , Kharbanda Kusum K.
Published: October 2023

The liver is a major metabolic organ that performs many essential biological functions such as detoxification and the synthesis of proteins and biochemicals necessary for digestion and growth. Any disruption in normal liver function can lead to the development of more severe liver disorders. Overall, about 3 million Americans have some type of liver disease and 5.5 million people have progressive liver disease or cirrhosis, in which scar tissue replaces the healthy liver tissue. An estimated 20% to 30% of adults have excess fat in their livers, a condition called steatosis. The most common etiologies for steatosis development are (1) high caloric intake that causes non-alcoholic fatty liver disease (NAFLD) and (2) excessive alcohol consumption, which results in alcohol-associated liver disease (ALD). NAFLD is now termed “metabolic-dysfunction-associated steatotic liver disease” (MASLD), which reflects its association with the metabolic syndrome and conditions including diabetes, high blood pressure, high cholesterol and obesity. ALD represents a spectrum of liver injury that ranges from hepatic steatosis to more advanced liver pathologies, including alcoholic hepatitis (AH), alcohol-associated cirrhosis (AC) and acute AH, presenting as acute-on-chronic liver failure. The predominant liver cells, hepatocytes, comprise more than 70% of the total liver mass in human adults and are the basic metabolic cells. Mitochondria are intracellular organelles that are the principal sources of energy in hepatocytes and play a major role in oxidative metabolism and sustaining liver cell energy needs. In addition to regulating cellular energy homeostasis, mitochondria perform other key physiologic and metabolic activities, including ion homeostasis, reactive oxygen species (ROS) generation, redox signaling and participation in cell injury/death. Here, we discuss the main mechanism of mitochondrial dysfunction in chronic liver disease and some treatment strategies available for targeting mitochondria.
LAM2: An Unusual Laminaran Structure for a Novel Plant Elicitor Candidate
Authors: Mirande-Ney Cathleen , Arnaudin Quentin , Durambur Gaëlle , Plasson Carole , Bernard Sophie , Chamot Christophe , Grivotte Julie , Mati-Baouche Narimane , Driouich Azeddine , Brebion Jeremy , Hennequart Franck , Lerouge Patrice , Boulogne Isabelle
Published: October 2023

Laminarans are of interest because they have been shown to induce various immune responses in animals and plants. These β-D-glucans differ from each other by their branching rate, which is possibly responsible for their biological activities. In the present study, we characterized a laminaran fraction extracted from Laminaria hyperborea and named LAM2 using sugar composition and structural analyses (NMR). Then, we evaluated its activity as a potential plant elicitor in vitro on tomato seedlings using gene expression analysis and cell wall immunofluorescence labeling. Our study showed that LAM2 isolated from L. hyperborea is a succinylated laminaran which significantly enhanced the plant defense of tomato seedlings and induced cell wall modifications, suggesting a higher elicitor activity than the laminaran standard extracted from Laminaria digitata.
Outcomes and Adverse Effects of Voretigene Neparvovec Treatment for Biallelic RPE65-Mediated Inherited Retinal Dystrophies in a Cohort of Patients from a Single Center
Authors: Kiraly Peter , Cottriall Charles L. , Taylor Laura J. , Jolly Jasleen K. , Cehajic-Kapetanovic Jasmina , Yusuf Imran H. , Martinez-Fernandez de la Camara Cristina , Shanks Morag , Downes Susan M. , MacLaren Robert E. , Fischer M. Dominik
Published: October 2023

Our study evaluated the morphological and functional outcomes, and the side effects, of voretigene neparvovec (VN) gene therapy for RPE65-mediated inherited retinal dystrophies (IRDs) in 12 eyes (six patients) at the Oxford Eye Hospital with a mean follow-up duration of 8.2 (range 1–12) months. All patients reported a subjective vision improvement 1 month after gene therapy. Best-corrected visual acuity (BCVA) remained stable (baseline: 1.28 (±0.71) vs. last follow-up: 1.46 (±0.60); p = 0.25). Average white Full-Field Stimulus Testing (FST) showed a trend towards improvement (baseline: −4.41 (±10.62) dB vs. last follow-up: −11.98 (±13.83) dB; p = 0.18). No changes in central retinal thickness or macular volume were observed. The side effects included mild intraocular inflammation (two eyes) and cataracts (four eyes). Retinal atrophy occurred in 10 eyes (eight mild, two severe) but did not impact FST measurements during the follow-up period. Increased intraocular pressure (IOP) was noted in three patients (six eyes); four eyes (two patients) required glaucoma surgery. The overall safety and effectiveness of VN treatment in our cohort align with previous VN clinical trials, except for the higher occurrence of retinal atrophy and increased IOP in our cohort. This suggests that raised IOP and retinal atrophy may be more common than previously reported.
Legend or Truth: Mature CD4+CD8+ Double-Positive T Cells in the Periphery in Health and Disease
Authors: Hagen Magdalena , Pangrazzi Luca , Rocamora-Reverte Lourdes , Weinberger Birgit
Published: October 2023

The expression of CD4 and CD8 co-receptors defines two distinct T cell populations with specialized functions. While CD4+ T cells support and modulate immune responses through different T-helper (Th) and regulatory subtypes, CD8+ T cells eliminate cells that might threaten the organism, for example, virus-infected or tumor cells. However, a paradoxical population of CD4+CD8+ double-positive (DP) T cells challenging this paradigm has been found in the peripheral blood. This subset has been observed in healthy as well as pathological conditions, suggesting unique and well-defined functions. Furthermore, DP T cells express activation markers and exhibit memory-like features, displaying an effector memory (EM) and central memory (CM) phenotype. A subset expressing high CD4 (CD4bright+) and intermediate CD8 (CD8dim+) levels and a population of CD8bright+CD4dim+ T cells have been identified within DP T cells, suggesting that this small subpopulation may be heterogeneous. This review summarizes the current literature on DP T cells in humans in health and diseases. In addition, we point out that strategies to better characterize this minor T cell subset’s role in regulating immune responses are necessary.
A Floating Capsule Electrochemical System for In Situ and Multichannel Ion-Selective Sensing
Authors: Yang Jie , Ding Ao , Zhou Jia-Le , Yan Bing-Yong , Gu Zhen , Wang Hui-Feng
Published: October 2023

Free-floating electrochemical sensors are promising for in situ bioprocess monitoring with the advantages of movability, a lowered risk of contamination, and a simplified structure of the bioreactor. Although floating sensors were developed for the measurement of physical and chemical indicators such as temperature, velocity of flow, pH, and dissolved oxygen, it is the lack of available electrochemical sensors for the determination of the inorganic ions in bioreactors that has a significant influence on cell culture. In this study, a capsule-shaped electrochemical system (iCapsuleEC) is developed to monitor ions including K+, NH4+, Na+, Ca2+, and Mg2+ based on solid-contact ion-selective electrodes (SC-ISEs). It consists of a disposable electrochemical sensor and signal-processing device with features including multichannel measurement, self-calibration, and wireless data transmission. The capacities of the iCapsuleEC were demonstrated not only for in situ measurement of ion concentrations but also for the optimization of the sensing electrodes. We also explored the possibility of the system for use in detection in simulated cell culture media.
Research on a New Intelligent and Rapid Screening Method for Depression Risk in Young People Based on Eye Tracking Technology
Authors: Tao Zhanbo , Sun Ningxia , Yuan Zhen , Chen Zeyuan , Liu Jiakang , Wang Chen , Li Shuwu , Ma Xiaowen , Ji Bin , Li Kai
Published: October 2023

Depression is a prevalent mental disorder, with young people being particularly vulnerable to it. Therefore, we propose a new intelligent and rapid screening method for depression risk in young people based on eye tracking technology. We hypothesized that the “emotional perception of eye movement” could characterize defects in emotional perception, recognition, processing, and regulation in young people at high risk for depression. Based on this hypothesis, we designed the “eye movement emotional perception evaluation paradigm” and extracted digital biomarkers that could objectively and accurately evaluate “facial feature perception” and “facial emotional perception” characteristics of young people at high risk of depression. Using stepwise regression analysis, we identified seven digital biomarkers that could characterize emotional perception, recognition, processing, and regulation deficiencies in young people at high risk for depression. The combined effectiveness of an early warning can reach 0.974. Our proposed technique for rapid screening has significant advantages, including high speed, high early warning efficiency, low cost, and high intelligence. This new method provides a new approach to help effectively screen high-risk individuals for depression.
Find Joy in Sorrows: The Role of Hope in Buffering the Psychological Impact of COVID-19 on Chinese University Students in Hong Kong
Authors: Chan Stephen Cheong Yu , Huang Qi Lu , Low Andrew Yiu Tsang
Published: October 2023

The global coronavirus disease 2019 (COVID-19) crisis has exerted significant psychological impacts on university students who have faced drastic changes in the learning mode and suspension of classes. Despite these challenges, many students maintained subjective well-being. In this study, we examined the role of “hope” as a potential protector to maintain their subjective well-being when facing adversity during this global crisis. Specifically, we explored the mediating role of two hope components (agency thinking and pathways thinking) on the association of positive emotions and life satisfaction among Chinese university students. We conducted an online survey at a local university and recruited a total of 315 undergraduates from the humanities, creative arts, and social sciences programs through convenience sampling. Participants confirmed their informed consent and completed a set of self-administered questionnaires measuring positive emotions, hope, life satisfaction, and demographic variables. The results of mediation testing indicated that, during a global crisis such as COVID-19, positive emotions indirectly influenced life satisfaction through agency thinking rather than pathways thinking. The findings highlight the importance of agency thinking among Chinese university students in adverse situations and provide valuable insights for psychological interventions during a crisis. The article concludes by discussing possible explanations and implications of the findings in a post-pandemic world.
Verification of a Modeling Toolkit for the Design of Building Electrical Distribution Systems
Authors: Waghale Anay , Pratoomratana Shat , Woodstock Tianna-Kaye , Devaprasad Karthikeya , Poplawski Michael
Published: October 2023

DC electrical distribution systems offer many potential advantages over their AC counterparts. They can facilitate easier integration with distributed energy resources, improve system energy efficiency by eliminating AC/DC converters at end-use devices (e.g., laptop chargers), and reduce installation material, time, and cost. However, DC electrical distribution systems present additional design considerations, largely resulting from potentially greater magnitude and variation in cable losses. Modeling and simulation are rarely used to design such systems. However, the greater dependency of DC system energy efficiency on design choices such as distribution voltages, architecture, and integration of PV and BESS suggests that modeling and simulation may be required. Such system performance analysis is currently not a standard practice, in part due to limited availability and validation of capable software tools. This paper characterizes the accuracy of a Modelica-based Building Electrical Efficiency Analysis Model (BEEAM) toolkit, as a precursor for validating its use to perform system performance analysis and inform design decisions. The study builds upon previous verification research by characterizing complete systems comprised of commercially available equipment, and providing a more detailed analysis of simulation results. Five lighting systems with varying electrical distribution architectures were designed using market-available equipment, installed in a laboratory environment, modeled using BEEAM, and simulated using three Modelica integrated development environments (IDEs). Simulated and measured results were compared to characterize toolkit accuracy. Initial results revealed that simulated performance was mostly within ±5% of measured system-level and device-level performance. While simulation results were not found to be dependent on the IDE, some Modelica compiler interoperability issues were identified. Although the BEEAM toolkit showed promise for the targeted use case, further work is needed to determine whether the demonstrated 5% accuracy is sufficient for making real-world design decisions, and for BEEAM to advance from an interesting research tool to one that can impact real-world building projects.
SMARTS-Based Decision Support Model for CMMS Selection in Integrated Building Maintenance Management
Authors: Rodrigues Rui Calejo , Sousa Hipólito , Gondim Ivo Almino
Published: October 2023

An Integrated Maintenance System (IMS) represents a coordinated methodology including different maintenance policies, such as preventive and corrective. These systems rely on Computerized Maintenance Management Systems (CMMSs), specialized software available from multiple suppliers. Given the diverse features of commercial CMMS software, this work aims to develop a decision support model for CMMS evaluation emphasizing an integrated perspective within IMS. A Simple Multi-Attribute Rating Technique using Swings (SMARTS) method was used to build the decision model. Five existing market software were evaluated, and a minimum profile was defined for IMS requirements. Three of the assessed software types met these minimum IMS requirements, while the absence of certain features limited scores for others. The results obtained from the decision support model provide a simple and synthetic way to support decision-makers and promote a systemic view of the software features. The evaluation model has the advantage of adopting criteria that integrate software evaluation; its framing in a building maintenance management model; and new technological trends, such as Building information modeling (BIM), Virtual Reality (VR), Augmented Reality (AR), and Internet of Things (IoT). Considering these outcomes, future developments and alternatives can capitalize on these trends.
Impact of the COVID-19 Pandemic on the Diagnosis of Colorectal Cancer within a Population-Based Organized Screening Program
Authors: Cubiella Joaquín , Calderón-Cruz Beatriz , Almazán Raquel , Gómez-Amorín Ángel
Published: October 2023

Background: The interruption of the activity of population-based organized colorectal cancer (CRC) screening programs due to the COVID pandemic may have affected their results in terms of the detection of preneoplastic lesions and CRC. We evaluated the impact of the COVID pandemic on the delays, participation, adherence to colonoscopies, lesions detected, and CRC stage at diagnosis in a CRC screening program. Methods: We analyzed all the invitations between 1 January 2019 and 31 December 2021. We defined the pandemic period as the period after 12 March 2020. We calculated the delay intervals (successive and all rounds), the rates of participation, adherence to colonoscopy after a positive fecal immunochemical test (FIT), and the diagnostic yield of colonoscopy, specifically of CRC and colorectal neoplasia (CRC and/or adenoma), as well as the CRC stage at diagnosis. Results: In the period analyzed, 976,187 invitations were sent (61.0% in the pandemic period), 439,687 FIT were returned (62.4% in the pandemic period) and 23,092 colonoscopies were performed (59.1% in the pandemic period). The colonoscopies were normal in 7378 subjects (32.4%) and CRC was detected in 916 subjects (4.0%). In successive rounds, the delay increased significantly by seven months during the pandemic period (p < 0.001). In all the invitations, the delay from the invitation to the colonoscopy increased significantly by 8 days (p < 0.001). Once adjusted for the confounding variables, the participation in the screening program increased significantly (OR = 1.1; 95% CI = 1.09–1.11), with no changes in the adherence to colonoscopy (OR = 0.9; 95% CI = 0.8–1.0). We found no differences in the diagnostic yield of colonoscopy in terms of CRC (OR = 0.90; 95% CI = 0.78–1.02) or colorectal neoplasia (OR = 0.98; 95% CI = 0.92–1.03) detection. Finally, we found no differences in the CRC stage at diagnosis (p = 0.2). Conclusions: Although the interruption of the CRC screening program due to the COVID pandemic increased the delays, it did not reduce participation, adherence to colonoscopy, or the diagnostic yield of colonoscopy.
The Combined Inhibition of Autophagy and Diacylglycerol Acyltransferase-Mediated Lipid Droplet Biogenesis Induces Cancer Cell Death during Acute Amino Acid Starvation
Authors: Jusović Maida , Starič Pia , Jarc Jovičić Eva , Petan Toni
Published: October 2023

Lipid droplets (LDs) are dynamic organelles involved in the management of fatty acid trafficking and metabolism. Recent studies suggest that autophagy and LDs serve complementary roles in the protection against nutrient stress, but the autophagy–LD interplay in cancer cells is not well understood. Here, we examined the relationship between autophagy and LDs in starving HeLa cervical cancer- and MDA-MB-231 breast cancer cells. We found that acute amino acid depletion induces autophagy and promotes diacylglycerol acyltransferase 1 (DGAT1)-mediated LD accumulation in HeLa cells. Inhibition of autophagy via late-stage autophagy inhibitors, or by knocking down autophagy-related 5 (ATG5), reduced LD accumulation in amino acid-starved cancer cells, suggesting that autophagy contributes to LD biogenesis. On the contrary, knockdown of adipose triglyceride lipase (ATGL) increased LD accumulation, suggesting that LD breakdown is mediated by lipolysis under these conditions. Concurrent inhibition of autophagy by silencing ATG5 and of LD biogenesis using DGAT inhibitors was effective in killing starving HeLa cells, whereas cell survival was not compromised by suppression of ATGL-mediated lipolysis. Autophagy-dependent LD biogenesis was also observed in the aggressive triple-negative MDA-MB-231 breast cancer cells deprived of amino acids, but these cells were not sensitized to starvation by the combined inhibition of LD biogenesis and autophagy. These findings reveal that while targeting autophagy-driven and DGAT-mediated LD biogenesis reduces the resilience of HeLa cervical cancer cells to amino acid deprivation, this strategy may not be successful in other cancer cell types.
An Overview of the Role of Furin in Type 2 Diabetes
Authors: Marafie Sulaiman K. , Al-Mulla Fahd
Published: October 2023

Post-translational modifications (PTMs) play important roles in regulating several human diseases, like cancer, neurodegenerative disorders, and metabolic disorders. Investigating PTMs’ contribution to protein functions is critical for modern biology and medicine. Proprotein convertases (PCs) are irreversible post-translational modifiers that have been extensively studied and are considered as key targets for novel therapeutics. They cleave proteins at specific sites causing conformational changes affecting their functions. Furin is considered as a PC model in regulating growth factors and is involved in regulating many pro-proteins. The mammalian target of the rapamycin (mTOR) signaling pathway is another key player in regulating cellular processes and its dysregulation is linked to several diseases including type 2 diabetes (T2D). The role of furin in the context of diabetes has been rarely explored and is currently lacking. Moreover, furin variants have altered activity that could have implications on overall health. In this review, we aim to highlight the role of furin in T2D in relation to mTOR signaling. We will also address furin genetic variants and their potential effect on T2D and β-cell functions. Understanding the role of furin in prediabetes and dissecting it from other confounding factors like obesity is crucial for future therapeutic interventions in metabolic disorders.