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Objective: To apply the multistep model of pathogenesis in amyotrophic lateral sclerosis (ALS) to data from a multiethnic Malaysian registry. Methods: Clinical data, including age at symptom onset, was collected from 289 patients who presented to our multidisciplinary clinic from 2016 until 2024. A least squares linear regression model was constructed from the logarithm of approximated incidence and the logarithm of age. Population incidence was approximated by adjusting the absolute numbers of patients in 5 year groups by the size of the general population in the respective age group. Results: A linear relationship between log of incidence versus log of age was observed, with a slope of 4.57 (95% CI, 3.3–5.8) and an r2 value of 0.93, suggesting a 6-step process. Conclusion: Progression toward symptom onset in Malaysian ALS patients appears consistent with a multistep model of disease as observed in other cohorts. [ABSTRACT FROM AUTHOR]

Today, accumulating evidence highlights the impact of oxidative stress (OS) on semen quality. It is considered to be a key factor contributing to the decline in male fertility. OS is detected in 30–80% of men with infertility, highlighting its strong association with impaired reproductive function and with clinical outcomes following the use of assisted reproductive technologies. Spermatozoa are particularly vulnerable to oxidative damage due to their high content of polyunsaturated fatty acids (PUFAs) and limited antioxidant defense abilities. OS arises from an imbalance between the production of reactive oxygen species and the capacity to neutralize or repair their adverse effects. Evidence indicates that OS leads to lipid peroxidation, protein oxidation, mitochondrial dysfunction, and genomic instability. Micronutrient–antioxidant therapies can play a key role in infertility improvement by neutralizing free radicals and preventing cellular damage. Many different micronutrients, including L-carnitine, L-glutathione, coenzyme Q10, selenium, and zinc, as well as vitamins complexes, are proposed to improve sperm parameters and male fertility potential. This study aims to review the impact of antioxidant supplementation on semen parameters, including sperm volume, motility, concentration, morphology, genome integrity (maturity and fragmentation), and in vitro fertilization (IVF) outcomes. Antioxidant intake and a balanced lifestyle reduce oxidative stress and mitochondrial dysfunction, enhancing the spermatogenesis and spermiogenesis processes, improving sperm quality, and protecting DNA integrity. [ABSTRACT FROM AUTHOR]

Intermediate CAG repeats from 29 to 33 in the ATXN2 gene contributes to the risk of amyotrophic lateral sclerosis (ALS) in European and Asian populations. In this study, 148 ALS patients of multiethnic descent: Chinese (56.1%), Malay (24.3%), Indian (12.8%), others (6.8%) and 100 neurologically normal controls were screened for the ATXN2 CAG repeat expansion. The most common repeat length in both the controls and patients was 22. No familial ALS patients were positive for the intermediate repeat sizes (29–33), while four sporadic patients (2.8%) were positive, with one harbouring a rare ATXN2 homozygous 32 repeat expansion, and a likely pathogenic variant in SPAST. All four patients had limb-onset ALS. Despite representing the smallest ethnic group in our patient cohort, three of the four patients with intermediate repeat sizes were of Indian ancestry. This study, which is the first in Malaysia and Southeast Asia, shows that ATXN2 intermediate risk expansions are relevant to ALS in these populations and will help to inform future genetic testing strategies in the clinic. [ABSTRACT FROM AUTHOR]

Background Determinants of maternal-fetal cytomegalovirus (CMV) transmission and factors influencing the severity of congenital CMV (cCMV) infection are not well understood. Methods We conducted a descriptive, multicenter study in pregnant women ≥18 years old with primary CMV infection and their newborns to explore maternal immune responses to CMV and determine potential immunologic/virologic correlates of cCMV following primary infection during pregnancy. We developed alternative approaches looking into univariate/multivariate factors associated with cCMV, including a participant clustering/stratification approach and an interpretable predictive model–based approach using trained decision trees for risk prediction (post hoc analyses). Results Pregnant women were grouped in 3 distinct clusters with similar baseline characteristics, particularly gestational age at diagnosis. We observed a trend for higher viral loads in urine and saliva samples from mothers of infants with cCMV versus without cCMV. When using a trained predictive-model approach that accounts for interaction effects between variables, anti-pentamer immunoglobulin G antibody concentration and viral load in saliva were identified as biomarkers jointly associated with the risk of maternal-fetal CMV transmission. Conclusions We identified biomarkers of CMV maternal-fetal transmission. After validation in larger studies, our findings will guide the management of primary infection during pregnancy and the development of vaccines against cCMV. Clinical Trials Registration NCT01251744. [ABSTRACT FROM AUTHOR]

Allergen-specific immunotherapy (AIT) induces immune tolerance, showing the highest success rate (>95%) for insect venom while a much lower chance for pollen allergy. However, the molecular switches leading to successful durable tolerance restoration remain elusive. The primary outcome of this observational study is the comprehensive immunological cellular characterization during the AIT initiation phase, whereas the secondary outcomes are the serological and Th2-cell-type-specific transcriptomic analyses. Here we apply a multilayer-omics approach to reveal dynamic peripheral immune landscapes during the AIT-initiation phase in venom allergy patients (VAP) versus pollen-allergic and healthy controls. Already at baseline, VAP exhibit altered abundances of several cell types, including classical monocytes (cMono), CD4+ hybrid type 1-type 17 cells (Th1-Th17 or Th1/17) and CD8+ counterparts (Tc1-Tc17 or Tc1/17). At 8-24 h following AIT launch in VAP, we identify a uniform AIT-elicited pulse of late-transitional/IL-10-producing B cells, IL-6 signaling within Th2 cells and non-inflammatory serum-IL-6 levels. Sequential induction of activation and survival protein markers also immediately occur. A disequilibrium between serum IL-6 and cMono in VAP baseline is restored at day seven following AIT launch. Our longitudinal analysis discovers molecular switches during initiation-phase insect-venom AIT that secure long-term outcomes. Trial number: NCT02931955. Allergen specific immunotherapy (AIT) is both, safe and effective in reducing systemic symptoms of venom allergy in individuals. Here the authors examine the underlying immune cell changes after venom specific AIT in early time points after therapy initiation showing indicative changes in specific immune cell populations. [ABSTRACT FROM AUTHOR]

This paper examines the dynamics of employment in the financial sector in the European Union and the United Kingdom since the early 1990s. Using the EU Labor Force Survey at the national (NUTS0), regional (NUTS1), and subregional (NUTS2) levels, we document several stylized facts about the evolution of financial centers. Despite the global financial and sovereign debt crises, the total number of workers in the financial sector has increased from less than 5 million in 1993 to more than 6.5 million in 2020. At the same time, however, the share of employees in the financial sector has decreased from 3.5% to 2.8%. We find large regional differences in the degree of financial specialization, with Luxembourg at the top end (11% of their total workforce), followed by Ireland and the United Kingdom (4%), then France, Germany or Italy (around 3%). We also explore the dynamics of concentration. The main conclusion is that the degree of concentration depends on the scale of measurement employed. We show a contrasting concentration trend: centripetal at the national level and centrifugal at lower levels (regional or sub-regional). Furthermore, newer financial centers showed faster growth. JEL codes : E44, G2, R1 [ABSTRACT FROM AUTHOR]

Skin disorders among individuals receiving palliative care may be associated with the primary condition or underlying comorbidities and patients may experience pruritus, discomfort or pain. Common conditions include xerosis, pressure ulcers, intertrigo, superficial fungal infections, telogen effluvium, pruritus, herpes zoster, eczematous disorders and edema. During end-of-life care, there is reduced skin perfusion and metabolism hence leading to susceptibility to infection, pressure and injury. Other factors affecting the skin include limited mobility, nutritional deficits and immunosuppression. Although treatment strategies for each skin condition are usually aligned with standard protocols, considerations among these patients include limited life-expectancies, potential treatment burden, drug-drug interactions as well as comfort-directed rather than cure-directed therapy. For patients with xerosis cutis, the regular use of moisturisers is recommended. The management and prevention of pressure ulcers include the strategies of skin assessment and care, pressure redistribution, nutrition and hydration and ulcer care. Superficial fungal infections require treatment with appropriate topical and/or systemic antifungals while antivirals and adjunctive treatment can be prescribed for herpes zoster. Treatment and symptom control of skin disorders in this population can improve quality of life and patients' comfort level. [ABSTRACT FROM AUTHOR]

Covering: up to October 2023 Many bioactive natural products are synthesized by microorganisms that are either difficult or impossible to cultivate under laboratory conditions, or that produce only small amounts of the desired compound. By transferring biosynthetic gene clusters (BGCs) into alternative host organisms that are more easily cultured and engineered, larger quantities can be obtained and new analogues with potentially improved biological activity or other desirable properties can be generated. Moreover, expression of cryptic BGCs in a suitable host can facilitate the identification and characterization of novel natural products. Heterologous expression therefore represents a valuable tool for natural product discovery and engineering as it allows the study and manipulation of their biosynthetic pathways in a controlled setting, enabling innovative applications. Bacillus is a genus of Gram-positive bacteria that is widely used in industrial biotechnology as a host for the production of proteins from diverse origins, including enzymes and vaccines. However, despite numerous successful examples, Bacillus species remain underexploited as heterologous hosts for the expression of natural product BGCs. Here, we review important advantages that Bacillus species offer as expression hosts, such as high secretion capacity, natural competence for DNA uptake, and the increasing availability of a wide range of genetic tools for gene expression and strain engineering. We evaluate different strain optimization strategies and other critical factors that have improved the success and efficiency of heterologous natural product biosynthesis in B. subtilis. Finally, future perspectives for using B. subtilis as a heterologous host are discussed, identifying research gaps and promising areas that require further exploration. [ABSTRACT FROM AUTHOR]

The long‐term sustainability of natural and bottom‐cultured mussel beds relies on the availability of spat (i.e. juvenile mussels). Traditional spat collection methods, which disrupt the donor population and its habitat, have prompted the adoption of suspended mussel spat collectors (SMCs) as an ecologically sustainable alternative. However, practical experience has demonstrated that SMC efficiency is subject to significant spatiotemporal variability, with the underlying biotic and abiotic drivers remaining unresolved.Based on 11‐year SMC practices in the Dutch Wadden Sea, we first validated, through field experiments, the inference that larval abundance and settlement rate in seawater are the primary determinants of SMC efficiency. Secondly, we screened the key factors driving variation in SMC efficiency using an integrated dataset that includes both management options (i.e. user‐defined factors, like SMC types) and environmental conditions (i.e. site‐specific factors, such as hydrodynamics). Lastly, we developed a predictive model to explore the sensitivity of SMC efficiency to these key factors.The efficiency of SMCs was not affected by larval abundance and settlement rate, but rather regulated by management options and environmental conditions, with the key factors identified as SMC type, substrate size, mean wave height and starfish abundance.Rope‐based SMCs outperform net‐based SMCs in terms of harvest efficiency. Both types of SMCs exhibit consistent sensitivity to environmental conditions, with harvest efficiency higher in areas with lower mean wave height and fewer starfish. Increasing substrate size (i.e. rope length and net area) in these areas has the potential to further improve SMC efficiency.Synthesis and applications: Our study highlights the importance of environmental conditions over life cycle‐related factors in regulating SMC efficiency. This offers optimistic prospects for investment in larger‐scale deployment of SMCs and maximizing efficiency through site suitability assessments beforehand. The predictive model we developed can provide information for this purpose. Furthermore, strategically adjusting management options would further optimize SMC efficiency, but it is necessary to balance the associated benefits and costs. Overall, our study underscores the predictability and controllability of SMC efficiency and informs management to maximize sustainable spat supply in both mussel culture and restoration. [ABSTRACT FROM AUTHOR]

The present study examines the poor fit between the idea of school meritocracy and the successful inclusion of students with special educational needs (SEN). Because students with SEN are assigned negative stereotypes related to suffering, failure, and difficulty regarding their school achievement, we argue that, if they succeed at levels comparable to those of regular students, they may experience backlash, a sanction for challenging the status quo. The results of two studies show that backlash can manifest itself in the form of lower assigned competence to students with special educational needs who succeed. More precisely, across a pilot and a main study, our findings indicate that while performing as well as students without special educational needs, the perceived competence of students with special educational needs was evaluated as lower by participants (pre- and in-service teachers), particularly when these students benefitted from an accommodation perceived as "unfair". Due to its potential role in justifying inequities within educational contexts, the backlash effect is discussed as an ideological barrier to the inclusion of students with special educational needs. [ABSTRACT FROM AUTHOR]

The discovery of upstream regulatory genes of a gene of interest still remains challenging. Here we applied a scalable computational method to unbiasedly predict candidate regulatory genes of critical transcription factors by searching the whole genome. We illustrated our approach with a case study on the master regulator FOXP3 of human primary regulatory T cells (Tregs). While target genes of FOXP3 have been identified, its upstream regulatory machinery still remains elusive. Our methodology selected five top-ranked candidates that were tested via proof-of-concept experiments. Following knockdown, three out of five candidates showed significant effects on the mRNA expression of FOXP3 across multiple donors. This provides insights into the regulatory mechanisms modulating FOXP3 transcriptional expression in Tregs. Overall, at the genome level this represents a high level of accuracy in predicting upstream regulatory genes of key genes of interest. [ABSTRACT FROM AUTHOR]

The different peaks of somatosensory-evoked potentials (SEP) originate from a variety of anatomical sites in the central nervous system. The origin of the median nerve subcortical N18 SEP has been studied under various conditions, but the exact site of its generation is still unclear. While it has been claimed to be located in the thalamic region, other studies indicated its possible origin below the pontomedullary junction. Here, we scrutinized and compared SEP recordings from median nerve stimulation through deep brain stimulation (DBS) electrodes implanted in various subcortical targets. We studied 24 patients with dystonia, Parkinson's disease, and chronic pain who underwent quadripolar electrode implantation for chronic DBS and recorded median nerve SEPs from globus pallidus internus (GPi), subthalamic nucleus (STN), thalamic ventral intermediate nucleus (Vim), and ventral posterolateral nucleus (VPL) and the centromedian–parafascicular complex (CM-Pf). The largest amplitude of the triphasic potential of the N18 complex was recorded in Vim. Bipolar recordings confirmed the origin to be close to Vim electrodes (and VPL/CM-Pf) and less close to STN electrodes. GPi recorded only far-field potentials in unipolar derivation. Recordings from DBS electrodes located in different subcortical areas allow determining the origin of certain subcortical SEP waves more precisely. The subcortical N18 of the median nerve SEP—to its largest extent—is generated ventral to the Vim in the region of the prelemniscal radiation/ zona incerta. [ABSTRACT FROM AUTHOR]

Transplantations of organisms in aquatic ecosystems play an important role in ecological restoration and commercial practices. However, success rates of these transplantations, especially when ecosystem engineers are involved, are often low. To enhance transplantation success, the promotion of self‐facilitation between transplants that mitigate environmental stressors is crucial. Besides, spatial patterns resulting from self‐facilitation can enhance ecosystem resilience. Using blue mussels as a model organism, we explored the possibility of increasing transplantation success in a subtidal ecosystem. We used biodegradable structures ("BioShell‐SMCs") to ameliorate self‐facilitating feedback mechanisms to overcome environmental stressors in the initial post‐transplantation phase, and to increase transplantation success by implementing large‐scale spatial configurations, mimicking natural mussel bed patterns. The structures are an innovation of traditional seed mussel collectors (SMCs) used in mussel cultivation. They consist of a biodegradable net based on a compound of aliphatic polyesters, filled with empty cockle shells around a coconut fiber rope. We tested whether different spatial configurations could increase transplantation success of mussel seed: low versus high density labyrinth pattern and banded pattern. The results of this experiment showed high losses (approximately 75%), with no significant variation between configurations. The lack of migration due to unexpected retention of the biodegradable net hindered the initiation of natural aggregations, resulting in increased competition among mussels. Besides, factors such as hydrodynamic dislodgement, burial and interannual variation likely contributed to the observed losses. While the BioShell‐SMC has not demonstrated large‐scale success, this research contributes to understanding the mechanisms that underlie successful transplantation strategies in aquatic ecosystems. [ABSTRACT FROM AUTHOR]

Objective: Carpal tunnel syndrome (CTS) is the most common nerve entrapment neuropathy in the USA. In this study, we define anatomical landmarks to assess symptomatic and asymptomatic cohorts with persistent CTS using MRI imaging. Materials and methods: Distal vs proximal incomplete release was determined using the distal most aspect of the hook of hamate and the distal wrist crease. An incomplete release showed the transverse carpal ligament (TCL) intact at either boundary. Twenty-one patients with persistent CTS were analyzed for incomplete release, median nerve enlargement and T2 signal hyperintensity, and flattening ratio using postoperative wrist MRI. These findings were compared to a ten-patient asymptomatic persistent CTS control group. Fisher's exact and a Student's two-tailed t-tests were used to determine statistical significance. Results: In the symptomatic persistent CTS group, 13 (61.9%) incomplete releases were identified, 5 (38.5%) incomplete distally, and 1 (7.7%) incomplete proximally. There was no statistical significance in the rate of incomplete releases when compared to the asymptomatic group (p = 1.00). T2 signal hyperintensity and enlargement at the site of release showed no statistical significance, (p = 0.319 and p = 0.999, respectively). The mean flattening ratio at the site of release in the symptomatic group (2.45 ± 0.7) was statistically significant compared to the asymptomatic group (1.48 ± 0.46), (p = 0.007). Conclusion: Utilizing the established landmarks, the full length of the TCL can be assessed via MRI. Additionally, evaluation of the median nerve flattening ratio at the level of the incomplete release may be utilized as an aid to the clinical management of persistent CTS. [ABSTRACT FROM AUTHOR]

Previous studies have shown that undoped and doped SnO2 thin films have better optical and electrical properties. This study aims to investigate the thermoelectric properties of two distinct semiconducting oxide thin films, namely SnO2 and F-doped SnO2 (FTO), by the nebulizer spray pyrolysis technique. An X-ray diffraction study reveals that the synthesized films exhibit a tetragonal structure with the (200) preferred orientation. The film structural quality increases from SnO2 to FTO due to the substitution of F− ions into the host lattice. The film thickness increases from 530 nm for SnO2 to 650 nm for FTO films. Room-temperature electrical resistivity decreases from (8.96 ± 0.02) × 10−2 Ω·cm to (4.64 ± 0.01) × 10−3 Ω·cm for the SnO2 and FTO thin films, respectively. This is due to the increase in the carrier density of the films, (2.92 ± 0.02) × 1019 cm−3 (SnO2) and (1.63 ± 0.03) × 1020 cm−3 (FTO), caused by anionic substitution. It is confirmed that varying the temperature (K) enhances the electron transport properties. The obtained Seebeck coefficient (S) increases as the temperature is increased, up to 360 K. The synthesized films exhibit the S value of −234 ± 3 μV/K (SnO2) and −204 ± 3 μV/K (FTO) at 360 K. The estimated power factor (PF) drastically increases from ~70 (μW/m·K2) to ~900 (μW/m·K2) for the SnO2 and FTO film, respectively. [ABSTRACT FROM AUTHOR]

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Artificial structures are often used as a tool for habitat restoration and the recreation of degraded coastal ecosystems and their associated food webs. However, it is often unknown if and how these artificial structures may influence the habitat use of target species, thereby hampering restoration goals. In this study, we test how artificial barriers, deployed to enhance the creation of an intertidal mussel bed, influenced the mussel‐habitat use by two bird species under pressure, Eurasian oystercatchers and Eurasian curlews. Average bird presence was monitored using time‐lapse camera's from the start of the mussel bed restoration in August 2018 until April 2019. We found that in the first few months of the experiment, both oystercatchers and curlews avoided the restored mussel beds containing artificial structures in the form of metal barriers that act as traps for dislodged mussels. Thereafter, the presence of barriers had no negative influence on the average presence of oystercatchers or curlews. In fact, curlews were significantly attracted to the mussel beds with barriers in January and February. In addition, we found a negative effect of the presence of European herring gulls on the presence of oystercatchers and curlews. The higher herring gull densities in the first 2 months of the experiment might explain the lower‐than‐expected curlew and oystercatcher densities observed in August. To our knowledge, no other studies have investigated the effect of artificial restoration structures on the abundance or habitat use of specific shorebirds. [ABSTRACT FROM AUTHOR]

In this theoretical article we present our hypothesis on the incompatibility of the inclusive education policy toward students with special educational needs with the meritocratic principle of education. If considering and recognizing the needs of these students is necessary to achieve a successful inclusive environment, we propose that this goal cannot be achieved within current educational systems driven by a meritocratic ideology. We base our rationale on social psychology theories such as system justification and backlash to argue that such incompatibility is particularly visible during the evaluation process. Finally, if we provide some incentives toward greater inclusion while considering the diverse contradictions such inclusivity generates, we also invite researchers to further empirically examine these contradictions in order to guide policy makers within their choices. [ABSTRACT FROM AUTHOR]

Introduction: Recent research has emphasized that achievement motivation is context-sensitive and varies within individual students. Ubiquitous temporal landmarks such as exams or deadlines are evident contextual factors that could systematically explain variation in motivation. Indeed, research has consistently found that university students increase their study efforts as exams come closer in time, indicating increasing study motivation. However, changes in study motivation for a specific exam as it comes closer have rarely been investigated. Instead, research on developmental changes in expectancy and value beliefs has consistently founds that achievement motivation declines over a semester. Surprisingly, declining motivation thus apparently coincides with increasing study efforts for end-of-semester exams. Methods: The present research investigates this apparent contradiction by assessing how exam-specific motivation and study behavior change under equal methodological conditions as an exam draws closer. Using parallel growth curve models, we examine changes in expectancy-value beliefs, performance approach and avoidance motivation and study behavior as well as motivational want- and should-conflicts among 96 students over eight weekly measurement points. Results and discussion: Results show that students study more for their exam as it comes closer and increase their use of surface learning strategies more rapidly than their use of deep learning strategies. However, even exam-specific expectancy and attainment value beliefs decline while performance-avoidance motivation increases over time, indicating that students increasingly study out of fear to fail as exams come closer. Consistent with these findings, students' experience of should conflicts decreases while their want conflicts increase over time. We discuss several possible mechanisms underlying our findings in addition to potential theoretical consequences and suggest future research opportunities to better understand students' changes in situative motivation and study behavior in the context of temporal landmarks. [ABSTRACT FROM AUTHOR]

In recent years, there has been a resurgence of interest in graphene quantum dots (i.e., large polycyclic aromatic hydrocarbons) in particular due to their interesting properties as single‐quantum emitters. Herein, a thorough study of a graphene quantum dot made of 96 carbon atoms in a D2h symmetry is reported. In particular, experiments at the single‐molecule level reveal that this graphene quantum dot structure is a bright and photostable single‐photon emitter at room temperature. Finally, a statistical study of the emission wavelength as a function of the graphene quantum dot concentration highlights the high purity and degree of control on the samples. [ABSTRACT FROM AUTHOR]

Neuroinflammation in the brain contributes to the pathogenesis of Parkinson's disease (PD), but the potential dysregulation of peripheral immunity has not been systematically investigated for idiopathic PD (iPD). Here we showed an elevated peripheral cytotoxic immune milieu, with more terminally-differentiated effector memory (TEMRA) CD8 T, CD8+ NKT cells and circulating cytotoxic molecules in fresh blood of patients with early-to-mid iPD, especially females, after analyzing > 700 innate and adaptive immune features. This profile, also reflected by fewer CD8+FOXP3+ T cells, was confirmed in another subcohort. Co-expression between cytotoxic molecules was selectively enhanced in CD8 TEMRA and effector memory (TEM) cells. Single-cell RNA-sequencing analysis demonstrated the accelerated differentiation within CD8 compartments, enhanced cytotoxic pathways in CD8 TEMRA and TEM cells, while CD8 central memory (TCM) and naïve cells were already more-active and transcriptionally-reprogrammed. Our work provides a comprehensive map of dysregulated peripheral immunity in iPD, proposing candidates for early diagnosis and treatments. Men are at a greater risk to develop Parkinson's disease (PD). However, Hefeng and team revealed enhanced cytotoxicity and terminal differentiation in CD8 T cells of early-to-mid stage idiopathic PD, especially for females, using systems immunology. [ABSTRACT FROM AUTHOR]

Seasonal influenza vaccines must be updated annually and suboptimally protect against strains mismatched to the selected vaccine strains. We previously developed a subunit vaccine antigen consisting of a stabilized trimeric influenza A group 1 hemagglutinin (H1) stem protein that elicits broadly neutralizing antibodies. Here, we further optimized the stability and manufacturability of the H1 stem antigen (H1 stem v2, also known as INFLUENZA G1 mHA) and characterized its formulation and potency with different adjuvants in vitro and in animal models. The recombinant H1 stem antigen (50 µg) was administered to influenza-naïve non-human primates either with aluminum hydroxide [Al(OH)3] + NaCl, AS01B, or SLA-LSQ formulations at week 0, 8 and 34. These SLA-LSQ formulations comprised of varying ratios of the synthetic TLR4 agonist 'second generation synthetic lipid adjuvant' (SLA) with liposomal QS-21 (LSQ). A vaccine formulation with aluminum hydroxide or SLA-LSQ (starting at a 10:25 µg ratio) induced HA-specific antibodies and breadth of neutralization against a panel of influenza A group 1 pseudoviruses, comparable with vaccine formulated with AS01B, four weeks after the second immunization. A formulation with SLA-LSQ in a 5:2 μg ratio contained larger fused or aggregated liposomes and induced significantly lower humoral responses. Broadly HA stem-binding antibodies were detectable for the entire period after the second vaccine dose up to week 34, after which they were boosted by a third vaccine dose. These findings inform about potential adjuvant formulations in clinical trials with an H1 stem-based vaccine candidate. [ABSTRACT FROM AUTHOR]

In this study, we examine texturing features on soda-lime (SDL) silicate glass bottles achieved using a Carbon Dioxide (CO2) laser with continuous wave power (25 W at 10.6 µm). SDL glass samples were subjected to irradiation in both static and dynamic modes. In the static mode, exposure time (τON) varied from 10 µs to 2 ms, while the dynamic mode involved scan velocities (line) ranging from 20 mm/s to 3 m/s. Our evaluation focused on engraving rate, fracture morphologies, and damaged zone characteristics. Using optical microscopy and stylus profilometry, we identified three distinct process regimes: partial texturing, full texturing, and material removal. To gain insights into the underlying mechanisms of the process, we developed a 2D axisymmetric thermo-mechanical model using COMSOL Multiphysics®. This model allowed us to compute the transient laser-induced thermal stress and the relaxation occurring in the viscoelastic state of SDL. Remarkably, our simulation demonstrated a correlation between the tensile cracking threshold of SDL (0.1 GPa) and experimental data. By comapring the experimental and simulation results, we were able to estimate the damaged zone diameter with an accuracy of ±3% in the partial texturing regime and an overall accuracy of ±8% across all regimes in the static mode. [ABSTRACT FROM AUTHOR]

Aggregation into groups may affect performance of individuals through the balance and strength of facilitative versus competitive interactions. We studied in situ how seasonal variation in abiotic environment affects this balance for blue mussels, a semi-sessile species. We hypothesize that seasonal variation in stresses and resources affects the strength of the interaction. We expected that, in benign conditions (here: high food availability, medium temperatures, low hydrodynamic stress), performance is dominated by growth and is better at low densities, while at adverse conditions (here: low food availability, low or high temperatures, high hydrodynamic stress), performance is dominated by survival and higher at high densities. Mussels were kept in shallow subtidal exclosures at 10 different densities for a one-month period. This exact procedure was repeated seven times at the same location within a one-year period. We measured development in mussel patch shape, performance, and environmental parameters. Environmental conditions for mussels were most benign in summer and most adverse in winter. Patches developed into less complex shapes at lower densities, but also after stronger hydrodynamic disturbances. Towards summer, mussels became more active, aggregation behavior increased, and interactions became more pronounced. Towards winter, mussels became less active: aggregation behavior and growth rates declined and at the lowest temperatures survival started to decrease with mussel density. Survival and growth (by proxy of mussel condition) were both density-dependent; however, contrary to our expectations we found positive interactions between density and survival at the most benign conditions in summer and negative interactions at the most adverse conditions in winter. In between the two seasons, the strength of the interactions increased towards summer and decreased towards winter following a bell-shaped pattern. This pattern might be explained by the environmental mediated aggregation behavior of the mussels. The obvious seasonal pattern in balance and strength of density-dependent interactions demonstrates that strength and direction of intra-specific interactions are both strongly affected by environmental context. [ABSTRACT FROM AUTHOR]

Background: Autoimmune gastritis (AIG), characterized with the presence of anti-parietal-cell antibodies (APCA), is a risk factor for gastric cancer. However, AIG may go underdiagnosed, especially in the case of H. pylori infection and the presence of gastric precancerous lesions (GPL), due to the ambiguous pathology and delayed symptom onset. Aim: Investigate the prevalence and characteristics of AIG in GPL patients. Methods: Prevalence of AIG was determined with the presence of APCA in patients with GPL (n = 256) and the control group (n = 70). Pathological characteristics and levels of gastrin 17 (G17), pepsinogen (PG) I and II and anti-Helicobacter pylori IgG were assessed in GPL cases, and the severity of intestinal metaplasia and gastric atrophy was scored by expert pathologists. Results: APCA positivity was observed in 18% of cases vs. 7% of controls (p = 0.033). Only 3/256 patients were previously diagnosed with AIG. The presence of APCA was associated with corpus-limited and extended GPL. A receiver operating curve analysis demonstrated that the G17 and PGI/II ratio could identify APCA-positive patients within GPL cases (AUC: 0.884). Conclusions: The prevalence of AIG is higher in patients with GPL but goes undiagnosed. Using G17 and PG I/II as diagnostic markers can help to identify patients with AIG and improve surveillance programs for patients with GPL. [ABSTRACT FROM AUTHOR]

The seroprevalence to orthoebolaviruses was studied in 9594 bats (5972 frugivorous and 3622 insectivorous) from Cameroon, the Democratic Republic of Congo (DRC) and Guinea, with a Luminex-based serological assay including recombinant antigens of four orthoebolavirus species. Seroprevalence is expressed as a range according to different cut-off calculations. Between 6.1% and 18.9% bat samples reacted with at least one orthoebolavirus antigen; the highest reactivity was seen with Glycoprotein (GP) antigens. Seroprevalence varied per species and was higher in frugivorous than insectivorous bats; 9.1–27.5% versus 1.3–4.6%, respectively. Seroprevalence in male (13.5%) and female (14.4%) bats was only slightly different and was higher in adults (14.9%) versus juveniles (9.4%) (p < 0.001). Moreover, seroprevalence was highest in subadults (45.4%) when compared to mature adults (19.2%), (p < 0.001). Our data suggest orthoebolavirus circulation is highest in young bats. More long-term studies are needed to identify birthing pulses for the different bat species in diverse geographic regions and to increase the chances of detecting viral RNA in order to document the genetic diversity of filoviruses in bats and their pathogenic potential for humans. Frugivorous bats seem more likely to be reservoirs of orthoebolaviruses, but the role of insectivorous bats has also to be further examined. [ABSTRACT FROM AUTHOR]

Background: The respective benefits of high and low doses of dexamethasone (DXM) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) and acute respiratory failure (ARF) are controversial, with two large triple-blind RCTs reaching very important difference in the effect-size. In the COVIDICUS trial, no evidence of additional benefit of high-dose dexamethasone (DXM20) was found. We aimed to explore whether some specific patient phenotypes could benefit from DXM20 compared to the standard of care 6 mg dose of DXM (DXMSoC). Methods: We performed a post hoc exploratory Bayesian analysis of 473 patients who received either DXMSoc or DXM20 in the COVIDICUS trial. The outcome was the 60 day mortality rate of DXM20 over DXMSoC, with treatment effect measured on the hazard ratio (HR) estimated from Cox model. Bayesian analyses allowed to compute the posterior probability of a more than trivial benefit (HR < 0.95), and that of a potential harm (HR > 1.05). Bayesian measures of interaction then quantified the probability of interaction (Pr Interact) that the HR of death differed across the subsets by 20%. Primary analyses used noninformative priors, centred on HR = 1.00. Sensitivity analyses used sceptical and enthusiastic priors, based on null (HR = 1.00) or benefit (HR = 0.95) effects. Results: Overall, the posterior probability of a more than trivial benefit and potential harm was 29.0 and 51.1%, respectively. There was some evidence of treatment by subset interaction (i) according to age (Pr Interact, 84%), with a 86.5% probability of benefit in patients aged below 70 compared to 22% in those aged above 70; (ii) according to the time since symptoms onset (Pr Interact, 99%), with a 99.9% probability of a more than trivial benefit when lower than 7 days compared to a < 0.1% probability when delayed by 7 days or more; and (iii) according to use of remdesivir (Pr Interact, 91%), with a 90.1% probability of benefit in patients receiving remdesivir compared to 19.1% in those who did not. Conclusions: In this exploratory post hoc Bayesian analysis, compared with standard-of-care DXM, high-dose DXM may benefit patients aged less than 70 years with severe ARF that occurred less than 7 days after symptoms onset. The use of remdesivir may also favour the benefit of DXM20. Further analysis is needed to confirm these findings. Trial registration: NCT04344730, date of registration April 14, 2020 (https://clinicaltrials.gov/ct2/show/NCT04344730?term=NCT04344730&draw=2&rank=1); EudraCT: 2020-001457-43 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=2020-001457-43). [ABSTRACT FROM AUTHOR]

In this article, we present the development of a mini scanner device to characterize the full transverse spatial density of a charged particle beam using computed tomography. The profiler consists of a wire mounted on a linear translator that can rotate around the beam. Tests were performed on a millimeter electron beam with 200 eV energy and 100 nA intensity, which allowed us to control and monitor both beam focusing and deflection. [ABSTRACT FROM AUTHOR]

Advanced age has been reported to negatively affect sperm parameters and spermatozoa DNA integrity. A decline in sperm criteria was also associated with altered epigenetic marks such as DNA methylation with a potential downstream impact on in vitro fertilization success and clinical outcomes. The aim of the present retrospective study was to clarify the association between advanced paternal age (APA) and sperm parameters, DNA integrity and DNA methylation profile. A total of 671 patients consulting for infertility underwent sperm analysis, sperm DNA integrity assessment and methylation level measurement. The principal finding was that individuals over 40 years of age exhibit a significant increase in DNA fragmentation levels compared to the younger group (15% versus 9%, respectively, p = 0.04). However, there was no significant difference in DNA decondensation and sperm parameters in association with APA. In addition, a drop in the global methylation level was also found in men over 40 years (6% in the young group versus 2% in the old group, p = 0.03). As a conclusion, men over 40 years are at higher risk of elevated sperm DNA fragmentation and lower methylation level. Based on these observations, it is recommended that the assessment of sperm DNA fragmentation should be taken into consideration particularly after the age of 40. Our findings support the idea that paternal age is a crucial factor that should not be neglected during fertility evaluation and treatment since it is associated with epigenetics changes in sperm. Although the underlying mechanism remains to be clarified, we believe that environmental and professional exposure factors are likely involved in the process. [ABSTRACT FROM AUTHOR]

Aims: The distinction between CNS WHO grade 2 and grade 3 is instrumental in choosing between observational follow‐up and adjuvant treatment for resected astrocytomas IDH‐mutant. However, the criteria of CNS WHO grade 2 vs 3 have not been updated since the pre‐IDH era. Methods: Maximal mitotic activity in consecutive high‐power fields corresponding to 3 mm2 was examined for 118 lower‐grade astrocytomas IDH‐mutant. The prognostic value for time‐to‐treatment (TTT) and overall survival (OS) of mitotic activity and other putative prognostic factors (including age, performance status, pre‐surgical tumour volume, multilobar involvement, post‐surgical residual tumour volume and midline involvement) was assessed for tumours with ATRX loss and the absence of CDKN2A homozygous deletion or CDK4 amplification, contrast enhancement, histological necrosis and microvascular proliferation. Results: Seventy‐one per cent of the samples had <6 mitoses per 3 mm2. Mitotic activity, residual volume and multilobar involvement were independent prognostic factors of TTT. The threshold of ≥6 mitoses per 3 mm2 identified patients with a shorter TTT (median 18.5 months). A residual volume ≥1 cm3 also identified patients with a shorter TTT (median 24.5 months). The group defined by <6 mitoses per 3 mm2 and a residual volume <1 cm3 had the longest TTT (median 73 months) and OS (100% survival at 7 years). These findings were confirmed in a validation cohort of 52 tumours. Conclusions: Mitotic activity and post‐surgical residual volume can be combined to evaluate the prognosis for patients with resected astrocytomas IDH‐mutant. Patients with <6 mitoses per 3 mm2 and a residual volume <1 cm3 were the best candidates for observational follow‐up. [ABSTRACT FROM AUTHOR]

According to the United Nations' Food and Agriculture Organization, the quantities of pesticide used around the world have increased regularly since the 1990s. Given that pesticides may be classified as carcinogenic, mutagenic, neurotoxic, or toxic for reproduction, some have endocrine-disrupting properties that might be associated with a decline in sperm parameters in general and sperm DNA integrity in particular. These days, a sperm analysis is not enough to determine the etiology of male infertility. Genome integrity analysis is a key step in clarifying a large proportion of cases of male infertility. The objective of the present retrospective study was to assess the impact of self-reported pesticide exposure on sperm parameters and sperm DNA integrity in men consulting for infertility. In a retrospective study, a population of 671 men living in the Picardy region of France were assessed in a conventional sperm parameter analysis, Shorr staining, a DNA fragmentation assay (terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling), and chromatin decondensation with aniline blue staining. The exposed and the non-exposed groups did not differ significantly in some of the conventional sperm parameters (including volume, sperm count, and percent typical forms). However, vitality, progressive motility, and non-progressive motility were significantly lower in the exposed group. Levels of DNA fragmentation and chromatin decondensation were moderately higher in the exposed group. [ABSTRACT FROM AUTHOR]

PURPOSE: The Lynch syndrome (LS)-glioma association is poorly documented. As for mismatch repair deficiency (MMRd) in glioma, a hallmark of LS-associated tumors, there are only limited data available. We determined MMRd and LS prevalence in a large series of unselected gliomas, and explored the associated characteristics. Both have major implications in terms of treatment, screening, and prevention. METHODS: Somatic next-generation sequencing was performed on 1,225 treatment-naive adult gliomas referred between 2017 and June 2022. For gliomas with ≥1 MMR pathogenic variant (PV), MMR immunohistochemistry (IHC) was done. Gliomas with ≥1 PV and protein expression loss were considered MMRd. Eligible patients had germline testing. To further explore MMRd specifically in glioblastomas, isocitrate dehydrogenase (IDH)-wild type (wt), we performed IHC, and complementary sequencing when indicated, in a series of tumors diagnosed over the 2007-2021 period. RESULTS: Nine gliomas were MMRd (9/1,225; 0.73%). Age at glioma diagnosis was <50 years for all but one case. Eight were glioblastomas, IDH-wt, and one was an astrocytoma, IDH-mutant. ATRX (n = 5) and TP53 (n = 8) PV were common. There was no TERT promoter PV or EGFR amplification. LS prevalence was 5/1,225 (0.41%). One 77-year-old patient was a known LS case. Four cases had a novel LS diagnosis, with germline PV in MSH2 (n = 3) and MLH1 (n = 1). One additional patient had PMS2 -associated constitutional mismatch repair deficiency. Germline testing was negative in three MSH6-deficient tumors. In the second series of glioblastomas, IDH-wt, MMRd prevalence was 12.5% in the <40-year age group, 2.6% in the 40-49 year age group, and 1.6% the ≥50 year age group. CONCLUSION: Screening for MMRd and LS should be systematic in glioblastomas, IDH-wt, diagnosed under age 50 years. Early-onset #glioblastoma, IDH-wild type is a red flag for both mismatch repair deficiency and #Lynchsyndrome. [ABSTRACT FROM AUTHOR]

In this work, our new experimental setup has been used to study the ionization and fragmentation of a prebiotic molecule, hydantoin, by electron impact. Scanning of the incident electron energy allows the determination of the appearance thresholds of the cations. The vertical ionization potential was found to be in good agreement with previous data. Dissociation thresholds for the main fragmentation patterns were also measured. In parallel, thanks to quantum chemical calculations, reaction schemes compatible with the experimental results are given. [ABSTRACT FROM AUTHOR]

Despite their technical advancements, commercially available telerobots are limited in social interaction capabilities for both pilot and local users, specifically in nonverbal communication. Our group hypothesizes that the introduction of expressive gesturing and tangible interaction capabilities (e.g., handshakes, fist bumps) will enhance telerobotic interactions and increase social connection between users. To investigate the affordances to social connection that gestures and tangible interactions provide in telerobot-mediated interactions, we designed and integrated a lightweight manipulator terminating in an anthropomorphic end effector onto a commercially available telerobot (Anybots QB 2.0). Through virtual reality tracking of the pilot user's arm and hand, expressive gestures and social contact interactions are recreated via the manipulator, enabling a pilot user and a local user to engage in a tangible exchange. To assess the usability and effectiveness of the gesturing system, we present evaluations from both the local and pilot user perspectives. First, we present a validation study to assess usability of the control system by the pilot user. Our results demonstrate that pilot user interactions can be replicated with a greater than 80% pass rate and mean ease of use rating of \(7.08 \pm 1.32\) (out of 10) with brief training. Finally, we present a user study to assess the social impacts of (1) using the telerobot without the manipulator from both the pilot user and local user perspectives and (2) using the control system and telerobotic manipulator from both the pilot user and local user perspectives. Results demonstrate that the robot with the manipulator elicited a more positive social experience than the robot without the arm for local users but no significant difference in conditions for pilot users. Future work will focus on improving the pilot user experience to support social contact interactions. [ABSTRACT FROM AUTHOR]

We fielded experiments to compare temperatures measured simultaneously by pyrometry and Raman spectroscopy in toluene shocked to 9 GPa. A 0.5 mm thick toluene sample was compressed between sapphire windows by plate impact from a gas gun. As the shock wave reverberated between the windows, the pressure increased stepwise to about 9 GPa. While the sample was near its peak pressure, we measured the Raman spectrum and determined temperature from the ratio of the Stokes and anti-Stokes intensities. Simultaneously, we measured the sample thermal radiance from the C-H vibration bands that occur between 3.2 and 3.6 μm to determine temperature pyrometrically. The pyrometer used a biased indium antimonide detector paired with a custom transimpedance amplifier, a system capable of temperature measurements as low as about 400 K. The Raman measurements gave a temperature of 530 ± 25 K in the bulk volume of toluene. Pyrometry gave a temperature of 496 + 15/−20 K, which is in reasonable agreement with the Raman measurement. Comparisons of this type are necessary to validate pyrometry as a temperature diagnostic in dynamic experiments. [ABSTRACT FROM AUTHOR]

We aimed to identify cardiopulmonary long-term effects after severe COVID-19 disease as well as predictors of Long-COVID in a prospective registry. A total of 150 consecutive, hospitalized patients (February 2020 and April 2021) were included six months post hospital discharge for a clinical follow-up. Among them, 49% experienced fatigue, 38% exertional dyspnea and 75% fulfilled criteria for Long-COVID. Echocardiography detected reduced global longitudinal strain (GLS) in 11% and diastolic dysfunction in 4%. Magnetic resonance imaging revealed traces of pericardial effusion in 18% and signs of former pericarditis or myocarditis in 4%. Pulmonary function was impaired in 11%. Chest computed tomography identified post-infectious residues in 22%. Whereas fatigue did not correlate with cardiopulmonary abnormalities, exertional dyspnea was associated with impaired pulmonary function (OR 3.6 [95% CI: 1.2–11], p = 0.026), reduced GLS (OR 5.2 [95% CI: 1.6–16.7], p = 0.003) and/or left ventricular diastolic dysfunction (OR 4.2 [95% CI: 1.03–17], p = 0.04). Predictors of Long-COVID included length of in-hospital stay (OR: 1.15 [95% CI: 1.05–1.26], p = 0.004), admission to intensive care unit (OR cannot be computed, p = 0.001) and higher NT-proBNP (OR: 1.5 [95% CI: 1.05–2.14], p = 0.026). Even 6 months after discharge, a majority fulfilled criteria for Long-COVID. While no associations between fatigue and cardiopulmonary abnormalities were found, exertional dyspnea correlated with impaired pulmonary function, reduced GLS and/or diastolic dysfunction. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, yet it remains refractory to systemic therapy. Elimination of senescent cells has emerged as a promising new treatment approach against cancer. Here, we investigated the contribution of senescent cells to GBM progression. Senescent cells are identified in patient and mouse GBMs. Partial removal of p16Ink4a-expressing malignant senescent cells, which make up less than 7 % of the tumor, modifies the tumor ecosystem and improves the survival of GBM-bearing female mice. By combining single cell and bulk RNA sequencing, immunohistochemistry and genetic knockdowns, we identify the NRF2 transcription factor as a determinant of the senescent phenotype. Remarkably, our mouse senescent transcriptional signature and underlying mechanisms of senescence are conserved in patient GBMs, in whom higher senescence scores correlate with shorter survival times. These findings suggest that senolytic drug therapy may be a beneficial adjuvant therapy for patients with GBM. Senescence can have beneficial and detrimental impact on cancer progression depending on the cellular context. Here the authors show that NRF2 regulates the senescence phenotype in malignant cells which consequently contribute to glioblastoma progression. [ABSTRACT FROM AUTHOR]

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The pea root rot complex is a major concern for green pea production worldwide. This study aimed at characterizing its composition and dynamics throughout a cropping season in northern France. To this end, fungi and oomycetes were isolated from green pea plant roots with symptoms sampled at the flowering stage in 22 fields in 2017, and at the pea emergence, elongation and flowering stages in two fields in 2018. Out of 646 isolates collected, 317 were identified using molecular markers. Fusarium oxysporum, F. solani and F. redolens were highly predominant. Pathogenicity tests separated the isolates into four aggressiveness groups. F. solani isolates were the most aggressive. Phylogenetic analysis of their TEF1 sequences showed that they mainly belonged to the F. pisi lineage, and that F. oxysporum isolates were genetically close to isolates from the UK that did not belong to the forma specialis pisi. In addition, several Clonostachys rhizophaga isolates are reported for the first time to cause pea root rot. The oomycetes were rarely found and were represented by a few Pythium spp. isolates. Lastly, this study shows that the fungal and oomycete communities associated with pea root rot change during the cropping season. The level of dissimilarity of the root‐rot‐associated communities decreased throughout the cropping season towards a more similar composition at the flowering stage, dominated by F. solani, F. oxysporum and F. redolens. The proportion of nonpathogenic to weakly pathogenic isolates decreased progressively during the growing season in favour of moderately to highly pathogenic isolates. [ABSTRACT FROM AUTHOR]

The failure probability and the reliability index have been determined for a pipe submitted to internal pressure, exhibiting a corrosion defect, embedded in a soil with a ground reaction, and submitted to displacement due to seismic activity. Results are obtained by computing the condition of failure: strain demand higher than strain resistance which is typically the Strain Based Design (SBD) basis. From the probabilistic point of view, this condition results as the product of the two probability distributions, demand and resistance. An analytical method is proposed to compute the common area between the strain demand and resistance distribution and then get the probability of failure. The strain demand is assumed to follow a power-law distribution and the strain resistance, a Normal one. The strain demand is computed assuming that the probability density of seism follows a Gutenberg –Richter distribution law as it is found in the south of France. This simple method is also used to predict the failure probability of different reference periods or seismic zone. It is also used to examine the influence of the coefficient of variation of the strain resistance distribution when using vintage pipe steels. [ABSTRACT FROM AUTHOR]