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The clinical relevance of the colorectal cancer serrated pathway is evident, but the screening of serrated lesions remains challenging. We aimed to characterize the serum methylome of the serrated pathway and to evaluate circulating cell‐free DNA (cfDNA) methylomes as a potential source of biomarkers for the non‐invasive detection of serrated lesions. We collected serum samples from individuals with serrated adenocarcinoma (SAC), traditional serrated adenomas, sessile serrated lesions, hyperplastic polyps and individuals with no colorectal findings. First, we quantified cfDNA methylation with the MethylationEPIC array. Then, we compared the methylation profiles with tissue and serum datasets. Finally, we evaluated the utility of serum cfDNA methylation biomarkers. We identified a differential methylation profile able to distinguish high‐risk serrated lesions from no serrated neoplasia, showing concordance with tissue methylation from SAC and sessile serrated lesions. Serum methylation profiles are pathway‐specific, clearly separating serrated lesions from conventional adenomas. The combination of ninjurin 2 (NINJ2) and glutamate‐rich 1 (ERICH1) methylation discriminated high‐risk serrated lesions and SAC with 91.4% sensitivity (64.4% specificity), while zinc finger protein 718 (ZNF718) methylation reported 100% sensitivity for the detection of SAC (96% specificity). This is the first study exploring the serum methylome of serrated lesions. Differential methylation of cfDNA can be used for the non‐invasive detection of colorectal serrated lesions.

Tras la reforma cisneriana, las clarisas de Salamanca se convierten en un importante monasterio dentro de las redes de espiritualidad femenina de la meseta ibérica. Entre su modesta colección de reliquias se distinguen algunas manufacturas conventuales realizadas en papel, núcleos espirituales originadores de prácticas de visualización y oración como productos creados para la unión en Dios. Son estos relicarios oraciones convertidas en imágenes, en los que los significados adheridos al proceso de creación, a los materiales y a los espacios en los que se veneran los distinguen de otros vestigios sacros al uso. Para ellos se plantea un estudio que trasciende las aparentes contradicciones presentes en estos pequeños lugares para la contemplación y que pretende resituarlos en sus contextos propios de peregrinación interior y religiosidad encerrada en movimiento, de raíces medievales y ecos carmelitanos.

Abstract Exercise training represents a health behavior for the treatment and management of the multi-faceted manifestations of multiple sclerosis (MS). This paper provides a comprehensive overview of evidence from randomized controlled trials (RCTs) regarding benefits, safety, participation, and guidelines for exercise training in MS, based on systematic reviews and meta-analyses. The paper then provides our opinions based on extensive experience regarding challenges for improving and expanding future RCTs that will advance our understanding of exercise training in MS. The comprehensive review of evidence from RCTs indicates that exercise training yields substantial improvements in aerobic and muscle fitness, mobility, fatigue and depression, quality of life, and participation outcomes. There is a non-significant increase in the risk of adverse events or serious adverse events with exercise training compared with control conditions or healthy populations. Rates of adherence and compliance with exercise training (i.e., participation) approximate 80% and 70%, respectively. The current prescriptive guidelines suggest 2–3 days per week of aerobic and resistance exercise training as the minimal dose for safely benefiting from exercise training in MS. We propose 10 important topics as avenues for expanding the body of research and improving its scope for evidence-based practice in MS. Overall, the research on exercise training in MS is strong, but it can get stronger. The expansion and advancement of evidence are critical for moving exercise training into the clinical armamentarium of MS disease treatment and management.

Abstract An important consideration in studies of the relationship between greenspace exposure and health is the use of mapped data to assign geographic exposures to participants. Previous studies have used validated data from municipal park departments to describe the boundaries of public greenspaces. However, this approach assumes that these data accurately describe park boundaries, that formal parks fully capture the park and greenspace exposure of residents, and (for studies that use personal GPS traces to assign participant exposures) that time spent within these boundaries represents time spent in greenspace. These assumptions are tested using a comparison and ground-truthing of four sources of mapped park and greenspace data in Philadelphia, Pennsylvania: PAD-US-AR, Philadelphia Parks and Recreation, the Delaware Valley Regional Planning Commission, and Open Street Maps. We find several important differences and tradeoffs in these data: the incorporation of highways and building lots within park boundaries, the inclusion or exclusion of formal park spaces (federal, state, and nonprofit), the exclusion of informal parks and greenspaces, and inconsistent boundaries for a linear park. Health researchers may wish to consider these issues when conducting studies using boundary data to assign park exposure.

Abstract Increasing access to water quality tests in low-income communities is a crucial strategy toward achieving global water equality. Recent studies in the Water Sanitation and Hygiene (WASH) sector underscore the importance of addressing practical concerns in water testing, such as robustness and results communication. In response, we present the WaterScope testing kit; an open-source, validated platform for drinking water quality assessment. It modernises the testing process with the inclusion of a unique cartridge/slider mechanism, machine-learning-enhanced classification and full digitalisation of results. WaterScope’s equivalency to conventional methods for quantifying E. coli is established through extensive validation experiments in both laboratory and field environments. This versatile platform provides potential to expand its applications to test other bacteria, perform colorimetric assays, and analyse clinical samples such as blood/urine samples. We anticipate that the system’s ease-of-use, portability, affordability, robustness, and digital nature will accelerate progress toward global water equality.

Abstract Background Genome-wide functional screening using the CRISPR-Cas9 system is a powerful tool to uncover tumor-specific and common genetic dependencies across cancer cell lines. Current CRISPR-Cas9 knockout libraries, however, primarily target protein-coding genes. This limits functional genomics-based investigations of miRNA function. Methods We designed a novel CRISPR-Cas9 knockout library (lentiG-miR) of 8107 distinct sgRNAs targeting a total of 1769 human miRNAs and benchmarked its single guide RNA (sgRNA) composition, predicted on- and off-target activity, and screening performance against previous libraries. Using a total of 45 human cancer cell lines, representing 16 different tumor entities, we performed negative selection screens to identify miRNA fitness genes. Fitness miRNAs in each cell line were scored using a combination of supervised and unsupervised essentiality classifiers. Common essential miRNAs across distinct cancer cell lines were determined using the 90th percentile method. For subsequent validation, we performed knockout experiments for selected common essential miRNAs in distinct cancer cell lines and gene expression profiling. Results We found significantly lower off-target activity for protein-coding genes and a higher miRNA gene coverage for lentiG-miR as compared to previously described miRNA-targeting libraries, while preserving high on-target activity. A minor fraction of miRNAs displayed robust depletion of targeting sgRNAs, and we observed a high level of consistency between redundant sgRNAs targeting the same miRNA gene. Across 45 human cancer cell lines, only 217 (12%) of all targeted human miRNAs scored as a fitness gene in at least one model, and fitness effects for most miRNAs were confined to small subsets of cell lines. In contrast, we identified 49 common essential miRNAs with a homogenous fitness profile across the vast majority of all cell lines. Transcriptional profiling verified highly consistent gene expression changes in response to knockout of individual common essential miRNAs across a diverse set of cancer cell lines. Conclusions Our study presents a miRNA-targeting CRISPR-Cas9 knockout library with high gene coverage and optimized on- and off-target activities. Taking advantage of the lentiG-miR library, we define a catalogue of miRNA fitness genes in human cancer cell lines, providing the foundation for further investigation of miRNAs in human cancer.

The majority of people who are travelling like to stay in hotels, or rent rooms which are considered dangerous sites for patients and vectors, and environments suitable for outbreaks and disease spreading. Bacterial contamination in hotels is a crucial concern for guests as it can cause serious infections. This study aimed to evaluate the contamination of some local hotel bedsheets with bacteria. For this, forty samples were collected (pillow covers, sheets, blankets, and mattresses) from different hotels during the summer holidays of July- August 2023. Several bacterial diagnosis tests were carried out to identify these bacterial species. Then, an antibacterial sensitivity test for ten different antibiotics and the bacteria that exhibited the highest antibiotic resistance were selected to test their sensitivity to natural plant extract and industrial disinfectant. Results showed that the highest level of bacterial contamination was registered in pillows and sheets (22.33x103cfu/g) and (21.33x103cfu/g) respectively. Also, ten bacterial species were isolated from all bedsheet types and most of them were normal flora. Moreover, Gram-positive bacteria were the most prevalent species. The antibiotic sensitivity tests showed that Micrococcus sp. was the most sensitive bacteria to antibiotics at 50%, while Bacillus cereus was more resistant to antibiotics at 80%. Also, as a result of the sensitivity of bacteria to disinfectant, crude lemon was recorded as the perfect natural disinfectant for Staphylococcus sp. whereas, a liquid industrial disinfectant (LID) was most effective against Escherichia coli, Bacillus cereus and Klebsiella sp. Therefore, it is preferable to use LID and lemon as a disinfectant and sterilizer when washing fabrics.

ABSTRACT Giant clams (Tridacna and Hippopus) are large marine bivalves occupying tropical and subtropical reefs in the Indo‐Pacific. Giant clam populations have declined in many areas of the Indo‐Pacific and continue to be threatened by harvesting and environmental change. The small giant clam (Tridacna maxima) occurs throughout the Indo‐Pacific and has been subject to several phylogeographic studies across its range. However, given its broad range, there are several areas where the genetic diversity and connectivity of T. maxima populations has not been characterised. Here, we analyse the mitochondrial marker cytochrome oxidase 1 (CO1) to examine the genetic diversity and connectivity of T. maxima in two regions: Australia's Coral Sea Marine Park and the Cook Islands. Samples were collected from 13 reefs within the Coral Sea Marine Park and ten islands within the Cook Islands archipelago. Tridacna maxima across the sampled region of the Coral Sea did not display any population structure, whereas significant population structure was detected for T. maxima within the Cook Islands. For the Cook Islands, most pairwise comparisons involving an island in the northern group (Manihiki) were significant, as were comparisons for Palmerston (a more centrally located island) and the southern islands, Rarotonga and Mangaia. Both regions displayed high haplotype diversities (> 0.90), indicating that they are important repositories of genetic diversity. Additional CO1 data from throughout T. maxima's distribution showed that the Coral Sea clams belonged to the clade occurring in the South‐Western Pacific Ocean, whilst those from the Cook Islands belonged to a unique clade found in the Central Pacific Ocean. This clade extended from Fiji in the west to French Polynesia in the east and the atolls of Palmyra and Tarawa (Kiribati) in the north. Our assessment of genetic diversity and population structure in these regions will assist with management decisions for the species.

Ginger is a culinary spice with a millennia-old tradition due to its extensive therapeutic applications, recently validated by scientific studies. In particular [6]-Gingerol, a key active molecule in ginger, exhibits extraordinary capabilities in addressing a wide spectrum of health issues. However, its therapeutic potential is limited by its rather low bioavailability. The incorporation of [6]-Gingerol into membrane systems of liposomes, micelles, or exosomes is a promising strategy to overcome this limitation. In this contribution, we report the hitherto unexplored surface properties of [6]-Gingerol at the air-water interface. Our comprehensive study, which includes a detailed analysis of surface pressure and surface potential vs. area per molecule isotherms, surface compression modulus, and Brewster Angle Microscopy, demonstrates the capability of [6]-Gingerol to form Langmuir films. These films can be transferred onto solid substrates, forming remarkably homogeneous Langmuir-Blodgett films which have been characterized by Quartz Crystal Microbalance and Atomic Force Microscopy. This study may be of interest as it paves the way for future research on introducing [6]-Gingerol into membrane systems and transporting it into living cells.

Resumo O artigo discute o tema do conhecimento pático, enunciado por Félix Guattari, que trata de saberes e aprendizados da ordem das sensações, ambiências e atmosferas. Em ressonância com o método da cartografia, que supõe o pesquisador imerso na problemática investigada, nesta pesquisa um procedimento expressivo possível se deu por meio da produção de narrativas que capturam pequenas cenas e expressam brechas sensíveis, interstícios afetivos, atmosferas páticas em experiências de formação em psicologia. Com a aposta em acompanhar climas e escrever com acontecimentos vivos, incidiram questões do pensamento contemporâneo que problematizam o superinvestimento na racionalidade tecnicista, nos protocolos e na transformação da noção de experiência em comportamento apresentado. Assim, pôde-se sustentar o patos como possibilidade de preensão de complexidades frequentemente reduzidas à mera psicologia individual, contornadas pela ciência positivista e pelas políticas de subjetivação capitalísticas. Não há, enfim, pretensão de encerrar a temática e propor respostas, mas de, através de aproximações e distanciamentos na formação, compor ferramentas vivas, geralmente colocadas entre parênteses, experimentações.

The pollution of indoor environments and the consequent health risks associated with thirdhand smoke (THS) are increasingly recognized in recent years. However, the carcinogenic potential of THS and its underlying mechanisms have yet to be thoroughly explored. In this study, we examined the effects of short-term THS exposure on the development of gastric cancer (GC) in vitro and in vivo. In a mouse model of spontaneous GC, CC036, we observed a significant increase in gastric tumor incidence and a decrease in tumor-free survival upon THS exposure as compared to control. RNA sequencing of primary gastric epithelial cells derived from CC036 mice showed that THS exposure increased expression of genes related to the extracellular matrix and cytoskeletal protein structure. We then identified a THS exposure-induced 91-gene expression signature in CC036 and a homologous 84-gene signature in human GC patients that predicted the prognosis, with secreted phosphoprotein 1 (SPP1) and tribbles pseudokinase 3 (TRIB3) emerging as potential targets through which THS may promote gastric carcinogenesis. We also treated human GC cell lines in vitro with media containing various concentrations of THS, which, in some exposure dose range, significantly increased their proliferation, invasion, and migration. We showed that THS exposure could activate the epithelial-mesenchymal transition (EMT) pathway at the transcript and protein level. We conclude that short-term exposure to THS is associated with an increased risk of GC and that activation of the EMT program could be one potential mechanism. Increased understanding of the cancer risk associated with THS exposure will help identify new preventive and therapeutic strategies for tobacco-related disease as well as provide scientific evidence and rationale for policy decisions related to THS pollution control to protect vulnerable subpopulations such as children.

Background: The prevalence of sexually transmitted infections (STIs) among young adults aged 18 to 25 in the U.S. is particularly high. Parental communication about sex is crucial in reducing sexual risk behaviors among this group. Due to cultural taboos about sex among Asian and Latino families, little is known about parental sex communication’s prevalence among these groups and its impact on young adults’ sexual behaviors and attitudes. Methods: This study aimed to explore the association between parental sex communication, attitudes toward sex communication, and sexual behaviors among Asian, Latino, and White young adults. A sample of 205 young adults, including 63 Asian, 48 Latino, and 94 non-Hispanic White young adults (Age M = 20.04, SD = 1.22; 68% females; 70% sexually active), completed an online survey. Results: Asian young adults reported significantly lower rates of parental sex communication (39.7%) compared to Latino (69.6%) and White young adults (67.7%) (χ2 = 14.07, df = 2, p < 0.001). Parental sex communication predicted viewing sexual topics as cultural taboos among Latino young adults (p < 0.05), subsequently predicting sexual risk behaviors like having multiple partners (β = −4.05, SE = 1.45, p = 0.03). Conclusions: Asian participants’ attitudes and sexual risk behaviors may be influenced by factors beyond familial discussions due to the lack of parental sex communication. Conversely, parental discussions among Latino participants negatively impact attitudes and behaviors related to sexual risk. Strategies for reducing sexual risk behaviors should guide parents in navigating sensitive discussions, especially within Asian and Latino families where such topics are taboo.

Lebanon's economic crisis has disrupted the country's energy and water sectors, highlighting their interdependence. The methodology involves surveying 150 municipalities across all Lebanese governorates, ensuring a comprehensive coverage of public and private water resources. Data on water and energy were collected before and during the crisis to explore this nexus during periods of economic turmoil. The findings reveal a decline in water provision during the crisis, with the average weekly water supply plummeting from 49 h in 2019 to 22 h in 2023. Concurrently, the use of water tankers has surged from 26 to 44%, indicating a concerning shift in water acquisition methods. Despite the crisis, conventional water sources remain predominant, while unconventional sources account for less than 1% of the total supply. In response to the energy shortage, renewable energy sources have gained traction in residential, commercial, and industrial sectors. The scarcity and rising cost of electricity have driven the adoption of solar photovoltaics in the water sector, reaching 4.8% for extraction from underground reservoirs and 2.8% for distribution. Similarly, the use of solar water heaters has increased from 7.9 to 15.4% in 2023. These findings underscore the interplay between energy and water security during periods of economic instability. HIGHLIGHTS Currency devaluation exposes vulnerability in the water–energy nexus.; Significant decrease in water availability during the economic downturn with household access dropping from 49 to 22 h per week.; A notable shift in water acquisition methods with 44% of the population relying on water tankers.; Emerging adoption of solar photovoltaic technology in the water sector.;

Abstract Background Patient outcomes following low-trauma hip fracture are suboptimal resulting in increased healthcare costs and poor functional outcomes at 1 year. Providing early and intensive in-hospital physiotherapy could help improve patient outcomes and reduce costs following hip fracture surgery. The HIP fracture Supplemental Therapy to Enhance Recovery (HIPSTER) trial will compare usual care physiotherapy to intensive in-hospital physiotherapy for patients following hip fracture surgery. The complex environments in which the intervention is implemented present unique contextual challenges that may impact intervention effectiveness. This study aims to complete a process evaluation to identify barriers and facilitators to implementation and explore the patient, carer and clinician experience of intensive therapy following hip fracture surgery. Methods and analysis The process evaluation is embedded within a two-arm randomised, controlled, assessor-blinded trial recruiting 620 participants from eight Australian hospitals who have had surgery for a hip fracture sustained via a low-trauma injury. A theory-based mixed method process evaluation will be completed in tandem with the HIPSTER trial. Patient and carer semi-structured interviews will be completed at 6 weeks following hip fracture surgery. The clinician experience will be explored through online surveys completed pre- and post-implementation of intensive therapy and mapped to domains of the Theoretical Domains Framework (TDF). Translation and behaviour change success will be assessed using the Reach Effectiveness-Adoption Implementation Maintenance (RE-AIM) framework and a combination of qualitative and quantitative data collection methods. These data will assist with the development of an Implementation Toolkit aiding future translation into practice. Discussion The embedded process evaluation will help understand the interplay between the implementation context and the intensive therapy intervention following surgery for low-trauma hip fracture. Understanding these mechanisms, if effective, will assist with transferability into other contexts and wider translation into practice. Trial registration ACTRN 12622001442796.

Abstract This pilot study focusing on Sickle Cell Anemia (SCA) patients offers a comprehensive and integrative evaluation of respiratory, cardiovascular, hemodynamic, and metabolic variables during exercise. Knowing that diastolic dysfunction is frequent in this population, we hypothesize that a lack of cardiac adaptation through exercise might lead to premature increase in blood lactate concentrations in SCA patients, a potential trigger for acute disease complication. SCA patients were prospectively included in PHYSIO-EXDRE study and underwent a comprehensive stress test with a standardized incremental exercise protocol up to 4 mmol L−1 blood lactate concentration (BL4). Gas exchange, capillary lactate concentration and echocardiography were performed at baseline, during stress test (at ∼ 2 mmol L−1) and BL4. The population was divided into two groups and compared according to the median value of percentage of theoretical peak oxygen uptake (% $${\dot{\text{V}}\text{O}}_{2peakth}$$ V ˙ O 2 p e a k t h ) at BL4. Twenty-nine patients were included (42 ± 12 years old, 48% of women). Most patients reached BL4 at low-intensity exercise [median value of predicted power output (W) was 37%], which corresponds to daily life activities. The median value of % $${\dot{\text{V}}\text{O}}_{2peakth}$$ V ˙ O 2 p e a k t h at BL4 was 39%. Interestingly, diastolic maladaptation using echocardiography during stress test along with hemoglobin concentration were independently associated to early occurrence of BL4. As BL4 occurs for low-intensity exercises, SCA patients may be subject to acidosis-related complications even during their daily life activities. Beyond assessing physical capacities, our study underlines that diastolic maladaptation during exercise is associated with an early increase in blood lactate concentration.

Abstract Multiplexed assays of variant effect (MAVEs) have emerged as a powerful approach for interrogating thousands of genetic variants in a single experiment. The flexibility and widespread adoption of these techniques across diverse disciplines have led to a heterogeneous mix of data formats and descriptions, which complicates the downstream use of the resulting datasets. To address these issues and promote reproducibility and reuse of MAVE data, we define a set of minimum information standards for MAVE data and metadata and outline a controlled vocabulary aligned with established biomedical ontologies for describing these experimental designs.

Abstract Background Magnetic resonance imaging (MRI) studies have identified brain changes associated with anxiety disorders (ADs), but the results remain mixed, particularly at a younger age. One key predictor of ADs is behavioral inhibition (BI), a childhood tendency for high avoidance of novel stimuli. This study aimed to evaluate the relationships between candidate brain regions, BI, and ADs among children using baseline data from the Adolescent Brain Cognitive Development (ABCD) study. Methods We analyzed global and regional brain volumes of 9,353 children (9–10 years old) in relation to BI and current ADs, using linear mixed models accounting for family clustering and important demographic and socioeconomic covariates. We further investigated whether and how past anxiety was related to brain volumes. Results Among included participants, 249 (2.66%) had a current AD. Larger total white matter (Beta = -0.152; 95% CI [-0.281, -0.023]), thalamus (Beta = -0.168; 95% CI [-0.291, -0.044]), and smaller hippocampus volumes (Beta = 0.094; 95% CI [-0.008, 0.196]) were associated with lower BI scores. Amygdala volume was not related to BI. Larger total cortical (OR = 0.751; 95% CI [0.580;0.970]), amygdala (OR = 0.798; 95%CI [0.666;0.956]), and precentral gyrus (OR = 0.802; 95% CI [0.661;0.973]) volumes were associated with lower odds of currently having ADs. Children with past ADs had smaller total white matter and amygdala volumes. Conclusions The results show associations between brain volumes and both BI and ADs at an early age. Importantly, results suggest that ADs and BI have different neurobiological correlates and that earlier occurrences of ADs may influence brain structures related to BI and ADs, motivating research that can better delineate the similarities and divergence in the neurobiological underpinnings and building blocks of BI and ADs across their development in early life.

Abstract Aims Frailty and dependence are frequent in patients admitted for acute heart failure (AHF), but their prognostic significance is unknown, especially in young adults. We aimed to study in adults admitted for AHF, regardless of age, the effect of frailty and dependence on the incidence of mortality and a combined event of mortality, readmissions for AHF, and visits to the emergency room (ER) for AHF at 1 and 6 months. Methods and results We designed a prospective cohort study by including all the patients with AHF admitted in our Cardiology Department from July 2020 through May 2021. A multidimensional geriatric assessment was performed during the admission. We clinically followed up the patients 6 months after discharge. We enrolled 202 patients. The mean age was 73 ± 12.32 years, and 100 (49.5%) of the patients were elderly (>75 years). Just 78 patients (38.6%) were women, and 100 (49.5%) had previous HF. Frailty (FRAIL ≥ 3) was observed in 68 (33.7%) patients (mean FRAIL score: 1.88 ± 1.48). Dependence (Barthel

As the aging populations, both nationwide and worldwide, rapidly increase, falls leading to unintentional injury and death subsequently increase. Thus, developing an understanding of biomechanical postural control strategies used to maintain balance in aging healthy adults, and those that have suffered stroke, are critical. Here, we were interested in how one’s body segments stabilize relative to one another, and in space, in order to maintain balance. To accomplish this goal, we studied 30 healthy individuals and 8 survivors of stroke between 60 and 85 years old, both before and after several weeks of sensory training. Motion capture data were acquired to assess participants’ body kinematics during walking: forward (easiest), forward-tandem, backward, and backward-tandem walking (most challenging). Deviations (via the observation of the absolute angle with deviations, or AADs) of the head, thorax, and lumbar areas relative to an earth vertical reference, as well as how one body segment stabilized in space or relative to the inferior body segment (via the observation of anchoring indices, or AIs), were explored. The results provide metrics (AADs and AIs) that can assess aging posture. Further, the results show an initial indication that, for aging individuals, training could lead to improved head and body stabilization in space.

Abstract Magnetic resonance imaging (MRI) has increasingly been used to characterize structure–function relationships during white matter neuroplasticity. Biological sex differences may be an important factor that affects patterns of neuroplasticity, and therefore impacts learning and rehabilitation. The current study examined a participant cohort before and after visuo-motor training to characterize sex differences in microstructural measures. The participants (N = 27) completed a 10-session (4 week) complex visuo-motor training task with their non-dominant hand. All participants significantly improved movement speed and their movement speed variability over the training period. White matter neuroplasticity in females and males was examined using fractional anisotropy (FA) and myelin water fraction (MWF) along the cortico-spinal tract (CST) and the corpus callosum (CC). FA values showed significant differences in the middle portion of the CST tract (nodes 38–51) across the training period. MWF showed a similar cluster in the inferior portion of the tract (nodes 18–29) but did not reach significance. Additionally, at baseline, males showed significantly higher levels of MWF measures in the middle body of the CC. Combining data from females and males would have resulted in reduced sensitivity, making it harder to detect differences in neuroplasticity. These findings offer initial insights into possible female versus male differences in white matter neuroplasticity during motor learning. This warrants investigations into specific patterns of white matter neuroplasticity for females versus males across the lifespan. Understanding biological sex-specific differences in white matter neuroplasticity may have significant implications for the interpretation of change associated with learning or rehabilitation.

Abstract Background The DNA damage response (DDR) is a physiological network preventing malignant transformation, e.g. by halting cell cycle progression upon DNA damage detection and promoting DNA repair. Glioblastoma are incurable primary tumors of the nervous system and DDR dysregulation contributes to acquired treatment resistance. Therefore, DDR targeting is a promising therapeutic anti-glioma strategy. Here, we investigated Ataxia telangiectasia and Rad3 related (ATR) inhibition (ATRi) and functionally-instructed combination therapies involving ATRi in experimental glioma. Methods We used acute cytotoxicity to identify treatment efficacy as well as RNAseq and DigiWest protein profiling to characterize ATRi-induced modulations within the molecular network in glioma cells. Genome-wide CRISPR/Cas9 functional genomic screens and subsequent validation with functionally-instructed compounds and selected shRNA-based silencing were employed to discover and investigate molecular targets modifying response to ATRi in glioma cell lines in vitro, in primary cultures ex vivo and in zebrafish and murine models in vivo. Results ATRi monotherapy displays anti-glioma efficacy in vitro and ex vivo and modulates the molecular network. We discovered molecular targets by genome-wide CRISPR/Cas9 loss-of-function and activation screens that enhance therapeutic ATRi effects. We validated selected druggable targets by a customized drug library and functional assays in vitro, ex vivo and in vivo. Conclusion In conclusion, our study leads to the identification of novel combination therapies involving ATRi that could inform future preclinical studies and early phase clinical trials.

IntroductionIn past work we demonstrated different patterns of white matter (WM) plasticity in females versus males associated with learning a lab-based unilateral motor skill. However, this work was completed in neurologically intact older adults. The current manuscript sought to replicate and expand upon these WM findings in two ways: (1) we investigated biological sex differences in neurologically intact young adults, and (2) participants learned a dynamic full-body balance task.Methods24 participants (14 female, 10 male) participated in the balance training intervention, and 28 were matched controls (16 female, 12 male). Correlational tractography was used to analyze changes in WM from pre- to post-training.ResultsBoth females and males demonstrated skill acquisition, yet there were significant differences in measures of WM between females and males. These data support a growing body of evidence suggesting that females exhibit increased WM neuroplasticity changes relative to males despite comparable changes in motor behavior (e.g., balance).DiscussionThe biological sex differences reported here may represent an important factor to consider in both basic research (e.g., collapsing across females and males) as well as future clinical studies of neuroplasticity associated with motor function (e.g., tailored rehabilitation approaches).

The introduction of pediatric-inspired regimens in adult Philadelphia-negative acute lymphoblastic leukemia (Ph-ALL) has significantly improved patients’ prognosis. Within the Campus ALL network we analyzed the outcome of adult Ph-ALL patients treated according to the GIMEMA LAL1913 protocol outside the clinical trial, to compare the real-life data with the study results. We included 421 consecutive patients, with a median age of 42 years. The complete remission (CR) rate after the first course of chemotherapy was 94% and a measurable residual disease (MRD) negativity after the third course was achieved in 72% of patients. The 3-year overall survival (OS) and disease-free survival (DFS) were 67% and 57%, respectively. In a multivariate analysis, MRD positivity negatively influenced DFS. In a time-dependent analysis including only very high risk (VHR) and MRD positive cases, transplanted (HSCT) patients had a significantly better DFS than non-HSCT ones (P=0.0017). During induction, grade ≥2 pegaspargase-related hepato-toxicity was observed in 25% of patients (vs 12% in the GIMEMA LAL1913 trial, P=0.0003). In this large real-life cohort of Ph-ALL, we confirmed the very high CR rate and a superimposable OS and DFS compared to the GIMEMA LAL1913 clinical trial: CR rate after C1 94% vs 85%, P=0.0004; 3-year OS 67% vs 67%, P=0.94; 3-year DFS 57% vs 63%, P=0.17. HSCT confirms its important role in VHR and MRD-positive patients. The rate of pegaspargase-related toxicity was significantly higher in the real-life setting, emphasizing the importance of dose adjustment in the presence of risk factors to avoid excessive toxicity.

No artigo Efeitos da Pandemia na Polícia Militar: Vulnerabilidades das polícias e do policiamento no Brasil, com número de DOI: https://doi.org/10.4322/dilemas.v16.n.3.51834, publicado no periódico Dilemas - , Rev. Estud. Conflito Controle Soc., volume 16, número 3 (2023), elocation e51834, na página 1: Onde se lia: “Susana Soares Brandão Durão” Leia-se: “Susana Durão” No artigo Efeitos da Pandemia na Polícia Militar: Vulnerabilidades das polícias e do policiamento no Brasil, com número de DOI: https://doi.org/10.4322/dilemas.v16.n.3.51834, publicado no periódico Dilemas - , Rev. Estud. Conflito Controle Soc., volume 16, número 3 (2023), elocation e51834, na página 25: Onde se lia: “Susana Soares Brandão Durão” Leia-se: “Susana Durão”

BackgroundSmartphone apps may provide an opportunity to deliver mental health resources and interventions in a scalable and cost-effective manner. However, young people from marginalized and underserved groups face numerous and unique challenges to accessing, engaging with, and benefiting from these apps. ObjectiveThis study aims to better understand the acceptability (ie, perceived usefulness and satisfaction with an app) and feasibility (ie, the extent to which an app was successfully used) of mental health apps for underserved young people. A secondary aim was to establish whether adaptations can be made to increase the accessibility and inclusivity of apps for these groups. MethodsWe conducted 2 sequential studies, consisting of a systematic literature review of mental health apps for underserved populations followed by a qualitative study with underserved young male participants (n=20; age: mean 19). Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, an electronic search of 5 databases was conducted in 2021. The search yielded 18,687 results, of which 14 articles met the eligibility criteria. ResultsThe included studies comprised a range of groups, including those affected by homelessness, having physical health conditions, living in low- and middle-income countries, and those with sexual and gender minority identities. Establishing and maintaining user engagement was a pervasive challenge across mental health apps and populations, and dropout was a reported problem among nearly all the included studies. Positive subjective reports of usability, satisfaction, and acceptability were insufficient to determine users’ objective engagement. ConclusionsDespite the significant amount of funding directed to the development of mental health apps, juxtaposed with only limited empirical evidence to support their effectiveness, few apps have been deliberately developed or adapted to meet the heterogeneous needs of marginalized and underserved young people. Before mental health apps are scaled up, a greater understanding is needed of the types of services that more at-risk young people and those in limited-resource settings prefer (eg, standard vs digital) followed by more rigorous and consistent demonstrations of acceptability, effectiveness, and cost-effectiveness. Adopting an iterative participatory approach by involving young people in the development and evaluation process is an essential step in enhancing the adoption of any intervention, including apps, in “real-world” settings and will support future implementation and sustainability efforts to ensure that marginalized and underserved groups are reached. Trial RegistrationPROSPERO CRD42021254241; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=254241

Trichoderma afroharzianum, a ubiquitous soil-borne fungus found on plant roots and decaying residues, displays competitive traits and mycoparasitic behavior against diverse microorganisms. Selected strains of this fungus are known in agriculture for their beneficial effects on plant growth and as bio-fungicides. However, recent findings have pinpointed Trichoderma afroharzianum as the causal agent behind maize ear rot disease in Europe since 2018, notably impacting maize cobs in Germany, France, and Italy. This study aims to evaluate the severity of Trichoderma ear rot disease on maize fresh matter content and specific quality parameters under semi-field conditions. Two distinct maize varieties were artificially inoculated with a pathogenic Trichoderma isolate at the flowering stage using needle pin or silk channel methods. Disease severity was assessed visually at the time of harvest based on the percentage of infected kernels according to EPPO Guidelines (PP 1/285). Fresh matter content and quality parameters such as alpha-amylase activity, C/N ratio, water, and sugar content were analyzed. Results showed that needle pin inoculation led to higher disease severity (60%) compared to silk channel inoculation (39%). Cob weight decreased significantly at the highest disease severity level by up to 50% compared to control plants. In both varieties, alpha-amylase activity increased significantly with higher Trichoderma disease severity, resulting in starch degradation and increased glucose release. The germination rate was severely affected by the infection, with only 22% of grains germinating, and the seedlings showed shortened and deformed growth. This is the first report on Trichoderma ear rot infection and its effect on fresh matter content and quality parameters in maize after artificial inoculation under field conditions. The results address an important knowledge gap and provide valuable insights into the infection pathway and impact on maize quality.

Kombucha, a beverage traditionally obtained through the fermentation of tea, is believed to have beneficial health properties. Therefore, characterizing the microorganisms responsible for this fermentation is essential to demonstrate its potential health benefits and to identify candidates for new probiotics. In this study, four probiotic yeast strains isolated from kombucha tea were identified, by the PCR-RFLP analysis of the ribosomal ITS region and the sequence of the D1/D2 domain of the 26S rDNA, as Brettanomyces bruxellensis (UVI55 and UVI56) and B. anomalus (UVI57 and UVI58). Properties relevant to probiotics were also studied in these strains. All of them showed excellent survival in simulated gastric (99%–100%) and duodenal (95%–100%) juices. The ability to self-aggregate (38%–100%), adhesion to xylene (15%–50%) and, above all, adhesion to Caco-2 cells (4%–21%), revealed its potential capacity to adhere to the intestinal epithelium. In addition, the tested strains showed excellent antioxidant capacity (82%–94%), antimicrobial activity against different pathogens (Escherichia coli, Staphylococcus aureus, Salmonella enterica, Listeria monocytogenes, and Bacillus cereus), as well as remarkable cytotoxic activity against colon, melanoma and ovarian tumor cell lines. Finally, using Caenorhabditis elegans as a model, strain UVI56 exhibited ability to both extend the lifespan of the nematode and protect it against infection by S. enterica. These results support the probiotic and functional properties of the analyzed strains. In conclusion, the study revealed that kombucha tea could be a source of potential probiotics that contribute to its health-promoting properties and that the characterized Brettanomyces strains could be exploited directly as probiotics or for the development of new functional foods.

Introduction: Many invasive and noninvasive neurotechnologies are being developed to help treat neurological pathologies and disorders. Making a brain implant safe, stable, and efficient in the long run is one of the requirements to conform with neuroethics and overcome limitations for numerous promising neural treatments. A main limitation is low biocompatibility, characterized by the damage implants create in brain tissue and their low adhesion to it. This damage is partly linked to friction over time due to the mechanical mismatch between the soft brain tissue and the more rigid wires.Methods: Here, we performed a short biocompatibility assessment of bio-inspired intra-cortical implants named “Neurosnooper” made of a microelectrode array consisting of a thin, flexible polymer–metal–polymer stack with microwires that mimic axons. Implants were assembled into poly-lactic-glycolic acid (PLGA) biodegradable needles for their intra-cortical implantation.Results and Discussion: The study of glial scars around implants, at 7 days and 2 months post-implantation, revealed a good adhesion between the brain tissue and implant wires and a low glial scar thickness. The lowest corresponds to electrode wires with a section size of 8 μm × 10 μm, compared to implants with the 8 μm × 50 μm electrode wire section size, and a straight shape appears to be better than a zigzag. Therefore, in addition to flexibility, size and shape parameters are important when designing electrode wires for the next generation of clinical intra-cortical implants.

Objective: to evaluate the effectiveness of a program in increasing coping strategies focused on military firefighters’ problems and emotions. Method: randomized, parallel, single-masked clinical trial. The sample consisted of 51 participants in the intervention group and 49 in the control group. The intervention group received the intervention program including coping strategies based on the Nursing Interventions Classification, lasting six consecutive weeks, one day a week. The control group followed the Service Unit routine. Descriptive statistics, Student’s T test with Welch’s correction and the Mann-Whitney test were used for the analyses. The magnitude of the intervention effect was calculated using Cohen’s d index. A p-value of ≤0.05% was considered. Results: in the analysis of the mean difference between the scores in the groups, the means of the intervention group increased significantly for the coping strategies: social support (p = 0.009), acceptance of responsibility (p = 0.03), problem solving (p = 0.05) and positive reappraisal (p = 0.05). The impact of the intervention was moderate in magnitude for social support (d = 0.54). Conclusion: the intervention program enabled the increase of coping strategies focused on military firefighters’ problems and emotions. ReBEC: RBR-8dmbzc.

Abstract Background The determinants of early-onset obesity ( International Obesity Task Force [IOTF] 30) of different etiologies (hypothalamic obesity [HO], intellectual disability with obesity [IDO], common polygenic obesity [CO]) were prospectively included. BMI history and responses from the Dykens’ Hyperphagia Questionnaire and an in-house Impulsivity Questionnaire at first visit were compared between groups. Results This cohort of 75 children (39 girls; mean age ± standard deviation [SD] 10.8 ± 4.4 years) had severe, early-onset obesity at an age of 3.8 ± 2.7 years, with a BMI Z-score of 4.9 ± 1.5. BMI history varied between the 3 groups, with earlier severe obesity in the HO group versus 2 other groups (BMI > IOTF40 at 3.4 ± 1.6 vs. 4.6 ± 1.6 and 8.4 ± 4.1 years for the IDO and CO groups, respectively [P 19) and impulsivity (score > 7) were found in 50 (67%) and 11 children (15%), respectively, with no difference between the HO, IDO and CO groups regarding the number of patients with hyperphagia (10 [67%], 14 [74%], and 26 [63%] children, respectively) or impulsivity (2 [13%], 1 [7%], and 8 [19%] children, respectively). Children with food impulsivity had significantly higher total and severity scores on the Dykens’ Questionnaire versus those without impulsivity. Conclusion The Dykens’ and Impulsivity questionnaires can help diagnose severe hyperphagia with/without food impulsivity in children with early-onset obesity, regardless of disease origin. Their systematic use can allow more targeted management of food access control in clinical practice and monitor the evolution of eating behavior in the case of innovative therapeutic targeting hyperphagia.

Germinal matrix hemorrhage (GMH) is a critical condition affecting premature infants, commonly diagnosed through cranial ultrasound imaging. This study presents an advanced deep learning approach for automated GMH grading using the YOLOv8 model. By analyzing a dataset of 586 infants, we classified ultrasound images into five distinct categories: Normal, Grade 1, Grade 2, Grade 3, and Grade 4. Utilizing transfer learning and data augmentation techniques, the YOLOv8 model achieved exceptional performance, with a mean average precision (mAP50) of 0.979 and a mAP50-95 of 0.724. These results indicate that the YOLOv8 model can significantly enhance the accuracy and efficiency of GMH diagnosis, providing a valuable tool to support radiologists in clinical settings.

Legume crops play a key role in hastening both the agroecological and protein transition and improving the sustainability of cropping systems. Among legumes, chickpea (Cicer arietinum L.) is a valuable source of protein, fibers, and nutraceutical compounds, providing important agri-environmental effects. Nevertheless, few studies have explored the effect of genetic characteristics on production and quality traits in chickpea. Chickpea landraces seem particularly interesting for their positive agronomic and quality characteristics, opening the door for innovation in sustainable food systems. Thus, the present study aimed to characterize two chickpea Tuscan landraces (Rugoso della Maremma and Cappuccio della Valtiberina) in comparison with widely distributed commercial chickpea varieties (Ares, Maragià, Pascià, Principe, Reale, Sultano, and Vittoria). Our findings highlighted positive agronomic traits of landraces in terms of seed yield and yield components, demonstrating performance that is either superior or comparable to commercial varieties. Notably, Cappuccio della Valtiberina showed the highest 1000-seed weight (425.50 g), followed by Maragià (432.92 g), Principe (392.32 g), and Reale (382.79 g), and the highest harvest index (0.55), similar to Reale (0.55). Overall, landraces achieved 18.75% higher yields than commercial varieties. Regarding chickpea quality, landraces exhibited profiles comparable to those of commercial genotypes in terms of protein and oil content, as well as nutraceuticals. Interestingly, the two landraces had the most favorable ω-6/ω-3 ratios (Cappuccio della Valtiberina, 12.45; Rugoso della Maremma, 13.71) among the genotypes except for Maragià (11.78), indicating better nutritional quality compared to commercial varieties (>14.00). These results demonstrated that landraces could offer promising prospects for future chickpea breeding programs, aiding in the selection of genotypes capable of adapting to changing growing conditions and supporting the development of sustainable food systems.

Our goal is to further understand how a simulated extravehicular mobility unit (xEMU) spacesuit affects the relative movement of one’s body segments. The effect of the xEMU spacesuit on gait is not yet fully understood. Here, gait was examined in terms of postural strategies, defined by the absolute angle with standard deviation (AAD) and the anchoring index (AI). The AAD values allowed the measurement of the absolute angles of body segments and their standard deviation, whereas the AI provided a measure of how stable a body segment was relative to a global reference frame and the inferior body segment. The body segments examined were the head, thorax, lumbar, and pelvis segments of 17 participants (26.53 ± 6.51 years old). The configurations tested included unsuited, or using a xEMU Vest or a hard upper body torso (HUT) for four walking conditions: eyes open/closed, with either forward or backward walking. The AAD values of the xEMU Vest were insignificant compared to those of the unsuited condition. The HUT significantly affected the AAD values compared to the unsuited condition. The AI for the HUT also indicates a new unique postural strategy being employed by the HUT group that was not previously observed.

Hyperventilation (HV) is an activation technique performed during clinical practices to trigger epileptiform activities, supporting the neurophysiological evaluation of patients with epilepsy. Although the role of HV has often been questioned, especially in the case of focal epilepsy, no studies have ever assessed how cortical structures respond to such a maneuver via intracranial EEG recordings. This work aims to fill this gap by evaluating the HV effects on the Stereo-EEG (SEEG) signals from a cohort of 10 patients with drug-resistant focal epilepsy. We extracted multiple quantitative metrics from the SEEG signals and compared the results obtained during HV, awake status, non-REM sleep, and seizure onset. Our findings show that the cortical connectivity, estimated via the phase transfer entropy (PTE) algorithm, strongly increases during the HV maneuver, similar to non-REM sleep. The opposite effect is observed during seizure onset, as ictal transitions involve the desynchronization of the brain structures within the epileptogenic zone. We conclude that HV promotes a conductive environment that may facilitate the propagation of epileptiform activities but is not sufficient to trigger seizures in focal epilepsy.

False news refers to false, fake, or misleading information presented as real news. In recent years, there has been a noticeable increase in false news on the Internet. The goal of this paper was to study the automatic detection of such false news using machine learning and natural language processing techniques and to determine which techniques work the most effectively. This article first studies what constitutes false news and how it differs from other types of misleading information. We also study the results achieved by other researchers on the same topic. After building a foundation to understand false news and the various ways of automatically detecting it, this article provides its own experiments. These experiments were carried out on four different datasets, one that was made just for this article, using 10 different machine learning methods. The results of this article were satisfactory and provided answers to the original research questions set up at the beginning of this article. This article could determine from the experiments that passive aggressive algorithms, support vector machines, and random forests are the most efficient methods for automatic false news detection. This article also concluded that more complex experiments, such as using multiple levels of identifying false news or detecting computer-generated false news, require more complex machine learning models.

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83–0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.

Introducción: el suicidio es responsable del 1,5% de las muertes mundiales, totalizando aproximadamente 800 000 muertes al año. Se estima que se convertirá en uno de los mayores contribuyentes a la carga mundial de morbilidad en las próximas 2 décadas. La formación clínica adecuada en el campo de la suicidología y la prevención de la conducta suicida resulta de especial relevancia en el contexto de la sala de internación de Psiquiatría. El presente estudio tiene como objetivo analizar los factores que contribuyen a la ideación y al comportamiento suicida en pacientes hospitalizados en la sala de internación de Psiquiatría de un hospital general universitario. Materiales y métodos: se realizó un estudio transversal de pacientes hospitalizados durante un año (octubre de 2018 a septiembre de 2019, n=254). Se examinaron las variables sociodemográficas, culturales y clínicas asociadas al suicidio. Resultados: el 39,4% de los pacientes que ingresaron en el período de estudio refería ideación suicida, el 13,4% un plan suicida y el 10,6% había presentado un intento de suicidio. Las mujeres tuvieron mayor chance de hospitalización debido a ideación suicida (OR=2,22, IC 95% [1,28-3,77]), plan suicida (OR=2,77, IC 95% [1,15-6,62]) e intento suicida (OR=3,12, IC 95% [1,13-8,47]). El 70% de los pacientes mayores de 65 años que tenían un plan suicida vivían solos, mientras que dicho porcentaje fue del 80% para quienes ingresaron luego de un intento de suicidio. Conclusiones: la mayor parte de los datos epidemiológicos en relación con la conducta suicida provienen de países desarrollados. Tratándose de un fenómeno de suma complejidad, creemos necesario incorporar al análisis aristas sociales, político-económicas, culturales y de género. La aplicación del método ideográfico podría brindar una herramienta útil para avanzar nuestro entendimiento en el campo de la suicidología, planteando un abordaje que se nutra de información tanto cuantitativa como cualitativa centrada en la persona, en un proceso iterativo que parta del individuo y luego busque elementos comunes contextualizados.

IntroductionIn the evolving healthcare landscape, precision medicine's rise necessitates adaptable doctoral training. The European Union has recognized this and promotes the development of international, training-focused programmes called Innovative Training Networks (ITNs). In this article, we introduce TranSYS, an ITN focused on educating the next generation of precision medicine researchers. In an ambition to go beyond describing the consortium goals, our article explores two key aspects of ITNs: the training and collaboration.MethodsUsing self-report questionnaires, we evaluate the scientific, professional, and personal growth of ESRs over the duration of the ITN and investigate whether this can be linked to network activities.ResultsOur quantitative analysis approach reveals substantial improvements in scientific, professional, and social skills among young researchers facilitated by the engagement in this interdisciplinary network. We provide case studies underlining the advantages of collaborative environments, featuring innovative scientific exchange within TranSYS.DiscussionWhile challenging, ITNs foster positive growth in young researchers, yet exhibit weaknesses such as balancing stakeholder interests and partner commitment. We believe this study may benefit a variety of stakeholders, from prospective ITN creators to industry partners, to design better sustainable training networks going forward.

IntroductionNecrotizing meningoencephalitis (NME) in pugs is a potentially fatal disease, which needs lifelong treatment with immunosuppressive or immunomodulatory drugs and shares parallels with acute fulminating multiple sclerosis. Genetic variants of the DLA class II gene are associated with an increased risk for NME. Genetic testing is recommended prior to breeding. The aim of this study was to describe the current allele frequency of a previously identified NME risk variant in the European pug population. A secondary aim was to investigate the association of the NME risk variant with the clinical phenotype in pugs.MethodsResults of genetic testing for the CFA12:2605517delC variant in European pugs between 2012 and 2020 were retrieved (n = 5,974). A validated questionnaire was mailed to all submitters of samples for further information on neurological signs, diagnostic tests, and disease course.ResultsThe allele frequency of the CFA12 NME risk variant was 25.7% in the European pug population dogs; 7.4% of the dogs were homozygous and 36.7% were heterozygous for the NME risk variant on CFA12. Completed questionnaires were available in 203 dogs including 25 dogs with epileptic seizures or other neurological signs. The clinical phenotype was consistent with NME in 3.9% with a median age of onset of 1.0 years, and indicative of idiopathic epilepsy in 2.9% with a median onset of 2.5 years. Eleven dogs remained unclassified. Pugs with the NME phenotype were significantly more frequently homozygous for the NME risk variant on CFA12 compared to pugs ≥6 years without neurological signs or seizures (p = 0.008).DiscussionThe CFA12:2605517delC genetic risk variant is widely distributed in the European pug population and frequently homozygous in pugs with a NME phenotype. The data support the clinical relevance of the CFA12:2605517delC genetic risk variant.

El debate desarrollado en torno a la personalidad creadora de Teresa Díez, a partir de la inscripción con su nombre que se conservó en los frescos góticos del convento de clarisas de Toro, da prueba del interés que han venido despertando las firmas medievales en la historia del arte. La relevancia de esta decisión epigráfica por parte de la dama toresana trasciende, empero, el estudio de tal documento como fuente para la mera atestación del rol de Teresa como autora o comitente de los ciclos pictóricos. Aspectos tales como la carga simbólica que posee desde antiguo la palabra en su condición de signo visual, o la ubicación de las grafías dentro de un espacio de clausura femenina permiten profundizar en algunos de los usos dados a esta inscripción en su calidad de imagen. Desde tal punto de vista, su revisión permite aseverar, para este me fecit, una función ligada al ejercicio de la memoria personal e institucional a través de la enunciación del nombre de la dama, del recuerdo de su linaje y de una intención de vinculación atemporal con la obra.

Abstract Background and Study Aims Our aim was to determine the impact of the SARS‐CoV‐2 pandemic on the diagnosis and prognosis of colorectal cancer (CRC). Patients and Methods This prospective cohort study included individuals diagnosed with CRC between March 13, 2019 and June 20, 2021 across 21 Spanish hospitals. Two time periods were compared: prepandemic (from March 13, 2019 to March 13, 2020) and pandemic (from March 14, 2020 to June 20, 2021, lockdown period and 1 year after lockdown). Results We observed a 46.9% decrease in the number of CRC diagnoses (95% confidence interval (CI): 45.1%–48.7%) during the lockdown and 29.7% decrease (95% CI: 28.1%–31.4%) in the year after the lockdown. The proportion of patients diagnosed at stage I significantly decreased during the pandemic (21.7% vs. 19.0%; p = 0.025). Centers that applied universal preprocedure SARS‐CoV‐2 PCR testing experienced a higher reduction in the number of colonoscopies performed during the pandemic post‐lockdown (34.0% reduction; 95% CI: 33.6%–34.4% vs. 13.7; 95% CI: 13.4%–13.9%) and in the number of CRCs diagnosed (34.1% reduction; 95% CI: 31.4%–36.8% vs. 26.7%; 95% CI: 24.6%–28.8%). Curative treatment was received by 87.5% of patients diagnosed with rectal cancer prepandemic and 80.7% of patients during the pandemic post‐lockdown period (p = 0.002). Conclusions The COVID‐19 pandemic has led to a decrease in the number of diagnosed CRC cases and in the proportion of stage I CRC. The reduction in the number of colonoscopies and CRC diagnoses was higher in centers that applied universal SARS‐CoV‐2 PCR screening before colonoscopy. In addition, the COVID‐19 pandemic has affected curative treatment of rectal cancers.

The term “lovebirds” is often used to describe the loving behaviors and interactions between two romantic partners, but what specific processes distinguish these flourishing lovebird relationships from other committed but “numbed” relationships? The present study aimed to address this knowledge gap through the development and preliminary validation of the Lovebird Scale. The Lovebird Scale describes the thoughts, feelings, behaviors, and habits that constitute and maintain relationship flourishing, which in turn could promote aspects of individual flourishing such as positive affect. We conducted three studies using data collected from 996 English-speaking U.S. adults (64.2% Female, M = 39.2 years old) who reported being in a romantic relationship for at least six months (M = 11.2 years). In Study 1, we conducted an exploratory factor analysis to determine the underlying factor structure. In Study 2, confirmatory factor analyses revealed a three-factor model nested within a higher-order factor representing lovebird relationships. In Study 3, we cross-validated the higher-order structure, examined the construct validity of the scale, and explored associations between the Lovebird Scale and affective state. Finally, we discuss how the Lovebird Scale contributes to the growing field of positive relationship science as well as conceptual and clinical implications of the scale.

This study compared the transcutaneous target level irradiances from the thoracic to lumbar segments of the interior spinal canal in three cadaver dogs, measured for light at four wavelengths (808 nm, 915 nm, 975 nm, and 1064 nm), common in photobiomodulation therapy (PBMT). Intra-spinal irradiances at nine sites spanning approximately 8 cm in length were measured using a flexible intra-spinal probe under surface application of continuous-wave (CW) light with powers ranging from 0.5 W to 2 W. Surface illumination was applied using an acupuncture treatment head in three modes: non-contact with skin removed, non-contact with skin intact, and contact with skin intact. During surface application, the treatment head was positioned over the spinal canal near the 13th vertebrae (T13, surface site 1), and approximately 4 cm (surface site 5) and 8 cm (surface site 9) caudal to T13. At each position of the treatment head, the light was multiplexed among the four wavelengths at the same power setting. In all three modes of surface application, the target level irradiance at the 1064 nm wavelength was significantly greater than that at the other three wavelengths (p ≤ 0.0017). At a surface irradiance of ~157 mW/cm2, corresponding to 0.5 W light applied with the treatment head directly in contact with the skin, the intra-spinal irradiance at 1064 nm reached 0.137 ± 0.095 mW/cm2. Obtaining a dosage of PBMT-associative wavelengths of this magnitude at the level of the spinal canal may guide focused research into the transcutaneous applicability of PBMT for spinal cord injuries.

The effects of immunodeficiency associated with chronic HIV infection on COVID-19 disease and viral persistence have not been directly addressed in a controlled setting. In this pilot study, we exposed two pigtail macaques (PTMs) chronically infected with SIVmac239, exhibiting from very low to no CD4 T cells across all compartments, to SARS-CoV-2. We monitored the disease progression, viral replication, and evolution, and compared these outcomes with SIV-naïve PTMs infected with SARS-CoV-2. No overt signs of COVID-19 disease were observed in either animal, and the SARS-CoV-2 viral kinetics and evolution in the SIVmac239 PTMs were indistinguishable from those in the SIV-naïve PTMs in all sampled mucosal sites. However, the single-cell RNA sequencing of bronchoalveolar lavage cells revealed an infiltration of functionally inert monocytes after SARS-CoV-2 infection. Critically, neither of the SIV-infected PTMs mounted detectable anti-SARS-CoV-2 T-cell responses nor anti-SARS-CoV-2 binding or neutralizing antibodies. Thus, HIV-induced immunodeficiency alone may not be sufficient to drive the emergence of novel viral variants but may remove the ability of infected individuals to mount adaptive immune responses against SARS-CoV-2.

Background: People with dementia have poorer outcomes after hip fracture and this may be due in part to variation in care. We aimed to compare care and outcomes for people with and without cognitive impairment after hip fracture. Methods: Retrospective cohort study using Australian and New Zealand Hip Fracture Registry data for people ≥50 years of age who underwent hip fracture surgery (n = 49,063). Cognitive impairment or known dementia and cognitively healthy groups were defined using preadmission cognitive status. Descriptive statistics and multivariable mixed effects models were used to compare groups. Results: In general, cognitively impaired people had worse care and outcomes compared to cognitively healthy older people. A lower proportion of the cognitively impaired group had timely pain assessment (≤30 min of presentation: 61% vs 68%; p < 0.0001), were given the opportunity to mobilise (89% vs 93%; p < 0.0001) and achieved day-1 mobility (34% vs 58%; p < 0.0001) than the cognitively healthy group. A higher proportion of the cognitively impaired group had delayed pain management (>30 mins of presentation: 26% vs 20%; p < 0.0001), were malnourished (27% vs 15%; p < 0.0001), had delirium (44% vs 13%; p < 0.0001) and developed a new pressure injury (4% vs 3%; p < 0.0001) than the cognitively healthy group. Fewer of the cognitively impaired group received rehabilitation (35% vs 64%; p < 0.0001), particularly patients from RACFs (16% vs 39%; p < 0.0001) and were prescribed bone protection medication on discharge (24% vs 27%; p < 0.0001). Significantly more of the cognitively impaired group had a new transfer to residential care (46% vs 11% from private residence; p < 0.0001) and died at 30-days (7% vs 3% from private residence; 15% vs 10% from RACF; both p < 0.0001). In multivariable models adjusting for covariates with facility as the random effect, the cognitively impaired group had a greater odds of being malnourished, not achieving day-1 walking, having delirium in the week after surgery, dying within 30 days, and in those from private residences, having a new transfer to a residential care facility than the cognitively healthy group. Conclusions: We have identified several aspects of care that could be improved for patients with cognitive impairment – management of pain, mobility, nutrition and bone health, as well as delirium assessment, prevention and management strategies and access to rehabilitation. Further research is needed to determine whether improvements in care will reduce hospital complications and improve outcomes for people with dementia after hip fracture.

Background Aortic stenosis has pathophysiological similarities with atherosclerosis, including the deposition of cholesterol‐containing lipoproteins. The resulting cholesterol crystals activate the NLRP3 (NOD‐like receptor protein 3) inflammasome, leading to inflammation and cardiovascular diseases. We aimed to investigate the cholesterol crystal dissolution rate (CCDR) of serum in patients with aortic stenosis and to assess the prognostic value of this biomarker. Methods and Results The study included 348 patients with aortic stenosis undergoing transcatheter aortic valve replacement. The CCDR was measured using flow cytometry to enumerate cholesterol crystals that were added to a serum solution, at baseline and after 2 hours of incubation. Based on the median CCDR, the cohort was stratified into high and low cholesterol crystal dissolvers. The incidence of the primary end point, a composite of 1‐year all‐cause mortality and major vascular complication, was significantly lower in the high CCDR group (7.3 per 100 person‐years) compared with the low CCDR group (17.0 per 100 person‐years, P=0.01). This was mainly driven by a lower 1‐year mortality rate in patients with a high CCDR (7.3 versus 15.1 per 100 person‐years, P=0.04). Unplanned endovascular interventions were significantly less frequent in high cholesterol crystal dissolvers (12.8 versus 22.6 per 100 person‐years, P=0.04). Although low‐density lipoprotein cholesterol levels were comparable in both groups (101.8±37.3 mg/dL versus 97.9±37.6 mg/dL, P=0.35), only patients with a low CCDR showed a benefit from statin treatment. In multivariate analysis, low CCDR (hazard ratio, 2.21 [95% CI, 0.99–4.92], P=0.04) was significantly associated with 1‐year mortality. Conclusions The CCDR is a novel biomarker associated with outcome in patients with aortic stenosis undergoing transcatheter aortic valve replacement. It may provide new insights into patients' anti‐inflammatory capacity and additional prognostic information beyond classic risk assessment.

Abstract Gynoid lipodystrophy, also called cellulite, is defined as a metabolic disorder of the subcutaneous tissue that alters body contour. It is rare in men but affects 80%–90% of adult women.The authors describe a technique for the treatment of cellulite with non‐traumatic subcisionTM of septa by cannula associated with large‐gel‐particle hyaluronic acid (HA). It uses a special marking, a safe plan and a specific product. The product being used is Subskin Aeskins, in a subcutaneous plan as no major blood vessels were found.The authors report good aesthetic results with the proposed technique. The patients reported a high degree of satisfaction.The product chosen has high G prime and large particles, which accounts for resistance to deformation and a high lifting power. Moreover, HA is a biocompatible, absorbable product and considered a safe filler. This technique allows the treatment of an area with various surface irregularities.The Square Technique proved to be a minimally invasive technique, with fast results, no major risks and little downtime, bringing satisfaction to patients and improving their self‐confidence and quality of life.