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Event segmentation is a neurocognitive process bridging perception and episodic memory. To our knowledge, almost all segmentation work is framed towards humans, yet evolutionarily conserved mechanisms in event cognition exist across species. Here, we addressed segmentation in a way that is applicable to humans and non-human animals, inspired by research in rats; specifically, the fragmentation of grid-cell spatial representations following the insertion of boundaries into an environment (forming a corridor maze). Participants indicated when they felt a meaningful unit of activity ended and another began, while watching an agent traverse from a first-person perspective. A virtual corridor maze (experiment 1) and two other mazes were used (experiment 2), with participants viewing/segmenting the same stimuli twice. We found that people segmented more during turns relative to corridors, with elevated segmentation occurring in discrete moments around turns. Interestingly, we also found that boundaries of the corridor maze facilitated an increase in segmentation within and across viewings. These results suggest that segmentation can be driven by recognized repeating activity that can become more meaningful over time, highlighting an important link between event segmentation and pattern separation that is relevant to many species in their formation of episodic-(like) memory.

Toxicokinetic (TK) models have been used for decades to estimate concentrations of per-and polyfluoroalkyl substances (PFAS) in serum. However, model complexity has varied across studies depending on the application and the state of the science. This scoping effort seeks to systematically map the current landscape of PFAS TK models by categorizing different trends and similarities across model type, PFAS, and use scenario. A literature review using Web of Science and SWIFT-Review was used to identify TK models used for PFAS. The assessment covered publications from 2005–2020. PFOA, the PFAS for which most models were designed, was included in 69 of the 92 papers, followed by PFOS with 60, PFHxS with 22, and PFNA with 15. Only 4 of the 92 papers did not include analysis of PFOA, PFOS, PFNA, or PFHxS. Within the corpus, 50 papers contained a one-compartment model, 17 two-compartment models were found, and 33 used physiologically based pharmacokinetic (PBTK) models. The scoping assessment suggests that scientific interest has centered around two chemicals—PFOA and PFOS—and most analyses use one-compartment models in human exposure scenarios.

The history of environmental standards, the emergence of environmental architectural and construction design in Russia and the forerunners of environmental certification systems in construction are studied. Historical material is analysed and data is systematised chronologically. Development stages of ecological architectural and construction design in our country are highlighted, their main features are given: Stage 1 (late 17th – mid 20th centuries) — the history of the formation of environmental requirements for the conservation of natural resources and the creation of a comfortable environment for life in urban areas; Stage 2 (mid XXth – early XXIth centuries) — the formation of environmental legislation, the opening of the first Russian Green Building councils, the adaptation of international environmental standards in construction to Russian realities; Stage 3 (the beginning of the XXIth century – the present) — the creation of sustainable requirements in the Russian Federation, increasing the viability of the architectural and construction environment, the introduction of a number of Russian environmental standards in construction, the formation of a national Tech-nical Committee 366 to develop national standards to GOST R series on green construction and promoting green standardization at the national and international levels with the introduction of new green technologies, materials and products for a comfortable living environment. Today in Russia, a new architectural and construction environment is emerging, aimed at saving resources, preserving health, energy conservation, reducing waste, safety, comfort, preserving biodiversity and creating holistic conditions. To intensify the development of this area, it is necessary to introduce new environmental standards for the design of sustainable space in Russian cities, using best world practice.

Abstract Introduction To determine anatomical, functional, and intraocular pressure (IOP) responses to diabetic macular edema (DME) treatments pre- and post-0.2 µg/day fluocinolone acetonide (FAc) implant administration compared with baseline and the preceding 3 years. Methods This was a retrospective, chart review, cohort study in four U.S. centers. Patients received the 0.2 µg/day FAc implant for the treatment of DME in at least one eye before January 1, 2016. DME treatments administered up to 36 months pre-FAc implant and up to 24 months post-FAc implant were recorded, and treatment frequency was calculated. Visual acuity (VA) was assessed using a Snellen eye chart and converted to early treatment diabetic retinopathy study (ETDRS) letters, and central subfield thickness (CST) was measured using optical coherence tomography (OCT). Treatment frequency, mean VA, mean CST, percentage of patients with CST of ≤ 300 µm, mean IOP, IOP events, and IOP treatments pre- and post-FAc implant administration were measured. Positive and negative predictive values for the IOP response to prior steroid therapy were also determined. Results In total, 160 eyes of 130 patients were studied. VA was maintained at pre-FAc levels from baseline to month 24, despite a significant reduction in treatment frequency from one treatment every 2.9 months pre-FAc implant to one treatment every 14.3 months post-FAc implant. Patients with better baseline VA required fewer DME treatments post-FAc than did patients with worse baseline VA. The majority of patients did not require additional DME treatment during the post-FAc follow-up period. A significant reduction in CST and an increase in the percentage of patients with CST of ≤ 300 µm were seen up to month 21 post-FAc implant. Pre-FAc implant IOP was maintained during the post-FAc implant period; increased IOP with prior steroid therapy was found to be highly predictive of increased IOP post-FAc implant. Conclusion The results of this study confirm the positive safety and efficacy profile of the FAc implant and demonstrate for the first time the effectiveness of the U.S. label indication of FAc in reducing the incidence of post-treatment pressure elevation. The FAc implant significantly reduced treatment burden in the overall population without significantly increasing the risk of steroid-induced pressure elevation. Funding Alimera Sciences.

Exposure to chemicals is influenced by associations between the individual’s location and activities as well as demographic and physiological characteristics. Currently, many exposure models simulate individuals by drawing distributions from population-level data or use exposure factors for single individuals. The Residential Population Generator (RPGen) binds US surveys of individuals and households and combines the population with physiological characteristics to create a synthetic population. In general, the model must be supported by internal consistency; i.e., values that could have come from a single individual. In addition, intraindividual variation must be representative of the variation present in the modeled population. This is performed by linking individuals and similar households across income, location, family type, and house type. Physiological data are generated by linking census data to National Health and Nutrition Examination Survey data with a model of interindividual variation of parameters used in toxicokinetic modeling. The final modeled population data parameters include characteristics of the individual’s community (region, state, urban or rural), residence (size of property, size of home, number of rooms), demographics (age, ethnicity, income, gender), and physiology (body weight, skin surface area, breathing rate, cardiac output, blood volume, and volumes for body compartments and organs). RPGen output is used to support user-developed chemical exposure models that estimate intraindividual exposure in a desired population. By creating profiles and characteristics that determine exposure, synthetic populations produced by RPGen increases the ability of modelers to identify subgroups potentially vulnerable to chemical exposures. To demonstrate application, RPGen is used to estimate exposure to Toluene in an exposure modeling case example.

Spontaneous recognition tasks are widely used as a laboratory measure of memory in animals but give rise to high levels of behavioral noise leading to a lack of reliability. Previous work has shown that a modification of the procedure to allow continual trials testing (in which many trials are run concurrently in a single session) decreases behavioral noise and thus significantly reduces the numbers of rats required to retain statistical power. Here, we demonstrate for the first time that this improved method of testing extends to mice, increasing the overall power of the approach. Moreover, our results show that the new continual trials approach provides the additional benefits of heightened sensitivity and thus provides greater insight into the mechanisms at play. Standard (c57) and transgenic Alzheimer model (TASTPM) mice were tested both at 7 and 10 months of age in both object recognition (OR) and object-location (OL) spontaneous recognition tasks using the continual trials methodology. Both c57 and TASTPM mice showed age-dependent changes in performance in OR. While c57 mice also showed age-related changes in performance of OL, TASTPM mice were unable to perform OL at either age. Significantly, we demonstrate that differences in OL performance in c57s and TASTPM animals is a result of proactive interference rather than an absolute inability to recognize OL combinations. We argue that these continual trials approaches provide overall improved reliability and better interpretation of the memory ability of mice, as well as providing a significant reduction in overall animal use.

CRISPR technology has rapidly changed the face of biological research, such that precise genome editing has now become routine for many labs within several years of its initial development. What makes CRISPR/Cas9 so revolutionary is the ability to target a protein (Cas9) to an exact genomic locus, through designing a specific short complementary nucleotide sequence, that together with a common scaffold sequence, constitute the guide RNA bridging the protein and the DNA. Wild-type Cas9 cleaves both DNA strands at its target sequence, but this protein can also be modified to exert many other functions. For instance, by attaching an activation domain to catalytically inactive Cas9 and targeting a promoter region, it is possible to stimulate the expression of a specific endogenous gene. In principle, any genomic region can be targeted, and recent efforts have successfully generated pooled guide RNA libraries for coding and regulatory regions of human, mouse and Drosophila genomes with high coverage, thus facilitating functional phenotypic screening. In this review, we will highlight recent developments in the area of CRISPR-based functional genomics and discuss potential future directions, with a special focus on mammalian cell systems and arrayed library screening.

The go-to cognitive enhancers of today are those that are widely available rather than optimal for the user, including drugs typically prescribed for treatment of ADHD and sleep disturbances such as narcolepsy. While highly effective in their intended therapeutic role, performance gains in healthy populations are modest at best and profoundly inconsistent across subgroups and individuals. We propose a method for in silico screening of possible novel cognitive enhancers followed by high-throughput in vivo and in vitro validation. The proposed method uses gene expression data to evaluate the the collection of activated or suppressed signaling pathways in tissues or neurons of the cognitively enhanced brain. An algorithm maps expression data onto signaling pathways and quantifies their individual activation strength. The collective pathways and their activation form, a biological fingerprint of cognitive enhancement (or any other condition of interest). Drugs can then be screened and ranked based on their ability to minimize, mimic, or exaggerate pathway activation or suppression within that cloud. Using this approach, one may predict the efficacy of many drugs that may enhance various aspects of cognition.

Volatile organic compounds (VOCs) are emitted from all plants and these VOCs are important means of communication between plants and insects. It has been documented that pathogen infections alter VOC profiles rendering infected plants more attractive to specific vectors transmitting these pathogens than uninfected plants, thus potentially aiding in pathogen propagation. Mimicking these chemical cues might enable insect attraction away from the plant or disruption of host finding behavior of the vector. However, the practical implications have not been fully explored. We used citrus, Diaphorina citri and huanglongbing (HLB) as a model host-vector-disease system because HLB threatens citrus production worldwide and is similar to other critical diseases of food crops, such as Zebra Chip affecting potato. We formulated a synthetic chemical blend using selected HLB-specific biomarker compounds, and tested the blend with the Attenu assay system for chemosensory proteins. The Attenu assay system is a procedure that identifies interactions between insect chemosensory proteins and their ligands. We found that an equimolar mixture of compounds mimicking the volatile profile of HLB-infected citrus bound chemosensory proteins. Further investigation of this blend in laboratory behavioral assays resulted in development of a synthetic lure that was more attractive to D. citri than natural citrus tree volatiles. This strategy could provide a new route to produce chemical lures for vector population control for a variety of plant and/or animal systems and it may result in the development of a practical lure for monitoring vectors of disease, such as D. citri.

The discovery of the tissue-protective activities of erythropoietin (EPO) has underlined the importance of some cytokines in tissue protection, repair and remodeling. As such activities have been reported for other cytokines, we asked whether we could define a class of tissue-protective cytokines. We therefore explored a novel approach based on functional clustering. In this pilot study, we started by analyzing a small number of cytokines (30). We functionally classified the 30 cytokines according to their interactions by using the bioinformatics tool STRING (Search Tool for the Retrieval of Interacting Genes), followed by hierarchical cluster analysis. The results of this functional clustering were different from those obtained by clustering cytokines simply according to their sequence. We previously reported that the protective activity of EPO in a model of cerebral ischemia was paralleled by an upregulation of synaptic plasticity genes, particularly early growth response 2 (EGR2). To assess the predictivity of functional clustering, we tested some of the cytokines clustering close to EPO (interleukin-11, IL-11; kit ligand, KITLG; leukemia inhibitory factor, LIF; thrombopoietin, THPO) in an in vitro model of human neuronal cells for their ability to induce EGR2. Two of these, LIF and IL-11, induced EGR2 expression. Although these data would need to be extended to a larger number of cytokines and the biological validation should be done using more robust in vivo models, rather then just one cell line, this study shows the feasibility of this approach. This type of functional cluster analysis could be extended to other fields of cytokine research and help design biological experiments.

Neotropical orchid bees (Euglossini) are often cited as classic examples of trapline-foragers with potentially extensive foraging ranges. If long-distance movements are habitual, rare plants in widely scattered locations may benefit from euglossine pollination services. Here we report the first successful use of micro radio telemetry to track the movement of an insect pollinator in a complex and forested environment. Our results indicate that individual male orchid bees (Exaerete frontalis) habitually use large rainforest areas (at least 42-115 ha) on a daily basis. Aerial telemetry located individuals up to 5 km away from their core areas, and bees were often stationary, for variable periods, between flights to successive localities. These data suggest a higher degree of site fidelity than what may be expected in a free living male bee, and has implications for our understanding of biological activity patterns and the evolution of forest pollinators.

Recycling of H(+)-ATPase to the apical plasma membrane, mediated by vesicular exocytosis and endocytosis, is an important mechanism for controlling H(+) secretion by the collecting duct. We hypothesized that SNAREs (soluble N-ethylmaleimide-sensitive factor attachment proteins) may be involved in the targeting of H(+)-ATPase-coated vesicles. Using a tissue culture model of collecting duct H(+) secretory cells (inner medullary collecting duct (IMCD) cells), we demonstrated that they express the proteins required for SNARE-mediated exocytosis and form SNARE-fusion complexes upon stimulation of H(+)-ATPase exocytosis. Furthermore, exocytic amplification of apical H(+)-ATPase is sensitive to clostridial toxins that cleave SNAREs and thereby inhibit secretion. Thus, SNAREs are critical for H(+)-ATPase cycling to the plasma membrane. The process in IMCD cells has a feature distinct from that of neuronal cells: the SNARE complex includes and requires the vesicular cargo (H(+)-ATPase) for targeting. Using chimeras and truncations of syntaxin 1, we demonstrated that there is a specific cassette within the syntaxin 1 H3 domain that mediates binding of the SNAREs and a second distinct H3 region that binds H(+)-ATPase. Utilizing point mutations of the B1 subunit of the H(+)-ATPase, we document that this subunit contains specific targeting information for the H(+)-ATPase itself. In addition, we found that Munc-18-2, a regulator of exocytosis, plays a multifunctional role in this system: it regulates SNARE complex formation and the affinity of syntaxin 1 for H(+)-ATPase. [ABSTRACT FROM AUTHOR]

Background High-quality translations of radiology reports are essential for optimal patient care. Because of limited availability of human translators with medical expertise, large language models (LLMs) are a promising solution, but their ability to translate radiology reports remains largely unexplored. Purpose To evaluate the accuracy and quality of various LLMs in translating radiology reports across high-resource languages (English, Italian, French, German, and Chinese) and low-resource languages (Swedish, Turkish, Russian, Greek, and Thai). Materials and Methods A dataset of 100 synthetic free-text radiology reports from CT and MRI scans was translated by 18 radiologists between January 14 and May 2, 2024, into nine target languages. Ten LLMs, including GPT-4 (OpenAI), Llama 3 (Meta), and Mixtral models (Mistral AI), were used for automated translation. Translation accuracy and quality were assessed with use of BiLingual Evaluation Understudy (BLEU) score, translation error rate (TER), and CHaRacter-level F-score (chrF++) metrics. Statistical significance was evaluated with use of paired t tests with Holm-Bonferroni corrections. Radiologists also conducted a qualitative evaluation of translations with use of a standardized questionnaire. Results GPT-4 demonstrated the best overall translation quality, particularly from English to German (BLEU score: 35.0 ± 16.3 [SD]; TER: 61.7 ± 21.2; chrF++: 70.6 ± 9.4), to Greek (BLEU: 32.6 ± 10.1; TER: 52.4 ± 10.6; chrF++: 62.8 ± 6.4), to Thai (BLEU: 53.2 ± 7.3; TER: 74.3 ± 5.2; chrF++: 48.4 ± 6.6), and to Turkish (BLEU: 35.5 ± 6.6; TER: 52.7 ± 7.4; chrF++: 70.7 ± 3.7). GPT-3.5 showed highest accuracy in translations from English to French, and Qwen1.5 excelled in English-to-Chinese translations, whereas Mixtral 8x22B performed best in Italian-to-English translations. The qualitative evaluation revealed that LLMs excelled in clarity, readability, and consistency with the original meaning but showed moderate medical terminology accuracy. Conclusion LLMs showed high accuracy and quality for translating radiology reports, although results varied by model and language pair. © RSNA, 2024 Supplemental material is available for this article.

A knowledge gap exists between apheresis medicine (AM) physicians and providers who request the service, presenting challenges when coordinating care. We investigated an educational intervention consisting of a 40-min in-person evidence-based lecture for neurology residents, neurology attending physicians, and nephrology fellows. Pre-/post-testing demonstrated substantially improved understanding of apheresis mechanics, indications, complications, and patient consent. We advocate for more educational sessions about AM for the non-apheresis providers to increase awareness about apheresis and foster collaborative interdisciplinary efforts., (© 2024 Wiley Periodicals LLC.)

Background: Ambient fine particulate matter (PM 2.5 ) is a risk factor for atherosclerosis disease. We aimed to assess whether nitric oxide stable metabolites (NOx) and l-arginine mediate the association between PM 2.5 and carotid intima media thickness (cIMT) increase., Methods: We selected 251 participants from the control group of GEA (Genetics of Atheroslerosis Disease Mexican) study (2008-2013) in Mexico City. Mediation models were carried out using pathway analyses, a special case of structural equation models., Results: The median concentration of PM 2.5 area under the curve (auc) was 25.2 µg/m 3 (interquartile range: 24.2-26.4 µg/m 3 ). Employing participants with observed values for both biomarkers (n = 117), the total effect of PM 2.5auc on mean cIMT at bilateral, right, and left was 19.27 µm (95% confidence interval [CI]: 5.77, 32.78; P value = 0.005), 12.69 µm (95% CI: 0.67, 24.71; P value = 0.039), and 25.86 µm (95% CI: 3.18, 48.53; P value = 0.025) per each 1 µg/m 3 increase of PM 2.5auc . The direct effect of PM 2.5auc (per 1 µg/m 3 increase) was 18.89 µm (95% CI: 5.37, 32.41; P value = 0.006) for bilateral, 13.65 µm (95% CI: 0.76, 26.55; P value = 0.038) for right, and 24.13 µm (95% CI: 3.22, 45.03; P value = 0.024) for left. The indirect effects of NOx and l-arginine were not statistically significant showing that endothelial function biomarkers did not mediate PM 2.5 and cIMT associations. Although l-arginine was not a mediator in the PM 2.5 and cIMT pathway, a decrease in l-arginine was significantly associated with PM 2.5auc ., Conclusions: In this study of adults from Mexico City, we found that PM 2.5 was associated with an increase in cIMT at bilateral, left, and right, and these associations were not mediated by endothelial function biomarkers (l-arginine and NOx)., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Medical students' efforts to learn person-centered thinking and behavior can fall short due to the dissonance between person-centered clinical ideals and the prevailing epistemological stereotypes of medicine, where physicians' life events, relations, and emotions seem irrelevant to their professional competence. This paper explores how reflecting on personal life experiences and considering the relevance for one's future professional practice can inform first-year medical students' initial explorations of professional identities. In this narrative inquiry, we undertook a dialogical narrative analysis of 68 essays in which first-year medical students reflected on how personal experiences from before medical school may influence them as future doctors. Students wrote the texts at the end of a 6-month course involving 20 patient encounters, introduction to person-centered theory, peer group discussions, and reflective writing. The analysis targeted medical students' processes of interweaving and delineating personal and professional identities. The analysis yielded four categories. (1) How medical students told their stories of illness, suffering, and relational struggles in an interplay with context that provided them with new perspectives on their own experiences. Students formed identities with a person-centered orientation to medical work by: (2) recognizing and identifying with patients' vulnerability, (3) experiencing the healing function of sharing stories, and (4) transforming personal experiences into professional strength. Innovative approaches to medical education that encourage and support medical students to revisit, reflect on, and reinterpret their emotionally charged life experiences have the potential to shape professional identities in ways that support person-centered orientations to medical work., (© 2024. The Author(s).)

Background: Endovascular aortic repair (EVAR) requires extensive preoperative, intraoperative, and postoperative imaging for planning, surveillance, and detection of endo-leaks. There have been manyadvancements in imaging modalities to achieve this purpose. This review discussed different imaging modalities used at different stages of treatment of complex EVAR., Methods: We conducted a literature review of all the imaging modalities utilized in EVAR by searching various databases., Results: Preoperative techniques include analysis of images obtained via modified central line using analysis software and intravascular ultrasound. Fusion imaging (FI), carbon dioxide (CO2) angiography, intravascular ultrasound, and Fiber Optic RealShape (FORS) technology have been crucial in obtaining real-time imaging for the detection of endo-leaks during operative procedures. Conventional imaging modalities like computed tomography (CT) angiography (CTA) and magnetic resonance (MR) angiography are still employed for postoperative surveillance along with computational fluid dynamics and contrast-enhanced ultrasound (CEUS). The advancements in artificial intelligence (AI) have been the breakthrough in developing robust imaging applications., Conclusions: This review explains the advantages, disadvantages, and side-effect profile of the abovementioned imaging modalities., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Development of rapid bacterial identification from blood cultures has been an area of intense study in diagnostic microbiology. Shortened turnaround time coupled with antimicrobial stewardship interventions have been shown to improve patient outcomes and decrease healthcare-associated costs., Objectives: We report the validation of a short incubation method for Gram-positive and Gram-negative bacterial identification utilizing MALDI-TOF MS without additional instrumentation, processing or cost compared with current practice., Methods: Prospective, observational, single-centre study in a quaternary care academic hospital encompassing 376 blood cultures subjected to bacterial identification after short incubation periods of 3-4 and 6-8 h., Results: There was 97.5% species-level identification agreement with tests undertaken after 3-4 h incubation with 83.6% isolates identified, and 99.7% species-level identification agreement after 6-8 h incubation with 96.7% isolates identified., Conclusions: The short incubation method provides a rapid MALDI-TOF MS bacterial identification method, reducing turnaround time by 10-18 h compared with standard practice without additional cost, processing or instrumentation., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Liquid phase exfoliation (LPE) of graphene is a potentially scalable method to produce conductive graphene inks for printed electronic applications. Among LPE methods, wet jet milling (WJM) is an emerging approach that uses high-speed, turbulent flow to exfoliate graphene nanoplatelets from graphite in a continuous flow manner. Unlike prior WJM work based on toxic, high-boiling-point solvents such as n-methyl-2-pyrollidone (NMP), this study uses the environmentally friendly solvent ethanol and the polymer stabilizer ethyl cellulose (EC). Bayesian optimization and iterative batch sampling are employed to guide the exploration of the experimental phase space (namely, concentrations of graphite and EC in ethanol) in order to identify the Pareto frontier that simultaneously optimizes three performance criteria (graphene yield, conversion rate, and film conductivity). This data-driven strategy identifies vastly different optimal WJM conditions compared to literature precedent, including an optimal loading of 15 wt% graphite in ethanol compared to 1 wt% graphite in NMP. These WJM conditions provide superlative graphene production rates of 3.2 g hr -1 with the resulting graphene nanoplatelets being suitable for screen-printed micro-supercapacitors. Finally, life cycle assessment reveals that ethanol-based WJM graphene exfoliation presents distinct environmental sustainability advantages for greenhouse gas emissions, fossil fuel consumption, and toxicity., (© 2024 The Authors. Small published by Wiley‐VCH GmbH.)

Autism Spectrum Disorder (ASD) displays a notable male bias in prevalence. Research into rare (<0.1) genetic variants on the X chromosome has implicated over 20 genes in ASD pathogenesis, such as MECP2 , DDX3X , and DMD . The "female protective effect" in ASD suggests that females may require a higher genetic burden to manifest similar symptoms as males, yet the mechanisms remain unclear. Despite technological advances in genomics, the complexity of the biological nature of sex chromosomes leave them underrepresented in genome-wide studies. Here, we conducted an X chromosome-wide association study (XWAS) using whole-genome sequencing data from 6,873 individuals with ASD (82% males) across Autism Speaks MSSNG, Simons Simplex Cohort SSC, and Simons Foundation Powering Autism Research SPARK, alongside 8,981 population controls (43% males). We analyzed 418,652 X-chromosome variants, identifying 59 associated with ASD (p-values 7.9×10 -6 to 1.51×10 -5 ), surpassing Bonferroni-corrected thresholds. Key findings include significant regions on chrXp22.2 (lead SNP=rs12687599, p=3.57×10 -7 ) harboring ASB9 / ASB11 , and another encompassing DDX53/PTCHD1-AS long non-coding RNA (lead SNP=rs5926125, p=9.47×10 -6 ). When mapping genes within 10kb of the 59 most significantly associated SNPs, 91 genes were found, 17 of which yielded association with ASD ( GRPR , AP1S2 , DDX53 , HDAC8 , PCDH19 , PTCHD1 , PCDH11X , PTCHD1-AS , DMD , SYAP1 , CNKSR2 , GLRA2 , OFD1 , CDKL5 , GPRASP2 , NXF5 , SH3KBP1 ). FGF13 emerged as a novel X-linked ASD candidate gene, highlighted by sex-specific differences in minor allele frequencies. These results reveal significant new insights into X chromosome biology in ASD, confirming and nominating genes and pathways for further investigation., Competing Interests: At the time of this study and its publication, S.W.S. served on the Scientific Advisory Committee of Population Bio. Intellectual property from aspects of his research held at The Hospital for Sick Children are licensed to Athena Diagnostics and Population Bio. These relationships did not influence data interpretation or presentation during this study but are disclosed for potential future considerations.

Background and Purpose: Treatment-induced effects are difficult to differentiate from progressive disease in radiologically progressing diffuse gliomas after treatment. This retrospective, single-center cohort study investigated the diagnostic value of arterial spin-labeling perfusion in differentiating progressive disease from treatment-induced effects in irradiated patients with a high-grade glioma., Materials and Methods: Adults with a high-grade glioma diagnosed between January 1, 2012, and December 31, 2018, with a new or increasing contrast-enhancing lesion after radiotherapy with or without chemotherapy and arterial spin-labeling were consecutively included. Arterial spin-labeling is part of the routine follow-up examinations of patients with a high-grade glioma. The outcomes of progressive disease or treatment-induced effects were defined after histologic or >6 weeks radiologic follow-up. Two neuroradiologists graded the arterial spin-labeling visually as negative (hypointense to gray matter) or positive (iso-/hyperintense). Additionally, the arterial spin-labeling signal intensity in the enhancing lesion was compared quantitatively with that in the contralateral normal brain. Diagnostic test properties and the Cohen κ inter- and intrarater reliability were determined. We present data according to the time after radiation therapy., Results: We included 141 patients with 173 lesions (median age, 63 years). Ninety-four (54%) lesions showed treatment-induced effects, and 79 (46%), progressive disease. For visual analysis, the ORs of an arterial spin-labeling positive for progressive disease in the group with progression within 3, between 3 and 6, and after 6 months after radiation therapy were 0.65 (95% CI, 0.28-1.51; P  = .319), 3.5 (95% CI, 0.69-17.89; P  = .132), and 6.8 (95% CI, 1.48-32; P  = .014). The areas under the curve were 0.456, 0.652, and 0.719. In quantitative analysis, the areas under the curve were 0.520, 0.588, and 0.587 in these groups. Inter- and intrarater reliability coefficients were 0.67 and 0.62., Conclusions: Arterial spin-labeling performed poorly in differentiating progressive disease from treatment-induced effects in high-grade gliomas within 6 months after radiation therapy, with fair performance after this period. Arterial spin-labeling may need to be combined with other imaging features and clinical information for better performance., (© 2024 by American Journal of Neuroradiology.)

Introduction: In today's world, digital technologies have become pervasive, impacting every aspect of our lives. Even in subjects such as Health and Physical Education (HPE), which traditionally emphasizes experiential, active, and corporeal learning, there is a growing interest in the role and influence of new technologies. These technologies not only have the potential to transform human movement and health cultures, but they also offer valuable tools to facilitate teachers' work and enhance student learning. Considering the context of the Research Network on Interactive Digital Didactic Materials, which includes researchers from Iberoamerican countries, this research examines how media and digital technologies are considered in the official Physical Education and curriculum documents from Brazil, Uruguay, Chile, Colombia, and Spain., Methods: The research comprises a content analysis of official National Curricular Proposals of the selected countries. Considering the specificities of each country to publish their curricula policies, we selected eight different documents from five countries (Brazil, Uruguay, Spain, Colombia, and Chile). We looked for indicators expressed by terms such as "media," "digital culture," and "technology" in the documents, all of them related to Physical Education., Results: The findings show arguments and proposals for using technology in Physical Education in all documents. However, the curricula trigger this theme in different forms, as an autonomous or transversal character integrated into subjects such as HPE. This fact may be highlighted by the goals of learning areas, which sometimes trigger teaching themes through technology., Discussion: Under the Media-Education theory lens, we argue that there is no standard for educational investment in curricula in media and technology. Some documents point to the technology use dimension, while others point to the critical or productive dimension that technology makes possible. The literature highlights the need for an organic approach between these dimensions, and educators and policymakers are asked to rethink their curriculum proposals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 de Araújo, Xavier, Moya-Mata, da Costa, Canon-Buitrago, Oliverira and Carvalho.)

A critical body of knowledge has developed through advances in protein microscopy, protein-fold modeling, structural biology software, availability of sequenced bacterial genomes, large-scale mutation databases, and genome-scale models. Based on these recent advances, we develop a computational framework that; i) identifies the oligomeric structural proteome encoded by an organism's genome from available structural resources; ii) maps multi-strain alleleomic variation, resulting in the structural proteome for a species; and iii) calculates the 3D orientation of proteins across subcellular compartments with residue-level precision. Using the platform, we; iv) compute the quaternary E. coli K-12 MG1655 structural proteome; v) use a dataset of 12,000 mutations to build Random Forest classifiers that can predict the severity of mutations; and, in combination with a genome-scale model that computes proteome allocation, vi) obtain the spatial allocation of the E. coli proteome. Thus, in conjunction with relevant datasets and increasingly accurate computational models, we can now annotate quaternary structural proteomes, at genome-scale, to obtain a molecular-level understanding of whole-cell functions., Significance: Advancements in experimental and computational methods have revealed the shapes of multi-subunit proteins. The absence of a unified platform that maps actionable datatypes onto these increasingly accurate structures creates a barrier to structural analyses, especially at the genome-scale. Here, we describe QSPACE, a computational annotation platform that evaluates existing resources to identify the best-available structure for each protein in a user's query, maps the 3D location of actionable datatypes ( e.g. , active sites, published mutations) onto the selected structures, and uses third-party APIs to determine the subcellular compartment of all amino acids of a protein. As proof-of-concept, we deployed QSPACE to generate the quaternary structural proteome of E. coli MG1655 and demonstrate two use-cases involving large-scale mutant analysis and genome-scale modelling.

Introduction: Clinical workplaces offer unrivalled learning opportunities if students get pedagogic and affective support that enables them to confidently participate and learn from clinical activities. If physicians do not greet new students, the learners are deprived of signals of social respect and inclusion. This study explored how physicians' non-greeting behaviour may impact medical students' participation, learning, and professional identity formation in clinical placements., Methods: We analysed 16 senior Norwegian medical students' accounts of non-greeting behaviours among their physician supervisors in a reflexive thematic analysis of focus group interview data., Results: The main themes were: A) Descriptions of non-greeting . Not being met with conduct signalling rapport, such as eye contact, saying hello, using names, or introducing students at the workplace, was perceived as non-greeting, and occurred across clinical learning contexts. B) Effects on workplace integration . Non-greeting was experienced as a rejection that hurt students' social confidence, created distance from the physician group, and could cause avoidance of certain workplace activities or specific medical specialties. C) Impact on learning . Non-greeting triggered avoidance and passivity, reluctance to ask questions or seek help or feedback, and doubts about their suitability for a medical career., Conclusion: Medical students' accounts of being ignored or treated with disdain by physician superiors upon entering the workplace suggest that unintended depersonalising behaviour is ingrained in medical culture. Interaction rituals like brief eye contact, a nod, a "hello", or use of the student's name, can provide essential affective support that helps medical students thrive and learn in the clinic., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Context: The development of porous devices using materials modified with various natural agents has become a priority for bone healing processes in the oral and maxillofacial field. There must be a balance between the proliferation of eukaryotic and the inhibition of prokaryotic cells to achieve proper bone health. Infections might inhibit the formation of new alveolar bone during bone graft augmentation. Objective: This study aimed to evaluate the in vitro osteogenic behavior of human bone marrow stem cells and assess the antimicrobial response to 3D-printed porous scaffolds using propolis-modified wollastonite. Methodology: A fractional factorial design of experiments was used to obtain a 3D printing paste for developing scaffolds with a triply periodic minimal surface (TPMS) gyroid geometry based on wollastonite and modified with an ethanolic propolis extract. The antioxidant activity of the extracts was characterized using free radical scavenging methods (DPPH and ABTS). Cell proliferation and osteogenic potential using Human Bone Marrow Stem Cells (bmMSCs) were assessed at different culture time points up to 28 days. MIC and inhibition zones were studied from single strain cultures, and biofilm formation was evaluated on the scaffolds under co-culture conditions. The mechanical strength of the scaffolds was evaluated. Results: Through statistical design of experiments, a paste suitable for printing scaffolds with the desired geometry was obtained. Propolis extracts modifying the TPMS gyroid scaffolds showed favorable cell proliferation and metabolic activity with osteogenic potential after 21 days. Additionally, propolis exhibited antioxidant activity, which may be related to the antimicrobial effectiveness of the scaffolds against S. aureus and S. epidermidis cultures. The mechanical properties of the scaffolds were not affected by propolis impregnation. Conclusion: These results demonstrate that propolis-impregnated porous wollastonite scaffolds might have the potential to stimulate bone repair in maxillofacial tissue engineering applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Moreno Florez, Malagon, Ocampo, Leal-Marin, Ossa, Glasmacher, Garcia and Pelaez-Vargas.)

Background & Aims: Irritable bowel syndrome (IBS) shows genetic predisposition, and large-scale genome-wide association studies (GWAS) are emerging, based on heterogeneous disease definitions. We investigated the genetic architecture of IBS defined according to gold standard Rome Criteria., Methods: We conducted GWAS meta-analyses of Rome III IBS and its subtypes in 24,735 IBS cases and 77,149 asymptomatic control subjects from 2 independent European cohorts (UK Biobank and Lifelines). Single-nucleotide polymorphism (SNP)-based heritability (h 2 SNP ) and genetic correlations (r g ) with other traits were calculated. IBS risk loci were functionally annotated to identify candidate genes. Sensitivity and conditional analyses were conducted to assess impact of confounders. Polygenic risk scores were computed and tested in independent datasets., Results: Rome III IBS showed significant SNP-heritability (up to 13%) and similar genetic architecture across subtypes, including those with manifestations at the opposite ends of the symptom spectrum (r g  = 0.48 between IBS-D and IBS-C). Genetic correlations with other traits highlighted commonalities with family history of heart disease and hypertension, coronary artery disease, and angina pectoris (r g  = 0.20-0.45), among others. Four independent GWAS signals (P < 5×10 -8 ) were detected, including 2 novel loci for IBS (rs2035380) and IBS-mixed (rs2048419) that had been previously associated with hypertension and coronary artery disease. Functional annotation of GWAS risk loci revealed genes implicated in circadian rhythm (BMAL1), intestinal barrier (CLDN23), immunomodulation (MFHAS1), and the cyclic adenosine monophosphate pathway (ADCY2). Polygenic risk scores allowed the identification of individuals at increased risk of IBS (odds ratio, 1.34; P = 1.1×10 -3 )., Conclusions: Rome III Criteria capture higher SNP-heritability than previously estimated for IBS. The identified link between IBS and cardiovascular traits may contribute to the delineation of alternative therapeutic strategies, warranting further investigation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This paper proposes a new methodology for the automatic detection of magnetic disturbances from magnetic inertial measurement unit (MIMU) sensors based on deep learning. The proposed approach considers magnetometer data as input to a long short-term memory (LSTM) neural network and obtains a labeled time series output with the posterior probabilities of magnetic disturbance. We trained our algorithm on a data set that reproduces a wide range of magnetic perturbations and MIMU motions in a repeatable and reproducible way. The model was trained and tested using 15 folds, which considered independence in sensor, disturbance direction, and signal type. On average, the network can adequately detect the disturbances in 98% of the cases, which represents a significant improvement over current threshold-based detection algorithms.

The growing recognition of differences in health outcomes across populations has led to a slow but increasing shift towards transparent reporting of patient outcomes. In addition, pay-for-equity initiatives, such as those proposed by the Centers for Medicare and Medicaid, will require the reporting of health outcomes across subgroups over time. Dashboards offer one means of visualising data in the health-care context that can highlight essential disparities in clinical outcomes, guide targeted quality-improvement efforts, and ultimately improve health equity. In this Viewpoint, we evaluate all studies that have reported the successful development of a disparity dashboard and share the data collected and unintended consequences reported. We propose a framework for systematic equality improvement through incentivisation of the collecting and reporting of health data and through implementation of reward systems to reduce health disparities., Competing Interests: Declaration of interests ID-M declares leadership or fiduciary roles and stock or stock options in IBM Watson Health, Merative, and Marti Health. SK declares institutional grants or contracts from IBM Corporation for research related to health equity dashboard design. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

ObjectiveSuh et al (2019) found that treatments for perfectionism, even online, reduce perfectionism and concomitant psychopathology. This meta-analysis investigated the efficacy of Internet interventions and psychotherapeutic interventions for perfectionism as potential tools for overburdened college counseling centers where perfectionism is particularly prevalent. Method : PubMed, MEDLINE, and PsycINFO were searched for relevant treatment studies. Comprehensive Meta-analysis V3 was used to compute and pool effect sizes for perfectionism and concomitant psychopathology. Results : Psychological interventions ( N  = 18) for perfectionism yielded significant reductions in perfectionistic strivings ( g  = .394; n  = 16), concerns ( g  = .603; n  = 17), and clinical perfectionism ( g  = .960; n  = 8). Effect sizes were small-to-medium for depression ( g  = .601; n  = 12), anxiety ( g  = .399; n  = 13), and eating disorder symptoms ( g  = .477; n  = 7). Effect sizes were similar for Internet-mediated and non-Internet-mediated interventions. Most interventions used 8-10-session cognitive-behavioral therapy of perfectionism. Conclusion : Internet interventions for perfectionism reduce perfectionism and concomitant psychopathology. College counseling centers could eventually use them to reduce demand for in-person services.