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Introduction/Justification: The use of artificial intelligence using convolutional neural networks in clinical practice is recent. Thus, a growing need exists to validate software performance in different tasks in different diseases. Objectives: To evaluate the performance of artificial intelligence software to determine metabolic tumor burden in the primary staging of rectal cancer. Materials and Methods: A cross-sectional retrospective analysis was conducted on 51 histology-proven rectal cancer patients (35% females; mean age = 61 years) who underwent a staging 18F-FDG PET/CT. Whole-body metabolic tumor burden parameters (wbMTV and wbTLG) were quantified semi-automatically and through AI algorithm (Syngovia VB60; Siemens Healthineers Medical Solutions). The AI software's ability to correctly identify and classify the primary lesion, regional lymph nodes, and distant metastases was evaluated. In addition, the intraclass correlation coefficient (ICC) was applied to evaluate concordance between the AI-based software and the semiautomatic software in determining wbMTV and wbTLG. Values above 0.7 were considered to indicate substantial agreement. Resultados: The AI and semiautomatic tumor burden metrics correlated strongly for both wbMTV (ICC = 1.00; 95% CI = 0.94 - 0.99; P < 0.0000) and wbTLG (ICC = 1.00; 95% CI = 0.80 – 0.90; P < 0.0000). Additionally, the AI software's ability to correctly identify lesions compared to the documented staging was better for the identification of distant metastasis (78,57% of patients), mildly adequate to identify regional lymph nodes (50,00%) and had poor performance for identification of the primary lesion (5,76%). On the other hand, the time spent calculating these metrics was less by AI than by the semiautomatic method, especially in patients with advanced disease. Conclusion: The determination of whole-body metabolic tumor burden on 18F-FDG PET/CT with artificial intelligence software is challenging because of the physiologic bowel activity. However, deep learning may have the ability to overcome these challenges and may therefore improve the primary staging of rectal cancer.

Civil society has played an important role in meeting the challenges of refugee migration in recent years. This commentary documents the importance of civic engagement for the integration of refugees by linking individual survey data on refugees to a regional measure of civic engagement in Germany. Using the density of newly established civic associations at the county level as a measure of civic engagement, we exploit regional differences in civic engagement in order to estimate its association with refugee integration outcomes. We find that in regions with particularly high levels of civic engagement, refugees have significantly more frequent contact to Germans, higher life satisfaction, and better German language skills. This correlation is robust to regional contextual factors such as the local population structure, economic strength, and the state of the labor market. In terms of language acquisition, women and refugees with a low level of education benefit the most from high civic engagement. Moreover, refugees with university degrees find significantly better-paying jobs in areas with higher civic engagement. However, no direct correlation could be established between civic engagement and the likelihood that refugees are employed. Nonetheless, the results suggest that support from civil society translates into improved access to government benefits. Our findings highlight that local civic engagement is an important complement to public assistance services and policy makers should give a high priority to partnering with the civil society to improve refugees’ integration outcomes.

Anophelinae mosquitoes are exposed to a variety of microbes including Plasmodium parasites that cause malaria. When infected, mosquitoes mount versatile immune responses, including the production of antimicrobial peptides. Cecropins are one of the most widely distributed families of antimicrobial peptides in insects and all previously studied Anopheles members are playing roles in adult mosquito immunity. We have identified and characterized a novel member of the Anopheles gambiae cecropin family, cecropin D (CecD), that is uniquely expressed and immune-responsive at late larval stages to promote microbial clearance through its broad-spectrum antibacterial activity during larval-pupal developmental transition. Interestingly, Cecropin D also exhibited highly potent activity against Plasmodium falciparum sporozoites, the malaria parasite stage that is transmitted from mosquitoes and infects humans and thereby holds promise as a malaria transmission-blocking agent. Finally, we have defined unequivocal cecropin-specific molecular signatures to systematically organize the diversity of the cecropin family in malaria vectors., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Barreto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In technology education, there has been a paradigmatic shift towards student-centered approaches such as learning by doing, constructionism, and experiential learning. Educational robotics allows students to experiment with building and interacting with their creations while also fostering collaborative work. However, understanding the student's response to these approaches is crucial to adapting them during the teaching-learning process. In this sense, neuroscientific tools such as Functional Near-Infrared Spectroscopy and Eye-tracker could be useful, allowing the investigation of relevant states experienced by students. Although they have already been used in educational research, their practical relevance in the teaching-learning process has not been extensively investigated. In this perspective article expressing our position, we bring four examples of learning experiences in a robotics class with children, in which we illustrate the usefulness of these tools., Competing Interests: Declaration of competing interest We declare no conflict of interest in this publication., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting individuals worldwide and characterized by deficits in social interaction along with the presence of restricted interest and repetitive behaviors. Despite decades of behavioral research, little is known about the brain mechanisms that influence social behaviors among children with ASD. This, in part, is due to limitations of traditional imaging techniques specifically targeting pediatric populations. As a portable and scalable optical brain monitoring technology, functional near infrared spectroscopy (fNIRS) provides a measure of cerebral hemodynamics related to sensory, motor, or cognitive function. Here, we utilized fNIRS to investigate the prefrontal cortex (PFC) activity of young children with ASD and with typical development while they watched social and nonsocial video clips. The PFC activity of ASD children was significantly higher for social stimuli at medial PFC, which is implicated in social cognition/processing. Moreover, this activity was also consistently correlated with clinical measures, and higher activation of the same brain area only during social video viewing was associated with more ASD symptoms. This is the first study to implement a neuroergonomics approach to investigate cognitive load in response to realistic, complex, and dynamic audiovisual social stimuli for young children with and without autism. Our results further confirm that new generation of portable fNIRS neuroimaging can be used for ecologically valid measurements of the brain function of toddlers and preschool children with ASD.

Spatial cognition plays a crucial role in academic achievement, particularly in science, technology, engineering, and mathematics (STEM) domains. Immersive virtual environments (VRs) have the growing potential to reduce cognitive load and improve spatial reasoning. However, traditional methods struggle to assess the mental effort required for visuospatial processes due to the difficulty in verbalizing actions and other limitations in self-reported evaluations. In this neuroergonomics study, we aimed to capture the neural activity associated with cognitive workload during visuospatial tasks and evaluate the impact of the visualization medium on visuospatial task performance. We utilized functional near-infrared spectroscopy (fNIRS) wearable neuroimaging to assess cognitive effort during spatial-reasoning-based problem-solving and compared a VR, a computer screen, and a physical real-world task presentation. Our results reveal a higher neural efficiency in the prefrontal cortex (PFC) during 3D geometry puzzles in VR settings compared to the settings in the physical world and on the computer screen. VR appears to reduce the visuospatial task load by facilitating spatial visualization and providing visual cues. This makes it a valuable tool for spatial cognition training, especially for beginners. Additionally, our multimodal approach allows for progressively increasing task complexity, maintaining a challenge throughout training. This study underscores the potential of VR in developing spatial skills and highlights the value of comparing brain data and human interaction across different training settings.

Background: Despite current improvements in systemic cancer treatment, brain metastases (BM) remain incurable, and there is an unmet clinical need for effective targeted therapies., Methods: Here, we sought common molecular events in brain metastatic disease. RNA sequencing of thirty human BM identified the upregulation of UBE2C , a gene that ensures the correct transition from metaphase to anaphase, across different primary tumor origins., Results: Tissue microarray analysis of an independent BM patient cohort revealed that high expression of UBE2C was associated with decreased survival. UBE2C-driven orthotopic mouse models developed extensive leptomeningeal dissemination, likely due to increased migration and invasion. Early cancer treatment with dactolisib (dual PI3K/mTOR inhibitor) prevented the development of UBE2C-induced leptomeningeal metastases., Conclusions: Our findings reveal UBE2C as a key player in the development of metastatic brain disease and highlight PI3K/mTOR inhibition as a promising anticancer therapy to prevent late-stage metastatic brain cancer., (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

BACKGROUND Endometriosis is a chronic inflammatory disease caused by endometrial tissue that grows outside the uterus. Deep endometriosis surgery is associated with considerable rates of complications, although such rates are lower in surgical procedures carried out by expert surgical teams. This report details a case of a rare but life-threatening complication in the postoperative period following 72 h of endometriosis surgery: a giant subcapsular hepatic hematoma, which was successfully managed conservatively. CASE REPORT Here we describe the case of a 39-year-old woman with deep endometriosis with ureteral, ovarian, and intestinal involvement requiring multidisciplinary surgery. She presented with severe anemia, respiratory distress, and oliguria 72 h postoperatively. A 3-phase computed tomography (CT) scan revealed a giant intrahepatic subcapsular hematoma (180×165×50 mm) lateral to the right hepatic lobe, which was managed conservatively. The patient evolved favorably and the hematoma was reduced (77×16 mm) in a follow-up CT scan performed 5 months later. CONCLUSIONS Giant liver hematoma is a rare, life-threatening complication. The current experience relating to its management remains largely limited owing to the rarity of the condition and paucity of published cases. Actually, we found no articles on hepatic hematoma in the context of endometriosis surgery. Early diagnosis and treatment are essential to reduce the patient's risk of death. Imaging diagnosis plays an essential role.

Purpose: Spasticity is the result of a variety of lesions to the central nervous system and one of the most common causes of disability worldwide. Selective peripheral neurectomy (SPN) is a surgical procedure that permanently decreases focal spasticity. The authors' objective is to provide recommendations, in terms of probabilities, for locating terminal motor entry points to muscles of the thigh, as alternatives for proximal incision sites to SPN., Methods: The femoral, obturator, and sciatic nerves, and its corresponding motor rami, were systematically dissected on cadaveric specimens, and terminal motor entry points to each muscle of the thigh were located and carefully measured, relative to the length of the thigh. Measurement distributions were obtained and normal transformations were used when necessary., Results: In 23 adult cadaveric specimens, 779 motor rami were dissected. Entry points' locations are presented as a percentage of the length of the thigh in means and standard deviations, which roughly corresponds to 64 and 95% probability of finding a motor entry point., Conclusion: Alternative incisions directly over the motor entry points, for the muscles of the thigh, may be helpful when considering SPN as treatment for focal spasticity. A prior degree of certainty of the location of the nerve to be severed may simplify surgical approach., (© 2022. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Crustins represent the largest and most diverse family of antimicrobial peptides (AMPs) found in crustaceans. They are classically defined as disulfide-rich peptides/polypeptides holding a typical Whey Acidic Protein (WAP) domain at the C-terminal end. This WAP domain has eight cysteine residues forming a tightly packed structure, the four-disulfide core (4DSC) motif, that is also found in other proteins displaying protease inhibitory properties. Crustins are highly diverse in terms of primary structure, size and biochemical features, thus exhibiting a series of biological functions beyond their antimicrobial properties. In order to better categorize the distinct crustin members, different classification systems have been proposed. In this review, we discuss the current classification systems and explore the biological implication of the impressive molecular diversity of this unique AMP family. We also summarize the recent findings on the role of these effectors in crustacean immunity and homeostasis as well as in host-microbe interactions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier Ltd.)

Hyperscanning is a promising tool for investigating the neurobiological underpinning of social interactions and affective bonds. Recently, graph theory measures, such as modularity, have been proposed for estimating the global synchronization between brains. This paper proposes the bootstrap modularity test as a way of determining whether a pair of brains is coactivated. This test is illustrated as a screening tool in an application to fNIRS data collected from the prefrontal cortex and temporoparietal junction of five dyads composed of a teacher and a preschooler while performing an interaction task. In this application, graph hub centrality measures identify that the dyad's synchronization is critically explained by the relation between teacher's language and number processing and the child's phonological processing. The analysis of these metrics may provide further insights into the neurobiological underpinnings of interaction, such as in educational contexts., 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 © 2022 Oku, Barreto, Bruneri, Brockington, Fujita and Sato.)

Background and Aims: Central line-associated bloodstream infections (CLABSIs) are the main complication in children with home parenteral nutrition (HPN) and some patients develop recurrent CLABSIs (REC-CLABSIs), defined as two or more infections within six months. Our aims were to assess the incidence and to characterize the risk factors of REC-CLABSIs in children with HPN., Methods: We characterized 79 HPN children from 2014 to 2019 and calculated the incidence of CLABSIs. To minimize the risk of bias related to the exposure time of the septic risk, we paired the patients according to their central venous catheter (CVC) dwell time. After analyzing the whole cohort, a univariate and multivariate unconditional logistic regression was performed on the paired cohort., Results: We included 75 (94.9%) children with a mean age of 7.11 years. The rate of septicemia was 1.55/1000 CVC days, mainly with Staphyloccocus sp. The patients with recurrent CLABSIs (REC group) represented 25% of the cohort, with an incidence of 2.99/1000 CVC days. In the whole cohort, a higher risk of recurrent infections was significantly associated with a longer CVC dwell time (OR = 1.04, IC 95% [1.01-1.06], p = 0.004), and with care located in rehabilitation care facilities (RCF) compared to home (OR = 6, IC 95% [1.5-26.6], p = 0.012). When children were paired according to their CVC dwell time, only in univariate analysis did the care in RCF remain significant (OR = 6.27, IC 95% [1.21-32.5], p = 0.03)., Conclusions: Recurrent CLABSIs incidence was 2.99/1000 CVC days. Our study suggests that preventive measures should be implemented especially in RCFs to reduce the proportion of children with recurrent infections. A multicenter study is needed to confirm our results in a larger cohort with several RCFs., Competing Interests: Conflict of interest The authors disclose no conflicts of interest., (Copyright © 2022 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

A total of 92 coronavirus disease 2019 clusters involving 1,156 individuals (729 patients and 427 healthcare workers) occurred in Lyon University Hospital between September 1, 2020 and March 31, 2021, mostly on medical and geriatric wards. The number of clusters was closely correlated to the trend in coronavirus disease 2019 community incidence over time; in-hospital clusters did not persist when community incidence decreased. Recommended preventive measures were not fully applicable due to specific ward-associated determinants and patient characteristics., (Copyright © 2022 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Few standard treatment options are available for patients with metastatic sarcomas. We did this trial to evaluate the efficacy, safety, and changes in the tumour microenvironment for durvalumab, an anti-PD-L1 drug, and tremelimumab, an anti-CTLA-4 drug, across multiple sarcoma subtypes., Methods: In this single-centre phase 2 trial, done at The University of Texas MD Anderson Cancer Center (Houston, TX USA), patients aged 18 years or older with advanced or metastatic sarcoma with an Eastern Cooperative Oncology Group performance status of 0 or 1 who had received at least one previous line of systemic therapy were enrolled in disease subtype-specific groups (liposarcoma, leiomyosarcoma, angiosarcoma, undifferentiated pleomorphic sarcoma, synovial sarcoma, osteosarcoma, alveolar soft-part sarcoma, chordoma, and other sarcomas). Patients received 1500 mg intravenous durvalumab and 75 mg intravenous tremelimumab for four cycles, followed by durvalumab alone every 4 weeks for up to 12 months. The primary endpoint was progression-free survival at 12 weeks in the intention-to-treat population (all patients who received at least one dose of treatment). Safety was also analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02815995, and is completed., Findings: Between Aug 17, 2016, and April 9, 2018, 62 patients were enrolled, of whom 57 (92%) received treatment and were included in the intention-to-treat population. With a median follow-up of 37·2 months (IQR 1·8-10·1), progression-free survival at 12 weeks was 49% (95% CI 36-61). 21 grade 3-4 treatment-related adverse events were reported, the most common of which were increased lipase (four [7%] of 57 patients), colitis (three [5%] patients), and pneumonitis (three [5%] patients). Nine (16%) patients had a treatment related serious adverse event. One patient had grade 5 pneumonitis and colitis., Interpretation: The combination of durvalumab and tremelimumab is an active treatment regimen for advanced or metastatic sarcoma and merits evaluation in specific subsets in future trials., Funding: AstraZeneca., Competing Interests: Declaration of interests NS participated in the advisory board of Boehringer Ingelheim. APC reports consulting fees from Deciphera, Inhibrx, Bayer, and Genentech; and participated in the advisory board of Applied Clinical Intelligence. CH reports research funding from Dragonfly and Lovance; salary supported in part by National Institute for Health (NIH) grants (P30CA016672, P50CA221703, U24CA224285, and R01CA236905); consulting fees from Nanobiotix; honoraria from Society for Immunotherapy of Cancer; and stock options from Briacell. SS reports support for attending meetings and travel from Medtronic, and stocks from Inari. AJL reports research funding and consulting fees from, and advisory board membership for AstraZeneca. CLR reports research funding from Bristol Myers Squibb. AF reports research funding paid to institution from NIH (U01 CA224044-02). J-CS reports a leadership role as a fulltime employee at AstraZeneca from September, 2017, to December, 2019; a leadership role as a fulltime employee at Amgen since August, 2021; and is a stock owner from Relay Therapeutics and Gritstone Bio. IIW reports research funding to their institution from Genentech, HTG Molecular, Merck, Bristol Myers Squibb, MedImmune, Adaptive, Adaptimmune, EMD Serono, Pfizer, Takeda, Amgen, Karus, Johnson & Johnson, Bayer, Iovance, 4D, Novartis, and Akoya; scientific and financial support for the institutional Cancer Immune Monitoring and Analysis Center-Cancer Immunologic Data Commons Network through the National Cancer Institute of the NIH Cooperative Agreement U24CA224285); consulting fees from Roche, Bayer, Bristol Myers Squibb, AstraZeneca, Pfizer, HTG Molecular, Merck, GlaxoSmithKline, Guardant Health, Novartis, Flame, Sanofi, Janssen, Daiichi Sankyo, Oncocyte, Amgen, and MSD; and honoraria from Medscape, Roche, Pfizer, AstraZeneca, Platform Health, and Merck. PH reports advisory board membership for Dragonfly Scientific Advisory Board (SAB) and Immatics SAB. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The current climate crisis demands replacement of fossil energy sources with sustainable alternatives. In this scenario, second-generation bioethanol, a product of lignocellulosic biomass fermentation, represents a more sustainable alternative. However, Saccharomyces cerevisiae cannot metabolize pentoses, such as xylose, present as a major component of lignocellulosic biomass. Xylose isomerase (XI) is an enzyme that allows xylose consumption by yeasts, because it converts xylose into xylulose, which is further converted to ethanol by the pentose-phosphate pathway. Only a few XI were successfully expressed in S. cerevisiae strains. This work presents a new bacterial XI, named GR-XI 1, obtained from a Brazilian goat rumen metagenomic library. Phylogenetic analysis confirmed the bacterial origin of the gene, which is related to Firmicutes XIs. After codon optimization, this enzyme, renamed XySC1, was functionally expressed in S. cerevisiae, allowing growth in media with xylose as sole carbon source. Overexpression of XySC1 in S. cerevisiae allowed the recombinant strain to efficiently consume and metabolize xylose under aerobic conditions., (© 2022 The Society for Applied Microbiology.)

Amniotic band syndrome (ABS) is a congenital disease that causes a variable degree of deformity and tissue disruption. Surgical excision of fibrotic tissue and advancement of local flaps is the gold standard for constriction bands of the upper limb. We report the use of an adipofascial Superficial Circumflex Iliac Artery perforator (SCIP) flap to improve contour following amniotic band resection in the upper extremity in two patients with ABS. The use of this microsurgical technique can be considered in the occasional patient when there is a deficit of soft tissues after release of the contracture band that cannot be addressed with locally available tissue.

The introduction of immune checkpoint inhibitors represented a breakthrough treatment for metastatic melanoma, but the effect of these agents is not limited to a single cancer type. Promising results have been reported in various solid tumors, for example, lung cancer. The success of these drugs depends on the activation of tumor-infiltrating lymphocytes and primary and acquired resistance have been reported alongside a high rate of immune-related adverse events when agents targeting different immune checkpoints are given in combination. Numerous other targets have been investigated to overcome the resistance, improve the activity, and reduce the toxicity of checkpoint inhibitor therapy. Among these, the most promising is Lymphocyte-activation gene 3 (LAG-3), a transmembrane protein involved in cytokine release and inhibitory signaling in T cells. Preclinical data showed that LAG-3 is a negative regulator of both CD4 + T cell and CD8 + T cell and the activity on CD8 + T cell is independent of CD4 + activation. On the CD8 + T cell, LAG-3 activation abrogates the antigen presentation whereas on the CD4 + T cell, arrests the S phase of the cell cycle. The blockade of LAG-3 has been tested in several combination therapies, and recent clinical data showed a good safety profile and a synergistic effect with anti-PD-1, suggesting that this combination could become a standard treatment for metastatic melanoma. In this review, we report the available preclinical data and the new clinical data on LAG-3 blockade in different solid tumors, and we discuss LAG-3 as potential prognostic and predictive factor, together with possible future applications., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Proteomic analyses have become an essential part of the toolkit of the molecular biologist, given the widespread availability of genomic data and open source or freely accessible bioinformatics software. Tools are available for detecting homologous sequences, recognizing functional domains, and modeling the three-dimensional structure for any given protein sequence, as well as for predicting interactions with other proteins or macromolecules. Although a wealth of structural and functional information is available for many cytoskeletal proteins, with representatives spanning all of the major subfamilies, the majority of cytoskeletal proteins remain partially or totally uncharacterized. Moreover, bioinformatics tools provide a means for studying the effects of synthetic mutations or naturally occurring variants of these cytoskeletal proteins. This chapter discusses various freely available proteomic analysis tools, with a focus on in silico prediction of protein structure and function. The selected tools are notable for providing an easily accessible interface for the novice while retaining advanced functionality for more experienced computational biologists., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The yellow-billed cuckoo, Coccyzus americanus, is a threatened passerine bird native to North America that migrates to overwinter in South America. Although migratory birds have drawn broad attention, given their assumed role in the long-distance dispersal of parasites, studies on the helminth fauna of this cuculid are scarce. In the present study, nematodes found in the gastrointestinal tract of a specimen of C. americanus found in Belo Horizonte, State of Minas Gerais, southeastern Brazil, were characterized morphologically. Five species of gastrointestinal nematodes belonging to 4 families were identified: Synhimantus (Dispharynx) nasuta (Rudolphi, 1819) and Synhimantus (Dispharynx) resticulaCanavan, 1929 (Acuariidae), Microtetrameres sp. (Tetrameridae), and Cyrnea piayaeSandground, 1929 (Habronematidae) and Subulura halli Barreto, 1918 (Subuluridae). Except for Microtetrameres sp., all other nematodes are reported in this host for the first time. Although it is difficult to accurately determine the geographical origin of infections, it is important to note that Sy. (D.) resticula and Su. halli are reported for the first time in Brazil. Additionally, the absence of the former species infecting hosts where the widespread and generalist Sy. (D.) nasuta was found may indicate that Sy. (D.) resticula have either been overlooked in previous studies or that this nematode is rare indeed. Finally, the geographical distribution of Su. halli is greatly expanded and now includes the Americas. Aspects related to the dispersion of these parasites, both in migrating and native hosts, are briefly discussed., (© American Society of Parasitologists 2021.)