Search

Traumatic brain injury impairs function of the glymphatic system, a perivascular network involved in waste clearance. Enlarged perivascular spaces visible on MRI are an emerging biomarker of glymphatic function. This study characterized enlarged perivascular spaces in acute head injury with 7 T MRI. Healthy controls ( n = 8) and patients ( n = 11) with mild traumatic brain injury underwent MRI within 7 days of injury and were evaluated for lifetime history of head injury, neurobehavioral symptoms and sleep disturbances. MRI-visible perivascular spaces were quantified and assessed according to published criteria. The number of enlarged perivascular spaces was significantly higher in traumatic brain injury patients than controls ( P = 0.015). Among healthy controls, 6/8 scored 'none' or 'mild' on the perivascular space rating scale, while 10/11 patients scored 'moderate', 'frequent' or 'severe'. There was an inverse relationship between perivascular space number and number of lifetime head injuries. Patients with more prior head injuries exhibited fewer enlarged perivascular spaces ( P = 0.014). These results indicate that mild head injury results in acute alterations in perivascular space number, and this effect is mediated by previous head injury history. Enlarged perivascular spaces may reflect a glymphatic response that is diminished after multiple head injuries, although this will require further study., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Drug-induced gene expression profiles can identify potential mechanisms of toxicity. We focus on obtaining signatures for cardiotoxicity of FDA-approved tyrosine kinase inhibitors (TKIs) in human induced-pluripotent-stem-cell-derived cardiomyocytes, using bulk transcriptomic profiles. We use singular value decomposition to identify drug-selective patterns across cell lines obtained from multiple healthy human subjects. Cellular pathways affected by cardiotoxic TKIs include energy metabolism, contractile, and extracellular matrix dynamics. Projecting these pathways to published single cell expression profiles indicates that TKI responses can be evoked in both cardiomyocytes and fibroblasts. Integration of transcriptomic outlier analysis with whole genomic sequencing of our six cell lines enables us to correctly reidentify a genomic variant causally linked to anthracycline-induced cardiotoxicity and predict genomic variants potentially associated with TKI-induced cardiotoxicity. We conclude that mRNA expression profiles when integrated with publicly available genomic, pathway, and single cell transcriptomic datasets, provide multiscale signatures for cardiotoxicity that could be used for drug development and patient stratification., (© 2024. The Author(s).)

Species within nearly all extant animal lineages are capable of regenerating body parts. However, it remains unclear whether the gene expression programme controlling regeneration is evolutionarily conserved. Brittle stars are a species-rich class of echinoderms with outstanding regenerative abilities, but investigations into the genetic bases of regeneration in this group have been hindered by the limited genomic resources. Here we report a chromosome-scale genome assembly for the brittle star Amphiura filiformis. We show that the brittle star genome is the most rearranged among echinoderms sequenced so far, featuring a reorganized Hox cluster reminiscent of the rearrangements observed in sea urchins. In addition, we performed an extensive profiling of gene expression during brittle star adult arm regeneration and identified sequential waves of gene expression governing wound healing, proliferation and differentiation. We conducted comparative transcriptomic analyses with other invertebrate and vertebrate models for appendage regeneration and uncovered hundreds of genes with conserved expression dynamics, particularly during the proliferative phase of regeneration. Our findings emphasize the crucial importance of echinoderms to detect long-range expression conservation between vertebrates and classical invertebrate regeneration model systems., (© 2024. The Author(s).)

Background: Dengue fever remains a significant public health challenge in tropical and subtropical regions, with its transmission dynamics being influenced by both environmental factors and human mobility. The Dominican Republic, a biodiversity hotspot in the Caribbean, has experienced recurrent dengue outbreaks, yet detailed understanding of the virus's transmission pathways and the impact of climatic factors remains limited. This study aims to elucidate the recent transmission dynamics of the dengue virus (DENV) in the Dominican Republic, utilizing a combination of genomic sequencing and epidemiological data analysis, alongside an examination of historical climate patterns., Methods: We conducted a comprehensive study involving the genomic sequencing of DENV samples collected from patients across different regions of the Dominican Republic over a two-year period. Phylogenetic analyses were performed to identify the circulation of DENV lineages and to trace transmission pathways. Epidemiological data were integrated to analyze trends in dengue incidence and distribution. Additionally, we integrated historical climate data spanning several decades to assess trends in temperature and their potential impact on DENV transmission potential., Results: Our results highlight a previously unknown north-south transmission pathway within the country, with the co-circulation of multiple virus lineages. Additionally, we examine the historical climate data, revealing long-term trends towards higher theoretical potential for dengue transmission due to rising temperatures., Conclusion: This multidisciplinary study reveals intricate patterns of dengue virus transmission in the Dominican Republic, characterized by the co-circulation of multiple DENV lineages and a novel transmission pathway. The observed correlation between rising temperatures and increased dengue transmission potential emphasizes the need for integrated climate-informed strategies in dengue control efforts. Our findings offer critical insights for public health authorities in the Dominican Republic and similar settings, guiding resource allocation and the development of preparedness strategies to mitigate the impacts of climate change on dengue transmission., (© 2024. The Author(s).)

Acoel flatworms have played a relevant role in classical (and current) discussions on the evolutionary origin of bilaterian animals. This is mostly derived from the apparent simplicity of their body architectures. This tenet has been challenged over the last couple of decades, mostly because detailed studies of their morphology and the introduction of multiple genomic technologies have unveiled a complexity of cell types, tissular arrangements and patterning mechanisms that were hidden below this 'superficial' simplicity. One tissue that has received a particular attention has been the nervous system (NS). The combination of ultrastructural and single cell methodologies has revealed unique cellular diversity and developmental trajectories for most of their neurons and associated sensory systems. Moreover, the great diversity in NS architectures shown by different acoels offers us with a unique group of animals where to study key aspects of neurogenesis and diversification od neural systems over evolutionary time.In this review we revisit some recent developments in the characterization of the acoel nervous system structure and the regulatory mechanisms that contribute to their embryological development. We end up by suggesting some promising avenues to better understand how this tissue is organized in its finest cellular details and how to achieve a deeper knowledge of the functional roles that genes and gene networks play in its construction., (© 2024. The Author(s).)

Background and Aim: Until the May 2022 Monkeypox (MPXV) outbreak, which spread rapidly to many non-endemic countries, the virus was considered a viral zoonosis limited to some African countries. The Andalusian circuit of genomic surveillance was rapidly applied to characterize the MPXV outbreak in the South of Spain., Methods: Whole genome sequencing was used to obtain the genomic profiles of samples collected across the south of Spain, representative of all the provinces of Andalusia. Phylogenetic analysis was used to study the relationship of the isolates and the available sequences of the 2022 outbreak., Results: Whole genome sequencing of a total of 160 MPXV viruses from the different provinces that reported cases were obtained. Interestingly, we report the sequences of MPXV viruses obtained from two patients who died. While one of the isolates bore no noteworthy mutations that explain a potential heightened virulence, in another patient the second consecutive genome sequence, performed after the administration of tecovirimat, uncovered a mutation within the A0A7H0DN30 gene, known to be a prime target for tecovirimat in its Vaccinia counterpart. In general, a low number of mutations were observed in the sequences reported, which were very similar to the reference of the 2022 outbreak (OX044336), as expected from a DNA virus. The samples likely correspond to several introductions of the circulating MPXV viruses from the last outbreak. The virus sequenced from one of the two patients that died presented a mutation in a gene that bears potential connections to drug resistance. This mutation was absent in the initial sequencing before treatment., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Aquatic invertebrates play a pivotal role in (eco)toxicological assessments because they offer ethical, cost-effective and repeatable testing options. Additionally, their significance in the food chain and their ability to represent diverse aquatic ecosystems make them valuable subjects for (eco)toxicological studies. To ensure consistency and comparability across studies, international (eco)toxicology guidelines have been used to establish standardised methods and protocols for data collection, analysis and interpretation. However, the current standardised protocols primarily focus on a limited number of aquatic invertebrate species, mainly from Arthropoda, Mollusca and Annelida. These protocols are suitable for basic toxicity screening, effectively assessing the immediate and severe effects of toxic substances on organisms. For more comprehensive and ecologically relevant assessments, particularly those addressing long-term effects and ecosystem-wide impacts, we recommended the use of a broader diversity of species, since the present choice of taxa exacerbates the limited scope of basic ecotoxicological studies. This review provides a comprehensive overview of (eco)toxicological studies, focusing on major aquatic invertebrate taxa and how they are used to assess the impact of chemicals in diverse aquatic environments. The present work supports the use of a broad-taxa approach in basic environmental assessments, as it better represents the natural populations inhabiting various ecosystems. Advances in omics and other biochemical and computational techniques make the broad-taxa approach more feasible, enabling mechanistic studies on non-model organisms. By combining these approaches with in vitro techniques together with the broad-taxa approach, researchers can gain insights into less-explored impacts of pollution, such as changes in population diversity, the development of tolerance and transgenerational inheritance of pollution responses, the impact on organism phenotypic plasticity, biological invasion outcomes, social behaviour changes, metabolome changes, regeneration phenomena, disease susceptibility and tissue pathologies. This review also emphasises the need for harmonised data-reporting standards and minimum annotation checklists to ensure that research results are findable, accessible, interoperable and reusable (FAIR), maximising the use and reusability of data. The ultimate goal is to encourage integrated and holistic problem-focused collaboration between diverse scientific disciplines, international standardisation organisations and decision-making bodies, with a focus on transdisciplinary knowledge co-production for the One-Health approach., (© 2023 Cambridge Philosophical Society.)

During the COVID-19 vaccination rollout from March 2021- December 2022, the Centers for Disease Control and Prevention funded 110 primary and 1051 subrecipient partners at the national, state, local, and community-based level to improve COVID-19 vaccination access, confidence, demand, delivery, and equity in the United States. The partners implemented evidence-based strategies among racial and ethnic minority populations, rural populations, older adults, people with disabilities, people with chronic illness, people experiencing homelessness, and other groups disproportionately impacted by COVID-19. CDC also expanded existing partnerships with healthcare professional societies and other core public health partners, as well as developed innovative partnerships with organizations new to vaccination, including museums and libraries. Partners brought COVID-19 vaccine education into farm fields, local fairs, churches, community centers, barber and beauty shops, and, when possible, partnered with local healthcare providers to administer COVID-19 vaccines. Inclusive, hyper-localized outreach through partnerships with community-based organizations, faith-based organizations, vaccination providers, and local health departments was critical to increasing COVID-19 vaccine access and building a broad network of trusted messengers that promoted vaccine confidence. Data from monthly and quarterly REDCap reports and monthly partner calls showed that through these partnerships, more than 295,000 community-level spokespersons were trained as trusted messengers and more than 2.1 million COVID-19 vaccinations were administered at new or existing vaccination sites. More than 535,035 healthcare personnel were reached through outreach strategies. Quality improvement interventions were implemented in healthcare systems, long-term care settings, and community health centers resulting in changes to the clinical workflow to incorporate COVID-19 vaccine assessments, recommendations, and administration or referrals into routine office visits. Funded partners' activities improved COVID-19 vaccine access and addressed community concerns among racial and ethnic minority groups, as well as among people with barriers to vaccination due to chronic illness or disability, older age, lower income, or other factors., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jane R. Nilson reports a relationship with Astrazeneca (AZN), Amcor (AMCR), and Organon (OGN) and Mutual fund Eventide Healthcare and Life Fund that includes: equity or stocks. Sara Adelsberg, Theresa Bailey, Alexa Frank, and Claire Perkins: CDC has contracted with Deloitte Consulting, LLP, since December 2019 to support CDC’s Immunization Services Division in developing, standing up, and implementing a comprehensive, multi-faceted program focused on reducing racial and ethnic disparities in adult immunization. Deloitte Consulting, LLP, is a large organization that receives funding from many organizations and agencies. CDC funded a number of activities implemented by Deloitte and others. These authors do not have any reason to believe that any activities beyond those included in this support have any material relationship to this manuscript. Elizabeth Sobczyk: serves on an advisory committee for Sanofi Pasteur related to pertussis, separate from her time with AMDA. Julie Zajac: served on the Cooperative Extension System’s Health Innovation Task Force from March 2020 to March 2022. Since December 2022, she has served on the Extension Foundation’s Health Leadership Committee., (Published by Elsevier Ltd.)

In this work, biobased rigid polyurethane foams (PUFs) were developed with the aim of achieving thermal and fireproofing properties that can compete with those of the commercially available products. First, the synthesis of a biopolyol from a wood residue by means of a scaled-up process with suitable yield and reaction conditions was carried out. This biopolyol was able to substitute completely the synthetic polyols that are typically employed within a polyurethane formulation. Different formulations were developed to assess the effect of two flame retardants, namely, polyhedral oligomeric silsesquioxane (POSS) and amino polyphosphate (APP), in terms of their thermal properties and degradation and their fireproofing mechanism. The structure and the thermal degradation of the different formulations was evaluated via Fourier Transformed Infrared Spectroscopy (FTIR) and thermogravimetric analysis (TGA). Likewise, the performance of the different PUF formulations was studied and compared to that of an industrial PUF. From these results, it can be highlighted that the addition of the flame retardants into the formulation showed an improvement in the results of the UL-94 vertical burning test and the LOI. Moreover, the fireproofing performance of the biobased formulations was comparable to that of the industrial one. In addition to that, it can be remarked that the biobased formulations displayed an excellent performance as thermal insulators (0.02371-0.02149 W·m -1 ·K -1 ), which was even slightly higher than that of the industrial one.

Extreme storms can trigger abrupt and often lasting changes in ecosystems by affecting foundational (habitat-forming) species. While the frequency and intensity of extreme events are projected to increase under climate change, its impacts on seagrass ecosystems remain poorly documented. In January 2020, the Spanish Mediterranean coast was hit by Storm Gloria, one of the most devastating recent climate events in terms of intensity and duration. We conducted rapid surveys of 42 Posidonia oceanica meadows across the region to evaluate the extent and type of impact (burial, unburial and uprooting). We investigated the significance of oceanographic (wave impact model), geomorphological (latitude, depth, exposure), and structural (patchiness) factors in predicting impact extent and intensity. The predominant impact of Storm Gloria was shoot unburial. More than half of the surveyed sites revealed recent unburial, with up to 40 cm of sediment removed, affecting over 50 % of the meadow. Burial, although less extensive, was still significant, with 10-80 % of meadow cover being buried under 7 cm of sediment, which is considered a survival threshold for P. oceanica. In addition, we observed evident signs of recently dead matte in some meadows and large amounts of detached drifting shoots on the sea bottom or accumulated as debris on the beaches. Crucially, exposed and patchy meadows were much more vulnerable to the overall impact than sheltered or continuous meadows. Given how slow P. oceanica is able to recover after disturbances, we state that it could take from decades to centuries for it to recoup its losses. Seagrass ecosystems play a vital role as coastal ecological infrastructure. Protecting vulnerable meadows from anthropogenic fragmentation is crucial for ensuring the resilience of these ecosystems in the face of the climate crisis., Competing Interests: Declaration of competing interest 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., (Copyright © 2023. Published by Elsevier B.V.)

The potential to regenerate a damaged body part is expressed to a different extent in animals. Echinoderms, in particular starfish, are known for their outstanding regenerating potential. Differently, humans have restricted abilities to restore organ systems being dependent on limited sources of stem cells. In particular, the potential to regenerate the central nervous system is extremely limited, explaining the lack of natural mechanisms that could overcome the development of neurodegenerative diseases and the occurrence of trauma. Therefore, understanding the molecular and cellular mechanisms of regeneration in starfish could help the development of new therapeutic approaches in humans. In this study, we tackle the problem of starfish central nervous system regeneration by examining the external and internal anatomical and behavioral traits, the dynamics of coelomocyte populations, and neuronal tissue architecture after radial nerve cord (RNC) partial ablation. We noticed that the removal of part of RNC generated several anatomic anomalies and induced behavioral modifications (injured arm could not be used anymore to lead the starfish movement). Those alterations seem to be related to defense mechanisms and protection of the wound. In particular, histology showed that tissue patterns during regeneration resemble those described in holothurians and in starfish arm tip regeneration. Flow cytometry coupled with imaging flow cytometry unveiled a new coelomocyte population during the late phase of the regeneration process. Morphotypes of these and previously characterized coelomocyte populations were described based on IFC data. Further studies of this new coelomocyte population might provide insights on their involvement in radial nerve cord regeneration., (© 2023. The Author(s).)

The strength of electrostatic interactions (EIs) between electrons and holes within semiconductor nanocrystals profoundly affects the performance of their optoelectronic systems, and different optoelectronic devices demand distinct EI strength of the active medium. However, achieving a broad range and fine-tuning of the EI strength for specific optoelectronic applications is a daunting challenge, especially in quasi two-dimensional core-shell semiconductor nanoplatelets (NPLs), as the epitaxial growth of the inorganic shell along the direction of the thickness that solely contributes to the quantum confined effect significantly undermines the strength of the EI. Herein we propose and demonstrate a doubly gradient (DG) core-shell architecture of semiconductor NPLs for on-demand tailoring of the EI strength by controlling the localized exciton concentration via in-plane architectural modulation, demonstrated by a wide tuning of radiative recombination rate and exciton binding energy. Moreover, these exciton-concentration-engineered DG NPLs also exhibit a near-unity quantum yield, high photo- and thermal stability, and considerably suppressed self-absorption. As proof-of-concept demonstrations, highly efficient color converters and high-performance light-emitting diodes (external quantum efficiency: 16.9%, maximum luminance: 43,000 cd/m 2 ) have been achieved based on the DG NPLs. This work thus provides insights into the development of high-performance colloidal optoelectronic device applications.

We reviewed the historical pathway that paved the way for the creation and implementation of public policies for food security in Brazilian schools. We then analyzed the implementation of such policies in Paraíba state (northeastern Brazil) in terms of the investment in purchasing food from familiar agriculture , i.e. agricultural production in small farm units where the labor comes from the owner's family that lives on the farm and receives gross income from agriculture. We conducted this study to determine the extent to which public policies for food security in schools promote income to family farmers in Paraíba state. We obtained data from the Management and Accountability System (SIGPC) to quantify the municipalities in Paraíba state that comply with the national school feeding program denominated Programa Nacional de Alimentação Escolar (PNAE). The fiscal years from 2015 to 2017 were used as a reference period because no data is available for the upcoming years. PNAE has been created to underpin programs offering free meals to school-age children, thus allowing for basic learning conditions while tackling hunger among social groups in poverty. PNAE became a public policy subsidiary of familiar agriculture through the Law 11,947 of 2009 which requires the minimal investment of 30% of PNAE funds to purchase food from family farmers. In Paraíba state, 80% of the municipalities buy food through PNAE. However, nearly 40% of the municipalities do not apply the minimum investment to purchase food from family farmers during the evaluated period (2011-2017). We identified that logistics and transportation of food coordinated by the school feeding councils are the main constraints for greater efficiency of the program. Despite such constraints, PNAE offers a unique opportunity to enhance human wellbeing by fostering family farmers to adopt conservation practices and provide healthy, local food to school-aged children., 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., (© 2023 The Authors.)

Colloidal quantum wells (CQWs), also known as nanoplatelets (NPLs), are exciting material systems for numerous photonic applications, including lasers and light-emitting diodes (LEDs). Although many successful type-I NPL-LEDs with high device performance have been demonstrated, type-II NPLs are not fully exploited for LED applications, even with alloyed type-II NPLs with enhanced optical properties. Here, we present the development of CdSe/CdTe/CdSe core/crown/crown (multi-crowned) type-II NPLs and systematic investigation of their optical properties, including their comparison with the traditional core/crown counterparts. Unlike traditional type-II NPLs such as CdSe/CdTe, CdTe/CdSe, and CdSe/CdSe x Te 1- x core/crown heterostructures, here the proposed advanced heterostructure reaps the benefits of having two type-II transition channels, resulting in a high quantum yield (QY) of 83% and a long fluorescence lifetime of 73.3 ns. These type-II transitions were confirmed experimentally by optical measurements and theoretically using electron and hole wave function modeling. Computational study shows that the multi-crowned NPLs provide a better-distributed hole wave function along the CdTe crown, while the electron wave function is delocalized in the CdSe core and CdSe crown layers. As a proof-of-concept demonstration, NPL-LEDs based on these multi-crowned NPLs were designed and fabricated with a record high external quantum efficiency (EQE) of 7.83% among type-II NPL-LEDs. These findings are expected to induce advanced designs of NPL heterostructures to reach a fascinating level of performance, especially in LEDs and lasers.

Sea urchins are emblematic models in developmental biology and display several characteristics that set them apart from other deuterostomes. To uncover the genomic cues that may underlie these specificities, we generated a chromosome-scale genome assembly for the sea urchin Paracentrotus lividus and an extensive gene expression and epigenetic profiles of its embryonic development. We found that, unlike vertebrates, sea urchins retained ancestral chromosomal linkages but underwent very fast intrachromosomal gene order mixing. We identified a burst of gene duplication in the echinoid lineage and showed that some of these expanded genes have been recruited in novel structures (water vascular system, Aristotle's lantern, and skeletogenic micromere lineage). Finally, we identified gene-regulatory modules conserved between sea urchins and chordates. Our results suggest that gene-regulatory networks controlling development can be conserved despite extensive gene order rearrangement., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

The ability to learn and form memories allows animals to adapt their behavior based on previous experiences. Associative learning, the process through which organisms learn about the relationship between two distinct events, has been extensively studied in various animal taxa. However, the existence of associative learning, prior to the emergence of centralized nervous systems in bilaterian animals, remains unclear. Cnidarians such as sea anemones or jellyfish possess a nerve net, which lacks centralization. As the sister group to bilaterians, they are particularly well suited for studying the evolution of nervous system functions. Here, we probe the capacity of the starlet sea anemone Nematostella vectensis to form associative memories by using a classical conditioning approach. We developed a protocol combining light as the conditioned stimulus with an electric shock as the aversive unconditioned stimulus. After repetitive training, animals exhibited a conditioned response to light alone-indicating that they learned the association. In contrast, all control conditions did not form associative memories. Besides shedding light on an aspect of cnidarian behavior, these results root associative learning before the emergence of NS centralization in the metazoan lineage and raise fundamental questions about the origin and evolution of cognition in brainless animals.

Background: Improvements in the early diagnosis of dengue are urgently needed, especially in resource-limited settings where the distinction between dengue and other febrile illnesses is crucial for patient management., Methods: In this prospective, observational study (IDAMS), we included patients aged 5 years and older with undifferentiated fever at presentation from 26 outpatient facilities in eight countries (Bangladesh, Brazil, Cambodia, El Salvador, Indonesia, Malaysia, Venezuela, and Viet Nam). We used multivariable logistic regression to investigate the association between clinical symptoms and laboratory tests with dengue versus other febrile illnesses between day 2 and day 5 after onset of fever (ie, illness days). We built a set of candidate regression models including clinical and laboratory variables to reflect the need of a comprehensive versus parsimonious approach. We assessed performance of these models via standard measures of diagnostic values., Findings: Between Oct 18, 2011, and Aug 4, 2016, we recruited 7428 patients, of whom 2694 (36%) were diagnosed with laboratory-confirmed dengue and 2495 (34%) with (non-dengue) other febrile illnesses and met inclusion criteria, and were included in the analysis. 2703 (52%) of 5189 included patients were younger than 15 years, 2486 (48%) were aged 15 years or older, 2179 (42%) were female and 3010 (58%) were male. Platelet count, white blood cell count, and the change in these variables from the previous day of illness had a strong association with dengue. Cough and rhinitis had strong associations with other febrile illnesses, whereas bleeding, anorexia, and skin flush were generally associated with dengue. Model performance increased between day 2 and 5 of illness. The comprehensive model (18 clinical and laboratory predictors) had sensitivities of 0·80 to 0·87 and specificities of 0·80 to 0·91, whereas the parsimonious model (eight clinical and laboratory predictors) had sensitivities of 0·80 to 0·88 and specificities of 0·81 to 0·89. A model that includes laboratory markers that are easy to measure (eg, platelet count or white blood cell count) outperformed the models based on clinical variables only., Interpretation: Our results confirm the important role of platelet and white blood cell counts in diagnosing dengue, and the importance of serial measurements over subsequent days. We successfully quantified the performance of clinical and laboratory markers covering the early period of dengue. Resulting algorithms performed better than published schemes for distinction of dengue from other febrile illnesses, and take into account the dynamic changes over time. Our results provide crucial information needed for the update of guidelines, including the Integrated Management of Childhood Illness handbook., Funding: EU's Seventh Framework Programme., Translations: For the Bangla, Bahasa Indonesia, Portuguese, Khmer, Spanish and Vietnamese translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests TJ reports personal fees from the Roche Severe Dengue Advisory Board, Takeda Pharmaceutical Company, Merck Pharmaceuticals, and Emergent Biosolutions, as a member of advisory boards, outside the submitted work. BAW reports personal fees from Takeda Pharmaceutical Company and from the Roche Severe Dengue Advisory Board, outside the submitted work. SY reports personal fees from Roche, outside the submitted work. 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.)

Characterized by their strong 1D confinement and long-lifetime red-shifted emission spectra, colloidal nanoplatelets (NPLs) with type-II electronic structure provide an exciting ground to design complex heterostructures with remarkable properties. This work demonstrates the synthesis and optical characterization of CdSe/CdSeTe/CdTe core/crown/crown NPLs having a step-wise gradient electronic structure and disproportional wavefunction distribution, in which the excitonic properties of the electron and hole can be finely tuned through adjusting the geometry of the intermediate crown. The first crown with staggered configuration gives rise to a series of direct and indirect transition channels that activation/deactivation of each channel is possible through wavefunction engineering. Moreover, these NPLs allow for switching between active channels with temperature, where lattice contraction directly affects the electron-hole (e-h) overlap. Dominated by the indirect transition channels over direct transitions, the lifetime of the NPLs starts to increase at 9 K, indicative of low dark-bright exciton splitting energy. The charge transfer states from the two type-II interfaces promote a large number of indirect transitions, which effectively increase the absorption of low-energy photons critical for nonlinear properties. As a result, these NPLs demonstrate exceptionally high two-photon absorption cross-sections with the highest value of 12.9 × 10 6 GM and superlinear behavior., (© 2023 Wiley-VCH GmbH.)

Symsagittifera roscoffensis is a well-known member of the order Acoela that lives in symbiosis with the algae Tetraselmis convolutae during its adult stage. Its natural habitat is the eastern coast of the Atlantic, where at specific locations thousands of individuals can be found, mostly, lying in large pools on the surface of sand at low tide. As a member of the Acoela it has been thought as a proxy for ancestral bilaterian animals; however, its phylogenetic position remains still debated. In order to understand the basic structural characteristics of the acoel genome, we sequenced and assembled the genome of aposymbiotic species S. roscoffensis. The size of this genome was measured to be in the range of 910-940 Mb. Sequencing of the genome was performed using PacBio Hi-Fi technology. Hi-C and RNA-seq data were also generated to scaffold and annotate it. The resulting assembly is 1.1 Gb large (covering 118% of the estimated genome size) and highly continuous, with N50 scaffold size of 1.04 Mb. The repetitive fraction of the genome is 61%, of which 85% (half of the genome) are LTR retrotransposons. Genome-guided transcriptome assembly identified 34,493 genes, of which 29,351 are protein coding (BUSCO score 97.6%), and 30.2% of genes are spliced leader trans-spliced. The completeness of this genome suggests that it can be used extensively to characterize gene families and conduct accurate phylogenomic reconstructions., Competing Interests: Conflicts of interest None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Genetics Society of America.)

Recombination is an evolutionary strategy to quickly acquire new viral properties inherited from the parental lineages. The systematic survey of the SARS-CoV-2 genome sequences of the Andalusian genomic surveillance strategy has allowed the detection of an unexpectedly high number of co-infections, which constitute the ideal scenario for the emergence of new recombinants. Whole genome sequence of SARS-CoV-2 has been carried out as part of the genomic surveillance programme. Sample sources included the main hospitals in the Andalusia region. In addition to the increase of co-infections and known recombinants, three novel SARS-CoV-2 delta-omicron and omicron-omicron recombinant variants with two break points have been detected. Our observations document an epidemiological scenario in which co-infection and recombination are detected more frequently. Finally, we describe a family case in which co-infection is followed by the detection of a recombinant made from the two co-infecting variants. This increased number of recombinants raises the risk of emergence of recombinant variants with increased transmissibility and pathogenicity.

Background: The development of adipose tissue during adolescence may provide valuable insights into obesity-associated diseases. We propose an automated convolutional neural network (CNN) approach using Dixon-based magnetic resonance imaging (MRI) to quantity abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in children and adolescents., Methods: 474 abdominal Dixon MRI scans of 136 young healthy volunteers (aged 8-18) were included in this study. For each scan, an axial fat-only Dixon image located at the L2-L3 disc space and another image at the L4-L5 disc space were selected for quantification. For each image, an outer and an inner region around the abdomen wall, as well as SAT and VAT pixel masks, were generated by expert readers as reference standards. A standard U-Net CNN architecture was then used to train two models: one for region segmentation and one for fat pixel classification. The performance was evaluated using the dice similarity coefficient (DSC) with fivefold cross-validation, and by Pearson correlation and the Student's t-test against the reference standards., Results: For the DSC results, means and standard deviations of the outer region, inner region, SAT, and VAT comparisons were 0.974 ± 0.026, 0.997 ± 0.003, 0.981 ± 0.025, and 0.932 ± 0.047, respectively. Pearson coefficients were 1.000 for both outer and inner regions, and 1.000 and 0.982 for SAT and VAT comparisons, respectively (all p = NS)., Conclusion: These results show that our method not only provides excellent agreement with the reference SAT and VAT measurements, but also accurate abdominal wall region segmentation. The proposed combined region- and pixel-based CNN approach provides automated abdominal wall segmentation as well as SAT and VAT quantification with Dixon MRI and enables objective longitudinal assessment of adipose tissues in children during adolescence.

The geographic and evolutionary origins of the SARS-CoV-2 Omicron variant (BA.1), which was first detected mid-November 2021 in Southern Africa, remain unknown. We tested 13,097 COVID-19 patients sampled between mid-2021 to early 2022 from 22 African countries for BA.1 by real-time RT-PCR. By November-December 2021, BA.1 had replaced the Delta variant in all African sub-regions following a South-North gradient, with a peak Rt of 4.1. Polymerase chain reaction and near-full genome sequencing data revealed genetically diverse Omicron ancestors already existed across Africa by August 2021. Mutations, altering viral tropism, replication and immune escape, gradually accumulated in the spike gene. Omicron ancestors were therefore present in several African countries months before Omicron dominated transmission. These data also indicate that travel bans are ineffective in the face of undetected and widespread infection.

Background: The management of a vascular injury during cholecystectomy is still very complicated, especially in centers not specialized in complex hepatobiliary surgery., Methods: This was a multi-institutional retrospective study in patients with vascular injuries during cholecystectomy from 18 centers in 4 countries. The aim of the study was to analyze the management of vascular injuries focusing on referral, time to perform the repair, and different treatments options outcomes., Results: A total of 104 patients were included. Twenty-nine patients underwent vascular repair (27.9%), 13 (12.5%) liver resection, and 1 liver transplant as a first treatment. Eighty-four (80.4%) vascular and biliary injuries occurred in nonspecialized centers and 45 (53.6%) were immediately transferred. Intraoperative diagnosed injuries were rare in referred patients (18% vs 84%, P = .001). The patients managed at the hospital where the injury occurred had a higher number of reoperations (64% vs 20%, P ˂ .001). The need for vascular reconstruction was associated with higher mortality (P = .04). Two of the 4 patients transplanted died., Conclusion: Vascular lesions during cholecystectomy are a potentially life-threatening complication. Management of referral to specialized centers to perform multiple complex multidisciplinary procedures should be mandatory. Late vascular repair has not shown to be associated with worse results., (Copyright © 2022 Elsevier Inc. All rights reserved.)

BAFF system plays an essential role in B cells homeostasis and tolerance, although it has widely not been tested in transplantation with doubtful results. The main purpose was to study the BAFF soluble forms and their correlation with acute rejection (AR) and donor-specific antibodies production. Serum levels of BAFF, APRIL, and soluble forms of their receptors were analyzed in renal recipients with and without acute rejection (AR/NAR) appearance. All molecules were evaluated at pre- and post-transplantation. sTACI showed a significant correlation with BAFF and sR-BAFF levels, and sBCMA also showed a positive correlation with sAPRIL levels. A significant increase in sAPRIL levels in patients suffering AR was also found, and ROC curves analysis showed an AUC = 0.724, a concentration of 6.05 ng/ml (sensitivity: 66.7%; specificity: 73.3%), the best cutoff point for predicting AR. In the post-transplant dynamics of sAPRIL levels in the longitudinal cohort, we observed a significant decrease at 3 and 6 month post-transplantation compared to pretransplantation status. We also observed that recipients with high pre-transplant levels of sAPRIL generated antibodies earlier than those with lower sAPRIL levels, although their long-term post-transplantation was not different. Our results show that elevated serum levels of APRIL may be helpful as a biomarker for the diagnosis of AR, although the longitudinal study shows that it is not helpful as a prognostic biomarker., (© 2022. L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland.)

Introduction: Advances in comprehensive genomic profiling (CGP) of lung adenocarcinomas (LUADs) led to personalized treatment for patients. This study evaluated medical oncologists' attitudes toward CGP in a scenario where sponsored funding for CGP was available., Methods: We designed an online survey assessing CGP use and treating physicians' confidence, composed of three self-confidence domains, which are as follows: confidence in interpreting CGP results, confidence in treating oncogenic-driven LUAD, and confidence in managing tyrosine kinase inhibitor adverse events. The survey was distributed to medical oncologists who treat lung cancer in Brazil. Comparisons between groups were performed using the chi-square or Fisher's exact test. Univariable and multivariable (adjusted OR) analyses were performed., Results: Among 104 respondents who treat patients with lung cancer, 55% were from the Southeast region, 28% had high lung cancer clinical load, and 33% had in-house molecular testing. More than half (51%) of the participants request CGP systematically to stage IV LUAD. As for provider confidence, 67% stated being confident in all three domains: 76% confident in interpreting CGP, 84% confident in treating oncogenic-driven LUAD, and 81% in managing tyrosine kinase inhibitor adverse events. Providers' confidence was associated with systematically requesting CGP to stage IV LUAD ( p  = 0.013). After controlling for the variables of interest, systematic requesting CGP for stage IV LUAD revealed a significant association with the provider's confidence (adjusted OR = 0.35, p  = 0.028, 95% CI: 0.14-0.84). The major challenge for properly requesting CGP was the long turnaround time and the fear of treatment delays., Conclusions: Even though CGP for stage IV LUAD in Brazil is fully sponsored, only half of the oncologists in our survey systematically request it.. Requesting CGP was associated with providers' confidence. Improving access and promoting providers' awareness of CGP utility is necessary to increase CGP use and better inform treatment decisions., (© 2022 The Authors.)

Objectives: More than two years into the COVID-19 pandemic, SARS-CoV-2 still remains a global public health problem. Successive waves of infection have produced new SARS-CoV-2 variants with new mutations for which the impact on COVID-19 severity and patient survival is uncertain., Methods: A total of 764 SARS-CoV-2 genomes, sequenced from COVID-19 patients, hospitalized from 19th February 2020 to 30 April 2021, along with their clinical data, were used for survival analysis., Results: A significant association of B.1.1.7, the alpha lineage, with patient mortality (log hazard ratio (LHR) = 0.51, C.I. = [0.14,0.88]) was found upon adjustment by all the covariates known to affect COVID-19 prognosis. Moreover, survival analysis of mutations in the SARS-CoV-2 genome revealed 27 of them were significantly associated with higher mortality of patients. Most of these mutations were located in the genes coding for the S, ORF8, and N proteins., Conclusions: This study illustrates how a combination of genomic and clinical data can provide solid evidence for the impact of viral lineage on patient survival.

The identity and function of a given cell type relies on the differential expression of gene batteries that promote diverse phenotypes and functional specificities. Therefore, the identification of the molecular and morphological fingerprints of cell types across taxa is essential for untangling their evolution. Here we use a multidisciplinary approach to identify the molecular and morphological features of an exocrine, pancreas-like cell type harbored within the sea urchin larval gut. Using single cell transcriptomics, we identify various cell populations with a pancreatic-like molecular fingerprint that are enriched within the S. purpuratus larva digestive tract. Among these, in the region where they reside, the midgut/stomach domain, we find that populations of exocrine pancreas-like cells have a unique regulatory wiring distinct from the rest the of the cell types of the same region. Furthermore, Serial Block-face scanning Electron Microscopy (SBEM) of the exocrine cells shows that this reported molecular diversity is associated to distinct morphological features that reflect the physiological and functional properties of this cell type. Therefore, we propose that these sea urchin exocrine cells are homologous to the well-known mammalian pancreatic acinar cells and thus we trace the origin of this particular cell type to the time of deuterostome diversification. Overall, our approach allows a thorough characterization of a complex cell type and shows how both the transcriptomic and morphological information contribute to disentangling the evolution of cell types and organs such as the pancreatic cells and pancreas., 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 Paganos, Ronchi, Carl, Mizzon, Martinez, Benvenuto and Arnone.)

Background: Iatrogenic bile duct injury (IBDI) is a challenging surgical complication. IBDI management can be guided by artificial intelligence models. Our study identified the factors associated with successful initial repair of IBDI and predicted the success of definitive repair based on patient risk levels., Methods: This is a retrospective multi-institution cohort of patients with IBDI after cholecystectomy conducted between 1990 and 2020. We implemented a decision tree analysis to determine the factors that contribute to successful initial repair and developed a risk-scoring model based on the Comprehensive Complication Index., Results: We analyzed 748 patients across 22 hospitals. Our decision tree model was 82.8% accurate in predicting the success of the initial repair. Non-type E (p < 0.01), treatment in specialized centers (p < 0.01), and surgical repair (p < 0.001) were associated with better prognosis. The risk-scoring model was 82.3% (79.0-85.3%, 95% confidence interval [CI]) and 71.7% (63.8-78.7%, 95% CI) accurate in predicting success in the development and validation cohorts, respectively. Surgical repair, successful initial repair, and repair between 2 and 6 weeks were associated with better outcomes., Discussion: Machine learning algorithms for IBDI are a novel tool may help to improve the decision-making process and guide management of these patients., (© 2022. The Author(s).)

A series of novel chitosan/tannin/montmorillonite (Cs/Tn/MMT) films were synthesised by loading different (from 0.2 to 0.5 wt%) and MMT (from 0.5 to 1.5 wt%) ratios, to be used as promising low-cost biosorbents for methyl orange (MO) removal from aqueous media. The prepared films were characterised using different techniques such as x-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), water contact angle, optical properties, colourimetric measurement, porosity, swelling and thickness. The effects of various parameters, i.e. initial MO concentration, adsorbent dose, pH and temperature, were studied. The Cs/Tn0.2/MMT1 film showed a high removal efficiency of 95.62% and maximum adsorption capacity of 57.37 mg/g under the optimum adsorption conditions (initial methyl orange concentration 60 mg/L, pH 7 and 25 °C). The adsorption kinetic followed the pseudo second order kinetic model and the experimental data were a good fit for the Langmuir isotherm indicating a homogeneous and monolayer adsorption process. The thermodynamic parameters suggested physical adsorption and exothermic behaviour. Consequently, Cs/Tn/MMT films showed effective potential for the uptake of anionic dyes., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The transmission patterns and genetic diversity of dengue virus (DENV) circulating in Africa remain poorly understood. Circulation of the DENV serotype 1 (DENV1) in Angola was detected in 2013, while DENV serotype 2 (DENV2) was detected in 2018. Here, we report results from molecular and genomic investigations conducted at the Ministry of Health national reference laboratory (INIS) in Angola on suspected dengue cases detected between January 2017 and February 2019., Methods: A total of 401 serum samples from dengue suspected cases were collected in 13 of the 18 provinces in Angola. Of those, 351 samples had complete data for demographic and epidemiological analysis, including age, gender, province, type of residence, clinical symptoms, as well as dates of onset of symptoms and sample collection. RNA was extracted from residual samples and tested for DENV-RNA using two distinct real time RT-PCR protocols. On-site whole genome nanopore sequencing was performed on RT-PCR+ samples. Bayesian coalescent models were used to estimate date and origin of outbreak emergence, as well as population growth rates., Results: Molecular screening showed that 66 out of 351 (19%) suspected cases were DENV-RNA positive across 5 provinces in Angola. DENV RT-PCR+ cases were detected more frequently in urban sites compared to rural sites. Of the DENV RT-PCR+ cases most were collected within 6 days of symptom onset. 93% of infections were confirmed by serotype-specific RT-PCR as DENV2 and 1 case (1.4%) was confirmed as DENV1. Six CHIKV RT-PCR+ cases were also detected during the study period, including 1 co-infection of CHIKV with DENV1. Most cases (87%) were detected in Luanda during the rainy season between April and October. Symptoms associated with severe dengue were observed in 11 patients, including 2 with a fatal outcome. On-site nanopore genome sequencing followed by genetic analysis revealed an introduction of DENV2 Cosmopolitan genotype (also known as DENV2-II genotype) possibly from India in or around October 2015, at least 1 year before its detection in the country. Coalescent models suggest relatively moderately rapid epidemic growth rates and doubling times, and a moderate expansion of DENV2 in Angola during the studied period., Conclusion: This study describes genomic, epidemiological and demographic characteristic of predominately urban transmission of DENV2 in Angola. We also find co-circulation of DENV2 with DENV1 and CHIKV and report several RT-PCR confirmed severe dengue cases in the country. Increasing dengue awareness in healthcare professional, expanding the monitorization of arboviral epidemics across the country, identifying most common mosquito breeding sites in urban settings, implementing innovative vector control interventions and dengue vaccination campaigns could help to reduce vector presence and DENV transmission in Angola., Competing Interests: The authors declare no conflict of interest.

While trends in tropical deforestation are alarming, conservation biologists are increasingly recognizing the potential for species survival in human-modified landscapes. Identifying the factors underlying such persistence, however, requires basic ecological knowledge of a species' resource use. Here, we generate such data to guide conservation of an understudied venomous mammal, the Hispaniolan solenodon ( Solenodon paradoxus ), that occupies a mosaic landscape of agriculture and forest fragments in the western Dominican Republic. Using feces collected in both wet and dry seasons, we found significant differences in the stable isotope values of carbon (δ 13 C) between pasture (-24.63 ± 2.31‰, Las Mercedes) and agroforestry (-28.07 ± 2.10‰, Mencia). Solenodon populations in agricultural areas occupied wider isotopic niche spaces, which may be explained by more diverse resource within these patches or individuals combining resources across habitats. We detected elevated δ 15 N values in the dry season of pasture areas (8.22 ± 2.30‰) as compared to the wet season (5.26 ± 2.44‰) and overall narrower isotopic niche widths in the dry season, suggestive of the impacts of aridity on foraging behavior. Our work highlights the importance of considering a more nuanced view of variations in 'modified' or "agricultural" landscapes as compared with strictly protected national parks. We suggest that seasonal differences in foraging should be considered as they intersect with landscape modification by landowners for maintaining resources for focal consumers. This work adds to a growing body of literature highlighting that fecal stable isotopes are a non-invasive and cost-effective monitoring tool that is particularly well-suited for cryptic small mammal species, ensuring actionable and evidenced-based conservation practices in the tropic's rapidly changing landscapes., Competing Interests: The authors declare no conflict of interest associated with this study., (© 2022 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Adult stem cells (ASCs) in vertebrates and model invertebrates (e.g. Drosophila melanogaster) are typically long-lived, lineage-restricted, clonogenic and quiescent cells with somatic descendants and tissue/organ-restricted activities. Such ASCs are mostly rare, morphologically undifferentiated, and undergo asymmetric cell division. Characterized by 'stemness' gene expression, they can regulate tissue/organ homeostasis, repair and regeneration. By contrast, analysis of other animal phyla shows that ASCs emerge at different life stages, present both differentiated and undifferentiated phenotypes, and may possess amoeboid movement. Usually pluri/totipotent, they may express germ-cell markers, but often lack germ-line sequestering, and typically do not reside in discrete niches. ASCs may constitute up to 40% of animal cells, and participate in a range of biological phenomena, from whole-body regeneration, dormancy, and agametic asexual reproduction, to indeterminate growth. They are considered legitimate units of selection. Conceptualizing this divergence, we present an alternative stemness metaphor to the Waddington landscape: the 'wobbling Penrose' landscape. Here, totipotent ASCs adopt ascending/descending courses of an 'Escherian stairwell', in a lifelong totipotency pathway. ASCs may also travel along lower stemness echelons to reach fully differentiated states. However, from any starting state, cells can change their stemness status, underscoring their dynamic cellular potencies. Thus, vertebrate ASCs may reflect just one metazoan ASC archetype., (© 2021 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.)

COVID-19 affects multiple organs. Clinical data from the Mount Sinai Health System show that substantial numbers of COVID-19 patients without prior heart disease develop cardiac dysfunction. How COVID-19 patients develop cardiac disease is not known. We integrated cell biological and physiological analyses of human cardiomyocytes differentiated from human induced pluripotent stem cells (hiPSCs) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the presence of interleukins (ILs) with clinical findings related to laboratory values in COVID-19 patients to identify plausible mechanisms of cardiac disease in COVID-19 patients. We infected hiPSC-derived cardiomyocytes from healthy human subjects with SARS-CoV-2 in the absence and presence of IL-6 and IL-1β. Infection resulted in increased numbers of multinucleated cells. Interleukin treatment and infection resulted in disorganization of myofibrils, extracellular release of troponin I, and reduced and erratic beating. Infection resulted in decreased expression of mRNA encoding key proteins of the cardiomyocyte contractile apparatus. Although interleukins did not increase the extent of infection, they increased the contractile dysfunction associated with viral infection of cardiomyocytes, resulting in cessation of beating. Clinical data from hospitalized patients from the Mount Sinai Health System show that a significant portion of COVID-19 patients without history of heart disease have elevated troponin and interleukin levels. A substantial subset of these patients showed reduced left ventricular function by echocardiography. Our laboratory observations, combined with the clinical data, indicate that direct effects on cardiomyocytes by interleukins and SARS-CoV-2 infection might underlie heart disease in COVID-19 patients. IMPORTANCE SARS-CoV-2 infects multiple organs, including the heart. Analyses of hospitalized patients show that a substantial number without prior indication of heart disease or comorbidities show significant injury to heart tissue, assessed by increased levels of troponin in blood. We studied the cell biological and physiological effects of virus infection of healthy human iPSC-derived cardiomyocytes in culture. Virus infection with interleukins disorganizes myofibrils, increases cell size and the numbers of multinucleated cells, and suppresses the expression of proteins of the contractile apparatus. Viral infection of cardiomyocytes in culture triggers release of troponin similar to elevation in levels of COVID-19 patients with heart disease. Viral infection in the presence of interleukins slows down and desynchronizes the beating of cardiomyocytes in culture. The cell-level physiological changes are similar to decreases in left ventricular ejection seen in imaging of patients' hearts. These observations suggest that direct injury to heart tissue by virus can be one underlying cause of heart disease in COVID-19.

Echinoderms are marine invertebrate deuterostomes known for their amazing regenerative abilities throughout all life stages. Though some species can undergo whole-body regeneration (WBR), others exhibit more restricted regenerative capabilities. Asteroidea (starfish) comprise one of the few echinoderm taxa capable of undergoing WBR. Indeed, some starfish species can restore all tissues and organs not only during larval stages, but also from arm fragments as adults. Arm explants have been used to study cells, tissues and genes involved in starfish regeneration. Here, we describe methods for obtaining and studying regeneration of arm explants in starfish, in particular animal collection and husbandry, preparation of arm explants, regeneration tests, microscopic anatomy techniques (including transmission electron microscopy, TEM) used to analyze the regenerating explant tissues and cells plus a downstream RNA extraction protocol needed for subsequent molecular investigations., (© 2022. The Author(s).)

Background: The current SARS-CoV-2 pandemic has emphasized the utility of viral whole-genome sequencing in the surveillance and control of the pathogen. An unprecedented ongoing global initiative is producing hundreds of thousands of sequences worldwide. However, the complex circumstances in which viruses are sequenced, along with the demand of urgent results, causes a high rate of incomplete and, therefore, useless sequences. Viral sequences evolve in the context of a complex phylogeny and different positions along the genome are in linkage disequilibrium. Therefore, an imputation method would be able to predict missing positions from the available sequencing data., Results: We have developed the impuSARS application, which takes advantage of the enormous number of SARS-CoV-2 genomes available, using a reference panel containing 239,301 sequences, to produce missing data imputation in viral genomes. ImpuSARS was tested in a wide range of conditions (continuous fragments, amplicons or sparse individual positions missing), showing great fidelity when reconstructing the original sequences, recovering the lineage with a 100% precision for almost all the lineages, even in very poorly covered genomes (<20%)., Conclusions: Imputation can improve the pace of SARS-CoV-2 sequencing production by recovering many incomplete or low-quality sequences that would be otherwise discarded. ImpuSARS can be incorporated in any primary data processing pipeline for SARS-CoV-2 whole-genome sequencing., (© The Author(s) 2021. Published by Oxford University Press GigaScience.)

Fossils provide insights into how organs may have diversified over geological time. 1 However, diversification already accomplished early in evolution can obscure ancestral events leading to it. For example, already by the mid-Cambrian period, euarthropods had condensed brains typifying modern mandibulate lineages. 2 However, the demonstration that extant euarthropods and chordates share orthologous developmental control genes defining the segmental fore-, mid-, and hindbrain suggests that those character states were present even before the onset of the Cambrian. 3 Fossilized nervous systems of stem Euarthropoda might, therefore, be expected to reveal ancestral segmental organization, from which divergent arrangements emerged. Here, we demonstrate unsurpassed preservation of cerebral tissue in Kaili leanchoiliids revealing near-identical arrangements of bilaterally symmetric ganglia identified as the proto-, deuto-, and tritocerebra disposed behind an asegmental frontal domain, the prosocerebrum, from which paired nerves extend to labral ganglia flanking the stomodeum. This organization corresponds to labral connections hallmarking extant euarthropod clades 4 and to predicted transformations of presegmental ganglia serving raptorial preocular appendages of Radiodonta. 5 Trace nervous system in the gilled lobopodian Kerygmachela kierkegaardi 6 suggests an even deeper prosocerebral ancestry. An asegmental prosocerebrum resolves its location relative to the midline asegmental sclerite of the radiodontan head, which persists in stem Euarthropoda. 7 Here, data from two Kaili Leanchoilia, with additional reference to Alalcomenaeus, 8 , 9 demonstrate that Cambrian stem Euarthropoda confirm genomic and developmental studies 10-15 claiming that the most frontal domain of the euarthropod brain is a unique evolutionary module distinct from, and ancestral to, the fore-, mid-, and hindbrain., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Silicon is the most prevalent material system for light-harvesting applications; however, its inherent indirect bandgap and consequent weak absorption limits its potential in optoelectronics. This paper proposes to address this limitation by combining the sensitization of silicon with extraordinarily large absorption cross sections of quasi-2D colloidal quantum well nanoplatelets (NPLs) and to demonstrate excitation transfer from these NPLs to bulk silicon. Here, the distance dependency, d, of the resulting Förster resonant energy transfer from the NPL monolayer into a silicon substrate is systematically studied by tuning the thickness of a spacer layer (of Al 2 O 3 ) in between them (varied from 1 to 50 nm in thickness). A slowly varying distance dependence of d -1 with 25% efficiency at a donor-acceptor distance of 20 nm is observed. These results are corroborated with full electromagnetic solutions, which show that the inverse distance relationship emanates from the delocalized electric field intensity across both the NPL layer and the silicon because of the excitation of strong in-plane dipoles in the NPL monolayer. These findings pave the way for using colloidal NPLs as strong light-harvesting donors in combination with crystalline silicon as an acceptor medium for application in photovoltaic devices and other optoelectronic platforms., (© 2021 Wiley-VCH GmbH.)

Context: Abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are frequent accompaniments of depression, and studies have documented the role of stress and stressful life events in the ontogeny of perimenopausal depressions (PMD). Because HPA axis function in women is further modulated both by aging and ovarian steroids, it is possible that a dysregulated HPA axis contributes to the increased risk of PMD., Objective: We examined HPA axis function in perimenopausal women with and without depression using the combined dexamethasone-corticotropin-releasing hormone (Dex/CRH) test., Methods: Dex/CRH tests were performed on 20 women with PMD and 20 women who were also perimenopausal but without current or past depression (control women). Main outcome measures were plasma levels of cortisol and adrenocorticotropin (ACTH) and 24-hour urinary free cortisol (UFC). Five women took chronic stable medications, otherwise all women were medically healthy, and both groups were comparable with respect to reproductive stage and age. Standardized symptom rating scales were administered to each woman prior to Dex/CRH testing., Results: No group differences were present in either baseline or stimulated ACTH and cortisol secretion. Baseline plasma measures of estradiol, progesterone, and 24-hour UFC levels similarly did not differ in PMD and control women., Conclusion: Despite reports of increased stress responsiveness in PMD, we observed no abnormalities of HPA axis activity associated with PMD compared with women without depression. These findings suggest that PMD is not uniformly associated with HPA dysregulation and could reflect underlying pathophysiologic processes that are distinct from women with nonreproductive-related depressions., (Published by Oxford University Press on behalf of the Endocrine Society 2021.)

In this work, we systematically studied the shape- and size-controlled monodisperse synthesis of iron oxide nanocrystals (IONCs) for their use as building blocks in the formation of mesocrystals. For this aim, on understanding the influence of the oleic acid concentration, iron-oleate concentration, and heating rate on the synthesis of robust and reproducible IONCs with desired sizes and shapes, we synthesized highly monodisperse ∼11 nm sized nanocubes and nanospheres. Magnetic measurements of both cubic and spherical IONCs revealed the presence of mixed paramagnetic and superparamagnetic phases in these nanocrystals. Moreover, we observed that the magnetic moments of the nanocubes are more substantial compared to their spherical counterparts. We then demonstrated a simple magnetic-field-assisted assembly of nanocubes into three-dimensional (3D) cuboid mesocrystals while nanospheres did not form any mesocrystals. These findings indicate that small cubic nanocrystals hold great promise as potential building blocks of 3D magnetic hierarchical structures with their superior magnetic properties and mesocrystal assembly capability, which may have high relevance in various fields ranging from high-density data storage to biomedical applications., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Purpose: High-dose-rate (HDR) prostate brachytherapy is an established technique for whole-gland treatment. For transrectal ultrasound (TRUS)-guided HDR prostate brachytherapy, image fusion with a magnetic resonance image (MRI) can be performed to make use of its soft-tissue contrast. The MIM treatment planning system has recently introduced image registration specifically for HDR prostate brachytherapy and has incorporated a Predictive Fusion workflow, which allows clinicians to attempt to compensate for differences in patient positioning between imaging modalities. In this study, we investigate the accuracy of the MIM algorithms for MRI-TRUS fusion, including the Predictive Fusion workflow., Materials and Methods: A radiation oncologist contoured the prostate gland on both TRUS and MRI. Four registration methodologies to fuse the MRI and the TRUS images were considered: rigid registration (RR), contour-based (CB) deformable registration, Predictive Fusion followed by RR (pfRR), and Predictive Fusion followed by CB deformable registration (pfCB). Registrations were compared using the mean distance to agreement and the Dice similarity coefficient for the prostate as contoured on TRUS and the registered MRI prostate contour., Results: Twenty patients treated with HDR prostate brachytherapy at our center were included in this retrospective evaluation. For the cohort, mean distance to agreement was 2.1 ± 0.8 mm, 0.60 ± 0.08 mm, 2.0 ± 0.5 mm, and 0.59 ± 0.06 mm for RR, CB, pfRR, and pfCB, respectively. Dice similarity coefficients were 0.80 ± 0.05, 0.93 ± 0.02, 0.81 ± 0.03, and 0.93 ± 0.01 for RR, CB, pfRR, and pfCB, respectively. The inclusion of the Predictive Fusion workflow did not significantly improve the quality of the registration., Conclusions: The CB deformable registration algorithm in the MIM treatment planning system yielded the best geometric registration indices. MIM offers a commercial platform allowing for easier access and integration into clinical departments with the potential to play an integral role in future focal therapy applications for prostate cancer., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Hospitals host vulnerable people with potentially enhanced sensitivity to air pollutants. We measured particulate matter (PM) including PM 1 , PM 2.5 , and PM 10 with a portable device in a hospital, a nearby reference building, and ambient air in Shiraz, Iran. Indoor/outdoor (I/O) ratio values were calculated to infer on the origin of size-fractioned PM. The mean hospital indoor concentrations of PM 2.5 and PM 10 (4.7 and 38.7 μg/m 3 , respectively) but not PM 1 were higher than in the reference building and lower than in ambient air. The highest hospital PM 10 mean concentrations were found in the radiotherapy ward (77.5 μg/m 3 ) and radiology ward (70.4 μg/m 3 ) while the lowest were found in the bone marrow transplantation (BMT) ward (18.5 μg/m 3 ) and cardiac surgery ward (19.8 μg/m 3 ). The highest PM 2.5 concentrations were found in the radiology (8.7 μg/m 3 ) and orthopaedic wards (7.7 μg/m 3 ) while the lowest were found in the BMT ward (2.8 μg/m 3 ) and cardiac surgery ward (2.8 μg/m 3 ). The I/O ratios and the timing of peak concentrations during the day (7 a.m. to 4 p.m.) indicated the main roles of outdoor air and human activity on the indoor levels. These suggest the need for mechanical ventilation with PM control for a better indoor air quality (IAQ) in the hospital., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The estimated 20-30% of women who develop perimenopausal depression (PMD) are at an increased risk of cardiovascular and all-cause mortality. The therapeutic benefits of estradiol (E2) and symptom-provoking effects of E2-withdrawal (E2-WD) suggest that a greater sensitivity to changes in E2 at the cellular level contribute to PMD. We developed an in vitro model of PMD with lymphoblastoid cell lines (LCLs) derived from participants of a prior E2-WD clinical study. LCLs from women with past PMD (n = 8) or control women (n = 9) were cultured in three experimental conditions: at vehicle baseline, during E2 treatment, and following E2-WD. Transcriptome analysis revealed significant differences in transcript expression in PMD in all experimental conditions, and significant overlap in genes that were changed in PMD regardless of experimental condition. Of these, chemokine CXCL10, previously linked to cardiovascular disease, was upregulated in women with PMD, but most so after E2-WD (p < 1.55 × 10 -5 ). CYP7B1, an enzyme intrinsic to DHEA metabolism, was upregulated in PMD across experimental conditions (F (1,45)  = 19.93, p < 0.0001). These transcripts were further validated via qRT-PCR. Gene networks dysregulated in PMD included inflammatory response, early/late E2-response, and cholesterol homeostasis. Our results provide evidence that differential behavioral responsivity to E2-WD in PMD reflects intrinsic differences in cellular gene expression. Genes such as CXCL10, CYP7B1, and corresponding proinflammatory and steroid biosynthetic gene networks, may represent biomarkers and molecular targets for intervention in PMD. Finally, this in vitro model allows for future investigations into the mechanisms of genes and gene networks involved in the vulnerability to, and consequences of, PMD., (© 2020. The Author(s), under exclusive licence to Springer Nature Limited.)

Delineating the relationship between human neurodevelopment and the maturation of the hypothalamic-pituitary-gonadal (HPG) axis during puberty is critical for investigating the increase in vulnerability to neuropsychiatric disorders that is well documented during this period. Preclinical research demonstrates a clear association between gonadal production of sex steroids and neurodevelopment; however, identifying similar associations in humans has been complicated by confounding variables (such as age) and the coactivation of two additional endocrine systems (the adrenal androgenic system and the somatotropic growth axis) and requires further elucidation. In this paper, we present the design of, and preliminary observations from, the ongoing NIMH Intramural Longitudinal Study of the Endocrine and Neurobiological Events Accompanying Puberty. The aim of this study is to directly examine how the increase in sex steroid hormone production following activation of the HPG-axis (i.e., gonadarche) impacts neurodevelopment, and, additionally, to determine how gonadal development and maturation is associated with longitudinal changes in brain structure and function in boys and girls. To disentangle the effects of sex steroids from those of age and other endocrine events on brain development, our study design includes 1) selection criteria that establish a well-characterized baseline cohort of healthy 8-year-old children prior to the onset of puberty (e.g., prior to puberty-related sex steroid hormone production); 2) temporally dense longitudinal, repeated-measures sampling of typically developing children at 8-10 month intervals over a 10-year period between the ages of eight and 18; 3) contemporaneous collection of endocrine and other measures of gonadal, adrenal, and growth axis function at each timepoint; and 4) collection of multimodal neuroimaging measures at these same timepoints, including brain structure (gray and white matter volume, cortical thickness and area, white matter integrity, myelination) and function (reward processing, emotional processing, inhibition/impulsivity, working memory, resting-state network connectivity, regional cerebral blood flow). This report of our ongoing longitudinal study 1) provides a comprehensive review of the endocrine events of puberty; 2) details our overall study design; 3) presents our selection criteria for study entry (e.g., well-characterized prepubertal baseline) along with the endocrinological considerations and guiding principles that underlie these criteria; 4) describes our longitudinal outcome measures and how they specifically relate to investigating the effects of gonadal development on brain development; and 5) documents patterns of fMRI activation and resting-state networks from an early, representative subsample of our cohort of prepubertal 8-year-old children., (Copyright © 2021. Published by Elsevier Inc.)

Beginning in March 2020, the COVID-19 pandemic and response, which included physical distancing and stay-at-home orders, disrupted daily life in the United States. Compared with the rate in 2019, a 31% increase in the proportion of mental health-related emergency department (ED) visits occurred among adolescents aged 12-17 years in 2020 (1). In June 2020, 25% of surveyed adults aged 18-24 years reported experiencing suicidal ideation related to the pandemic in the past 30 days (2). More recent patterns of ED visits for suspected suicide attempts among these age groups are unclear. Using data from the National Syndromic Surveillance Program (NSSP),* CDC examined trends in ED visits for suspected suicide attempts † during January 1, 2019-May 15, 2021, among persons aged 12-25 years, by sex, and at three distinct phases of the COVID-19 pandemic. Compared with the corresponding period in 2019, persons aged 12-25 years made fewer ED visits for suspected suicide attempts during March 29-April 25, 2020. However, by early May 2020, ED visit counts for suspected suicide attempts began increasing among adolescents aged 12-17 years, especially among girls. During July 26-August 22, 2020, the mean weekly number of ED visits for suspected suicide attempts among girls aged 12-17 years was 26.2% higher than during the same period a year earlier; during February 21-March 20, 2021, mean weekly ED visit counts for suspected suicide attempts were 50.6% higher among girls aged 12-17 years compared with the same period in 2019. Suicide prevention measures focused on young persons call for a comprehensive approach, that is adapted during times of infrastructure disruption, involving multisectoral partnerships (e.g., public health, mental health, schools, and families) and implementation of evidence-based strategies (3) that address the range of factors influencing suicide risk., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

The study aimed to evaluate the short-term clinical effect, therapeutic response rate (TRR%), and therapy safety of a single intra-articular autologous MFAT injection for symptomatic knee OA. Secondly, patient- and pathology-related parameters were investigated to tighten patient selection for MFAT therapy. Sixty-four subjects with symptomatic mild-severe knee OA were enrolled in a single-center trial and received a unilateral ( n = 37) or bilateral ( n = 27) MFAT injection. After liposuction, the adipose tissue was mechanically processed with the Lipogem ® device, which eventually produced 8-10 cc of MFAT. Subjects were clinically assessed by means of the KOOS, NRS, UCLA, and EQ-5D at baseline and 1, 3, 6, and 12 months after injection. Adverse events were recorded at each follow-up timepoint. The TRR was defined according to the OMERACT-OARSI criteria and baseline MRI was scored following the MOAKS classification. The TRR of the index knee was 64% at 3 months and 45% at 12 months after injection. Therapy responders at 12 months improved with 28.3 ± 11.4 on KOOS pain, while non-responders lost -2.1 ± 11.2 points. All clinical scores, except the UCLA, improved significantly at follow-up compared to baseline ( p < 0.05). In the bilateral cohort, no difference in baseline scores or TRR was found between the index knee and contralateral knee (n.s.). An inflammatory reaction was reported in 79% of knees and resolved spontaneously within 16.6 ± 13.5 days after MFAT administration. Numerous bone marrow lesions (BML) were negatively correlated with the TRR at 12 months ( p = 0.003). The study demonstrated an early clinical improvement but a mediocre response rate of 45% at 12 months after a single intra-articular injection with autologous MFAT. Assessment of bone marrow lesions on MRI can be helpful to increase the therapeutic responsiveness of MFAT up to 70% at 12 months. In comparison to repetitive injection therapies such as cortisone, hyaluronic acid, and PRP, administration of MFAT might become a relevant alternative in well-selected patients with symptomatic knee OA.

Substantial evidence suggests that circulating ovarian steroids modulate behavior differently in women with PMDD than in those without this condition. However, hormonal state-related abnormalities of neural functioning in PMDD remain to be better characterized. In addition, while altered neural function in PMDD likely co-exists with alterations in intrinsic cellular function, such a relationship has not been explored. Here, we investigated the effects of ovarian steroids on basal, resting regional cerebral blood flow (rCBF) in PMDD, and, in an exploratory analysis, we tested whether the rCBF findings were linked to the expression of ESC/E(Z) genes, which form an essential ovarian steroid-regulated gene-silencing complex. Resting rCBF was measured with oxygen-15 water PET (189 PET sessions in 43 healthy women and 20 women with PMDD) during three self-as-own-control conditions: GnRH agonist (Lupron)-induced ovarian suppression, estradiol add-back, and progesterone add-back. ESC/E(Z) gene expression data were obtained from RNA-sequencing of lymphoblastoid cell lines performed in a previous study and were examined in relation to hormone-induced changes in rCBF. In the rCBF PET data, there was a significant diagnosis-by-hormone interaction in the subgenual cingulate (P FDR  = 0.05), an important neuroanatomical hub for regulating affective state. Whereas control women showed no hormonally-related changes in resting rCBF, those with PMDD showed decreased resting rCBF during both estradiol (P = 0.02) and progesterone (P = 0.0002) add-back conditions. In addition, in PMDD, ESC/E(Z) gene expression correlated with the change in resting rCBF between Lupron-alone and progesterone conditions (Pearson r = -0.807, P = 0.016). This work offers a formulation of PMDD that integrates behavioral, neural circuit, and cellular mechanisms, and may provide new targets for future therapeutic interventions.