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This study addressed whether combining tinkering with digital storytelling (i.e., narrating and reflecting about experiences to an imagined audience) can engender engineering learning opportunities. Eighty-four families with 5- to 10-year-old (M = 7.69) children (48% female children; 57% White, 11% Asian, 6% Black) watched a video introducing a tinkering activity and were randomly assigned either to a digital storytelling condition or a no digital storytelling condition during tinkering. After tinkering, families reflected on their tinkering experience and were randomly assigned to either engage in digital storytelling or not. Children in the digital storytelling condition during tinkering spoke most to an imagined audience during tinkering, talked most about engineering at reflection, and remembered the most information about the experience weeks later.

Detecting houses through high-resolution satellite images has received increasing attention in recent years and is considered a basic but difficult task in the field of remote sensing. Although, there are many methods that have been developed in this field, there is still a need for an in-depth review of recent articles about Extracting buildings and houses from high-resolution satellite images. This study aims to provide a comprehensive review of articles published in the scientific literature including developments that have occurred in recent years in this field. The topic of house detection is a popular, widespread and rapidly emerging research topic in domain of remote sensing. Because its importance in many fields, including drawing and updating urban maps, monitoring change, detecting damage resulting from environmental disasters, land use analysis, population estimation, and other applications. In addition to Availability of high-resolution images produced by the new generation to satellites. Topics of automatic detection of houses, object-based approaches, machine learning, and deep learning through high-resolution RGB images.

Abstract Mutations in the NRF2-KEAP1 pathway are common in non-small cell lung cancer (NSCLC) and confer broad-spectrum therapeutic resistance, leading to poor outcomes. Currently, there is no means to non-invasively identify NRF2 activation in living subjects. Here, we show that positron emission tomography imaging with the system xc − radiotracer, [18F]FSPG, provides a sensitive and specific marker of NRF2 activation in orthotopic, patient-derived, and genetically engineered mouse models of NSCLC. We found a NRF2-related gene expression signature in a large cohort of NSCLC patients, suggesting an opportunity to preselect patients prior to [18F]FSPG imaging. Furthermore, we reveal that system xc − is a metabolic vulnerability that can be therapeutically targeted with an antibody-drug conjugate for sustained tumour growth suppression. Overall, our results establish [18F]FSPG as a predictive marker of therapy resistance in NSCLC and provide the basis for the clinical evaluation of both imaging and therapeutic agents that target this important antioxidant pathway.

Anthropogenic climate change, primarily driven by greenhouse gas emissions, is reshaping ecosystems and creating conditions that affect 58% of all known human infectious diseases, including fungal infections. Specifically, increasing temperatures, changing precipitation patterns, and extreme weather events are influencing fungal growth, distribution, and virulence. These factors may expand the geographic range of pathogenic fungi, exposing populations to novel, potentially more virulent, or drug-resistant strains. Simultaneously, human factors such as declining immunity, aging populations, and increased use of immunosuppressive therapies are enhancing host susceptibility. This review explores the intricate relationship between climate change and fungal infections, highlighting pathogens that may demonstrate increased virulence and antifungal resistance, along with emerging novel pathogens. The clinical implications are profound, with increased morbidity, mortality, and the spread of fungal infections into new regions. Immediate action is required to develop policies, educational initiatives, and novel antifungal therapies, enhance early diagnostic capabilities, and address healthcare disparities to mitigate the growing burden of fungal infections.

Acute lymphoblastic leukaemia is the most common childhood malignancy that remains a leading cause of death in childhood. It may be characterised by multiple known recurrent genetic aberrations that inform prognosis, the most common being hyperdiploidy and t(12;21) ETV6::RUNX1. We aimed to assess the applicability of a new imaging flow cytometry methodology that incorporates cell morphology, immunophenotype, and fluorescence in situ hybridisation (FISH) to identify aneuploidy of chromosomes 4 and 21 and the translocation ETV6::RUNX1. We evaluated this new “immuno-flowFISH” platform on 39 cases of paediatric ALL of B-lineage known to have aneuploidy of chromosomes 4 and 21 and the translocation ETV6::RUNX1. After identifying the leukaemic population based on immunophenotype (i.e., expression of CD34, CD10, and CD19 antigens), we assessed for copy numbers of loci for the centromeres of chromosomes 4 and 21 and the ETV6 and RUNX1 regions using fluorophore-labelled DNA probes in more than 1000 cells per sample. Trisomy 4 and 21, tetrasomy 21, and translocations of ETV6::RUNX1, as well as gains and losses of ETV6 and RUNX1, could all be identified based on FISH spot counts and digital imagery. There was variability in clonal makeup in individual cases, suggesting the presence of sub-clones. Copy number alterations and translocations could be detected even when the cell population comprised less than 1% of cells and included cells with a mature B-cell phenotype, i.e., CD19-positive, lacking CD34 and CD10. In this proof-of-principle study of 39 cases, this sensitive and specific semi-automated high-throughput imaging flow cytometric immuno-flowFISH method has been able to show that alterations in ploidy and ETV6::RUNX1 could be detected in the 39 cases of paediatric ALL. This imaging flow cytometric FISH method has potential applications for diagnosis and monitoring disease and marrow regeneration (i.e., distinguishing residual ALL from regenerating haematogones) following chemotherapy.

Surgeons must be confident that the instruments they use do not pose risk of infection to patients due to bioburden or contamination. Despite this importance, surgeons are not necessarily aware of the steps required to ensure that an instrument has been properly sterilized, processed, and prepared for the next operation. At the end of an operation, instruments must be transported to the sterile processing unit. There, instruments are decontaminated before being sterilized by heat, chemical, or radiation-based methods. Following this, they are stored before being brought back into use. This review highlights the intricacies of the processing of surgical instruments at the conclusion of an operation so that they are ready for the next one.

The data deduplication technique efficiently reduces and removes redundant data in big data storage systems. The main issue is that the data deduplication requires expensive computational effort to remove duplicate data due to the vast size of big data. The paper attempts to reduce the time and computation required for data deduplication stages. The chunking and hashing stage often requires a lot of calculations and time. This paper initially proposes an efficient new method to exploit the parallel processing of deduplication systems with the best performance. The proposed system is designed to use multicore computing efficiently. First, The proposed method removes redundant data by making a rough classification for the input into several classes using the histogram similarity and k-mean algorithm. Next, a new method for calculating the divisor list for each class was introduced to improve the chunking method and increase the data deduplication ratio. Finally, the performance of the proposed method was evaluated using three datasets as test examples. The proposed method proves that data deduplication based on classes and a multicore processor is much faster than a single-core processor. Moreover, the experimental results showed that the proposed method significantly improved the performance of Two Threshold Two Divisors (TTTD) and Basic Sliding Window BSW algorithms.

This study isolated bacteria from spent engine oil-contaminated soil and optimized their production of polyhydroxybutyrate (PHB), a biodegradable polymer belonging to the polyesters classes that are of interest as bioderived and biodegradable plastics. Out of 12 bacterial isolates (species of Bacillus, Pseudomonas, Staphylococcus and Lactobacillus) recovered from the spent engine oil contaminated soils, and screened for their capacity to accumulate polyhydroxybutyrate (PHB), only two bacterial isolates (Lysinibacillus fusiformis and Metabacillus indicus), showed significant PHB production. L. fusiformis produced PHB at a concentration of 1.5 g/L, while M. indicus produced PHB at a concentration of 1.0 g/L. Optimal production conditions included a temperature of 35°C, agitation speed of 100 rpm, neutral pH of 7.0, glucose as the carbon source, and peptone as the nitrogen source. Gas chromatography-mass spectrometry confirmed the presence of PHB in the extracted samples, with hexadecanoic acid methyl ester identified as the predominant peak. These findings highlight the potential of bacteria from engine oil-contaminated soil as efficient PHB producers and contribute to the development of sustainable and biodegradable plastics.

When platelet concentrates (PCs) were first introduced in the 1960s as a blood component therapy, they were stored in the cold. As platelet transfusion became more important for the treatment of chemotherapy-induced thrombocytopenia, research into ways to increase supply intensified. During the late 1960s/early 1970s, it was demonstrated through radioactive labeling of platelets that room temperature platelets (RTP) had superior post-transfusion recovery and survival compared with cold-stored platelets (CSP). This led to a universal switch to room temperature storage, despite CSP demonstrating superior hemostatic effectiveness upon being transfused. There has been a global resurgence in studies into CSP over the last two decades, with an increase in the use of PC to treat acute bleeding within hospital and pre-hospital care. CSP demonstrate many benefits over RTP, including longer shelf life, decreased bacterial risk and easier logistics for transport, making PC accessible in areas where they have not previously been, such as the battlefield. In addition, CSP are reported to have greater hemostatic function than RTP and are thus potentially better for the treatment of bleeding. This review describes the history of CSP, the functional and metabolic assays used to assess the platelet storage lesion in PC and the current research, benefits and limitations of CSP. We also discuss whether the application of new technology for studying mitochondrial and glycolytic function in PC could provide enhanced understanding of platelet metabolism during storage and thus contribute to the continued improvements in the manufacturing and storage of PC.

Abstract Background Predation pressure and herbivory exert cascading effects on coral reef health and stability. However, the extent of these cascading effects can vary considerably across space and time. This variability is likely a result of the complex interactions between coral reefs’ biotic and abiotic dimensions. A major biological component that has been poorly integrated into the reefs' trophic studies is the microbial community, despite its role in coral death and bleaching susceptibility. Viruses that infect bacteria can control microbial densities and may positively affect coral health by controlling microbialization. We hypothesize that viral predation of bacteria has analogous effects to the top-down pressure of macroorganisms on the trophic structure and reef health. Results Here, we investigated the relationships between live coral cover and viruses, bacteria, benthic algae, fish biomass, and water chemistry in 110 reefs spanning inhabited and uninhabited islands and atolls across the Pacific Ocean. Statistical learning showed that the abundance of turf algae, viruses, and bacteria, in that order, were the variables best predicting the variance in coral cover. While fish biomass was not a strong predictor of coral cover, the relationship between fish and corals became apparent when analyzed in the context of viral predation: high coral cover (> 50%) occurred on reefs with a combination of high predator fish biomass (sum of sharks and piscivores > 200 g m−2) and high virus-to-bacteria ratios (> 10), an indicator of viral predation pressure. However, these relationships were non-linear, with reefs at the higher and lower ends of the coral cover continuum displaying a narrow combination of abiotic and biotic variables, while reefs at intermediate coral cover showed a wider range of parameter combinations. Conclusions The results presented here support the hypothesis that viral predation of bacteria is associated with high coral cover and, thus, coral health and stability. We propose that combined predation pressures from fishes and viruses control energy fluxes, inhibiting the detrimental accumulation of ecosystem energy in the microbial food web.

Data on geographically restricted SARS-CoV-2 variants is lacking in some regions. In this nationwide effort including 18 public health labs, the authors used genomic epidemiology and travel data to understand the origin and spread of 2 variants of interest that predominated during the second wave of the pandemic in Nigeria.

Purpose: This study aimed to describe visual outcomes in cases of pediatric uveitis in an Indian population and to analyze various factors affecting these outcomes. Methods: Single-center, retrospective chart review of 277 cases of uveitis in patients under the age of 18 years. Variables assessed included age and sex distribution, anatomical location of uveitis, systemic associations, complications, and various treatment strategies used, including long-term immunomodulation and surgical management of complications if required. The main outcome was the final visual acuity. Results: At the final visit, 51.5% of the eyes showed improvement in the final visual acuity, while vision remained stable in 28.7% and 19.7% of the eyes showed worsening of vision at the final follow-up. A total of 19.4% of patients were blind in at least one eye at the final visit, and 16 patients (5.77%) remained bilaterally blind at the final follow-up. The presence of cataract (p = 0), posterior uveitis (p = 0.005), and retinal detachment (p = 0.014) were the most significant risk factors for predicting worse visual outcomes. More than half (65.7%) of patients reported a complication at some point in their follow-up, and the most common complication was cataract. In total, 50.9% of patients required long-term immunomodulatory therapy. Conclusion: Pediatric uveitis remains a challenging condition to treat and follow-up, and the visual outcome remains guarded for most patients.

Today's world is heading towards complete digital transformation, and with all its advantages, this transformation involves many risks, the most important of which is phishing. This paper proposes a system that classifies the email as phishing or legitimate. Initially, the samples were brought from different data sets, and then the system extracts the features from all parts of the email. The proposed system uses one of the machine learning algorithms (K-means algorithm) to select the valuable features; the proposed system uses four methods to calculate the distance in the K-means algorithm. After features selection, The paper uses ANN as a classifier to classify emails into phishing and ham, and the proposed system tunes the parameters of ANN to obtain a high percentage of accuracy. The proposed system gave an accuracy equal to 99.4%.

Abstract Managing for the effects of climate change on species whose populations are currently imperiled requires detailed knowledge of the relationship between their demographic rates and climate variables. We sought this information for the West Coast breeding population of snowy plover (Charadrius nivosus), which was federally listed as threatened in 1993 due to substantial declines in the numbers of plovers breeding along the coast and in the number of sites occupied for breeding. Snowy plovers employ a serially polygamous breeding system in which the male typically tends chicks to independence. This unusual breeding system is favored by male‐biased sex ratios in local populations. As part of a multispecies study of the effect of climate change on population growth, we used mark–capture models to examine climate drivers of adult survival for 1219 snowy plovers banded at Monterey Bay over 38 years and known to overwinter on the surrounding north‐central California outer coast. Nonclimate variables, including sex and unmeasured annual mortality risks (e.g., predator abundance), were the primary factors affecting adult survival. However, there is evidence that cold weather, particularly extended cold snaps with daily low temperatures below 2°C and daily high temperatures below 10°C, decreases overwinter survival. Exceptionally cold winters had a particularly strong effect on adult female plovers, contributing to the male‐biased adult sex ratios. Future winter climate on the north‐central California coast is projected to be generally warmer with fewer and shorter cold snaps. Reduced mortality from cold winter weather may mitigate other threats faced by plovers, such as anthropogenically enhanced predator populations, habitat loss, and accelerated sea level rise, while altering the adult sex ratio and potentially shifting the evolutionary landscape maintaining the plover's unusual breeding system.

Data reduction has gained growing emphasis due to the rapidly unsystematic increase in digital data and has become a sensible approach to big data systems. Data deduplication is a technique to optimize the storage requirements and plays a vital role to eliminate redundancy in large-scale storage. Although it is robust in finding suitable chunk-level break-points for redundancy elimination, it faces key problems of (1) low chunking performance, which causes chunking stage bottleneck, (2) a large variation in chunk-size that reduces the efficiency of deduplication, and (3) hash computing overhead. To handle these challenges, this paper proposes a technique for finding proper cut-points among chunks using a set of commonly repeated patterns (CRP), it picks out the most frequent sequences of adjacent bytes (i.e., contiguous segments of bytes) as breakpoints. Besides to scalable lightweight triple-leveled hashing function (LT-LH) is proposed, to mitigate the cost of hashing function processing and storage overhead; the number of hash levels used in the tests was three, these numbers depend on the size of data to be de-duplicated. To evaluate the performance of the proposed technique, a set of tests was conducted to analyze the dataset characteristics in order to choose the near-optimal length of bytes used as divisors to produce chunks. Besides this, the performance assessment includes determining the proper system parameter values leading to an enhanced deduplication ratio and reduces the system resources needed for data deduplication. Since the conducted results demonstrated the effectiveness of the CRP algorithm is 15 times faster than the basic sliding window (BSW) and about 10 times faster than two thresholds two divisors (TTTD). The proposed LT-LH is faster five times than Secure Hash Algorithm 1 (SHA1) and Message-Digest Algorithm 5 (MD5) with better storage saving.

Abstract When faced with difficult choices, the possible outcomes are considered through a process known as deliberation. In rats, deliberation is thought to be reflected by pause-and-reorienting behaviors, better known as vicarious trial and errors (VTEs). While VTEs are thought to require medial prefrontal cortex (mPFC) and dorsal hippocampal (dHPC) interactions, no empirical evidence has yet demonstrated such a dual requirement. The nucleus reuniens (Re) of the ventral midline thalamus is anatomically connected with both the mPFC and dHPC, is required for HPC-dependent spatial memory tasks, and is critical for mPFC-dHPC neural synchronization. Currently, it is unclear if, or how, the Re is involved in deliberation. Therefore, by examining the role of the Re on VTE behaviors, we can better understand the anatomical and physiological mechanisms supporting deliberation. Here, we examined the impact of Re suppression on VTE behaviors and mPFC-dHPC theta synchrony during asymptotic performance of a HPC-dependent delayed alternation (DA) task. Pharmacological suppression of the Re increased VTE behaviors that occurred with repetitive choice errors. These errors were best characterized as perseverative behaviors, in which some rats repeatedly selected a goal arm that previously yielded no reward. We then examined the impact of Re suppression on mPFC-dHPC theta synchrony during VTEs. We found that during VTEs, Re inactivation was associated with a reduction in mPFC-dHPC theta coherence and mPFC-to-dHPC theta directionality. Our findings suggest that the Re contributes to deliberation by coordinating mPFC-dHPC neural interactions.

Abstract Mosquito vectors are a tremendous public health threat. One in six diseases worldwide is vector-borne transmitted mainly by mosquitoes. In the last couple of years, there have been active Yellow fever virus (YFV) outbreaks in many settings in Nigeria, and nationwide, entomological surveillance has been a significant effort geared towards understanding these outbreaks. In this study, we used a metagenomic sequencing approach to characterize viruses present in vector samples collected during various outbreaks of Yellow fever (YF) in Nigeria between 2017 and 2020. Mosquito samples were grouped into pools of 1 to 50 mosquitoes, each based on species, sex and location. Twenty-five pools of Aedes spp and one pool of Anopheles spp collected from nine states were sequenced and metagenomic analysis was carried out. We identified a wide diversity of viruses belonging to various families in this sample set. Seven different viruses detected included: Fako virus, Phasi Charoen-like virus, Verdadero virus, Chaq like-virus, Aedes aegypti totivirus, cell fusing agent virus and Tesano Aedes virus. Although there are no reports of these viruses being pathogenic, they are an understudied group in the same families and closely related to known pathogenic arboviruses. Our study highlights the power of next generation sequencing in identifying Insect specific viruses (ISVs), and provide insight into mosquito vectors virome in Nigeria.

Snow reliability is a key climatic impact driver for the ski tourism industry, although there are only a few studies addressing past changes in snow reliability in ski resorts accounting for snow management practices (grooming and snowmaking, in particular). This study provides an assessment of past changes in natural and managed snow cover reliability from 1961 to 2019 in the French Alps. In particular, we used snowmaking investment figures to infer the evolution of snowmaking coverage at the ski resort scale for 16 ski resorts in the French Alps, which we used together with a detailed snow cover modelling system driven by a local atmospheric reanalysis. We find different benefits of snow management to reduce the variability and long-term decrease in snow cover reliability because of the heterogeneity of the snowmaking deployment trajectories across ski resorts. The frequency of challenging conditions for ski resort operation over the 1991–2019 period increased in November and February to April compared to the 30-year reference period 1961–1990. In general, snowmaking had a positive impact on snow reliability, especially in December to January. While for the highest-elevation ski resorts, snowmaking improved snow reliability for the core of the winter season, it did not counterbalance the decreasing trend in snow cover reliability for lower-elevation ski resorts and in the spring.

Background: Over the years, the morbidity and mortality due to cancer have continued to increase worldwide. Plants are well utilized in Nigeria ethno-medicine for cancer treatment. However, scientific evidence, particularly at the molecular level, has been lacking, and biodiversity loss is a threat. Aim of the study: The cytotoxic activity of the leaves of six plants used in Nigeria ethno-medicine was investigated and the molecular pathway of cytotoxic action of two active extracts on four cancer cell lines (A549, RD, MCF-7, and HeLa) was also assessed. Materials and methods: Cytotoxic activities of the plant extracts were assessed on breast (MCF-7), lung (A549), cervical (HeLa), adenocarcinoma and rhabdomyosarcoma (RD) cells using MTT cell viability assay in a time-dependent manner. The sandwich ELISA method was used to assess the protein expressions (Bcl-2, BAX, and executioner caspase 3) involved in the apoptotic pathway in cancer cells after treatment with cytotoxic extracts. UHPLC-MS/MS approach was used to analyze the possible bioactive phytochemicals of the cytotoxic plant extract. Results: Uvaria chamae and Dicliptera paniculata extracts displayed good cytotoxicity across all cell lines in a time- and concentration-dependent manner (CC50

Background:. Seroma formation is the most common complication after mastectomy. While the exact pathophysiology behind seroma development has not been entirely elucidated, seromas are associated with negative outcomes in breast reconstruction. The utilization of drains is one method to combat seroma. However, the current state of plastic surgery is divided as to whether one drain or two drains is optimal in reducing seroma formation. We hypothesized that using two drains instead of one drain would reduce the risk of seroma more so than one drain. Methods:. This was a retrospective cohort study of patients who underwent prepectoral direct to implant reconstruction at a single institution by a single surgeon. Each patient underwent reconstruction with either one or two drains. Patients were followed postoperatively for rates of seroma formation. Seroma were classified as either minor or major. Secondary variables including drain duration, infection, and necrosis were also analyzed. Results:. A total of 99 breasts and 71 patients experienced breast reconstruction with two drains, and 163 breasts corresponding to 135 patients received reconstruction with one drain. In the two drain cohort, 14 (14.1%) developed a seroma, with 11 (11.1%) being minor seromas and three (3.03%) being major seromas. In comparison, out of the one drain cohort, 41 (25.2%) developed a seroma, with 35 (21.5%) being a minor seroma and six (3.68%) being classified as major. Conclusion:. This study suggests that two drains decreases the rate and risk of seroma formation compared to one drain in prepectoral breast reconstruction with an acellular dermal matrix.

Background Immunotherapy in high-risk neuroblastoma (HR-NBL) does not live up to its full potential due to inadequate (adaptive) immune engagement caused by the extensive immunomodulatory capacity of HR-NBL. We aimed to tackle one of the most notable immunomodulatory processes in neuroblastoma (NBL), absence of major histocompatibility complex class I (MHC-I) surface expression, a process greatly limiting cytotoxic T cell engagement. We and others have previously shown that MHC-I expression can be induced by cytokine-driven immune modulation. Here, we aimed to identify tolerable pharmacological repurposing strategies to upregulate MHC-I expression and therewith enhance T cell immunogenicity in NBL.Methods Drug repurposing libraries were screened to identify compounds enhancing MHC-I surface expression in NBL cells using high-throughput flow cytometry analyses optimized for adherent cells. The effect of positive hits was confirmed in a panel of NBL cell lines and patient-derived organoids. Compound-treated NBL cell lines and organoids were cocultured with preferentially expressed antigen of melanoma (PRAME)-reactive tumor-specific T cells and healthy-donor natural killer (NK) cells to determine the in vitro effect on T cell and NK cell cytotoxicity. Additional immunomodulatory effects of histone deacetylase inhibitors (HDACi) were identified by transcriptome and translatome analysis of treated organoids.Results Drug library screening revealed MHC-I upregulation by inhibitor of apoptosis inhibitor (IAPi)- and HDACi drug classes. The effect of IAPi was limited due to repression of nuclear factor kappa B (NFκB) pathway activity in NBL, while the MHC-I-modulating effect of HDACi was widely translatable to a panel of NBL cell lines and patient-derived organoids. Pretreatment of NBL cells with the HDACi entinostat enhanced the cytotoxic capacity of tumor-specific T cells against NBL in vitro, which coincided with increased expression of additional players regulating T cell cytotoxicity (eg, TAP1/2 and immunoproteasome subunits). Moreover, MICA and MICB, important in NK cell cytotoxicity, were also increased by entinostat exposure. Intriguingly, this increase in immunogenicity was accompanied by a shift toward a more mesenchymal NBL cell lineage.Conclusions This study indicates the potential of combining (immuno)therapy with HDACi to enhance both T cell-driven and NKcell-driven immune responses in patients with HR-NBL.

Abstract Background Malaria diagnosis in many malaria-endemic countries relies mainly on the use of rapid diagnostic tests (RDTs). The majority of commercial RDTs used in Africa detect the Plasmodium falciparum histidine-rich protein 2 (PfHRP2). pfhrp2/3 gene deletions can therefore lead to false-negative RDT results. This study aimed to evaluate the frequency of PCR-confirmed, false-negative P. falciparum RDT results in Monrovia, Liberia. Methods PfHRP2-based RDT (Paracheck Pf®) and microscopy results from 1038 individuals with fever or history of fever (n = 951) and pregnant women at first antenatal care (ANC) visit (n = 87) enrolled in the Saint Joseph’s Catholic Hospital (Monrovia) from March to July 2019 were used to assess the frequency of false-negative RDT results. True–false negatives were confirmed by detecting the presence of P. falciparum DNA by quantitative PCR in samples from individuals with discrepant RDT and microscopy results. Samples that were positive by 18S rRNA qPCR but negative by PfHRP2-RDT were subjected to multiplex qPCR assay for detection of pfhrp2 and pfhrp3. Results One-hundred and eighty-six (19.6%) and 200 (21.0%) of the 951 febrile participants had a P. falciparum-positive result by RDT and microscopy, respectively. Positivity rate increased with age and the reporting of joint pain, chills and shivers, vomiting and weakness, and decreased with the presence of coughs and nausea. The positivity rate at first ANC visit was 5.7% (n = 5) and 8% (n = 7) by RDT and microscopy, respectively. Out of 207 Plasmodium infections detected by microscopy, 22 (11%) were negative by RDT. qPCR confirmed absence of P. falciparum DNA in the 16 RDT-negative but microscopy-positive samples which were available for molecular testing. Among the 14 samples that were positive by qPCR but negative by RDT and microscopy, 3 only amplified pfldh, and among these 3 all were positive for pfhrp2 and pfhrp3. Conclusion There is no qPCR-confirmed evidence of false-negative RDT results due to pfhrp2/pfhrp3 deletions in this study conducted in Monrovia (Liberia). This indicates that these deletions are not expected to affect the performance of PfHRP2-based RDTs for the diagnosis of malaria in Liberia. Nevertheless, active surveillance for the emergence of PfHRP2 deletions is required.

Abstract Prisons in the United States have become a hotbed for spreading COVID-19 among incarcerated individuals. COVID-19 cases among prisoners are on the rise, with more than 143,000 confirmed cases to date. However, there is paucity of data addressing clinical outcomes and mortality in prisoners hospitalized with COVID-19. An observational study of all patients hospitalized with COVID-19 between March 10 and May 10, 2020 at two Henry Ford Health System hospitals in Michigan. Clinical outcomes were compared amongst hospitalized prisoners and non-prisoner patients. The primary outcomes were intubation rates, in-hospital mortality, and 30-day mortality. Multivariable logistic regression and Cox-regression models were used to investigate primary outcomes. Of the 706 hospitalized COVID-19 patients (mean age 66.7 ± 16.1 years, 57% males, and 44% black), 108 were prisoners and 598 were non-prisoners. Compared to non-prisoners, prisoners were more likely to present with fever, tachypnea, hypoxemia, and markedly elevated inflammatory markers. Prisoners were more commonly admitted to the intensive care unit (ICU) (26.9% vs. 18.7%), required vasopressors (24.1% vs. 9.9%), and intubated (25.0% vs. 15.2%). Prisoners had higher unadjusted inpatient mortality (29.6% vs. 20.1%) and 30-day mortality (34.3% vs. 24.6%). In the adjusted models, prisoner status was associated with higher in-hospital death (odds ratio, 2.32; 95% confidence interval (CI), 1.33 to 4.05) and 30-day mortality (hazard ratio, 2.00; 95% CI, 1.33 to 3.00). In this cohort of hospitalized COVID-19 patients, prisoner status was associated with more severe clinical presentation, higher rates of ICU admissions, vasopressors requirement, intubation, in-hospital mortality, and 30-day mortality.

Abstract Spatial transcriptomic and proteomic technologies have provided new opportunities to investigate cells in their native microenvironment. Here we present Giotto, a comprehensive and open-source toolbox for spatial data analysis and visualization. The analysis module provides end-to-end analysis by implementing a wide range of algorithms for characterizing tissue composition, spatial expression patterns, and cellular interactions. Furthermore, single-cell RNAseq data can be integrated for spatial cell-type enrichment analysis. The visualization module allows users to interactively visualize analysis outputs and imaging features. To demonstrate its general applicability, we apply Giotto to a wide range of datasets encompassing diverse technologies and platforms.

Background and Aims: The coronavirus disease 2019 (COVID-19) pandemic has initiated modified protocols for aerosol-generating procedures. A simulation study using dye was conducted to highlight contamination at intubation and extubation and to encourage adherence to the new COVID-19 protocol among anaesthesia personnel in our institution. Methods: A video demonstrating the new COVID-19 protocols was circulated in the Department of Anaesthesiology a week prior to the study. Thirty teams, each comprising an anaesthesia resident and a staff technician, were enroled. Each team was asked to demonstrate the steps of preparation, intubation and extubation on a mannequin in a COVID-19 scenario. Checklists were used to assess points of contamination and adherence to the protocols. Following debriefing, a repeat simulation was conducted. The use of a dye highlighted the points of contamination. The study subjects provided feedback on the usefulness of the session and practical difficulties encountered in adapting to the new protocols. Results: The average contamination scores decreased by 3.4 (95% confidence interval (CI): 2.4–4.4, P < 0.001) in the post-debrief session. Adherence to the steps of the modified protocol improved by a score of 2.7 (CI: 3.6–1.83) among anaesthesiologists and by 4.3 (CI: 5.3–3.3) among technicians. Further, 93% felt that the use of the colour indicator reinforced awareness of the possible points of contamination. Conclusion: Simulation with a low-fidelity mannequin by using colour indicator for secretions is an effective teaching tool to reduce health hazards during airway management in COVID-19 times.

Effective disease outbreak response has historically been a challenging accomplishment for the Nigerian health system due to an array of hurdles not unique to Nigeria but also found in other African nations which share its large size and complexity. However, the efficiency of the response mounted against the Ebola Virus Disease (EVD) outbreak of 2014 proved that indeed, though challenging, proactive and effective outbreak response is not impossible. With over 20 public health emergencies and infectious disease outbreaks between 2016 and 2018 alone, Nigeria is one of only five members of the World Health Organization (WHO) African Region to report five or more public health events per annum. There are many lessons that can be drawn from Nigeria's experience in handling outbreaks of infectious diseases. In this review, we discuss the history of emerging and re-emerging infectious disease outbreaks in Nigeria and explore the response strategies mounted towards each. We also highlight the significant successes and note-worthy limitations, which we have then utilized to proffer policy recommendations to strengthen the Nigerian public health emergency response systems.

We have studied the evolution of the Greenland ice sheet under a range of constant climates typical of those projected for the end of the present century using a dynamical ice sheet model (Glimmer) coupled to an atmosphere general circulation model (FAMOUS–ice AGCM). The ice sheet surface mass balance (SMB) is simulated within the AGCM by a multilayer snow scheme from snowfall and surface energy fluxes, including refreezing and dependence on altitude within AGCM grid boxes. Over millennia under any warmer climate, the ice sheet reaches a new steady state, whose mass is correlated with the magnitude of global climate change imposed. If a climate that gives the recently observed SMB were maintained, global-mean sea level rise (GMSLR) would reach 0.5–2.5 m. For any global warming exceeding 3 K, the contribution to GMSLR exceeds 5 m. For the largest global warming considered (about +5 K), the rate of GMSLR is initially 2.7 mm yr−1, and eventually only a small ice cap endures, resulting in over 7 m of GMSLR. Our analysis gives a qualitatively different impression from previous work in that we do not find a sharp threshold warming that divides scenarios in which the ice sheet suffers little reduction from those in which it is mostly lost. The final steady state is achieved by withdrawal from the coast in some places and a tendency for increasing SMB due to enhancement of cloudiness and snowfall over the remaining ice sheet by the effects of topographic change on atmospheric circulation, outweighing the tendency for decreasing SMB from the reduction in surface altitude. If late 20th-century climate is restored after the ice sheet mass has fallen below a threshold of about 4 m of sea level equivalent, it will not regrow to its present extent because the snowfall in the northern part of the island is reduced once the ice sheet retreats from there. In that case, about 2 m of GMSLR would become irreversible. In order to avoid this outcome, anthropogenic climate change must be reversed before the ice sheet has declined to the threshold mass, which would be reached in about 600 years at the highest rate of mass loss within the likely range of the Fifth Assessment Report of the Intergovernmental Panel on Climate Change.

The imperiled pallid sturgeon (Scaphirhynchus albus) and closely related, but more common, shovelnose sturgeon (S. platorynchus) are believed to broadcast adhesive, demersal eggs in the current and over coarse substrate in turbid rivers of the North American midcontinent. It has been hypothesized that eggs settle immediately following fertilization, but field conditions preclude direct observation. We conducted laboratory studies to characterize the diameter, shape, settling velocity, and specific gravity of pallid sturgeon and shovelnose sturgeon eggs. Based on these laboratory measurements, we then modeled the potential fate of pallid sturgeon eggs by considering these physical properties in the context of two field sites where spawning has occurred. Although eggs of pallid sturgeon and shovelnose sturgeon were of a similar size and shape, shovelnose sturgeon eggs had slightly higher specific gravity and settling velocity. For representative hydraulic conditions at documented spawning sites in the mainstem Missouri and Lower Yellowstone Rivers, eggs of both species will likely be concentrated near the bed although some eggs may be distributed throughout the water column. Simulations of egg transport indicate that eggs may be transported up to several hundred meters downstream from spawning locations in the approximate length of time required for eggs to become adhesive. Estimates of egg transport presented here rely on simplifying assumptions about river hydraulics and limited understanding of how eggs interact with the complex substrates and flow near the bed; results highlight the need for additional studies to evaluate the fate of eggs and fertilized embryos of both species.

ABSTRACT Due to its high transmissibility, Klebsiella pneumoniae is one of the leading causes of nosocomial infections. Here, we studied the biological cost of colistin resistance, an antibiotic of last resort, in this opportunistic pathogen using a murine model of gut colonization and transmission. Colistin resistance in K. pneumoniae is commonly the result of the inactivation of the small regulatory protein MgrB. Without a functional MgrB, the two-component system PhoPQ is constitutively active, leading to an increase in lipid A modifications and subsequent colistin resistance. Using an isogenic mgrB deletion mutant (MgrB−), we demonstrate that the mutant’s colistin resistance is not associated with a fitness defect under in vitro growth conditions. However, in our murine model of K. pneumoniae gastrointestinal (GI) colonization, the MgrB− colonizes the gut poorly, allowing us to identify a fitness cost. Moreover, the MgrB− mutant has higher survival outside the host compared with the parental strain. We attribute this enhanced survivability to dysregulation of the PhoPQ two-component system and accumulation of the master stress regulator RpoS. The enhanced survival of MgrB− may be critical for its rapid host-to-host transmission observed in our model. Together, our data using multiple clinical isolates demonstrate that MgrB-dependent colistin resistance in K. pneumoniae comes with a biological cost in gut colonization. However, this cost is mitigated by enhanced survival outside the host and consequently increases its host-to-host transmission. Additionally, it underscores the importance of considering the entire life cycle of a pathogen to determine the actual biological cost associated with antibiotic resistance. IMPORTANCE The biological cost associated with colistin resistance in Klebsiella pneumoniae was examined using a murine model of K. pneumoniae gut colonization and fecal-oral transmission. A common mutation resulting in colistin resistance in K. pneumoniae is a loss-of-function mutation of the small regulatory protein MgrB that regulates the two-component system PhoPQ. Even though colistin resistance in K. pneumoniae comes with a fitness defect in gut colonization, it increases bacterial survival outside the host enabling it to transmit more effectively to a new host. The enhanced survival is dependent upon the accumulation of RpoS and dysregulation of the PhoPQ. Hence, our study expands our understanding of the underlying molecular mechanism contributing to the transmission of colistin-resistant K. pneumoniae.

The design of bioinspired polymers has long been an area of intense study, however, applications to the design of concrete admixtures for improved materials performance have been relatively unexplored. In this work, we functionalized poly(acrylic acid) (PAA), a simple analogue to polycarboxylate ether admixtures in concrete, with dopamine to form a catechol-bearing polymer (PAA-g-DA). Synthetic routes using hydroxybenzotriazole (HOBt) as an activating agent were examined for their ability in grafting dopamine to the PAA backbone. Previous literature using the traditional coupling reagent 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) to graft dopamine to PAA were found to be inconsistent and the sensitivity of EDC coupling reactions necessitated a search for an alternative. Additionally, HOBt allowed for greater control over per cent functionalization of the backbone, is a simple, robust reaction, and showed potential for scalability. This finding also represents a novel synthetic pathway for amide bond formation between dopamine and PAA. Finally, we performed preliminary adhesion studies of our polymer on rose granite specimens and demonstrated a 56% improvement in the mean adhesion strength over unfunctionalized PAA. These results demonstrate an early study on the potential of PAA-g-DA to be used for improving the bonds within concrete.

When a recent accreditation review report and an assessment consultant report both identified issues with assessment and shared governance, the three faculty governing bodies of National University met with the Provost and President to brainstorm and discuss a shared governance action plan to address these issues. As a result of this meeting, the Faculty Senate, Graduate Council, Undergraduate Council, and the Council of Chairs (not a governing body) representatives made a presentation to the Provost and President to improve the academic assessment process at the University by implementing a shared governance plan that would revitalize the faculty and move both the faculty and the administration toward a culture of academic assessment and excellence. The President concurred with the shared governance assessment plan approach proposed by the faculty governing bodies and approved implementation of the plan. This paper explores relevant research on this subject and provides a chronology of the events that comprised the efforts to improve shared governance between the faculty and the administration at National University in order to achieve academic assessment and learning excellence.

PurposeCyclin-dependent kinases (CDKs) that have critical roles in RNA polymerase II (Pol II)-mediated gene transcription are emerging as therapeutic targets in cancer. We have previously shown that THZ1, a covalent inhibitor of CDKs 7/12/13, leads to cytotoxicity in MYCN-amplified neuroblastoma through the downregulation of super-enhancer-associated transcriptional upregulation. Here we determined the effects of YKL-5-124, a novel covalent inhibitor with greater selectivity for CDK7 in neuroblastoma cells.Experimental DesignWe tested YKL-5-124 in MYCN-amplified and nonamplified neuroblastoma cells individually and in combination with other inhibitors in cell line and animal models. Cell viability, target validation, effects on cell cycle and transcription were analyzed.ResultsCDK7 inhibition with YKL-5-124 did not lead to significant cell death, but resulted in aberrant cell cycle progression especially in MYCN-amplified cells. Unlike THZ1, YKL-5-124 had minimal effects on Pol II C-terminal domain phosphorylation, but significantly inhibited that of the CDK1 and CDK2 cell cycle kinases. Combining YKL-5-124 with the BRD4 inhibitor JQ1 resulted in synergistic cytotoxicity. A distinct MYCN-gene expression signature associated with resistance to BRD4 inhibition was suppressed with the combination. The synergy between YKL-5-124 and JQ1 translated into significant tumor regression in cell line and patient-derived xenograft mouse models of neuroblastoma.ConclusionsThe combination of CDK7 and BRD4 inhibition provides a therapeutic option for neuroblastoma and suggests that the addition of YKL-5-124 could improve the therapeutic efficacy of JQ1 and delay resistance to BRD4 inhibition.

Dans les Alpes, les impacts du réchauffement climatique sont déjà bien visibles et dépassent les frontières, nécessitant une adaptation des territoires. Dans la région tranfrontalière du Mont-Blanc, le projet « AdaPT Mont-Blanc » a réuni les collectivités et les acteurs du territoire pendant trois ans sur l'adaptation de la planification territoriale aux changements climatiques. Cet article présente l'expérience du bureau d'étude ACTeon dans l'accompagnement et la mise en œuvre de la démarche participative du projet, en mettant l'accent sur les enseignements et la plus value de la démarche pour définir une stratégie locale d'adaptation aux changements attendus.

In most cancers, mutations that lead to oncogene activation and tumor suppressor inactivation synergize to promote tumorigenesis. However, in neuroblastomas, MYCN amplification and ATRX mutations are mutually exclusive and incompatible.