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Abstract Recent findings suggest that adding a visual depiction of a nose to virtual reality displays (virtual nose) can reduce motion sickness. If so, this would be a simple intervention that could improve the experience of a variety of VR applications. However, only one peer-reviewed study has reported a benefit from a virtual nose, and the effect was observed in a single low-powered experiment. To further test the effectiveness of a virtual nose for mitigating motion sickness in VR, we performed a preregistered experiment with higher power and better control. Subjects were presented with simulated movement in a virtual environment using a head-mounted display, and the resulting motion sickness was measured using the Fast Motion Sickness Scale (FMS) and the Simulator Sickness Questionnaire (SSQ). Conditions with and without a virtual nose were tested in separate sessions on different days, and the mean habituation effects were removed analytically. Awareness of the manipulation was assessed with a funnel debriefing procedure. The sample size (n = 32) was chosen to have over 90% power to detect the estimated effect size based on previous data (d z = 0.6). We found no significant difference between motion sickness in conditions with and without the virtual nose. The estimated effect size was close to zero, d z = − 0.02, with a 95% credible interval [− 0.37, 0.33]. Results from a Bayesian analysis imply that any benefit from a virtual nose is unlikely to be more than a 26% reduction in FMS scores, and any cost is unlikely to be more than a 23% increase. Our results do not support the hypothesis that a virtual nose is a general and effective way to relieve motion sickness in virtual reality.

Abstract Background Critical bleeding events in adults and children with ITP are medical emergencies; however, evidence-based treatment protocols are lacking. Due to the severe thrombocytopenia, (typically platelet count less than 20 × 109/L), a critical bleed portends a high risk of death or disability. We plan to perform a systematic review and meta-analysis of treatments for critical bleeding in patients with ITP that will inform evidence-based recommendations. Methods Literature searches will be conducted in four electronic databases: Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed. Eligible studies will be randomized controlled trials or observational studies that enrolled patients with ITP describing one or more interventions for the management of critical bleeding. Title and abstract screening, full-text screening, data extraction, and risk of bias evaluation will be conducted independently and in duplicate using Covidence and Excel. Outcomes will be pooled for meta-analysis where appropriate or summarized descriptively. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology will be used to evaluate the certainty of the evidence. Primary outcomes of interest will include frequency of critical bleeds, mortality and bleeding-related mortality, bleeding resolution, platelet count, and disability. Discussion Evidence-based treatments for critical bleeding in patients with ITP are needed to improve patient outcomes and standardize care in the emergency setting. Systematic review registration CRD42020161206.

Abstract Probing the surface of proteins to predict the binding site and binding affinity for a given small molecule is a critical but challenging task in drug discovery. Blind docking addresses this issue by performing docking on binding regions randomly sampled from the entire protein surface. However, compared with local docking, blind docking is less accurate and reliable because the docking space is too largetly sampled. Cavity detection-guided blind docking methods improved the accuracy by using cavity detection (also known as binding site detection) tools to guide the docking procedure. However, it is worth noting that the performance of these methods heavily relies on the quality of the cavity detection tool. This constraint, namely the dependence on a single cavity detection tool, significantly impacts the overall performance of cavity detection-guided methods. To overcome this limitation, we proposed Consensus Blind Dock (CoBDock), a novel blind, parallel docking method that uses machine learning algorithms to integrate docking and cavity detection results to improve not only binding site identification but also pose prediction accuracy. Our experiments on several datasets, including PDBBind 2020, ADS, MTi, DUD-E, and CASF-2016, showed that CoBDock has better binding site and binding mode performance than other state-of-the-art cavity detector tools and blind docking methods.

Corn (Zea mays) biomass accumulation and nutrient uptake by the six-leaf collar (V6) growth stage are low, and therefore, synchronizing nutrient supply with crop demand could potentially minimize nutrient loss and improve nutrient use efficiency. Knowledge of corn’s response to nutrient stress in the early growth stages could inform such nutrient management. Field studies were conducted to assess corn recovery from when no fertilizer application is made until the V6 growth stage, and thereafter, applying fertilizer rates as those in non-stressed conditions. The early season nutrient stress and non-stress conditions received the same amount of nutrients. As the availability of nutrients for plant uptake is largely dependent on soil moisture, corn recovery from the early season nutrient stress was assessed under different soil moisture regimes induced via irrigation scheduling at 50% and 80% field capacity under overhead and subsurface drip irrigation (SSDI) systems. Peanut (Arachis hypogaea) was the previous crop under all conditions, and the fields were under cereal rye (Secale cereale) cover crop prior to planting corn. At the V6 growth stage, the nutrient concentrations of the early season-stressed crops, except for copper, were above the minimum threshold of sufficiency ranges reported for corn. However, the crops showed poor growth, with biomass accumulation being reduced by over 50% compared to non-stressed crops. Also, the uptake of all nutrients was significantly lower under the early season nutrient stress conditions. The recovery of corn from the early season nutrient stress was low. Compared to non-stress conditions, the early season nutrient stress caused 1.58 Mg ha-1 to 3.4 Mg ha-1 yield reduction. The percent yield reduction under the SSDI system was 37.6-38.2% and that under the overhead irrigation system was 11.7-13%. The high yield reduction from the early season nutrient stress under the SSDI system was because of water stress conditions in the topsoil soil layer. The findings of the study suggest ample nutrient supply in the early season growth stage is critical for corn production, and thus, further studies are recommended to determine the optimum nutrient supply for corn at the initial growth stages.

Lint yield in cotton is governed by light intercepted by the canopy (IPAR), radiation use efficiency (RUE), and harvest index (HI). However, the conventional methods of measuring these yield-governing physiological parameters are labor-intensive, time-consuming and requires destructive sampling. This study aimed to explore the use of low-cost and high-resolution UAV-based RGB and multispectral imagery 1) to estimate fraction of IPAR (IPARf), RUE, and biomass throughout the season, 2) to estimate lint yield using the cotton fiber index (CFI), and 3) to determine the potential use of biomass and lint yield models for estimating cotton HI. An experiment was conducted during the 2021 and 2022 growing seasons in Tifton, Georgia, USA in randomized complete block design with five different nitrogen treatments. Different nitrogen treatments were applied to generate substantial variability in canopy development and yield. UAV imagery was collected bi-weekly along with light interception and biomass measurements throughout the season, and 20 different vegetation indices (VIs) were computed from the imagery. Generalized linear regression was performed to develop models using VIs and growing degree days (GDDs). The IPARf models had R2 values ranging from 0.66 to 0.90, and models based on RVI and RECI explained the highest variation (93%) in IPARf during cross-validation. Similarly, cotton above-ground biomass was best estimated by models from MSAVI and OSAVI. Estimation of RUE using actual biomass measurement and RVI-based IPARf model was able to explain 84% of variation in RUE. CFI from UAV-based RGB imagery had strong relationship (R2 = 0.69) with machine harvested lint yield. The estimated HI from CFI-based lint yield and MSAVI-based biomass models was able to explain 40 to 49% of variation in measured HI for the 2022 growing season. The models developed to estimate the yield-contributing physiological parameters in cotton showed low to strong performance, with IPARf and above-ground biomass having greater prediction accuracy. Future studies on accurate estimation of lint yield is suggested for precise cotton HI prediction. This study is the first attempt of its kind and the results can be used to expand and improve research on predicting functional yield drivers of cotton.

Brassica carinata is a non-food industrial oilseed crop that can be grown in the winter in the southeast US without impacting food, feed, or fiber crops. Carinata is a low carbon advanced renewable fuel feedstock and a good source of animal protein. Carinata research in the SE US through a public-private partnership has developed a comprehensive body of knowledge regarding carinata agronomics, life cycle analysis, best management practices and economics. This article aims to help growers and others interested in carinata to understand its biology, agronomy, and production aspects.

The Benue Trough Basin (BTB) of Nigeria is geologically and geo-morphologically subdivided into upper, middle, and lower segments. The BTB is the subject of geological research due to its rich coal deposits that have the potential for oil and gas. The purpose of the present study is to examine the origins, depositional environments, and thermal history of the selected coals and the processes that influence their quality. Coal samples from different open cast coal mines in the middle BTB were examined using proximate and ultimate, x-ray diffraction (XRD), x-ray fluorescence (XRF), laser ablation induced coupled plasma (LA-ICPMS), and petrographical analyses. The coal samples contained mainly quartz, kaolinite, and organic carbon. The XRD spectra peaks revealed the triclinic and monoclinic structure of kaolin. The SiO2/Al2O3 ratios confirmed the dominance of quartz and kaolinite. The Ni/Co versus V/Cr, Cu/Zn, and V/Mo values in the studied coals suggest oxic depositional environments, whereas the V/(Ni + V) and V/(V + Cr) values indicate oxic to suboxic conditions. The Ce/Ce∗ values are slightly below 1, which indicates a suboxic depositional environment. Maceral texture is indicative of transformations from sub-bituminous to high volatile C or B bituminous coal. The maceral components and mineral matter (≥10%) of the studied coals imply deposition in the planar margin mire, and a river system of planar margin mire environments, respectively. The high gelification index (GI) and tissue preservation index (TPI) values indicate peat accumulation developed within a wet forest swamp. The ternary diagram of the maceral component suggests deposition in a wet moor environment with intermittent moderate to high flooding episodes. The studied coals are sub-hydrous vitrinite inferring hydrogen-poor and thermally immature characteristics. The low V and Ni contents, low H/C and high O/C, indicate Type Ⅲ terrestrial organic matter with the potential to generate gaseous hydrocarbons. The investigated coals were deposited by the river within telmatic, limnic, and limno-telmatic zones in the planar margin mire depositional environments. Overall, the integrated petrologic and geochemical data used in this study provides a reliable approach for the assessment of coal depositional environments.

We developed a bioinformatics-led substrate discovery workflow to expand the known substrate repertoire of MALT1. Our approach, termed GO-2-Substrates, integrates protein function information, including GO terms from known substrates, with protein sequences to rank substrate candidates by similarity. We applied GO-2-Substrates to MALT1, a paracaspase and master regulator of NF-κB signalling in adaptive immune responses. With only 12 known substrates, the evolutionarily conserved paracaspase functions and phenotypes of Malt1 –/– mice strongly implicate the existence of undiscovered substrates. We tested the ranked predictions from GO-2-Substrates of new MALT1 human substrates by co-expression of candidates transfected with the oncogenic constitutively active cIAP2-MALT1 fusion protein or CARD11/BCL10/MALT1 active signalosome. We identified seven new MALT1 substrates by the co-transfection screen: TANK, TAB3, CASP10, ZC3H12D, ZC3H12B, CILK1 and ILDR2. Using catalytically inactive cIAP2-MALT1 (Cys464Ala), a MALT1 inhibitor, MLT-748, and noncleavable P1-Arg to Ala mutant versions of each substrate in dual transfections, we validated the seven new substrates in vitro. We confirmed the cleavage of endogenous TANK and the RNase ZC3H12D in B cells by Western blotting and mining TAILS N-terminomics datasets, where we also uncovered evidence for these and 12 other candidate substrates by endogenous MALT1. Thus, protein function information improves substrate predictions. The new substrates and other high-ranked MALT1 candidate substrates should open new biological frontiers for further validation and exploration of the function of MALT1 within and beyond NF-κB regulation.

Parasitoids forage for hosts in dynamic ecosystems and generally have a short period of time to access hosts. The current study examined the optimal reproductive attributes of two egg parasitoids, Paratelenomus saccharalis Dodd (Hymenoptera: Platygastridae) and Ooencyrtus nezarae Ishii (Hymenoptera: Encyrtidae), of the kudzu bug, Megacopta cribraria Fabricius (Hemiptera: Plataspidae). The proportion of O. nezarae and P. saccharalis adult offspring that emerged from M. cribraria eggs and the sex ratio of the parasitoid offspring were compared among treatments for the effects of different adult parasitoid food sources, host egg-to-adult parasitoid ratios, and host exposure times. Our results suggest that honey solution as a food source, a 21:7 host-to-parasitoid ratio, and three-to-five days of exposure time optimized the production of female O. nezarae offspring. For P. saccharalis, honey solution as a food source, a 21:7 host-to-parasitoid ratio, and one day were optimal for maximizing female offspring production. These findings provide new information about the biology of these egg parasitoids.

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Biodegradable plastic mulch is potentially a suitable alternative to conventional polyethylene mulch because of the limited disposal options of the latter. However, biodegradable plastic mulch must perform better or comparably to polyethylene mulch to be widely adopted. Gas exchange and soil microclimate are important factors impacted by the use of plastic mulch, which in turn have implications on crop productivity. A controlled-environment study was established in a greenhouse to assess gas exchange and soil microclimate dynamics under biodegradable plastic, polyethylene, and paper mulches with and without planting holes, as well as the impact of the mulches on the growth of sweet corn (Zea mays). A no-mulch condition was included as control. In addition, we monitored CO2 concentrations in the vicinity of planting holes (chimney effect) in a greenhouse and agricultural field conditions under sweet corn production. The plastic mulches (both biodegradable plastic and polyethylene mulches) decreased the soil O2concentration to a minimum of 181–183 mmol mol-1, and when compared to the no-mulch, the plastic mulches reduced water loss within 50 days by 35–68 mm. The paper mulch inhibited light penetration more than did the plastic mulches. There was an increase in the CO2 concentration at 2.5 cm above the planting holes in the plastic mulches compared to that under the no-mulch. However, the differences were not discernible at 15 cm above the ground. Consequently, we did not observe significant impacts on the growth of sweet corn, possibly, because the canopy height of sweet corn was more than 15 cm within a few days after planting. Overall, the plastic mulches did not reduce O2 concentration below 100 mmol mol-1, the minimum level in which plant growth becomes impaired. Also, the often reported improved growth of sweet corn from plastic mulching could be attributable to other factors, such as weed control, reduced water loss, and early season soil warming, rather than elevated CO2 concentrations and fluxes in the vicinity of planting holes. Highlights - Gas exchange and soil microclimate dynamics under biodegradable plastic, polyethylene, and paper mulches were assessed - Elevated CO2 levels were observed near planting holes of plastic mulches (both biodegradable and polyethylene) - The plastic mulches inhibited O2 exchange, but not to a level that could impair plant growth - Polyethylene mulch conserved soil water better than biodegradable plastic and paper mulches - Paper mulch inhibited light penetration better than plastic mulches

Abstract Background KRAS (KRAS proto-oncogene, GTPase; OMIM: 190,070) encodes one of three small guanosine triphosphatase proteins belonging to the RAS family. This group of proteins is responsible for cell proliferation, differentiation and inhibition of apoptosis. Gain-of-function variants in KRAS are commonly found in human cancers. Non-malignant somatic KRAS variants underlie a subset of RAS-associated autoimmune leukoproliferative disorders (RALD). RALD is characterized by splenomegaly, persistent monocytosis, hypergammaglobulinemia and cytopenia, but can also include autoimmune features and lymphadenopathy. In this report, we describe a non-malignant somatic variant in KRAS with prominent clinical features of massive splenomegaly, thrombocytopenia and lymphopenia. Case presentation A now-11-year-old girl presented in early childhood with easy bruising and bleeding, but had an otherwise unremarkable medical history. After consulting for the first time at 5 years of age, she was discovered to have massive splenomegaly. Clinical follow-up revealed thrombocytopenia, lymphopenia and increased polyclonal immunoglobulins and C-reactive protein. The patient had an unremarkable bone marrow biopsy, flow cytometry showed no indication of expanded double negative T-cells, while malignancy and storage disorders were also excluded. When the patient was 8 years old, whole exome sequencing performed on DNA derived from whole blood revealed a heterozygous gain-of-function variant in KRAS (NM_004985.5:c.37G > T; (p.G13C)). The variant was absent from DNA derived from a buccal swab and was thus determined to be somatic. Conclusions This case of idiopathic splenomegaly in childhood due to a somatic variant in KRAS expands our understanding of the clinical spectrum of RAS-associated autoimmune leukoproliferative disorder and emphasizes the value of securing a molecular diagnosis in children with unusual early-onset presentations with a suspected monogenic origin.

Abstract While emerging data suggest nucleotide oligomerization domain receptor 1 (NOD1), a cytoplasmic pattern recognition receptor, may play an important and complementary role in the immune response to bacterial infection, its role in cancer metastasis is entirely unknown. Hence, we sought to determine the effects of NOD1 on metastasis. NOD1 expression in paired human primary colon cancer, human and murine colon cancer cells were determined using immunohistochemistry and immunoblotting (WB). Clinical significance of NOD1 was assessed using TCGA survival data. A series of in vitro and in vivo functional assays, including adhesion, migration, and metastasis, was conducted to assess the effect of NOD1. C12-iE-DAP, a highly selective NOD1 ligand derived from gram-negative bacteria, was used to activate NOD1. ML130, a specific NOD1 inhibitor, was used to block C12-iE-DAP stimulation. Stable knockdown (KD) of NOD1 in human colon cancer cells (HT29) was constructed with shRNA lentiviral transduction and the functional assays were thus repeated. Lastly, the predominant signaling pathway of NOD1-activation was identified using WB and functional assays in the presence of specific kinase inhibitors. Our data demonstrate that NOD1 is highly expressed in human colorectal cancer (CRC) and human and murine CRC cell lines. Clinically, we demonstrate that this increased NOD1 expression negatively impacts survival in patients with CRC. Subsequently, we identify NOD1 activation by C12-iE-DAP augments CRC cell adhesion, migration and metastasis. These effects are predominantly mediated via the p38 mitogen activated protein kinase (MAPK) pathway. This is the first study implicating NOD1 in cancer metastasis, and thus identifying this receptor as a putative therapeutic target.

Growers rely on nutrient sufficiency ranges (NSRs) after plant tissue analysis to inform timely nutrient management decisions. The NSRs are typically established from survey studies across multiple locations, which could be confounded by several abiotic and biotic factors. We conducted field studies in 2020, 2021, and 2022 to validate the lower thresholds of the NSRs for corn (Zea mays) at the early growth stage as reported in the Southern Cooperative Series Bulletin #394. We induced various corn nutritional levels by making different nutrient application rates. If the NSRs are valid, samples within the same replication that satisfy the NSRs of all nutrients should have similar biomass accumulation. The results showed that the NSRs were not valid under the conditions tested. In total, 47.6% of the samples satisfied all the lower thresholds of the NSRs, and 25.4% of those samples had relative biomass

B-cell lymphoma/leukemia 11B (BCL11B) is a C2H2 zinc finger transcription factor that is critically important for regulating the development and function of a variety of systems including the central nervous system, the skin, and the immune system. Germline heterozygous variants are associated with a spectrum of clinical disorders, including severe combined immunodeficiency as well as neurological, craniofacial, and dermal defects. Of these individuals, ~50% present with severe allergic disease. Here, we report the detailed clinical and laboratory workup of one of the most severe BCL11B-dependent atopic cases to date. Leveraging a zebrafish model, we were able to confirm a strong T-cell defect in the patient. Based on these data, we classify germline BCL11B-dependent atopic disease as a novel primary atopic disorder.

Nuclear factor kappa B (NF-κB) is a critical transcription factor involved in regulating cell activation, inflammation, and survival. The linear ubiquitin chain assembly complex (LUBAC) which consists of HOIL1, HOIP, and SHARPIN, catalyzes the linear ubiquitination of target proteins—a post-translational modification that is essential for NF-κB activation. Human germline pathogenic variants that dysregulate linear ubiquitination and NF-κB signaling are associated with immunodeficiency and/or autoinflammation including dermatitis, recurrent fevers, systemic inflammation and enteropathy. We previously identified MALT1 paracaspase as a novel negative regulator of LUBAC by proteolytic cleavage of HOIL1. To directly investigate the impact of HOIL1 cleavage activity on the inflammatory response, we employed a stable transduction system to express and directly compare non-cleavable HOIL1 with wild-type HOIL1 in primary HOIL1-deficient patient skin fibroblasts. We discovered that non-cleavable HOIL1 resulted in enhanced NF-κB signaling in response to innate stimuli. Transcriptomics revealed enrichment of inflammation and proinflammatory cytokine-related pathways after stimulation. Multiplexed cytokine assays confirmed a ‘hyperinflammatory’ phenotype in these cells. This work highlights the physiological importance of MALT1-dependent cleavage and modulation of HOIL1 on NF-κB signaling and inflammation, provides a mechanism for the autoinflammation observed in MALT1-deficient patients, and will inform the development of therapeutics that target MALT1 paracaspase and LUBAC function in treating autoinflammatory skin diseases.

Summary: Provoked by sterile/nonsterile insults, prolonged monocyte mobilization and uncontrolled monocyte/macrophage activation can pose imminent or impending harm to the affected organs. Curiously, folate receptor beta (FRβ), with subnanomolar affinity for the vitamin folic acid (FA), is upregulated during immune activation in hematopoietic cells of the myeloid lineage. This phenomenon has inspired a strong interest in exploring FRβ-directed diagnostics/therapeutics. Previously, we have reported that FA-targeted aminopterin (AMT) therapy can modulate macrophage function and effectively treat animal models of inflammation. Our current investigation of a lead compound (EC2319) leads to discovery of a highly FR-specific mechanism of action independent of the root causes against inflammatory monocytes. We further show that EC2319 suppresses interleukin-6/interleukin-1β release by FRβ+ monocytes in a triple co-culture leukemic model of cytokine release syndrome with anti-CD19 chimeric antigen receptor T cells. Because of its chemical stability and metabolically activated linker, EC2319 demonstrates favorable pharmacokinetic characteristics and cross-species translatability to support future pre-clinical and clinical development.

Modern cotton (Gossypium spp. L) cultivars are efficient in nutrient uptake and utilization, and thus, may potentially tolerate nutrient stress. Early- and late-season nutrient stress (E-stress and L-stress, respectively) effects on cotton productivity and quality were assessed under different production conditions in Camilla and Midville, GA, USA. The E-stress received no nutrient application in the early season, but the full rates were split-applied equally at the initiation of squares and the second week of bloom stages. The L-stress received 30–40% of the full nutrient rates only at the initial stage of planting. The effects of nutrient stress on cotton productivity and fiber quality were not consistent across the different production conditions. Compared to the full nutrient rate, the E-stress did not adversely impact cotton yield, but rather it improved the lint and cottonseed yields under one production condition by 17.5% and 19.3%, respectively. Averaged across all production conditions, the L-stress decreased the lint and cottonseed yields by 34.4% and 36.2%, respectively. The minimal effects of E-stress on cotton suggest nutrient rates at the early season could be reduced and more tailored rates, informed by soil and plant tissue analyses, applied shortly before the reproductive phase.

The present study investigated egg parasitoid interspecific interactions between a generalist, Ooencyrtus nezarae Ishii (Hymenoptera: Encyrtidae) and a specialist, Paratelenomus saccharalis Dodd (Hymenoptera: Platygastridae) in a laboratory setting using kudzu bug (Megacopta cribraria Fabricius, (Hemiptera: Plataspidae)) eggs as their shared host. Three experiments were conducted to evaluate the emergence of wasps from parasitized hosts after the simultaneous and sequential release of wasps, monitor aggressive behavior of P. saccharalis, and quantify intraguild predation of O. nezarae larvae on heterospecific P. saccharalis larvae. Results showed that total host egg parasitism was higher when both wasps were released simultaneously than if wasps were released sequentially. Ooencyrtus nezarae produced more total offspring than P. saccharalis in all sequential/simultaneous treatments but produced male offspring in most cases. In the aggressive behavioral experiment, specialist, P. saccharalis used head butting to fight O. nezarae, but no other aggressions were observed. In an experiment examining intraguild predation, O. nezarae was able to develop in host eggs parasitized by P. saccharalis four days earlier, acting as a superior larval competitor. These findings shed light on the potential interspecific interactions between O. nezarae and P. saccharalis, which may determine their relative abundance and influence their compatibility in kudzu bug biological control programs.

Recently, the rise of generative AI tools such as "ChatGPT" have prompted deep and wide considerations about teaching and learning, student success, research and development, and the use of data for informed institutional decision making. In this volume, authors discuss specific concepts, considerations for use, and some specific tools and applications of advanced data analytics and artificial intelligence that are gaining prominence in higher education. Although these tools and our perceptions about the tools will continue to evolve, we believe that aspects of advanced data analytics and artificial intelligence will remain in our midst in the future. We believe that members of our community will become better educators and higher education managers as we engage deeply with these tools, stay vigilant about the risks and limitations, and establish policies that ensure student and institution success.

Abstract Background Management of Ebola virus disease (EVD) has historically focused on infection prevention, case detection and supportive care. Several specific anti-Ebola therapies have been investigated, including during the 2014–2016 West African outbreak. Our objective was to conduct a systematic review of the effect of anti-Ebola virus therapies on clinical outcomes to guide their potential use and future evaluation. Methods We searched PubMed, EMBASE, Global Health, Cochrane Library, African Index Medicus, WHOLIS (inception-9 April 2018), and trial registries for observational studies or clinical trials, in any language, that enrolled patients with confirmed EVD who received therapy targeting Ebola virus and reported on mortality, symptom duration, or adverse effects. Results From 11,257 citations and registered trials, we reviewed 55 full-text citations, of which 35 met eligibility criteria (1 randomized clinical trial (RCT), 8 non-randomized comparative studies, 9 case series and 17 case reports) and collectively examined 21 anti-Ebola virus agents. The 31 studies performed during the West African outbreak reported on 4.8% (1377/28616) of all patients with Ebola. The only RCT enrolled 72 patients (0.25% of all patients with Ebola) and compared the monoclonal antibody ZMapp vs. standard care (mortality, 22% vs. 37%; 95% confidence interval for risk difference, − 36 to 7%). Studies of convalescent plasma, interferon-β-1a, favipiravir, brincidofovir, artesunate-amodiaquine and TKM-130803 were associated with at least moderate risk of bias. Conclusions Research evaluating anti-Ebola virus agents has reached very few patients with EVD, and inferences are limited by non-randomized study designs. ZMapp has the most promising treatment signal.

Age-related macular degeneration (AMD), a degenerative disease of the outer retina, is the leading cause of blindness among the elderly. A hallmark of geographic atrophy (GA), an advanced type of nonneovascular AMD (dry AMD), is photoreceptor and retinal pigment epithelium (RPE) cell death. Currently, there are no FDA-approved therapies for GA due to a lack of understanding of the disease-causing mechanisms. Increasing evidence suggests that chronic inflammation plays a predominant role in the pathogenesis of dry AMD. Dead or stressed cells release danger signals and inflammatory factors, which causes further damage to neighboring cells. It has been reported that type I interferon (IFN) response is activated in RPE cells in patients with AMD. However, how RPE cells sense stress to initiate IFN response and cause further damage to the retina are still unknown. Although it has been reported that RPE can respond to extracellularly added dsRNA, it is unknown whether and how RPE detects and senses internally generated or internalized nucleic acids. Here, we elucidated the molecular mechanism by which RPE cells sense intracellular nucleic acids. Our data demonstrate that RPE cells can respond to intracellular RNA and induce type I IFN responses via the RIG-I (DExD/H-box helicase 58, DDX58) RNA helicase. In contrast, we showed that RPE cells were unable to directly sense and respond to DNA through the cGAS-STING pathway. We demonstrated that this was due to the absence of the cyclic GMP-AMP synthase (cGAS) DNA sensor in these cells. The activation of IFN response via RIG-I induced expression of cell death effectors and caused barrier function loss in RPE cells. These data suggested that RPE-intrinsic pathways of nucleic acid sensing are biased toward RNA sensing.

Plastic mulch films are used globally in crop production but incur considerable disposal and environmental pollution issues. Biodegradable plastic mulch films (BDMs), an alternative to polyethylene (PE)-based films, are designed to be tilled into the soil where they are expected to be mineralized to carbon dioxide, water and microbial biomass. However, insufficient research regarding the impacts of repeated soil incorporation of BDMs on soil microbial communities has partly contributed to limited adoption of BDMs. In this study, we evaluated the effects of BDM incorporation on soil microbial community structure and function over two years in two geographical locations: Knoxville, TN, and in Mount Vernon, WA, USA. Treatments included four plastic BDMs (three commercially available and one experimental film), a biodegradable cellulose paper mulch, a non-biodegradable PE mulch and a no mulch plot. Bacterial community structure determined using 16S rRNA gene amplicon sequencing revealed significant differences by location and season. Differences in bacterial communities by mulch treatment were not significant for any season in either location, except for Fall 2015 in WA where differences were observed between BDMs and no-mulch plots. Extracellular enzyme assays were used to characterize communities functionally, revealing significant differences by location and sampling season in both TN and WA but minimal differences between BDMs and PE treatments. Overall, BDMs had comparable influences on soil microbial communities to PE mulch films.

This is a collection of 7 articles from the AFLA 25 conference held in 2018. The papers cover a full range synchronic descriptions of Austronesian languages.

This paper presents a methodology for building a consensus among the stakeholders based on the level of importance of each evaluation criterion to choose the best final design, approach, or solution for a project. The proposed methodology adopts an improved vague set minimum-cost consensus model (MCCM) and a modified Delphi method. This paper discusses several shortcomings of the traditional MCCM and the Delphi method. It argues that humans' resistance to change based on a numerical rating scale follows a natural logarithm pattern instead of a linear or quadratic pattern as claimed in other studies. Hence, the traditional MCCM needs to be revised accordingly. In addition, an experiment was concluded to compare the proposed consensus-building methodology with the traditional Delphi method. The experiment showed that the proposed methodology is better than the traditional Delphi method regarding using fewer rounds to reach a consensus. At last, this paper applies the proposed methodology to the field of road junction design selection.

Objective: Radical nephroureterectomy with bladder-cuff excision has been the traditional treatment for upper tract urothelial carcinoma because of its high rate of recurrence. However, given the morbidity of nephrectomy and the risk of developing chronic kidney disease or dialysis-dependent renal failure, the nephron-sparing approach may be preferable in selected patients. Materials and methods: A total of 118 patients who received unilateral distal ureterectomy with reimplantation at a single center in Taiwan were included, using surgical code numbers, from March 2006 to December 2014. A total of 82 patients were excluded due to nonmalignancy and 17 due to concomitant bladder cancer. Finally, 19 patients with primary, solitary, unilateral ureter lesions and confirmed to have ureter malignancy (urothelial carcinoma, n = 18; squamous cell carcinoma, n = 1) were included. Results: Of the 19 patients (13 males and 6 females) included, the mean age was 69.3 ± 10.7 years. Tumor pathological staging was Tis (n = 1), Ta (n = 3), T1 (n = 2), T2 (n = 6), and T3 (n = 5). Histopathology grading was low grade (n = 3) and high grade (n = 13). No local recurrence was noted; nine patients had bladder recurrence (47.4%), three had distant metastasis (15.8%), and two had progression and finally underwent radical nephroureterectomy (10.5%). The mean time to bladder recurrence was 12.4 months (3–24 months); the mean follow-up time was 28.1 months (1–90 months). The 5-year overall survival rate was 73.7% (14/19); four patients were lost to follow-up, and one patient expired. The mean 5-year progression-free survival was 67.74%. The mean preoperative creatinine level was 1.61 mg/dL, and at 12 months after operation it was 1.56 mg/dL (p = 0.95). Conclusion: In selected patients, distal ureterectomy with reimplantation, in our experience, is a feasible option for distal ureter tumor. Favorable postoperative outcomes with a low local recurrence rate, a low rate of progression to nephroureterectomy, and renal function preservation may prove the value of this modality and should be taken into consideration in suitable patients.

Background: Spinal anaesthesia is now a popular choice for Caesarean sections in Africa but one of the draw-back is the development of post-dural puncture headache (PDPH) and it could be quite distressing to a mother. Identifying risk factors and reducing the prevalence is pertinent. This study sought to determine the prevalence of PDPH among patients who underwent Caesarean sections in a tertiary hospital in Jos, Plateau State, Nigeria and some of its possible associated factors. Method: It was a prospective study of all Caesarean sections done under spinal anaesthesia between November 2016 and June 2017. Spinal anaesthesia was performed on 236 parturients using Quincke-type needles sizes 23-26G. In the postoperative period, all the patients were followed-up to determine the incidence, onset, and severity of post-dural puncture headache. Epi-info version 7 was used for data analysis. Results: The prevalence of PDPH was 22.03%. Most of the parturients who developed PDPH in our study were of mild to moderate intensity using the numeric rating scale. Twenty six (11%) had mild, while 11 (4.7%) had moderate intensity of headache and which was resolved with treatment. Conclusion: The prevalence of PDPH is high in the obstetric population especially with the use of traumatic Quincke-type needles. Deliberate efforts must be made to reduce its occurrence by acquiring of small calibre pencil-point needles and training staff on how to use it

This is a collection of 6 articles from the AFLA 24 conference held in 2017. The papers cover a full range synchronic descriptions of Austronesian languages.

Control valve stiction is a common problem faced by the process industries, which can have a strong adverse effect on the profitable operation of plants. Although various stiction detection methods based on neural networks have been proposed, few of these studies have considered the performance of stiction detection based on the use of 2D representations of the process signals. In this paper, such an approach is proposed, based on the use of a pretrained convolutional neural network, AlexNet. The proposed convolutional neural network stiction detection (CNN-SD) method showed highly satisfactory performance, which can be further applied on real industrial data.

The high surface area to volume ratio of terrestrial insects makes them highly susceptible to desiccation mainly through the cuticle. Cuticular permeability (CP) is usually the most important factor limiting water loss in terrestrial insects. Water loss rate, percentage of total body water (%TBW) content, CP, and desiccation tolerance were investigated in workers of four Solenopsis species in the southeastern USA. We hypothesized that tropical/subtropical ants (S. invicta and S. geminata) will have lower CP values and tolerate higher levels of desiccation than temperate ants (S. richteri and S. invicta × S. richteri). The %TBW content was similar among species. Solenopsis invicta had a 1.3-fold and 1.1-fold lower CP value than S. invicta × S. richteri and S. richteri, respectively. Solenopsis geminata had a 1.3-fold lower CP value than S. invicta × S. richteri, and a 1.2-fold lower CP value than S. richteri. The LT50 values (lethal time to kill 50% of the population) ranged from 1.5 h (small S. geminata) to 8.5 h (large S. invicta). Desiccation tolerance ranged between 36 and 50 %TBW lost at death and was not related to a species’ location of origin. This study is the first report of water relations of S. invicta × S. richteri. It demonstrates that desiccation stress differentially can affect the survival of different Solenopsis species and implies that environmental stress can affect the distribution of these species in the southeastern USA.

Dielectric elastomer actuators have been widely studied theoretically and experimentally thanks to its superior attributes such as large deformation. The actuator failure has long been an issue placing barriers to large deformation in practical applications. In this paper, we investigate the various failure modes and the maximum stretch of the circular dielectric elastomer actuator. An analytical model depicting the actuation mechanism of the dielectric elastomer actuator is proposed to help analyze the failure onset. Several types of normally observed failure modes, i.e. electromechanical instability, loss of tension, and electrical breakdown, are analyzed theoretically based on the proposed model. A 3D figure that interprets the relationship of the corresponding factors and the possible failure modes are proposed as well, by which we could know the possible failure onset, as well as the associated maximum stretch under specific conditions. Experiments are carried out and the results are in accordance with the prediction by the proposed 3D figure.

Objective: Gallbladder agenesis (GBA) is a rare congenital disorder with an estimated incidence of about 0.06%. Despite the absence of a gallbladder, these patients may present with symptoms mimicking biliary colic or cholecystitis. Ultrasound findings and liver function tests are often misleading. Some of these patients undergo laparoscopy without successful identification of gallbladder and paradoxically report symptom relief. Case: We present a case of GBA in a 54 year-old female, who presented with right-sided abdominal pain. The clinical history and examination were consistent with biliary colic. Initial investigations, including liver function tests, upper endoscopy and ultrasound did not demonstrate upper gastrointestinal pathology and did not clearly identify a gallbladder. Subsequent HIDA scan and CT of the abdomen did not visualize a gallbladder. An MRCP confirmed gallbladder agenesis. The patient was managed conservatively and was symptom free on discharge and follow-up. Discussion: We wish to highlight four learning points: 1. Patients with gallbladder agenesis often present with biliary symptoms. 2. Ultrasound and CT of the liver may not always identify this anomaly. 3. MRCP is the gold standard for making a diagnosis of gall- bladder agenesis. 4. Surgeons must have a high index of suspicion of GBA when the gallbladder is poorly visualized or not identified on ultrasound.

The caspase recruitment domain family member 11 (CARD11 or CARMA1)—B cell CLL/lymphoma 10 (BCL10)—MALT1 paracaspase (MALT1) [CBM] signalosome complex serves as a molecular bridge between cell surface antigen receptor signaling and the activation of the NF-κB, JNK, and mTORC1 signaling axes. This positions the CBM complex as a critical regulator of lymphocyte activation, proliferation, survival, and metabolism. Inborn errors in each of the CBM components have now been linked to a diverse group of human primary immunodeficiency diseases termed “CBM-opathies.” Clinical manifestations range from severe combined immunodeficiency to selective B cell lymphocytosis, atopic disease, and specific humoral defects. This surprisingly broad spectrum of phenotypes underscores the importance of “tuning” CBM signaling to preserve immune homeostasis. Here, we review the distinct clinical and immunological phenotypes associated with human CBM complex mutations and introduce new avenues for targeted therapeutic intervention.

Background: Laparoscopic radical prostatectomy (LRP) is a challenging technique that is associated with a steep learning curve. We describe a novel technique to develop bladder neck traction using a Foley catheter during extraperitoneal LRP to enhance bladder neck dissection, thereby improving patient and procedural outcomes. Materials and methods: The novel technique employed a four-trocar approach to prostatectomy, which involved the introduction of a 1-0 Vicryl suture into the extraperitoneal space using an Endo Close needle to pull up the Foley catheter tip and make the bladder neck prominent. From June 2006 to November 2012, clinicopathological data of 71 patients who underwent four-port extraperitoneal LRP (modified extraperitoneal LRP, Group 1) were assessed and compared with those from 22 patients who underwent transperitoneal LRP (Group 2) retrospectively. Results: The two groups were comparable in terms of pathological staging and Gleason score. The operative time was significantly shorter (p

microRNAs are small non-coding RNAs that are important regulators of gene expression in a range of animals, including nematodes. We have analysed a cluster of four miRNAs from the pathogenic nematode species Haemonchus contortus that are closely linked in the genome. We find that the cluster is conserved only in clade V parasitic nematodes and in some ascarids, but not in other clade III species nor in clade V free-living nematodes. Members of the cluster are present in parasite excretory-secretory products and can be detected in the abomasum and draining lymph nodes of infected sheep, indicating their release in vitro and in vivo. As observed for other parasitic nematodes, H. contortus adult worms release extracellular vesicles (EV). Small RNA libraries were prepared from vesicle-enriched and vesicle-depleted supernatants from both adult worms and L4 stage larvae. Comparison of the miRNA species in the different fractions indicated that specific miRNAs are packaged within vesicles, while others are more abundant in vesicle-depleted supernatant. Hierarchical clustering analysis indicated that the gut is the likely source of vesicle-associated miRNAs in the L4 stage, but not in the adult worm. These findings add to the growing body of work demonstrating that miRNAs released from parasitic helminths may play an important role in host-parasite interactions.

STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder.

Secondary mean motions of Prandtl's second kind near an undulatory surface are explained in terms of the turbulent blocking effect and kinematic boundary conditions at the surface, and the order of magnitude is estimated. The isotropic turbulence is distorted by the undulatory surface with a low slope h/λ, where λ is the wavelength and h is the amplitude. The prime mechanism for generating the mean flow is that the far-field isotropic turbulence is distorted by the nonlocal blocking effect of the surface to become the anisotropic axisymmetric turbulence near the surface with a principal axis that is not aligned with the local curvature (slope) of the undulation. Then, the local analysis can be applied and the mechanism is similar to that of the mean flow generation by the impingement of homogeneous axisymmetric turbulence over a planar surface, i.e. the gradient of the Reynolds stress caused by the turbulent blocking effect generates the mean motion. The results from this simple analysis are consistent with the previous exact analysis, in which the effects of the curvature are taken into account. The results also qualitatively agree with the flow visualization over an undulatory surface in a mixing box.