Search

Case Presentation: A 32-year-old male who recently immigrated from Kenya presented to the emergency department (ED) with a painful, enlarging, right-sided neck mass for eight weeks duration. Point-of-care ultrasound was used to reveal a large cystic mass with internal septations and numerous hypoechoic round lesions. Initial tuberculosis blood test ordered in the ED was positive with cultures ultimately growing Mycobaceterium tuberculosis. Discussion: Scrofula should be considered in the differential in patients presenting with enlarging neck masses who have epidemiological risk factors for tuberculosis.

Shock experiments give a unique insight into the behavior of matter subjected to extremely high pressures and temperatures. Understanding the behavior of materials under such extreme conditions is key to modeling material failure and deformation dynamics under impact. While studies on pure silica are extensive, the shock behavior of other commercial silicates that contain additional oxides has not been systematically investigated. To better understand the role of composition in the dynamic behavior of silicates, we performed laser-driven dynamic compression experiments on soda-lime glass (SLG) up to 315 GPa. Using the accurate pulse shaping offered by the long pulse laser system at the Matter in Extreme Conditions end-station at the Linac Coherent Light Source, SLG was shock compressed along the Hugoniot to multiple pressure-temperature points. Velocity Interferometer System for Any Reflector was used to measure the velocity and determine the pressure inside the SLG. The U s -u p relationship obtained agrees well with the previous parallel plate impact studies. Within the error bars, no transformation to the crystalline phase was observed up to 70 GPa, which is in contrast to the behavior of pure silica under shock compression. Our studies show that the glass composition strongly influences the shock compression behavior of the silicate glasses.

The University of California, Irvine’s (UCI) Innovation and Entrepreneurship Librarian partnered with UCI’s New Venture Competition to provide embedded research support for teams participating in the competition, including a research workshop and individual team research consultations. To assess the impact of these library services, a quantitative study of three years of competition scores was conducted involving a control group and two experimental groups; the difference in the experimental groups was the mode in which the services were provided: in-person and virtually. The study hypothesized that teams who received information literacy training (i.e., attended a research workshop and/or participated in a research consultation) earned higher Concept Paper scores, as well as higher evidence question scores (i.e., scores for a rubric question related to providing evidence in support of claims made in the Concept Paper), than teams who did not receive information literacy training. Statistical analysis showed significant increases in both Concept Paper scores and evidence question scores for both experimental groups when compared to the control group, indicating that information literacy training positively impacted teams’ performance. Additional analysis revealed no statistically significant differences in teams’ scores based on training delivery mode, in-person or virtual. The results are of value to librarians seeking to initiate partnerships with entrepreneurship competitions on campus, as well as entrepreneurship educators interested in enhancing existing entrepreneurship competitions by incorporating research and information literacy training.

Climate warming and associated accelerated permafrost thaw in the Arctic lead to a shift in landscape patterns, hydrologic conditions, and release of carbon. In this context, the lateral transport of carbon and shifts therein following thaw remain poorly understood. Crucial hydrologic factors affecting the lateral distribution of carbon include the depth of the saturated zone above the permafrost table with respect to changes in water table and thaw depth and the connectivity of water-saturated zones. Landscape conditions are expected to change in the future due to rising temperatures and polygonal or flat floodplain Arctic tundra areas in various states of degradation; hydrologic conditions will also change. This study is focused on an experimental site near Chersky, northeast Siberia, where a drainage ditch was constructed in 2004 to simulate landscape degradation features that result in drier soil conditions and channeled water flow. We compared water levels and thaw depths in the drained area (dry soil conditions) with those in an adjacent control area (wet soil conditions). We also identified the sources of water at the site via stable water isotope analysis. We found substantial spatiotemporal changes in the water conditions at the drained site: (i) lower water tables resulting in drier soil conditions, (ii) quicker water flow through drier areas, (iii) larger saturation zones in wetter areas, and (iv) a higher proportion of permafrost meltwater in the liquid phase towards the end of the growing season. These findings suggest decreased lateral connectivity throughout the drained area. Shifts in hydraulic connectivity in combination with a shift in vegetation abundance and water sources may impact carbon sources and sinks as well as transport pathways. Identifying lateral transport patterns in areas with degrading permafrost is therefore crucial.

Abstract The transforming growth factor (TGF)-β3 is a well-known inducer for tenogenic differentiation, signaling via the Smad2/3 pathway. Furthermore, other factors like extracellular matrix or mechanical force can induce tenogenic differentiation and possibly alter the response to TGF-β3 by signaling via the Rho/ROCK pathway. The aim of this study was to investigate the interplay of Rho/ROCK and TGF-β3/Smad signaling in tenogenic differentiation, with the Smad2/3 molecule hypothesized as a possible interface. Cultured as monolayers or on collagen I matrices, mesenchymal stromal cells (MSC) were treated with the ROCK inhibitor Y-27632 (10 µM), TGF-β3 (10 ng/ml) or both combined. Control cells were cultured accordingly, without Y-27632 and/or without TGF-β3. At different time points, MSC were analyzed by real-time RT-PCR, immunofluorescence, and Western blot. Cultivation of MSC on collagen matrices and ROCK inhibition supported tenogenic differentiation and fostered the effect of TGF-β3. The phosphorylation of the linker region of Smad2 was reduced by cultivation on collagen matrices, but not by ROCK inhibition. The latter, however, led to increased phosphorylation of the linker region of Smad3. In conclusion, collagen matrices and the Rho/ROCK signaling pathway influence the TGF-β3/Smad2/3 pathway by regulating different phosphorylation sites of the Smad linker region.

Therapeutic management of patients with leptomeningeal carcinomatosis (LC) may require treatment of concomitant hydrocephalus (HC) in addition to intrathecal chemotherapy (ITC). Ventriculoperitoneal shunts (VPS) equipped with a valve for manual deactivation of shunt function and a concomitant reservoir for application of ITC pose an elegant solution to both problems. The present study evaluates indication, feasibility, and safety of such a modified shunt/reservoir design (mS/R). All patients with LC aged ≥ 18 years who had undergone mS/R implantation between 2013 and 2020 at the authors’ institution were further analyzed. ITC was indicated following the recommendation of the neuro-oncological tumor board and performed according to a standardized protocol. Sixteen patients with LC underwent mS/R implantation for subsequent ITC and concomitant treatment of HC. Regarding HC-related clinical symptoms, 69% of patients preoperatively exhibited lethargy, 38% cognitive impairment, and 38% (additional) visual disturbances. Postoperatively, 86% of patients achieved subjective improvement of HC-related symptoms. Overall, postoperative complications occurred in three patients (19%). No patient encountered cancer treatment-related complications. The present study describes a combination procedure consisting of a standard VPS-system and a standard reservoir for patients suffering from LC and HC. No cancer treatment-related complications occurred, indicating straightforward handling and thus safety.

Abstract Background The efficacy of oncolytic viruses (OV) in cancer treatment depends on their ability to successfully infect and destroy tumor cells. However, patients’ tumors vary, and in the case of individual insensitivity to an OV, therapeutic efficacy is limited. Here, we present a protocol for rapid generation of tumor cell-specific adapted oncolytic coxsackievirus B3 (CVB3) with enhanced oncolytic potential and a satisfactory safety profile. This is achieved by combining directed viral evolution (DVE) with genetic modification of the viral genome and the use of a microRNA-dependent regulatory tool. Methods The oncolytic CVB3 variant PD-H was adapted to the refractory colorectal carcinoma cell line Colo320 through serial passaging. XTT assays and virus plaque assays were used to determine virus cytotoxicity and virus replication in vitro. Recombinant PD-H variants were generated through virus mutagenesis. Apoptosis was detected by Western blots, Caspase 3/7 assays, and DAPI staining. The therapeutic efficacy and safety of the adapted recombinant OV PD-SK-375TS were assessed in vivo using a subcutaneous Colo320 xenograft mouse model. Results PD-H was adapted to the colorectal cancer cell line Colo320 within 10 passages. Sequencing of passage 10 virus P-10 revealed a heterogenous virus population with five nucleotide mutations resulting in amino acid substitutions. The genotypically homogeneous OV PD-SK was generated by inserting the five detected mutations of P-10 into the genome of PD-H. PD-SK showed significantly stronger replication and cytotoxicity than PD-H in Colo320 cells, but not in other colorectal carcinoma cell lines. Increase of apoptosis induction was detected as key mechanisms of Colo320 cell-specific adaptation of PD-SK. For in vivo safety PD-SK was engineered with target sites of the miR-375 (miR-375TS) to exclude virus replication in normal tissues. PD-SK-375TS, unlike the PD-H-375TS not adapted homolog suppressed the growth of subcutaneous Colo320 tumors in nude mice without causing any side effects. Conclusion Taken together, here we present an optimized protocol for the rapid generation of tumor cell-specific adapted oncolytic CVB3 based on the oncolytic CVB3 strain PD-H. The protocol is promising for the generation of personalized OV for tumor therapy and has the potential to be applied to other OV.

Engraved ochres and ostrich eggshells from the South African Blombos Cave and Diepkloof Rock Shelter are among the earliest expressions of human symbolic behavior. Furthermore, they appear to document a continuous practice of abstract mark-making across ~40.000 years. During this time, the engraved patterns change from simpler unstructured patterns to complex, ordered and symmetric cross-hatchings. To inform discussions of the possible function of the engravings, we conducted a two-part experimental study. Based on the assumption that the pragmatic use of an artifact will motivate incremental adaptive refinements, we used transmission chain experiments to reconstruct the original trajectory of changes. We then conducted five experiments to assess the cognitive implications of changes to the patterns and compared these to the original engravings. Although we observe interesting similarities, our findings suggest the Blombos and Diepkloof engravings are not only a product of human cognitive biases and constraints on working memory.

Germline genetic variants modulate human immune response. We present analytical pipelines for assessing the contribution of hosts' genetic background to the immune landscape of solid tumors using harmonized data from more than 9,000 patients in The Cancer Genome Atlas (TCGA). These include protocols for heritability, genome-wide association studies (GWAS), colocalization, and rare variant analyses. These workflows are developed around the structure of TCGA but can be adapted to explore other repositories or in the context of cancer immunotherapy. For complete details on the use and execution of this protocol, please refer to Sayaman et al. (2021).

We live in times of humanitarian and environmental crises. The effects of climate change add to the economic, physical, and mental suffering caused by social discrimination, in the form of gender, class, and race inequalities. Encounters with and creation of arts have been suggested as a potential remedy, allowing to stay with the trouble rather than running from it, and imagining a different future rather than manifesting the past. But what are the concrete chances that all this really happens? Similar questions can be raised in relation to immersive media. The latter have been claimed to possess an unprecedented prosocial potential. However, what are the appropriate strategies to ensure that such potential is actually expressed? For this issue of AN-ICON. Studies in Environmental Images, we selected diverse contributions investigating the role of the arts and media in rethinking (and acting upon) societal and environmental problems, focussing on immersive experiences in particular.

BackgroundPreterm birth and fetal growth restriction are the main determinants of perinatal mortality. In the absence of therapeutic interventions, management is restricted to the observation of fetal growth and fetoplacental perfusion to determine the timing of delivery. Fetal circulatory redistribution, known as “brain sparing,” represents a sign of fetal hypoxia and has been implemented in algorithms for when to deliver. In the absence of any other option, the nitric oxide donor pentaerythrityl tetranitrate (PETN), which has been shown to improve fetoplacental flow and reduce preterm birth in high-risk patients, is offered to patients as a personal therapy attempt. The aim of this study was to evaluate determinants related to pregnancy, including PETN intake during pregnancy, on immediate neonatal outcomes in a cohort of growth-restricted infants born before 32 completed weeks of gestation.MethodsWe performed a retrospective cohort study of 98 infants born with a birth weight below the 10th percentile before 32 completed weeks of gestation at our tertiary care center between 2010 and 2019. PETN was offered to all mothers with a history of severe adverse pregnancy outcomes who were at high risk of developing fetal growth restriction as an individual therapy attempt.ResultsThe mean gestational age at birth was 188.5 days, and the mean birth weight was 549 g, corresponding to a median percentile of three. In 73 (79.3%) cases, brain sparing occurred during pregnancy. A total of 22 (22.4%) neonates were stillborn, 20 died postnatally, and 37.3% developed a severe complication. Multivariable analysis revealed birth weight percentile, gestational age at birth, and gestational age when brain sparing first occurred to be robust predictors of mortality or severe neonatal morbidity. In 39 neonates of mothers taking PETN, this impact of brain sparing was not observed.ConclusionOur study is the first to demonstrate a significant association between the early occurrence of brain-sparing and severe neonatal outcomes in a cohort of very early preterm, growth-restricted newborns. The data suggest that PETN intake may ameliorate the effect of brain sparing in the affected neonates.

Objectives To train, test and validate the performance of a convolutional neural network (CNN)-based approach for the automated assessment of bone erosions, osteitis and synovitis in hand MRI of patients with inflammatory arthritis.Methods Hand MRIs (coronal T1-weighted, T2-weighted fat-suppressed, T1-weighted fat-suppressed contrast-enhanced) of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients from the rheumatology department of the Erlangen University Hospital were assessed by two expert rheumatologists using the Outcome Measures in Rheumatology-validated RA MRI Scoring System and PsA MRI Scoring System scores and were used to train, validate and test CNNs to automatically score erosions, osteitis and synovitis. Scoring performance was compared with human annotations in terms of macro-area under the receiver operating characteristic curve (AUC) and balanced accuracy using fivefold cross-validation. Validation was performed on an independent dataset of MRIs from a second patient cohort.Results In total, 211 MRIs from 112 patients (14 906 region of interests (ROIs)) were included for training/internal validation using cross-validation and 220 MRIs from 75 patients (11 040 ROIs) for external validation of the networks. The networks achieved high mean (SD) macro-AUC of 92%±1% for erosions, 91%±2% for osteitis and 85%±2% for synovitis. Compared with human annotation, CNNs achieved a high mean Spearman correlation for erosions (90±2%), osteitis (78±8%) and synovitis (69±7%), which remained consistent in the validation dataset.Conclusions We developed a CNN-based automated scoring system that allowed a rapid grading of erosions, osteitis and synovitis with good diagnostic accuracy and using less MRI sequences compared with conventional scoring. This CNN-based approach may help develop standardised cost-efficient and time-efficient assessments of hand MRIs for patients with arthritis.

Abstract Background Intervertebral disk (IVD) degeneration affects both humans and canines and is a major cause of low back pain (LBP). Mast cell (MC) and macrophage (MØ) infiltration has been identified in the pathogenesis of IVD degeneration (IVDD) in the human and rodent model but remains understudied in the canine. MC degranulation in the IVD leads to a pro‐inflammatory cascade and activates protease activated receptor 2 (PAR2) on IVD cells. The objectives of the present study are to: (1) highlight the pathophysiological changes observed in the degenerate canine IVD, (2) further characterize the inflammatory effect of MCs co‐cultured with canine nucleus pulposus (NP) cells, (3) evaluate the effect of construct stiffness on NP and MCs, and (4) identify potential therapeutics to mitigate pathologic changes in the IVD microenvironment. Methods Canine IVD tissue was isolated from healthy autopsy research dogs (beagle) and pet dogs undergoing laminectomy for IVD herniation. Morphology, protein content, and inflammatory markers were assessed. NP cells isolated from healthy autopsy (Mongrel hounds) tissue were co‐cultured with canine MCs within agarose constructs and treated with cromolyn sodium (CS) and PAR2 antagonist (PAR2A). Gene expression, sulfated glycosaminoglycan content, and stiffness of constructs were assessed. Results CD 31+ blood vessels, mast cell tryptase, and macrophage CD 163+ were increased in the degenerate surgical canine tissue compared to healthy autopsy. Pro‐inflammatory genes were upregulated when canine NP cells were co‐cultured with MCs and the stiffer microenvironment enhanced these effects. Treatment with CS and PAR2 inhibitors mediated key pro‐inflammatory markers in canine NP cells. Conclusion There is increased MC, MØs, and vascular ingrowth in the degenerate canine IVD tissue, similar to observations in the clinical population with IVDD and LBP. MCs co‐cultured with canine NP cells drive inflammation, and CS and PAR2A are potential therapeutics that may mitigate the pathophysiology of IVDD in vitro.

Abstract Bee declines pose a serious risk to agricultural sustainability, wild plant diversity, and the commercial bee industry, generating local and global concerns about bee health. Parasites, including micro‐parasites and macro‐parasites, negatively impact bee population dynamics. Management of parasites requires an understanding of the cyclic trends in prevalence and the factors impacting these patterns. In this study, we advance understanding of parasite epidemiology and transmission among members of the bee community toward the goal of improving predictability of parasite prevalence seasonally. Honey bees and bumble bees were collected throughout an active season and across multiple overwintering periods. These bees were molecularly tested for two common bee viruses—deformed wing virus (DWV) and black queen cell virus (BQCV)—and morphologically screened for Vairimorpha spp., nematodes, and parasitic flies to determine whether these parasites exhibit unique seasonal trends, if overwintering behavior impacts parasite survival, and how these patterns differ between honey bees and bumble bees. The results suggest consistent seasonal trends between honey bees and bumble bees; however, these trends are parasite‐specific. Honey bees consistently exhibited a higher magnitude of viral prevalence compared with bumble bees. Both honey bees and bumble bees reduced viral prevalence over the winter; however, only in bumble bees did this drop to negligible prevalence each spring. These data suggest that honey bees may have a larger impact on parasite transmission, as they pose to reinfect bees which otherwise would have very low prevalence each spring and sustain high levels of infection in communities year‐round.

We utilize hybrid quantum deep reinforcement learning to learn navigation tasks for a simple, wheeled robot in simulated environments of increasing complexity. For this, we train parameterized quantum circuits (PQCs) with two different encoding strategies in a hybrid quantum-classical setup as well as a classical neural network baseline with the double deep Q network (DDQN) reinforcement learning algorithm. Quantum deep reinforcement learning (QDRL) has previously been studied in several relatively simple benchmark environments, mainly from the OpenAI gym suite. However, scaling behavior and applicability of QDRL to more demanding tasks closer to real-world problems e.g., from the robotics domain, have not been studied previously. Here, we show that quantum circuits in hybrid quantum-classic reinforcement learning setups are capable of learning optimal policies in multiple robotic navigation scenarios with notably fewer trainable parameters compared to a classical baseline. Across a large number of experimental configurations, we find that the employed quantum circuits outperform the classical neural network baselines when equating for the number of trainable parameters. Yet, the classical neural network consistently showed better results concerning training times and stability, with at least one order of magnitude of trainable parameters more than the best-performing quantum circuits. However, validating the robustness of the learning methods in a large and dynamic environment, we find that the classical baseline produces more stable and better performing policies overall. For the two encoding schemes, we observed better results for consecutively encoding the classical state vector on each qubit compared to encoding each component on a separate qubit. Our findings demonstrate that current hybrid quantum machine-learning approaches can be scaled to simple robotic problems while yielding sufficient results, at least in an idealized simulated setting, but there are yet open questions regarding the application to considerably more demanding tasks. We anticipate that our work will contribute to introducing quantum machine learning in general and quantum deep reinforcement learning in particular to more demanding problem domains and emphasize the importance of encoding techniques for classic data in hybrid quantum-classical settings.

Abstract Background Foot lesions in suckling piglets have been associated with poor flooring in several studies and were recently proposed to be indicative of swine inflammatory and necrosis syndrome. However, identical findings are also the typical outcome of various non-infectious causes; thus, further risk analysis is needed. The objective of this study was to describe the development of heel bruising, coronary band lesions and forelimb skin abrasion in suckling pigs up to 5 days of age. Furthermore, the effects of various intrinsic and extrinsic factors were examined. On each of four commercial piglet-producing farms, piglets from two or three batches of eight sows were studied. The piglets were included within 18 h after birth. Each piglet was individually scored four times. The score for the heels differentiated six (0–5) and for the coronary band and forelimb skin abrasion three stages (0–2). The body weight was measured two times. The effect of the floor was estimated by allocating the sows randomly to farrowing pens equipped with either soft rubber mats covered with litter or fully slatted plastic floors. Results The final analysis comprised data from 1045 piglets. Foot lesions were not found at birth but started to develop on day 1. On day 5, heel bruising was found in 94%, main claw coronary band lesions in 49% and forelimb skin abrasion in 73% of the piglets. In a multifactorial logistic regression analysis, it was shown that a slatted plastic floor significantly increased the odds of heel bruising and coronary band lesions, while a rubber floor with litter increased the odds of forelimb skin abrasions. Conclusion Foot and forelimb lesions in new-born piglets are mainly induced by the floor. The effect of slatted plastic floors on heel bruising showed an overwhelming OR of 52.89 (CI 26.29–106.43). Notably, coronary band lesions in young suckling piglets occur on slatted as well as non-slatted floors, indicating that the piglets incur these injuries not only from the wedging of their feet into the gaps between slats but also from contact with the floor while suckling. Based on these findings, preventive measures should be redirected to the improvement of the floor in the farrowing pen, particularly in the area under the sow’s udder.

Undernutrition is an important global health problem, especially in children and older adults. Both reversal of maternal and child undernutrition and heathy ageing have become United Nations-supported global initiatives, leading to increased attention to nutritional interventions targeting undernutrition. One feasible option is microalgae, the precursor of all terrestrial plants. Most commercially farmed microalgae are photosynthetic single-celled organisms producing organic carbon compounds and oxygen. This review will discuss commercial opportunities to grow microalgae. Microalgae produce lipids (including omega-3 fatty acids), proteins, carbohydrates, pigments and micronutrients and so can provide a suitable and underutilised alternative for addressing undernutrition. The health benefits of nutrients derived from microalgae have been identified, and thus they are suitable candidates for addressing nutritional issues globally. This review will discuss the potential benefits of microalgae-derived nutrients and opportunities for microalgae to be converted into food products. The advantages of microalgae cultivation include that it does not need arable land or pesticides. Additionally, most species of microalgae are still unexplored, presenting options for further development. Further, the usefulness of microalgae for other purposes such as bioremediation and biofuels will increase the knowledge of these microorganisms, allowing the development of more efficient production of these microalgae as nutritional interventions.

Recent advances in sensor technology for air pollution monitoring open new possibilities in the field of environmental epidemiology. The low spatial resolution of fixed outdoor measurement stations and modelling uncertainties currently limit the understanding of personal exposure. In this context, air quality sensor systems (AQSSs) offer significant potential to enhance personal exposure assessment. A pilot study was conducted to investigate the feasibility of the NO2 sensor model B43F and the particulate matter (PM) sensor model OPC-R1, both from Alphasense (UK), for use in epidemiological studies. Seven patients with chronic obstructive pulmonary disease (COPD) or asthma had built-for-purpose sensor systems placed inside and outside of their homes at fixed locations for one month. Participants documented their indoor activities, presence in the house, window status, and symptom severity and performed a peak expiratory flow test. The potential inhaled doses of PM2.5 and NO2 were calculated using different data sources such as outdoor data from air quality monitoring stations, indoor data from AQSSs, and generic inhalation rates (IR) or activity-specific IR. Moreover, the relation between indoor and outdoor air quality obtained with AQSSs, an indoor source apportionment study, and an evaluation of the suitability of the AQSS data for studying the relationship between air quality and health were investigated. The results highlight the value of the sensor data and the importance of monitoring indoor air quality and activity patterns to avoid exposure misclassification. The use of AQSSs at fixed locations shows promise for larger-scale and/or long-term epidemiological studies.

Extreme events, such as those caused by climate change, economic or geopolitical shocks, and pest or disease epidemics, threaten global food security. The complexity of causation, as well as the myriad ways that an event, or a sequence of events, creates cascading and systemic impacts, poses significant challenges to food systems research and policy alike. To identify priority food security risks and research opportunities, we asked experts from a range of fields and geographies to describe key threats to global food security over the next two decades and to suggest key research questions and gaps on this topic. Here, we present a prioritization of threats to global food security from extreme events, as well as emerging research questions that highlight the conceptual and practical challenges that exist in designing, adopting, and governing resilient food systems. We hope that these findings help in directing research funding and resources toward food system transformations needed to help society tackle major food system risks and food insecurity under extreme events.