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Abstract At least four mechanisms have been proposed to elucidate how neurons in the retrotrapezoid (RTN) region sense changes in CO2/H+ to regulate breathing (i.e., function as respiratory chemosensors). These mechanisms include: (1) intrinsic neuronal sensitivity to H+ mediated by TASK‐2 and GPR4; (2) paracrine activation of RTN neurons by CO2‐responsive astrocytes (via a purinergic mechanism); (3) enhanced excitatory synaptic input or disinhibition; and (4) CO2‐induced vascular contraction. Although blood flow can influence tissue CO2/H+ levels, there is limited understanding of how control of vascular tone in central CO2 chemosensitive regions might contribute to respiratory output. In this review, we focus on recent evidence that CO2/H+‐induced purinergic‐dependent vasoconstriction in the ventral parafacial region near RTN neurons supports respiratory chemoreception. This mechanism appears to be unique to the ventral parafacial region and opposite to other brain regions, including medullary chemosensor regions, where CO2/H+ elicits vasodilatation. We speculate that this mechanism helps to maintain CO2/H+ levels in the vicinity of RTN neurons, thereby maintaining the drive to breathe. Important next steps include determining whether disruption of CO2/H+ vascular reactivity contributes to or can be targeted to improve breathing problems in disease states, such as Parkinson's disease.

Abstract The plant virus, Impatiens necrotic spot virus (INSV), is an economically important pathogen of vegetables, fruits, and ornamental crops. INSV is vectored by the western flower thrips, Frankliniella occidentalis, a small insect pest that is globally distributed. In recent years, INSV outbreaks have reached epidemic levels in the Salinas Valley of California—an agriculturally rich region where most of the lettuce (Lactuca sativa) is produced in the United States. Due to the obligate nature in which virus transmission occurs, new tools that could rapidly detect INSV from thrips vectors would enhance our ability to predict where virus outbreaks may occur. Here, we report on the development of a reverse transcription-recombinase polymerase amplification (RT-RPA) assay that can detect INSV from individual thrips. The assay uses crude extraction methods, is performed at a single temperature of 42 °C, can be completed in 25 min, and provides sensitivity levels that are comparable to other available detection methods. When the assay was used on field populations of thrips, INSV was successfully identified and quantified from individual larvae and adults. The work provides a new cost-effective surveillance tool that can rapidly detect INSV from its insect vector and from plants.

Abstract Stroke is a leading cause of mortality and disability. Emergent diagnosis and intervention are critical, and predicated upon initial brain imaging; however, existing clinical imaging modalities are generally costly, immobile, and demand highly specialized operation and interpretation. Low-energy microwaves have been explored as a low-cost, small form factor, fast, and safe probe for tissue dielectric properties measurements, with both imaging and diagnostic potential. Nevertheless, challenges inherent to microwave reconstruction have impeded progress, hence conduction of microwave imaging remains an elusive scientific aim. Herein, we introduce a dedicated experimental framework comprising a robotic navigation system to translate blood-mimicking phantoms within a human head model. An 8-element ultra-wideband array of modified antipodal Vivaldi antennas was developed and driven by a two-port vector network analyzer spanning 0.6–9.0 GHz at an operating power of 1 mW. Complex scattering parameters were measured, and dielectric signatures of hemorrhage were learned using a dedicated deep neural network for prediction of hemorrhage classes and localization. An overall sensitivity and specificity for detection >0.99 was observed, with Rayleigh mean localization error of 1.65 mm. The study establishes the feasibility of a robust experimental model and deep learning solution for ultra-wideband microwave stroke detection.

The future of humanity depends on successfully adapting key cropping systems for food security, such as corn (Zea mays L.), to global climatic changes, including changing air temperatures. We monitored the effects of climate change on harvested yields using long-term research plots that were established in 2001 near Fort Collins, Colorado, and long-term average yields in the region (county). We found that the average temperature for the growing period of the irrigated corn (May to September) has increased at a rate of 0.023 °C yr−1, going from 16.5 °C in 1900 to 19.2 °C in 2019 (p < 0.001), but precipitation did not change (p = 0.897). Average minimum (p < 0.001) temperatures were positive predictors of yields. This response to temperature depended on N fertilizer rates, with the greatest response at intermediate fertilizer rates. Maximum (p < 0.05) temperatures and growing degree days (GDD; p < 0.01) were also positive predictors of yields. We propose that the yield increases with higher temperatures observed here are likely only applicable to irrigated corn and that irrigation is a good climate change mitigation and adaptation practice. However, since pan evaporation significantly increased from 1949 to 2019 (p < 0.001), the region’s dryland corn yields are expected to decrease in the future from heat and water stress associated with increasing temperatures and no increases in precipitation. This study shows that increases in GDD and the minimum temperatures that are contributing to a changing climate in the area are important parameters that are contributing to higher yields in irrigated systems in this region.

Abstract Heat stress poses a significant environmental challenge that profoundly impacts wheat productivity. It disrupts vital physiological processes such as photosynthesis, by impeding the functionality of the photosynthetic apparatus and compromising plasma membrane stability, thereby detrimentally affecting grain development in wheat. The scarcity of identified marker trait associations pertinent to thermotolerance presents a formidable obstacle in the development of marker-assisted selection strategies against heat stress. To address this, wheat accessions were systematically exposed to both normal and heat stress conditions and phenotypic data were collected on physiological traits including proline content, canopy temperature depression, cell membrane injury, photosynthetic rate, transpiration rate (at vegetative and reproductive stage and ‘stay-green’. Principal component analysis elucidated the most significant contributors being proline content, transpiration rate, and canopy temperature depression, which exhibited a synergistic relationship with grain yield. Remarkably, cluster analysis delineated the wheat accessions into four discrete groups based on physiological attributes. Moreover, to explore the relationship between physiological traits and DNA markers, 158 wheat accessions were genotyped with 186 SSRs. Allelic frequency and polymorphic information content value were found to be highest on genome A (4.94 and 0.688), chromosome 1A (5.00 and 0.712), and marker Xgwm44 (13.0 and 0.916). Population structure, principal coordinate analysis and cluster analysis also partitioned the wheat accessions into four subpopulations based on genotypic data, highlighting their genetic homogeneity. Population diversity and presence of linkage disequilibrium established the suitability of population for association mapping. Additionally, linkage disequilibrium decay was most pronounced within a 15–20 cM region on chromosome 1A. Association mapping revealed highly significant marker trait associations at Bonferroni correction P

Abstract Background Identifying factors associated with post-disaster youth substance use is a crucial element of developing evidence-based prevention and intervention efforts. Hurricane María struck Puerto Rico in September of 2017 and the wide-spread impact from this disaster, including exposure to trauma, displacement, and disrupted social supports had the potential to negatively impact levels of substance use among youth across the archipelago. However, post-disaster substance use remains under-investigated in this context. The current study sought to identify risk and protective factors associated with substance use among Puerto Rican youth in the aftermath of Hurricane Maria. Methods Cross-sectional, secondary data analyses were conducted using school-based survey data collected at all schools in Puerto Rico between February 1 and June 29, 2018 (5–9 months after Hurricane María). Social supports, substance use, and trauma symptoms were assessed. An ordinal regression analysis was conducted to identify student factors associated with greater likelihood of post-disaster substance use. Results A total of 36,485 participants (50.7% female, grades 7–12), were included in an ordinal regression analysis that compared the likelihood of respondents endorsing high, low, or no substance use after Hurricane María based on reported adult social support, counselor/teacher social support, peer social support, ptsd symptomatology, and gender. Findings showed that, when compared to students that endorsed low or no substance use, those who reported having adult social support demonstrated a 58% reduction in odds (OR = 0.42, 95% CI: 0.34-0.53) of reporting high substance use after Hurricane María, while students who reported having teacher/counselor social support demonstrated a 21% reduction in odds (OR = 0.79, 95% CI: 0.69-0.89) of reporting high substance use. Additionally, those that reported having peer social support demonstrated a 31% increase in odds (OR = 1.31, 95% CI: 1.10 to 1.58) of reporting higher substance use, compared to those that reported low or no substance use. Conclusions While social support was generally protective, prevention efforts to build positive family and community connections may be indicated. Evidence-based school screenings of substance use and trauma may help direct intervention to those most at risk for co-occurring issues.

Abstract Surface passivation, a desirable natural consequence during initial oxidation of alloys, is the foundation for functioning of corrosion and oxidation resistant alloys ranging from industrial stainless steel to kitchen utensils. This initial oxidation has been long perceived to vary with crystal facet, however, the underlying mechanism remains elusive. Here, using in situ environmental transmission electron microscopy, we gain atomic details on crystal facet dependent initial oxidation behavior in a model Ni-5Cr alloy. We find the (001) surface shows higher initial oxidation resistance as compared to the (111) surface. We reveal the crystal facet dependent oxidation is related to an interfacial atomic sieving effect, wherein the oxide/metal interface selectively promotes diffusion of certain atomic species. Density functional theory calculations rationalize the oxygen diffusion across Ni(111)/NiO(111) interface, as contrasted with Ni(001)/NiO(111), is enhanced. We unveil that crystal facet with initial fast oxidation rate could conversely switch to a slow steady state oxidation.

Abstract The sequencing platform and workflow strongly influence microbial community analyses through potential errors at each step. Effective diagnostics and experimental controls are needed to validate data and improve reproducibility. This cross-laboratory study evaluates sources of variability and error at three main steps of a standardized amplicon sequencing workflow (DNA extraction, polymerase chain reaction [PCR], and sequencing) using Oxford Nanopore MinION to analyze agricultural soils and a simple mock community. Variability in sequence results occurs at each step in the workflow with PCR errors and differences in library size greatly influencing diversity estimates. Common bioinformatic diagnostics and the mock community are ineffective at detecting PCR abnormalities. This work outlines several diagnostic checks and techniques to account for sequencing depth and ensure accuracy and reproducibility in soil community analyses. These diagnostics and the inclusion of a reference soil can help ensure data validity and facilitate the comparison of multiple sequencing runs within and between laboratories.

Abstract The Quantum Approximate Optimization Algorithm (QAOA) is a variational quantum algorithm for Near-term Intermediate-Scale Quantum computers (NISQ) providing approximate solutions for combinatorial optimization problems. The QAOA utilizes a quantum-classical loop, consisting of a quantum ansatz and a classical optimizer, to minimize some cost function, computed on the quantum device. This paper presents an investigation into the impact of realistic noise on the classical optimizer and the determination of optimal circuit depth for the Quantum Approximate Optimization Algorithm (QAOA) in the presence of noise. We find that, while there is no significant difference in the performance of classical optimizers in a state vector simulation, the Adam and AMSGrad optimizers perform best in the presence of shot noise. Under the conditions of real noise, the SPSA optimizer, along with ADAM and AMSGrad, emerge as the top performers. The study also reveals that the quality of solutions to some 5 qubit minimum vertex cover problems increases for up to around six layers in the QAOA circuit, after which it begins to decline. This analysis shows that increasing the number of layers in the QAOA in an attempt to increase accuracy may not work well in a noisy device.

Abstract Statin drugs lower blood cholesterol levels for cardiovascular disease prevention. Women are more likely than men to experience adverse statin effects, particularly new-onset diabetes (NOD) and muscle weakness. Here we find that impaired glucose homeostasis and muscle weakness in statin-treated female mice are associated with reduced levels of the omega-3 fatty acid, docosahexaenoic acid (DHA), impaired redox tone, and reduced mitochondrial respiration. Statin adverse effects are prevented in females by administering fish oil as a source of DHA, by reducing dosage of the X chromosome or the Kdm5c gene, which escapes X chromosome inactivation and is normally expressed at higher levels in females than males. As seen in female mice, we find that women experience more severe reductions than men in DHA levels after statin administration, and that DHA levels are inversely correlated with glucose levels. Furthermore, induced pluripotent stem cells from women who developed NOD exhibit impaired mitochondrial function when treated with statin, whereas cells from men do not. These studies identify X chromosome dosage as a genetic risk factor for statin adverse effects and suggest DHA supplementation as a preventive co-therapy.

Objective: To evaluate the completeness and reliability of recurrence data from an institutional cancer registry for patients with head and neck cancer. Patients and Methods: Recurrence information was collected by radiation oncology and otolaryngology researchers. This was compared with the institutional cancer registry for continuous patients treated with radiation therapy for head and neck cancer at a tertiary cancer center. The sensitivity and specificity of institutional cancer registry data was calculated using manual review as the gold standard. False negative recurrences were compared to true positive recurrences to assess for differences in patient characteristics. Results: A total of 1338 patients who were treated from January 1, 2010, through December 31, 2017, were included in a cancer registry and underwent review. Of them, 375 (30%) had confirmed cancer recurrences, 45 (3%) had concern for recurrence without radiologic or pathologic confirmation, and 31 (2%) had persistent disease. Most confirmed recurrences were distant (37%) or distant plus locoregional (29%), whereas few were local (11%), regional (9%), or locoregional (14%) alone. The cancer registry accuracy was 89.4%, sensitivity 61%, and specificity 99%. Time to recurrence was associated with registry accuracy. True positives had recurrences at a median of 414 days vs 1007 days for false negatives. Conclusion: Currently, institutional cancer registry recurrence data lacks the required accuracy for implementation into studies without manual confirmation. Longer follow-up of cancer status will likely improve sensitivity. No identified differences in patients accounted for differences in sensitivity. New, ideally automated, data abstraction tools are needed to improve detection of cancer recurrences and minimize manual chart review.

Mobile phone applications (MPAs) for substance use disorder (SUD) treatment are increasingly used by patients. Although pilot studies have shown promising results, multiple previous systematic reviews noted insufficient evidence for MPA use in SUD treatment—many of the previously published reviews evaluated different trials. Subsequently, we aimed to conduct an umbrella review of previously published reviews investigating the efficacy of MPAs for SUD treatment, excluding nicotine/tobacco because umbrella reviews have been done in this population and the nicotine/tobacco MPA approach often differs from SUD-focused MPAs. No previous reviews have included a statistical meta-analysis of clinical trials to quantify an estimated overall effect. Seven reviews met inclusion criteria, and 17 unique studies with available data were taken from those reviews for the meta-analysis. Overall, reviews reported a lack of evidence for recommending MPAs for SUD treatment. However, MPA-delivered recovery support services, cognitive behavioral therapy, and contingency management were identified across multiple reviews as having promising evidence for SUD treatment. Hedges g effect size for an MPA reduction in substance use–related outcomes relative to the control arm was insignificant (0.137; 95% CI, −0.056 to 0.330; P=.16). In subgroup analysis, contingency management (1.29; 95% CI, 1.088-1.482; τ2=0; k=2) and cognitive behavioral therapy (0.02; 95% CI, 0.001-0.030; τ2=0; k=2) were significant. Although contingency management’s effect was large, both trials were small (samples of 40 and 30). This review includes an adapted framework for the American Psychiatric Association’s MPA guidelines that clinicians can implement to review MPAs critically with patients.

Summary: The hypothalamic supramammillary nucleus (SuM) projects heavily to the hippocampus to regulate hippocampal activity and plasticity. Although the projections from the SuM to the dentate gyrus (DG) and CA2 have been extensively studied, whether the SuM projects to CA1, the main hippocampal output region, is unclear. Here, we report a glutamatergic pathway from the SuM that selectively excites CA1 interneurons in the border between the stratum radiatum (SR) and the stratum lacunosum-moleculare (SLM). We find that the SuM projects selectively to a narrow band in the CA1 SR/SLM and monosynaptically excites SR/SLM interneurons, including vasoactive intestinal peptide-expressing (VIP+) and neuron-derived neurotrophic factor-expressing (NDNF+) cells, but completely avoids making monosynaptic contacts with CA1 pyramidal neurons (PNs) or parvalbumin-expressing (PV+) or somatostatin-expressing (SOM+) cells. Moreover, SuM activation drives spikes in most SR/SLM interneurons to suppress CA1 PN excitability. Taken together, our findings reveal that the SuM can directly regulate hippocampal output region CA1, bypassing CA2, CA3, and the DG.

Background Among patients diagnosed with high blood pressure (BP), initial dual therapy has been recommended for patients with high pretreatment systolic BP (≥160 mm Hg) since 2003, and first‐line β‐blocker use without a compelling condition has fallen out of favor in US guidelines. Methods and Results This serial cross‐sectional study of national Veterans Health Administration data included adult Veterans with incident hypertension initiating antihypertensive medication between January 1, 2000, and December 31, 2019. We assessed annual trends in initial regimens dispensed (index date: first antihypertensive dispense date) by number of classes and unique class combinations used overall and by pretreatment systolic BP (

Background: Inflammation has long been a key tenet in the diagnosis and management of malignancies, likely contributing to cancer incidence, staging, and progression. Systemic inflammation, in particular, is often elevated prior to and during cancer development. Systemic inflammation in the context of cancer diagnosis and monitoring is measured by various inflammatory indexes such as the systemic inflammatory response index (SIRI), plasma-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), and neutrophil-to-lymphocyte ratio (NLR). We set out to determine the relationship between pre- and post-treatment levels of these inflammatory indexes and the prognosis and outcomes of oropharyngeal cancer (OPC). Methods: A retrospective chart review was performed of 172 patients with OPC who underwent treatment for oropharyngeal cancer at University Medical Center in Lubbock, TX between May 2013 to May 2023. Sites of primary cancer were obtained through chart review. HPV infection status and differentiation of the tumor were noted for each patient. Treatment modalities were classified as surgery, radiation, chemotherapy, or concurrent chemotherapy and radiation. Treatment outcomes were classified based on recurrence and death secondary to disease. The relationships between treatment outcome and the described inflammatory indexes were evaluated. Appropriate parametric tests were selected based on the large number of variables. Results: Pre-treatment SIRI and Albumin levels were positively predictive in determining locoregional recurrence (p = 0.031 and p = 0.039). NLR, SII, and SIRI levels taken at three months post-treatment were also found to be positively predictive of locoregional recurrence (p = 0.005, p < 0.0005, and p = 0.007). SIRI taken at six months post-treatment was also found to be positively predictive of locoregional recurrence (p = 0.008). SII at six months post-treatment was found to be positively predictive of survival (p = 0.027). Conclusion: This study suggested that post-treatment levels of several inflammatory indexes, particularly SIRI, NLR, and SII, may be useful in determining the long-term outlook and recurrence of head and neck cancer following treatment.

Abstract Background The current report investigates fusion rates and patient-reported outcomes following lumbar spinal surgery using cellular bone allograft (CBA) in patients with risk factors for non-union. Methods A prospective, open label study was conducted in subjects undergoing lumbar spinal fusion with CBA (NCT 02969616) to assess fusion success rates and patient-reported outcomes in subjects with risk factors for non-union. Subjects were categorized into low-risk (≤ 1 risk factors) and high-risk (> 1 risk factors) groups. Radiographic fusion status was evaluated by an independent review of dynamic radiographs and CT scans. Patient-reported outcome measures included quality of life (EQ-5D), Oswestry Disability Index (ODI) and Visual Analog Scales (VAS) for back and leg pain. Adverse event reporting was conducted throughout 24-months of follow-up. Results A total of 274 subjects were enrolled: 140 subjects (51.1%) were categorized into the high-risk group (> 1 risk factor) and 134 subjects (48.9%) into the low-risk group (≤ 1 risk factors). The overall mean age at screening was 58.8 years (SD 12.5) with a higher distribution of females (63.1%) than males (36.9%). No statistical difference in fusion rates were observed between the low-risk (90.0%) and high-risk (93.9%) groups (p > 0.05). A statistically significant improvement in patient-reported outcomes (EQ-5D, ODI and VAS) was observed at all time points (p

Abstract Legacy phosphorus (P) is a reservoir of sparingly available P, and its recovery could enhance sustainable use of nonrenewable mineral fertilizers. Domestication has affected P acquisition, but it is unknown if subsequent breeding efforts, like the Green Revolution (GR), had a similar effect. We examined how domestication and breeding events altered P acquisition by growing wild, traditional (pre-GR), and modern (post-GR) tomato in soil with legacy P but low bioavailable P. Wild tomatoes, particularly accession LA0716 (Solanum pennellii), heavily cultured rhizosphere P solubilizers, suggesting reliance on microbial associations to acquire P. Wild tomato also had a greater abundance of other putatively beneficial bacteria, including those that produce chelating agents and antibiotic compounds. Although wild tomatoes had a high abundance of these P solubilizers, they had lower relative biomass and greater P stress factor than traditional or modern tomato. Compared to wild tomato, domesticated tomato was more tolerant to P deficiency, and both cultivated groups had a similar rhizosphere bacterial community composition. Ultimately, this study suggests that while domestication changed tomato P recovery by reducing microbial associations, subsequent breeding processes have not further impacted microbial P acquisition mechanisms. Selecting microbial P-related traits that diminished with domestication may therefore increase legacy P solubilization.

Abstract Magnetic resonance imaging (MRI) has experienced remarkable advancements in the integration of artificial intelligence (AI) for image acquisition and reconstruction. The availability of raw k-space data is crucial for training AI models in such tasks, but public MRI datasets are mostly restricted to DICOM images only. To address this limitation, the fastMRI initiative released brain and knee k-space datasets, which have since seen vigorous use. In May 2023, fastMRI was expanded to include biparametric (T2- and diffusion-weighted) prostate MRI data from a clinical population. Biparametric MRI plays a vital role in the diagnosis and management of prostate cancer. Advances in imaging methods, such as reconstructing under-sampled data from accelerated acquisitions, can improve cost-effectiveness and accessibility of prostate MRI. Raw k-space data, reconstructed images and slice, volume and exam level annotations for likelihood of prostate cancer are provided in this dataset for 47468 slices corresponding to 1560 volumes from 312 patients. This dataset facilitates AI and algorithm development for prostate image reconstruction, with the ultimate goal of enhancing prostate cancer diagnosis.

Abstract Background Much evidence-based physical activity (PA) interventions have been tested and implemented in urban contexts. However, studies that adapt, implement, and evaluate the effectiveness of these interventions in micropolitan rural contexts are needed. The study aimed to evaluate the effectiveness of the Active Ottumwa intervention to promote PA in a micropolitan community. Methods Between 2013 – 2019, we implemented Active Ottumwa in a micropolitan setting, and subsequently implemented and evaluated its effectiveness using a Hybrid Type I design. In this paper, we describe the intervention’s effectiveness in promoting PA. We collected PA data over 24 months from a cohort of community residents using accelerometers and PA data from two cross-sectional community surveys administered in 2013 and 2018, using the Global Physical Activity Questionnaire. Results From the cohort, we found significant change in PA over 24 months (P = 0.03) corresponding to a 45-min daily decrease in sedentary activity, a daily increase of 35-min in light PA and 9 min in moderate-to-vigorous PA. There was a statistically significant (P = 0.01) increasing trend at the population-level in the moderate-to-vigorous composition of 7 min between the two cross-sectional assessments (95% CI: 0.1%—1.34%). Conclusions The study demonstrates that the adapted evidence-based PA interventions in a micropolitan context is effective.

Abstract With the advent of distributed multi-sensory networks of devices, vast troves of real-time data can be gathered about our interactions with the built environment. These rich data sets can be mined to achieve improved and informed data-driven designs of buildings, neighborhoods, and potentially entire cities. Among those, integrated developments have the peculiarity of combining multiple functions within a compact space and, as such, behave as microcosms of a city that can help address the problem of urban sprawl and density. However, a general lack of data and framework about integrated developments hinders our ability to test design hypotheses about the complex interplay between heterogeneity in both space and function. Here, we apply a data-driven approach to analyze the joint influence of topology and function on user movement within a state-of-the-art integrated development in Singapore. Specifically, we leverage the network representation of the building and use movement data collected from 51 individuals over a month. We show evidence of correlation (40%) between the spatial network features and human movement at the building level. We are also able to quantify the relationship between the functional and spatial components of the integrated development through user movement. Previous studies have shown a 60% or higher correlation between the topology and human movement at the city or country scales. Our moderate correlation, therefore, implies that more factors influencing user movement are at play. The heterogeneity in the spatial function introduced trips with diverse origins and destinations. A further data-driven analysis integrating origins and destinations reveals both qualitative and quantitative means of studying the relationship between the built environment and the processes that take place in them.

Abstract Astrocytes in the retrotrapezoid nucleus (RTN) stimulate breathing in response to CO2/H+, however, it is not clear how these cells detect changes in CO2/H+. Considering Kir4.1/5.1 channels are CO2/H+-sensitive and important for several astrocyte-dependent processes, we consider Kir4.1/5.1 a leading candidate CO2/H+ sensor in RTN astrocytes. To address this, we show that RTN astrocytes express Kir4.1 and Kir5.1 transcripts. We also characterized respiratory function in astrocyte-specific inducible Kir4.1 knockout mice (Kir4.1 cKO); these mice breathe normally under room air conditions but show a blunted ventilatory response to high levels of CO2, which could be partly rescued by viral mediated re-expression of Kir4.1 in RTN astrocytes. At the cellular level, astrocytes in slices from astrocyte-specific inducible Kir4.1 knockout mice are less responsive to CO2/H+ and show a diminished capacity for paracrine modulation of respiratory neurons. These results suggest Kir4.1/5.1 channels in RTN astrocytes contribute to respiratory behavior.

Abstract Dense wintertime fog regularly impacts Delhi, severely affecting road and rail transport, aviation and human health. Recent decades have seen an unexplained increase in fog events over northern India, coincident with a steep rise in wintertime irrigation associated with the introduction of double-cropping. Accurate fog forecasting is challenging due to a high sensitivity to numerous processes across many scales, and uncertainties in representing some of these in state-of-the-art numerical weather prediction models. Here we show fog event simulations over northern India with and without irrigation, revealing that irrigation counteracts a common model dry bias, dramatically improving the simulation of fog. Evaluation against satellite products and surface measurements reveals a better spatial extent and temporal evolution of the simulated fog events. Increased use of irrigation over northern India in winter provides a plausible explanation for the observed upward trend in fog events, highlighting the critical need for optimisation of irrigation practices.

Abstract Background Pre-operative risk assessment can help clinicians prepare patients for surgery, reducing the risk of perioperative complications, length of hospital stay, readmission and mortality. Further, it can facilitate collaborative decision-making and operational planning. Objective To develop effective pre-operative risk assessment algorithms (referred to as Patient Optimizer or POP) using Machine Learning (ML) that predict the development of post-operative complications and provide pilot data to inform the design of a larger prospective study. Methods After institutional ethics approval, we developed a base model that encapsulates the standard manual approach of combining patient-risk and procedure-risk. In an automated process, additional variables were included and tested with 10-fold cross-validation, and the best performing features were selected. The models were evaluated and confidence intervals calculated using bootstrapping. Clinical expertise was used to restrict the cardinality of categorical variables (e.g. pathology results) by including the most clinically relevant values. The models were created with logistic regression (LR) and extreme gradient-boosted trees using XGBoost (Chen and Guestrin, 2016). We evaluated performance using the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC). Data was obtained from a metropolitan university teaching hospital from January 2015 to July 2020. Data collection was restricted to adult patients undergoing elective surgery. Results A total of 11,475 adult admissions were included. The performance of XGBoost and LR was very similar across endpoints and metrics. For predicting the risk of any post-operative complication, kidney failure and length-of-stay (LOS), POP with XGBoost achieved an AUROC (95%CI) of 0.755 (0.744, 0.767), 0.869 (0.846, 0.891) and 0.841 (0.833, 0.847) respectively and AUPRC of 0.651 (0.632, 0.669), 0.336 (0.282, 0.390) and 0.741 (0.729, 0.753) respectively. For 30-day readmission and in-patient mortality, POP with XGBoost achieved an AUROC (95%CI) of 0.610 (0.587, 0.635) and 0.866 (0.777, 0.943) respectively and AUPRC of 0.116 (0.104, 0.132) and 0.031 (0.015, 0.072) respectively. Conclusion The POP algorithms effectively predicted any post-operative complication, kidney failure and LOS in the sample population. A larger study is justified to improve the algorithm to better predict complications and length of hospital stay. A larger dataset may also improve the prediction of additional specific complications, readmission and mortality.

Abstract Designing complex synthetic materials for enzyme immobilization could unlock the utility of biocatalysis in extreme environments. Inspired by biology, we investigate the use of random copolymer brushes as dynamic immobilization supports that enable supra-biological catalytic performance of immobilized enzymes. This is demonstrated by immobilizing Bacillus subtilis Lipase A on brushes doped with aromatic moieties, which can interact with the lipase through multiple non-covalent interactions. Incorporation of aromatic groups leads to a 50 °C increase in the optimal temperature of lipase, as well as a 50-fold enhancement in enzyme activity. Single-molecule FRET studies reveal that these supports act as biomimetic chaperones by promoting enzyme refolding and stabilizing the enzyme’s folded and catalytically active state. This effect is diminished when aromatic residues are mutated out, suggesting the importance of π-stacking and π-cation interactions for stabilization. Our results underscore how unexplored enzyme-support interactions may enable uncharted opportunities for using enzymes in industrial biotransformations.

Background: Articular cartilage is a fiber reinforced hydrated solid that serves a largely mechanical role of supporting load and enabling low friction joint articulation. Daily activities that load cartilage, lead to fluid exudation and compressive axial strain. To date, the only mechanism shown to recover this cartilage strain in vivo is unloading (e.g., lying supine). Based on recent work in cartilage explants, we hypothesized that loaded joint activity (walking) would also be capable of strain recovery in cartilage. Methods: Eight asymptomatic young adults performed a fixed series of tasks, each of which was followed by magnetic resonance imaging to track changes in their knee cartilage thickness. The order of tasks was as follows: 1) stand for 30 ​min, 2) walk for 10 ​min, 3) stand for 30 ​min, and 4) lie supine for 50 ​min. The change in cartilage thickness was used to compute the axial cartilage strain. Results: Standing produced an average axial strain of −5.1 ​% (compressive) in the tibiofemoral knee cartilage, while lying supine led to strain recovery. In agreement with our hypothesis, walking also led to cartilage strain recovery. Interestingly, the recovery rate during walking (0.19 ​% strain/min) was nearly 3-fold faster than lying supine (0.07 ​% strain/min). Conclusions: This study represents the first in vivo demonstration that joint activity is capable of recovering compressive strain in cartilage. These findings indicate that joint activities such as walking may play a key role in maintaining and recovering cartilage strain, with implications for maintaining cartilage health and preventing or delaying cartilage degeneration.

Background Persons seeking emergency injury care are often from higher-risk and underserved key populations (KPs) and priority populations (PPs) for HIV programming. While facility-based HIV Testing Services (HTS) in Kenya are effective, emergency department (ED) delivery is limited, despite the potential to reach underserved persons. Methods This quasi-experimental prospective study evaluated implementation of the HIV Enhanced Access Testing in Emergency Departments (HEATED) at Kenyatta National Hospital ED in Nairobi, Kenya. The HEATED program was designed as a multi-component intervention employing setting appropriate strategies for HIV care sensitization and integration, task shifting, resource reorganization, linkage advocacy, skills development and education to promote ED-HTS with a focus on higher-risk persons. KPs included sex workers, gay men, men who have sex with men, transgender persons and persons who inject drugs. PPs included young persons (18–24 years), victims of interpersonal violence, persons with hazardous alcohol use and persons never HIV tested. Data were obtained from systems-level records, enrolled injured patient participants and healthcare providers. Systems and patient-level data were collected during a pre-implementation period (6 March − 16 April 2023) and post-implementation (period 1, 1 May − 26 June 2023). Additional, systems-level data were collected during a second post-implementation (period 2, 27 June − 20 August 2023). HTS data were evaluated as facility-based HIV testing (completed in the ED) and distribution of HIV self-tests independently, and aggregated as ED-HTS. Evaluation analyses were completed across reach, effectiveness, adoption, implementation and maintenance framework domains. Results All 151 clinical staff were reached through trainings and sensitizations on the HEATED program. Systems-level ED-HTS among all presenting patients increased from 16.7% pre-implementation to 23.0% post-implementation periods 1 and 2 (RR = 1.31, 95% CI: 1.21–1.43; p

Globally, the incidence of hypertensive disorders of pregnancy, especially preeclampsia, remains high, particularly in low- and middle-income countries. The burden of adverse maternal and perinatal outcomes is particularly high for women who develop a hypertensive disorder remote from term (

IntroductionCancer-associated cachexia (CC) is a progressive syndrome characterized by unintentional weight loss, muscle atrophy, fatigue, and poor outcomes that affects most patients with pancreatic ductal adenocarcinoma (PDAC). The ability to identify and classify CC stage along its continuum early in the disease process is challenging but critical for management.ObjectivesThe main objective of this study was to determine the prevalence of CC stage overall and by sex and race and ethnicity among treatment-naïve PDAC cases using clinical, nutritional, and functional criteria. Secondary objectives included identifying the prevalence and predictors of higher symptom burden, supportive care needs, and quality of life (QoL), and examining their influence on overall survival (OS).Materials and methodsA population-based multi-institutional prospective cohort study of patients with PDAC was conducted between 2018 and 2021 by the Florida Pancreas Collaborative. Leveraging patient-reported data and laboratory values, participants were classified at baseline into four stages [non-cachexia (NCa), pre-cachexia (PCa), cachexia (Ca), and refractory cachexia (RCa)]. Multivariate regression, Kaplan Meier analyses, and Cox regression were conducted to evaluate associations.ResultsCC stage was estimated for 309 PDAC cases (156 females, 153 males). The overall prevalence of NCa, PCa, Ca, and RCa was 12.9%, 24.6%, 54.1%, and 8.4%, respectively. CC prevalence across all CC stages was highest for males and racial and ethnic minorities. Criteria differentiated NCa cases from other groups, but did not distinguish PCa from Ca. The most frequently reported symptoms included weight loss, fatigue, pain, anxiety, and depression, with pain significantly worsening over time. The greatest supportive care needs included emotional and physical domains. Males, Black people, and those with RCa had the worst OS.ConclusionsUsing clinical, nutritional, and functional criteria, nearly one-quarter of the PDAC cases in our diverse, multi-institutional cohort had PCa and 62.5% had Ca or RCa at the time of diagnosis. The PCa estimate is higher than that reported in prior studies. We recommend these criteria be used to aid in CC classification, monitoring, and management of all incident PDAC cases. Findings also highlight the recommendation for continued emotional support, assistance in alleviating pain, and supportive care needs throughout the PDAC treatment journey.

Abstract Coproduction represents an inclusive approach for developing decision‐support resources because it seeks to integrate scientific knowledge and end‐user needs. Unfortunately, spatial decision support systems (SDSS) coproduction has sometimes resulted in limited utility for end‐users, partially due to scarce SDSS coproduction guidance. To initiate coproduction, we held a series of workshops to co‐design a spatial conservation prioritization tool for sagebrush ecosystems in the western United States. We share four themes derived from participant feedback and our reflections to guide future SDSS codesign efforts. We found end‐user confidence in data inputs and transparency regarding SDSS assumptions generated trust. Workshop participants noted our virtual format, with smaller break‐out groups, effectively facilitated discussions. Ultimately, end‐users appreciated the conservation context provided by regional‐scale SDSS but preferred local‐scale prioritization efforts for site‐level planning. Therefore, we are shifting ongoing co‐design efforts to consider local‐scale tool development, which can scale up to larger geographic extents.

ABSTRACT Asexual replication in the apicomplexan Sarcocystis neurona involves two main developmental stages: the motile extracellular merozoite and the sessile intracellular schizont. Merozoites invade host cells and transform into schizonts that undergo replication via endopolygeny to form multiple (64) daughter merozoites that are invasive to new host cells. Given that the capabilities of the merozoite vary significantly from the schizont, the patterns of transcript levels throughout the asexual lifecycle were determined and compared in this study. RNA-Seq data were generated from extracellular merozoites and four intracellular schizont development time points. Of the 6,938 genes annotated in the S. neurona genome, 6,784 were identified in the transcriptome. Of these, 4,111 genes exhibited significant differential expression between the merozoite and at least one schizont development time point. Transcript levels were significantly higher for 2,338 genes in the merozoite and 1,773 genes in the schizont stages. Included in this list were genes encoding the secretory pathogenesis determinants (SPDs), which encompass the surface antigen and SAG-related sequence (SAG/SRS) and the secretory organelle proteins of the invasive zoite stage (micronemes, rhoptries, and dense granules). As anticipated, many of the S. neurona SPD gene transcripts were abundant in merozoites. However, several SPD transcripts were elevated in intracellular schizonts, suggesting roles unrelated to host cell invasion and the initial establishment of the intracellular niche. The hypothetical genes that are potentially unique to the genus Sarcocystis are of particular interest. Their conserved expression patterns are instructive for future investigations into the possible functions of these putative Sarcocystis-unique genes.IMPORTANCEThe genus Sarcocystis is an expansive clade within the Apicomplexa, with the species S. neurona being an important cause of neurological disease in horses. Research to decipher the biology of S. neurona and its host-pathogen interactions can be enhanced by gene expression data. This study has identified conserved apicomplexan orthologs in S. neurona, putative Sarcocystis-unique genes, and gene transcripts abundant in the merozoite and schizont stages. Importantly, we have identified distinct clusters of genes with transcript levels peaking during different intracellular schizont development time points, reflecting active gene expression changes across endopolygeny. Each cluster also has subsets of transcripts with unknown functions, and investigation of these seemingly Sarcocystis-unique transcripts will provide insights into the interesting biology of this parasite genus.

Objective: Current treatment for knee Osteoarthritis (OA) includes exercise and intra-articular injections with corticosteroid (CS), hyaluronic acid (HA), etc., which address OA-related pain and functional limitation. While these interventions can be given together, little is known about the efficacy of a multi-modal approach. The purpose of this scoping review is to examine studies that compare combining exercise and intra-articular knee injections to exercise alone for the management of knee OA. Methods: A search was performed using PubMed, CINAHL, and Clinicaltrials.gov with MeSH terms “knee osteoarthritis” AND “exercise” AND “injections”. Abstracts were screened to meet inclusion criteria of both intervention groups including exercise and one group receiving an injection for treatment of knee OA. Full text articles were screened to meet inclusion criteria and rated using the Pedro Scale. Results: 11 studies that met inclusion criteria. The included studies utilized CS, hyaluronic acid (HA), and Bone Marrow Concentrate (BMC), botulinum toxin A, or a combination of dextrose and lidocaine injections. Most studies included supervised exercise interventions with all studies including strengthening of the quadriceps. CS and exercise compared to exercise alone showed similar improvements in pain. The HA injection studies yielded mixed results with two studies finding HA and exercise was not superior than exercise alone while two other studies found that HA and exercise were superior. Conclusion: There was a paucity of literature investigating multimodal approaches. Most of the included studies did not find superior effects of adding a knee injection to exercise compared to exercise alone for knee OA.

Summary: De novo genome assemblies are common tools for examining novel biological phenomena in non-model organisms. Here, we present a protocol for preparing Drosophila genomic DNA to create chromosome-level de novo genome assemblies. We describe steps for high-molecular-weight DNA preparation with phenol or Genomic-tips, quality control, long-read nanopore sequencing, short-read DNA library preparation, and sequencing. We then detail procedures of genome assembly, annotation, and assessment that can be used for downstream comparison and functional analysis.For complete details on the use and execution of this protocol, please refer to Sperling et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract We consider as a model of Weyl semimetal thermoelectric transport a (3 + 1)-dimensional charged, relativistic and relaxed fluid with a U(1) V × U(1) A chiral anomaly. We take into account all possible mixed energy, momentum, electric and chiral charge relaxations, and discover which are compatible with electric charge conservation, Onsager reciprocity and a finite DC conductivity. We find that all relaxations respecting these constraints necessarily render the system open and violate the second law of thermodynamics. We then demonstrate how the relaxations we have found arise from kinetic theory and a modified relaxation time approximation. Our results lead to DC conductivities that differ from those found in the literature opening the path to experimental verification.

Abstract Online retailers in emerging markets like South Africa are adopting Bitcoin payments. This study explores factors driving consumer adoption and word-of-mouth (WOM) recommendations for Bitcoin in online transactions. Using an integrated model combining valency theory, social contagion theory, and the technology acceptance model (TAM), we analyse data from 521 South African online shoppers. Findings reveal that perceived usefulness, ease of use, social pressures, trust, and perceived risk significantly influence both adoption and WOM. Importantly, self-efficacy moderates the relationship between these factors and behaviour. This research contributes to the literature by offering a comprehensive understanding of Bitcoin adoption. For business and policy actors, enhancing consumer self-efficacy can foster trust, ease concerns, and encourage positive WOM, ultimately aiding successful Bitcoin implementation and promotion.

Abstract Melanoma incidence and mortality rates are historically higher for men than women. Although emerging studies have highlighted tumorigenic roles for the male sex hormone androgen and its receptor (AR) in melanoma, cellular and molecular mechanisms underlying these sex-associated discrepancies are poorly defined. Here, we delineate a previously undisclosed mechanism by which androgen-activated AR transcriptionally upregulates fucosyltransferase 4 (FUT4) expression, which drives melanoma invasiveness by interfering with adherens junctions (AJs). Global phosphoproteomic and fucoproteomic profiling, coupled with in vitro and in vivo functional validation, further reveal that AR-induced FUT4 fucosylates L1 cell adhesion molecule (L1CAM), which is required for FUT4-increased metastatic capacity. Tumor microarray and gene expression analyses demonstrate that AR-FUT4-L1CAM-AJs signaling correlates with pathological staging in melanoma patients. By delineating key androgen-triggered signaling that enhances metastatic aggressiveness, our findings help explain sex-associated clinical outcome disparities and highlight AR/FUT4 and its effectors as potential prognostic biomarkers and therapeutic targets in melanoma.

Oblatopyrochroa bellula, a new genus and species of Pyrochroinae Latreille, 1807 from Xizang, China, is described and illustrated. The antennae, cranial apparatus, and genitalia of the new genus form a truly unique set of characters not observed in any other pyrochroid genus. The taxonomic position and phylogenetic relationships of Oblatopyrochroa gen. nov. are also discussed but appear difficult to resolve.

Home-based exercises are an important component of stroke rehabilitation but are seldom fully completed. Past studies of exercise perseverance in the general public have suggested the importance of early exercise frequency and schedule consistency (in terms of which days of the week exercises are performed) because they encourage habit formation. To test whether these observations apply after a stroke, we leveraged data from 2,583 users of a sensor-based system (FitMi) developed to motivate movement exercises at home. We grouped users based on their early exercise frequency (defined across the initial 6 weeks of use) and calculated the evolution of habit score (defined as exercise frequency multiplied by exercise duration) across 6 months. We found that habit score decayed exponentially over time but with a slower decay constant for individuals with higher early frequency. Only the group with an early exercise frequency of 4 days/week or more had non-zero habit score at six months. Within each frequency group, dividing individuals into higher and lower consistency subgroups revealed that the higher consistency subgroups had significantly higher habit scores. These results are consistent with previous studies on habit formation in exercise and may help in designing effective home rehabilitation programs after stroke.

Abstract Palmitic acid (PAM) can be provided in the diet or synthesized via de novo lipogenesis (DNL), primarily, from glucose. Preclinical work on the origin of brain PAM during development is scarce and contrasts results in adults. In this work, we use naturally occurring carbon isotope ratios (13C/12C; δ13C) to uncover the origin of brain PAM at postnatal days 0, 10, 21 and 35, and RNA sequencing to identify the pathways involved in maintaining brain PAM, at day 35, in mice fed diets with low, medium, and high PAM from birth. Here we show that DNL from dietary sugars maintains the majority of brain PAM during development and is augmented in mice fed low PAM. Importantly, the upregulation of hepatic DNL genes, in response to low PAM at day 35, demonstrates the presence of a compensatory mechanism to maintain total brain PAM pools compared to the liver; suggesting the importance of brain PAM regulation.

Abstract Objectives It is now recognized that blood brain barrier (BBB) leakage occurs in cerebral small vascular disease (CSVD) and plays a significant role in the pathophysiology of vascular dementia. We hypothesized that genetic polymorphisms of junctional adhesion molecule‐A (JAM‐A) (which may result in compromised structure of tight junction proteins that form the BBB) in combination with cerebrovascular risk factors hypertension, lipid disorders, and type 2 diabetes may result in BBB leakage and increase the individual's risk of CSVD‐related dementia. Methods In this case–control study, 97 controls with a mean Mini‐Mental State Exam (MMSE) score of 29 and 38 CSVD‐related vascular dementia participants (mean MMSE score of 19) were recruited. Bloods were collected for the analysis of two common single nucleotide polymorphisms (SNPs) of the JAM‐A genotypes rs790056 and rs2481084 using real‐time polymerase chain reaction (PCR) assay. Medical history of hypertension, hyperlipidemia, and diabetes was collected for all participants. Results Polymorphisms of genotype JAM‐A SNP rs790056 showed statistically significant result when the subgroup with hyperlipidemia was analyzed (OR = 3.130, p = 0.042 for TC + CC genotypes with hyperlipidaemia vs controls). Similar result was found with diabetes (OR = 4.670, p = 0.031 for TC + CC genotypes vs controls). No significant result was found with hypertension. Borderline results of statistical significance were found for JAM‐A SNP rs2481084 with hyperlipidemia (OR = 3.210, p = 0.054 for TC + CC genotypes vs controls) and with diabetes (OR = 3.620, p = 0.069 for TC + CC genotypes vs controls) but not for hypertension. The borderline results might have been due to lack of statistical power because of small sample size. Conclusions These results lend further support that cerebrovascular risk factors interact with genetic polymorphisms of BBB proteins to increase the risk of vascular dementia.

Abstract Background Chronic infection with HBV is responsible for >50% of all hepatocellular cancer cases globally and disproportionately affects sub-Saharan African (sSA) countries. Migration from these countries to Europe has increased substantially in recent years, posing unique challenges to health systems. The aim of this study was to carry out a community-based intervention to increase HBV screening, vaccination, and linkage to care among sSA migrants in Catalonia, Spain. Methods This was a prospective cohort study. Participants ≥18 years were offered community-based HBV screening between 20/11/20 and 21/01/22. Rapid HBV testing and blood sample collection utilizing plasma separation cards were carried out and linkage to care was offered to all participants. HBV vaccination and post-test counseling were performed at a second visit in the community. The main outcome was the odds of those with current HBV infection being successfully linked to hepatology. Rates of completing the care cascade of this model were analyzed. Results In the present study, 444 people undergo screening, with 50.6% of participants showing evidence of past or current HBV infection, including an HBsAg prevalence of 9.2%. Migrants with current HBV infection exhibit 5.2 times higher odds of successful linkage to care compared to those in need of post-test counseling or vaccination. The study achieves a successful linkage to care rate of 72% for all participants, with specialist appointments arranged within 15.5 days. Conclusions This community-based HBV screening program provides evidence of a successful model for identifying and providing care, including vaccination, to west African migrants at high risk of HBV infection who may otherwise not engage in care.

By tonnage, corn (Zea mays L.) is the #1 crop produced globally, and recent research has suggested that no-till (NT) systems can lead to reduced yields of this important crop. Additionally, there is a lack of long-term data about the effects of tillage and N management on cropping systems. Corn is the most nitrogen (N)-fertilized crop in the USA, and N losses to the environment contribute to significant impacts on air and water quality. We conducted long-term studies on conventional tillage (CT) and conservation tillage systems, such as strip tillage (ST) and NT, under different N rates. We found that immediately after conversion to NT, yields from NT were significantly lower than yields from CT (p < 0.1), but after five years of NT, the NT yields were 1.5% higher than the CT yields (p < 0.1). Initially, the NT yields were lower than the ST (p < 0.01), but after seven years of NT, the NT yields were comparable to ST grain yields. Although the total aboveground N uptake with NT immediately after conversion to NT was lower than with CT and ST, these differences were not significant in the long run. The nitrogen use efficiency (NUE) with NT increased over time. The present work highlights the importance of long-term research for determining the cumulative impacts of best management practices such as NT. We found that NT becomes a more viable practice after five or seven years of implementation, demonstrating the high importance of long-term research.

Abstract Humans and animals can be exposed to fecally-transmitted pathogens in both private and public domain environments. Animals may also acquire pathogen infections from these two environments and transmit them to humans through different pathways. Evidence on how often and where interactions occur between the two environments could improve the effectiveness of public health programs for preventing zoonotic disease transmission and response to disease outbreaks. This study aimed to develop a protocol for using geo-trackers to measure the spatial-temporal movement and interaction between animals and children in households and public areas in low- and middle-income categories of urban neighbourhoods in Kenya. It also aimed to identify opportunities and challenges for the scale-up of these methods’ for surveillance of other zoonotic diseases of public health significance. One commercial geo-tracker device with the best technological performance and usability that met pre-defined criteria for the study context was identified. Community engagement meetings were then conducted to gather input on a proposed study protocol. Afterwards, infants and animals were geo-tracked in 10 households in urban informal settlements of Kibera and Jericho, Nairobi over two consecutive weeks with iterative improvements to protocols. The effectiveness of the geo-tracking exercise was evaluated through in-depth interviews with Community Health Volunteers (CHVs) and infant caregivers. Animal and infant behaviour and battery reliability of the geo-trackers were also monitored; and observed opportunities and challenges in implementing the protocol during the exercise were documented. Community members were receptive and accepted the use of geo-trackers on animals and children. In pilot testing, there was no change of behaviour from 10 infants tracked. Discomfort was observed for up to 30 min after the placement for some of the seven animals tracked, but the animals quickly adjusted. The battery for all geo-tracker devices lasted for the 24-h geo-tracking period. Some caregivers and CHVs were concerned whether the geo-trackers could record personal information. It was shown that geo-tracker devices can be successfully deployed to study animal-child interactions and movement in different categories of urban neighbourhoods. Recommendations have been made on the lessons learnt from the study to help scientists who would use geo-trackers for future community-based human and animal research. One Health impact statement Assessing human and animal risks of acquiring enteric infections from environmental contamination, or contributing to pathogen contamination of the environment requires understanding spatial-temporal patterns of human and animal movement between private households and the community. Movement of domestic animals is relevant for understanding household-community spatial patterns of pathogen transmission because animal ownership and contact with humans is common, and free-roaming animals carrying enteric pathogens can spread diverse faecal pathogens between environments. The community-based participatory research approach of this study evaluated implementation feasibility from the lens of technical usability and reliability of geo-tracking devices, as well as social acceptability and ethics related to using such devices for the community-based study of human and animal subjects in urban settings. Evidence and recommendations from this study will be useful to anyone interested in understanding human-animal-environment interactions and their contributions to infectious disease transmission.

Parkinson’s disease (PD) is characterized by three main motor symptoms: bradykinesia, rigidity and tremor. PD is also associated with diverse non-motor symptoms that may develop in parallel or precede motor dysfunctions, ranging from autonomic system dysfunctions and impaired sensory perception to cognitive deficits and depression. Here, we examine the role of the progressive loss of dopaminergic transmission in behaviors related to the non-motor symptoms of PD in a mouse model of the disease (the TIF-IADATCreERT2 strain). We found that in the period from 5 to 12 weeks after the induction of a gradual loss of dopaminergic neurons, mild motor symptoms became detectable, including changes in the distance between paws while standing as well as the swing speed and step sequence. Male mutant mice showed no apparent changes in olfactory acuity, no anhedonia-like behaviors, and normal learning in an instrumental task; however, a pronounced increase in the number of operant responses performed was noted. Similarly, female mice with progressive dopaminergic neuron degeneration showed normal learning in the probabilistic reversal learning task and no loss of sweet-taste preference, but again, a robustly higher number of choices were performed in the task. In both males and females, the higher number of instrumental responses did not affect the accuracy or the fraction of rewarded responses. Taken together, these data reveal discrete, dopamine-dependent non-motor symptoms that emerge in the early stages of dopaminergic neuron degeneration.

Under traditional circumstances, most clinical trials rely on in-person operations to identify, recruit, and enroll study participants and to complete study-related visits. During unusual circumstances, such as the COVID-19 pandemic, the typical clinical trial model is challenged and forced to explore alternative approaches to implementing study recruitment, participant enrollment, and data collection strategies. One such alternative is a direct-to-participant approach which leverages electronic resources and relevant technological devices (e.g., smart phones) available to researchers and patients. This approach functions under the assumption that a participant has access to a device that connects to the internet such as a smart phone, tablet, or computer. Researchers are then able to transition a typical paper-based, in-person model to an electronic-based, siteless, remote study. This article describes the challenges clinicians and researchers faced when implementing a direct-to-participant study approach during the COVID-19 pandemic. The lessons learned during this study of infant populations could help increase efficiency of future trials, specifically, by lessening the burden on participants and clinicians as well as streamlining the process for enrollment and data collection. While direct-to-adult participant recruitment is not a novel approach, our findings suggest that studies attempting to recruit the infant population may benefit from such a direct-to-participant approach.

Quantum key distribution (QKD) has matured in recent years from laboratory proof-of-principle demonstrations to commercially available systems. One of the major bottlenecks is the limited communication distance in fiber networks due to the exponential signal damping. To bridge intercontinental distances, low Earth orbit satellites transmitting quantum signals over the atmosphere can be used. These free-space links, however, can only operate during the night, as the sunlight otherwise saturates the detectors used to measure the quantum states. For applying QKD in a global quantum internet with continuous availability and high data rates, operation during daylight is required. In this work, we model a satellite-to-ground quantum channel for different quantum light sources to identify the optimal wavelength for free-space QKD under ambient conditions. Daylight quantum communication is possible within the Fraunhofer lines or in the near-infrared spectrum, where the intrinsic background from the sun is comparably low. The highest annual secret key length considering the finite key effect is achievable at the Hα Fraunhofer line. More importantly, we provide the fundamental model that can be adapted, in general, to any other specific link scenario taking into account the required modifications. We also propose a true single-photon source based on a color center in hexagonal boron nitride coupled to a microresonator that can implement such a scheme. Our results can also be applied in roof-to-roof scenarios and are, therefore, relevant for near-future quantum networks.

Interpretation of extracellular recordings can be challenging due to the long range of electric field. This challenge can be mitigated by estimating the current source density (CSD). Here we introduce kCSD-python, an open Python package implementing Kernel Current Source Density (kCSD) method and related tools to facilitate CSD analysis of experimental data and the interpretation of results. We show how to counter the limitations imposed by noise and assumptions in the method itself. kCSD-python allows CSD estimation for an arbitrary distribution of electrodes in 1D, 2D, and 3D, assuming distributions of sources in tissue, a slice, or in a single cell, and includes a range of diagnostic aids. We demonstrate its features in a Jupyter Notebook tutorial which illustrates a typical analytical workflow and main functionalities useful in validating analysis results.