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Abstract Landscape fragmentation is statistically correlated with both increases and decreases in wildfire burned area (BA). These different directions-of-impact are not mechanistically understood. Here, road density, a land fragmentation proxy, is implemented in a CMIP6 coupled land-fire model, to represent fragmentation edge effects on fire-relevant environmental variables. Fragmentation caused modelled BA changes of over ±10% in 16% of [0.5°] grid-cells. On average, more fragmentation decreased net BA globally (−1.5%), as estimated empirically. However, in recently-deforested tropical areas, fragmentation drove observationally-consistent BA increases of over 20%. Globally, fragmentation-driven fire BA decreased with increasing population density, but was a hump-shaped function of it in forests. In some areas, fragmentation-driven decreases in BA occurred alongside higher-intensity fires, suggesting the decoupling of fire severity traits. This mechanistic model provides a starting point for quantifying policy-relevant fragmentation-fire impacts, whose results suggest future forest degradation may shift fragmentation from net global fire inhibitor to net fire driver.

Abstract Microbial carbon use efficiency (CUE) affects the fate and storage of carbon in terrestrial ecosystems, but its global importance remains uncertain. Accurately modeling and predicting CUE on a global scale is challenging due to inconsistencies in measurement techniques and the complex interactions of climatic, edaphic, and biological factors across scales. The link between microbial CUE and soil organic carbon relies on the stabilization of microbial necromass within soil aggregates or its association with minerals, necessitating an integration of microbial and stabilization processes in modeling approaches. In this perspective, we propose a comprehensive framework that integrates diverse data sources, ranging from genomic information to traditional soil carbon assessments, to refine carbon cycle models by incorporating variations in CUE, thereby enhancing our understanding of the microbial contribution to carbon cycling.

ObjectivesIn 2020, firearm injuries surpassed automobile collisions as the leading cause of death in US children. Annual automobile fatalities have decreased during 40 years through a multipronged approach. To develop similarly targeted public health interventions to reduce firearm fatalities, there is a critical need to first characterize firearm injuries and their outcomes at a granular level. We sought to compare firearm injuries, outcomes, and types of shooters at trauma centers in four pediatric health systems across the USA.MethodsWe retrospectively extracted data from each institution's trauma registry, paper and electronic health records. Study included all patients less than 19 years of age with a firearm injury between 2003 and 2018. Variables collected included demographics, intent, resources used, and emergency department and hospital disposition. Descriptive statistics were reported using medians and IQRs for continuous data and counts with percentages for categorical data. χ2 test or Fisher's exact test was conducted for categorical comparisons.ResultsOur cohort (n=1008, median age 14 years) was predominantly black and male. During the study period, there was an overall increase in firearm injuries, driven primarily by increases in the South (S) site (β=0.11 (SE 0.02), p=

All children and adolescents deserve access to quality health care regardless of their race/ethnicity, health conditions, financial resources, or geographic location. Despite improvements over the past decades, severe disparities in the availability and access to high-quality health care for children and adolescents continue to exist throughout the United States. Economic and racial factors, geographic maldistribution of primary care pediatricians, and limited availability of pediatric medical subspecialists and pediatric surgical specialists all contribute to inequitable access to pediatric care. Robust, comprehensive telehealth coverage is critical to improving pediatric access and quality of care and services, particularly for under-resourced populations.

Parkinson disease is a complex, age-related, neurodegenerative disease associated with dopamine deficiency and both motor and nonmotor deficits. Many environmental and genetic factors influence Parkinson disease risk, with different factors predominating in different patients. These factors converge on specific pathways, including mitochondrial dysfunction, oxidative stress, protein aggregation, impaired autophagy, and neuroinflammation. Ultimately, treatment of Parkinson disease may focus on targeted therapies for pathophysiologically defined subtypes of Parkinson disease patients.

Abstract Background Identifying and reducing cardiometabolic risks driven by obesity remains a healthcare challenge. The metabolic syndrome is associated with abdominal obesity and inflammation and is predictive of long-term risk of developing type 2 diabetes and cardiovascular disease in otherwise healthy individuals living with obesity. Therefore, we investigated the effects of adherent exercise, a glucagon-like peptide 1 receptor agonist (GLP-1 RA), or the combination on severity of metabolic syndrome, abdominal obesity, and inflammation following weight loss. Methods This was a randomized, double-blinded, placebo-controlled trial. During an 8-week low-calorie diet (800 kcal/day), 195 adults with obesity and without diabetes lost 12% in body weight. Participants were then evenly randomized to four arms of one-year treatment with: placebo, moderate-to-vigorous exercise (minimum of 150 min/week of moderate-intensity or 75 min/week of vigorous-intensity aerobic physical activity or an equivalent combination of both), the GLP-1 RA liraglutide 3.0 mg/day, or a combination (exercise + liraglutide). A total of 166 participants completed the trial. We assessed the prespecified secondary outcome metabolic syndrome severity z-score (MetS-Z), abdominal obesity (estimated as android fat via dual-energy X-ray absorptiometry), and inflammation marker high-sensitivity C-reactive protein (hsCRP). Statistical analysis was performed on 130 participants adherent to the study interventions (per-protocol population) using a mixed linear model. Results The diet-induced weight loss decreased the severity of MetS-Z from 0.57 to 0.06, which was maintained in the placebo and exercise groups after one year. MetS-Z was further decreased by liraglutide (− 0.37, 95% CI − 0.58 to − 0.16, P

Abstract Background and purpose Tumor-infiltrating lymphocytes (TILs) are associated with locoregional control (LRC) in head-and-neck squamous cell carcinoma (HNSCC) patients undergoing (chemo)radiotherapy. As immunosenescence results in reduced immune activity, the role of TILs in elderly HNSCC patients may differ compared to younger patients, providing a rationale to study the prognostic role of TILs and immune checkpoints (ICs) in this population. Material and methods Sixty-three HNSCC patients aged ≥ 65 years undergoing definitive (chemo)radiotherapy between 2010 and 2019 with sufficient material from pre-treatment biopsies were included in the analysis. Immunohistochemical stainings of CD3, CD4, CD8, PD-L1, TIM3, LAG3, TIGIT and CD96, and of osteopontin as an immunosenescence-associated protein were performed. Overall survival (OS) and progression-free survival (PFS) were determined using the Kaplan–Meier method, and Fine-Gray's models were used for locoregional failure (LRF) analyses. Results While there was no correlation between patient age and IC expression, osteopontin levels correlated with increasing age (r = 0.322, p

The gold standard for a definitive diagnosis of Parkinson disease (PD) is the pathologic finding of aggregated α-synuclein into Lewy bodies and for Alzheimer disease (AD) aggregated amyloid into plaques and hyperphosphorylated tau into tangles. Implicit in this clinicopathologic-based nosology is the assumption that pathologic protein aggregation at autopsy reflects pathogenesis at disease onset. While these aggregates may in exceptional cases be on a causal pathway in humans (e.g., aggregated α-synuclein in SNCA gene multiplication or aggregated β-amyloid in APP mutations), their near universality at postmortem in sporadic PD and AD suggests they may alternatively represent common outcomes from upstream mechanisms or compensatory responses to cellular stress in order to delay cell death. These 3 conceptual frameworks of protein aggregation (pathogenic, epiphenomenon, protective) are difficult to resolve because of the inability to probe brain tissue in real time. Whereas animal models, in which neither PD nor AD occur in natural states, consistently support a pathogenic role of protein aggregation, indirect evidence from human studies does not. We hypothesize that (1) current biomarkers of protein aggregates may be relevant to common pathology but not to subgroup pathogenesis and (2) disease-modifying treatments targeting oligomers or fibrils might be futile or deleterious because these proteins are epiphenomena or protective in the human brain under molecular stress. Future precision medicine efforts for molecular targeting of neurodegenerative diseases may require analyses not anchored on current clinicopathologic criteria but instead on biological signals generated from large deeply phenotyped aging populations or from smaller but well-defined genetic-molecular cohorts.

The current COVID-19 pandemic shows how little many people know about viruses. Yet apart from COVID-19, the world has observed epidemic spread of another SARS virus, of the Ebola virus, and of the Zika virus during the last two decades. The human immunodeficiency virus (HIV) is still one of the most dangerous viruses worldwide. Some types of the human papillomavirus (HPV) are the main cause of cervical cancer. Cases of measles, also caused by a virus, increase in numbers due to lack of access to or refusal of vaccination. Furthermore, there is the widespread belief that viruses are similar to bacteria and may thus be fought off with antibiotics. Yet viruses have no metabolism. Thus, antibiotics cannot work against them, but may instead cause more harm than help, given side effects such as killing beneficial bacteria (e.g., in the intestine). Second, misuse of antibiotics is one key factor in the evolution of antibiotic-resistant bacterial strains -- a strong public health issue nowadays. This article informs readers what viruses are, how they are distinct from bacteria, how they may have evolved, and how diseases they cause may be prevented. Additionally, insights from studies concerning students' virus-related knowledge are summarized.

Blood vessel imaging provides crucial information for physiological monitoring and disease diagnosis. Optical‐resolution photoacoustic microscopy (PAM) is gaining intense attention in high‐resolution in vivo imaging of blood vessels. However, its applicability in clinical settings is hindered by the requirement of bulky and costly pulsed lasers as well as complex alignment procedures. Here, as a novel approach to high‐quality and cost‐effective microvasculature imaging, a dual‐wavelength fiber‐coupled laser diode‐based PAM (FC‐LD‐PAM) system is demonstrated on the mouse ear and brain in vivo. Furthermore, assisted with a deep learning method, the proposed technique effectively combines the advantages when using both small and large core‐size multimode fibers—successfully enhances the resolution of blurry mouse microvascular images obtained using a large core‐size fiber, revealing fine details that are comparable to those achieved using a small core‐size fiber; significantly reduces the overall time for data acquisition up to fourfold, improving the efficiency significantly in the imaging process. In addition, the proposed approach can achieve accurate and high‐resolution mapping of oxygen saturation in vivo, providing functional insight on living tissue. Therefore, the FC‐LD‐PAM can serve as a translational tool for high‐resolution imaging with enhanced accessibility and versatility in the biomedical field. [ABSTRACT FROM AUTHOR]

Fire interacts with many parts of the Earth system. However, its drivers are myriad and complex, interacting differently in different regions depending on prevailing climate regimes, vegetation types, socioeconomic development, and land use and management. Europe is facing strong increases in projected fire weather danger as a consequence of climate change and has experienced extreme fire seasons and events in recent years. Here, we focus on understanding and simulating burnt area across a European study domain using remote sensing data and generalised linear models (GLMs). We first examined fire occurrence across land cover types and found that all non-cropland vegetation (NCV) types (comprising 26 % of burnt area) burnt with similar spatial and temporal patterns, which were very distinct from those in croplands (74 % of burnt area). We then used GLMs to predict cropland and NCV burnt area at ∼9×9 km and monthly spatial and temporal resolution, respectively, which together we termed BASE (Burnt Area Simulator for Europe). Compared to satellite burnt area products, BASE effectively captured the general spatial and temporal patterns of burning, explaining 32 % (NCV) and 36 % (cropland) of the deviance, and performed similarly to state-of-the-art global fire models. The most important drivers were fire weather and monthly indices derived from gross primary productivity followed by coarse socioeconomic indicators and vegetation properties. Crucially, we found that the drivers of cropland and NCV burning were very different, highlighting the importance of simulating burning in different land cover types separately. Through the choice of predictor variables, BASE was designed for coupling with dynamic vegetation and Earth system models and thus enabling future projections. The strong model skill of BASE when reproducing seasonal and interannual dynamics of NCV burning and the novel inclusion of cropland burning indicate that BASE is well suited for integration in land surface models. In addition to this, the BASE framework may serve as a basis for further studies using additional predictors to further elucidate drivers of fire in Europe. Through these applications, we suggest BASE may be a useful tool for understanding, and therefore adapting to, the increasing fire risk in Europe. [ABSTRACT FROM AUTHOR]

Students with learning disabilities score lower than other at-risk groups on state standardized assessment tests. Educators are searching for intervention strategies to improve math achievement for students with learning disabilities. The study examined the effects of a mathematics intervention known as Cover, Copy, and Compare for learning basic math computation skills. Fifteen students diagnosed with learning disabilities participated in this study using Curriculum Based Assessment probes to collect the data. There was a significant difference in math achievement from pre- to post-test scores for students with learning disabilities who participated in the Cover, Copy, and Compare treatment, t (14) = -15.09, p < 0.001. An analysis of covariance determined the efficacy of a Cover, Copy, and Compare intervention was not related to gender or ethnicity. One recommendation for future research is to conduct studies regarding Cover, Copy, and Compare instruction's impact on student achievement for younger and older students with learning disabilities.

(1) Many undergraduate students struggle to produce a good literature review in their dissertations, as they are not experienced, do not have sufficient time, and do not have the required skills to articulate information. (2) Subsequently, we deployed Litstudy and NLP tools and developed a recommendation system to analyze articles in an academic database to help the students produce literature reviews. (3) The recommendation system successfully performed three levels of analysis. The elementary-level analysis provided demographic statistical analysis to the students, helping them understand the background information of the selected articles they would review. The intermediate-level analysis provided visualization of citations in network graphs for the students to understand the relationships of the articles’ authors, regions, and institutes so that the flow of ideas, development, and similarity of the selected articles can be better analyzed. The advanced level of analysis provided topic modeling functions for the students to understand the high-level themes of the selected articles to improve productivity as they read through them and simultaneously boost their creativity. (4) The three levels of analysis successfully analyzed the selected articles to provide innovative results and triggered the students to handle literature reviews in a new way. Further enhancement opportunities were identified in integrating the NLP technologies with large language models to facilitate the generation of research ideas/insights. This would be an exciting opportunity to have AI/NLP integrated to help the students with their research.

Arabidopsis thaliana INNER NO OUTER (INO) is a YABBY protein that is essential for the initiation and development of the outer integument of ovules. Other YABBY proteins have been shown to be involved in both negative and positive regulation of expression of putative target genes. YABBY proteins have also been shown to interact with the corepressor LEUNIG (LUG) in several systems. In support of a repressive role for INO, we confirm that INO interacts with LUG and also find that INO directly interacts with SEUSS (SEU), a known corepressive partner of LUG. Further, we find that INO can directly interact with ADA2b/PROPORZ1 (PRZ1), a transcriptional coactivator that is known to interact with the histone acetyltransferase GENERAL CONTROL NONREPRESSIBLE PROTEIN 5 (GCN5, also known as HAG1). Mutations in LUG, SEU, and ADA2b/PRZ1 all lead to pleiotropic effects including a deficiency in the extension of the outer integument. Additive and synergistic effects of ada2b/prz1 and lug mutations on outer integument formation indicate that these two genes function independently to promote outer integument growth. The ino mutation is epistatic to both lug and ada2b/prz1 in the outer integument, and all three proteins are present in the nuclei of a common set of outer integument cells. This is consistent with a model where INO utilizes these coregulator proteins to activate and repress separate sets of target genes. Other Arabidopsis YABBY proteins were shown to also form complexes with ADA2b/PRZ1, and have been previously shown to interact with SEU and LUG. Thus, interaction with these corepressors and coactivator may represent a general mechanism to explain the positive and negative activities of YABBY proteins in transcriptional regulation. The LUG, SEU, and ADA2b/PRZ1 proteins would also separately be recruited to targets of other transcription factors, consistent with their roles as general coregulators, explaining the pleiotropic effects not associated with YABBY function.

ObjectiveTo explore the association between metabolic syndrome and the Unified Parkinson's Disease Rating Scale (UPDRS) scores and, secondarily, the Symbol Digit Modalities Test (SDMT).MethodsThis is a secondary analysis of data from 1,022 of 1,741 participants of the National Institute of Neurological Disorders and Stroke Exploratory Clinical Trials in Parkinson Disease Long-Term Study 1, a randomized, placebo-controlled trial of creatine. Participants were categorized as having or not having metabolic syndrome on the basis of modified criteria from the National Cholesterol Education Program Adult Treatment Panel III. Those who had the same metabolic syndrome status at consecutive annual visits were included. The change in UPDRS and SDMT scores from randomization to 3 years was compared in participants with and without metabolic syndrome.ResultsParticipants with metabolic syndrome (n = 396) compared to those without (n = 626) were older (mean [SD] 63.9 [8.1] vs 59.9 [9.4] years; p < 0.0001), were more likely to be male (75.3% vs 57.0%; p < 0.0001), and had a higher mean uric acid level (men 5.7 [1.3] vs 5.3 [1.1] mg/dL, women 4.9 [1.3] vs 3.9 [0.9] mg/dL, p < 0.0001). Participants with metabolic syndrome experienced an additional 0.6- (0.2) unit annual increase in total UPDRS (p = 0.02) and 0.5- (0.2) unit increase in motor UPDRS (p = 0.01) scores compared with participants without metabolic syndrome. There was no difference in the change in SDMT scores.ConclusionsPersons with Parkinson disease meeting modified criteria for metabolic syndrome experienced a greater increase in total UPDRS scores over time, mainly as a result of increases in motor scores, compared to those who did not. Further studies are needed to confirm this finding.Clinicaltrialsgov identifierNCT00449865.

Parkinson disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms and signs. Many reports suggest that diminished heart rate variability occurs early, even prior to the cardinal signs of PD. In a longitudinal study of PD, we evaluated whether heart rate variability (HRV) obtained using a 10-second ECG tracing, and the electrocardiographic QT-interval would be associated with PD severity and progression. Subjects were derived from a longitudinal study of 1741 individuals with early, stable PD. The severity of PD was measured using the global statistical test (GST). In a subset, the heart rate corrected QT-interval (QTcB) was calculated for each electrocardiogram (ECG). The HRV was measured for each ECG and then transformed to fit a normal distribution. The baseline analysis included 653 subjects, with 256 completing the 5-year follow up study. There was an association (P

BackgroundRecognizing the factors associated with falling in Parkinson's disease (PD) would improve identification of at-risk individuals.ObjectiveTo examine frequency of falling and baseline characteristics associated with falling in PD using the National Institute of Neurological Disorders and Stroke (NINDS) Exploratory Trials in PD Long-term Study-1 (NET-PD LS-1) dataset.MethodsThe LS-1 database included 1741 early treated PD subjects (median 4year follow-up). Baseline characteristics were tested for a univariate association with post-baseline falling during the trial. Significant variables were included in a multivariable logistic regression model. A separate analysis using a negative binomial model investigated baseline factors on fall rate.Results728 subjects (42%) fell during the trial, including at baseline. A baseline history of falls was the factor most associated with post-baseline falling. Men had lower odds of post-baseline falling compared to women, but for men, the probability of a post-baseline fall increased with age such that after age 70, men and women had similar odds of falling. Other baseline factors associated with a post-baseline fall and increased fall rate included the Unified PD Rating Scale (UPDRS) Activities of Daily Living (ADL) score, total functional capacity (TFC), baseline ambulatory capacity score and dopamine agonist monotherapy.ConclusionFalls are common in early treated PD. The biggest risk factor for falls in PD remains a history of falling. Measures of functional ability (UPDRS ADL, TFC) and ambulatory capacity are novel clinical risk factors needing further study. A significant age by sex interaction may help to explain why age has been an inconsistent risk factor for falls in PD.