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In this study, a small sample of patients’ neuromonitoring data was analyzed using machine learning (ML) tools to provide proof of concept for quantifying complex signals. Intraoperative neurophysiological monitoring (IONM) is a valuable asset for monitoring the neurological status of a patient during spine surgery. Notably, this technology, when operated by neurophysiologists and surgeons familiar with proper alarm criteria, is capable of detecting neurological deficits. However, non-surgical factors, such as volatile anesthetics like sevoflurane, can negatively influence robust IONM signal generation. While sevoflurane has been shown to affect the latency and amplitude of somatosensory evoked potential (SSEP), a more complex and nuanced analysis of the SSEP waveform has not been performed. In this study, signal processing and machine learning techniques were used to more intricately characterize and predict SSEP waveform changes as a function of varying end-tidal sevoflurane concentration. With data from ten patients who underwent spinal procedures, features describing the SSEP waveforms were generated using principal component analysis (PCA), phase space curves (PSC), and time-frequency analysis (TFA). A minimum redundancy maximum relevance (MRMR) feature selection technique was then used to identify the most important SSEP features associated with changing sevoflurane concentrations. Once the features carrying the maximum amount of information about the majority of signal waveform variability were identified, ML models were used to predict future changes in SSEP waveforms. Linear regression, regression trees, support vector machines, and neural network ML models were then selected for testing. Using SSEP data from eight patients, the models were trained using a range of features selected during MRMR calculations. During the training phase of model development, the highest performing models were identified as support vector machines and regression trees. After identifying the highest performing models for each nerve group, we tested these models using the remaining two patients’ data. We compared the models’ performance metrics using the root mean square error values (RMSEs). The feasibility of the methodology described provides a general framework for the applications of machine learning strategies to further delineate the effects of surgical and non-surgical factors affecting IONM signals.

Abstract Advances in measurement technology are producing increasingly time-resolved environmental exposure data. We aim to gain new insights into exposures and their potential health impacts by moving beyond simple summary statistics (e.g., means, maxima) to characterize more detailed features of high-frequency time series data. This study proposes a novel variant of the Self-Organizing Map (SOM) algorithm called Dynamic Time Warping Self-Organizing Map (DTW-SOM) for unsupervised pattern discovery in time series. This algorithm uses DTW, a similarity measure that optimally aligns interior patterns of sequential data, both as the similarity measure and training guide of the neural network. We applied DTW-SOM to a panel study monitoring indoor and outdoor residential temperature and particulate matter air pollution (PM2.5) for 10 patients with asthma from 7 households near Salt Lake City, UT; the patients were followed for up to 373 days each. Compared to previous SOM algorithms using timestamp alignment on time series data, the DTW-SOM algorithm produced fewer quantization errors and more detailed diurnal patterns. DTW-SOM identified the expected typical diurnal patterns in outdoor temperature which varied by season, as well diurnal patterns in PM2.5 which may be related to daily asthma outcomes. In summary, DTW-SOM is an innovative feature engineering method that can be applied to highly time-resolved environmental exposures assessed by sensors to identify typical diurnal (or hourly or monthly) patterns and provide new insights into the health effects of environmental exposures.

The eucentrosauran centrosaurines Einiosaurus procurvicornis and Achelousaurus horneri are the two most commonly recovered ceratopsids from the Campanian Two Medicine Formation of northwestern Montana, USA. Einiosaurus procurvicornis is known from at least 15 individuals recovered from two monospecific bonebeds, while Achelousaurus horneri is primarily known from one articulated adult cranium as well as two isolated subadult individuals previously referred to the taxon. Previous assessments of ontogeny in these taxa, alongside closely related centrosaurines, focused primarily on crania of mature individuals and disarticulated elements of immature individuals. Here we describe an articulated subadult Einiosaurus procurvicornis skull (MOR 456 8-8-87-1) from the Einiosaurus procurvicornis type locality bonebed and compare its cranial ornamental development with the only identically sized articulated subadult eucentrosauran skull from the Two Medicine Formation, MOR 591. These individuals represent the only known articulated subadult skulls from the hypothesized eucentrosauran lineage in the Two Medicine Formation, thereby enabling comparison of early ontogenetic developmental sequence and timing of all three primary cranial ornaments (nasal, supraorbital, and parietosquamosal frill). Comparison indicates that parietosquamosal frill and supraorbital ornamentation development may have preceded nasal horncore development in these taxa. MOR 456 8-8-87-1 fills a gap between the plesiomorphic morphology of juvenile Einiosaurus procurvicornis supraorbital horncores and the rounded, spheroid mass of bone which characterizes adults. The complete left squamosal of MOR 456 8-8-87-1 is of adult size, in contrast to its shorter face and immature facial ornamentation, which suggests that in Einiosaurus procurvicornis, the face and facial ornamentation development occurred after the parietosquamosal frill had reached adult size.

Munson et al. develop a high-throughput Galectin-9 reporter based endosomal escape imaging assay to probe correlations between nanoparticle-mediated uptake, endosomal escape frequency, and mRNA translation. By screening various delivery systems, modulators and combinations of nanoparticle components, the authors demonstrate how nanomedicines can be optimized for superior escape properties and efficacy in specific applications.

The purpose of this study was to examine the writing performance and motivational beliefs of students who were identified by their school district as English language learners. The study included 880 students (463 girls; 417 boys) in grades three to eight who wrote an informative/explanatory essay on information technology and completed a motivational survey assessing their intrinsic, extrinsic, and self-regulation incentives for writing. Ninety-seven percent of students’ scores on the writing measure did not meet grade-level proficiency for writing, girls received higher scores than boys, and writing scores generally increased across the six grade-levels. A majority of students agreed that intrinsic and extrinsic incentives drive their writing behavior, but only 38% of students indicated that self-regulation incentives had such an effect. Gender was not related to students’ motivational scores, but scores for the three motivational incentives declined from lower to higher grades. Recommendations for future research and suggestions for classroom practice were provided.

The P23H mutation in rhodopsin (Rho), the rod visual pigment, is the most common allele associated with autosomal-dominant retinitis pigmentosa (adRP). The fate of misfolded mutant Rho in rod photoreceptors has yet to be elucidated. We generated a new mouse model, in which the P23H-Rho mutant allele is fused to the fluorescent protein Tag-RFP-T (P23HhRhoRFP). In heterozygotes, outer segments formed, and wild-type (WT) rhodopsin was properly localized, but mutant P23H-Rho protein was mislocalized in the inner segments. Heterozygotes exhibited slowly progressing retinal degeneration. Mislocalized P23HhRhoRFP was contained in greatly expanded endoplasmic reticulum (ER) membranes. Quantification of mRNA for markers of ER stress and the unfolded protein response revealed little or no increases. mRNA levels for both the mutant human rhodopsin allele and the WT mouse rhodopsin were reduced, but protein levels revealed selective degradation of the mutant protein. These results suggest that the mutant rods undergo an adaptative process that prolongs survival despite unfolded protein accumulation in the ER. The P23H-Rho-RFP mouse may represent a useful tool for the future study of the pathology and treatment of P23H-Rho and adRP. This article has an associated First Person interview with the first author of the paper.

For residents of East-Southeast Asia’s megacities, interactions with “nature” may be largely limited to interactions taking place in urban parks. Urban parks provide refuges for ecologically-important biodiversity, such as insect pollinators. While residents may be unlikely to notice small insects, butterflies are more likely to be noticed and to provide positive human-“nature” interactions. Engaging residents and city planners in promoting habitat for butterflies is valid conservation practice and has well-understood educational and well-being benefits. Surveying and monitoring is an essential activity to corroborate, improve and communicate the outcomes of conservation practices amongst city governments, scientists and other stakeholders. Here we present the data from a survey of butterflies in urban parks in the megacity of the Bangkok Metropolitan Region as part of the "Urban biodiversity and human well-being in East-Southeast Asia's megacities" project organised by the "Urban Butterflies in Asia Research Network".We recorded 51 species of butterflies from ten urban parks in the Bangkok Metropolitan Region. This was more than double the 25 species reported in Bangkok's City Biodiversity Index application. However, this was lower than that recorded in other megacities in Southeast Asia, such as Kuala Lumpur at 60 species. Most of the butterflies recorded were common and widespread species. DNA barcodes are provided for most of the butterflies sampled.

Serum is the body fluid most often used in biomarker discovery. Albumin, the most abundant serum protein, contributes approximately 50% of the serum protein content, with an additional dozen abundant proteins dominating the rest of the serum proteome. To profile this challenging protein mixture by proteomics, the abundant proteins must be depleted to allow for detection of the low-abundant proteins, the primary biomarker targets. Current serum depletion approaches for proteomics are costly and relatively complex to couple with protein digestion. We demonstrate a simple, affordable serum depletion methodology that, within a few minutes of processing, results in two captured serum fractions – albumin-depleted and albumin-rich – which are digested in situ. We believe our method is a useful addition to the biomarker sample preparation toolbox.

Collagen production by lung cells is critical to maintain organ architecture but can also drive pathological scarring. Here the authors perform single cell RNA sequencing of collagen-producing lung cells identifying a subset of pathologic fibroblasts characterized by Cthrc1 expression which are concentrated within fibroblastic foci in fibrotic lungs and show a pro-fibrotic phenotype.

Cardiovascular device infection due to rapidly growing mycobacteria (RGM) is rarely encountered in clinical practice. Due to the increasing number of indications and use of cardiovascular devices in an aging population, optimized management of these infections is of great importance. We report seven cases of RGM cardiovascular device infection. Three patients had left-ventricular assist device (LVAD) infections; two patients had cardiovascular implantable device (CIED) infections; and one had an aortic vascular stent infection. Specific cardiac valvular infection was not detected among any of the patients. All patients had a high number of comorbidities which limited some patients from receiving optimal combination antimicrobial therapy. The prognosis of cardiovascular device infections with RGM is guarded with only four patients still alive; however, the treatment approach for each patient varied considerably and often based on concurrent medical conditions, overall adjustments to goals of care, and specific patient preferences. Further analysis of cardiovascular device infections with RGM is warranted to establish a more systematic approach in successful management.

Acute renal artery thrombosis is rare and even rarer in the thrombus occluding the main renal artery and compromising the entire kidney. We report on a 46-year-old female smoker with no past medical history and no hypercoagulability who developed sudden severe left flank pain, hematuria, acute renal failure, and severe hypertension. A CT angiogram showed totally occluded renal artery at the ostium with a thrombus and severely hypoperfused left kidney with multiple infarcts. Initial course of treatment was with intravenous heparin but with no improvement after 50 hours since symptom onset; angiography was done. This revealed totally occluded renal artery at ostium with no vessels or kidney blush seen. After aspiration thrombectomy, blush was seen in kidney parenchyma along with flow in the arcuate renal arteries although with some distal embolic events. The ostial lesion was treated with a drug eluting stent with excellent result angiographically. However, 8 months later, severe restenosis occurred. This time, the patient did not flank pain or renal failure but had progressive hypertension. The patient was treated this time with rheolytic thrombectomy followed by intravascular ultrasound-guided drug-eluting stenting. The patient has been followed for a year and a half since and recent CT scan revealed widely patent renal arteries bilaterally with normal kidney function, BP, and good perfusion to the left kidney with only tiny areas of infarct. Ultrasound of the kidneys also showed the size of the left kidney as within normal range now, and she has good distal flow velocities in the branch renal arteries. Our case report shows that even delayed reperfusion of complete renal artery occlusion with jeopardized arterial flow to the entire kidney could result in restoration of function to most of the kidney.

A promising tsunami warning system outlined here links Total Electron Content (TEC) disturbances in the ionosphere detected by GNSS satellites to maps of inundated areas along the affected coastlines. This will be accomplished through a pipeline of earthquake, ionosphere, and tsunami simulations. The focus of this paper is to demonstrate the feasibility and validity of our tsunami simulator for use in this simulation pipeline. The simulator we have developed is called Tsunami Squares, a computationally inexpensive program that employs a unique method of propagating water according to shallow water theory. Unlike other wave simulators, Tsunami Squares can easily propagate waves from sea to land, allowing flooded areas along the coast to be mapped. To validate its accuracy, a comparison is made to the Regional Ocean Modeling System tsunami simulator, which solves the Navier Stokes equations directly using a finite-difference method. The two simulation techniques show good agreement when compared over the 2011 Japan event and the 2010 Chile event. In addition, examples of inundation plots are displayed here to demonstrate its capability for such a warning system.

Abstract While the spatial resolution of exposure surfaces has greatly improved, our ability to locate people in space remains a limiting factor in accurate exposure assessment. In this case‐control study, two approaches to geocoding participant locations were used to study the impact of geocoding uncertainty on the estimation of ambient pesticide exposure and breast cancer risk among women living in California's Central Valley. Residential and occupational histories were collected and geocoded using a traditional point‐based method along with a novel area‐based method. The standard approach to geocoding uses centroid points to represent all geocoded locations, and is unable to adapt exposure areas based on geocode quality, except through the exclusion of low‐certainty locations. In contrast, area‐based geocoding retains the complete area to which an address matched (the same area from which the centroid is returned), and therefore maintains the appropriate level of precision when it comes to assessing exposure by geography. Incorporating the total potential exposure area for each geocoded location resulted in different exposure classifications and resulting odds ratio estimates than estimates derived from the centroids of those same areas (using a traditional point‐based geocoder). The direction and magnitude of these differences varied by pesticide, but in all cases odds ratios differed by at least 6% and up to 35%. These findings demonstrate the importance of geocoding in exposure estimation and suggest it is important to consider geocode certainty and quality throughout exposure assessment, rather than simply using the best available point geocodes.

When compartmentally mislocalized within cells, nucleic acids can be exceptionally immunostimulatory and can even trigger the immune-mediated elimination of cancer. Specifically, the accumulation of double-stranded DNA in the cytosol can efficiently promote antitumor immunity by activating the cGAMP synthase (cGAS) / stimulator of interferon genes (STING) cellular signaling pathway. Targeting this cytosolic DNA sensing pathway with interferon stimulatory DNA (ISD) is therefore an attractive immunotherapeutic strategy for the treatment of cancer. However, the therapeutic activity of ISD is limited by several drug delivery barriers, including susceptibility to deoxyribonuclease degradation, poor cellular uptake, and inefficient cytosolic delivery. Here, we describe the development of a nucleic acid immunotherapeutic, NanoISD, which overcomes critical delivery barriers that limit the activity of ISD and thereby promotes antitumor immunity through the pharmacological activation of cGAS at the forefront of the STING pathway. NanoISD is a nanoparticle formulation that has been engineered to confer deoxyribonuclease resistance, enhance cellular uptake, and promote endosomal escape of ISD into the cytosol, resulting in potent activation of the STING pathway via cGAS. NanoISD mediates the local production of proinflammatory cytokines via STING signaling. Accordingly, the intratumoral administration of NanoISD induces the infiltration of natural killer cells and T lymphocytes into murine tumors. The therapeutic efficacy of NanoISD is demonstrated in preclinical tumor models by attenuated tumor growth, prolonged survival, and an improved response to immune checkpoint blockade therapy.

Abstract Background Displacement Encoding with Stimulated Echoes (DENSE) cardiovascular magnetic resonance (CMR) of the aortic wall offers the potential to improve patient-specific diagnostics and prognostics of diverse aortopathies by quantifying regionally heterogeneous aortic wall strain in vivo. However, before regional mapping of strain can be used to clinically assess aortic pathology, an evaluation of the natural variation of normal regional aortic kinematics is required. Method Aortic spiral cine DENSE CMR was performed at 3 T in 30 healthy adult subjects (range 18 to 65 years) at one or more axial locations that are at high risk for aortic aneurysm or dissection: the infrarenal abdominal aorta (IAA, n = 11), mid-descending thoracic aorta (DTA, n = 17), and/or distal aortic arch (DAA, n = 11). After implementing custom noise-reduction techniques, regional circumferential Green strain of the aortic wall was calculated across 16 sectors around the aortic circumference at each location and normalized by the mean circumferential strain for comparison between individuals. Results The distribution of normalized circumferential strain (NCS) was heterogeneous for all locations evaluated. Despite large differences in mean strain between subjects, comparisons of NCS revealed consistent patterns of strain distribution for similar groupings of patients by axial location, age, and/or mean displacement angle. NCS at local systole was greatest in the lateral/posterolateral walls in the IAAs (1.47 ± 0.27), medial wall in anteriorly displacing DTAs (1.28 ± 0.20), lateral wall in posteriorly displacing DTAs (1.29 ± 0.29), superior curvature in DAAs 50 years (2.29 ± 0.58). The distribution of strain was strongly influenced by the location of the vertebra and other surrounding structures unique to each location. Conclusions Regional in vivo circumferential strain in the adult aorta is unique to each axial location and heterogeneous around its circumference, but can be grouped into consistent patterns defined by basic patient-specific metrics following normalization. The heterogeneous strain distributions unique to each group may be due to local peri-aortic constraints (particularly at the aorto-vertebral interface), heterogeneous material properties, and/or heterogeneous flow patterns. These results must be carefully considered in future studies seeking to clinically interpret or computationally model patient-specific aortic kinematics.

Abstract Background Women recently released from incarceration have increased rates of co-occurring substance use, physical health, and mental health disorders. During re-entry, they face challenges navigating needed health services and social services stemming from these problems. Women’s Initiative Supporting Health Transitions Clinic (WISH-TC) is a primary care program that facilitates treatment access for re-entering women. Strategies include support and navigation assistance from peer community health workers. Methods Thirteen participants, of whom 11 had a substance use disorder, completed semi-structured interviews about their experiences in WISH-TC as part of a process evaluation. We conducted a qualitative framework analysis informed by self-determination theory. Results WISH-TC supported autonomy as staff helped motivate women to work toward personal health goals. Women were empowered to have their health needs met, and consequently, prioritized attending clinic. Regarding competence, WISH-TC built upon women’s existing knowledge to increase their health literacy and better understand their individual health needs. Relatedness support, both prior to re-entry and ongoing with clinic staff, was key in women’s satisfaction with their care. The clinic made procedural changes in response to the interviews, including providing orientation for the patients and training the clinic in trauma-informed practices. Conclusions Our findings highlight the potential of a program for re-entering women, including those with substance use disorders to strengthen their abilities to navigate complex healthcare and societal systems. WISH-TC helped women feel supported, motivated, and competent to address their substance use, physical, and mental health conditions.

Abstract Background Medical Visit Companions (MVCs) are encouraged for older adults’ routine medical encounters. Little data exist on the experiences and contributions of non-spouse companions for the growing population of older adults without a living spouse. Methods We conducted six focus groups with forty non-spouse MVCs identified through churches in Baltimore, Maryland. Thematic analysis was used to identify key issues before the visit, during the visit itself, after the visit, and in the overall companion experience. Results MVCs described their experiences positively but also highlighted many challenges related to the role that extended far beyond the visit itself. These included scheduling, transportation, communication, and coordination of care expectations. Conclusion Our increasingly complex healthcare system can be challenging for older adults to navigate successfully. The diverse nature of tasks performed by companions in this study highlight the many benefits of having a companion accompany older patients to medical visits. The positive experience of the companions studied and their willingness to continue their role in the future highlights the untapped potential for increased social facilitation to improve the quality of healthcare visits and achieve patient-centered care for all older patients.

Decisions to allocate management resources should be underpinned by estimates of the impacts of biological invasions that are comparable across species and locations. For the same reason, it is important to assess what type of impacts are likely to occur where, and if such patterns can be generalised. In this paper, we aim to understand factors shaping patterns in the type and magnitude of impacts of a subset of alien grasses. We used the Generic Impact Scoring System (GISS) to review and quantify published impact records of 58 grass species that are alien to South Africa and to at least one other biogeographical realm. Based on the GISS scores, we investigated how impact magnitudes varied across habitats, regions and impact mechanisms using multiple regression. We found impact records for 48 species. Cortaderia selloana had the highest overall impact score, although in contrast to five other species (Glyceria maxima, Nassella trichotoma, Phalaris aquatica, Polypogon monspeliensis, and Sorghum halepense) it did not score the highest possible impact score for any specific impact mechanism. Consistent with other studies, we found that the most frequent environmental impact was through competition with native plant species (with 75% of cases). Socio-economic impacts were recorded more often and tended to be greater in magnitude than environmental impacts, with impacts recorded particularly often on agricultural and animal production (57% and 51% of cases respectively). There was variation across different regions and habitats in impact magnitude, but the differences were not statistically significant. In conclusion, alien grasses present in South Africa have caused a wide range of negative impacts across most habitats and regions of the world. Reviewing impacts from around the world has provided important information for the management of alien grasses in South Africa, and, we believe, is an important component of management prioritisation processes in general.

Particulate matter (PM2.5) is a significant public health concern in China, and the Chinese government has implemented a series of laws, policies, regulations, and standards to improve air quality. This study documents the changes in PM2.5 and evaluates the effects of industrial transformation and clean air policies on PM2.5 levels in urban and suburban areas of China’s three largest urban agglomerations, Beijing–Tianjin–Hebei (BTH), the Yangtze River Delta (YRD), and the Pearl River Delta (PRD) based on a new degree of urbanization classification method. We used high-resolution PM2.5 concentration and population datasets to quantify the differences in PM2.5 concentrations in urban and suburban areas of these three urban agglomerations. From 2000 to 2020, the urban areas have expanded while the suburban areas have shrunk. PM2.5 concentrations in urban areas were approximately 32, 10, and 7 μg/m3 higher than those in suburban areas from 2000 to 2020 in BTH, YRD, and PRD, respectively. Since 2013, the PM2.5 concentrations in the urban regions of BTH, YRD, and PRD have declined at average annual rates of 7.30, 5.50, and 5.03 μg/m3/year, respectively, while PM2.5 concentrations in suburban areas have declined at average annual rates of 3.11, 4.23 and 4.69 μg/m3/year, respectively. By 2018, all of the urban and suburban areas of BTH, YRD, and PRD satisfied their specific targets in the Air Pollution and Control Action Plan. By 2020, the PM2.5 declines of BTH, YRD, and PRD exceeded the targets by two, three, and four times, respectively. However, the PM2.5 exposure risks in urban areas are 10–20 times higher than those in suburban areas. China will need to implement more robust air pollution mitigation policies to achieve the World Health Organization’s Air Quality Guideline (WHO-AQG) and reduce long-term PM2.5 exposure health risks.

Whilst increasing mental workload has been shown to have a detrimental effect on cycling performance and more generally to increase the risk of harm, no studies have measured how mental workload changes as a function of ultra-distance cycling, indoors or outdoors. Our objective was to measure the difference in mental workload, as indicated by changes in EEG theta power, components of HRV and psychomotor vigilance and as reported using the ‘NASA Task Load Index questionnaire’, before and after a 5 h indoor ride and outdoor ride completed at 65% of functional threshold power. Results of the NASA-TLX indicated the mental demand of outdoor cycling to be significantly less than that of indoor cycling. There were significant differences in the PVT results between the pre and the post outdoor ride average and median response times. The slowest 10% PVT responses were significantly slower pre than post the indoor ride. There were significant differences in HRV between pre and post outdoor and indoor rides, specifically, in the average RR intervals, RMSSD (ms2), LFPower (ms2), NN50. There were modest changes in indicators of mental workload during an ultra-distance cycle ride. As such, mental workload during ultra-distance cycling is unlikely to be a contributory factor to decreases in performance or to an increased likelihood of accident and injury.