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Patients with cancer experience high rates of alterations in mental status. The mechanisms for altered mental status (AMS) in this population are manifold. The cancer itself may cause AMS through direct invasion of the central nervous system or as metastatic leptomeningeal spread. However, cancer patients are also vulnerable to tumor-associated complications such as seizures, cerebral edema, strokes, or cancer treatment-related complications such as infections, direct neural injury from radiation or chemotherapy, edema, or dysregulated autoimmune response from immunotherapies. Both during treatment and as sequelae, patients may suffer neurocognitive complications from chemotherapy and radiation, medications or opportunistic infections, as well as toxic–metabolic, nutritional, and endocrine complications. In this review, we describe a clinical approach to the cancer patient presenting with AMS and discuss the differential drivers of AMS in this patient population. While common etiologies of AMS in noncancer patients (toxic–metabolic or infectious encephalopathy, delirium) are also applicable to cancer patients, we additionally provide a cancer-specific differential diagnosis that warrants special consideration in the cancer patient with AMS. [ABSTRACT FROM AUTHOR]

Introduction: Brodalumab is a human interleukin-17 receptor A antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. Although the US prescribing information for brodalumab includes a boxed warning regarding suicidal ideation and behavior, no causal association has been demonstrated. Here, we summarize 5 years of pharmacovigilance data, from August 15, 2017, through August 14, 2022, reported to Ortho Dermatologics by US patients and healthcare providers. Methods: Prevalence of the most common adverse events (AEs) listed in the brodalumab package insert (incidence ≥ 1%) and AEs of special interest are described. Brodalumab exposure was estimated as the time from the first to last prescription-dispensing authorization dates. Data were collected from 4744 patients in the USA, with an estimated exposure of 5815 patient-years. Results: Over 5 years, 11 cases of adjudicated major adverse cardiovascular events were reported (0.23 events/100 patients), a rate lower than that experienced by patients in the international Psoriasis Longitudinal Assessment and Registry. There were 106 serious infections. No serious fungal infections were reported. There were 40 confirmed and 2 suspected COVID-19 cases, with no new COVID-19-related deaths. Of 49 reported malignancies among 42 patients, 3 were deemed possibly related to brodalumab. No completed suicides and no new suicidal attempts were reported. Conclusion: Five-year pharmacovigilance data are consistent with the established safety profile reported in long-term clinical trials and previous pharmacovigilance reports, with no new safety signals. Plain Language Summary: Brodalumab is an injectable treatment approved for moderate-to-severe plaque psoriasis in adults who lacked response to previous treatments. In the USA, brodalumab is only available under a Risk Evaluation and Mitigation Strategy for increased suicidality risks; however, findings from 5 years of real-world safety data have demonstrated a lack of association. In this report, we discuss safety findings reported by US patients and healthcare providers for 4744 patients treated with brodalumab over 5 years. Joint pain (known as arthralgia) was the most common safety finding, with 122 cases reported over 5 years. Other safety findings of interest across 5 years included 106 serious infections (defined as prolonged infections or infections requiring treatment), 54 cases of depression, 49 cases of cancer (in 42 patients), 40 confirmed cases of COVID-19, and 11 cases of major cardiovascular events (such as stroke or heart attack). No completed suicides occurred throughout 5 years, and no new suicidal attempts were reported in year 5. In indirect comparisons with safety data from patients with psoriasis receiving or eligible to receive similar treatments, brodalumab was not associated with an increased risk of serious infection, cancer, major cardiovascular events, or inflammatory bowel disease. Taken together, these data are consistent with safety findings from long-term clinical trials and previous safety reports of brodalumab. [ABSTRACT FROM AUTHOR]

Although most songwriting teams in the Great American Songbook wrote music first and lyrics second, most studies of music-text interaction in this repertoire still evince a lyrics-first mindset, in which the music is viewed as text-setting. In this article, I propose the opposite approach: considering lyrics as a form of music-setting, in which the lyricist's superimposition of a verbal form (the rhyme scheme) upon the composer's pre-existing musical form counts as an act of analysis. I examine in turn: (1) the most common phrase structures and their associated rhyme schemes in songs from 1919 to 1943; (2) Lorenz Hart's negotiation of the unusual XYYZ phrase structure that Richard Rodgers frequently employed; and (3) special cases where the lyricist contests the composer's form and the effect that this can have on performers' choices. [ABSTRACT FROM AUTHOR]

Multi-criteria optimization (MCO) function has been available on commercial radiotherapy (RT) treatment planning systems to improve plan quality; however, no study has compared Eclipse and RayStation MCO functions for prostate RT planning. The purpose of this study was to compare prostate RT MCO plan qualities in terms of discrepancies between Pareto optimal and final deliverable plans, and dosimetric impact of final deliverable plans. In total, 25 computed tomography datasets of prostate cancer patients were used for Eclipse (version 16.1) and RayStation (version 12A) MCO-based plannings with doses received by 98% of planning target volume having 76 Gy prescription (PTV76D98%) and 50% of rectum (rectum D50%) selected as trade-off criteria. Pareto optimal and final deliverable plan discrepancies were determined based on PTV76D98% and rectum D50% percentage differences. Their final deliverable plans were compared in terms of doses received by PTV76 and other structures including rectum, and PTV76 homogeneity index (HI) and conformity index (CI), using a t-test. Both systems showed discrepancies between Pareto optimal and final deliverable plans (Eclipse: −0.89% (PTV76D98%) and −2.49% (Rectum D50%); RayStation: 3.56% (PTV76D98%) and −1.96% (Rectum D50%)). Statistically significantly different average values of PTV76D98%,HI and CI, and mean dose received by rectum (Eclipse: 76.07 Gy, 0.06, 1.05 and 39.36 Gy; RayStation: 70.43 Gy, 0.11, 0.87 and 51.65 Gy) are noted, respectively (p < 0.001). Eclipse MCO-based prostate RT plan quality appears better than that of RayStation. [ABSTRACT FROM AUTHOR]

Light detection and ranging (lidar) has emerged as a valuable tool for examining the fine‐scale characteristics of vegetation. However, lidar is rarely used to examine coastal wetland vegetation or the habitat selection of small mammals. Extensive anthropogenic modification has threatened the endemic species in the estuarine wetlands of the California coast, such as the endangered salt marsh harvest mouse (Reithrodontomys raviventris; SMHM). A better understanding of SMHM habitat selection could help managers better protect this species. We assessed the ability of airborne topographic lidar imagery in measuring the vegetation structure of SMHM habitats in a coastal wetland with a narrow range of vegetation heights. We also aimed to better understand the role of vegetation structure in habitat selection at different spatial scales. Habitat selection was modeled from data compiled from 15 small mammal trapping grids collected in the highly urbanized San Francisco Estuary in California, USA. Analyses were conducted at three spatial scales: microhabitat (25 m2), mesohabitat (2025 m2), and macrohabitat (~10,000 m2). A suite of structural covariates was derived from raw lidar data to examine vegetation complexity. We found that adding structural covariates to conventional habitat selection variables significantly improved our models. At the microhabitat scale in managed wetlands, SMHM preferred areas with denser and shorter vegetation and selected for proximity to levees and taller vegetation in tidal wetlands. At the mesohabitat scale, SMHM were associated with a lower percentage of bare ground and with pickleweed (Salicornia pacifica) presence. All covariates were insignificant at the macrohabitat scale. Our results suggest that SMHM preferentially selected microhabitats with access to tidal refugia and mesohabitats with consistent food sources. Our findings showed that lidar can contribute to improving our understanding of habitat selection of wildlife in coastal wetlands and help to guide future conservation of an endangered species. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The study aimed to compare the efficacies and safety of 14-day hybrid therapy, 14-day high-dose dual therapy, and10-day bismuth quadruple therapy in the first-line treatment ofHelicobacterpylori infections. METHODS: In this multicenter, open-label, randomized trial, we recruited adult H. pylori-infected patients from 9 centers in Taiwan. Subjects were randomly assigned (1:1:1) to 14-day hybrid therapy, 14-day high-dose dual therapy, or 10-day bismuth quadruple therapy. Eradication status was determined by the 13C-urea breath test. The primary outcome was the eradication rate of H. pylori assessed in the intention-to-treat population. RESULTS: Between August 1, 2018, and December 2021, 918 patients were randomly assigned in this study. The intention-to-treat eradication rates were 91.5% (280/306; 95% confidence interval [CI] 88.4%-94.6%) for 14-day hybrid therapy, 83.3% (255/306; 95% CI 87.8%-95.0%) for 14-day high-dose dual therapy, and 90.2% (276/306; 95% CI 87.8%-95.0%) for 10-day bismuth quadruple therapy. Both hybrid therapy (difference 8.2%; 95% CI 4.5%-11.9%; P = 0.002) and bismuth quadruple therapy (difference 6.9%; 95% CI 1.6%-12.2%; P = 0.012) were superior to high-dose dual therapy and were similar to one another. The frequency of adverse events was 27% (81/303) with 14-day hybrid therapy, 13% (40/305) with 14-day high-dose dual therapy, and 32% (96/303) with 10-day bismuth quadruple therapy. Patients receiving high-dose dual therapy had the fewest adverse events (both P < 0.001). INTRODUCTION: The study aimed to compare the efficacies and safety of 14-day hybrid therapy, 14-day high-dose dual therapy, and10-day bismuth quadruple therapy in the first-line treatment ofHelicobacterpylori infections. METHODS: In this multicenter, open-label, randomized trial, we recruited adult H. pylori-infected patients from 9 centers in Taiwan. Subjects were randomly assigned (1:1:1) to 14-day hybrid therapy, 14-day high-dose dual therapy, or 10-day bismuth quadruple therapy. Eradication status was determined by the 13C-urea breath test. The primary outcome was the eradication rate of H. pylori assessed in the intention-to-treat population. RESULTS: Between August 1, 2018, and December 2021, 918 patients were randomly assigned in this study. The intention-to-treat eradication rates were 91.5% (280/306; 95% confidence interval [CI] 88.4%-94.6%) for 14-day hybrid therapy, 83.3% (255/306; 95% CI 87.8%-95.0%) for 14-day high-dose dual therapy, and 90.2% (276/306; 95% CI 87.8%-95.0%) for 10-day bismuth quadruple therapy. Both hybrid therapy (difference 8.2%; 95% CI 4.5%-11.9%; P = 0.002) and bismuth quadruple therapy (difference 6.9%; 95% CI 1.6%-12.2%; P = 0.012) were superior to high-dose dual therapy and were similar to one another. The frequency of adverse events was 27% (81/303) with 14-day hybrid therapy, 13% (40/305) with 14-day high-dose dual therapy, and 32% (96/303) with 10-day bismuth quadruple therapy. Patients receiving high-dose dual therapy had the fewest adverse events (both P < 0.001). [ABSTRACT FROM AUTHOR]

The gut microbiota is an integral part of the human metaorganism that is required to shape physiologic host immune responses including host defense against pathogens. Disease-associated gut dysbiosis has been characterized by blooms of pathobionts, which are bacterial species that can drive disease under certain conditions. Pathobionts like Enterobacteriaceae often bloom during flares of inflammatory bowel disease (IBD) and are causally linked with IBD in murine models. In this issue of the JCI, Hecht and colleagues investigated how simple carbohydrates are causally linked to the bloom of the gut pathobiont Klebsiella pneumoniae, which belong to the Enterobacteriaceae family. Notably, the presence of fiber reduced the dissemination of K. pneumoniae into the blood and liver in a colitis model. Their findings provide a diet-related mechanism for gut dysbiosis, which has implications in the management of IBD and other conditions in which gut dysbiosis is an underlying factor. [ABSTRACT FROM AUTHOR]

Magnetic reconnection is a fundamental mechanism through which energy stored in magnetic fields is released explosively on a massive scale, they could be presented as eruptive or confined flares, depending on their association with coronal mass ejections (CMEs). Several previous works have concluded that there is no correlation between flare duration and flare class, however, their sample sizes are skewed towards B and C classes; they hardly represent the higher classes. Therefore, we studied a sample without extreme events in order to determine the correlation between flare duration and flare type (confined and eruptive). We examined 33 flares with classes between M5 to X5 within 45° of the disk centres, using data from the Atmospheric Imaging Assembly (AIA) and the Helioseismic and Magnetic Imager (HMI). We find that the linear correlation between flare class against flare duration by full width half maximum (FWHM) in general is weak (r = 0.19 ); however, confined flares have a significant correlation (r = 0.58 ) compared to eruptive types (r = 0.08 ). Also, the confined M class flares' average duration is less than half of the eruptive flares. Similarly, confined flares have a higher correlation (r = 0.89 ) than eruptive flares (r = 0.60 ) between flare classes against magnetic reconnection flux. In this work, a balanced sample size between flare types is an important strategy for obtaining a reliable quantitative comparison. [ABSTRACT FROM AUTHOR]

Controlling non-native plant invasions that reduce the quality of preferred wetland habitats is a challenge for many wetland managers. Herbicides may be used to control invasions, but it may be difficult to find effective application methods depending on the terrain. Manned aircraft cover large patches, but aerial use is limited by high costs, weather conditions, and overspray concerns. Ground applications target smaller patches, but their effectiveness may be limited by accessibility, labor costs, and applicator health concerns. Considering these difficulties, unmanned aerial systems (UAS) have emerged as a viable alternative for more effectively treating plant invasions. We tested the use of a specialized UAS to control invasive perennial pepperweed (Lepidium latifolium) in Suisun Marsh in northern California, USA. This "spray drone" flew at an altitude of 2–3 m, a speed of 24 kmph, and applied herbicide with a swath width of 6 m. We applied herbicide with the spray drone to treat small patches before they expanded. To delineate invasive patch boundaries, we first flew a survey drone with a 4K resolution camera to detect emerging plants with color imagery and conduct an initial classification analysis. We subsequently visited areas with suspected invasive patches based on the classification, and observers manually confirmed the presence of the invasive species. We then flew the spray drone on transects to treat the patches and examined the results with post-treatment survey drone imagery and plots along ground transects. In total, we sprayed 14 ha of Lepidium across eight sites and found that 87% of the Lepidium was discernibly affected by our herbicide treatment. Furthermore, we measured the overspray, which was substantially less than that reported for other aerial application methods such as helicopter-spraying, and our estimated operational costs were lower. Our results indicated that applying remote-sensing imagery for the identification of invasive species patches and the use of a spray drone for treatment may be an effective means of controlling invasive plants with high precision at a reasonable cost. In the near future, a unified UAS system that both identifies invasive species and then treats them in a single pass should be a promising goal for early detection and rapid response in wetland management. [ABSTRACT FROM AUTHOR]

Molecular crystal structure prediction (CSP) seeks the most stable periodic structure given the chemical composition of molecule and pressure-temperature conditions. Modern CSP solvers use global optimization methods to search for structures with minimal free energy within a complex energy landscape induced by intermolecular potentials. A major caveat of these methods is that initial configurations are random, making the search susceptible to convergence at local minima. Providing initial configurations that are densely packed with respect to the geometric representation of a molecule can significantly accelerate CSP. Motivated by these observations, we define a class of periodic packings restricted to crystallographic symmetry groups (CSG) and design a search method for the densest CSG packings in an information-geometric framework. Since CSG induces a toroidal topology on the configuration space, a non-Euclidean trust region method is performed on a statistical manifold consisting of probability distributions defined on an n-dimensional flat unit torus by extending the multivariate von Mises distribution. Introducing an adaptive quantile reformulation of the fitness function into the optimization schedule provides the algorithm with a geometric characterization through local dual geodesic flows. Moreover, we examine the geometry of the adaptive selection-quantile defined trust region and show that the algorithm performs a maximization of stochastic dependence among elements of the extended multivariate von Mises distributed random vector. We experimentally evaluate the behavior and performance of the algorithm on various densest packings of convex polygons in 2-dimensional CSGs for which optimal solutions are known, and we demonstrate its application in the pentacene thin-film CSP. [ABSTRACT FROM AUTHOR]

Wild waterbirds, and especially wild waterfowl, are considered to be a reservoir for avian influenza viruses, with transmission likely occurring at the agricultural-wildlife interface. In the past few decades, avian influenza has repeatedly emerged in China along the East Asian-Australasian Flyway (EAAF), where extensive habitat conversion has occurred. Rapid environmental changes in the EAAF, especially distributional changes in rice paddy agriculture, have the potential to affect both the movements of wild migratory birds and the likelihood of spillover at the agricultural-wildlife interface. To begin to understand the potential implications such changes may have on waterfowl and disease transmission risk, we created dynamic Brownian Bridge Movement Models (dBBMM) based on waterfowl telemetry data. We used these dBBMM models to create hypothetical scenarios that would predict likely changes in waterfowl distribution relative to recent changes in rice distribution quantified through remote sensing. Our models examined a range of responses in which increased availability of rice paddies would drive increased use by waterfowl and decreased availability would result in decreased use, predicted from empirical data. Results from our scenarios suggested that in southeast China, relatively small decreases in rice agriculture could lead to dramatic loss of stopover habitat, and in northeast China, increases in rice paddies should provide new areas that can be used by waterfowl. Finally, we explored the implications of how such scenarios of changing waterfowl distribution may affect the potential for avian influenza transmission. Our results provide advance understanding of changing disease transmission threats by incorporating real-world data that predicts differences in habitat utilization by migratory birds over time. [ABSTRACT FROM AUTHOR]

It is a great honor to be invited to write a reflections article on my scientific journey and lifelong bile acid research for the Journal of Biological Chemistry, in which I am proud to have published 24 articles. I have also published 21 articles in the Journal of Lipid Research, another journal of the American Society of Biochemistry and Molecular Biology. I begin my reflections from my early education in Taiwan, my coming to America for graduate study, and continue with my postdoctoral training in cytochrome P450 research, and my lifelong bile acid research career at Northeast Ohio Medical University. I have witnessed and helped in the transformation of this rural not so visible medical school to a well-funded leader in liver research. Writing this reflections article on my long and rewarding journey in bile acid research brings back many good memories. I am proud of my scientific contributions and attribute my academic success to hard work, perseverance, good mentoring, and networking. I hope these reflections of my academic career would help inspire young investigators to pursue an academic career in biochemistry and metabolic diseases. [ABSTRACT FROM AUTHOR]

A number of one-dimensional models have been developed to inform the design of piezoelectric transducers. The majority of these models are in the frequency domain. In this paper, we develop a one-dimensional time-domain model for the mechanical response of a piezoelectric layer. Secondary effects, resulting from feedback between the acoustic and electric variables, are included in the model. Our approach utilizes Green's function for the Helmholtz equation with radiation boundary conditions and the methods of complex analysis. The model predictions are validated by comparison with a finite-difference time-domain numerical simulation of the governing acoustic equations in and outside the layer. This time-domain model enables efficient calculation of the secondary piezoelectric action effects and provides the mechanical response to an arbitrary electrical source. [ABSTRACT FROM AUTHOR]

Grapes are prone to Pseudocercospora vitis fungus which causes Isariopsis leaf speck disease to the crop's leaves, flower, and most importantly the fruit. Typical manual inspection of vineyard farmers is normally ineffective, destructive, and laborious. To address this, the use of integrated computer vision, machine learning, and computational intelligence techniques were realized to sort out healthy grape leaf image from a fungus-specked leaf image and to estimate the specked area percentage (SAP). A dataset made up of 343 normally healthy and 200 fungus-specked grape leaf images were initially pre-processed and segmented via graph cut prior to feature extraction and selection. Significant features were identified using classification tree (CTree). A multigene genetic programming tool called GPTIPSv2 was utilized to generate the fitness function needed for the optimization process done via genetic algorithm (GA). An optimal hidden neuron counts of 110, 50, and 10 were selected for a three-layered GA-optimized recurrent neural network (GA-RNN). Linear discriminant analysis (LDA) topped other disease recognition models with an accuracy of 99.99%. The developed GA-RNN model outperformed Gaussian process regression (GPR), regression tree (RTree), regression support vector machine (RSVM), and linear regression (RLinear) in performing leaf specked area estimation with an R2 value of 0.822. The developed CTree-LDA2-GA-RNN2 hybrid model has been proven to be the most viable model for this task. [ABSTRACT FROM AUTHOR]

This study aims to improve the photometric redshifts (photo-zs) of galaxies by integrating two contemporary methods: template-fitting and machine learning. Finding the synergy between these two methods was not a high priority in the past, but now that our computer processing power and observational accuracy have increased, we deem it worth investigating. We compared two methods to improve galaxy photometric redshift estimations by using the algorithms ANNz2 and BPz on different photometric and spectroscopic samples from the Sloan Digital Sky Survey (SDSS). We find that the photometric redshift performance of ANNz2 (machine learning) is better than that of BPz (galactic templates), and with the utilization of the merging technique we introduced, we see that there is an improvement in photo-z when the two strategies are consolidated, providing improvements in and up to [0] in LRG sample and [0] in the Stripe-82 sample. This simple demonstration can be used for photo-zs of galaxies in fainter and deeper sky surveys, and future work is required to prove its viability in these samples. [ABSTRACT FROM AUTHOR]

Auerbach's solution is to devise a "universal nomenclature for pitch and rhythm motives", so that a motive's name immediately conveys a wealth of information. Narrative archetypes and complex motivic analysis Before moving on to CMA, Auerbach introduces his narrative archetypes. He presents not one but two original approaches to motivic analysis - called Basic Motivic Analysis (BMA) and Complex Motivic Analysis (CMA). [Extracted from the article]

3D printing has numerous applications in the food industry that may enhance diversity, quality, healthiness, and sustainability. This innovative additive manufacturing technology has the ability to specifically tailor food properties for individuals. Nevertheless, several challenges still need to be overcome before 3D printing can be utilized more widely in the food industry. This article focuses on the development and characterization of "food inks" suitable for 3D printing of foods. Specifically, the main factors impacting successfully printed foods are highlighted, including material properties and printing parameters. The creation of a 3D printed food with the appropriate quality and functional attributes requires understanding and control of these factors. Food ink printability is an especially important factor that depends on their composition, structure, and physicochemical properties. Previous studies do not sufficiently describe the precise design and operation of 3D printers in sufficient detail, which makes comparing results challenging. Additionally, important physicochemical characteristics utilized in traditional food are not consistently reported in 3D inks, such as moisture content, water activity, and microbial contamination, which limits the practical application of the results. For this reason, we highlight important factors impacting 3D ink formulation and performance, then provide suggestions for standardizing and optimizing 3D printed foods. [ABSTRACT FROM AUTHOR]

1. Identify patients who would benefit from a trial of buprenorphine low-dose initiation. 2. Review approaches to performing a buprenorphine low-dose initiation to decrease total opioid use in patients with cancer and non-cancer-related pain. Buprenorphine low-dose initiation is a novel approach that harnesses the unique pharmacological profile of this partial-opioid agonist to reduce both risk of precipitated opioid withdrawal and need for prolonged opioid tapers in vulnerable patients. Buprenorphine low-dose initiation is a novel approach that harnesses the unique pharmacological profile of this partial-opioid agonist to reduce both risk of precipitated opioid withdrawal and need for prolonged opioid tapers in vulnerable patients (1). A 65-year-old man with metastatic bladder cancer and significant non-cancer-related orthopedic spine concerns is followed in the palliative care clinic for both cancer and non-cancer-related pain. He was being treated with a multimodal pharmacologic approach, involving opioid therapy (hydromorphone 8mg every 4 hours), neuropathic agents (amitriptyline and pregabalin), muscle relaxants (baclofen), and anti-inflammatory agents (celecoxib). With this, he had recently noted improvement in his pain level and had a desire to wean opioids due to bothersome side-effects of fatigue, cognitive fogging, and occasional myoclonus. Given his chronic opioid use, a rotation to buprenorphine was performed using a low-dose initiation protocol with subutex (buprenorphine tablets). The patient successfully weaned his opioid use from 48mg oral hydromorphone daily to 12mg oral subutex with resolution of his opioid side-effects. Buprenorphine low-dose initiation involves adding increasing low-dose formulations of buprenorphine to an amount where the opioid receptors are nearly fully occupied, then reducing the frequency and dose of full-agonist opioids. In patients with both chronic non-cancer-related and cancer-related pain, this strategy can provide relief from opioid-related side effects, while still achieving good pain control. Evidence supports the use of buprenorphine rotation to reduce chronic pain, without precipitating opioid withdrawal or other serious adverse side effects (2). Managing Suffering and Distress / Pharmacotherapeutics / Pharmacopalliation [ABSTRACT FROM AUTHOR]

The statistical relationship between supplemental adaptive intra-volume low-level scan (SAILS) usage on the Weather Surveillance Radar-1988 Doppler and National Weather Service severe storm warning performance during 2014–20 is analyzed. Results show statistically significant improvement in severe thunderstorm (SVR), flash flood (FF), and tornado (TOR) warning performance associated with SAILS-on versus SAILS-off. Within the three possible SAILS modes of one (SAILSx1), two (SAILSx2), and three (SAILSx3) additional base scans per volume, for SVR, SAILSx2 and SAILSx3 are associated with better warning performance compared to SAILSx1; for FF and TOR, SAILSx3 is associated with better warning performance relative to SAILSx1 and SAILSx2. Two severe storm cases (one that spawned a tornado, one that did not) are presented where SAILS usage helped forecasters make the correct TOR warning decision, lending real-life credence to the statistical results. Furthermore, a statistical analysis of automated volume scan evaluation and termination effects, parsed by SAILS usage and mode, yield a statistically significant association between volume scan update rate and SVR warning lead time. [ABSTRACT FROM AUTHOR]

A 69-year-old man with myelofibrosis presented with a two-day history of left periorbital swelling, blurred vision, and non-radiating dull orbital pain. On examination, there was restricted left-sided extraocular motility with conjunctival injection, chemosis, and periorbital edema. Magnetic resonance imaging demonstrated left-sided pre- and post-septal fat stranding concerning for orbital cellulitis. Two weeks before symptom onset, the patient began fedratinib therapy for myelofibrosis but discontinued this medication upon hospital admission. After restarting fedratinib, he presented with similar right-sided ophthalmic signs. A review of his medication history revealed a temporal relationship between symptom onset and fedratinib use. After medication discontinuation, his symptoms improved rapidly. [ABSTRACT FROM AUTHOR]

The vascular endothelium dynamically responds to environmental cues and plays a pivotal role in maintaining vascular homeostasis by regulating vasomotor tone, blood cell trafficking, permeability and immune responses. However, endothelial dysfunction results in various pathological conditions. Inflammasomes are large intracellular multimeric complexes activated by pathogens or cellular damage. Inflammasomes in vascular endothelial cells (ECs) initiate innate immune responses, which have emerged as significant mediators in endothelial dysfunction, contributing to the pathophysiology of an array of diseases. This review summarizes the mechanisms and ramifications of inflammasomes in ECs and related vascular diseases such as atherosclerosis, abdominal aortic aneurysm, stroke, and lung and kidney diseases. We also discuss potential drugs targeting EC inflammasomes and their applications in treating vascular diseases. [ABSTRACT FROM AUTHOR]

Dual therapy with vonoprazan and amoxicillin is as effective as triple therapy with vonoprazan, amoxicillin and clarithromycin for eradication of Helicobacter pylori. These include the need to collect antibiotic sensitivity profiles (if possible) before treatment, and to prescribe tailored therapy (precise treatment), while understanding that the current standard of using first-line therapies (empiric treatment) is more practical with real-life clinical scenarios. PPI-amoxicillin dual therapy four times daily is superior to guidelines recommended regimens in the Helicobacter pylori eradication therapy within Asia: A systematic review and meta-analysis. In an era with rising antibiotic resistance to clarithromycin and metronidazole, rifabutin-containing triple therapy should be considered when patients fail triple therapy or BQT, an approach recommended by most treatment guidelines since the prevalence of rifabutin resistance is still very low or non-existent.3-5 In the U.S., a low-dose (50mg TID) rifabutin-containing triple therapy was recently approved by the Food and Drug Administration (FDA) with superior efficacy vs HDDT30 but its use has not been included in most practice guidelines. [Extracted from the article]

• Diarrhoeagenic Escherichia coli pathotypes were identified using multiplex polymerase chain reaction (PCR). • The enterotoxigenic (ETEC) pathotype was predominant, followed by the enteroaggregative (EAEC), enteropathogenic (EPEC) and enterohaemorrhagic (EHEC) pathotypes. • EAEC/ETEC was the predominant hybrid pathotype detected. • The phylogenetic groups of pathotypes were determined using Clermont quadruplex PCR. • Phylogroup B2 was predominant, followed by phylogroups B1, C and E, and A and D. : Diarrhoeagenic Escherichia coli pose a significant risk to human health. As such, determining the source(s) of these bacteria when isolated from patients with diarrhoea is an important step in disease prevention. : To identify the presence of genes coding for virulence and phylogroups among E. coli isolated from children hospitalized due to diarrhoea in Limpopo Province, South Africa. : E. coli isolates were identified using the VITEK-2 automated system. An 11-gene multiplex polymerase chain reaction (PCR) was used to differentiate five pathogenic types of E. coli : enteroaggregative (EAEC), enteroinvasive (EIEC), enterohaemorrhagic (EHEC), enteropathogenic (EPEC) and enterotoxigenic (ETEC). The Clermont quadruplex PCR method was used to identify phylogroups of isolates. : From the 133 isolates tested, 79 were confirmed as E. coli. Of these, 19.0% (15/79) were commensals and 81.0% (64/79) were positive for at least one pathotype, of which ETEC was predominant (16.5%, 13/79), followed by EAEC (10.1%, 8/79), EPEC (7.6%, 6/79) and EHEC (2.5%, 2/79). Hybrid pathotypes were also detected and EAEC/ETEC was predominant (25.3%, 20/79). Phylogroup B2 was predominant (30.4%, 24/79), followed by phylogroup B1 (22.8%, 18/79), and phylogroups C and E (both 12.7%, 10/79). Just over 6% (5/79) of isolates were non-typable. : There was a high distribution of diarrhoeagenic E. coli associated with different phylogroups among children living in Limpopo Province, South Africa. This emphasizes the importance of future monitoring of virulence and phylogroup distribution of E. coli isolates in this province in particular and in South Africa as a whole. [ABSTRACT FROM AUTHOR]

Introduction: Clinical success of donation after circulatory death (DCD) heart transplantation is leading to growing adoption of this technique. In comparison to procurement from a brain‐dead donor, DCD requires additional resources. The economic impact of DCD heart transplantation from the hospital perspective is not well known. Methods: We compared the financial data of patients who received DCD allografts to those who received a DBD organ at our institution from January 1, 2021 to December 31, 2022. We also compared the cost of ex‐situ machine perfusion to in‐situ organ perfusion employed during DCD recovery. Results: We performed 58 DBD and 22 DCD heart‐alone transplantations during the study period. Out of 22 DCD grafts, 16 were recovered with thoracoabdominal normothermic regional perfusion (TA‐NRP) and six with direct procurement followed by normothermic machine perfusion (DP‐NMP). The contribution margin per case for DBD versus DCD was $234,362 and $235,440 (P =.72). The direct costs did not significantly differ between the two groups ($171,949 and 186,250; P =.49). In comparing the two methods of procuring hearts from DCD donors, the direct cost of TA‐NRP was $155,955 in comparison to $223,399 for DP‐NMP (P =.21). This difference translated into a clinically meaningful but not statistically significant greater contribution margin for TA‐NRP ($242, 657 vs. $175,768; P =.34). Conclusions: Our data showed that the adoption of DCD procurement did not have a negative financial impact on the contribution margin in our institution. Programs considering starting DCD heart transplantation, and those who are currently performing DCD procurement should evaluate their own financial situation. [ABSTRACT FROM AUTHOR]

We study the performance of the hybrid template machine learning photometric redshift (photo- z) algorithm delight , which uses Gaussian processes, on a subset of the early data release of the Physics of the Accelerating Universe Survey (PAUS). We calibrate the fluxes of the 40 PAUS narrow bands with six broad-band fluxes (uBVriz) in the Cosmic Evolution Survey (COSMOS) field using three different methods, including a new method that utilizes the correlation between the apparent size and overall flux of the galaxy. We use a rich set of empirically derived galaxy spectral templates as guides to train the Gaussian process, and we show that our results are competitive with other standard photometric redshift algorithms. delight achieves a photo- z 68th percentile error of σ68 = 0.0081(1 + z) without any quality cut for galaxies with i auto < 22.5 as compared to 0.0089(1 + z) and 0.0202(1 + z) for the bpz and annz 2 codes, respectively. delight is also shown to produce more accurate probability distribution functions for individual redshift estimates than bpz and annz 2. Common photo- z outliers of delight and bcnz 2 (previously applied to PAUS) are found to be primarily caused by outliers in the narrow-band fluxes, with a small number of cases potentially indicating spectroscopic redshift failures in the reference sample. In the process, we introduce performance metrics derived from the results of bcnz 2 and delight , allowing us to achieve a photo- z quality of σ68 < 0.0035(1 + z) at a magnitude of i auto < 22.5 while keeping 50 per cent objects of the galaxy sample. [ABSTRACT FROM AUTHOR]

Noninvasive fluorescent imaging requires far-red and near-infrared fluorescent proteins for deeper imaging. Near-infrared light penetrates biological tissue with blood vessels due to low absorbance, scattering, and reflection of light and has a greater signal-tonoise due to less autofluorescence. Far-red and near-infrared fluorescent proteins absorb light >600 nm to expand the color palette for imaging multiple biosensors and noninvasive in vivo imaging. The ideal fluorescent proteins are bright, photobleach minimally, express well in the desired cells, do not oligomerize, and generate or incorporate exogenous fluorophores efficiently. Coral-derived red fluorescent proteins require oxygen for fluorophore formation and release two hydrogen peroxide molecules. New fluorescent proteins based on phytochrome and phycobiliproteins use biliverdin IXα as fluorophores, do not require oxygen for maturation to image anaerobic organisms and tumor core, and do not generate hydrogen peroxide. The small Ultra-Red Fluorescent Protein (smURFP) was evolved from a cyanobacterial phycobiliprotein to covalently attach biliverdin as an exogenous fluorophore. The small Ultra-Red Fluorescent Protein is biophysically as bright as the enhanced green fluorescent protein, is exceptionally photostable, used for biosensor development, and visible in living mice. Novel applications of smURFP include in vitro protein diagnostics with attomolar (10−18 M) sensitivity, encapsulation in viral particles, and fluorescent protein nanoparticles. However, the availability of biliverdin limits the fluorescence of biliverdin-attaching fluorescent proteins; hence, extra biliverdin is needed to enhance brightness. New methods for improved biliverdin bioavailability are necessary to develop improved bright far-red and near-infrared fluorescent proteins for noninvasive imaging in vivo. [ABSTRACT FROM AUTHOR]

A 37-year-old female presented with 2 months of headache, blurry vision, and a partial CN3 palsy. MRI demonstrated a right-sided heterogeneously enhancing mass causing compression at the right pons, midbrain, and peduncle. Decision was made to take the patient for a retrosigmoid trans-tentorial approach (RSTTA) for resection of the lesion, which was demonstrated to be a trochlear schwannoma. The patient did well postoperatively with improvement in her CN 3 palsy.By Rachel Blue; Sonia Ajmera and John Y. K. LeeReported by Author; Author; Author [Extracted from the article]

Although most CD8+ T cells are equipped to kill infected or transformed cells, a subset may regulate immune responses and preserve self-tolerance. Here, we describe a CD8 lineage that is instructed to differentiate into CD8 T regulatory cells (Tregs) by a surprisingly restricted set of T cell receptors (TCRs) that recognize MHC-E (mouse Qa-1) and several dominant self-peptides. Recognition and elimination of pathogenic target cells that express these Qa-1-self-peptide complexes selectively inhibits pathogenic antibody responses without generalized immune suppression. Immunization with synthetic agonist peptides that mobilize CD8 Tregs in vivo efficiently inhibit antigraft antibody responses and markedly prolong heart and kidney organ graft survival. Definition of TCR-dependent differentiation and target recognition by this lineage of CD8 Tregs may open the way to new therapeutic approaches to inhibit pathogenic antibody responses. [ABSTRACT FROM AUTHOR]

OSIRIS‐REx began observing particle ejection events shortly after entering orbit around near‐Earth asteroid (101955) Bennu in January 2019. For some of these events, the only observations of the ejected particles come from the first two images taken immediately after the event by OSIRIS‐REx's NavCam 1 imager. Without three or more observations of each particle, traditional orbit determination is not possible. However, by assuming that the particles all ejected at the same time and location for a given event, and approximating that their velocities remained constant after ejection (a reasonable approximation for fast‐moving particles, i.e., with velocities on the order of 10 cm/s or greater, given Bennu's weak gravity), we show that it is possible to estimate the particles' states from only two observations each. We applied this newly developed technique to reconstruct the particle ejection events observed by the OSIRIS‐REx spacecraft during orbit about Bennu. Particles were estimated to have ejected with inertial velocities ranging from 7 cm/s to 3.3 m/s, leading to a variety of trajectory types. Most (>80%) of the analyzed events were estimated to have originated from midlatitude regions and to have occurred after noon (local solar time), between 12:44 and 18:52. Comparison with higher‐fidelity orbit determination solutions for the events with sufficient observations demonstrates the validity of our approach and also sheds light on its biases. Our technique offers the capacity to meaningfully constrain the properties of particle ejection events from limited data. Key Points: We show how Bennu's particle ejection events can be reconstructed using only two observationsFor each event, we estimate the particle velocities and ejection locationVelocities ranged from 7 cm/s to 3.3 m/s, and most observed events took place after noon [ABSTRACT FROM AUTHOR]

Introduction: A common criticism of the peer-review process is the often disparate nature of reviewer recommendations when a decision is rendered which belies the supposed uniformity of the process. The purpose of this investigation was to examine level of agreement between reviewers for Foot & Ankle International (FAI) and analyze variables which may have influenced agreement in order to better understand the peer-review process.Methods: Approval to conduct this investigation was obtained from the Executive Board and Editor in Chief of FAI. All manuscripts submitted to FAI during the calendar year 2016 which underwent formal peer-review were included in the analysis. For each reviewed manuscript, demographic data was collected regarding specific reviewer and manuscript characteristics in a de-identified manner.Results: 442 manuscripts underwent formal blinded peer-review by two independent reviewers during the study period. Only 199 manuscripts (45%) had a decision rendered in which both reviewers agreed on the same initial recommendation. There were no differences in demographic characteristics between the group of reviewers who agreed as compared to those who disagreed on the initial round of peer review. A similar number of indexed peer-reviewed publications between reviewers correlated with increased levels of agreement.Conclusions: During the study period, there was 45% initial agreement between reviewers for FAI when assessing the same manuscript. Aside from research productivity, no other reviewer-specific variables examined in this investigation were found to correlate with agreement. Specific recommendations and changes may be considered to increase the efficiency and effectiveness of the peer-review process. [ABSTRACT FROM AUTHOR]

Listener expectations are a fundamental consideration in formal analysis, common to cognitive and hermeneutic approaches alike. Such approaches maintain that listeners use statistical regularities of musical style to predict where a piece of music is going and then assess what actually happens in terms of what they expected to happen. Although expectation is frequently invoked when considering very local phenomena (e.g., step-by-step progressions) or very global ones (e.g., the action spaces of a sonata), it has not played a systematic role in the analysis of basic theme types as formulated by William Caplin. This article proposes a framework for modeling expectation at the theme and phrase level. This is premised on the idea that conventional beginning-ending pairs condition listeners to expect certain endings when they hear certain beginnings. An expansion of Caplin's categories is provided to classify such pairs. This reframing of phrasestructural analysis in predictive terms opens it up to the hermeneutic strategies of dialogic analysis, by allowing for the exploration of the rhetorical and expressive effects of failed predictions. This article further proposes a way to use corpus studies to identify theme types in later musical styles in which Caplin's definitions do not necessarily apply. The utility of this approach is demonstrated in analyses of waltzes by Johann Strauss II. [ABSTRACT FROM AUTHOR]

A monetized flash flood casualty reduction benefit model is constructed for application to meteorological radar networks. Geospatial regression analyses show that better radar coverage of the causative rainfall improves flash flood warning performance. Enhanced flash flood warning performance is shown to decrease casualty rates. Consequently, these two effects in combination allow a model to be formed that links radar coverage to flash flood casualty rates. When this model is applied to the present-day contiguous U.S. weather radar network, results yield a flash flood–based benefit of $316 million (M) yr−1. The remaining benefit pools are more modest ($13 M yr−1 for coverage improvement and $69 M yr−1 maximum for all areas of radar quantitative precipitation estimation improvements), indicative of the existing weather radar network's effectiveness in supporting the flash flood warning decision process. [ABSTRACT FROM AUTHOR]

The neural retina metabolizes glucose through aerobic glycolysis generating large amounts of lactate. Lactate flux into and out of cells is regulated by proton‐coupled monocarboxylate transporters (MCTs), which are encoded by members of the Slc16a family. MCT1, MCT3, and MCT4 are expressed in the retina and require association with the accessory protein basigin, encoded by Bsg, for maturation and trafficking to the plasma membrane. Bsg−/− mice have severely reduced electroretinograms (ERGs) and progressive photoreceptor degeneration, which is presumed to be driven by metabolic dysfunction resulting from loss of MCTs. To understand the basis of the Bsg−/− phenotype, we generated mice with conditional deletion of Bsg in rods (RodΔBsg), cones (Cone∆Bsg), or retinal pigment epithelial cells (RPEΔBsg). RodΔBsg mice showed a progressive loss of photoreceptors, while ConeΔBsg mice did not display a degenerative phenotype. The RPEΔBsg mice developed a distinct phenotype characterized by severely reduced ERG responses as early as 4 weeks of age. The loss of lactate transporters from the RPE most closely resembled the phenotype of the Bsg−/− mouse, suggesting that the regulation of lactate levels in the RPE and the subretinal space is essential for the viability and function of photoreceptors. [ABSTRACT FROM AUTHOR]

The author responds to the article "Public Theology and Public Missiology" by Robert S. Heaney that was published within the issue. Topics discussed include theology of public life that upholds a particularist point of view, interfaith dialogue, and the locus, plurality, and modus operandi of a missiological approach to public witness.

Induction of longstanding immunologic tolerance is essential for survival of transplanted organs and tissues. Despite recent advances in immunosuppression protocols, allograft damage inflicted by antibody specific for donor organs continues to represent a major obstacle to graft survival. Here we report that activation of regulatory CD8 T cells (CD8 Treg) that recognize the Qa-1 class Ib major histocompatibility complex (MHC), a mouse homolog of human leukocyte antigen-E (HLA-E), inhibits antibody-mediated immune rejection of heart allografts. We analyzed this response using a mouse model that harbors a point mutation in the class Ib MHC molecule Qa-1, which disrupts Qa-1 binding to the T cell receptor (TCR)-CD8 complex and impairs the CD8 Treg response. Despite administration of cytotoxic T lymphocyte antigen 4 (CTLA-4) immunoglobulin (Ig), Qa-1 mutant mice developed robust donor-specific antibody responses and accelerated heart graft rejection. We show that these allo-antibody responses reflect diminished Qa-1-restricted CD8 Treg-mediated suppression of host follicular helper T cell-dependent antibody production. These findings underscore the critical contribution of this Qa-1/HLA-E-dependent regulatory pathway to maintenance of transplanted organs and suggest therapeutic approaches to ameliorate allograft rejection. [ABSTRACT FROM AUTHOR]

Bile acid synthesis is the most significant pathway for catabolism of cholesterol and for maintenance of whole body cholesterol homeostasis. Bile acids are physiological detergents that absorb, distribute, metabolize, and excrete nutrients, drugs, and xenobiotics. Bile acids also are signal molecules and metabolic integrators that activate nuclear farnesoid X receptor (FXR) and membrane Takeda G proteincoupled receptor 5 (TGR5; i.e., G protein-coupled bile acid receptor 1) to regulate glucose, lipid, and energy metabolism. The gut-to-liver axis plays a critical role in the transformation of primary bile acids to secondary bile acids, in the regulation of bile acid synthesis to maintain composition within the bile acid pool, and in the regulation of metabolic homeostasis to prevent hyperglycemia, dyslipidemia, obesity, and diabetes. High-fat and high-calorie diets, dysbiosis, alcohol, drugs, and disruption of sleep and circadian rhythms cause metabolic diseases, including alcoholic and nonalcoholic fatty liver diseases, obesity, diabetes, and cardiovascular disease. Bile acid-based drugs that target bile acid receptors are being developed for the treatment of metabolic diseases of the liver. [ABSTRACT FROM AUTHOR]

It is widely assumed that reinforcers are biologically relevant stimuli, or stimuli that have been associated with biologically relevant stimuli. However, brief, arbitrary stimuli have also been reported to have reinforcement‐like effects, despite being unrelated to biologically relevant stimuli like food. The present study explored the potential reinforcement‐like effects of brief stimuli across 5 experiments. In Experiments 1 through 4, pigeon subjects responded for food reinforcement and brief stimulus presentations in a 2‐component multiple schedule. Neither baseline response rates nor resistance to change during disruption tests were systematically greater in a component with versus without brief stimulus presentations. Increasing the rate and duration of brief stimulus presentations in Experiment 4 did not reveal reinforcement‐like effects when compared directly with food. In Experiment 5, pigeons chose between independent terminal links in a concurrent‐chains procedure. Across conditions, varying the location, duration, and rate of brief stimulus presentations in the terminal links had no systematic effects on preference. In contrast, varying rates of food reinforcers resulted in large and reliable shifts in preference. Therefore, the present study found no systematic evidence that brief stimuli unrelated to food reliably increase response rates, resistance to change, or preference. These data demonstrate the value of systematic replication, and a behavioral momentum approach to assessing potential reinforcement‐like effects. [ABSTRACT FROM AUTHOR]

Most solid cancers are treated by surgical resections to reduce the burden of disease. Surgeons often face the challenge of detecting small areas of residual neoplasm after resection or finding small primary tumors for the initial resection. Intraoperative molecular imaging (IMI) is an emerging technology with the potential to dramatically improve cancer surgery operations by allowing surgeons to better visualize areas of neoplasm using fluorescence imaging. Over the last two years, two molecular optical contrast agents received U.S. Food and Drug Administration approval, and several more drugs are now on the horizon. Thus a conference was organized at the University of Pennsylvania to bring together oncologic surgeons from different specialties to discuss the current clinical status of IMI trials with a specific focus on phase 2 and phase 3 studies. In addition, phase 1 and experimental trials were also discussed briefly, to highlight other novel techniques. Our review summarizes the discussions from the conference and delves into the types of cancers discussed, different contrast agents in human trials, and the clinical value being studied. [ABSTRACT FROM AUTHOR]

The article discusses various reports published within the issue, including one by Sarah J. Moore on the monumental status of the Library of Congress, another by Sally Webster on decorations for the Library of Congress, and another by Tom Somma on sculpture in the Library of Congress.

Recent experimental studies have shown that some inhomogeneously strained bulk solid dielectrics have large flexoelectric coefficients. Here we report the experimental observation of the converse flexoelectric effect, i.e., the elastic stress induced in a Ba0.67Sr0.33TiO3 (BST) composition trapezoid block under the inhomogeneous electric fields generated by its chosen boundary shape. This BST composition has a very high electric susceptibility value χ and a ferroelectric Curie point that is close to room temperature. The quantitative measurement of the flexoelectric coefficient μ11 at a temperature just above the Curie point indicates that an enhanced converse flexoelectric effect exists in the BST sample in good agreement with the earlier measured direct effect. This observed phenomenon agrees with the theoretical predictions of Tagantsev’s phenomenological model. Furthermore, our experimental results suggest that we may be able to develop a method to design some unusual but useful piezocomposites with microscale artificial geometry shapes, which are completely fabricated from nonpiezoelectric materials. [ABSTRACT FROM AUTHOR]

We describe here a new procedure for the simultaneous investigation of sedimentation and diffusion of a colloidal particle in close proximity to a solid, planar wall. The measurements were made using the optical technique of total internal reflection microscopy, coupled with optical radiation pressure, for dimensionless separation distances (gap width/radius of particle) ranging from 0.01 to 0.05. In this region, the hydrodynamic mobility and diffusion coefficient are substantially reduced below bulk values. The procedure involved measuring the mean and the variance of vertical displacements of a Brownian particle settling under gravity toward the plate. The spatially varying diffusion coefficient was calculated from the displacements at small times (where diffusive motion was dominant). The mobility relationship for motion normal to a flat plate was tested by measuring the average distance of travel versus time as the particle settled under the constant force of gravity. For the simple Newtonian fluid used here (aqueous salt solution), the magnitude of the diffusion coefficient and mobility, plus their dependence on separation distance, showed excellent agreement with predictions. This new technique could be of great value in measuring the mobility and diffusion coefficient for near-contact motion in more complex fluids for which the hydrodynamic correction factors are not known a priori, such as shear-thinning fluids. [ABSTRACT FROM AUTHOR]

Objective Methods Results Interpretation To systematically evaluate which lesion‐based imaging features and methods allow for the best statistical prediction of poststroke deficits across independent datasets.We utilized imaging and clinical data from three independent datasets of patients experiencing acute stroke (N1 = 109, N2 = 638, N3 = 794) to statistically predict acute stroke severity (NIHSS) based on lesion volume, lesion location, and structural and functional disconnection with the lesion location using normative connectomes.We found that prediction models trained on small single‐center datasets could perform well using within‐dataset cross‐validation, but results did not generalize to independent datasets (median R2N1 = 0.2%). Performance across independent datasets improved using large single‐center training data (R2N2 = 15.8%) and improved further using multicenter training data (R2N3 = 24.4%). These results were consistent across lesion attributes and prediction models. Including either structural or functional disconnection in the models outperformed prediction based on volume or location alone (P < 0.001, FDR‐corrected).We conclude that (1) prediction performance in independent datasets of patients with acute stroke cannot be inferred from cross‐validated results within a dataset, as performance results obtained via these two methods differed consistently, (2) prediction performance can be improved by training on large and, importantly, multicenter datasets, and (3) structural and functional disconnection allow for improved prediction of acute stroke severity. [ABSTRACT FROM AUTHOR]

Background: Restless legs syndrome (RLS) is frequent in patients with hemodialysis (HD) and occurs predominantly in its most severe forms. The study was conducted to evaluate the efficacy and safety of acupuncture for RLS in patients with end-stage renal disease (ESRD) at hospital-based HD center. Methods: This single-blind, randomized controlled trial was performed on patients with HD and RLS who were randomly assigned to the experimental group and control group. Data were collected using the International Restless Legs Syndrome Rating Scale (IRLSRS), Insomnia Severity Index (ISI), and heart rate variability (HRV) records at baseline, after the therapeutic course (12 times/4 weeks), and 1-week follow-up. Result: A total of 47 patients were evaluated with IRLSRS score from 11 to 30 in this study. There were 41 patients enrolled in the study based on inclusion/exclusion criteria and allocated randomly into two groups. A total of 35 participants completed the trial, including 18 subjects in the experimental group and 17 subjects in the control group. The comparison of IRLSRS and ISI showed a significant reduction between two groups after acupuncture treatment (p = 0.002, p = 0.003). The ISI after 1-week follow-up also revealed significant decrease (p = 0.003). This HRV results showed that high frequency (HF%) increased significantly (p = 0.021) and low frequency (LF%) decreased significantly in the acupuncture group (p = 0.021). The generalized estimating equation showed that the IRLSRS improved by 2.902 points (p < 0.001) in the acupuncture group compared with the control group and by 1.340 points (p = 0.003) after 1-week follow-up. There were no adverse effects observed during HD in this study. Discussion: The authors conclude that acupuncture could effectively improve the symptoms of RLS significantly. The results from this study provide clinical evidence on the efficacy and safety of acupuncture to treat the patients with RLS at the HD center. [ABSTRACT FROM AUTHOR]

Optogenetic techniques provide genetically targeted, spatially and temporally precise approaches to correlate cellular activities and physiological outcomes. In the nervous system, G protein-coupled receptors (GPCRs) have essential neuromodulatory functions through binding extracellular ligands to induce intracellular signaling cascades. In this work, we develop and validate an optogenetic tool that disrupts Gαq signaling through membrane recruitment of a minimal regulator of G protein signaling (RGS) domain. This approach, Photo-induced Gα Modulator--Inhibition of Gαq (PiGM-Iq), exhibited potent and selective inhibition of Gαq signaling. Using PiGM-Iq we alter the behavior of Caenorhabditis elegans and Drosophila with outcomes consistent with GPCR-Gαq disruption. PiGM-Iq changes axon guidance in cultured dorsal root ganglia neurons in response to serotonin. PiGM-Iq activation leads to developmental deficits in zebrafish embryos and larvae resulting in altered neuronal wiring and behavior. Furthermore, by altering the minimal RGS domain, we show that this approach is amenable to Gαi signaling. Our unique and robust optogenetic Gα inhibiting approaches complement existing neurobiological tools and can be used to investigate the functional effects neuromodulators that signal through GPCR and trimeric G proteins. [ABSTRACT FROM AUTHOR]

Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 is one of the major foodborne and waterborne pathogens causing severe diseases and outbreaks worldwide. There is scarcity of EHEC O157:H7 data in South Africa. This study was carried out to determine the molecular characteristics and genotypic diversity of EHEC O157:H7 isolates in the Gauteng region, South Africa. Samples were cultured on selective chromogenic media. Antibiotic susceptibility profile of isolates was determined using the VITEK®-2 automated system. Isolates were characterised using multiplex PCR assays and the genetic diversity was determined using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). A total of 520 samples of which 270 environmental water samples and 250 stool specimens were collected and analysed. Overall, EHEC O157:H7 was recovered from 2.3% (12/520) of samples collected. Environmental water samples and clinical stool specimens showed a prevalence of 4.07% (11/270) and 0.4% (1/250) respectively. Antibiotic susceptibility profile varied from isolates with full susceptibility to isolates with resistance to multiple antibiotics. Most resistance was detected to the penicillins, specifically ampicillin (7/12), amoxicillin (3/12) and piperacillin/Tazobactam (3/12) followed by one of the folate inhibitors, trimethoprim (3/12) and the carbapenems, imipenem and meropenem (2/12) each. Three isolates harboured a combination of Shiga-toxins (Stx)-2, intimin (eae) and enterohaemolysin (hly A) genes, while two isolates harboured the Stx -1, Stx- 2 and hly A genes. The PFGE performed showed that EHEC O157:H7 isolates were genetically diverse, with two minor pulsotypes and eight singletons. The MLST analysis identified three sequence types (STs) (ST10, ST11 and ST1204) that have been previously reported associated with outbreaks. The STs identified in this study pose a potential public health risk to consumers of untreated environmental water and closed human contacts. There is necessity to enhance surveillance in reducing the propagation of this bacterium which is a public health problem. Unlabelled Image • Environmental water samples and clinical stool specimens were analysed for the detection of EHEC O157:H7 • The EHEC O157:H7 isolates were more prevalent in environmental samples than in clinical specimens • The combination of virulence genes was detected among EHEC O157:H7 isolates • The EHEC O157:H7 isolates were genetically diverse. Three sequence types (ST10, ST11, ST1204) were identified in this study that have never been reported in South Africa • These STs pose potential public health risk to consumers of untreated water and closed human contacts [ABSTRACT FROM AUTHOR]

Purpose: To evaluate prognostic factors and survival of patients with sebaceous carcinoma of the eyelid through a population-based analysis. Methods: A total of 940 patients with primary sebaceous carcinoma of the eyelid were derived from the Surveillance, Epidemiology, and End Results (SEER) database in the United States from 1973 to 2013. Kaplan–Meier univariate analysis and Cox Regression multivariate analysis were performed to examine prognostic factors in overall survival (OS). 5- and 10-year survival rates, median survival, and prognostic variables with statistical significance were measured. Results: Kaplan-Meier analysis showed that OS is 66% and 44% at 5 years and 10 years respectively. Median OS is 9.4 years. Multivariate Cox regression analysis demonstrated that independent prognostic factors for OS are age at diagnosis (HR = 4.61 [95% CI 1.93–11.0], P = 0.001), surgical treatment (HR = 0.196 [95% CI 0.07–0.55], P = 0.002), combined surgical and radiation treatment (HR = 0.227 [95% CI 0.06–0.81], P = 0.023), and greater tumor size at diagnosis (HR = 3.381, [95% CI 1.77–6.45], P < 0.001). Conclusion: We report the largest population study to date to evaluate prognostic factors of patients with sebaceous carcinoma of the eyelid. Multivariate analysis shows that older age, and greater tumor size correlate with decreased overall survival, whereas surgical treatment or combined surgical and radiation treatment correlate with increased overall survival. Interestingly, tumor grade, lymph node involvement, and distant extent of tumor have not demonstrated to be independent prognostic factors for overall survival. [ABSTRACT FROM AUTHOR]