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Wolverine distribution contracted along the southern periphery of its range in North America during the 19th and 20th centuries due primarily to human influences. This history, along with low densities, sensitivity to climate change, and concerns about connectivity among fragmented habitats spurred the recent US federal listing of threatened status and special concern status in Canada. To help inform large scale landscape connectivity, we collected 882 genetic samples genotyped at 19 microsatellite loci. We employed multiple statistical models to assess the landscape factors (terrain complexity, human disturbance, forest configuration, and climate) associated with wolverine genetic connectivity across 2.2 million km2 of southwestern Canada and the northwestern contiguous United States. Genetic similarity (positive spatial autocorrelation) of wolverines was detected up to 555 km and a high-to-low gradient of genetic diversity occurred from north-to-south. Landscape genetics analyses confirmed that wolverine genetic connectivity has been negatively influenced by human disturbance at broad scales and positively influenced by forest cover and snow persistence at fine- and broad–scales, respectively. This information applied across large landscapes can be used to guide management actions with the goal of maintaining or restoring population connectivity. [ABSTRACT FROM AUTHOR]

We employed two compelling and distinct methods, Fourier Transform Infrared Spectroscopy (FTIR) and Ramped Pyrolysis Oxidation (Ramped PyrOx), to examine the quality of organic matter (OM) stored in four peatlands located along a latitudinal gradient (Tropical (4˚N), Subtropical (27˚N), Boreal (48˚N), and Polar (68˚N)). FTIR was used to quantify the relative abundance of carbohydrates, a relatively labile compound class, and aromatics, which are more recalcitrant, in a sample set of four peat cores. These samples were then prepared using Ramped PyrOx, a second, independent method of determining OM quality that mimics the natural diagenetic maturation of OM that would take place over long timescales. Previous large-scale studies using FTIR to evaluate OM quality have observed that it generally increases with increasing latitude (more carbohydrates, less aromatics). Here, we demonstrate that the Ramped PyrOx approach both validates and complements the FTIR approach. The data stemming from each Ramped PyrOx preparation was input to a model that generates an estimated probability density function of the activation energy (E) required to break the C bonds in the sample. We separated these functions into three fractions ("low E," "medium E," and "high E") to create Ramped PyrOx variables that could be quantitatively compared to the compound class abundance data from FTIR. In assessing the agreement between the two methods, we found three significant relationships between Ramped PyrOx and FTIR variables. Low E fractions and carbohydrate content were positively correlated (R2 = 0.51) while low E fractions were negatively correlated with aromatic content (R2 = 0.58). Medium E fractions were found to be positively correlated with aromatics (R2 = 0.69). [ABSTRACT FROM AUTHOR]

Purpose: The Speech Accessibility Project (SAP) intends to facilitate research and development in automatic speech recognition (ASR) and other machine learning tasks for people with speech disabilities. The purpose of this article is to introduce this project as a resource for researchers, including baseline analysis of the first released data package. Method: The project aims to facilitate ASR research by collecting, curating, and distributing transcribed U.S. English speech from people with speech and/or language disabilities. Participants record speech from their place of residence by connecting their personal computer, cell phone, and assistive devices, if needed, to the SAP web portal. All samples are manually transcribed, and 30 per participant are annotated using differential diagnostic pattern dimensions. For purposes of ASR experiments, the participants have been randomly assigned to a training set, a development set for controlled testing of a trained ASR, and a test set to evaluate ASR error rate. Results: The SAP 2023-10-05 Data Package contains the speech of 211 people with dysarthria as a correlate of Parkinson's disease, and the associated test set contains 42 additional speakers. A baseline ASR, with a word error rate of 3.4% for typical speakers, transcribes test speech with a word error rate of 36.3%. Fine-tuning reduces the word error rate to 23.7%. Conclusions: Preliminary findings suggest that a large corpus of dysarthric and dysphonic speech has the potential to significantly improve speech technology for people with disabilities. By providing these data to researchers, the SAP intends to significantly accelerate research into accessible speech technology. [ABSTRACT FROM AUTHOR]

Introduction: Myelomeningocele (MMC) is the most common neural tube defect, but rarely seen in premature infants. Most centers advocate for closure of MMC within 24 h of birth. However, this is not always possible in severely premature infants. Given the rarity of this patient population, we aimed to share our institutional experience and outcomes of severely premature infants with MMC. Methods: We performed a retrospective, observational review of premature infants (≤ 32 weeks gestational age) identified through our multidisciplinary spina bifida clinic (1995–2021) and surgical logs. Descriptive statistics were compiled about this sample including timing of MMC closure and incidence of adverse events such as sepsis, CSF diversion, meningitis, and death. Results: Eight patients were identified (50% male) with MMC who were born ≤ 32 weeks gestational age. Mean gestational age of the population was 27.3 weeks (SD 3.5). Median time to MMC closure was 1.5 days (IQR = 1—80.8). Five patients were taken for surgery within the recommended 48 h of birth; 2 patients underwent significantly delayed closure (107 and 139 days); and one patient's defect epithelized without surgical intervention. Six of eight patients required permanent cerebrospinal fluid (CSF) diversion (2 patients were treated with ventriculoperitoneal shunting (VPS), three were treated with endoscopic third ventriculostomy (ETV) with choroid plexus cauterization (CPC) and 1 patient treated with ETV; mean of 3 years after birth, ranging from 1 day to 16 years). Two patients required more than one permanent CSF diversion procedure. Two patients developed sepsis (defined as meeting at least 2/4 SIRS criteria). In both cases of sepsis, patients developed signs and symptoms more than 72 h after birth. Notably, both instances of sepsis occurred unrelated to operative intervention as they occurred before permanent MMC closure. Two patients had intraventricular hemorrhage (both grade III). No patients developed meningitis (defined as positive CSF cultures) prior to MMC closure. Median follow up duration was 9.7 years. During this time epoch, 3 patients died: Two before 2 years of age of causes unrelated to surgical intervention. One of the two patients with grade III IVH died within 24 h of MMC closure. Conclusions: In our institutional experience with premature infants with MMC, some patients underwent delayed MMC closure. The overall rate of meningitis, sepsis, and mortality for preterm children with MMC was similar to MMC patients born at term. [ABSTRACT FROM AUTHOR]

Background: Postoperative carotid endarterectomy (CEA) patch infection is a rare but well‐recognized complication of CEA. It is important for otolaryngologists to be aware of the presentation and challenges in its diagnosis. Methods: Patients who presented with a neck mass or hemorrhage and a known prior history of carotid endarterectomy with synthetic patch reconstruction were worked up with ultrasound, CT, or MRI imaging. In one case, fine needle aspiration biopsy was performed. Ultimately, all patients were taken to the operating room for neck exploration. Results: Of the three patients presented in this case series, two presented with a chronic neck mass, two‐to‐three years after carotid endarterectomy. One patient presented acutely with hemorrhage from the carotid endarterectomy site. Carotid patch infection was diagnosed after neck exploration in all cases. Vascular surgery was consulted intra‐operatively to perform definitive vascular repair. Conclusions: Infected carotid patch should be suspected in patients with a history of prior CEA, as many of the presenting complaints may resemble or mimic pathology managed by otolaryngology. The onset of symptoms can be perioperative or very delayed. A multidisciplinary approach with vascular surgery and infectious disease is required for appropriate management of these patients. [ABSTRACT FROM AUTHOR]

The approval of teplizumab to delay the onset of type 1 diabetes is an important inflection point in the decades-long pursuit to treat the cause of the disease rather than its symptoms. The National Institute of Diabetes and Digestive and Kidney Diseases convened a workshop of the Diabetes Mellitus Interagency Coordinating Committee titled "Evolving Concepts in Pathophysiology, Screening, and Prevention of Type 1 Diabetes" to review this accomplishment and identify future goals. Speakers representing Type 1 Diabetes TrialNet (TrialNet) and the Immune Tolerance Network emphasized that the ability to robustly identify individuals destined to develop type 1 diabetes was essential for clinical trials. The presenter from the U.S. Food and Drug Administration described how regulatory approval relied on data from the single clinical trial of TrialNet with testing of teplizumab for delay of clinical diagnosis, along with confirmatory evidence from studies in patients after diagnosis. The workshop reviewed the etiology of type 1 diabetes as a disease involving multiple immune pathways, highlighting the current understanding of prognostic markers and proposing potential strategies to improve the therapeutic response of disease-modifying therapies based on the mechanism of action. While celebrating these achievements funded by the congressionally appropriated Special Diabetes Program, panelists from professional organizations, nonprofit advocacy/funding groups, and industry also identified significant hurdles in translating this research into clinical care. [ABSTRACT FROM AUTHOR]

Chiari malformation type 1 (CM1) is a structural defect that involves the herniation of the cerebellar tonsils through the foramen magnum, causing mild to severe neurological symptoms. Little is known about the molecular and developmental mechanisms leading to its pathogenesis, prompting current efforts to elucidate genetic drivers. Inherited genetic disorders are reported in 2–3% of CM1 patients; however, CM1, including familial forms, is predominantly non-syndromic. Recent work has focused on identifying CM1-asscoiated variants through the study of both familial cases and de novo mutations using exome sequencing. This article aims to review the current understanding of the genetics of CM1. We discuss three broad classes of CM1 based on anatomy and link them with genetic lesions, including posterior fossa-linked, macrocephaly-linked, and connective tissue disorder-linked CM1. Although the genetics of CM1 are only beginning to be understood, we anticipate that additional studies with diverse patient populations, tissue types, and profiling technologies will reveal new insights in the coming years. [ABSTRACT FROM AUTHOR]

In the Spring of 2020, the United States of America (USA) deployed COVID-19 convalescent plasma (CCP) to treat hospitalized patients. Over 500,000 patients were treated with CCP during the first year of the pandemic. In this study, we estimated the number of actual inpatient lives saved by CCP treatment in the United States of America based on CCP weekly use, weekly national mortality data, and CCP mortality reduction data from meta-analyses of randomized controlled trials and real-world data. We also estimate the potential number of lives saved if CCP had been deployed for 100% of hospitalized patients or used in 15 to 75% of outpatients. Depending on the assumptions modeled in stratified analyses, we estimated that CCP saved between 16,476 and 66,296 lives. The CCP ideal use might have saved as many as 234,869 lives and prevented 1,136,133 hospitalizations. CCP deployment was a successful strategy for ameliorating the impact of the COVID-19 pandemic in the USA. This experience has important implications for convalescent plasma use in future infectious disease emergencies. [ABSTRACT FROM AUTHOR]

Synthetic cannabinoids emerged in the early 21st century and have continued to evolve and flourish to present day. Like other novel psychoactive substances (NPS), synthetic cannabinoids have been sold under the guise of legitimate products. Some examples include "potpourri," "incense," and herbal material. Between May 2020 and December 2023, the United States Army Criminal Investigation Laboratory, Drug Chemistry Division (USACIL) received 29 seized drug cases mentioning "blue lotus" or "valerian root." In 90% of these cases, at least one exhibit contained one or more synthetic cannabinoids. During the same timeframe, the Armed Forces Medical Examiner System, Division of Forensic Toxicology received 65 toxicology cases that contained synthetic cannabinoids and/or their corresponding metabolites where case history mentioned "blue lotus." The most frequently observed synthetic cannabinoids between laboratories were 5F-MDMB-PICA, ADB-BUTINACA, and MDMB-4en-PINACA. Innocuous branding and marketing may deceive law enforcement, investigators, and healthcare providers into believing that the adverse effects of erratic behavior, sedation, slurred speech, and hallucinations are a result of toxicity from botanical extracts (e.g. apomorphine and nuciferine in blue lotus). Due to the dangerous nature of these NPS, synthetic cannabinoid screening is recommended for all cases where there is suspected use of vaping products suggested to contain "blue lotus" or "valerian root" as vendors continue to conceal the presence of these compounds. [ABSTRACT FROM AUTHOR]

Objective: To design and validate a disease‐specific quality of life instrument for Meniere's disease. Methods: We used a sequential process of expert input, patient focus groups, and analyses of responses to draft questionnaires to create a 24‐item Meniere's disease quality of life (MenQOL) instrument. The MenQOL and the SF‐36v2 were administered to a cohort of 50 patients with Meniere's disease and 60 comparison patients with tinnitus, vertigo, or hearing loss from other causes identified at a tertiary academic center. We performed exploratory factor analysis, Cronbach's α, between group comparisons of total MenQOL scores, and regression analyses between the MenQOL and SF‐36v2 to evaluate the instrument's factor structure, internal consistency, face validity, and external validity. Segregation of the instrument into domains was assessed by exploratory factor analysis. Results: Exploratory factor analysis revealed that the MenQOL has a single domain. Cronbach's α = 0.914 indicated high internal consistency for the instrument as a whole. Mean MenQOL scores showing significantly worse quality of life among patients with Meniere's disease than comparison participants (52.5 ± 15.8 vs. 43.2 ± 12.6; p = 0.0051), indicating good construct validity. Significant inverse relationships in bivariate linear regressions between total MenQOL scores and SF‐36v2 physical (slope = −0.94, p < 0.0001) and mental (slope = −1.16, p < 0.0001) composite scores showed acceptable concurrent validity. Conclusions: We have described the initial development of the MenQOL, a simple, valid patient‐reported outcome measure that, subject to further study, may be used to assess the effects of treatment on disease‐specific quality of life in patients with Meniere's disease. Level of Evidence: 3 Laryngoscope, 134:4351–4357, 2024 [ABSTRACT FROM AUTHOR]

Background: Mobile health (mHealth) has an emerging potential for remote assessment of traumatic dental injuries (TDI) and support of emergency care. This study aimed to determine the diagnostic accuracy of TDI detection from smartphone-acquired photographs. Methods: The upper and lower anterior teeth of 153 individuals aged ≥ 6 years were photographed using a smartphone camera app. The photos of 148 eligible participants were reviewed independently by a dental specialist, two general dentists, and two dental therapists, using predetermined TDI classification and criteria. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and inter-rater reliability were estimated to evaluate the diagnostic performance of the photographic method relative to the reference standard established by the dental specialist. Results: Of the 1,870 teeth screened, one-third showed TDI; and one-seventh of the participants had primary or mixed dentitions. Compared between the specialist's reference standard and four dental professionals' reviews, the diagnostic sensitivity and specificity for TDI versus non-TDI were 59–95% and 47–93%, respectively, with better performance for urgent types of TDI (78–89% and 99–100%, separately). The diagnostic consistency was also better for the primary/mixed dentitions than the permanent dentition. Conclusion: This study suggested a valid mHealth practice for remote assessment of TDI. A better diagnostic performance in the detection of urgent types of TDI and examination of the primary/mixed dentition was also reported. Future directions include professional development activities involving dental photography and photographic assessment, incorporation of a machine learning technology to aid photographic reviews, and randomized controlled trials in multiple clinical settings. [ABSTRACT FROM AUTHOR]

Targeted oxygen delivery during cardiopulmonary bypass (CPB) has received significant attention due to its influence on patient outcomes, especially in mitigating acute kidney injury. While it has gained popularity in select institutions, there remains a gap in establishing it globally across multiple centers. The purpose of this investigation was to describe the development of a quality improvement process of targeted oxygen delivery during CPB across hospitals throughout the United States. A systematic approach to utilize oxygen delivery index (DO2i) as a key performance indicator within hospitals serviced by a national provider of perfusion services. The process included a review of the current literature on DO2i, which yielded a target nadir value (272 mL/min/m2) and an area under the curve (DO2i272AUC) cut off of 632. All data is displayed on a dashboard with results categorized across multiple levels from system-wide to individual clinician performance. From January 2020 through December 2022, DO2i data from 91 hospitals and 11,165 coronary artery bypass graft procedures were collected. During this period the monthly proportion of DO2i measurements above the target nadir DO2i272 ranged from 60.5% to 78.4% with a mean+/−SD of 70.8 +/- 4.2%. Binary logistic regression for the first 7 months following monthly DO2i performance reporting has shown a statistically significant positive linear trend in the probability of achieving the target DO2i272 (p <.001), with a crude increase of approximately 7.8% for DO2i272AUC, and a 73.8% success rate (p <.001). A survey was sent to all individuals measuring oxygen delivery during CPB to assess why a target DO2i272 could not be reached. The two most common responses were an 'inability to improve CPB flow rates' and 'restrictive allogeneic red blood cell transfusion policies'. This study demonstrates that targeting a minimum level of oxygen delivery can serve as a key performance indicator during CPB using a structured quality improvement process. [ABSTRACT FROM AUTHOR]

This study determined the relationship between test anxiety and learning process distraction in private senior high schools. The descriptive research design was utilized and employed to the selected students through a survey with a total of 140 senior high school students as sample. Data Collection was done through a survey. Data analysis was done through mean, standard deviation, and pearson-r. Results revealed that the Level of of Test Anxiety with the mean of 3.22 and the Level of Learning Process Distraction with mean of 3.37 are all Moderately High, this means that item identified is sometimes manifested/observed. A positive correlation between the level of Test Anxiety and Learning Process Distraction in Private Senior High School was proven in the study. The findings affirmed that there is a significant relationship between the two variables. [ABSTRACT FROM AUTHOR]

Background: The TrialNet Oral Insulin (OI) prevention trial showed no overall treatment effect, using the diagnosis of type 1 diabetes as an endpoint. A significant delay in onset was only found in a high‐risk stratum (termed secondary stratum 1) of participants with low first‐phase insulin release (FPIR). Methods: Since trials with an endpoint of type 1 diabetes take years to complete, in this post hoc analysis, we assessed whether a novel combination of glucose and C‐peptide markers could identify a therapeutic benefit after 1 year of follow‐up (trial participants followed for a median 2.7 years). Results: Participants were relatives with multiple islet autoantibodies and low FPIR (n = 40). Glucose rose, and C‐peptide declined in the placebo group, whereas glucose rose minimally, and C‐peptide increased in the OI group. When glucose and C‐peptide were plotted on two‐dimensional grids using 30–120‐min oral glucose tolerance test (OGTT) time points, changes in ratios of their central points (centroid ratio) differed between groups (p = 0.037 adjusted for age, BMI, and baseline C‐peptide and glucose). Conclusions: These findings support a favorable early effect of OI on combined glucose and C‐peptide endpoints in high‐risk individuals, indicating metabolic benefit. With further study, these measures may allow for shorter trials compared to the standard endpoint of type 1 diabetes diagnosis. [ABSTRACT FROM AUTHOR]

Symptoms of the Post-COVID-19 Condition are often non-specific making it a challenge to distinguish them from symptoms due to other medical conditions. In this study, we compare the proportion of emergency department patients who developed symptoms consistent with the World Health Organization's Post-COVID-19 Condition clinical case definition between those who tested positive for Severe Acute Respiratory Syndrome Coronavirus-2 infection and time-matched patients who tested negative. Our results show that over one-third of emergency department patients with a proven acute infection meet Post-COVID-19 Condition criteria 3 months post-index visit. However, one in five test-negative patients who claim never having been infected also report symptoms consistent with Post-COVID-19 Condition highlighting the lack of specificity of the clinical case definition. Testing for SARS-CoV-2 during the acute phase of a suspected infection should continue until specific biomarkers of Post-COVID-19 Condition become available for diagnosis and treatment. In this study of more than 6500 emergency department patients, symptoms consistent with Long COVID are reported by 38.9% of SARS-CoV-2 test-positive and 20.7% of test-negative patients three months after their visit. A documented SARS-CoV-2 infection increased the risk fourfold of reporting Long COVID symptoms. [ABSTRACT FROM AUTHOR]

Advances in genomics and transcriptomics accompanying the rapid accumulation of omics data have provided new tools that have transformed and expanded the traditional concepts of model fungi. Evolutionary genomics and transcriptomics have flourished with the use of classical and newer fungal models that facilitate the study of diverse topics encompassing fungal biology and development. Technological advances have also created the opportunity to obtain and mine large datasets. One such continuously growing dataset is that of the Sordariomycetes, which exhibit a richness of species, ecological diversity, economic importance, and a profound research history on amenable models. Currently, 3,574 species of this class have been sequenced, comprising nearly one-third of the available ascomycete genomes. Among these genomes, multiple representatives of the model genera Fusarium, Neurospora, and Trichoderma are present. In this review, we examine recently published studies and data on the Sordariomycetes that have contributed novel insights to the field of fungal evolution via integrative analyses of the genetic, pathogenic, and other biological characteristics of the fungi. Some of these studies applied ancestral state analysis of gene expression among divergent lineages to infer regulatory network models, identify key genetic elements in fungal sexual development, and investigate the regulation of conidial germination and secondary metabolism. Such multispecies investigations address challenges in the study of fungal evolutionary genomics derived from studies that are often based on limited model genomes and that primarily focus on the aspects of biology driven by knowledge drawn from a few model species. Rapidly accumulating information and expanding capabilities for systems biological analysis of Big Data are setting the stage for the expansion of the concept of model systems from unitary taxonomic species/genera to inclusive clusters of well-studied models that can facilitate both the in-depth study of specific lineages and also investigation of trait diversity across lineages. The Sordariomycetes class, in particular, offers abundant omics data and a large and active global research community. As such, the Sordariomycetes can form a core omics clade, providing a blueprint for the expansion of our knowledge of evolution at the genomic scale in the exciting era of Big Data and artificial intelligence, and serving as a reference for the future analysis of different taxonomic levels within the fungal kingdom. [ABSTRACT FROM AUTHOR]

While extreme weather events are often localized, the potential effects on global forests can be far reaching due to the interconnected nature of forest product markets. To better understand these dynamics, this study leverages historical forest‐based wind damage data in the United States and applies this information as shocks within a global forest sector outlook model. A large, localized wind event modeled as a shock to the US South creates a one‐time increase of 18.7 million m3 from salvage harvest operations, equal to over 4% of national harvest. This crowds out traditional harvest activities, leading to downward pressure on prices in the short run, followed by a persistent effect that could take approximately 25 years to dissipate from markets. Average annual wind damage contributes downward pressure on roundwood prices between 1% and 4% in the United States, and this effect is distributed to other countries. The findings suggest that large, localized shocks reverberate across regions and wood product markets due to their interconnected supply chains and trade patterns, and these impacts have important temporal dynamics. Another key result is that the magnitude of these effects are offset by endogenous market reactions in other markets. In other words, unaffected regions change their harvesting patterns in order to compensate for changes in the availability of fiber, shedding light on the importance of capturing global channels as large shocks materialize in changes in market dynamics internationally. Monte Carlo simulations suggest a wide confidence band on salvage harvest rates and prices. Plain Language Summary: Extreme weather events can have significant impacts on global forests despite being localized, thanks to the interconnected nature of forest product markets. This study investigates this relationship by analyzing historical wind damage data from US forests. It finds that a major wind event in the US South led to a substantial increase in salvage harvest, equivalent to over 4% of the national harvest. This surge in harvest disrupted traditional activities, causing short‐term price drops and long‐lasting effects over about 25 years due to tree loss. Wind damage annually contributes to 1%–4% price decreases in US roundwood, affecting other countries too. The study emphasizes how such shocks ripple across regions and markets due to intertwined supply chains and trade patterns. It also highlights how unaffected regions adapt their harvesting to balance fiber availability, underscoring the importance of understanding global dynamics. Monte Carlo simulations reveal wide confidence bands on salvage harvest rates and prices, underlining the uncertainty surrounding these estimates. Key Points: Extreme weather events, while localized, but can have far reaching consequences on forests due to the interconnected wood product marketsThe effect of extreme weather events on wood product markets is mitigated through endogenous market reactions in other regions [ABSTRACT FROM AUTHOR]

Netherton syndrome (NS) is a rare autosomal recessive disorder that occurs due to a loss-of-function mutation in SPINK5; this loss results in significant inflammation, as well as perturbations of the skin barrier's integrity and functionality. While it is unclear which inflammatory pathways contribute to the development of NS, recent studies have demonstrated the expression of interleukin (IL)-17/IL-36, as well as several Th2 cytokines. Consequently, immunohistochemistry (IHC) with IL-36 may serve as a potential tool for aiding the histopathological diagnosis of this condition. In this case series, we present two cases of NS and capture their immunostaining pattern with IL-36. Both cases demonstrated robust expression of IL-36. This finding bolsters the hypothesis that NS is partially driven by Th17 activation and suggests the potential utility of IL-36 IHC as part of the workup for this rare and diagnostically elusive entity. LEKTI IHC was negative in one biopsy, revealing a limitation of this stain in diagnosing NS. [ABSTRACT FROM AUTHOR]

The mechanical response and fracture behavior of two architected 3D-printed hardened cement paste (hcp) elements, 'lamellar' and 'Bouligand', were investigated under uniaxial compression. A lab-based X-ray microscope was used to characterize the post-fracture crack pattern. The mechanical properties and crack patterns were analyzed and compared to cast hcp. The role of materials architecture and 3D-printing-induced weak interfaces on the mechanical properties and fracture behavior are discussed. The pore architecture that inadvertently forms in the design of solid architected materials dictated the overall mechanical response and fracture behaviors in both 3D-printed architected materials. While no specific crack pattern or microcracking was observed in the cast element, lamellar architecture demonstrated a crack pattern following weak vertical interfaces. Bouligand architectures, on the other hand, exhibited a helical crack pattern with distributed interfacial microcracking aligned with the helical orientation of filaments. As a result, the bouligand architected elements showed a significant 40% increase in work-of-failure compared to cast counterparts. The enhanced energy absorption was obtained without sacrificing the strength and was attributed to higher fractured surface and microcracking, both of which follow the weak helical interfaces. [ABSTRACT FROM AUTHOR]

Boreal chorus frogs (Pseudacris maculata Agassiz 1850) are a widespread amphibian in North America, but several populations are in decline. Specifically, we are developing captive breeding and reintroduction methods for the Great Lakes/St. Lawrence–Canadian Shield population. Here we present the effects of tadpole density, food variety, and addition of supplemental minerals to rearing water on the growth, development, and survival during the larval and metamorph/juvenile stages. We conducted two experiments using a factorial design. We found that low tadpole density (1 vs. 2 tadpoles/L) and high food variety (five food items vs. three food items) significantly increased tadpole body length and Gosner stage after 2 weeks (p <.001), increased survival to metamorphosis (p <.001), decreased time to metamorphosis (p <.001), and increased weight after metamorphosis (p <.001). On average, tadpoles in the high density/low food treatment, compared to the low density/high food, were 25% smaller after 2 weeks, had 3.9× lower survival to metamorphosis, took 1.25× longer to reach metamorphosis, and weighed 1.5× less after metamorphosis. In contrast, neither density (0.5 vs. 1 tadpole/L) nor mineral supplemented water affected growth and development, but tadpole survival was higher at 1 tadpole/L. Our findings demonstrate the feasibility of rearing boreal chorus frogs in captivity and provide guidelines for rearing this and similar species in a laboratory environment. [ABSTRACT FROM AUTHOR]

Background Antibiotic treatment for complicated urinary tract infections (cUTI)/acute pyelonephritis (AP) is often followed by recurrent bacteriuria in the absence of clinical symptoms. To understand factors predictive of clinical and microbiologic outcomes in patients with cUTI/AP, multivariable analyses were undertaken using pooled data from a global, phase 3 cUTI study. Methods Using data from 366 tebipenem pivoxil hydrobromide– and 378 ertapenem-treated patients from the Study to Assess the Efficacy, Safety and Pharmacokinetics of Orally Administered Tebipenem Pivoxil Hydrobromide (SPR994) Compared to Intravenous Ertapenem in Participants With Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP) infected with Enterobacterales uropathogens, multivariable analyses for dichotomous efficacy endpoints were performed using logistic regression and pharmacokinetic-pharmacodynamic relationships were evaluated. Results Urinary tract anatomical disorders and functional urinary tract or metabolic disorders were predictive of nonresponse across all efficacy endpoints assessed at test-of-cure (TOC) and late follow-up (LFU) visits, with greater impact on overall and microbiologic than clinical nonresponse. Independent variables predictive of increased probabilities of successful overall response at TOC and microbiologic response at TOC or LFU were baseline creatinine clearance >50 mL/min and baseline pathogen fluoroquinolone susceptibility. Infection with a phenotypic extended-spectrum beta-lactamase–positive Enterobacterales pathogen was predictive of reduced probabilities of success for microbiologic response at LFU and clinical response at TOC. Meaningful relationships between efficacy endpoints and plasma pharmacokinetic-pharmacodynamic indices were not identified. Conclusions Reductions of overall and microbiologic response in patients with cUTI/AP were associated with anatomical or functional urinary tract disorders, but not with the magnitude or duration of plasma antibiotic exposure. Results of these analyses serve to advance our understanding of factors predictive of outcome in patients with cUTI/AP. [ABSTRACT FROM AUTHOR]

A variety of LSD analogs have emerged in recent years with dual purposes of avoiding prosecution from possession while providing new options for those willing to experiment with hallucinogenic drugs. In this study, a previously published automated sample preparation method for LSD and its primary metabolite (OH‐LSD) was utilized to extract LSD, OH‐LSD, and nine LSD analogs from urine. The liquid chromatography tandem mass spectrometry (LC–MS/MS) method was modified from the previously published LC conditions to utilize a different analytical column and gradient elution program. Mobile phases of 10 mM ammonium formate with 0.1% formic acid in deionized water (mobile phase A) and 0.1% formic acid in methanol (mobile phase B) were employed. The method was validated to ANSI/ASB Standard 036 with a 0.1 ng/mL limit of detection for all analytes and was utilized for the analysis of 325 urine specimens. Although no LSD analogs were observed in the samples analyzed, this validated method was demonstrated to be suitable for the analysis of these compounds in laboratories seeking to expand their testing scope. Automated sample preparation allows for the efficient analysis of these analytically challenging compounds with minimal manual handling. Additionally, there was no increased analytical time burden when the LC column and gradient were modified to target nine additional analytes. Detection may improve as new reference standards are developed to allow laboratories to focus on the metabolic products of these analogs. For now, this validated procedure can assist with the routine analysis and surveillance of these emerging substances. [ABSTRACT FROM AUTHOR]

3D printing (3DP) technologies have transformed the processing of advanced ceramics for small‐scale and custom designs during the past three decades. Simple and complex parts are designed and manufactured using 3DP technologies for structural, piezoelectric, and biomedical applications. Manufacturing simple or complex geometries or one‐of‐a‐kind components without part‐specific tooling saves significant time and creates new applications for advanced ceramic materials. Although development and innovations in 3DP of ceramics are far behind compared with metals or polymers, with the availability of different commercial machines in recent years for 3DP of ceramics, exponential growth is expected in this field in the coming decade. This article details various 3DP technologies for advanced ceramic materials, their advantages and challenges for manufacturing parts for various applications, and perspectives on future directions. We envision this work will be helpful to advanced ceramic researchers in industry and academia who are using different 3DP processes in the coming days. [ABSTRACT FROM AUTHOR]

A diverse antibody repertoire is essential for humoral immunity. Antibody diversification requires the introduction of deoxyuridine (dU) mutations within immunoglobulin genes to initiate somatic hypermutation (SHM) and class switch recombination (CSR). dUs are normally recognized and excised by the base excision repair (BER) protein uracil-DNA glycosylase 2 (UNG2). However, FAM72A downregulates UNG2 permitting dUs to persist and trigger SHM and CSR. How FAM72A promotes UNG2 degradation is unknown. Here, we show that FAM72A recruits a C-terminal to LisH (CTLH) E3 ligase complex to target UNG2 for proteasomal degradation. Deficiency in CTLH complex components result in elevated UNG2 and reduced SHM and CSR. Cryo-EM structural analysis reveals FAM72A directly binds to MKLN1 within the CTLH complex to recruit and ubiquitinate UNG2. Our study further suggests that FAM72A hijacks the CTLH complex to promote mutagenesis in cancer. These findings show that FAM72A is an E3 ligase substrate adaptor critical for humoral immunity and cancer development. Antibody diversification relies on the intentional mutagenesis of immunoglobulin genes for adaptive immune responses. Here, the authors identified a CTLH E3 ubiquitin ligase complex that co-opts FAM72A to recruit and degrade the UNG2 base excision repair factor to permit mutagenesis. [ABSTRACT FROM AUTHOR]

Distracted driving is responsible for nearly 1 million crashes each year in the United States alone, and a major source of driver distraction is handheld phone use. We conducted a randomized, controlled trial to compare the effectiveness of interventions designed to create sustained reductions in handheld use while driving (NCT04587609). Participants were 1,653 consenting Progressive® Snapshot® usage-based auto insurance customers ages 18 to 77 who averaged at least 2 min/h of handheld use while driving in the month prior to study invitation. They were randomly assigned to one of five arms for a 10-wk intervention period. Arm 1 (control) got education about the risks of handheld phone use, as did the other arms. Arm 2 got a free phone mount to facilitate hands-free use. Arm 3 got the mount plus a commitment exercise and tips for hands-free use. Arm 4 got the mount, commitment, and tips plus weekly goal gamification and social competition. Arm 5 was the same as Arm 4, plus offered behaviorally designed financial incentives. Postintervention, participants were monitored until the end of their insurance rating period, 25 to 65 d more. Outcome differences were measured using fractional logistic regression. Arm 4 participants, who received gamification and competition, reduced their handheld use by 20.5% relative to control (P < 0.001); Arm 5 participants, who additionally received financial incentives, reduced their use by 27.6% (P < 0.001). Both groups sustained these reductions through the end of their insurance rating period. [ABSTRACT FROM AUTHOR]

Background: An abnormal postoperative lordosis distribution index (LDI), which quantifies the ratio between the lordosis at L4 to S1 and the lordosis at L1 to S1, contributes to the development of adjacent segment disease and increased revision rates in patients undergoing short-segment lumbar intervertebral fusions. Incorporating preoperative spinopelvic parameters and LDI into the surgical plan for short-segment fusion is important for guiding alignment restoration and preserving normal preoperative alignment in unfused segments. This study examined changes in LDI, segmental lordosis, and lordosis of the unfused levels in patients treated with personalized interbody cage (PIC) implants. Methods: This retrospective study evaluated radiographic measurements from 111 consecutively treated patients diagnosed with degenerative spinal conditions and treated with a short-segment fusion of L4 to L5, L5 to S1, or L4 to S1 using PIC implant(s) within 6 months of the fusion procedure. Comparisons of intervertebral lordosis for treated and untreated levels as well as LDI pre- and postoperatively were performed. Results: In patients with a preoperative hypolordotic distribution (LDI < 50%), statistically significant increases were found in LDI postoperatively, approaching the normal LDI range (LDI 50%-80%). Likewise, patients with hyperlordotic distribution preoperatively (LDI > 80%) experienced a decrease in LDI postoperatively, trending toward the normal range, although the changes were not statistically significant. Intervertebral lordosis for the L5 to S1 level increased significantly following the placement of a PIC in the normal and hypolordotic LDI groups. Changes in intervertebral lordosis for L5 to S1 were not significant for patients with preoperative hyperlordotic LDI. Reciprocal changes in intervertebral lordosis at L1 to L4 were not observed in any groups. Conclusions: PIC implants may provide a benefit for patients, particularly those with hypolordotic distributions preoperatively. They have the potential to further improve patient outcomes by helping surgeons to achieve patient-specific lordosis goals, which may help to reduce the risk of adjacent segment disease and revisions in patients undergoing short-segment lumbar intervertebral fusions. Clinical Relevance: Personalized implants can help surgeons achieve patient-specific alignment goals, potentially prevent adjacent segment disease, and reduce long-term reinterventions. [ABSTRACT FROM AUTHOR]

Background: Emerging data have highlighted the significance of planning and aligning total and segmental lumbar lordosis with pelvic morphology when performing short-segment fusion with the goal of reducing the risk of adjacent segment disease while also decreasing spine-related disability. This study evaluates the impact of personalized interbody implants in restoring pelvic incidence-lumbar lordosis (PI-LL) mismatch compared with a similar study using stock interbody implants. Methods: This multicenter retrospective analysis assessed radiographic pre- and postoperative spinopelvic alignment (PI-LL) in patients who underwent 1- or 2-level lumbar fusions with personalized interbody implants for degenerative (nondeformity) indications. The aim was to assess the incidence of malalignment (PI-LL = 10°) both before and after fusion surgery and to determine the rate of alignment preservation and/or correction in this population. Results: There were 135 patients included in this study. Of 83 patients who were aligned preoperatively, alignment was preserved in 76 (91.6%) and worsened in 7 (8.4%). Among the 52 preoperatively malaligned patients, alignment was restored in 23 (44.2%), and 29 (55.8%) were not fully corrected. Among patients who were preoperatively aligned, there was no statistically significant difference in either the "preserved" or "worsened" groups between stock devices and personalized interbody devices. In contrast, among patients who were preoperatively malaligned, there was a statistically significant increase in the "restored" group (P = 0.046) and a statistically significant decrease in the "worsened" groups in patients with personalized interbodies compared with historical stock device data (P < 0.05). Conclusions: Compared with a historical cohort with stock implants, personalized interbody implants in short-segment fusions have shown a statistically significant improvement in restoring patients to normative PI-LL. Using 3-dimensional preoperative planning combined with personalized implants provides an important tool for planning and achieving improvement in spinopelvic parameters. [ABSTRACT FROM AUTHOR]

Repeats can mediate rearrangements and recombination in plant mitochondrial genomes and plastid genomes. While repeat accumulations are linked to heightened evolutionary rates and complex structures in specific lineages, debates persist regarding the extent of their influence on sequence and structural evolution. In this study, 75 Plantago plastomes were analyzed to investigate the relationships between repeats, nucleotide substitution rates, and structural variations. Extensive repeat accumulations were associated with significant rearrangements and inversions in the large inverted repeats (IRs), suggesting that repeats contribute to rearrangement hotspots. Repeats caused infrequent recombination that potentially led to substoichiometric shifting, supported by long-read sequencing. Repeats were implicated in elevating evolutionary rates by facilitating localized hypermutation, likely through DNA damage and repair processes. This study also observed a decrease in nucleotide substitution rates for loci translocating into IRs, supporting the role of biased gene conversion in maintaining lower substitution rates. Combined with known parallel changes in mitogenomes, it is proposed that potential dysfunction in nuclear-encoded genes associated with DNA replication, recombination, and repair may drive the evolution of Plantago organellar genomes. These findings contribute to understanding how repeats impact organellar evolution and stability, particularly in rapidly evolving plant lineages. [ABSTRACT FROM AUTHOR]

Aims: The link between nocturia and cardiovascular disease (CVD) is frequently discussed in literature, yet the precise nature of this relationship remains poorly characterized. The existing literature was reviewed in order to address issues concerning the origin, diagnosis, management, and implications of the co‐occurrence of CVD and nocturia. Methods: This review summarizes literature and recommendations regarding the link between CVD and nocturia discussed during a think‐tank meeting held at the 2023 International Consultation on Incontinence‐Research Society. Results: Cardiovascular disorders are often underestimated contributors to nocturia, with various potential mechanisms influencing nighttime urination, such as impact on fluid retention, atrial natriuretic peptide, and glomerular filtration rate. The redistribution of fluid from leg edema in supine position can lead nocturnal polyuria (NP). Additionally, sleep disturbances due to nocturia in itself may lead to CVD through an increase in blood pressure, insulin resistance, and inflammation. Disrupted circadian rhythms (e.g., in sleep pattern and urine production) were identified as critical factors in most etiologies of nocturia, and their contribution is deemed imperative in future research and treatment approaches, particularly in the aging population. NP can be detected through a simple bladder diary and can even be used to distinguish cardiac from noncardiac causes of nocturia. For the treatment of NP, desmopressin can be effective in select patients, however, caution and close monitoring is warranted for those with CVD due to increased risk of side effects. Conclusions: Gaps were identified in the available evidence and clear cut recommendations were put forth for future research. It is essential to gain a deeper understanding of the mechanisms linking nocturia and CVD to develop optimal management strategies. [ABSTRACT FROM AUTHOR]

CD4+ T cells can either enhance or inhibit tumour immunity. Although regulatory T cells have long been known to impede antitumour responses1–5, other CD4+ T cells have recently been implicated in inhibiting this response6,7. Yet, the nature and function of the latter remain unclear. Here, using vaccines containing MHC class I (MHC-I) neoantigens (neoAgs) and different doses of tumour-derived MHC-II neoAgs, we discovered that whereas the inclusion of vaccines with low doses of MHC-II-restricted peptides (LDVax) promoted tumour rejection, vaccines containing high doses of the same MHC-II neoAgs (HDVax) inhibited rejection. Characterization of the inhibitory cells induced by HDVax identified them as type 1 regulatory T (Tr1) cells expressing IL-10, granzyme B, perforin, CCL5 and LILRB4. Tumour-specific Tr1 cells suppressed tumour rejection induced by anti-PD1, LDVax or adoptively transferred tumour-specific effector T cells. Mechanistically, HDVax-induced Tr1 cells selectively killed MHC-II tumour antigen-presenting type 1 conventional dendritic cells (cDC1s), leading to low numbers of cDC1s in tumours. We then documented modalities to overcome this inhibition, specifically via anti-LILRB4 blockade, using a CD8-directed IL-2 mutein, or targeted loss of cDC2/monocytes. Collectively, these data show that cytotoxic Tr1 cells, which maintain peripheral tolerance, also inhibit antitumour responses and thereby function to impede immune control of cancer.Type 1 regulatory T cells (Tr1) represent a major obstacle that compromises naturally occurring and therapeutically induced tumour-specific immunity. [ABSTRACT FROM AUTHOR]

Studying the nervous system underlying animal motor control can shed light on how animals can adapt flexibly to a changing environment. We focus on the neural basis of feeding control in Aplysia californica. Using the Synthetic Nervous System framework, we developed a model of Aplysia feeding neural circuitry that balances neurophysiological plausibility and computational complexity. The circuitry includes neurons, synapses, and feedback pathways identified in existing literature. We organized the neurons into three layers and five subnetworks according to their functional roles. Simulation results demonstrate that the circuitry model can capture the intrinsic dynamics at neuronal and network levels. When combined with a simplified peripheral biomechanical model, it is sufficient to mediate three animal-like feeding behaviors (biting, swallowing, and rejection). The kinematic, dynamic, and neural responses of the model also share similar features with animal data. These results emphasize the functional roles of sensory feedback during feeding. [ABSTRACT FROM AUTHOR]

The coordination of complex behavior requires knowledge of both neural dynamics and the mechanics of the periphery. The feeding system of Aplysia californica is an excellent model for investigating questions in soft body systems' neuromechanics because of its experimental tractability. Prior work has attempted to elucidate the mechanical properties of the periphery by using a Hill-type muscle model to characterize the force generation capabilities of the key protractor muscle responsible for moving Aplysia's grasper anteriorly, the I2 muscle. However, the I1/I3 muscle, which is the main driver of retractions of Aplysia's grasper, has not been characterized. Because of the importance of the musculature's properties in generating functional behavior, understanding the properties of muscles like the I1/I3 complex may help to create more realistic simulations of the feeding behavior of Aplysia, which can aid in greater understanding of the neuromechanics of soft-bodied systems. To bridge this gap, in this work, the I1/I3 muscle complex was characterized using force-frequency, length-tension, and force-velocity experiments and showed that a Hill-type model can accurately predict its force-generation properties. Furthermore, the muscle's peak isometric force and stiffness were found to exceed those of the I2 muscle, and these results were analyzed in the context of prior studies on the I1/I3 complex's kinematics in vivo. [ABSTRACT FROM AUTHOR]

Summary Pool sequencing is an efficient method for capturing genome-wide allele frequencies from multiple individuals, with broad applications such as studying adaptation in Evolve-and-Resequence experiments, monitoring of genetic diversity in wild populations, and genotype-to-phenotype mapping. Here, we present grenedalf, a command line tool written in C++ that implements common population genetic statistics such as θ , Tajima's D , and F ST for Pool sequencing. It is orders of magnitude faster than current tools, and is focused on providing usability and scalability, while also offering a plethora of input file formats and convenience options. Availability and implementation grenedalf is published under the GPL-3, and freely available at github.com/lczech/grenedalf. [ABSTRACT FROM AUTHOR]

Introduction: For patients with epidermal growth factor receptor-mutated (EGFRm) locally advanced/metastatic non-small cell lung cancer (mNSCLC) whose disease has progressed on or after osimertinib and platinum-based chemotherapy (PBC), no uniformly accepted standard of care exists. Moreover, limited efficacy of standard treatments indicates an unmet medical need, which is being addressed by ongoing clinical investigations, including the HERTHENA-Lung01 (NCT04619004) study of patritumab deruxtecan (HER3‑DXd). However, because limited information is available on real-world clinical outcomes in such patients, early-phase trials of investigational therapies lack sufficient context for comparison. This study describes the real-world clinical characteristics, treatments, and outcomes for patients with EGFRm mNSCLC who initiated a new line of therapy following previous osimertinib and PBC, including a subset matched to the HERTHENA-Lung01 population. Methods: This retrospective analysis used a US database derived from deidentified electronic health records. The reference cohort included patients with EGFRm mNSCLC who had initiated a new line of therapy between November 13, 2015 and June 30, 2021, following prior osimertinib and PBC. A subset of patients resembling the HERTHENA-Lung01 population was then extracted from the reference cohort; this matched subset was optimized using propensity score (PS) weighting. Endpoints were real-world overall survival (rwOS) and real-world progression-free survival (rwPFS). Confirmed real-world objective response rate (rwORR; partial/complete response confirmed ≥ 28 days later) was calculated for the response-evaluable subgroups of patients (with ≥ 2 response assessments spaced ≥ 28 days apart). Results: In the reference cohort (N = 273), multiple treatment regimens were used, and none was predominant. Median rwPFS and rwOS were 3.3 and 8.6 months, respectively; confirmed rwORR (response evaluable, n = 123) was 13.0%. In the matched subset (n = 126), after PS weighting, median rwPFS and rwOS were 4.2 and 9.1 months, respectively; confirmed rwORR (response evaluable, n = 57) was 14.1%. Conclusion: The treatment landscape for this heavily pretreated population of patients with EGFRm mNSCLC is fragmented, with no uniformly accepted standard of care. A high unmet need exists for therapeutic options that provide meaningful improvements in clinical benefit. [ABSTRACT FROM AUTHOR]