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Metagenomic studies have revolutionized the study of novel phages. However these studies trade depth of coverage for breadth. We show that the targeted sequencing of a small region of a phage terminase family can provide sufficient sequence diversity to serve as an individual-specific barcode or a "phageprint", defined as the relative abundance profile of the variants within a terminase family. By collecting ~700 oral samples from ~100 individuals living on multiple continents, we found a consistent trend wherein each individual harbors one or two dominant variants that coexist with numerous low-abundance variants. By tracking phageprints over the span of a month across ten individuals, we observed that phageprints were generally stable, and found instances of concordant temporal fluctuations of variants shared between partners. To quantify these patterns further, we built machine learning models that, with high precision and recall, distinguished individuals even when we eliminated the most abundant variants and further downsampled phageprints to 2% of the remaining variants. Except between partners, phageprints are dissimilar between individuals, and neither country-of-residence, genetics, diet nor cohabitation seem to play a role in the relatedness of phageprints across individuals. By sampling from six different oral sites, we were able to study the impact of millimeters to a few centimeters of separation on an individual's phageprint and found that such limited spatial separation results in site-specific phageprints. [ABSTRACT FROM AUTHOR]

Although Jewish people in the US are often racialized (i.e., perceived by others) as White, Jewish Americans vary in the extent to which they consider themselves White, and in how strongly they identify with being Jewish. Based on prior findings that identifying with a White ethnic subgroup (e.g., Irish, Italian) can reduce prejudice toward racial and ethnic minorities, we predicted that strongly identified Jewish Americans would exhibit less intergroup bias than weakly identified Jewish Americans. For the present research, we recruited participants whose religious affiliation was Jewish but who self-identified as racially White. In a preregistered correlational study, Jewish identification was associated with lower bias, whereas White identification was associated with greater bias, toward Whites relative to racial/ethnic minorities. The relationship between Jewish identification and intergroup bias was accounted for by high Jewish identifiers’ perceptions that they could personally contribute to diversity in groups and organizations. Across three meta-analyzed experiments, participants whose religious minority (Jewish) identity was made salient exhibited less intergroup bias than did control participants, and in one preregistered experiment, perceived personal contributions to diversity mediated the effect of condition on intergroup bias. Implications for the forms of ethnic identity that predict more versus less intergroup bias in an increasingly multicultural society are discussed. [ABSTRACT FROM AUTHOR]

Summary: Changes to flowering phenology are a key response of plants to climate change. However, we know little about how these changes alter temporal patterns of reproductive overlap (i.e. phenological reassembly).We combined long‐term field (1937–2012) and herbarium records (1850–2017) of 68 species in a flowering plant community in central North America and used a novel application of Bayesian quantile regression to estimate changes to flowering season length, altered richness and composition of co‐flowering assemblages, and whether phenological shifts exhibit seasonal trends.Across the past century, phenological shifts increased species' flowering durations by 11.5 d on average, which resulted in 94% of species experiencing greater flowering overlap at the community level. Increases to co‐flowering were particularly pronounced in autumn, driven by a greater tendency of late season species to shift the ending of flowering later and to increase flowering duration.Our results demonstrate that species‐level phenological shifts can result in considerable phenological reassembly and highlight changes to flowering duration as a prominent, yet underappreciated, effect of climate change. The emergence of an autumn co‐flowering mode emphasizes that these effects may be season‐dependent. [ABSTRACT FROM AUTHOR]

Purpose of Review: To reduce pain, improve function and possibly mitigate the risk for development of osteoarthritis in patients with functionally deficient meniscus pathology, meniscal allograft transplantation (MAT) can be used to restore native joint biomechanics and increase knee joint longevity. This review explores the senior author's preferred bridge-in-slot technique and recently published long-term clinical and radiographic outcomes following MAT. Recent Findings: Recent literature demonstrates MAT to be a safe and largely successful procedure for patients with functional meniscus deficiency. A majority of patients reach established minimal clinically important difference (MCID) values. Graft survivorship is approximately 80% at 10 years, significantly delaying and in some cases, preventing the need for future joint reconstruction procedures in these young patients. Return to sport rates are over 70%, revealing meniscal allografts can withstand high impact activities. Cartilage damage at the time of MAT increases the risk for graft and clinical failure, though this may be mitigated with a concomitant cartilage restoration procedure. Summary: Meniscal allograft transplantation can provide a durable and effective long-term solution to meniscal deficiency in symptomatic patients who wish to decrease the risk of symptomatic progression and possibly further osteoarthritis and continue activities of daily life and sports with less pain and more function. By restoring more normal joint biomechanics, MAT can mitigate the potential need for future knee arthroplasty in this young active patient population. [ABSTRACT FROM AUTHOR]

This article argues that a renewed focus on how dominant international practices produce ontological insecurity can help better orient ontological security studies (OSS) to injustice in world politics, particularly as it affects structurally marginalized political actors at multiple levels. It makes this case by bringing the work of Iris Marion Young to bear on OSS, particularly her theory of justice as the elimination of domination and oppression. Drawing on Young's "Five Faces of Oppression," this paper argues that multiple injustices endemic to the international system should be understood as key producers of ontological insecurity in the international system, both in their direct ability to destabilize identities and in their undermining of disadvantaged actors' ontological security-seeking practices. On international scales, these processes transcend levels of analysis, affecting individuals, social groups, and even states in differing ways. Incorporating Young's work into OSS not only helps build a vital bridge between the oft estranged sub-disciplines of political theory and IR, but also can provide scholars a means of better theorizing how ontological insecurity is so often a product of the international system's injustices. The paper thus concludes by proposing a normative turn within OSS, asking whether global justice should be understood as a precondition for ontological security-seeking among multiple co-existing actors. [ABSTRACT FROM AUTHOR]

This research delves into nature-inspired designs for creating materials with exceptional impact resistance, leveraging cutting-edge 3D printing techniques. Our composite design features a nacre-like outer layer combined with a tubulane-resembling core, aiming to enhance energy dissipation significantly. By emulating the dense aragonite structure found in natural nacre and the unique porosity of tubulane, we were able to enhance ballistic impact resistance. To validate its effectiveness, we conducted ballistics tests using a 40-grain lead-tipped .22 LR bullet at an initial velocity of 330.7 m/s, with a specialized chronograph setup to measure both initial and post-penetration bullet velocities, quantifying energy absorption precisely. This study opens new frontiers in aviation safety, structural engineering, and personal protective equipment, showcasing the transformative potential of biomimicry and additive manufacturing in advancing public safety and material science. [ABSTRACT FROM AUTHOR]

Summary: Drought‐induced xylem embolism is a primary cause of plant mortality. Although c. 70% of cycads are threatened by extinction and extant cycads diversified during a period of increasing aridification, the vulnerability of cycads to embolism spread has been overlooked.We quantified the vulnerability to drought‐induced embolism, pressure–volume curves, in situ water potentials, and a suite of xylem anatomical traits of leaf pinnae and rachises for 20 cycad species. We tested whether anatomical traits were linked to hydraulic safety in cycads.Compared with other major vascular plant clades, cycads exhibited similar embolism resistance to angiosperms and pteridophytes but were more vulnerable to embolism than noncycad gymnosperms. All 20 cycads had both tracheids and vessels, the proportions of which were unrelated to embolism resistance. Only vessel pit membrane fraction was positively correlated to embolism resistance, contrary to angiosperms. Water potential at turgor loss was significantly correlated to embolism resistance among cycads.Our results show that cycads exhibit low resistance to xylem embolism and that xylem anatomical traits – particularly vessels – may influence embolism resistance together with tracheids. This study highlights the importance of understanding the mechanisms of drought resistance in evolutionarily unique and threatened lineages like the cycads. [ABSTRACT FROM AUTHOR]

Background: Cancer‐related cognitive impairment (CRCI) and anxiety co‐occur in patients with cancer. Little is known about mechanisms for the co‐occurrence of these two symptoms. The purposes of this secondary analysis were to evaluate for perturbed pathways associated with the co‐occurrence of self‐reported CRCI and anxiety in patients with low versus high levels of these two symptoms and to identify potential mechanisms for the co‐occurrence of CRCI and anxiety using biological processes common across any perturbed neurodegenerative disease pathways. Methods: Patients completed the Attentional Function Index and the Spielberger State‐Trait Anxiety Inventory six times over two cycles of chemotherapy. Based on findings from a previous latent profile analysis, patients were grouped into none versus both high levels of these symptoms. Gene expression was quantified, and pathway impact analyses were performed. Signaling pathways for evaluation were defined with the Kyoto Encyclopedia of Genes and Genomes database. Results: A total of 451 patients had data available for analysis. Approximately 85.0% of patients were in the none class and 15.0% were in the both high class. Pathway impact analyses identified five perturbed pathways related to neurodegenerative diseases (i.e., amyotrophic lateral sclerosis, Huntington disease, Parkinson disease, prion disease, and pathways of neurodegeneration–multiple diseases). Apoptosis, mitochondrial dysfunction, oxidative stress, and endoplasmic reticulum stress were common biological processes across these pathways. Conclusions: This study is the first to describe perturbations in neurodegenerative disease pathways associated with CRCI and anxiety in patients receiving chemotherapy. These findings provide new insights into potential targets for the development of mechanistically based interventions. This study provides new information on associations between the co‐occurrence of cancer‐related cognitive impairment and anxiety and perturbations in neurodegenerative disease pathways. These findings suggest that biological processes associated with neurodegeneration may be associated with cancer‐related cognitive impairment and anxiety in patients with cancer receiving chemotherapy. [ABSTRACT FROM AUTHOR]

Objective To address challenges in large-scale electronic health record (EHR) data exchange, we sought to develop, deploy, and test an open source, cloud-hosted app "listener" that accesses standardized data across the SMART/HL7 Bulk FHIR Access application programming interface (API). Methods We advance a model for scalable, federated, data sharing and learning. Cumulus software is designed to address key technology and policy desiderata including local utility, control, and administrative simplicity as well as privacy preservation during robust data sharing, and artificial intelligence (AI) for processing unstructured text. Results Cumulus relies on containerized, cloud-hosted software, installed within a healthcare organization's security envelope. Cumulus accesses EHR data via the Bulk FHIR interface and streamlines automated processing and sharing. The modular design enables use of the latest AI and natural language processing tools and supports provider autonomy and administrative simplicity. In an initial test, Cumulus was deployed across 5 healthcare systems each partnered with public health. Cumulus output is patient counts which were aggregated into a table stratifying variables of interest to enable population health studies. All code is available open source. A policy stipulating that only aggregate data leave the institution greatly facilitated data sharing agreements. Discussion and Conclusion Cumulus addresses barriers to data sharing based on (1) federally required support for standard APIs, (2) increasing use of cloud computing, and (3) advances in AI. There is potential for scalability to support learning across myriad network configurations and use cases. [ABSTRACT FROM AUTHOR]

A woman in her 30s presents to the Differences in Sexual Development Programme at a tertiary care academic medical centre with vaginal stenosis and scarring. Her medical history is significant for virilisation in utero due to a maternal luteoma of pregnancy. Laboratory investigations at the time of birth showed elevated androgens in both mother and daughter. During infancy, she underwent clitoroplasty and vaginoplasty for correction of posterior vaginal fusion. She represented as an adult with vaginal stenosis, with associated physical and psychosocial implications. She was not able to insert a tampon or have penetrative intercourse. After examination and shared decisionmaking, the patient underwent cystoscopy, vaginoscopy and posterior vaginoplasty with the goal to create a normal calibre vagina. Postoperative dilator use was recommended to prevent restenosis of the introitus. In clinic follow-up, the patient was observed to have a normal calibre vagina. [ABSTRACT FROM AUTHOR]

Spermatogenesis produces male gametes from spermatogonial stem cells (SSC), beginning at puberty. Modern-day laboratory techniques allow for the long-term culture of SSC and in vitro spermatogenesis. The specific biochemical processes that occur during spermatogenesis remain poorly understood. One particular element of spermatogenesis that has yet to be characterized is the role of microRNAs (miRNA), short, non-transcribed RNAs that act as post-translational regulators of gene activity. In this study, we seek to describe the presence of miRNA in a two-dimensional (2D) SSC culture and a 3D human testis organoid (HTO) system. Testicular cells were isolated from the frozen tissue of three brain-dead subjects, propagated in cultures for four to five weeks, and used to form 3D HTOs. Following organoid formation, differentiation of testicular cells was induced. RNA was isolated from the whole testis tissue (WT) showing in vivo conditions, HTO Day Zero (2D SSC culture), Day 2 HTOs, and Day 23 differentiated HTOs, then analyzed for changes in miRNA expression using the Nanostring nCounter miRNA panel. One hundred ninety-five miRNAs met the criteria for expression in WT, 186 in 2D culture, 190 in Day 2 HTOs, and 187 in differentiated HTOs. One hundred thirty-three miRNAs were common across all conditions, and 41, 17, 6, and 11 miRNAs were unique for WT, 2D culture, Day 2 HTOs, and differentiated HTOs, respectively. Twenty-two miRNAs were similar between WT and differentiated HTOS. We evaluated the miRNA expression profiles of progressively complex stages of testicular cell culture, culminating in a 3D organoid model capable of meiotic differentiation, and compared these to WT. We identified a great variance between the native tissue and the culture system; however, some miRNAs are preserved. These data may provide avenues for deeper understanding of spermatogenesis and the ability to improve this process in the laboratory. Research on miRNA continues to be an essential avenue for understanding human spermatogenesis. [ABSTRACT FROM AUTHOR]

PURPOSE: To characterize the relationship between Decipher genomic classifier scores and prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)–based metastatic spread. MATERIALS AND METHODS: We identified patients from four institutions who underwent PSMA PET/CT scans pretreatment for primary staging or postradical prostatectomy (RP) for suspected recurrence and had Decipher transcriptomic data available from biopsy or RP specimens. PSMA PET/CT-based patterns of spread were classified as localized (miT + N0M0) or nonlocalized (miN1M0 or miM1a-c). We calculated the association between Decipher scores and the risk of nonlocalized disease on PSMA PET/CT using multivariable logistic regression for pretreatment patients and multivariable Cox regression for post-RP patients. We also compared select transcriptomic signatures between patients with localized and nonlocalized diseases. RESULTS: Five hundred eighty-six patients were included (pretreatment: n = 329; post-RP: n = 257). Higher Decipher scores were associated with nonlocalized disease on PSMA PET/CT both pretreatment (odds ratio, 1.18 [95% CI, 1.03 to 1.36] per 0.1 increase in Decipher score, P =.02) and post-RP (hazard ratio, 1.15 [95% CI, 1.05 to 1.27] per 0.1 increase in Decipher score, P =.003). In the pretreatment setting, nonlocalized disease was associated with higher rates of TP53 mutations and lower rates of PAM50 luminal A subtype compared with localized disease. In the post-RP setting, overexpression of signatures related to metabolism, DNA repair, and androgen receptor signaling were associated with higher rates of nonlocalized disease. CONCLUSION: Higher Decipher scores were associated with nonlocalized disease identified on PSMA PET/CT both pretreatment and post-RP. There were several transcriptomic differences between localized and nonlocalized diseases in both settings. [ABSTRACT FROM AUTHOR]

The monocyte–macrophage system plays an important role in phagocytosis of pathogens and cellular debris following infection or tissue injury in several pathophysiological conditions. We examined ENaC/ASIC subunit transcript expression and the importance of select subunits in migration of bone marrow derived monocytes (freshly isolated) and macrophages (monocytes differentiated in culture). We also examined the effect of select subunit deletion on macrophage phenotype. BM monocytes were harvested from the femurs of male and female WT and KO mice (6–12 weeks of age). Our results show that α, β, γENaC, and ASIC1‐5 transcripts are expressed in BM macrophages and monocytes to varying degrees. At least αENaC, βENaC, and ASIC2 subunits contribute to chemotactic migration responses in BM monocyte–macrophages. Polarization markers (CD86, soluble TNFα) in BM macrophages from mice lacking ASIC2a plus βENaC were shifted towards the M1 phenotype. Furthermore, select M1 phenotypic markers were recovered with rescue of βENaC or ASIC2. Taken together, these data suggest that βENaC and ASIC2 play an important role in BM macrophage migration and loss of βENaC and/or ASIC2 partially polarizes macrophages to the M1 phenotype. Thus, targeting ENaC/ASIC expression in BM macrophages may regulate their ability to migrate to sites of injury. [ABSTRACT FROM AUTHOR]

Malaria-causing protozoa of the genus Plasmodium have exerted one of the strongest selective pressures on the human genome, and resistance alleles provide biomolecular footprints that outline the historical reach of these species1. Nevertheless, debate persists over when and how malaria parasites emerged as human pathogens and spread around the globe1,2. To address these questions, we generated high-coverage ancient mitochondrial and nuclear genome-wide data from P. falciparum, P. vivax and P. malariae from 16 countries spanning around 5,500 years of human history. We identified P. vivax and P. falciparum across geographically disparate regions of Eurasia from as early as the fourth and first millennia bce, respectively; for P. vivax, this evidence pre-dates textual references by several millennia3. Genomic analysis supports distinct disease histories for P. falciparum and P. vivax in the Americas: similarities between now-eliminated European and peri-contact South American strains indicate that European colonizers were the source of American P. vivax, whereas the trans-Atlantic slave trade probably introduced P. falciparum into the Americas. Our data underscore the role of cross-cultural contacts in the dissemination of malaria, laying the biomolecular foundation for future palaeo-epidemiological research into the impact of Plasmodium parasites on human history. Finally, our unexpected discovery of P. falciparum in the high-altitude Himalayas provides a rare case study in which individual mobility can be inferred from infection status, adding to our knowledge of cross-cultural connectivity in the region nearly three millennia ago.Genomic analysis of Plasmodium DNA from 36 ancient individuals provides insight into the global distribution and spread of malaria-causing species during around 5,500 years of human history. [ABSTRACT FROM AUTHOR]

Stomatal anatomy and behaviour are key to managing gas exchange fluxes, which require coordination with the plant vascular system to adequately supply leaves with water. Stomatal response times and regulation of water loss are generally understudied in ferns, especially across habits (i.e. epiphytic and terrestrial) and habitats (i.e. wet mesic and dry xeric environments). Our objectives were to (i) determine if hydraulic and anatomical traits that control water use are correlated with their habitats (i.e. xeric, mesic) and habits (i.e. epiphytic, terrestrial) for ferns and lycophytes across taxa, and (ii) explore how those traits and others like average leaf water residence time correlate with stomatal function using a subset of closely related species. Epiphytic species had lower vein densities than terrestrial species, while xeric species had higher vein densities than mesic species. Xeric ferns also had smaller stomata than mesic ferns but had similar stomatal densities. Further, in a subset of mesic and xeric ferns, the xeric ferns had higher maximum stomatal conductance and water content, as well as shorter average stomatal opening responses to light intensity, but stomatal closing times did not differ. Finally, shorter stomatal opening and closing responses were correlated with shorter water residence time. Our study highlights anatomical and physiological differences between ferns and lycophytes, which may partially explain habitat preference based on their optimization of light and water. [ABSTRACT FROM AUTHOR]

Previous research suggests that underrepresentation in medical curricula perpetuates inequities in healthcare. This study aimed to quantify the prevalence of human phenotypic diversity (e.g., skin tone, sex, body size, and age) across 11 commonly used anatomy atlases and textbooks in pre‐clerkship medical education, published from 2015 to 2020. A systematic visual content analysis was conducted on 5001 images in which at least one phenotypic attribute was quantifiable. Anatomy images most prevalently portrayed light skin tones, males, persons with intermediate body sizes, and young to middle‐aged adults. Of the 3883 images in which there was a codable skin tone, 81.2% (n = 3154) depicted light, 14.3% (n = 554) depicted intermediate, and 4.5% (n = 175) depicted dark skin tones. Of the 2384 images that could be categorized into a sex binary, 38.4% (n = 915) depicted females and 61.6% (n = 1469) depicted males. A male bias persisted across all whole‐body and regional‐body images, including those showing sex organs or those showing characteristics commonly associated with a specific sex (e.g. for males, facial hair and/or muscle hypertrophy). Within sex‐specific contexts, darker skin was underrepresented, but male depictions displayed greater overall skin tone variation. Although most images could not be assigned to a body size or age category, when codable, these images overwhelmingly depicted adults (85.0%; 482 of 567) with smaller (34.7%; 93 of 268) or intermediate (64.6%; 173 of 268) body sizes. Ultimately, these outcomes provide reference metrics for monitoring ongoing and future efforts to address representation inequalities portrayed in anatomical imagery. [ABSTRACT FROM AUTHOR]

Stellar and black hole feedback heat and disperse surrounding cold gas clouds, launching gas flows off circumnuclear and galactic disks, producing a dynamic interstellar medium. On large scales bordering the cosmic web, feedback drives enriched gas out of galaxies and groups, seeding the intergalactic medium with heavy elements. In this way, feedback shapes galaxy evolution by shutting down star formation and ultimately curtailing the growth of structure after the peak at redshift 2–3. To understand the complex interplay between gravity and feedback, we must resolve both the key physics within galaxies and map the impact of these processes over large scales, out into the cosmic web. The Advanced X-ray Imaging Satellite (AXIS) is a proposed X-ray probe mission for the 2030s with arcsecond spatial resolution, large effective area, and low background. AXIS will untangle the interactions of winds, radiation, jets, and supernovae with the surrounding interstellar medium across the wide range of mass scales and large volumes driving galaxy evolution and trace the establishment of feedback back to the main event at cosmic noon. This white paper is part of a series commissioned for the AXIS Probe mission concept; additional AXIS white papers can be found at the AXIS website. [ABSTRACT FROM AUTHOR]

The digital economy is changing faster than the law can respond and has challenged legal systems worldwide. In the tax space, the digital economy has undermined traditional tax systems in ways that have created significant tax compliance and enforcement challenges, substantial tax revenue losses, and unwarranted distortions in the market between digital and traditional transactions. These problems are well recognized both in the legal literature and in the public sphere. Unfortunately, the legal reforms that are needed in this space have been slowed by a combination of technical, conceptual, and political impediments. This Article focuses on the digital tax landscape at the U.S. subnational level to demonstrate how those factors are preventing meaningful legal reform and why a novel approach to tax reform may be successful in breaking the current impasse. The difficulty of reform is particularly problematic in the tax context because reform ideally includes multijurisdictional uniformity on fundamental aspects like tax bases, the characterization of digital income, and sourcing rules. Legal reform is complicated enough on a unilateral basis. Asking for uniformity in those reforms across jurisdictions can seem all but impossible. To respond to these issues, many scholars apply a fiscal federalism lens to evaluate whether reform responsibility is better assigned to the U.S. federal government rather than to the states themselves. However, this Article disagrees that the digital tax impasse will be fixed through state or federal efforts alone. Instead, we argue that the conditions in this area of the law may require policymakers to explore a cooperative federalism framework. A cooperative federalism structure represents a middle-ground solution where Congress could use its resources to incentivize interstate uniformity but leave the substantive tax rulemaking to the states. This targeted type of federal intervention would better harness the strengths of both the federal and state governments, preserve state tax sovereignty, and overcome many of the shortcomings of past digital tax reform efforts. [ABSTRACT FROM AUTHOR]

We assessed the effect of visual learning and recall impairment on Victoria Symptom Validity Test (VSVT) accuracy and response latency for Easy, Difficult, and Total Items. A sample of 163 adult patients administered the VSVT and Brief Visuospatial Memory Test-Revised were classified as valid (114/163) or invalid (49/163) groups via independent criterion performance validity tests (PVTs). Classification accuracies for all VSVT indices were examined for the overall sample, and separately for subgroups based on visual memory functioning. In the overall sample, all indices produced acceptable classification accuracy (areas under the curve [AUCs] ≥ 0.79). When stratified by visual learning/recall impairment, accuracy indices yielded acceptable classification for both the unimpaired (AUCs ≥0.79) and impaired subsamples (AUCs ≥0.75). Latency indices had acceptable classification accuracy for the unimpaired subsample (AUCs ≥0.74), but accuracy and sensitivity dropped for the impaired sample (AUCs ≥0.67). VSVT accuracy and response latency yielded acceptable classification accuracies in the overall sample, and this effect was maintained in those with and without visual learning/recall impairment for the accuracy indices. Findings indicate that the VSVT is a psychometrically robust PVT with largely invariant cut-scores, even in the presence of bona fide visual learning/recall impairment. [ABSTRACT FROM AUTHOR]

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Dietary restriction (DR), the process of decreasing overall food consumption over an extended period of time, has been shown to increase longevity across evolutionarily diverse species and delay the onset of age-associated diseases in humans. In Caenorhabditis elegans, the Myc-family transcription factors (TFs) MXL-2 (Mlx) and MML-1 (MondoA/ChREBP), which function as obligate heterodimers, and PHA-4 (orthologous to FOXA) are both necessary for the full physiological benefits of DR. However, the adaptive transcriptional response to DR and the role of MML-1::MXL-2 and PHA-4 remains elusive. We identified the transcriptional signature of C. elegans DR, using the eat-2 genetic model, and demonstrate broad changes in metabolic gene expression in eat-2 DR animals, which requires both mxl-2 and pha-4. While the requirement for these factors in DR gene expression overlaps, we found many of the DR genes exhibit an opposing change in relative gene expression in eat-2;mxl-2 animals compared to wild-type, which was not observed in eat-2 animals with pha-4 loss. Surprisingly, we discovered more than 2000 genes synthetically dysregulated in eat-2;mxl-2, out of which the promoters of down-regulated genes were substantially enriched for PQM-1 and ELT-1/3 GATA TF binding motifs. We further show functional deficiencies of the mxl-2 loss in DR outside of lifespan, as eat-2;mxl-2 animals exhibit substantially smaller brood sizes and lay a proportion of dead eggs, indicating that MML-1::MXL-2 has a role in maintaining the balance between resource allocation to the soma and to reproduction under conditions of chronic food scarcity. While eat-2 animals do not show a significantly different metabolic rate compared to wild-type, we also find that loss of mxl-2 in DR does not affect the rate of oxygen consumption in young animals. The gene expression signature of eat-2 mutant animals is consistent with optimization of energy utilization and resource allocation, rather than induction of canonical gene expression changes associated with acute metabolic stress, such as induction of autophagy after TORC1 inhibition. Consistently, eat-2 animals are not substantially resistant to stress, providing further support to the idea that chronic DR may benefit healthspan and lifespan through efficient use of limited resources rather than broad upregulation of stress responses, and also indicates that MML-1::MXL-2 and PHA-4 may have distinct roles in promotion of benefits in response to different pro-longevity stimuli. [ABSTRACT FROM AUTHOR]

Genetically heterogeneous UM-HET3 mice born in 2020 were used to test possible lifespan effects of alpha-ketoglutarate (AKG), 2,4-dinitrophenol (DNP), hydralazine (HYD), nebivolol (NEBI), 16α-hydroxyestriol (OH_Est), and sodium thiosulfate (THIO), and to evaluate the effects of canagliflozin (Cana) when started at 16 months of age. OH_Est produced a 15% increase (p = 0.0001) in median lifespan in males but led to a significant (7%) decline in female lifespan. Cana, started at 16 months, also led to a significant increase (14%, p = 0.004) in males and a significant decline (6%, p = 0.03) in females. Cana given to mice at 6 months led, as in our previous study, to an increase in male lifespan without any change in female lifespan, suggesting that this agent may lead to female-specific late-life harm. We found that blood levels of Cana were approximately 20-fold higher in aged females than in young males, suggesting a possible mechanism for the sex-specific disparities in its effects. NEBI was also found to produce a female-specific decline (4%, p = 0.03) in lifespan. None of the other tested drugs provided a lifespan benefit in either sex. These data bring to 7 the list of ITP-tested drugs that induce at least a 10% lifespan increase in one or both sexes, add a fourth drug with demonstrated mid-life benefits on lifespan, and provide a testable hypothesis that might explain the sexual dimorphism in lifespan effects of the SGLT2 inhibitor Cana. [ABSTRACT FROM AUTHOR]

Biological resilience, broadly defined as the ability to recover from an acute challenge and return to homeostasis, is of growing importance to the biology of aging. At the cellular level, there is variability across tissue types in resilience and these differences are likely to contribute to tissue aging rate disparities. However, there are challenges in addressing these cell-type differences at regional, tissue, and subject level. To address this question, we established primary cells from aged male and female baboons between 13.3 and 17.8 years spanning across different tissues, tissue regions, and cell types including (1) fibroblasts from skin and from the heart separated into the left ventricle (LV), right ventricle (RV), left atrium (LA), and right atrium (RA); (2) astrocytes from the prefrontal cortex and hippocampus; and (3) hepatocytes. Primary cells were characterized by their cell surface markers and their cellular respiration was assessed with Seahorse XFe96. Cellular resilience was assessed by modifying a live-cell imaging approach; we previously reported that monitors proliferation of dividing cells following response and recovery to oxidative (50 µM-H2O2), metabolic (1 mM-glucose), and proteostasis (0.1 µM-thapsigargin) stress. We noted significant differences even among similar cell types that are dependent on tissue source and the diversity in cellular response is stressor-specific. For example, astrocytes had a higher oxygen consumption rate and exhibited greater resilience to oxidative stress (OS) than both fibroblasts and hepatocytes. RV and RA fibroblasts were less resilient to OS compared with LV and LA, respectively. Skin fibroblasts were less impacted by proteostasis stress compared to astrocytes and cardiac fibroblasts. Future studies will test the functional relationship of these outcomes to the age and developmental status of donors as potential predictive markers. [ABSTRACT FROM AUTHOR]

Context: Intervention studies for chronic ankle instability (CAI) often focus on improving physical impairments of the ankle complex. However, using an impairments-focused approach may miss psychological factors that may mediate function and recovery. Patient-reported outcome (PRO) measures can be used to assess several dimensions of the health-related quality of life (HRQoL) and deliver enhanced patient-centered care. Therefore, the purpose of this investigation was to evaluate group-level improvements in HRQoL and treatment response rates following various interventions in patients with CAI. Design: Cross-sectional. Methods: Data from 7 previous studies were pooled by the chronic ankle instability outcomes network for participant-level analysis, resulting in 136 patients with CAI. Several interventions were assessed including balance training, gait biofeedback, joint mobilizations, stretching, and strengthening, with treatment volume ranging from 1 to 4 weeks. Outcome measures were PROs that assessed ankle-specific function (Foot and Ankle Ability Measure), injury-related fear (Tampa Scale of Kinesiophobia and Fear Avoidance Belief Questionnaire), and global well-being (Disablement in the Physically Active); the PROs assessed varied between studies. Preintervention to postintervention changes were evaluated using separate Wilcoxon signed-rank tests and effect sizes, and a responder analysis was conducted for each PRO. Results: Significant, moderate to large improvements were observed in PROs that assessed ankle-specific function, injury-related fear, and global well-being following intervention (P <.001). Responder rates ranged from 39.0% to 53.3%, 12.8% to 51.4%, and 37.8% for ankle specific function, injury-related fear, and global well-being, respectively. Conclusions: Various interventions can lead to positive improvements in HRQoL in patients with CAI. Treatment response rates at improving HRQoL are similar to response rates at improving impairments such as balance, further reinforcing the need for individualized treatment approaches when treating a patient with CAI. [ABSTRACT FROM AUTHOR]

Age-related osteoarthritis (OA) is a degenerative joint disease characterized by pathological changes in nearly every intra- and peri-articular tissue that contributes to disability in older adults. Studying the etiology of age-related OA in humans is difficult due to an unpredictable onset and insidious nature. A barrier in developing OA modifying therapies is the lack of translational models that replicate human joint anatomy and age-related OA progression. The purpose of this study was to determine whether the common marmoset is a faithful model of human age-related knee OA. Semi-quantitative microCT scoring revealed greater radiographic OA in geriatric versus adult marmosets, and the age-related increase in OA prevalence was similar between marmosets and humans. Quantitative assessments indicate greater medial tibial cortical and trabecular bone thickness and heterogeneity in geriatric versus adult marmosets which is consistent with an age-related increase in focal subchondral bone sclerosis. Additionally, marmosets displayed an age-associated increase in synovitis and calcification of the meniscus and patella. Histological OA pathology in the medial tibial plateau was greater in geriatric versus adult marmosets driven by articular cartilage damage, proteoglycan loss, and altered chondrocyte cellularity. The age-associated increase in medial tibial cartilage OA pathology and meniscal calcification was greater in female versus male geriatric marmosets. Overall, marmosets largely replicate human OA as evident by similar 1) cartilage and skeletal morphology, 2) age-related progression in OA pathology, and 3) sex differences in OA pathology with increasing age. Collectively, these data suggest that the common marmoset is a highly translatable model of the naturally occurring, age-related OA seen in humans. [ABSTRACT FROM AUTHOR]

Objective: Misophonia is a psychiatric condition characterized by strong emotional and/or behavioral responses to auditory stimuli, leading to distress and functional impairment. Despite previous attempts to define and categorize this condition, misophonia is not currently included in the Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases. The lack of formal diagnostic consensus presents challenges for research aimed at assessing and treating this clinical presentation. Methods: The current study presents clinical characteristics of youth (N = 47) with misophonia in the largest treatment‐seeking sample to date. We examined demographic characteristics of the sample, frequency of comorbid disorders, frequency of specific misophonia symptoms (i.e., triggers, emotional and behavioral responses, and impairments), and caregiver‐child symptom agreement. Misophonia symptoms were evaluated using a multimodal assessment including clinician, youth, and caregiver reports on empirically established misophonia measures, and concordance among measures was assessed. Results: Youth seeking treatment for misophonia presented with marked misophonia symptoms and an array of comorbid conditions. Youth and caregivers identified various triggers of misophonia symptoms (e.g., chewing sounds, breathing sounds), as well as a wide range of emotional (e.g., anger, annoyance, disgust) and behavioral (e.g., aggression, avoidance) responses to triggers. Youth and caregivers exhibited high agreement on misophonia triggers but lower agreement on symptom severity and associated impairment. Compared to younger children (aged 8−13), older children (aged 14+) appeared to report symptom severity and associated impairment more reliably. Conclusion: Misophonia is a heterogenous and impairing clinical condition that warrants future investigation and evidence‐based treatment development. [ABSTRACT FROM AUTHOR]

Background: While the biomechanical properties of the native medial patellofemoral ligament (MPFL) have been well studied, there is no comprehensive summary of the biomechanics of MPFL reconstruction (MPFLR). An accurate understanding of the kinematic properties and functional behavior of current techniques used in MPFLR is imperative to restoring native biomechanics and improving outcomes. Purpose: To provide a comprehensive review of the biomechanical effects of variations in MPFLR, specifically to determine the effect of graft choice and reconstruction technique. Study Design: Systematic review. Methods: A systematic review was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 32 studies met inclusion criteria: (1) using ≥8 human cadaveric specimens, (2) reporting on a component of MPFLR, and (3) having multiple comparison groups. Results: Gracilis, semitendinosus, and quadriceps grafts demonstrated an ultimate load to failure (N) of 206.2, 102.8, and 190.0 to 205.0 and stiffness (N/mm) of 20.4, 8.5, and 21.4 to 33.6, respectively. Single-bundle and double-bundle techniques produced an ultimate load to failure (N) of 171 and 213 and stiffness (N/mm) of 13.9 and 17.1, respectively. Anchors placed centrally and superomedially in the patella produced the smallest degree of length changes throughout range of motion in contrast to anchors placed more proximally. Sutures, suture anchors, and transosseous tunnels all produced similar ultimate load to failure, stiffness, and elongation data. Femoral tunnel malpositioning resulted in significant increases in contact pressures, patellar translation, tilt, and graft tightening or loosening. Low tension grafts (2 N) most closely restored the patellofemoral contact pressures, translation, and tilt. Graft fixation angles variably and inconsistently altered contact pressures, and patellar translation and tilt. Conclusion: Data demonstrated that placement of the MPFLR femoral tunnel at the Schöttle point is critical to success. Femoral tunnel diameter should be ≥2 mm greater than graft diameter to limit graft advancement and overtensioning. Graft fixation, regardless of graft choice or fixation angle, is optimally performed under minimal tension with patellar fixation at the medial and superomedial patella. However, lower fixation angles may reduce graft strain, and higher fixation angles may exacerbate anisometry and length changes if femoral tunnel placement is nonanatomic. [ABSTRACT FROM AUTHOR]

Nuclear hormone receptors exist in dynamic equilibrium between transcriptionally active and inactive complexes dependent on interactions with ligands, proteins, and chromatin. The present studies examined the hypothesis that endogenous ligands activate peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in keratinocytes. The phorbol ester treatment or HRAS infection of primary keratinocytes increased fatty acids that were associated with enhanced PPARβ/δ activity. Fatty acids caused PPARβ/δ-dependent increases in chromatin occupancy and the expression of angiopoietin-like protein 4 (Angptl4) mRNA. Analyses demonstrated that stearoyl Co-A desaturase 1 (Scd1) mediates an increase in intracellular monounsaturated fatty acids in keratinocytes that act as PPARβ/δ ligands. The activation of PPARβ/δ with palmitoleic or oleic acid causes arrest at the G2/M phase of the cell cycle of HRAS-expressing keratinocytes that is not found in similarly treated HRAS-expressing Pparb/d-null keratinocytes. HRAS-expressing Scd1-null mouse keratinocytes exhibit enhanced cell proliferation, an effect that is mitigated by treatment with palmitoleic or oleic acid. Consistent with these findings, the ligand activation of PPARβ/δ with GW0742 or oleic acid prevented UVB-induced non-melanoma skin carcinogenesis, an effect that required PPARβ/δ. The results from these studies demonstrate that PPARβ/δ has endogenous roles in keratinocytes and can be activated by lipids found in diet and cellular components. [ABSTRACT FROM AUTHOR]

The most dynamically relaxed clusters of galaxies play a special role in cosmological studies as well as astrophysical studies of the intracluster medium (ICM) and active galactic nucleus feedback. While high-spatial-resolution imaging of the morphology of the ICM has long been the gold standard for establishing a cluster's dynamical state, such data are not available from current or planned surveys, and thus require separate, pointed follow-up observations. With optical and/or near-IR photometric imaging, and red-sequence cluster finding results from those data, expected to be ubiquitously available for clusters discovered in upcoming optical and millimeter-wavelength surveys, it is worth asking how effectively photometric data alone can identify relaxed cluster candidates, before investing in, e.g., high-resolution X-ray observations. Here we assess the ability of several simple photometric measurements, based on the redMaPPer cluster finder run on Sloan Digital Sky Survey data, to reproduce X-ray classifications of dynamical state for an X-ray selected sample of massive clusters. We find that two simple metrics contrasting the bright central galaxy (BCG) to other cluster members can identify a complete sample of relaxed clusters with a purity of ∼40% in our data set. Including minimal ICM information in the form of a center position increases the purity to ∼60%. However, all three metrics depend critically on correctly identifying the BCG, which is presently a challenge for optical red-sequence cluster finders. [ABSTRACT FROM AUTHOR]

Cadmium telluride (CdTe) solar cells represent a commercially successful photovoltaic technology, with an annual production capacity approaching 20 GW. However, improving the open‐circuit voltage (VOC) remains challenging. This study aims to deepen the understanding of charge carrier recombination in CdTe solar cells and to explore alternative dynamical characterization methods that address the limitations found in conventionally used time‐resolved photoluminescence for CdTe solar cells. Transient photovoltage and transient photocurrent techniques are utilized to investigate charge carrier dynamics under conditions resembling real‐world solar cell operation. The results reveal that an effective nonradiative recombination lifetime of 580 ns dominates the charge dynamics at VOC values below 850 mV. Above this threshold, radiative recombination becomes significant, with a radiative recombination coefficient of 1.1 × 10−9 cm3 s−1. Additionally, the stationary charge carrier density at 1 sun is determined to be around 1 × 1014 cm−3. By accurately determining both radiative and nonradiative recombination, this work provides a comprehensive understanding of carrier dynamics in high‐performing CdTe devices and paves the way for improving the VOC and performance of CdTe solar cells. [ABSTRACT FROM AUTHOR]

Stellar feedback-driven outflows are important regulators of the gas–star formation cycle. However, resolving outflow physics requires high-resolution observations that can only be achieved in very nearby galaxies, making suitable targets rare. We present the first results from the new VLT/MUSE large programme MAUVE (MUSE and ALMA Unveiling the Virgo Environment), which aims to understand the gas–star formation cycle within the context of the Virgo cluster environment. Outflows are a key part of this cycle, and we focus on the peculiar galaxy NGC 4383, which hosts a |$\sim\!\! 6\,$| kpc bipolar outflow fuelled by one of Virgo's most H  i -rich discs. The spectacular MUSE data reveal the clumpy structure and complex kinematics of the ionized gas in this M82-like outflow at 100 pc resolution. Using the ionized gas geometry and kinematics, we constrain the opening half-angle to θ = 25–35°, while the average outflow velocity is |$\sim\!\! 210\ \text{km} \, \text{s}^{-1}$|⁠. The emission line ratios reveal an ionization structure where photoionization is the dominant excitation process. The outflowing gas shows a marginally elevated gas-phase oxygen abundance compared to the disc but lower than the central starburst, highlighting the contribution of mixing between the ejected and entrained gas. Making some assumptions about the outflow geometry, we estimate an integrated mass outflow rate of |$\sim\!\! 1.8~\mathrm{M}_{\odot } \, \mathrm{yr}^{-1}$| and a corresponding mass-loading factor in the range of 1.7–2.3. NGC 4383 is a useful addition to the few nearby examples of well-resolved outflows, and will provide a useful baseline for quantifying the role of outflows within the Virgo cluster. [ABSTRACT FROM AUTHOR]

Powdery mildew is one of the most problematic diseases in strawberry production. To date, few commercial strawberry cultivars are deemed to have complete resistance and as such, an extensive spray programme must be implemented to control the pathogen. Here, a large-scale field experiment was used to determine the powdery mildew resistance status of leaf and fruit tissues across a diverse panel of strawberry genotypes. This phenotypic data was used to identify Quantitative Trait Nucleotides (QTN) associated with tissue- specific powdery mildew resistance. In total, six stable QTN were found to be associated with foliar resistance, with one QTN on chromosome 7D associated with a 61% increase in resistance. In contrast to the foliage results, there were no QTN associated with fruit disease resistance and there was a high level of resistance observed on strawberry fruit, with no genetic correlation observed between fruit and foliar symptoms, indicating a tissue-specific response. Beyond the identification of genetic loci, we also demonstrate that genomic selection can lead to rapid gains in foliar resistance across genotypes, with the potential to capture >50% of the genetic foliage resistance present in the population. To date, breeding of robust powdery mildew resistance in strawberry has been impeded by the quantitative nature of natural resistance and a lack of knowledge relating to the genetic control of the trait. These results address this shortfall, through providing the community with a wealth of information that could be utilized for genomic informed breeding, implementation of which could deliver a natural resistance strategy for combatting powdery mildew. [ABSTRACT FROM AUTHOR]

Electric grids with buses that are mapped to geographic latitude and longitude are useful for a growing number of applications, such as data visualization, geomagnetically induced current calculations, and multi-energy coupled infrastructure simulations. This paper presents a methodology for validating the quality of geographic coordinates for a power system model, and to assign coordinates to buses with missing or low-quality coordinates. This method takes advantage of geographic indicators already intrinsic to a grid model, such as branch length as implied by impedance and susceptance parameters. The coordinate assignment process uses an approach inspired by graph drawing, that lays out the vertices (buses) and edges (transmission lines), formulated as a nonlinear programming problem with soft edge length constraints. The layout method is very computationally fast and scalable to large power system cases. The method is demonstrated in this paper using a 37-bus test case and a 6717-bus test case, both publicly available, along with a large actual grid model. The results show that, for cases with only a few errors in the coordinates, cases with no coordinates known beforehand, and others in between, this method is able to assign reasonable geographic coordinates to best match known data about the grid. [ABSTRACT FROM AUTHOR]

Objective To evaluate the real-world performance of the SMART/HL7 Bulk Fast Health Interoperability Resources (FHIR) Access Application Programming Interface (API), developed to enable push button access to electronic health record data on large populations, and required under the 21st Century Cures Act Rule. Materials and Methods We used an open-source Bulk FHIR Testing Suite at 5 healthcare sites from April to September 2023, including 4 hospitals using electronic health records (EHRs) certified for interoperability, and 1 Health Information Exchange (HIE) using a custom, standards-compliant API build. We measured export speeds, data sizes, and completeness across 6 types of FHIR. Results Among the certified platforms, Oracle Cerner led in speed, managing 5-16 million resources at over 8000 resources/min. Three Epic sites exported a FHIR data subset, achieving 1-12 million resources at 1555-2500 resources/min. Notably, the HIE's custom API outperformed, generating over 141 million resources at 12 000 resources/min. Discussion The HIE's custom API showcased superior performance, endorsing the effectiveness of SMART/HL7 Bulk FHIR in enabling large-scale data exchange while underlining the need for optimization in existing EHR platforms. Agility and scalability are essential for diverse health, research, and public health use cases. Conclusion To fully realize the interoperability goals of the 21st Century Cures Act, addressing the performance limitations of Bulk FHIR API is critical. It would be beneficial to include performance metrics in both certification and reporting processes. [ABSTRACT FROM AUTHOR]

Meaning making efforts, such as perceiving posttraumatic growth (PPTG), may relate to mental health (MH), especially when creating meaning in life (MIL). We tested this assertion using mediation analyses to see whether PPTG leads to subsequent MH through MIL and if PPTG leads to increased MIL, which predicts increased MH. 402 Post-9/11 military veterans were assessed at baseline, 6 months (T2), and 12 months (T3) later. PPTG predicted subsequent MH, effects entirely mediated by T2 MIL. PPTG also predicted increased T2 MIL but not increased T3 MH, although increased T2 MIL led to increased T3 MH. Findings suggest a stable association between PPTG and MH, an effect fully mediated by MIL. Further, PPTG relates to subsequent MH only when resulting in increased MIL. Future research examining meaning making in studies of PPTG is needed to better understand the conditions under which PPTG is adaptive. [ABSTRACT FROM AUTHOR]

Simple Summary: Vitamin D3 is a steroid hormone that has been shown to prevent tumor growth in prostate cells. Not having enough vitamin D3 in the blood has been linked to advanced prostate cancer and mortality, especially in African American men. We wanted to understand how vitamin D affected pathways that keep prostate cells from becoming cancerous, which could lead to new therapeutic targets and treatments, especially for African American men who tend to be more prone to being vitamin D deficient compared to European men. Here, we studied a non-cancerous African American prostate cell line treated with the active form of vitamin D with a concentration similar to what is found in the body for 24 h. Using RNA whole-transcriptome sequencing, we compared these treated cells with untreated cells to assess genes and pathways significantly changed due to treatment. We found that vitamin D affected the activity of 1601 genes, mainly suppressing pathways linked to prostate cell movement, growth, and viability. Only two genes, ANLN and ECT2, were strongly correlated with prostate cancer prognosis and patients tended to have better survival rates when these genes were less active. Furthermore, downregulation of ANLN and ECT2 was also shown to repress signaling pathways involved in prostate cell movement, growth, malignant transformation, and viability. Our results suggest that vitamin D decreases the activity of these genes and could be important for preventing prostate cancer, especially for African American men. This could lead to the development of new treatments targeting specific genes and pathways involved in prostate cancer growth. Vitamin D3 is a steroid hormone that confers anti-tumorigenic properties in prostate cells. Serum vitamin D3 deficiency has been associated with advanced prostate cancer (PCa), particularly affecting African American (AA) men. Therefore, elucidating the pleiotropic effects of vitamin D on signaling pathways, essential to maintaining non-malignancy, may provide additional drug targets to mitigate disparate outcomes for men with PCa, especially AA men. We conducted RNA sequencing on an AA non-malignant prostate cell line, RC-77N/E, comparing untreated cells to those treated with 10 nM of vitamin D3 metabolite, 1α,25(OH)2D3, at 24 h. Differential gene expression analysis revealed 1601 significant genes affected by 1α,25(OH)2D3 treatment. Pathway enrichment analysis predicted 1α,25(OH)2D3- mediated repression of prostate cancer, cell proliferation, actin cytoskeletal, and actin-related signaling pathways (p < 0.05). Prioritizing genes with vitamin D response elements and associating expression levels with overall survival (OS) in The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA PRAD) cohort, we identified ANLN (Anillin) and ECT2 (Epithelial Cell Transforming 2) as potential prognostic PCa biomarkers. Both genes were strongly correlated and significantly downregulated by 1α,25(OH)2D3 treatment, where low expression was statistically associated with better overall survival outcomes in the TCGA PRAD public cohort. Increased ANLN and ECT2 mRNA gene expression was significantly associated with PCa, and Gleason scores using both the TCGA cohort (p < 0.05) and an AA non-malignant/tumor-matched cohort. Our findings suggest 1α,25(OH)2D3 regulation of these biomarkers may be significant for PCa prevention. In addition, 1α,25(OH)2D3 could be used as an adjuvant treatment targeting actin cytoskeleton signaling and actin cytoskeleton-related signaling pathways, particularly among AA men. [ABSTRACT FROM AUTHOR]

Purpose: Trochleoplasty has become increasingly utilised to address patellar instability in the setting of severe trochlear dysplasia. There remains a paucity of literature on the outcomes of 'thick'‐ versus 'thin'‐osteochondral flap trochleoplasty. The purpose of this study is to compare clinical and radiographic outcomes between patients with patellar instability with symptomatic trochlear dysplasia treated using a 'thick' versus 'thin' osteochondral flap trochleoplasty. Methods: A systematic review and meta‐analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines using a PRISMA checklist. Quality assessment of final articles was conducted by two blinded reviewers. Articles were separated based on the use of a 'thick' versus 'thin' flap trochleoplasty. Data collection consisted of recording the following variables: patient demographics, indications for trochleoplasty, mean follow‐up time, additional procedures performed during trochleoplasty, patient‐reported outcome measures (PROMs), radiographic outcomes (tibial tubercle‐trochlear groove [TT‐TG] distance, Caton–Deschamps Index [CDI] and sulcus angle [SA]) and the incidence of any postoperative complications and patellar redislocation rates. Results: A total of 24 studies, consisting of 927 patients, were identified as meeting inclusion criteria. A total of five papers described a 'thick' flap technique, while 19 papers described the use of a 'thin' flap technique. No significant difference in the mean improvement of Kujala scores was appreciated when comparing 'thick' versus 'thin' techniques (p > 0.05). Improvements in mean radiographic outcomes based on TT‐TG, CDI and SA were observed in both 'thick' and 'thin' flap trochleoplasty groups. The overall redislocation rate was 0.35%. Conclusion: No significant difference in Kujala scores was observed in patients undergoing trochleoplasty utilising 'thick' versus 'thin' technique, while improvements in mean TT‐TG, CDI and SA were noted in both technique groups, with an overall redislocation rate of 0.35%. Level of Evidence: Level IV. [ABSTRACT FROM AUTHOR]

High‐resolution records from past interglacial climates help constrain future responses to global warming, yet are rare. Here, we produce seasonally resolved climate records from subarctic‐Canada using micron‐scale measurements of oxygen isotopes (δ18O) in speleothems with apparent annual growth bands from three interglacial periods—Marine Isotope Stages (MIS) 11, 9, and 5e. We find 3‰ lower δ18O values during MIS 11 than MIS 5e, despite MIS 11 likely being warmer. We explore controls on high‐latitude speleothem δ18O and suggest low MIS 11 δ18O values reflect greater contribution of cold‐season precipitation to dripwater from longer annual ground thaw durations. Other potential influences include changes in precipitation source and/or increased fraction of cold‐season precipitation from diminished sea ice in MIS 11. Our study highlights the potential for high‐latitude speleothems to yield detailed isotopic records of Northern Hemisphere interglacial climates beyond the reach of Greenland ice cores and offers a framework for interpreting them. Plain Language Summary: Few climate records pre‐dating the last ice age exist from high‐latitude North America, which inhibits our understanding of how regions with permafrost responded to past warming and how they might change in the future. Here, we help fill this data gap by using six speleothems (cave mineral deposits) from a cave in the Northwest Territories, Canada to produce climate records that span thousands of years during former warm periods of Earth's history. We find that speleothems that grew during an exceptionally warm super‐interglacial period 400,000 years ago have 3‰ lower oxygen isotope (δ18O) values compared to those that grew during a likely cooler interglacial 125,000 years ago. We explore potential explanations for the difference in δ18O across interglacials, and suggest that lower δ18O values during warmer periods reflect greater infiltration of cool‐season precipitation with longer annual ground thaw durations. This study highlights the importance of high‐latitude speleothems to provide detailed climate records beyond the range available from Greenland ice cores. Key Points: Long high‐latitude terrestrial climate records are rare in the Northern HemisphereHigh‐latitude speleothems can provide ultra‐high‐resolution climate records beyond the reach of Greenland ice coresMean oxygen isotopes of Arctic and subarctic speleothems likely are controlled by annual ground thaw durations [ABSTRACT FROM AUTHOR]

Hypersonic vehicles must withstand extreme conditions during flights that exceed five times the speed of sound. These systems have the potential to facilitate rapid access to space, bolster defense capabilities, and create a new paradigm for transcontinental earth-to-earth travel. However, extreme aerothermal environments create significant challenges for vehicle materials and structures. This work addresses the critical need to develop resilient refractory alloys, composites, and ceramics. We will highlight key design principles for critical vehicle areas such as primary structures, thermal protection, and propulsion systems; the role of theory and computation; and strategies for advancing laboratory-scale materials to manufacturable flight-ready components. Hypersonic vehicles experience extreme temperatures, high heat fluxes, and aggressive oxidizing environments. Here, the authors highlight key materials design principles for critical vehicle areas and strategies for advancing laboratory-scale materials to flight-ready components. [ABSTRACT FROM AUTHOR]

The hybrid skyrmion, a type of magnetic skyrmion with intermediate helicity between Bloch and Néel skyrmion, has gained more attraction. It is tolerant toward the skyrmion Hall effect and a potential candidate for quantum bits. We investigated the stabilization and helicity control of the hybrid skyrmion in a two-dimensional magnetic system using an analytical model and micromagnetic simulation. We look at the interplaying factors of the bulk (Db) and interfacial (Di) Dzyaloshinskii–Moriya interactions (DMI) along with the dipolar interaction. We show that the hybrid skyrmion can stabilize through the interplay between interfacial DMI and either bulk DMI or dipolar interaction. We can also control the helicity of the hybrid skyrmion by tuning the ratio of D i / D b when there is no dipolar interaction, or simply by adjusting the Di when the Db is absent. Our results suggest that hybrid skyrmions can exist within 0 < | D i | < 0.4 mJ m−2 for Co-based magnetic systems. [ABSTRACT FROM AUTHOR]

Oral health plays a significant role in the quality of life and overall well-being of the aging population. However, age-related changes in oral health are not well understood due to challenges with current animal models. In this study, we analyzed the oral health and microbiota of a short-lived non-human primate (i.e., marmoset), as a step towards establishing a surrogate for studying the changes that occur in oral health during human aging. We investigated the oral health of marmosets using cadaveric tissues in three different cohorts: young (aged ≤6 years), middle-aged, and older (>10 years) and assessed the gingival bacterial community using analyses of the V3–V4 variable region of 16S rRNA gene. The oldest cohort had a significantly higher number of dental caries, increased dental attrition/erosion, and deeper periodontal pocket depth scores. Oral microbiome analyses showed that older marmosets had a significantly greater abundance of Escherichia-Shigella and Propionibacterium, and a lower abundance of Agrobacterium/Rhizobium at the genus level. Alpha diversity of the microbiome between the three groups showed no significant differences; however, principal coordinate analysis and non-metric multidimensional scaling analysis revealed that samples from middle-aged and older marmosets were more closely clustered than the youngest cohort. In addition, linear discriminant analysis effect size (LEFSe) identified a higher abundance of Esherichia-Shigella as a potential pathogenic biomarker in older animals. Our findings confirm that changes in the oral microbiome are associated with a decline in oral health in aging marmosets. The current study suggests that the marmoset model recapitulates some of the changes in oral health associated with human aging and may provide opportunities for developing new preventive strategies or interventions which target these disease conditions. [ABSTRACT FROM AUTHOR]

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