bluuebunny/crossref_metadata_2025 huggingface dataset:
Digest: Scarce pollen resources and asymmetric reproductive isolation
Authors: Gross Karin
Published: November 2024

What mechanisms cause asymmetries in reproductive success in crosses between closely related species that differ in floral style length? Feller et al. (2024) found that in 5 Phlox species, short-styled species produced smaller pollen grains than long-styled species. The smaller pollen of short-styled species lacked the resources to grow pollen tubes long enough to reach the ovules of long-styled species. This asymmetric pollen-style-length incompatibility may considerably affect patterns of gene flow among species.
Beyond Peto’s paradox: expanding the study of cancer resistance across species
Authors: Dujon Antoine M , Boddy Amy M , Hamede Rodrigo , Ujvari Beata , Thomas Frédéric
Published: November 2024

Peto’s paradox, which highlights the lower-than-expected cancer rates in larger and/or longer-lived species, is a cornerstone of discussions at the intersection of ecology, evolution, and cancer research. It prompts investigations into how species with traits that theoretically increase cancer risk manage to exhibit cancer resistance, with the ultimate goal of uncovering novel therapies for humans. Building on these foundational insights, we propose expanding the research focus to species that, despite possessing traits beyond size and longevity that theoretically increase their cancer risk, exhibit unexpected cancer resistance. Testing Peto’s paradox without interference from transient dynamics also requires considering species that are at an equilibrium between cancer risks and defenses, which is increasingly challenging due to anthropogenic activities. Additionally, we argue that transmissible cancers could significantly help in understanding how the metastatic process might be naturally suppressed. This research perspective is timely and aims to support the continued and in-depth identification of anti-cancer adaptations retained throughout evolution in the animal kingdom.
Megavariate methods capture complex genotype-by-environment interactions
Authors: Xavier Alencar , Runcie Daniel , Habier David
Published: November 2024

Genomic prediction models that capture genotype-by-environment (GxE) interaction are useful for predicting site-specific performance by leveraging information among related individuals and correlated environments, but implementing such models is computationally challenging. This study describes the algorithm of these scalable approaches, including 2 models with latent representations of GxE interactions, namely MegaLMM and MegaSEM, and an efficient multivariate mixed-model solver, namely Pseudo-expectation Gauss–Seidel (PEGS), fitting different covariance structures [unstructured, extended factor analytic (XFA), Heteroskedastic compound symmetry (HCS)]. Accuracy and runtime are benchmarked on simulated scenarios with varying numbers of genotypes and environments. MegaLMM and PEGS-based XFA and HCS models provided the highest accuracy under sparse testing with 100 testing environments. PEGS-based unstructured model was orders of magnitude faster than restricted maximum likelihood (REML) based multivariate genomic best linear unbiased predictions (GBLUP) while providing the same accuracy. MegaSEM provided the lowest runtime, fitting a model with 200 traits and 20,000 individuals in ∼5 min, and a model with 2,000 traits and 2,000 individuals in less than 3 min. With the genomes-to-fields data, the most accurate predictions were attained with the univariate model fitted across environments and by averaging environment-level genomic estimated breeding values (GEBVs) from models with HCS and XFA covariance structures.
Grandchild Care and Grandparents’ Well-Being in Context: The Impact of the COVID-19 pandemic
Authors: Bünning Mareike , Huxhold Oliver
Published: November 2024

Background and Objectives

This study investigates whether the association between supplementary grandchild care and grandparents’ subjective well-being—measured as life satisfaction, perceived stress, and loneliness—is moderated by the contextual environment. We use the coronavirus disease (COVID-19) pandemic as an example of contextual differences. Drawing on role theory, we argue that the costs and benefits of grandparenting may have differed between pandemic and prepandemic times. On the one hand, providing grandchild care during the pandemic may have been particularly stressful, prompting more negative effects on well-being. On the other hand, grandchild care may have been particularly relevant for enhancing well-being, as it protected grandparents from social isolation. Moreover, the association between grandparenting and well-being may have differed by gender.

Research Design and Methods

Using unbalanced panel data from the German Ageing Survey (DEAS) 2014 (n = 3,619), 2017 (n = 2,458), and 2020 (n = 2,021), we applied maximum likelihood structural equation modeling (ML-SEM)—a method that combines dynamic panel modeling with fixed-effects analysis—to examine whether there were differences in the relationship between grandchild care and grandparents’ well-being when comparing pandemic and prepandemic times and by grandparents’ gender.

Results

Grandchild care was associated with lower loneliness for both grandmothers and grandfathers. For grandfathers, this association was even stronger during the pandemic. Grandmothers experienced higher life satisfaction when taking care of grandchildren during the pandemic, but there was no evidence that grandchild care increased perceived stress for either grandmothers or grandfathers.

Discussion and Implications

In line with role enhancement theory, this study highlights that supplementary grandchild care can be beneficial for grandparents’ well-being. Moreover, the context in which grandchild care takes place shapes the costs and rewards associated with it. Our results suggest that supportive policies and programs facilitating grandchild care can enhance grandparents’ well-being, especially in challenging contexts.
Genetic and QTL analyses of sugar and acid content in sweet cherry (Prunus avium L.)
Authors: Gracia Clara , Calle Alejandro , Gasic Ksenija , Arias Esther , Wünsch Ana
Published: November 2024

Sweet cherry is very appreciated by consumers because of its attractive appearance and taste, which is determined by the balanced sweet–sour flavor. In this work, the genetics of soluble solid content (SSC), titratable acidity (TA), sugars, and organic acids was investigated in sweet cherry to facilitate breeding improvement for fruit quality. The fruits of five sweet cherry populations (N = 372), three F1 and two F2, were sampled over two years to evaluate SSC, TA, and the content of individual sugars (glucose, fructose, sorbitol, and sucrose) and organic acids (malic, quinic, oxalic, citric, and shikimic) by ultra-performance liquid chromatography. Glucose, followed by fructose, was the most abundant sugar, while malic acid was the predominant acid. Sorbitol and malic acid were the most stable compounds between years, and had the highest heritability, being also the best correlated to SSC and TA, respectively, revealing their relevance for breeding. Significantly positive correlations were observed among sugars and SSC, and acids and TA, but high interannual variability between years was observed for all traits. Quantitative trait loci (QTL) mapping for SSC, sugars, TA, and organic acids was performed using a multi-family approach with FlexQTL™. Twenty QTLs were detected consistently during the two phenotyped years, and several relevant regions with overlapping QTLs for sugars and acids were also identified. The results confirmed major stable SSC and TA QTLs on the linkage groups 4 and 6, respectively. Within the main LG4 SSC QTL region, where maturity and fruit development time QTLs have been previously detected, three stable sugar (glucose, sorbitol, and sucrose) and two acid (quinic, shikimic) QTLs were also identified, suggesting a pleiotropic effect of ripening date on the content of these compounds. The major malic acid QTL overlapped with TA QTL on LG6; thus, TA QTL mapping on LG6 may correspond to malic acid QTLs. Haplotype analyses of major SSC and sugars QTL on LG4, and TA and malic acid on LG6 revealed haplotypes of breeding interest. Several candidate genes previously identified in other Prunus fruit species, like peach, were found to collocate with the QTLs detected herein. This work reports QTLs regions and haplotypes of sugar and acid content in a Prunus nonclimacteric stone fruit for the first time.
Learning from the euro crisis: A new method of government for the European Union’s economic policy coordination after the pandemic
Authors: Fasone Cristina , Lupo Nicola
Published: November 2024

Has the European Union been able to learn from the experience of the euro crisis to shape its response to the economic consequences of the pandemic? This article aims to show that an effective learning process was set in motion in the aftermath of the pandemic emergency, although it looks still incomplete. To address the economic consequences of the COVID-19 outbreak and drawing on lessons from the euro crisis, a new method of government has been forged through the NextGenerationEU. Grounded in a creative interpretation of legal foundations and shaped by a process that is both national and European, involving domestic and supranational institutions, the governance of the Recovery and Resilience Facility (RRF) unfolds through the setting of EU-wide priorities, their articulation in national medium-term, performance-based plans, and continuous monitoring by the Commission to ensure compliance with multiple conditionality regimes. The first years of implementation of the RRF have proved successful not only for the use of the Fund by the member states but also for the spread of the RRF method of government in other areas of EU law, including the European Semester, REPowerEU, and the revised Stability and Growth Pact, despite the uncertainties surrounding the temporary nature of the instrument and some weaknesses in terms of democratic accountability.
High-affinity T cell receptor ImmTAC® bispecific efficiently redirects T cells to kill tumor cells expressing the cancer–testis antigen PRAME
Authors: Ribeiro Ana R , Britton-Rivet Camille , Collins Laura , Carreira Ricardo J , Moureau Sylvie , Benlahrech Adel , Stanhope Sarah , Harper Stephen , Liddy Nathaniel , Mahon Tara M , Petrovic Kristina , Fife Mark , Depoil David , Addis Philip , Bedke Nicole , Bouard Lucie , O’Dwyer Ronan , Gascoyne Duncan , Ranade Koustubh
Published: November 2024

Background

PRAME (Preferentially expressed Antigen in Melanoma) is a cancer–testis antigen expressed in several tumor indications, representing an attractive anticancer target. However, its intracellular location limits targeting by traditional methods. PRAME peptides are presented on the surface of tumor cells by human leukocyte antigen (HLA) molecules, indicating that a T cell receptor (TCR)-based strategy that redirects T cells to kill PRAME+ tumors could be a novel immunotherapeutic option. We confirm that PRAME protein is expressed in cutaneous melanoma, including rare subtypes with limited treatment options, as well as primary and metastatic lung, breast, endometrial, and ovarian tumors. Furthermore, PRAME is expressed homogeneously across tumors with distinct oncogenic mutations, mutation burden, PD-L1 expression, immune infiltration, and features of immune checkpoint resistance. Immunopeptidomic analysis of primary tumors detected HLA class I-restricted PRAME peptides.

Methods

A TCR recognizing PRAME peptide SLLQHLIGL was engineered to high affinity and fused to a CD3 engaging domain to create a TCRxCD3 bispecific molecule (Immune-mobilizing monoclonal TCR Against Cancer, ImmTAC®) with the ability to redirect polyclonal T cells to efficiently kill PRAME+ cells.

Rs

The degree of T cell activation was positively correlated with peptide–HLA abundance, with as few as 10 epitopes per cell sufficient for target cell killing. Impaired ImmTAC®-redirected cytotoxicity of exhausted T cells was rescued using an anti-PD-1 antibody, supporting the use of a combination strategy to treat tumors with active PDL1-PD1 axes.

Conclusions

Our data demonstrate selective and efficient T cell activation and killing by a PRAME-directed TCRxCD3 bispecific, supporting further investigation in multiple cancer indications.
Bacterial and fungal components of the microbiome have distinct roles in Hawaiian drosophila reproduction
Authors: Medeiros Matthew J , Seo Laura , Macias Aziel , Price Donald K , Yew Joanne Y
Published: November 2024

The microbiome provides numerous physiological benefits for host animals. The role of bacterial members of microbiomes to host physiology is well-documented. However, much less is known about the contributions and interactions of fungal members, even though fungi are integral components of many microbiomes, including those of humans and insects. Here, we used antibacterial and antifungal drugs to manipulate the gut microbiome of a Hawaiian picture-wing Drosophila species, Drosophila grimshawi, and identified distinct effects for each treatment on microbiome community stability, reproduction, and lipid metabolism. Female oogenesis, fecundity, and mating drive were significantly diminished with antifungal treatment. In contrast, male fecundity was affected by antibacterial but not antifungal treatment. For males and females, simultaneous treatment with both antibacterial and antifungal drugs resulted in severely reduced fecundity and changes in fatty acid levels and composition. Microbial transplants using frass harvested from control flies partially restored microbiome composition and female fecundity. Overall, our results reveal that antibacterial and antifungal treatments have distinct effects on host fecundity, mating behavior, and lipid metabolism, and that interkingdom interactions contribute to microbial community stability and reproduction.
Pregnancy affects maternal performance, feed intake, and digestion kinetics parameters in beef heifers
Authors: Moreira Gabriel Miranda , Aguiar Gleidson Luz , Meneses Javier Andrés Moreno , Nascimento Karolina Batista , Ramírez-Zamudio Germán Darío , Costa Thais Correia , Duarte Marcio de Souza , Casagrande Daniel Rume , Gionbelli Mateus Pies
Published: November 2024

This study aimed to quantify the effects of physiological status (PS) and the potential interaction of this factor with days of pregnancy (DOP) on beef heifers’ weight variation, intake, and digestion kinetics. Twelve rumen-cannulated zebu beef heifers (n = 7 pregnant; n = 5 nonpregnant) were used. Heifers were placed in individual pens and fed medium-quality corn silage plus a protein-based supplement. Heifers’ body weight was assessed at the beginning and end of each collection period. The feed intake was measured daily. Target outcomes were evaluated at 107, 170, 208, 240, 267, and 286 DOP. The apparent total-tract digestibility was determined considering the fecal spot collection, during 5 d within each collection period. Omasal and ruminal digesta samples were collected at 107, 208, and 267 DOP for determination of partial digestibilities and diet component outflow. For these purposes, Co-EDTA and indigestible neutral detergent fiber (iNDF) were used as indicators. All data were analyzed using a mixed model framework, considering the PS and DOP as fixed effects and the animal as a random effect. Significant differences were declared when P ≤ 0.05. Pregnant heifers showed an increase in body reserves (+35 kg) from 107 to 240 DOP, but experienced a decrease in shrunk body weight (−36 kg) from 240 to 286 DOP. The intake of dry matter (DM), organic matter (OM), crude protein (CP), and ash- and protein-free neutral detergent fiber (apNDF) increased as pregnancy progressed (P < 0.04). The apparent total-tract digestibility of DM tended to be lower (P = 0.09), and the apparent total-tract digestibility of apNDF was reduced (P < 0.01) in pregnant heifers. The digestibility of CP was higher (P < 0.01) on days 267 and 286 in pregnant cows compared to nonpregnant heifers. The ruminal digestibility of OM tended to be lower (P = 0.09) in pregnant beef heifers, while the ruminal digestibility of apNDF was lower (P = 0.02) in pregnant heifers compared to nonpregnant ones. The ruminal pool of wet matter and DM was lower (P ≤ 0.01) in pregnant heifers at 267 DOP. In all periods, the outflow tended to be greater (P = 0.06) in pregnant heifers compared to nonpregnant heifers. Pregnant beef heifers exhibited a faster (P = 0.01) digesta passage rate during late gestation. In conclusion, late-gestating beef heifers are less efficient in extracting energy from feed compared to nonpregnant animals.
Dietary bile acids alleviate corticosterone-induced fatty liver and hepatic glucocorticoid receptor suppression in broiler chickens
Authors: Liu Jie , Zhang Ke , Zhao Mindie , Chen Liang , Chen Huimin , Zhao Yulan , Zhao Ruqian
Published: November 2024

The aim of this study was to investigate the alleviating effects and mechanisms of bile acids (BA) on corticosterone-induced fatty liver in broiler chickens. Male Arbor Acres chickens were randomly divided into 3 groups: control group (CON), stress model group (CORT), and BA-treated group (CORT-BA). The CORT-BA group received a diet with 250 mg/kg BA from 21 d of age. From days 36 to 43, both the CORT and CORT-BA groups received subcutaneous injections of corticosterone to simulate chronic stress. The results indicated that BA significantly mitigated the body weight loss, liver enlargement, and hepatic lipid deposition caused by corticosterone (P < 0.05). Liver RNA-seq analysis showed that BA alleviated corticosterone-induced fatty liver by inhibiting lipid metabolism pathways, including fatty acid biosynthesis, triglyceride biosynthesis, and fatty acid transport. Additionally, BA improved corticosterone-induced downregulation of glucocorticoid receptor (GR) expression (P < 0.05). Molecular docking and cellular thermal shift assays revealed that hyodeoxycholic acid (HDCA), a major component of compound BA, could bind to GR and enhance its stability. In conclusion, BA alleviated corticosterone-induced fatty liver in broilers by inhibiting lipid synthesis pathways and mitigating the suppression of hepatic GR expression.
Ecological and social drivers of Mexican Wolf home range size across spatiotemporal scales
Authors: Lichwa-Schneringer Evelyn M , Cain James W , Wan Ho Yi , Fuller Genevieve , Millberry Cyrenea , Szykman Gunther Micaela
Published: November 2024

Elucidating factors influencing home range size is fundamental to the ecology and management of wildlife species, particularly those of conservation concern, because they can provide insight into how species utilize and interact with their environment. Variation in home range size can be related to intraspecific competition and social organization, energetic requirements in relation to habitat productivity, allometric relationships, and population density. The Mexican Gray Wolf (Canis lupus baileyi) is an endangered subspecies of the Gray Wolf whose home range size has not yet been studied. We examined ecological and social drivers of home range size of 22 Mexican Wolf packs between 2017 and 2021 across 4 biological time frames: annual; denning; post-denning; and non-denning. We used a 95% Brownian Bridge Movement Model home range estimator and generalized linear mixed-effect models to assess these relationships. Home range size was inversely correlated with estimated ungulate biomass, which was the most influential driver of home range size at annual and post-denning time frames. Larger packs utilized larger ranges during denning and post-denning time frames, while packs with larger litters had smaller ranges during the denning season. Snow depth was inversely related to home range size during the non-denning season. Our results indicate that both ecological and social factors are important and seasonally dependent in driving Mexican Wolf home range size. Use of a multiscale approach in future home range studies could discern relevant factors for species during time frames of interest.
Ticks and hemoplasma screening in dromedary camels (Camelus dromedarius) from Somalia
Authors: Collere Flávia C M , Ferrari Larissa D R , Osman Aamir M , Hassan-Kadle Ahmed A , Shair Mohamed A , Coradi Vanessa S , Ibrahim Abdalla M , Martins Thiago F , Yusuf Abdulkarim A , de Barros-Filho Ivan R , Lange Rogério R , André Marcos R , Vieira Thállitha S W J , Machado Rosangela Z , Vieira Rafael F C
Published: November 2024

Hemotropic mycoplasmas (hemoplasmas) are small pleomorphic bacteria that parasitize the surface of red blood cells of mammals. Hemoplasmas have been described in different species from the Camelidae Family, such as llamas and alpacas (South American camelids), but data on dromedary camels (Camelus dromedarius) are limited to a few reports. Somalia has one of the world’s largest dromedary camel populations, and studies on hemoplasmas and tick-borne pathogens are lacking. Accordingly, this study aimed to screen dromedaries from Somalia for hemoplasmas by PCR-based assays. A total of 155 dromedary camel blood samples from 2 different areas of Mogadishu (n = 104) and the Lower Shabelle Region (n = 51) of the country were collected. All blood DNA samples were screened for hemoplasmas using a SYBR Green Universal Real-Time PCR (qPCR), nested PCR (nPCR), and conventional PCR (cPCR) assays targeting the 16S rRNA gene of hemoplasmas. Five out of 155 animals (3.23%; 95% confidence interval [CI]: 1.39–7.33%) were positive for hemoplasmas. A total of 346 (228 M, 117 F, and 1 nymph) ticks were collected from 79/155 (50.9%; 95% CI: 42.8–59.1%) dromedary camels with a mean of 4.4 ticks per animal. Ticks were identified as Rhipicephalus pulchellus (174/346; 50.3%), Hyalomma dromedarii (103/346; 29.8%), Hyalomma rufipes (35/346; 10.1%), Hyalomma marginatum (16/346; 4.6%), Rhipicephalus humeralis (14/346; 4.0%), Amblyomma lepidum (2/346; 0.6%), Amblyomma gemma (1/346; 0.3%), and Ornithodoros sp. (1/185; 0.5). This is the first study on the molecular screening for hemoplasmas in dromedary camels from Somalia and the first report of A. lepidum and R. humeralis in Somali dromedary camels.
Advances in grape and pathogen genomics toward durable grapevine disease resistance
Authors: Paineau Manon , Zaccheo Mirella , Massonnet Mélanie , Cantu Dario
Published: November 2024

The future sustainability of viticulture depends on the development of grapevine cultivars with genetic resistance to diseases such as powdery mildew, downy mildew, and Pierce’s disease. Recent advances in grape and pathogen genomics have dramatically improved our approach to durable disease resistance. The availability of diploid genome references for wild species, combined with the ability to phase resistance haplotypes and conduct genome-wide association and expression analyses, has greatly enhanced our ability to dissect genetic resistance loci. This progress is yielding candidate genes that will form the foundation for precise breeding, gene stacking, and genome editing in grape improvement programs. As resistance genes are deployed in vineyards, pathogen populations evolve to adapt and evade these defenses, posing ongoing challenges. Understanding the adaptive mechanisms of grapevine pathogens in response to resistant cultivars is crucial. Grape pathogenomics is advancing rapidly, marked by the sequencing of many pathogen genomes, the discovery of effectors, including the first ones responsible for disease resistance breakdown, and the development of graph-based pangenomes. These advancements offer valuable insights into pathogen evolution and inform strategies for sustainable disease management. Together, these genomic tools and insights are paving the way for developing resilient grapevine varieties, ensuring the long-term sustainability of viticulture.
Mechanisms of Injury for Traumatic Brain Injury Among U.S. Military Service Members Before and During the COVID-19 Pandemic
Authors: Hai Tajrina , Agimi Yll , Deressa Tesfaye , Haddad Olivia
Published: November 2024

Objective

To understand the mechanisms of injury and demographic risk factors associated with traumatic brain injury (TBI) patients among active and reserve service members in the U.S. Military before and during the COVID-10 pandemic.

Methods

Active and reserve service members diagnosed with an incident TBI from January 2019 through September 2021 were selected. Traumatic brain injury patients diagnosed before March 1, 2020 were categorized as pre-COVID (PC), and patients diagnosed on or after March 1, 2020 were categorized as the intra-COVID (IC) group, aligning closely with the date when the World Health Organization officially proclaimed the pandemic. We determined the frequency of causes of injuries associated with TBI separate by sex, age, occupation, and TBI severity. In addition, we conducted multivariate logistic regression analyses to assess the demographic risk factors associated with TBI severity during the PC and IC eras.

Results

Our cohort included 48,562 TBI patients: 22,819 (47.0%) diagnosed during the PC era and 25,743 (53.0%) diagnosed during the IC era. The major mechanisms of injury within our TBI cohort were being struck by/against objects, falls/slips/trips, and motor vehicle traffic accidents before and during the pandemic. The most common causes of TBI were not impacted by COVID, but motor vehicle accidents did increase during the IC era. The mechanisms of injury associated with TBI differed by TBI severity: being struck by or against an object caused more mild and moderate TBI; motor vehicle accidents caused more severe TBI; and firearms was a major cause of penetrating TBI. In addition, the percentage of severe TBI because of firearms rose sharply during the IC era. Further, women were more likely to be diagnosed with mild TBI compared to men.

Conclusion

Military leaders should consider how different causes of injury are associated with differing TBI severities and how certain demographic groups were vulnerable to specific TBI severities when developing injury prevention programs.
STEMI in an Adolescent: A Critical Case of Kawasaki Disease
Authors: Robinson Nodia , Haran James B , Venkataraman Ramesh , Kisling Adam J
Published: November 2024

Acute coronary syndrome (ACS) is a rare cause of chest pain in adolescents and young adults. Kawasaki disease (KD) is an uncommon illness, but coronary artery aneurysms secondary to KD are implicated in approximately 5% of cases of ACS in young adults. Patients with KD may present with catastrophic coronary disease at a young age and thus early recognition of this disease process and lifelong follow-up is essential. Here we discuss a 19-year-old active duty male with no previously recognized medical history who presented with crushing chest pain while deployed. He was diagnosed with an ST elevation myocardial infarction and was found to have a giant aneurysm of the left main coronary artery with obstructive thrombus treated with emergent thrombectomy and balloon angioplasty. He developed cardiogenic shock requiring mechanical circulatory and ventilatory support. After a prolonged recovery and more in-depth history-taking, he was discovered to have been diagnosed with KD as a child without follow-up. Diagnosing ACS in young adults can be challenging, but a history of KD should increase suspicion for coronary disease. This case demonstrates the importance of screening after a childhood diagnosis of KD, specifically when caring for the tactical athlete. It also highlights the impact that social determinants of health can have on patient outcomes. Finally, it demonstrates the importance of communication and coordination between military and civilian medical centers across the globe driving the care of our deployed injured and ill active-duty military personnel.
Repeated Shifts in Sociality Are Associated With Fine-tuning of Highly Conserved and Lineage-Specific Enhancers in a Socially Flexible Bee
Authors: Jones Beryl M , Webb Andrew E , Geib Scott M , Sim Sheina , Schweizer Rena M , Branstetter Michael G , Evans Jay D , Kocher Sarah D
Published: November 2024

Comparative genomic studies of social insects suggest that changes in gene regulation are associated with evolutionary transitions in social behavior, but the activity of predicted regulatory regions has not been tested empirically. We used self-transcribing active regulatory region sequencing, a high-throughput enhancer discovery tool, to identify and measure the activity of enhancers in the socially variable sweat bee, Lasioglossum albipes. We identified over 36,000 enhancers in the L. albipes genome from 3 social and 3 solitary populations. Many enhancers were identified in only a subset of L. albipes populations, revealing rapid divergence in regulatory regions within this species. Population-specific enhancers were often proximal to the same genes across populations, suggesting compensatory gains and losses of regulatory regions may preserve gene activity. We also identified 1,182 enhancers with significant differences in activity between social and solitary populations, some of which are conserved regulatory regions across species of bees. These results indicate that social trait variation in L. albipes is associated with the fine-tuning of ancient enhancers as well as lineage-specific regulatory changes. Combining enhancer activity with population genetic data revealed variants associated with differences in enhancer activity and identified a subset of differential enhancers with signatures of selection associated with social behavior. Together, these results provide the first empirical map of enhancers in a socially flexible bee and highlight links between cis-regulatory variation and the evolution of social behavior.
Validation and next-generation update of a DNA methylation–based recurrence predictor for meningioma: A multicenter prospective study
Authors: Landry Alexander P , Wang Justin Z , Patil Vikas , Gui Chloe , Mamatjan Yasin , Patel Zeel , Yakubov Rebecca , Kaloti Ramneet , Habibi Parnian , Wilson Mark , Ajisebutu Andrew , Ellenbogen Yosef , Wei Qingxia , Singh Olivia , Sosa Julio , Mansouri Sheila , Wilson Christopher , Cohen-Gadol Aaron A , Virtanen Piiamaria , Burket Noah , Blackwell Matthew , Koenig Jenna , Alfonso Anthony , Davis Joseph , Zaazoue Mohamed A , Tabatabai Ghazaleh , Tatagiba Marcos , Behling Felix , Barnholtz-Sloan Jill S , Sloan Andrew E , Chotai Silky , Chambless Lola B , Mansouri Alireza , Ehret Felix , Capper David , Tsang Derek S , Aldape Kenneth , Gao Andrew ,   The International Consortium on Meningiomas (ICOM), Nassiri Farshad , Zadeh Gelareh
Published: November 2024

Background

We previously developed a DNA methylation–based risk predictor for meningioma, which has been used locally in a prospective fashion since its original publication. As a follow-up, we validate this model using a large prospective cohort and introduce a streamlined next-generation predictor compatible with newer methylation arrays.

Methods

Genome-wide methylation profiles were generated with the Illumina EPICArray. The performance of our next-generation predictor was compared with our original model and standard-of-care 2021 WHO grade using time-dependent receiver operating characteristic curves. An nomogram was generated by incorporating our methylation predictor with WHO grade and the extent of resection.

Results

A total of 1347 meningioma cases were utilized in the study, including 469 prospective cases from 3 institutions and an external cohort of 100 WHO grade 2 cases for model validation. Both the original and next-generation models significantly outperform the 2021 WHO grade in predicting early postoperative recurrence. Dichotomizing patients into grade-specific risk subgroups was predictive of outcomes within both WHO grades 1 and 2 tumors (P < .05), whereas all WHO grade 3 tumors were considered high-risk. Multivariable Cox regression demonstrated the benefit of adjuvant radiotherapy (RT) in high-risk cases specifically, reinforcing its informative role in clinical decision-making. Finally, our next-generation predictor contains nearly 10-fold fewer features than the original model, allowing for targeted arrays.

Conclusions

This next-generation DNA methylation–based meningioma outcome predictor significantly outperforms the 2021 WHO grading in predicting time to recurrence. We make this available as a point-and-click tool that will improve prognostication, inform patient selection for RT, and allow for molecularly stratified clinical trials.
Bilateral orthotopic lung transplantation for the patient with lung-limited invasive mucinous adenocarcinoma: a case-based literature review
Authors: Chae Young Kwang , Oh Youjin , Kim Leeseul , Park Joo Hee , Djunadi Trie Arni , Shah Zunairah , Chung Liam Il-Young , Yoon Sung Mi , Duan Richard , Lee Jeeyeon , Kim Samuel , Bharat Ankit
Published: November 2024

Invasive mucinous adenocarcinoma (IMA) of lung is a unique subset of adenocarcinomas characterized by an intrapulmonary aerogenous spread resulting in multicentric, multilobar, and bilateral lesions with a low frequency of distant metastasis. The treatment options for IMA are limited, and advanced IMA has a poor prognosis, with a median survival of less than a year. Lung transplantation performed in a handful of selected patients showed improved survival outcomes and clinical improvement. However, high postoperative recurrence rates have been observed and recurrence appeared to originate from the primary tumor in many cases. Techniques, such as non-sequential double lung transplantation utilizing cardiopulmonary bypass, have been performed to reduce recurrence. Here, we present the first case of bilateral lung transplantation employing cardiopulmonary bypass in a patient with stage ⅣA lung-limited IMA without lymph node or distant metastasis. At 15 months post-transplantation, the patient remains stable with no evidence of disease recurrence or organ rejection. Additionally, we describe the classification, clinical outcomes, protein expression, and genetic characteristics of IMA. IMA was previously classified as a subset of bronchioalveolar carcinoma (BAC), which is invasive and mucinous with goblet or columnar cells secreting mucin. We reviewed and summarized the lung transplantation cases reported to date for BAC. The 5-year overall survival and disease-free survival have been reported approximately 50% (range, 39-100) and 50% (range, 35–100), respectively. The literature shows these outcomes are comparable to bilateral lung transplantation performed for non-cancerous pulmonary disease.
Breast cancer incidence and mortality, by age, stage and molecular subtypes, by race/ethnicity in Canada
Authors: Wilkinson Anna N , Ng Carmina , Ellison Larry F , Seely Jean M
Published: November 2024

Background

Breast cancer (BC) characteristics and outcomes in Canada related to race/ethnicity are not currently documented.

Methods

Age-specific and age-standardized BC incidence and mortality rates, age distribution of cases, proportions of stage, and molecular subtypes were calculated for women aged 20+, by race/ethnicity, using 2006 and 2011 Canadian Census Health and Environment Cohort databases of linked census, cancer, and death data.

Results

In 47 105 BC cases, age-specific incidence rates were higher in Filipina (rate ratio (RR) = 1.27, 95%CI, 1.11-1.46) and multiethnicity (RR = 1.57, 95% CI, 1.18-2.08) compared to White women aged 40-49; and Filipina (RR = 1.16, 95% CI, 1.02-1.31) and Arab (RR = 1.3, 95% CI, 1.02-1.65) women aged 50-59. Median age at diagnosis was 63 among White women and 52-60 among other race/ethnicity groups, with 22.4%-41.1% of cases (P < .001) diagnosed before age 50 compared to 16.6% among White women. BC was diagnosed at stage I less frequently among Filipina (38.6%), Black (39.2%), South Asian (40.6%), and First Nations (40.7%) compared to White (46.5%) and Chinese (49.6%) (P < .05) women. Black women had higher proportions of BC diagnoses at stages III and IV combined (26.3%) than White women (17.0%, P = .001). The proportion of triple-negative BC among Black women (20.5%) was higher than among White (9.5%, P < .001). Compared to White, age-specific BC mortality rates were higher among Black women aged 40-49 (RR = 1.4, 1.06-1.85) as well as First Nations (RR = 1.21, 1.01-1.45) and Métis (RR = 1.48, 1.15-1.91) women aged 60-69.

Interpretation

Compared to White women, other Canadian women had an earlier peak age of BC diagnosis and higher proportions of cases diagnosed under age 50. Although many race/ethnicity groups had lower BC incidence and mortality than White, the higher age-specific BC mortality among Black 40-49 and First Nations and Métis women 60-69 merits further investigation.
Catch the wind: Optimizing wind turbine power generation by addressing wind veer effects
Authors: Gao Linyue , Milliren Christopher , Dasari Teja , Knoll Alexander A , Hong Jiarong
Published: November 2024

Wind direction variability with height, known as “wind veer,” results in power losses for wind turbines (WTs) that rely on single-point wind measurements at the turbine nacelles. To address this challenge, we introduce a yaw control strategy designed to optimize turbine alignment by adjusting the yaw angle based on specific wind veer conditions, thereby boosting power generation efficiency. This strategy integrates modest yaw offset angles into the existing turbine control systems via a yaw-bias-look-up table, which correlates the adjustments with wind speed, and wind veer data. We evaluated the effectiveness of this control strategy through extensive month-long field campaigns for an individual utility-scale WT and at a commercial wind farm. This included controlling one turbine using our strategy against nine others in the vicinity using standard controls with LiDAR-derived wind veer data and a separate 2.5 MW instrumented research turbine continuously managed using our method with wind profiles provided by meteorological towers. Results from these campaigns demonstrated notable energy gains, with potential net gains exceeding 10% during extreme veering conditions. Our economic analysis, factoring in various elements, suggests an annual net gain of up to approximately $700 K for a 100-MW wind farm, requiring minimal additional investment, with potential for even larger gains in offshore settings with the power of individual turbines exceeding 10 MW nowadays. Overall, our findings underscore the considerable opportunities to improve individual turbine performance under realistic atmospheric conditions through advanced, cost-effective control strategies.
Effectiveness of non-invasive brain stimulation on depressive symptoms targeting prefrontal cortex in functional magnetic resonance imaging studies: a combined systematic review and meta-analysis
Authors: Xiao Yao , Dong Shuai , Pan Chunyu , Guo Huiling , Tang Lili , Zhang Xizhe , Wang Fei
Published: November 2024

The prefrontal cortex (PFC) is a critical non-invasive brain stimulation (NIBS) target for treating depression. However, the alterations of brain activations post-intervention remain inconsistent and the clinical moderators that could improve symptomatic effectiveness are unclear. The study aim was to systematically review the effectiveness of NIBS on depressive symptoms targeting PFC in functional magnetic resonance imaging (fMRI) studies. In our study, we delivered a combined activation likelihood estimation (ALE) meta-analysis and meta-regression. Until November 2020, three databases (PubMed, Web of Science, EMBASE) were searched and 14 studies with a total sample size of 584 were included in the ALE meta-analysis; after NIBS, four clusters in left cerebrum revealed significant activation while two clusters in right cerebrum revealed significant deactivation (P < 0.001, cluster size >150 mm3). Eleven studies were statistically reanalyzed for depressive symptoms pre–post active-NIBS and the pooled effect size was very large [(d = 1.82, 95%CI (1.23, 2.40)]; significant moderators causing substantial heterogeneity (Chi squared = 75.25, P < 0.01; I2 = 87%) were detected through subgroup analysis and univariate meta-regression. Multivariate meta-regression was then conducted accordingly and the model suggested good fitness (Q = 42.32, P < 0.01). In all, NIBS targeting PFC balanced three core depressive-related neurocognitive networks (the salience network, the default mode network, and the central executive network); the striatum played a central role and might serve as a candidate treatment biomarker; gender difference, treatment-resistant condition, comorbidity, treatment duration, and localization all contributed to moderating depressive symptoms during NIBS. More high-quality, multi-center randomized controlled trails delivering personalized NIBS are needed for clinical practice in the future.
Retina in Clinical High-Risk and First-Episode Psychosis
Authors: Demirlek Cemal , Arslan Berat , Eyuboglu Merve S , Yalincetin Berna , Atas Ferdane , Cesim Ezgi , Demir Muhammed , Uzman Ozbek Simge , Kizilay Elif , Verim Burcu , Sut Ekin , Baykara Burak , Kaya Mahmut , Akdede Berna B , Bora Emre
Published: November 2024

Background and Hypothesis

Abnormalities in the retina are observed in psychotic disorders, especially in schizophrenia.

Study Design

Using spectral-domain optical coherence tomography, we investigated structural retinal changes in relatively metabolic risk-free youth with clinical high-risk (CHR, n = 34) and first-episode psychosis (FEP, n = 30) compared with healthy controls (HCs, n = 28).

Study Results

Total retinal macular thickness/volume of the right eye increased in FEP (effect sizes, Cohen’s d = 0.69/0.66) and CHR (d = 0.67/0.76) compared with HCs. Total retinal thickness/volume was not significantly different between FEP and CHR. Macular retinal nerve fiber layer (RNFL) thickness/volume of the left eye decreased in FEP compared with HCs (d = −0.75/−0.66). Peripapillary RNFL thickness was not different between groups. The ganglion cell (GCL), inner plexiform (IPL), and inner nuclear (INL) layers thicknesses/volumes of both eyes increased in FEP compared with HCs (d = 0.70–1.03). GCL volumes of both eyes, IPL thickness/volume of the left eye, and INL thickness/volume of both eyes increased in CHR compared with HCs (d = 0.64–1.01). In the macula, while central sector thickness/volume decreased (d = −0.62 to −0.72), superior outer (peri-foveal) sector thickness/volume of both eyes increased (d = 0.81 to 0.86) in FEP compared with HCs.

Conclusions

The current findings suggest that distinct regions and layers of the retina may be differentially impacted during the emergence and early phase of psychosis. Consequently, oculomics could play significant roles, not only as a diagnostic tool but also as a mirror reflecting neurobiological changes at axonal and cellular levels.
Precancerous Lesions of HPV-independent Vulvar Squamous Cell Carcinoma: Clinicopathologic Consideration of an Evolving Spectrum
Authors: Watkins Jaclyn , Fadare Oluwole
Published: November 2024

HPV-independent squamous cell carcinomas of the vulva comprise the majority of vulvar cancers, but their putative precancers represent only a small proportion of the vulvar squamous intraepithelial lesions that are encountered in routine practice. The precancerous lesions of HPV-independent vulvar squamous cell carcinoma encompass a spectrum of lesions that, collectively, may pose significant diagnostic challenges. Included in this spectrum are differentiated vulvar intraepithelial neoplasia [dVIN], the prototypical lesion of the group, which is characterized by a high propensity for progression, a relatively short duration to progression, frequent association with lichen sclerosus, and according to our review of the recent literature, TP53/p53 aberration in 50% to 95% (mean 77.4%) of cases. Regarding the latter, some authors consider TP53/p53 aberration to be a diagnostic requirement for dVIN, although this is controversial, as discussed further herein. Also included in the spectrum of lesions that are considered in this review are possibly related HPV-independent, p53-wild type lesions that have historically been reported as “vulvar acanthosis with altered differentiation” (VAAD), “differentiated exophytic vulvar intraepithelial lesion” (DEVIL), “verruciform lichen simplex chronicus” (vLSC), and which more recently, have collectively been described as “verruciform acanthotic vulvar intraepithelial neoplasia (vaVIN)” or “vulvar aberrant maturation (VAM).” In this review, we perform a comprehensive clinicopathologic review of putative precancerous lesions of HPV-independent squamous cell carcinomas of the vulva, with an emphasis on recent developments in terminology, practical diagnostic issues, biomarkers, and pathogenesis.
Ovarian Sex Cord-Stromal Neoplasms: An Overview of Molecular Events and How to Correlate Morphology With Molecular Findings
Authors: Rabban Joseph T. , McCluggage W. Glenn
Published: November 2024

Since the discovery in 2009 that missence pathogenic variants/mutations in FOXL2 are extremely common in ovarian adult granulosa cell tumours, the last 2 decades have witnessed significant developments in our understanding of the molecular events underlying the pathogenesis of other ovarian sex cord-stromal tumours (SCSTs). In this review, we cover the molecular events in ovarian SCSTs and provide practical guidance to the reporting pathologist as to how and when molecular testing may be useful in diagnosis. We stress the need to correlate the morphology and molecular since most of the molecular events are not entirely specific for a particular tumour type and our knowledge is continually evolving with the elucidation of “new” molecular events. We also discuss that in some tumours, molecular testing is helpful in triaging the patient for genetic referral and germline testing since some of the molecular events may be germline in nature.
Early Conservative Physical Therapy Management of Babies With Obstetric Brachial Plexus Injury to Facilitate Spontaneous Recovery
Authors: Mahrouck Hanan , Almatrafi Nahla , Tamboosi Mohammad
Published: November 2024

Objective:

To evaluate the effect of early immobilization and proper handling techniques in infants with Obstetric Brachial Plexus Injury (OBPI) in the first 2 weeks of life.

Method:

Six 1-day-old infants (2 males and 4 females) with OBPI were included. The assessments were done at baseline, post-intervention, and 3-month follow-up, which involved a physical exam, Narakas classification, Active Movement Scale, and gross and fine motor skills evaluation.

Result:

All infants had upper Erb’s palsy. They had statistically significant improvement in the Active Movement Scale scores post-intervention with a large effect size. These improvements were maintained at follow-up. All infants achieved age-appropriate gross and fine motor skills with the affected upper limb at 3 months of age.

Conclusion:

Early conservative physical therapy management had a statistically significant effect on enhancing spontaneous recovery and preventing further nerve injury in OBPI infants.