bluuebunny/crossref_metadata_2025 huggingface dataset:
Cortical tracking of speakers’ spectral changes predicts selective listening
Authors: Cervantes Constantino Francisco , Caputi Ángel
Published: December 2024

A social scene is particularly informative when people are distinguishable. To understand somebody amid a “cocktail party” chatter, we automatically index their voice. This ability is underpinned by parallel processing of vocal spectral contours from speech sounds, but it has not yet been established how this occurs in the brain’s cortex. We investigate single-trial neural tracking of slow frequency modulations in speech using electroencephalography. Participants briefly listened to unfamiliar single speakers, and in addition, they performed a cocktail party comprehension task. Quantified through stimulus reconstruction methods, robust tracking was found in neural responses to slow (delta-theta range) modulations of frequency contours in the fourth and fifth formant band, equivalent to the 3.5–5 KHz audible range. The spectral spacing between neighboring instantaneous frequency contours (ΔF), which also yields indexical information from the vocal tract, was similarly decodable. Moreover, EEG evidence of listeners’ spectral tracking abilities predicted their chances of succeeding at selective listening when faced with two-speaker speech mixtures. In summary, the results indicate that the communicating brain can rely on locking of cortical rhythms to major changes led by upper resonances of the vocal tract. Their corresponding articulatory mechanics hence continuously issue a fundamental credential for listeners to target in real time.
Freezing delay of water droplets in a vacuum caused by polyol addition
Authors: Yoshioka Takuya , Kusumoto Tamon , Handa Takefumi , Arakawa Masashi , Terasaki Akira
Published: December 2024

Droplets of pure water and polyol aqueous solutions with a diameter of several tens of micrometers were introduced into a vacuum to observe their freezing processes. The freezing time, i.e. the time elapsed from droplet generation to freezing, was found to become delayed as the polyol concentration increases. It was also found that the freezing time does not show significant dependence on the type of polyol at the same concentration. The observed delay caused by the addition of polyols is explainable by a plausible decrease in the homogeneous-ice nucleation temperature rather than by a drop in the vapor pressure.
Uncharged Lewis superacidic silicon complexes—perfluoropinacolato-stabilized systems for homogenous catalysis
Authors: Hanusch Franziska , Franz Daniel , Inoue Shigeyoshi
Published: December 2024

Lewis superacids are defined as species that exceed the Lewis acidity of SbF5, which was known as the strongest Lewis acid until the isolation of C6H5FAl(OC(CF3)3)3 in 2008. While strong Lewis acids and their prospects in synthesis and catalysis have been recognized for a long time, uncharged and four-coordinated silanes have been overlooked until recent years. In this contribution, we want to highlight the special features of highly Lewis acidic and Lewis superacidic tetranes. Specifically, we put emphasis on the synthesis, characterization, and catalytic application of silanes and germanes, stabilized by the perfluoropinacolato ligand. Our findings are put into context with previously prepared Lewis superacidic silanes [e.g. bis(catecholato)tetranes and Si(OTf)4 (OTf = trifluoromethanesulfonate)].
Lower Respiratory Tract Infections Following Respiratory Syncytial Virus Monoclonal Antibody Nirsevimab Immunization Versus Placebo: Analysis From a Phase 3 Randomized Clinical Trial (MELODY)
Authors: Arbetter Doug , Gopalakrishnan Vancheswaran , Aksyuk Anastasia A , Ahani Bahar , Chang Yue , Dagan Ron , Esser Mark T , Hammitt Laura L , Mankad Vaishali S , Saez-Llorens Xavier , Shen David , Leach Amanda , Kelly Elizabeth J , Villafana Tonya , Wilkins Deidre
Published: December 2024

Background

Nirsevimab is an extended half-life, highly potent, anti-respiratory syncytial virus (RSV) fusion protein neutralizing monoclonal antibody with efficacy against RSV-associated medically attended (MA) lower respiratory tract infection (LRTI) in infants and medically vulnerable children (aged ≤24 months). This post hoc exploratory analysis examined the incidence of LRTI from RSV and other respiratory pathogens during MELODY: a 2:1 randomized, double-blind, placebo-controlled, phase 3 study of nirsevimab in healthy term and late preterm (ie, gestational age ≥35 weeks) infants entering their first RSV season.

Methods

A total of 3012 participants were randomized to nirsevimab (n = 2009) or placebo (n = 1003). Nasopharyngeal swabs were collected from infants who presented with an LRTI and tested for 22 different respiratory pathogens using the BioFire® Respiratory 2.1 Panel. Incidence of RSV and non-RSV MA-LRTIs through day 511 and LRTI severity were assessed.

Results

A total of 852 nasopharyngeal swabs were collected from 561 participants through day 511: 519 swabs from 337 nirsevimab participants and 333 swabs from 224 placebo participants. RSV and non-RSV infections were detected in 193 of 852 (22.7%) and 55 of 852 (64.7%) swabs, respectively. RSV infection rates were lower with nirsevimab compared with placebo, including RSV–rhinovirus/enterovirus coinfections. Rates of other viral infections were similar between study arms. Approximately 70% of single RSV infections and RSV coinfections were adjudicated as mild, and 26.2% of single RSV infections and 24.5% of RSV coinfections required hospitalization.

Conclusions

Nirsevimab protected against RSV single and coinfections, with no evidence of replacement of RSV with other respiratory viruses.

Clinical Trials Registration. NCT03979313.
Gastric conduit in patients with previous endoscopic resection of the stomach for esophageal squamous cell carcinoma
Authors: Kwon Yelee , Yun Jae Kwang , Lee Geun Dong , Choi Se Hoon , Kim Yong-Hee , Kim Hyeong Ryul
Published: December 2024

This study investigated the clinical outcomes of gastric conduits for esophageal reconstruction in esophageal squamous cell carcinoma (ESCC) patients who had previously undergone endoscopic resection of the stomach. From January 2006 to April 2023, a total of 1964 patients underwent surgery for esophageal cancer at our institution. After initially excluding 125 of these cases due to a histology other than ESCC, we identified 147 patients in the remaining population who had previously undergone a gastric endoscopic resection, among which 56 patients (67.0 ± 6.5 years) were included in the present study cohort. A gastric conduit event was defined as any new lesions at the gastric conduit. The diagnoses of a previous gastric lesion included early gastric cancer (EGC) in 32 patients (57.1%), adenoma in 23 patients (41.1%), and dysplasia in 1 (1.8%) patient. The endoscopic procedures involved an endoscopic submucosal dissection (ESD) in 36 patients (64.3%) and an endoscopic mucosal resection in 20 patients (35.7%). The 10-year event-free survival rate for the gastric conduit was 43.7%. Five patients were diagnosed with metachronous gastric neoplasm (EGC in two and adenoma in three patients). Endoscopic procedures were available for all five cases, but one patient with a metachronous EGC required a colon interposition with a total gastrectomy. In ESCC patients who have undergone an endoscopic resection of their gastric lesions, subsequent esophageal reconstruction with a gastric conduit could be a viable option if followed by regular endoscopic surveillance for the early detection and endoscopic curability of any lesions.
Effect of low-dose administration of carperitide for acute heart failure: the LASCAR-AHF trial
Authors: Honda Satoshi , Nagai Toshiyuki , Honda Yasuyuki , Nakano Hiroki , Kawabata Takanori , Maeda Hirotada , Asakura Koko , Iwakami Naotsugu , Takenaka Sakae , Kato Yoshiya , Tokuda Yusuke , Yamane Takafumi , Furukawa Yutaka , Kitai Takeshi , Asaumi Yasuhide , Nishihara Shuzo , Mizuno Atsushi , Yamaguchi Tetsuo , Noguchi Teruo , Yasuda Satoshi , Anzai Toshihisa
Published: December 2024

Aims

The effects of low-dose carperitide on long-term clinical outcomes of patients with acute heart failure (AHF) have not yet been fully elucidated. This study aimed to evaluate the effects of low-dose intravenous carperitide on the long-term clinical outcomes of patients with AHF.

Methods and results

In this multicentre, open-label, randomized controlled trial, 247 patients with AHF received low-dose carperitide intravenously with standard treatment or matching standard treatment for 72 h from November 2014 to March 2021 across nine sites in Japan. The primary endpoint was a composite of all-cause death and heart failure hospitalization within 2 years. The primary endpoint was observed in 36 of 122 patients (29.5%) and 35 of 125 patients (28.0%) in the carperitide group and standard treatment groups, respectively [hazard ratio 1.26; 95% confidence interval (CI) 0.78–2.06, P = 0.827]. No significant differences were observed in the secondary endpoints, including cumulative urine volume at 72 h; change in the degree of dyspnoea over 72 h; and changes in brain natriuretic peptide, cystatin C, renin, aldosterone, and catecholamine levels at 72 h post-randomization between the groups. A greater decrease in the estimated glomerular filtration rate was observed in the carperitide group compared with the standard treatment group (inter-group difference −3.9 mL/min/1.73 m2; 95% CI −7.0 to −0.8).

Conclusion

In patients with AHF, low-dose carperitide did not reduce long-term mortality or hospitalization events when combined with standard treatment. Because patient enrolment was terminated prematurely, the study was underpowered and inconclusive.
End-stage heart failure and heart transplant in cardiac sarcoidosis: a case series
Authors: Scuppa Maria Francesca , Accietto Antonella , Corsini Anna , Graziosi Maddalena , Biagini Elena , Baldovini Chiara , Sabatino Mario , Potena Luciano
Published: December 2024

Background

Diagnosing cardiac sarcoidosis (CS) is challenging. Immunosuppressive therapies are less effective in end-stage disease, and often heart transplant (HT) is the only available option. We present a series of advanced CS cases, requiring HT, along with a review of the literature evidence in this field.

Case summary

Case 1: a 49-year-old man initially suspected of having arrhythmogenic cardiomyopathy (ACM) presented with heart failure (HF) and recurrent ventricular arrhythmias. The rapid clinical deterioration raised suspicion of an inflammatory aetiology, which was confirmed through endomyocardial biopsy, diagnosing CS. Despite immunosuppressive therapy, HT was required. Case 2: a 36-year-old woman presented with high-grade atrioventricular block and dilated cardiomyopathy (DCM), initially diagnosed as idiopathic. Due to worsening HF, she required HT. The pathological examination of the explanted heart revealed CS. Chronic subclinical antibody-mediated rejection was observed after HT. Case 3: a 44-year-old man presented with syncope and imaging suggesting ACM. He was referred for HT due to high ventricular arrhythmic burden. Cardiac sarcoidosis diagnosis was suspected due to pulmonary involvement and then confirmed on post-explant pathological exam. Post-HT pulmonary and cutaneous sarcoidosis reactivation were observed. Case 4: a 43-year-old man was diagnosed with pulmonary sarcoidosis after lung biopsy. Progression towards DCM was observed despite immunosuppressive therapy. Post-HT was characterized by multiple episodes of graft rejection.

Discussion

This case series provides insights into mid- and long-term outcomes after HT for CS, highlighting the need for careful management of immunosuppression in these patients, balancing the adverse effects of chronic immunosuppression with the prevention of rejection and sarcoidosis recurrence.
Balloon-assisted bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction with en face view for patients exhibiting severe calcified leaflet: a case report
Authors: Kobayashi Yuta , Enta Yusuke , Nakashima Masaki , Tada Norio
Published: December 2024

Background

Balloon-assisted bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction (BA-BASILICA) enables valve-in-valve transcatheter aortic valve implantation (ViV-TAVI) in patients at risk of coronary artery obstruction. However, its efficacy in patients with severely calcified leaflets remains unclear.

Case summary

We report a 78-year-old woman with a deteriorated 21 mm Carpentier-Edwards PERIMOUNT Magna valve. Computed tomography showed severe calcification in the left coronary leaflet, extending above the left coronary artery (LCA) ostium, with a virtual transcatheter heart valve to coronary ostium distance of 3.7 mm, indicating a high risk of coronary obstruction after ViV-TAVI. We performed ViV-TAVI using the BA-BASILICA because of the patient’s high surgical risks. Traversal of the calcified leaflet was successfully achieved using both en face and side views to visualize the traversal system’s position in an area without calcification and in front of the LCA. After traversal, the leaflet was dilated with a balloon and accidentally split into two. A 20 mm SAPIEN 3 Ultra RESILIA valve was deployed. Despite initial procedural success, severe LCA stenosis developed due to leaflet compression. This was resolved by orthotopic stenting using an en face view to identify cells not covered by the bioprosthetic leaflet generated by BA-BASILICA.

Discussion

To our knowledge, this is the first report of ViV-TAVI using the BA-BASILICA with an en face view of severely calcified leaflets. This case suggests that BA-BASILICA with an en face view could be effective for patients at high risk of coronary obstruction with severely calcified leaflets.
Is Secessionism Mostly About Income or Identity? A Global Analysis of 3,153 Subnational Regions
Authors: Desmet Klaus , Ortín Ignacio Ortuño , Özak Ömer
Published: December 2024

This paper analyses whether the propensity to secede by subnational regions responds mostly to differences in income per capita or to distinct ethnolinguistic identities. We explore this question in a quantitative political economy model where people’s willingness to finance a public good depends on their income and identity. Using high-resolution economic and linguistic data for the entire globe, we predict the propensity to secede of 3,153 subnational regions in 177 countries. We validate the model-based predictions with data on secessionist movements, state fragility, regional autonomy, and conflict, as well as with an application to the dissolution of the Soviet Union. Counterfactual analysis shows that removing ethnolinguistic identity differences reduces the average support for secession from 10.1% to 0.2% of the population, while removing income differences has no major quantitative impact. Although both forces affect secessionism, identity trumps income in determining a region’s propensity to secede.
Transport and urban growth in the First Industrial Revolution
Authors: Alvarez-Palau Eduard J , Bogart Dan , Satchell Max , Shaw-Taylor Leigh
Published: December 2024

The Industrial Revolution led to dramatic economic changes which persist to the present. This paper focuses on urban areas in England and Wales, the birthplace of the First Industrial Revolution, and the role of early transport improvements, like improving rivers and roads, building canals, and reducing sailing costs. We estimate how much inter-urban freight transport costs declined from all such innovations between 1680 and 1830 using a new multi-modal transport model. We find that relative to producer prices, transport costs declined by nearly 75%. We then estimate how lower trade costs led to significantly higher urban population through increased market access. Our empirical strategy addresses confounding factors and potential endogeneity. A counterfactual suggests that without any change in the ratio of transport costs to producer prices between 1680 and 1830, the population in 1841 would have been more coastal and inland towns would have been 20 to 25% smaller. In extensions, we show that levels of market access in 1830 had persistent, positive effects on urban population up to 1911. It also led to significantly higher property income, more migration, and fewer unskilled occupations by the mid-nineteenth century. Broadly, early transport improvements significantly shaped the spatial structure of urban economies during the First Industrial Revolution and beyond.
Effects of postoperative glucocorticoids on mitigation of organ dysfunction in patients with type A aortic dissection: a randomized controlled trial
Authors: Luo Ming-Hao , Luo Jing-Chao , Xu Xin , He Zhen-Hua , Huang Yin-Rui , Chen Chen , Su Ying , Hou Jun-Yi , Wang Chun-Sheng , Lai Hao , Tu Guo-Wei , Luo Zhe
Published: December 2024

OBJECTIVES

This study aims to evaluate the organ-protective efficacy of postoperative glucocorticoid in patients with type A aortic dissection.

METHODS

Postoperative type A aortic dissection patients were randomly allocated to receive either postoperative glucocorticoid or standard-of-care treatment. Intravenous methylprednisolone was administered for 3 days. The primary outcome was the reduction of Sequential Organ Failure Assessment score on postoperative day 4 compared to baseline (on postoperative day 1 before methylprednisolone administration).

RESULTS

Two hundred twelve patients were included in the intention-to-treat analysis. The primary outcome was significantly different between groups: 3.16 ± 2.52 in the control group versus 4.36 ± 2.82 in the glucocorticoid group (absolute difference 1.20 [95% CI 0.52–1.93], P = 0.001). The glucocorticoid group showed markedly lower median high-sensitivity C-reactive protein levels compared to the control group (91.0 mg/l vs 182.0 mg/l; absolute difference: –91 (95% CI –122 to –57), P = 0.009) on postoperative day 4. Fewer patients in the glucocorticoid group required continuous renal replacement therapy (8.5% vs 19.8% in the control group; absolute difference: –10.4 [95% CI –19.1 to –1.3], P = 0.03).

CONCLUSIONS

This trial demonstrates that postoperative glucocorticoid in patients with type A aortic dissection significantly reduces postoperative inflammation and improves recovery of early organ dysfunction. These findings advocate for the implementation of glucocorticoid in the early phase after surgery for enhanced organ protection.
Integration of genetic testing into diagnostic pathways for cardiomyopathies: a clinical consensus statement by the ESC Council on Cardiovascular Genomics
Authors: Elliott Perry , Schunkert Heribert , Bondue Antoine , Behr Elijah , Carrier Lucie , Van Duijn Cornelia , García-Pavía Pablo , van der Harst Pim , Kavousi Maryam , Loeys Bart , Rocha Lopes Luis , Pinto Yigal , Di Toro Alessandro , Thum Thomas , Kääb Stefan , Urtis Mario , Arbustini Eloisa
Published: December 2024

In the modern era, cardiologists managing patients and families with cardiomyopathies need to be familiar with every stage of the diagnostic pathway from clinical phenotyping to the prescription and interpretation of genetic tests. This clinical consensus statement from the ESC Council for Cardiovascular Genomics aims to promote the integration of genetic testing into routine cardiac care of patients with cardiomyopathies, as recommended in the 2023 ESC guidelines for cardiomyopathies. The document describes the types of genetic tests currently available and provides advice on their prescription and for counselling after the return of genetic findings, including the approach in patients and families with variants of unknown significance.
Associations of step accelerations and cardiometabolic risk markers in early adulthood
Authors: Stenbäck Ville , Lehtonen Inka , Leppäluoto Juhani , Gagnon Dominique , Järvelin Marjo-Riitta , Tulppo Mikko , Herzig Karl-Heinz
Published: December 2024

Physical activity (PA) has a positive effect on risk factors related to cardiometabolic health yet amount of PA and time of onset is unclear. Therefore, we investigated the relationship of PA estimates and cardiometabolic risk factors in a large healthy population of an understudied age group of young adults using a standard gravity-based method on body adiposity and risk markers. In 856 (532 women, 324 men, 32–35 years) subjects we evaluated the association of PA and cardiometabolic risk factors in early adulthood. PA was measured using accelerometers for a period of two weeks. Step counts were divided into light (LPA), moderate (MPA), and vigorous (VPA) intensity classes. Income of the household was 63 446 ± 46 899€ and 57.5% had higher education. Total daily step numbers were 11962.5 ± 5163.2, LPA 5459.6 ± 2986.6, MPA 5932 ± 3404.6, and VPA 572.3 ± 668. Higher total PA volume was associated with lower weight, BMI, % body fat, smaller visceral fat area (VFA) and waist circumference, lower total cholesterol, LDL, and reflection coefficient of the pulse wave. LPA correlated with weight, BMI, waist circumference, total cholesterol, LDL, and central pulse pressure (cPP). Percent body fat (%BF), VFA, total cholesterol, LDL, reflection coefficient, heart minute index, and heart minute volume were significantly associated with MPA and VPA intensity PA volume. Lower PA in early adulthood correlates with increased cardiometabolic risk markers which should be translated into specific recommendations to thrive for a healthier lifestyle to delay and decrease their onset.
Measuring individual colony MICs is a more sensitive method to detect the effect of antimicrobials on antimicrobial susceptibility than the proportion of colonies resistant
Authors: Ledesma Vergel , Vanbaelen Thibaut , Gestels Zina , Panis Nele , Abdellati Said , de Block Tessa , De Baetselier Irith , Van den Bossche Dorien , Manoharan-Basil Sheeba Santhini , Kenyon Chris
Published: December 2024

The ResistAZM randomized controlled trial found that the receipt of ceftriaxone/azithromycin, compared to ceftriaxone was not associated with an increase in the proportion of oral commensal Neisseria spp. and streptococci with azithromycin resistance 14 days after treatment. We repeated the analyses by measuring the minimum inhibitory concentrations (MICs) of azithromycin and ceftriaxone for individual colonies of commensal Neisseria spp. and streptococci at day 0 and day 14 in both arms. The receipt of ceftriaxone/azithromycin but not ceftriaxone was associated with an increase in azithromycin MIC for both Neisseria spp. (P < 0.0001) and streptococci (P = 0.0076). Likewise, ceftriaxone/azithromycin but not ceftriaxone monotherapy was associated with an increase in ceftriaxone MICs in Neisseria spp. (P = 0.0035). Whereas the proportion method failed to detect an association between the receipt of azithromycin and increased macrolide resistance, the MIC distribution method detected this effect. The MIC distribution method is thus a more sensitive method to assess the effect of antimicrobials on antimicrobial susceptibility. Background: The ResistAZM randomized controlled trial found that the receipt of ceftriaxone/azithromycin, compared to ceftriaxone was not associated with an increase in the proportion of oral commensal Neisseria spp. and streptococci with azithromycin resistance 14 days after treatment. Methods: We repeated the analyses by measuring the minimum inhibitory concentrations (MICs) of azithromycin and ceftriaxone for individual colonies of commensal Neisseria spp. and streptococci at day 0 and day 14 in both arms. Results: The receipt of ceftriaxone/azithromycin but not ceftriaxone was associated with an increase in azithromycin MIC for both Neisseria spp. (P < 0.0001) and streptococci (P = 0.0076). Likewise, ceftriaxone/azithromycin but not ceftriaxone monotherapy was associated with an increase in ceftriaxone MICs in Neisseria spp. (P = 0.0035). Conclusions: Whereas the proportion method failed to detect an association between the receipt of azithromycin and increased macrolide resistance, the MIC distribution method detected this effect. The MIC distribution method is thus a more sensitive method to assess the effect of antimicrobials on antimicrobial susceptibility.
Specific growth rates and growth stoichiometries of Saccharomycotina yeasts on ethanol as sole carbon and energy substrate
Authors: Warmerdam Marieke , Vieira-Lara Marcel A , Mans Robert , Daran Jean Marc , Pronk Jack T
Published: December 2024

Emerging low-emission production technologies make ethanol an interesting substrate for yeast biotechnology, but information on growth rates and biomass yields of yeasts on ethanol is scarce. Strains of 52 Saccharomycotina yeasts were screened for growth on ethanol. The 21 fastest strains, among which representatives of the Phaffomycetales order were overrepresented, showed specific growth rates in ethanol-grown shake-flask cultures between 0.12 and 0.46 h−1. Seven strains were studied in aerobic, ethanol-limited chemostats (dilution rate 0.10 h−1). Saccharomyces cerevisiae and Kluyveromyces lactis, whose genomes do not encode Complex-I-type NADH dehydrogenases, showed biomass yields of 0.59 and 0.56 gbiomass gethanol−1, respectively. Different biomass yields were observed among species whose genomes do harbour Complex-I-encoding genes: Phaffomyces thermotolerans (0.58 g g−1), Pichia ethanolica (0.59 g g−1), Saturnispora dispora (0.66 g g−1), Ogataea parapolymorpha (0.67 g g−1), and Cyberlindnera jadinii (0.73 g g−1). Cyberlindnera jadinii biomass showed the highest protein content (59 ± 2%) of these yeasts. Its biomass yield corresponded to 88% of the theoretical maximum that is reached when growth is limited by assimilation rather than by energy availability. This study suggests that energy coupling of mitochondrial respiration and its regulation will become key factors for selecting and improving yeast strains for ethanol-based processes.
Fast analysis of biobank-size data and meta-analysis using the BGLR R-package
Authors: Pérez-Rodríguez Paulino , de los Campos Gustavo , Wu Hao , Vazquez Ana I , Jones Kyle
Published: December 2024

Analyzing human genomic data from biobanks and large-scale genetic evaluations often requires fitting models with a sample size exceeding the number of DNA markers used (n>p). For instance, developing polygenic scores for humans and genomic prediction for genetic evaluations of agricultural species may require fitting models involving a few thousand SNPs using data with hundreds of thousands of samples. In such cases, computations based on sufficient statistics are more efficient than those based on individual genotype–phenotype data. Additionally, software that admits sufficient statistics as inputs can be used to analyze data from multiple sources jointly without the need to share individual genotype–phenotype data. Therefore, we developed functionality within the BGLR R-package that generates posterior samples for Bayesian shrinkage and variable selection models from sufficient statistics. In this article, we present an overview of the new methods incorporated in the BGLR R-package, demonstrate the use of the new software through simple examples, provide several computational benchmarks, and present a real-data example using data from the UK-Biobank, All of Us, and the Hispanic Community Health Study/Study of Latinos cohort demonstrating how a joint analysis from multiple cohorts can be implemented without sharing individual genotype–phenotype data, and how a combined analysis can improve the prediction accuracy of polygenic scores for Hispanics—a group severely under-represented in genome-wide association studies data.
Biased social chromosome transmission in males of the fire ant Solenopsis invicta
Authors: Hettesheimer Daniel R , Zeng Haolin , Hunt Brendan G , Ross Kenneth G
Published: December 2024

Selfish genetic elements subvert the normal rules of inheritance to unfairly propagate themselves, often at the expense of other genomic elements and the fitness of individuals carrying them. Social life provides diverse avenues for the propagation of such elements. In the fire ant Solenopsis invicta, polymorphic social organization is controlled by a social chromosome, one variant of which (Sb) enhances its own transmission in polygyne colonies through effects on caste development and queen acceptance by workers. Whether the selfish effects of Sb extend to haploid (reproductive) males in this system is less clear. Here, we demonstrate a strong overrepresentation of the Sb social chromosome haplotype in reproductive males, relative to Mendelian expectations, in both the pupal and adult stages. We tested for the presence of selective execution of adult SB males by workers but did not detect such behavior. Combined with the presence of a strong imbalance in the haplotype frequencies already early in the pupal stage, these results indicate that the Sb supergene may distort male haplotype frequencies during larval or embryonic development. These findings are significant because they demonstrate yet another mode by which the selfish tendencies of the Sb supergene are manifested, illuminate complex interactions between Sb and the fire ant breeding system, inform the development of models of the population dynamics of Sb, and illustrate how a selfish supergene can increase in frequency in a population despite harboring deleterious mutations.
Complex Genomic Landscape of Inversion Polymorphism in Europe's Most Destructive Forest Pest
Authors: Mykhailenko Anastasiia , Zieliński Piotr , Bednarz Aleksandra , Schlyter Fredrik , Andersson Martin N , Antunes Bernardo , Borowski Zbigniew , Krokene Paal , Melin Markus , Morales-García Julia , Müller Jörg , Nowak Zuzanna , Schebeck Martin , Stauffer Christian , Viiri Heli , Zaborowska Julia , Babik Wiesław , Nadachowska-Brzyska Krystyna
Published: December 2024

In many species, polymorphic genomic inversions underlie complex phenotypic polymorphisms and facilitate local adaptation in the face of gene flow. Multiple polymorphic inversions can co-occur in a genome, but the prevalence, evolutionary significance, and limits to complexity of genomic inversion landscapes remain poorly understood. Here, we examine genome-wide genetic variation in one of Europe's most destructive forest pests, the spruce bark beetle Ips typographus, scan for polymorphic inversions, and test whether inversions are associated with key traits in this species. We analyzed 240 individuals from 18 populations across the species' European range and, using a whole-genome resequencing approach, identified 27 polymorphic inversions covering ∼28% of the genome. The inversions vary in size and in levels of intra-inversion recombination, are highly polymorphic across the species range, and often overlap, forming a complex genomic architecture. We found no support for mechanisms such as directional selection, overdominance, and associative overdominance that are often invoked to explain the presence of large inversion polymorphisms in the genome. This suggests that inversions are either neutral or maintained by the combined action of multiple evolutionary forces. We also found that inversions are enriched in odorant receptor genes encoding elements of recognition pathways for host plants, mates, and symbiotic fungi. Our results indicate that the genome of this major forest pest of growing social, political, and economic importance harbors one of the most complex inversion landscapes described to date and raise questions about the limits of intraspecific genomic architecture complexity.
Neo-Sex Chromosome Evolution in Treehoppers Despite Long-Term X Chromosome Conservation
Authors: Palmer Droguett Daniela H , Fletcher Micah , Alston Ben T , Kocher Sarah , Cabral-de-Mello Diogo C , Wright Alison E
Published: December 2024

Sex chromosomes follow distinct evolutionary trajectories compared to the rest of the genome. In many cases, sex chromosomes (X and Y or Z and W) significantly differentiate from one another resulting in heteromorphic sex chromosome systems. Such heteromorphic systems are thought to act as an evolutionary trap that prevents subsequent turnover of the sex chromosome system. For old, degenerated sex chromosome systems, chromosomal fusion with an autosome may be one way that sex chromosomes can “refresh” their sequence content. We investigated these dynamics using treehoppers (hemipteran insects of the family Membracidae), which ancestrally have XX/X0 sex chromosomes. We assembled the most complete reference assembly for treehoppers to date for Umbonia crassicornis and employed comparative genomic analyses of 12 additional treehopper species to analyze X chromosome variation across different evolutionary timescales. We find that the X chromosome is largely conserved, with one exception being an X-autosome fusion in Calloconophora caliginosa. We also compare the ancestral treehopper X with other X chromosomes in Auchenorrhyncha (the clade containing treehoppers, leafhoppers, spittlebugs, cicadas, and planthoppers), revealing X conservation across more than 300 million years. These findings shed light on chromosomal evolution dynamics in treehoppers and the role of chromosomal rearrangements in sex chromosome evolution.
SpudDB: a database for accessing potato genomic data
Authors: Hamilton John P , Brose Julia , Buell C Robin
Published: December 2024

Potato is a key food crop with a complex, polyploid genome. Advancements in sequencing technologies coupled with improvements in genome assembly algorithms have enabled generation of phased, chromosome-scale genome assemblies for cultivated tetraploid potato. The SpudDB database houses potato genome sequence and annotation, with the doubled monoploid DM 1–3 516 R44 (hereafter DM) genome serving as the reference genome and haplotype. Diverse annotation data types for DM genes are provided through a suite of Gene Report Pages including gene expression profiles across 438 potato samples. To further annotate potato genes based on expression, 65 gene co-expression modules were constructed that permit the identification of tightly co-regulated genes within DM across development and responses to wounding, abiotic stress, and biotic stress. Genome browser views of DM and 28 other potato genomes are provided along with a download page for genome sequence and annotation. To link syntenic genes within and between haplotypes, syntelogs were identified across 25 cultivated potato genomes. Through access to potato genome sequences and associated annotations, SpudDB can enable potato biologists, geneticists, and breeders to continue to improve this key food crop.
Objectively Measured Physical Activity Using Wrist-Worn Accelerometers as a Predictor of Incident Alzheimer’s Disease in the UK Biobank
Authors: Zhao Angela , Cui Erjia , Leroux Andrew , Zhou Xinkai , Muschelli John , Lindquist Martin A , Crainiceanu Ciprian M
Published: December 2024

Background

Alzheimer’s disease (AD) affects over 6 million people and is the seventh-leading cause of death in the United States. This study compares wrist-worn accelerometry-derived PA measures against traditional risk factors for incident AD in the UK Biobank.

Methods

Of 42 157 UK Biobank participants 65 years and older who had accelerometry data and no prior AD diagnosis, 157 developed AD by April 1, 2021 (264 988 person-years or on average 6.2 years of follow-up). Twelve traditional predictors and 8 accelerometer-based physical activity (PA) measures were used in single- and multivariate Cox models. Their predictive performances for future AD diagnosis were compared across models using the repeated cross-validated concordance (rcvC). To account for potential reverse causality, sensitivity analyses were conducted by removing dropouts and cases within the first 6 months, 1 year, and 2 years.

Results

The best-performing individual predictors of incident AD were age (p < .0001, rcvC = 0.658) and moderate-to-vigorous PA (MVPA, p = .0001, rcvC = 0.622). Forward selection produced a model that included age, diabetes, and MVPA (rcvC = 0.681). Adding MVPA to the model containing age and diabetes improved its rcvC from 0.665 to 0.681 (p = .0030), more than all other potential risk factors considered.

Conclusions

Objective PA summaries are the best single predictors among modifiable risk factors with a predictive performance close to that of age. Adding PA summaries to traditional risk factors for AD substantially increases the predictive performance of these models. Increasing MVPA by 14.5 minutes per day reduces the hazard substantially, equivalent to 2 years younger.
Intentional Strategic Changes in the National Institute on Aging’s RCMAR Program: Broadening its Scope and Reach to Strengthen its Impact
Authors: Gerald Melissa S , Major Laura
Published: December 2024

Since 1997, the Resource Centers for Minority Aging Research (RCMAR) program, supported by the Division of Behavioral and Social Research (BSR) at the National Institute on Aging, has served as BSR’s flagship mentoring program for early-career scientists from diverse backgrounds. Over the years, it has undergone significant changes to address evolving institutional priorities and societal needs. This article highlights the motivations behind programmatic shifts in the fifth funding cycle (2018–2023) and the guiding principles for RCMAR VI (2023–present). Key developments in RCMAR V included the launch of RCMARs focused on Alzheimer’s disease (AD) and Alzheimer’s disease-related dementias (ADRD), a refined emphasis on behavioral and social research, and the decoupling of workforce diversity from health disparities research. Building on lessons learned from the prior funding cycle—amid challenges posed by the coronavirus disease 2019 pandemic and leadership transitions—RCMAR VI offers enriched research, training, and mentorship opportunities while introducing equitable governance structures and clearer, broader expectations for success. The new RCMAR National Coordinating Center plays a crucial role in fostering collaboration, standardizing evaluation, and leading activities to broaden the program’s impact. With a renewed focus on high-priority behavioral and social research on aging, AD/ADRD, and health disparities, RCMAR VI is poised to diversify the scientific workforce and advance discoveries.
GPU-accelerated Kendall distance computation for large or sparse data
Authors: Akhtyamov Pavel , Nabi Ausaaf , Gafurov Vladislav , Sizykh Alexey , Favorov Alexander , Medvedeva Yulia , Stupnikov Alexey
Published: December 2024

Background

Current experimental practices typically produce large multidimensional datasets. Distance matrix calculation between elements (e.g., samples) for such data, although being often necessary in preprocessing for statistical inference or visualization, can be computationally demanding. Data sparsity, which is often observed in various experimental data modalities, such as single-cell sequencing in bioinformatics or collaborative filtering in recommendation systems, may pose additional algorithmic challenges.

Results

We present GPU-Assisted Distance Estimation Software (GADES), a graphical processing unit (GPU)–enhanced package that allows for massively paralleled Kendall-$\tau$ distance matrices computation. The package’s architecture involves specific memory management, which lifts the limits for the data size imposed by GPU memory capacity. Additional algorithmic solutions provide a means to address the data sparsity problem and reinforce the acceleration effect for sparse datasets. Benchmarking against available central processing unit–based packages on simulated and real experimental single-cell RNA sequencing or single-cell ATAC sequencing datasets demonstrated significantly higher speed for GADES compared to other methods for both sparse and dense data processing, with additional performance boost for the sparse data.

Conclusions

This work significantly contributes to the development of computational strategies for high-performance Kendall distance matrices computation and allows for the efficient processing of Big Data with the power of GPU. GADES is freely available at https://github.com/lab-medvedeva/GADES-main.
A novel prenatal alcohol use risk perception model: feedback from a Delphi process
Authors: Erng May Na , Reid Natasha , Moritz Karen M , van Driel Mieke
Published: December 2024

Understanding prenatal alcohol exposure (PAE) risk perception is important for the communication and prevention of alcohol use during pregnancy. A previous systematic review has explored the dimensions and influencing factors of women’s PAE risk perceptions, leading to the construction of Pregnancy Alcohol Use Risk Perception (PARP) conceptual model. This study aims to refine the PARP model using a Delphi process. A total of 37 international experts participated, 17 completed all three online surveys between May 2022 and December 2022. The online survey consisted of Likert-scale and free-text responses on the usefulness and clarity of the components and the design of the PARP model. Likert-scale responses were analysed using descriptive statistics. Free-text responses were analysed using a reflexive thematic analysis approach. The model was amended following participants’ responses. Four characteristics underpinned the revised model—relevance-to-self and the negotiations of risks, inter-relatedness of affect with the cognitive processing of risk, contextual influences of individual, sociocultural and institutional/political/organizational rendering a socioecological perspective to PAE risks perception and the dynamic characteristics of PAE risk perception. The acknowledgement of PAE risk perceptions and the contextual influences can support development of targeted and tailored messages and health education materials.
A novel insight into the antidepressant effect of cannabidiol: possible involvement of the 5-HT1A, CB1, GPR55, and PPARγ receptors
Authors: Miao Yang , Zhao Fei , Guan Wei
Published: December 2024

Background

Depression is a prevalent and disabling disorder that poses serious problems in mental health care, and rapid antidepressants are novel treatments for this disorder. Cannabidiol (CBD), a non-intoxicating phytocannabinoid, is thought to have therapeutic potential due to its important neurological and anti-inflammatory properties. Despite major advances in pharmacotherapy in experimental animals, the exact mechanism of antidepressant-like effects remains to be elucidated.

Methods

In this paper, we review the current state of knowledge on the antidepressant properties of CBD in numerous experimental and clinical studies.

Results

Accumulating evidence suggests that CBD has antidepressant properties in humans and animals with few side effects, suggesting that CBD may be a potential antidepressant. Furthermore, we discuss CBD may therefore provide a potential treatment to exert antidepressant-like effects through various molecular targets, reducing inflammation, and enhancing neurogenesis.

Conclusions

Taken together with the growing popularity of CBD as a medicine, these findings extend the limited knowledge on the antidepressant effects of CBD. This potentially opens up new therapeutic means for the patients with depression.
Impact of Pandemic-Induced Service Disruptions and Behavioral Changes on Hepatitis C Virus and HIV Transmission Amongst People Who Inject Drugs: A Modeling Study
Authors: Wang Jasmine , Genberg Becky L , Feder Kenneth A , Kirk Gregory D , Mehta Shruti H , Grantz Kyra , Wesolowski Amy
Published: December 2024

Background

The coronavirus disease 2019 (COVID-19) pandemic may have disproportionally impacted vulnerable groups such as people who inject drugs (PWID) through reduced health care services as well as social changes from pandemic mitigation measures. Understanding how the COVID-19 pandemic and associated mitigation strategies subsequently changed the trajectory of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) transmission is critical to estimating disease burdens, identifying outbreak risk, and developing informed intervention strategies.

Methods

Using behavioral data from the AIDS Linked to the IntraVenous Experience (ALIVE) study, an ongoing community-based cohort of PWID in Baltimore, United States, and an individual-based network model, we explored the impacts of service disruptions combined with changes in social networks and injecting behaviors of PWID on HCV and HIV transmission.

Results

Analyses of ALIVE data showed that during the pandemic, there was an acceleration in injection cessation trajectories overall, but those who continued injecting increased the frequency of injection; at the same time, individual drug-use networks became smaller and the probability of injecting with others decreased. Simulation results demonstrated that HCV and HIV prevalence increased from service disruptions alone, but these effects were mitigated when including observed behavior changes in addition.

Conclusions

Model results combined with rich individual behavioral data indicated that pandemic-induced behavioral changes of PWID that lasted longer than service disruptions could have offset the increasing disease burden caused by disrupted service access during the pandemic.
The Neisseria meningitidis Urethritis Clade (NmUC) Acts as a “Chimeric Pathogen” During Infection of Primary, Human Male, Urethral Epithelial Cells
Authors: Tzeng Yih-Ling , Esposito Danillo L A , Nederveld Andrew G , Hardison Rachael L , Carter Alexandria M , Stephens David S , Norris Turner Abigail , Bazan Jose A , Edwards Jennifer L
Published: December 2024

Background

Male urethritis cases, caused by a novel clade of nongroupable Neisseria meningitidis (NmUC, “the clade”), have been reported globally.

Methods

To test whether genetic features unique to NmUC confer a colonization and survival advantage to NmUC during urethral infection, NmUC, gonococcal, and nonclade meningococcal strains were comparatively evaluated in primary, human male, urethral epithelial cell (UEC) infection studies.

Results

NmUC strains were more invasive in UECs than the gonococcal strains tested, which could not be attributed to loss of capsule expression alone. Whereas gonococci and NmUC strains survived and proliferated within UECs, negligible survival was observed for nonclade meningococcal strains. NmUC infection of UECs was impaired when host receptors known to mediate gonococcal or meningococcal interactions with epithelial cells were blocked. We found that fHbp contributes to clade survival independent of its ability to bind extracellular factor H, and that the gonococcal denitrification pathway, particularly NorB, plays an important role in promoting clade intracellular survival.

Conclusions

Whereas mechanisms used by NmUC to infect UECs are shared with other neisserial strains, hybrid mechanisms unique to the clade also mediate infection and allow adaptation to the male urethra. Thus, NmUC is a “chimeric pathogen,” displaying facets of gonococcal and meningococcal pathogenesis.