bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognosis and clinical management of asymptomatic family members with RYR2-mediated catecholaminergic polymorphic ventricular tachycardia: a review
Authors: Peltenburg Puck J. , Gibson Harry , Wilde Arthur A. M. , van der Werf Christian , Clur Sally-Ann B. , Blom Nico A. 
Published: April 2024

AbstractDespite its low prevalence, the potential diagnosis of catecholaminergic polymorphic ventricular tachycardia (CPVT) should be at the forefront of a paediatric cardiologists mind in children with syncope during exercise or emotions. Over the years, the number of children with a genetic diagnosis of CPVT due to a (likely) pathogenic RYR2 variant early in life and prior to the onset of symptoms has increased due to cascade screening programmes. Limited guidance for this group of patients is currently available. Therefore, we aimed to summarise currently available literature for asymptomatic patients with a (likely) pathogenic RYR2 variant, particularly the history of CPVT and its genetic architecture, the currently available diagnostic tests and their limitations, and the development of a CPVT phenotype – both electrocardiographically and symptomatic – of affected family members. Their risk of arrhythmic events is presumably low and a phenotype seems to develop in the first two decades of life. Future research should focus on this group in particular, to better understand the development of a phenotype over time, and therefore, to be able to better guide clinical management – including the frequency of diagnostic tests, the timing of the initiation of drug therapy, and lifestyle recommendations.
Racial, ethnic, and socio-economic disparities in neonatal ICU admissions among neonates born with cyanotic CHD in the United States, 2009–2018
Authors: Reddy Kriyana P. , Ludomirsky Avital B. , Jones Andrea L. , Shustak Rachel J. , Faerber Jennifer A. , Naim Maryam Y. , Lopez Keila N. , Mercer-Rosa Laura M. 
Published: April 2024

AbstractIntroduction:Disparities in CHD outcomes exist across the lifespan. However, less is known about disparities for patients with CHD admitted to neonatal ICU. We sought to identify sociodemographic disparities in neonatal ICU admissions among neonates born with cyanotic CHD.Materials & Methods:Annual natality files from the US National Center for Health Statistics for years 2009–2018 were obtained. For each neonate, we identified sex, birthweight, pre-term birth, presence of cyanotic CHD, and neonatal ICU admission at time of birth, as well as maternal age, race, ethnicity, comorbidities/risk factors, trimester at start of prenatal care, educational attainment, and two measures of socio-economic status (Special Supplemental Nutrition Program for Women, Infants, and Children [WIC] status and insurance type). Multivariable logistic regression models were fit to determine the association of maternal socio-economic status with neonatal ICU admission. A covariate for race/ethnicity was then added to each model to determine if race/ethnicity attenuate the relationship between socio-economic status and neonatal ICU admission.Results:Of 22,373 neonates born with cyanotic CHD, 77.2% had a neonatal ICU admission. Receipt of WIC benefits was associated with higher odds of neonatal ICU admission (adjusted odds ratio [aOR] 1.20, 95% CI 1.1–1.29, p < 0.01). Neonates born to non-Hispanic Black mothers had increased odds of neonatal ICU admission (aOR 1.20, 95% CI 1.07–1.35, p < 0.01), whereas neonates born to Hispanic mothers were at lower odds of neonatal ICU admission (aOR 0.84, 95% CI 0.76–0.93, p < 0.01).Conclusion:Maternal Black race and low socio-economic status are associated with increased risk of neonatal ICU admission for neonates born with cyanotic CHD. Further work is needed to identify the underlying causes of these disparities.
Pension reforms in Hungary: have they gone too far?
Authors: Dedák István , Fiser Noémi 
Published: April 2024

AbstractAs a result of unfavorable demographic processes, the pension systems in the Central and Eastern European (CEE) EU countries face significant challenges, which has made the implementation of reforms inevitable in the last decade. Relying on economic theory, this paper analyses the effects of the Hungarian pension reforms in comparison with those of other CEE countries, and discusses the consequences from the point of view of social policy and the sustainability of the pension schemes. We explore the reasons why the reforms in Hungary ultimately did not improve sustainability but rather contributed to dismantling the social care system. Therefore, the Hungarian case provides useful lessons for other countries, and at the same time underlines the importance of automatic adjustment mechanisms. The study pays particular attention to the theoretical analysis of pension indexation because its accurate quantitative effects are far from being sufficiently clarified in the literature, although it is vital for a thoughtful evaluation of pension reforms.
The Toba Eruption 74,000 Years ago Strengthened the Indian Winter Monsoon‐Evidence From Coccolithophores
Authors: Guballa Jose Dominick , Bollmann Jörg , Schmidt Katherine , Lückge Andreas 
Published: April 2024

AbstractThe global impact of the Youngest Toba Tuff (YTT) supereruption is still heavily debated, ranging from having little effects on climate to significantly affecting modern human evolution. Climate models and proxy records show that the eruption may have caused cooling of the Asian landmass, thus impacting regional climate such as the Indian monsoon system. However, the immediate effect of the eruption on the Indian monsoon has not been indisputably demonstrated in any proxy record. Here, we present a paleo‐primary productivity (PP) record in core SO130‐289KL from the northeastern Arabian Sea based on the coccolithophore species Florisphaera profunda transfer function. Florisphaera profunda decreased from ∼30% before the YTT eruption to ∼8% right after the YTT eruption, which translates to an increase in PP by ∼65% from a long‐term average of ∼200 gC/m2/yr for about 8–19 years after the eruption. The duration was estimated using a new error‐weighted mean age of the YTT eruption (73.9 ± 0.1 ka, 2σ uncertainties) based on recent age estimates from ice cores, radiometric dating, and speleothem records. The elevated PP is most likely linked to the deepening of the surface ocean mixed layer driven by strengthened northeasterly Indian winter monsoon winds. This hypothesis is supported by stable oxygen isotope records from speleothem and ice cores, which show indications of a strengthening of the Indian winter monsoon during times of increased PP. Our results support previous modeling studies and provide unequivocal evidence from a marine record for an Indian monsoon response to the supereruption.
Liver stiffness measurements predict Sinusoidal Obstructive Syndrome after hematopoietic stem cell transplantation
Authors: Davidov Yana , Shem-Tov Noga , Yerushalmi Ronit , Hod Tammy , Ben-Ari Ziv , Nagler Arnon , Shimoni Avichai , Danylesko Ivetta 
Published: April 2024

AbstractSinusoidal Obstructive Syndrome (SOS) is a life-threatening complication after hematopoietic stem-cell transplantation (HSCT), characterized by post-sinusoidal portal hypertension. FibroScan is used to assess portal hypertension non-invasively. We assessed transient elastography (TE) applicability in diagnosing SOS. The study included 27 adult patients, 11 underwent TE for high SOS risk pre-HSCT, 17 underwent TE post-HSCT due to bilirubin ≥2 mg/dl with no definite diagnosis of SOS. The first group had median Liver Stiffness Measurement (LSM) of 7.4 kPa (range, 3.3–22.5). Based on LSM results, conditioning regimen was modified for six patients and two of them developed SOS. Only one patient who did not have protocol adjustment experienced SOS. No patient with LSM < 7 kPa developed SOS. The second group had median LSM of 7.7 kPa (4.4–31.5). Median LSM after HSCT was significantly higher in patients who subsequently developed established SOS (n = 10) compared to patients who did not (n = 8), with values of 10.7 kPa (5.6–31.5) and 5.9 kPa (4.4–13.8), respectively (p = 0.02). An LSM cut-off of 7.5 kPa had a sensitivity and specificity of 75 and 80% for diagnosing SOS. In conclusion, pre-HSCT LSM can help adjustment of conditioning regimen in patients with high-risk for SOS. Post-HSCT LSM can help in early diagnosis of SOS.
Discovery of recessive effect of human polymerase δ proofreading deficiency through mutational analysis of POLD1-mutated normal and cancer cells
Authors: Andrianova Maria A. , Seplyarskiy Vladimir B. , Terradas Mariona , Sánchez-Heras Ana Beatriz , Mur Pilar , Soto José Luis , Aiza Gemma , Borràs Emma , Kondrashov Fyodor A. , Kondrashov Alexey S. , Bazykin Georgii A. , Valle Laura 
Published: April 2024

AbstractConstitutional heterozygous pathogenic variants in the exonuclease domain of POLE and POLD1, which affect the proofreading activity of the corresponding polymerases, cause a cancer predisposition syndrome characterized by increased risk of gastrointestinal polyposis, colorectal cancer, endometrial cancer and other tumor types. The generally accepted explanation for the connection between the disruption of the proofreading activity of polymerases epsilon and delta and cancer development is through an increase in the somatic mutation rate. Here we studied an extended family with multiple members heterozygous for the pathogenic POLD1 variant c.1421T>C p.(Leu474Pro), which segregates with the polyposis and cancer phenotypes. Through the analysis of mutational patterns of patient-derived fibroblasts colonies and de novo mutations obtained by parent-offspring comparisons, we concluded that heterozygous POLD1 L474P just subtly increases the somatic and germline mutation burden. In contrast, tumors developed in individuals with a heterozygous mutation in the exonuclease domain of POLD1, including L474P, have an extremely high mutation rate (>100 mut/Mb) associated with signature SBS10d. We solved this contradiction through the observation that tumorigenesis involves somatic inactivation of the wildtype POLD1 allele. These results imply that exonuclease deficiency of polymerase delta has a recessive effect on mutation rate.
Towards ethical drug pricing: the European Orphan Genomic Therapies Fund
Authors: Risse Johanna , Krzemien Merlin , Schnalke Jan , Heinemann Thomas 
Published: April 2024

AbstractAn increasing number of novel genomic therapies are expected to become available for patients with rare or ultra-rare diseases. However, the primary obstacle to equal patient access to these orphan genomic therapies are currently very high prices charged by manufacturers in the context of limited healthcare budgets. Taking into account ethical pricing theories, the paper proposes the implementation of a pricing infrastructure covering all European member states, which has the potential to promote distributive justice while maintaining the attractiveness of genomic therapy development.
Automated in vivo enzyme engineering accelerates biocatalyst optimization
Authors: Orsi Enrico , Schada von Borzyskowski Lennart , Noack Stephan , Nikel Pablo I. , Lindner Steffen N. 
Published: April 2024

AbstractAchieving cost-competitive bio-based processes requires development of stable and selective biocatalysts. Their realization through in vitro enzyme characterization and engineering is mostly low throughput and labor-intensive. Therefore, strategies for increasing throughput while diminishing manual labor are gaining momentum, such as in vivo screening and evolution campaigns. Computational tools like machine learning further support enzyme engineering efforts by widening the explorable design space. Here, we propose an integrated solution to enzyme engineering challenges whereby ML-guided, automated workflows (including library generation, implementation of hypermutation systems, adapted laboratory evolution, and in vivo growth-coupled selection) could be realized to accelerate pipelines towards superior biocatalysts.
A giant virus infecting the amoeboflagellate Naegleria
Authors: Arthofer Patrick , Panhölzl Florian , Delafont Vincent , Hay Alban , Reipert Siegfried , Cyran Norbert , Wienkoop Stefanie , Willemsen Anouk , Sifaoui Ines , Arberas-Jiménez Iñigo , Schulz Frederik , Lorenzo-Morales Jacob , Horn Matthias 
Published: April 2024

AbstractGiant viruses (Nucleocytoviricota) are significant lethality agents of various eukaryotic hosts. Although metagenomics indicates their ubiquitous distribution, available giant virus isolates are restricted to a very small number of protist and algal hosts. Here we report on the first viral isolate that replicates in the amoeboflagellate Naegleria. This genus comprises the notorious human pathogen Naegleria fowleri, the causative agent of the rare but fatal primary amoebic meningoencephalitis. We have elucidated the structure and infection cycle of this giant virus, Catovirus naegleriensis (a.k.a. Naegleriavirus, NiV), and show its unique adaptations to its Naegleria host using fluorescence in situ hybridization, electron microscopy, genomics, and proteomics. Naegleriavirus is only the fourth isolate of the highly diverse subfamily Klosneuvirinae, and like its relatives the NiV genome contains a large number of translation genes, but lacks transfer RNAs (tRNAs). NiV has acquired genes from its Naegleria host, which code for heat shock proteins and apoptosis inhibiting factors, presumably for host interactions. Notably, NiV infection was lethal to all Naegleria species tested, including the human pathogen N. fowleri. This study expands our experimental framework for investigating giant viruses and may help to better understand the basic biology of the human pathogen N. fowleri.
Long-term monitoring of SARS-CoV-2 seroprevalence and variants in Ethiopia provides prediction for immunity and cross-immunity
Authors: Merkt Simon , Ali Solomon , Gudina Esayas Kebede , Adissu Wondimagegn , Gize Addisu , Muenchhoff Maximilian , Graf Alexander , Krebs Stefan , Elsbernd Kira , Kisch Rebecca , Betizazu Sisay Sirgu , Fantahun Bereket , Bekele Delayehu , Rubio-Acero Raquel , Gashaw Mulatu , Girma Eyob , Yilma Daniel , Zeynudin Ahmed , Paunovic Ivana , Hoelscher Michael , Blum Helmut , Hasenauer Jan , Kroidl Arne , Wieser Andreas 
Published: April 2024

AbstractUnder-reporting of COVID-19 and the limited information about circulating SARS-CoV-2 variants remain major challenges for many African countries. We analyzed SARS-CoV-2 infection dynamics in Addis Ababa and Jimma, Ethiopia, focusing on reinfection, immunity, and vaccination effects. We conducted an antibody serology study spanning August 2020 to July 2022 with five rounds of data collection across a population of 4723, sequenced PCR-test positive samples, used available test positivity rates, and constructed two mathematical models integrating this data. A multivariant model explores variant dynamics identifying wildtype, alpha, delta, and omicron BA.4/5 as key variants in the study population, and cross-immunity between variants, revealing risk reductions between 24% and 69%. An antibody-level model predicts slow decay leading to sustained high antibody levels. Retrospectively, increased early vaccination might have substantially reduced infections during the delta and omicron waves in the considered group of individuals, though further vaccination now seems less impactful.
F-actin architecture determines the conversion of chemical energy into mechanical work
Authors: Sakamoto Ryota , Murrell Michael P. 
Published: April 2024

AbstractMechanical work serves as the foundation for dynamic cellular processes, ranging from cell division to migration. A fundamental driver of cellular mechanical work is the actin cytoskeleton, composed of filamentous actin (F-actin) and myosin motors, where force generation relies on adenosine triphosphate (ATP) hydrolysis. F-actin architectures, whether bundled by crosslinkers or branched via nucleators, have emerged as pivotal regulators of myosin II force generation. However, it remains unclear how distinct F-actin architectures impact the conversion of chemical energy to mechanical work. Here, we employ in vitro reconstitution of distinct F-actin architectures with purified components to investigate their influence on myosin ATP hydrolysis (consumption). We find that F-actin bundles composed of mixed polarity F-actin hinder network contraction compared to non-crosslinked network and dramatically decelerate ATP consumption rates. Conversely, linear-nucleated networks allow network contraction despite reducing ATP consumption rates. Surprisingly, branched-nucleated networks facilitate high ATP consumption without significant network contraction, suggesting that the branched network dissipates energy without performing work. This study establishes a link between F-actin architecture and myosin energy consumption, elucidating the energetic principles underlying F-actin structure formation and the performance of mechanical work.
Patrilineal segmentary systems provide a peaceful explanation for the post-Neolithic Y-chromosome bottleneck
Authors: Guyon Léa , Guez Jérémy , Toupance Bruno , Heyer Evelyne , Chaix Raphaëlle 
Published: April 2024

AbstractStudies have found a pronounced decline in male effective population sizes worldwide around 3000–5000 years ago. This bottleneck was not observed for female effective population sizes, which continued to increase over time. Until now, this remarkable genetic pattern was interpreted as the result of an ancient structuring of human populations into patrilineal groups (gathering closely related males) violently competing with each other. In this scenario, violence is responsible for the repeated extinctions of patrilineal groups, leading to a significant reduction in male effective population size. Here, we propose an alternative hypothesis by modelling a segmentary patrilineal system based on anthropological literature. We show that variance in reproductive success between patrilineal groups, combined with lineal fission (i.e., the splitting of a group into two new groups of patrilineally related individuals), can lead to a substantial reduction in the male effective population size without resorting to the violence hypothesis. Thus, a peaceful explanation involving ancient changes in social structures, linked to global changes in subsistence systems, may be sufficient to explain the reported decline in Y-chromosome diversity.
Correlation between two distant quasiparticles in separate superconducting islands mediated by a single spin
Authors: Estrada Saldaña Juan Carlos , Vekris Alexandros , Pavešič Luka , Žitko Rok , Grove-Rasmussen Kasper , Nygård Jesper 
Published: April 2024

AbstractControlled coupling between distant particles is a key requirement for the implementation of quantum information technologies. A promising platform are hybrid systems of semiconducting quantum dots coupled to superconducting islands, where the tunability of the dots is combined with the macroscopic coherence of the islands to produce states with non-local correlations, e.g. in Cooper pair splitters. Electrons in hybrid quantum dots are typically not amenable to long-distance spin alignment as they tend to be screened into a localized singlet state by bound superconducting quasiparticles. However, two quasiparticles coming from different superconductors can overscreen the quantum dot into a doublet state, leading to ferromagnetic correlations between the superconducting islands. We present experimental evidence of a stabilized overscreened state, implying correlated quasiparticles over a micrometer distance. We propose alternating chains of quantum dots and superconducting islands as a novel platform for controllable large-scale spin coupling.
IFT cargo and motors associate sequentially with IFT trains to enter cilia of C. elegans
Authors: Mitra Aniruddha , Loseva Elizaveta , Peterman Erwin J. G. 
Published: April 2024

AbstractIntraflagellar transport (IFT) orchestrates entry of proteins into primary cilia. At the ciliary base, assembled IFT trains, driven by kinesin-2 motors, can transport cargo proteins into the cilium, across the crowded transition zone. How trains assemble at the base and how proteins associate with them is far from understood. Here, we use single-molecule imaging in the cilia of C. elegans chemosensory neurons to directly visualize the entry of kinesin-2 motors, kinesin-II and OSM-3, as well as anterograde cargo proteins, IFT dynein and tubulin. Single-particle tracking shows that IFT components associate with trains sequentially, both in time and space. Super-resolution maps of IFT components in wild-type and mutant worms reveal ciliary ultrastructure and show that kinesin-II is essential for axonemal organization. Finally, imaging cilia lacking kinesin-II and/or transition zone function uncovers the interplay of kinesin-II and OSM-3 in driving efficient transport of IFT trains across the transition zone.
Goal-directed and flexible modulation of syllable sequence within birdsong
Authors: Kawaji Takuto , Fujibayashi Mizuki , Abe Kentaro 
Published: April 2024

AbstractSongs constitute a complex system of vocal signals for inter-individual communication in songbirds. Here, we elucidate the flexibility which songbirds exhibit in the organizing and sequencing of syllables within their songs. Utilizing a newly devised song decoder for quasi-real-time annotation, we execute an operant conditioning paradigm, with rewards contingent upon specific syllable syntax. Our analysis reveals that birds possess the capacity to modify the contents of their songs, adjust the repetition length of particular syllables and employing specific motifs. Notably, birds altered their syllable sequence in a goal-directed manner to obtain rewards. We demonstrate that such modulation occurs within a distinct song segment, with adjustments made within 10 minutes after cue presentation. Additionally, we identify the involvement of the parietal-basal ganglia pathway in orchestrating these flexible modulations of syllable sequences. Our findings unveil an unappreciated aspect of songbird communication, drawing parallels with human speech.
Flower-shaped 2D crystals grown in curved fluid vesicle membranes
Authors: Wan Hao , Jeon Geunwoong , Xin Weiyue , Grason Gregory M. , Santore Maria M. 
Published: April 2024

AbstractThe morphologies of two-dimensional (2D) crystals, nucleated, grown, and integrated within 2D elastic fluids, for instance in giant vesicle membranes, are dictated by an interplay of mechanics, permeability, and thermal contraction. Mitigation of solid strain drives the formation of crystals with vanishing Gaussian curvature (i.e., developable domain shapes) and, correspondingly, enhanced Gaussian curvature in the surrounding 2D fluid. However, upon cooling to grow the crystals, large vesicles sustain greater inflation and tension because their small area-to-volume ratio slows water permeation. As a result, more elaborate shapes, for instance, flowers with bendable but inextensible petals, form on large vesicles despite their more gradual curvature, while small vesicles harbor compact planar crystals. This size dependence runs counter to the known cumulative growth of strain energy of 2D colloidal crystals on rigid spherical templates. This interplay of intra-membrane mechanics and processing points to the scalable production of flexible molecular crystals of controllable complex shape.