bluuebunny/crossref_metadata_2025_split huggingface dataset:
Female germline expression of OVO transcription factor bridges Drosophila generations
Authors: Benner Leif , Muron Savannah , Wingfield Charli L , Oliver Brian 
Published: November 2024

Abstract
OVO is required for female germ cell viability but has no known function in the male germline in Drosophila. ovo is autoregulated by 2 antagonistic isoforms, OVO-A and OVO-B. All ovo− alleles were created as partial revertants of the antimorphic ovoD1 allele. Creation of new targeted alleles in an ovo+ background indicated that disrupting the germline-specific exon extension of ovo-B leads to an arrested egg chamber phenotype, rather than germ cell death. RNA sequencing analysis, including &gt;1 K full-length cDNAs, indicates that ovo has several unannotated splice variations in the extended exon and a minor population of ovo-B transcripts has an alternative splice. This indicates that classical ovo alleles, such as ovoD1rv23, are not truly null for ovo and are likely to be weak antimorphs. To generate bonafide nulls, we deleted the ovo-A and ovo-B promoters showing that only ovo-B is required for female germ cell viability, and there is an early and continual developmental requirement for ovo-B in the female germline. To visualize OVO expression and localization, we endogenously tagged ovo and found nuclear OVO in all differentiating female germ cells throughout oogenesis in adults. We also found that OVO is maternally deposited into the embryo, where it showed nuclear localization in newly formed pole cells. Maternal OVO persisted in embryonic germ cells until zygotic OVO expression was detectable, suggesting that there is continuous nuclear OVO expression in the female germline in the transition from one generation to the next.
Sex Differences in Response to Diet Enriched With Glutathione Precursors in the Aging Heart
Authors: Angelini Aude , Garcia Marquez Grecia , Malovannaya Anna , Fiorotto Marta L , Saltzman Alexander , Jain Antrix , Trial JoAnn , Taffet George E , Cieslik Katarzyna A 
Published: November 2024

Abstract
Common features of the aging heart are dysregulated metabolism, inflammation, and fibrosis. Elevated oxidative stress is another hallmark of cardiac aging that can exacerbate each of these conditions. We hypothesize that by increasing natural antioxidant levels (glutathione), we will improve cardiac function. Twenty-one-month-old mice were fed glycine and N-acetyl cysteine (GlyNAC; glutathione precursors)-supplemented or control diets for 12 weeks. Heart function was monitored longitudinally, and the exercise performance was determined at the end of the study. We found that the GlyNAC diet was beneficial for old male but not old female mice, leading to an increase of Ndufb8 expression (a subunit of the mitochondrial respiratory chain complex), and higher enzymatic activity for CPT1b and CrAT, 2 carnitine acyltransferases that are critical to cardiomyocyte metabolism. Although no quantifiable change of collagen turnover was detected, hearts from GlyNAC-fed old males exhibited a slight but significant enrichment in Fmod, a protein that can inhibit collagen fibril formation, possibly reducing extracellular matrix stiffness and thus improving diastolic function. Cardiac diastolic function was modestly improved in males but not females, and surprisingly GlyNAC-fed female mice showed a decline in exercise performance. In summary, our work supports the concept that aged male and female hearts are phenotypically different. These basic differences may affect the response to pharmacological and diet interventions, including antioxidants.
The new geopolitics of EU cybersecurity: security, economy and sovereignty
Authors: Farrand Benjamin , Carrapico Helena , Turobov Aleksei 
Published: November 2024

Abstract
The European Union (EU) is currently experiencing significant geopolitical shifts and is concerned that its dependence on externally produced or foreign-owned technologies risks its strategic autonomy, with implications for its security and economy. In response, it has placed sovereignty at the forefront of its agenda and at the centre of its relations with the world. Academic literature has so far paid limited attention to understanding the interactions between geopolitics, perceptions of technological dependence, and the impact on policy governance in cybersecurity. Bearing this gap in mind, the article asks how the EU's discourse of sovereignty and reducing external dependencies is shaping its approach to cybersecurity. Applying regulatory mercantilism and policy analysis to three case-studies—focusing on control of semiconductors, data server location, and cybersecurity certification— the article finds that the EU's depiction of its cybersecurity as impacted by dependence on externally manufactured products resulted in the merging of security and economic rationales. This has translated into efforts for greater control, either through promoting production within the European physical space through security-influenced industrial policies or—when this is not possible—by exerting regulatory influence beyond Europe's borders. Where globalization is believed to have failed, regulatory mercantilism becomes more likely as a policy approach.
Cyber risk logics and their implications for cybersecurity
Authors: Backman Sarah , Stevens Tim 
Published: November 2024

Abstract
Cybersecurity in national and international security is frequently discussed in an existential register. However, most cybersecurity activities are normal and routine, including diverse practices of cyber risk management. The intricacies of cyber risk and its connection to security and threat politics have received surprisingly little attention in the cyber politics literature. This article addresses this gap through a twofold theoretical proposition. The first argues that cyber risk in policy and practice inhabits a continuum between ‘classical’ risk and security postures. The second proposes the existence of multiple risk logics, located at different points along this continuum. To illustrate this, we outline two distinct cyber risk logics: ‘risk as potential threats’ and ‘risk as uncertainty’. Through an exploratory case-study of cyber risk policy and guidance in the United Kingdom, we find indications of the simultaneous existence of these risk logics, including in specific organizational contexts. We propose that the ‘risk as potential threats’ logic, in particular, acts as a ‘bridge’ between conventional risk and security. We conclude by discussing how differentiating cyber risk logics facilitates a more finely grained appreciation of cybersecurity policy and practice and provides opportunities for disciplinary engagement with the organizational and institutional politics of cybersecurity and ‘the international’.
Recurrent association between Trichodesmium colonies and calcifying amoebae
Authors: Zhang Futing , Wang Siyuan , Visser Anna-Neva , Koedooder Coco , Eichner Meri , Anderson O Roger , Dyhrman Sonya T , Shaked Yeala 
Published: November 2024

Abstract
Colonies of the N2-fixing cyanobacterium Trichodesmium spp. constitute a consortium with multiple microorganisms that collectively exert ecosystem-level influence on marine carbon and nitrogen cycling, shunting newly fixed nitrogen to low nitrogen systems, and exporting both carbon and nitrogen to the deep sea. Here we identify a seasonally recurrent association between puff colonies and amoebae through a two-year survey involving over 10 000 Trichodesmium colonies in the Red Sea. This association was most commonly found in near-shore populations during spring. Microscopic observations revealed consistent amoebae morphology throughout the study, and both morphological characteristics and 18S rRNA gene sequencing suggested that these amoebae are likely to belong to the species Trichosphaerium micrum, an amoeba that forms a CaCO3 shell. Co-cultures of Trichosphaerium micrum and Trichodesmium grown in the laboratory suggest that the amoebae feed on heterotrophic bacteria and not Trichodesmium, which adds a consumer dynamic to the complex microbial interactions within these colonies. Sinking experiments with fresh colonies indicated that the presence of the CaCO3-shelled amoebae decreased colony buoyancy. As such, this novel association may accelerate Trichodesmium sinking rates and facilitate carbon and nitrogen export to the deep ocean. Amoebae have previously been identified in Trichodesmium colonies in the western North Atlantic (Bermuda and Barbados), suggesting that this type of association may be widespread. This association may add a new critical facet to the microbial interactions underpinning carbon and nitrogen fixation and fate in the present and future ocean.
Clinical Performance of an N-Terminal Pro-B-Type Natriuretic Peptide Assay in Acute Heart Failure Diagnosis
Authors: Daniels Lori B , Ajongwen Patience , Christenson Robert H , Clark Carol L , Diercks Deborah B , Fermann Gregory J , Mace Sharon E , Mahler Simon A , Pang Peter S , Rafique Zubaid , Runyon Michael S , Tauras James , deFilippi Christopher R 
Published: November 2024

Abstract

Background
We evaluated the Vitros® Immunodiagnostic Products N-terminal pro B-type natriuretic peptide (NT-proBNP) II assay for aiding in diagnosis of heart failure (HF) in patients with acute dyspnea.

Methods
Serum concentrations of NT-proBNP were measured in patient samples from 20 emergency departments across the United States. Study endpoints included sensitivity, specificity, likelihood ratios, and predictive values for diagnosis of acute HF according to age-stratified cutoffs (450, 900, and 1800 pg/mL), and a rule-out age-independent cutoff (300 pg/mL). Additional measures were area under the curve (AUC) for receiver operating characteristic (ROC) curves. Results were also interpreted in patient subgroups with relevant comorbidities, and gray zone/intermediate assay values.

Results
Of 2200 patients, 1095 (49.8%) were diagnosed with HF by clinical adjudication. Sensitivity and specificity for Vitros NT-proBNP II ranged from 84.0% to 92.1%, and 81.4% to 86.5%, respectively, within and across age groups, and positive predictive values were 80.4% to 85.7%. Using the rule-out cutoff, the negative predictive value was 97.9%, with a negative likelihood ratio of 0.02. In subgroups with comorbidities potentially affecting NT-proBNP concentrations, sensitivities ranged from 82.6% to 89.5%, and AUCs for ROC curves were 0.899 to 0.915.

Conclusions
The Vitros NT-proBNP II assay demonstrated excellent clinical performance using age-stratified cutoffs along with other clinical information for supporting diagnosis of HF, and can rule out HF with a high negative predictive value using the age-independent cutoff. The assay retained utility in patient subgroups with conditions that influence NT-proBNP concentration, and for those with gray zone results.

ClinicalTrials.gov Registration Number
NCT03548909.
Biological Variation of Hemostasis Analytes in Atrial Fibrillation Patients Using Dabigatran
Authors: Tilly Martijn J , Donkel Samantha J , Kavousi Maryam , de Groot Natasja M S , de Maat Moniek P M 
Published: November 2024

Abstract

Background
Analytical criteria for laboratory analysis based on biological variation are considered state-of-the-art. While biological variance should ideally be measured in patient populations for whom the tests are relevant, data are mostly only available from healthy individuals. We determined the biological variance of activated partial thromboplasmin time (APTT), prothrombin time (PT), fibrinogen, and trough dabigatran levels in patients with atrial fibrillation (AF) who were treated with dabigatran.

Methods
Between 2019 and 2022, patients with AF treated &gt;3 months with dabigatran were included. Blood was collected monthly up to 10 times for the measurement of APTT, PT, fibrinogen, and trough dabigatran levels. Between-subject variance (CVG), within-subject variance (CVI), and analytical variance (CVA) were calculated.

Results
Eighteen participants (median age 65.8 years, 22.2% women) were included, with 130 samples in total. For APTT, the CVG was 11.5%, the CVI 8.8%, and the CVA 1.1%. For PT, these values were 5.2%, 4.0%, and 1.0% and for fibrinogen 13.6%, 11.8%, and 1.6%, respectively. For the dabigatran levels, the percentages were 37.9%, 33.0%, and 3.4%, respectively.

Conclusions
We assessed the biological variance of APTT, PT, fibrinogen, and dabigatran in a patient population with long-term dabigatran use. The analytical performances of coagulation laboratory tests in patients with AF treated with dabigatran were comparable to those in healthy volunteers.
CCMO Registration Number: NL67304.078.18
Goldilocks mastectomy with immediate reconstruction: enhancing aesthetic outcomes and preserving nipple complex
Authors: Binks Matthew , Ayeni Femi E , Edirimanne Senarath , Meybodi Farid 
Published: November 2024

Abstract
Despite significant advancements in early breast cancer detection, mastectomy remains a crucial treatment option for some patients. Immediate breast reconstruction post-mastectomy has emerged as an ideal procedure to minimize physical and psychosocial patient impacts, striving for improved cosmetic results. The “enhanced “Goldilocks mastectomy technique, characterized by nipple preservation or grafting and utilizing the fifth perforator anatomy, offers a sound approach to reconstruction in comorbid and large-breasted patients. This paper discusses the advantages, disadvantages, and real-world application of Goldilocks mastectomy in enhancing breast reconstruction outcomes and meeting patients' diverse needs.
How does social law (not) assess surrogacy as female reproductive labour? The Netherlands as a case study
Authors: Cammu Nola 
Published: November 2024

Abstract
The legal implementation of a surrogacy framework poses many challenges of both civil and criminal legal nature. Controversies aside, a global trend towards an increasing regulation of surrogacy has been noticed. By proposing a stream of proposals for a legal surrogacy framework between 2016 and 2023, the Netherlands is finding itself in line with the aforementioned global trend. This article employs document analysis to map the thematic policy discussions that preceded and followed these legal proposals. The focus lies on policy assessments of surrogacy as (not) being ‘female reproductive labour’ and its consequences regarding notions of ‘exploitation’ and ‘compensation’ from a labour (social) law perspective. This combined analytic approach results in a broader understanding of the interplay between legal and policy debates on surrogacy in the Netherlands between the years 2016–2019 (preliminary workings) and 2019–2023 (parliamentary phase). Regarding the evolving notions of exploitation in/and of surrogacy, from national to foreign, links with ‘altruistic’ (versus: ‘commercial’) surrogacy and qualifications of surrogacy as ‘volunteering acts of service’ (versus: ‘work’) under a compensatory model, were palpable. Some critical questions with regard to the future legislative framework of surrogacy remain.
Specialization Restricts the Evolutionary Paths Available to Yeast Sugar Transporters
Authors: Crandall Johnathan G , Zhou Xiaofan , Rokas Antonis , Hittinger Chris Todd 
Published: November 2024

Abstract
Functional innovation at the protein level is a key source of evolutionary novelties. The constraints on functional innovations are likely to be highly specific in different proteins, which are shaped by their unique histories and the extent of global epistasis that arises from their structures and biochemistries. These contextual nuances in the sequence–function relationship have implications both for a basic understanding of the evolutionary process and for engineering proteins with desirable properties. Here, we have investigated the molecular basis of novel function in a model member of an ancient, conserved, and biotechnologically relevant protein family. These Major Facilitator Superfamily sugar porters are a functionally diverse group of proteins that are thought to be highly plastic and evolvable. By dissecting a recent evolutionary innovation in an α-glucoside transporter from the yeast Saccharomyces eubayanus, we show that the ability to transport a novel substrate requires high-order interactions between many protein regions and numerous specific residues proximal to the transport channel. To reconcile the functional diversity of this family with the constrained evolution of this model protein, we generated new, state-of-the-art genome annotations for 332 Saccharomycotina yeast species spanning ∼400 My of evolution. By integrating phylogenetic and phenotypic analyses across these species, we show that the model yeast α-glucoside transporters likely evolved from a multifunctional ancestor and became subfunctionalized. The accumulation of additive and epistatic substitutions likely entrenched this subfunction, which made the simultaneous acquisition of multiple interacting substitutions the only reasonably accessible path to novelty.
Faster and more accurate assessment of differential transcript expression with Gibbs sampling and edgeR v4
Authors: Baldoni Pedro L , Chen Lizhong , Smyth Gordon K 
Published: November 2024

Abstract
This article further develops edgeR's divided-count approach for differential transcript expression (DTE) analysis of RNA-seq data to produce a faster and more accurate pipeline. The divided-count approach models the precision of transcript quantifications from the kallisto and Salmon software tools and divides the estimated overdispersions out of the transcript read counts, after which the divided-counts can be analysed by statistical tools developed for gene-level counts. This article adds three new refinements to the pipeline that dramatically decrease the computational overhead and storage requirements so that DTE analysis of very large datasets becomes practical. The new pipeline replaces bootstrap with Gibbs resampling and replaces edgeR v3 with v4. Both of these changes improve statistical power and accuracy and provide better resolution for low-count transcripts. The accuracy of overdispersion estimation is shown to depend on the total number of resamples across the whole dataset rather than on individual samples, dramatically reducing the recommended number of technical samples for large datasets. Test data and extensive simulations data show that the new pipeline is more powerful and efficient than previous DTE pipelines while providing correct control of the false discovery rate for any sample size.
Development and validation of a clinical risk model for postoperative outcome in newly diagnosed glioblastoma: a report of the RANO resect group
Authors: Karschnia Philipp , Young Jacob S , Youssef Gilbert C , Dono Antonio , Häni Levin , Sciortino Tommaso , Bruno Francesco , Juenger Stephanie T , Teske Nico , Dietrich Jorg , Weller Michael , Vogelbaum Michael A , van den Bent Martin , Beck Juergen , Thon Niklas , Gerritsen Jasper K W , Hervey-Jumper Shawn , Cahill Daniel P , Chang Susan M , Rudà Roberta , Bello Lorenzo , Schnell Oliver , Esquenazi Yoshua , Ruge Maximilian I , Grau Stefan J , Huang Raymond Y , Wen Patrick Y , Berger Mitchel S , Molinaro Annette M , Tonn Joerg-Christian 
Published: November 2024

Abstract

Background
Following surgery, patients with newly diagnosed glioblastoma frequently enter clinical trials. Nuanced risk assessment is warranted to reduce imbalances between study arms. Here, we aimed (I) to analyze the interactive effects of residual tumor with clinical and molecular factors on outcome and (II) to define a postoperative risk assessment tool.

Methods
The response assessment in neuro-oncology (RANO) resect group retrospectively compiled an international, seven-center training cohort of patients with newly diagnosed glioblastoma. The combined associations of residual tumor with molecular or clinical factors and survival were analyzed, and recursive partitioning analysis was performed for risk modeling. The resulting model was prognostically verified in a separate external validation cohort.

Results
Our training cohort compromised 1003 patients with newly diagnosed isocitrate dehydrogenase-wildtype glioblastoma. Residual tumor, O6-methylguanine DNA methyltransferase (MGMT) promotor methylation status, age, and postoperative Karnofsky Performance Score were prognostic for survival and incorporated into regression tree analysis. By individually weighting the prognostic factors, an additive score (range, 0–9 points) integrating these four variables distinguished patients with low (0–2 points), intermediate (3–5 points), and high risk (6–9 points) for inferior survival. The prognostic value of our risk model was retained in treatment-based subgroups and confirmed in an external validation cohort of 258 patients with glioblastoma. Compared to previously postulated models, goodness-of-fit measurements were superior for our model.

Conclusions
The novel RANO risk model serves as an easy-to-use, yet highly prognostic tool for postoperative patient stratification prior to further therapy. The model may serve to guide patient management and reduce imbalances between study arms in prospective trials.
Breakthrough Rectal Neisseria gonorrhoeae Infections After Meningococcal B Vaccination: Microbiological and Clinical Features
Authors: Raccagni Angelo Roberto , Diotallevi Sara , Lolatto Riccardo , Bruzzesi Elena , Martearena Garcia Maria del Carmen , Mainardi Ilaria , Candela Caterina , Canetti Diana , Piromalli Girolamo , Clementi Nicola , Burioni Roberto , Castagna Antonella , Nozza Silvia 
Published: November 2024

Abstract

Background
4CMenB appears to be effective in reducing Neisseria gonorrhoeae (Ng) infections. Aims are to assess factors associated with breakthrough rectal Ng after 4CMenB and evaluate clinical and microbiological characteristics of breakthrough infections compared with before vaccination.

Methods
This was a retrospective study of gay, bisexual, and other men who have sex with men (GBMSM) vaccinated with 4CMenB (2 doses) between 2017 and 2023 at the San Raffaele Scientific Institute for Research, Hospitalization and Healthcare (IRCCS San Raffaele Scientific Institute), Milan, Italy, and tested for rectal Ng. Rectal Ng infection is considered breakthrough if it occurs &gt;1 month after the second 4CMenB dose and with positive nucleic acid amplification test (NAAT) result. Follow-up was from July 2017 (first 4CMenB vaccination) to November 2023 (data freeze). Rectal Ng was screened with both NAAT and gonococcal-specific cultures. Characteristics of individuals with or without breakthrough Ng and of Ng infections before or after 4CMenB were compared using Mann-Whitney and χ2/Fisher tests.

Results
Overall, 473 GBMSM vaccinated with 4CMenB were included, with a median age (interquartile range) of 43 (37–51) years; 451 of 473 were living with human immunodeficiency virus. The percentage of NAAT-positive rectal Ng swab samples was 76 of 957 (7.7%) after 4CMenB and 51 of 456 (11.1%) before. Breakthrough rectal Ng after baseline were 76 in 57 of 473 people. People with rectal Ng after 4CMenB were younger, more likely to have a previous sexually transmitted infection, and had more sexual partners than those without (all P &lt; .001). Breakthrough rectal Ng infections were less frequently symptomatic (34.2% vs 66.7%; P = .001) and more likely with negative gonococcal-specific culture (55.3% vs 19.6%; P &lt; .001) compared with before vaccination.

Conclusions
Breakthrough rectal Ng infections after 4CMenB were 76 in 57/473 people, preferentially identified in GBMSM with higher-risk sexual behaviors, were less often symptomatic, and more often with negative gonococcal-specific cultures, suggesting lower infection virulence.