bluuebunny/crossref_metadata_2025 huggingface dataset:
Archaeological site detection on remote-sensed images using U-net
Authors: Gomes Adriano , Pascoal Rodrigo , Canedo Daniel , Neves António J. R. , Georgieva Petia
Published: November 2024

This project aims to develop a model to identify archeological sites (tumulus and hillforts) on LiDAR data through multiclass semantic segmentation. The data used is from the Alto-Minho region in the north of Portugal and was obtained within the scope of the ODYSSEY project. In this work, it was used a U-net model, that achieved a recall and precision of 64% and 94% (class-wise metrics), respectively, regarding the identification of hillforts, and was not able to identify any of the tumulus presented on the data.
Research on Computer Vision Models for Deep Learning in Autonomous Mobile Robots
Authors: Slavov Danail , Slavova Anastasiya , Hristov Vladimir
Published: November 2024

We propose a computer vision model for semantic and instance segmentation, based on YOLOv8 architecture and partial convolution modules. Transfer learning on the Cityscapes dataset is performed and results show comparable to the SOTA model accuracy. Furthermore, a speed comparison in terms of inference time is conducted, the results of which show that the proposed model is faster when processing larger input images using smaller batch sizes. Our research enhances the potentialities for further improvement in application of fast deep learning models in mobile robotics for complex vision tasks assisting their intelligent behaviour. It also suggests opportunities to increase the suitability of the improved models when implemented on low-resource hardware, such as edge devices and single-board computers, which in turn can facilitate integration of intelligent features and into various autonomous mobile robots in tasks such as self-driving, avoiding and detouring obstacles, optimal trajectory/path selection, increasing safety and reliability.
CMC/Gel/GO 3D-printed cardiac patches: GO and CMC improve flexibility and promote H9C2 cell proliferation, while EDC/NHS enhances stability
Authors: Arıcı Şule , Kamali Ali Reza , Ege Duygu
Published: November 2024

In this research, carboxymethyl cellulose (CMC)/gelatin (Gel)/graphene oxide (GO)-based scaffolds were produced by using extrusion-based 3D printing for cardiac tissue regeneration. Rheological studies were conducted to evaluate the printability of CMC/Gel/GO inks, which revealed that CMC increased viscosity and enhanced printability. The 3D-printed cardiac patches were crosslinked with N-(3-dimethylaminopropyl)-n’-ethylcarbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS) (100:20 mM, 50:10 mM, 25:5 mM) and then characterized by mechanical analysis, electrical conductivity testing, contact angle measurements and degradation studies. Subsequently, cell culture studies were conducted to evaluate the viability of H9C2 cardiomyoblast cells by using the Alamar Blue assay and fluorescence imaging. A high concentration of EDC/NHS (100:20 mM) led to the stability of the patches; however, it drastically reduced the flexibility of the scaffolds. Conversely, a concentration of 25:5 mM resulted in flexible but unstable scaffolds in phosphate buffer saline solution. The suitable EDC/NHS concentration was found to be 50:10 mM, as it produced flexible, stable, and stiff cardiac scaffolds with high ultimate tensile strength. Mechanical characterization revealed that % strain at break of C15/G7.5/GO1 exhibited a remarkable increase of 61.03% compared to C15/G7.5 samples. The improvement of flexibility was attributed to the hydrogen bonding between CMC, Gel and GO. The electrical conductivity of 3D printed CMC/Gel/GO cardiac patches was 7.0 × 10−3 S cm−1, demonstrating suitability for mimicking the desired electrical conductivity of human myocardium. The incorporation of 1 wt% of GO and addition of CMC concentration from 7.5 wt% to 15 wt% significantly enhanced relative % cell viability. Overall, although this research is at its infancy, CMC/Gel/GO cardiac patches have potential to improve the physiological function of cardiac tissue.
The anti-fouling activity of solvothermally synthesized Nb2O5-coated Fe ship strip on optimal interactions at the targeted interfaces of barnacle attachments -An Insilico study
Authors: Vanangamudi Aravindhan , Punniyakoti Sathyanarayanan
Published: November 2024

Fouling is a major issue occurring in water-going vessels, such as ships that cause increased surface roughness and drag resistance. The fouling organisms produce extracellular polymeric substances (EPS), which negatively impact water-going vessels. The settlement-inducing protein complex (SIPC) is a contact pheromone that promotes the gregarious settling of barnacle larvae (cyprids). The SIPC can be found in both adult barnacle cuticles and cyprids as transient adhesive secretions (footprints). The presence of SIPC in the footprints plays a critical role during the initial adhesion, which facilitates further settlement. The adsorption of of SIPC on Iron/Fe ship strip(FSS) surface was often found to be irreversible even after physical treatements. For the antifouling studies, Nb2O5 coated FSS were constructed and simulated to analyze the interaction of barnacles Aacp20K protein. For simulation studies, the homology model of barnacles Aacp20K protein is fabricated using the SWISS automated comparative modeling platform. The result of homology model showed a good 3D secondary structure of Aacp20K protein, especially 7q1y template protein. Adsorption location analysis results illustrate that the surface of the FSS coated with Nb2O5 film disfavour the binding of SIPC inhibiting the binding of barnacle cuticles and cyprids. For validating the simulation results, Nb2O5 nanostructure film was synthesized using a solvothermal process and characterized using XRD,SEM and EDS. Furthermore, the wetting behaviour was studied experimentally. The simulations and experimental results indicate Nb2O5-coated FSS as potent anti-fouling surfaces.
Accelerating data acquisition with FPGA-based edge machine learning: a case study with LCLS-II
Authors: Mehdi Rahimifar Mohammad , Wingering Quentin , Gouin-Ferland Berthié , Coffee Ryan , Therrien Audrey C
Published: November 2024

New scientific experiments and instruments generate vast amounts of data that need to be transferred for storage or further processing, often overwhelming traditional systems. Edge machine learning (EdgeML) addresses this challenge by integrating machine learning (ML) algorithms with edge computing, enabling real-time data processing directly at the point of data generation. EdgeML is particularly beneficial for environments where immediate decisions are required, or where bandwidth and storage are limited. In this paper, we demonstrate a high-speed configurable ML model in a fully customizable EdgeML system using a field programmable gate array (FPGA). Our demonstration focuses on an angular array of electron spectrometers, referred to as the ‘CookieBox,’ developed for the Linac Coherent Light Source II project. The EdgeML system captures 51.2 Gbps from a 6.4 GS s−1 analog to digital converter and is designed to integrate data pre-processing and ML inside an FPGA. Our implementation achieves an inference latency of 0.2 µs for the ML model, and a total latency of 0.4 µs for the complete EdgeML system, which includes pre-processing, data transmission, digitization, and ML inference. The modular design of the system allows it to be adapted for other instrumentation applications requiring low-latency data processing.
Gaussian unitary ensembles with jump discontinuities, PDEs, and the coupled Painlevé IV system
Authors: Chen Yang , Lyu Shulin
Published: November 2024

We study the Hankel determinant generated by the Gaussian weight with jump discontinuities at

t
1

t_1

, …,

t
m

t_m

. By making use of a pair of ladder operators satisfied by the associated monic orthogonal polynomials and three supplementary conditions, we show that the logarithmic derivative of the Hankel determinant satisfies a second-order partial differential equation which is reduced to the

σ
\sigma

-form of a Painlevé IV equation when

m
=
1

m=1

. Moreover, under the assumption that

t
k

−

t
1

t_k-t_1

is fixed for

k
=
2

k=2

, …,

m
m

, by considering the Riemann-Hilbert problem for the orthogonal polynomials, we construct direct relationships between the auxiliary quantities introduced in the ladder operators and solutions of a coupled Painlevé IV system.
RecGOBD: accurate recognition of gene ontology related brain development protein functions through multi-feature fusion and attention mechanisms
Authors: Xia Zhiliang , Ma Shiqiang , Li Jiawei , Guo Yan , Jiang Limin , Tang Jijun
Published: November 2024

Motivation

Protein function prediction is crucial in bioinformatics, driven by the growth of protein sequence data from high-throughput technologies. Traditional methods are costly and slow, underscoring the need for computational solutions. While deep learning offers powerful tools, many models lack optimization for brain development datasets, critical for neurodevelopmental disorder research. To address this, we developed RecGOBD (Recognition of Gene Ontology-related Brain Development protein function), a model tailored to predict protein functions essential to brain development.

Result

RecGOBD targets 10 key gene ontology (GO) terms for brain development, embedding protein sequences associated with these terms. Leveraging advanced pre-trained models, it captures both sequence and structure data, aligning them with GO terms through attention mechanisms. The category attention layer enhances prediction accuracy. RecGOBD surpassed five benchmark models in AUROC, AUPR, and Fmax metrics and was further used to predict autism-related protein functions and assess mutation impacts on GO terms. These findings highlight RecGOBD’s potential in advancing protein function prediction for neurodevelopmental disorders.

Availability and implementation

All Python codes associated with this study are available at https://github.com/ZL-Xia/RECGOBD.git.
Assessing variable importance in survival analysis using machine learning
Authors: Wolock C J , Gilbert P B , Simon N , Carone M
Published: November 2024

Given a collection of features available for inclusion in a predictive model, it may be of interest to quantify the relative importance of a subset of features for the prediction task at hand. For example, in HIV vaccine trials, participant baseline characteristics are used to predict the probability of HIV acquisition over the intended follow-up period, and investigators may wish to understand how much certain types of predictors, such as behavioral factors, contribute toward overall predictiveness. Time-to-event outcomes such as time to HIV acquisition are often subject to right censoring, and existing methods for assessing variable importance are typically not intended to be used in this setting. We describe a broad class of algorithm-agnostic variable importance measures for prediction in the context of survival data. We propose a nonparametric efficient estimation procedure that incorporates flexible learning of nuisance parameters, yields asymptotically valid inference, and enjoys double-robustness. We assess the performance of our proposed procedure via numerical simulations and analyze data from the HVTN 702 vaccine trial to inform enrollment strategies for future HIV vaccine trials.
Dual-energy metal artefact reduction for iodine-125 seed identification in postimplant CT after prostate brachytherapy
Authors: Suzuki Chiaki , Matsubara Kosuke , Ujihara Yuta , Isogai Kenta
Published: November 2024

Objectives

To assess the metal artefact reductions of dual-energy CT high-energy virtual monochromatic images (VMI) combined with the Single-Energy Metal Artifact Reduction (SEMAR) (CANON MEDICAL SYSTEMS, Otawara, Japan) processing techniques for iodine (I)-125 seed identification in postimplant CT after prostate brachytherapy

Methods

Dual-energy acquisition with fast tube voltage switching was performed on a prostate phantom with simulated seeds and six clinical cases treated with I-125 prostate brachytherapy. The images were retrospectively reconstructed at VMI energy levels of 65–200 keV and with and without SEMAR (SEMAR and non-SEMAR images). To estimate seed swelling, the calibre of iodine-125 seed was calculated as the full width at half maximum. The metal artefacts were evaluated using the artefact index (AI). The dose distributions were calculated and were compared among the high-energy VMI (SEMAR and non-SEMAR images) and low-energy VMI (SEMAR images).

Results

The blooming artefacts decreased at higher energy levels. In addition, the SEMAR process markedly reduced AI, which helped reduce overestimation of high dose ranges in the treatment planning dose map.

Conclusions

The locations and number of iodine-125 seed were clearly identified in the dose distribution map of the treatment planning using 200 keV VMI with SEMAR.

Advances in knowledge

The high-energy VMI of the dual-energy CT in combination with SEMAR is appropriate for the postimplant planning process of I-125 prostate brachytherapy.
Multiple delayed-onset metachronous ileal stenoses after transcatheter arterial embolization using N-butyl-2-cyanoacrylate for upper gastrointestinal bleeding: factors of complication and importance of plain CT evaluations
Authors: Sekikawa Zenjiro , Kamide Hiroyuki , Kobayashi Yusuke , Terauchi Miki
Published: November 2024

A 63-year-old man underwent transcatheter arterial embolization (TAE) using a mixture of N-butyl-2-cyanoacrylate (NBCA) and iodized oil to treat acute gastrointestinal (GI) bleeding. The procedure was initially successful; however, the patient developed ileus >1 month later and subsequently underwent several surgeries to treat the multiple metachronous ileal stenoses. The flux of a small amount of off-target glue was the primary cause of these complications. As the patient had few symptoms in the first month post-TAE, however, affirming the diagnosis took time. A detailed review of plain CT scans was a decisive factor in achieving the final diagnosis. This case demonstrates that TAE using an NBCA–iodized oil mixture effectively treats acute GI bleeding. However, a complication such as off-target embolization is likelier to occur because of a combination of certain factors such as vascular anatomy, complexity of the procedure, and NBCA dilution. Close observation using plain CT should be performed for the identification of off-target embolization occurrence even in cases of successful TAE.
dmTGS: Precise Targeted Enrichment Long-Read Sequencing Panel for Tandem Repeat Detection
Authors: Yang Kang , Liu Yue , Zhang Ji , Yu Qian , Xu Feng , Liu Jiyuan , Li Yuting , Zhang Xiaojie , Wang Zhiqiang , Wang Ning , Li Yuezhen , Shi Yan , Chen Wan-Jin
Published: November 2024

Background

Tandem repeats (TRs) are abundant in the human genome and associated with repeat expansion disorders. Our study aimed to develop a tandem repeat panel utilizing targeted long-read sequencing to evaluate known TRs associated with these disorders and assess its clinical utility.

Methods

We developed a targeted long-read sequencing panel for 70 TR loci, termed dynamic mutation third-generation sequencing (dmTGS), using the PacBio Sequel II platform. We tested 108 samples with suspected repeat expansion disorders and compared the results with conventional molecular methods.

Results

For 108 samples, dmTGS achieved an average of 8000 high-fidelity reads per sample, with a mean read length of 4.7 kb and read quality of 99.9%. dmTGS outperformed repeat-primed-PCR and fluorescence amplicon length analysis-PCR in distinguishing expanded from normal alleles and accurately quantifying repeat counts. The method demonstrated high concordance with confirmatory methods (rlinear = 0.991, P < 0.01), and detected mosaicism with sensitivities of 1% for FMR1 CGG premutation and 5% for full mutations. dmTGS successfully identified interruptive motifs in genes that conventional methods had missed. For variable number TRs in the PLIN4 gene, dmTGS identified precise repeat counts and sequence motifs. Screening 57 patients with suspected genetic muscular diseases, dmTGS confirmed repeat expansions in genes such as GIPC1, NOTCH2NLC, NUTM2B-AS1/LOC642361, and DMPK. Additionally, dmTGS detected CCG interruptions in CTG repeats in 8 myotonic dystrophy type 1 patients with detailed characterization.

Conclusions

dmTGS accurately detects repeat sizes and interruption motifs associated with repeat expansion disorders and demonstrates superior performance compared to conventional molecular methods.
Estimating Reference Change Values Using Routine Patient Data: A Novel Pathology Database Approach
Authors: Røys Eirik Åsen , Viste Kristin , Kellmann Ralf , Guldhaug Nora Alicia , Alaour Bashir , Sylte Marit Sverresdotter , Torsvik Janniche , Strand Heidi , Marber Michael , Omland Torbjørn , Theodorsson Elvar , Jones Graham Ross Dallas , Aakre Kristin Moberg
Published: November 2024

Background

The reference change value (RCV) is calculated by combining the within-subject biological variation (CVI) and local analytical variation (CVA). These calculations do not account for the variation seen in preanalytical conditions in routine practice or CVI in patients presenting for treatment. As a result, the RCVs may not reflect routine practice or align with clinicians’ experiences. We propose a novel RCV approach based on routine patient data that is potentially more clinically relevant.

Methods

This study used the refineR algorithm to determine RCVs using serial patient data extracted from a local Laboratory Information System (LIS). The model was applied to biomarkers with a range of result ratio distributions varying from normal to log-normal. Results were compared against conventional formula-based RCVs using CVI estimates from a state-of-the-art biological variation study. Monte Carlo simulations were also used to validate the LIS data approach.

Results

The RCVs estimated from LIS data were: 11-deoxycortisol (men): −70%/+196%, 17-hydroxyprogesterone (men): −49%/+100%, albumin: −10%/+11%, androstenedione (men): −47%/+96%, cortisol (men): −54%/+51%, cortisone (men): −32%/+51%, creatinine: −16%/+14%, phosphate (women): −23%/+29%, phosphate (men): −27%/+29%, testosterone (men): −38%/+60%. The formula-based RCV estimates showed similar but slightly lower results, and the Monte Carlo simulations confirmed the applicability of the new approach.

Conclusions

RCVs may be estimated from patient results without prior assumptions about the shape of the ratios between serial results. Laboratories can determine RCVs based on local practice and population.
Impact of genetic risk information for cardiovascular disease on behavioural changes, psychological responses and risk factor modification: a systematic review
Authors: Chen Ruofei (Trophy) , Pearson Vincent , Suebkinorn Orathai , Bulto Lemma N , Pincha Baduge Mihirika , Anderson Alice , Nelson Adam J , Zoungas Sophia , Clark Robyn A , Nicholls Stephen J
Published: November 2024

Aims

Cardiovascular disease (CVD) remains a significant public health concern, influenced by both genetic susceptibility and lifestyle factors. Integrating genetic risk information into clinical practice shows promise but has yielded mixed results regarding its impact on CVD prevention and management. This systematic review aimed to assess the impact of providing genetic CVD risk information on health behaviours, psychological outcomes, and risk factors.

Methods and results

Following Joanna Briggs Institute methodology and PRISMA 2020 guidelines, four electronic databases and two trial registries were searched for randomized controlled trials evaluating the impact of genetic risk information on the CVD risk profile. Data were synthesized using a narrative synthesis approach. Of the 3596 articles retrieved, 11 studies were eligible. Genetic risk information showed modest improvements in dietary behaviour but had inconclusive effects on physical activity and medication adherence. Minimal changes in psychological outcomes were noted, including a slight decrease in depression. The impact on traditional risk factors, such as systolic blood pressure and total cholesterol, was also limited. Bias across all studies was noted.

Conclusion

Genetic CVD risk information has limited effects on clinical outcomes and psychological factors, despite its potential to encourage some health behaviour changes. These findings suggest that genetic risk information alone may not be sufficient to significantly reduce cardiovascular risk, highlighting the need for further research to better understand its long-term effects.
Female germline expression of OVO transcription factor bridges Drosophila generations
Authors: Benner Leif , Muron Savannah , Wingfield Charli L , Oliver Brian
Published: November 2024

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 >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

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

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

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

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

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

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 >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

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

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

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

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

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

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 >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 < .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 < .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.
Lack of Detection of Norwalk Virus in Saliva Samples From a Controlled Human Infection Model
Authors: Atmar Robert L , Neill Frederick H , Hayes Nicole M , Opekun Antone R , Graham David Y , Estes Mary K , Ramani Sasirekha
Published: November 2024

Following recent reports of norovirus replication in salivary gland cells, we examined whether the prototype norovirus strain, Norwalk virus (GI.1), could be detected in the saliva of 21 experimentally infected persons. Viral RNA was not detected in saliva 2 and 7 days after challenge despite high levels being present in feces.
Crimson Behemoth: A massive clumpy structure hosting a dusty AGN at z=4.91
Authors: Tanaka Takumi S , Silverman John D , Nakazato Yurina , Onoue Masafusa , Shimasaku Kazuhiro , Fudamoto Yoshinobu , Fujimoto Seiji , Ding Xuheng , Faisst Andreas L , Valentino Francesco , Jin Shuowen , Hayward Christopher C , Kokorev Vasily , Ceverino Daniel , Kalita Boris S , Casey Caitlin M , Liu Zhaoxuan , Kaminsky Aidan , Fei Qinyue , Andika Irham T , Lambrides Erini , Akins Hollis B , Kartaltepe Jeyhan S , Koekemoer Anton M , McCracken Henry Joy , Rhodes Jason , Robertson Brant E , Franco Maximilien , Liu Daizhong , Chartab Nima , Gillman Steven , Gozaliasl Ghassem , Hirschmann Michaela , Huertas-Company Marc , Massey Richard , Roy Namrata , Sattari Zahra , Shuntov Marko , Sterling Joseph , Toft Sune , Trakhtenbrot Benny , Yoshida Naoki , Zavala Jorge A
Published: November 2024

The current paradigm for the co-evolution of galaxies and their supermassive black holes postulates that dust-obscured active galactic nuclei (AGNs) represent a transitional phase towards a more luminous and unobscured state. However, our understanding of dusty AGNs and their host galaxies at early cosmic times is inadequate due to observational limitations. Here, we present JWST observations of CID-931, an X-ray-detected AGN at a spectroscopic redshift of $z_{\rm spec}=4.91$. Multiband NIRCam imaging from the COSMOS-Web program reveals an unresolved red core, similar to JWST-discovered dusty AGNs. Strikingly, the red core is surrounded by at least eight massive star-forming clumps spread over ${1{^{\prime \prime}_{.}}6} \approx 10\,\,{\rm kpc}$, each of which has a stellar mass of $10^9$–$10^{10}\, M_{\odot }$ and a radius of $\sim$0.1–1 kpc. The whole system amounts to $10^{11}\, M_{\odot }$ in stellar mass, higher than typical star-forming galaxies at the same epoch. In this system, gas inflows and/or complex merger events may trigger clump formation and AGN activity, thus leading to the rapid formation of a massive galaxy hosting a supermassive black hole. Future follow-up observations will provide new insights into the evolution of the galaxy–black hole relationship during such transitional phases in the early universe.