bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haematogenous seeding in mycosis fungoides and Sézary syndrome: current evidence and clinical implications
Authors: Gniadecki Robert , Guenova Emmanuella , Querfeld Christiane , Nicolay Jan P , Scarisbrick Julia , Sokol Lubomir 
Published: November 2024

Abstract
Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of diseases characterized by abnormal neoplastic T-cell growth in the skin. Mycosis fungoides (MF), the most common CTCL, manifests as erythematous skin patches and/or plaques, tumours or erythroderma. The disease may involve blood, lymph nodes and rarely viscera. Sézary syndrome (SS) is a unique leukaemia/lymphoma syndrome related to MF, which presents with blood and skin involvement at diagnosis.
The pathogenesis of MF/SS is not fully elucidated. The presence of skin lesions at distant sites underpins a hypothesis that MF/SS lesions may develop through haematogenous seeding. Phenotypic similarities between malignant and normal T cells led to the notion that disease-initiating mutations occur in specific subtypes of mature T cells, which are responsible for most CTCLs. However, this mature T-cell precursor model is not always consistent with clinical observations and research on MF/SS pathogenesis.
Here, we review evidence supporting an alternative model of pathogenesis for MF/SS involving haematogenous seeding as a key process responsible for the initiation and progression of the disease. According to this hypothesis, malignant transformation occurs at an early stage of T-cell development (probably in bone marrow or thymus), yielding circulating neoplastic T cells which colonize the skin where the microenvironment is most permissive for proliferation and evolution. These mutated precursor cells seed the skin where they find a suitable niche to develop into clinically perceptible disease. Subsequently, malignant T cells can re-enter the bloodstream, re-seed pre-existing lesions and seed new areas of the skin, causing synchronous and convergent changes in the transcriptomic profile of lesions and tumours, and clinical disease progression – ‘consecutive haematogenous seeding’ captures this temporal phenomenon.
This model radically changes the current understanding of CTCL pathogenesis, transforming it from a primarily cutaneous disease with secondary involvement of blood, to a systemic disease, where the spread of malignant cells through the blood to the skin is not a phenomenon of advanced disease but is an essential component of pathogenesis.
This understanding of MF/SS could have several clinical implications, including standardizing our approach to assessing blood tumour burden, potential advances in prognosis and monitoring, and investigating combination treatments to improve patient outcomes.
Outcome prediction comparison of ischaemic areas’ radiomics in acute anterior circulation non-lacunar infarction
Authors: Zhou Xiang , Meng Jinxi , Zhang Kangwei , Zheng Hui , Xi Qian , Peng Yifeng , Xu Xiaowen , Gu Jianjun , Xia Qing , Wei Lai , Wang Peijun 
Published: November 2024

Abstract
The outcome prediction of acute anterior circulation non-lacunar infarction (AACNLI) is important for the precise clinical treatment of this disease. However, the accuracy of prognosis prediction is still limited. This study aims to develop and compare machine learning models based on MRI radiomics of multiple ischaemic-related areas for prognostic prediction in AACNLI. This retrospective multicentre study consecutively included 372 AACNLI patients receiving MRI examinations and conventional therapy between October 2020 and February 2023. These were grouped into training set, internal test set and external test set. MRI radiomics features were extracted from the mask diffusion-weighted imaging, mask apparent diffusion coefficient (ADC) and mask ADC620 by AACNLI segmentations. Grid search parameter tuning was performed on 12 feature selection and 9 machine learning algorithms, and algorithm combinations with the smallest rank-sum of area under the curve (AUC) was selected for model construction. The performances of all models were evaluated in the internal and external test sets. The AUC of radiomics model was larger than that of non-radiomics model with the same machine learning algorithm in the three mask types. The radiomics model using least absolute shrinkage and selection operator—random forest algorithm combination gained the smallest AUC rank-sum among all the algorithm combinations. The AUC of the model with ADC620 was 0.98 in the internal test set and 0.91 in the external test set, and the weighted average AUC in the three sets was 0.96, the largest among three mask types. The Shapley additive explanations values of the maximum of National Institute of Health Stroke Scale score within 7 days from onset (7-d NIHSSmax), stroke-associated pneumonia and admission Glasgow coma scale score ranked top three among the features in AACNLI outcome prediction. In conclusion, the random forest model with mask ADC620 can accurately predict the AACNLI outcome and reveal the risk factors leading to the poor prognosis.
Mutant huntingtin protein decreases with CAG repeat expansion: implications for therapeutics and bioassays
Authors: Landles Christian , Osborne Georgina F , Phillips Jemima , Canibano-Pico Maria , Nita Iulia M , Ali Nadira , Bobkov Konstantin , Greene Jonathan R , Sathasivam Kirupa , Bates Gillian P 
Published: November 2024

Abstract
Huntington’s disease is an inherited neurodegenerative disorder caused by a CAG repeat expansion that encodes a polyglutamine tract in the huntingtin (HTT) protein. The mutant CAG repeat is unstable and expands in specific brain cells and peripheral tissues throughout life. Genes involved in the DNA mismatch repair pathways, known to act on expansion, have been identified as genetic modifiers; therefore, it is the rate of somatic CAG repeat expansion that drives the age of onset and rate of disease progression. In the context of an expanded CAG repeat, the HTT pre-mRNA can be alternatively processed to generate the HTT1a transcript that encodes the aggregation prone and highly pathogenic HTT1a protein. This may be a mechanism through which somatic CAG repeat expansion exerts its pathogenic effects, as the longer the CAG repeat, the more HTT1a and HTT1a is produced. The allelic series of knock-in mouse models, HdhQ20, HdhQ50, HdhQ80, HdhQ111, CAG140 and zQ175 with polyglutamine expansions of 20, 50, 80, 111, 140 and ∼190, can be used to model the molecular and cellular consequences of CAG repeat expansion within a single neuron. By western blot of cortical lysates, we found that mutant HTT levels decreased with increasing CAG repeat length; mutant HTT was only 23 and 10% of wild-type levels in CAG140 and zQ175 cortices, respectively. To identify the optimal bioassays for detecting the full-length HTT and HTT1a isoforms, we interrogated the pairwise combinations of seven well-characterized antibodies on both the ‘homogeneous time-resolved fluorescence’ and ‘Meso Scale Discovery’ platforms. We tested 32 assays on each platform to detect ‘full-length mutant HTT’, HTT1a, ‘total mutant HTT’ (full-length HTT and HTT1a) and ‘total full-length HTT’ (mutant and wild type). None of these assays recapitulated the full-length mutant HTT levels as measured by western blot. We recommend using isoform- and species-specific assays that detect full-length mutant HTT, HTT1a or wild-type HTT as opposed to those that detect more than one isoform simultaneously. Our finding that as the CAG repeat expands, full-length mutant HTT levels decrease, while HTT1a and HTT1a levels increase has implications for therapeutic strategies. If mutant HTT levels in cells containing (CAG)200 are only 10% of wild-type, HTT-lowering strategies targeting full-length HTT at sequences 3ʹ to Intron 1 HTT will predominantly lower wild-type HTT, as mutant HTT levels in these cells are already depleted. These data support a therapeutic strategy that lowers HTT1a and depletes levels of the HTT1a protein.
Game on: a performance comparison of interpolation techniques applied to Shamir’s secret sharing
Authors: Voudouris Anastassis , Tressos Aristomenis , Zarras Apostolis , Xenakis Christos 
Published: November 2024

Abstract
Public-key encryption is typically managed through a public key infrastructure. However, it relies on a central control point, the certification authority, which acts as a single point of failure. Recent technological advancements have led to the need for decentralized cryptographic protocols. This paper presents a comprehensive study on enhancing public-key encryption via threshold cryptography and multiparty computation to ensure robust security in decentralized systems. The focus lies in exploring various polynomial interpolation techniques within Shamir’s secret sharing scheme, particularly addressing the efficiency and practicality of Newton interpolation, fast Fourier transformation (FFT), and advanced versions of Lagrange’s method. Utilizing SageMath for a dedicated testing environment, the research investigates the swiftest interpolation methods for secret recovery, introducing new shares into the system, and evaluating the impact of optimizations on performance. The findings highlight FFT as the most effective interpolation method in speed and efficiency, albeit with limitations on the number of shares that can be processed. This paper critically evaluates these interpolation techniques against practical constraints and aims to answer pivotal research questions regarding the optimal approach for large-scale scenarios, challenging existing notions on the efficiency of Newton’s method and providing experimental evidence to support the superiority of FFT in specific contexts.
Menaquinone production in genetically engineered E. coli
Authors: Jumpathong Jomkwan , Nishida Ikuhisa , Kaino Tomohiro , Kawamukai Makoto 
Published: November 2024

Abstract
Menaquinone (MK) is an important electron transporter in Escherichia coli. This isoprenoid quinone can transfer electrons to many terminal acceptors, such as fumarate and nitrate, which helps this organism survive under diverse and challenging conditions. As isoprenoid quinones with various lengths of isoprenyl tail are widely distributed in nature, the heterologous expression of polyprenyl diphosphate synthases (PDSs) has been investigated using its counterpart, ubiquinone (UQ). In this study, we investigated the MK production by the expression of various heterologous PDS genes from prokaryotic and eukaryotic species, including Saccharomyces cerevisiae COQ1 (hexa-PDS), Haemophilus influenzae hi0881 (hepta-PDS), Synechocystis sp. strain PCC6803 slr0611 (nona-PDS), and Gluconobacter suboxydans ddsA (deca-PDS) in E. coli. We detected specific isoforms of MK, including MK7, MK9, and MK10, via the expression of HI0881, Slr0611, and DdsA respectively, but barely detected MK6 via the expression of Coq1. As UQ6 was detected in E. coli harboring COQ1, the acceptance of the side chain lengths by MenA (prenyl transferase for MK) was narrower than UbiA (prenyl transferase for UQ). We also identified a mutation in menA in the E. coli AN386 strain and a transposon insertion of IS186 in menC in E. coli KO229 (∆ispB) and its parental strain FS1576. Taken together, these results elucidate the different nature of MenA from UbiA.
A multidimensional assessment of in-host fitness costs of drug resistance in the opportunistic fungal pathogen Candida glabrata
Authors: Arastehfar Amir , Daneshnia Farnaz , Hovhannisyan Hrant , Cabrera Nathaly , Ilkit Macit , Desai Jigar V , Gabaldón Toni , Shor Erika , Perlin David S 
Published: November 2024

Abstract
Drug-resistant microbes typically carry mutations in genes involved in critical cellular functions and may therefore be less fit under drug-free conditions than susceptible strains. Candida glabrata is a prevalent opportunistic yeast pathogen with a high rate of fluconazole resistance (FLZR), echinocandin resistance (ECR), and multidrug resistance (MDR) relative to other Candida. However, the fitness of C. glabrata MDR isolates, particularly in the host, is poorly characterized, and studies of FLZR isolate fitness have produced contradictory findings. Two important host niches for C. glabrata are macrophages, in which it survives and proliferates, and the gut. Herein, we used a collection of clinical and lab-derived C. glabrata isolates to show that FLZR C. glabrata isolates are less fit inside macrophages than susceptible isolates and that this fitness cost is reversed by acquiring ECR mutations. Interestingly, dual-RNAseq revealed that macrophages infected with drug-resistant isolates mount an inflammatory response whereas intracellular drug-resistant cells downregulate processes required for in-host adaptation. Furthermore, drug-resistant isolates were outcompeted by their susceptible counterparts during gut colonization and in infected kidneys, while showing comparable fitness in the spleen. Collectively, our study shows that macrophage-rich organs, such as the spleen, favor the retention of MDR isolates of C. glabrata.
The recombination landscape of the barn owl, from families to populations
Authors: Topaloudis Alexandros , Cumer Tristan , Lavanchy Eléonore , Ducrest Anne-Lyse , Simon Celine , Machado Ana Paula , Paposhvili Nika , Roulin Alexandre , Goudet Jérôme 
Published: November 2024

Abstract
Homologous recombination is a meiotic process that generates diversity along the genome and interacts with all evolutionary forces. Despite its importance, studies of recombination landscapes are lacking due to methodological limitations and limited data. Frequently used approaches include linkage mapping based on familial data that provides sex-specific broad-scale estimates of realized recombination and inferences based on population linkage disequilibrium that reveal a more fine-scale resolution of the recombination landscape, albeit dependent on the effective population size and the selective forces acting on the population. In this study, we use a combination of these 2 methods to elucidate the recombination landscape for the Afro-European barn owl (Tyto alba). We find subtle differences in crossover placement between sexes that lead to differential effective shuffling of alleles. Linkage disequilibrium-based estimates of recombination are concordant with family-based estimates and identify large variation in recombination rates within and among linkage groups. Larger chromosomes show variation in recombination rates, while smaller chromosomes have a universally high rate that shapes the diversity landscape. We find that recombination rates are correlated with gene content, genetic diversity, and GC content. We find no conclusive differences in the recombination landscapes between populations. Overall, this comprehensive analysis enhances our understanding of recombination dynamics, genomic architecture, and sex-specific variation in the barn owl, contributing valuable insights to the broader field of avian genomics.
Temporal Sequence of Incident Mild Cognitive Impairment, Incident Parkinsonism, and Risk of Death in Unimpaired Community-Dwelling Older Adults
Authors: Zammit Andrea R , Yu Lei , Oveisgharan Shahram , Schneider Julie A , Bennett David A , Buchman Aron S 
Published: November 2024

Abstract

Background
Mild cognitive impairment (MCI) and parkinsonism affect many older adults. The objective of this study was to determine the sequence of their occurrence and associated risk of death.

Methods
A total of 1255 community-dwelling unimpaired participants from 2 epidemiological cohorts were examined annually. MCI was based on neuropsychological testing and parkinsonism was based on the motor portion of the modified Unified Parkinson’s Disease Rating Scale. A multistate Cox proportional hazards model simultaneously examined incidences of MCI, parkinsonism, and death.

Results
The average age at baseline was 76.5 years (standard deviation [SD] = 7.2) and 73% were female. Incident MCI occurred almost as commonly as incident parkinsonism, yet compared with no impairment, the risk of death was higher for MCI (hazard ratio [HR] = 1.82, 95% confidence interval [CI] = 1.34, 2.47), but it was not different for parkinsonism (HR = 1.29; 95% CI =0.95, 1.75). The risk of death for participants with incident MCI who progressed to parkinsonism (40%) was not significantly different from those with MCI alone (HR = 1.25, 95% CI = 0.93, 1.69). However, the risk of death for participants with incident parkinsonism who progressed to MCI (51%) was significantly higher than those who did not progress (HR = 1.67, 95% CI = 1.27, 2.18), indicating that the risk of death is highest with the incidence of MCI.

Conclusions
The varied patterns of sequential occurrence of cognitive and motor impairment and associated risk of death suggest much greater heterogeneity than previously recognized. Further work is needed to determine the biology underlying the temporal evolution of these phenotypes, and if identification of the various subtypes improves risk stratification.
Local Knowledges in International Peacebuilding: Acquisition, Filtering, and Systematic Bias
Authors: von Billerbeck Sarah , Coleman Katharina P , Eckhard Steffen , Zyla Benjamin 
Published: November 2024

Abstract
There is widespread consensus among peacebuilding practitioners and scholars on the importance of integrating local knowledge into the design, planning, and implementation of international peace interventions. However, the concept of local knowledge remains undertheorized, and the dynamics of local knowledge integration in international activities have not yet been fully explored. This paper reconceptualizes “local knowledge” in peacebuilding as local knowledges in the plural, highlighting seven categories of relevant local knowledge and the contestation within each. We then draw on organizational theory to identify the processes by which particular types of local knowledge become more or less likely to be incorporated into internationally led peacebuilding activities. Specifically, we argue that knowledge incorporation consists of two stages: acquisition and filtering. In both, international actors control who is able to contribute knowledges and which knowledges are recognized. Systematic biases result: knowledges that confirm previously held beliefs or that simplify complexity are incorporated more regularly. We illustrate our argument by focusing on the UN, but suggest that our findings apply to other international actors, including non-governmental organizations, and extend beyond peacebuilding.
Competition law through the lenses of national constitutions: connecting competitive markets with socio-economic and environmental values
Authors: Bernatt Maciej 
Published: November 2024

Abstract
This article analyses competition legislation through the lenses of national constitutions, given that these constitutions establish the foundational structures of national legal systems to which competition laws inherently belong. Building on existing constitutional literature, it posits that competition laws should be construed in accordance with the values promoted in national constitutions. The analysis is situated within the contemporary discourse surrounding the ongoing ‘just transition’ towards a carbon-neutral economy, i.e., a process in which socio-economic values (pertaining to the right to work, right to healthcare, and right to food) and environmental values (pertaining to a clean environment, biodiversity, and reducing emissions) constitute guiding tenets. Such a context invites the question of whether competition laws should be built and interpreted in a manner that facilitates the enhanced integration of socio-economic and environmental values enshrined in national constitutions. These contemplations are pivotal, since law plays a constitutive role in designing socio-economic structures, with the structuring of competitive markets being no exception. In light of this, the paper conducts a review of how national constitutions across the world safeguard competitive markets, socio-economic values, and environmental values. Specifically, the article categorizes the regulatory frameworks identified within all 52 national constitutions that explicitly protect competitive markets alongside socio-economic and environmental values. Subsequently, the paper transitions to an examination of two countries—Poland and South Africa—to elucidate how national competition laws reflect constitutional choices. It demonstrates that their constitutions and competition laws were shaped in a manner that offers a different space for incorporation of socio-economic and environmental values in the interpretation of competition laws. The article relies on an analysis of the texts of national constitutions and competition statutes, as well as selected case law of constitutional courts and ordinary courts. Overall, the article seeks to incite an academic discourse regarding the significance of national constitutions in the realm of antitrust. At the same time, it expands upon the literature concerning economic constitutions, especially regarding the European Union and its Member States.
Machine learning-based prediction models in medical decision-making in kidney disease: patient, caregiver, and clinician perspectives on trust and appropriate use
Authors: Sperling Jessica , Welsh Whitney , Haseley Erin , Quenstedt Stella , Muhigaba Perusi B , Brown Adrian , Ephraim Patti , Shafi Tariq , Waitzkin Michael , Casarett David , Goldstein Benjamin A 
Published: November 2024

Abstract

Objectives
This study aims to improve the ethical use of machine learning (ML)-based clinical prediction models (CPMs) in shared decision-making for patients with kidney failure on dialysis. We explore factors that inform acceptability, interpretability, and implementation of ML-based CPMs among multiple constituent groups.

Materials and Methods
We collected and analyzed qualitative data from focus groups with varied end users, including: dialysis support providers (clinical providers and additional dialysis support providers such as dialysis clinic staff and social workers); patients; patients’ caregivers (n = 52).

Results
Participants were broadly accepting of ML-based CPMs, but with concerns on data sources, factors included in the model, and accuracy. Use was desired in conjunction with providers’ views and explanations. Differences among respondent types were minimal overall but most prevalent in discussions of CPM presentation and model use.

Discussion and Conclusion
Evidence of acceptability of ML-based CPM usage provides support for ethical use, but numerous specific considerations in acceptability, model construction, and model use for shared clinical decision-making must be considered. There are specific steps that could be taken by data scientists and health systems to engender use that is accepted by end users and facilitates trust, but there are also ongoing barriers or challenges in addressing desires for use. This study contributes to emerging literature on interpretability, mechanisms for sharing complexities, including uncertainty regarding the model results, and implications for decision-making. It examines numerous stakeholder groups including providers, patients, and caregivers to provide specific considerations that can influence health system use and provide a basis for future research.