bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic bias in malaria parasite relatedness estimation
Authors: Mehra Somya , Neafsey Daniel E , White Michael , Taylor Aimee R 
Published: January 2025

Abstract
Genetic studies of Plasmodium parasites increasingly feature relatedness estimates. However, various aspects of malaria parasite relatedness estimation are not fully understood. For example, relatedness estimates based on whole-genome-sequence (WGS) data often exceed those based on sparser data types. Systematic bias in relatedness estimation is well documented in the literature geared towards diploid organisms, but largely unknown within the malaria community. We characterise systematic bias in malaria parasite relatedness estimation using three complementary approaches: theoretically, under a non-ancestral statistical model of pairwise relatedness; numerically, under a simulation model of ancestry; and empirically, using data on parasites sampled from Guyana and Colombia. We show that allele frequency estimates encode, locus-by-locus, relatedness averaged over the set of sampled parasites used to compute them. Plugging sample allele frequencies into models of pairwise relatedness can lead to systematic underestimation. However, systematic underestimation can be viewed as population-relatedness calibration, i.e., a way of generating measures of relative relatedness. Systematic underestimation is unavoidable when relatedness is estimated assuming independence between genetic markers. It is mitigated when relatedness is estimated using WGS data under a hidden Markov model (HMM) that exploits linkage between proximal markers. The extent of mitigation is unknowable when a HMM is fit to sparser data, but downstream analyses that use high relatedness thresholds are relatively robust regardless. In summary, practitioners can either resolve to use relative relatedness estimated under independence, or try to estimate absolute relatedness under a HMM. We propose various tools to help practitioners evaluate their situation on a case-by-case basis.
Inferring demographic and selective histories from population genomic data using a two-step approach in species with coding-sparse genomes: an application to human data
Authors: Soni Vivak , Jensen Jeffrey D 
Published: January 2025

Abstract
The demographic history of a population, and the distribution of fitness effects (DFE) of newly arising mutations in functional genomic regions, are fundamental factors dictating both genetic variation and evolutionary trajectories. Although both demographic and DFE inference has been performed extensively in humans, these approaches have generally either been limited to simple demographic models involving a single population, or, where a complex population history has been inferred, without accounting for the potentially confounding effects of selection at linked sites. Taking advantage of the coding-sparse nature of the genome, we propose a 2-step approach in which coalescent simulations are first used to infer a complex multi-population demographic model, utilizing large non-functional regions that are likely free from the effects of background selection. We then use forward-in-time simulations to perform DFE inference in functional regions, conditional on the complex demography inferred and utilizing expected background selection effects in the estimation procedure. Throughout, recombination and mutation rate maps were used to account for the underlying empirical rate heterogeneity across the human genome. Importantly, within this framework it is possible to utilize and fit multiple aspects of the data, and this inference scheme represents a generalized approach for such large-scale inference in species with coding-sparse genomes.
Genomes reveal pervasive distant hybridization in nature among cyprinid fishes
Authors: Ren Li , Tu Xiaolong , Luo Mengxue , Liu Qizhi , Cui Jialin , Gao Xin , Zhang Hong , Tai Yakui , Zeng Yiyan , Li Mengdan , Wu Chang , Li Wuhui , Wang Jing , Wu Dongdong , Liu Shaojun 
Published: January 2025

Abstract

Background
Genomic data have unveiled a fascinating aspect of the evolutionary past, showing that the mingling of different species through hybridization has left its mark on the histories of numerous life forms. However, the relationship between hybridization events and the origins of cyprinid fishes remains unclear.

Results
In this study, we generated de novo assembled genomes of 8 cyprinid fishes and conducted phylogenetic analyses on 24 species. Widespread allele sharing across species boundaries was observed within 7 subfamilies of cyprinid fishes. Based on a systematic analysis of multiple tissues, we found that the testis exhibited a conserved pattern of divergence between the herbivorous Megalobrama amblycephala and the carnivorous Culter alburnus, suggesting a potential link to incomplete reproductive isolation. Significant differences in the expression of 4 genes (dpp2, ctrl, psb7, and ppce) in the liver and intestine, accompanied by variations in enzyme activities, indicated swift divergence in digestive enzyme secretion. Moreover, we identified introgressed genes linked to organ development in sympatric fishes with analogous feeding habits within the Cultrinae and Leuciscinae subfamilies.

Conclusions
Our findings highlight the significant role played by incomplete reproductive isolation and frequent gene flow events, particularly those associated with the development of digestive organs, in driving speciation among cyprinid fishes in diverse freshwater ecosystems.
Relationship between COVID-19 cases and monthly mortality from all causes, cancer, cardiovascular diseases and diabetes in 16 countries, 2020–21
Authors: Pizzato Margherita , Santucci Claudia , Islam Nazrul , La Vecchia Carlo , Alicandro Gianfranco 
Published: January 2025

Abstract

Background
During the COVID-19 pandemic, mortality from some chronic diseases increased. In this study, we evaluated monthly excess mortality from all causes, cancer, cardiovascular diseases (CVD) and diabetes during the months of 2020 and 2021, examining its relationship with COVID-19 cases.

Methods
Monthly cause-specific mortality data were downloaded from public repositories of national statistics offices or directly requested from them, and population data were obtained from the United Nations archives. Excess deaths were estimated as the difference between observed and expected deaths. Monthly expected deaths for 2020 and 2021 were calculated using a quasi-Poisson regression model trained on 2010–19 data (or a shorter timespan if the full decade of data was not available). To quantify the correlation between COVID-19 cases and monthly excess mortality, we used the Spearman’s correlation coefficient (rs).

Results
The study included 16 countries that provided monthly national data on causes of death (Argentina, Austria, Brazil, Switzerland, Chile, the Czech Republic, Germany, Georgia, Hungary, Italy, Lithuania, Latvia, Mexico, Serbia, Slovakia and the USA). A positive correlation was found between COVID-19 cases and monthly excess mortality from all causes in all countries (rs ranging from 0.61 to 0.91), from CVD in 11 countries (rs ranging from 0.45 to 0.85) and for diabetes in 13 countries (rs ranging from 0.42 to 0.79). Excess mortality above 5% was estimated from all causes in 14 countries for both 2020 and 2021, from CVD in seven countries for 2020 and in nine countries for 2021, and from diabetes in 11 countries for 2020 and in 12 countries for 2021. No excess above 5% was estimated for cancer mortality in any of the countries considered.

Conclusions
Excess mortality from CVD and diabetes persisted in several countries throughout 2021. These increases coincide with COVID-19 peaks, supporting a short-term impact of the COVID-19 pandemic on mortality from these causes.
Host-response testing with MeMed BV in community-acquired pneumonia: an economic evaluation from the UK NHS perspective
Authors: Gregg Emily , Graziadio Sara , Green William , Afonso Daniela , Garrett Monica , Watts Karina , Watkins Deborah , Carrol Enitan D , Cooke Jonathan , Felton Tim 
Published: January 2025

Abstract

Background
Community-acquired pneumonia (CAP) remains a leading cause of hospital admissions and mortality. A novel host-response test, MeMed BV (MMBV), has been developed for discriminating between bacterial and viral infection that could improve the clinical management of CAP.

Objectives
To evaluate the cost-effectiveness of using MMBV to guide antibiotic decisions in the clinical management of CAP in the UK.

Methods
An economic model was developed to understand the incremental cost per person associated with the implementation of MMBV from the UK NHS perspective. A qualitative care pathway analysis was performed to inform the standard of care (SOC) and SOC plus MMBV (SOC + MMBV) clinical pathways captured in the model.

Results
In the base case analysis, the SOC + MMBV strategy for a hypothetical cohort of 1000 patients (adults and children modelled independently) presenting to the emergency department with suspected CAP was estimated to provide total cost savings of £134 018 and £105 750 for adults and children, respectively. Cost savings were associated with reductions in total antibiotic treatment, the number of patients receiving additional diagnostic tests, and hospital admissions. Deterministic sensitivity analysis revealed that the specificity of SOC + MMBV and sensitivity of the SOC were primary drivers of the cost model for adults, whereas the specificity of SOC and SOC + MMBV were primary drivers for paediatrics.

Conclusions
Overall, the model predicts that the introduction of SOC + MMBV has the potential to be cost-saving and promote antimicrobial stewardship for both adult and paediatric CAP patients.
Replication across O6-methylguanine activates futile cycling of DNA mismatch repair attempts assisted by the chromatin-remodelling enzyme Smarcad1
Authors: Shigenobu-Ueno Karin , Sakamoto Reihi , Kanatsu Eiichiro , Kawasoe Yoshitaka , Takahashi Tatsuro S 
Published: January 2025

Abstract
SN1-type alkylating reagents generate O6-methylguanine (meG) lesions that activate the mismatch repair (MMR) response. Since post-replicative MMR specifically targets the nascent strand, meG on the template strand is refractory to rectification by MMR and, therefore, can induce non-productive MMR reactions. The cycling of futile MMR attempts is proposed to cause DNA double-strand breaks in the subsequent S phase, leading to ATR-checkpoint-mediated G2 arrest and apoptosis. However, the mechanistic details of futile MMR cycling, especially how this reaction is maintained in chromatin, remain unclear. Using replication-competent Xenopus egg extracts, we herein establish an in vitro system that recapitulates futile MMR cycling in the chromatin context. The meG–T mispair, but not the meG–C pair, is efficiently targeted by MMR in our system. MMR attempts on the meG-strand result in the meG-to-A correction, whilst those on the T-strand induce iterative cycles of strand excision and resynthesis. Likewise, replication across meG generates persistent single-strand breaks on the daughter DNA containing meG. Moreover, the depletion of Smarcad1, a chromatin remodeller previously reported to facilitate MMR, impairs the retention of single-strand breaks. Our study thus provides experimental evidence that chromatin replication across meG induces futile MMR cycling that is assisted by Smarcad1.
Oncogenic FLT3 internal tandem duplications (ITD) and CD45/PTPRC control osteoclast functions and bone microarchitecture
Authors: Lossius-Cott Carolin , Annoh Akua , Bens Martin , Nietzsche Sandor , Hoffmann Bianca , Figge Marc Thilo , Rauner Martina , Hofbauer Lorenz C , Müller Jörg P 
Published: January 2025

Abstract
Activating internal tandem duplications (ITD) in the juxtamembrane domain of receptor tyrosine kinase FLT3 occur frequently in patients with acute myeloid leukemia (AML). Constitutive active FLT3-ITD mutations induce aberrant signaling and promote leukemic cell transformation. Inactivation of the attenuating receptor protein tyrosine phosphatase CD45 (PTPRC) in FLT3-ITD mice resulted in the development of a severe hematopoietic phenotype with characteristics of AML. In addition, abnormal bone structures and ectopic bone formation were observed in these mice, suggesting a previously unknown role of FLT3 to control bone development and remodeling. While Ptprc knockout and Flt3-ITD mutant mice showed a largely normal bone microarchitecture, micro-CT analysis of femurs from Flt3-ITD Ptprc knockout mice revealed trabecularization of the cortical bone. This resulted in increased trabecular bone volume at the metaphysis, while the cortical bone at the diaphysis was thinner and less dense. In the metaphysis, severely reduced osteoclast and osteoblast numbers were observed. Reduced capacity of ex vivo differentiation of CD11b-positive bone marrow stem cells to mature osteoclast was accompanied by their abnormal morphology and reduced size. Transcriptome analysis revealed reduced expression of osteoclastogenic genes. Unexpectedly, cumulative resorption activity of osteoclasts was increased. Size and structure of resorption pits of differentiated osteoclasts remained similar to those observed in osteoclast cultures derived from control animals. Enhanced proliferation of cells in osteoclast cultures derived from FLT3-ITD–expressing mice was mediated by increased expression of STAT5 target genes. Transcriptome analysis of differentiated osteoclasts showed dysregulated signaling pathways influencing their differentiation as well as the coupling of bone resorption and formation. Taken together, inactivation of attenuating CD45 in mice expressing oncogenic FLT3-ITD resulted in marked abnormalities of the osteo-hematopoietic niche, which can be explained by aberrant STAT5 activation.
Two volatiles from anthracnose-infected blueberries trigger electrophysiological and aversive behavioral responses in Drosophila suzukii (Diptera: Drosophilidae)
Authors: Quadrel Amanda , Ferguson Beth , Rering Caitlin C , Urbaneja-Bernat Pablo , Rodriguez-Saona Cesar 
Published: January 2025

Abstract
Native to Southeast Asia, the spotted-wing drosophila (Drosophila suzukii Matsumura) is an economically important invasive pest of thin-skinned fruits such as raspberries, blueberries, and strawberries worldwide. To reduce the reliance on insecticides for managing this pest, alternative strategies like behavioral manipulation are needed. Previous studies have shown that D. suzukii adults avoid blueberry fruits infected with the fungal pathogen Colletotrichum fioriniae Marcelino & Gouli, which causes anthracnose fruit rot, leading to the identification of 9 potential repellent compounds. In this study, we further investigated the two most potent of these compounds—ethyl butanoate and ethyl (E)-but-2-enoate—to assess their repellent properties on the antennal and behavioral responses of D. suzukii. Electroantennogram (EAG) assays revealed that both esters elicited similar dose-dependent responses in male and female D. suzukii, which were often stronger than those triggered by 2-pentylfuran, a known repellent of this species. Additionally, we examined the behavioral responses of adult D. suzukii to these 3 repellent compounds under semi-field and field conditions using outdoor cages containing potted and planted blueberry bushes, respectively. Results from the cage studies showed that all 3 tested compounds can significantly reduce D. suzukii oviposition and adult emergence from blueberry fruits, with ethyl (E)-but-2-enoate sometimes outperforming the other compounds. Our findings indicate that the esters ethyl butanoate and ethyl (E)-but-2-enoate, which are induced from C. fioriniae-infected blueberries, elicit dose-dependent effects on D. suzukii antennae and act as effective oviposition deterrents. This supports their potential as promising tools for managing this pest through behavioral strategies.
Predictive variables for intraoperative blood loss and surgical time in resection of malignant soft tissue tumors without reconstruction
Authors: Nakamura Tomoki , Kobayashi Eisuke , Takenaka Satoshi , Endo Makoto , Hayashi Katsuhiro , Nakata Eiji , Ohshika Shusa , Kawashima Hiroyuki , Hamada Tetsuya , Horiuchi Keisuke , Nishida Yoshihiro , Hasegawa Masahiro , Morii Takeshi 
Published: January 2025

Abstract

Background
Procedural techniques such as dissection and separation of blood vessels or nerves from the tumor for preserving limbs and functions involves high surgical difficulty. We hypothesized the relation of vessel and/or nerve preservation to surgical time and blood loss, accurately reflecting surgical difficulty. In this study, we elucidated the variables affecting surgical time and intraoperative bleeding in patients with malignant soft tissue tumors who did not undergo any reconstruction after tumor resection.

Methods
We included 153 patients with malignant oft tissue tumors in the trunk (n = 72), thigh (n = 68), and upper arm (n = 13) at nine institutions. We analyzed the possible predictive variables affecting surgical time and intraoperative bleeding.

Results
Overall, the study included 153 patients (85 men and 68 women) with a mean age of 65 years. The tumors were primary soft tissue sarcoma (STS) (n = 114), local recurrent STS (n = 25), and soft tissue metastasis (n = 14). The median number of participating surgeons was three. The mean and median surgical time were 144.6 and 123 min, respectively. The mean and median intraoperative bleeding were 157.1 and 55 mL, respectively. Tumor size, depth, dissection and separation of blood vessels from the tumor, dissection and separation of nerve from the tumor, and the number of participating surgeons were significantly related to the surgical time and intraoperative bleeding.

Conclusions
The procedure of dissection and separation of blood vessels and nerves from the tumor were related to surgical time and intraoperative bleeding in patients with malignant soft tissue tumors, especially large and deep tumors.
Phenotypic and genomic characterization of Levilactobacillus brevis YT108: a potential probiotic strain capable of metabolizing xylo-oligosaccharides
Authors: Chen Yang , Zhou Jun , Li Xin , Li Xin-yao , Qiu Shi-xiu , Xu Zhen-ying , Yang Jian-xia , Zhu Yuan-ting , Zhang Xin-rui , Yan Lang 
Published: January 2025

Abstract
Levilactobacillus brevis YT108, identified for its ability to metabolize prebiotic xylo-oligosaccharides (XOS), emerges as a candidate for probiotic use in synbiotic food formulations. This study aimed to investigate the metabolic and genomic traits associated with XOS metabolism in YT108 and to assess its probiotic attributes through whole genome sequencing and in vitro assays. Strain YT108 exhibited robust growth kinetics on XOS as the sole carbon source, with a growth profile comparable to that on glucose, achieving a pH reduction to 4.68 and an OD600nm of 1.603 after 48 h. Three key gene clusters (xylCDEPFRT, xylHTG, and xylABT) and key enzymes (1,4-β-xylosidase) were identified as potentially involved in XOS metabolism. In vitro assays confirmed the strain’s remarkable physiological properties, including tolerance to acid, bile, heat, and NaCl, as well as resistance to simulated gastrointestinal juices and antioxidant capacity. Furthermore, strain YT108 was sensitive to five commonly used antibiotics and lacked transferable resistance genes. Taken together, these results highlight the potential of L. brevis YT108 as a probiotic candidate with beneficial traits for XOS utilization, suggesting its promising application in the formulation of next-generation synbiotic products.
Synaptic Plasticity in the Hippocampus
Authors: Bliss Tim , Collingridge Graham , Cooke Sam , Georgiou John , Morris Richard 
Published: January 2025

Abstract
This chapter provides an overview of activity-dependent synaptic plasticity in the hippocampus. It outlines the basic properties of long-term potentiation (LTP) and long-term depression (LTD) in the pathways that form the core hippocampal trisynaptic circuit, notably the Schaffer collateral/commissural (SCC) pathway connecting CA3 to CA1 pyramidal cells. Other significant pathways include the projections from medial and later entorhinal cortex (EC) to the distal dendrites of principal cells in all hippocampal subfields and the mossy fiber projection from dendate granule cells to CA3 pyramidal cells. The chapter then delves into the physiological and cell biological mechanisms of hippocampal synaptic plasticity and its contribution to hippocampus-dependent memory, including the relationship of synaptic plasticity to engrams. Another major focus is the role of dysregulated synaptic plasticity in synaptopathies, with a particular emphasis on neurodevelopmental, psychiatric and neurodegenerative brain disorders.
Hippocampal Physiology in the Behaving Animal
Authors: Krupic Julija , O’Keefe John 
Published: January 2025

Abstract
This chapter tackles the electrophysiological activity of the hippocampus in the behaving animal. It elaborates on the hippocampal local field potential (LFP) and its role in organizing hippocampal cellular activity. The LFP represents the state of the hippocampus as it shifts from an active mode in which the hippocampus controls the behavior of the animal to a more passive state with large amplitude irregular activity (LIA) and sharpwave ripples (SWRs). Moreover, hippocampal theta activity dominates the local field potential when the animal is actively attending to and moving around the environment. The chapter discusses the different cell types in the hippocampal formation and the properties of spatial cells.
Functions of the Human Hippocampus
Authors: Barry Daniel N. , Maguire Eleanor A. 
Published: January 2025

Abstract
This chapter describes the journey of signals once they enter the brain, and the roles played by the human hippocampus in their processing. This includes perception, short-term maintenance of information, replay, consolidation, and how representations are transformed or lost over time. The reconstruction of representations during retrieval is then considered, along with other flexible applications of hippocampal representations such as future planning, imagination, navigating through physical, conceptual and social space, and decision making. Coming full circle, we outline how prior experiences influence subsequent perception, attention and memory. The chapter ends by discussing hippocampal theories and whether they can account for extant data, identifying where knowledge gaps remain, and how they might be bridged in the future using new technologies.
Computational Models of Hippocampal Cognitive Function
Authors: Bush Daniel , Burgess Neil 
Published: January 2025

Abstract
Computational models of the hippocampus are invaluable in exploring the link between neurons and behavior, enabling hypothetical mechanisms to be defined precisely and examined quantitatively. This chapter reviews many of these, including models of spatial and mnemonic function, models that stress feedforward processing through the hippocampal system, and those stressing recurrent processing within it. It reviews the spatial models first, then those of associative or episodic memory function. Finally, it reviews recent proposals to unify the spatial and mnemonic functions of the hippocampus. These models are based on two related considerations: the correspondence between place or index-like representations in spatial or mnemonic models and low dimensional latent variables that efficiently describe the underlying causes of sensory input; and the benefit of finding representations that capture common relational structure across multiple contexts for prediction and generalization. Overall, these models instantiate cognitive maps of states or concepts and the relationships between them.