bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anlotinib plus chemotherapy as a first-line treatment for gastrointestinal cancer patients with unresectable liver metastases: a multicohort, multicenter, exploratory trial
Authors: Wu Jun-Wei , Zhou Chen-Fei , Han Zheng-Xiang , Zhang Huan , Yan Jun , Chen Jun , Wang Chun-Bin , Qin Zhi-Quan , Mao Yong , Tang Xin-Yu , Zhu Liang-Jun , Wei Xiao-Wei , Cui Dong-Hai , Yang Xiu-Li , Shi Min , Zhao Li-Qin , Jiang Jin-Ling , Zhu Wei-You , Wang Hong-Mei , Wang Chun , Zhu Ling-Jun , Zhang Jun 
Published: December 2024

AbstractThis multicohort phase II trial (ALTER-G-001; NCT05262335) aimed to assess the efficacy of first-line anlotinib plus chemotherapy for gastrointestinal (GI) cancer patients with unresectable liver metastases. Eligible patients with colorectal cancer (Cohort A) or noncolorectal and nonesophageal GI cancer (Cohort C) received six cycles of anlotinib plus standard chemotherapeutic regimens followed by anlotinib plus metronomic capecitabine as a maintenance therapy. Liver metastasectomy can be performed when liver metastases are converted to resectable lesions. The primary outcome was the investigator-confirmed objective response rate (ORR) in the intention-to-treat population. Among the 47 patients in Cohort A, the ORR was 40.4% (95% CI 26.4–55.7), including 1 with a complete response (CR) and 18 who achieved a partial response (PR). The median progression-free survival (PFS) was 8.7 months (95% CI 7.3-NE), and the median overall survival (OS) was not reached. In Cohort C, 14 of 44 patients achieved a PR, with an ORR of 31.8% (95% CI 18.6–47.6). The PFS and OS were 5.8 months (95% CI 4.8–6.5) and 11.4 months (95% CI 5.8–19.3), respectively. The liver metastasectomy rate in patients with liver-limited disease was 22.7% (5/22) in Cohort A and 6.7% (2/30) in Cohort C. For pancreatic cancer patients, the ORR of the efficacy-evaluable population was 36.0% (9/25), and those with liver-limited metastasis had better survival. Moreover, no new safety concerns emerged. In conclusion, an anlotinib-based first-line regimen demonstrated promising antitumor activity among GI cancer patients with unresectable liver metastases and led to liver metastasectomy in selected patients.
What can echolocation recordings reveal about the species composition, habitat specificity and structure of mangrove bat communities in the Northern Territory?
Authors: McKenzie N. L. , Bullen R. D. , Milne D. J. 
Published: December 2024

In June 2021 we used ultrasonic recorders to inventory zoophagic bats at mangrove patches in three bioregions on the Northern Territory coast: Darwin Coastal, Arnhem Coast and Gulf Coastal. All species could be separated in terms of their search-mode echolocation sequences using tropical Western Australian and Northern Territory reference libraries based on pulse peak frequency (Fpeak), fineness-of-tuning (Q−6dB), repetition-rate and shape. Twenty-five of the 27 species that comprise the ‘Top End’ zoophagic bat fauna are now known to occur in its mangroves, an average of 21.3 ± 0.3 (s.e.) species per bioregion. Northern Territory and Western Australian populations of all but three species show few discernable differences in the four echolocation metrics assessed. Unlike the tropical bioregions in Western Australia, no bat species is confined to mangroves in the Northern Territory. Even so, analysis of data from these and adjacent bioregions shows that bat community structures throughout tropical north-western Australia are adapted to their environmental setting.
Using stable-isotope analysis to assess recent diet and habitat use of stranded green turtles (Chelonia mydas)
Authors: Glen Joshua J. , Buelow Christina A. , Campbell Max D. , Day Joanna , Meagher Phoebe J. B. , van de Merwe Jason P. , Pearson Ryan M. 
Published: December 2024

Context Gaining a better understanding of the foraging ecology of green turtles (Chelonia mydas) in different regions can improve the effectiveness of conservation and management strategies for this species. New South Wales (NSW), in eastern Australia, has been identified as a region requiring improved information on foraging ecology and habitat use by green turtles. Aims The aim of this study was to use stable-isotope analyses to investigate diet composition and foraging ecology of green turtles found stranded along the NSW coastline from 2018 to 2021. Methods This study measured δ13C, δ15N, and δ34S in macrophyte (mangrove, seagrass, and algae) samples collected along the NSW coastline, between March and June 2021, and epidermis tissue from green turtles that stranded in the same region between 2018 and 2021. In addition, stable-isotope values for animals known, or expected, to be consumed by green turtles were sourced from the literature. Macrophyte stable-isotope values were mapped to display spatial variations, then combined with literature-sourced animal matter and measured epidermis isotope values into stable-isotope mixing models. Mixing models were used to determine diet structure for each stranded green turtle, and their similarity to regional macrophyte isotope values to infer potential foraging locations. Key results High variation was present in δ13C, δ15N, and δ34S values of macrophyte sources along the NSW coastline, limiting the potential to infer the recent foraging locations of stranded green turtles. High δ15N values in green turtle epidermis samples indicated that most sampled turtles were feeding two to three trophic levels above primary producers within algal-based food webs. Mixing models suggested that these food webs were predominantly supported by algae (mean ± s. d. = 51.2 ± 6.1%) and animal material (31.4 ± 4.7%), with mangrove (13.4 ± 2.0%) and seagrass (4.0 ± 2.5%) representing much smaller proportions of overall diet composition. Conclusions The results showed that green turtles stranded along the NSW coastline feed primarily in algae-dominated food webs, with evidence of omnivory. These findings suggest that sampled individuals display diet compositions alternative to those of their Queensland counterparts, who feed primarily in seagrass-dominated habitats. Management and conservation programs in NSW should focus on limiting anthropogenic disturbances in algae-dominated habitats. Implications This novel finding demonstrated the importance of algae-dominated habitats for green turtle conservation and management in south-eastern Australia. The generated isoscapes are useful in examining isotopic variations in macrophytes along the NSW coastline.
Lexical anticipation in bilinguals
Authors: Moreno Eva M. , Martin Clara D. , Foucart Alice 
Published: December 2024

Abstract
This chapter aims to acknowledge Prof. Albert
Costa’s contribution to the research field of language anticipation
in L2 readers/listeners. It starts with a brief introduction to
contrasting psycholinguistic models regarding the issue of lexical
pre-activation during language comprehension and it describes how
the Event Related Potential (ERP) technique advanced the
anticipation/integration debate in native (L1) speakers. Then, the
first studies looking at lexical anticipation in a second language
(L2) with ERPs conducted by Costa’s lab are reported. The following
section describes the influence of Costa’s results in the debate on
the pre-activation of the phonological form of predictable words, as
well as how his original work developed into further work on lexical
anticipation in L2 at sentence and discourse levels. Costa’s
heritage extended to other linguistic aspects related to L2, like
processing foreign-accented speech. The chapter ends with some
conclusions and future directions.
Discovery of the closest free-living relative of the domesticated “magic mushroom”Psilocybe cubensisin Africa
Authors: Bradshaw Alexander J , Sharp Cathy , Van Der Merwe Breyten , Tremble Keaton , Dentinger Bryn T.M. 
Published: December 2024

AbstractThe “magic mushroom”Psilocybe cubensisis cultivated worldwide for recreational and medicinal uses. Described initially from Cuba in 1904, there has been substantial debate about its origin and diversification. The prevailing view, first proposed by thePsilocybeexpert Gastón Guzmán in 1983, is thatP. cubensiswas inadvertently introduced to the Americas when cattle were introduced to the continents from Africa and Europe (∼1500 CE), but that its progenitor was endemic to Africa. This hypothesis has never been tested. Here, we report the discovery of the closest wild relative ofP. cubensisfrom sub-Saharan Africa,P. ochraceocentratanom. prov. Using DNA sequences from type specimens of all known and accessable African species ofPsilocybe, multi-locus phylogenetic and molecular clock analysis strongly support recognizing the African samples as a new species that last shared a common ancestor withP. cubensis∼1.5 million years ago (∼710k - 2.55M years ago 95% HPD). Even at the latest estimated time of divergence, this long predates cattle domestication and the origin of modern humans. Both species are associated with herbivore dung, suggesting this habit likely predisposedP. cubensisto its present specialization on domesticated cattle dung. Ecological niche modeling using bioclimatic variables for global records of these species indicates historical presence across Africa, Asia, and the Americas over the last 3 million years. This discovery sheds light on the wild origins of domesticatedP. cubensisand provides new genetic resources for research on psychedelic mushrooms.
Evolution of ivermectin resistance in the nematode modelCaenorhabditis elegans: critical influence of population size and unexpected cross-resistance to emodepside
Authors: Hellinga Jacqueline , Trubenova Barbora , Wagner Jessica , Regoes Roland R. , Krücken Jürgen , Schulenburg Hinrich , von Samson-Himmelstjerna Georg 
Published: December 2024

AbstractThe emergence and spread of anthelmintic resistance represent a major challenge for treating parasitic nematodes, threatening mass-drug control programs in humans and zoonotic species. Currently, experimental evidence to understand the influence of management (e.g., treatment intensity and frequency) and parasite-associated factors (e.g., genetic variation, population size and mutation rates) is lacking. To rectify this knowledge gap, we performed controlled evolution experiments with the model nematodeCaenorhabditis elegansand further evaluated the evolution dynamics with a computational model. Large population size was critical for rapid ivermectin resistance evolutionin vitroandin silico. Male nematodes were favored during resistance evolution, indicating a selective advantage of sexual recombination under drug pressurein vitro. Ivermectin resistance evolution led to the expected emergence of cross-resistance to the structurally related anthelmintic moxidectin but unexpectedly also to the structurally unrelated anthelmintic emodepside that has an entirely different mode of action. In contrast, albendazole, levamisole, and monepantel efficacy were not influenced by the evolution of Ivermectin resistance. We conclude that combining computational modeling within vitroevolution experiments to test specific aspects of evolution directly represents a promising approach to guide the development of novel treatment strategies to anticipate and mitigate resistance evolution in parasitic nematodes.
Genetic differentiation in theMAT-proximal region is not sufficient for suppressing recombination inPodospora anserina
Authors: Grognet Pierre , Debuchy Robert , Giraud Tatiana 
Published: December 2024

ABSTRACTRecombination is advantageous over the long-term, as it allows efficient selection and purging deleterious mutations. Nevertheless, recombination suppression has repeatedly evolved in sex chromosomes and mating-type chromosomes. The evolutionary causes for recombination suppression and the proximal mechanisms preventing crossing overs are still poorly understood. Several hypotheses have recently been suggested based on theoretical models, and in particular, that divergence could accumulate neutrally around a sex-determining region and reduce recombination rates, a self-reinforcing process that could foster progressive extension of recombination suppression. The ascomycete fungusPodospora anserinais an excellent model for investigating these questions. A 0.8 Mb region around the mating-type locus is non-recombining, despite being collinear between the two mating types. This fungus is mostly selfing, so that strains are highly homozygous, except in the non-recombining region around the mating-type locus that displays differentiation between mating types. Here, we generated a mutant to test the hypothesis that sequence divergence alone is responsible for recombination cessation. We replaced themat-idiomorph by the sequence of themat+idiomorph, to obtain a strain that is sexually compatible with themat-reference strain and isogenic to this strain in theMAT-proximal region. Crosses showed that recombination was still suppressed in theMAT-proximal region in the mutant strains, indicating that other proximal mechanisms than inversions or mere sequence divergence are responsible for recombination suppression in this fungus. This finding suggests that selective mechanisms likely acted for suppressing recombination, as the neutral model does not seem to hold, at least in this fungus.ARTICLE SUMMARYIn many organisms, a non-recombining region is observed around the sex-determining locus. In the fungusPodospora anserina, recombination is suppressed within an 800kb region around the mating-type locus. In natural strains, the genome is isogenic between two mating-types, except in this region displaying heterozygosity. To determine if this heterozygosity can be responsible for the lack of recombination, compatible strains were engineered to be isogenic, including in the non-recombining region. Recombination inhibition persisted, indicating that mere sequence divergence does not cause recombination suppression. Our study provides an interesting insight on the molecular and evolutionary causes of recombination inhibition.
GraphVelo allows for accurate inference of multimodal velocities and molecular mechanisms for single cells
Authors: Chen Yuhao , Zhang Yan , Gan Jiaqi , Ni Ke , Chen Ming , Bahar Ivet , Xing Jianhua 
Published: December 2024

AbstractRNA velocities and generalizations emerge as powerful approaches for extracting time-resolved information from high-throughput snapshot single-cell data. Yet, several inherent limitations restrict applying the approaches to genes not suitable for RNA velocity inference due to complex transcriptional dynamics, low expression, or lacking splicing dynamics, or data of non-transcriptomic modality. Here, we present GraphVelo, a graph-based machine learning procedure that uses as input the RNA velocities inferred from existing methods and infers velocity vectors lying in the tangent space of the low-dimensional manifold formed by the single cell data. GraphVelo preserves vector magnitude and direction information during transformations across different data representations. Tests on multiple synthetic and experimental scRNA-seq data including viral-host interactome and multi-omics datasets demonstrate that GraphVelo, together with downstream generalized dynamo analyses, extends RNA velocities to multi-modal data and reveals quantitative nonlinear regulation relations between genes, virus and host cells, and different layers of gene regulation.
An RNAi screen of Rab GTPase genes inC. elegansreveals that somatic cells of the reproductive system depend onrab-1for morphogenesis but not stem cell niche maintenance
Authors: Scott Kayt , Singh Noor , Gordon Kacy Lynn 
Published: December 2024

ABSTRACTMembrane trafficking is a crucial function of all cells and is regulated at multiple levels from vesicle formation, packaging, and localization to fusion, exocytosis, and endocytosis. Rab GTPase proteins are core regulators of eukaryotic membrane trafficking, but developmental roles of specific Rab GTPases are less well characterized, potentially because of their essentiality for basic cellular function.C. elegansgonad development entails the coordination of cell growth, proliferation, and migration—processes in which membrane trafficking is known to be required. Here we take an organ-focused approach to Rab GTPase functionin vivoto assess the roles of Rab genes in reproductive system development. We performed a whole-body RNAi screen of the entire Rab family inC. elegansto uncover Rabs essential for gonad development. Notable gonad defects resulted from RNAi knockdown ofrab-1,the key regulator of ER-Golgi trafficking. We then examined the effects of tissue-specific RNAi knockdown ofrab-1in somatic reproductive system and germline cells. We interrogated the dual functions of the distal tip cell (DTC) as both a leader cell of gonad organogenesis and the germline stem cell niche. We find thatrab-1functions cell-autonomously and non-cell-autonomously to regulate both somatic gonad and germline development. Gonad migration, elongation, and gamete differentiation—but surprisingly not germline stem niche function—are highly sensitive torab-1RNAi.SUMMARYThe Rab family of GTPases regulate vesicular trafficking in cells. This study assessed the consequences for the growth of the gonad of RNAi-mediated gene knockdown of all Rab GTPase genes inC. elegans. The highly conserved primary regulator of ER-Golgi trafficking,rab-1, is essential for normal gonad and germline development. Further experiments found thatrab-1is required in the somatic gonad for gonad elongation and migration, germline proliferation, and proper gamete formation. Surprisingly, the ability of the germline stem cell niche to maintain germ cells in the proliferative stem-like state was not affected byrab-1RNAi knockdown.
Dietary intervention in captive-bred hares fails to enrich gut microbiomes with wild-like functions
Authors: Aizpurua Ostaizka , Martin-Bideguren Garazi , Gaun Nanna , Alberdi Antton 
Published: December 2024

AbstractReintroducing captive-bred animals into the wild often faces limited success, with the underlying causes frequently unclear. One emerging hypothesis is that maladapted gut microbiota may play a significant role in these challenges. To investigate this possibility, we employed genome-resolved metagenomics to analyse the taxonomic and functional differences in the gut microbiota of wild and captive European hares (Lepus europaeus), as well as to assess the impact of a dietary switch to grass aimed at pre-adapting captive hares to wild conditions. Our analyses recovered 860 metagenome-assembled genomes, with 87% of them representing novel species. We found significant taxonomic and functional differences between the gut microbiota of wild and captive hares, notably the absence of Spirochaetota in captive animals and differences in amino acid and sugar degradation capacities. While the dietary switch to grass induced some minor changes in the gut microbiota, it did not result in a shift towards a more wild-like microbial community. The increased capacity for degrading amino acids and specific sugars observed in wild hares suggest that, instead of bulk grass, dietary interventions tailored to their specific dietary preferences might be necessary for pre-adapting hare gut microbiota to wild conditions.ImportanceThis study sheds light on the critical role of gut microbiota in the success of reintroducing captive-bred animals into the wild. By comparing the gut microbiota of wild and captive European hares, we identified significant taxonomic and functional differences, including the absence of key microbial groups in captive hares. Dietary interventions, such as switching to grass, showed limited success in restoring a wild-like microbiota, highlighting the need for tailored approaches to mimic natural diets. With 87% of recovered microbial genomes representing novel species, this research also enriches our understanding of microbial diversity in wildlife. These findings emphasise that maladapted gut microbiota may hinder the survival and adaptation of reintroduced animals, suggesting that microbiome-targeted strategies could improve conservation efforts and the success of animal rewilding programs.
Identification of an Outbreak of Bivalve Transmissible Neoplasia in Soft-Shell Clams (Mya arenaria) in the Puget Sound Using Hemolymph and eDNA Surveys
Authors: Weinandt Sydney A. , Child Zachary J. , Lartey Dorothy , Santos Angel , Maxfield Holden , Sevigny Jordana K. , Garrett Fiona E. S. , Smith Peter D. , Giersch Rachael M. , Hart Samuel F. M. , Perez Franchesca , Rabins Lucas , Kaiser Samuel , Boyar Anna , Newton Jan , Kerr Jesse , Dimond James L. , Metzger Michael J. 
Published: December 2024

ABSTRACTBivalve transmissible neoplasia (BTN) is one of three known types of naturally transmissible cancer— cancers in which the whole cancer cells move from individual to individual, spreading through natural populations. BTN is a lethal leukemia-like cancer that has been observed throughout soft-shell clam (Mya arenaria) populations on the east coast of North America, with two distinct sublineages circulating at low enzootic levels in New England, USA, and Prince Edward Island, Canada. Major cancer outbreaks likely due toMya arenariaBTN (MarBTN) were reported in 1980s and the 2000s and the disease has been observed since the 1970s, but it has not been observed in populations of this clam species on the US west coast. In 2022, we collected soft-shell clams from several sites in Puget Sound, Washington, USA, and unexpectedly found high prevalence of BTN in two sites (Triangle Cove on Camano Island and near Stanwood in South Skagit Bay). Prevalence of BTN increased in subsequent years, reaching >75% in both sites in 2024, while it was not observed in other sites, suggesting the early stages of a severe disease outbreak following recent introduction. We observed that these cancer cells contain several somatic transposing insertion sites found only in the USA-sublineage of MarBTN, showing that it likely was recently transplanted from New England to this location. We then developed a sensitive environmental DNA (eDNA) assay, using qPCR to target somatic mutations in the MarBTN mitogenome, and showed that MarBTN can be detected in seawater at Triangle Cove, as well as several kilometers outside of the cove. We then used this assay to survey 50 sites throughout Puget Sound, confirming that the disease can be detected at high levels at Triangle Cove and South Skagit Bay, and showing that it extends beyond these known sites. However, while normal soft-shell clam mtDNA was widely detected, MarBTN was undetectable throughout most of Puget Sound and currently remains limited to the South Skagit Bay area and north Port Susan. These results identify a previously unknown severe outbreak of a transmissible cancer due to long-distance transplantation of disease from another ocean, and they demonstrate the utility of eDNA methods to track the spread of BTN through the environment.