bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic Donor Kidney Transplant Outcomes: Comparing Early US Experiences Using Optimal Matching
Authors: Yamauchi Junji , Raghavan Divya , Rofaiel George , Zimmerman Michael , Potluri Vishnu S. , Baker Talia , Campsen Jeffrey , Hall Isaac E. , Molnar Miklos Z. 
Published: November 2023

Background.
Therapeutic donors (TDs) are individuals who undergo organ removal for medical treatment with no replacement organ, and the organ is then transplanted into another person. Transplant centers in the United States have started using TDs for kidney transplantation (KT). TD-KT recipient outcomes may be inferior to those of non-TD-living-donor (non-TD-LD)-KT or deceased-donor (DD)-KT because of the conditions that led to nephrectomy; however, these outcomes have not been sufficiently evaluated.

Methods.
This was a retrospective cohort study using Organ Procurement and Transplantation Network data. Via optimal matching methods, we created 1:4 fivesomes with highly similar characteristics for TD-KT and non-TD-LD-KT recipients and then separately for TD-KT and DD-KT recipients. We compared a 6-mo estimated glomerular filtration rate (eGFR) between groups (primary endpoint) and a composite of death, graft loss, or eGFR <30 mL/min/1.73 m2 at 6 mo (secondary).

Results.
We identified 36 TD-KT recipients with 6-mo eGFR. There was also 1 death and 2 graft losses within 6 mo. Mean ± SD 6-mo eGFR was not significantly different between TD-KT, non-TD-LD-KT, and DD-KT recipients (59.9 ± 20.7, 63.3 ± 17.9, and 59.9 ± 23.0 mL/min/1.73 m2, respectively; P > 0.05). However, the 6-mo composite outcome occurred more frequently with TD-KT than with non-TD-LD-KT and DD-KT (18%, 2% [P < 0.001], and 8% [P = 0.053], respectively).

Conclusions.
Early graft function was no different between well-matched groups, but TD-KT demonstrated a higher risk of otherwise poor 6-mo outcomes compared with non-TD-LD-KT and DD-KT. Our results support selective utilization of TD kidneys; however, additional studies are needed with more detailed TD kidney information to understand how to best utilize these kidneys.
Oncogenic RAS-Pathway Activation Drives Oncofetal Reprogramming and Creates Therapeutic Vulnerabilities in Juvenile Myelomonocytic Leukemia
Authors: Hartmann Mark , Schönung Maximilian , Rajak Jovana , Maurer Valentin , Hai Ling , Bauer Katharina , Hakobyan Mariam , Staeble Sina , Langstein Jens , Jardine Laura , Rölz Roland , Bohler Sheila , Khabirova Eleonora , Maag Abdul-Habib , Vonficht Dominik , Lebrecht Dirk , Bernt Katrin M. , Tan Kai , Chen Changya , Alikarami Fatemeh , Boch Tobias , Flore Viktoria , Lutsik Pavlo , Milsom Michael D. , Raffel Simon , Buske Christian , Haas Simon , Haniffa Muzlifah , Mallm Jan-Philipp , Behjati Sam , Bonder Marc-Jan , Fröhling Stefan , Niemeyer Charlotte M. , Hey Joschka , Flotho Christian , Plass Christoph , Erlacher Miriam , Schlesner Matthias , Lipka Daniel B. 
Published: November 2023

AbstractAberrant fetal gene expression facilitates tumor-specific cellular plasticity by hijacking molecular programs of embryogenesis1. Persistent fetal gene signatures in childhood malignancies are typically explained by their prenatal origins2–6. In contrast, reactivation of fetal gene expression is considered a consequence of oncofetal reprogramming (OFR) in adult malignancies and is associated with aggressive disease7–10. To date, OFR has not been described in the context of childhood malignancies. Here, we performed a comprehensive multi-layered molecular characterization of juvenile myelomonocytic leukemia (JMML) and identified OFR as a hallmark of aggressive JMML. We observed that hematopoietic stem cells (HSCs) aberrantly express mixed developmental programs in JMML. Expression of fetal gene signatures combined with a postnatal epigenetic landscape suggested OFR, which was validated in a JMML mouse model, demonstrating that postnatal activation of RAS signaling is sufficient to induce fetal gene signatures. Integrative analysis identified the fetal HSC maturation marker CD52 as a novel therapeutic target for aggressive JMML. Anti-CD52 treatment depleted human JMML HSCs and disrupted disease propagationin vivo. In summary, this study implicates OFR, defined as postnatal acquisition of fetal transcription signatures, in the pathobiology of a childhood malignancy. We provide evidence for the direct involvement of oncogenic RAS signaling in OFR. Finally, we demonstrate how OFR can be leveraged for the development of novel treatment strategies.Highlights▪ Epigenomic and transcriptomic landscape of juvenile myelomonocytic leukemia (JMML) in the context of hematopoietic development.▪ The presence of fetal transcription signatures in childhood malignancies is not indicative of a developmental maturation block.▪ High-risk JMML is characterized by oncofetal reprogramming of postnatal hematopoietic stem cells (HSCs).▪ RAS-pathway mutations induce fetal-like gene expression signatures in murine postnatal HSCs.▪ The fetal maturation marker CD52 is a novel therapeutic target in high-risk JMML.
Modern wheat breeding selection synergistically improves above- and below-ground traits
Authors: Zhao Peng , Liu Zihui , Shi Xue , Hou Wenyang , Cheng Mingzhu , Liu Yuxiu , Simmonds James , Ji Wanquan , Uauy Cristobal , Xu Shengbao , Wang Xiaoming 
Published: November 2023

AbstractThe root system, as a fundamental organ for uptaking water and nutrients and interacting with the local environmental conditions, has been postulated to be the foundation for a second Green Revolution. However, the status of the root system during modern wheat breeding remains to be elucidated. Here, by analyzing the phenotypes of 406 wheat accessions on a large scale, we found the root systems of modern cultivars were synchronisely changed along with the above-ground traits. Furthermore, the genomic blocks with phenotypic effects on both above- and below-ground traits were observed to be enriched in the selection sweeps, highlighting that modern wheat breeding contributed to the synchronised changes. More importantly, the haplotypes selected by breeders within the selection sweeps synergistically improved both the above- and below-ground traits, suggesting that modern wheat breeding has improved the root system indirectly, which may contribute to the higher grain yields of modern wheat cultivars. Our results demonstrated that modern wheat breeding synergistically improved the above- and below-ground traits.
From museum drawer to tree: historical DNA phylogenomics clarifies the systematics of rare dung beetles (Coleoptera: Scarabaeinae) from museum collections
Authors: Lopes Fernando , Gunter Nicole , Gillett Conrad P.D.T. , Montanaro Giulio , Rossini Michele , Losacco Federica , Daniel Gimo M. , Straube Nicolas , Tarasov Sergei 
Published: November 2023

ABSTRACTAlthough several methods exist for extracting and sequencing historical DNA originating from drypreserved insect specimens deposited in natural history museums, no consensus exists as to what is the optimal approach. We demonstrate that a customized, low-cost archival DNA extraction protocol (∼ €10 per sample), in combination with Ultraconserved Elements (UCEs), is an effective tool for insect phylogenomic studies. We successfully tested our approach by sequencing DNA from scarab dung beetles preserved in both wet and dry collections, including unique primary type and rare historical specimens from internationally important natural history museums in London, Paris and Helsinki. The focal specimens comprise enigmatic dung beetle genera (Nesosisyphus, OnychotechusandHelictopleurus) that varied in age and preservation. The oldest specimen, the holotype of the now possibly extinct Mauritian endemicNesosisyphus rotundatus, was collected in 1944. We obtained high-quality DNA from all studied specimens to enable the generation of a UCE-based dataset that revealed an insightful and well-supported phylogenetic tree of dung beetles. The resulting phylogeny suggested the reclassification ofOnychotechus(previouslyincertae sedis) within the tribe Coprini. Our approach demonstrates the feasibility and effectiveness of combining DNA data from historic and recent museum specimens to provide novel insights. The proposed archival DNA protocol is available at DOI 10.17504/protocols.io.81wgbybqyvpk/v1HighlightsWe combined custom low-cost archival DNA extractions and Ultraconserved Element phylogenomicsDNA from rare museum specimens of enigmatic dung beetles revealed their phylogenetic connectionsGenomic data was obtained from the holotype of a potentially extinct monoinsular endemic speciesGenomic data allowed a rare and enigmatic species of previously unknown affinity to be classifiedThe morphology of museum specimens remained intact following non-destructive DNA extractionAbstract Figure
The majority of Germany’s small agricultural streams are in poor ecological status
Authors: von Gönner Julia , Gröning Jonas , Grescho Volker , Neuer Lilian , Hänsch Veit G. , Laue Benjamin , Molsberger-Lange Eva , Wilharm Elke , Liess Matthias , Bonn Aletta 
Published: November 2023

AbstractAgricultural pesticides, nutrients, and habitat degradation are major causes of insect declines in lowland streams. To effectively conserve and restore stream habitats, standardized stream monitoring data and societal support for freshwater protection are needed. Here, we sampled 137 small stream sites across Germany, 83% of which were located in agricultural catchments, with more than 900 citizen scientists in 96 monitoring groups. Sampling was carried out according to Water Framework Directive standards as part of the citizen science freshwater monitoring program FLOW in spring and summer 2021, 2022 and 2023. The biological indicator SPEARpesticideswas used to assess pesticide exposure and effects based on benthic invertebrate community composition. Overall, 58% of the monitored agricultural stream sites did not achieve a good ecological status in terms of macroinvertebrate community composition and indicated high pesticide exposure (SPEARpesticidesstatus class: 29% ‘moderate’, 19% ‘poor’, 11% ‘bad’). The indicated pesticide pressure in streams was related to the proportion of agricultural land in the catchment area (R2=0.23, p<0.001). With regards to hydromorphology, monitoring results revealed that 65% of the agricultural stream sites failed to reach a good status. The data base produced by citizen science groups was characterized by a high degree of accuracy. This was quantified by a comparative survey of SPEARpesticidesindex (R2=0.79, p<0.001) and hydromorphology index values (R2=0.72, p<0.001) by citizen scientists and professionals. Such citizen-driven monitoring of the status of watercourses could play a crucial role in monitoring and implementing the objective of the European Water Framework Directive, thus contributing to restoring and protecting freshwater ecosystems.Graphical abstractHighlights-Assessment of ecological status of small agricultural streams in Germany-Pesticides affected invertebrates (bioindicator SPEAR) in 58% of agricultural streams-Failure to reach good hydromorphological status in 65% of agricultural streams-Citizen science monitoring achieves high data accuracy-Citizen science can support European Water Framework Directive monitoring
A novel phylogenomics pipeline reveals complex pattern of reticulate evolution in Cucurbitales
Authors: Ortiz Edgardo M. , Höwener Alina , Shigita Gentaro , Raza Mustafa , Maurin Olivier , Zuntini Alexandre , Forest Félix , Baker William J. , Schaefer Hanno 
Published: November 2023

AbstractA diverse range of high-throughput sequencing data, such as target capture, RNA-Seq, genome skimming, and high-depth whole genome sequencing, are used for phylogenomic analyses but the integration of such mixed data types into a single phylogenomic dataset requires a number of bioinformatic tools and significant computational resources. Here, we present a novel pipeline, CAPTUS, to analyze mixed data in a fast and efficient way. CAPTUS assembles these data types, allows searching of the assemblies for loci of interest, and finally produces alignments filtered for paralogs. Compared to other software, CAPTUS allows the recovery of a greater number of more complete loci across a larger number of species. We apply CAPTUS to assemble a comprehensive mixed dataset, comprising the four types of sequencing data for the angiosperm order Cucurbitales, a clade of about 3,100 species in eight mainly tropical plant families, including begonias (Begoniaceae) and gourds (Cucurbitaceae). Our phylogenomic results support the currently accepted circumscription of Cucurbitales except for the position of the holoparasitic Apodanthaceae, which group with Rafflesiaceae in Malpighiales. A subset of mitochondrial gene regions supports the earlier position of Apodanthaceae in Cucurbitales. However, the nuclear regions and majority of mitochondrial regions place Apodanthaceae in Malpighiales. Within Cucurbitaceae, we confirm the monophyly of all currently accepted tribes but also reveal deep reticulation patterns both in Cucurbitales and within Cucurbitaceae. We show that contradicting results among earlier phylogenetic studies in Cucurbitales can be reconciled when accounting for gene tree conflict and demonstrate the efficiency of CAPTUS for complex datasets.
Pitfalls in performing genome-wide association studies on ratio traits
Authors: McCaw Zachary R , Dey Rounak , Somineni Hari , Amar David , Mukherjee Sumit , Sandor Kaitlin ,   insitro Research Team, Karaletsos Theofanis , Koller Daphne , Aschard Hugues , Davey Smith George , MacArthur Daniel , O’Dushlaine Colm , Soare Thomas W 
Published: November 2023

AbstractGenome-wide association studies (GWAS) are often performed on ratios composed of a numerator trait divided by a denominator trait. Examples include body mass index (BMI) and the waist-to-hip ratio, among many others. Explicitly or implicitly, the goal of forming the ratio is typically to adjust for an association between the numerator and denominator. While forming ratios may be clinically expedient, there are several important issues with performing GWAS on ratios. Forming a ratio does not “adjust” for the denominator in the sense of conditioning on it, and it is unclear whether associations with ratios are attributable to the numerator, the denominator, or both. Here we demonstrate that associations arising in ratio GWAS can be entirely denominator-driven, implying that at least some associations uncovered by ratio GWAS may be due solely to a putative adjustment variable. In a survey of 10 common ratio traits, we find that the ratio model disagrees with the adjusted model (performing GWAS on the numerator while conditioning on the denominator) at around 1/3 of loci. Using BMI as an example, we show that variants detected by only the ratio model are more strongly associated with the denominator (height), while variants detected by only the adjusted model are more strongly associated with the numerator (weight). Although the adjusted model provides effect sizes with a clearer interpretation, it is susceptible to collider bias. We propose and validate a simple method of correcting for the genetic component of collider bias via leave-one-chromosome-out polygenic scoring.
RETINOID ORPHAN RECEPTOR GAMMA T (RORγT) PROMOTES INFLAMMATORY EOSINOPHILIA BUT IS DISPENSABLE FOR INNATE IMMUNE-MEDIATED COLITIS
Authors: Torres-Huerta Alvaro , Ruley-Haase Katelyn , Reed Theodore , Boger-May Antonia , Rubadeux Derek , Mayer Lauren , Rajashekara Arpitha Mysore , Hiller Morgan , Frech Madeleine , Roncagli Connor , Pederson Cameron , Camacho Mary Catherine , Hollmer Lauren , English Lauren , Kane Grace , Boone David L. 
Published: November 2023

ABSTRACTInflammatory bowel diseases (IBD) result from uncontrolled inflammation in the intestinal mucosa leading to damage and loss of function. Both innate and adaptive immunity contribute to the inflammation of IBD and innate and adaptive immune cells reciprocally activate each other in a forward feedback loop. In order to better understand innate immune contributions to IBD, we developed a model of spontaneous 100% penetrant, early onset colitis that occurs in the absence of adaptive immunity by crossing villin-TNFAIP3 mice to RAG1−/−mice (TRAG mice). This model is driven by microbes and features increased levels of innate lymphoid cells in the intestinal mucosa. To investigate the role of type 3 innate lymphoid cells (ILC3) in the innate colitis of TRAG mice, we crossed them to retinoid orphan receptor gamma t deficient (Rorγt−/−) mice. Rorγt−/−x TRAG mice exhibited markedly reduced eosinophilia in the colonic mucosa, but colitis persisted in these mice. Colitis in Rorγt−/−x TRAG mice was characterized by increased infiltration of the intestinal mucosa by neutrophils, inflammatory monocytes, macrophages and other innate cells. RNA and cellular profiles of Rorγt−/−x TRAG mice were consistent with a lack of ILC3 and ILC3 derived cytokines, reduced antimicrobial factors, increased activation oof epithelial repair processes and reduced activation of epithelial cell STAT3. The colitis in Rorγt−/−x TRAG mice was ameliorated by antibiotic treatment indicating that microbes contribute to the ILC3-independent colitis of these mice. Thus, Rorγt promotes eosinophilia but Rorγt and Rorγt-dependent ILC3 are dispensable for the innate colitis in TRAG mice.
LSD1 inhibition improves efficacy of adoptive T cell therapy by enhancing CD8+T cell responsiveness
Authors: Pallavicini Isabella , Frasconi Teresa Maria , Ceccaci Elena , Tiberti Silvia , Nava Lauson Carina B , Preto Elisa , Bigogno Alberto , Mangione Marta , Sala Eleonora , Iannacone Matteo , Kuka Mirela , Nezi Luigi , Minucci Saverio , Manzo Teresa 
Published: November 2023

ABSTRACTThe lysine-specific histone demethylase 1A (LSD1) has been described to play a role in antitumor immunity; however, the role of LSD1 in shaping CD8+ T cell (CTL) differentiation and function is not understood. Here, we showed that pharmacological inhibition of LSD1 (LSD1i) in CTL elicited phenotypic and functional alterations of the CTL that led to robust antitumor immunity in the context of adoptive T cell therapy (ACT). In addition, the combination of anti-PDL1 therapy with LSD1i-based ACT resulted in a complete tumor eradication and long-lasting tumor-free survival. This study demonstrated that LSD1i together with anti-PDL1 therapy complement each other’s deficiencies and produce a better tumor response in a melanoma model, in which both immune and epigenetic therapy alone have shown limited efficacy. Collectively, these results set the translational potential of modulating LSD1 to improve antitumoral responses generated by ACT and anti-PDL1 therapy, which provide a strong rationale for a combination trial of LSD1i and immunotherapy.
Acute effects of psilocybin on the dynamics of gaze fixations during visual aesthetic perception
Authors: Muller Stephanie , Cavanna Federico , de la Fuente Laura , Bruno Nicolás , D’Amelio Tomás Ariel , Pallavicini Carla , Tagliazucchi Enzo 
Published: November 2023

AbstractRationaleSerotonergic psychedelics are remarkable for their capacity to induce variable yet reproducible modifications to human consciousness The most salient acute effects of these compounds include perceptual alterations, predominantly in the visual domain, yet to date these alterations have been mostly documented only by subjective reports.ObjectivesWe used eye-tracking to quantify the effects of low vs. high doses of psilocybin mushrooms on the eye movements that underlie the exploration of complex visual stimuli, focusing on the particular case of aesthetic perception.ResultsFollowing a double-blind placebo-controlled design under semi-naturalistic conditions, we demonstrated that high doses of psilocybin result in a more local visual exploration of paintings, and thus in a less entropic fixation probability distribution. Participants reported heightened emotional response and state of flow under the high dose condition.ConclusionsThese findings are consistent with an effect of psilocybin on gaze fixation mediated by altered perception of low-level visual information, such as textures, shapes and colors. Our work also highlights the possibility of investigating psychedelics by addressing their effect on behavior under complex naturalistic conditions, which contributes to maintaining subject engagement while also increasing the ecological validity of the findings.
Global remapping emerges as the mechanism for renewal of context-dependent behavior in a reinforcement learning model
Authors: Kappel David , Cheng Sen 
Published: November 2023

AbstractThe hippocampal formation exhibits complex and context-dependent activity patterns and dynamics, e.g., place cell activity during spatial navigation in rodents or remapping of place fields when the animal switches between contexts. Furthermore, rodents show context-dependent renewal of extinguished behavior. However, the link between context-dependent neural codes and context-dependent renewal is not fully understood. We use a reinforcement learning agent based on deep neural networks to study the learning dynamics that occur during spatial learning and context switching in a simulated ABA extinction and renewal paradigm in a 3D virtual environment. Despite its simplicity, the network exhibits a number of features typically found in the CA1 and CA3 regions of the hippocampus. A significant proportion of neurons in deeper layers of the network are tuned to a specific spatial position of the agent in the environment - similar to place cells in the hippocampus. These spatial representations exhibit global remapping when the agent is exposed to a new context. The spatial maps are restored when the agent returns to the previous context, accompanied by renewal of the conditioned behavior. Remapping is facilitated by memory replay of experiences during training. These complex spatial representations and dynamics occur spontaneously in the hidden layer of a deep network during learning. Our results show that integrated codes that jointly represent spatial and task-relevant contextual variables are the mechanism underlying renewal in a simulated DQN agent.