bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of Fully Robotic Recipient Living Donor Liver Transplant in Relation to the Open Approach
Authors: Broering Dieter C. , Elsheikh Yasser , Malago Massimo , Alnemary Yasir , Alabbad Saleh , Boehnert Markus U. , Raptis Dimitri A. 
Published: June 2024

Background.
Over the past 20 y, robotic surgery has entered nearly all surgical disciplines, aiming to improve patient outcomes. Liver transplantation has evolved with these advancements, and fully robotic liver transplants represent the latest innovation in this field. This study reports on the world’s first series of fully robotic recipient liver transplants from robotic living donors, comparing them with matched cases from the standard open transplant approach.

Methods.
A case-control study was conducted at our center from August to December 2023. Patient selection criteria for robotic recipient liver transplantation included a Model for End-stage Liver Disease score of ≤25, specific anatomical characteristics, and logistics. A propensity score analysis with a 1:4 matching ratio was used.

Results.
The study analyzed 10 fully robotic living donor and robotic recipient liver transplant pairs with a median donor age of 29 y and a recipient age of 61 y. The main indication for transplantation was nonalcoholic steatohepatitis (6/10). There was 1 robotic to open conversion, and the median operation time was 10 h, with a median hospital stay of 13 d, shorter than the 18 d in the open group. Three recipients experienced a complication, and there was no mortality.

Conclusions.
The first-ever series of fully robotic living donor recipient liver transplants showed encouraging initial results with a markedly reduced hospital stay. The ultimate goal is to refine the technique to offer robotic liver transplants to the majority of recipients, overcoming the current selection criteria. Further research and a planned randomized controlled trial will aim to confirm these results.
Renalase inhibition regulates β cell metabolism to defend against acute and chronic stress
Authors: MacDonald Tara , Ryback Birgitta , da Silva Pereira Jessica Aparecida , Wei Siying , Mendez Bryhan , Cai Erica , Ishikawa Yuki , Weir Gordon , Bonner-Weir Susan , Kissler Stephan , Yi Peng 
Published: June 2024

AbstractRenalase (Rnls), annotated as an oxidase enzyme, is a GWAS gene associated with Type 1 Diabetes (T1D) risk. We previously discovered that Rnls inhibition delays diabetes onset in mouse models of T1Din vivo, and protects pancreatic β cells against autoimmune killing, ER and oxidative stressin vitro. The molecular biochemistry and functions of Rnls are entirely uncharted. Here we find that Rnls inhibition defends against loss of β cell mass and islet dysfunction in chronically stressed Akita micein vivo. We used RNA sequencing, untargeted and targeted metabolomics and metabolic function experiments in mouse and human β cells and discovered a robust and conserved metabolic shift towards glycolysis, amino acid abundance and GSH synthesis to counter protein misfolding stress,in vitro. Our work illustrates a function for Rnls in mammalian cells, and suggests an axis by which manipulating intrinsic properties of β cells can rewire metabolism to protect against diabetogenic stress.
Genomic and morphological characterization ofTrichuris incognita, a Human-InfectingTrichurisspecies
Authors: Bär Max A. , Kouamé Nadège A. , Touré Sadikou , Coulibaly Jean T. , Schneeberger Pierre H. H. , Keiser Jennifer 
Published: June 2024

AbstractTrichuriasis is a neglected tropical disease that affects as many as 500 million individuals and can cause significant morbidity. For decades, it was thought to be caused by one species of whipworm,Trichuris trichiura. Significant differences in response rates to the best available anthelmintic treatment — a combination of albendazole and ivermectin — for trichuriasis exist across clinical trial reports yet the underlying reasons are unclear. Here, we present and characterize a human-infectingTrichurisspecies that we namedTrichuris incognita. Combining long- and short-read sequencing approaches, we assembled a high-quality reference genome ofT. incognitato construct the species tree of theTrichurisgenus using 12434 orthologous groups. We sequenced a total of 747 individual worms which were used to confirm the phylogenetic placement. Comparative genomic analysis of genes implied in the resistance of either albendazole or ivermectin in helminths revealed a high copy number of the beta-tubulin (TUBB) gene, present in the whole population ofT. incognita, compared to the canonicalT. trichiuraspecies. We conducted a genome wide association study (GWAS) comparing 160 albendazole-ivermectin sensitive to 492 drug non-sensitive worms, which did not point towards an adaptation to drug pressure within the same species. Our results demonstrate that trichuriasis can be caused by multiple species of whipworm. This discovery, coupled with high tolerability ofT. incognitato albendazole-ivermectin marks a significant shift in how we understand and approach whipworm infections.
Virtual Colon: Spatiotemporal modelling of metabolic interactions in a computational colonic environment
Authors: Marinos Georgios , Zimmermann Johannes , Taubenheim Jan , Kaleta Christoph 
Published: June 2024

AbstractHost-microbial metabolic interactions have been recognised as an essential factor in host health and disease. Genome-scale metabolic modelling approaches have made important contributions to our understanding of the interactions in such communities. One particular such modelling approach is BacArena in which metabolic models grow, reproduce, and interact as independent agents in a spatiotemporal metabolic environment. Here, we present a modelling application of BacArena, a virtual colonic environment, which reveals spatiotemporal metabolic interactions in a computational colonic environment. This environment resembles the crypt space together with the mucus layers, the lumen and fluid dynamics. Our proof-of-principle experiments include mono-colonisation simulations of context-specific colonic cells and simulations of context-specific colonic cells with the SIHUMIx minimal model microbiome. Our simulations propose host-microbial and microbial-microbial interactions that can be verified based on the literature. Most importantly, the Virtual Colon offers visualisation of interactions through time and space, adding another dimension to the genome-scale metabolic modelling approaches. Lastly, like BacArena, it is freely available and can be easily adapted to model other spatially structured environments (http://www.github.com/maringos/VirtualColon).
Synthesis of ionizable lipopolymers using split-Ugi reaction for pulmonary delivery of various size RNAs and gene editing
Authors: Vlasova K. Yu. , Kerr A. , Pennock N.D. , Jozic A. , Sahel D.K. , Gautam M. , Murthy N.T.V. , Roberts A. , Ali M.W. , MacDonald K.D. , Walker J. , Luxenhofer R. , Sahay G. 
Published: June 2024

AbstractWe present an efficient approach for synthesizing cationic poly(ethylene imine) derivatives using the multicomponent split-Ugi reaction to rapidly create a library of complex functional ionizable lipopolymers. We synthesized a diverse library of 155 polymers, formulated them into polyplexes to establish structure-activity relationships crucial for endosomal escape and efficient transfection. After discovering a lead structure, lipopolymer-lipid hybrid nanoparticles are introduced to preferentially deliver to and elicit effective mRNA transfection in lung endothelium and immune cells, including T cells with lowin vivotoxicity. The lipopolymer-lipid hybrid nanoparticles showed 300-fold improvement in systemic mRNA delivery to the lung compared toin vivo-JetPEI®. Lipopolymer-lipid hybrid nanoparticles demonstrated efficient delivery of mRNA-based therapeutics for treatment of two different disease models. Lewis Lung cancer progression was significantly delayed after treatment with loaded IL-12 mRNA in U155@lipids after repeated i.v. administration. Systemic delivery of human CFTR (hCFTR) mRNA resulted in production of functional form of CFTR protein in the lungs. The functionality of hCFTR protein was confirmed by restoration of CFTR- mediated chloride secretion in conductive airway epithelia in CFTR knockout mice after nasal instillation of hCFTR mRNA loaded U155@lipids. We further showed that, U155@lipids nanoparticles can deliver complex CRISPR-Cas9 based RNA cargo to the lung, achieving 5.6 ± 2.4 % gene editing in lung tissue. Moreover, we demonstrated successful PD-1 gene knockout of T cellsin vivo. Our results highlight a versatile delivery platform for systemic delivering of mRNA of various sizes for gene therapy for a variety of therapeutics.
Bridging health registry data acquisition and real-time data analytics
Authors: Schmidt Johannes , Arjune Sita , Böhm Volker , Müller Roman-Ulrich , Antczak Philipp 
Published: June 2024

AbstractThe number of clinical studies and associated research has increased significantly in the last few years. Particularly in rare diseases, an increased effort has been made to integrate, analyse, and develop new knowledge to improve patient stratification and wellbeing. Clinical databases, including digital medical records, hold significant amount of information that can help understand the impact and progression of diseases. Combining and integrating this data however, has provided a challenge for data scientists due to the complex structures of digital medical records and the lack of site wide standardisation of data entry. To address these challenges we present a python backed tool, Meda, which aims to collect data from different sources and combines these in a unified database structure for near real-time monitoring of clinical data. Together with an R shiny interface we can provide a near complete platform for real-time analysis and visualization.
Pre-stimulus beta power mediates explicit and implicit perceptual biases in distinct cortical areas
Authors: Forster Carina , Stephani Tilman , Grund Martin , Panagoulas Eleni , Al Esra , Hofmann Simon M. , Nikulin Vadim V. , Villringer Arno 
Published: June 2024

AbstractPerception is biased by expectations and previous actions. Pre-stimulus brain oscillations are a potential candidate for implementing biases in the brain. In two EEG studies on somatosensory near-threshold detection, we investigated the pre-stimulus neural correlates of an (implicit) previous choice bias and an explicit bias. The explicit bias was introduced by informing participants about stimulus probability on a single-trial level (volatile context) or block-wise (stable context). Behavioural analysis confirmed adjustments in the decision criterion and confidence ratings according to the cued probabilities and choice history biases. Pre-stimulus beta power with distinct sources in sensory and higher-order cortical areas predicted explicit and implicit biases, respectively, on a subject level and partially mediated the impact of previous choice and stimulus probability on the detection response. We suggest pre-stimulus beta oscillations in distinct brain areas as a neural correlate of explicit and implicit biases in somatosensory perception.
Phollow: Visualizing Gut Bacteriophage Transmission within Microbial Communities and Living Animals
Authors: Ortiz de Ora Lizett , Wiles Elizabeth T , Zünd Mirjam , Bañuelos Maria S , Haro-Ramirez Nancy , Suder Diana S , Ujagar Naveena , Angulo Julio Ayala , Trinh Calvin , Knitter Courtney , Gonen Shane , Nicholas Dequina A , Wiles Travis J 
Published: June 2024

ABSTRACTBacterial viruses (known as “phages”) shape the ecology and evolution of microbial communities, making them promising targets for microbiome engineering. However, knowledge of phage biology is constrained because it remains difficult to study phage transmission dynamics within multi-member communities and living animal hosts. We therefore created “Phollow”: a live imaging-based approach for tracking phage replication and spread in situ with single-virion resolution. Combining Phollow with optically transparent zebrafish enabled us to directly visualize phage outbreaks within the vertebrate gut. We observed that virions can be rapidly taken up by intestinal tissues, including by enteroendocrine cells, and quickly disseminate to extraintestinal sites, including the liver and brain. Moreover, antibiotics trigger waves of interbacterial transmission leading to sudden shifts in spatial organization and composition of defined gut communities. Phollow ultimately empowers multiscale investigations connecting phage transmission to transkingdom interactions that have the potential to open new avenues for viral-based microbiome therapies.
Spatio-temporal learning in a mass-recruiting leaf-cutting ant (Acromyrmex subterraneus)
Authors: Ferreira Fernanda Tiemi Nakashima , Constantino Pedro Brisola , de Toledo Marcelo Arruda Fiuza , Helene André Frazão 
Published: June 2024

ABSTRACTThe ability to anticipate periodically available resources is observed in several animals and improves performance in obtaining resources and adaptability. Spatio-temporal learning occurs when they associate the correct time and location of future events. We evaluate whether leaf-cutting antsAcromyrmex subterraneuscan anticipate the presence of sucrose and examine potential anticipatory effects. Five colonies were used in an experimental setup where, from a central tray, two trails in opposite directions gave access to either the sucrose or to nothing. For 21 consecutive days sucrose was offered at the same place and the same time. Cameras recorded the flow of individuals at 4 different phases: before feeding (10h00-11h00), pre-feeding (11h30–12h00), feeding (12h00-13h00) and after feeding (14h00-15h00). On the 22ndday sugar was not supplied. On the 21stday the ants were marked and the next day, observed. Our results shows that: (1) the ants responded positively to the stimulus presented by forming the foraging trail to collect sucrose; (2) before feeding there was no significant difference in ant flow between the trails, but after feeding, the ant flow was consistently higher on trail that led to sucrose, which we called a keep going behavior; (3) there was a progressive spatio-temporal learning, given that ants began to appear earlier in pre-feeding throghout the weeks; (4) on the 22ndday, the ants presented themselves 10 minutes in advance and remained in the correct place; (5) the marked ants indicated that even without any resource the empty place continued to be explored. The colonies were able to learn where and when to look for food. Due to the adjustment of the ants to the stimuli of the environment it was possible to prepare for the collection of sucrose and the success in foraging for the colony.Summary statementLeaf-cutting ants are capable of spatio-temporal learning and this process has relevance on mass foraging recruitment and overall social organization of the colony.
External morphometric and microscopic analysis of the reproductive system inin- vitroreared stingless bee queens,Heterotrigona itama, and their mating frequency
Authors: Wongsa Kanyanat , Duangphakdee Orawan , Poolprasert Pisit , Rattanawannee Atsalek 
Published: June 2024

AbstractStingless bees, prevalent in tropical and subtropical regions, are a tribe of eusocial bees that are crucial pollinators for economic crops and native plants, producing honey and pollen. However, colony expansion is limited by a shortage of queens for new colonies. Therefore, mass artificial rearing of virgin queens could address this in commercially managed meliponiculture. Furthermore, the in vitro rearing of queen stingless bees can improve meliponiculture management and conservation efforts. Herein, we explored the efficacy of in vitro queen rearing forHeterotrigona itamaassessing the queen’s body size, reproductive organ size (ovary and spermatheca), acceptance rate into new, small colonies, and mating frequency.H. itamalarvae developed into queens when fed with 120 µL–150 µL of larval food, resulting inin vitroqueens having body sizes similar to those of naturally produced queens. Microscopic analysis revealed well-developed ovaries and spermathecae inin vitro-reared queens, unlike the smaller ovaries and the absence of spermathecae in the naturally produced workers. Acceptance ofin vitro-reared queens was independent of worker age, and mating frequency was low but not significantly different from naturally produced queens. These findings could enhance stingless beekeeping practices and conservation efforts for the native stingless bee species.
Description of new micro-colonial fungi speciesNeophaeococcomyces mojavensis,Coniosporium tulheliwenetii, and Taxawa tesnikishiicultured from biological soil crusts
Authors: Kurbessoian Tania , Ahmed Sarah A. , Quan Yu , de Hoog Sybren , Stajich Jason E. 
Published: June 2024

AbstractBlack yeasts and relatives comprise Micro-Colonial Fungi (MCFs) which are slow-growing stress-tolerant micro-eukaryotes that specialize in extreme environments. MCFs are paraphyletic and found in the OrdersChaetothyriales(Eurotiomycetes) andDothideales(Dothidiomycetes). We have isolated and described three new MCFs species from desert biological soil crusts (BSCs) collected from two arid land regions: Joshua Tree National Park (Mojave Desert) and UC Natural Reserve at Boyd Deep Canyon (confluence of Mojave and Sonoran Deserts). BSCs are composite assemblages of cyanobacteria, eukaryotic algae, fungi, lichens, and bryophytes embedded into the surface of desert soils, providing a protective buffer against the harsh desert environment. Our work focused on one type of desert BSC, the cyanolichen crust dominated byCollema sp.Using culture-dependent protocols, three MCFs were axenically isolated from their respective samples along with the extracted DNA. Their genomes were sequenced using Illumina and Nanopore, and finally assembled and annotated using hybrid assembly approaches and established bioinformatics pipelines to conduct final taxonomic phylogenetic analysis and placement. The three species described here are unique specimen from desert BSCs, here we introduce,Neophaeococcomyces mojavensis(Chaetothyriales),Cladosporium tulheliwenetii(Dothideales), andTaxawa tesnikishii(Dothideales).
Small nuclear RNAs enhance protein-free RNA-programmable base conversion on mammalian coding transcripts
Authors: Smargon Aaron A. , Pant Deepak , Glynne Sofia , Gomberg Trent A. , Yeo Gene W. 
Published: June 2024

ABSTRACTEndogenous U small nuclear RNAs (U snRNAs) form RNA-protein complexes responsible for eukaryotic processing of pre-mRNA into mature mRNA. Previous studies have demonstrated the utility of guide-programmable U snRNAs in targeted exon inclusion and exclusion. We investigated whether snRNAs can also enhance conversion of RNA bases over state-of-the-art RNA targeting technologies in human cells. When compared to adenosine deaminase acting on RNA (ADAR)-recruiting circular RNAs, we find that guided A>I snRNAs consistently increase adenosine-to-inosine editing efficiency for genes with higher exon counts, perturb substantially fewer genes in the transcriptome, and localize more persistently to the nucleus where ADAR is expressed. A>I snRNAs can also edit pre-mRNA 3′ splice sites to promote splicing changes. Finally, snRNA fusions to H/ACA box snoRNAs (U>Ψ snRNAs) increase targeted RNA pseudouridylation efficiency. Altogether, our results advance the protein-free RNA base conversion toolbox and enhance minimally invasive RNA targeting technologies to treat genetic diseases.
Clinical validation of an RSV neutralization assay and testing of cross-sectional sera pre- and post- RSV outbreaks from 2021-2023
Authors: Piliper Eli A. , Reed Jonathan , Greninger Alexander L. 
Published: June 2024

AbstractBackgroundRespiratory syncytial virus (RSV) is a leading cause of acute respiratory infections and hospitalization in infants and the elderly. Newly approved vaccines and the prophylactic antibody nirsevimab have heightened interest in RSV immunologic surveillance, necessitating development of high-throughput assays assessing anti-RSV neutralizing activity.ObjectivesWe validated an RSV focus-reduction neutralization test (RSV FRNT), a high-throughput, automation-ready neutralization assay using RSV strain A2. The assay was then used to investigate the immunity debt hypothesis for resurgent RSV outbreaks in the 2022-2023 season.Study designWe evaluated precision, sensitivity, specificity, linearity, and accuracy of RSV FRNT using reference sera, contrived specimens, and clinical remnant specimens. RSV neutralizing activity of remnant serum specimens, sampled for HSV-1/2 antibody testing during and after the COVID-19 pandemic (February and September 2022 & 2023), was measured and correlated with concurrent trends in RSV prevalence.ResultsRSV FRNT was shown to be accurate, generating reference serum neutralizing titers within 2-fold of established assays, with a linear analytical measurement range between 20 to 4,860 ND50 and ND80 units. Neutralizing activity measured with the assay was positively correlated with antibody titer determined via indirect ELISA (ρ = 1.0, p = 0.0014). Among individuals sampled within 3 months of RSV PCR test, RSV positives had a 9.14-fold higher geometric mean neutralizing titer (GMT) relative to RSV PCR negatives (p = 0.09). There was no difference in geometric mean anti-RSV neutralizing titers between sera sampled pre- and post-2023 RSV outbreak (p = 0.93).ConclusionsWe validated a high-throughput assay for assessing anti-RSV neutralizing activity and found no significant difference in neutralizing titers between pre- and post-pandemic outbreak specimens.HighlightsWe report the full clinical validation of an RSV neutralization assayNo evidence of immune debt found in Washington State RSV 2022-2023 outbreakOur assay offers high throughput testing applicable to vaccine/drug studies
Acetylation of the yeast Hsp40 chaperone protein Ydj1 fine-tunes proteostasis and translational fidelity
Authors: Omkar Siddhi , Shrader Courtney , Hoskins Joel R. , Kline Jake T. , Mitchem Megan M. ,   Nitika, Fornelli Luca , Wickner Sue , Truman Andrew W. 
Published: June 2024

AbstractProteostasis, the maintenance of cellular protein balance, is essential for cell viability and is highly conserved across all organisms. Newly synthesized proteins, or “clients,” undergo sequential processing by Hsp40, Hsp70, and Hsp90 chaperones to achieve proper folding and functionality. Despite extensive characterization of post-translational modifications (PTMs) on Hsp70 and Hsp90, the modifications on Hsp40 remain less understood. This study aims to elucidate the role of lysine acetylation on the yeast Hsp40, Ydj1. By mutating acetylation sites on Ydj1’s J-domain to either abolish or mimic constitutive acetylation, we observed that preventing acetylation had no noticeable phenotypic impact, whereas acetyl-mimic mutants exhibited various defects indicative of impaired Ydj1 function. Proteomic analysis revealed several Ydj1 interactions affected by J-domain acetylation, notably with proteins involved in translation. Further investigation uncovered a novel role for Ydj1 acetylation in stabilizing ribosomal subunits and ensuring translational fidelity. Our data suggest that acetylation may facilitate the transfer of Ydj1 between Ssa1 and Hsp82. Collectively, this work highlights the critical role of Ydj1 acetylation in proteostasis and translational fidelity.Author SummaryCells require a suite of chaperone and co-chaperone proteins to maintain a healthy balance of functional proteins. A large number of modifications on chaperone and co-chaperone proteins have been identified, but their functional importance has not been fully explored. In this study, we identify acetylation sites on the yeast co-chaperone Ydj1 that impact its interactions with major chaperones and client proteins including those involved in protein synthesis. This work sheds light on how modifications on co-chaperones can also play an important role in the health of the proteome.