bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment outcome according to genetic tumour alterations and clinical characteristics in digestive high-grade neuroendocrine neoplasms
Authors: Elvebakken Hege , Venizelos Andreas , Perren Aurel , Couvelard Anne , Lothe Inger Marie B. , Hjortland Geir O. , Myklebust Tor Å. , Svensson Johanna , Garresori Herish , Kersten Christian , Hofsli Eva , Detlefsen Sönke , Vestermark Lene W. , Knappskog Stian , Sorbye Halfdan 
Published: June 2024

Abstract
Background
Chemotherapy has limited efficacy in advanced digestive high-grade neuroendocrine neoplasms (HG-NEN) and prognosis is dismal. Predictive markers for palliative chemotherapy are lacking, and prognostic markers are limited.

Methods
Digestive HG-NEN patients (n = 229) were prospectively included 2013–2017. Pathological re-assessment revealed 188 neuroendocrine carcinomas (NEC) and 41 neuroendocrine tumours (NET G3). Tumour-DNA was sequenced across 360 cancer-related genes, assessing mutations (mut) and copy number alterations. We linked sequencing results to clinical information and explored potential markers for first-line chemotherapy efficacy and survival.

Results
In NEC given cis/carboplatin and etoposide (PE), TP53mut predicted inferior response rate in multivariate analyses (p = 0.009) and no BRAFmut NEC showed response. In overall assessment of PE-treated NEC, no genetic alterations were prognostic for OS. For small-cell NEC, TP53mut were associated with longer OS (p = 0.011) and RB1 deletions predicted lack of immediate-progression (p = 0.003). In non-small cell NEC, APC mut were associated with immediate-progression and shorter PFS (p = 0.008/p = 0.004). For NET G3, ATRXmut, ARID1A- and ERS1 deletions were associated with shorter PFS.

Conclusion
Correlations between genetic alterations and response/immediate-progression to PE were frequent in NEC but affected PFS or OS only when subdividing for cell-type. The classification of digestive NEC into large- and small-cell seems therefore molecularly and clinically relevant.
Interactomic exploration of LRRC8A in volume-regulated anion channels
Authors: Carpanese Veronica , Festa Margherita , Prosdocimi Elena , Bachmann Magdalena , Sadeghi Soha , Bertelli Sara , Stein Frank , Velle Angelo , Abdel-Salam Mostafa A. L. , Romualdi Chiara , Pusch Michael , Checchetto Vanessa 
Published: June 2024

AbstractIon channels are critical in enabling ion movement into and within cells and are important targets for pharmacological interventions in different human diseases. In addition to their ion transport abilities, ion channels interact with signalling and scaffolding proteins, which affects their function, cellular positioning, and links to intracellular signalling pathways. The study of “channelosomes” within cells has the potential to uncover their involvement in human diseases, although this field of research is still emerging. LRRC8A is the gene that encodes a crucial protein involved in the formation of volume-regulated anion channels (VRACs). Some studies suggest that LRRC8A could be a valuable prognostic tool in different types of cancer, serving as a biomarker for predicting patients’ outcomes. LRRC8A expression levels might be linked to tumour progression, metastasis, and treatment response, although its implications in different cancer types can be varied. Here, publicly accessible databases of cancer patients were systematically analysed to determine if a correlation between VRAC channel expression and survival rate exists across distinct cancer types. Moreover, we re-evaluated the impact of LRRC8A on cellular proliferation and migration in colon cancer via HCT116 LRRC8A-KO cells, which is a current topic of debate in the literature. In addition, to investigate the role of LRRC8A in cellular signalling, we conducted biotin proximity-dependent identification (BioID) analysis, revealing a correlation between VRAC channels and cell-cell junctions, mechanisms that govern cellular calcium homeostasis, kinases, and GTPase signalling. Overall, this dataset improves our understanding of LRRC8A/VRAC and explores new research avenues while identifying promising therapeutic targets and promoting inventive methods for disease treatment.
Realising a global One Health disease surveillance approach: insights from wastewater and beyond
Authors: Hill Richard , Stentiford Grant D. , Walker David I. , Baker-Austin Craig , Ward Georgia , Maskrey Benjamin H. , van Aerle Ronny , Verner-Jeffreys David , Peeler Edmund , Bass David 
Published: June 2024

AbstractOne Health is a recognition of the shared environment inhabited by humans, animals and plants, and the impact of their interactions on the health of all organisms. The COVID-19 pandemic highlighted the need for a framework of pathogen surveillance in a tractable One Health paradigm to allow timely detection and response to threats to human and animal health. We present case studies centered around the recent global approach to tackle antimicrobial resistance and the current interest in wastewater testing, with the concept of “one sample many analyses” to be further explored as the most appropriate means of initiating this endeavor.
TENT5-mediated polyadenylation of mRNAs encoding secreted proteins is essential for gametogenesis in mice
Authors: Brouze Michał , Czarnocka-Cieciura Agnieszka , Gewartowska Olga , Kusio-Kobiałka Monika , Jachacy Kamil , Szpila Marcin , Tarkowski Bartosz , Gruchota Jakub , Krawczyk Paweł , Mroczek Seweryn , Borsuk Ewa , Dziembowski Andrzej 
Published: June 2024

AbstractCytoplasmic polyadenylation plays a vital role in gametogenesis; however, the participating enzymes and substrates in mammals remain unclear. Using knockout and knock-in mouse models, we describe the essential role of four TENT5 poly(A) polymerases in mouse fertility and gametogenesis. TENT5B and TENT5C play crucial yet redundant roles in oogenesis, with the double knockout of both genes leading to oocyte degeneration. Additionally, TENT5B-GFP knock-in females display a gain-of-function infertility effect, with multiple chromosomal aberrations in ovulated oocytes. TENT5C and TENT5D both regulate different stages of spermatogenesis, as shown by the sterility in males following the knockout of either gene. Finally, Tent5a knockout substantially lowers fertility, although the underlying mechanism is not directly related to gametogenesis. Through direct RNA sequencing, we discovered that TENT5s polyadenylate mRNAs encoding endoplasmic reticulum-targeted proteins essential for gametogenesis. Sequence motif analysis and reporter mRNA assays reveal that the presence of an endoplasmic reticulum-leader sequence represents the primary determinant of TENT5-mediated regulation.
Observation of Mermin-Wagner behavior in LaFeO3/SrTiO3 superlattices
Authors: Kiaba M. , Suter A. , Salman Z. , Prokscha T. , Chen B. , Koster G. , Dubroka A. 
Published: June 2024

AbstractTwo-dimensional magnetic materials can exhibit new magnetic properties due to the enhanced spin fluctuations that arise in reduced dimension. However, the suppression of the long-range magnetic order in two dimensions due to long-wavelength spin fluctuations, as suggested by the Mermin-Wagner theorem, has been questioned for finite-size laboratory samples. Here we study the magnetic properties of a dimensional crossover in superlattices composed of the antiferromagnetic LaFeO3 and SrTiO3 that, thanks to their large lateral size, allowed examination using a sensitive magnetic probe — muon spin rotation spectroscopy. We show that the iron electronic moments in superlattices with 3 and 2 monolayers of LaFeO3 exhibit a static antiferromagnetic order. In contrast, in the superlattices with single LaFeO3 monolayer, the moments do not order and fluctuate to the lowest measured temperature as expected from the Mermin-Wagner theorem. Our work shows how dimensionality can be used to tune the magnetic properties of ultrathin films.
Distinct basal ganglia contributions to learning from implicit and explicit value signals in perceptual decision-making
Authors: Balsdon Tarryn , Pisauro M. Andrea , Philiastides Marios G. 
Published: June 2024

AbstractMetacognitive evaluations of confidence provide an estimate of decision accuracy that could guide learning in the absence of explicit feedback. We examine how humans might learn from this implicit feedback in direct comparison with that of explicit feedback, using simultaneous EEG-fMRI. Participants performed a motion direction discrimination task where stimulus difficulty was increased to maintain performance, with intermixed explicit- and no-feedback trials. We isolate single-trial estimates of post-decision confidence using EEG decoding, and find these neural signatures re-emerge at the time of feedback together with separable signatures of explicit feedback. We identified these signatures of implicit versus explicit feedback along a dorsal-ventral gradient in the striatum, a finding uniquely enabled by an EEG-fMRI fusion. These two signals appear to integrate into an aggregate representation in the external globus pallidus, which could broadcast updates to improve cortical decision processing via the thalamus and insular cortex, irrespective of the source of feedback.
MethPhaser: methylation-based long-read haplotype phasing of human genomes
Authors: Fu Yilei , Aganezov Sergey , Mahmoud Medhat , Beaulaurier John , Juul Sissel , Treangen Todd J. , Sedlazeck Fritz J. 
Published: June 2024

AbstractThe assignment of variants across haplotypes, phasing, is crucial for predicting the consequences, interaction, and inheritance of mutations and is a key step in improving our understanding of phenotype and disease. However, phasing is limited by read length and stretches of homozygosity along the genome. To overcome this limitation, we designed MethPhaser, a method that utilizes methylation signals from Oxford Nanopore Technologies to extend Single Nucleotide Variation (SNV)-based phasing. We demonstrate that haplotype-specific methylations extensively exist in Human genomes and the advent of long-read technologies enabled direct report of methylation signals. For ONT R9 and R10 cell line data, we increase the phase length N50 by 78%-151% at a phasing accuracy of 83.4-98.7% To assess the impact of tissue purity and random methylation signals due to inactivation, we also applied MethPhaser on blood samples from 4 patients, still showing improvements over SNV-only phasing. MethPhaser further improves phasing across HLA and multiple other medically relevant genes, improving our understanding of how mutations interact across multiple phenotypes. The concept of MethPhaser can also be extended to non-human diploid genomes. MethPhaser is available at https://github.com/treangenlab/methphaser.
Tunable translation-level CRISPR interference by dCas13 and engineered gRNA in bacteria
Authors: Kim Giho , Kim Ho Joon , Kim Keonwoo , Kim Hyeon Jin , Yang Jina , Seo Sang Woo 
Published: June 2024

AbstractAlthough CRISPR-dCas13, the RNA-guided RNA-binding protein, was recently exploited as a translation-level gene expression modulator, it has still been difficult to precisely control the level due to the lack of detailed characterization. Here, we develop a synthetic tunable translation-level CRISPR interference (Tl-CRISPRi) system based on the engineered guide RNAs that enable precise and predictable down-regulation of mRNA translation. First, we optimize the Tl-CRISPRi system for specific and multiplexed repression of genes at the translation level. We also show that the Tl-CRISPRi system is more suitable for independently regulating each gene in a polycistronic operon than the transcription-level CRISPRi (Tx-CRISPRi) system. We further engineer the handle structure of guide RNA for tunable and predictable repression of various genes in Escherichia coli and Vibrio natriegens. This tunable Tl-CRISPRi system is applied to increase the production of 3-hydroxypropionic acid (3-HP) by 14.2-fold via redirecting the metabolic flux, indicating the usefulness of this system for the flux optimization in the microbial cell factories based on the RNA-targeting machinery.
A photocatalytic redox cycle over a polyimide catalyst drives efficient solar-to-H2O2 conversion
Authors: Chi Wenwen , Dong Yuming , Liu Bing , Pan Chengsi , Zhang Jiawei , Zhao Hui , Zhu Yongfa , Liu Zeyu 
Published: June 2024

AbstractCircumventing the conventional two-electron oxygen reduction pathway remains a great problem in enhancing the efficiency of H2O2 photosynthesis. A promising approach to achieve outstanding photocatalytic activity involves the utilization of redox intermediates. Here, we engineer a polyimide aerogel photocatalyst with photoreductive carbonyl groups for non-sacrificial H2O2 production. Under photoexcitation, carbonyl groups on the photocatalyst surface are reduced, forming an anion radical intermediate. The produced intermediate is oxidized by O2 to produce H2O2 and subsequently restores the carbonyl group. The high catalytic efficiency is ascribed to a photocatalytic redox cycle mediated by the radical anion, which not only promotes oxygen adsorption but also lowers the energy barrier of O2 reduction reaction for H2O2 generation. An apparent quantum yield of 14.28% at 420 ± 10 nm with a solar-to-chemical conversion efficiency of 0.92% is achieved. Moreover, we demonstrate that a mere 0.5 m2 self-supported polyimide aerogel exposed to natural sunlight for 6 h yields significant H2O2 production of 34.3 mmol m−2.
Strain dynamics of contaminating bacteria modulate the yield of ethanol biorefineries
Authors: de Oliveira Lino Felipe Senne , Garg Shilpa , Li Simone S. , Misiakou Maria-Anna , Kang Kang , Vale da Costa Bruno Labate , Beyer-Pedersen Tobias Svend-Aage , Giacon Thamiris Guerra , Basso Thiago Olitta , Panagiotou Gianni , Sommer Morten Otto Alexander 
Published: June 2024

AbstractBioethanol is a sustainable energy alternative and can contribute to global greenhouse-gas emission reductions by over 60%. Its industrial production faces various bottlenecks, including sub-optimal efficiency resulting from bacteria. Broad-spectrum removal of these contaminants results in negligible gains, suggesting that the process is shaped by ecological interactions within the microbial community. Here, we survey the microbiome across all process steps at two biorefineries, over three timepoints in a production season. Leveraging shotgun metagenomics and cultivation-based approaches, we identify beneficial bacteria and find improved outcome when yeast-to-bacteria ratios increase during fermentation. We provide a microbial gene catalogue which reveals bacteria-specific pathways associated with performance. We also show that Limosilactobacillus fermentum overgrowth lowers production, with one strain reducing yield by ~5% in laboratory fermentations, potentially due to its metabolite profile. Temperature is found to be a major driver for strain-level dynamics. Improved microbial management strategies could unlock environmental and economic gains in this US $ 60 billion industry enabling its wider adoption.
Neutralizing antibodies reveal cryptic vulnerabilities and interdomain crosstalk in the porcine deltacoronavirus spike protein
Authors: Du Wenjuan , Debski-Antoniak Oliver , Drabek Dubravka , van Haperen Rien , van Dortmondt Melissa , van der Lee Joline , Drulyte Ieva , van Kuppeveld Frank J. M. , Grosveld Frank , Hurdiss Daniel L. , Bosch Berend-Jan 
Published: June 2024

AbstractPorcine deltacoronavirus (PDCoV) is an emerging enteric pathogen that has recently been detected in humans. Despite this zoonotic concern, the antigenic structure of PDCoV remains unknown. The virus relies on its spike (S) protein for cell entry, making it a prime target for neutralizing antibodies. Here, we generate and characterize a set of neutralizing antibodies targeting the S protein, shedding light on PDCoV S interdomain crosstalk and its vulnerable sites. Among the four identified antibodies, one targets the S1A domain, causing local and long-range conformational changes, resulting in partial exposure of the S1B domain. The other antibodies bind the S1B domain, disrupting binding to aminopeptidase N (APN), the entry receptor for PDCoV. Notably, the epitopes of these S1B-targeting antibodies are concealed in the prefusion S trimer conformation, highlighting the necessity for conformational changes for effective antibody binding. The binding footprint of one S1B binder entirely overlaps with APN-interacting residues and thus targets a highly conserved epitope. These findings provide structural insights into the humoral immune response against the PDCoV S protein, potentially guiding vaccine and therapeutic development for this zoonotic pathogen.
Long-term balancing selection for pathogen resistance maintains trans-species polymorphisms in a planktonic crustacean
Authors: Cornetti Luca , Fields Peter D. , Du Pasquier Louis , Ebert Dieter 
Published: June 2024

AbstractBalancing selection is an evolutionary process that maintains genetic polymorphisms at selected loci and strongly reduces the likelihood of allele fixation. When allelic polymorphisms that predate speciation events are maintained independently in the resulting lineages, a pattern of trans-species polymorphisms may occur. Trans-species polymorphisms have been identified for loci related to mating systems and the MHC, but they are generally rare. Trans-species polymorphisms in disease loci are believed to be a consequence of long-term host-parasite coevolution by balancing selection, the so-called Red Queen dynamics. Here we scan the genomes of three crustaceans with a divergence of over 15 million years and identify 11 genes containing identical-by-descent trans-species polymorphisms with the same polymorphisms in all three species. Four of these genes display molecular footprints of balancing selection and have a function related to immunity. Three of them are located in or close to loci involved in resistance to a virulent bacterial pathogen, Pasteuria, with which the Daphnia host is known to coevolve. This provides rare evidence of trans-species polymorphisms for loci known to be functionally relevant in interactions with a widespread and highly specific parasite. These findings support the theory that specific antagonistic coevolution is able to maintain genetic diversity over millions of years.
Divergent and gram-scale syntheses of (–)-veratramine and (–)-cyclopamine
Authors: Hou Wenlong , Lin Hao , Wu Yanru , Li Chuang , Chen Jiajun , Liu Xiao-Yu , Qin Yong 
Published: June 2024

AbstractVeratramine and cyclopamine, two of the most representative members of the isosteroidal alkaloids, are valuable molecules in agricultural and medicinal chemistry. While plant extraction of these compounds suffers from uncertain supply, efficient chemical synthesis approaches are in high demand. Here, we present concise, divergent, and scalable syntheses of veratramine and cyclopamine with 11% and 6.2% overall yield, respectively, from inexpensive dehydro-epi-androsterone. Our synthesis readily provides gram quantities of both target natural products by utilizing a biomimetic rearrangement to form the C-nor-D-homo steroid core and a stereoselective reductive coupling/(bis-)cyclization sequence to establish the (E)/F-ring moiety.
A benchmarking study of quantum algorithms for combinatorial optimization
Authors: Sankar Krishanu , Scherer Artur , Kako Satoshi , Reifenstein Sam , Ghadermarzy Navid , Krayenhoff Willem B. , Inui Yoshitaka , Ng Edwin , Onodera Tatsuhiro , Ronagh Pooya , Yamamoto Yoshihisa 
Published: June 2024

AbstractWe study the performance scaling of three quantum algorithms for combinatorial optimization: measurement-feedback coherent Ising machines (MFB-CIM), discrete adiabatic quantum computation (DAQC), and the Dürr–Høyer algorithm for quantum minimum finding (DH-QMF) that is based on Grover’s search. We use MaxCut problems as a reference for comparison, and time-to-solution (TTS) as a practical measure of performance for these optimization algorithms. For each algorithm, we analyze its performance in solving two types of MaxCut problems: weighted graph instances with randomly generated edge weights attaining 21 equidistant values from −1 to 1; and randomly generated Sherrington–Kirkpatrick (SK) spin glass instances. We empirically find a significant performance advantage for the studied MFB-CIM in comparison to the other two algorithms. We empirically observe a sub-exponential scaling for the median TTS for the MFB-CIM, in comparison to the almost exponential scaling for DAQC and the proven $$\widetilde{{{{\mathcal{O}}}}}\left(\sqrt{{2}^{n}}\right)$$

O

̃

2

n

scaling for DH-QMF. We conclude that the MFB-CIM outperforms DAQC and DH-QMF in solving MaxCut problems.
Fitness effects of synthetic and natural diet preservatives on the edible insect Bombyx mori
Authors: Lei Xiaoyu , Qian Zhaoyi , Zhu Xinyue , Zhang Nan , He Jintao , Xiao Jian , Shen Xiaoqiang , Muhammad Abrar , Sun Chao , Shao Yongqi 
Published: June 2024

AbstractSilkworm pupae as widely consumed insect products are good biosources of protein and micronutrients. Silkworm rearing throughout the year can be achieved by feeding them an artificial diet instead of native plants, facilitating extensive pupa production. However, artificial diets are prone to spoilage caused by bacterial contamination. Here, we evaluated the antiseptic effect of ethylparaben (EP, chemical preservative) and medium-chain fatty acids (MCFA, natural preservative) in a silkworm artificial diet. Results showed that both preservatives effectively inhibited pathogenic bacterial growth. Furthermore, the addition of EP or MCFA did not negatively impact the production capacity of silkworms and the homeostasis of gut microbiota. However, the expression of genes involved in detoxification such as Ugt2, and immune response such as Cecropin B, were upregulated after EP consumption. Therefore, natural preservative MCFA emerges as a suitable option from a safety perspective. These findings highlight future directions for improving insect artificial diet formulation.
CODC-v1: a quality-controlled and bias-corrected ocean temperature profile database from 1940–2023
Authors: Zhang Bin , Cheng Lijing , Tan Zhetao , Gouretski Viktor , Li Fuchao , Pan Yuying , Yuan Huifeng , Ren Huanping , Reseghetti Franco , Zhu Jiang , Wang Fan 
Published: June 2024

AbstractHigh-quality ocean in situ profile observations are fundamental for ocean and climate research and operational oceanographic applications. Here we describe a new global ocean subsurface temperature profile database named the Chinese Academy of Science (CAS) Oceanography Data Center version 1 (CODC-v1). This database contains over 17 million temperature profiles between 1940–2023 from all available instruments. The major data source is the World Ocean Database (WOD), but CODC-v1 also includes some data from some Chinese institutes which are not available in WOD. The data are quality-controlled (QC-ed) by a new QC system that considers the skewness of local temperature distributions, topographic barriers, and the shift of temperature distributions due to climate change. Biases in Mechanical Bathythermographs (MBTs), eXpendable Bathythermographs (XBTs), and Bottle data (OSD) are all corrected using recently proposed correction schemes, which makes CODC-v1 a bias-corrected dataset. These aspects ensure the data quality of the CODC-v1 database, making it suitable for a wide spectrum of ocean and climate research and applications.