bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Perioperative Dexamethasone in the Context of Neurosurgical Brain Metastasis Resection
Authors: Wasilewski David , Bukatz Jan , Peukert Ricarda , Shaked Zoe , Poeser Paul , Karbe Anna-Gila , Anna-Trelinska-Finger  , Jelgersma Claudius , Früh Anton , Raspe Matthias , Radbruch Helena , Capper David , Schlaak Max , Thuss-Patience Peter , Bischoff Philip , Horst David , Krenzke Marcel , Xu Ran , Ehret Felix , Kaul David , Misch Martin , Bullinger Lars , Frost Nikolaj , Vajkoczy Peter , Onken Julia 
Published: January 2023

AbstractBackgroundPatients with brain metastases that undergo brain metastasis resection regularly receive perioperative dexamethasone. We sought to evaluate whether perioperative dexamethasone in brain metastases is linked to survival.MethodsRetrospective data on perioperative dexamethasone dosage in resected brain metastasis patients at three hospital sites of the Charité from 2010-2022 were collected. Cut-off values for cumulative perioperative dexamethasone dose as a continuous predictor variable for survival were determined using maximally selected rank statistics. Patients were dichotomized based on determined cut-offs of cumulative dexamethasone (pre-operative: < 40 mg vs ≥40 mg; post-operative: < 180 mg vs ≥ 180 mg) and pre- and postoperative: < 281 mg vs ≥ 281 mg). Medical records included baseline demographic, radiological, histopathological and treatment-related characteristics. Based on cut-off values for dexamethasone downstream statistical analyses included Kaplan-Meier, Cox proportional hazards regression for overall survival with adjustment for potential confounders including age, gender, Karnofsky performance status and presence of extracranial metastasis via propensity score matching.Results539 patients were included. Median follow-up time was 58,97 months. After adjusting for age, gender, Karnofsky performance status and presence of extracranial metastasis patients with higher cumulative perioperative dexamethasone (≥281 mg) showed shorter survival (HR: 1.47 (1.20-1.80, p<0.001) as compared to patients with lower cumulative doses (<281 mg). This effect remained significant after correction for patients that died within 2 months after resection and for patients with KPS below 50% and, independently from this approach performing propensity score matched-based analysis of the total cohort of patients, respectively.ConclusionCumulative perioperative dexamethasone is associated with decreased survival in the context of brain metastasis resection. Strict dosage, down taper or methods reducing corticosteroid dependency should be regularly evaluated in clinical practice in patients with brain metastases.
Clinical characteristics and results of patients who underwent minor salivary gland biopsy with the suspicion of Sjogren syndrome
Authors: Kutluk Oznur , Cay Hasan Fatih 
Published: January 2023

ABSTRACTOBJECTIVESTo evaluate the value and accuracy of biopsy in diagnosing Sjogren’s syndrome (SS) by evaluating the results of patients who underwent mınor salivary gland biopsy (MSGB) with the suspicion of SS.MATERIALS and METHODSThe study was planned with retrospective assessment of 127 patients with biopsy performed for SS diagnosis. The clinical and laboratory characteristics of the patients who underwent MSGB were recorded from their files. SS diagnosis was placed using the rating system according to 2016 ACR/EULAR classification criteria or based on expert opinion.RESULTS113 patients met the ınclusion criteria. 72 patients diagnosed with SS. 56 were diagnosed according to the 2016 ACR/EULAR classification criteria and 16 were diagnosed according to expert opinion. There were 57 patients with positive MSGB outcome (55 SS, 2 not SS). There were 56 patients with MSGB negative outcome (17 SS, 39 not SS). The sensitivity of MSGB for SS diagnosis was 76.4%, and specificity was 95.1%.CONCLUSIONAll of our patients had antibody test results, but the number of objective tests included in the classification criteria such as salivary flow rate and Schirmer was low. Although MSGB is considered an invasive technique, it appears to be a safe technique as long as it is performed by experienced professionals. It will assist in the final decision for patients with SS suspicion and who cannot undergo other objective tests.
Putative APOBEC3 deaminase editing in MPXV as evidence for sustained human transmission since at least 2016
Authors: O’Toole Áine , Neher Richard A. , Ndodo Nnaemeka , Borges Vitor , Gannon Ben , Gomes João Paulo , Groves Natalie , King David J , Maloney Daniel , Lemey Philippe , Lewandowski Kuiama , Loman Nicholas , Myers Richard , Suchard Marc A. , Worobey Michael , Chand Meera , Ihekweazu Chikwe , Ulaeto David , Adetifa Ifedayo , Rambaut Andrew 
Published: January 2023

AbstractMpox is often described as being endemic in West and Central Africa as a zoonotic disease that transmits through contact with the reservoir rodent host, likely a species of African squirrel. In May 2022, human cases of Mpox were detected spreading internationally beyond countries with known endemic reservoirs. At time of writing, 84,700 confirmed cases have been reported in 110 countries. When the first cases from 2022 were sequenced, it was seen that they shared 42 single nucleotide differences from the closest mpox virus (MPXV) genome sampled in 2018. This number of changes within 3-4 years is unexpectedly large and points to a much greater evolutionary rate than expected for a poxvirus. Strikingly, most nucleotide changes are of a specific type – a dinucleotide change from TC->TT or its reverse complement GA->AA. This mutation type is characteristic of the action of APOBEC3 deaminases; host-enzymes with reported antiviral function. Analysis of MPXV genomes sampled from 2017 to 2022 showed further evidence of TC->TT mutation pattern enrichment, with 93% of transmitted single nucleotide mutations since 2017 consistent with APOBEC3 editing. Assuming APOBEC-editing is characteristic of MPXV infection in human hosts, we propose an APOBEC clock that – at a rate of ~6 APOBEC3 mutations per year – estimates MPXV has been circulating in humans since 2016. This evolutionary pattern of host-enzyme editing has implications for the longer-term fitness of the virus in this epidemic as such mechanisms are primarily antiviral in function, but in the context of a poxvirus also provide a source of variation that may conceivably facilitate adaptation.
Improvements to the Gulf PipefishSyngnathus scovelliGenome
Authors: Ramesh B , Small CM , Healey H , Johnson B , Barker E , Currey M , Bassham S , Myers M , Cresko WA , Jones AG 
Published: January 2023

AbstractThe Gulf pipefishSyngnathus scovellihas emerged as an important species in the study of sexual selection, development, and physiology, among other topics. The fish family Syngnathidae, which includes pipefishes, seahorses, and seadragons, has become an increasingly attractive target for comparative research in ecological and evolutionary genomics. These endeavors depend on having a high-quality genome assembly and annotation. However, the first version of theS. scovelligenome assembly was generated by short-read sequencing and annotated using a small set of RNA-sequence data, resulting in limited contiguity and a relatively poor annotation. Here, we present an improved genome assembly and an enhanced annotation, resulting in a new official gene set forS. scovelli. By using PacBio long-read high-fidelity (Hi-Fi) sequences and a proximity ligation (Hi-C) library, we fill small gaps and join the contigs to obtain 22 chromosome-level scaffolds. Compared to the previously published genome, the gaps in our novel genome assembly are smaller, the N75 is much larger (13.3 Mb), and this new genome is around 95% BUSCO complete. The precision of the gene models in the NCBI’s eukaryotic annotation pipeline was enhanced by using a large body of RNA-Seq reads from different tissue types, leading to the discovery of 28,162 genes, of which 8,061 were non-coding genes. This new genome assembly and the annotation are tagged as a RefSeq genome by NCBI and thus provide substantially enhanced genomic resources for future research involvingS. scovelli.
Regulation of the hypertonic stress response by the 3’ mRNA cleavage and polyadenylation complex
Authors: Urso Sarel J. , Sathaseevan Anson , Derry W. Brent , Lamitina Todd 
Published: January 2023

AbstractMaintenance of osmotic homeostasis is one of the most aggressively defended homeostatic setpoints in physiology. One major mechanism of osmotic homeostasis involves the upregulation of proteins that catalyze the accumulation of solutes called organic osmolytes. To better understand how osmolyte accumulation proteins are regulated, we conducted forward genetic screen inC. elegansfor mutants with no induction of osmolyte biosynthesis gene expression (Nio mutants).nio-3mutants encoded a missense mutation incpf-2/CstF64 whilenio-7mutants encoded a missense mutation insymk-1/Symplekin. Bothcpf-2andsymk-1are nuclear components of the highly conserved 3’ mRNA cleavage and polyadenylation complex.cpf-2andsymk-1block the hypertonic induction ofgpdh-1and other osmotically induced mRNAs, suggesting they act at the transcriptional level. We generated a functional auxin-inducible degron (AID) allele forsymk-1and found that acute, post-developmental degradation in the intestine and hypodermis was sufficient to cause the Nio phenotype.symk-1andcpf-2exhibit genetic interactions that strongly suggest they function through alterations in 3’ mRNA cleavage and/or alternative polyadenylation. Consistent with this hypothesis, we find that inhibition of several other components of the mRNA cleavage complex also cause a Nio phenotype.cpf-2andsymk-1specifically affect the osmotic stress response since heat shock-induced upregulation of ahsp-16.2::GFPreporter is normal in these mutants. Our data suggest a model in which alternative polyadenylation of one or more mRNAs is essential to regulate the hypertonic stress response.
Natural methylation epialleles correlate with gene expression in maize
Authors: Zeng Yibing , Dawe R. Kelly , Gent Jonathan I. 
Published: January 2023

ABSTRACTDNA methylation (5-methylcytosine) represses transposon activity and contributes to inaccessible chromatin structure of repetitive DNA in plants. It is depleted from cis regulatory elements in and near genes but is present in some gene bodies, including exons. Methylation in exons solely in the CG context is called gene body methylation (gbM). Methylation in exons in both CG and non-CG contexts is called TE-like methylation (teM). Assigning functions to both forms of methylation in genes has proven to be challenging. Toward that end, we utilized recent genome assemblies, gene annotations, transcription data, and methylome data to quantify common patterns of gene methylation and their relations to gene expression in maize. To compare between genomes, we analyzed each data source relative to its own genome assembly rather than the easier but less accurate method of using one assembly as reference for all. We found that gbM genes exist in a continuum of CG methylation levels without a clear demarcation between unmethylated genes and gbM genes. Analysis of expression levels across diverse maize stocks and tissues revealed a weak but highly significant positive correlation between gbM and gene expression except in endosperm. gbM epialleles were associated with an approximately 3% increase in steady-state expression level relative to unmethylated epialleles. In contrast to gbM genes, which were conserved and were broadly expressed across tissues, we found that teM genes, which make up about 12% of genes, are mainly silent, are limited to specific maize stocks, and exhibit evidence of annotation errors. We used these data to flag all teM genes in the 26 NAM founder genome assemblies. While some teM genes are likely functional, these data suggest that the majority are not, and their inclusion can confound interpretation of whole-genome studies.
Conformationally responsive dyes enable protein-adaptive differential scanning fluorimetry
Authors: Wu Taiasean , Yu Joshua C. , Suresh Arundhati , Gale-Day Zachary J. , Alteen Matthew G. , Woo Amanda S. , Millbern Zoe , Johnson Oleta T. , Carroll Emma C. , Partch Carrie L. , Fourches Denis , Vinueza Nelson R. , Vocadlo David J. , Gestwicki Jason E. 
Published: January 2023

AbstractFlexiblein vitromethods alter the course of biological discoveries. Differential Scanning Fluorimetry (DSF) is a particularly versatile technique which reports protein thermal unfolding via fluorogenic dye. However, applications of DSF are limited by widespread protein incompatibilities with the available DSF dyes. Here, we enable DSF applications for 66 of 70 tested proteins (94%) including 10 from the SARS-CoV2 virus using a chemically diverse dye library, Aurora, to identify compatible dye-protein pairs in high throughput. We find that this protein-adaptive DSF platform (paDSF) not only triples the previous protein compatibility, but also fundamentally extends the processes observable by DSF, including interdomain allostery in O-GlcNAc Transferase (OGT). paDSF enables routine measurement of protein stability, dynamics, and ligand binding.One-Sentence SummaryNext generation protein-adaptive DSF (paDSF) enables rapid and general measurements of protein stability and dynamics.
Genome-wide CRISPR screens identify noncanonical translation factor eIF2A as an enhancer of SARS-CoV-2 programmed –1 ribosomal frameshifting
Authors: Wei Lian-Huan , Sun Yu , Guo Junjie U. 
Published: January 2023

ABSTRACTMany positive-strand RNA viruses, including all known coronaviruses, employ programmed –1 ribosomal frameshifting (–1 PRF) to regulate the translation of polycistronic viral RNAs. However, only a few host factors have been shown to regulate –1 PRF. Through a reporter-based genome-wide CRISPR/Cas9 knockout screen, we identified several host factors that either suppressed or enhanced –1 PRF of SARS-CoV-2. One of these factors is eukaryotic translation initiation factor 2A (eIF2A), which specifically and directly enhanced –1 PRF in vitro and in cells. Consistent with the crucial role of efficient –1 PRF in transcriptase/replicase expression, loss of eIF2A reduced SARS-CoV-2 replication in cells. Transcriptome-wide analysis of eIF2A-interacting RNAs showed that eIF2A primarily interacted with 18S ribosomal RNA near the contacts between the SARS-CoV-2 frameshift-stimulatory element (FSE) and the ribosome. Thus, our results revealed an unexpected role for eIF2A in modulating the translation of specific RNAs independent of its previously described role during initiation.
Mechanism of glycoform specificity and protection against antibody dependent enhancement by an anti-afucosylated IgG nanobody
Authors: Gupta Aaron , Kao Kevin , Yamin Rachel , Oren Deena A. , Goldgur Yehuda , Du Jonathan , Lollar Pete , Sundberg Eric J. , Ravetch Jeffrey V. 
Published: January 2023

AbstractImmunoglobulin G (IgG) antibodies contain a single, complexN-glycan on each IgG heavy chain protomer embedded in the hydrophobic pocket between its Cγ2 domains. The presence of this glycan contributes to the structural organization of the Fc domain and determines its specificity for Fcγ receptors, thereby determining distinct cellular responses. On the Fc, the variable construction of this glycan structure leads to a family of highly-related, but non-equivalent glycoproteins known as glycoforms. We previously reported the development of synthetic nanobodies that distinguish IgG glycoforms without cross-reactivity to off-target glycoproteins or free glycans. Here, we present the X-ray crystal structure of one such nanobody, X0, in complex with its specific binding partner, the Fc fragment of afucosylated IgG1. Two X0 nanobodies bind a single afucosylated Fc homodimer at the upper Cγ2 domain, making both protein-protein and protein-carbohydrate contacts and overlapping the binding site for Fcγ receptors. Upon binding, the elongated CDR3 loop of X0 undergoes a conformational shift to access the buriedN-glycan and acts as a ‘glycan sensor’, forming hydrogen bonds with the afucosylated IgGN-glycan that would otherwise be sterically hindered by the presence of a core fucose residue. Based on this structure, we designed X0 fusion constructs that disrupt pathogenic afucosylated IgG1-FcγRIIIa interactions and rescue mice in a model of dengue virus infection.
Quantifying paddling kinematic through muscle activation and whole body coordination during maximal sprint of different duration on a kayak ergometer: a pilot study
Authors: Garnier Y.M. , Hilt P. M. , Sirandre C. , Ballay Y. , Lepers R. , Paizis C. 
Published: January 2023

AbstractPaddling technique and stroke kinematics are important performance factors in flatwater sprint kayaking that require important energetic demand and high strength from the muscles of the trunk and upper limb. The various distance competed (from 200-m to 1000-m) requires the athletes to optimize their pacing strategy to maximize power output distribution throughout the race. This study aims to characterize paddling technique and stroke kinematics during two maximal sprints of different duration. Nine national-trained participants performed a 40-seconds and a 4-min sprint at maximal intensity on a kayak ergometer. The main findings demonstrated a significantly greater mean stroke power (237 ± 80 W vs 170 ± 48 W) and rate (131 ± 8 spm vs 109 ± 7 spm) during the 40-s sprint compared to the 4-min sprint. Athletes used an all-out strategy for the 40-sec exercise and a parabolic-shape strategy during the 4-min. Despite different strategies implemented and higher muscular activation during the 40-s sprint, no change in paddling technique and body coordination occurred during the sprints. The findings of the present study suggest that athletes constructed a well-defined profile that is not affected by fatigue despite a decrease in power output during the all-out strategy. Also, they regulate paddling kinematics during longer exercise with no change in paddling technique and body coordination.
Y-complex nucleoporins independently contribute to nuclear pore assembly and gene regulation in neuronal progenitors
Authors: Orniacki Clarisse , Verrico Annalisa , Pelletier Stéphane , Souquet Benoit , Coulpier Fanny , Jourdren Laurent , Benetti Serena , Doye Valérie 
Published: January 2023

ABSTRACTFrom their essential function in building up the nuclear pore complexes, nucleoporins have expanded roles beyond nuclear transport. Hence, their contribution to chromatin organization and gene expression has set them as critical players in development and pathologies. We previously reported that Nup133 and Seh1, two components of the Y-complex subunit of the nuclear pore scaffold, are dispensable for mouse embryonic stem cell viability but required for their survival during neuroectodermal differentiation. Here, a transcriptomic analysis revealed that Nup133 regulates a subset of genes at early stages of neuroectodermal differentiation, includingLhx1 and Nup210L, encoding a newly validated nucleoporin. These genes were also misregulated inNup133∆Midneuronal progenitors, in which NPC basket assembly is impaired, as previously observed in pluripotent cells. However, a four-fold reduction of Nup133, despite affecting basket assembly, is not sufficient to alterNup210LandLhx1regulation. Finally, these two genes are also misregulated inSeh1-deficient neural progenitors that only show a mild decrease in NPC density. Together these data reveal a shared function of Y-complex nucleoporins in gene regulation during neuroectodermal differentiation, which seem independent of nuclear pore basket assembly.
A miniature cellulosome with novel interaction modes
Authors: Allan John , Black Gary W 
Published: January 2023

AbstractCellulosomes are efficient enzymatic nanomachines which have arisen for the degradation of cellulosic biomass. They are found abundantly in soil-dwelling microbes and bacteria which thrive in the stomachs of ruminant mammals. Two protein domains, cohesins and dockerins, characterise cellulosomes. These domains interact with each other to form enormous complexes with as many as 130 individual proteins. Annotation of the genome ofCellulosilyticum lenotcellumDSM 5427 revealed one single cohesin and one single dockerin domain. This pales in comparison to most cellulosomal organisms. We have recombinantly produced the proteins which bear these domains and demonstrated cellulase activity, which is enhanced by interaction between the two proteins. Moreover we have identified additional novel interacting partners for this unique cellulosome complex. This broadens the repertoire and definitions of cellulosomes overall.
Neo-natal castration leads to subtle differences in porcine anterior cruciate ligament morphology and function in adolescence
Authors: Thompson Jacob D. , Howe Danielle , Griffith Emily H. , Fisher Matthew B. 
Published: January 2023

AbstractFemale adolescent athletes are at a higher risk of tearing their anterior cruciate ligament (ACL) than male counterparts. While most work related to hormones has focused on the effects of estrogen to understand the increased risk of ACL injury, there are other understudied factors, including testosterone. The purpose of this study was to determine how surgical castration in the male porcine model influences ACL size and function across skeletal growth. Thirty-six male Yorkshire crossbreed pigs were raised to 3 (juvenile), 4.5 (early adolescent), and 6 months (adolescent) of age. Animals were either castrated (barrows) within 1-2 weeks after birth or were left intact (boars). Post-euthanasia, joint and ACL size were assessed via MRI, and biomechanics were assessed via a robotic testing system. Joint size increased throughout age, yet barrows had smaller joints than boars (p<0.001 for all measures). ACL cross-sectional area (CSA), length, volume, and stiffness increased with age (p<0.0001), as did ACL anteromedial (AM) bundle percent contribution to resisting loads (p=0.012). Boar ACL, AM bundle, and PL bundle volumes were 19% (p=0.002), 25% (p=0.003), and 15% (p=0.04) larger than barrows across ages. However, CSA, stiffness, and bundle contribution were similar between boars and barrows (p>0.05). The barrows had smaller temporal increases in AM bundle percent function than boars, but these data were highly variable. Thus, early and sustained loss in testosterone leads to subtle differences in ACL morphology, but may not influence measures associated with increased injury risk, such as CSA or bundle forces in response to applied loads.