bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-efficiency EGFR genotyping using cell-free DNA in bronchial washing fluid
Authors: Murata Yoshihiko , Nakajima Yumi , Sato Yukio , Hizawa Nobuyuki , Yamakawa Daichi , Matsubara Daisuke , Noguchi Masayuki , Minami Yuko 
Published: March 2024

Abstract

Background
EGFR mutation testing is required for treatment of lung adenocarcinoma using epidermal growth factor receptor-tyrosine kinase inhibitor. However, the amounts of tumor tissue or tumor cells obtained by bronchoscopy are often insufficient. Bronchial washing fluid, obtained by lavage with saline after tumor biopsy or brushing, and the supernatant of bronchial washing fluid are thought to contain cell-free DNA that would be potentially applicable for EGFR testing.

Methods
From among patients with suspected adenocarcinoma or non-small cell lung carcinoma diagnosed from biopsy or surgical specimens at the University of Tsukuba Hospital between 2015 and 2019, cell-free DNAs from 80 specimens of supernatant of bronchial washing fluid (50 with EGFR mutation and 30 with wild type EGFR) and 8 blood serum samples were examined for EGFR mutation using droplet digital PCR.

Results
Among the 50 patients harboring EGFR mutation, the rate of positivity for cell-free DNA extracted from supernatant of bronchial washing fluid was 80% (40/50). In nine of the EGFR mutation-positive cases, tumor cells were not detected by either biopsy or cytology, but the mutation was detected in four cases (4/9, 44%). Comparison of the cell-free DNA mutation detection rate between supernatant of bronchial washing fluid and blood serum in six cases showed that mutations were detected from the former in all cases (6/6, 100%), but from the latter in only one case (1/6, 17%).

Conclusions
Using supernatant of bronchial washing fluid samples, the detection rate of EGFR mutation was high, and EGFR mutations were detectable even when no tumor cells had been detectable by biopsy or cytology. Supernatant of bronchial washing fluid might be an effective sample source for EGFR mutation testing.
Testing SIPA1L2 as a modifier of CMT1A using mouse models
Authors: Murray George C , Hines Timothy J , Tadenev Abigail L D , Xu Isaac , Züchner Stephan , Burgess Robert W 
Published: March 2024

Abstract
Charcot-Marie-Tooth disease type 1A (CMT1A) is a demyelinating peripheral neuropathy caused by the duplication of peripheral myelin protein 22 (PMP22), leading to muscle weakness and loss of sensation in the hands and feet. A recent case-only genome-wide association study of CMT1A patients conducted by the Inherited Neuropathy Consortium identified a strong association between strength of foot dorsiflexion and variants in signal induced proliferation associated 1 like 2 (SIPA1L2), indicating that it may be a genetic modifier of disease. To validate SIPA1L2 as a candidate modifier and to assess its potential as a therapeutic target, we engineered mice with deletion of exon 1 (including the start codon) of the Sipa1l2 gene and crossed them to the C3-PMP22 mouse model of CMT1A. Neuromuscular phenotyping showed that Sipa1l2 deletion in C3-PMP22 mice preserved muscular endurance assayed by inverted wire hang duration and changed femoral nerve axon morphometrics such as myelin thickness. Gene expression changes suggest involvement of Sipa1l2 in cholesterol biosynthesis, a pathway that is also implicated in C3-PMP22 mice. Although Sipa1l2 deletion did impact CMT1A-associated phenotypes, thereby validating a genetic interaction, the overall effect on neuropathy was mild.
Phylogenetically diverse wild plant species use common biochemical strategies to thrive in the Atacama Desert
Authors: Dussarrat Thomas , Nilo-Poyanco Ricardo , Moyano Tomás C , Prigent Sylvain , Jeffers Tim L , Díaz Francisca P , Decros Guillaume , Audi Lauren , Sondervan Veronica M , Shen Bingran , Araus Viviana , Rolin Dominique , Shasha Dennis , Coruzzi Gloria M , Gibon Yves , Latorre Claudio , Pétriacq Pierre , Gutiérrez Rodrigo A 
Published: March 2024

Abstract
The best ideotypes are under mounting pressure due to increased aridity. Understanding the conserved molecular mechanisms that evolve in wild plants adapted to harsh environments is crucial in developing new strategies for agriculture. Yet our knowledge of such mechanisms in wild species is scant. We performed metabolic pathway reconstruction using transcriptome information from 32 Atacama and phylogenetically related species that do not live in Atacama (sister species). We analyzed reaction enrichment to understand the commonalities and differences of Atacama plants. To gain insights into the mechanisms that ensure survival, we compared expressed gene isoform numbers and gene expression patterns between the annotated biochemical reactions from 32 Atacama and sister species. We found biochemical convergences characterized by reactions enriched in at least 50% of the Atacama species, pointing to potential advantages against drought and nitrogen starvation, for instance. These findings suggest that the adaptation in the Atacama Desert may result in part from shared genetic legacies governing the expression of key metabolic pathways to face harsh conditions. Enriched reactions corresponded to ubiquitous compounds common to extreme and agronomic species and were congruent with our previous metabolomic analyses. Convergent adaptive traits offer promising candidates for improving abiotic stress resilience in crop species.
ATRX guards against aberrant differentiation in mesenchymal progenitor cells
Authors: Fang Yan , Barrows Douglas , Dabas Yakshi , Carroll Thomas S , Singer Sam , Tap William D , Nacev Benjamin A 
Published: March 2024

Abstract
Alterations in the tumor suppressor ATRX are recurrently observed in mesenchymal neoplasms. ATRX has multiple epigenetic functions including heterochromatin formation and maintenance and regulation of transcription through modulation of chromatin accessibility. Here, we show in murine mesenchymal progenitor cells (MPCs) that Atrx deficiency aberrantly activated mesenchymal differentiation programs. This includes adipogenic pathways where ATRX loss induced expression of adipogenic transcription factors and enhanced adipogenic differentiation in response to differentiation stimuli. These changes are linked to loss of heterochromatin near mesenchymal lineage genes together with increased chromatin accessibility and gains of active chromatin marks. We additionally observed depletion of H3K9me3 at transposable elements, which are derepressed including near mesenchymal genes where they could serve as regulatory elements. Finally, we demonstrated that loss of ATRX in a mesenchymal malignancy, undifferentiated pleomorphic sarcoma, results in similar epigenetic disruption and de-repression of transposable elements. Together, our results reveal a role for ATRX in maintaining epigenetic states and transcriptional repression in mesenchymal progenitors and tumor cells and in preventing aberrant differentiation in the progenitor context.
Catalytic residues of microRNA Argonautes play a modest role in microRNA star strand destabilization in C. elegans
Authors: Kotagama Kasuen , Grimme Acadia L , Braviner Leah , Yang Bing , Sakhawala Rima M , Yu Guoyun , Benner Lars Kristian , Joshua-Tor Leemor , McJunkin Katherine 
Published: March 2024

Abstract
Many microRNA (miRNA)-guided Argonaute proteins can cleave RNA (‘slicing’), even though miRNA-mediated target repression is generally cleavage-independent. Here we use Caenorhabditis elegans to examine the role of catalytic residues of miRNA Argonautes in organismal development. In contrast to previous work, mutations in presumed catalytic residues did not interfere with development when introduced by CRISPR. We find that unwinding and decay of miRNA star strands is weakly defective in the catalytic residue mutants, with the largest effect observed in embryos. Argonaute-Like Gene 2 (ALG-2) is more dependent on catalytic residues for unwinding than ALG-1. The miRNAs that displayed the greatest (albeit minor) dependence on catalytic residues for unwinding tend to form stable duplexes with their star strand, and in some cases, lowering duplex stability alleviates dependence on catalytic residues. While a few miRNA guide strands are reduced in the mutant background, the basis of this is unclear since changes were not dependent on EBAX-1, an effector of Target-Directed miRNA Degradation (TDMD). Overall, this work defines a role for the catalytic residues of miRNA Argonautes in star strand decay; future work should examine whether this role contributes to the selection pressure to conserve catalytic activity of miRNA Argonautes across the metazoan phylogeny.
Comprehensive transcriptome analysis reveals altered mRNA splicing and post-transcriptional changes in the aged mouse brain
Authors: Kumar Nisha Hemandhar , Kluever Verena , Barth Emanuel , Krautwurst Sebastian , Furlan Mattia , Pelizzola Mattia , Marz Manja , Fornasiero Eugenio F 
Published: March 2024

Abstract
A comprehensive understanding of molecular changes during brain aging is essential to mitigate cognitive decline and delay neurodegenerative diseases. The interpretation of mRNA alterations during brain aging is influenced by the health and age of the animal cohorts studied. Here, we carefully consider these factors and provide an in-depth investigation of mRNA splicing and dynamics in the aging mouse brain, combining short- and long-read sequencing technologies with extensive bioinformatic analyses. Our findings encompass a spectrum of age-related changes, including differences in isoform usage, decreased mRNA dynamics and a module showing increased expression of neuronal genes. Notably, our results indicate a reduced abundance of mRNA isoforms leading to nonsense-mediated RNA decay and suggest a regulatory role for RNA-binding proteins, indicating that their regulation may be altered leading to the reshaping of the aged brain transcriptome. Collectively, our study highlights the importance of studying mRNA splicing events during brain aging.
Viral reprogramming of host transcription initiation
Authors: Ungerleider Nathan A , Roberts Claire , O’Grady Tina M , Nguyen Trang T , Baddoo Melody , Wang Jia , Ishaq Eman , Concha Monica , Lam Meggie , Bass Jordan , Nguyen Truong D , Van Otterloo Nick , Wickramarachchige-Dona Nadeeshika , Wyczechowska Dorota , Morales Maria , Ma Tianfang , Dong Yan , Flemington Erik K 
Published: March 2024

Abstract
Viruses are master remodelers of the host cell environment in support of infection and virus production. For example, viruses typically regulate cell gene expression through modulating canonical cell promoter activity. Here, we show that Epstein Barr virus (EBV) replication causes ‘de novo’ transcription initiation at 29674 new transcription start sites throughout the cell genome. De novo transcription initiation is facilitated in part by the unique properties of the viral pre-initiation complex (vPIC) that binds a TATT[T/A]AA, TATA box-like sequence and activates transcription with minimal support by additional transcription factors. Other de novo promoters are driven by the viral transcription factors, Zta and Rta and are influenced by directional proximity to existing canonical cell promoters, a configuration that fosters transcription through existing promoters and transcriptional interference. These studies reveal a new way that viruses interact with the host transcriptome to inhibit host gene expression and they shed light on primal features driving eukaryotic promoter function.
Molecular basis of A. thaliana KEOPS complex in biosynthesizing tRNA t6A
Authors: Zheng Xinxing , Su Chenchen , Duan Lei , Jin Mengqi , Sun Yongtao , Zhu Li , Zhang Wenhua 
Published: March 2024

Abstract
In archaea and eukaryotes, the evolutionarily conserved KEOPS is composed of four core subunits―Kae1, Bud32, Cgi121 and Pcc1, and a fifth Gon7/Pcc2 that is found in fungi and metazoa. KEOPS cooperates with Sua5/YRDC to catalyze the biosynthesis of tRNA N6-threonylcarbamoyladenosine (t6A), an essential modification needed for fitness of cellular organisms. Biochemical and structural characterizations of KEOPSs from archaea, yeast and humans have determined a t6A-catalytic role for Kae1 and auxiliary roles for other subunits. However, the precise molecular workings of KEOPSs still remain poorly understood. Here, we investigated the biochemical functions of A. thaliana KEOPS and determined a cryo-EM structure of A. thaliana KEOPS dimer. We show that A. thaliana KEOPS is composed of KAE1, BUD32, CGI121 and PCC1, which adopts a conserved overall arrangement. PCC1 dimerization leads to a KEOPS dimer that is needed for an active t6A-catalytic KEOPS–tRNA assembly. BUD32 participates in direct binding of tRNA to KEOPS and modulates the t6A-catalytic activity of KEOPS via its C-terminal tail and ATP to ADP hydrolysis. CGI121 promotes the binding of tRNA to KEOPS and potentiates the t6A-catalytic activity of KEOPS. These data and findings provide insights into mechanistic understanding of KEOPS machineries.
Clinical impact of the Kidney Failure Risk Equation for vascular access planning
Authors: Hahn Lundström Ulrika , Ramspek Chava L , Dekker Friedo W , van Diepen Merel , Carrero Juan Jesus , Hedin Ulf , Evans Marie 
Published: March 2024

ABSTRACT

Background
Risk-based thresholds for arteriovenous (AV) access creation has been proposed to aid vascular access planning. We aimed to assess the clinical impact of implementing the Kidney Failure Risk Equation (KFRE) for vascular access referral.

Methods
A total of 16 102 nephrology-referred chronic kidney disease (CKD) patients from the Swedish Renal Registry 2008–18 were included. The KFRE was calculated repeatedly, and the timing was identified for when the KFRE risk exceeded several pre-defined thresholds and/or the estimated glomerular filtration rate was &lt;15 mL/min/1.73 m2 (eGFR15). To assess the utility of the KFRE/eGFR thresholds, cumulative incidence curves of kidney replacement therapy (KRT) or death, and decision-curve analyses were computed at 6 and 12 months, and 2 years. The potential impact of using the different thresholds was illustrated by an example from the Swedish access registry.

Results
The 12-month specificity for KRT initiation was highest for KFRE &gt;50% {94.5 [95% confidence interval (CI) 94.3–94.7]} followed by KFRE &gt;40% [90.0 (95% CI 89.7–90.3)], while sensitivity was highest for KFRE &gt;30% [79.3 (95% CI 78.2–80.3)] and eGFR &lt;15 mL/min/1.73 m2 [81.2 (95% CI 80.2–82.2)]. The 2-year positive predictive value was 71.5 (95% CI 70.2–72.8), 61.7 (95% CI 60.4–63.0) and 47.2 (95% CI 46.1–48.3) for KFRE &gt;50%, KFRE &gt;40% and eGFR &lt;15, respectively. Decision curve analyses suggested the largest net benefit for KFRE &gt;40% over 2 years and KFRE &gt;50% over 12 months when it is important to avoid the harm of possibly unnecessary surgery. In Sweden, 54% of nephrology-referred patients started hemodialysis in a central venous catheter (CVC), of whom only 5% had AV access surgery &gt;6 months before initiation. Sixty percent of the CVC patients exceeded KFRE &gt;40% a median of 0.8 years (interquartile range 0.4–1.5) before KRT initiation.

Conclusions
The utility of using KFRE &gt;40% and KFRE &gt;50% is higher compared with the more traditionally used eGFR threshold &lt;15 mL/min/1.73 m2 for vascular access planning.
Low-CO2-inducible bestrophins outside the pyrenoid sustain high photosynthetic efficacy in diatoms
Authors: Nigishi Minori , Shimakawa Ginga , Yamagishi Kansei , Amano Ryosuke , Ito Shun , Tsuji Yoshinori , Nagasato Chikako , Matsuda Yusuke 
Published: March 2024

Abstract
Anion transporters sustain a variety of physiological states in cells. Bestrophins (BSTs) belong to a Cl− and/or HCO3− transporter family conserved in bacteria, animals, algae, and plants. Recently, putative BSTs were found in the green alga Chlamydomonas reinhardtii, where they are upregulated under low CO2 (LC) conditions and play an essential role in the CO2-concentrating mechanism (CCM). The putative BST orthologs are also conserved in diatoms, secondary endosymbiotic algae harboring red-type plastids, but their physiological functions are unknown. Here, we characterized the subcellular localization and expression profile of BSTs in the marine diatoms Phaeodactylum tricornutum (PtBST1 to 4) and Thalassiosira pseudonana (TpBST1 and 2). PtBST1, PtBST2, and PtBST4 were localized at the stroma thylakoid membrane outside of the pyrenoid, and PtBST3 was localized in the pyrenoid. Contrarily, TpBST1 and TpBST2 were both localized in the pyrenoid. These BST proteins accumulated in cells grown in LC but not in 1% CO2 (high CO2 [HC]). To assess the physiological functions, we generated knockout mutants for the PtBST1 gene by genome editing. The lack of PtBST1 decreased photosynthetic affinity for dissolved inorganic carbon to the level comparable with the HC-grown wild type. Furthermore, non-photochemical quenching in LC-grown cells was 1.5 to 2.0 times higher in the mutants than in the wild type. These data suggest that HCO3− transport at the stroma thylakoid membranes by PtBST1 is a critical part of the CO2-evolving machinery of the pyrenoid in the fully induced CCM and that PtBST1 may modulate photoprotection under CO2-limited environments in P. tricornutum.
Dialogues Across Time: Perspectives on Historical and Contemporary Democratization
Authors: Golden Miriam A 
Published: March 2024

Abstract
This review article leverages Isabela Mares’ Protecting the Ballot: How First-Wave Democracies Ended Electoral Corruption as a jumping off point to consider how to construct a dialogue between scholars of contemporary electoral malfeasance and historical political economists. It makes two main points. First, because both scholars of history and of the contemporary world are usually engaged in mixed-method case study research, both grapple with issues of case generalizability and external validity. This produces a naturally shared research agenda, although one that has largely gone unrecognized. Generalizability would be improved if both groups mapped their cases onto larger distributions of the phenomenon of interest. Second, the very substantial differences between party systems of first-wave and recent democratizers suggest that political elites will support reforms aimed at improving election integrity differently across the two periods. Contemporary electoral competition is unlikely to naturally give rise to the emergence of programmatic politics, instead locking parties into clientelism and various types of election malfeasance. I discuss what might be required for politicians today to support reforms aimed at curbing election malfeasance, and when the shift to programmatic politics becomes in the political interests of elected officials.
A comparison of two obesity-related hypoventilation disorders: Impact on sleep, quality of life and neurocognitive outcomes and the effects of positive airway pressure therapy
Authors: Zheng Yizhong , Yee Brendon J , Wong Keith , Grunstein Ronald R , Piper Amanda J 
Published: March 2024

Abstract

Study Objectives
Symptom impact and neurocognitive function have not been previously compared between patients with obesity-associated hypoventilation disorders (obesity hypoventilation syndrome [OHS]) and hypoventilation in the setting of obesity and obstructive airways disease (OHAD). The aim of this study is to compare baseline sleep-related symptoms, health-related quality of life, and neurocognitive function between OHS and OHAD and the impact of PAP therapy on these outcomes.

Methods
Epworth Sleepiness Scale (ESS), Pittsburgh Sleepiness Quality Index (PSQI), SF36, and various neurocognitive tests, in addition to anthropometric, polysomnography, lung function, and blood gas data from participants with OHS and participants with OHAD, were included in the analysis. These data were originally collected in their respective randomized clinical trials, comparing the efficacy of different PAP modes (bilevel PAP vs. CPAP) in resolving hypercapnia. Between groups (OHS vs OHAD), pre- and post-treatment (with 3 months of positive airway pressure) comparisons were made using linear mixed modeling.

Results
45 OHS participants (mean age 51 years old, 33% female, BMI 52 kg/m2, FER 0.81, PaCO2 54 mmHg, AHI 87/h) and 32 OHAD participants (mean age 61years old, 31% female, BMI 43kg/m2, FER 0.60, PaCO2 54 mmHg, AHI 59/h) were included in the analysis. Both OHS and OHAD had similar baseline ESS (14(5.6) vs. 12(5.4)), Global PSQI (10(3.2) vs. 11(4.8)), SF36 and neurocognitive test performances (other than OHAD had lower digit symbol substitution test performance). Treatment with PAP therapy resulted in similar ESS, Global PSQI, and SF36 improvements in both groups. Neurocognitive performance did not significantly improve after PAP therapy in either group.

Conclusions
The symptom impact between two separate hypoventilation disorders (OHS and OHAD), in terms of sleepiness, sleep quality, quality of life, and cognitive function, were similar. OHS and OHAD had similar treatment responses in these parameters after 3 months of PAP therapy.
Nocturnal ventilatory support in OHS.
The Use and Impact of Antibiotics in Plant Agriculture: A Review
Authors: Batuman Ozgur , Britt-Ugartemendia Kellee , Kunwar Sanju , Yilmaz Salih , Fessler Lauren , Redondo Ana , Chumachenko Kseniya , Chakravarty Shourish , Wade Tara 
Published: March 2024

Growers have depended on the specificity and efficacy of streptomycin and oxytetracycline as a part of their plant disease arsenal since the middle of the 20th century. With climate change intensifying plant bacterial epidemics, the established success of these antibiotics remains threatened. Our strong reliance on certain antibiotics for devastating diseases eventually gave way to resistance development. Although antibiotics in plant agriculture equal to less than 0.5% of overall antibiotic use in the United States, it is still imperative for humans to continue to monitor usage, environmental residues, and resistance in bacterial populations. This review provides an overview of the history and use, resistance and mitigation, regulation, environmental impact, and economics of antibiotics in plant agriculture. Bacterial issues, such as the ongoing Huanglongbing (citrus greening) epidemic in Florida citrus production, may need antibiotics for adequate control. Therefore, preserving the efficacy of our current antibiotics by utilizing more targeted application methods, such as trunk injection, should be a major focus.[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .