bluuebunny/crossref_metadata_2025_split huggingface dataset:
High resistance barrier and prophylactic protection in preclinical models of SARS-CoV-2 with two siRNA combination
Authors: Anglero-Rodriguez Yesseinia I , Lempp Florian A , Subramanian Megha , McIninch James , Schlegel Mark K , Bohan Dana , Wong Emily , Brown Christopher R , Foster Donald J , Castoreno Adam B , Nguyen Tuyen , Cuffe Dara , Montiel-Ruiz Martin , Kaiser Hannah , Sahakyan Anna , Spreafico Roberto , Morskaya Svetlana Shulga , Barry Joseph D , Berman Daniel , Zhang Ligang , Lefebvre Stephanie , Kasper Anne , Racie Timothy , Weddle Diann , Mobley Melissa , Wassarman Kelly , Bisbe Anna , Zlatev Ivan , Rogers Arlin , Nechev Lubomir , Dybowski Joseph , Chong Saeho , Nair Jayaprakash , Simon Amy , Sloan Kevin , Hwang Seungmin , Virgin Herbert W , Fitzgerald Kevin , Maier Martin A , Hinkle Gregory , Hebner Christy M , Akinc Akin , Jadhav Vasant 
Published: December 2024

Abstract
RNA interference is a natural antiviral mechanism that could be harnessed to combat SARS-CoV-2 infection by targeting and destroying the viral RNA. We identified potent lipophilic small interfering RNA (siRNA) conjugates targeting highly conserved regions of SARS-CoV-2 outside of the spike-encoding region capable of achieving ≥3-log viral reduction. Serial passaging studies demonstrated that a two-siRNA combination prevented development of resistance compared to a single siRNA approach. Viral resistance to single siRNA treatment occurred due to emergence of point mutations at critical positions required for siRNA-mediated target binding and cleavage, which led to a loss of siRNA efficacy. With a two-siRNA combination, emergence of mutations within the siRNA binding site was abolished. When delivered intranasally, two-siRNA combination protected Syrian hamsters from weight loss and lung pathology by viral infection upon prophylactic administration but not following onset of infection. Together, the data support potential utility of RNAi as a prophylactic approach with high resistance barrier to counteract SARS-CoV-2 emergent variants and complement vaccination. Most importantly, given that the siRNAs can be rapidly developed from a new pathogen sequence, this strategy has implications as a new type of preventive medicine that may protect against future coronavirus pandemics.
Genome-wide mapping of spontaneous DNA replication error-hotspots using mismatch repair proteins in rapidly proliferating Escherichia coli
Authors: Hasenauer Flavia C , Barreto Hugo C , Lotton Chantal , Matic Ivan 
Published: December 2024

Abstract
Fidelity of DNA replication is crucial for the accurate transmission of genetic information across generations, yet errors still occur despite multiple control mechanisms. This study investigated the factors influencing spontaneous replication errors across the Escherichia coli genome. We detected errors using the MutS and MutL mismatch repair proteins in rapidly proliferating mutH-deficient cells, where errors can be detected but not corrected. Our findings reveal that replication error hotspots are non-randomly distributed along the chromosome and are enriched in sequences with distinct features: lower thermal stability facilitating DNA strand separation, mononucleotide repeats prone to DNA polymerase slippage and sequences prone to forming secondary structures like cruciforms and G4 structures, which increase likelihood of DNA polymerase stalling. These hotspots showed enrichment for binding sites of nucleoid-associated proteins, RpoB and GyrA, as well as highly expressed genes, and depletion of GATC sequence. Finally, the enrichment of single-stranded DNA stretches in the hotspot regions establishes a nexus between the formation of secondary structures, transcriptional activity and replication stress. In conclusion, this study provides a comprehensive genome-wide map of replication error hotspots, offering a holistic perspective on the intricate interplay between various mechanisms that can compromise the faithful transmission of genetic information.
The binding of RbgA to a critical 50S assembly intermediate facilitates YphC function in bacterial ribosomal assembly
Authors: Arpin Dominic , Palacios Armando , Basu Kaustuv , Ortega Joaquin 
Published: December 2024

Abstract
The intricate process of 50S ribosomal subunit assembly in Bacillus subtilis involves multiple parallel pathways converging into a crucial intermediate known as the 45S particle. RbgA and YphC, play pivotal roles in completing the maturation of the functional sites in the 45S particle. In this work, we found that RbgA and YphC can independently bind the 45S particle with high affinity, but when RbgA binds first to the particle, it significantly increases the binding affinity of YphC. Using cryo-electron microscopy, we determined that the changes exerted by RbgA and YphC when binding independently closely resemble those observed when the two factors bind to the 45S particle simultaneously. However, the structural analysis revealed that RbgA binding causes a conformational change that uncovers the binding site for YphC, thus increasing its binding affinity. We concluded that the functional interplay between RbgA and YphC primarily revolves around one factor promoting the binding of the other, rather than the binding of the two factors inducing entirely new conformational changes compared with those induced by the factors individually. These results highlight the synergic mechanism between two essential assembly factors, underscoring the intricate mechanism bacteria use to maximize the efficiency of the ribosome assembly process.
In silico and in vivo analyses of a novel variant in MYO6 identified in a family with postlingual non-syndromic hearing loss from Argentina
Authors: Buonfiglio Paula I , Bruque Carlos D , Salatino Lucía , Lotersztein Vanesa , Pace Mariela , Grinberg Sofia , Elgoyhen Ana B , Plazas Paola V , Dalamón Viviana 
Published: December 2024

Abstract
Hereditary hearing loss stands as the most prevalent sensory disorder, with over 124 non-syndromic genes and approximately 400 syndromic forms of deafness identified in humans. The clinical presentation of these conditions spans a spectrum, ranging from mild to profound hearing loss. The aim of this study was to identify the genetic cause of hearing loss in a family and functionally validate a novel variant identified in the MYO6 gene. After Whole Exome Sequencing analysis, the variant c.2775G&gt;C p.Arg925Ser in MYO6 was detected in a family with postlingual non-syndromic hearing loss. By protein modeling a change in the electrostatic charge of the single alpha helix domain surface was revealed. Through a knockdown phenotype rescue assay in zebrafish, the detrimental effects of the identified variant on the auditory system was determined. These findings underscore the significance of a comprehensive approach, integrating both in silico and in vivo strategies, to ascertain the pathogenicity of this candidate variant. Such an approach has demonstrated its effectiveness in achieving an accurate genetic diagnosis and in promoting a more profound comprehension of the mechanisms that underlie the pathophysiology of hearing.
Presentation, management, and outcomes of central nervous system metastases in Africa: Systematic review and meta-analysis
Authors: O’Leary Sean , Yevudza W Elorm , Odiase Peace , Haider Muhammad Ammar , Newsome-Cuby Takara , Okikioluwa Odesanya , Darko Kwadwo , Weiss Hannah , Barrie Umaru , Banson Mabel , Totimeh Teddy 
Published: December 2024

Abstract

Background
Central nervous system (CNS) metastases are a significant health challenge, particularly in Africa. This study evaluates the preclinical characteristics, primary causes, management strategies, and outcomes of CNS metastases in Africa.

Methods
A systematic review of the literature was conducted using PubMed, Google Scholar, and Web of Science following PRISMA guidelines to identify studies on CNS metastases in Africa.

Results
Thirty-one articles were reviewed, including 28 retrospective studies and 3 case reports. The retrospective studies comprised 12 552 patients, with 681 (5.42%) diagnosed with CNS metastases. Nigeria reported the highest number of cases (323), followed by Tunisia (180). The mean patient age was 48.20 years (range: 44.48-51.93), with a higher proportion in women (69.97%, 95% confidence interval [CI]: 54.59-85.35). Common symptoms were headaches (44.87%, 95% CI: 20.76-68.97) and motor deficits (21.39%, 95% CI: 6.40-36.38). Diagnostic tools included MRI (38.27%, 95% CI: 18.08-58.47) and CT (51.28%, 95% CI: 29.13-73.42). The most common primary tumor sites were breast (41.33%, 95% CI: 24.87-57.79) and lung (14.85%, 95% CI: 4.90-24.79). Treatment strategies involved surgery (62.01%, 95% CI: 33.01-91.01), radiotherapy (68.97%, 95% CI: 41.31-96.63), and chemotherapy (60.72%, 95% CI: 32.95-88.50). Outcomes included improved disease status in 34.99% (95% CI: 13.92-56.07), mortality in 44.88% (95% CI: 20.88-68.89), and loss to follow-up in 1.83% (95% CI: 0-3.72).

Conclusion
CNS metastases in Africa show a higher proportion in women, with breast and lung cancers as the primary sources. Improved diagnostic and treatment strategies are essential to better patient outcomes.
Diagnostic Accuracy of Lung and Abdominal Ultrasound for Tuberculosis in a German Multicenter Cohort of Patients With Presumed Tuberculosis Disease
Authors: Weber Stefan Fabian , Wolf Peter , Wetzstein Nils , Küpper-Tetzel Claus , Vehreschild Maria , Suárez Isabelle , Rybniker Jan , Klingmüller Angela , Weber Tim , Güttlein Maximilian , Tobian Frank , Koeppel Lisa , Beck Julia Selena , Wolf Rebecca , Manten Katharina , Zimmermann Stefan , Christopher Devasahayam Jesudas , Herth Felix , Bélard Sabine , Denkinger Claudia M ,   For the ALL POCUS TB Germany Study group, Ruby Lisa C , Gaeddert Mary , Weise Michael , Eichinger Monika , Blöck Benjamin , Sattaf Fabian , Prey Anna-Lia , Drummer Alena , Rauschning Dominic , Ludwig-Bettin Daniel , Pracht Elisa 
Published: December 2024

Abstract

Background
There is limited evidence on point-of-care ultrasound for tuberculosis (TB), but studies suggest high sensitivity, especially for lung ultrasound (LUS). However, insufficient data are available on specificity of the examination and its generalizability to a broader patient population.

Aims
Our study aimed to establish accuracy for lung, chest, and abdominal ultrasound, individually and in combination, for TB diagnosis.

Methods
We conducted a prospective diagnostic accuracy study among consecutive adult out- and inpatients with probable TB in three German referral hospitals. We applied a comprehensive standardized ultrasound protocol. TB diagnosis was established by a microbiological reference standard including polymerase chain reaction and culture.

Results
A total of 102 participants originating from 30 different countries were enrolled. HIV prevalence was 7/99 (7%) and 73/102 (72%) had confirmed TB. TB was limited to the lungs in 15/34 (44%) of refugees and 27/39 (69%) in nonrefugees. Focused assessment with sonography for HIV-associated tuberculosis had a sensitivity of 40% (95% confidence interval [CI], 30–52) and specificity of 55% (95% CI, 38–72). Additional findings, such as small subpleural consolidations on LUS had a high sensitivity (88%; 95% CI, 78–93), but a low specificity (17%; 95% CI, 8–35). Larger consolidations in the lung apices had a sensitivity of 19% (95% CI, 12–30) and a specificity of 97% (95% CI, 83–100).

Conclusions
Our study establishes the first data on LUS performance against a comprehensive reference standard. Overall, our data suggest that ultrasound does not meet the requirements for triage but previously described and novel ultrasound targets in combination could aid in the clinical decision making.
Registry: DRKS00026636
Efficient in situ epitope tagging of rice genes by nuclease-mediated prime editing
Authors: Li Xueqi , Zhang Sujie , Wang Chenyang , Ren Bin , Yan Fang , Li Shaofang , Spetz Carl , Huang Jinguang , Zhou Xueping , Zhou Huanbin 
Published: December 2024

Abstract
In situ epitope tagging is crucial for probing gene expression, protein localization, and the dynamics of protein interactions within their natural cellular context. However, the practical application of this technique in plants presents considerable hurdles. Here, we comprehensively explored the potential of the CRISPR/Cas nuclease-mediated prime editing and different DNA repair pathways in epitope tagging of endogenous rice (Oryza sativa) genes. We found that a SpCas9 nuclease/microhomology-mediated end joining (MMEJ)-based prime editing (PE) strategy (termed NM-PE) facilitates more straightforward and efficient gene tagging compared to the conventional and other derivative PE methods. Furthermore, the PAM-flexible SpRY and ScCas9 nucleases-based prime editors have been engineered and implemented for the tagging of endogenous genes with diverse epitopes, significantly broadening the applicability of NM-PE in rice. Moreover, NM-PE has been successfully adopted in simultaneous tagging of the MAP kinase (MPK) genes OsMPK1 and OsMPK13 in rice plants with c-Myc and HA tags, respectively. Taken together, our results indicate great potential of the NM-PE toolkit in the targeted gene tagging for Rice Protein Tagging Project, gene function study and genetic improvement.
Arabidopsis RNA–binding proteins interact with viral structural proteins and modify turnip yellows virus accumulation
Authors: Kiervel Déborah , Boissinot Sylvaine , Piccini Céline , Scheidecker Danile , Villeroy Claire , Gilmer David , Brault Véronique , Ziegler-Graff Véronique 
Published: December 2024

Abstract
As obligate intracellular parasites, viruses depend on host proteins and pathways for their multiplication. Among these host factors, specific nuclear proteins are involved in the life cycle of some cytoplasmic replicating RNA viruses, although their role in the viral cycle remains largely unknown. The polerovirus turnip yellows virus (TuYV) encodes a major coat protein (CP) and a 74 kDa protein known as the readthrough (RT) protein. The icosahedral viral capsid is composed of the CP and a minor component RT*, arising from a C-terminal cleavage of the full-length RT. In this study, we identified Arabidopsis (Arabidopsis thaliana) ALY family proteins as interacting partners of TuYV structural proteins using yeast 2-hybrid assays and co-immunoprecipitations in planta. ALY proteins are adaptor proteins of the THO-TREX-1 complex essential to the nuclear export of mature messenger RNAs (mRNAs). Although all 4 ALY proteins colocalized with the CP and the RT protein in the nucleus upon co-expression in agro-infiltrated Nicotiana benthamiana leaves, only the CP remained nuclear and colocalized with ALY proteins in TuYV-infected cells, suggesting that the CP is an essential partner of ALY proteins. Importantly, TuYV-infected A. thaliana 4xaly knock-out mutants showed a significant increase in viral accumulation, indicating that TuYV infection is affected by an unknown ALY-mediated antiviral defense mechanism or impairs the cellular mRNA export pathway to favor viral RNA translation. This finding underpins the crucial role played by nuclear factors in the life cycle of cytoplasmic RNA viruses.
Update on the structure and regulated biosynthesis of the apoplastic polymers cutin and suberin
Authors: Kosma Dylan K , Graça José , Molina Isabel 
Published: December 2024

Abstract
The plant lipid polymers cutin and suberin play a critical role in many aspects of plant growth, development, and physiology. The mechanisms of cutin and suberin biosynthesis are relatively well understood thanks to just over 2 decades of work with primarily Arabidopsis (Arabidopsis thaliana) mutants. Recent advances in our understanding of cutin and suberin structure have arisen through the application of novel chemistries targeted at quantitative comprehension of intermolecular linkages, isolating intact suberins and cutins, and the application of advanced analytical techniques. The advent of high-throughput transcription factor binding assays and next-generation sequencing has facilitated the discovery of numerous cutin and suberin-regulating transcription factors and their gene promoter targets. Herein we provide an overview of aspects of cutin and suberin structure, biosynthesis, and transcriptional regulation of their synthesis highlighting recent developments in our understanding of these facets of cutin and suberin biology. We further identify outstanding questions in these respective areas and provide perspectives on how to advance the field to address these questions.
Chronic pain education: past, present, and future of psychedelics for the management of chronic pain
Authors: Robinson Christopher L , Solanki Pawan K , Snyder Sean , Amir Adam , Barreveld Antje , Mather Rory Vu , Cerda Ivo H , Motoc Michael , Chopra Harman , Yong Robert Jason , Castellanos Joel , Furnish Timothy , Kaye Alan D , Orhurhu Vwaire , Emerick Trent 
Published: December 2024

Abstract
Curricula involving psychedelic education are not a traditional part of most medical training programs. With an increase in awareness of psychedelics, research studies involving psychedelics, and prevalence of non-prescribed use, it is more important than ever for physicians and clinicians to understand the mechanisms, interactions, and potential side effects of this class of substances.
How do roses build failure-resistant anchoring tools?
Authors: Levavi Liat , Bar-On Benny 
Published: December 2024

Abstract
Rose prickles are small-scale, plant-based anchoring tools of multifunctional biomechanical roles, combining physical defense against herbivores and growth support on surrounding objects. By employing multiscale structural observations, nanomechanical characterizations, and finite-element simulations, we unveil that the dog rose (Rosa canina Linnaeus) prickle incorporates structural–mechanical modifications at different length scales, resulting in macroscopic stress-locking effects that provide the prickle extreme damage-resistant capabilities and secure its functional form against catastrophic failures. These functional design strategies, unique to plant-based biomechanical tools, may promote futuristic micro-engineered anchoring platforms for micro-robotics locomotion, biomedical microinjection, and micromechanical systems.
Half-Integer Random Resonance Compensation for Further Beam Power Ramp-up in the 3-GeV Rapid Cycling Synchrotron of the Japan Proton Accelerator Research Complex
Authors: Kojima Kunihiro , Harada Hiroyuki , Tamura Fumihiko , Okita Hidefumi , Chimura Motoki , Saha Pranab Kumar 
Published: December 2024

Abstract
A comprehensive study on random resonances was conducted to mitigate beam losses and ensure sufficient tunability of the operating point for further beam power ramp-up in the 3-GeV rapid cycling synchrotron of the Japan Proton Accelerator Research Complex. Low-intensity beam studies revealed considerable excitation of the half-integer random resonance. This half-integer random resonance was successfully compensated for using trim quadrupole magnets without exciting other higher-order resonances. By implementing a conventional theoretical procedure based on resonance driving terms, we identified the leakage field from extraction magnets as the primary source of the error field driving the random resonance. High-intensity beam studies confirmed that our resonance compensation approach substantially mitigated beam loss in higher-tune regions, making it highly effective in improving operating point tunability.
Costs of Financing U.S. Federal Debt Under a Gold Standard: 1791-1933
Authors: Payne Jonathan , Szőke Bálint , Hall George , Sargent Thomas J 
Published: December 2024

Abstract
From a new data set, we infer time series of term structures of yields on U.S. federal bonds during the gold standard era from 1791–1933 and use our estimates to reassess historical narratives about how the United States expanded its fiscal capacity. We show that U.S. debt carried a default risk premium until the end of the nineteenth century, when it started being priced as an alternative safe asset to U.K. debt. During the Civil War, investors expected the United States to return to a gold standard so the federal government was able to borrow without facing denomination risk. After the introduction of the National Banking System, the slope of the yield curve switched from down to up and the premium on U.S. debt with maturity less than one year disappeared.
Artificial intelligence software for detecting unsuspected lung cancer on chest radiographs in an asymptomatic population
Authors: Kim Taehee , Shin Heejun , Song Yong Sub , Lee Jong Hyuk , Kim Hyungjin , Shin Dongmyung 
Published: December 2024

Abstract

Background
Detecting clinically unsuspected lung cancer on chest radiographs is challenging. Artificial intelligence (AI) software that performs comparably to radiologists may serve as a useful tool.

Purpose
To evaluate the lung cancer detection performance of a commercially available AI software and to that of humans in a healthy population.

Materials and Methods
This retrospective study used chest radiographs from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial in the United States between November 1993 and July 2001 with pathological cancer diagnosis follow-up to 2009 (median 11.3 years). The software's predictions were compared to the PLCO radiologists' reads. A reader study was performed with a subset comparing the software to 3 experienced radiologists.

Results
The analysis included 24 370 individuals (mean age 62.6±5.4; median age 62; cancer rate 2%), with 213 individuals (mean age 63.6±5.5; median age 63; cancer rate 46%) for the reader study. AI achieved higher specificity (0.910 for AI vs. 0.803 for radiologists, P &lt; .001), positive predictive value (0.054 for AI vs. 0.032 for radiologists, P &lt; .001), but lower sensitivity (0.326 for AI vs. 0.412 for radiologists, P = .001) than the PLCO radiologists. When we calibrated the sensitivity of AI to match it with the PLCO radiologists, AI had higher specificity (0.815 for AI vs. 0.803 for radiologists, P &lt; .001). In the reader study, AI achieved higher sensitivity than readers 1 and 3 (0.608 for AI vs. 0.588 for reader 1, P = .789 vs. 0.588 for reader 3, P = .803) but lower specificity than reader 1 (0.888 for AI vs. 0.905 for reader 1, P = .814). Compared to reader 2, AI showed higher specificity (0.888 for AI vs. 0.819 for reader 2, P = .153) but lower sensitivity (0.888 for AI vs. 0.905 for reader 1, P = .814).

Conclusion
AI detects lung cancer on chest radiographs among asymptomatic individuals with comparable performance to experienced radiologists.