bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutagenesis and functional analysis of the varicella-zoster virus portal protein
Authors: Visalli Melissa A. , Nale Lovett Dakota J. , Kornfeind Ellyn M. , Herrington Haley , Xiao Yi Tian , Lee Daniel , Plair Patience , Wilder S. Garrett , Garza Bret K. , Young Ashton , Visalli Robert J. 
Published: March 2024

ABSTRACT

Herpesviruses replicate by cleaving concatemeric dsDNA into single genomic units that are packaged through an oligomeric portal present in preformed procapsids. In contrast to what is known about phage portal proteins, details concerning herpesvirus portal structure and function are not as well understood. A panel of 65 Varicella-Zoster virus (VZV) recombinant portal proteins with five amino acid in-frame insertions were generated by random transposon mutagenesis of the VZV portal gene, ORF54. Subsequently, 65 VZV
LUC
recombinant viruses (TNs) were generated via recombineering. Insertions were mapped to predicted portal domains (clip, wing, stem, wall, crown, and β-hairpin tunnel-loop) and recombinant viruses were characterized for plaque morphology, replication kinetics, pORF54 expression, and classified based on replication in non-complementing (ARPE19) or complementing (ARPE54C50) cell lines. The N- and C-termini were tolerant to insertion mutagenesis, as were certain clip sub-domains. The majority of mutants mapping to the wing, wall, β-hairpin tunnel loop, and stem domains were lethal. Elimination of the predicted ORF54 start codon revealed that the first 40 amino acids of the N-terminus were not required for viral replication. Stop codon insertions in the C-terminus showed that the last 100 amino acids were not required for viral replication. Lastly, a putative protease cleavage site was identified in the C-terminus of pORF54. Cleavage was likely orchestrated by a viral protease; however, processing was not required for DNA encapsidation and viral replication. The panel of recombinants should prove valuable in future studies to dissect mammalian portal structure and function.

IMPORTANCE
Though nucleoside analogs and a live-attenuated vaccine are currently available to treat some human herpesvirus family members, alternate methods of combating herpesvirus infection could include blocking viral replication at the DNA encapsidation stage. The approval of Letermovir provided proof of concept regarding the use of encapsidation inhibitors to treat herpesvirus infections in the clinic. We propose that small-molecule compounds could be employed to interrupt portal oligomerization, assembly into the capsid vertex, or affect portal function/dynamics. Targeting portal at any of these steps would result in disruption of viral DNA packaging and a decrease or absence of mature infectious herpesvirus particles. The oligomeric portals of herpesviruses are structurally conserved, and therefore, it may be possible to find a single compound capable of targeting portals from one or more of the herpesvirus subfamilies. Drug candidates from such a series would be effective against viruses resistant to the currently available antivirals.
Replication-independent change in the frequencies of distinct genome segments of a multipartite virus during its transit within aphid vectors
Authors: Villegas Mathilde , Yvon Michel , Le Blaye Sophie , Mathieu Laura , Blanc Stéphane , Zeddam Jean-Louis 
Published: March 2024

ABSTRACT

Multipartite viruses exhibit a fragmented genome composed of several nucleic acid segments individually packaged in distinct viral particles. The genome of all species of the genus
Nanovirus
holds eight segments, which accumulate at a very specific and reproducible relative frequency in the host plant tissues. In a given host species, the steady state pattern of the segments’ relative frequencies is designated the genome formula and is thought to have an adaptive function through the modulation of gene expression. Nanoviruses are aphid-transmitted circulative non-propagative viruses, meaning that the virus particles are internalized into the midgut cells, transferred to the hemolymph, and then to the saliva, with no replication during this transit. Unexpectedly, a previous study on the faba bean necrotic stunt virus revealed that the genome formula changes after ingestion by aphids. We investigate here the possible mechanism inducing this change by first comparing the relative segment frequencies in different compartments of the aphid. We show that changes occur both in the midgut lumen and in the secreted saliva but not in the gut, salivary gland, or hemolymph. We further establish that the viral particles differentially resist physicochemical variations, in particular pH, ionic strength, and/or type of salt, depending on the encapsidated segment. We thus propose that the replication-independent genome formula changes within aphids are not adaptive, contrary to changes occurring in plants, and most likely reflect a fortuitous differential degradation of virus particles containing distinct segments when passing into extra-cellular media such as gastric fluid or saliva.

IMPORTANCE
The genome of multipartite viruses is composed of several segments individually packaged into distinct viral particles. Each segment accumulates at a specific frequency that depends on the host plant species and regulates gene expression. Intriguingly, the relative frequencies of the genome segments also change when the octopartite faba bean necrotic stunt virus (FBNSV) is ingested by aphid vectors, despite the present view that this virus travels through the aphid gut and salivary glands without replicating. By monitoring the genomic composition of FBNSV populations during the transit in aphids, we demonstrate here that the changes take place extracellularly in the gut lumen and in the saliva. We further show that physicochemical factors induce differential degradation of viral particles depending on the encapsidated segment. We propose that the replication-independent changes within the insect vector are not adaptive and result from the differential stability of virus particles containing distinct segments according to environmental parameters.
The Zaozigou orogenic gold-antimony deposit, West Qinling Orogen, China: Structural controls on multiple mineralization events
Authors: Qiu Kun-Feng , Deng Jun , Yu Hao-Cheng , Rasbury Troy , Tang Yan-Wen , Zhu Rui , Zhang Peng-Cong , Goldfarb Richard 
Published: March 2024

Abstract
Orogenic gold deposits are generally thought to represent one perhaps protracted event. However, recent research on orogenic gold deposits increasingly offers evidence for some deposits forming through multiple and clearly discreet hydrothermal episodes. The giant Zaozigou orogenic Au-Sb deposit in the Triassic to Cretaceous West Qinling Orogen, central China, includes both steeply dipping and gently dipping orebodies. The two distinct mineralization styles provide a valuable setting for investigating a multiple mineralization model by integrating structural analysis within a robust geochronological framework. Through fieldwork and geochronology, we define a progression of major tectonic events in the area of the Zaozigou deposit. The deposit is hosted within a well-bedded sequence of Early Triassic metasedimentary rocks of the South Qinling Terrane. Pre-mineralization E-W shortening (D1) during subduction of the Mianlue oceanic slab include folding with resulting axial planes striking N-S, emplacement of Triassic ENE-striking and WNW-striking dacite dikes accompanied by Middle Triassic greenschist facies metamorphism. Late Triassic gold-stibnite quartz vein and disseminated mineralization formed along ENE-striking and steeply dipping D2 brittle to ductile sinistral faults. Their orientations suggest a link to the regional NNE-SSW maximum principal stress coinciding with transpression caused by the Late Triassic collision between the South China Block and South Qinling Terrane. Overprinting Early Cretaceous quartz-stibnite veins developed along gently dipping (20° to 40°) brittle D3 normal fault zones, which exhibit a NE-SW minimum principal stress. This younger deformation event is interpreted to be related to the Early Cretaceous tectonic transition from shortening to extension of the West Qinling Orogen. Therefore, the Zaozigou deposit reveals a model of multiple orogenic gold mineralizing events, with migration of hydrothermal fluids during discrete deformation episodes and the resulting formation of a single composite deposit formed along overprinting structures at separate times of orogenesis.
Ice? Salt? Pressure? Sediment deformation structures as evidence of late-stage shallow groundwater in Gale crater, Mars
Authors: Banham Steven G. , Roberts Amelie L. , Gupta Sanjeev , Davis Joel M. , Thompson Lucy M. , Rubin David M. , Paar Gerhard , Siebach Kirsten L. , Dietrich William E. , Fraeman Abigail A. , Vasavada Ashwin R. 
Published: March 2024

Abstract
Persistence of near-surface water during the late evolution of Gale crater, Mars, would have been fundamental for maintaining a habitable environment. Sedimentation in aqueous conditions is evident during the early stages of crater infilling, where accumulation of lower Mount Sharp group strata is characterized by fluviolacustrine sedimentary rocks. The basal unit of the Siccar Point group—the Stimson formation—which unconformably overlies the Mount Sharp group and represents conditions postdating the exhumation of Aeolis Mons, is characterized by accumulation of aeolian strata under arid conditions. Water was largely absent near the surface during its deposition. At the Feòrachas outcrop, discovery of soft sediment deformation structures in aeolian Stimson strata challenges the notion that Gale crater was devoid of water during its later depositional phase. We identified deformed wind-rippled and vertically laminated sandstones, hosted within erosion-resistant ridges forming boxwork patterns. Broadly, these structures are diagnostic of water (as liquid or as ice) in the shallow subsurface. Comparison with Earth analogues suggests formation by subsurface fluid escape, freeze-thaw processes, or evaporite deformation. Regardless of the mechanism, these structures signify the presence of water at or near the surface much later than previously documented and may extend the habitability window in Gale crater.
Association between chronic pain and attrition: a prospective analysis of a national sample of midlife adults in the USA, 2004–2014
Authors: Liang Yunlong 
Published: March 2024

BackgroundHealth conditions of participants can significantly affect longitudinal drop-out in population-based epidemiological surveys, yet few studies have examined the association between chronic pain (CP) and follow-up attrition.MethodsThe Midlife in the United States study (MIDUS) was used to explore the longitudinal association between CP and survey attrition. CP was assessed by three measures: the presence of CP, CP interference and the number of pain sites at MIDUS 2. The types of sample attrition at MIDUS 3 encompassed several categories: complete, refusal to participate, inability to participate due to physical or mental constraints, deceased, non-working numbers, participants consistently unavailable for interviews, global refusal or withdrew from the study and not fielded. Multinomial logistic regression was employed to examine these relationships and to explore the moderation effects of sociodemographic variables and multiple chronic conditions on these associations.ResultsHigh-interference pain was associated with a 162% increased risk (RR 2.62, 95% CI 1.12 to 6.16, p=0.026) of being physically and mentally unable to participate in MIDUS 3. Individuals reporting the presence of CP (RR 0.65, 95% CI 0.45 to 0.95, p=0.028) and those with three or more CP sites (RR 0.48, 95% CI 0.27 to 0.87, p=0.016) were less likely to refuse participation in MIDUS 3. However, no further significant associations or moderating effects were identified.ConclusionPopulation-based epidemiological surveys may be susceptible to attrition bias from participants with CP, necessitating the adoption of adaptive survey methodologies.
Distribution of case volumes in surgery: an analysis of the British Spine Registry
Authors: Koh Chan Hee , Muirhead William , Khan Danyal Zaman , Layard Horsfall Hugo , Prezerakos George , Sayal Parag , Marcus Hani J 
Published: March 2024

ObjectivesTo characterize the distribution of case volumes within a surgical field.DesignAn analysis of British Spine Registry.Setting295 centers in England that conducted at least one spinal operation either within the NHS or private settings between 1 May 2016 and 27 February 2021.Participants644 surgeons.Main outcome measuresMathematical descriptions of distributions of cases among surgeons and the extent of workforce-level case-volume concentration as a surrogate marker.ResultsThere were wide variations in monthly caseloads between surgeons, ranging from 0 to average monthly high of 81.8 cases. The curves showed that 37.7% of surgeons were required to perform 80% of all spinal operations, which is substantially less than in fields outside of healthcare.With the COVID-19 pandemic, the case volumes of surgeons with the highest volumes dropped dramatically, whereas those with the lowest case numbers remained nearly unchanged. This, along with the relatively low level of case-volume concentration within spinal surgery, may indicate an inevitability of at least some level of surgical care being provided by the relatively lower volume surgeons.ConclusionsWhile there is a reasonable degree of workforce-level case volume concentration within spinal surgery, with high volume spinal surgeons providing a large proportion of care, it is not clear whether a further concentration of case volumes into those few hands is possible or desirable.
Targeting refractory/recurrent neuroblastoma and osteosarcoma with anti-CD3×anti-GD2 bispecific antibody armed T cells
Authors: Yankelevich Maxim , Thakur Archana , Modak Shakeel , Chu Roland , Taub Jeffrey , Martin Alissa , Schalk Dana , Schienshang Amy , Whitaker Sarah , Rea Katie , Lee Daniel W , Liu Qin , Shields Anthony F , Cheung Nai-Kong V , Lum Lawrence G 
Published: March 2024

BackgroundThe survival benefit observed in children with neuroblastoma (NB) and minimal residual disease who received treatment with anti-GD2 monoclonal antibodies prompted our investigation into the safety and potential clinical benefits of anti-CD3×anti-GD2 bispecific antibody (GD2Bi) armed T cells (GD2BATs). Preclinical studies demonstrated the high cytotoxicity of GD2BATs against GD2+cell lines, leading to the initiation of a phase I/II study in recurrent/refractory patients.MethodsThe 3+3 dose escalation phase I study (NCT02173093) encompassed nine evaluable patients with NB (n=5), osteosarcoma (n=3), and desmoplastic small round cell tumors (n=1). Patients received twice-weekly infusions of GD2BATs at 40, 80, or 160×106GD2BATs/kg/infusion complemented by daily interleukin-2 (300,000 IU/m2) and twice-weekly granulocyte macrophage colony-stimulating factor (250 µg/m2). The phase II segment focused on patients with NB at the dose 3 level of 160×106GD2BATs/kg/infusion.ResultsOf the 12 patients enrolled, 9 completed therapy in phase I with no dose-limiting toxicities. Mild and manageable cytokine release syndrome occurred in all patients, presenting as grade 2–3 fevers/chills, headaches, and occasional hypotension up to 72 hours after GD2BAT infusions. GD2-antibody-associated pain was minimal. Median overall survival (OS) for phase I and the limited phase II was 18.0 and 31.2 months, respectively, with a combined OS of 21.1 months. A phase I NB patient had a complete bone marrow response with overall stable disease. In phase II, 10 of 12 patients were evaluable: 1 achieved partial response, and 3 showed clinical benefit with prolonged stable disease. Over 50% of evaluable patients exhibited augmented immune responses to GD2+targets post-GD2BATs, as indicated by interferon-gamma (IFN-γ) EliSpots, Th1 cytokines, and/or chemokines.ConclusionsThis study demonstrated the safety of GD2BATs up to 160×106 cells/kg/infusion. Coupled with evidence of post-treatment endogenous immune responses, our findings support further investigation of GD2BATs in larger phase II clinical trials.
Prediction of progressive fibrosing interstitial lung disease in patients with systemic sclerosis: insight from the CRDC cohort study
Authors: Hui Min , Duan Xinwang , Zhou Jiaxin , Li Mengtao , Wang Qian , Zhao Jiuliang , Hou Yong , Xu Dong , Zeng Xiaofeng 
Published: March 2024

BackgroundThis study aims to establish a reliable prediction model of progressive fibrosing interstitial lung disease (PF-ILD) in patients with systemic sclerosis (SSc)-ILD, to achieve early risk stratification and to help better in preventing disease progression.Methods304 SSc-ILD patients with no less than three pulmonary function tests within 6–24 months were included. We collected data at baseline and compared differences between SSc patients with and without PF-ILD. Least absolute shrinkage and selection operator regularisation regression and multivariable Cox regression were used to construct the prediction model, which were presented as nomogram and forest plot.ResultsAmong the 304 patients with SSc-ILD included, 92.1% were women, with a baseline average age of 46.7 years. Based on the 28 variables preselected by comparison between SSc patients without PF-ILD group (n=150) and patients with SSc PF-ILD group (n=154), a 9-variable prediction model was constructed, including age≥50 years (HR 1.8221, p=0.001), hyperlipidemia (HR 4.0516, p<0.001), smoking history (HR 3.8130, p<0.001), diffused cutaneous SSc subtype (HR 1.9753, p<0.001), arthritis (HR 2.0008, p<0.001), shortness of breath (HR 2.0487, p=0.012), decreased serum immunoglobulin A level (HR 2.3900, p=0.002), positive anti-Scl-70 antibody (HR 1.9573, p=0.016) and usage of cyclophosphamide/mycophenolate mofetil (HR 0.4267, p<0.001). The concordance index after enhanced bootstrap resampling adjustment was 0.874, while the optimism-corrected Brier Score was 0.144 in internal validation.ConclusionThis study developed the first prediction model for PF-ILD in patients with SSc-ILD, and internal validation showed favourable accuracy and stability of the model.
Medication utilisation trends during pregnancy and factors influencing adverse pregnancy outcomes in patients with rheumatoid arthritis
Authors: Song Yeo-Jin , Cho Soo-Kyung , Jung Yu-Seon , Jung Sun-Young , Keum Jihyun , Nam Eunwoo , Sung Yoon-Kyoung , Yoo Dae Hyun 
Published: March 2024

ObjectivesWe aimed to investigate medication utilisation trends during pregnancy and identify factors associated with adverse pregnancy outcomes (APOs) in patients with rheumatoid arthritis (RA).MethodsFemale patients with RA aged 20–50 years were identified from the Korean national health insurance database between 2010 and 2020. Pregnancy episodes were divided into two groups according to pregnancy outcome: the delivery group and the APO group (abortion and stillbirth). The characteristics and medication utilisation patterns were compared between the two groups, and multivariable logistic regression analysis was conducted to identify the factors associated with APOs.ResultsA total of 5728 pregnancy episodes were included, comprising 4576 delivery episodes and 1152 APO episodes. The mean maternal age for all pregnancy episodes was 33.7 years; 33.3 years in the delivery group and 33.7 years in the APO group. Hydroxychloroquine was the most commonly used conventional synthetic disease-modifying antirheumatic drug (DMARD) during the preconception period and pregnancy in both groups. The prescription rate of all DMARDs decreased rapidly during pregnancy. In the multivariable analysis, use of methotrexate (adjusted OR (aOR): 2.14, 95% CI 1.57 to 2.92) and leflunomide (aOR: 2.68, 95% CI 1.39 to 5.15) within 3 months before conception was associated with APOs.ConclusionMethotrexate and leflunomide are associated with an increased possibility of APOs, emphasising the importance of appropriate medication adjustment when planning for pregnancy.
High-rate tests on resistive plate chambers operated with eco-friendly gas mixtures
Authors: Abbrescia M. , Aielli G. , Aly R. , Arena M. C. , Barroso M. , Benussi L. , Bianco S. , Bordon F. , Boscherini D. , Bruni A. , Buontempo S. , Busato M. , Camarri P. , Cardarelli R. , Congedo L. , De Jesus Damiao D. , De Serio M. , Di Ciaccio A. , Di Stante L. , Dupieux P. , Eysermans J. , Ferretti A. , Galati G. , Gagliardi M. , Guida R. , Iaselli G. , Joly B. , Lee K. S. , Liberti B. , Lucero Ramirez D. , Mandelli B. , Manen S. P. , Massa L. , Pastore A. , Pastori E. , Piccolo D. , Pizzimento L. , Polini A. , Proto G. , Pugliese G. , Quaglia L. , Ramos D. , Rigoletti G. , Rocchi A. , Romano M. , Samalan A. , Salvini P. , Santonico R. , Saviano G. , Simone S. , Terlizzi L. , Tytgat M. , Vercellin E. , Verzeroli M. , Zaganidis N. 
Published: March 2024

AbstractResults obtained by the RPC ECOgas@GIF++ Collaboration, using Resistive Plate Chambers operated with new, eco-friendly gas mixtures, based on tetrafluoropropene and carbon dioxide, are shown and discussed in this paper. Tests aimed to assess the performance of this kind of detectors in high-irradiation conditions, analogous to the ones foreseen for the coming years at the Large Hadron Collider experiments, were performed, and demonstrate a performance basically similar to the one obtained with the gas mixtures currently in use, based on tetrafluoroethane, which is being progressively phased out for its possible contribution to the greenhouse effect. Long term aging tests are also being carried out, with the goal to demonstrate the possibility of using these eco-friendly gas mixtures during the whole High Luminosity phase of the Large Hadron Collider.
Mass splitting and spin alignment for $$\phi $$ mesons in a magnetic field in NJL model
Authors: Sheng Xin-Li , Yang Shu-Yun , Zou Yao-Lin , Hou Defu 
Published: March 2024

AbstractBased on the Nambu–Jona–Lasinio (NJL) model, we develop a framework for calculating the spin alignment of vector mesons and applied it to study $$\phi $$
ϕ
mesons in a magnetic field. We calculate mass spectra for $$\phi $$
ϕ
mesons and observe mass splitting between the longitudinally polarized state and transversely polarized states. The $$\phi $$
ϕ
meson in a thermal equilibrium system is preferred to occupy the state with spin $$\lambda =0$$

λ
=
0

than those with spin $$\lambda =\pm 1$$

λ
=
±
1

, because the former state has a smaller energy. As a consequence, we conclude that the spin alignment will be larger than 1/3 if one measures along the direction of the magnetic field, which is qualitatively consistent with the recent STAR data. Around the critical temperature $$T_{C}=150~\hbox {MeV}$$

T
C

=
150

MeV

, the positive deviation from 1/3 is proportional to the square of the magnetic field strength, which agrees with the result from the non-relativistic coalescence model. Including the anomalous magnetic moments for quarks will modify the dynamical masses of quarks and thus affect the mass spectra and spin alignment of $$\phi $$
ϕ
mesons. The discussion of spin alignment in the NJL model may help us better understand the formation of hadron’s spin structure during the chiral phase transition.