bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 hospitalization risk after outpatient nirmatrelvir/ritonavir use, January to August 2022, North Carolina
Authors: Henderson Heather I , Wohl David A , Fischer William A , Bartelt Luther A , van Duin David , Agil Deana M , Browne Lindsay E , Li Kuo-Ping , Moy Amanda , Eron Joseph J , Napravnik Sonia 
Published: February 2024

Abstract

Background
In the USA, nirmatrelvir/ritonavir is authorized for the treatment of mild-to-moderate COVID-19 in patients at least 12 years of age, at high risk for progression to severe COVID-19.

Objectives
To estimate the impact of outpatient nirmatrelvir/ritonavir on COVID-19 hospitalization risk in a US healthcare system.

Methods
We conducted a cohort study using electronic health records among outpatients with a positive SARS-CoV-2 PCR test between January and August 2022. We evaluated the association of nirmatrelvir/ritonavir therapy with time to hospitalization by estimating adjusted HRs and assessed the impact of nirmatrelvir/ritonavir on predicted COVID-19 hospitalizations using machine-learning methods.

Results
Among 44 671 patients, 4948 (11%) received nirmatrelvir/ritonavir, and 201 (0.4%) were hospitalized within 28 days of COVID-19 diagnosis. Nirmatrelvir/ritonavir recipients were more likely to be older, white, vaccinated, have comorbidities and reside in areas with higher average socioeconomic status. The 28 day cumulative incidence of hospitalization was 0.06% (95% CI: 0.02%–0.17%) among nirmatrelvir/ritonavir recipients and 0.52% (95% CI: 0.46%–0.60%) among non-recipients. For nirmatrelvir/ritonavir versus no therapy, the age-adjusted HR was 0.08 (95% CI: 0.03–0.26); the fully adjusted HR was 0.16 (95% CI: 0.05–0.50). In the machine-learning model, the primary features reducing predicted hospitalization risk were nirmatrelvir/ritonavir, younger age, vaccination, female gender and residence in a higher socioeconomic status area.

Conclusions
COVID-19 hospitalization risk was reduced by 84% among nirmatrelvir/ritonavir recipients in a large, diverse healthcare system during the Omicron wave. These results suggest that nirmatrelvir/ritonavir remained highly effective in a setting substantially different than the original clinical trials.
Molecular structure and function of mysterin/RNF213
Authors: Morito Daisuke 
Published: February 2024

Abstract
Mysterin is a large intracellular protein harboring a RING finger ubiquitin ligase domain and is also referred to as RING finger protein 213 (RNF213). The author performed the first molecular cloning of the mysterin gene as the final step in genetic exploration of cerebrovascular moyamoya disease (MMD) and initiated the next round of exploration to understand its molecular and cellular functions. Although much remains unknown, accumulating findings suggest that mysterin functions in cells by targeting massive intracellular structures, such as lipid droplets (LDs) and various invasive pathogens. In the latter case, mysterin appears to directly surround and ubiquitylate the surface of pathogens and stimulate cell-autonomous antimicrobial reactions, such as xenophagy and inflammatory response. To date, multiple mutations causing MMD have been identified within and near the RING finger domain of mysterin; however, their functional relevance remains largely unknown. Besides the RING finger, mysterin harbors a dynein-like ATPase core and an RZ finger, another ubiquitin ligase domain unique to mysterin, while functional exploration of these domains has also just commenced. In this review, the author attempts to summarize the core findings regarding the molecular structure and function of the mysterin protein, with an emphasis on the perspective of MMD research.
Fructooligosaccharides act on the gut–bone axis to improve bone independent of Tregs and alter osteocytes in young adult C57BL/6 female mice
Authors: Islam Proapa , Ice John A , Alake Sanmi E , Adedigba Pelumi , Hatter Bethany , Robinson Kara , Clarke Stephen L , Ford Versypt Ashlee N , Ritchey Jerry , Lucas Edralin A , Smith Brenda J 
Published: February 2024

Abstract
Targeting the gut–bone axis with probiotics and prebiotics is considered as a promising strategy to reduce the risk of osteoporosis. Gut-derived short chain fatty acids (SCFA) mediate the effects of probiotics on bone via Tregs, but it is not known whether prebiotics act through a similar mechanism. We investigated how 2 different prebiotics, tart cherry (TC) and fructooligosaccharide (FOS), affect bone, and whether Tregs are required for this response. Eight-wk-old C57BL/6 female mice were fed with diets supplemented with 10% w/w TC, FOS, or a control diet (Con; AIN-93M) diet, and they received an isotype control or CD25 Ab to suppress Tregs. The FOS diet increased BMC, density, and trabecular bone volume in the vertebra (~40%) and proximal tibia (~30%) compared to the TC and control diets (Con), irrespective of CD25 treatment. Both prebiotics increased (P &lt; .01) fecal SCFAs, but the response was greater with FOS. To determine how FOS affected bone cells, we examined genes involved in osteoblast and osteoclast differentiation and activity as well as genes expressed by osteocytes. The FOS increased the expression of regulators of osteoblast differentiation (bone morphogenetic protein 2 [Bmp2], Wnt family member 10b [Wnt10b] and Osterix [Osx]) and type 1 collagen). Osteoclasts regulators were unaltered. The FOS also increased the expression of genes associated with osteocytes, including (Phex), matrix extracellular phosphoglycoprotein (Mepe), and dentin matrix acidic phosphoprotein 1 (Dmp-1). However, Sost, the gene that encodes for sclerostin was also increased by FOS as the number and density of osteocytes increased. These findings demonstrate that FOS has a greater effect on the bone mass and structure in young adult female mice than TC and that its influence on osteoblasts and osteocytes is not dependent on Tregs.
The MeerKAT 1.3 GHz Survey of the Small Magellanic Cloud
Authors: Cotton W D , Filipović M D , Camilo F , Indebetouw R , Alsaberi R Z E , Anih J O , Baker M , Bastian T S , Bojičić I , Carli E , Cavallaro F , Crawford E J , Dai S , Haberl F , Levin L , Luken K , Pennock C M , Rajabpour N , Stappers B W , van Loon J Th , Zijlstra A A , Buchner S , Geyer M , Goedhart S , Serylak M 
Published: February 2024

ABSTRACT
We present new radio continuum images and a source catalogue from the MeerKAT survey in the direction of the Small Magellanic Cloud. The observations, at a central frequency of 1.3 GHz across a bandwidth of 0.8 GHz, encompass a field of view ∼7° × 7° and result in images with resolution of 8 arcsec. The median broad-band Stokes I image Root Mean Squared noise value is ∼11 μJy beam−1. The catalogue produced from these images contains 108 330 point sources and 517 compact extended sources. We also describe a UHF (544–1088 MHz) single pointing observation. We report the detection of a new confirmed Supernova Remnant (SNR; MCSNR J0100–7211) with an X-ray magnetar at its centre and 10 new SNR candidates. This is in addition to the detection of 21 previously confirmed SNRs and two previously noted SNR candidates. Our new SNR candidates have typical surface brightness an order of magnitude below those previously known, and on the whole they are larger. The high sensitivity of the MeerKAT survey also enabled us to detect the bright end of the SMC Planetary Nebulae (PNe) sample – point-like radio emission is associated with 38 of 102 optically known PNe, of which 19 are new detections. Lastly, we present the detection of three foreground radio stars amidst 11 circularly polarized sources, and a few examples of morphologically interesting background radio galaxies from which the radio ring galaxy ESO 029–G034 may represent a new type of radio object.
A multiresolution method for modelling galaxy and massive black hole mergers
Authors: Attard Kate , Gualandris Alessia , Read Justin I , Dehnen Walter 
Published: February 2024

ABSTRACT
The coalescence of the most massive black hole (MBH) binaries releases gravitational waves (GWs) within the detectable frequency range of pulsar timing arrays (PTAs; 10−9 to 10−6 Hz). The incoherent superposition of GWs from MBH mergers, the stochastic gravitational wave background (GWB), can provide unique information on MBH parameters and the large-scale structure of the Universe. The recent evidence for a GWB reported by the PTAs opens an exciting new window on to MBHs and their host galaxies. However, the astrophysical interpretation of the GWB requires accurate estimations of MBH merger time-scales for a statistically representative sample of galaxy mergers. This is numerically challenging; a high numerical resolution is required to avoid spurious relaxation and stochastic effects, while a large number of simulations are needed to sample a cosmologically representative volume. Here, we present a new multimass modelling method to increase the central resolution of a galaxy model at a fixed particle number. We follow mergers of galaxies hosting central MBHs with the fast multiple method code griffin at two reference resolutions and with two refinement schemes. We show that both refinement schemes are effective at increasing central resolution, reducing spurious relaxation and stochastic effects. A particle number of N ≥ 106 within a radius of five times the sphere of influence of the MBHs is required to reduce numerical scatter in the binary eccentricity and the coalescence time-scale to &lt;30 per cent, a resolution that can only be reached at present with the mass refinement scheme.
A model of solar magnetic flux rope eruption initiated primarily by magnetic reconnection
Authors: Liu Qingjun , Jiang Chaowei , Bian Xinkai , Feng Xueshang , Zuo Pingbing , Wang Yi 
Published: February 2024

ABSTRACT
There is a heated debate regarding the specific roles played by ideal magnetohydrodynamic (MHD) instability and magnetic reconnection in triggering solar eruptions. In the context of a pre-existing magnetic flux rope (MFR) before an eruption, it is widely believed that an ideal MHD instability, in particular, the torus instability, is responsible for triggering and driving the eruption, while reconnection, as invoked in the wake of the erupting MFR, plays a secondary role. Here, we present a new numerical MHD model in which the eruption of a pre-existing MFR is primarily triggered and driven by reconnection. In this model, a stable MFR embedded in a strapping field is set as the initial condition. A surface converging flow is then applied at the lower boundary, pushing magnetic flux towards the main polarity inversion line. It drives a quasi-static evolution of the system, during which a current layer is built up below the MFR with decreasing thickness. Once reconnection starts in the current sheet, the eruption commences, which indicates that the reconnection plays a determining role in triggering the eruption. By further analysing the works done by the magnetic flux of the pre-existing MFR and the newly reconnected flux during the acceleration stage of the eruption, we find that the latter plays a major role in driving the eruption. Such a model may explain observed eruptions in which the pre-eruption MFR has not reached the conditions for ideal instability.
Variety of disc wind-driven explosions in massive rotating stars
Authors: Crosato Menegazzi Ludovica , Fujibayashi Sho , Takahashi Koh , Ishii Ayako 
Published: February 2024

ABSTRACT
We perform a set of two-dimensional, non-relativistic, hydrodynamics simulations for supernova-like explosions associated with stellar core collapse of rotating massive stars into a system of a black hole and a disc connected by the transfer of matter and angular momentum. Our model of the central engine also includes the contribution of the disc wind. This study is carried out using the open-source hydrodynamic code athena++, for which we implement a method to calculate self-gravity for axially symmetric density distributions. We investigate the explosion properties and the 56Ni production of a star with the zero-age main-sequence mass of $M_\mathrm{ZAMS}=20\, M_\odot$ varying some features of the wind injection. We find a large variety of explosion energy with Eexpl ranging from ∼0.049 × 1051 to ∼34 × 1051 erg and ejecta mass Mej from 0.58 to 6 M⊙, which shows a bimodal distribution in high- and low-energy branches. We demonstrate that the resulting outcome of a highly or sub-energetic explosion for a certain stellar structure is mainly determined by the competition between the ram pressure of the injected matter and that of the infalling envelope. In the nucleosynthesis analysis the 56Ni mass produced in our models goes from &lt;0.2 M⊙ in the sub-energetic explosions to 2.1 M⊙ in the highly energetic ones. These results are consistent with the observational data of stripped-envelope and high-energy SNe such as broad-lined Type Ic SNe.
Correcting 4sU induced quantification bias in nucleotide conversion RNA-seq data
Authors: Berg Kevin , Lodha Manivel , Delazer Isabel , Bartosik Karolina , Garcia Yilliam Cruz , Hennig Thomas , Wolf Elmar , Dölken Lars , Lusser Alexandra , Prusty Bhupesh K , Erhard Florian 
Published: February 2024

Abstract
Nucleoside analogues like 4-thiouridine (4sU) are used to metabolically label newly synthesized RNA. Chemical conversion of 4sU before sequencing induces T-to-C mismatches in reads sequenced from labelled RNA, allowing to obtain total and labelled RNA expression profiles from a single sequencing library. Cytotoxicity due to extended periods of labelling or high 4sU concentrations has been described, but the effects of extensive 4sU labelling on expression estimates from nucleotide conversion RNA-seq have not been studied. Here, we performed nucleotide conversion RNA-seq with escalating doses of 4sU with short-term labelling (1h) and over a progressive time course (up to 2h) in different cell lines. With high concentrations or at later time points, expression estimates were biased in an RNA half-life dependent manner. We show that bias arose by a combination of reduced mappability of reads carrying multiple conversions, and a global, unspecific underrepresentation of labelled RNA emerging during library preparation and potentially global reduction of RNA synthesis. We developed a computational tool to rescue unmappable reads, which performed favourably compared to previous read mappers, and a statistical method, which could fully remove remaining bias. All methods developed here are freely available as part of our GRAND-SLAM pipeline and grandR package.
Human NTHL1 expression and subcellular distribution determines cisplatin sensitivity in human lung epithelial and non-small cell lung cancer cells
Authors: Kar Anirban , Degtyareva Natalya P , Doetsch Paul W 
Published: February 2024

Abstract
Base excision repair is critical for maintaining genomic stability and for preventing malignant transformation. NTHL1 is a bifunctional DNA glycosylase/AP lyase that initiates repair of oxidatively damaged pyrimidines. Our recent work established that transient over-expression of NTHL1 leads to acquisition of several hallmarks of cancer in non-tumorigenic immortalized cells likely through interaction with nucleotide excision repair protein XPG. Here, we investigate how NTHL1 expression levels impact cellular sensitivity to cisplatin in non-tumorigenic immortalized cells and five non-small cell lung carcinomas cell lines. The cell line with lowest expression of NTHL1 (H522) shows the highest resistance to cisplatin indicating that decrease in NTHL1 levels may modulate resistance to crosslinking agents in NSCLC tumors. In a complementation study, overexpression of NTHL1 in H522 cell line sensitized it to cisplatin. Using NTHL1 N-terminal deletion mutants defective in nuclear localization we show that cisplatin treatment can alter NTHL1 subcellular localization possibly leading to altered protein-protein interactions and affecting cisplatin sensitivity. Experiments presented in this study reveal a previously unknown link between NTHL1 expression levels and cisplatin sensitivity of NSCLC tumor cells. These findings provide an opportunity to understand how altered NTHL1 expression levels and subcellular distribution can impact cisplatin sensitivity in NSCLC tumor cells.
An Erdős–Kac theorem for integers with dense divisors
Authors: Tenenbaum Gérald , Weingartner Andreas 
Published: February 2024

Abstract
We show that for large integers n, whose ratios of consecutive divisors are bound above by an arbitrary constant, the number of prime factors follows an approximate normal distribution, with mean $C \log_2 n$ and variance $V \log_2 n$, where $C=1/(1-{\rm e}^{-\gamma})\approx 2.280$ and V ≈ 0.414. This result is then generalized in two different directions.
Views and opinions of farmers and consumers on the trajectory of agriculture in times of military conflict: Insights from a Q-study in Germany
Authors: Noack Marlene E , Tietjens Florian , Latacz-Lohmann Uwe 
Published: February 2024

Abstract
After three decades of orienting agriculture towards ecological and social sustainability goals, the Ukraine war catapulted productivity and supply goals back onto the political agenda. Against this background, the present study aimed to establish how farmers and food consumers envision the future of agriculture. Application of Q-methodology revealed three opinion groups for both farmers and consumers. In conclusion, the Ukraine war has not significantly shifted the balance between old and new societal demands on agriculture. Old discrepancies in the views of farmers and the non-farming population persist. While among the farmers surveyed the group of those who adhere to ‘business as usual’ predominates, there is no group among the consumers surveyed who share this view. Rather, there is a majority desire among consumers for the sector to continue to be aligned with sustainability goals. Security of supply is only an issue for a small proportion of the consumers surveyed.
News from the United Nations Commission on International Trade Law (UNCITRAL): the work of the fifty-sixth commission session
Authors: Mostad-Jensen Anne 
Published: February 2024

Abstract
The United Nations Commission on International Trade Law (UNCITRAL) is the core legal body of the United Nations system in the field of international trade law. It has been carrying out its mandate to further the progressive harmonization and unification of international trade law since 1966. This article provides an overview of the fifty-sixth session of UNCITRAL and the activities of its working groups and Secretariat since its last session.
A New Multiplex TaqMan qPCR for Precise Detection and Quantification of Clavibacter michiganensis in Seeds and Plant Tissue
Authors: Brochu Anne-Sophie , Dumonceaux Tim J. , Valenzuela Miryam , Bélanger Richard , Pérez-López Edel 
Published: February 2024

Bacterial canker of tomato caused by Clavibacter michiganensis (Cm) is one of the most devastating bacterial diseases affecting the tomato industry worldwide. As the result of Cm colonization of the xylem, the susceptible host shows typical symptoms of wilt, marginal leaf necrosis, stem cankers, and ultimately plant death. However, what makes Cm an even more dangerous pathogen is its ability to infect seeds and plants without causing symptoms. Unfortunately, there are no resistant cultivars or effective chemical or biological control methods available to growers against Cm. Its control relies heavily on prevention. The implementation of a rapid and accurate detection tool is imperative to monitor the presence of Cm and prevent its spread. In this study, we developed a specific and sensitive multiplex TaqMan qPCR assay to detect Cm and distinguish it from related bacterial species that affect tomato plants. Two Cm chromosomal virulence-related genes, rhuM and tomA, were used as specific targets. The plant internal control tubulin alpha-3 was included in each of the multiplexes to improve the reliability of the assay. Specificity was evaluated with 37 bacterial strains including other Clavibacter spp. and related and unrelated bacterial pathogens from different geographic locations affecting a wide variety of hosts. Results showed that the assay is able to discriminate Cm strains from other related bacteria. The assay was validated on tissue and seed samples following artificial infection, and all tested samples accurately detected the presence of Cm. The tool described here is highly specific, sensitive, and reliable for the detection of Cm and allows the quantification of Cm in seeds, roots, stems, and leaves. The diagnostic assay can also be adapted for multiple purposes such as seed certification programs, surveillance, biosafety, the effectiveness of control methods, border protection, and epidemiological studies. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Real-Time Machine Learning Alerts to Prevent Escalation of Care: A Nonrandomized Clustered Pragmatic Clinical Trial*
Authors: Levin Matthew A. , Kia Arash , Timsina Prem , Cheng Fu-yuan , Nguyen Kim-Anh-Nhi , Kohli-Seth Roopa , Lin Hung-Mo , Ouyang Yuxia , Freeman Robert , Reich David L. 
Published: February 2024

OBJECTIVES:
Machine learning algorithms can outperform older methods in predicting clinical deterioration, but rigorous prospective data on their real-world efficacy are limited. We hypothesized that real-time machine learning generated alerts sent directly to front-line providers would reduce escalations.

DESIGN:
Single-center prospective pragmatic nonrandomized clustered clinical trial.

SETTING:
Academic tertiary care medical center.

PATIENTS:
Adult patients admitted to four medical-surgical units. Assignment to intervention or control arms was determined by initial unit admission.

INTERVENTIONS:
Real-time alerts stratified according to predicted likelihood of deterioration sent either to the primary team or directly to the rapid response team (RRT). Clinical care and interventions were at the providers’ discretion. For the control units, alerts were generated but not sent, and standard RRT activation criteria were used.

MEASUREMENTS AND MAIN RESULTS:
The primary outcome was the rate of escalation per 1000 patient bed days. Secondary outcomes included the frequency of orders for fluids, medications, and diagnostic tests, and combined in-hospital and 30-day mortality. Propensity score modeling with stabilized inverse probability of treatment weight (IPTW) was used to account for differences between groups. Data from 2740 patients enrolled between July 2019 and March 2020 were analyzed (1488 intervention, 1252 control). Average age was 66.3 years and 1428 participants (52%) were female. The rate of escalation was 12.3 vs. 11.3 per 1000 patient bed days (difference, 1.0; 95% CI, –2.8 to 4.7) and IPTW adjusted incidence rate ratio 1.43 (95% CI, 1.16–1.78; p < 0.001). Patients in the intervention group were more likely to receive cardiovascular medication orders (16.1% vs. 11.3%; 4.7%; 95% CI, 2.1–7.4%) and IPTW adjusted relative risk (RR) (1.74; 95% CI, 1.39–2.18; p < 0.001). Combined in-hospital and 30-day-mortality was lower in the intervention group (7% vs. 9.3%; –2.4%; 95% CI, –4.5% to –0.2%) and IPTW adjusted RR (0.76; 95% CI, 0.58–0.99; p = 0.045).

CONCLUSIONS:
Real-time machine learning alerts do not reduce the rate of escalation but may reduce mortality.