bluuebunny/crossref_metadata_2025_split huggingface dataset:
The EBLM Project XII. An eccentric, long-period eclipsing binary with a companion near the hydrogen-burning limit
Authors: Davis Yasmin T , Triaud Amaury H M J , Freckelton Alix V , Mortier Annelies , Sebastian Daniel , Brahm Rafael , Baycroft Thomas , Dransfield Georgina , Duck Alison , Henning Thomas , Hobson Melissa J , Jordán Andrés , Kunovac Vedad , Martin David V , Maxted Pierre F L , Sairam Lalitha , Standing Matthew R , Swayne Matthew I , Trifonov Trifon , Udry Stéphane 
Published: April 2024

ABSTRACT
In the hunt for Earth-like exoplanets, it is crucial to have reliable host star parameters, as they have a direct impact on the accuracy and precision of the inferred parameters for any discovered exoplanet. For stars with masses between 0.35 and 0.5 M⊙, an unexplained radius inflation is observed relative to typical stellar models. However, for fully convective objects with a mass below 0.35 M⊙, it is not known whether this radius inflation is present, as there are fewer objects with accurate measurements in this regime. Low-mass eclipsing binaries present a unique opportunity to determine empirical masses and radii for these low-mass stars. Here, we report on such a star, EBLM J2114−39 B. We have used HARPS and FEROS radial velocities and TESS photometry to perform a joint fit of the data and produce one of the most precise estimates of a very low mass star’s parameters. Using a precise and accurate radius for the primary star using Gaia DR3 data, we determine J2114−39 to be a M1 = 0.998 ± 0.052 M⊙ primary star hosting a fully convective secondary with mass $M_2~=~0.0993~\pm 0.0033~\, \mathrm{M_{\odot }}$, which lies in a poorly populated region of parameter space. With a radius $R_2 =~0.1250~\pm 0.0016~\, \mathrm{R_{\odot }}$, similar to TRAPPIST-1, we see no significant evidence of radius inflation in this system when compared to stellar evolution models. We speculate that stellar models in the regime where radius inflation is observed might be affected by how convective overshooting is treated.
Impact of astrophysical effects on the dark matter mass constraint with 21 cm intensity mapping
Authors: Murakami Koya , Nishizawa Atsushi J , Nagamine Kentaro , Shimizu Ikko 
Published: April 2024

ABSTRACT
We present an innovative approach to constraining the non-cold dark matter model using a convolutional neural network (CNN). We perform a suite of hydrodynamic simulations with varying dark matter particle masses and generate mock 21 cm radio intensity maps to trace the dark matter distribution at z = 3 in the postreionization epoch. Our proposed method complements the traditional power-spectrum analysis. We compare the results of the CNN classification between the mock maps with different dark matter masses with those from the two-dimensional power spectrum of the differential brightness temperature map of 21 cm radiation. We find that the CNN outperforms the power spectrum. Moreover, we investigate the impact of baryonic physics on the dark matter model constraint, including star formation, self-shielding of H i gas, and ultraviolet background model. We find that these effects may introduce some contamination in the dark matter constraint, but they are insignificant compared to the system noise of the SKA instruments.
The long non-coding RNA Meg3 mediates imprinted gene expression during stem cell differentiation
Authors: Farhadova Sabina , Ghousein Amani , Charon François , Surcis Caroline , Gomez-Velazques Melisa , Roidor Clara , Di Michele Flavio , Borensztein Maud , De Sario Albertina , Esnault Cyril , Noordermeer Daan , Moindrot Benoit , Feil Robert 
Published: April 2024

Abstract
The imprinted Dlk1-Dio3 domain comprises the developmental genes Dlk1 and Rtl1, which are silenced on the maternal chromosome in different cell types. On this parental chromosome, the domain's imprinting control region activates a polycistron that produces the lncRNA Meg3 and many miRNAs (Mirg) and C/D-box snoRNAs (Rian). Although Meg3 lncRNA is nuclear and associates with the maternal chromosome, it is unknown whether it controls gene repression in cis. We created mouse embryonic stem cells (mESCs) that carry an ectopic poly(A) signal, reducing RNA levels along the polycistron, and generated Rian−/− mESCs as well. Upon ESC differentiation, we found that Meg3 lncRNA (but not Rian) is required for Dlk1 repression on the maternal chromosome. Biallelic Meg3 expression acquired through CRISPR-mediated demethylation of the paternal Meg3 promoter led to biallelic Dlk1 repression, and to loss of Rtl1 expression. lncRNA expression also correlated with DNA hypomethylation and CTCF binding at the 5′-side of Meg3. Using Capture Hi-C, we found that this creates a Topologically Associating Domain (TAD) organization that brings Meg3 close to Dlk1 on the maternal chromosome. The requirement of Meg3 for gene repression and TAD structure may explain how aberrant MEG3 expression at the human DLK1-DIO3 locus associates with imprinting disorders.
Quantifying the activity profile of ASO and siRNA conjugates in glioblastoma xenograft tumors in vivo
Authors: Sarli Samantha L , Fakih Hassan H , Kelly Karen , Devi Gitali , Rembetsy-Brown Julia M , McEachern Holly R , Ferguson Chantal M , Echeverria Dimas , Lee Jonathan , Sousa Jacquelyn , Sleiman Hanadi F , Khvorova Anastasia , Watts Jonathan K 
Published: April 2024

Abstract
Glioblastoma multiforme is a universally lethal brain tumor that largely resists current surgical and drug interventions. Despite important advancements in understanding GBM biology, the invasiveness and heterogeneity of these tumors has made it challenging to develop effective therapies. Therapeutic oligonucleotides—antisense oligonucleotides and small-interfering RNAs—are chemically modified nucleic acids that can silence gene expression in the brain. However, activity of these oligonucleotides in brain tumors remains inadequately characterized. In this study, we developed a quantitative method to differentiate oligonucleotide-induced gene silencing in orthotopic GBM xenografts from gene silencing in normal brain tissue, and used this method to test the differential silencing activity of a chemically diverse panel of oligonucleotides. We show that oligonucleotides chemically optimized for pharmacological activity in normal brain tissue do not show consistent activity in GBM xenografts. We then survey multiple advanced oligonucleotide chemistries for their activity in GBM xenografts. Attaching lipid conjugates to oligonucleotides improves silencing in GBM cells across several different lipid classes. Highly hydrophobic lipid conjugates cholesterol and docosanoic acid enhance silencing but at the cost of higher neurotoxicity. Moderately hydrophobic, unsaturated fatty acid and amphiphilic lipid conjugates still improve activity without compromising safety. These oligonucleotide conjugates show promise for treating glioblastoma.
Interaction between a J-domain co-chaperone and a specific Argonaute protein contributes to microRNA function in animals
Authors: Frédérick Pierre-Marc , Jannot Guillaume , Banville Isabelle , Simard Martin J 
Published: April 2024

Abstract
MicroRNAs (miRNAs) are essential regulators of several biological processes. They are loaded onto Argonaute (AGO) proteins to achieve their repressive function, forming the microRNA-Induced Silencing Complex known as miRISC. While several AGO proteins are expressed in plants and animals, it is still unclear why specific AGOs are strictly binding miRNAs. Here, we identified the co-chaperone DNJ-12 as a new interactor of ALG-1, one of the two major miRNA-specific AGOs in Caenorhabditis elegans. DNJ-12 does not interact with ALG-2, the other major miRNA-specific AGO, and PRG-1 and RDE-1, two AGOs involved in other small RNA pathways, making it a specific actor in ALG-1-dependent miRNA-mediated gene silencing. The loss of DNJ-12 causes developmental defects associated with defective miRNA function. Using the Auxin Inducible Degron system, a powerful tool to acutely degrade proteins in specific tissues, we show that DNJ-12 depletion hampers ALG-1 interaction with HSP70, a chaperone required for miRISC loading in vitro. Moreover, DNJ-12 depletion leads to the decrease of several miRNAs and prevents their loading onto ALG-1. This study uncovers the importance of a co-chaperone for the miRNA function in vivo and provides insights to explain how different small RNAs associate with specific AGO in animals.
CRISPR-Cas tools for simultaneous transcription & translation control in bacteria
Authors: Cardiff Ryan A L , Faulkner Ian D , Beall Juliana G , Carothers James M , Zalatan Jesse G 
Published: April 2024

Abstract
Robust control over gene translation at arbitrary mRNA targets is an outstanding challenge in microbial synthetic biology. The development of tools that can regulate translation will greatly expand our ability to precisely control genes across the genome. In Escherichia coli, most genes are contained in multi-gene operons, which are subject to polar effects where targeting one gene for repression leads to silencing of other genes in the same operon. These effects pose a challenge for independently regulating individual genes in multi-gene operons. Here, we use CRISPR-dCas13 to address this challenge. We find dCas13-mediated repression exhibits up to 6-fold lower polar effects compared to dCas9. We then show that we can selectively activate single genes in a synthetic multi-gene operon by coupling dCas9 transcriptional activation of an operon with dCas13 translational repression of individual genes within the operon. We also show that dCas13 and dCas9 can be multiplexed for improved biosynthesis of a medically-relevant human milk oligosaccharide. Taken together, our findings suggest that combining transcriptional and translational control can access effects that are difficult to achieve with either mode independently. These combined tools for gene regulation will expand our abilities to precisely engineer bacteria for biotechnology and perform systematic genetic screens.
Stereo-EEG features of temporal and frontal lobe seizures with loss of consciousness
Authors: Campora Nuria , Princich Juan Pablo , Nasimbera Alejandro , Cordisco Santiago , Villanueva Manuela , Oddo Silvia , Giagante Brenda , Kochen Silvia 
Published: April 2024

Abstract
The loss of consciousness (LOC) during seizures is one of the most striking features that significantly impact the quality of life, even though the neuronal network involved is not fully comprehended. We analyzed the intracerebral patterns in patients with focal drug-resistant epilepsy, both with and without LOC. We assessed the localization, lateralization, stereo electroencephalography (SEEG) patterns, seizure duration, and the quantification of contacts exhibiting electrical discharge. The degree of LOC was quantified using the Consciousness Seizure Scale. Thirteen patients (40 seizures) with focal drug-resistant epilepsy underwent SEEG. In cases of temporal lobe epilepsy (TLE, 6 patients and 15 seizures), LOC occurred more frequently in seizures with mesial rather than lateral temporal lobe onset. On the other hand, in cases of frontal lobe epilepsy (7 patients; 25 seizures), LOC was associated with pre-frontal onset, a higher number of contacts with epileptic discharge compared to the onset count and longer seizure durations. Our study revealed distinct characteristics during LOC depending on the epileptogenic zone. For temporal lobe seizures, LOC was associated with mesial seizure onset, whereas in frontal lobe epilepsy, seizure with LOC has a significant increase in contact showing epileptiform discharge and a pre-frontal onset. This phenomenon may be correlated with the broad neural network required to maintain consciousness, which can be affected in different ways, resulting in LOC
Rituximab or cyclosporine A for the treatment of membranous nephropathy: economic evaluation of the MENTOR trial
Authors: Kadatz Matthew , Klarenbach Scott , So Helen , Fervenza Fernando C , Cattran Daniel C , Barbour Sean J ,   MENTOR Study Investigators, Fervenza F C , Cattran D C , Appel G , Gipson D , Kretzler M , Rovin B , Fervenza F C , Lieske J C , Leung N , Erickson S B , Radhakrishnan J , Bomback A , Hogan J , Canetta P , Ahn W , Lafayette R , Arora N , Nargund P , Rovin B , Alvarado A , Parikh S , Hebert L A , Aslam N , Porter I , Gipson P , Kretzler M , Plattner B , Gipson D , Mariani L , Garg P , Rao P , Sedor J , O'Toole J , Jefferson J A , Nelson P J , McCarthy E , Yarlagadda S , Jain N , Rizk D , Simon J , Gebreselassie S , Blumenthal S , Beara-Lasic L , Zhdanova O , Thomas L , Cohen I , Keddis M , Sussman A , Thajudeen B , Juncos L , Fulop T , Craici I , Wagner S , Dreisbach A , Monga D , Green D , Mattiazzi A , Nayer A , Thomas D , Barisoni L , Li T , Vijayan A , Cattran D C , Reich H , Hladunewich M , Barbour S , Levin A , Philibert D , Mac-Way F , Desmeules S , Ankawi G , Sethi S , Avila-Casado C , Beanlands H 
Published: April 2024

ABSTRACT

Background and hypothesis
The MENTOR trial (MEmbranous Nephropathy Trial Of Rituximab) showed that rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria and was superior in maintaining proteinuria remission. However, the cost of rituximab may prohibit first-line use for some patients and health-care payers.

Methods
A Markov model was used to determine the incremental cost-effectiveness ratio (ICER) of rituximab compared with cyclosporine for the treatment membranous nephropathy from the perspective of a health-care payer with a lifetime time horizon. The model was informed by data from the MENTOR trial where possible; additional parameters including cost and utility inputs were obtained from the literature. Sensitivity analyses were performed to evaluate the impact of reduced-cost biosimilar rituximab.

Results
Rituximab for the treatment of membranous nephropathy was cost effective (assuming a willingness-to-pay threshold of $50 000 per quality-adjusted life year (QALY) gained; in $US 2021) compared with cyclosporine, with an ICER of $8373/QALY over a lifetime time horizon. The incremental cost of rituximab therapy was $28 007 with an additional 3.34 QALYs compared with cyclosporine. Lower cost of rituximab biosimilars resulted in a more favorable ICER, and in some cases resulted in rituximab being dominant (lower cost and great benefit) compared to cyclosporine.

Conclusions
Despite the greater cost of rituximab, it may be a cost-effective option for the treatment of membranous nephropathy when compared with cyclosporine. The cost-effectiveness of rituximab is further improved with the use of less expensive biosimilars.
Remdesivir is Associated with Reduced Mortality in Patients Hospitalized for COVID-19 Not Requiring Supplemental Oxygen
Authors: Mozaffari Essy , Chandak Aastha , Chima-Melton Chidinma , Kalil Andre C , Jiang Heng , Lee EunYoung , Der-Torossian Celine , Thrun Mark , Berry Mark , Haubrich Richard , Gottlieb Robert L 
Published: April 2024

Abstract

Background
Remdesivir has demonstrated benefit in some hospitalized patients with coronavirus disease 2019 (COVID-19) on supplemental oxygen and in nonhospitalized patients breathing room air. The durability of this benefit across time periods with different circulating severe acute respiratory syndrome coronavirus 2 variants of concern (VOC) is unknown. This comparative effectiveness study in patients hospitalized for COVID-19 and not receiving supplemental oxygen at admission compared those starting remdesivir treatment in the first 2 days of admission with those receiving no remdesivir during their hospitalization across different VOC periods.

Method
Using a large, multicenter US hospital database, in-hospital mortality rates were compared among patients hospitalized for COVID-19 but not requiring supplemental oxygen at admission between December 2020 and April 2022. Patients receiving remdesivir at hospital admission were matched 1:1 to those not receiving remdesivir during hospitalization, using propensity score matching. Cox proportional hazards models were used to assess 14- and 28-day in-hospital mortality rates or discharge to hospice.

Results
Among the 121 336 eligible patients, 58 188 remdesivir-treated patients were matched to 17 574 unique patients not receiving remdesivir. Overall, 5.4% of remdesivir-treated and 7.3% in the non-remdesivir group died within 14 days, and 8.0% and 9.8%, respectively, died within 28 days. Remdesivir treatment was associated with a statistically significant reduction in the in-hospital mortality rate compared with non-remdesivir treatment (14-day and 28-day adjusted hazard ratios [95% confidence interval], 0.75 [0.68–0.83] and 0.83 [0.76–0.90], respectively). This significant mortality benefit endured across the different VOC periods.

Conclusions
Remdesivir initiation in patients hospitalized for COVID-19 and not requiring supplemental oxygen at admission was associated with a significantly reduced in-hospital mortality rate. These findings highlight a potential survival benefit when clinicians initiated remdesivir on admission across the dominant variant eras of the evolving pandemic.
National HIV and HCV Screening Rates for Hospitalized People who Use Drugs Are Suboptimal and Heterogeneous Across 11 US Hospitals
Authors: Westgard Leo Knudsen , Sato Taisuke , Bradford William S , Eaton Ellen F , Pilcher Finlay , Hale Andrew J , Singh Devika , Martin Marlene , Appa Ayesha A , Meyer Jaimie P , Weimer Melissa B , Barakat Lydia A , Felsen Uriel R , Akiyama Matthew J , Ridgway Jessica P , Grussing Emily D , Thakarar Kinna , White Amy , Mutelayi John , Krsak Martin , Montague Brian T , Nijhawan Ank , Balakrishnan Harini , Marks Laura R , Wurcel Alysse G 
Published: April 2024

Abstract

Background
To end the HIV and hepatitis C virus (HCV) epidemics, people who use drugs (PWUD) need more opportunities for testing. While inpatient hospitalizations are an essential opportunity to test people who use drugs (PWUD) for HIV and HCV, there is limited research on rates of inpatient testing for HIV and HCV among PWUD.

Methods
Eleven hospital sites were included in the study. Each site created a cohort of inpatient encounters associated with injection drug use. From these cohorts, we collected data on HCV and HIV testing rates and HIV testing consent policies from 65 276 PWUD hospitalizations.

Results
Hospitals had average screening rates of 40% for HIV and 32% for HCV, with widespread heterogeneity in screening rates across facilities. State consent laws and opt-out testing policies were not associated with statistically significant differences in HIV screening rates. On average, hospitals that reflexed HCV viral load testing on HCV antibody testing did not have statistically significant differences in HCV viral load testing rates. We found suboptimal testing rates during inpatient encounters for PWUD. As treatment (HIV) and cure (HCV) are necessary to end these epidemics, we need to prioritize understanding and overcoming barriers to testing.
Incidence of Herpes Zoster and Postherpetic Neuralgia and Herpes Zoster Vaccination Uptake in a US Administrative Claims Database
Authors: Marcum Zachary A , Jain Purva , Embry Alan , Arakaki Brent , Estevez Irisdaly , Viscidi Emma 
Published: April 2024

Abstract

Background
The objective of this study was to estimate the annual incidence rates of herpes zoster (HZ) and postherpetic neuralgia (PHN) among individuals aged ≥19 years and the proportion who received HZ vaccination among those aged ≥50 years.

Methods
This observational cohort study was conducted with administrative claims data from HealthVerity and included insured individuals across the US. Crude and US age- and sex-standardized incidence rates of HZ and PHN were calculated from 1 January 2019 to 31 May 2022 by calendar year in persons aged ≥19 years. Outcomes were defined as ≥1 ICD-10 diagnosis code for HZ or PHN. Analyses were stratified by age, sex, and immunocompromised status. Among those aged ≥50 years, the proportion who received 1 or 2 doses of recombinant zoster vaccine (Shingrix) or 1 dose of Zostavax was calculated.

Results
Standardized annual incidence rates from 2019 to 2021 were 542 to 685 per 100 000 person-years for HZ and 35 to 38 per 100 000 person-years for PHN. Rates were highest among females, older adults, and individuals who were immunocompromised. From 1 January 2019 to 31 May 2022, 4.3% and 9.0% of persons aged ≥50 years received 1 and 2 doses of Shingrix, respectively, and 0.2% received 1 dose of Zostavax.

Conclusions
In this US claims database analysis, HZ and PHN were more frequent among older adults, females, and individuals who were immunocompromised. Between 1 January 2019 and 31 May 2022, 9% of persons aged ≥50 years received 2 doses of the Shingrix vaccine. Greater efforts are needed to increase vaccine uptake against HZ, especially for those at highest risk.
Predictors of nutritional recovery time in children aged 6–59 months with severe acute malnutrition in Sofala Province, Mozambique: survival analysis approach
Authors: Victor Audêncio , Antônio Bélio Castro , Gotine Ana Raquel Manuel , Mahoche Manuel , Pedro Xavier Sancho , Silva Rodrigues Osiyallê Akanni , Ferreira Andrêa J F , Rondó Patrícia H 
Published: April 2024

Abstract

Background
Malnutrition is a public health problem that affects physical and psychosocial well-being. It manifests as a rapid deterioration in nutritional status and bilateral edema due to inadequate food intake or illness.

Methods
This study is a retrospective cohort of 1208 children with severe acute malnutrition (SAM) in Sofala Province from 2018 to 2022. It includes hospitalized children aged 6–59 months with SAM and related complications. The dependent variable is recovery, and the independent variables include age, sex of the child, vomiting, dehydration, hypoglycemia, nutritional edema and anthropometry. Survival curves were plotted using the Kaplan–Meier method, and bivariable and multivariable Cox regression analyses were performed.

Results
The crude analysis revealed significant factors for nutritional recovery in children with SAM, including age, weight, height, malaria, diarrhea and dehydration. Children under 24 months had a 28% lower likelihood of recovery. Weight below 6.16 kg decreased the likelihood by 2%, and height above 71.1 cm decreased it by 20%. Conversely, malaria, diarrhea and dehydration increased the likelihood of recovery. However, after adjustment, only diarrhea remained a significant predictor of nutritional recovery.

Conclusion
This study found that diarrhea is a predictor of nutritional recovery in children with SAM.
Euler-Poincaré Formulae for Positive Depth Bernstein Projectors
Authors: Moy Allen , Savin Gordan 
Published: April 2024

ABSTRACT
Work of Bezrukavnikov–Kazhdan–Varshavsky uses an equivariant system of trivial idempotents of Moy–Prasad groups to obtain an Euler–Poincaré formula for the r-depth Bernstein projector. Barbasch–Ciubotaru–Moy use depth-zero cuspidal representations of parahoric subgroups to decompose the Euler–Poincaré presentation of the depth-zero projector. For positive depth r, we establish a decomposition of the Euler–Poincaré presentation of the r-depth Bernstein projector based on a notion of associate classes of cuspidal pairs for Moy–Prasad quotients. We apply these new Euler–Poincaré presentations to obtain decompositions of the resolutions of Schneider–Stuhler and Bestvina–Savin.