bluuebunny/crossref_metadata_2025_split huggingface dataset:
The case of HD 106906 debris disc: a binary’s revenge
Authors: Farhat Mohammad A , Sefilian Antranik A , Touma Jihad R 
Published: January 2023

ABSTRACTDebris disc architecture presents [exo-]planetary scientists with precious clues for processes of planet formation and evolution, including constraints on planetary mass perturbers. This is particularly true of the disc in HD 106906, which in early HST, then follow up polarimetric observations, presented asymmetries and needle-like features that have been attributed to perturbations by a massive, and unusually distant external planetary companion. Here, we revisit the long-term secular dynamical evolution of the HD 106906 disc allowing for the combined gravitational action of the planetary companion and the inner stellar binary which holds the system together. We argue that the binary is strong enough to impose a dynamical break at the disc’s location, resulting in distinctive observational signatures which we render via simulated surface density maps and vertical structure profiles. Within uncertainties on the planet’s orbit, we show that the disc can go from being fully dominated by the inner binary to significantly so, and is hardly ever outside its reach. The extent of binary dominance impacts the disc’s mean eccentricity, a metric which we map as a function of the planet’s semimajor axis and orbital eccentricity, with and without radiation pressure. We can thus constrain the planet’s orbit to ease the tension between evident axisymmetry in the millimeter, and apparent asymmetry in scattered light. We discuss phase space structure, then inclination distribution, arguing for the relevance of our results to a variety of hierarchical systems, as we set the stage for generalizations that allow for disc self-gravity and collisional evolution.
VLBI astrometry on the white dwarf pulsar AR Scorpii
Authors: Jiang Pengfei , Cui Lang , Yang Jun , Zhang Bo , Xu Shuangjing , Shu Fengchun , Jiang Wu , Chen Wen , Li Guanghui , Xia Bo , Weston Stuart , Gulyaev Sergei , Cao Hongmin , Liu Xiang , An Tao 
Published: January 2023

ABSTRACT
AR Scorpii (AR Sco), the only-known radio-pulsing white dwarf binary, shows unusual pulsating emission at the radio, infrared, optical, and ultraviolet bands. To determine its astrometric parameters at the radio band independently, we conducted multi-epoch Very Long Baseline Interferometry (VLBI) phase-referencing observations with the European VLBI Network at 5 GHz and the Chinese VLBI Network plus the Warkworth 30-m telescope (New Zealand) at 8.6 GHz. By using the differential VLBI astrometry, we provide high-precision astrometric measurements on the parallax ($\pi =8.52_{-0.07}^{+0.04}$ mas) and proper motion ($\mu _{\alpha }=9.48_{-0.07}^{+0.04}$ mas yr−1, $\mu _{\delta }=-51.32_{-0.38}^{+0.22}$ mas yr−1). The new VLBI results agree with the optical Gaia astrometry. Our kinematic analysis reveals that the Galactic space velocities of AR Sco are quite consistent with that of both intermediate polars and polars. Combined with the previous tightest VLBI constraint on the size, our parallax distance suggests that the radio emission of AR Sco should be located within the light cylinder of its white dwarf.
Parallelized gene cluster editing illuminates mechanisms of epoxyketone proteasome inhibitor biosynthesis
Authors: Huang Chuan , Zabala Daniel , de los Santos Emmanuel L C , Song Lijiang , Corre Christophe , Alkhalaf Lona M , Challis Gregory L 
Published: January 2023

AbstractAdvances in DNA sequencing technology and bioinformatics have revealed the enormous potential of microbes to produce structurally complex specialized metabolites with diverse uses in medicine and agriculture. However, these molecules typically require structural modification to optimize them for application, which can be difficult using synthetic chemistry. Bioengineering offers a complementary approach to structural modification but is often hampered by genetic intractability and requires a thorough understanding of biosynthetic gene function. Expression of specialized metabolite biosynthetic gene clusters (BGCs) in heterologous hosts can surmount these problems. However, current approaches to BGC cloning and manipulation are inefficient, lack fidelity, and can be prohibitively expensive. Here, we report a yeast-based platform that exploits transformation-associated recombination (TAR) for high efficiency capture and parallelized manipulation of BGCs. As a proof of concept, we clone, heterologously express and genetically analyze BGCs for the structurally related nonribosomal peptides eponemycin and TMC-86A, clarifying remaining ambiguities in the biosynthesis of these important proteasome inhibitors. Our results show that the eponemycin BGC also directs the production of TMC-86A and reveal contrasting mechanisms for initiating the assembly of these two metabolites. Moreover, our data shed light on the mechanisms for biosynthesis and incorporation of 4,5-dehydro-l-leucine (dhL), an unusual nonproteinogenic amino acid incorporated into both TMC-86A and eponemycin.
SMAP design: a multiplex PCR amplicon and gRNA design tool to screen for natural and CRISPR-induced genetic variation
Authors: Develtere Ward , Waegneer Evelien , Debray Kevin , De Saeger Jonas , Van Glabeke Sabine , Maere Steven , Ruttink Tom , Jacobs Thomas B 
Published: January 2023

Abstract
Multiplex amplicon sequencing is a versatile method to identify genetic variation in natural or mutagenized populations through eco-tilling or multiplex CRISPR screens. Such genotyping screens require reliable and specific primer designs, combined with simultaneous gRNA design for CRISPR screens. Unfortunately, current tools are unable to combine multiplex gRNA and primer design in a high-throughput and easy-to-use manner with high design flexibility. Here, we report the development of a bioinformatics tool called SMAP design to overcome these limitations. We tested SMAP design on several plant and non-plant genomes and obtained designs for more than 80–90% of the target genes, depending on the genome and gene family. We validated the designs with Illumina multiplex amplicon sequencing and Sanger sequencing in Arabidopsis, soybean, and maize. We also used SMAP design to perform eco-tilling by tilling PCR amplicons across nine candidate genes putatively associated with haploid induction in Cichorium intybus. We screened 60 accessions of chicory and witloof and identified thirteen knockout haplotypes and their carriers. SMAP design is an easy-to-use command-line tool that generates highly specific gRNA and/or primer designs for any number of loci for CRISPR or natural variation screens and is compatible with other SMAP modules for seamless downstream analysis.
SARS-CoV-2 seroprevalence in workers from a Colombian University Hospital
Authors: Moreno-Medina K , Sáenz Pérez L D , Villar J C , Váquiro Herrera E , Pérez Franco J E , Varón-Vega F A , Guanes Cortés R , Steevens Gualdrón A , Sarmiento Becerra M S 
Published: January 2023

AbstractBackgroundAntibody (Ab) tests for SARS-CoV-2 virus allows for the estimation of incidence, level of exposure and duration of immunity acquired by a previous infection. In health workers, the hospital setting might convey a greater risk of infection.AimsTo describe the frequency of immunoglobulin G (IgG) Abs (IgG-Abs) to the SARS-CoV-2 virus among workers at a third-level university hospital in Colombia.MethodsIn this cross-sectional study, we included medical and non-medical personnel with at least one real-time polymerase chain reaction (RT–PCR)/antigen test between March 2020 and March 2021. In April 2021, an IgG-Ab test against SARS-CoV-2 was conducted for all participants and replicated 2 weeks later in a random sample (10%). The frequency of IgG-Abs is presented based on status (positive/negative) and time elapsed since RT–PCR/antigen test (&lt;3 months, 3–6 months, &gt;6 months).ResultsWe included 1021 workers (80% women, median age 34 years (interquartile range 28–42), 73% medical personnel, 23% with previous positive RT–PCR/antigen). The overall seroprevalence was 35% (95% CI 31.6–37.4, 35% in medical and 33% in non-medical personnel). For those with a previous positive RT–PCR/antigen test, the seroprevalence was 90% (&lt;3 months), 82% (3–6 months) and 48% (&gt;6 months). In participants with a previous negative RT–PCR/antigen test, the seroprevalence was 17% (&lt;3 months), 21% (3–6 months) and 29% (&gt;6 months).ConclusionsHigh IgG-Ab positivity was found in hospital personnel, regardless of work activities. The prevalence of detectable Abs differed by previous RT–PCR/antigen status and time elapsed since the diagnostic test.
Predictors of combat training attrition in Israel Defense Forces soldiers
Authors: Gendler S , Talmy T , Shapiro M , Tzur D , Kedem R , Landau R , Zubkov K 
Published: January 2023

AbstractBackgroundAttrition from combat service carries significant organizational and personal ramifications, but predicting factors associated with attrition remains challenging.AimsTo evaluate medical and psychosocial factors associated with attrition from basic combat training (BCT) in the Israel Defense Forces (IDF). In addition, we identify subsets of the recruit population which exhibit certain trends in terms of medical corresponding with a high risk of attrition.MethodsA cross-sectional study of IDF combat trainees undergoing infantry BCT between 2012 and 2017. Data were collected from the soldiers’ electronic medical and administrative records. We used multivariable logistic regression and the SAS® decision-tree tool to analyse key predictive factors for attrition.ResultsA total of 46 472 soldiers enlisted to BCT during the research period. The mean body mass index (BMI) was 21.8 (SD 3.54). The overall attrition rate was 10%. The following factors were associated with attrition from BCT: ethnicity (P &lt; 0.01), BMI (P &lt; 0.01), pre-enlisting motivation score (P &lt; 0.01) and the number of mental health officer visits (P &lt; 0.01). Using a decision-tree model, we found a high attrition rate among soldiers who had &gt;5.2 to primary care physician visits (11% attrition rate versus 3%) or more than 11 sick leave days (59% versus 19%).ConclusionsThis study sheds light on unique measures relating to attrition. Attrition is associated with several demographic and psychosocial factors. Early prediction of motivation and monitoring of healthcare utilization may enable early identification and focused interventions targeting soldiers at high risk for attrition. These findings need to be further translated into actionable directives and further investigations.
Characterization of a Novel Pathogen in Immunocompromised Patients:Elizabethkingia anophelis—Exploring the Scope of Resistance to Contemporary Antimicrobial Agents and β-lactamase Inhibitors
Authors: Yasmin Mohamad , Rojas Laura J , Marshall Steven H , Hujer Andrea M , Cmolik Anna , Marshall Emma , Boucher Helen W , Vila Alejandro J , Soldevila Maxime , Diene Seydina M , Rolain Jean-Marc , Bonomo Robert A 
Published: January 2023

AbstractBackgroundElizabethkingia anophelis is an emerging Gram-negative nonlactose fermenter in the health care setting, where it causes life-threatening infections in immunocompromised patients. We aimed to characterize the molecular mechanisms of antimicrobial resistance and evaluate the utility of contemporary antibiotics with the intent to offer targeted therapy against an uncommonly encountered pathogen.MethodsWhole-genome sequencing (WGS) was conducted to accurately identify isolate species and elucidate the determinants of β-lactam resistance. Antimicrobial susceptibility testing was performed using broth microdilution and disk diffusion assays. To assess the functional contribution of the major metallo-β-lactamase (MBL) encoding genes to the resistance profile, blaBlaB was cloned into pBCSK(-) phagemid vector and transformed into Escherichia coli DH10B.ResultsWGS identified the organism as E. anophelis. MBL genes blaBlaB-1 and blaGOB-26 were identified, in addition to blaCME-2, which encodes for an extended-spectrum β-lactamase (ESBL). Plasmids were not detected. The isolate was nonsusceptible to all commonly available β-lactams, carbapenems, newer β-lactam β-lactamase inhibitor combinations, and to the combination of aztreonam (ATM) with ceftazidime-avibactam (CAZ-AVI). Susceptibility to the novel siderophore cephalosporin cefiderocol was determined. A BlaB-1 transformant E. coli DH10B isolate was obtained and demonstrated increased minimum inhibitory concentrations to cephalosporins, carbapenems, and CAZ-AVI, but not ATM.ConclusionsUsing WGS, we accurately identified and characterized an extensively drug-resistant E. anophelis in an immunocompromised patient. Rapid evaluation of the genetic background can guide accurate susceptibility testing to better inform antimicrobial therapy selection.
Apoplast-Localized β-Glucosidase Elevates Isoflavone Accumulation in the Soybean Rhizosphere
Authors: Matsuda Hinako , Yamazaki Yumi , Moriyoshi Eiko , Nakayasu Masaru , Yamazaki Shinichi , Aoki Yuichi , Takase Hisabumi , Okazaki Shin , Nagano Atsushi J , Kaga Akito , Yazaki Kazufumi , Sugiyama Akifumi 
Published: January 2023

Abstract
Plant specialized metabolites (PSMs) are often stored as glycosides within cells and released from the roots with some chemical modifications. While isoflavones are known to function as symbiotic signals with rhizobia and to modulate the soybean rhizosphere microbiome, the underlying mechanisms of root-to-soil delivery are poorly understood. In addition to transporter-mediated secretion, the hydrolysis of isoflavone glycosides in the apoplast by an isoflavone conjugate–hydrolyzing β-glucosidase (ICHG) has been proposed but not yet verified. To clarify the role of ICHG in isoflavone supply to the rhizosphere, we have isolated two independent mutants defective in ICHG activity from a soybean high-density mutant library. In the root apoplastic fraction of ichg mutants, the isoflavone glycoside contents were significantly increased, while isoflavone aglycone contents were decreased, indicating that ICHG hydrolyzes isoflavone glycosides into aglycones in the root apoplast. When grown in a field, the lack of ICHG activity considerably reduced isoflavone aglycone contents in roots and the rhizosphere soil, although the transcriptomes showed no distinct differences between the ichg mutants and wild-types (WTs). Despite the change in isoflavone contents and composition of the root and rhizosphere of the mutants, root and rhizosphere bacterial communities were not distinctive from those of the WTs. Root bacterial communities and nodulation capacities of the ichg mutants did not differ from the WTs under nitrogen-deficient conditions either. Taken together, these results indicate that ICHG elevates the accumulation of isoflavones in the soybean rhizosphere but is not essential for isoflavone-mediated plant–microbe interactions.
The gauge-invariant formulation of the local expansion rate driven by the local average density in an inhomogeneous universe
Authors: Tomonaga Masanori , Kasai Masumi , Futamase Toshifumi 
Published: January 2023

Abstract
The Hubble tension casts a blight on the standard cosmology. As a possible solution to the problem, the local variation of the expansion rate has been proposed where the spatial averaging over a finite domain was introduced in order to restore the local Friedmannian behavior in an inhomogeneous cosmology. So far, however, the approaches are limited to the particular choices of the gauges, and it has been unclear whether the results are gauge invariant. In this paper, we present the gauge-invariant formulation of the local expansion rate, which is driven by the spatial average of the gauge-invariant inhomogeneous density. We show that the local cosmological parameters in the finite domain may change from the global parameters, and the relations between them are expressed by the gauge-invariant averaged density.
The Brain Medicine Fellowship: A Competency-Based Training Program to Treat Complex Brain Disorders
Authors: Levitt Sarah , Henri-Bhargava Alex , Hogan David B. , Shulman Kenneth , Mitchell Sara B. 
Published: January 2023

ProblemComplex brain disorders involve symptoms in the domains of affect, behavior, and cognition. It is increasingly recognized that there is a need for a novel type of physician who can treat individuals with these conditions in an interdisciplinary fashion to best address their complexity. Few training programs have focused on the education of such practitioners.ApproachThe authors outline the development and practices of the Brain Medicine Fellowship, an innovative, competency-based fellowship program at the University of Toronto Temerty Faculty of Medicine that accepts trainees from multiple brain medicine–related specialty training programs to develop expertise in integrative assessment and treatment of complex brain disorders. The authors describe how brain medicine competencies were generated, the current assessment process, and the seminal clinical experience associated with the fellowship—the Brain Medicine Clinic—and explain how it exemplifies brain medicine in action.OutcomesThe first fellow was registered from July 2019 to December 2020. As of December 2022, 3 fellows have entered the program, with 3 more anticipated to begin in July 2023. More than 26 supervisors are associated with the fellowship, who offer a diversity of experiences for fellows to choose from in developing their individualized learning plans. The Brain Medicine Fellowship not only fosters the development of a novel type of clinician (a brain medicine specialist) but also is innovative in its educational design as one of the first nonsurgical fellowships to implement competency-based medical education and has resulted in original clinical programming in the form of the Brain Medicine Clinic, which benefits patients and their caregivers.Next StepsThe development of the Brain Medicine Fellowship continues with competency refinement and translation into entrustable professional activities and constituent milestones. A comprehensive program evaluation will be completed by 2025.
Parental Perspectives on the Impact of the COVID-19 Pandemic on Infant, Child, and Adolescent Development
Authors: Raffa Brittany J. , Heerman William J. , Lampkin Jacarra , Perrin Eliana M. , Flower Kori B. , Delamater Alan M. , Yin H. Shonna , Rothman Russell L. , Sanders Lee , Schilling Samantha 
Published: January 2023

Abstract:

Objective:
The purpose of this study is to understand how families from diverse sociodemographic backgrounds perceived the impact of the pandemic on the development of their children.

Methods:
We used a multimethod approach guided by Bronfenbrenner's Ecological Systems Theory, which identifies 5 developmental systems (micro, meso, exo, macro, and chrono). Semistructured interviews were conducted in English or Spanish with parents living in 5 geographic regions of the United States between July and September 2021. Participants also completed the COVID-19 Exposure and Family Impact Survey.

Results:
Forty-eight families participated, half of whose preferred language was Spanish, with a total of 99 children ages newborn to 19 years. Most qualitative themes pertained to developmental effects of the microsystem and macrosystem. Although many families described negative effects of the pandemic on development, others described positive or no perceived effects. Some families reported inadequate government support in response to the pandemic as causes of stress and potential negative influences on child development. As context for their infant's development, families reported a variety of economic hardships on the COVID-19 Exposure and Family Impact Survey, such as having to move out of their homes and experiencing decreased income.

Conclusion:
In addition to negative impacts, many parents perceived positive pandemic-attributed effects on their child's development, mainly from increased time for parent-child interaction. Families described economic hardships that were exacerbated by the pandemic and that potentially affect child development and insufficient government responses to these hardships. These findings hold important lessons for leaders who wish to design innovative solutions that address inequities in maternal, family, and child health.
Confounding by Conception Seasonality in Studies of Temperature and Preterm Birth: A Simulation Study
Authors: Huang Mengjiao , Strickland Matthew J. , Richards Megan , Warren Joshua L. , Chang Howard H. , Darrow Lyndsey A. 
Published: January 2023

Background:
Seasonal patterns of conception may confound acute associations between birth outcomes and seasonally varying exposures. We aim to evaluate four epidemiologic designs (time-stratified case-crossover, time-series, pair-matched case-control, and time-to-event) commonly used to study acute associations between ambient temperature and preterm births.

Methods:
We conducted simulations assuming no effect of temperature on preterm birth. We generated pseudo-birth data from the observed seasonal patterns of birth in the United States and analyzed them in relation to observed temperatures using design-specific seasonality adjustments.

Results:
Using the case-crossover approach (time-stratified by calendar month), we observed a bias (among 1,000 replicates) = 0.016 (Monte-Carlo standard error 95% CI: 0.015–0.018) in the regression coefficient for every 10°C increase in mean temperature in the warm season (May–September). Unbiased estimates obtained using the time-series approach required accounting for both the pregnancies-at-risk and their weighted probability of birth. Notably, adding the daily weighted probability of birth from the time-series models to the case-crossover models corrected the bias in the case-crossover approach. In the pair-matched case-control design, where the exposure period was matched on gestational window, we observed no bias. The time-to-event approach was also unbiased but was more computationally intensive than others.

Conclusions:
Most designs can be implemented in a way that yields estimates unbiased by conception seasonality. The time-stratified case-crossover design exhibited a small positive bias, which could contribute to, but not fully explain, previously reported associations.
Does the addition of serum antimüllerian hormone concentrations to the Framingham Risk Score and Pooled Cohort Equations improve the prediction of cardiovascular disease?
Authors: Amiri Mina , Ahmadi Narjes , Hadaegh Farzad , Mousavi Maryam , Azizi Fereidoun , Ramezani Tehrani Fahimeh 
Published: January 2023

Abstract

Objective
The current study aimed to examine the added value of serum antimüllerian hormone (AMH) concentration to the Framingham Risk Score (FRS) and Pooled Cohort Equations (PCE) in predicting the risk of cardiovascular disease (CVD) in women of reproductive age.

Methods
Women 30 years and older were considered eligible for this population-based prospective study. The univariate and multivariate Cox proportional hazard models were used to evaluate the association between the serum concentrations of AMH and the risk of CVD.

Results
In the enhanced model, which integrated AMH into FRS and PCE and was adjusted for family history of premature CVD, AMH showed a significant association with the risk of CVD during a 19-year follow-up of 800 women (hazard ratio, 0.77 [95% CI, 0.60-0.99] and hazard ratio, 0.64 [95% CI, 0.48-0.84], respectively). According to the likelihood-ratio test, the addition of AMH measurements to FRS and PCE could significantly improve the risk prediction of CVD (P = 0.02 and P < 0.001, respectively); however, the integration of this biomarker did not improve the classification of risk categories.

Conclusions
The present findings revealed that the addition of serum AMH concentrations to FRS and PCE could potentially improve the risk prediction of CVD.