bluuebunny/crossref_metadata_2025_split huggingface dataset:
A 49-bp deletion of PmAP2L results in a double flower phenotype in Prunus mume
Authors: Liu Weichao , Zheng Tangchun , Qiu Like , Guo Xiaoyu , Li Ping , Yong Xue , Li Lulu , Ahmad Sagheer , Wang Jia , Cheng Tangren , Zhang Qixiang 
Published: December 2023

Abstract
The double flower is an important trait with substantial ornamental value. While mutations in PETALOSA TOE-type or AG (AGAMOUS) genes play a crucial role in enhancing petal number in ornamental plants, the complete mechanism underlying the formation of double flowers remains to be fully elucidated. Through the application of bulked segregant analysis (BSA), we identified a novel gene, APETALA2-like (PmAP2L), characterized by a 49-bp deletion in double-flowered Prunus mume. β-Glucuronidase (GUS) staining and luciferase reporter assays confirmed that the 49-bp deletion in PmAP2L reduced its binding with Pmu-miRNA172a. Phylogenetic analysis and microsynteny analysis suggested that PmAP2L was not a PETALOSA TOE-type gene, and it might be a new gene controlling the formation of double flower in P. mume. Subsequently, overexpression of PmAP2L-D in tobacco led to a significant rise in the number of stamens and the conversion of stamens to petals. Furthermore, silencing of the homologue of RC5G0530900 in rose significantly reduced the number of petals. Using transient gene expression in P. mume flower buds, we determined the functional differences between PmAP2L-D and PmAP2-S in controlling flower development. Meanwhile, DNA-affinity purification sequencing (DAP-seq), yeast hybrid assays and luciferase reporter assays indicated that PmAP2L negatively regulated the floral organ identity genes by forming a repressor complex with PmTPL and PmHDA6/19. Overall, these findings indicate that the variation in PmAP2L is associated with differences in the regulation of genes responsible for floral organ identity, providing new insights into the double-flower trait and double-flower breeding in plants.
Deciphering the intricate hierarchical gene regulatory network: unraveling multi-level regulation and modifications driving secondary cell wall formation
Authors: Wei Zhigang , Wei Hairong 
Published: December 2023

Abstract
Wood quality is predominantly determined by the amount and the composition of secondary cell walls (SCWs). Consequently, unraveling the molecular regulatory mechanisms governing SCW formation is of paramount importance for genetic engineering aimed at enhancing wood properties. Although SCW formation is known to be governed by a hierarchical gene regulatory network (HGRN), our understanding of how a HGRN operates and regulates the formation of heterogeneous SCWs for plant development and adaption to ever-changing environment remains limited. In this review, we examined the HGRNs governing SCW formation and highlighted the significant key differences between herbaceous Arabidopsis and woody plant poplar. We clarified many confusions in existing literatures regarding the HGRNs and their orthologous gene names and functions. Additionally, we revealed many network motifs including feed-forward loops, feed-back loops, and negative and positive autoregulation in the HGRNs. We also conducted a thorough review of post-transcriptional and post-translational aspects, protein–protein interactions, and epigenetic modifications of the HGRNs. Furthermore, we summarized how the HGRNs respond to environmental factors and cues, influencing SCW biosynthesis through regulatory cascades, including many regulatory chains, wiring regulations, and network motifs. Finally, we highlighted the future research directions for gaining a further understanding of molecular regulatory mechanisms underlying SCW formation.
A surgically salvaged case: emergency Root-Commando procedure for infective endocarditis and chronic dissecting aneurysm of the sinus of Valsalva
Authors: Nosaka Yu , Kato Hiroki , No Hironari 
Published: December 2023

Abstract
The Commando procedure for infective endocarditis is a high-risk intervention. However, infective endocarditis involving the intervalvular fibrosa is fatal in the absence of surgery. A 41-year-old man with no medical history visited a doctor with chest pain and dyspnoea. Ascending aortic dissection and vegetation on the mitral valve were noted on echocardiography, so he was transferred to our hospital. The diagnosis was dissecting aneurysm of the sinus of Valsalva and acute heart failure due to aortic regurgitation, mitral regurgitation and infective endocarditis. We decided on emergency surgery. Intraoperatively, we confirmed abscess extending to the left atrial roof and destruction of the intervalvular fibrosa, so we performed the Root-Commando procedure. The patient was saved and discharged 47 days after transfer to our hospital through the reoperation on postoperative day 30.
Epidemiology, clinical outcomes and risk factors of third-generation cephalosporin-resistant Escherichia coli hospitalized infections in remote Australia—a case–control study
Authors: Camilleri Shayne , Tsai Danny , Langham Freya , Ullah Shahid , Chiong Fabian 
Published: December 2023

Abstract

Background
Incidence of third-generation cephalosporin-resistant (3GCR) Escherichia coli infections has increased in remote Australia from 2012 to 2018.

Objectives
To describe the epidemiology of 3GCR E. coli in Central Australia.

Methods
A case–control study was conducted in the primary Central Australian hospital. Patient characteristics, antibiotic usage and clinical outcomes were compared between adult hospitalizations with 3GCR and susceptible E. coli isolates in 2018–19. Poisson regression was used to compare the incidence of 3GCR hospitalizations between Indigenous and non-Indigenous individuals. Patient characteristics and antibiotic usage were tested for associations with 3GCR isolates using univariate analysis.

Results
A total of 889 E. coli isolates were identified, of which 187 (21%) were 3GCR. The incidence of 3GCR E. coli infection was 2.15 per 1000 person-years, with an incidence rate ratio of 6.8 (95% CI 4.6–10.1) between Indigenous and non-Indigenous individuals. When compared with the control group, 3GCR E. coli infections were associated with a higher Charlson comorbidity index (CCI ≥3 in 30.7% versus 15.0%, P &lt; 0.001) and were more commonly healthcare associated (52.4% versus 26.7%, P &lt; 0.001). A higher 1 year mortality was observed in the 3GCR group after adjustment for comorbidity (OR = 4.43, P = 0.002), but not at 30 days (2.4% versus 0.0%, P = 0.2). The 3GCR group used more antibiotics in the past 3 months (OR = 5.75, P &lt; 0.001) and 12 months (OR = 3.65, P &lt; 0.001).

Conclusions
3GCR E. coli infections in remote Australia disproportionally affect Indigenous peoples and are associated with a high burden of comorbidities and antibiotic use. Strategies to enhance antimicrobial stewardship should be considered in this remote setting.
Patient-Centric Quantitative Microsampling for Accurate Determination of Urine Albumin to Creatinine Ratio (UACR) in a Clinical Setting
Authors: Löfgren Lars , von Euler Chelpin Marianne , Bhat Maria , Althage Magnus , Hober Andreas , Edfors Fredrik , Ruckh Tim , Challis Benjamin , Davidsson Pia , Miliotis Tasso 
Published: December 2023

Abstract

Background
Developing and implementing new patient-centric strategies for drug trials lowers the barrier to participation for some patients by reducing the need to travel to research sites. In early chronic kidney disease (CKD) trials, albuminuria is the key measure for determining treatment effect prior to pivotal kidney outcome trials.

Methods
To facilitate albuminuria sample collection outside of a clinical research site, we developed 2 quantitative microsampling methods to determine the urinary albumin to creatinine ratio (UACR). Readout was performed by LC-MS/MS.

Results
For the Mitra device the within-batch precision (CV%) was 2.8% to 4.6% and the between-batch precision was 5.3% to 6.1%. Corresponding data for the Capitainer device were 4.0% to 8.6% and 6.7% to 9.0%, respectively. The storage stability at room temperature for 3 weeks was 98% to 103% for both devices. The recovery for the Mitra and Capitainer devices was 104% (SD 7.0%) and 95 (SD 7.4%), respectively. The inter-assay comparison of UACR assessment generated results that were indistinguishable regardless of microsampling technique. The accuracy based on LC-MS/MS vs analysis of neat urine using a clinical chemistry analyzer was assessed in a clinical setting, resulting in 102 ± 8.0% for the Mitra device and 95 ± 10.0% for the Capitainer device.

Conclusions
Both UACR microsampling measurements exhibit excellent accuracy and precision compared to a clinical chemistry analyzer using neat urine. We applied our patient-centric sampling strategy to subjects with heart failure in a clinical setting. Precise UACR measurements using quantitative microsampling at home would be beneficial in clinical drug development for kidney therapies.
Standing up to problematic content on social media: which objection strategies draw the audience’s approval?
Authors: Zhao Pengfei , Bazarova Natalie N , DiFranzo Dominic , Hui Winice , Kizilcec René F , Margolin Drew 
Published: December 2023

Abstract
Problematic content on social media can be countered through objections raised by other community members. While intended to deter offenses, objections can influence the surrounding audience observing the interaction, leading to their collective approval or disapproval. The results of an experiment manipulating seven types of objections against common types of offenses indicate audiences’ support for objections that implore via appeals and disapproval of objections that threaten the offender, as they view the former as more moral, appropriate, and effective compared to the latter. Furthermore, audiences tend to prefer more benign and less threatening objections regardless of the offense severity (following the principle of “taking the high road”) instead of objections proportionate to the offense (“an eye for an eye”). Taken together, these results show how objections to offensive behaviors may impact collective perceptions on social media, paving the way for interventions to foster effective objection strategies in social media discussions.
Reliability assessment of methylthioadenosine phosphorylase immunohistochemistry as a surrogate biomarker for CDKN2A homozygous deletion in adult-type IDH-mutant diffuse gliomas
Authors: Gundogdu Fatma , Babaoglu Berrin , Soylemezoglu Figen 
Published: December 2023

Abstract
According to the 2021 World Health Organization classification of brain tumors, astrocytomas containing a CDKN2A/B homozygous deletion (HD) are designated as grade 4 even when no microvascular proliferation and/or necrosis is present. In this study, we aimed to investigate the relationship between CDKN2A HD and loss of methylthioadenosine phosphorylase (MTAP) expression in adult-type IDH-mutant gliomas and to assess the sensitivity and specificity of MTAP immunohistochemistry (IHC) along with interobserver agreement as a surrogate biomarker for CDKN2A HD. Eighty-eight astrocytomas and 71 oligodendrogliomas cases that were diagnosed between 2014 and 2021 at Hacettepe University were selected and tissue microarrays were conducted to perform CDKN2A fluorescence in situ hybridization and MTAP IHC. Twenty-five (15.7%) cases harbored CDKN2A HD. MTAP loss was detected in 28 (15.7%) cases by the first observer and 27 (17%) cases by the second observer. The sensitivity and specificity of MTAP were calculated as 88% and 95.52%-96.27% for 2 observers. A very good/perfect agreement was noted between the observers (Cohen kappa coefficient = 0.938). Intratumoral heterogeneity was observed in 4 cases. MTAP IHC was found to be a reliable surrogate biomarker as a possible alternative to CDKN2A HD identification with a high sensitivity and specificity along with high interobserver agreement.
Association between the telecommuting environment and somatic symptoms among teleworkers in Japan
Authors: Kanamori Satoru , Tabuchi Takahiro , Kai Yuko 
Published: December 2023

Abstract
Objectives: This study aimed to clarify the association between telecommuting environments and somatic symptoms among teleworkers in Japan.
Methods: This cross-sectional study, conducted from September 27 to October 29, 2021, used data from the Japan COVID-19 and Society Internet Survey (JACSIS study) in Japan. Of the 31 000 male and female respondents, who were Japanese residents aged 15-79 years and were randomly selected from the panel members of an internet survey company, 4569 home-based teleworkers were finally included in the analysis; 26 431 respondents who met the exclusion criteria were excluded. The analysis included 4 cut-offs (≥4, 8, 12, and 16 points) for somatic symptoms on the Somatic Symptom Scale-8 as objective variables, and the telecommuting environment, such as having adequate desk light and a quiet environment, as explanatory variables. Adjusted Poisson regression analysis was conducted using demographic variables as covariates.
Results: The prevalence ratio (PR) for somatic symptoms increased significantly as the number of poor telecommuting conditions increased, regardless of the cut-off value for somatic symptoms or the frequency of teleworking. In the telecommuting environment, the PR for somatic symptoms was significantly higher for the following 6 items: poor teleworking space to concentrate, inadequate foot space, poor communication environment, poor space for relaxation, noise, and inappropriate temperature and humidity.
Conclusions: These results suggest that for home-based teleworkers, the more inadequate the telecommuting environment, especially in the aforementioned 6 areas, the higher the likelihood of somatic symptoms. Improving these environments may be useful in preventing various somatic symptoms.
Whole-exome sequencing uncovers a novel EFEMP2 gene variant (c.C247T) associated with dominant nonsyndromic thoracic aortic aneurysm
Authors: Sadeghipour Parham , Valuian Marzieh , Ghasemi Serwa , Rafiee Farnaz , Pourirahim Maryam , Mahmoodian Mehran , Maleki Majid , Kalayinia Samira 
Published: December 2023

Abstract

Background
Thoracic aortic aneurysm (TAA) is a multifactorial disorder. Familial TAA, which is more clinically aggressive, is associated with a high risk of lethal dissection or rupture. Genetic evaluation can provide TAA patients with personalized treatment and help in predicting risk to family members.

Objective
The purpose of this investigation was to report a likely pathogenic variant in the EFEMP2 gene that may contribute to TAA in a family with a documented history of the condition.

Methods
In the index patient, the causative genetic predisposition was identified using whole-exome sequencing. The potential likely pathogenic effect of the candidate variant was further analyzed through bioinformatics analysis, homology modeling, and molecular docking.

Results
The results revealed a likely pathogenic heterozygous variant, c.247C&gt;T p.Arg83Cys, in exon 4 of the EFEMP2 gene (NM_016938), which was predicted to have disease-causing effects by MutationTaster, PROVEAN, SIFT, and CADD (phred score = 27.6).

Conclusion
In this study, a likely pathogenic variant in the EFEMP2 gene was identified in an Iranian family with a dominant pattern of autosomal inheritance of TAA. This finding underscores the importance of conducting molecular genetic evaluations in families with nonsyndromic TAA and the significance of early detection of at-risk family members.
Galactic cosmic ray transport in the absence of resonant scattering
Authors: Pezzi O , Blasi P 
Published: December 2023

ABSTRACT
Galactic cosmic ray transport relies on the existence of turbulence on scales comparable with the gyration radius of the particles and with wavenumber vector oriented along the local magnetic field. In the standard picture, in which turbulence is injected at large scales and cascades down to smaller scales, it is all but guaranteed that the turbulent fluctuations at the scales relevant for resonant scattering may be present, either because of anisotropic cascading or because of the onset of damping processes. This raises questions on the nature of cosmic ray scattering, especially at energies ≳1 TeV, where self-generation is hardly relevant. Here, by means of numerical simulations of charged test particles in a prescribed magnetic field, we perform a gedankenexperiment aimed at investigating particle diffusion in a situation in which turbulence is mainly present at large scales, and discuss possible implications of this set-up for cosmic ray transport phenomenology.
Ruling out strongly interacting dark matter–dark radiation models from joint observations of cosmic microwave background and quasar absorption spectra
Authors: Chatterjee Atrideb , Mitra Sourav , Banerjee Amrita 
Published: December 2023

ABSTRACT
The cold dark matter paradigm provides a remarkably good description of the Universe’s large-scale structure. However, some discrepancies exist between its predictions and observations at very small sub-galactic scales. To address these issues, the consideration of a strong interaction between dark matter particles and dark radiation emerges as an intriguing alternative. In this study, we explore the constraints on those models using joint observations of cosmic microwave background and quasars absorption spectra with our previously built parameter estimation package cosmoreionmc. At 2σ confidence limits, this analysis rules out the strongly interacting dark matter–dark radiation models within the recently proposed effective theory of structure formation framework, representing the most stringent constraint on those models to the best of our knowledge. Future research using a 21-cm experiment holds the potential to reveal stronger constraints or uncover hidden interactions within the dark sector.
Strongly magnetized accretion in two ultracompact binary systems
Authors: Maccarone Thomas J , Kupfer Thomas , Casarrubias Edgar Najera , Sandoval Liliana E Rivera , Shaw Aarran W , Britt Christoper T , van Roestel Jan , Zurek David R 
Published: December 2023

ABSTRACT
We present the discoveries of two of AM CVn systems, Gaia14aae and SDSS J080449.49+161624.8, which show X-ray pulsations at their orbital periods, indicative of magnetically collimated accretion. Both also show indications of higher rates of mass transfer relative to the expectations from binary evolution driven purely by gravitational radiation, based on existing optical data for Gaia14aae, which show a hotter white dwarf temperature than expected from standard evolutionary models, and X-ray data for SDSS J080449.49+161624.8 which show a luminosity 10−100 times higher than those for other AM CVn at similar orbital periods. The higher mass transfer rates could be driven by magnetic braking from the disc wind interacting with the magnetosphere of the tidally locked accretor. We discuss implications of this additional angular momentum transport mechanism for evolution and gravitational wave detectability of AM CVn objects.
Simulations of Sequence Evolution: How (Un)realistic They Are and Why
Authors: Trost Johanna , Haag Julia , Höhler Dimitri , Jacob Laurent , Stamatakis Alexandros , Boussau Bastien 
Published: December 2023

Abstract

Motivation
Simulating multiple sequence alignments (MSAs) using probabilistic models of sequence evolution plays an important role in the evaluation of phylogenetic inference tools and is crucial to the development of novel learning-based approaches for phylogenetic reconstruction, for instance, neural networks. These models and the resulting simulated data need to be as realistic as possible to be indicative of the performance of the developed tools on empirical data and to ensure that neural networks trained on simulations perform well on empirical data. Over the years, numerous models of evolution have been published with the goal to represent as faithfully as possible the sequence evolution process and thus simulate empirical-like data. In this study, we simulated DNA and protein MSAs under increasingly complex models of evolution with and without insertion/deletion (indel) events using a state-of-the-art sequence simulator. We assessed their realism by quantifying how accurately supervised learning methods are able to predict whether a given MSA is simulated or empirical.

Results
Our results show that we can distinguish between empirical and simulated MSAs with high accuracy using two distinct and independently developed classification approaches across all tested models of sequence evolution. Our findings suggest that the current state-of-the-art models fail to accurately replicate several aspects of empirical MSAs, including site-wise rates as well as amino acid and nucleotide composition.
Beyond MitoCarta—expanding the list of candidate proteins involved in mitochondrial functions using a biological network approach
Authors: Leyfer Dmitriy , Fetterman Jessica L 
Published: December 2023

AbstractMitochondrial diseases are the result of pathogenic variants in genes involved in the diverse functions of the mitochondrion. A comprehensive list of mitochondrial genes is needed to improve gene prioritization in the diagnosis of mitochondrial diseases and development of therapeutics that modulate mitochondrial function. MitoCarta is an experimentally derived catalog of proteins localized to mitochondria. We sought to expand this list of mitochondrial proteins to identify proteins that may not be localized to the mitochondria yet perform important mitochondrial functions. We used a computational approach to assign statistical significance to the overlap between STRING database gene network neighborhoods and MitoCarta proteins. Using a data-driven stringent significance threshold, 2059 proteins that were not located in MitoCarta were identified, which we termed mitochondrial proximal (MitoProximal) proteins. We identified all of the oxidative phosphorylation complex subunits and 90% of 149 genes that contain confirmed oxidative phosphorylation disease causal variants, lending validation to our methodology. Among the MitoProximal proteins, 134 are annotated to be localized to mitochondria but are not in the MitoCarta 3.0 database. We extend MitoCarta nearly 3-fold, generating a more comprehensive list of mitochondrial genes, a resource to facilitate the identification of pathogenic variants in mitochondrial and metabolic diseases.
Risk Factors for Invasive Fungal Infection in Lung Transplant Recipients on Universal Antifungal Prophylaxis
Authors: Huggins Jonathan P , Arthur David , Chow Shein-Chung , Pease Robert , Stanly Kelly , Workman Adrienne , Reynolds John , Alexander Barbara D 
Published: December 2023

Abstract

Background
Many centers use universal antifungal prophylaxis after lung transplant, but risk factors for invasive fungal infection (IFI) in this setting are poorly described.­

Methods
This retrospective, single-center cohort study including 603 lung transplant recipients assessed risk factors for early (within 90 days of transplant) invasive candidiasis (IC) and invasive mold infection (IMI) and late (90–365 days after transplant) IMI using Cox proportional hazard regression.

Results
In this cohort, 159 (26.4%) patients had 182 IFIs. Growth of yeast on donor culture (hazard ratio [HR], 3.30; 95% CI, 1.89–5.75) and prolonged length of stay (HR, 1.02; 95% CI, 1.01–1.03) were associated with early IC risk, whereas transplantation in 2016 or 2017 (HR, 0.21; 95% CI, 0.06–0.70; HR, 0.25; 95% CI, 0.08–0.80, respectively) and female recipient sex (HR, 0.53; 95% CI, 0.30–0.93) were associated with reduced risk. Antimold therapy (HR, 0.21; 95% CI, 0.06–0.78) was associated with lower early IMI risk, and female donor sex (HR, 0.40; 95% CI, 0.22–0.72) was associated with lower late IMI risk. Recent rejection was a risk factor for late IMI (HR, 1.73; 95% CI, 1.02–2.95), and renal replacement therapy predisposed to early IC, early IMI, and late IMI (HR, 5.67; 95% CI, 3.01–10.67; HR, 7.54; 95% CI, 1.93–29.45; HR, 5.33; 95% CI, 1.46–19.49, respectively).

Conclusions
In lung transplant recipients receiving universal antifungal prophylaxis, risk factors for early IC, early IMI, and late IMI differ.