bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phased telomere-to-telomere reference genome and pangenome reveal an expansion of resistance genes during apple domestication
Authors: Su Ying , Yang Xuanwen , Wang Yuwei , Li Jialei , Long Qiming , Cao Shuo , Wang Xu , Liu Zhenya , Huang Siyang , Chen Zhuyifu , Peng Yanling , Zhang Fan , Xue Hui , Cao Xuejing , Zhang Mengyan , Yisilam Gulbar , Chu Zhenzhou , Gao Yuan , Zhou Yongfeng , Liu Zhongjie , Xiao Hua , Tian Xinmin 
Published: May 2024

Abstract
The cultivated apple (Malus domestica Borkh.) is a cross-pollinated perennial fruit tree of great economic importance. Earlier versions of apple reference genomes were unphased, fragmented, and lacked comprehensive insights into the apple's highly heterozygous genome, which impeded advances in genetic studies and breeding programs. In this study, we assembled a haplotype-resolved telomere-to-telomere (T2T) reference genome for the diploid apple cultivar Golden Delicious. Subsequently, we constructed a pangenome based on 12 assemblies from wild and cultivated species to investigate the dynamic changes of functional genes. Our results revealed the gene gain and loss events during apple domestication. Compared with cultivated species, more gene families in wild species were significantly enriched in oxidative phosphorylation, pentose metabolic process, responses to salt, and abscisic acid biosynthesis process. Our analyses also demonstrated a higher prevalence of different types of resistance gene analogs (RGAs) in cultivars than their wild relatives, partially attributed to segmental and tandem duplication events in certain RGAs classes. Structural variations, mainly deletions and insertions, have affected the presence and absence of TIR-NB-ARC-LRR, NB-ARC-LRR, and CC-NB-ARC-LRR genes. Additionally, hybridization/introgression from wild species has also contributed to the expansion of resistance genes in domesticated apples. Our haplotype-resolved T2T genome and pangenome provide important resources for genetic studies of apples, emphasizing the need to study the evolutionary mechanisms of resistance genes in apple breeding.
News and Asset Pricing: A High-Frequency Anatomy of the SDF
Authors: Aleti Saketh , Bollerslev Tim 
Published: May 2024

Abstract
Utilizing real-time newswire data, together with a robustly estimated intraday stochastic discount factor (SDF), we identify and quantify the economic news that is priced. News related to monetary policy and finance on average accounts for most of the variation in the SDF, followed by news about international affairs and macroeconomic data. We also document nontrivial temporal variation in the relative importance of the news, along with marked differences in the estimated news risk premiums in the “factor zoo.” To further highlight the economic mechanisms at work, we associate the different news effects with interest rate, growth, and risk premium shocks.
Can the dose of belimumab be reduced in patients with systemic lupus erythematosus?
Authors: Rua-Figueroa Iñigo , Altabás-González Irene , Mouriño Coral , Roberts Karen , Hernández-Martín Andrea , Casafont-Solé Ivette , Font-Urgelles Judit , Román-Ivorra Jose A , de la Rubia Navarro Marta , Galindo-Izquierdo Maria , Salman-Monte Tarek C , Narváez Javier , Vidal-Montal Paola , García-Villanueva Maria Jesús , Garrote-Corral Sandra , Blazquez-Canamero Maria Angeles , Fernandez-Cid Carlos Marras , Piqueras-García Maria , Martínez-Barrio Julia , Sánchez-Lucas Marina , Cortés-Hernández Josefina , Penzo Eleonora , Calvo-Alén Jaime , de Dios Juan Ramón , Alvarez-Rodríguez Belén , Vasques-Rocha Margarida , Tomero Eva , Menor-Almagro Raul , Gandía Myriam , Gómez-Puerta José A , Frade-Sosa Beatriz , Ramos-Giráldez Consuelo , Trapero-Pérez Carmen , Diez Elvira , Moriano Clara , Muñoz-Jiménez Alejandro , Pego-Reigosa José María 
Published: May 2024

Abstract

Objectives
The aims of this study were to investigate the prevalence of dose reduction in patients with SLE treated with belimumab (BEL) in Spain, analyse treatment modalities, and determine impact on control of disease activity.

Methods
Retrospective longitudinal and multicentre study of SLE patients treated with BEL. Data on disease activity, treatments and outcomes were recorded before and after reduction (6–12 months), and they were compared.

Results
A total of 324 patients were included. The dose was reduced in 29 patients (8.9%). The dosing interval was increased in nine patients receiving subcutaneous BEL and in six patients receiving intravenous BEL. The dose per administration was reduced in 16 patients. Pre-reduction status was remission (2021 DORIS) in 15/26 patients (57.7%) and LLDAS in 23/26 patients (88.5%). After reduction, 2/24 patients (8.3%) and 3/22 patients (13.6%) lost remission at 6 months and 12 months, respectively [not statistically significant (NS)]. As for LLDAS, 2/23 patients (8.7%) and 2/21 patients (9.5%) lost their status at 6 and 12 months, respectively (NS). Significantly fewer patients were taking glucocorticoids (GCs) at their 12-month visit, although the median dose of GCs was higher at the 12-month visit (5 [0.62–8.75] vs 2.5 [0–5] at baseline).

Conclusion
Doses of BEL can be reduced with no relevant changes in disease activity—at least in the short term—in a significant percentage of patients, and most maintain the reduced dose. However, increased clinical or serologic activity may be observed in some patients. Consequently, tighter post-reduction follow-up is advisable.
Biosensor capability of the endometrium is mediated in part, by altered miRNA cargo from conceptus‐derived extracellular vesicles
Authors: De Bem Tiago H. C. , Bridi Alessandra , Tinning Haidee , Sampaio Rafael Vilar , Malo‐Estepa Irene , Wang Dapeng , Vasconcelos Elton J. R. , Nociti Ricardo Perecin , de Ávila Ana C. F. C. M. , Rodrigues Sangalli Juliano , Motta Igor Garcia , Arantes Ataíde Jr Gilmar , da Silva Júlio C. B. , Fumie Watanabe Yeda , Gonella‐Diaza Angela , da Silveira Juliano C. , Pugliesi Guilherme , Vieira Meirelles Flávio , Forde Niamh 
Published: May 2024

AbstractWe tested the hypothesis that the biosensor capability of the endometrium is mediated in part, by the effect of different cargo contained in the extracellular vesicles secreted by the conceptus during the peri‐implantation period of pregnancy. We transferred Bos taurus taurus embryos of different origin, in vivo (high developmental potential (IV)), in vitro (intermediate developmental potential (IVF)), or cloned (low developmental potential (NT)), into Bos taurus indicus recipients. Extracellular vesicles (EVs) recovered from Day 16 conceptus‐conditioned medium were characterized and their microRNA (miRNA) cargo sequenced alongside RNA sequencing of their respective endometria. There were substantial differences in the endometrial response to in vivo versus in vitro and in vivo versus cloned conceptuses (1153 and 334DEGs respectively) with limited differences between in vitro Vs cloned conceptuses (36 DEGs). The miRNA cargo contained in conceptus‐derived EVs was similar between all three groups (426 miRNA in common). Only 8 miRNAs were different between in vivo and cloned conceptuses, while only 6 miRNAs were different between in vivo and in vitro‐derived conceptuses. Treatment of endometrial epithelial cells with mimic or inhibitors for miR‐128 and miR‐1298 changed the proteomic content of target cells (96 and 85, respectively) of which mRNAs are altered in the endometrium in vivo (PLXDC2, COPG1, HSPA12A, MCM5, TBL1XR1, and TTF). In conclusion, we have determined that the biosensor capability of the endometrium is mediated in part, by its response to different EVs miRNA cargo produced by the conceptus during the peri‐implantation period of pregnancy.
Application of the Estimand Framework to Anesthesia Trials
Authors: De Silva Anurika P. , Leslie Kate , Braat Sabine , Grobler Anneke C. 
Published: May 2024

SUMMARY
Events occurring after randomization, such as use of rescue medication, treatment discontinuation, or death, are common in randomized trials. These events can change either the existence or interpretation of the outcome of interest. However, appropriate handling of these intercurrent events is often unclear. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E9(R1) addendum introduced the estimand framework, which aligns trial objectives with the design, conduct, statistical analysis, and interpretation of results. This article describes how the estimand framework can be used in anesthesia trials to precisely define the treatment effect to be estimated, key attributes of an estimand, common intercurrent events in anesthesia trials with strategies for handling them, and use of the estimand framework in a hypothetical anesthesia trial on postoperative delirium. When planning anesthesia trials, clearly defining the estimand is vital to ensure that what is being estimated is clearly understood, is clinically relevant, and helps answer the clinical questions of interest.
Lithium Exposure and Risk of Major Neurocognitive Disorders
Authors: Huang Qing , Ma Xue-qin , Chen Hui-fang 
Published: May 2024

Abstract

Background
Published studies on the association between lithium use and the decreased risk of major neurocognitive disorders (MNCDs) have shown disparities in their conclusions. We aimed to provide updated evidence of this association.

Methods
A comprehensive literature search was performed in PubMed, EMBASE, and Cochrane Library from inception until August 31, 2023. All the observational studies evaluating the association between lithium use and MNCD risk were eligible for inclusion. Pooled odds ratios (ORs) and 95% prediction intervals were computed using random-effects models.

Results
Eight studies with 377,060 subjects were included in the analysis. In the general population on the association between lithium use versus nonuse and dementia, the OR was 0.94 (95% confidence interval [CI] = 0.77–1.24). Further analysis also demonstrated that lithium use was not associated with an increased risk of Alzheimer's disease (OR = 0.69, 95% CI: 0.31–1.65). When the analysis was restricted to individuals with bipolar disorder to reduce the confounding by clinical indication, lithium exposure was also not associated with a decreased risk of MNCD (OR = 0.9, 95% CI = 0.71–1.15).

Conclusion
The results of this systematic review and meta-analysis do not support a significant association between lithium use and the risk of MNCD.
Prevalence and Risk Factors of Constipation in Trauma Patients: A Prospective Cohort Study
Authors: Liersch Kellie M. , Gumm Kellie M. , Read David J. 
Published: May 2024

BACKGROUND:
Hospitalized patients are well described as having a high prevalence of constipation. While the risks associated with constipation in trauma patients are well known, the prevalence rate is not.

OBJECTIVE:
This study aims to measure the prevalence of constipation and associated risk factors in trauma patients.

METHODS:
This study is a single-center analytic cross-sectional study on constipation in hospitalized trauma patients aged 18–65 years, admitted from January 2021 to July 2021 to the trauma service at The Royal Melbourne Hospital, a Level I major trauma and teaching hospital servicing the state of Victoria, Australia. Exclusion criteria include patients with traumatic brain injury, blunt or penetrating abdominal or spinal injuries, pregnancy, and gastrointestinal comorbidities.

RESULTS:
A total of N = 99 patients were studied, of which n = 78 (78.8%) were male with a median (interquartile range) age of 46 years (33–58). The overall prevalence of constipation was 76%. The univariate analysis demonstrated higher constipation rates in males and patients with multisystem injuries. However, in the multivariate analysis, mode of toileting and mobility were not associated with constipation after adjusting for confounding factors.

CONCLUSION:
This study demonstrated a high prevalence of constipation in all trauma patients. There is a strong association between the development of constipation in patients with multisystem injuries when compared to those with single system.
Training Opportunities for Managers in Home Health, Hospice, and Community-Based Care Settings
Authors: Nguyen Ann M. , Tallia Alfred F. , Videon Tami M. , Rosati Robert J. 
Published: May 2024

OBJECTIVE
The aim of this study was to identify areas for developing management skills-focused continuing education for managers working in home health, hospice, and community-based settings.

BACKGROUND
Healthcare managers play a vital role in organizations, yet they have a range of management training.

METHODS
Researchers conducted a cross-sectional survey of managers at a large Visiting Nurse Association. Descriptive and bivariate analyses were performed to examine confidence in management skills by respondent characteristic. Factor and cluster analyses were used to examine differences by role.

RESULTS
For all 33 management tasks, managers with 6+ years of experience reported greater confidence than managers with 0 to 5 years of experience. Tasks with the lowest confidence were budgeting, interpreting annual reports, strategic planning, measuring organizational performance, and project planning. Managers were clustered into 5 “profiles.”

CONCLUSION
Management training is not 1-size-fits-all. Healthcare organizations should consider investing in training specific to the identified low-confidence areas and manager roles to better support and develop a robust management workforce.
Correlation of Serum High-Sensitivity C-Reactive Protein, Homocysteine, and Macrophage Migration Inhibitory Factor Levels With Symptom Severity and Cognitive Function in Patients With Schizophrenia
Authors: Weng Saizheng , Zheng Rongyan , Lin Ruiqian 
Published: May 2024

ObjectiveThis trial analyzed high-sensitivity C-reactive protein (hs-CRP), homocysteine (Hcy), and macrophage migration inhibitory factor (MIF) level in serum and their correlation with symptom severity and cognitive function in patients with schizophrenia (SP).MethodsSixty-eight SP patients were enrolled in the SP group, and 68 healthy volunteers were in the control (CN) group. Serum hs-CRP, Hcy, and MIF were measured, and symptom severity was assessed with the Positive and Negative Symptom Scale (PANSS). Cognitive function was determined with the MATRICS Consensus Cognitive Battery (MCCB). The SP group was divided into high PANSS score (PANSS ≥70 points) and low PANSS score (PANSS <70 points), or the mild cognitive dysfunction group and severe cognitive dysfunction group according to the median MCCB score. The correlation between serum hs-CRP, Hcy, and MIF levels and PANSS and MCCB scores in SP patients was examined by Pearson correlation analysis.ResultsSP patients had higher serum hs-CRP, Hcy, and MIF levels and showed higher PANSS scores and lower MCCB total score. Serum hs-CRP, Hcy, and MIF levels in the high PANSS group were higher than those in the low PANSS group and in the severe cognitive dysfunction group than in the mild cognitive dysfunction group. Serum hs-CRP, Hcy, and MIF levels in SP patients were positively correlated with PANSS total score and negatively correlated with MCCB total score.ConclusionHigh serum hs-CRP, Hcy, and MIF levels in SP patients are correlated with symptom severity and cognitive dysfunction.
Specialized Pericyte Subtypes in the Pulmonary Capillary
Authors: Klouda Timothy , Kim Yunhye , Baek Seung-Han , Bhaumik Mantu , Liu Yu , Liu Tiffany , Que Jianwen , Wu Joseph C , Raby Benjamin A , de Jesus Perez Vinicio , Yuan Ke 
Published: May 2024

AbstractPericytes (PCs) play crucial roles in capillary maturation, stability, and homeostasis. Impaired PC coverage and function are implicated in various diseases, including pulmonary arterial hypertension (PAH). Challenges investigating PC biology are largely due to the lack of a concise marker, resulting in difficulty distinguishing PCs from other mural cell populations, including smooth muscle cells (SMCs) and fibroblasts (FBs). Utilizing bioinformatic analysis and RNAscope, we identified HIG hypoxia-inducible domain family member 1B (Higd1b) as a unique and conserved gene marker for PCs and generated a novel knockin mouse line,Higd1b-CreERT2, which precisely labels PCs in the lung and heart. Human lung single-cell RNAseq suggested the presence of twoHIGD1B+ PC subtypes with different functions. By lineage tracing pulmonaryHigd1b+cells exposed to hypoxiain vivo, we identified Type 1 PCs remained in the capillary network, while Type 2 PCs accumulated in the arterioles and coexpressed SMC markers and increased levels of Vimentin, associated with focal adhesion pathways. These results suggest that Type 1 PCs are specialized for supporting capillary EC homeostasis and quiescent, while Type 2 PCs are lineage active and located close to the border zone of the arterioles and capillaries, which may be motile and transition to SMC-like cells in hypoxia-induced pulmonary hypertension. The discovery of PC-type specialization in capillaries transforms our understanding of the structure, function and regulation of pulmonary capillary circulation and their contribution to vascular remodeling.
BCG immunization induced KLRG1+ NK cells show memory-like responses to mycobacterial and HIV antigens
Authors: Gunasena Manuja , Alles Mario , Demberg Thorsten , Mulhern Will , Liyanage Namal P.M. 
Published: May 2024

AbstractThe live-attenuated Bacille-Calmette-Guérin (BCG) vaccine is the only approved vaccine againstMycobacterium tuberculosis(MTB), offering broad protection against tuberculosis (TB) and other infectious diseases. ‘Trained immunity’, a process where innate immune cells develop memory-like features, is considered one of the BCG vaccine’s protective mechanisms. In this study, we investigated the effect of BCG vaccination on Natural Killer (NK) cells, a key subset of the innate immune system, and their ability to give rise to heterologous memory-like responses to HIV antigens. Here we found that BCG vaccine-induced KLRG1+ NK cells exhibit memory-like responses to both MTB and HIV antigens, as evidenced by their increased production of IFNγ upon exposure to MTB and HIV-gag antigens. This finding is of great importance, as co-infection with HIV and TB is highly relevant in Asia and Africa where BCG is administered. Understanding these responses is crucial for the development of more effective vaccines and therapeutics for both TB and HIV.
Tumor immune microenvironment permissive to metastatic progression of ING4-deficient breast cancer
Authors: Tsutsumi Emily , Macy Anne M. , LoBello Janine , Hastings Karen T. , Kim Suwon 
Published: May 2024

AbstractDeficiencies in the ING4 tumor suppressor are associated with advanced stage tumors and poor patient survival in cancer. ING4 was shown to inhibit NF-κB in several cancers. As NF-κB is a key mediator of immune response, the ING4/NF-κB axis is likely to manifest in tumor-immune modulation but has not been investigated. To characterize the tumor immune microenvironment associated with ING4-deficient tumors, three approaches were employed in this study: First, tissue microarrays composed of 246 primary breast tumors including 97 ING4-deficient tumors were evaluated for the presence of selective immune markers, CD68, CD4, CD8, and PD-1, using immunohistochemical staining. Second, an immune-competent mouse model of ING4-deficient breast cancer was devised utilizing CRISPR-mediated deletion ofIng4in aTp53deletion-derived mammary tumor cell line; mammary tumors were evaluated for immune markers using flow cytometry. Lastly, the METABRIC gene expression dataset was evaluated for patient survival related to the immune markers associated withIng4-deleted tumors. The results showed that CD68, CD4, CD8, or PD-1, was not significantly associated with ING4-deficient breast tumors, indicating no enrichment of macrophages, T cells, or exhausted T cell types. In mice,Ing4-deleted mammary tumors had a growth rate comparable toIng4-intact tumors but showed increased tumor penetrance and metastasis. Immune marker analyses ofIng4-deleted tumors revealed a significant increase in tumor-associated macrophages (Gr-1loCD11b+F4/80+) and a decrease in granzyme B-positive (GzmB+) CD4+T cells, indicating a suppressive and/or less tumoricidal immune microenvironment. The METABRIC data analyses showed that low expression ofGZMBwas significantly associated with poor patient survival, as wasING4-low expression, in the basal subtype of breast cancer. Patients withGZMB-low/ING4-low tumors had the worst survival outcomes (HR=2.80, 95% CI 1.36-5.75, p=0.0004), supportive of the idea that theGZMB-low immune environment contributes to ING4-deficient tumor progression. Collectively, the study results demonstrate that ING4-deficient tumors harbor a microenvironment that contributes to immune evasion and metastasis.
Construction of a breast cancer predictive nomogram based on diverse cell death methods and reveal tumor microenvironment characterization
Authors: Wu Rihan , Wang Zirui , Dong Chunhui , Liu Yihui , Chen Ling 
Published: May 2024

AbstractObjectiveTo develop a robust predictive model and nomogram for breast cancer (BC) linked to genes associated with diverse cell death methods.MethodsThe prognostic model was constructed using the LASSO Cox method. Model performance was assessed using K-M analysis, ROC curves, and independent prognostic analysis. Subsequently, we constructed a nomogram and analyzed differences in tumor microenvironment and drug sensitivity between different subgroups. The enrichment of differentially expressed genes between different subgroups was assessed. Additionally, we overexpressed CD24 in BC cell lines to assess its impact on cellular proliferation using CCK8 assays, migration through scratch and transwell assays, and apoptosis via flow cytometry.ResultsA prognostic model comprising twelve genes (CREB3L1, SFRP1, SHARPIN, AIFM1, IL-18, CD24, EDA2R, CRIP1, XBP1, BCL2A1, NKX3-1, and NME5) was constructed. BC patients were categorized into different subgroups, with the low-risk subgroup demonstrating superior survival. Additionally, we constructed a nomogram. The nomogram was validated as a reliable independent predictor of outcome. The enrichment analyses imply a connection between patient risk and immune response. The low-risk subgroup had a higher TME score. Patients in the high-risk group had improved responses to lapatinib, BI-2536, OSI-027, and SB505124, while those in the low-risk subgroup showed improved sensitivity to axitinib, epirubicin, fulvestrant, and olaparib. Furthermore, CD24 overexpression was found to promote proliferation and migration, while inhibiting apoptosis.ConclusionThese findings contribute to the individualization of treatment and aid in uncovering the tumor microenvironment characterization for BC patients.