bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rethinking coagulation: from enzymatic cascade and cell-based reactions to a convergent model involving innate immune activation
Authors: Yong Jun , Toh Cheng-Hock 
Published: October 2023

Abstract
Advancements in the conceptual thinking of hemostasis and thrombosis have been catalyzed by major developments within health research over several decades. The cascade model of coagulation was first described in the 1960s, when biochemistry gained prominence through innovative experimentation and technical developments. This was followed by the cell-based model, which integrated cellular coordination to the enzymology of clot formation and was conceptualized during the growth period in cell biology at the turn of the millennium. Each step forward has heralded a revolution in clinical therapeutics, both in procoagulant and anticoagulant treatments to improve patient care. In current times, the COVID-19 pandemic may also prove to be a catalyst: thrombotic challenges including the mixed responses to anticoagulant treatment and the vaccine-induced immune thrombotic thrombocytopenia have exposed limitations in our preexisting concepts while simultaneously demanding novel therapeutic approaches. It is increasingly clear that innate immune activation as part of the host response to injury is not separate but integrated into adaptive clot formation. Our review summarizes current understanding of the major molecules facilitating such a cross talk between immunity, inflammation and coagulation. We demonstrate how such effects can be layered upon the cascade and cell-based models to evolve conceptual understanding of the physiology of immunohemostasis and the pathology of immunothrombosis.
Optimizing platelet transfusion through a personalized deep learning risk assessment system for demand management
Authors: Engelke Merlin , Schmidt Cynthia Sabrina , Baldini Giulia , Parmar Vicky , Hosch René , Borys Katarzyna , Koitka Sven , Turki Amin T. , Haubold Johannes , Horn Peter A. , Nensa Felix 
Published: October 2023

Abstract
Platelet demand management (PDM) is a resource-consuming task for physicians and transfusion managers of large hospitals. Inpatient numbers and institutional standards play significant roles in PDM. However, reliance on these factors alone commonly results in platelet shortages. Using data from multiple sources, we developed, validated, tested, and implemented a patient-specific approach to support PDM that uses a deep learning–based risk score to forecast platelet transfusions for each hospitalized patient in the next 24 hours. The models were developed using retrospective electronic health record data of 34 809 patients treated between 2017 and 2022. Static and time-dependent features included demographics, diagnoses, procedures, blood counts, past transfusions, hematotoxic medications, and hospitalization duration. Using an expanding window approach, we created a training and live-prediction pipeline with a 30-day input and 24-hour forecast. Hyperparameter tuning determined the best validation area under the precision-recall curve (AUC-PR) score for long short-term memory deep learning models, which were then tested on independent data sets from the same hospital. The model tailored for hematology and oncology patients exhibited the best performance (AUC-PR, 0.84; area under the receiver operating characteristic curve [ROC-AUC], 0.98), followed by a multispecialty model covering all other patients (AUC-PR, 0.73). The model specific to cardiothoracic surgery had the lowest performance (AUC-PR, 0.42), likely because of unexpected intrasurgery bleedings. To our knowledge, this is the first deep learning–based platelet transfusion predictor enabling individualized 24-hour risk assessments at high AUC-PR. Implemented as a decision-support system, deep-learning forecasts might improve patient care by detecting platelet demand earlier and preventing critical transfusion shortages.
The challenge of clinical end points in sickle cell disease
Authors: Ataga Kenneth I. 
Published: October 2023

Abstract
As most patients with sickle cell disease (SCD) do not have access to curative therapies, the availability of drug therapies that can modify disease severity remains highly desirable. Despite an increased understanding of the pathophysiology of SCD, only 4 drugs are approved by the US Food and Drugs Administration. Most drug trials in SCD have involved the use of acute pain episodes as the primary clinical end point. These studies have typically been to prevent or shorten the duration of such episodes. To date, no drug has received regulatory approval for shortening the duration of acute vaso-occlusive complications, likely highlighting the complex pathophysiology of acute pain episodes. Trials to prevent acute pain episodes have largely evaluated those episodes requiring health care use as a surrogate end point. However, with differences in culture and health care practices among countries, health care use may not reliably predict clinically important effects on acute pain episodes. This article discusses issues related to the use of health care use as the primary end point for prevention trials of acute pain episodes and highlights the importance of evaluating patient-reported outcomes as well as other SCD-related complications as outcome measures.
N6-methyladenosine-modified oncofetal lncRNA MIR4435-2HG contributed to stemness features of hepatocellular carcinoma cells by regulating rRNA 2′-O methylation
Authors: Zhu Yiqing , Xiao Bang , Liu Meng , Chen Meiting , Xia Ningqi , Guo Haiyan , Huang Jinfeng , Liu Zhiyong , Wang Fang 
Published: October 2023

Abstract
Background
The unique expression pattern endows oncofetal genes with great value in cancer diagnosis and treatment. However, only a few oncofetal genes are available for clinical use and the underlying mechanisms that drives the fetal-like reprogramming of cancer cells remain largely unknown.

Methods
Microarray assays and bioinformatic analyses were employed to screen for potential oncofetal long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC). The expression levels of MIR4435-2HG, NOP58 ribonucleoprotein (NOP58), insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) and stem markers were detected by quantitative polymerase chain reaction. The 2′-O-methylation (2′-O-Me) status of rRNA were detected through reverse transcription at low dNTP concentrations followed by PCR. The regulation of MIR4435-2HG by IGF2BP1 was explored by RNA immunoprecipitation (RIP), methylated RIP (MeRIP) and dual-luciferase assays. The interaction between MIR4435-2HG and NOP58 was investigated by RNA Pulldown, RIP and protein stability assays. In vitro and in vivo function assays were performed to detect the roles of MIR4435-2HG/NOP58 in HCC.

Results
MIR4435-2HG was an oncofetal lncRNA associated with poor prognosis in HCC. Functional experiments showed that overexpression of MIR4435-2HG remarkably enhanced the stem-cell properties of HCC cells, promoting tumorigenesis in vitro and in vivo. Mechanically, MIR4435-2HG directly bound NOP58 and IGF2BP1. IGF2BP1 upregulated MIR4435-2HG expression in HCC through N6-methyladenosine (m6A) modification. Moreover, MIR4435-2HG protected NOP58 from degradation, which raised rRNA 2’-O-Me levels and promoted internal ribosome entry site (IRES)-dependent translation of oncogenes.

Conclusions
This study identified an oncofetal lncRNA MIR4435-2HG, characterized the role of MIR4435-2HG/NOP58 in stemness maintenance and proliferation of HCC cells, and confirmed m6A as a ‘driver’ that reactivated MR4435-2HG expression in HCC.
Cellular senescence in skeletal disease: mechanisms and treatment
Authors: He Xu , Hu Wei , Zhang Yuanshu , Chen Mimi , Ding Yicheng , Yang Huilin , He Fan , Gu Qiaoli , Shi Qin 
Published: October 2023

AbstractThe musculoskeletal system supports the movement of the entire body and provides blood production while acting as an endocrine organ. With aging, the balance of bone homeostasis is disrupted, leading to bone loss and degenerative diseases, such as osteoporosis, osteoarthritis, and intervertebral disc degeneration. Skeletal diseases have a profound impact on the motor and cognitive abilities of the elderly, thus creating a major challenge for both global health and the economy. Cellular senescence is caused by various genotoxic stressors and results in permanent cell cycle arrest, which is considered to be the underlying mechanism of aging. During aging, senescent cells (SnCs) tend to aggregate in the bone and trigger chronic inflammation by releasing senescence-associated secretory phenotypic factors. Multiple signalling pathways are involved in regulating cellular senescence in bone and bone marrow microenvironments. Targeted SnCs alleviate age-related degenerative diseases. However, the association between senescence and age-related diseases remains unclear. This review summarises the fundamental role of senescence in age-related skeletal diseases, highlights the signalling pathways that mediate senescence, and discusses potential therapeutic strategies for targeting SnCs.
Graphical Abstract
Comparative chloroplast genomics reveals the phylogeny and the adaptive evolution of Begonia in China
Authors: Xiong Chao , Huang Yang , Li Zhenglong , Wu Lan , Liu Zhiguo , Zhu Wenjun , Li Jianhui , Xu Ran , Hong Xin 
Published: October 2023

Abstract
Background
The Begonia species are common shade plants that are mostly found in southwest China. They have not been well studied despite their medicinal and decorative uses because gene penetration, decreased adaptability, and restricted availability are all caused by frequent interspecific hybridization.

Result
To understand the patterns of mutation in the chloroplast genomes of different species of Begonia, as well as their evolutionary relationships, we collected seven Begonia species in China and sequenced their chloroplast genomes. Begonia species exhibit a quadripartite structure of chloroplast genomes (157,634 − 169,694 bp), consisting of two pairs of inverted repeats (IR: 26,529 − 37,674 bp), a large single copy (LSC: 75,477 − 86,500 bp), and a small single copy (SSC: 17,861 − 18,367 bp). 128–143 genes (comprising 82–93 protein-coding genes, 8 ribosomal RNAs, and 36–43 transfer RNAs) are found in the chloroplast genomes. Based on comparative analyses, this taxon has a relatively similar genome structure. A total of six substantially divergent DNA regions (trnT-UGU-trnL-UAA, atpF-atpH, ycf4-cemA, psbC-trnS-UGA, rpl32-trnL-UAG, and ccsA-ndhD) are found in the seventeen chloroplast genomes. These regions are suitable for species identification and phylogeographic analysis. Phylogenetic analysis shows that Begonia species that were suited to comparable environments grouped in a small clade and that all Begonia species formed one big clade in the phylogenetic tree, supporting the genus’ monophyly. In addition, positive selection sites were discovered in eight genes (rpoC1, rpoB, psbE, psbK, petA, rps12, rpl2, and rpl22), the majority of which are involved in protein production and photosynthesis.

Conclusion
Using these genome resources, we can resolve deep-level phylogenetic relationships between Begonia species and their families, leading to a better understanding of evolutionary processes. In addition to enhancing species identification and phylogenetic resolution, these results demonstrate the utility of complete chloroplast genomes in phylogenetically and taxonomically challenging plant groupings.
Vitamin D and biomarkers of inflammation and oxidative stress among pregnant women: a systematic review of observational studies
Authors: Motamed Soudabe , Anari Razieh , Motamed Somayeh , Amani Reza 
Published: October 2023

Abstract
Objective
This systematic review aimed to map the evidence evaluated the relationship between vitamin D and redox and inflammatory status during gestation.

Methods
Three databases (PubMed/MEDLINE, Scopus, and Web of Science (WoS)) and reference list of included documents were searched for related observational studies published until 2nd October 2023. To determine the quality of the selected observational studies, the Newcastle-Ottawa Scale (NOS) was used.

Results
After a primary search of three databases, 19492records were appeared. When duplicates and irrelevant documents were removed, 14 articles were found to have eligible criteria. The design of the identified studies was cross-sectional, case-control and cohort. Evidence showed an adverse association between 25(OH)D and the biomarkers of inflammation, such as high-sensitivity C-reactive protein (hs-CRP), Interleukin-1beta (IL-1β), Interleukin-6 (IL-6), and tumor necrosis factor- alfa (TNF-α) during pregnancy. On the contrary, some studies represented that 25(OH)D positively correlated with hs-CRP in the cord blood. One study suggested a direct association between serum concentrations of 25(OH)D and Interleukin-8 (IL-8), macrophage inflammatory protein (MIP), and TNF-α levels in mothers with gestational diabetes mellitus (GDM). A case-control study showed that lower serum concentration of 25(OH)D positively correlated with total antioxidant capacity (TAC) levels in participants.

Conclusions
Evidence confirmed the supposition of the direct relationship between vitamin D levels and biomarkers with anti-inflammatory and anti-oxidative properties. However, the Existence of inconsistent evidence confirms the need for further studies in mothers with GDM and hypertensive disorders.

PROSPERO registration code
CRD42020202600.
Limited effects of azithromycin on the oropharyngeal microbiome in children with CF and early pseudomonas infection
Authors: Wagner Brandie D. , Zemanick Edith T. , Sagel Scott D. , Robertson Charles E. , Stevens Mark J. , Mayer-Hamblett Nicole , Retsch-Bogart George , Ramsey Bonnie W. , Harris J. Kirk 
Published: October 2023

Abstract
Background
Tobramycin inhalation solution (TIS) and chronic azithromycin (AZ) have known clinical benefits for children with CF, likely due to antimicrobial and anti-inflammatory activity. The effects of chronic AZ in combination with TIS on the airway microbiome have not been extensively investigated. Oropharyngeal swab samples were collected in the OPTIMIZE multicenter, randomized, placebo-controlled trial examining the addition of AZ to TIS in 198 children with CF and early P. aeruginosa infection. Bacterial small subunit rRNA gene community profiles were determined. The effects of TIS and AZ were assessed on oropharyngeal microbial diversity and composition to uncover whether effects on the bacterial community may be a mechanism of action related to the observed changes in clinical outcomes.

Results
Substantial changes in bacterial communities (total bacterial load, diversity and relative abundance of specific taxa) were observed by week 3 of TIS treatment for both the AZ and placebo groups. On average, these shifts were due to changes in non-traditional CF taxa that were not sustained at the later study visits (weeks 13 and 26). Bacterial community measures did not differ between the AZ and placebo groups.

Conclusions
This study provides further evidence that the mechanism for AZ’s effect on clinical outcomes is not due solely to action on airway microbial composition.
The synergistic effects of soil-applied boron and foliar-applied silicon on cotton fiber quality and yield
Authors: da Silva Liber Lopes Priscilla Maria , Campos Cid Naudi Silva , Teodoro Paulo Eduardo , Costa Milton Garcia , de Souza Júnior Jonas Pereira , de Mello Prado Renato 
Published: October 2023

AbstractStudies of boron (B) and silicon (Si) synergy in cotton crops have shown promising results; however, the focus was on the foliar application of B and Si. Nonetheless, B is an element with little mobility in the plant and its best form of application is in the soil. Thus, the objective of this study was to evaluate the synergistic effect of soil applied B and foliar applied sSi on fiber quality and crop yield of cotton. For this purpose, a field experiment was carried out using cotton cultivar FM 985 GLTP. The soil’s B in the experimental site is classified as low for cotton cultivation. The experiment was conducted in a randomized complete-block design, in a 3 × 2 factorial scheme, with three doses of B: 0.0 kg ha−1 (deficiency), 2.0 kg ha−1 (recommended dose), and 4.0 kg ha−1 (high dose) in the absence and presence (920 g L−1) of Si, with four replications. One week after the 4th application of Si, B and Si leaf content was determined. At boll opening, crop yield was estimated, and fiber quality analysis was realized. Boron deficiency reduced cotton yield, in 11 and 9%, compared to the application of 2 and 4 kg ha−1 of B, respectively. The presence of Si, however, increased plant yield in 5% in the treatments with 0 and 2 kg ha−1 of B, respectively. Cotton fiber length and elongation were not influenced by the B doses and Si presence. Fiber breaking strength was increased in 5% by the presence of Si and was not influenced by B deficiency. Micronaire was 8% smaller in the treatment with 0 kg ha−1 of B and 6% smaller in the absence of Si. Short fiber index was 4% greater in the plants of the treatment with 0 kg ha−1 of B. The results of this study reports that the complementation with Si via foliar application increases fiber quality by enhance breaking strength and micronaire. In conclusion, the interaction between soil-applied B and foliar-applied Si is beneficial for cotton cultivation, resulting in high cotton yield with better fiber quality.
Multiplex CRISPR-Cas9 knockout of EIL3, EIL4, and EIN2L advances soybean flowering time and pod set
Authors: Cheng Yunqing , Li Yujie , Yang Jing , He Hongli , Zhang Xingzheng , Liu Jianfeng , Yang Xiangdong 
Published: October 2023

Abstract
Background
Ethylene inhibitor treatment of soybean promotes flower bud differentiation and early flowering, suggested that there is a close relationship between ethylene signaling and soybean growth and development. The short-lived ETHYLENE INSENSITIVE2 (EIN2) and ETHYLENE INSENSITIVE3 (EIN3) proteins play central roles in plant development. The objective of this study was carried out gene editing of EIL family members in soybeans and to examine the effects on soybean yield and other markers of growth.

Methods and results
By editing key-node genes in the ethylene signaling pathway using a multi-sgRNA-in-one strategy, we obtained a series of gene edited lines with variable edit combinations among 15 target genes. EIL3, EIL4, and EIN2L were editable genes favored by the T0 soybean lines. Pot experiments also show that the early flowering stage R1 of the EIL3, EIL4, and EIN2L triple mutant was 7.05 d earlier than that of the wild-type control. The yield of the triple mutant was also increased, being 1.65-fold higher than that of the control. Comparative RNA-seq revealed that sucrose synthase, AUX28, MADS3, type-III polyketide synthase A/B, ABC transporter G family member 26, tetraketide alpha-pyrone reductase, and fatty acyl-CoA reductase 2 may be involved in regulating early flowering and high-yield phenotypes in triple mutant soybean plants.

Conclusion
Our results provide a scientific basis for genetic modification to promote the development of earlier-flowering and higher-yielding soybean cultivars.
Weekend effect on the incidence and outcomes of cardiac surgery associated - acute kidney injury
Authors: Xie Qiwen , Shen Ziyan , Pan Mingzhen , Li Yang , Luo Zhe , Wang Chunsheng , Zhao Linxi , Fang Yi , Ding Xiaoqiang , Teng Jie , Xu Jiarui 
Published: October 2023

AbstractBackgroundThe effects of surgical day (workdays or weekends) on occurrence and outcome of cardiac surgery associated -acute kidney injury (CSA-AKI) remains unclear. This study aimed to compare the incidence and short-term outcomes of CSA-AKI in patients undergoing surgery on workdays and weekends.Materials and methodsPatients who underwent cardiac surgery from July 2020 to December 2020 were retrospectively enrolled in this study. These patients were divided into a weekend group and workday group. The primary endpoint was the incidence of CSA-AKI. The secondary endpoints included renal function recovery and in-hospital mortality. The logistic regression model was used to explore the risk factors for CSA-AKI. Stratification analysis was performed to estimate the association between CSA-AKI and weekend surgery stratified by emergency surgery.ResultsA total of 1974 patients undergoing cardiac surgery were enrolled. The incidence of CSA-AKI in the weekend group was significantly higher than that in the workday group (42.8% vs. 34.7%,P = 0.038). Further analysis of patients with CSA-AKI showed that there was no difference in renal function recovery between the workday AKI group and weekend AKI group. There was no difference in in-hospital mortality between the weekend group and workday group (3.6% vs. 2.4%,P = 0.327); however, the in-hospital mortality of the weekend AKI group was significantly higher than that of the workday AKI group (8.5% vs. 2.9%,P = 0.014). Weekend surgery and emergency surgery were independent risk factors for CSA-AKI. The multiplicative model showed an interaction between weekend surgery and emergency surgery; weekend surgery was related to an increased risk of AKI among patients undergoing emergency surgery [adjusted OR (95% CI): 1.96 (1.012-8.128)].ConclusionsThe incidence of CSA-AKI in patients undergoing cardiac surgery on weekends was significantly higher compared to that in patients undergoing cardiac surgery on workdays. Weekend surgery did not affect the in-hospital mortality of all patients but significantly increased the mortality of AKI patients. Weekend surgery and emergency surgery were independent risk factors for CSA-AKI. Weekend emergency surgery significantly increased the risk of CSA-AKI.
Kinetics of adaptive immune responses after administering mRNA-Based COVID-19 vaccination in individuals with and without prior SARS-CoV-2 infections
Authors: Yoon Sun-Woo , Widyasari Kristin , Jang Jieun , Lee Seungjun , Kang Taejoon , Kim Sunjoo 
Published: October 2023

Abstract
Objective
We aimed to compare the adaptive immune response in individuals with or without prior SARS-CoV-2 infections following the administration of mRNA-based COVID-19 vaccines.

Methods
A total of 54 participants with ages ranging from 37 to 56 years old, consisting of 23 individuals without a history of SARS-CoV-2 infection (uninfected group) and 31 individuals with prior infection of SARS-CoV-2 (infected group) who have received two doses of mRNA SARS-CoV-2 vaccines were enrolled in this study. We measured the IFN-γ level upon administration of BNT162b2 (PF) or mRNA-1273 (MO) by QuantiFERON SARS-CoV-2. The production of neutralizing antibodies was evaluated by a surrogate virus neutralization assay, and the neutralizing capacity was assessed by a plaque reduction neutralization test (PRNT50). The immune response was compared between the two groups.

Results
A significantly higher level of IFN-γ (p < 0.001) and neutralization antibodies (p < 0.001) were observed in the infected group than those in the uninfected group following the first administration of vaccines. The infected group demonstrated a significantly higher PRNT50 titer than the uninfected group against the Wuhan strain (p < 0.0001). Still, the two groups were not significantly different against Delta (p = 0.07) and Omicron (p = 0.14) variants. Following the second vaccine dose, T- and B-cell levels were not significantly increased in the infected group.

Conclusion
A single dose of mRNA-based COVID-19 vaccines would boost immune responses in individuals who had previously contracted SARS-CoV-2.