bluuebunny/crossref_metadata_2025_split huggingface dataset:
AGAMOUS regulates various target genes via cell cycle–coupled H3K27me3 dilution in floral meristems and stamens
Authors: Pelayo Margaret Anne , Morishita Fumi , Sawada Haruka , Matsushita Kasumi , Iimura Hideaki , He Zemiao , Looi Liang Sheng , Katagiri Naoya , Nagamori Asumi , Suzuki Takamasa , Širl Marek , Soukup Aleš , Satake Akiko , Ito Toshiro , Yamaguchi Nobutoshi 
Published: May 2023

Abstract
The MADS domain transcription factor AGAMOUS (AG) regulates floral meristem termination by preventing maintenance of the histone modification lysine 27 of histone H3 (H3K27me3) along the KNUCKLES (KNU) coding sequence. At 2 d after AG binding, cell division has diluted the repressive mark H3K27me3, allowing activation of KNU transcription prior to floral meristem termination. However, how many other downstream genes are temporally regulated by this intrinsic epigenetic timer and what their functions are remain unknown. Here, we identify direct AG targets regulated through cell cycle–coupled H3K27me3 dilution in Arabidopsis thaliana. Expression of the targets KNU, AT HOOK MOTIF NUCLEAR LOCALIZED PROTEIN18 (AHL18), and PLATZ10 occurred later in plants with longer H3K27me3-marked regions. We established a mathematical model to predict timing of gene expression and manipulated temporal gene expression using the H3K27me3-marked del region from the KNU coding sequence. Increasing the number of del copies delayed and reduced KNU expression in a polycomb repressive complex 2– and cell cycle–dependent manner. Furthermore, AHL18 was specifically expressed in stamens and caused developmental defects when misexpressed. Finally, AHL18 bound to genes important for stamen growth. Our results suggest that AG controls the timing of expression of various target genes via cell cycle–coupled dilution of H3K27me3 for proper floral meristem termination and stamen development.
Computer models of cell polarity establishment in plants
Authors: Marconi Marco , Wabnik Krzysztof 
Published: May 2023

Abstract
Plant development is a complex task, and many processes involve changes in the asymmetric subcellular distribution of cell components that strongly depend on cell polarity. Cell polarity regulates anisotropic growth and polar localization of membrane proteins and helps to identify the cell’s position relative to its neighbors within an organ. Cell polarity is critical in a variety of plant developmental processes, including embryogenesis, cell division, and response to external stimuli. The most conspicuous downstream effect of cell polarity is the polar transport of the phytohormone auxin, which is the only known hormone transported in a polar fashion in and out of cells by specialized exporters and importers. The biological processes behind the establishment of cell polarity are still unknown, and researchers have proposed several models that have been tested using computer simulations. The evolution of computer models has progressed in tandem with scientific discoveries, which have highlighted the importance of genetic, chemical, and mechanical input in determining cell polarity and regulating polarity-dependent processes such as anisotropic growth, protein subcellular localization, and the development of organ shapes. The purpose of this review is to provide a comprehensive overview of the current understanding of computer models of cell polarity establishment in plants, focusing on the molecular and cellular mechanisms, the proteins involved, and the current state of the field.
Cyclophilin 37 maintains electron transport via the cytochrome b6/f complex under high light in Arabidopsis
Authors: Yang Xiaoxia , Che Yufen , García Veder J , Shen Jianqiang , Zheng Yutong , Su Zhezheng , Zhu Li , Luan Sheng , Hou Xin 
Published: May 2023

Abstract
Plants have evolved multiple mechanisms to cope with diverse types of light stress, particularly the regulation of the electron transport chain (ETC). Under high light (HL) conditions, the balance of electron flux in the ETC is disturbed, which leads to the overaccumulation of reactive oxygen species (ROS) and results in photodamage and photoinhibition. The cytochrome (Cyt) b6/f complex, which coordinates electron transfer between photosystems I and II (PSI and PSII), plays an essential role in regulating the ETC and initiating photoprotection. However, how the Cyt b6/f complex is maintained under HL conditions remains unclear. Here, we report that the activity of the Cyt b6/f complex is sustained by thylakoid-localized cyclophilin 37 (CYP37) in Arabidopsis (Arabidopsis thaliana). Compared with wild-type plants, cyp37 mutants displayed an imbalance in electron transport from Cyt b6/f to PSI under HL stress, which led to increased ROS accumulation, decreased anthocyanin biosynthesis, and increased chlorophyll degradation. Surprisingly, CYP37's role in regulating ETC balance was independent of photosynthesis control, which was indicated by a higher Y (ND), an indicator of P700 oxidation in PSI. Furthermore, the interaction between CYP37 and photosynthetic electron transfer A (PetA), a subunit of the Cyt b6/f complex, suggests that the central function of CYP37 is to maintain Cyt b6/f complex activity rather than to serve as an assembly factor. Our study provides insights into how plants balance electron flow between PSII and PSI via Cyt b6/f complex under HL.
Psychologically Informed Practice: The Importance of Communication in Clinical Implementation
Authors: Main Chris J , Ballengee Lindsay A , George Steven Z , Beneciuk Jason M , Greco Carol M , Simon Corey B 
Published: May 2023

Abstract
There has been increasing interest in the secondary prevention of chronic pain and pain-associated disability over the past 3 decades. In 2011, psychologically informed practice (PiP) was suggested as a framework for managing persistent and recurrent pain, and, since then, it has underpinned the development of stratified care linking risk identification (screening). Although PiP research trials have demonstrated clinical and economic advantage over usual care, pragmatic studies have been less successful, and qualitative studies have identified implementation difficulties in both system delivery and individual clinical management. Effort has been put into the development of screening tools, the development of training, and the assessment of outcomes; however, the nature of the consultation has remained relatively unexplored. In this Perspective, a review of the nature of clinical consultations and the clinician–patient relationship is followed by reflections on the nature of communication and the outcome of training courses. Consideration is given to the optimization of communication, including the use of standardized patient-reported measures and the role of the therapist in facilitating adaptive behavior change. Several challenges in implementing a PiP approach in day-to-day practice are then considered. Following brief consideration of the impact of recent developments in health care, the Perspective concludes with a brief introduction to the PiP Consultation Roadmap (the subject of a companion paper), the use of which is suggested as a way of structuring the consultation with the flexibility required for a patient-centered approach to guided self-management of chronic pain conditions.
Model design for nonparametric phylodynamic inference and applications to pathogen surveillance
Authors: Didelot Xavier , Franceschi Vinicius , Frost Simon D. W , Dennis Ann , Volz Erik M 
Published: May 2023

Abstract
Inference of effective population size from genomic data can provide unique information about demographic history and, when applied to pathogen genetic data, can also provide insights into epidemiological dynamics. The combination of nonparametric models for population dynamics with molecular clock models which relate genetic data to time has enabled phylodynamic inference based on large sets of time-stamped genetic sequence data. The methodology for nonparametric inference of effective population size is well-developed in the Bayesian setting, but here we develop a frequentist approach based on nonparametric latent process models of population size dynamics. We appeal to statistical principles based on out-of-sample prediction accuracy in order to optimize parameters that control shape and smoothness of the population size over time. Our methodology is implemented in a new R package entitled mlesky. We demonstrate the flexibility and speed of this approach in a series of simulation experiments and apply the methodology to a dataset of HIV-1 in the USA. We also estimate the impact of non-pharmaceutical interventions for COVID-19 in England using thousands of SARS-CoV-2 sequences. By incorporating a measure of the strength of these interventions over time within the phylodynamic model, we estimate the impact of the first national lockdown in the UK on the epidemic reproduction number.
MFG‐E8 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells through GSK3β/β‐catenin signaling pathway
Authors: Bai Jinwu , Zhang Weijun , Zhou Chenwei , Zhao Guangfeng , Zhong Huiming , Hang Kai , Xu Jianxiang , Zhang Wei , Chen Erman , Wu Jiaqi , Liu Ling , Xue Deting 
Published: May 2023

AbstractFracture nonunion and bone defects are challenging for orthopedic surgeons. Milk fat globule‐epidermal growth factor 8 (MFG‐E8), a glycoprotein possibly secreted by macrophages in a fracture hematoma, participates in bone development. However, the role of MFG‐E8 in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is unclear. We investigated the osteogenic effect of MFG‐E8 in vitro and in vivo. The CCK‐8 assay was used to assess the effect of recombinant human MFG‐E8 (rhMFG‐E8) on the viability of hBMSCs. Osteogenesis was investigated using RT‐PCR, Western blotting, and immunofluorescence. Alkaline phosphatase (ALP) and Alizarin red staining were used to evaluate ALP activity and mineralization, respectively. An enzyme‐linked immunosorbent assay was conducted to evaluate the secretory MFG‐E8 concentration. Knockdown and overexpression of MFG‐E8 in hBMSCs were established via siRNA and lentivirus vector transfection, respectively. Exogenous rhMFG‐E8 was used to verify the in vivo therapeutic effect in a tibia bone defect model based on radiographic analysis and histological evaluation. Endogenous and secretory MFG‐E8 levels increased significantly during the early osteogenic differentiation of hBMSCs. Knockdown of MFG‐E8 inhibited the osteogenic differentiation of hBMSCs. Overexpression of MFG‐E8 and rhMFG‐E8 protein increased the expression of osteogenesis‐related genes and proteins and enhanced calcium deposition. The active β‐catenin to total β‐catenin ratio and the p‐GSK3β protein level were increased by MFG‐E8. The MFG‐E8‐induced enhanced osteogenic differentiation of hBMSCs was partially attenuated by a GSK3β/β‐catenin signaling inhibitor. Recombinant MFG‐E8 accelerated bone healing in a rat tibial‐defect model. In conclusion, MFG‐E8 promotes the osteogenic differentiation of hBMSCs by regulating the GSK3β/β‐catenin signaling pathway and so, is a potential therapeutic target.
Preoperative HbA1c and Postoperative Outcomes in Spine Surgery
Authors: Tao Xu , Matur Abhijith V. , Palmisciano Paolo , Conteh Fatu S. , Onyewadume Louisa , Duah Henry O. , Shukla Geet , Vorster Phillip , Gupta Sahil , Chilakapati Sai S. , Adogwa Owoicho 
Published: May 2023

Study Design.
Systematic review and meta-analysis.

Objective.
To perform a systematic review and meta-analysis of previous studies on HbA1c in preoperative risk stratification in patients undergoing spinal procedures and provide an overview of the consensus recommendations.

Summary of Background Data.
Diabetes mellitus (DM) and hyperglycemia have been shown to be independent risk factors for increased surgical complications. Glycated Hemoglobin A1C (HbA1c), a surrogate for long term glycemic control, is an important preoperative parameter that may be optimized to reduce surgical complications and improve patient-reported outcomes. However, comprehensive systematic reviews on preoperative HbA1c and postoperative outcomes in spine surgery have been limited.

Methods.
We systematically searched PubMed, EMBASE, Scopus, and Web-of-Science for English-language studies from inception through April 5th, 2022, including references of eligible articles. The search was conducted according to PRISMA guidelines. Only studies in patients undergoing spine surgery with preoperative HbA1c values and postoperative outcomes available were included.

Results.
A total of 22 articles (18 retrospective cohort studies, 4 prospective observational studies) were identified with level of evidence III or greater. The majority of studies (n=17) found that elevated preoperative HbA1c was associated with inferior outcomes or increased risk of complications. Random-effect meta-analysis demonstrated that patients with preoperative HbA1c >8.0% had increased risk(s) of postoperative complications (RR: 1.85, 95% CI: [1.48, 2.31], P<0.01) and that patients with surgical site infection (SSI) had higher preoperative HbA1c (Mean Difference: 1.49%, 95% CI: [0.11, 2.88], P=0.03).

Conclusion.
The findings of this study suggest that HbA1c >8.0% is associated with an increased risk of complications. HbA1c was higher by 1.49% on average among patients with SSI when compared to patients who did not experience SSI. These results suggest that elevated HbA1c is associated with less favorable outcomes following spine surgery.

Level of Evidence.
IV
Predictors of Relevant Changes in Pain and Function for Adolescents With Idiopathic Scoliosis Following Surgery
Authors: Alamrani Samia , Gardner Adrian , Rushton Alison B. , Falla Deborah , Heneghan Nicola R. 
Published: May 2023

Study Design.Retrospective analysis of longitudinal data.Objective.To evaluate clinically relevant change in surgical outcomes for Adolescents with Idiopathic Scoliosis (AIS), comparing those who achieved smallest detectable change (SDC) in pain and function at 1-year post-surgery with those who did not, and to evaluate the influencing factors.Summary of Background Data.The SDC is recommended to evaluate the surgical outcomes of AIS. However, little is known about the use of SDC in AIS and its influencing factors.Materials and Methods.This was a retrospective analysis of longitudinal data from patients who underwent surgical correction at a tertiary spinal centre from 2009 to 2019. Surgical outcomes were assessed at short-term (6 wk, 6 mo) and long-term (1- and 2-years) post-surgery using the Scoliosis Research Society questionnaire (SRS-22r). The difference between “successful” (≥SDC) and “unsuccessful” (<SDC) groups was assessed using an independent t-test. Univariate and logistic regression analyses enabled the assessment of influencing factors.Results.All SRS-22r domains decreased in the short term, except for self-image and satisfaction. In the long term, self-image increased by 1.21 and function increased by 0.2, and pain decreased by 0.1. In all SRS-22r domains “successful” group had low pre-surgery scores and were statistically different to the “unsuccessful group”. The difference remained statistically significant at 1-year for most SRS-22r domains. Being older and having low pre-surgery SRS-22r scores increased the chances of achieving SDC in function at 1-year. Achieving SDC in the pain domain was significantly associated with age, sex, length of hospital stay, and SRS-22r pre-surgery scores.Conclusion.Notably, the self-image domain showed the largest change compared to other SRS-22r domains. A low pre-surgery score increases the likelihood of clinical benefit from surgery. These findings demonstrate the utility of SDC for assessing the benefits and factors that may underpin surgical benefit in AIS.
Role of steroid receptor-associated and regulated protein in tumor progression and progesterone receptor signaling in endometrial cancer
Authors: Liu Jie , Wang Zhiqi , Zhou Jingyi , Wang Jiaqi , He Xiangjun , Wang Jianliu 
Published: May 2023

Abstract

Background:
Steroid receptor-associated and regulated protein (SRARP) suppresses tumor progression and modulates steroid receptor signaling by interacting with estrogen receptors and androgen receptors in breast cancer. In endometrial cancer (EC), progesterone receptor (PR) signaling is crucial for responsiveness to progestin therapy. The aim of this study was to investigate the role of SRARP in tumor progression and PR signaling in EC.

Methods:
Ribonucleic acid sequencing data from the Cancer Genome Atlas, Clinical Proteomic Tumor Analysis Consortium, and Gene Expression Omnibus were used to analyze the clinical significance of SRARP and its correlation with PR expression in EC. The correlation between SRARP and PR expression was validated in EC samples obtained from Peking University People's Hospital. SRARP function was investigated by lentivirus-mediated overexpression in Ishikawa and HEC-50B cells. Cell Counting Kit-8 assays, cell cycle analyses, wound healing assays, and Transwell assays were used to evaluate cell proliferation, migration, and invasion. Western blotting and quantitative real-time polymerase chain reaction were used to evaluate gene expression. The effects of SRARP on the regulation of PR signaling were determined by co-immunoprecipitation, PR response element (PRE) luciferase reporter assay, and PR downstream gene detection.

Results:
Higher SRARP expression was significantly associated with better overall survival and disease-free survival and less aggressive EC types. SRARP overexpression suppressed growth, migration, and invasion in EC cells, increased E-cadherin expression, and decreased N-cadherin and Wnt family member 7A (WNT7A) expression. SRARP expression was positively correlated with PR expression in EC tissues. In SRARP-overexpressing cells, PR isoform B (PRB) was upregulated and SRARP bound to PRB. Significant increases in PRE-based luciferase activity and expression levels of PR target genes were observed in response to medroxyprogesterone acetate.

Conclusions:
This study illustrates that SRARP exerts a tumor-suppressive effect by inhibiting the epithelial-mesenchymal transition via Wnt signaling in EC. In addition, SRARP positively modulates PR expression and interacts with PR to regulate PR downstream target genes.
Targeted therapeutic strategies for melanoma
Authors: Zhang Shiwei , Xie Ruxin , Zhong Ai , Chen Junjie 
Published: May 2023

Abstract
Melanoma accounts for a small proportion of skin cancers diagnosed each year, but it has a high degree of malignancy and rapid progression, resulting in a short survival period for patients. The incidence of melanoma continues to rise, and now melanoma accounts for 1.7% of cancer diagnoses worldwide and is the fifth most common cancer in the United States. With the development of high-throughput sequencing technologies, the understanding of the pathophysiology of melanoma had also been improved. The most common activating mutations in melanoma cells are BRAF, NRAS, and KIT mutations, which disrupt cell signaling pathways related to tumor proliferation. The progress has led to the emergence of molecularly targeted drugs, which extends the survival of patients with advanced melanoma. A large number of clinical trials have been conducted to confirm that targeted therapy for patients with advanced melanoma can improve progression-free survival and overall survival, and for stage III patients after radical tumor resection targeted therapy can reduce the recurrence of melanoma. Patients who were originally stage III or IV inoperable have the opportunity to achieve tumor radical resection after targeted therapy. This article reviewed the clinical trial data and summarized the clinical benefits and limitations of these therapies.
Prognostic Value of Lymph Node Parameters in Elderly Patients With Stage III Serous Ovarian Cancer Based on Competing Risk Model
Authors: Sun Xiangmei , Peng Yaru , Chen Jiaojiao , Lei Jiahao , Liu Weizong , Li Zhengyi 
Published: May 2023

Objectives:
Competing risk models were used in this study. The purpose of this study was to assess the predictive usefulness of lymph node characteristics in elderly patients with stage III serous ovarian cancer.

Methods:
We conducted a retrospective analysis on 148,598 patients from 2010 to 2016 using the surveillance, epidemiology, and end results database. Lymph node characteristics were collected and examined, including the number of lymph nodes retrieved the number of lymph nodes examined (ELN) and the number of positive lymph nodes (PN). Using competing risk models, we evaluated the connection between these variables and overall survival (OS) and disease-specific survival (DSS).

Results:
This study included a total of 3457 ovarian cancer patients. Multivariate analysis using the COX proportional hazards model found that ELN>22 was an independent predictive factor for both OS (hazard ratio [HR] [95% CI]=0.688 [0.553 to 0.856], P<0.05) and DSS (HR [95% CI]=0.65 [0.512 to 0.826], P<0.001), PN>8 was identified as a significant risk factor for both OS (HR [95% CI]=0.908 [0.688 to 1.199], P=0.497) and DSS (HR [95% CI]=0.926 [0.684 to 1.254], P=0.62). Subsequently, using the competing risk model, ELN>22 was found to be an independent protective factor for DSS (HR [95% CI]=0.738 [0.574 to 0.949], P=0.018), while PN>8 was identified as a risk factor for DSS (HR [95% CI]=0.999 [0.731 to 1.366], P=1).

Conclusions:
Our findings demonstrate the robustness of the competing risk model to evaluate the results of the COX proportional hazards model analysis.
Long COVID in people living with HIV
Authors: Peluso Michael J. , Antar Annukka A.R. 
Published: May 2023

Purpose of review
It is now recognized that SARS-CoV-2 infection can have a long-term impact on health. This review summarizes the current state of knowledge regarding Long COVID in people living with HIV (PLWH).

Recent findings
PLWH may be at elevated risk of experiencing Long COVID. Although the mechanisms contributing to Long COVID are incompletely understood, there are several demographic and clinical factors that might make PLWH vulnerable to developing Long COVID.

Summary
PLWH should be aware that new or worsening symptoms following SARS-CoV-2 infection might represent Long COVID. HIV providers should be aware of this clinical entity and be mindful that their patients recovering from SARS-CoV-2 infection may be at higher risk.
Engineering strategies of Anti-HIV antibody therapeutics in clinical development
Authors: Pihlstrom Nicole , Bournazos Stylianos 
Published: May 2023

Purpose of review
Anti-human immunodeficiency virus (HIV) antibody-based therapeutics offer an alternative treatment option to current antiretroviral drugs. This review aims to provide an overview of the Fc- and Fab-engineering strategies that have been developed to optimize broadly neutralizing antibodies and discuss recent findings from preclinical and clinical studies.

Recent findings
Multispecific antibodies, including bispecific and trispecific antibodies, DART molecules, and BiTEs, as well as Fc-optimized antibodies, have emerged as promising therapeutic candidates for the treatment of HIV. These engineered antibodies engage multiple epitopes on the HIV envelope protein and human receptors, resulting in increased potency and breadth of activity. Additionally, Fc-enhanced antibodies have demonstrated extended half-life and improved effector function.

Summary
The development of Fc and Fab-engineered antibodies for the treatment of HIV continues to show promising progress. These novel therapies have the potential to overcome the limitations of current antiretroviral pharmacologic agents by more effectively suppressing viral load and targeting latent reservoirs in individuals living with HIV. Further studies are needed to fully understand the safety and efficacy of these therapies, but the growing body of evidence supports their potential as a new class of therapeutics for the treatment of HIV.