bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of risk factor burden and genetic predisposition with the 10-year risk of atrial fibrillation: observations from a large prospective study of 348,904 participants
Authors: Zhang Junguo , Chen Ge , Wang ChongJian , Wang Xiaojie , Qian Zhengmin , Cai Miao , Vaughn Michael G. , Bingheim Elizabeth , Li Haitao , Gao Yanhui , Lip Gregory Y. H. , Lin Hualiang 
Published: April 2023

Abstract
Background
Understanding the effects of risk factor burden and genetic predisposition on the long-term risk of atrial fibrillation (AF) is important to improve public health initiatives. However, the 10-year risk of AF considering risk factor burden and genetic predisposition is unknown.

Methods
A total of 348,904 genetically unrelated participants without AF at baseline from the UK were categorized into three groups: index ages 45 years (n = 84,206), 55 years (n=117,520), and 65 years (n=147,178). Optimal, borderline, or elevated risk factor burden was determined by body mass index, blood pressure, diabetes mellitus, alcohol consumption, smoking status, and history of myocardial infarction or heart failure. Genetic predisposition was estimated using the polygenic risk score (PRS), constructed using 165 predefined genetic risk variants. The combined effects of risk factor burden and PRS on the risk of incident AF in 10 years were estimated for each index age. Fine and Gray models were developed to predict the 10-year risk of AF.

Results
The overall 10-year risk of AF was 0.67% (95% CI: 0.61–0.73%) for index age 45 years, 2.05% (95% CI: 1.96–2.13%) for index age 55 years, and 6.34% (95% CI: 6.21–6.46%) for index age 65 years, respectively. An optimal risk factor burden was associated with later AF onset regardless of genetic predisposition and sex (P < 0.001). Significant synergistic interactions were observed for risk factor burden with PRS at each index age (P < 0.05). Participants with an elevated risk factor burden and high PRS had the highest 10-year risk of AF in reference to those who had both an optimal risk factor burden and a low PRS. At younger ages, optimal risk burden and high PRS might also lead to later onset of AF, compared to the joint effect of elevated risk burden and low/intermediate PRS.

Conclusions
Risk factor burden together with a genetic predisposition is associated with the 10-year risk of AF. Our results may be helpful in selecting high-risk individuals for primary prevention of AF and facilitating subsequent health interventions.
Molecular subtypes predict therapeutic responses and identifying and validating diagnostic signatures based on machine learning in chronic myeloid leukemia
Authors: Zhong Fang-Min , Yao Fang-Yi , Yang Yu-Lin , Liu Jing , Li Mei-Yong , Jiang Jun-Yao , Zhang Nan , Xu Yan-Mei , Li Shu-Qi , Cheng Ying , Xu Shuai , Huang Bo , Wang Xiao-Zhong 
Published: April 2023

AbstractChronic myeloid leukemia (CML) is a hematological tumor derived from hematopoietic stem cells. The aim of this study is to analyze the biological characteristics and identify the diagnostic markers of CML. We obtained the expression profiles from the Gene Expression Omnibus (GEO) database and identified 210 differentially expressed genes (DEGs) between CML and normal samples. These DEGs are mainly enriched in immune-related pathways such as Th1 and Th2 cell differentiation, primary immunodeficiency, T cell receptor signaling pathway, antigen processing and presentation pathways. Based on these DEGs, we identified two molecular subtypes using a consensus clustering algorithm. Cluster A was an immunosuppressive phenotype with reduced immune cell infiltration and significant activation of metabolism-related pathways such as reactive oxygen species, glycolysis and mTORC1; Cluster B was an immune activating phenotype with increased infiltration of CD4 + and CD8 + T cells and NK cells, and increased activation of signaling pathways such as interferon gamma (IFN-γ) response, IL6-JAK-STAT3 and inflammatory response. Drug prediction results showed that patients in Cluster B had a higher therapeutic response to anti-PD-1 and anti-CTLA4 and were more sensitive to imatinib, nilotinib and dasatinib. Support Vector Machine Recursive Feature Elimination (SVM-RFE), Least Absolute Shrinkage Selection Operator (LASSO) and Random Forest (RF) algorithms identified 4 CML diagnostic genes (HDC, SMPDL3A, IRF4 and AQP3), and the risk score model constructed by these genes improved the diagnostic accuracy. We further validated the diagnostic value of the 4 genes and the risk score model in a clinical cohort, and the risk score can be used in the differential diagnosis of CML and other hematological malignancies. The risk score can also be used to identify molecular subtypes and predict response to imatinib treatment. These results reveal the characteristics of immunosuppression and metabolic reprogramming in CML patients, and the identification of molecular subtypes and biomarkers provides new ideas and insights for the clinical diagnosis and treatment.
Factors influencing treatment status of syphilis among pregnant women: a retrospective cohort study in Guangzhou, China
Authors: Liu Huihui , Chen Niannian , Tang Weiming , Shen Songying , Yu Jia , Xiao Huiyun , Zou Xingwen , He Jianrong , Tucker Joseph D. , Qiu Xiu 
Published: April 2023

Abstract
Background
Many syphilis infected pregnant women do not receive treatment, representing a major missed opportunity to reduce the risk of syphilis-related adverse pregnancy outcomes. This study explored correlates of treatment among pregnant women with syphilis in Guangzhou, China.

Methods
Pregnant women with a diagnosis of syphilis in Guangzhou between January 2014 and December 2016 were included. Information of syphilis treatment and correlates were extracted from a comprehensive national case-reporting system. Multivariate logistic regression was used to identify the correlations between information on the demographic characteristics, previous history, clinical characteristics about current syphilis, information of diagnosing hospital, and receiving no treatment or inadequate treatment among syphilis-seropositive pregnant women. A causal mediation analysis was used to explore the potential mediating role of the timing of syphilis diagnosis in the correlates.

Results
Among 1248 syphilis-seropositive pregnant women, 379 (30.4%) women received no treatment or inadequate treatment. Migrant pregnant women (adjusted OR = 1.83, 95% CI: 1.25–2.73), multiparous participants (adjusted OR = 3.68, 95% CI: 2.51–5.50), unmarried participants (adjusted OR = 3.21, 95% CI: 1.97–5.28) and unemployed participants (adjusted OR = 2.43, 95% CI: 1.41–4.39) were more likely to receive no treatment or inadequate treatment. Participants who with history of syphilis infection (adjusted OR = 0.59, 95% CI: 0.42–0.82) and with high school and higher education participants (adjusted OR = 0.69, 95% CI: 0.49–0.97) were less likely to receive untreated or inadequately treatment. And that the impact of all these factors (except for the migrants) on treatment status are fully mediated through the syphilis diagnosis time, with the direct effect of migrants that would have resulted in a higher rate of no or inadequate treatment (OR = 2.34, 95% CI: 1.08–5.32) was partially cancelled out by the syphilis diagnosis time.

Conclusions
Pregnant women who were migrant without local residence and women with syphilis diagnosed at a later gestational age were more likely to slip through the cracks of the existing antenatal care system. More programs should focus on eliminating these gaps of residence-related health inequalities. This research highlights actionable elements for health services interventions that could increase syphilis treatment rates among pregnant women.
Anlotinib dramatically improved pulmonary hypertension and hypoxia caused by Pulmonary Tumor Thrombotic Microangiopathy (PTTM) associated with gastric carcinoma: a case report
Authors: Wang Yang , Ning Wei-wei , Jin Yi-fan , Zhu Qing-qing , Wang Zai-liang , Su Nan , Chen Yan-bin , Huang Jian-an , Chen Cheng 
Published: April 2023

Abstract
Background
Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare malignancy-related respiratory complication, demonstrating rapid progression of pulmonary hypertension (PH) and respiratory failure. Although a number of treatments have been attempted for patients diagnosed with or suspected of having PTTM, successful-treated cases of PTTM were mainly from imatinib therapy, which was a PDGF receptor inhibitor. Anlotinib was a novel tyrosine kinase inhibitor that targets VEGFR, FGFR, PDGFR, and c-kit.

Case presentation
We reported a patient of PTTM associated with gastric carcinoma, whom were treated with anlotinib, thereby exhibiting significant improvement of PH and respiratory dysfunction.

Conclusion
Our case provides a new understanding of therapy to PTTM, with implications for defining anlotinib as candidate drug for PTTM. Clinical diagnosis and prompt initiation of anlotinib might be one of the strategies in patients with unstable PTTM.
Optical coherence tomography angiography measurements in multiple sclerosis: a systematic review and meta-analysis
Authors: Mohammadi Soheil , Gouravani Mahdi , Salehi Mohammad Amin , Arevalo J. Fernando , Galetta Steven L. , Harandi Hamid , Frohman Elliot M. , Frohman Teresa C. , Saidha Shiv , Sattarnezhad Neda , Paul Friedemann 
Published: April 2023

AbstractBackground and objectivesRecent literature on multiple sclerosis (MS) demonstrates the growing implementation of optical coherence tomography–angiography (OCT-A) to discover potential qualitative and quantitative changes in the retina and optic nerve. In this review, we analyze OCT-A studies in patients with MS and examine its utility as a surrogate or precursor to changes in central nervous system tissue.MethodsPubMed and EMBASE were systematically searched to identify articles that applied OCT-A to evaluate the retinal microvasculature measurements in patients with MS. Quantitative data synthesis was performed on all measurements which were evaluated in at least two unique studies with the same OCT-A devices, software, and study population compared to controls. A fixed-effects or random-effects model was applied for the meta-analysis based on the heterogeneity level.ResultsThe study selection process yielded the inclusion of 18 studies with a total of 1552 evaluated eyes in 673 MS-associated optic neuritis (MSON) eyes, 741 MS without optic neuritis (MSNON eyes), and 138 eyes without specification for the presence of optic neuritis (ON) in addition to 1107 healthy control (HC) eyes. Results indicated that MS cases had significantly decreased whole image superficial capillary plexus (SCP) vessel density when compared to healthy control subjects in the analyses conducted on Optovue and Topcon studies (bothP < 0.0001). Likewise, the whole image vessel densities of deep capillary plexus (DCP) and radial peripapillary capillary (RPC) were significantly lower in MS cases compared to HC (allP < 0.05). Regarding optic disc area quadrants, MSON eyes had significantly decreased mean RPC vessel density compared to MSNON eyes in all quadrants except for the inferior (allP < 0.05). Results of the analysis of studies that used prototype Axsun machine revealed that MSON and MSNON eyes both had significantly lower ONH flow index compared to HC (bothP < 0.0001).ConclusionsThis systematic review and meta-analysis of the studies reporting OCT-A measurements of people with MS confirmed the tendency of MS eyes to exhibit reduced vessel density in the macular and optic disc areas, mainly in SCP, DCP, and RPC vessel densities.
Development and validation of a novel scale for antiretroviral therapy readiness among pregnant women in urban Zambia with newly diagnosed HIV infection
Authors: Mubiana-Mbewe Mwangelwa , Bosomprah Samuel , Saroj Rakesh Kumar , Kadota Jillian , Koyuncu Aybuke , Thankian Kusanthan , Vinikoor Michael J. 
Published: April 2023

Abstract
Background
Women who are newly diagnosed with HIV infection during pregnancy may not be ready to immediately initiate lifelong antiretroviral therapy (ART; called Option B +) as is recommended. Lack of “readiness” drives early disengagement from care and undermines prevention of HIV transmission to infants. Several studies have shown high early attrition of women initiating ART in pregnancy. Although poor ART uptake and adherence have been attributed to various factors including stigma, disclosure issues and structural issues, there is no standard way of determining which pregnant woman will face challenges and therefore need additional support. We developed and validated a novel ART readiness tool in Lusaka, Zambia.

Methods
The aim of this study was to develop and validate a tool that could be used to assess how ready a newly diagnosed pregnant woman living with HIV would be to initiate ART on the day of diagnosis. Using a mixed method design, we conducted this study in three public-setting health facilities in Lusaka, Zambia. Informed by qualitative research and literature review, we identified 27 candidate items. We assessed content validity using expert and target population judgment approaches. We administered the 27-item questionnaire to 454 newly diagnosed pregnant women living with HIV, who were enrolled into a randomized trial (trials number NCT02459678). We performed item reduction analysis and used Cronbach’s alpha coefficient of 0.70 as threshold for reliability.

Results
A total of 454 pregnant women living with HIV enrolled in the study between March 2017 and December 2017; 452 had complete data for analysis. The correlation coefficient between the 27 items on the completed ART readiness scale ranged from 0.31 to 0.70 while item discrimination index ranged from -0.01 to 2.38. Sixteen items were selected for the final scale, representing three domains, which we classified as “internalized and anticipated HIV stigma”, “partner support” and “anticipated structural barriers”.

Conclusion
We developed and validated a tool that could be used to assess readiness of newly diagnosed women living with HIV to initiate ART. This ART readiness tool could allow clinics to tailor limited resources to pregnant women living with HIV needing additional support to initiate and remain on ART.
Cooperative NF-κB and Notch1 signaling promotes macrophage-mediated MenaINV expression in breast cancer
Authors: Duran Camille L. , Karagiannis George S. , Chen Xiaoming , Sharma Ved P. , Entenberg David , Condeelis John S. , Oktay Maja H. 
Published: April 2023

AbstractMetastasis is a multistep process that leads to the formation of clinically detectable tumor foci at distant organs and frequently to patient demise. Only a subpopulation of breast cancer cells within the primary tumor can disseminate systemically and cause metastasis. To disseminate, cancer cells must express MenaINV, an isoform of the actin regulatory protein Mena, encoded by the ENAH gene, that endows tumor cells with transendothelial migration activity, allowing them to enter and exit the blood circulation. We have previously demonstrated that MenaINV mRNA and protein expression is induced in cancer cells by macrophage contact. In this study, we discovered the precise mechanism by which macrophages induce MenaINV expression in tumor cells. We examined the promoter of the human and mouse ENAH gene and discovered a conserved NF-κB transcription factor binding site. Using live imaging of an NF-κB activity reporter and staining of fixed tissues from mouse and human breast cancer, we further determined that for maximal induction of MenaINV in cancer cells, NF-κB needs to cooperate with the Notch1 signaling pathway. Mechanistically, Notch1 signaling does not directly increase MenaINV expression, but it enhances and sustains NF-κB signaling through retention of p65, an NF-κB transcription factor, in the nucleus of tumor cells, leading to increased MenaINV expression. In mice, these signals are augmented following chemotherapy treatment and abrogated upon macrophage depletion. Targeting Notch1 signaling in vivo decreased NF-κB signaling activation and MenaINV expression in the primary tumor and decreased metastasis. Altogether, these data uncover mechanistic targets for blocking MenaINV induction that should be explored clinically to decrease cancer cell dissemination and improve survival of patients with metastatic disease.
FIPRESCI: droplet microfluidics based combinatorial indexing for massive-scale 5′-end single-cell RNA sequencing
Authors: Li Yun , Huang Zheng , Zhang Zhaojun , Wang Qifei , Li Fengxian , Wang Shufang , Ji Xin , Shu Shaokun , Fang Xiangdong , Jiang Lan 
Published: April 2023

AbstractSingle-cell RNA sequencing methods focusing on the 5′-end of transcripts can reveal promoter and enhancer activity and efficiently profile immune receptor repertoire. However, ultra-high-throughput 5′-end single-cell RNA sequencing methods have not been described. We introduce FIPRESCI, 5′-end single-cell combinatorial indexing RNA-Seq, enabling massive sample multiplexing and increasing the throughput of the droplet microfluidics system by over tenfold. We demonstrate FIPRESCI enables the generation of approximately 100,000 single-cell transcriptomes from E10.5 whole mouse embryos in a single-channel experiment, and simultaneous identification of subpopulation differences and T cell receptor signatures of peripheral blood T cells from 12 cancer patients.
Reading and writing of mRNA m6A modification orchestrate maternal-to-zygotic transition in mice
Authors: Zhu Wencheng , Ding Yufeng , Meng Juan , Gu Lei , Liu Wenjun , Li Li , Chen Hongyu , Wang Yining , Li Ziyi , Li Chen , Sun Yidi , Liu Zhen 
Published: April 2023

AbstractN6-methyladenosine (m6A) modification has been shown to regulate RNA metabolism. Here, we investigate m6A dynamics during maternal-to-zygotic transition (MZT) in mice through multi-omic analysis. Our results show that m6A can be maternally inherited or de novo gained after fertilization. Interestingly, m6A modification on maternal mRNAs not only correlates with mRNA degradation, but also maintains the stability of a small group of mRNAs thereby promoting their translation after fertilization. We identify Ythdc1 and Ythdf2 as key m6A readers for mouse preimplantation development. Our study reveals a key role of m6A mediated RNA metabolism during MZT in mammals.
Insights on the in-vitro binding interaction between donepezil and bovine serum albumin
Authors: El Gammal Reem N. , Elmansi Heba , El-Emam Ali A. , Belal Fathalla , Elzahhar Perihan A. , Belal Ahmed S. F. , Hammouda Mohammed E. A. 
Published: April 2023

AbstractIn this work, the binding mechanism between donepezil (DNP) and bovine serum albumin (BSA) was established using several techniques, including fluorimetry, UV- spectrophotometry, synchronous fluorimetry (SF), fourier transform infrared (FTIR), fluorescence resonance energy transfer (FRET) besides molecular docking study. The fluorescence quenching mechanism of DNP-BSA binding was a combined dynamic and static quenching. The thermodynamic parameters, binding forces, binding constant, and the number of binding sites were determined using a different range of temperature settings. Van't Hoff's equation was used to calculate the reaction parameters, including enthalpy change (ΔHο) and entropy change (ΔSο). The results pointed out that the DNP-BSA binding was endothermic. It was shown that the stability of the drug-protein system was predominantly due to the intermolecular hydrophobic forces. Additionally, the site probing method revealed that subdomain IIA (Site I) is where DNP and BSA's binding occurs. This was validated using a molecular docking study with the most stable DNP configuration. This study might help to understand DNP's pharmacokinetics profile and toxicity as well as provides crucial information for its safe use and avoiding its toxicity.
Shell field morphogenesis in the polyplacophoran mollusk Acanthochitona rubrolineata
Authors: Xia Yuxiu , Huan Pin , Liu Baozhong 
Published: April 2023

Abstract
Background
The polyplacophoran mollusks (chitons) possess serially arranged shell plates. This feature is unique among mollusks and believed to be essential to explore the evolution of mollusks as well as their shells. Previous studies revealed several cell populations in the dorsal epithelium (shell field) of polyplacophoran larvae and their roles in the formation of shell plates. Nevertheless, they provide limited molecular information, and shell field morphogenesis remains largely uninvestigated.

Results
In the present study, we investigated shell field development in the chiton Acanthochitona rubrolineata based on morphological characteristics and molecular patterns. A total of four types of tissue could be recognized from the shell field of A. rubrolineata. The shell field comprised not only the centrally located, alternatively arranged plate fields and ridges, but also the tissues surrounding them, which were the precursors of the girdle and we termed as the girdle field. The girdle field exhibited a concentric organization composed of two circularly arranged tissues, and spicules were only developed in the outer circle. Dynamic engrailed expression and F-actin (filamentous actin) distributions revealed relatively complicated morphogenesis of the shell field. The repeated units (plate fields and ridges) were gradually established in the shell field, seemingly different from the manners used in the segmentation of Drosophila or vertebrates. The seven repeated ridges also experienced different modes of ontogenesis from each other. In the girdle field, the presumptive spicule-formation cells exhibited different patterns of F-actin aggregations as they differentiate.

Conclusions
These results reveal the details concerning the structure of polyplacophoran shell field as well as its morphogenesis. They would contribute to exploring the mechanisms of polyplacophoran shell development and molluscan shell evolution.
Diagnostic accuracy of ultra-low-dose CT compared to standard-dose CT for identification of non-displaced fractures of the shoulder, knee, ankle, and wrist
Authors: Xiao Mengqiang , Zhang Meng , Lei Ming , Lin Fenghuan , Chen Yanxia , Chen Jun , Liu Jinfeng , Ye Jingzhi 
Published: April 2023

Abstract
Objectives
To compare the performance of ultra-low-dose computed tomography (ULD-CT) with standard-dose computed tomography (SD-CT) for the diagnosis of non-displaced fractures of the shoulder, knee, ankle, and wrist.

Methods
This prospective study enrolled 92 patients receiving conservative treatment for limb joint fractures who underwent SD-CT followed by ULD-CT at a mean interval of 8.85 ± 1.98 days. Fractures were characterized as displaced or non-displaced. Objective (signal-to-noise ratio, contrast-to-noise ratio) and subjective CT image quality were evaluated. Observer performance for ULD-CT and SD-CT detecting non-displaced fractures was estimated by calculating the area under the receiver operating characteristic (ROC) curve (Az).

Results
The effective dose (ED) for the ULD-CT protocol was significantly lower than the ED for the SD-CT protocol (F = 422.21~2112.25, p < 0.0001); 56 patients (65 fractured bones) had displaced fractures, and 36 patients (43 fractured bones) had non-displaced fractures. Two non-displaced fractures were missed by SD-CT. Four non-displaced fractures were missed by ULD-CT. Objective and subjective CT image quality was significantly improved for SD-CT compared to ULD-CT. The sensitivity, specificity, PPV, NPV, and diagnostic accuracy of SD-CT and ULD-CT for non-displaced fractures of the shoulder, knee, ankle and wrist were similar: 95.35% and 90.70%; 100% and 100%; 100% and 100%; 99.72% and 99.44%; and 99.74% and 99.47%, respectively. The Az was 0.98 for SD-CT and 0.95 for ULD-CT (p = 0.32).

Conclusion
ULD-CT has utility for the diagnosis of non-displaced fractures of the shoulder, knee, ankle, and wrist and can support clinical decision-making.