bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell resolution analysis reveals the preparation for reprogramming the fate of stem cell niche in cotton lateral meristem
Authors: Zhu Xiangqian , Xu Zhongping , Wang Guanying , Cong Yulong , Yu Lu , Jia Ruoyu , Qin Yuan , Zhang Guangyu , Li Bo , Yuan Daojun , Tu Lili , Yang Xiyan , Lindsey Keith , Zhang Xianlong , Jin Shuangxia 
Published: August 2023

Abstract
Background
Somatic embryogenesis is a major process for plant regeneration. However, cell communication and the gene regulatory network responsible for cell reprogramming during somatic embryogenesis are still largely unclear. Recent advances in single-cell technologies enable us to explore the mechanism of plant regeneration at single-cell resolution.

Results
We generate a high-resolution single-cell transcriptomic landscape of hypocotyl tissue from the highly regenerable cotton genotype Jin668 and the recalcitrant TM-1. We identify nine putative cell clusters and 23 cluster-specific marker genes for both cultivars. We find that the primary vascular cell is the major cell type that undergoes cell fate transition in response to external stimulation. Further developmental trajectory and gene regulatory network analysis of these cell clusters reveals that a total of 41 hormone response-related genes, including LAX2, LAX1, and LOX3, exhibit different expression patterns in the primary xylem and cambium region of Jin668 and TM-1. We also identify novel genes, including CSEF, PIS1, AFB2, ATHB2, PLC2, and PLT3, that are involved in regeneration. We demonstrate that LAX2, LAX1 and LOX3 play important roles in callus proliferation and plant regeneration by CRISPR/Cas9 editing and overexpression assay.

Conclusions
This study provides novel insights on the role of the regulatory network in cell fate transition and reprogramming during plant regeneration driven by somatic embryogenesis.
CircRNA_15430 reduced by Helicobacter pylori infection and suppressed gastric cancer progression via miR-382-5p/ZCCHC14 axis
Authors: Liu Yun , Cao Jia , Yang Qi , Zhu Linqi , Zhao Wenjun , Wang Xiuping , Yao Jun , Zhou Yong , Shao Shihe 
Published: August 2023

Abstract
Background
Helicobacter pylori (H.pylori, HP) is one of the main causes of gastric cancer (GC). CircRNAs have been reported to play a crucial role in developing many types of cancer. However, the role of circRNAs in the development and progression of HP infected-GC has not been studied.

Methods
The location of circRNA_15430 in GC cells were detected by nuclear and cytoplasmic RNA fractionation and RNA fluorescence in situ hybridization analysis (FISH) assays, and circRNA_15430, miR-382-5p and ZCCHC14 expression in GC cell lines and tissues were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The function of circRNA_15430 in GC cells were examined by using colony formation, cell counting kit-8 (CCK-8) and Transwell assays, flow cytometry and laser scanning confocal microscopy. The protein levels were detected by Western blotting. Whether circRNA_15430 sponges miR-382-5p was monitored with a dual-luciferase reporter assay. Furthermore, circRNA_15430 was analyzed in vivo in tumor growth with nude mice.

Results
CircRNA_15430 is primarily localized in the cytoplasm of GC cells, and downregulated in the GC cell lines and tissues, and is negatively correlated with the tumor size. Downregulation of circRNA_15430 promotes proliferation, migration and suppresses cell apoptosis and autophagy in GC cells. Mechanically, circRNA_15430 acts as a miR-382-5p sponge, alleviating the inhibitory effect of miR-382-5p on its target ZCCHC14. Knockdown circRNA_15430 enhances tumor growth in vivo. In addition, circRNA_15430 was reduced in HP + gastritis tissues and HP-infected MGC-803 cells, reversing the pro-HP effect on autophagy. Additionally, miR-382-5p was increased in HP + gastritis tissue and HP-infected MGC-803 cells while ZCCHC14 decreased in HP-infected MGC-803 cells. MiR-382-5p reverses the effect of si-ZCCHC14 on autophagosome numbers in MGC-803 cells.

Conclusions
Therefore, circRNA_15430 plays an inhibitory role in GC and regulates the progression of HP infection-related GC, providing a novel molecular marker for GC therapy.
The Smooth Away From Expected (SAFE) non-inferiority frontier: theory and implementation with an application to the D3 trial
Authors: Quartagno Matteo , Chan Man , Turkova Anna , Ford Deborah , White Ian R. 
Published: August 2023

Abstract
Background
In a non-inferiority trial, the choice of margin depends on the expected control event risk. If the true risk differs from expected, power and interpretability of results can be affected. A non-inferiority frontier pre-specifies an appropriate non-inferiority margin for each value of control event risk. D3 is a non-inferiority trial comparing two treatment regimens in children living with HIV, designed assuming a control event risk of 12%, a non-inferiority margin of 10%, 80% power and a significance level (α) of 0.025. We consider approaches to choosing and implementing a frontier for this already funded trial, where changing the sample size substantially would be difficult.

Methods
In D3, we fix the non-inferiority margin at 10%, 8% and 5% for control event risks of ≥9%, 5% and 1%, respectively. We propose four frontiers which fit these fixed points, including a Smooth Away From Expected (SAFE) frontier. Analysis approaches considered are as follows: using the pre-specified significance level (α=0.025); always using a reduced significance level (to achieve α≤0.025 across control event risks); reducing significance levels only when the control event risk differs significantly from expected (control event risk <9%); and using a likelihood ratio test. We compare power and type 1 error for SAFE with other frontiers.

Results
Changing the significance level only when the control event risk is <9% achieves approximately nominal (<3%) type I error rate and maintains reasonable power for control event risks between 1 and 15%. The likelihood ratio test method performs similarly, but the results are more complex to present. Other analysis methods lead to either inflated type 1 error or badly reduced power. The SAFE frontier gives more interpretable results with low control event risks than other frontiers (i.e. it uses more reasonable non-inferiority margins). Other frontiers do not achieve power close (i.e. within 1%) to SAFE across the range of likely control event risks while controlling type I error.

Conclusions
The SAFE non-inferiority frontier will be used in D3, and the non-inferiority margin and significance level will be modified if the control event risk is lower than expected. This ensures results will remain interpretable if design assumptions are incorrect, while achieving similar power. A similar approach could be considered for other non-inferiority trials where the control event risk is uncertain.
Midgut volvulus due to congenital malrotation in an adult: a case report
Authors: Eltayb Almuntasir beallah , Hegazi Albra , Elhag Osaman , Abdelgadir Amro 
Published: August 2023

Abstract
Background
Intestinal Malrotation is congenital that complicates 1 in every 200 births. It results from abnormal fixation and rotation of the gut tube during fetal development. It is usually asymptomatic and most cases are diagnosed during childhood and the condition is seldom seen in adults. Also, it can present as an incidental finding in imaging or patients undergoing laparotomy for other reasons. Midgut Volvulus can lead to small obstruction it warrants surgical intervention.

Case presentation
Our case is a 20 years old black African male from Khartoum (Sudan) who presented to the emergency department with features of intestinal obstruction he was resuscitated and underwent a CT scan of the abdomen that showed malrotation of the intestine with volvulus for which he underwent a Ladd procedure.

Conclusion
Small bowel obstruction due to volvulus complicating malrotation is a rare presentation in adulthood and the Ladd procedure can be utilized to manage such case.
Training audio transformers for cover song identification
Authors: Zeng Te , Lau Francis C. M. 
Published: August 2023

AbstractIn the past decades, convolutional neural networks (CNNs) have been commonly adopted in audio perception tasks, which aim to learn latent representations. However, for audio analysis, CNNs may exhibit limitations in effectively modeling temporal contextual information. Analogous to the successes of transformer architecture used in the fields of computer vision and audio classification, to capture long-range global contexts better, we here extend this line of work and propose anAudio Similarity Transformer(ASimT), a convolution-free, purely transformer network-based architecture for learning effective representations of audio signals. Furthermore, we introduce a novel lossMAPLoss, used in tandem with classification loss, to directly enhance the mean average precision. In the experiments, ASimT demonstrates its state-of-the-art performance in cover song identification on public datasets.
Tracking longitudinal biomarkers in burn patients with sepsis and acute kidney injury: an unsupervised clustering approach
Authors: Kim Myongjin , Kym Dohern , Hur Jun , Park Jongsoo , Yoon Jaechul , Cho Yong Suk , Chun Wook , Yoon Dogeon 
Published: August 2023

Abstract
Background
Sepsis is a grave medical disorder characterized by a systemic inflammatory response to infection. Furthermore, it is a leading cause of morbidity and mortality, especially in hospitalized patients. Acute kidney injury (AKI) is a common complication of sepsis and is associated with increased morbidity and mortality. Patients with burns are particularly vulnerable to developing sepsis and AKI due to the extensive tissue damage and immune suppression resulting from burn injury. In this study, unsupervised clustering algorithms were used to track longitudinal biomarkers in patients with burns and assess their impact on mortality.

Methods
This retrospective study included adult patients with burns aged ≥ 18 years, who were admitted to the burn intensive care unit of Hallym University and Hangang Sacred Heart Hospital between July 2010 and December 2021. The patients were divided into two subgroups: those with sepsis (538 patients) and those without sepsis (826 patients). The longitudinal biomarkers were grouped into three clusters using the k-means clustering algorithm. Each cluster was assigned a letter from A to C according to its mortality rate.

Results
The odds ratio (OR) of pH was 9.992 in the positive group and 31.745 in the negative group in cluster C. The OR for lactate dehydrogenase (LD) was 3.704 in the positive group and 6.631 in the negative group in cluster C. The OR for creatinine was 2.784 in the positive group and 8.796 in the negative group in cluster C. The OR for blood urea nitrogen (BUN) in the negative group was 0.348, indicating a negative predictor of mortality. Regarding the application of Continuous Renal Replacement Therapy (CRRT) and ventilation, ventilation was significant in both groups. In contrast, CRRT application was not significant in the sepsis-positive group. Furthermore, it was not selected as a variable in the negative group.

Conclusions
The pH, LD, and creatinine were significant in both groups, while lactate and platelets were significant in the sepsis-positive group. In addition, albumin, glucose, and BUN were significant in the sepsis-negative group. Continuous renal replacement therapy was not significant in either group. However, the use of a ventilator was associated with poor prognosis.
Biological effects and mechanisms of fisetin in cancer: a promising anti-cancer agent
Authors: Zhou Chenhui , Huang Yi , Nie Sheng , Zhou Shengjun , Gao Xiang , Chen Gao 
Published: August 2023

AbstractFisetin, a natural flavonoid, possesses numerous biological activities that have been extensively studied in various diseases. When it comes to cancer, fisetin exhibits a range of biological effects, such as suppressing cell growth, triggering programmed cell death, reducing the formation of new blood vessels, protecting against oxidative stress, and inhibiting cell migration. Moreover, fisetin has the ability to enhance the effectiveness of chemotherapy. The anticancer properties of fisetin can be attributed to a diverse array of molecules and signaling pathways, including vascular endothelial growth factor (VEGF), mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), PI3K/Akt/mTOR, and Nrf2/HO-1. Consequently, fisetin holds promise as a therapeutic agent for anticancer treatment. In this review, we place emphasis on the biological functions and various molecular targets of fisetin in anticancer therapy.
α-Synuclein-carrying astrocytic extracellular vesicles in Parkinson pathogenesis and diagnosis
Authors: Wang Pan , Lan Guoyu , Xu Bin , Yu Zhenwei , Tian Chen , Lei Xia , Meissner Wassilios G. , Feng Tao , Yang Ying , Zhang Jing 
Published: August 2023

AbstractBackgroundThe accumulation of α-synuclein (α-syn), an essential step in PD development and progression, is observed not only in neurons but also in glia, including astrocytes. The mechanisms regulating astrocytic α-syn level and aggregation remain unclear. More recently, it has been demonstrated that a part of α-syn spreading occurs through extracellular vesicles (EVs), although it is unknown whether this process is involved in astrocytes of PD. It is known, however, that EVs derived from the central nervous system exist in the blood and are extensively explored as biomarkers for PD and other neurodegenerative disorders.MethodsPrimary astrocytes were transfected with A53T α-syn plasmid or exposed to α-syn aggregates. The level of astrocyte-derived EVs (AEVs) was assessed by nanoparticle tracking analysis and immunofluorescence. The lysosomal function was evaluated by Cathepsin assays, immunofluorescence for levels of Lamp1 and Lamp2, and LysoTracker Red staining. The Apogee assays were optimized to measure the GLT-1+AEVs in clinical cohorts of 106 PD, 47 multiple system atrophy (MSA), and 103 healthy control (HC) to test the potential of plasma AEVs as a biomarker to differentiate PD from other forms of parkinsonism.ResultsThe number of AEVs significantly increased in primary astrocytes with α-syn deposition. The mechanism of increased AEVs was partially attributed to lysosomal dysfunction. The number of α-syn-carrying AEVs was significantly higher in patients with PD than in HC and MSA. The integrative model combining AEVs with total and aggregated α-syn exhibited efficient diagnostic power in differentiating PD from HC with an AUC of 0.915, and from MSA with an AUC of 0.877.ConclusionsPathological α-syn deposition could increase the astrocytic secretion of EVs, possibly through α-syn-induced lysosomal dysfunction. The α-syn-containing AEVs in the peripheral blood may be an effective biomarker for clinical diagnosis or differential diagnosis of PD.
The RNA m6A modification might participate in microglial activation during hypoxic–ischemic brain damage in neonatal mice
Authors: Su Xiaojuan , Huang Lingyi , Li Shiping , Ying Junjie , Zhao Fengyan , Wang Shaopu , Liu Qian , Qu Yi , Mu Dezhi 
Published: August 2023

Abstract
Background
The RNA m6A modification has been implicated in multiple neurological diseases as well as macrophage activation. However, whether it regulates microglial activation during hypoxic-ischemic brain damage (HIBD) in neonates remains unknown. Here, we aim to examine whether the m6A modification is involved in modulating microglial activation during HIBD. We employed an oxygen and glucose deprivation microglial model for in vitro studies and a neonatal mouse model of HIBD. The brain tissue was subjected to RNA-seq to screen for significant changes in the mRNA m6A regulator. Thereafter, we performed validation and bioinformatics analysis of the major m6A regulators.

Results
RNA-seq analysis revealed that, among 141 m6A regulators, 31 exhibited significant differential expression (FC (abs) ≥ 2) in HIBD mice. We then subjected the major m6A regulators Mettl3, Mettl14, Fto, Alkbh5, Ythdf1, and Ythdf2 to further validation, and the results showed that all were significantly downregulated in vitro and in vivo. GO analysis reveals that regulators are mainly involved in the regulation of cellular and metabolic processes. The KEGG results indicate the involvement of the signal transduction pathway.

Conclusions
Our findings demonstrate that m6A modification of mRNA plays a crucial role in the regulation of microglial activation in HIBD, with m6A-associated regulators acting as key modulators of microglial activation.
Male characteristics and contraception in four districts of the central region, Ghana
Authors: Longla Terence A. , Ogum-Alangea Deda , Addo-Lartey Adolphina , Manu Adom A. , Adanu Richard M.K. 
Published: August 2023

Abstract
Background
A lack of male involvement in contraception can negatively affect its practice. To promote male participation in family planning, there is a dire need to understand male attributes that play a role in contraception. This study focuses on the male characteristics that influence the practice of traditional and modern methods of contraception.

Methods
This study is a secondary analysis of quantitative data obtained from the baseline assessment of the Ghana Community-Based Action Teams Study that aimed to prevent violence against women in the Central Region of Ghana in 2016. The analysis included 1742 partnered males aged 18–60 years. Chi-square test, t-test and logistic regression analyses were used to assess the association between male characteristics and the practice of contraception (significance level = 0.05).

Results
The prevalence of contraception was 24.4% (95% CI = 20.8–28.5). Significant male characteristics that were positively associated with the practice of contraception in adjusted models were: post-primary education (AOR = 1.96, 95% CI = 1.27–3.04), perpetration of Intimate Partner Violence (AOR = 1.83, 95% CI = 1.49–2.26), and the number of main sexual partners (AOR = 1.78, 95% CI = 1.15–2.75). However, wanting the first child (AOR = 0.71, 95% CI = 0.54–0.94) and male controlling behaviour (AOR = 0.7, 95% CI = 0.49–0.99) statistically significantly associated with reduced odds of practicing contraception.

Conclusion
Male partner characteristics influence the practice of contraception. Family planning sensitization and education programs should target males who are less likely to practice contraception.
Ramp lesion in anterior cruciate ligament injury: a review of the anatomy, biomechanics, epidemiology, and diagnosis
Authors: Bae Bo Seung , Yoo Sunin , Lee Sang Hak 
Published: August 2023

AbstractRamp lesions, commonly observed in patients with anterior cruciate ligament (ACL) injuries, have been previously defined as longitudinal tears around the meniscocapsular junction. However, the definitions and interpretations of ramp lesions have varied, emphasizing the need to confirm their presence before surgery and the importance of direct visualization using arthroscopy. Recent histological studies have reported new findings on ramp lesions, shedding light on their attachment mechanisms. The anatomical structures around the ramp lesion, such as the posterior horn of medial meniscus (PHMM), semimembranosus (SM), posteromedial (PM) capsule, and meniscotibial ligament (MTL), were assessed regarding how these structures could be attached to each other. The studies of ramp lesions have also contributed to the progression of biomechanical studies explaining the cause and effects of ramp lesions. Ramp lesion has been proven to stabilize the anteroposterior (AP) instability of ACL. In addition, various laboratory studies have demonstrated the relationship between rotational instability of the knee joint and ramp lesions. The analysis of risk factors of ramp lesion helped to understand the injury mechanism of the lesion. Many authors have evaluated the prevalence of ramp lesions in patients with ACL injuries. The development of arthroscopy techniques has influenced the outcomes of ACL reconstruction with the easy detection of ramp lesions. This review article aims to analyze the past findings and recent advancements in anatomical, biomechanical, and epidemiological studies of ramp lesions in patients who underwent ACL reconstruction, and provide various perspectives ramp lesions in patients with ACL reconstruction.
Artificial Intelligence Model Assisting Thyroid Nodule Diagnosis and Management: A Multicenter Diagnostic Study
Authors: Ha Eun Ju , Lee Jeong Hoon , Lee Da Hyun , Moon Jayoung , Lee Haein , Kim You Na , Kim Minji , Na Dong Gyu , Kim Ji-hoon 
Published: August 2023

Abstract

Context
It is not clear how to integrate artificial intelligence (AI)-based models into diagnostic workflows.

Objective
To develop and validate a deep-learning–based AI model (AI-Thyroid) for thyroid cancer diagnosis, and to explore how this improves diagnostic performance.

Methods
The system was trained using 19 711 images of 6163 patients in a tertiary hospital (Ajou University Medical Center; AUMC). It was validated using 11 185 images of 4820 patients in 24 hospitals (test set 1) and 4490 images of 2367 patients in AUMC (test set 2). The clinical implications were determined by comparing the findings of six physicians with different levels of experience (group 1: 4 trainees, and group 2: 2 faculty radiologists) before and after AI-Thyroid assistance.

Results
The area under the receiver operating characteristic (AUROC) curve of AI-Thyroid was 0.939. The AUROC, sensitivity, and specificity were 0.922, 87.0%, and 81.5% for test set 1 and 0.938, 89.9%, and 81.6% for test set 2. The AUROCs of AI-Thyroid did not differ significantly according to the prevalence of malignancies (&gt;15.0% vs ≤15.0%, P = .226). In the simulated scenario, AI-Thyroid assistance changed the AUROC, sensitivity, and specificity from 0.854 to 0.945, from 84.2% to 92.7%, and from 72.9% to 86.6% (all P &lt; .001) in group 1, and from 0.914 to 0.939 (P = .022), from 78.6% to 85.5% (P = .053) and from 91.9% to 92.5% (P = .683) in group 2. The interobserver agreement improved from moderate to substantial in both groups.

Conclusion
AI-Thyroid can improve diagnostic performance and interobserver agreement in thyroid cancer diagnosis, especially in less-experienced physicians.
Protective Factors and the Pathogenesis of Complications in Diabetes
Authors: Yu Marc Gregory , Gordin Daniel , Fu Jialin , Park Kyoungmin , Li Qian , King George Liang 
Published: August 2023

Abstract
Chronic complications of diabetes are due to myriad disorders of numerous metabolic pathways that are responsible for most of the morbidity and mortality associated with the disease. Traditionally, diabetes complications are divided into those of microvascular and macrovascular origin. We suggest revising this antiquated classification into diabetes complications of vascular, parenchymal, and hybrid (both vascular and parenchymal) tissue origin, since the profile of diabetes complications ranges from those involving only vascular tissues to those involving mostly parenchymal organs. A major paradigm shift has occurred in recent years regarding the pathogenesis of diabetes complications, in which the focus has shifted from studies on risks to those on the interplay between risk and protective factors. While risk factors are clearly important for the development of chronic complications in diabetes, recent studies have established that protective factors are equally significant in modulating the development and severity of diabetes complications. These protective responses may help explain the differential severity of complications, and even the lack of pathologies, in some tissues. Nevertheless, despite the growing number of studies on this field, comprehensive reviews on protective factors and their mechanisms of action are not available. This review thus focused on the clinical, biochemical, and molecular mechanisms that support the idea of endogenous protective factors, and their roles in the initiation and progression of chronic complications in diabetes. In addition, this review also aimed to identify the main needs of this field for future studies.