bluuebunny/crossref_metadata_2025_split huggingface dataset:
HapKled: a haplotype-aware structural variant calling approach for Oxford nanopore sequencing data
Authors: Zhang Zhendong , Liu Yue , Li Xin , Liu Yadong , Wang Yadong , Jiang Tao 
Published: July 2024

Introduction: Structural Variants (SVs) are a type of variation that can significantly influence phenotypes and cause diseases. Thus, the accurate detection of SVs is a vital part of modern genetic analysis. The advent of long-read sequencing technology ushers in a new era of more accurate and comprehensive SV calling, and many tools have been developed to call SVs using long-read data. Haplotype-tagging is a procedure that can tag haplotype information on reads and can thus potentially improve the SV detection; nevertheless, few methods make use of this information. In this article, we introduce HapKled, a new SV detection tool that can accurately detect SVs from Oxford Nanopore Technologies (ONT) long-read alignment data.Methods: HapKled utilizes haplotype information underlying alignment data by conducting haplotype-tagging using Whatshap on the reads to improve the detection performance, with three unique calling mechanics including altering clustering conditions according to haplotype information of signatures, determination of similar SVs based on haplotype information, and slack filtering conditions based on haplotype quality.Results: In our evaluations, HapKled outperformed state-of-the-art tools and can deliver better SV detection results on both simulated and real sequencing data. The code and experiments of HapKled can be obtained from https://github.com/CoREse/HapKled.Discussion: With the superb SV detection performance that HapKled can deliver, HapKled could be useful in bioinformatics research, clinical diagnosis, and medical research and development.
Treatment of rosacea with upadacitinib and abrocitinib: case report and review of evidence for Janus kinase inhibition in rosacea
Authors: Zhang Ting , Liu Xu , Zhang Lu , Jiang Xian 
Published: July 2024

IntroductionConventional rosacea treatments are not uniformly pervasive, and the adverse reactions can potentially constrain their utility. The clinical use of JAK1 inhibitors upadacitinib and abrocitinib in the treatment of refractory rosacea has rarely been explored.Case reportWe presented two cases of patients who received the JAK1 inhibitor upadacitinib and four cases of patients who received the JAK1 inhibitor abrocitinib for the treatment of refractory rosacea.DiscussionThe JAK1 inhibitors upadacitinib and abrocitinib may be promising medical options for patients with refractory rosacea. However, the long-term safety and efficacy of upadacitinib and abrocitinib require prospective controlled studies to assess them more comprehensively.
Integrating bioinformatics and multiple machine learning to identify mitophagy-related targets for the diagnosis and treatment of diabetic foot ulcers: evidence from transcriptome analysis and drug docking
Authors: Guo Hui , Xiao Kui , Zheng Yanhua , Zong Jianchun 
Published: July 2024

BackgroundDiabetic foot ulcers are the most common and serious complication of diabetes mellitus, the high morbidity, mortality, and disability of which greatly diminish the quality of life of patients and impose a heavy socioeconomic burden. Thus, it is urgent to identify potential biomarkers and targeted drugs for diabetic foot ulcers.MethodsIn this study, we downloaded datasets related to diabetic foot ulcers from gene expression omnibus. Dysregulation of mitophagy-related genes was identified by differential analysis and weighted gene co-expression network analysis. Multiple machine algorithms were utilized to identify hub mitophagy-related genes, and a novel artificial neural network model for assisting in the diagnosis of diabetic foot ulcers was constructed based on their transcriptome expression patterns. Finally, potential drugs that can target hub mitophagy-related genes were identified using the Enrichr platform and molecular docking methods.ResultsIn this study, we identified 702 differentially expressed genes related to diabetic foot ulcers, and enrichment analysis showed that these genes were associated with mitochondria and energy metabolism. Subsequently, we identified hexokinase-2, small ribosomal subunit protein us3, and l-lactate dehydrogenase A chain as hub mitophagy-related genes of diabetic foot ulcers using multiple machine learning algorithms and validated their diagnostic performance in a validation cohort independent of the present study (The areas under roc curve of hexokinase-2, small ribosomal subunit protein us3, and l-lactate dehydrogenase A chain are 0.671, 0.870, and 0.739, respectively). Next, we constructed a novel artificial neural network model for the molecular diagnosis of diabetic foot ulcers, and the diagnostic performance of the training cohort and validation cohort was good, with areas under roc curve of 0.924 and 0.840, respectively. Finally, we identified retinoic acid and estradiol as promising anti-diabetic foot ulcers by targeting hexokinase-2 (−6.6 and −7.2 kcal/mol), small ribosomal subunit protein us3 (−7.5 and −8.3 kcal/mol), and l-lactate dehydrogenase A chain (−7.6 and −8.5 kcal/mol).ConclusionThe present study identified hexokinase-2, small ribosomal subunit protein us3 and l-lactate dehydrogenase A chain, and emphasized their critical roles in the diagnosis and treatment of diabetic foot ulcers through multiple dimensions, providing promising diagnostic biomarkers and targeted drugs for diabetic foot ulcers.
Stochastic electrical stimulation of the thoracic or cervical regions with surface electrodes facilitates swallow in rats
Authors: Kitamura In , Frazure Michael , Iceman Kimberly , Koike Takuji , Pitts Teresa 
Published: July 2024

IntroductionAspiration pneumonia, a leading cause of mortality, poses an urgent challenge in contemporary society. Neuromuscular electrical stimulation (NMES) has been commonly used in dysphagia rehabilitation. However, given that NMES at motor threshold targets only specific muscles, it carries a potential risk of further compromising functions related to swallowing, respiration, and airway protection. Considering that the swallow motor pattern is orchestrated by the entire swallow pattern generator (the neural mechanism governing a sequence of swallow actions), a rehabilitation approach that centrally facilitates the entire circuit through sensory nerve stimulation is desirable. In this context, we propose a novel stimulation method using surface electrodes placed on the back to promote swallowing.MethodsThe efficacy of the proposed method in promoting swallowing was evaluated by electrically stimulating sensory nerves in the back or neck. Probabilistic stimulus was applied to either the back or neck of male and female rats. Swallows were evoked by an oral water stimulus, and electromyographic (EMG) activity of the mylohyoid, thyroarytenoid, and thyropharyngeus muscles served as the primary outcome measure.ResultsGaussian frequency stimulation applied to the skin surface of the thoracic back elicited significant increases in EMG amplitude of all three swallow-related muscles. Neck stimulation elicited a significant increase in EMG amplitude of the thyroarytenoid during swallow, but not the mylohyoid or thyropharyngeus muscles.DiscussionWhile the targeted thoracic spinal segments T9-T10 have been investigated for enhancing respiration, the promotion of swallowing through back stimulation has not been previously studied. Furthermore, this study introduces a new probabilistic stimulus based on Gaussian distribution. Probabilistic stimuli have been reported to excel in nerve stimulation in previous research. The results demonstrate that back stimulation effectively facilitated swallow more than neck stimulation and suggest potential applications for swallowing rehabilitation.
Effects of the feeding protocol during blood transfusion on splanchnic tissue oxygenation and complications in very premature infants
Authors: He Jianghua , Sun Xueshi , Xu Xiaoming , Luo Hanwen , Tang Jun , Xiong Tao , Zhao Jing , Shi Jing 
Published: July 2024

BackgroundThe effects of blood transfusions on splanchnic oxygenation and complications related to blood transfusions, including red blood cell (RBC) transfusions, in premature infants undergoing enteral feeding, to provide clinical evidence for a management protocol for premature infants during the peri-transfusion period.MethodsThis single-blind, randomized, controlled trial enrolled sixty eligible preterm infants who were randomly divided into the withholding feeding group (n = 30) or feeding group (n = 30). Enteral feeding was withheld for 8 h, beginning from the start of transfusion infants in the feeding group were fed according to the pre-transfusion feeding approach during and after RBC transfusion.ResultsBaseline characteristics of those in the withholding and feeding groups were as follows: gestational age (weeks) 27.52 (24.86–30.14) and 27.13 (25.43–30.14); birth weight (g), 1,027 (620–1,450) and 1,027 (620–1,270); blood transfusion day, 48 (14–79) and 39 (10–78); and hemoglobin before blood transfusion (g/L), 81.67 (±10.56) and 85.93 (±14.77). No significant differences were observed between groups at baseline. No significant differences were observed in the average splanchnic tissue oxygenation changes or clinical results at any time. One patient in the withholding feeding group experienced transfusion-associated necrotizing enterocolitis.ConclusionsNo differences in splanchnic oxygenation observed these feeding protocols. This study suggests the feasibility of a sizable trial to evaluate clinical outcomes. The risks of mesenteric ischemia and transfusion-related necrotizing enterocolitis for premature infants were not increased by enteral feeding during RBC transfusion.Clinical trial registrationChiCTR2200055726 (https://www.chictr.org.cn/).
High-purity 1,2-dimyristoyl-sn-glycero-3-phosphocholine: synthesis and emulsifying performance evaluation
Authors: Kim Se-Young , Park Ye-Lim , Ji Ha-Eun , Lee Hae-Se , Chang Hyeon-Jun , Bang Gyeong-Hee , Lee Jeung-Hee 
Published: July 2024

Introduction1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) is a promising emulsifier for bioactive delivery systems, but its industrial applications are limited by the lack of cost-effective and scalable synthetic routes. The purpose of this study was to economically produce high-purity DMPC by replacing commonly used column chromatography methods and to evaluate the emulsifying performance.MethodsDMPC was synthesized from sn-glycero-3-phosphocholine using Steglich esterification followed by sequential recrystallization from ethyl acetate and acetone. The structure of DMPC was identified and its purity was confirmed using various spectroscopy and chromatography techniques. The emulsifying performance was evaluated by examining the effects of storage on the properties of o/w emulsions prepared using soybean oil with (i) soy PC, (ii) soy PC + DMPC (1:1, w/w), and (iii) DMPC as emulsifiers.ResultsThe chemical impurities formed during the synthesis of DMPC was removed, and its final purity was 96%, and the melt transition temperature was 37.6°C. No visible difference between the three emulsions (soy PC, soy PC+DMPC, and DMPC) was observed during two-week storage, and the DMPC-based emulsion was more stable than soy PC emulsion, showing smaller particle size distribution during 6 months.DiscussionThe highly pure DMPC was synthesized by an economical method, and DMPC-based emulsions demonstrated physicochemical stable, highlighting its potential for food and pharmaceutical industry-related applications. Our findings suggest that DMPC holds promise as an emulsifier with broad applications in the food industry.
Gene signatures of copper metabolism related genes may predict prognosis and immunity status in Ewing’s sarcoma
Authors: Chen Yongqin , Zhang Wencan , Xu Xiao , Xu Biteng , Yang Yuxuan , Yu Haozhi , Li Ke , Liu Mingshan , Qi Lei , Jiao Xiejia 
Published: July 2024

BackgroundCuproptosis is copper-induced cell death. Copper metabolism related genes (CMRGs) were demonstrated that used to assess the prognosis out of tumors. In the study, CMRGs were tested for their effect on TME cell infiltration in Ewing’s sarcoma (ES).MethodsThe GEO and ICGC databases provided the mRNA expression profiles and clinical features for downloading. In the GSE17674 dataset, 22prognostic-related copper metabolism related genes (PR-CMRGs) was identified by using univariate regression analysis. Subsequently, in order to compare the survival rates of groups with high and low expression of these PR-CMRGs,Kaplan-Meier analysis was implemented. Additionally, correlations among them were examined. The study employed functional enrichment analysis to investigate probable underlying pathways, while GSVA was applied to evaluate enriched pathways in the ES (Expression Set). Through an unsupervised clustering algorithm, samples were classified into two clusters, revealing significant differences in survival rates and levels of immune infiltration.ResultsUsing Lasso and step regression methods, five genes (TFRC, SORD, SLC11A2, FKBP4, and AANAT) were selected as risk signatures. According to the Kaplan-Meier survival analysis, the high-risk group had considerably lower survival rates than the low-risk group(p=6.013e-09). The area under the curve (AUC) values for the receiver operating characteristic (ROC) curve were 0.876, 0.883, and 0.979 for 1, 3, and 5 years, respectively. The risk model was further validated in additional datasets, namely GSE63155, GSE63156, and the ICGC datasets. To aid in outcome prediction, a nomogram was developed that incorporated risk levels and clinical features. This nomogram’s performance was effectively validated through calibration curves.Additionally, the study evaluated the variations in immune infiltration across different risk groups, as well as high-expression and low-expression groups. Importantly, several drugs were identified that displayed sensitivity, offering potential therapeutic options for ES.ConclusionThe findings above strongly indicate that CMRGs play crucial roles in predicting prognosis and immune status in ES.
Radiomics analysis combining gray-scale ultrasound and mammography for differentiating breast adenosis from invasive ductal carcinoma
Authors: Li Wen , Song Ying , Qian Xusheng , Zhou Le , Zhu Huihui , Shen Long , Dai Yakang , Dong Fenglin , Li Yonggang 
Published: July 2024

ObjectivesTo explore the utility of gray-scale ultrasound (GSUS) and mammography (MG) for radiomic analysis in distinguishing between breast adenosis and invasive ductal carcinoma (IDC).MethodsData from 147 female patients with pathologically confirmed breast lesions (breast adenosis: 61 patients; IDC: 86 patients) between January 2018 and December 2022 were retrospectively collected. A training cohort of 113 patients (breast adenosis: 50 patients; IDC: 63 patients) diagnosed from January 2018 to December 2021 and a time-independent test cohort of 34 patients (breast adenosis: 11 patients; IDC: 23 patients) diagnosed from January 2022 to December 2022 were included. Radiomic features of lesions were extracted from MG and GSUS images. The least absolute shrinkage and selection operator (LASSO) regression was applied to select the most discriminant features, followed by logistic regression (LR) to construct clinical and radiomic models, as well as a combined model merging radiomic and clinical features. Model performance was assessed using receiver operating characteristic (ROC) analysis.ResultsIn the training cohort, the area under the curve (AUC) for radiomic models based on MG features, GSUS features, and their combination were 0.974, 0.936, and 0.991, respectively. In the test cohort, the AUCs were 0.885, 0.876, and 0.949, respectively. The combined model, incorporating clinical and all radiomic features, and the MG plus GSUS radiomics model were found to exhibit significantly higher AUCs than the clinical model in both the training cohort and test cohort (p&lt;0.05). No significant differences were observed between the combined model and the MG plus GSUS radiomics model in the training cohort and test cohort (p&gt;0.05).ConclusionThe effectiveness of radiomic features derived from GSUS and MG in distinguishing between breast adenosis and IDC is demonstrated. Superior discriminatory efficacy is shown by the combined model, integrating both modalities.
Immune-related adverse events in patients treated with immunotherapy for locally advanced or metastatic NSCLC in real-world settings: a systematic review and meta-analysis
Authors: Pasello Giulia , Pavan Alberto , De Nuzzo Mattia , Frega Stefano , Ferro Alessandra , Dal Maso Alessandro , Bonanno Laura , Guarneri Valentina , Girardi Fabio 
Published: July 2024

IntroductionRandomized clinical trials (RCTs) represent the mainstay for the approval of new treatments. However, stringent inclusion criteria often cause them to depart from the daily clinical practice. Real-world (RW) evidence have a complementing role, filling the gap between the efficacy of a treatment and its effectiveness. Immune checkpoint inhibitors (ICIs) have changed the treatment scenario for non-small cell lung cancer (NSCLC); immune-related adverse events (irAEs) could become life-threatening events, when not timely managed. We performed a systematic review and meta-analysis on the RW impact of irAEs through the years.MethodsThe systematic review focused on irAEs occurred in locally advanced or metastatic NSCLC patients, treated with ICIs in a RW setting. We queried two electronic databases (Embase and Medline) from 1996 to August 2022. We then conducted a meta-analysis dividing the results in two cohorts (2015-2018 and 2019-2021). We described the prevalence of patients with irAEs of any or severe grade (G). Estimates were expressed as proportions up to the second decimal point (effect size, ES). IrAEs of interest were those involving the skin, the liver, the endocrine system or the gastro-intestinal system.ResultsOverall, 21 RW studies on 5,439 patients were included in the quantitative and qualitative synthesis. The prevalence of G≥3 irAEs was slightly lower in the 2015-2018 subgroup, while the prevalence of irAEs of any grade was similar for both periods. Overall, we observed a higher ES for gastrointestinal, hepatic and lung irAEs, while a lower ES was reported for skin or endocrine irAEs. Endocrine irAEs were reported in 10 out of 21 studies, with a slight increase in the most recent studies, while cutaneous toxicities were mostly reported in two studies lead within the first time-period. Pulmonary, gastrointestinal, and hepatic toxicities, showed a more heterogeneous distribution of ES over time.DiscussionOur findings showed that the frequency of irAEs remained stable across the two calendar periods examined in our meta-analysis. This finding suggests that RW data might not be able to identify a potential learning curve in detection and management of irAEs.
Enhancing breast cancer treatment: mesoporous dopamine nanoparticles in synergy with chrysin for photothermal therapy
Authors: Zhu Jing , Zhang Heng , Lan Haomiao , Bi Bing , Peng Xianfeng , Li Dandan , Wang Haili , Zhu Ke , Shao Fuqiang , Yin Minggang 
Published: July 2024

IntroductionBreast cancer is one of the most prevalent cancers, primarily affecting women. Among its subtypes, estrogen receptor-positive (ER+) breast cancer is particularly common. Inhibiting estrogen's effects is crucial for treating ER+ breast cancer, but current therapies often have significant side effects and limitations. Chrysin, a natural flavonoid, has shown potential in reducing estrogen receptor expression, but its poor water solubility hampers clinical application. This study explores the use of mesoporous dopamine nanoparticles (mPDA) to enhance the delivery and efficacy of Chrysin, combined with photothermal therapy (PTT), for breast cancer treatment.MethodsChrysin-loaded mPDA nanoparticles (Chrysin@mPDA) were synthesized and characterized for their morphology, drug-loading efficiency, stability, and photothermal properties. Network pharmacology was used to predict Chrysin's mechanisms in breast cancer, which were validated through gene expression analysis in cell experiments. The therapeutic efficacy of Chrysin@mPDA with and without PTT was evaluated in a mouse model of breast cancer, with tumor volume and weight measured. Immunohistochemical analysis was conducted to assess estrogen receptor expression and immune cell infiltration in tumor tissues.ResultsChrysin@mPDA nanoparticles demonstrated a high drug-loading capacity and excellent stability. Photothermal studies confirmed the nanoparticles' ability to generate heat upon laser exposure, significantly enhancing Chrysin release in acidic conditions with laser irradiation. Network pharmacology identified key target genes affected by Chrysin, including ESR1, BRCA1, CTNNB1, and BAX, which were validated through qPCR. In vivo, the combination of Chrysin@mPDA and PTT significantly reduced tumor volume and weight, decreased estrogen receptor-positive cells, and increased infiltration of CD3+CD4+ and CD3+CD8+ T cells in tumor tissues.DiscussionThe study highlights the potential of Chrysin-loaded mPDA nanoparticles combined with PTT as an effective strategy for breast cancer treatment. This approach addresses the limitations of Chrysin's solubility and enhances its therapeutic efficacy through synergistic mechanisms. The dual action of Chrysin in modulating gene expression and PTT in inducing localized hyperthermia and immune response suggests a promising avenue for improved breast cancer prognosis and reduced recurrence.
S1P/S1PR1 signaling is involved in the development of nociceptive pain
Authors: Dong Daosong , Yu Xue , Tao Xueshu , Wang Qian , Zhao Lin 
Published: July 2024

BackgroundPain is a complex perception involving unpleasant somatosensory and emotional experiences. However, the underlying mechanisms that mediate its different components remain unclear. Sphingosine-1-phosphate (S1P), a metabolite of sphingomyelin and a potent lipid mediator, initiates signaling via G protein-coupled receptors (S1PRs) on cell surfaces. It serves as a second messenger in cellular processes such as proliferation and apoptosis. Nevertheless, the neuropharmacology of sphingolipid signaling in pain conditions within the central nervous system remains largely unexplored and controversial.MethodsChronic nociceptive pain models were induced in vivo by intraplantar injection of 20 μL complete Freund's adjuvant (CFA) into the left hind paws. We assessed S1P and S1PR1 expression in the spinal cords of CFA model mice. Functional antagonists of S1PR1 or S1PR1-specific siRNA were administered daily following CFA model establishment. Paw withdrawal response frequency (PWF) and paw withdrawal latency (PWL) were measured to evaluate mechanical allodynia and thermal hyperalgesia, respectively. RT-PCR assessed interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α levels. Western blotting and immunofluorescence were used to analyze glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule (Iba1), STAT3, ERK, and p38 MAPK protein expression.ResultsIn the chronic nociceptive pain model induced by CFA, S1P and S1PR1 expression levels were significantly elevated, leading to activation of spinal cord glial cells. S1PR1 activation also promoted MMP2-mediated cleavage of mature IL-1β. Additionally, S1PR1 activation upregulated phosphorylation of STAT3, ERK, and p38 MAPK in glial cells, profoundly impacting downstream signaling pathways and contributing to chronic nociceptive pain.ConclusionThe S1P/S1PR1 axis plays a pivotal role in the cellular and molecular mechanisms underlying nociceptive pain. This signaling pathway modulates glial cell activation and the expression of pain-related genes (STAT3, ERK, p38 MAPK) and inflammatory factors in the spinal dorsal horn. These findings underscore the potential of targeting the S1P system for developing novel analgesic therapies.