bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and mechanism of nourishing yin and purging fire therapy for central precocious puberty based on meta-analysis and network pharmacology
Authors: Ma Yuan , Sun Fengping , Zhang Erbing , Li Jing , Yue Shangsai , Fu Yunyun , Zhang Suling 
Published: December 2023

Background:
Central precocious puberty (CPP) is due to the early activation of the hypothalamus-pituitary-gonadal axis, and its incidence is on the rise. A number of studies have shown that nourishing yin and purging fire (NYPF) therapy can be beneficial for CPP. Therefore, we conducted this review to investigate the efficacy, safety, and mechanism of NYPF therapy for CPP.

Methods:
Electronic databases including PubMed, the Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wan-fang Database, and China Scientific Technical Journals Database and 2 platforms including Clinical Trials and Chinese Clinical Trial Registry were searched for randomized controlled trials of NYPF therapy for CPP. A meta-analysis was conducted using RevMan 5.3 and Stata 17.0 software. The core herb pair of NYPF was identified by data mining using IBM SPSS Modeler 18.0 software. The active ingredients and targets of the core herb pair were obtained through the TCMSP database. The main targets of CPP were acquired form the GeneCards, Disgenet and TTD databases. A protein-protein interaction network was carried out to select the core genes by using STRING platform and Cytoscape 3.7.2 software. Metascape platform was used to conduct gene ontology (GO) and KEGG enrichment analysis. The results were verified utilizing molecular docking.

Results:
A total of 23 studies were included. Meta-analysis shows the NYPF therapy could significantly improve the clinical efficacy rate and secondary sexual indicators (uterine volume, ovarian volume, breast nucleus diameter, follicular diameter), reduce TCM syndrome scores and serum sex hormone (FSH, LH, E2), and slow down bone age maturation compared to GnRHa therapy group. In addition, NYPF therapy was safe and has no obvious adverse events. Data mining revealed that the core herb pair of NYPF was “Anemarrhenae Rhizoma (Zhimu) - Phellodendri Chinensis Cortex (Huangbai).” Network pharmacology predicted that quercetin, kaempferol, beta-sitosterol, etc were the key components of Zhimu-Huangbai for treating CPP. The core targets were TP53, JUN, AKT1, ESR1, TNF, IL6, CCND1, MAPK1, BCL2, EGFR, IL1B, and PTGS2. They played a pivotal role in modulating multiple signaling pathways, such as Endocrine resistance, MAPK signaling pathway, and PI3K-Akt signaling pathway.

Conclusion:
This article revealed that NYPF therapy is effective and safe against CPP. The mechanism of the core herb pair of NYPF therapy for CPP through muti-components, muti-targets and muti-pathways.
Transformation from acute promyelocytic leukemia in pregnancy to acute myeloid leukemia with MLL-AF9 fusion gene: A case report and literature review
Authors: Gao Yang , Han Na , Jiang Yu , Lu Ziyuan 
Published: December 2023

Rationale:
Because there are few evidence-based guidelines and an extremely low incidence rate, managing and treating patients who have transitioned from acute promyelocytic leukemia (APL), which was diagnosed during pregnancy, to acute myeloid leukemia (AML), can be difficult.

Patient concerns:
In this case, a 34-year-old pregnant patient was diagnosed with APL in medium-risk group in June 2017. After the all-trans retinoic acid and arsenic trioxide-based full-course treatment, the patients achieved complete remission (CR) and were well-tolerated. After 5 years, the patient complained of fatigue for 3 months.

Diagnosis:
Bone marrow examination revealed hypercellularity with approximately 50% immunophenotypic abnormal myeloblasts with MLL-AF9 fusion gene. Based on the AML diagnosis criteria of the World Health Organization, the patient was eventually diagnosed with a rare transformation from APL to AML.

Interventions:
The patient was treated with two cycles of induction chemotherapy and an allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Outcomes:
Until now, the patient is in continuous remission with no signs of APL and AML.

Lessions:
Despite the rarity of APL to AML transformation, it is crucial to track the disease’s progress and administer treatment on time. It remains uncertain whether the risk stratification and clinical outcomes of secondary AML with MLL-AF9 are equivalent to those of de novo AML with MLL-AF9. The management and treatment of these patients should be personalized and require further observation.
Clinical observation of Gofried positive buttress reduction in the treatment of young femoral neck fracture: A systematic review and meta-analysis
Authors: Li Huankun , Chen Hongjun , She Ruihao , Li Yanhong , Qin Gang , Gan Fukai , Liang Huahui , Hu Baijun 
Published: December 2023

Background:
Femoral neck fractures in young adults(<65 years), have always been a difficult problem, characterized by high rates of nonunion and avascular necrosis (AVN). The clinical efficacy of anatomical reduction and non-anatomical reduction methods needs to be supported by clinical data. Therefore, we conduct a meta-analysis on the clinical efficacy of different reduction methods to better guide clinical practice.

Methods:
Relevant studies published using internal fixation to treat femoral neck fracture in several databases were searched. The outcomes sought included Harris score and the rate of AVN, nonunion and femoral neck shortening (<5 mm). Included studies were assessed for methodological bias and estimates of effect were calculated. Potential reasons for heterogeneity were explored.

Results:
The clinical results showed that compared with the anatomical reduction and positive buttress, there is no significant difference in the rate of AVN (OR = 0.87, 95%CI: 0.55–1.37, P = .55), nonunion (OR = 0.54, 95%CI: 0.21–1.41, P = .21), femoral neck shortening (<5 mm) (OR = 1.03,95%CI: 0.57–1.86, P = .92), the Harris score (MD = −0.28, 95%CI: −1.36–0.80, P = .61) and the excellent and good rate of Harris score (OR = 1.73, 95%CI: 0.84–3.56, P = .61). However, compared with negative buttress, the rate of AVN (OR = 0.62, 95%CI: 0.38–1.01, P = .05), nonunion (OR = 0.34, 95%CI: 0.12–1.00, P = .05) and femoral neck shortening (<5 mm) (OR = 0.27, 95%CI: 0.16–0.45, P < .00001) were significantly lower, and the Harris score (MD = 6.53, 95%CI: 2.55 ~ 10.51, P = .001) was significantly better in positive buttress.

Conclusions:
In the case of difficult to achieve anatomical reduction, for young patients (< 65 years) with femoral neck fracture, reduction with positive buttress can be an excellent alternative and negative buttress should be avoided as much as possible.
Effectiveness of whole-body vibration in patients with cerebral palsy: A systematic review and meta-analysis
Authors: Han Yong-Gu , Kim Myoung-Kwon 
Published: December 2023

Background:
This study examined the effects of systemic vibration exercises on cerebral palsy patients.

Methods:
Literature published in Cumulated Index to Nursing and Allied Health Literature (CINAHL), Cochrane library, Embase, Physiotherapy Evidence Database (PEDro), and PubMed was reviewed. A total of 2978 studies were initially retrieved. After further reading of the full texts 17 articles were finally included. A quality assessment of the included studies was conducted using the risk of bias (RoB) 2.0, and the Funnel plot and the Egger test were conducted to confirm the publication bias. Subgroup analysis was carried out according to the dependent variables, the international classification of functioning, disability, and health (ICF), frequency, treatment period and age.

Results:
The overall effect size of homogeneity was 0.474 (CI = 0.148–0.801). The analysis of the dependent variables showed the following order of the effect size: balance, muscle strength, spasticity, bone density, range of motion of the joint, gait function, and motor function. In the ICF classification, the effect size was observed to follow the order of body structure and function, activity, and participation. The effect size in the intervention according to the treatment period showed the following order: 7 to 12 weeks, 1 to 6 weeks, and 14 to 24 weeks. The age-dependent classification showed the following order in the effect size: school age, adolescent and adult, and infant and school age.

Conclusions:
Systemic vibration is the most effective intervention to improve the balance and gait in patients with cerebral palsy and improve the body structure and function according to the ICF.
Anti-Nasopharyngeal carcinoma mechanism of sanguinarine based on network pharmacology and molecular docking
Authors: Fan Jing-Ying , Liu Jie , Zhang Wen-Qing , Lin Ting , Hu Xi-Ran , Zhou Fang-Liang , Tang Le , He Ying-Chun , Shi Hong-Jian 
Published: December 2023

Background:
The purpose of this study was to investigate the mechanism of sanguinarine (SAN) against nasopharyngeal carcinoma (NPC) by means of network pharmacology, molecular docking technique, and experimental verification.

Methods:
The SAN action targets were predicted using the Swiss Target Prediction database, the related NPC targets were determined using the GEO database, and the intersection of drug and disease pathway targets were considered to be the potential targets of SAN against NPC. The target-protein interaction network map was constructed using the STRING database, and the core target genes of SAN against NPC were obtained via topological network analysis. “R” language gene ontology (GO) function and Kyoto encyclopedia of genes and genome (KEGG) pathway enrichment analyses were used to dock the core target genes with SAN with the help of AutodockVina. Cell proliferation was detected using MTT and xCELLigence real-time cell analysis. Apoptosis was identified via Hoechst 33342 staining, JC-1 mitochondrial membrane staining, and annexin V-FITC/PI double fluorescence staining, while protein expression was quantified using western blotting.

Results:
A total of 95 SAN against NPC targets were obtained using target intersection, and 8 core targets were obtained by topological analysis and included EGFR, TP53, F2, FN1, PLAU, MMP9, SERPINE1, and CDK1. Gene ontology enrichment analysis identified 530 items, and 42 items were obtained by Kyoto encyclopedia of genes and genome pathway enrichment analysis and were mainly related to the PI3K/AKT, MAPK, and p53 signaling pathways. Molecular docking results showed that SAN had good binding activity to the core target. SAN inhibited the proliferation of NPC cells, induced apoptosis, reduced the expression levels of survivin and Bcl2, and increased the expression levels of Bax and cleaved caspase-8. It also decreased the expression levels of the key proteins p-c-Raf, p-MEK, and p-ERK1/2 in the MAPK/ERK signaling pathway in NPC cells.

Conclusion:
SAN inhibits the proliferation and induces the apoptosis of NPC cells through the MAPK/ERK signaling pathway.
Effect of Liuzijue exercise in different periods on circadian rhythm of blood pressure in patients with essential hypertension: A randomized trial
Authors: Chen Yixiao , Liu Nannan , Guo Yuyan , Zheng Caiping , Fu Dijun , Cai Yugang , Nie Kaidi , Xia Lina 
Published: December 2023

Background:
Exercising at different times of the day is a widely employed strategy for treating essential hypertension, aimed at enhancing the circadian rhythm of blood pressure. This study aimed to investigate the effects of Liuzijue exercise in the morning and afternoon on the circadian rhythm of blood pressure in patients with essential hypertension.

Methods:
This clinical randomized trial recruited 36 patients. They were randomly divided into 3 groups: morning exercise, afternoon exercise, and waiting treatment group. Randomization was performed at a ratio of 1:1:1, ensuring an equal distribution of participants among the 3 groups. Based on maintaining routine work and rest and continuing the original drug treatment, the exercise performed Liuzijue exercise for 12 weeks. The exercise time was 9:00 to 10:00 in the morning exercise group and 14:00 to 15:00 in the afternoon exercise group. The waiting treatment group did not perform any form of fitness exercise. The subjects in the 3 groups were monitored by 24-hour ambulatory blood pressure on the day before and after the first day.

Results:
After the 12-week Liuzijue exercise intervention, mean systolic blood pressure during the night significantly decreased in the morning exercise group (P < .01). In contrast, the waiting group experienced substantial increases in 24-hour mean systolic blood pressure (24hSBP), 24-hour mean diastolic blood pressure (24hDBP), mean systolic blood pressure during the daytime (dSBP), and mean diastolic blood pressure during the daytime (dDBP) (P < .01). Further analysis showed that the morning exercise group had significantly lower 24hSBP, 24hDBP, dSBP, dDBP, and mean systolic blood pressure during the night than the waiting group (P < .05). Additionally, the morning exercise group had lower 24hSBP and dSBP levels than the afternoon exercise group (P < .05). In contrast, the afternoon exercise group had lower 24hDBP and dDBP than the waiting treatment group (P < .05).

Conclusions:
The 12-week Liuzijue exercise in the morning regimen demonstrated superior efficacy in reducing 24-hour ambulatory blood pressure levels among patients with essential hypertension. Moreover, it facilitates the transition of non-dipper blood pressure patterns to dippers, thereby rectifying aberrant circadian rhythms.
BIOFORMERS: A SCALABLE FRAMEWORK FOR EXPLORING BIOSTATES USING TRANSFORMERS
Authors: Amara-Belgadi Siham , Li Orion , Zhang David Yu , Gopinath Ashwin 
Published: December 2023

AbstractGenerative pre-trained models, such as BERT and GPT, have demonstrated remarkable success in natural language processing and computer vision. Leveraging the combination of large-scale, diverse datasets, transformers, and unsupervised learning, these models have emerged as a promising method for understanding complex systems like language. Despite the apparent differences, human language and biological systems share numerous parallels. Biology, like language, is a dynamic, interconnected network where biomolecules interact to create living entities akin to words forming coherent narratives. Inspired by this analogy, we explored the potential of using transformer-based unsupervised model development for analyzing biological systems and proposed a framework that can ingest vast amounts of biological data to create a foundational model of biology using BERT or GPT. This framework focuses on the concept of a ‘biostate,’ defined as a high-dimensional vector encompassing various biological markers such as genomic, proteomic, transcriptomic, physiological, and phenotypical data. We applied this technique to a small dataset of single-cell transcriptomics to demonstrate its ability to capture meaningful biological insights into genes and cells, even without any pre-training. Furthermore, the model can be readily used for gene network inference and genetic perturbation prediction.
EngineeredBacillus subtilisas oral probiotics to enhance clearance of blood lactate
Authors: Yang Mengdi , Hutchinson Noah , Ye Ningyuan , Yin Jianing , Guan Ming , Wang Zongqi , Chen Peiru , Yang Shaobo , Crane Justin D. , Zhang Ke , He Xuesong , Li Jiahe 
Published: December 2023

AbstractElevated lactate concentrations are implicated in various acute and chronic diseases such as sepsis and mitochondrial dysfunction, respectively. Conversely, ineffective lactate clearance is associated with poor clinical prognoses and high mortality in these diseases. While several groups have proposed using small molecule inhibitors and enzyme replacement to reduce circulating lactate, there are few practical and effective ways to manage this condition. Recent evidence suggests that lactate is exchanged between systemic circulation and the gut, allowing bidirectional modulation between the gut microbiota and peripheral tissues. Inspired by these findings, this work seeks to engineer spore-forming probioticB. subtilisstrains to enable intestinal delivery of lactate oxidase as a therapeutic enzyme. After strain optimization, we showed that oral administration of engineeredB. subtilisspores to the gut of mice reduced elevations in blood lactate in two different mouse models involving exogenous challenge or pharmacologic perturbation without disrupting gut microbiota composition, liver function, or immune homeostasis. Taken together, through the oral delivery of engineered probiotic spores to the gastrointestinal tract, our proof-of-concept study offers a practical strategy to aid in the management of disease states with elevated blood lactate and provides a new approach to ‘knocking down’ circulating metabolites to help understand their roles in host physiological and pathological processes.Significance StatementThis study pioneers the use of engineeredBacillus subtilisspores as an oral probiotic therapy to enhance the clearance of elevated blood lactate, a condition linked to severe health issues like sepsis and metabolic disorders. By genetically modifying these spores to deliver therapeutic enzymes directly to the gut, we demonstrated a practical, effective method to modulate systemic lactate levels. This approach leverages the natural exchange between the gut microbiota and systemic circulation, offering a new strategy for managing diseases associated with lactate dysregulation. The safety and efficacy of this method were validated in mouse models, providing a foundation for future clinical applications.
Constant-pH Molecular Dynamics Simulations of Closed and Open States of a Proton-gated Ion Channel
Authors: Jansen Anton , Bauer Paul , Howard Rebecca J. , Hess Berk , Lindahl Erik 
Published: December 2023

AbstractAlthough traditional molecular dynamics simulations successfully capture a variety of different molecular interactions, the protonation states of titratable residues are kept static. A recentconstant-pHmolecular dynamics implementation in the GROMACS package allows pH effects to be captured dynamically, and promises to provide both the accuracy and computational performance required for studying pH-mediated conformational dynamics in large, complex systems containing hundreds of titratable residues. Here, we demonstrate the applicability of this constant-pH implementation by simulating the proton-gated ion channel GLIC at resting and activating pH, starting from closed and open structures. Our simulations identify residues E26 and E35 as especially pH-sensitive, and reveal state-dependent pKashifts at multiple residues, as well as side chain and domain rearrangements in line with the early stages of gating. Our results are consistent with several previous experimental findings, demonstrating the applicability of constant-pH simulations to elucidate pH-mediated activation mechanisms in multidomain membrane proteins, likely extensible to other complex systems.Significance statementElectrostatic interactions play important roles in protein structure and function. Since changes in pH will (de)protonate residues and thereby modify such interactions, pH itself is a critical environmental parameter. However, protonation states of titratable residues are static during classical molecular dynamics simulations. Recently, aconstant-pHalgorithm was implemented in the GROMACS package, allowing pH effects to be captured dynamically. Here, we used this implementation to perform constant-pH simulations of the proton-gated ion channel GLIC, providing insight into its activation mechanism by revealing state-dependent shifts in protonation as well as pH-dependent side chain and domain-level rearrangements. The results show that constant-pH simulations are both accurate and capable of modeling dozens of titratable sites, with important implications for e.g. drug design.
Somatic Mosaicism in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Reveals Widespread Degeneration from Focal Mutations
Authors: Zhou Zinan , Kim Junho , Huang August Yue , Nolan Matthew , Park Junseok , Doan Ryan , Shin Taehwan , Miller Michael B. , Chhouk Brian , Morillo Katherine , Yeh Rebecca C. , Kenny Connor , Neil Jennifer E. , Lee Chao-Zong , Ohkubo Takuya , Ravits John , Ansorge Olaf , Ostrow Lyle W. , Lagier-Tourenne Clotilde , Lee Eunjung Alice , Walsh Christopher A. 
Published: December 2023

AbstractAlthough mutations in dozens of genes have been implicated in familial forms of amyotrophic lateral sclerosis (fALS) and frontotemporal degeneration (fFTD), most cases of these conditions are sporadic (sALS and sFTD), with no family history, and their etiology remains obscure. We tested the hypothesis that somatic mosaic mutations, present in some but not all cells, might contribute in these cases, by performing ultra-deep, targeted sequencing of 88 genes associated with neurodegenerative diseases in postmortem brain and spinal cord samples from 404 individuals with sALS or sFTD and 144 controls. Known pathogenic germline mutations were found in 20.6% of ALS, and 26.5% of FTD cases. Predicted pathogenic somatic mutations in ALS/FTD genes were observed in 2.7% of sALS and sFTD cases that did not carry known pathogenic or novel germline mutations. Somatic mutations showed low variant allele fraction (typically <2%) and were often restricted to the region of initial discovery, preventing detection through genetic screening in peripheral tissues. Damaging somatic mutations were preferentially enriched in primary motor cortex of sALS and prefrontal cortex of sFTD, mirroring regions most severely affected in each disease. Somatic mutation analysis of bulk RNA-seq data from brain and spinal cord from an additional 143 sALS cases and 23 controls confirmed an overall enrichment of somatic mutations in sALS. Two adult sALS cases were identified bearing pathogenic somatic mutations inDYNC1H1andLMNA,two genes associated with pediatric motor neuron degeneration. Our study suggests that somatic mutations in fALS/fFTD genes, and in genes associated with more severe diseases in the germline state, contribute to sALS and sFTD, and that mosaic mutations in a small fraction of cells in focal regions of the nervous system can ultimately result in widespread degeneration.
The exotic thymidine modification 5-hydroxymethyluridine in dinoflagellateAmphidinium carterae
Authors: Li Chongping , Li Ying , Wang Yuci , Meng Ruixiang , Shi Xiaoyan , Zhang Yangyi , Liang Nan , Huang Hongda , Li Yue , Zhou Hui , Xu Jiawei , Xu Wenqi , Chen Hao 
Published: December 2023

AbstractDinoflagellate chromosomes are extraordinary, as their organization is independent of architectural nucleosomes unlike typical eukaryotes and shows a cholesteric liquid crystal state. 5-hydroxymethyluridine (5hmU) is present at unusually high levels and its function remains an enigma in dinoflagellates chromosomal DNA. Here, we demonstrate that 5hmU exhibits content variations in different dinoflagellates and is generated at the poly-nucleotide level through hydroxylation of thymidine. Importantly, we identified the enzyme, which is a putative dinoflagellate TET/JBP homologue, catalyzing 5hmU production using eitherin vivoorin vitrobiochemical assay. Based on the near-chromosomal level genome assembly of dinoflagellateAmphidinium carterae, we depicted a comprehensive 5hmU landscape and found that most 5hmU peaks share a conserved TG-rich motif, and are significantly enriched in repeat elements, which mark partially overlapping regions with 5-methylcytosine (5mC) sites. Moreover, inhibition of 5hmU via dioxygenase inhibitor leads to transcriptional activation of 5hmU-marked transposable elements (TEs), implying that 5hmU appears to serve as epigenetic marks for silencing retrotransposon. Together, our results revealed the biogenesis, genome-wide landscape and molecular function of dinoflagellate 5hmU, providing mechanic insight into the function of this enigmatic DNA mark.