bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired Glymphatic System Actions in Obstructive Sleep Apnea Adults
Authors: Roy Bhaswati , Nunez Alba , Aysola Ravi S. , Kang Daniel W. , Vacas Susana , Kumar Rajesh 
Published: May 2022

Study ObjectivesObstructive sleep apnea (OSA) is accompanied by sleep fragmentation and altered sleep architecture, which can potentially hinder the glymphatic system, increasing risks for Alzheimer’s disease (AD), but the status is unclear in OSA. Our aim was to investigate the glymphatic system in OSA subjects and examine the relationships between OSA disease severity, sleep symptoms, and glymphatic system indices in OSA using diffusion tensor imaging (DTI).MethodsWe acquired DTI data from 59 OSA and 62 controls using a 3.0-Tesla MRI and examined OSA disease severity and sleep symptoms with the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). Diffusivity maps in the x-axis (Dxx), y-axis (Dyy), and z-axis (Dzz), as well as in x-y axis (Dxy), y-z axis (Dyz), and x-z axis (Dxz) were calculated, diffusion values for the projection and association fibers extracted, and the DTI analyses along the perivascular space (DTI-ALPS index) were performed. The glymphatic system indices were compared between groups and correlated with disease severity and sleep symptoms in OSA subjects.ResultsDzz values, derived from projection fiber areas, Dyy and Dzz values from association fiber areas, as well as ALPS and Dyzmean values were significantly reduced in OSA over controls. Significant correlations emerged between disease severity, sleep symptoms, and Dxy, Dxx, and Dzz values in OSA subjects.ConclusionOSA patients show abnormal glymphatic system function that may contribute to increased risks for AD. The findings suggest that the APLS method can be used to assess the glymphatic system in OSA patients.
The Altered Pattern of the Functional Connectome Related to Pathological Biomarkers in Individuals for Autism Spectrum Disorder Identification
Authors: Peng Liling , Liu Xiao , Ma Di , Chen Xiaofeng , Xu Xiaowen , Gao Xin 
Published: May 2022

ObjectiveAutism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by the development of multiple symptoms, with incidences rapidly increasing worldwide. An important step in the early diagnosis of ASD is to identify informative biomarkers. Currently, the use of functional brain network (FBN) is deemed important for extracting data on brain imaging biomarkers. Unfortunately, most existing studies have reported the utilization of the information from the connection to train the classifier; such an approach ignores the topological information and, in turn, limits its performance. Thus, effective utilization of the FBN provides insights for improving the diagnostic performance.MethodsWe propose the combination of the information derived from both FBN and its corresponding graph theory measurements to identify and distinguish ASD from normal controls (NCs). Specifically, a multi-kernel support vector machine (MK-SVM) was used to combine multiple types of information.ResultsThe experimental results illustrate that the combination of information from multiple connectome features (i.e., functional connections and graph measurements) can provide a superior identification performance with an area under the receiver operating characteristic curve (ROC) of 0.9191 and an accuracy of 82.60%. Furthermore, the graph theoretical analysis illustrates that the significant nodal graph measurements and consensus connections exists mostly in the salience network (SN), default mode network (DMN), attention network, frontoparietal network, and social network.ConclusionThis work provides insights into potential neuroimaging biomarkers that may be used for the diagnosis of ASD and offers a new perspective for the exploration of the brain pathophysiology of ASD through machine learning.
Honey Bee Products: Preclinical and Clinical Studies of Their Anti-inflammatory and Immunomodulatory Properties
Authors: El-Seedi Hesham R. , Eid Nehal , Abd El-Wahed Aida A. , Rateb Mostafa E. , Afifi Hanan S. , Algethami Ahmed F. , Zhao Chao , Al Naggar Yahya , Alsharif Sultan M. , Tahir Haroon Elrasheid , Xu Baojun , Wang Kai , Khalifa Shaden A. M. 
Published: May 2022

Graphical AbstractThe anti-inflammatory and immunomodulatory possible mechanisms of action of bee products suggested by preclinical and clinical studies.
Case Report: First Report of T-Cell Large Granular Lymphocytic Leukemia With NPL-DHX9 Gene Fusion Successfully Treated With Cladribine: Clinical Experience and Literature Review
Authors: Hu Qin , Li Yunfei , Zhang Ying , Sun Shusen , Wang Hui , Jiang Zhiping , Deng Sheng 
Published: May 2022

BackgroundT-cell large granular lymphocytic leukemia (T-LGLL) is a rare lymphoproliferative disorder that starts in T cells and is usually indolent. Long-term use of immunosuppressants, combined with agranulocytosis, is a double-edged sword, as both can lead to serious infections, especially in patients with combined hematologic malignancies and immune defects.Case PresentationA 30-year-old female patient was admitted to the hospital because of agranulocytosis for five years, with chest tightness, fatigue, and fever for two days. Pathology and metagenomic next-generation sequencing (mNGS) detected Aspergillus. Although she received cyclosporine and methylprednisolone, the patient showed drug intolerance and progression with invasive pulmonary fungal infections. After a bone marrow aspiration biopsy and other related examinations, she was diagnosed with T-LGLL and invasive pulmonary aspergillosis (IPA). T-cell immunophenotype was CD45+CD3dim+CD5-CD4-CD8+CD7+CD57p+CD25-CD30-, TCRγδ+, transducer and activator of transcripton-3 (STAT3) Y640F mutation and fusion gene NPL-DHX9 rearrangement were confirmed, which has never been reported in hematological diseases. After voriconazole regimen adjustment during treatment based on therapeutic drug concentration monitoring (TDM) and improvement in lung infection, the patient finally treated with purine nucleoside analogues (PNA) cladribine as a single agent at 0.14 mg/kg/d for 5 days. Complete response was achieved after four-cycles cladribine treatment (WBC 2.1*109/L, HGB 117 g/L, PLT 196*109/L, ANC 1.6*109/L, and ALC 0.2*109/L).ConclusionsTo our knowledge, this is the first case of T-LGLL with a rare γδ type and fusion gene NPL-DHX9 rearrangement. The patient was successfully treated with cladribine, suggesting that this regimen could be a promising therapeutic strategy for patients with aggressive T-LGLL.
Berberine and Oligomeric Proanthocyanidins Exhibit Synergistic Efficacy Through Regulation of PI3K-Akt Signaling Pathway in Colorectal Cancer
Authors: Okuno Keisuke , Garg Rachana , Yuan Yate-Ching , Tokunaga Masanori , Kinugasa Yusuke , Goel Ajay 
Published: May 2022

BackgroundNaturally occurring dietary botanicals offer time-tested safety and anti-cancer efficacy, and a combination of certain compounds has shown to overcome the elusive chemotherapeutic resistance, which is of great significance for improving the mortality of patients with colorectal cancer (CRC). Accordingly, herein, we hypothesized that berberine (BBR) and oligomeric proanthocyanidins (OPCs) might regulate synergistically multiple oncogenic pathways to exert a superior anti-cancer activity in CRC.MethodsWe performed a series of cell culture studies, followed by their interrogation in patient-derived organoids to evaluate the synergistic effect of BBR and OPCs against CRC. In addition, by performing whole genome transcriptomic profiling we identified the key targeted genes and pathways regulated by the combined treatment.ResultsWe first demonstrated that OPCs facilitated enhanced cellular uptake of BBR in CRC cells by measuring the fluorescent signal of BBR in cells treated individually or their combination. The synergism between BBR and OPCs were investigated in terms of their anti-tumorigenic effect on cell viability, clonogenicity, migration, and invasion. Furthermore, the combination treatment potentiated the cellular apoptosis in an Annexin V binding assay. Transcriptomic profiling identified oncogene MYB in PI3K-AKT signaling pathway might be critically involved in the anti-tumorigenic properties of the combined treatment. Finally, we successfully validated these findings in patient-derived CRC tumor organoids.ConclusionsCollectively, we for the first time demonstrate that a combined treatment of BBR and OPCs synergistically promote the anti-tumorigenic properties in CRC possibly through the regulation of cellular apoptosis and oncogene MYB in the PI3K-Akt signaling pathway.
Low CRIM1 Levels Predict Poor Prognosis in Breast Cancer Patients
Authors: Wen Wei , Jiang Baohong , Cao Xi , Xie Liming , Zhang Xiaoli , Li Yuehua , He Rongfang 
Published: May 2022

BackgroundCRIM1 is involved in the development and preservation of the nervous system, capillary development, and vascular maintenance. Although CRIM1 was reported to involve in multiple cancers, its role in breast cancer is unclear.MethodsWe investigated CRIM1 expression levels using Oncomine, HPA, and immunohistochemistry analyses. BC-GenExMiner was employed to evaluate the relationship of CRIM1 expression with the clinicopathological characteristics of breast cancer. Its association with breast cancer prognosis was assessed by Kaplan-Meier analysis and PrognoScan. The correlation of the expression of CRIM1 with tumor immune infiltration was explored via TIMER. Gene set enrichment analysis (GSEA) was utilized to determine the cascades that are linked to CRIM1 in breast cancer. Finally, we explored CRIM1 and its co-expressed genes using R (3.6.3).ResultsHere, we find that CRIM1 expression was downregulated in various subtypes of breast cancer, and it was lowest in triple-negative breast cancers. ER and PR status were positively correlated with CRIM1 expression, while HER-2 expression was negatively correlated with CRIM1 expression. But in our immunohistochemical results in breast cancer specimens collected from our laboratory, HER-2 expression was positively correlated with CRIM1 expression. The expression of CRIM1 was correlated with menopause status, T stage, pathologic stage, histological type, and P53 status but not with age, N-stage, M-stage, Radiation therapy, and BRCA1/2 status. Survival analysis found that low CRIM1 expression was correlated with poorer DMFS, RFS and OS. Notably, CRIM1 expression was positively linked to the level of infiltration by CD8+ T-cells, endothelial cells, and neutrophils, and negatively linked to NK, B-cells, CD4+ T-cells, tumor purity, macrophage M1, and Tregs. Besides, DIXDC1 and PFDN6 were correlated to CRIM1 possibly.ConclusionOur findings demonstrated that low CRIM1 expression predict poor prognosis of breast cancer and CRIM1 might be used as a possible treatment target or prognostic marker in breast cancer. More researches are needed to better understand the prognostic value of CRIM1 in breast cancer.
Responsive Behaviors and Pain Management in Hospital Dementia Care: A Before and After Comparison of the “Serial Trial Intervention”
Authors: Lukas Albert , Bienas Melanie , Mayer Benjamin , Radbruch Lukas , Gnass Irmela 
Published: May 2022

PurposeResponsive behavior, often referred to as behavioral and psychological symptoms of dementia (BPSD), is among the most critical disorders in dementia whereby nursing personnel in hospitals are increasingly confronted with such symptoms. The purpose was to reduce the level of BPSD in an acute hospital environment through a stepwise procedure followed by the initiation of a needs-oriented treatment.MethodsAn open, prospective, interventional study with before-after comparisons was used to implement “Serial Trial Intervention” (STI) in three hospital wards (internal medicine, surgery, geriatric) after its adaption for hospital setting which was supplemented with a detailed pain assessment. Participants were 65 years and older. Potential causes of BPSD were clarified in a stepwise procedure and, if possible, eliminated. The primary outcome was the reduction in BPSD measured by the Neuropsychiatric Inventory (NPI-Q-12) while secondary outcomes were through the use of non-pharmacological and pharmacological interventions.ResultsNo significant reduction in NPI-Q-12 could be found. However, significantly more mobilizations and changes of position were carried out. Higher antipsychotic use was seen in the after-groups presumably due to the higher rates of delirium and cognitive impairment. Furthermore, the data showed no increase in analgesic use.ConclusionNo significant reduction in NPI-Q-12 was observed in the before-after study. The use of antipsychotics even increased most probably due to a higher incidence of deliriousness in the after-group. However, STI seemed to improve attention to underlying causes of BPSD as well as pain. Proof that STI leads to NPI-Q-12 reduction in hospitals is still pending.
Periodontal Disease and Adverse Neonatal Outcomes: A Systematic Review and Meta-Analysis
Authors: Zhang Youzhen , Feng Wanbing , Li Jingyu , Cui Linlin , Chen Zi-Jiang 
Published: May 2022

ObjectiveThe aim of this study was to evaluate the association between maternal periodontal disease (PD) and three main adverse neonatal outcomes, namely, preterm birth (PTB), low birth weight (LBW), and small for gestational age (SGA).MethodsThe Ovid Medline, Web of Science, Embase, and Cochrane Library were searched up to 6 December 2020 for relevant observational studies on an association between PD and risk of PTB, LBW, and SGA. Eligibility criteria included observational studies which compared the prevalence of PTB and/or LBW and/or SGA between PD women and periodontal health controls. The exclusion criteria included incomplete data, animal research, and mixing up various pregnancy outcomes, such as “preterm low birth weight” and languages other than Chinese and English. Data were extracted and analyzed independently by two authors. The meta-analysis was performed using Stata Statistical Software, Release 12 (StataCorp LP, College Station, TX, USA). Odds ratio (OR), confidence intervals (CIs), and heterogeneity (I2) were computed.ResultsFourteen case-control studies and 10 prospective cohort studies, involving 15,278 participants, were identified. Based on fixed effect meta-analysis, PTB showed a significant association with PD (OR = 1.57, 95% CI: 1.39–1.77, P &lt; 0.00001) and LBW also showed a significant association with PD (OR = 2.43, 95% CI: 1.75–3.37, P &lt; 0.00001) in a random effect meta-analysis. However, a random effect meta-analysis showed no relationship between PD and SGA (OR = 1.62, 95% CI: 0.86–3.07, P = 0.136).ConclusionOur findings indicate that pregnant women with PD have a significantly higher risk of PTB and LBW. However, large prospective, blinded cohort studies with standardized diagnostic criteria of PD and adequate control of confounding factors are still required to confirm the relationship between PD and adverse neonatal outcomes.
Danhong Injection Price Trend and Its Utilization by Coronary Heart Disease Patients: Evidence From Hospital Records in China
Authors: Liu Liming , Xu Yue , Su Zihan , Man Xiaowei , Jiang Yan , Zhao Liying , Cheng Wei 
Published: May 2022

Background: Danhong injection (DHI) accounts for the highest proportion of drug costs for inpatients with coronary heart disease (CHD). However, if DHI price influences utilization remains unclear.Objective: The objective was to compare changes in the use of DHI for CHD patients during three stages after two comprehensive reforms of public hospitals in Beijing. These findings will provide support for controlling the drug burden of CHD patients and regulating drug use behavior.Research Design: CHD diagnosis and treatment data were extracted from the Hospital Information System (HIS) of 33 public hospitals. Patients were grouped according to different treatment methods and clinical classifications. Changes in the utilization of DHI, including the use rate (the percentage of CHD patients using DHI), number of prescribed units (average number of units of DHI prescribed per hospital stay), and cost of DHI per hospital stay (equal to the unit price multiplied by the number of prescribed units) between the three stages were statistically analyzed. Association rules were applied to identify changes in drug combinations.Results: After the two reforms, the unit price of DHI dropped from $6.46 to $5.61. At the same time, the use rate increased from 20.77 to 24.00%, the number of prescribed units dropped from 29.76 to 29.21, and the cost of DHI per hospital stay dropped from $192.12 to $163.96. The changes in the use rate and number of prescribed units varied among patients with different clinical types and treatment methods, and the cost of CHI per hospital stay was consistent with the overall situation. The variety of drugs used in combination with DHI remained relatively stable.Conclusion: The use rate of DHI for CHD patients increased, indicating increased applications of DHI in clinical practice. Due to the drop in price, the cost of using DHI decreased, and the financial burden of this drug was reduced.
In vitro Evaluation of Isoniazid Derivatives as Potential Agents Against Drug-Resistant Tuberculosis
Authors: Marquês Joaquim Trigo , Frazão De Faria Catarina , Reis Marina , Machado Diana , Santos Susana , Santos Maria da Soledade , Viveiros Miguel , Martins Filomena , De Almeida Rodrigo F. M. 
Published: May 2022

The upsurge of multidrug-resistant tuberculosis has toughened the challenge to put an end to this epidemic by 2030. In 2020 the number of deaths attributed to tuberculosis increased as compared to 2019 and newly identified multidrug-resistant tuberculosis cases have been stably close to 3%. Such a context stimulated the search for new and more efficient antitubercular compounds, which culminated in the QSAR-oriented design and synthesis of a series of isoniazid derivatives active against Mycobacterium tuberculosis. From these, some prospective isonicotinoyl hydrazones and isonicotinoyl hydrazides are studied in this work. To evaluate if the chemical derivatizations are generating compounds with a good performance concerning several in vitro assays, their cytotoxicity against human liver HepG2 cells was determined and their ability to bind human serum albumin was thoroughly investigated. For the two new derivatives presented in this study, we also determined their lipophilicity and activity against both the wild type and an isoniazid-resistant strain of Mycobacterium tuberculosis carrying the most prevalent mutation on the katG gene, S315T. All compounds were less cytotoxic than many drugs in clinical use with IC50 values after a 72 h challenge always higher than 25 µM. Additionally, all isoniazid derivatives studied exhibited stronger binding to human serum albumin than isoniazid itself, with dissociation constants in the order of 10−4–10−5 M as opposed to 10−3 M, respectively. This suggests that their transport and half-life in the blood stream are likely improved when compared to the parent compound. Furthermore, our results are a strong indication that the N′ = C bond of the hydrazone derivatives of INH tested is essential for their enhanced activity against the mutant strain of M. tuberculosis in comparison to both their reduced counterparts and INH.
Alterations of the Gut Microbiome and Fecal Metabolome in Colorectal Cancer: Implication of Intestinal Metabolism for Tumorigenesis
Authors: Du Xinhao , Li Qing , Tang Zhenzhen , Yan Li , Zhang Ling , Zheng Qiao , Zeng Xianghao , Chen Guimei , Yue Huawen , Li Jun , Zhao Ming , Han Yuan-Ping , Fu Xiangsheng 
Published: May 2022

Objective: The gut microbiota and its metabolites are important for host physiological homeostasis, while dysbiosis is related to diseases including the development of cancers such as colorectal cancer (CRC). In this study, we characterized the relationship of an altered gut microbiome with the fecal metabolome in CRC patients in comparison with volunteers having a normal colorectal mucous membrane (NC).Methods: The richness and composition of the microbiota in fecal samples of 30 CRC patients and 36 NC controls were analyzed through 16S rRNA gene sequencing, and the metabolome was determined by ultra-performance liquid chromatography coupled to tandem mass spectrometry. Spearman correlation analysis was to determine the correlation between the gut microbiome and fecal metabolome in CRC patients.Results: There were significant alterations in the gut microbiome and fecal metabolome in CRC patients compared with NC controls. Bacteroidetes, Firmicutes, Actinobacteriota, and Proteobacteria dominated the gut microbial communities at the phylum level in both groups. Compared with NC controls, CRC patients had a lower frequency of Blautia and Lachnospiracaea but a higher abundance of Bacteroides fragilis and Prevotella. Regarding the fecal metabolome, twenty-nine metabolites were identified as having significantly changed, showing increased levels of adrenic acid, decanoic acid, arachidonic acid, and tryptophan but a reduction in various monosaccharides in the fecal samples of CRC patients. Moreover, increased abundance of Bacteroides fragilis was strongly associated with decreased levels of monosaccharides, while Blautia was positively associated with the production of monosaccharides in the fecal samples.Conclusion: These results highlight alterations of gut microbiota in association with certain metabolites in CRC progression, implying potential diagnostic and intervention potential for CRC.
Breast Cancer Survivors’ Lived Experience of Adjuvant Hormone Therapy: A Thematic Analysis of Medication Side Effects and Their Impact on Adherence
Authors: Ibrar Maryam , Peddie Nicola , Agnew Sommer , Diserholt Amanda , Fleming Leanne 
Published: May 2022

ObjectivesSide effects from Hormone Therapy (HT) impact medication adherence in breast cancer survivors. Understanding the most distressing HT side effects and their impacts may inform the development and implementation of interventions to alleviate these side effects and maximise HT adherence. This study aimed to explore the lived experience of adjuvant HT and understand the impact of HT side effects on adherence in a sample of breast cancer survivors.MethodsTwenty-five female breast cancer survivors who were currently taking adjuvant HT participated in the study. One-to-one, online, semi-structured interviews were conducted to explore (i) specific side effects from HT and (ii) the impact of these side effects on HT adherence. Data were analysed using Thematic Analysis.ResultsThe most commonly reported side effects were sleep disturbance, hot flashes, anxiety, and joint pain. Data exploring the impacts of these side effects on HT adherence were thematically synthesised into four analytical themes: “A bitter pill to swallow,” “Seeking relief,” “Taking control,” and “The only way out is through.” These themes encompass 14 sub-themes that encapsulate participants’ daily struggle with HT side effects and the coping strategies developed to manage these.ConclusionAdverse side effects from HT, such as sleep disturbance, hot flashes, pain and anxiety, impair quality of life and increase the likelihood of participants’ becoming non-adherent to HT medication. In order to maximise HT adherence and reduce breast cancer mortality, HT side effects should be closely monitored to identify individuals who would benefit from targetted intervention strategies aimed at alleviating these side effects.