bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cerebral Ischemic Complications After Surgical Revascularization for Moyamoya Disease: Risk Factors and Development of a Predictive Model Based on Preoperative Nutritional Blood Parameters
Authors: Li Fangbao , Li Chuanfeng , Sun Yunwei , Bao Yue , Jiang Wenbo , Song Zuoyan , Wang Yongyi , Liu Mingxing , Wang Weimin , Li Tong , Li Luo 
Published: March 2022

ObjectivesCerebral ischemic complications are common after revascularization in patients with moyamoya disease (MMD). Risk factors from specific laboratory variables have only been assessed by limited research. This study was to investigate the association between postoperative cerebral ischemia and nutritional blood parameters and examine predictive values of such risk factors in adults.MethodsPreoperative demographics and nutritional blood parameters of patients with MMD who received revascularization at our institution from 2012 to 2021 were retrospectively reviewed. Univariate analysis and multivariable logistic regression were used to identify independent risk factors for the onset of postoperative cerebral ischemic complications. Predictive values were tested and a model incorporating these independent risk factors was created using the R program. Area under the receiver operating characteristic curve (AUC) was used for testing its discriminability.ResultsPostoperative cerebral ischemic complications occurred in 32 patients of 100 included procedures. Surgery on the left hemisphere, lower admission modified Rankin Scale (mRS) score, aberrant nutritional parameters including low white blood cell (WBC), and high total cholesterol (TC) were significantly associated with cerebral ischemic complications after revascularization. The intriguing role of WBC might be explained by altered immunomodulation. The AUC of this model with novel nutritional parameters yielded a value of 0.811, presenting better predictive accuracy. Additionally, the model was visualized in the form of a nomogram and translated into a user-friendly calculator to generate individual risk.ConclusionsSurgical side, admission mRS score, WBC, and TC were independent risk factors for postoperative cerebral ischemic complications. The model composed of these four parameters was promising to be adopted in clinical practice.
Trends in Disease Burden of Chronic Lymphocytic Leukemia at the Global, Regional, and National Levels From 1990 to 2019, and Projections Until 2030: A Population-Based Epidemiologic Study
Authors: Ou Yang , Long Yichen , Ji Lili , Zhan Yanxia , Qiao Tiankui , Wang Xiangdong , Chen Hao , Cheng Yunfeng 
Published: March 2022

BackgroundThe prognosis of chronic lymphocytic leukemia (CLL) has been improved dramatically, but there are limited studies focusing on CLL disease burden on a global scale. We aimed to evaluate the accurate assessment of the disease burden of CLL that may provide more detailed epidemiological information for rational policies.MethodsThe main source of the data was the Global Burden of Disease (GBD) study 2019. Incident cases, death cases, disability-adjusted life years (DALYs), and their corresponding age-standardized rates (ASRs) from 1990 to 2019 were used to describe the burden of CLL. Data about attributable risk factors were also extracted and analyzed. Bayesian age-period-cohort (BAPC) models were used to assess and project the incidence and mortality rates till 2030.ResultsGlobally, the incidence of CLL had been increasing. Deaths and DALYs decreased slightly. The burden of death and DALY is affected by socio-demographic index (SDI). The incidence rate, death rate, and DALY rate of CLL increased significantly with age. Male-to-female ratios of incidence rates varied in different SDI quintiles. Smoking, high body mass index, and occupational exposure to benzene or formaldehyde were the potential risk factors related to CLL. Global ASIRs might tend to increase until 2030, while ASDR would decrease until 2030.ConclusionThe disease burden of CLL decreased in higher SDI countries but increased in lower ones. Strategies for early detection of asymptomatic CLL, development of novel drugs, and measures against attributable factors should be implemented to combat CLL burden.
The Signaling Pathways Associated With Breast Cancer Bone Metastasis
Authors: Song Xuelian , Wei Changran , Li Xiangqi 
Published: March 2022

BackgroundBreast cancer (BC) is now the leading cause of cancer in women, and bone is the primary site of distant BC metastasis. BC bone metastasis seriously affects the quality of life of patients and increases the mortality rate. However, the mechanism of BC bone metastasis is not fully understood.Main BodyPaget’s “seed and soil” hypothesis led experts to explore the relationship between surface markers and receptors in breast tumors and various growth factors in bone. The relevant breast tumor markers serve as “seeds”, and the bone microenvironment that is suitable for the survival of the tumor serves as the “soil”. These factors interact to make up an entire system and form feedback pathways that accelerate the production of various cytokines, attracting BC cells to migrate to bone tissue, which worsens the development of BC and seriously affects the prognosis of patients. This process is a vicious cycle. At present, there are seven major signaling pathways involved in BC bone metastasis: the OPG/RANK/RANKL signaling pathway, TGF-β signaling pathway, IGF system, PI3K-AKT-mTOR signaling pathway, Wnt signaling pathway and Hippo signaling pathway. In addition, FGF-FGFR signaling pathway, androgen-AR/LSD1-target gene pathway, Notch signaling pathway, JAK-STAT signaling pathway and CaN/NFATC1 signaling pathway also seem to be associated with BC bone metastasis.ConclusionThis review focuses on the signaling pathways related to BC bone metastasis and explores the interactions among these pathways, which will lay a solid theoretical foundation for further understanding the mechanism of BC bone metastasis and developing effective targeted therapeutic drugs.
Is There Any Mosaicism in REarranged During Transfection Variant in Hirschsprung Disease’s Patients?
Authors: Iskandar Kristy , Simanjaya Susan , Indrawan Taufik , Kalim Alvin Santoso , Marcellus  , Heriyanto Didik Setyo , Gunadi  
Published: March 2022

BackgroundHirschsprung disease (HSCR) is a heterogeneous genetic disease characterized by the absence of ganglion cells in the intestinal tract. The REarranged during Transfection (RET) is the most responsible gene for its pathogenesis. RET’s somatic mosaicisms have been reported for HSCR; however, they are still under-recognized. Therefore, we determined the frequency of somatic mutation of RET rs2435357 in HSCR patients at our institution.MethodsWe performed RET rs2435357 genotyping from 73 HSCR formalin-fixed and paraffin-embedded (FFPE) rectal and 60 non-HSCR controls using the PCR-RFLP method. Subsequently, we compared those frequencies of genotypes for RET rs2435357 with our previous genotyping data from 93 HSCR blood specimens.ResultsThe frequencies of genotypes for RET rs2435357 in HSCR paraffin-embedded rectal were CC 0, CT 11 (15%), and TT 62 (85%), whereas their frequencies in HSCR blood samples were CC 4 (4.3%), CT 22 (23.7%), and TT 67 (72%). Those frequencies differences almost reached a significant level (p = 0.06). Moreover, the frequency of RET rs2435357 risk allele (T) was significantly higher in HSCR patients (135/146, 92.5%) than controls (46/120, 38.3%) (p = 3.4 × 10–22), with an odds ratio of 19.74 (95% confidence interval = 9.65–40.41).ConclusionOur study suggests somatic mosaicism in HSCR patients. These findings further imply the complexity of the pathogenesis of HSCR. Moreover, our study confirms the RET rs2435357 as a significant genetic risk factor for HSCR patients.
Characterizing Pharmacokinetics in Children With Obesity—Physiological, Drug, Patient, and Methodological Considerations
Authors: Gerhart Jacqueline G. , Balevic Stephen , Sinha Jaydeep , Perrin Eliana M. , Wang Jian , Edginton Andrea N. , Gonzalez Daniel 
Published: March 2022

Childhood obesity is an alarming public health problem. The pediatric obesity rate has quadrupled in the past 30 years, and currently nearly 20% of United States children and 9% of children worldwide are classified as obese. Drug distribution and elimination processes, which determine drug exposure (and thus dosing), can vary significantly between patients with and without obesity. Obesity-related physiological changes, such as increased tissue volume and perfusion, altered blood protein concentrations, and tissue composition can greatly affect a drug’s volume of distribution, which might necessitate adjustment in loading doses. Obesity-related changes in the drug eliminating organs, such as altered enzyme activity in the liver and glomerular filtration rate, can affect the rate of drug elimination, which may warrant an adjustment in the maintenance dosing rate. Although weight-based dosing (i.e., in mg/kg) is commonly practiced in pediatrics, choice of the right body size metric (e.g., total body weight, lean body weight, body surface area, etc.) for dosing children with obesity still remains a question. To address this gap, the interplay between obesity-related physiological changes (e.g., altered organ size, composition, and function), and drug-specific properties (e.g., lipophilicity and elimination pathway) needs to be characterized in a quantitative framework. Additionally, methodological considerations, such as adequate sample size and optimal sampling scheme, should also be considered to ensure accurate and precise top-down covariate selection, particularly when designing opportunistic studies in pediatric drug development. Further factors affecting dosing, including existing dosing recommendations, target therapeutic ranges, dose capping, and formulations constraints, are also important to consider when undergoing dose selection for children with obesity. Opportunities to bridge the dosing knowledge gap in children with obesity include modeling and simulating techniques (i.e., population pharmacokinetic and physiologically-based pharmacokinetic [PBPK] modeling), opportunistic clinical data, and real world data. In this review, key considerations related to physiology, drug parameters, patient factors, and methodology that need to be accounted for while studying the influence of obesity on pharmacokinetics in children are highlighted and discussed. Future studies will need to leverage these modeling opportunities to better describe drug exposure in children with obesity as the childhood obesity epidemic continues.
Anti-Seizure Medication Treatment of Benign Childhood Epilepsy With Centrotemporal Spikes: A Systematic Review and Meta-analysis
Authors: Cheng Wenwen , Yang Yan , Chen Ying , Shan Sharui , Li Changhui , Fang Ling , Zhang Weiguo , Lan Song , Zhang Xiong 
Published: March 2022

Background: This study aimed to evaluate the efficacy and tolerability of Anti-Seizure medication (ASM) treatment in patients with BECTS.Method: We searched PubMed, Cochrane Library, Embase, MEDLINE, Web of Science, China National Knowledge Infrastructure (CNKI), WANFANG DATA, and China Science and Technology Journal Database (VIP) between 1 Jan 1990, and 1 Sep 2021, for randomized controlled studies. Data on seizure freedom rate, rate of treatment withdrawal due to serious adverse events, rate of any adverse events and dropout, 50% remission rate, the proportion of patients whose EEG to be normalized, and improvement in cognitive function were extracted by two authors independently. The pooled data were meta-analyzed using a random effects model.Results: A total of 27 studies evaluating 9 ASMs were included, 19 of which were suitable for meta-analysis. Compared with sulthiame (STM), levetiracetam (LEV) was associated with a higher probability of treatment withdrawal due to serious adverse events [RR = 5.12, 95% CI (1.19, 22.01), I2 = 0.0%], experiencing any adverse events [RR = 5.12, 95% CI (1.19, 22.01)], and dropping out for any reason [RR = 3.17, 95% CI (1.36, 10.11)], while it did not affect the seizure freedom rate [RR = 0.90, 95% CI (0.75, 1.06)]. LEV significantly improved cognitive performance relative to carbamazepine (CBZ) but had no effect on the proportion of any adverse events [RR = 0.62, 95% CI (0.25, 1.59)] and EEG to be normalized [RR = 1.27, 95% CI (0.94, 1.71)]. There was no higher probability of a 50% remission rate when comparing valproic acid (VPA) to LEV [RR = 0.96, 95% CI (0.57, 1.61)] and oxcarbazepine (OXC) [RR = 0.61, 95% CI (0.31, 1.20)]. In addition, STM was related to a higher probability of EEG normalization than placebo [RR = 4.61, 95% CI (2.12, 10.01)]. The included single studies also provided some evidence for the efficacy and/or tolerability of other ASMs in BECTS, including topiramate, lamotrigine, clobazam, and clonazepam. The risk of bias of the included studies was frequently low or unclear.Conclusion: This study indicated some discrepancies in efficacy and tolerability among ASMs used in patients with BECTS. More randomized controlled trials (RCTs) comparing ASMs with larger populations are required to ascertain the optimum antiepileptic drug treatment to guide clinicians.
Unveiling Dynamic Changes of Chemical Constituents in Raw and Processed Fuzi With Different Steaming Time Points Using Desorption Electrospray Ionization Mass Spectrometry Imaging Combined With Metabolomics
Authors: Liu Yue , Yang Xuexin , Zhou Chao , Wang Zhang , Kuang Tingting , Sun Jiayi , Xu Binjie , Meng Xianli , Zhang Yi , Tang Ce 
Published: March 2022

Fuzi is a famous toxic traditional herbal medicine, which has long been used for the treatment of various diseases in China and many other Asian countries because of its extraordinary pharmacological activities and high toxicity. Different processing methods to attenuate the toxicity of Fuzi are important for its safe clinical use. In this study, desorption electrospray ionization mass spectrometry imaging (DESI-MSI) with a metabolomics-combined multivariate statistical analysis approach was applied to investigate a series of Aconitum alkaloids and explore potential metabolic markers to understand the differences between raw and processed Fuzi with different steaming time points. Moreover, the selected metabolic markers were visualized by DESI-MSI, and six index alkaloids’ contents were determined through HPLC. The results indicated visible differences among raw and processed Fuzi with different steaming times, and 4.0 h is the proper time for toxicity attenuation and efficacy reservation. A total of 42 metabolic markers were identified to discriminate raw Fuzi and those steamed for 4.0 and 8.0 h, which were clearly visualized in DESI-MSI. The transformation from diester-diterpenoid alkaloids to monoester-diterpenoid alkaloids and then to non-esterified diterpene alkaloids through hydrolysis is the major toxicity attenuation process during steaming. DESI-MSI combined with metabolomics provides an efficient method to visualize the changeable rules and screen the metabolic markers of Aconitum alkaloids during steaming. The wide application of this technique could help identify markers and reveal the possible chemical transition mechanism in the “Paozhi” processes of Fuzi. It also provides an efficient and easy way to quality control and ensures the safety of Fuzi and other toxic traditional Chinese medicine.
Perspectives on the Efficacy of Benralizumab for Treatment of Eosinophilic Granulomatosis With Polyangiitis
Authors: Koga Yasuhiko , Aoki-Saito Haruka , Kamide Yosuke , Sato Makiko , Tsurumaki Hiroaki , Yatomi Masakiyo , Ishizuka Tamotsu , Hisada Takeshi 
Published: March 2022

Two types of interleukin (IL)-5 antibody biologics, anti-IL-5 antibodies (mepolizumab) and anti-IL-5α receptor antibodies (benralizumab), are indicated for severe asthma. While high-dose mepolizumab is also indicated for EGPA, benralizumab is indicated only for severe asthma. Benralizumab is characterized by antibody-dependent cell-mediated cytotoxicity activity, giving them specific and rapid anti-IL-5α receptor binding abilities and the ability to target a high number of eosinophils in tissues as well as peripheral blood. Recently, reports on the efficacy of benralizumab as a treatment for EGPA have been published, along with reports on some cases that are difficult to treat with existing oral corticosteroids and mepolizumab. Therefore, we focus on the perspective of the efficacy and safety of benralizumab as a treatment for EGPA patients with steroid dependence in this review. A total of 41 patients with EGPA were treated with benralizumab. After the introduction of benralizumab, oral corticosteroids could be reduced to 10 mg/day or less in all cases and to less than 5 mg/day in 80% or more of the cases. Discontinuation of oral corticosteroids was achieved in more than 40% of patients with EGPA. Benralizumab was effective in patients with mepolizumab-refractory EGPA and intractable cardiac and neuropathy complications. Efficient elimination of eosinophils is expected to improve the remission rate of EGPA with benralizumab treatment. Although the total number of patients was small, benralizumab was safe and tolerable in a wide range of age groups, suggesting efficacy in severe cases with EGPA.
Listening-Based Communication Ability in Adults With Hearing Loss: A Scoping Review of Existing Measures
Authors: Neal Katie , McMahon Catherine M. , Hughes Sarah E. , Boisvert Isabelle 
Published: March 2022

IntroductionHearing loss in adults has a pervasive impact on health and well-being. Its effects on everyday listening and communication can directly influence participation across multiple spheres of life. These impacts, however, remain poorly assessed within clinical settings. Whilst various tests and questionnaires that measure listening and communication abilities are available, there is a lack of consensus about which measures assess the factors that are most relevant to optimising auditory rehabilitation. This study aimed to map current measures used in published studies to evaluate listening skills needed for oral communication in adults with hearing loss.MethodsA scoping review was conducted using systematic searches in Medline, EMBASE, Web of Science and Google Scholar to retrieve peer-reviewed articles that used one or more linguistic-based measure necessary to oral communication in adults with hearing loss. The range of measures identified and their frequency where charted in relation to auditory hierarchies, linguistic domains, health status domains, and associated neuropsychological and cognitive domains.Results9121 articles were identified and 2579 articles that reported on 6714 discrete measures were included for further analysis. The predominant linguistic-based measure reported was word or sentence identification in quiet (65.9%). In contrast, discourse-based measures were used in 2.7% of the articles included. Of the included studies, 36.6% used a self-reported instrument purporting to measures of listening for communication. Consistent with previous studies, a large number of self-reported measures were identified (n = 139), but 60.4% of these measures were used in only one study and 80.7% were cited five times or fewer.DiscussionCurrent measures used in published studies to assess listening abilities relevant to oral communication target a narrow set of domains. Concepts of communicative interaction have limited representation in current measurement. The lack of measurement consensus and heterogeneity amongst the assessments limit comparisons across studies. Furthermore, extracted measures rarely consider the broader linguistic, cognitive and interactive elements of communication. Consequently, existing measures may have limited clinical application if assessing the listening-related skills required for communication in daily life, as experienced by adults with hearing loss.
Associations Between Sympathetic Nervous System Synchrony, Movement Synchrony, and Speech in Couple Therapy
Authors: Tourunen Anu , Nyman-Salonen Petra , Muotka Joona , Penttonen Markku , Seikkula Jaakko , Kykyri Virpi-Liisa 
Published: March 2022

BackgroundResearch on interpersonal synchrony has mostly focused on a single modality, and hence little is known about the connections between different types of social attunement. In this study, the relationship between sympathetic nervous system synchrony, movement synchrony, and the amount of speech were studied in couple therapy.MethodsData comprised 12 couple therapy cases (24 clients and 10 therapists working in pairs as co-therapists). Synchrony in electrodermal activity, head and body movement, and the amount of speech and simultaneous speech during the sessions were analyzed in 12 sessions at the start of couple therapy (all 72 dyads) and eight sessions at the end of therapy (48 dyads). Synchrony was calculated from cross-correlations using time lags and compared to segment-shuffled pseudo synchrony. The associations between the synchrony modalities and speech were analyzed using complex modeling (Mplus).FindingsCouple therapy participants’ synchrony mostly occurred in-phase (positive synchrony). Anti-phase (negative) synchrony was more common in movement than in sympathetic nervous system activity. Synchrony in sympathetic nervous system activity only correlated with movement synchrony between the client-therapist dyads (r = 0.66 body synchrony, r = 0.59 head synchrony). Movement synchrony and the amount of speech correlated negatively between spouses (r = −0.62 body synchrony, r = −0.47 head synchrony) and co-therapists (r = −0.39 body synchrony, r = −0.28 head synchrony), meaning that the more time the dyad members talked during the session, the less bodily synchrony they exhibited.ConclusionThe different roles and relationships in couple therapy were associated with the extent to which synchrony modalities were linked with each other. In the relationship between clients and therapists, synchrony in arousal levels and movement “walked hand in hand”, whereas in the other relationships (spouse or colleague) they were not linked. Generally, more talk time by the therapy participants was associated with anti-phase movement synchrony. If, as suggested, emotions prepare us for motor action, an important finding of this study is that sympathetic nervous system activity can also synchronize with that of others independently of motor action.