bluuebunny/crossref_metadata_2025_split huggingface dataset:
An ALE Meta-Analysis of Specific Functional MRI Studies on Subcortical Vascular Cognitive Impairment
Authors: Xu Wenwen , Song Yu , Chen Shanshan , Xue Chen , Hu Guanjie , Qi Wenzhang , Ma Wenying , Lin Xingjian , Chen Jiu 
Published: September 2021

Background: Subcortical vascular cognitive impairment (sVCI), caused by cerebral small vessel disease, accounts for the majority of vascular cognitive impairment, and is characterized by an insidious onset and impaired memory and executive function. If not recognized early, it inevitably develops into vascular dementia. Several quantitative studies have reported the consistent results of brain regions in sVCI patients that can be used to predict dementia conversion. The purpose of the study was to explore the exact abnormalities within the brain in sVCI patients by combining the coordinates reported in previous studies.Methods: The PubMed, Embase, and Web of Science databases were thoroughly searched to obtain neuroimaging articles on the amplitude of low-frequency fluctuation, regional homogeneity, and functional connectivity in sVCI patients. According to the activation likelihood estimation (ALE) algorithm, a meta-analysis based on coordinate and functional connectivity modeling was conducted.Results: The quantitative meta-analysis included 20 functional imaging studies on sVCI patients. Alterations in specific brain regions were mainly concentrated in the frontal lobes including the middle frontal gyrus, superior frontal gyrus, medial frontal gyrus, and precentral gyrus; parietal lobes including the precuneus, angular gyrus, postcentral gyrus, and inferior parietal lobule; occipital lobes including the lingual gyrus and cuneus; temporal lobes including the fusiform gyrus and middle temporal gyrus; and the limbic system including the cingulate gyrus. These specific brain regions belonged to important networks known as the default mode network, the executive control network, and the visual network.Conclusion: The present study determined specific abnormal brain regions in sVCI patients, and these brain regions with specific changes were found to belong to important brain functional networks. The findings objectively present the exact abnormalities within the brain, which help further understand the pathogenesis of sVCI and identify them as potential imaging biomarkers. The results may also provide a basis for new approaches to treatment.
EEG Characteristics to Hyperventilation by Age and Sex in Patients With Various Neurological Disorders
Authors: Khachidze Irma , Gugushvili Manana , Advadze Maia 
Published: September 2021

Introduction: Hyperventilation provocation test(s) (HPT) concomitant to electroencephalography (EEG) may detect hidden disorders of the nervous system (CNS). There are various types of abnormal EEG in responses to HPT that provoke different interpretations. However, it is not evident how the onset time of pathological EEG responses to hyperventilation (PERH) reveals dysfunction of the CNS in humans. It is also not clear if age and biological sex affect EEG characteristics in response to HPT. Our previous studies have revealed three types of PERH (disorganization of basic rhythm, paroxysmal discharges, epileptiform activity) concerning the manifestation time of first, second, and third minutes. The current work aims to classify the PERH with regards to age (3–6, 7–12, 13–18, 19–30, 31–50, 50 &gt; year) and the biological sex of the patients.Methods: This study examined the EEG of 985 outpatients with various functional disorders of the CNS. The patients were assigned to one of three experimental groups based on the time occurrence of PERH in response to the HPT.Results: The disorganized basic EEG rhythm in the first, second, third minute of HPT was observed across all age and sex groups. All three types of PERH in the first minute were comparable for both sexes. However, some discrepancies between females compared to males were observed in the second and third minutes. All three types of PERH in the first and the second minutes were found only in women. The second type of PERH has revealed at the second minute of PHT in 13–18-year-old five girls.Conclusion: The three main types of PERH were detected at the first minute in all age groups and sex in patients with various CNS dysfunctions. It is diagnostically informative should be used as a marker during the monitoring of treatment. The specific activity of the brain's response to HPT depends on time, age, sex. The data indicate that taking into account sex differences and age during HPT leads to better results. The sensitivity and severity of the NS reaction toward hypocapnia, stress, and emotion increase in women. Therefore, in such cases should not be recommended to expand functional loads.
Effects of Slow Oscillatory Transcranial Alternating Current Stimulation on Motor Cortical Excitability Assessed by Transcranial Magnetic Stimulation
Authors: Geffen Asher , Bland Nicholas , Sale Martin V. 
Published: September 2021

Graphical AbstractThirty healthy participants received 60 trials of intermittent SO (0.75 Hz) tACS (1 trial = 16 s on + 16 s off) at an intensity of 2 mA. Motor cortical excitability was assessed using TMS-induced MEPs (blue waveforms) acquired across different oscillatory phases during (i.e., online; red arrows) and outlasting (i.e., offline; green arrows) tACS, as well as at the start and end of the stimulation session (blue arrows). Mean MEP amplitude increased by ∼41% from pre- to post-tACS (P = 0.013); however, MEP amplitudes were not modulated with respect to the tACS phase.
Evidence for Cognitive Decline in Chronic Pain: A Systematic Review and Meta-Analysis
Authors: Zhang Xueying , Gao Rui , Zhang Changteng , Chen Hai , Wang Ruiqun , Zhao Qi , Zhu Tao , Chen Chan 
Published: September 2021

Background: People with chronic pain (CP) sometimes report impaired cognitive function, including a deficit of attention, memory, executive planning, and information processing. However, the association between CP and cognitive decline was still not clear. Our study aimed to assess the association of CP as a risk factor with cognitive decline among adults.Methods: We included data from clinical studies. Publications were identified using a systematic search strategy from PubMed, Embase, and Cochrane Library databases from inception to October 10, 2020. We used the mean cognitive outcome data and the standard deviations from each group. The standardized mean difference (SMD) or odds ratio (OR), and 95% confidence intervals (CI) were performed for each cognitive decline outcome. I2-values were assessed to quantify the heterogeneities.Results: We included 37 studies with a total of 52,373 patients with CP and 80,434 healthy control participants. Because these studies used different evaluative methods, we analyzed these studies. The results showed CP was associated with cognitive decline when the short-form 36 health survey questionnaire (SF-36) mental component summary (SMD = −1.50, 95% CI = −2.19 to −0.81), the Montreal cognitive assessment (SMD = −1.11, 95% CI = −1.60 to −0.61), performance validity testing (SMD = 3.05, 95% CI = 1.74 to 4.37), or operation span (SMD = −1.83, 95% CI = −2.98 to −0.68) were used. However, we got opposite results when the studies using International Classification of Diseases and Related Health Problems classification (OR = 1.58, 95% CI = 0.97 to 2.56), the Mini-Mental State Examination (SMD = −0.42, 95% CI = −0.94 to 0.10; OR = 1.14, 95% CI = 0.91 to 1.42), and Repeatable Battery for the Assessment of Neuropsychological Status memory component (SMD = −0.06, 95% CI = −0.37 to 0.25).Conclusion: There may be an association between CP and the incidence of cognitive decline when some cognitive, evaluative methods were used, such as short-form 36 health survey questionnaire, Montreal cognitive assessment, performance validity testing, and operation span.
Analysis of Immune Landscape Reveals Prognostic Significance of Cytotoxic CD4+ T Cells in the Central Region of pMMR CRC
Authors: Qi Jingwen , Liu Xiaoyan , Yan Peian , He Shangwen , Lin Yuhao , Huang Zhiwei , Zhang Shenyan , Xie Siyu , Li Yanfeng , Lu Xiaofei , Wu Yingjun , Zhou Yangshu , Yuan Juanjuan , Cai Ting , Zheng Xiaojun , Ding Yanqing , Yang Wei 
Published: September 2021

BackgroundMismatch repair proficient colorectal cancer (pMMR CRC) lacks effective treatments and has a poor prognosis, which can be attributed to the complexity of tumor microenvironment. The coordinated function of immune cells is vital to anti-tumor immunity. However, the spatial characteristics of immune cells in the pMMR CRC immune microenvironment and their relationship with clinical prognosis are not fully understood. Meanwhile, the immune modulatory effect of neoadjuvant chemotherapy (NCT), which is the first-line treatment of pMMR CRC, needs further investigation. Therefore, this study aims to explore the spatial dynamics of immune cells and its prognostic value in pMMR CRC.MethodsWe analyzed the various immune cells in formalin-fixed, paraffin-embedded tumor tissues which were collected from 77 patients with stage II/III of pMMR CRC, including 39 non-NCT treated and 38 NCT treated patients. We used the optimized multiplex immunohistochemistry (mIHC) to identify and quantify the density, type and location of immune cells in pMMR CRC. Multivariate survival analysis was performed to assess the relationship of immune profiles and clinical prognosis of pMMR CRC patients.ResultsThe densities of most T cell subsets, B cells and macrophages were higher in the central region of the pMMR CRC than in the invasion margin. Tumor infiltrating lymphocytes (TILs), especially the infiltration of CD4+ GzmB+ T cells in the central region of the tumor was identified to be positively correlated with the prognosis of the patients. Multivariate analysis confirmed that CD4+ GzmB+ T cells population was an independent predictor of disease-free survival (DFS) in non-NCT group. Meanwhile, NCT enhanced the infiltration of CD4+ GzmB+ T cells in the central region of the pMMR CRC, which was also identified as an independent protective factor of overall survival (OS) and DFS in NCT group.ConclusionWe demonstrated that the level of CD4+ GzmB+ T cells located in the center of tumor could provide great prognostic value for pMMR CRC patients. And the application of neoadjuvant chemotherapy further improves the infiltration of CD4+ GzmB+ T cells in the central compartment. Further studies into the application of CD4+ GzmB+ T cells in tumor immunotherapy are needed.
Gene Expression Profiling for Differential Diagnosis of Liver Metastases: A Multicenter, Retrospective Cohort Study
Authors: Wang Qifeng , Li Fen , Jiang Qingming , Sun Yifeng , Liao Qiong , An Huimin , Li Yunzhu , Li Zhenyu , Fan Lifang , Guo Fang , Xu Qinghua , Wo Yixin , Ren Wanli , Yue Junqiu , Meng Bin , Liu Weiping , Zhou Xiaoyan 
Published: September 2021

BackgroundLiver metastases (LM) are the most common tumors encountered in the liver and continue to be a significant cause of morbidity and mortality. Identification of the primary tumor of any LM is crucial for the implementation of effective and tailored treatment approaches, which still represents a difficult problem in clinical practice.MethodsThe resection or biopsy specimens and associated clinicopathologic data were archived from seven independent centers between January 2017 and December 2020. The primary tumor sites of liver tumors were verified through evaluation of available medical records, pathological and imaging information. The performance of a 90-gene expression assay for the determination of the site of tumor origin was assessed.ResultA total of 130 LM covering 15 tumor types and 16 primary liver tumor specimens that met all quality control criteria were analyzed by the 90-gene expression assay. Among 130 LM cases, tumors were most frequently located in the colorectum, ovary and breast. Overall, the analysis of the 90-gene signature showed 93.1% and 100% agreement rates with the reference diagnosis in LM and primary liver tumor, respectively. For the common primary tumor types, the concordance rate was 100%, 95.7%, 100%, 93.8%, 87.5% for classifying the LM from the ovary, colorectum, breast, neuroendocrine, and pancreas, respectively.ConclusionThe overall accuracy of 93.8% demonstrates encouraging performance of the 90-gene expression assay in identifying the primary sites of liver tumors. Future incorporation of the 90-gene expression assay in clinical diagnosis will aid oncologists in applying precise treatments, leading to improved care and outcomes for LM patients.
Allergic Rhinitis Improvement in Asthmatic Children After Using Acaricidal Bait: A Randomized, Double-Blind, Cross-Placebo Study
Authors: Chen Ming , Wu Yufen , Yuan Shuhua , Tang Mingyu , Zhang Lei , Chen Jiande , Li Luanluan , Wu Jinhong , Zhang Jing , Yin Yong 
Published: September 2021

Objective: This study aimed to evaluate the effects of acaricidal bait use on the house dust mite (HDM) allergen concentration and occurrence of allergic rhinitis (AR) and asthma symptoms in children sensitized to HDMs.Study Design: Sixty-six children (3–12 years old) with AR and asthma sensitized to HDMs were randomly assigned to receive an acaricidal bait intervention for 8 weeks and a placebo intervention for 8 weeks separated by a 4-week washout period. The visual analog scale (VAS) score, rhinitis control assessment test (RCAT) score, rhinoconjunctivitis quality of life questionnaire (RQLQ) score, asthma control questionnaire-5 (ACQ-5) score and HDM allergen levels were monitored.Results: HDM allergen levels were significantly decreased after 8 weeks (Δder p2+f2 2.282 (3.516) μg/g vs. 0.147 (0.25) μg/g, P &lt; 0.05) in the acaricidal bait group compared with the placebo group. The VAS, RCAT and RQLQ scores in the acaricidal bait group were also significantly improved (ΔVAS 7.5 (16) vs. 3 (18), P &lt; 0.05; ΔRCAT−3 (5) vs. 0 (7), P &lt; 0.05; ΔRQLQ 4.5 (8) vs. 1 (8), P &lt; 0.05), but the ACQ-5 score did not improve (ΔACQ-5 0.2 (0.4) vs. 0 (0.65), P &gt; 0.05).Conclusion: Acaricidal bait reduced HDM exposure and improved rhinitis symptoms. This trial is registered at www.chictr.org.cn.
Use of Hypnosis in Paediatric Gastrointestinal Endoscopy: A Pilot Study
Authors: Tran Léa Chantal , Coopman Stéphanie , Rivallain Céline , Aumar Madeleine , Guimber Dominique , Nicolas Audrey , Darras Valérie , Turck Dominique , Gottrand Frédéric , Ley Delphine 
Published: September 2021

Objectives: Experience of hypnosis in gastrointestinal (GI) endoscopy is scarce in children. Our aims were to assess the rate of successful GI endoscopy performed using hypnosis alone or in combination with midazolam, with or without additional equimolar mixture of oxygen and nitrous oxide (EMONO), and to identify predictive factors of successful endoscopy in children.Methods: This prospective single-centre study included children older than 6 years requiring a diagnostic esophagogastroduodenoscopy (EGD) or rectosigmoidoscopy. Ericksonian hypnosis was performed alone or in combination with midazolam, with or without additional EMONO. Successful endoscopy was defined by a complete and well-tolerated procedure. Levels of satisfaction of the endoscopist, nurse, and patient were assessed.Results: One hundred forty children [70 boys, median age: 12 years (Q1–Q3: 9–14)] were included over a 14-month period. They underwent EGD in 51.4% (n = 72) and rectosigmoidoscopy in 48.6% (n = 68) of cases. EMONO and midazolam were combined with hypnosis in 136 cases (97.1%). Successful endoscopy rate reached 82.9%. The procedure was interrupted due to poor tolerance and was rescheduled under general anaesthesia in 11 patients (7.9%). Predictive factors for successful endoscopy were older age (13 vs. 8 years, OR: 1.34, CI 95% [1.10–1.62], p = 0.003) and type of endoscopy (EGD vs. rectosigmoidoscopy, OR: 16.34 [2.14–124.68], p = 0.007). A good cooperation of the patient was reported by the endoscopist and the nurse in 88.4 and 86.9% of cases, respectively. Ninety-two per cent of patients mentioned that the procedure went well.Conclusions: Our study suggests that hypnosis combined with EMONO and/or midazolam is of additional value to perform diagnostic EGD or rectosigmoidoscopy in children older than 6 years without systematic need for general anaesthesia.
Dissolving Polymer Microneedles for Transdermal Delivery of Insulin
Authors: Zhang Na , Zhou Xinxin , Liu Libo , Zhao Lini , Xie Hui , Yang Zhihang 
Published: September 2021

It’s of great significance to develop insulin-loaded dissolving microneedles (MNs) which are fabricated with various methods and materials for transdermal delivery of insulin to effectively and efficiently treat diabetes. In this work, we present a kind of FITC-insulin tip-loaded dissolving MNs fabricated with the mixture of polyvinyl alcohol (PVA) and sucrose using homemade PDMS MNs mold under vacuum conditions. The uniform appearance of MN arrays contributes to controlling the drug dosage well as required. Sufficient mechanical strength for penetrating tough stratum corneum can be obtained by vacuum frozen-drying for at least 6 h after peeling MNs off the mold. About 90% of the FITC-insulin is localized in the conical MN tips and can be released into the skin within 2 min after insertion. The in vivo insulin absorption study and hypoglycemic effect in diabetic mice demonstrate that the proposed insulin-loaded MNs can efficiently deliver the insulin to the systemic circulation and exhibit a similar effect to hypodermic injection on hypoglycemic administration. Together these results suggested that the efficient MN fabrication process proposed in this work shows great potential for mass production and practical application of drug-loaded dissolving MNs in the future.
Studies on Activities and Chemical Characterization of Medicinal Plants in Search for New Antimalarials: A Ten Year Review on Ethnopharmacology
Authors: Ceravolo Isabela P. , Aguiar Anna C. , Adebayo Joseph O. , Krettli Antoniana U. 
Published: September 2021

Malaria is an endemic disease that affected 229 million people and caused 409 thousand deaths, in 2019. Disease control is based on early diagnosis and specific treatment with antimalarial drugs since no effective vaccines are commercially available to prevent the disease. Drug chemotherapy has a strong historical link to the use of traditional plant infusions and other natural products in various cultures. The research based on such knowledge has yielded two drugs in medicine: the alkaloid quinine from Cinchona species, native in the Amazon highland rain forest in South America, and artemisinin from Artemisia annua, a species from the millenary Chinese medicine. The artemisinin-based combination therapies (ACTs), proven to be highly effective against malaria parasites, and considered as “the last bullet to fight drug-resistant malaria parasites,” have limited use now due to the emergence of multidrug resistance. In addition, the limited number of therapeutic options makes urgent the development of new antimalarial drugs. This review focuses on the antimalarial activities of 90 plant species obtained from a search using Pubmed database with keywords “antimalarials,” “plants” and “natural products.” We selected only papers published in the last 10 years (2011–2020), with a further analysis of those which were tested experimentally in malaria infected mice. Most plant species studied were from the African continent, followed by Asia and South America; their antimalarial activities were evaluated against asexual blood parasites, and only one species was evaluated for transmission blocking activity. Only a few compounds isolated from these plants were active and had their mechanisms of action delineated, thereby limiting the contribution of these medicinal plants as sources of novel antimalarial pharmacophores, which are highly necessary for the development of effective drugs. Nevertheless, the search for bioactive compounds remains as a promising strategy for the development of new antimalarials and the validation of traditional treatments against malaria. One species native in South America, Ampelozyzyphus amazonicus, and is largely used against human malaria in Brazil has a prophylactic effect, interfering with the viability of sporozoites in in vitro and in vivo experiments.
Tempol Reverses the Negative Effects of Morphine on Arterial Blood-Gas Chemistry and Tissue Oxygen Saturation in Freely-Moving Rats
Authors: Baby Santhosh M. , Discala Joseph F. , Gruber Ryan , Getsy Paulina M. , Cheng Feixiong , Damron Derek S. , Lewis Stephen J. 
Published: September 2021

We have reported that pretreatment with the clinically approved superoxide dismutase mimetic, Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), blunts the cardiorespiratory depressant responses elicited by a subsequent injection of fentanyl, in halothane-anesthetized rats. The objective of the present study was to determine whether Tempol is able to reverse the effects of morphine on arterial blood-gas (ABG) chemistry in freely-moving Sprague Dawley rats. The intravenous injection of morphine (10 mg/kg) elicited substantial decreases in pH, pO2 and sO2 that were accompanied by substantial increases in pCO2 and Alveolar-arterial gradient, which results in diminished gas-exchange within the lungs. Intravenous injection of a 60 mg/kg dose of Tempol 15 min after the injection of morphine caused minor improvements in pO2 and pCO2 but not in other ABG parameters. In contrast, the 100 mg/kg dose of Tempol caused an immediate and sustained reversal of the negative effects of morphine on arterial blood pH, pCO2, pO2, sO2 and Alveolar-arterial gradient. In other rats, we used pulse oximetry to determine that the 100 mg/kg dose of Tempol, but not the 60 mg/kg dose elicited a rapid and sustained reversal of the negative effects of morphine (10 mg/kg, IV) on tissue O2 saturation (SpO2). The injection of morphine caused a relatively minor fall in mean arterial blood pressure that was somewhat exacerbated by Tempol. These findings demonstrate that Tempol can reverse the negative effects of morphine on ABG chemistry in freely-moving rats paving the way of structure-activity and mechanisms of action studies with the host of Tempol analogues that are commercially available.
Asymmetry and Variability in the Transmission Spectra of Tidally Locked Habitable Planets
Authors: Song Xinyi , Yang Jun 
Published: September 2021

Spatial heterogeneity and temporal variability are general features in planetary weather and climate, due to the effects of planetary rotation, uneven stellar flux distribution, fluid motion instability, etc. In this study, we investigate the asymmetry and variability in the transmission spectra of 1:1 spin–orbit tidally locked (or called synchronously rotating) planets around low-mass stars. We find that for rapidly rotating planets, the transit atmospheric thickness of the evening terminator (east of the substellar region) is significantly larger than that of the morning terminator (west of the substellar region). The asymmetry is mainly related to the spatial heterogeneity in ice clouds, as the contributions of liquid clouds and water vapor are smaller. The underlying mechanism is that there are always more ice clouds on the evening terminator, due to the combined effect of coupled Rossby–Kelvin waves and equatorial superrotation that advect vapor and clouds to the east, especially at high levels of the atmosphere. For slowly rotating planets, the asymmetry reverses (the morning terminator has a larger transmission depth than the evening terminator), but the magnitude is small or even negligible. For both rapidly and slowly rotating planets, there is strong variability in the transmission spectra. The asymmetry signal is nearly impossible to be observed by the James Webb Space Telescope (JWST), because the magnitude of the asymmetry (about 10 ppm) is smaller than the instrumental noise and the high variability further increases the challenge.