bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Report: Amyloidosis Cutis Dyschromica: Dermoscopy and Reflectance Confocal Microscopy and Gene Mutation Analysis of a Chinese Pedigree
Authors: Wang Hui , Zhong Zhenyu , Wang Xiuli , Zheng Liyun , Wang Yifan , Wang Shan , Liu Siqi , Li Hui , Guo Ze , Gao Min 
Published: December 2021

Background: Amyloidosis cutis dyschromica (ACD) is a rare type of primary localized cutaneous amyloidosis. Non-invasive techniques can provide important clues for early diagnosis.Objectives: To highlight the characteristic imaging changes of ACD under dermoscopy and reflectance confocal microscopy (RCM), investigate gene mutations in a Chinese Han pedigree of ACD, and analyze the genotype–phenotype correlation.Methods: Dermoscopy and RCM examinations were completed together for the pedigree, and the imaging characteristics were described. The diagnosis of ACD was confirmed by pathological examination. Sequencing was performed followed by bioinformatics and genotype–phenotype correlation. ACD-related articles published on PubMed between January 1970 and March 2021 were reviewed and summarized.Results: In ACD, dermoscopy showed patchy white hypopigmentation and brownish spots, stripes, or hyperpigmented blotches and patches. RCM showed a highly refractive substance with clumpy, dotted, and linear structures inside the papillary dermis. Sequencing identified glycoprotein non-metastatic melanoma protein B (GPNMB) missense mutations [c.393T&gt;G (p.Y131X; NM_001005340.2)] and a frameshift deletion mutation [c.719_720delTG (p.V240fs; NM_001005340.2)]. The ANNOtate VARiation (ANNOVAR) software predicted that c.393T&gt;G is a pathogenic mutation. The literature review found 14 mutations, namely, 5 (35.7%) frameshift mutations, 4 (28.6%) non-sense mutations, 4 (28.6%) missense mutations, and 1 (7.1%) splice site mutation. Blisters and epidermolysis were observed in several cases, but there was no significant association between clinical manifestations and mutations in ACD.Conclusions: This study was the first to combine dermoscopy and RCM to describe ACD. Two GPNMB gene mutations were reported in a Chinese ACD pedigree. The genotype–phenotype correlation was analyzed for the first time; however, there was no significant correlation.
Serum CYR61 Is Associated With Airway Inflammation and Is a Potential Biomarker for Severity in Chronic Obstructive Pulmonary Disease
Authors: Tan Zhu-Xia , Fu Lin , Wang Wen-Jing , Zhan Ping , Zhao Hui , Wang Hua , Xu De-Xiang 
Published: December 2021

Background: Cysteine-rich 61 (CYR61) and inflammation was upregulated in the lungs of patients with chronic obstructive pulmonary disease (COPD). However, the association between CYR61 and inflammation was unclear in COPD patients. This study aimed to analyze the association of serum CYR61 with pulmonary inflammation and lung function indexes in COPD patients.Methods: One hundred and fifty COPD patients and 150 control subjects were enrolled. Serum and pulmonary CYR61 was detected. Lung function indexes were evaluated in COPD patients.Results: Serum CYR61 level was elevated and pulmonary CYR61 expression was upregulated in COPD patients. An increased CYR61 was associated with decreased pulmonary function indexes in COPD patients. Further analyses showed that nuclear factor-kappa B (NF-κB) p65-positive nuclei was elevated in the lungs of COPD patients with high level of CYR61. Accordingly, serum monocyte chemotactic protein (MCP)-1 and tumor necrosis factor α (TNF-α), two downstream inflammatory cytokines of NF-κB pathway, were increased in parallel with CYR61, among which serum MCP-1 and TNF-α were the highest in COPD patients with high level of CYR61. Moreover, a positive correlation, determined by multivariate regression that excluded the influence of age, gender and smoking, was observed between serum CYR61 and inflammatory cytokines in COPD patients.Conclusion: These results provide evidence that an increased CYR61 is associated with pulmonary inflammation and COPD progression. Inflammatory cytokines may be the mediators between CYR61 elevation and COPD progression.
Epidemiology of Extended-Spectrum Beta-Lactamase and Carbapenemase-Producing Enterobacterales in the Greater Mekong Subregion: A Systematic-Review and Meta-Analysis of Risk Factors Associated With Extended-Spectrum Beta-Lactamase and Carbapenemase Isolation
Authors: Singh Shweta R. , Teo Alvin Kuo Jing , Prem Kiesha , Ong Rick Twee-Hee , Ashley Elizabeth A. , van Doorn H. Rogier , Limmathurotsakul Direk , Turner Paul , Hsu Li Yang 
Published: December 2021

Background: Despite the rapid spread of extended-spectrum beta-lactamase (ESBL) producing-Enterobacterales (ESBL-E) and carbapenemase-producing Enterobacterales (CPE), little is known about the extent of their prevalence in the Greater Mekong Subregion (GMS). In this systematic review, we aimed to determine the epidemiology of ESBL-E and CPE in clinically significant Enterobacterales: Escherichia coli and Klebsiella pneumoniae from the GMS (comprising of Cambodia, Laos, Myanmar, Thailand, Vietnam and Yunnan province and Guangxi Zhuang region of China).Methods: Following a list of search terms adapted to subject headings, we systematically searched databases: Medline, EMBASE, Scopus and Web of Science for articles published on and before October 20th, 2020. The search string consisted of the bacterial names, methods involved in detecting drug-resistance phenotype and genotype, GMS countries, and ESBL and carbapenemase detection as the outcomes. Meta-analyses of the association between the isolation of ESBL from human clinical and non-clinical specimens were performed using the “METAN” function in STATA 14.Results: One hundred and thirty-nine studies were included from a total of 1,513 identified studies. Despite the heterogeneity in study methods, analyzing the prevalence proportions on log-linear model scale for ESBL producing-E. coli showed a trend that increased by 13.2% (95%CI: 6.1–20.2) in clinical blood specimens, 8.1% (95%CI: 1.7–14.4) in all clinical specimens and 17.7% (95%CI: 4.9–30.4) increase in carriage specimens. Under the log-linear model assumption, no significant trend over time was found for ESBL producing K. pneumoniae and ESBL-E specimens. CPE was reported in clinical studies and carriage studies past 2010, however a trend could not be determined because of the small dataset. Twelve studies were included in the meta-analysis of risk factors associated with isolation of ESBL. Recent antibiotic exposure was the most studied variable and showed a significant positive association with ESBL-E isolation (pooled OR: 2.9, 95%CI: 2.3–3.8) followed by chronic kidney disease (pooled OR: 4.7, 95%CI: 1.8–11.9), and other co-morbidities (pooled OR: 1.6, 95%CI: 1.2–2.9).Conclusion: Data from GMS is heterogeneous with significant data-gaps, especially in community settings from Laos, Myanmar, Cambodia and Yunnan and Guangxi provinces of China. Collaborative work standardizing the methodology of studies will aid in better monitoring, surveillance and evaluation of interventions across the GMS.
A Novel Diagnostic Biomarker, PZP, for Detecting Colorectal Cancer in Type 2 Diabetes Mellitus Patients Identified by Serum-Based Mass Spectrometry
Authors: Yang Jiayue , Fang Weigang , Wu Wenjun , Tian Zhen , Gao Rong , Yu Lu , Chen Dayang , Weng Xiaohua , Zhu Shengwei , Yang Cheng 
Published: December 2021

Background: Growing evidence has confirmed that populations with type 2 diabetes mellitus (T2DM) have an increasing risk of developing colorectal cancer (CRC). Thus, convenient and effective screening strategies for CRC should be developed for the T2DM population to increase the detection rate of CRC.Methods: Twenty serum samples extracted from five healthy participants, five T2DM patients, five CRC patients and five T2DM patients with CRC (T2DM + CRC) were submitted to data-independent acquisition mass spectrometry (DIA-MS) analysis to discover unique differentially altered proteins (DAPs) for CRC in patients with T2DM. Then, the diagnostic value of pregnancy zone protein (PZP) was validated by ELISA analysis in the validated cohort.Results: Based on DIA-MS analysis, we found eight unique proteins specific to T2DM patients with CRC. Among these proteins, four proteins showed different expression between the T2DM + CRC and T2DM groups, and PZP exhibited the largest difference. Next, the diagnostic value of serum PZP was validated by ELISA analysis with an AUC of 0.713. Moreover, the combination of PZP, CA199 and CEA exhibited encouraging diagnostic value, and the AUC reached 0.916.Conclusion: Overall, our current research implied that PZP could be regarded as a newfound serum biomarker for CRC medical diagnosis in T2DM patients.
Impaired Cognitive Function and Hippocampal Changes Following Chronic Diazepam Treatment in Middle-Aged Mice
Authors: Furukawa Tomonori , Nikaido Yoshikazu , Shimoyama Shuji , Masuyama Nozomu , Notoya Ayaka , Ueno Shinya 
Published: December 2021

Background: Gamma-aminobutyric acid (GABA) type A receptors are positively allosterically modulated by benzodiazepine binding, leading to a potentiated response to GABA. Diazepam (DZP, a benzodiazepine) is widely prescribed for anxiety, epileptic discharge, and insomnia, and is also used as a muscle relaxant and anti-convulsant. However, some adverse effects – such as tolerance, dependence, withdrawal effects, and impairments in cognition and learning – are elicited by the long-term use of DZP. Clinical studies have reported that chronic DZP treatment increases the risk of dementia in older adults. Furthermore, several studies have reported that chronic DZP administration may affect neuronal activity in the hippocampus, dendritic spine structure, and cognitive performance. However, the effects of chronic DZP administration on cognitive function in aged mice is not yet completely understood.Methods: A behavioral test, immunohistochemical analysis of neurogenic and apoptotic markers, dendritic spine density analysis, and long-term potentiation (LTP) assay of the hippocampal CA1 and CA3 were performed in both young (8 weeks old) and middle-aged (12 months old) mice to investigate the effects of chronic DZP administration on cognitive function. The chronic intraperitoneal administration of DZP was performed by implanting an osmotic minipump. To assess spatial learning and memory ability, the Morris water maze test was performed. Dendritic spines were visualized using Lucifer yellow injection into the soma of hippocampal neurons, and spine density was analyzed. Moreover, the effects of exercise on DZP-induced changes in spine density and LTP in the hippocampus were assessed.Results: Learning performance was impaired by chronic DZP administration in middle-aged mice but not in young mice. LTP was attenuated by DZP administration in the CA1 of young mice and the CA3 of middle-aged mice. The spine density of hippocampal neurons was decreased by chronic DZP administration in the CA1 of both young and middle-aged mice as well as in the CA3 of middle-aged mice. Neither neurogenesis nor apoptosis in the hippocampus was affected by chronic DZP administration.Conclusion: The results of this study suggest that the effects of chronic DZP are different between young and middle-aged mice. The chronic DZP-induced memory retrieval performance impairment in middle-aged mice can likely be attributed to decreased LTP and dendritic spine density in hippocampal neurons in the CA3. Notably, prophylactic exercise suppressed the adverse effects of chronic DZP on LTP and spine maintenance in middle-aged mice.
Low-Temperature Chemical Vapor Deposition Growth of MoS2 Nanodots and Their Raman and Photoluminescence Profiles
Authors: Mawlong Larionette P. L. , Biroju Ravi K. , Giri P. K. 
Published: December 2021

We report on the growth of an ordered array of MoS2 nanodots (lateral sizes in the range of ∼100–250 nm) by a thermal chemical vapor deposition (CVD) method directly onto SiO2 substrates at a relatively low substrate temperature (510–560°C). The temperature-dependent growth and evolution of MoS2 nanodots and the local environment of sulfur-induced structural defects and impurities were systematically investigated by field emission scanning electron microscopy, micro-Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS) techniques. At the substrate temperature of 560°C, we observed mostly few-layer MoS2, and at 510°C, multilayer MoS2 growth, as confirmed from the Raman line shape analysis. With reduced substrate temperature, the density of MoS2 nanodots decreases, and layer thickness increases. Raman studies show characteristic Raman modes of the crystalline MoS2 layer, along with two new Raman modes centered at ∼346 and ∼361 cm−1, which are associated with MoO2 and MoO3 phases, respectively. Room temperature photoluminescence (PL) studies revealed strong visible PL from MoS2 layers, which is strongly blue-shifted from the bulk MoS2 flakes. The strong visible emission centered at ∼ 658 nm signifies a free excitonic transition in the direct gap of single-layer MoS2. Position-dependent PL profiles show excellent uniformity of the MoS2 layers for samples grown at 540 and 560°C. These results are significant for the low-temperature CVD growth of a few-layer MoS2 dots with direct bandgap photoluminescence on a flexible substrate.
Characterizing the Neuroimaging and Histopathological Correlates of Cerebral Small Vessel Disease in Spontaneously Hypertensive Stroke-Prone Rats
Authors: Hannawi Yousef , Caceres Eder , Ewees Mohamed G. , Powell Kimerly A. , Bratasz Anna , Schwab Jan M. , Rink Cameron L. , Zweier Jay L. 
Published: December 2021

Introduction: Spontaneously hypertensive stroke-prone rats (SHRSP) are used to model clinically relevant aspects of human cerebral small vessel disease (CSVD). To decipher and understand the underlying disease dynamics, assessment of the temporal progression of CSVD histopathological and neuroimaging correlates is essential.Materials and Methods: Eighty age-matched male SHRSP and control Wistar Kyoto rats (WKY) were randomly divided into four groups that were aged until 7, 16, 24 and 32 weeks. Sensorimotor testing was performed weekly. Brain MRI was acquired at each study time point followed by histological analyses of the brain.Results: Compared to WKY controls, the SHRSP showed significantly higher prevalence of small subcortical hyperintensities on T2w imaging that progressed in size and frequency with aging. Volumetric analysis revealed smaller intracranial and white matter volumes on brain MRI in SHRSP compared to age-matched WKY. Diffusion tensor imaging (DTI) showed significantly higher mean diffusivity in the corpus callosum and external capsule in WKY compared to SHRSP. The SHRSP displayed signs of motor restlessness compared to WKY represented by hyperactivity in sensorimotor testing at the beginning of the experiment which decreased with age. Distinct pathological hallmarks of CSVD, such as enlarged perivascular spaces, microbleeds/red blood cell extravasation, hemosiderin deposits, and lipohyalinosis/vascular wall thickening progressively accumulated with age in SHRSP.Conclusions: Four stages of CSVD severity in SHRSP are described at the study time points. In addition, we find that quantitative analyses of brain MRI enable identification of in vivo markers of CSVD that can serve as endpoints for interventional testing in therapeutic studies.
Five-Years Angiographic Follow-Up of Wide-Neck Intracranial Aneurysms Treated With LEO Plus Stent
Authors: Pumar José M. , Sucasas Paula , Mosqueira Antonio , Vega Pedro , Murias Eduardo 
Published: December 2021

Background: This study aimed to evaluate the angiographic and clinical outcome, with an emphasis on long-term follow-up, of the LEO Plus stent for wide-neck intracranial aneurysms treated in a single center.Methods: We retrospectively examined a prospectively maintained database of patients treated with LEO Plus devices between January 2004 and December 2016. Data regarding patient demographics, aneurysm characteristics, and technical procedures were analyzed. Angiographic and clinical findings were recorded during the procedure and followed up over a period of at least 5 years.Results: We identified 101 patients with 116 aneurysms. In 16 patients, the stent could not safely be placed. Thus, a total of 97 LEO Plus devices were implanted in 97 aneurysms of 85 patients. Adverse events (acute and delayed) were observed in 21.6% of cases (17/85), and most were resolved (70.6%; 12/17). Moreover, 5 years after the procedure, total morbidity and mortality were 2.3% (2/85) and 3.5% (3/85), respectively. Long-term imaging follow-up showed complete occlusions, neck remnants, and residual aneurysms in 73.1% (57/78), 14.1% (11/78), and 12.8% (10/78) of cases, respectively.Conclusions: Long-term results of treatment of brain aneurysms with LEO stent show high rates of adequate and stable occlusion over time, with acceptable morbidity and mortality.
A National Representative, Cross-Sectional Study by the Hellenic Academy of NeuroImmunology (HEL.A.NI.) on COVID-19 and Multiple Sclerosis: Overall Impact and Willingness Toward Vaccination
Authors: Boziki Marina , Styliadis Charis , Bakirtzis Christos , Grigoriadou Eleni , Sintila Aggeliki-Styliani , Nikolaidis Ioannis , Vrienniou Aliki , Geys Lotte , Pelidou Sygkliti-Henrietta , Probert Lesley , Papazisis Georgios , Bamidis Panagiotis , Grigoriadis Nikolaos 
Published: December 2021

Background: In the context of the coronavirus disease 2019 (COVID-19) pandemic, the constant needs of people with multiple sclerosis (PwMS) and their caregivers were urgently highlighted.Aim: The present study aims to capture the effects of the COVID-19 pandemic in several aspects of the quality of life of PwMS, in perception and behavior to COVID-19 and multiple sclerosis (MS), as well as concerning healthcare, working conditions, and the willingness toward COVID-19 vaccination.Methods: This study is an initiative of the Hellenic Academy of Neuroimmunology (HEL.A.NI.) and it has been included in the MS Data Alliance (MSDA) Catalog, which can be accessed after creating an account on https://msda.emif-catalogue.eu/login. Two online questionnaires were administered: (i) impact of the COVID-19 pandemic on the quality of life, behavior, and healthcare of PwMS (Questionnaire A) and (ii) vaccination against COVID-19 (Questionnaire B). People with MS were invited to participate by the Hellenic Federation of Persons with Multiple Sclerosis (HFoPwMS).Results: Three-hundred-ninety PwMS responded to Questionnaire A, whereas 176 PwMS provided answers for Questionnaire B. Older age, longer disease duration, and higher MS-related disability were associated with the increased perceived sensitivity toward severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as well as the increased perceived severity of COVID-19 upon potential infection. A significant proportion of PwMS experienced restricted access to MS-related health professionals, disease-modifying therapy (DMT) prescription, and/or to MS-related laboratory examination due to the pandemic. Subgroups of PwMS reported exacerbated symptoms (i.e., chronic MS-related symptoms, fatigue and/or worsening of pre-existing fatigue, and sexual dysfunction and or/worsening of pre-existing sexual dysfunction). Overall, the majority of the participants reported either a strong willingness to get vaccinated against COVID-19 or a likeliness to undergo vaccination. Being aware of the HEL.A.NI. recommendations regarding COVID-19 vaccination for PwMS were reported to increase the willingness of the participants to receive the vaccine.Conclusions: Our results highlight the necessity of scientific and patient organizations in taking joint action to increase awareness on health-related issues during the pandemic and to provide accurate and up-to-date guidance for PwMS. Online information and communications technology (ICT) tools for polling public belief and behavior may prove valuable as means of retaining active routes of communication between stakeholders.
Frailty in Glioblastoma Is Independent From Chronological Age
Authors: Krenzlin Harald , Jankovic Dragan , Alberter Christoph , Kalasauskas Darius , Westphalen Christiane , Ringel Florian , Keric Naureen 
Published: December 2021

Objective: Treatment of glioblastoma in elderly patients is particularly challenging due to their general condition and comorbidities. Treatment decisions are often based on chronological age. Frailty screening tests promise an assessment tool to stratify geriatric patients and identify those at risk for an unfavorable outcome. This study aims to evaluate the impact of age and frailty on the surgical outcome and overall survival in geriatric patients with glioblastoma.Methods: Data acquisition was conducted as a single-center retrospective analysis. From January 1st 2015, and December 31st 2019, 104 glioblastoma patients over 70 years of age were included in our study. Demographic data, tumor size, Karnofsky Performance Score (KPS), and Eastern Cooperative Oncology Group Performance Status (ECOG), as well as treatment modalities, were assessed. The Geriatric 8 health status screening tool (G8) and Groningen Frailty Index (GFI) were compiled pre-and postoperatively.Results: The mean patient age was 76.86 ± 4.11 years. Forty-nine (47%) patients were female, 55 (53%) male. Sixty-seven patients underwent microsurgical tumor resection, 37 received tumor biopsy alone. Mean G8 on admission was 12.4 ± 2.0, mean GFI 5.0 ± 2.5. In our cohort, frailty was independent of patient age, tumor size, or localization. Frailty, defined by G8 and GFI, is associated with shorter overall survival (G8: p = 0.0035; GFI: p = 0.0136) and higher numbers of surgical complications (G8: p = 0.0326; GFI: p = 0.0388). Frailer patients are more likely to receive best supportive care (p = 0.004). Nevertheless, frailty did not affect adjuvant treatment decision-making toward either single-use of chemo- or radiation therapy, stratified treatment, or concomitant therapy. The surgical decision on the extent of resection was not based on pre-operative frailty.Conclusion: In our study, frailty is a predictor of poorer surgical outcomes, post-operative complications, and impaired overall survival independent of chronological age. Frailty screening tests offer an additional assessment tool to stratify geriatric patients with glioblastoma and identify those at risk for a detrimental outcome and thus should be implemented in therapeutic decision making.
Repeated Clinical Assessment Using Sensory Modality Assessment and Rehabilitation Technique for Diagnosis in Prolonged Disorders of Consciousness
Authors: da Conceição Teixeira Liliana , Blacker Danielle , Campos Carlos , Garrett Carolina , Duport Sophie , Rocha Nuno Barbosa 
Published: December 2021

Purpose: The recommended way to assess consciousness in prolonged disorders of consciousness is to observe the patient’s responses to sensory stimulation. Multiple assessment sessions have to be completed in order to reach a correct diagnosis. There is, however, a lack of data on how many sessions are sufficient for validity and reliability. The aim of this study was to identify the number of Sensory Modality Assessment and Rehabilitation Technique (SMART) assessment sessions needed to reach a reliable diagnosis. A secondary objective was to identify which sensory stimulation modalities are more useful to reach a diagnosis.Materials and Methods: A retrospective analysis of all the adult patients (who received a SMART assessment) admitted to a specialist brain injury unit over the course of 4 years was conducted (n = 35). An independent rater analyzed the SMART levels for each modality and session and provided a suggestive diagnosis based on the highest SMART level per session.Results: For the vast majority of patients between 5 and 6 sessions was sufficient to reach the final clinical diagnosis. The visual, auditory, tactile, and motor function modalities were found to be more associated with the final diagnosis than the olfactory and gustatory modalities.Conclusion: These findings provide for the first time a rationale for optimizing the time spent on assessing patients using SMART.