bluuebunny/crossref_metadata_2025 huggingface dataset:
High selectivity of photocatalytic reduction of CO2 to CO based on terpyridine ligand supported CuI metal organic framework
Authors: Zhang Wen-Dong , Wang Yun , Liang Yi , Jiang Ai-Lin , Gong Hao , Tian Xiao-Ying , Fu Wen-Sheng , Liao Jia-Zhen , Chen Peng , Ma Ying-Zhao
Published: August 2022

In this work, a 4’-(4-cynaophenyl)-4,2’:6′,4-terpyridine supported CuI MOFs photocatalyst (CuIMOF) was applied to the photocatalytic CO2 reduction for the first time. The micro-structural and physicochemical properties of the CuIMOF were systematically studied by the powder X-ray diffraction (PXRD), Single crystal X-ray diffraction (SCXRD), scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FT-IR), UV-Vis diffuse spectroscopy (UV-vis DRS), ns-level photoluminescence spectra (ns-level PL), Ultraviolet photoelectron spectroscopy (UPS), and N2 adsorption-desorption test (BET-BJH). Moreover, the in situ diffuse reflectance infrared fourier transform spectroscopy (in situ DRIFTS) was applied to investigate the adsorption and reaction intermediates of photocatalytic CO2 reduction. As a result, CuIMOF exhibited good performance and outstanding selectivity toward photocatalytic reduction of CO2 to CO under full-spectrum and visible light illumination. Notably, 100% selective photocatalytic conversion of CO2 to CO was achieved. Thus, the study presents the high selectivity and CO2 reduction efficiency of CuIMOF as a potential family of photocatalysts.
Shale Lithofacies and Its Effect on Reservoir Formation in Lower Permian Alkaline Lacustrine Fengcheng Formation, Junggar Basin, NW China
Authors: Tang Yong , He Wenjun , Zheng Menglin , Chang Qiusheng , Jin Zhijun , Li Jiao , Zhang Yuanyuan
Published: August 2022

Lower Permian Fengcheng Formation is considered to be a high-quality alkaline lacustrine shale oil resource in the Junggar Basin, NW China. Based on core and thin section observation, X-ray diffraction, scanning electron microscope, low-pressure N2 adsorption, and high-pressure mercury intrusion porosimetry, different shale lithofacies, and pore structures were examined. According to the mineral composition, shales in well My 1 are divided into five types: dolomitic mudstone, calcareous mudstone, siliceous mudstone, tuffaceous mudstone, and argillaceous mudstone, each of which shows its pore structure distribution. Intragranular pores, inter-crystalline pores associated with clays and pyrites, dissolution pores, and microfractures were commonly observed. There are three segments of pore structures including <50 nm, 50 nm-4 μm, and >4 μm. Clay minerals mainly contribute to mesopores, especially in argillaceous mudstones. The dissolution of carbonate minerals and feldspars is significant for macropores predominantly in dolomitic mudstones and tuffaceous mudstones, respectively. Micron-scale microfractures associated with laminae dominate in dolomitic mudstones. Therefore, the dolomitic mudstones, especially with lamination, and tuffaceous mudstones are proposed to be favored shale lithofacies with great exploration potential in the Mahu Sag.
Dose dependency of aliquot sizes and age models from modern alluvial fan deposits of Helan Mountain, China
Authors: Liu Xiuying , Li Xiao , Zhao Qiuyue , Pan Baolin , Wang Junping , Wei Mingjian
Published: August 2022

Alluvial fan deposits are identified as evidence of regional climatic variations and tectonic events; therefore, it is crucial to establish absolute time series by dating alluvial fan deposits. Limited exposure to light poses a challenge to accurately estimating the buried ages for alluvial deposits with optically stimulated luminescence (OSL). This challenge has been positively developed by controlling the number of grains on each disk to measure and choosing suitable statistical models for the equivalence dose (De) distribution to analyze. In this research, three modern alluvial samples and one modern loess-like sample were collected from the Dashuigou alluvial fan of Helan Mountain, China. The De distributions of these four samples were studied by the application of small aliquots (1-, 3-, and 5-mm aliquots) of quartz OSL with the average dose model, central age model, unlogged minimum age model (MAM), lowest 5%, internal/external consistency criterion minimum age model (IEU), and finite mixture model. It is concluded that an overestimation of De lower than 1 Gy can be obtained using quartz OSL dating of 1-mm aliquots (∼50 grains) with MAM and IEU for the alluvial sediments. The lowest 5% method may underestimate the De values of the 1-mm aliquots for young samples. This research makes the dose dependency of aliquot sizes and age models more definite and opens up the possibility of dating paleoalluvial deposits to establish a chronological framework to decipher the implications of paleoclimates and tectonics.
Critical slowing down theory provides early warning signals for sandstone failure
Authors: Tang Yao , Zhu Xing , He Chunlei , Hu Jiewei , Fan Jie
Published: August 2022

The critical point of rock mass transition from stable to unstable states is significant for the prevention and control of rock engineering hazards. This study explored the precursor characteristics of instability in sandstone containing prefabricated fractures and intact sandstone based on the critical slowing down (CSD) theory. The results demonstrated that as the input energy drove the dissipation energy dynamic system toward the critical point of two states, the CSD phenomenon appeared, which was manifested by the sudden increase in CSD time series metrics (skewness, kurtosis, and coefficient of variation) and autoregressive model metrics (variance and autocorrelation coefficient). The CSD characteristics of different dissipation energy dynamical systems were different, resulting in different times of CSD phenomena for distinct systems. In addition, the angle of the sandstone fracture affected the characteristics of the dissipation energy dynamical system and hence the appearance time of the precursor information. The precursor time of the sandstone containing 45° parallel fractures appeared earliest among all rock samples, and the ratio of the appearance time of the precursor point to the failure time of all rock samples reached more than 80%, which had good timeliness. The stress at the precursor point reached more than 80% of the peak stress, which corresponded to the plastic stage in the loading process, indicating that the CSD indicators constitute an effective monitoring index, which can provide an important reference for the stability monitoring and early warning of the field rock project.
Musical extracurricular activities and adjustment among children from immigrant families: A 2-year quasi-experimental study
Authors: Olivier Elizabeth , Dupéré Véronique , Archambault Isabelle , Meilleur Marilou , Thouin Éliane , Denault Anne-Sophie
Published: August 2022

This quasi-experimental study examines the impact on emotional/behavioral functioning (hyperactivity-inattention and internalizing symptoms) and school experiences (school engagement, positive experience in school) ofLa classe enchantée, a high-quality, non-selective extracurricular music program. Based on the program’s objectives and on the positive youth development model, it was anticipated that elementary school students participating inLa classe enchantéewould evolve more favorably in terms of these outcomes over the 2-year duration of the program spanning Grades 4 and 5, compared to non-participating schoolmates. The sample includes 72 children (25% in the intervention group, 47% girls, 93% first/second generation immigrants) from one low-income school, followed over 2 years starting in grade four (Mage= 9.30,SD= 0.49). Latent Growth Curve models show that, compared to classmates not in the program, children inLa classe enchantéeprogressed more favorably over time on self-reported measures of internalizing symptoms and positive experiences in school. For teacher-rated hyperactivity-inattention and school engagement, the slopes indicated stability over time in both groups, although hyperactivity-inattention tended to improve among those with relatively high initial levels in the intervention group. These results suggest that engagement in quality musical extracurricular activities might boost emotional and school well-being and potentially reduce hyperactivity-inattention among a specific subgroup of children from immigrant families.
Expression of glucocorticoid receptor (GR) and clinical significance in adrenocortical carcinoma
Authors: Wu Kan , Liu Zhihong , Liang Jiayu , Zhang Fuxun , Zhang Fan , Wang Yaohui , Lia Thongher , Liu Shenzhuo , Zhu Yuchun , Li Xiang
Published: August 2022

Adrenocortical carcinoma (ACC) is a rare endocrine tumor, and most cases present with hormone excess with poor prognosis. Our research aims to determine the clinical and biological significance of glucocorticoid receptor (GR) expression using large cohorts of ACC patients. Immunohistochemistry was used to assess the expression of GR in 78 ACC cases from the West China Hospital (WCH) cohort. RNA-seq data were retrieved from The Cancer Genome Atlas database (TCGA, n=79). Clinicopathological and follow-up data were obtained from two cohorts. The correlation between the GR gene and tumor immune status was estimated using TIMER and GEPIA2. Kaplan–Meier analysis was performed to identify the prognostic value of GR in ACC. In the WCH cohort, positive nuclear GR staining was identified in 90% of the primary ACC cases. Cortisol-secreting ACCs demonstrated significantly lower GR protein expression than did nonfunctioning tumors (P<0.001). This finding was validated by the mRNA data analysis of the TCGA cohort (P = 0.030). GR expression was found to be positively correlated with the immune cell infiltration level and immune-checkpoint-related gene expression in ACC. Survival comparison and multivariate analysis showed that GR expression is an independent prognostic predictor of disease-free survival and overall survival in ACC patients in both cohorts. Our findings suggest that low GR expression is significantly correlated with excess cortisol, immune signatures and poor survival in ACC patients. We propose that GR signaling may play an important role in ACC behavior and thus may be a therapeutic target, which deserves further research.
What is the status of immunotherapy in thyroid neoplasms?
Authors: Garcia-Alvarez Alejandro , Hernando Jorge , Carmona-Alonso Ana , Capdevila Jaume
Published: August 2022

Immunotherapy has changed the treatment of patients with advanced cancer, with different phase III trials showing durable responses across different histologies. This review focuses on the preclinical and clinical evidence of potential predictive biomarkers of response and efficacy of immunotherapy in thyroid neoplasms. Programmed death-ligand 1 (PD-L1) staining by immunohistochemistry has shown higher expression in anaplastic thyroid cancer (ATC) compared to other subtypes. The tumor mutational burden in thyroid neoplasms is low but seems to be higher in ATC. Immune infiltrates in the tumor microenvironment (TME) differ between the different thyroid neoplasm subtypes. In general, differentiated thyroid cancer (DTC) has a higher number of tumor-associated lymphocytes and regulatory T cells (Tregs), while ATC and medullary thyroid cancer (MTC) display a high density of tumor-associated macrophages (TAMs). Nevertheless, results from clinical trials with immunotherapy as monotherapy or combinations have shown limited efficacy. Further investigation into new strategies aside from anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4)/programmed death 1 (PD-1)/PD-L1 antibodies, validation of predictive biomarkers, and better population selection for clinical trials in thyroid neoplasms is more than needed in the near future.
Triglyceride glucose index is associated with cerebral small vessel disease burden and cognitive impairment in elderly patients with type 2 diabetes mellitus
Authors: Teng Zhenjie , Feng Jing , Dong Yanhong , Xu Jing , Jiang Xin , Chen Huifang , Qi Qianqian , Li Rui , Chen Weihong , Lv Peiyuan
Published: August 2022

Objective

To investigate the relations of Triglyceride glucose (TyG) index with cerebral small vessel disease (CSVD) burden and cognitive function in aged patients with type 2 diabetes mellitus (T2DM).

Methods

A total of 308 elderly patients with T2DM were included in this retrospective study. The standardized Chinese version of Mini-Mental State Examination was used to assess cognitive function. The total CSVD burden score was assessed by combining four imaging markers of CSVD, including the presence of white matter hyperintensity, cerebral microbleeds in the deep, lacunes and enlarged perivascular spaces in the basal ganglia. The TyG index was calculated as the formula of ln [fasting triglyceride (mg/dl) × fasting plasma glucose (mg/dl)/2]. We used logistic regression analysis and mediation analysis to investigate the relations of TyG index with CSVD and cognitive function.

Results

Multivariate binary logistic regression analysis showed that increased TyG index (OR: 2.241; 95% Confidence Interval(CI): 1.439 to 3.490; P <0.001), or severe CSVD burden (OR: 2.198; 95% CI: 1.283 to 3.763; P = 0.004) was associated with an increased risk of cognitive impairment in elderly patients with T2DM after adjusting for potential confounders. In addition, TyG index was an independent risk factor of severe CSVD burden (OR: 1.472; 95% CI: 1.003 to 2.160; P = 0.048) after controlling for potential confounders. Compared with the lowest TyG index tertile, the multivariable-adjusted OR of the highest tertile was 3.298 (95% CI: 1.685 to 6.452; P for trend <0.001) for cognitive impairment, 1.933 (95% CI: 1.010 to 3.698; P for trend = 0.047) for severe CSVD burden. Mediation analysis found a significant moderating effect of the severe CSVD burden on the association between higher TyG index levels and cognitive impairment.

Conclusions

The increased TyG index is an independent risk factor for cognitive impairment and severe CSVD burden in clinical practice. A proportion of the effect of increased TyG index on cognitive impairment may be due to the aggravation of CSVD burden.
Applying ecosystem services principles to the derivation of freshwater environmental quality standards
Authors: Maltby Lorraine , Brown Ross , Wilkinson Helen
Published: August 2022

Freshwater ecosystems provide many benefits to people (ecosystem services), but their biodiversity and functioning is threatened by anthropogenic stressors, including chemical pollution. Environmental quality standards (EQSs) for chemicals, are designed to protect species, but their derivation takes no account of ecosystem processes or species interactions and hence their links to biodiversity, ecosystem functioning and ecosystem services are uncertain. Here we explore a novel approach for the derivation of chemical EQSs to protect ecosystem service providing units (i.e., assemblages of species with ecological traits that underpin an ecosystem service) and ultimately protect ecosystem service delivery in different freshwater bodies and river basins. This approach, which was illustrated for two Water Framework Directive priority chemicals (a pyrethroid insecticide and polybrominated diphenyl ethers), is the first application of an ecosystem services framework to derive EQS values. The four-step approach enabled the derivation of ecosystem service-specific and river basin-specific standards that can inform spatially-defined and targeted management of chemical impacts on the aquatic (freshwater) environment. The derivation of ecosystem service specific EQS values also helps in communicating and highlighting the incremental benefits of improving water quality. A Tier I assessment focusing on protecting ecosystem service providing units was successfully undertaken based on available ecotoxicological effects data for each chemical. However, Tier II and Tier III assessments require further scientific research and tool development to quantify chemical impacts on ecosystem services delivery based on service providing taxa and their functional traits.
Development and validation of a robust necroptosis related classifier for colon adenocarcinoma
Authors: Yang Jie , Chen Hua , Wang Yongqiang , Chen Jian
Published: August 2022

Background: Necroptosis, a novel form of apoptosis, plays a crucial function in the progression of colon adenocarcinoma (COAD) and is expected to be triggered in cancer therapy for enhancing anti-tumor immunity. However, the function of necroptosis in tumors and its relationship with the tumor microenvironment (TME) remains largely unclear.

Methods: Necroptosis-related genes (NRGs) were collected from high-quality literature. Using The Cancer Genome Atlas (TCGA) (https://cancergenome.nih.gov) and the Gene Expression Omnibus (GEO) (www.ncbi.nlm.nih.gov/geo) meta-cohorts, a robust risk model was constructed to systematically examine the clinical value, functional status, the role of TME based on the risk model, as also the genomic variations.

Results: A risk model containing nine NRGs, including TNF receptor-associated factor (TRAF2), TNF receptor 1 associated via death domain (TRADD), ubiquitin carboxyl-terminal hydrolase 21 (USP21), TNF receptor superfamily, member 6 (FAS), tumor necrosis factor receptor superfamily 10B (TNFRSF10B), mitogen-activated protein kinase 8 (MAPK8), mixed lineage kinase domain-like (MLKL), TNF receptor-associated factor 5 (TRAF5), and recombinant receptor-interacting serine-threonine kinase 3 (RIPK3), was constructed. The risk model’s stability and accuracy were demonstrated in training, as also the validation cohorts; it was verified as an independent prognostic model for COAD. High-risk group patients developed “cold” tumors having active tumor proliferation and immunosuppression, while those in the low-risk group developed “hot” tumors with active immune and cell killing functions. Moreover, a higher number of copy number variations in the genome and fewer somatic mutations were found in high-risk group patients. Furthermore, higher sensitivity towards immunotherapy and chemotherapy was seen in patients of the low-risk group.

Conclusion: A reliable risk model based on NRGs to assess patient prognosis and guide clinical decision-making was constructed and validated. Our findings may contribute to the understanding of necroptosis and are expected to aid clinical management and guide precision treatment for patients with COAD.
Multifunctional regulation of VAMP3 in exocytic and endocytic pathways of RBL-2H3 cells
Authors: Mishima Satomi , Sakamoto Marin , Kioka Hikaru , Nagata Yuka , Suzuki Ryo
Published: August 2022

Mast cells (MCs) are inflammatory cells involved in allergic reactions. Crosslinking of the high-affinity receptor for IgE (FcϵRI) with multivalent antigens (Ags) induces secretory responses to release various inflammatory mediators. These responses are largely mediated by soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). Vesicle-associated membrane protein 3 (VAMP3) is a vesicular-SNARE that interacts with targeted SNARE counterparts, driving the fusion of MC secretory granules with the membrane and affecting subsequent assembly of the plasma membrane. However, the role of VAMP3 in FcϵRI-mediated MC function remains unclear. In this study, we comprehensively examined the role of VAMP3 and the molecular mechanisms underlying VAMP3-mediated MC function upon FcϵRI activation. VAMP3 shRNA transduction considerably decreased VAMP3 expression compared with non-target shRNA-transduced (NT) cells. VAMP3 knockdown (KD) cells were sensitized with an anti-DNP IgE antibody and subsequently stimulated with Ag. The VAMP3 KD cells showed decreased degranulation response upon Ag stimulation. Next, we observed intracellular granule formation using CD63-GFP fluorescence. The VAMP3 KD cells were considerably impaired in their capacity to increase the size of granules when compared to NT cells, suggesting that VAMP3 mediates granule fusion and therefore promotes granule exocytosis in MCs. Analysis of FcϵRI-mediated activation of signaling events (FcϵRI, Lyn, Syk, and intracellular Ca2+ response) revealed that signaling molecule activation was enhanced in VAMP3 KD cells. We also found that FcϵRI expression on the cell surface decreased considerably in VAMP3 KD cells, although the amount of total protein did not vary. VAMP3 KD cells also showed dysregulation of plasma membrane homeostasis, such as endocytosis and lipid raft formation. The difference in the plasma membrane environment in VAMP3 KD cells might affect FcϵRI membrane dynamics and the subsequent signalosome formation. Furthermore, IgE/Ag-mediated secretion of TNF-α and IL-6 is oppositely regulated in the absence of VAMP3, which appears to be attributed to both the activation of FcϵRI and defects in VAMP3-mediated membrane fusion. Taken together, these results suggest that enhanced FcϵRI-mediated signal transduction in VAMP3 KD cells occurs due to the disruption of plasma membrane homeostasis. Hence, a multifunctional regulation of VAMP3 is involved in complex secretory responses in MCs.
The role of the macrophage-to-myofibroblast transition in renal fibrosis
Authors: Wei Jia , Xu Zihao , Yan Xiang
Published: August 2022

Renal fibrosis causes structural and functional impairment of the kidney, which is a dominant component of chronic kidney disease. Recently, a novel mechanism, macrophage-to-myofibroblast transition (MMT), has been identified as a crucial component in renal fibrosis as a response to chronic inflammation. It is a process by which bone marrow-derived macrophages differentiate into myofibroblasts during renal injury and promote renal fibrosis. Here, we summarized recent evidence and mechanisms of MMT in renal fibrosis. Understanding this phenomenon and its underlying signal pathway would be beneficial to find therapeutic targets for renal fibrosis in chronic kidney disease.
Oral squamous cell carcinoma (OSCC) tumors from heavy alcohol consumers are associated with higher levels of TLR9 and a particular immunophenotype: Impact on patient survival
Authors: Bolesina Nicolás , Gatti Gerardo , López de Blanc Silvia , Dhooge Sabrina , Rocha Darío , Fernandez Elmer , Ferreyra Ruth , Palla Vanesa , Grupe Verónica , Morelatto Rosana , Maccioni Mariana
Published: August 2022

Oral squamous cell carcinoma (OSCC) is one of the most frequent types of oral cancer in developing countries and its burden correlates with exposure to tobacco and excessive alcohol consumption. Toll like receptors (TLRs) are major sensors of inflammatory stimuli, from both microbial and sterile causes and as such, they have been related to tumor progression and metastasis. Here, we evaluated the expression of TLR2, 4 and 9 as well as CD3+, CD8+ and Granzyme B+ cell infiltration by immunohistochemistry in oral samples of 30 patients with OSCC, classified according to their consumption of alcohol. Our findings indicate that there is a significant association between heavy alcohol consumption and tumors with higher expression levels of TLR9. Moreover, patients with TLR9high tumors, as well as those who indicated high consumption of alcohol exhibited a diminished overall survival. TCGA data analysis indicated that TLR9high tumors express a significant increase in some genes related with the oral cavity itself, inflammation and tumor promotion. Our analysis of tumor infiltrating leukocytes demonstrated that the major differences perceived in heavy alcohol consumers was the location of CD8+ T cells infiltrating the tumor, which showed lower numbers intratumorally. Our data suggest the existence of a pathogenic loop that involves alcohol consumption, high TLR9 expression and the immunophenotype, which might have a profound impact on the progression of the disease.
Case report: subacute thyroiditis after receiving SARS-CoV-2 vaccine, maybe not only adjuvants
Authors: Huang Yizhou , Chen Xingyu , Wang Qing , Lei Xiaowei , Zhang Lili
Published: August 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induced the new coronavirus disease 2019 (COVID-19) pandemic worldwide. SARS-CoV-2 vaccines are designed to control the transmission of the disease. However, post-vaccination subacute thyroiditis (SAT) also appears with increase vaccination rate. Three cases of SAT after SARS-CoV-2 vaccines are described in this study. We have reported the patients’ clinical symptoms, laboratory tests, and thyroid imaging. Tests for COVID-19 were all negative, and the patients did not report thyroid-related diseases, autoimmune diseases, or preceding upper respiratory system infections in their medical history. Three female patients showed neck pain on physical examination. The laboratory test results and imaging findings were consistent with the diagnostic criteria of SAT. The patients were carried out a standardized treatment according to their symptoms, and we closely followed up their response to the treatment. Clinicians must be aware of the possibility of SAT after receiving the vaccines and make timely therapy.
Operation analysis of the tele-critical care service demonstrates value delivery, service adaptation over time, and distress among tele-providers
Authors: Laudanski Krzysztof , Huffenberger Ann Marie , Scott Michael J. , Williams Maria , Wain Justin , Jablonski Juliane , Hanson C. William
Published: August 2022

Background

Our study addresses the gaps in knowledge of the characterizations of operations by remote tele-critical care medicine (tele-CCM) service providers interacting with the bedside team. The duration of engagements, the evolution of the tele-CCM service over time, and the distress during interactions with the bedside team have not been characterized systematically. These characteristics are critical for planning the deployment of teleICU services and preventing burnout among remote teleICU providers.

Methods

REDCap self-reported activity logs collected engagement duration, triggers (emergency button, tele-CCM software platform, autonomous algorithm, asymmetrical communication platform, phone), expediency, nature (proactive rounding, predetermined task, response to medical needs), communication modes, and acceptance. Seven hospitals with 16 ICUs were overseen between 9/2020 and 9/2021 by teams consisting of telemedicine medical doctors (eMD), telemedicine registered nurses (eRN), and telemedicine respiratory therapists (eRT).

Results

39,915 total engagements were registered. eMDs had a significantly higher percentage of emergent and urgent engagements (31.9%) vs. eRN (9.8%) or eRT (1.7%). The average tele-CCM intervention took 16.1 ± 10.39 min for eMD, 18.1 ± 16.23 for eRN, and 8.2 ± 4.98 min for eRT, significantly varied between engagement, and expediency, hospitals, and ICUs types. During the observation period, there was a shift in intervention triggers with an increase in autonomous algorithmic ARDS detection concomitant with predominant utilization of asynchronous communication, phone engagements, and the tele-CCM module of electronic medical records at the expense of the share of proactive rounding. eRT communicated more frequently with bedside staff (% MD = 37.8%; % RN = 36.8, % RT = 49.0%) but mostly with other eRTs. In contrast, the eMD communicated with all ICU stakeholders while the eRN communicated chiefly with other RN and house staff at the patient's bedside. The rate of distress reported by tele-CCM staff was 2% among all interactions, with the entity hospital being the dominant factor.

Conclusions

Delivery of tele-CCM services has to be tailored to the specific beneficiary of tele-CCM services to optimize care delivery and minimize distress. In addition, the duration of the average intervention must be considered while creating an efficient workflow.
Molecular characterisation of Acinetobacter baumannii isolates from bloodstream infections in a tertiary-level hospital in South Africa
Authors: Lowe Michelle , Singh-Moodley Ashika , Ismail Husna , Thomas Teena , Chibabhai Vindana , Nana Trusha , Lowman Warren , Ismail Arshad , Chan Wai Yin , Perovic Olga
Published: August 2022

Acinetobacter baumannii is an opportunistic pathogen and causes various infections in patients. This study aimed to describe the clinical, epidemiological and molecular characteristics of A. baumannii isolated from BCs in patients at a tertiary-level hospital in South Africa. Ninety-six isolates from bloodstream infections were collected. Clinical characteristics of patients were recorded from patient files. Organism identification and AST was performed using automated systems. PCR screening for the mcr-1 to mcr-5 genes was done. To infer genetic relatedness, a dendrogram was constructed using MALDI-TOF MS. All colistin-resistant isolates (n = 9) were selected for WGS. The patients were divided into three groups, infants (<1 year; n = 54), paediatrics (1–18 years; n = 6) and adults (≥19 years; n = 36) with a median age of 13 days, 1 and 41 years respectively. Of the 96 A. baumannii bacteraemia cases, 96.9% (93/96) were healthcare-associated. The crude mortality rate at 30 days was 52.2% (48/92). The majority of the isolates were multidrug-resistant (MDR). All isolates were PCR-negative for the mcr-1 to mcr-5 genes. The majority of the isolates belonged to cluster 1 (62/96) according to the MALDI-TOF MS dendrogram. Colistin resistance was confirmed in nine A. baumannii isolates (9.4%). The colistin-resistant isolates belonged to sequence type (ST) 1 (5/6) and ST2 (1/6). The majority of ST1 isolates showed low SNP diversity (≤4 SNPs). All the colistin-resistant isolates were resistant to carbapenems, exhibited an XDR phenotype and harboured the blaOXA–23 gene. The blaNDM gene was only detected in ST1 colistin-resistant isolates (n = 5). The lpsB gene was detected in all colistin-resistant isolates as well as various efflux pump genes belonging to the RND, the MFS and the SMR families. The lipooligosaccharide OCL1 was detected in all colistin-resistant ST1 and ST2 isolates and the capsular polysaccharide KL3 and KL17 were detected in ST2 and ST1 respectively. This study demonstrated a 9.4% prevalence of colistin-resistant ST1 and ST2 A. baumannii in BC isolates. The detection of the lpsB gene indicates a potential threat and requires close prospective monitoring.
The coat protein p25 from maize chlorotic mottle virus involved in symptom development and systemic movement of tobacco mosaic virus hybrids
Authors: Zhang Chao , Wang Di , Li Weimin , Zhang Baolong , Abdel-Fattah Ouf Gamal M. , Su Xiaofeng , Li Jun
Published: August 2022

Viral coat protein (CP) has numerous critical functions in plant infection, but little is known about p25, the CP of maize chlorotic mottle virus (MCMV; Machlomovirus), which causes severe yield losses in maize worldwide. Here, we investigated the roles of p25 in pathogenicity and systemic movement, as well as potential interactions with host plants, using a hybrid tobacco mosaic virus (TMV)-based expression system. Highly conserved protein p25 is predicted to contain a membrane-anchored nuclear localization signal (NLS) sequence and an extracellular sequence. In transgenic Nicotiana benthamiana plants containing the movement protein (MP) of TMV (TMV-MP), p25 induced severe symptoms, including dwarf and foliar necrosis, and was detected in inoculated and non-inoculated leaves. After the deletion of NLS from nuclear-located p25, the protein was found throughout the host cell, and plant stunting and starch granule deformity were reduced. Systemic movement and pathogenicity were significantly impaired when the C-terminal regions of p25 were absent. Using virus-induced gene silencing (VIGS), the transcript level of heat shock protein HSP90 was distinctly lower in host plants in association with the absence of leaf necrosis induced by TMV-p25. Our results revealed crucial roles for MCMV p25 in viral pathogenicity, long-distance movement, and interactions with N. benthamiana.
Antifungal susceptibility pattern of Candida isolated from cutaneous candidiasis patients in eastern Guangdong region: A retrospective study of the past 10 years
Authors: Bilal Hazrat , Hou Bing , Shafiq Muhammad , Chen Xinyu , Shahid Muhammad Akbar , Zeng Yuebin
Published: August 2022

Cutaneous candidiasis is one of the most prevalent mycotic infections caused by Candida species. The severity of infection mounts faster when the species shows antifungal resistance. In the current retrospective study, we aimed to analyze the occurrence, causes of cutaneous candidiasis, and antifungal susceptibility pattern of Candida isolates from Skin and Venereal Diseases Prevention and Control Hospital of Shantou, located in eastern Guangdong, China. The laboratory data of all patients (n = 3,113) suffering from various skin and venereal infections during January 2012 to December 2021 was analyzed through Excel and GraphPad prism. Our analysis indicate that cutaneous candidiasis was 22.29% (n = 694), of which 78.53% (n = 554) of patients were males and 21.47% (n = 149) of patients were females. The median age of patients with cutaneous candidiasis was 38-year [interquartile range (30–48)]. Most cases occurred in the adult age group (19–50  years). Regarding the species type, the Candida albicans were prominently detected (n = 664, 95.68%), while non-C. albicans were found only in 30 (4.32%) patients, which were C. glabrata (n = 18), C. krusei (n = 8), C. tropicalis (n = 3), and C. parapsilosis (n = 1). The C. albicans susceptibility rate for terbinafine, miconazole, voriconazole, itraconazole, fluconazole, ketoconazole, nystatin, 5-flucytosine and amphotericin B were 10.83, 29.32, 59.39, 78.53, 85.28, 87.75, 99.59, 99.41, and 100%, respectively. Finally, all C. glabrata isolates were found susceptible to all tested azole drugs with exception to miconazole against which 8.33% of isolates showed resistance. The findings of this study will help healthcare officials to establish better antifungal stewardship in the region.
It started with a Cys: Spontaneous cysteine modification during cryo-EM grid preparation
Authors: Klebl David P. , Wang Yiheng , Sobott Frank , Thompson Rebecca F. , Muench Stephen P.
Published: August 2022

Advances in single particle cryo-EM data collection and processing have seen a significant rise in its use. However, the influences of the environment generated through grid preparation, by for example interactions of proteins with the air-water interface are poorly understood and can be a major hurdle in structure determination by cryo-EM. Initial interactions of proteins with the air-water interface occur quickly and proteins can adopt preferred orientation or partially unfold within hundreds of milliseconds. It has also been shown previously that thin-film layers create hydroxyl radicals. To investigate the potential this might have in cryo-EM sample preparation, we studied two proteins, HSPD1, and beta-galactosidase, and show that cysteine residues are modified in a time-dependent manner. In the case of both HSPD1 and beta-galactosidase, this putative oxidation is linked to partial protein unfolding, as well as more subtle structural changes. We show these modifications can be alleviated through increasing the speed of grid preparation, the addition of DTT, or by sequestering away from the AWI using continuous support films. We speculate that the modification is oxidation by reactive oxygen species which are formed and act at the air-water interface. Finally, we show grid preparation on a millisecond timescale outruns cysteine modification, showing that the reaction timescale is in the range of 100s to 1,000s milliseconds and offering an alternative approach to prevent spontaneous cysteine modification and its consequences during cryo-EM grid preparation.
Neuronal ferroptosis after intracerebral hemorrhage
Authors: Ren Siying , Chen Yue , Wang Likun , Wu Guofeng
Published: August 2022

Intracerebral hemorrhage (ICH) is a devastating form of stroke with high rates of morbidity, mortality, and disability. It induces cell death that is responsible for the secondary brain injury (SBI). The underlying mechanism of SBI after ICH is still unclear, and whether it is related to iron overload is worthy to be discussed. Ferroptosis is an iron-dependent non-apoptotic modes of cell death and plays a particularly important role in the occurrence and progression of ICH. Many ICH-induced regulators and signalling pathways of ferroptosis have been reported as promising targets for treating ICH. In this article, we review the definition, characteristics, and inhibition methods of neuronal ferroptosis caused by iron deposition after ICH, and review the biomarkers for ferroptosis.
HSP70 and their co-chaperones in the human malaria parasite P. falciparum and their potential as drug targets
Authors: Barth Julian , Schach Tim , Przyborski Jude M.
Published: August 2022

As part of their life-cycle, malaria parasites undergo rapid cell multiplication and division, with one parasite giving rise to over 20 new parasites within the course of 48 h. To support this, the parasite has an extremely high metabolic rate and level of protein biosynthesis. Underpinning these activities, the parasite encodes a number of chaperone/heat shock proteins, belonging to various families. Research over the past decade has revealed that these proteins are involved in a number of essential processes within the parasite, or within the infected host cell. Due to this, these proteins are now being viewed as potential targets for drug development, and we have begun to characterize their properties in more detail. In this article we summarize the current state of knowledge about one particular chaperone family, that of the HSP70, and highlight their importance, function, and potential co-chaperone interactions. This is then discussed with regard to the suitability of these proteins and interactions for drug development.
Exendin-4 alleviates β-Amyloid peptide toxicity via DAF-16 in a Caenorhabditis elegans model of Alzheimer's disease
Authors: Song Xiangwei , Sun Yingqi , Wang Zhun , Su Yingying , Wang Yangkun , Wang Xueli
Published: August 2022

Epidemiological analyses indicate that type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer's disease (AD). They share common pathophysiological mechanisms. Thus, it has been increasingly suggested that several anti-T2DM drugs may have therapeutic potential in AD. Exendin-4, as a glucagon-like peptide-1 (GLP-1) receptor agonist, is an approved drug used to treat T2DM. In this research, the neuroprotective effect of Exendin-4 was investigated for the first time using transgenic Caenorhabditis elegans. Our results demonstrated that Exendin-4 attenuated the amyloid-β (1-42) (Aβ1-42) toxicity via multiple mechanisms, such as depressing its expression on protein and mRNA and reducing Aβ (1-42) accumulation. Exendin-4 at 0.5 mg/ml had been shown to extend life by 34.39% in CL4176 and delay the onset of paralysis in CL4176 and CL2006 which were increased by 8.18 and 8.02%, respectively. With the treatment of Exendin-4, the nuclear translocation of DAF-16 in the transgenic nematode TJ356 was enhanced. Superoxide dismutase-3 (SOD-3), as a downstream target gene regulated by DAF-16, was upregulated on mRNA level and activity. The reactive oxygen species (ROS) level was decreased. In contrast, we observed that the ability of Exendin-4 to regulate SOD was decreased in CL4176 worms with the DAF-16 gene silenced. The activity of SOD and the mRNA level of sod-3 were downregulated by 30.45 and 43.13%, respectively. Taken together, Exendin-4 attenuated Aβ (1-42) toxicity in the C. elegans model of AD via decreasing the expression and the accumulation of Aβ (1-42). Exendin-4 exhibited the ability of antioxidant stress through DAF-16. With continuous research, Exendin-4 would become a potential therapeutic strategy for treating AD.
Effects of vibration training on motor and non-motor symptoms for patients with multiple sclerosis: A systematic review and meta-analysis
Authors: Zhang Yang , Xu Peng , Deng Yu , Duan Wenxiu , Cui Juncai , Ni Chaomin , Wu Ming
Published: August 2022

Background

Vibration therapy is one of the rehabilitation programs that may be effective in treating both motor and non-motor symptoms in Multiple Sclerosis patients. We conducted a comprehensive systematic review and meta-analysis to assess the effects of vibration therapy on motor and non-motor symptoms (functional mobility, balance, walking endurance, gait speed, fatigue, and quality of life) of this population.

Methods

A systematic search of PubMed, Embase, the Cochrane Library, Web of Science, Physiotherapy Evidence Database, Scopus, Google Search Engine, and the China National Knowledge Infrastructure (CNKI). Two reviewers independently assessed the study quality.

Results

Fourteen studies with 393 participants were finally included in the meta-analysis. The pooled results showed that vibration therapy had a significant advantage over the control intervention in improving balance function [mean difference (MD) = 2.04, 95% confidence interval (CI): 0.24–3.84, P = 0.03], and walking endurance (SMD = 0.34, 95% CI: 0.07–0.61, P = 0.01). Meanwhile, the degree of disability subgroup analysis revealed that the Expanded Disability Status Scale (EDSS) score (3.5–6) significantly improved functional mobility (MD: −1.18, 95% CI: −2.09 to 0.28, P = 0.01) and balance function (MD: 3.04, 95% CI: 0.49–5.59, P = 0.02) compared with the control group, and the EDSS (0–3.5) were more beneficial in walking endurance. The duration subgroup analysis indicated a significant difference in the effect of the duration (<4 weeks) on enhancing walking endurance (SMD: 0.46, 95% CI: 0.04–0.87, P = 0.03). However, no significant improvement was found in functional mobility, gait speed, fatigue, and quality of life.

Conclusion

Vibration therapy may improve balance function and walking endurance, and the degree of disability and duration of intervention may affect outcomes. The evidence for the effects of vibration therapy on functional mobility, gait speed, fatigue, and quality of life remains unclear. More trials with rigorous study designs and a larger sample size are necessary to provide this evidence.

Systematic Review Registration

PROSPERO, https://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42022326852.
Correlation between neutrophil/lymphocyte ratio and cognitive impairment in cerebral small vessel disease patients: A retrospective study
Authors: Hou Lan , Zhang Shuhan , Qi Dandan , Jia Tongle , Wang Huan , Zhang Wei , Wei Shuyan , Xue Conglong , Wang Pei
Published: August 2022

Background and objective

The blood neutrophil/lymphocyte ratio (NLR) is an objective and convenient parameter of systemic inflammation. Elevated NLR is associated with an increased risk of mild cognitive impairment (CI) in the elderly. However, few data are available on the impact of the NLR on CI in patients with cerebral small vessel disease (CSVD).

Methods

A total of 66 CSVD subjects with CI and 81 CSVD subjects without CI were evaluated in this study. Clinical, laboratory, radiological, and cognitive parameters were collected. The NLR was obtained with the absolute neutrophil count being divided by the absolute lymphocyte count in fasting blood samples. Logistic regression analysis was performed to evaluate the factors associated with CI. Receiver operating characteristic curves were illustrated to predict factors associated with CI in patients with CSVD.

Results

The NLR of the CI group was significantly higher than that of subjects without CI (2.59 vs. 2.21, P = 0.003). In multivariate analysis, NLR was positively correlated to the CI (OR: 1.43, 95% CI: 1.05–1.96, P = 0.024). It was suggested that the optimum NLR cutoff point for CI was 1.89 with 69.7% sensitivity and 59.3% specificity. Subjects with NLR ≥ 1.89 showed higher possibilities of CI compared to those with NLR < 1.89 (OR: 3.38, 95% CI: 1.62–7.07).

Conclusions

Correlations were found between NLR and CI. Patients with CSVD who have higher NLR might have an increased risk of CI.
Tutorials in population neuroimaging: Using epidemiology in neuroimaging research
Authors: Godina Sara , Jacob Mini E. , Ganguli Mary
Published: August 2022

Epidemiology is the foundation of all public health research and practice. Epidemiology confers many important uses for the advancement of neuroimaging research. Epidemiology serves as a framework to organize pieces of data and guide critical thinking in the research process from the early stages of study design to the end goal of reaching appropriate inferences. Epidemiology accounts for the profound heterogeneity in populations, thoroughly describes study samples, and identifies consequential threats to study validity. Finally, epidemiology is a discovery tool that can lead researchers to uncover new risk factors, disease states, and subpopulations. The neuroimaging investigator with a grasp of the principles of epidemiology is in a unique position to undertake valid clinical epidemiology and etiological research.
Brain fog in neuropathic postural tachycardia syndrome may be associated with autonomic hyperarousal and improves after water drinking
Authors: Rodriguez Belén , Hochstrasser Annie , Eugster Philippe J. , Grouzmann Eric , Müri René M. , Z’Graggen Werner J.
Published: August 2022

Background

Brain fog is a common and highly disturbing symptom for patients with neuropathic postural tachycardia syndrome (POTS). Cognitive deficits have been measured exclusively in the upright body position and mainly comprised impairments of higher cognitive functions. The cause of brain fog is still unclear today. This study aimed to investigate whether increased autonomic activation might be an underlying mechanism for the occurrence of brain fog in neuropathic POTS. We therefore investigated cognitive function in patients with neuropathic POTS and a healthy control group depending on body position and in relation to catecholamine release as a sensitive indicator of acute stress. The second aim was to test the effect of water intake on cardiovascular regulation, orthostatic symptoms, cognitive function and catecholamine release.

Methods

Thirteen patients with neuropathic POTS and 15 healthy control subjects were included. All participants completed a total of four rounds of cognitive testing: two before and two after the intake of 500 ml still water, each first in the supine position and then during head-up tilt. At the end of each cognitive test, a blood sample was collected for determination of plasma catecholamines. After each head-up tilt phase participants were asked to rate their current symptoms on a visual analogue scale.

Results

Working memory performance in the upright body position was impaired in patients, which was associated with self-reported symptom severity. Patients had elevated plasma norepinephrine independent of body position and water intake that increased excessively in the upright body position. The excessive increase of plasma norepinephrine was related to heart rate and symptom severity. Water intake in patients decreased norepinephrine concentrations and heart rate, and improved symptoms as well as cognitive performance.

Conclusion

Brain fog and symptom severity in neuropathic POTS are paralleled by an excessive norepinephrine secretion. Bolus water drinking down-regulates norepinephrine secretion and improves general symptom severity including brain fog.