bluuebunny/crossref_metadata_2025 huggingface dataset:
Methodology for Evaluation of Contributions of Ostwald Ripening and Particle Agglomeration to Growth of Catalyst Particles in PEM Fuel Cells
Authors: Kregar A. , Kravos A. , Katrašnik T.
Published: July 2020

The degradation of the catalyst layer represents one of the main limiting factors in a wider adoption of fuel cells. The identification of the contributions of different mechanisms of catalyst degradation, namely the Ostwald ripening and particle agglomeration, is an important step in the development of mitigation strategies for increasing fuel cell reliability and prolonging its life time.

In this paper, the degradation phenomena in high temperature polymer electrolyte membrane fuel cell (HT‐PEMFC) are analyzed using a physically‐based model of fuel cell operation and catalyst degradation, describing carbon corrosion, platinum dissolution and consequent growth of catalyst particles. The model results indicate significantly different time dependence of catalyst particle growth resulting from different mechanisms: linear growth in the case of particle agglomeration and root‐like time dependence for the Ostwald ripening.

Based on these results, a new analytic method is proposed, performed by the fitting of a test root‐function to the time profile of the particle size growth and using best‐fit parameters to identify the prevailing growth mechanism. Using this method on a particle growth time trace deduced from in situ cyclic voltammetry measurement during HT‐PEMFC degradation, we are able to identify the agglomeration as the main mechanism of catalyst particle grow.
SNP‐HLA Reference Consortium (SHLARC): HLA and SNP data sharing for promoting MHC‐centric analyses in genomics
Authors: Vince Nicolas , Douillard Venceslas , Geffard Estelle , Meyer Diogo , Castelli Erick C. , Mack Steven J. , Limou Sophie , Gourraud Pierre‐Antoine
Published: July 2020

Genome‐wide associations studies have repeatedly identified the major histocompatibility complex genomic region (6p21.3) as key in immune pathologies. Researchers have also aimed to extend the biological interpretation of associations by focusing directly on human leukocyte antigen (HLA) polymorphisms and their combination as haplotypes. To circumvent the effort and high costs of HLA typing, statistical solutions have been developed to infer HLA alleles from single‐nucleotide polymorphism (SNP) genotyping data. Though HLA imputation methods have been developed, no unified effort has yet been undertaken to share large and diverse imputation models, or to improve methods. By training the HIBAG software on SNP + HLA data generated by the Consortium on Asthma among African‐ancestry Populations in the Americas (CAAPA) to create reference panels, we highlighted the importance of (a) the number of individuals in reference panels, with a twofold increase in accuracy (from 10 to 100 individuals) and (b) the number of SNPs, with a 1.5‐fold increase in accuracy (from 500 to 24,504 SNPs). Results showed improved accuracy with CAAPA compared to the African American models available in HIBAG, highlighting the need for precise population‐matching. The SNP‐HLA Reference Consortium is an international endeavor to gather data, enhance HLA imputation and broaden access to highly accurate imputation models for the immunogenomics community.
Ex vivo mesoscopic diffusion MRI correlates with seizure frequency in patients with uncontrolled mesial temporal lobe epilepsy
Authors: Ke Justin , Foley Lesley M. , Hitchens T. Kevin , Richardson R. Mark , Modo Michel
Published: July 2020

The role of hippocampal connectivity in mesial temporal lobe epilepsy (mTLE) remains poorly understood. The use of ex vivo hippocampal samples excised from patients with mTLE affords mesoscale diffusion magnetic resonance imaging (MRI) to identify individual cell layers, such as the pyramidal (PCL) and granule cell layers (GCL), which are thought to be impacted by seizure activity. Diffusion tensor imaging (DTI) of control (n = 3) and mTLE (n = 7) hippocampi on an 11.7 T MRI scanner allowed us to reveal intra‐hippocampal connectivity and evaluate how epilepsy affected mean (MD), axial (AD), and radial diffusivity (RD), as well as fractional anisotropy (FA). Regional measurements indicated a volume loss in the PCL of the cornu ammonis (CA) 1 subfield in mTLE patients compared to controls, which provided anatomical context. Diffusion measurements, as well as streamline density, were generally higher in mTLE patients compared to controls, potentially reflecting differences due to tissue fixation. mTLE measurements were more variable than controls. This variability was associated with disease severity, as indicated by a strong correlation (r = 0.87) between FA in the stratum radiatum and the frequency of seizures in patients. MD and RD of the PCL in subfields CA3 and CA4 also correlated strongly with disease severity. No correlation of MR measures with disease duration was evident. These results reveal the potential of mesoscale diffusion MRI to examine layer‐specific diffusion changes and connectivity to determine how these relate to clinical measures. Improving the visualization of intra‐hippocampal connectivity will advance the development of novel hypotheses about seizure networks.
Hepatocellular Carcinoma in Acute Hepatic Porphyrias: Results from the Longitudinal Study of the U.S. Porphyrias Consortium
Authors: Saberi Behnam , Naik Hetanshi , Overbey Jessica R. , Erwin Angelika L. , Anderson Karl E. , Bissell D. Montgomery , Bonkovsky Herbert L. , Phillips John D. , Wang Bruce , K.Singal Ashwani , M.McGuire Brendan , Desnick Robert J. , Balwani Manisha
Published: July 2020

Background and Aims

The risk for hepatocellular carcinoma (HCC) is increased in acute hepatic porphyrias (AHP). The aim of this study was to explore the clinicopathologic characteristics, outcomes, and frequency of HCC in patients with AHP in the United States.

Approach and Results

This cross‐sectional analysis evaluated patients with HCC in a multicenter, longitudinal study of AHP. Among 327 patients with AHP, 5 (1.5%) were diagnosed with HCC. Of the 5 HCC cases, 4 had acute intermittent porphyria and 1 had variegate porphyria, confirmed by biochemical and/or genetic testing. All patients were white females, with a median age of 27 years (range 21‐75) at diagnosis. The median age at HCC diagnosis was 69 years (range 61‐74). AHP was asymptomatic in 2 patients; 2 reported sporadic attacks; and 1 reported recurrent attacks (>4 attacks/year). All patients had a single HCC lesion on liver imaging that was 1.8‐6.5 centimeters in diameter. Serum alpha fetoprotein levels were below 10 ng/mL in all 4 patients with available results. Four patients underwent liver resection, and 1 was treated with radioembolization. No significant inflammation or fibrosis was found in adjacent liver tissues of 3 patients who underwent liver resection. Two patients developed recurrence of HCC at 22 and 26 months following liver resection. All patients are alive with survival times from HCC diagnosis ranging from 26‐153 months.

Conclusion

In this U.S. study, 1.5% of patients with AHP had HCC. HCC in AHP occurred in the absence of cirrhosis, which contrasts with other chronic liver diseases. Patients with AHP, regardless of clinical attacks, should be screened for HCC, beginning at age 50. The pathogenesis of hepatocarcinogenesis in AHP is unknown and needs further investigation.
Elevated Liver Biochemistries in Hospitalized Chinese Patients With Severe COVID‐19: Systematic Review and Meta‐analysis
Authors: Kovalic Alexander J. , Huang Glen , Thuluvath Paul J. , Satapathy Sanjaya K.
Published: July 2020

Background and Aims

Several recent studies have reported an abnormal liver chemistry profile among patients with coronavirus disease 2019 (COVID‐19), although its clinical significance remains unknown.

Approach and Results

This systematic review and meta‐analysis identified six studies of 586 patients delineating liver chemistries among patients with severe/critical illness versus mild cases of COVID‐19 infection. Patients with severe/critical illness with COVID‐19 infection have increased prevalence of coronary artery disease, cerebrovascular disease, and chronic obstructive pulmonary disease as compared with mild cases. A significant association between severe/critical COVID‐19 infections with elevations in aspartate aminotransferase (pooled mean difference [MD], 11.70 U/L; 95% confidence interval [CI], 2.97, 20.43; P = 0.009), elevated total bilirubin (pooled MD, 0.14 mg/dL; 95% CI, 0.06, 0.22; P = 0.0005), and decreased albumin (pooled MD, −0.68 g/L; 95% CI, −0.81, −0.55; P < 0.00001) was noted. There was also a trend toward elevated alanine aminotransferase levels among these severe cases (pooled MD, 8.84 U/L; 95% CI, −2.28, 19.97; P = 0.12); however, this did not reach statistical significance. More severe/critically ill cases were associated with leukocytosis, neutrophilia, lymphopenia, elevated creatinine kinase, elevated lactate dehydrogenase (LDH), and elevated prothrombin time (PT).

Conclusions

Comorbidities, including coronary artery disease, cerebrovascular disease and chronic obstructive pulmonary disease, are more prevalent in hospitalized Chinese patients with severe/critical illness from COVID‐19, and these patients are more likely to manifest with abnormal liver chemistries. Further prospective studies are crucial to understand the pathophysiologic mechanisms underlying the hepatic manifestations of the novel COVID‐19 infection and its clinical significance.
Liver Chemistries in Patients With COVID-19 Who Were Discharged Alive or Died: A Meta-analysis
Authors: Xing Qing-Qing , Dong Xuan , Ren Yan-Dan , Chen Wei-Ming , Zeng Dan-Yi , Cai Yan-Yan , Hong Mei-Zhu , Pan Jin-Shui
Published: July 2020

Although abnormal liver chemistries are linked to a higher risk of coronavirus disease 2019 (COVID-19)–related death, liver manifestations may be diverse and even confusing. Thus, we performed a meta-analysis of published liver manifestations and described the liver damage in patients with COVID-19 who died or discharged alive. We searched PubMed, Google Scholar, medRxiv, bioRxiv, the Cochrane Library, Embase, and three Chinese electronic databases through April 22, 2020. We analyzed pooled data on liver chemistries stratified by the main clinical outcome of COVID-19, using a fixed or random-effects model. In our meta-analysis of 19 studies, which included a total of 4,103 patients, the pooled mean alanine aminotransferase and aspartate aminotransferase levels were, respectively, 31.7 IU/L and 51.0 IU/L in the patients with COVID-19 who died and 27.7 IU/L and 32.9 IU/L in those discharged alive (both P < 0.0001). Compared with the patients discharged alive, those who died tended to have lower albumin levels but longer prothrombin time and higher international normalized ratio. Conclusion: In this meta-analysis, according to the main clinical outcome of COVID-19, we comprehensively describe three patterns of liver impairment related to COVID-19: hepatocellular injury, cholestasis, and hepatocellular disfunction. The patients who died from COVID-19 tended to have different liver chemistries from those discharged alive. Special caution should be given to the patients with a relatively higher index of liver chemistries.
Health literacy, digital health literacy and the implementation of digital health technologies in cancer care: the need for a strategic approach
Authors: Kemp Emma , Trigg Joshua , Beatty Lisa , Christensen Chris , Dhillon Haryana M. , Maeder Anthony , Williams Patricia A. H. , Koczwara Bogda
Published: July 2020

Issue addressed

Digital health technologies can potentially reduce health disparities in cancer care. However, the benefits of digital health technology depend partly on users’ digital health literacy, that is, “capabilities and resources required for individuals to use and benefit from digital health resources,” which combines health and digital literacy. We examined issues for digital health technology implementation in cancer care regarding digital health literacy, via stakeholder consultation.

Methods

Consumers, health care professionals, researchers, developers, nongovernment and government/policy stakeholders (N = 51) participated in focus groups/interviews discussing barriers, enablers, needs and opportunities for digital health implementation in cancer care. Researchers applied framework analysis to identify themes of digital health literacy in the context of disparity and inclusion.

Results

Limited digital and traditional health literacy were identified as barriers to digital technology engagement, with a range of difficulties identified for older, younger and socio‐economically or geographically disadvantaged groups. Digital health technology was a potential enabler of health care access and literacy, affording opportunities to increase reach and engagement. Education combined with targeted design and implementation were identified means of addressing health and digital literacy to effectively implement digital health in cancer care.

Conclusions

Implementing digital health in cancer care must address the variability of digital health literacy in recipients, including groups living with disadvantage and older and younger people, in order to be effective.

So what?

If cancer outcome disparity is to be reduced via digital health technologies, they must be implemented strategically to address digital health literacy needs. Health policy should reflect this approach.
Predictors of uptake of general and tailored services to improve employee health and wellbeing
Authors: Talati Zenobia , Grapes Carly , Davey Emily , Shilton Trevor , Pettigrew Simone
Published: July 2020

Issue addressed

Healthy workplace programs can improve employee health and wellbeing. However, there is little research on how they are adopted by organisations. The study aimed to investigate uptake and predictors of service use amongst organisations utilising a comprehensive government‐funded healthy workplace program.

Methods

Employees taking part in the Healthier Workplaces WA program can access general services (ie, basic information on workplace health and wellbeing) and tailored services (ie, personalised support on implementing changes). A sample of 358 eligible program participants from 204 organisations completed a service experience survey 6 months after engaging with any service. Predictors of service use were analysed using a Kruskal‐Wallis H test.

Results

On average, respondents accessed 3.4 (out of 7) services. General services were accessed more frequently than tailored services. The Kruskal‐Wallis H test showed that respondents working in Human Resources or Health and Safety and those from large organisations were more likely to access a greater range of services compared to employees in other roles and those working in small to medium organisations. Additionally, greater perceived support from management or co‐workers was associated with greater service use.

Conclusions

Respondents reported accessing general services more than tailored services. Service use was greater amongst those who perceived greater support from their managers and/or co‐workers, those who worked in large organisations and those who worked in HR/OHS.

So what?

These findings are informative for practitioners assisting organisations to improve health and wellbeing initiatives and service providers interested in increasing service uptake. A mix of general and tailored services is likely to be useful in building employees’ capacity to increase health and wellbeing in their workplace. Support from management and co‐workers is an important facilitator, and small organisations may require more focussed targeting due to the lower tendency to engage with these programs and increased benefits.
Progress in organic semiconducting materials with high thermal stability for organic light‐emitting devices
Authors: Lee Sooyong , Kim Hwajeong , Kim Youngkyoo
Published: July 2020

Organic light‐emitting devices (OLEDs) have been extensively studied over the past three decades and are still attracting attention owing to their potential use in flexible and foldable displays. To achieve highly durable OLED displays for flexible devices, constitutive OLED materials need to be stable in various environments, including those with thermally and mechanically severe conditions. To this end, the present review aims to investigate the progress of OLED material research over the past two decades with respect to thermal stability. The literature survey is first conducted using the keyword “OLEDs” and then narrowed down to “high thermal stability materials for OLEDs.” The number of search results indicates that creating OLED materials with high thermal stability is a widely studied topic in the field of OLED research and has undergone an average growth rate of approximately 15% per year over the past two decades. In this review, the OLED materials used as core layers (ie, the hole injection and transport layers, emission layers, and electron injection and transport layers) are thoroughly analyzed, and the best representative materials are discussed in detail by summarizing their major thermal and electronic characteristics. Finally, several previous reports on flexible and foldable OLED displays are analyzed to determine the importance of the stability of their constitutive materials.

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Stimuli‐responsive photofunctional materials for green and security printing
Authors: Ma Yun , Yu Yaxin , Li Jiangang , Liu Shujuan , Huang Wei , Zhao Qiang
Published: July 2020

Information recording on paper has always been the most important approach to keep records of human activity and to spread civilization. With the progress of science and technology, paper with different functions should be exploited to conform to the increasing demands in various scenarios. In one aspect, traditional paper can only be used once, and using large amounts of paper causes deforestation, additional solid waste treatment, environmental pollution, and high energy consumption. Consequently, the development of rewritable paper that is environment‐friendly, low cost, and can save resources is significant for green printing. In the other aspect, information leakage brings security issues, which may lead to severe consequences, such as war outbreak, economic loss, social problems, and so on. Therefore, the development of security printing has also attracted wide interests. Stimuli‐responsive photofunctional materials that have reversible variations in absorption or emission in response to changes in the external environmental have a great potential for the achievement of green and security printing. To date, much progress has been made in these research areas. This paper lists different smart materials that respond to various external stimuli, such as light, water, pH, heat, and metal ions, and summarizes the recent advances towards green and security printing. Also, we discuss the current challenges and future directions in this rapidly growing research field. It is expected that this review article will stimulate and guide future studies for the advanced green and security printing.

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What Constitutes Community? Ethnographic Perspectives on Adolescent and Adult Literacy Practice
Authors: Wargo Jon M. , Oliveira Gabrielle
Published: July 2020

Authors featured in this department share anthropological perspectives and qualitative insights to redefine community in adolescent and adult literacy practice.
Effects of acetyl L‐carnitine on zebrafish embryos: Phenotypic and gene expression studies
Authors: Gu Qiang , Ali Syed F. , Kanungo Jyotshna
Published: July 2020

Acetyl L‐carnitine (ALCAR), a dietary supplement and an antioxidant, plays a vital role in the bioenergetic process that produces ATP. Although there are reports on antioxidant toxicity, there is no information on the potential toxicity of ALCAR. Here, using zebrafish embryos, we explored whether ALCAR modulated ATP synthesis, generation of reactive oxygen species (ROS) and expression of specific genes related to major signaling pathways that control metabolism, growth, differentiation, apoptosis and oxidative stress. First, we show that ALCAR elicits a physiologic response, as ATP levels increased after ALCAR treatment. Simultaneously, an increase in the expression of ROS, a by‐product of ATP synthesis, was observed in the ALCAR‐treated embryos. Consistent with higher ROS expression, the level of cysteine, a precursor of glutathione, was significantly reduced. ALCAR did not have any drastic effect on overall development and heart rate. Polymerase chain reaction‐based gene expression array analyses showed no significant change in the expression of 83 genes related to 10 major signaling pathways including: the transforming growth factor β (TGFβ), Wingless and Int‐1 (Wnt), nuclear factor κ‐light‐chain‐enhancer of activated B cells (NF‐κB), Janus kinase/signal transducers and activators of transcription (JAK/STAT), p53, Notch, Hedgehog, Peroxisome proliferator‐activated receptor (PPAR), oxidative stress, and hypoxia pathways. Our results show that the expression of 83 genes related to these major signaling pathways did not change significantly.
Modulation of adipocyte size and fat pad weight via resveratrol releasing scaffolds implanted into the epididymal adipose tissue
Authors: Murphy Kendall P. , Hendley Michael A. , Patterson Alexandra T. , Hall Hayley E. , Carter Griffin J. , Isely Christopher , Gower R. Michael
Published: July 2020

Lipid overload of the adipose tissue, which can be caused by overnutrition, underlies metabolic disease. We hypothesized that increasing the energy demand of adipose tissue is a promising strategy to combat excessive lipid accumulation. Resveratrol, a natural polyphenol, activates lipid catabolism in fat tissue; however, its clinical success is hindered by poor bioavailability. Here, we implanted resveratrol releasing poly(lactide‐co‐glycolide) scaffolds into epididymal fat to overcome its poor bioavailability with the goal of enhancing local lipid catabolism. In lean mice, resveratrol scaffolds decreased adipocyte size relative to scaffolds with no drug, a response that correlated with AMP kinase activation. Immunohistochemistry indicated that macrophages and multinucleated giant cells within the scaffold expressed carnitine palmitoyltransferase 1 (CPT1) at higher levels than other cells in the adipose tissue. Furthermore, resveratrol increased CPT1 levels in cultured macrophages. Taken together, we propose that resveratrol scaffolds decrease adipocyte size because resveratrol increases lipid utilization in scaffold‐infiltrating immune cells, possibly through elevating CPT1 levels or activity. In a follow‐up study, mice that received resveratrol scaffolds 28‐day prior to a high‐fat diet exhibited decreased weight gain, adipose tissue expansion, and adipocyte hypertrophy compared to mice with control scaffolds. Notably, this scaffold‐based strategy required a single resveratrol administration compared to the daily regiment generally needed for oral administration. These results indicate that localized delivery of metabolism modulating agents to the adipose tissue may overcome issues with bioavailability and that the role of biomaterials should be further investigated in this therapeutic strategy for metabolic disease.
Fluorescent multiplexing of 3D spheroids: Analysis of biomarkers using automated immunohistochemistry staining platform and multispectral imaging
Authors: Bhaumik Srabani , Boyer Jean , Banerjee Chaitali , Clark Samantha , Sebastiao Noemi , Vela Elizabeth , Towne Penny
Published: July 2020

In preclinical cancer studies, three‐dimensional (3D) cell spheroids and aggregates are preferred over monolayer cell cultures due to their architectural and functional similarity to solid tumors. We performed a proof‐of‐concept study to generate physiologically relevant and predictive preclinical models using non–small cell lung adenocarcinoma, and colon and colorectal adenocarcinoma cell line‐derived 3D spheroids and aggregates. Distinct panels were designed to determine the expression profiles of frequently studied biomarkers of the two cancer subtypes. The lung adenocarcinoma panel included ALK, EGFR, TTF‐1, and CK7 biomarkers, and the colon and colorectal adenocarcinoma panel included BRAF V600E, MSH2, MSH6, and CK20. Recent advances in immunofluorescence (IF) multiplexing and imaging technology enable simultaneous detection and quantification of multiple biomarkers on a single slide. In this study, we performed IF staining of multiple biomarkers per section on formalin‐fixed paraffin‐embedded 3D spheroids and aggregates. We optimized protocol parameters for automated IF and demonstrated staining concordance with automated chromogenic immunohistochemistry performed with validated protocols. Next, post‐acquisition spectral unmixing of the captured fluorescent signals were utilized to delineate four differently stained biomarkers within a single multiplex IF image, followed by automated quantification of the expressed markers. This workflow has the potential to be adapted to preclinical high‐throughput screening and drug efficacy studies utilizing 3D spheroids from cancer cell lines and patient‐derived organoids. The process allows for cost, time, and resource savings through concurrent staining of several biomarkers on a single slide, the ability to study the interactions of multiple expressed proteins within a single region of interest, and enable quantitative assessment of biomarkers in cancer cells.
Predicting experimental electrophilicities from quantum and topological descriptors: A machine learning approach
Authors: Hoffmann Guillaume , Balcilar Muhammet , Tognetti Vincent , Héroux Pierre , Gaüzère Benoît , Adam Sébastien , Joubert Laurent
Published: July 2020

In this paper, we assess the ability of various machine learning methods, either linear or non‐linear, to efficiently predict Mayr's experimental scale for electrophilicity. To this aim, molecular and atomic descriptors rooted in conceptual density functional theory and in the quantum theory of atoms‐in‐molecules as well as topological features defined within graph theory were evaluated for a large set of molecules widely used in organic chemistry. State‐of‐the‐art regression tools belonging to the support vector machines family and decision tree models were in particular considered and implemented. They afforded a promising predictive model, validating the use of such methodologies for the study of chemical reactivity.
Peripheral blood cell count ratios are predictive biomarkers of clinical response and prognosis for non‐surgical esophageal squamous cell carcinoma patients treated with radiotherapy
Authors: Zhi Xiaohui , Jiang Kan , Shen Yue , Su Xinyu , Wang Ke , Ma Yuanyuan , Zhou Liqing
Published: July 2020

Background

Peripheral blood cell count ratios, including the neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and lymphocyte‐to‐monocyte ratio (LMR), have been reported to be prognostic factors in many malignancies as markers of inflammation and immune status. The aim of this study was to determine whether NLR, PLR, or LMR can be clinical response and prognostic biomarkers of non‐surgical esophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy.

Methods

193 non‐surgical ESCC patients who underwent radiotherapy were retrospectively analyzed. The peripheral blood cell count ratios were obtained before, during (weekly) and at the end of the treatment. Then, we compared the subsequent results with the corresponding pretreatment values and computed the rates of change, which were defined as cNLR, cPLR, and cLMR. Univariate and multivariate Cox regression analyses were used for overall survival (OS). Ordinal logistic regression was used to analyze the clinical response.

Results

In multivariate analysis, cNLR at week 4(P = .026) and week 5(P = .025) during radiotherapy were significantly associated with OS, along with BMI, tumor stage, tumor length, tumor location, and grade of adverse events. Besides, BMI, tumor stage, tumor length, adverse event grade, cNLR at week 4(P = .044) and week 5(P = .013), and cPLR at week 4(P = .034) and week 5(P = .015) were significantly associated with the clinical response in the multivariate logistic regression analysis.

Conclusions

The cNLR at weeks 4 and 5 was negatively correlated with the OS and clinical response of non‐surgical ESCC patients treated with radiotherapy. The elevated cPLR at weeks 4 and 5 was only related to poor clinical response.
The mRNA expression of visfatin and lipocalin‐2 in peripheral blood mononuclear cells from patients with pulmonary tuberculosis
Authors: Li Hong‐Miao , Huang Qian , Chen Shuang‐Shuang , Zhang Gen‐You , Shi Si‐Jiu , Hua Wang  , Li Ye , Zhang Tian‐Ping
Published: July 2020

Background

In this study, we aimed to assess mRNA expressions of visfatin and lipocalin‐2 in peripheral blood mononuclear cells (PBMCs) from patients with pulmonary tuberculosis (PTB).

Methods

Overall, 79 PTB patients and 71 healthy controls were enrolled. In PBMCs, mRNA expressions of visfatin and lipocalin‐2 were detected using real‐time quantitative polymerase chain reaction (qRT‐PCR), and the diagnostic value of these adipokine mRNAs in PTB patients was calculated through receiver operating characteristic (ROC) analysis.

Results

In PBMCs from PTB patients, the visfatin mRNA level was significantly higher than in healthy controls (P < .001), with no significant association between the lipocalin‐2 mRNA level and PTB patients (P = .933). In PTB patients, lipocalin‐2 mRNA expression positively correlated with the erythrocyte sedimentation rate (ESR) (P = .010). However, the visfatin mRNA level was not associated with any major clinical and laboratory parameter in PTB patients. The ROC curve demonstrated that visfatin could help distinguish PTB patients from healthy controls, with an optimal cutoff value of 0.645 and a corresponding sensitivity of 79.7%.

Conclusions

The altered visfatin mRNA expression indicated that this adipokine might play a role in PTB and could be an auxiliary biomarker for PTB diagnosis.
Holotomographic microscopy: A new approach to detect apoptotic cell features
Authors: Salucci Sara , Battistelli Michela , Burattini Sabrina , Sbrana Francesca , Falcieri Elisabetta
Published: July 2020

Holotomographic (HT) microscopy, combines two techniques, holography and tomography, and, in this way, it allows to quantitatively and noninvasively investigate cells and thin tissue slices, by obtaining three‐dimensional (3D) images and by monitoring inner morphological changes. HT has indeed two significant advantages: it is label‐free and low‐energy light passes through the specimen with minimal perturbation. Using quantitative phase imaging with optical diffraction tomography, it can produce 3D images by measuring the refraction index (RI). Therefore, based on RI values, HT can provide structural and chemical cell information, such as dry mass values, morphological changes, or cellular membrane dynamics. In this study, suspended and adherent culture cells have been processed for HT analyses. Some of them have been treated with known apoptotic drugs or pro‐oxidant agents and cell response has been investigated both by conventional microscopic approaches and by HT. The ultrastructural and fluorescence images have been compared to those obtained by HT and their congruence has been discussed, with particular attention to apoptotic cell death and on correlated plasma membrane changes. HT appears a valid approach to further characterize well‐known apoptotic features such as cell blebbing, chromatin condensation, micronuclei, and apoptotic bodies. Taken together, our data demonstrate that HT appears suitable to highlight suspended or adherent cell behavior under different conditions. In particular, this technique appears an important new tool to distinguish healthy cells from the apoptotic ones, as well as to monitor outer and inner cell changes in a rapid way and with a noninvasive, label‐free, approach.
Synthesis and antimicrobial activity of 2‐(4‐(benzo[d]thiazol‐5‐ylsulfonyl)piperazine‐1‐yl)‐N‐substituted acetamide derivatives
Authors: Shinde Ravindra R. , Gaikwad Dattatray , Farooqui Mazahar
Published: July 2020

A new series of 2‐(4‐(benzo[d]thiazol‐5‐ylsulfonyl)piperazin‐1‐yl)‐N‐substituted acetamide (5a‐5k) compounds have been synthesized, and these compounds were characterized with spectral data like IR, NMR, and Mass spectroscopy. All compounds were evaluated in vitro for their efficacy as antimicrobial against Gram‐positive and Gram‐negative pathogenic bacterial strains such as Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa using ciprofloxacin as a standard and fungal strains like Candida albicans and Aspergillus fumigatus as compared with standard drug Clotrimazole, and Molecular docking study shows that all these compounds were having good to excellent correlation binding energy as compared with binding energy of standard drugs.
International consensus guidelines for phosphoglucomutase 1 deficiency (PGM1‐CDG): Diagnosis, follow‐up, and management
Authors: Altassan Ruqaiah , Radenkovic Silvia , Edmondson Andrew C. , Barone Rita , Brasil Sandra , Cechova Anna , Coman David , Donoghue Sarah , Falkenstein Kristina , Ferreira Vanessa , Ferreira Carlos , Fiumara Agata , Francisco Rita , Freeze Hudson , Grunewald Stephanie , Honzik Tomas , Jaeken Jaak , Krasnewich Donna , Lam Christina , Lee Joy , Lefeber Dirk , Marques‐da‐Silva Dorinda , Pascoal Carlota , Quelhas Dulce , Raymond Kimiyo M. , Rymen Daisy , Seroczynska Malgorzata , Serrano Mercedes , Sykut‐Cegielska Jolanta , Thiel Christian , Tort Frederic , Vals Mari‐Anne , Videira Paula , Voermans Nicol , Witters Peter , Morava Eva
Published: July 2020

Phosphoglucomutase 1 (PGM1) deficiency is a rare genetic disorder that affects glycogen metabolism, glycolysis, and protein glycosylation. Previously known as GSD XIV, it was recently reclassified as a congenital disorder of glycosylation, PGM1‐CDG. PGM1‐CDG usually manifests as a multisystem disease. Most patients present as infants with cleft palate, liver function abnormalities and hypoglycemia, but some patients present in adulthood with isolated muscle involvement. Some patients develop life‐threatening cardiomyopathy. Unlike most other CDG, PGM1‐CDG has an effective treatment option, d‐galactose, which has been shown to improve many of the patients' symptoms. Therefore, early diagnosis and initiation of treatment for PGM1‐CDG patients are crucial decisions. In this article, our group of international experts suggests diagnostic, follow‐up, and management guidelines for PGM1‐CDG. These guidelines are based on the best available evidence‐based data and experts' opinions aiming to provide a practical resource for health care providers to facilitate successful diagnosis and optimal management of PGM1‐CDG patients.
Long term outcome of MPI‐CDG patients on D‐mannose therapy
Authors: Girard Muriel , Douillard Claire , Debray Dominique , Lacaille Florence , Schiff Manuel , Vuillaumier‐Barrot Sandrine , Dupré Thierry , Fabre Monique , Damaj Lena , Kuster Alice , Torre Stéphanie , Mention Karine , McLin Valérie , Dobbelaere Dries , Borgel Delphine , Bauchard Eric , Seta Nathalie , Bruneel Arnaud , De Lonlay Pascale
Published: July 2020

Mannose phosphate isomerase MPI‐CDG (formerly CDG‐1b) is a potentially fatal inherited metabolic disease which is readily treatable with oral D‐mannose. We retrospectively reviewed long‐term outcomes of patients with MPI‐CDG, all but one of whom were treated with D‐mannose. Clinical, biological, and histological data were reviewed at diagnosis and on D‐mannose treatment. Nine patients were diagnosed with MPI‐CDG at a median age of 3 months. The presenting symptoms were diarrhea (n = 9), hepatomegaly (n = 9), hypoglycemia (n = 8), and protein loosing enteropathy (n = 7). All patients survived except the untreated one who died at 2 years of age. Oral D‐mannose was started in eight patients at a median age of 7 months (mean 38 months), with a median follow‐up on treatment of 14 years 9 months (1.5‐20 years). On treatment, two patients developed severe portal hypertension, two developed venous thrombosis, and 1 displayed altered kidney function. Poor compliance with D‐mannose was correlated with recurrence of diarrhea, thrombosis, and abnormal biological parameters including coagulation factors and transferrin profiles. Liver fibrosis persisted despite treatment, but two patients showed improved liver architecture during follow‐up. This study highlights (i) the efficacy and safety of D‐mannose treatment with a median follow‐up on treatment of almost 15 years (ii) the need for life‐long treatment (iii) the risk of relapse with poor compliance, (iii) the importance of portal hypertension screening (iv) the need to be aware of venous and renal complications in adulthood.
Predominant and novel de novo variants in 29 individuals with ALG13 deficiency: Clinical description, biomarker status, biochemical analysis, and treatment suggestions
Authors: Ng Bobby G. , Eklund Erik A. , Shiryaev Sergey A. , Dong Yin Y. , Abbott Mary‐Alice , Asteggiano Carla , Bamshad Michael J. , Barr Eileen , Bernstein Jonathan A. , Chelakkadan Shabeed , Christodoulou John , Chung Wendy K. , Ciliberto Michael A. , Cousin Janice , Gardiner Fiona , Ghosh Suman , Graf William D. , Grunewald Stephanie , Hammond Katherine , Hauser Natalie S. , Hoganson George E. , Houck Kimberly M. , Kohler Jennefer N. , Morava Eva , Larson Austin A. , Liu Pengfei , Madathil Sujana , McCormack Colleen , Meeks Naomi J.L. , Miller Rebecca , Monaghan Kristin G. , Nickerson Deborah A. , Palculict Timothy Blake , Papazoglu Gabriela Magali , Pletcher Beth A. , Scheffer Ingrid E. , Schenone Andrea Beatriz , Schnur Rhonda E. , Si Yue , Rowe Leah J. , Serrano Russi Alvaro H. , Russo Rossana Sanchez , Thabet Farouq , Tuite Allysa , Villanueva María Mercedes , Wang Raymond Y. , Webster Richard I. , Wilson Dorcas , Zalan Alice ,   Undiagnosed Diseases Network, University of Washington Center for Mendelian Genomics (UW‐CMG), Wolfe Lynne A. , Rosenfeld Jill A. , Rhodes Lindsay , Freeze Hudson H.
Published: July 2020

Asparagine‐linked glycosylation 13 homolog (ALG13) encodes a nonredundant, highly conserved, X‐linked uridine diphosphate (UDP)‐N‐acetylglucosaminyltransferase required for the synthesis of lipid linked oligosaccharide precursor and proper N‐linked glycosylation. De novo variants in ALG13 underlie a form of early infantile epileptic encephalopathy known as EIEE36, but given its essential role in glycosylation, it is also considered a congenital disorder of glycosylation (CDG), ALG13‐CDG. Twenty‐four previously reported ALG13‐CDG cases had de novo variants, but surprisingly, unlike most forms of CDG, ALG13‐CDG did not show the anticipated glycosylation defects, typically detected by altered transferrin glycosylation. Structural homology modeling of two recurrent de novo variants, p.A81T and p.N107S, suggests both are likely to impact the function of ALG13. Using a corresponding ALG13‐deficient yeast strain, we show that expressing yeast ALG13 with either of the highly conserved hotspot variants rescues the observed growth defect, but not its glycosylation abnormality. We present molecular and clinical data on 29 previously unreported individuals with de novo variants in ALG13. This more than doubles the number of known cases. A key finding is that a vast majority of the individuals presents with West syndrome, a feature shared with other CDG types. Among these, the initial epileptic spasms best responded to adrenocorticotropic hormone or prednisolone, while clobazam and felbamate showed promise for continued epilepsy treatment. A ketogenic diet seems to play an important role in the treatment of these individuals.
Changes of compound hot and dry extremes on different land surface conditions in China during 1957–2018
Authors: Feng Yao , Liu Wenbin , Sun Fubao , Wang Hong
Published: July 2020

The co‐occurrence of hot and dry extremes (compound hot and dry extreme, CHDE) has attracted much attention due to the amplified impact on wildfire occurrence, agriculture production and human health. Most existing studies have reported the spatiotemporal variations of CHDE, changes in CHDE on different land surface conditions are barely discussed. The study investigated the spatial and temporal differences of CHDE over different regions and land covers in China during 1957–2018. On average over China, both day‐ and night‐time CHDEs have increased with a more rapid (2.6 times faster) and significant (p < .05) increasing trend in night‐time ones. Increasing trends are mainly distributed in north China with decreasing trends in central China. Moreover, increasing trends in night‐time mildly dry (0.07 per decade) and moderately hot (0.06 per decade) CHDEs are the largest among all dry and hot CHDEs. Regionally, the frequency of CHDE is the highest over the humid and sub‐humid regions for night‐ and day‐time CHDEs, but the lowest for both over the arid region. Meanwhile, CHDE has increased over the humid and sub‐humid regions in the recent decade but decreased over the arid region since 1957. For different land covers, the frequency of CHDE is the highest over forest but the lowest over grassland. Day‐time CHDEs of different hot magnitudes indicate the largest increasing trends over grassland caused by the largest increasing trends of day‐time heatwave. Significant (p < 0.05) increasing trends of day‐ and night‐time CHDEs over forest may increase the risks of tree mortality or forest fires after 2010 and larger increasing trends in night‐time CHDEs over urban may negatively impact human health.
Prognostic value of different metastatic sites for patients with FIGO stage IVB endometrial cancer after surgery: A SEER database analysis
Authors: Li Hui , Zhang Rusi , Chen Cuiying , Wu Chuling , Lin Haoliang , Li Jing , Lin Zhongqiu
Published: July 2020

Objective

This study aimed to investigate the association between different metastatic sites and survival in endometrial cancer (EC) patients with International Federation of Gynecology and Obstetrics (FIGO) stage IVB disease.

Methods

FIGO stage IVB patients with EC were selected from the surveillance, epidemiology, and end results database. Overall survival (OS) and cause‐specific survival (CSS) were analyzed with Kaplan‐Meier analysis and log‐rank tests. Univariate and multivariate Cox proportional hazard models were used to identify the prognostic factors for OS and CSS.

Results

A total of 929 FIGO stage IVB patients with EC were identified. Patients with peritoneum metastasis were associated with significantly better OS and CSS compared to those with organ‐specific metastasis (median OS: 29 vs 19 months, P = .005; median CSS: 47 vs 25 months, P < .001). Moreover, the survival superiority of peritoneum metastasis remained significant when organ‐specific metastasis was further classified into specific single‐organ metastasis. The multivariate analysis also indicated that compared with peritoneum metastasis, bone, brain, and lung metastasis were independent prognostic factors for worse OS. Similarly, distant lymph node, bone, brain, liver, and lung metastasis were associated with worse CSS.

Conclusion

Metastatic sites affected prognosis in FIGO stage IVB patients with EC. Patients with peritoneum metastasis had significantly better survival outcomes than those with organ‐specific metastasis.
Fetal Open and Closed Spina Bifida on a Routine Scan at 11 Weeks to 13 Weeks 6 Days
Authors: Liao Yimei , Wen Huaxuan , Luo Guoyang , Ouyang Shuyuan , Bi Jingru , Yuan Ying , Luo Dandan , Huang Yi , Zhang Kui , Tian Xiaoxian , Li Shengli
Published: July 2020

Objectives

This study aimed to determine the sensitivity of a first‐trimester routine scan in detecting spina bifida (SB) and evaluating the first‐trimester intracranial signs.

Methods

This retrospective study was a review of a prospectively collected database. All cases of SB diagnosed in a tertiary center from 2008 to 2015 were identified. The ultrasound images and medical records were reviewed. All cases of SB diagnosed prenatally were confirmed at birth or autopsy.

Results

A total of 24 cases of SB were diagnosed from 53,349 pregnancy cases. Except for 10 cases with a body stalk anomaly, craniorachischisis, or iniencephaly, 7 cases with open spina bifida (OSB) and 7 cases with closed spina bifida (CSB) were analyzed. The first‐trimester detection rates were 100% (7 of 7) for OSB and 28.5% (2 of 7) for CSB. Eight cases were highly suspected of SB in the first trimester because of an abnormal appearance of the posterior brain; 3 were false‐positive cases. Two isolated cases of OSB had first‐trimester intracranial signs. An obliterated cisterna magna (CM) showed the highest sensitivity for OSB but low specificity. Two cases of OSB had no discernible landmark of intracranial translucency and the CM, and 4 showed normal intracranial translucency with an obliterated CM. All CSB cases were coupled with a normal hind brain except for 2 cases.

Conclusions

A first‐trimester routine scan has high sensitivity in screening for OSB. The CM may be the most sensitive intracranial sign.
Using the Superb Microvascular Imaging Method in the Distinction of Intraductal Papilloma and Duct Ectasia With Secretion
Authors: Tek Cihat , Öztekin Pelin Seher , Celepli Pınar , Uçar Funda , Koşar Pınar Nercis
Published: July 2020

Objectives

To investigate the diagnostic value of a Superb Microvascular Imaging (SMI; Toshiba Medical Systems, Tokyo, Japan) Doppler examination for distinguishing intraductal papilloma (IDP) from duct ectasia with secretion in lesions smaller than 1 cm compared to color Doppler imaging (CDI) and power Doppler imaging (PDI).

Methods

Fifty‐nine lesions were evaluated by grayscale ultrasound, CDI, PDI, and SMI. Biopsied tissue samples were analyzed. Ultrasound evaluations and Doppler examinations were performed with a Toshiba Aplio 500 device. The lesions were divided into 2 groups, secretion and IDP, according to the pathologic results. Color Doppler imaging, PDI, and SMI data were compared statistically to investigate their diagnostic values.

Results

Of the 59 lesions, 22 were secretion, and 37 were IDP. The mean diameters ± SDs were 4.7 ± 0.6 mm in the secretion group and 4.9 ± 0.8 mm in the IDP group (P = .315). There was no significant difference in grayscale ultrasound features such as shape or margin between the groups (P > .05). No significant difference was found between the groups in CDI or PDI characteristics (P > .999; P = .702, respectively). The color SMI evaluation results showed no vascularity in 18 (81.8%) lesions in the secretion group. Vascularity was detected in 32 patients (86.5%) in the IDP group. In the receiver operating characteristic analysis, the areas under the curve were calculated as 0.842 (95% confidence interval [CI], 0.728–0.925) for SMI, 0.522 (95% CI, 0.388–0.654) for PDI, and 0.518 (95% CI, 0.384–0.650) for CDI.

Conclusions

Superb Microvascular Imaging is more accurate and has more diagnostic ability than CDI or PDI in distinguishing small IDPs from duct ectasia with secretion because of its ability to visualize slow flow speeds of vascular structures.