bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding equity of institutional delivery in public health centre by level of care in India: an assessment using benefit incidence analysis
Authors: Mohanty Sanjay K. , Mishra Radhe Shyam , Mishra Suyash , Sen Soumendu
Published: December 2020

Background

The National Health Mission (NHM), the largest ever publicly funded health programme worldwide, used over half of the national health budget in India and primarily aimed to improve maternal and child health in the country. Though large scale public health investment has improved the health care utilization and health outcomes across states and socio-economic groups in India, little is known on the equity concern of NHM. In this context, this paper examines the utilization pattern and net benefit of public subsidy for institutional delivery by the level of care in India.

Methods

Data from the most recent round of the National Family Health Survey (NFHS 4), conducted during 2015–16, was used in the study. A total of 148,645 last birth delivered in a health centre during the 5 years preceding the survey were used for the analyses. Out-of-pocket (OOP) payment on delivery care was taken as the dependent variable and was analysed by primary care and secondary level of care. Benefits Incidence Analysis (BIA), descriptive statistics, concentration index (CI), and concentration curve (CC) were used to do the analysis.

Results

Institutional delivery from the public health centres in India is pro-poor and has a strong economic gradient. However, about 28% mothers from richest wealth quintile did not pay for delivery in public health centres compared to 16% among the poorest wealth quintile. Benefit incidence analyses suggests a pro-poor distribution of institutional delivery both at primary and secondary level of care. In 2015–16, at the primary level, about 32.29% of subsidies were used by the poorest, 27.22% by poorer, 20.39% by middle, 13.36% by richer and 6.73% by the richest wealth quintile. The pattern at the secondary level was similar, though the magnitude was lower. The concentration index of institutional delivery in public health centres was − 0.161 [95% CI, − 0.158, − 0.165] compared to 0.296 [95% CI, 0.289, 0.303] from private health centres.

Conclusion

Provision and use of public subsidy for institutional delivery in public health centres is pro-poor in India. Improving the quality of service in primary health centres is recommended to increase utilisation and reduce OOP payment for health care in India.
Hepatic lipid profile in mice fed a choline-deficient, low-methionine diet resembles human non-alcoholic fatty liver disease
Authors: Haberl Elisabeth M. , Pohl Rebekka , Rein-Fischboeck Lisa , Höring Marcus , Krautbauer Sabrina , Liebisch Gerhard , Buechler Christa
Published: December 2020

Background

Emerging data support a role for lipids in non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) in humans. With experimental models such data can be challenged or validated. Mice fed a low-methionine, choline-deficient (LMCD) diet develop NASH and, when injected with diethylnitrosamine (DEN), HCC. Here, lipidomic analysis was used to elucidate whether the NASH and HCC associated lipid derangements resemble the lipid profile of the human disease.

Methods

Lipids were measured in the liver of mice fed a control or a LMCD diet for 16 weeks. DEN was injected at young age to initiate hepatocarcinogenesis. DEN treatment associated changes of the lipid composition and the tumor lipidome were evaluated.

Results

LMCD diet fed mice accumulated ceramides and triacylglycerols in the liver. Phospholipids enriched with monounsaturated fatty acids were also increased, whereas hepatic cholesterol levels remained unchanged in the LMCD model. Phosphatidylcholine and lysophosphatidylcholine concentrations declined in the liver of LMCD diet fed mice. The changes of most lipids associated with LMCD diet feeding were similar between water and DEN injected mice. Several polyunsaturated (PU) diacylglycerol species were already low in the liver of DEN injected mice fed the control diet. Tumors developed in the liver of LMCD diet fed mice injected with DEN. The tumor specific lipid profile, however, did not resemble the decrease of ceramides and PU phospholipids, which was consistently described in human HCC. Triacylglycerols declined in the cancer tissues, which is in accordance with a low expression of lipogenic enzymes in the tumors.

Conclusions

The LMCD model is suitable to study NASH associated lipid reprogramming. Hepatic lipid profile was modestly modified in the DEN injected mice suggesting a function of these derangements in carcinogenesis. Lipid composition of liver tumors did not resemble the human HCC lipidome, and most notably, lipogenesis and triacylglycerol levels were suppressed.
The DNA methylation of FOXO3 and TP53 as a blood biomarker of late-onset asthma
Authors: Yuan Lin , Wang Leyuan , Du Xizi , Qin Ling , Yang Ming , Zhou Kai , Wu Mengping , Yang Yu , Zheng Zhiyuan , Xiang Yang , Qu Xiangping , Liu Huijun , Qin Xiaoqun , Liu Chi
Published: December 2020

Background

Late-onset asthma (LOA) is beginning to account for an increasing proportion of asthma patients, which is often underdiagnosed in the elderly. Studies on the possible relations between aging-related genes and LOA contribute to the diagnosis and treatment of LOA. Forkhead Box O3 (FOXO3) and TP53 are two classic aging-related genes. DNA methylation varies greatly with age which may play an important role in the pathogenesis of LOA. We supposed that the differentially methylated sites of FOXO3 and TP53 associated with clinical phenotypes of LOA may be useful biomarkers for the early screening of LOA.

Methods

The mRNA expression and DNA methylation of FOXO3 and TP53 in peripheral blood of 43 LOA patients (15 mild LOA, 15 moderate LOA and 13 severe LOA) and 60 healthy controls (HCs) were determined. The association of methylated sites with age was assessed by Cox regression to control the potential confounders. Then, the correlation between differentially methylated sites (DMSs;p-value < 0.05) and clinical lung function in LOA patients was evaluated. Next, candidate DMSs combining with age were evaluated to predict LOA by receiver operating characteristic (ROC) analysis and principal components analysis (PCA). Finally, HDM-stressed asthma model was constructed, and DNA methylation inhibitor 5-Aza-2′-deoxycytidine (5-AZA) were used to determine the regulation of DNA methylation on the expression of FOXO3 and TP53.

Results

Compared with HCs, the mRNA expression and DNA methylation of FOXO3 and TP53 vary significantly in LOA patients. Besides, 8 DMSs from LOA patients were identified. Two of the DMSs, chr6:108882977 (FOXO3) and chr17:7591672 (TP53), were associated with the severity of LOA. The combination of the two DMSs and age could predict LOA with high accuracy (AUC values = 0.924). In HDM-stressed asthma model, DNA demethylation increased the expression of FOXO3 and P53.

Conclusions

The mRNA expression of FOXO3 and TP53 varies significantly in peripheral blood of LOA patients, which may be due to the regulation of DNA methylation. FOXO3 and TP53 methylation is a suitable blood biomarker to predict LOA, which may be useful targets for the risk diagnosis and clinical management of LOA.
Different expression pattern of human cytomegalovirus-encoded microRNAs in circulation from virus latency to reactivation
Authors: Zhou Wanqing , Wang Cheng , Ding Meng , Bian Yuying , Zhong Yujie , Shen Han , Wang Junjun , Zhang Chen-Yu , Zhang Chunni
Published: December 2020

Background

Human cytomegalovirus (HCMV) is a beta-hersvirinae that has a high latent infection rate worldwide and can cause serious consequences in immunocompromised patients when reactivation; however, the mechanism of how HCMV convert from latent to reactivation has rarely been investigated. In the present study, we aimed to perform a comprehensive analysis of the HCMV-encoded microRNA (miRNA) profile in serum of patients upon HCMV reactivation from latency and to further evaluate its clinical significance for the disease monitoring and preventing usefulness.

Methods

Serum samples from 59 viremia patients and 60 age-gender matched controls were enrolled in this study for screening and validation of different expression of HCMV miRNAs. Serum concentrations of 22 known HCMV miRNAs were determined by a hydrolysis probe-based stem-loop quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay. HCMV DNA was measured by quantitative real-time PCR (qPCR) with the whole blood sample. Serum HCMV IgG and IgM were assessed using enzyme linked immunosorbent assay (ELISA). Another 47 samples from 5 patients at different time points were collected to evaluate the monitoring effectiveness and disease prediction ability of differential expression HCMV-miRNAs during the antiviral treatment.

Results

The RT-qPCR analysis revealed that the serum levels of 16 of the 22 examined HCMV miRNAs were elevated in HCMV viremia patients compared with controls, and a profile of 8 HCMV miRNAs including hcmv-miR-US25-2-3p, hcmv-miR-US4-5p, hcmv-miR-US25-2-5p, hcmv-miR-US25-1-3p, hcmv-miR-US25-1, hcmv-miR-UL36, hcmv-miR-UL148D, hcmv-miR-US29-3p were markedly elevated (fold change > 2, P < 0.01). Receiver operating characteristic curve (ROC) analysis were performed on the selected HCMV-miRNAs in all of the patients and controls that enrolled in this study, and which ranged from 0.72 to 0.80 in the autoimmune patients. In addition, hcmv-miR-US25-1-3p levels were significantly correlated with HCMV DNA load (r = 0.349, P = 0.007), and were obviously higher in the reactivation set than the latency set in the autoimmune patients, which could be a predictor for the monitoring of the antiviral treatment.

Conclusions

HCMV miRNAs profile showed markedly shift-switch from latency to reactivation in circulation from HCMV infected patients and hcmv-miR-US25-1-3p may be served as a predictor for the switch upon reactivation from latency in patients suffered with autoimmune diseases.
Non-invasive biomarkers for monitoring the immunotherapeutic response to cancer
Authors: Nisar Sabah , Bhat Ajaz A. , Hashem Sheema , Yadav Santosh K. , Rizwan Arshi , Singh Mayank , Bagga Puneet , Macha Muzafar A. , Frenneaux Michael P. , Reddy Ravinder , Haris Mohammad
Published: December 2020

Immunotherapy is an efficient way to cure cancer by modulating the patient’s immune response. However, the immunotherapy response is heterogeneous and varies between individual patients and cancer subtypes, reinforcing the need for early benefit predictors. Evaluating the infiltration of immune cells in the tumor and changes in cell-intrinsic tumor characteristics provide potential response markers to treatment. However, this approach requires invasive sampling and may not be suitable for real-time monitoring of treatment response. The recent emergence of quantitative imaging biomarkers provides promising opportunities. In vivo imaging technologies that interrogate T cell responses, metabolic activities, and immune microenvironment could offer a powerful tool to monitor the cancer response to immunotherapy. Advances in imaging techniques to identify tumors' immunological characteristics can help stratify patients who are more likely to respond to immunotherapy. This review discusses the metabolic events that occur during T cell activation and differentiation, anti-cancer immunotherapy-induced T cell responses, focusing on non-invasive imaging techniques to monitor T cell metabolism in the search for novel biomarkers of response to cancer immunotherapy.
Correction to: LncRNA MYLK-AS1 facilitates tumor progression and angiogenesis by targeting miR-424-5p/E2F7 axis and activating VEGFR-2 signaling pathway in hepatocellular carcinoma
Authors: Teng Fei , Zhang Ju-Xiang , Chang Qi-Meng , Wu Xu-Bo , Tang Wei-Guo , Wang Jian-Fa , Feng Jin-Feng , Zhang Zi-Ping , Hu Zhi-Qiu
Published: December 2020

An amendment to this paper has been published and can be accessed via the original article.
Effect of duloxetine premedication for postherpetic neuralgia within 72 h of herpes zoster reactivation [PROCESS]: a study protocol for a randomized controlled trial
Authors: Chen Zheng , Shrestha Niti , Zhao Chunmei , Fan Bifa , Luo Fang
Published: December 2020

Background

Postherpetic neuralgia (PHN) is the most common complication attributed to herpes zoster, which involves the reactivation of residual varicella zoster virus. It has been reported previously that pre-emptive amitriptyline following acute herpes zoster has shown latent positive effects in the prevention of PHN. In this study, by interfering with the same targets, norepinephrine and serotonin, we aim to evaluate whether pre-emptive duloxetine may proactively prevent PHN development.

Methods

This is a nationwide multicentric, randomized, open-label, blinded-endpoint study that will recruit 750 participants from 18 primary centres in China. Patients aged more than 50 years who are diagnosed with uncomplicated HZ, present with vesicles within 72 h of their emergence, and have an average pain score of at least 40/100 mm on a visual analogue scale (VAS, 0 mm = no pain, 100 mm = worst possible pain, at opposite ends of a 100-mm line) will be recruited for this study. Participants will be randomized into a duloxetine arm and a control arm. Participants allocated to the duloxetine arm will be given antivirals, analgesics and duloxetine, while those allocated to the control arm will receive antivirals and analgesics but no duloxetine. The primary outcome of this study is preventive efficacy against PHN, which will be evaluated based on a 100 mm VAS. Any pain scores other than 0 mm on the VAS 12 weeks after HZ onset will be defined as PHN. The secondary outcomes will consist of the average weekly VAS score, the average weekly consumption of each analgesic, weekly feature of the pain, patients’ quality of life based on the 12-item Short-Form Health Survey, Patient Global Impression of Change Scale, sleep quality as evaluated by the Pittsburgh Sleep Quality Index and adverse events during the study period.

Discussion

This study will investigate a prophylactic approach for reducing the prevalence of postherpetic neuralgia with duloxetine and will add significant new knowledge on the preventive effects of duloxetine on PHN.

Trial registration

Clinicaltrials.gov NCT04313335. Registered on 18 March 2020.
A Klebsiella pneumoniae ST307 outbreak clone from Germany demonstrates features of extensive drug resistance, hypermucoviscosity, and enhanced iron acquisition
Authors: Heiden Stefan E. , Hübner Nils-Olaf , Bohnert Jürgen A. , Heidecke Claus-Dieter , Kramer Axel , Balau Veronika , Gierer Wolfgang , Schaefer Stephan , Eckmanns Tim , Gatermann Sören , Eger Elias , Guenther Sebastian , Becker Karsten , Schaufler Katharina
Published: December 2020

Background

Antibiotic-resistantKlebsiella pneumoniaeare a major cause of hospital- and community-acquired infections, including sepsis, liver abscess, and pneumonia, driven mainly by the emergence of successful high-risk clonal lineages. TheK. pneumoniaesequence type (ST) 307 lineage has appeared in several different parts of the world after first being described in Europe in 2008. From June to October 2019, we recorded an outbreak of an extensively drug-resistant ST307 lineage in four medical facilities in north-eastern Germany.

Methods

Here, we investigated these isolates and those from subsequent cases in the same facilities. We performed whole-genome sequencing to study phylogenetics, microevolution, and plasmid transmission, as well as phenotypic experiments including growth curves, hypermucoviscosity, siderophore secretion, biofilm formation, desiccation resilience, serum survival, and heavy metal resistance for an in-depth characterization of this outbreak clone.

Results

Phylogenetics suggest a homogenous phylogram with several sub-clades containing either isolates from only one patient or isolates originating from different patients, suggesting inter-patient transmission. We identified three large resistance plasmids, carrying either NDM-1, CTX-M-15, or OXA-48, whichK. pneumoniaeST307 likely donated to otherK. pneumoniaeisolates of different STs and even other bacterial species (e.g.,Enterobacter cloacae) within the clinical settings. Several chromosomally and plasmid-encoded, hypervirulence-associated virulence factors (e.g., yersiniabactin, metabolite transporter, aerobactin, and heavy metal resistance genes) were identified in addition. While growth, biofilm formation, desiccation resilience, serum survival, and heavy metal resistance were comparable to several control strains, results from siderophore secretion and hypermucoviscosity experiments revealed superiority of the ST307 clone, similar to an archetypical, hypervirulentK. pneumoniaestrain (hvKP1).

Conclusions

The combination of extensive drug resistance and virulence, partly conferred through a “mosaic” plasmid carrying both antibiotic resistance and hypervirulence-associated features, demonstrates serious public health implications.
Data of risk analysis management in university campuses
Authors: Dehdashti Alireza , Fatemi Farin , Janati Muhammadreza , Asadi Fatemeh , Kangarloo Marzieh Belji
Published: December 2020

Objectives

This data paper aims to provide the data set of a practical method to health, safety, and environmental risk assessment to assess and rank potential threats/hazards and to prevent and decrease the accidents and harmful consequences at an academic setting. Descriptive data on type of hazards, places, and persons at risk were collected. Quantitative data on risk probability and severity of identified hazards were determined. Additionally, the descriptive statistics and analytical tests were applied to create a concise perspective on health, safety and environmental hazards/threats situation in research location under study. The dataset further provides information on the prioritization of determined risks according to the relevant scores and levels for doing the relevant control measures to remove and mitigate the related risks.

Data description

This paper provides data of comprehensive risk assessment of health, safety and, environmental hazards of academic setting. For each identified hazard, the descriptive and numeric data are available. The information about the risk level and prevention or mitigation measure related to each hazard is provided. Additionally, the statistical tests are applied for determining the relations among the variables under study. The data and methodology on risk assessment in this article may be used to manage variety of risks in higher education institutions.
Factors affecting hospital mortality rate in Iran: a panel data analysis
Authors: Bayati Mohsen , Emadi Mehrnoosh
Published: December 2020

Objective

Hospital deaths account for a large number of community deaths. Moreover, one of the main indicators of inpatient services quality is the hospital death. This study was performed to investigate the factors affecting hospital death rate in Iran using panel data analysis.

Results

The net death rates in teaching and not-teaching hospitals were 6.24 and 5.58 per 1000 patients, respectively. Models' estimates showed, in teaching hospitals the number of surgeries (P < 0.05) and special beds (P < 0.01) had a significant positive relationship with death rate. In non-teaching hospitals, outpatient admissions (P < 0.01), number of surgeries (P < 0.05), number of special beds (P < 0.01), and length of stay (P < 0.01) had a positive and the number of inpatient admissions (P < 0.05) and active beds (P < 0.01) had a negative relationship with death rate.

Policy-making towards optimization of hospital service size and volume, standardization of length of stay, interventions to control nosocomial infections, and planning to control the complications of surgeries and anesthesia could effectively reduce hospital death rate.
Relationship between tumor mutational burden and maximum standardized uptake value in 2-[18F]FDG PET (positron emission tomography) scan in cancer patients
Authors: Haghighat Jahromi Amin , Barkauskas Donald A. , Zabel Matthew , Goodman Aaron M. , Frampton Garret , Nikanjam Mina , Hoh Carl K. , Kurzrock Razelle
Published: December 2020

Purpose

Deriving links between imaging and genomic markers is an evolving field. 2-[18F]FDG PET/CT (18F-fluorodeoxyglucose positron emission tomography–computed tomography) is commonly used for cancer imaging, with maximum standardized uptake value (SUVmax) as the main quantitative parameter. Tumor mutational burden (TMB), the quantitative variable obtained using next-generation sequencing on a tissue biopsy sample, is a putative immunotherapy response predictor. We report the relationship between TMB and SUVmax, linking these two important parameters.

Methods

In this pilot study, we analyzed 1923 patients with diverse cancers and available TMB values. Overall, 273 patients met our eligibility criteria in that they had no systemic treatment prior to imaging/biopsy, and also had 2-[18F]FDG PET/CT within 6 months prior to the tissue biopsy, to ensure acceptable temporal correlation between imaging and genomic evaluation.

Results

We found a linear correlation between TMB and SUVmax (p < 0.001). In the multivariate analysis, only TMB independently correlated with SUVmax, whereas age, gender, and tumor organ did not.

Conclusion

Our observations link SUVmax in readily available, routinely used, and noninvasive 2-[18F]FDG PET/CT imaging to the TMB, which requires a tissue biopsy and time to process. Since higher TMB has been implicated as a prognostic biomarker for better outcomes after immunotherapy, further investigation will be needed to determine if SUVmax can stratify patient response to immunotherapy.
A novel ELISA method to determine human MrgX2 in chronic urticaria
Authors: Ding Yuanyuan , Zhang Tao , Liu Rui , Che Delu , Wang Nan , He Langchong
Published: December 2020

Background

Mas-related G-protein coupled receptor member X2 (MrgX2) directly mediates drug-induced pseudo allergic reactions. Skin mast cell MrgX2 is upregulated in severe chronic urticaria (CU). Mast cells and leukocytes are key effector cells in allergic reactions and undergo degranulation upon stimulation. It is unknown whether circulating MrgX2 expression can be detected occurs in the whole blood of CU patients and reflects pseudo-allergic reaction. There is no effective method for its detection. Therefore, an enzyme-linked immuno-sorbent assay (ELISA) for MrgX2 was developed.

Methods

Monoclonal and polyclonal MrgX2 specific antibodies were obtained from rabbits and mice immunized by MrgX2 peptides prepared. Indirect ELISA and Dot blot were used to determine antibody titers before a sandwich ELISA for MrgX2 was established. The whole blood from healthy subjects and CU patients was used to detect MrgX2 concentrations. The use of feasibility of this MrgX2-ELISA as a clinical detection tool was explored and diagnostic purposes was assessed.

Results

The sandwich antibody ELISA method for MrgX2 was established with good linearity regression (R2 = 0.9910). The lowest detection limit was 3.125 ng/mL. The quantification limit was 6.25 ng/mL. The sandwich ELISA for MrgX2 have good stability and high specificity. The initial truncation value of MrgX2 was 60.91 ng/mL (95% confidence interval). The whole blood MrgX2 concentrations in CU patients (median 98.01 ± 4.317 ng/mL, n = 75) was significantly increased compared to healthy subjects (58.09 ± 1.418 ng/mL, n = 75), with significant difference (p < 0.0001) and higher accuracy of (AUC = 0.8795). Comprehensive the frequency analysis of MrgX2 expression in 75 CU patients reference frequency distribution and ROC curve analysis, determined the threshold for CU patients as 71.23 ng/mL, with 81.33% sensitivity and 90.67% specificity.

Conclusion

MrgX2-ELISA provides a useful and convenient method for detecting MrgX2 in whole blood samples. The MrgX2-ELISA will help improve the understanding of the role of MrgX2 in regulating chronic urticaria.
Disability-adjusted life years and mortality rate attributed to unsafe sex and drug use for AIDS in the Middle East and North Africa countries
Authors: Najafi Farid , Shadmani Fatemeh Khosravi , Ghalandari Mojtaba , Darbandi Mitra
Published: December 2020

Background

The Middle East and North Africa, is one of few regions where the number of new human immunodeficiency virus infections is increasing. The present study aimed to estimate the attributable burden of unsafe sex and drug use in Acquired immunodeficiency syndrome in the Middle East and North Africa countries.

Methods

We used the Global Burden of Disease data 2017 to estimate the attributable mortality and disability-adjusted life-years to unsafe sex and drug use in Acquired immunodeficiency syndrome in the Middle East and North Africa countries (21 countries) from 1990 to 2017 by region, sex and age. The percent change was calculated at three time points by country and sex.

Results

The rate of Disability-adjusted life years/100,000 attributed to drug use for Acquired immunodeficiency syndrome increased 1.10 (95% CI: 0.75–1.71) to 13.39 (95% CI: 9.98–18.17) in women of Middle East and North Africa countries from 1990 to 2017, and there is an increasing trend in Disability-adjusted life years attributable to drug use for Acquired immunodeficiency syndrome in men. The rate of Disability-adjusted life years/100,000 attributed to unsafe sex for Acquired immunodeficiency syndrome increased in women of Middle East and North Africa countries, 5.15 (95% CI: 3.34–8.07) to 53.44 (95% CI: 38.79–75.89); and 10.06 (95% CI: 6.61–16.18) to 46.16 (95% CI: 31.30–72.66) in men. Age-standardized mortality rate attributed to drug use and unsafe sex for Acquired immunodeficiency syndrome increased from 1990 to 2017 in both sex in Middle East and North Africa countries.

Conclusion

The rate of Disability-adjusted life years /100,000 and age-standardized mortality rate attributed to unsafe sex and drug use increased in Middle East and North Africa from 1990 to 2017. While most of such countries have traditional cultures with religious believes, such increase need to be addressed in more depth by all policy makers.
KMT2A/C mutations function as a potential predictive biomarker for immunotherapy in solid tumors
Authors: Zhang Rui , Wu Hao-Xiang , Xu Ming , Xie Xiaoyan
Published: December 2020

Epigenetic factors play important roles in tumor immunology. Histone-lysine N-methyltransferase 2 (KMT2) family genes exert histone H3 methylation, but its role in immunotherapy remains unclear. Our study is the first to investigate the correlation between KMT2 gene mutations and the clinical benefit of immune checkpoint inhibitors (ICI) treatment. We firstly collected a primary ICI-treated cohort (n = 546) and found that patients with KMT2A/C mutations yielded better prognosis in terms of progression-free survival (PFS, Hazard ratio [HR] = 0.66, P = 0.002), objective response rate (ORR, 40.9% vs 20.3%, P < 0.001), durable clinical benefit (DCB, 48.3% vs 29.8%, P = 0.001) and overall survival (OS, HR = 0.70, P = 0.033). Furthermore, we validated the predictive potential of KMT2A/C mutations in an expanded ICI-treated cohort (n = 1395). KMT2A/C-mutant patients achieved better OS compared with KMT2A/C-wildtype patients (HR = 0.68, P = 0.003); and the survival advantages appeared in the majority of cancer subtypes. Our study suggests that KMT2A/C mutations function as a novel and potential predictive biomarker for ICI treatment in multiple solid tumors and the underlying mechanism is worth investigating.
Tumor response prediction in 90Y radioembolization with PET-based radiomics features and absorbed dose metrics
Authors: Wei Lise , Cui Can , Xu Jiarui , Kaza Ravi , El Naqa Issam , Dewaraja Yuni K.
Published: December 2020

Purpose

To evaluate whether lesion radiomics features and absorbed dose metrics extracted from post-therapy 90Y PET can be integrated to better predict outcomes in microsphere radioembolization of liver malignancies

Methods

Given the noisy nature of 90Y PET, first, a liver phantom study with repeated acquisitions and varying reconstruction parameters was used to identify a subset of robust radiomics features for the patient analysis. In 36 radioembolization procedures, 90Y PET/CT was performed within a couple of hours to extract 46 radiomics features and estimate absorbed dose in 105 primary and metastatic liver lesions. Robust radiomics modeling was based on bootstrapped multivariate logistic regression with shrinkage regularization (LASSO) and Cox regression with LASSO. Nested cross-validation and bootstrap resampling were used for optimal parameter/feature selection and for guarding against overfitting risks. Spearman rank correlation was used to analyze feature associations. Area under the receiver-operating characteristics curve (AUC) was used for lesion response (at first follow-up) analysis while Kaplan-Meier plots and c-index were used to assess progression model performance. Models with absorbed dose only, radiomics only, and combined models were developed to predict lesion outcome.

Results

The phantom study identified 15/46 reproducible and robust radiomics features that were subsequently used in the patient models. A lesion response model with zone percentage (ZP) and mean absorbed dose achieved an AUC of 0.729 (95% CI 0.702–0.758), and a progression model with zone size nonuniformity (ZSN) and absorbed dose achieved a c-index of 0.803 (95% CI 0.790–0.815) on nested cross-validation (CV). Although the combined models outperformed the radiomics only and absorbed dose only models, statistical significance was not achieved with the current limited data set to establish expected superiority.

Conclusion

We have developed new lesion-level response and progression models using textural radiomics features, derived from 90Y PET combined with mean absorbed dose for predicting outcome in radioembolization. These encouraging, but limited results, will need further validation in independent and larger datasets prior to any clinical adoption.
Nodular fasciitis growing at the port site of robotic surgery for rectal cancer
Authors: Yamamoto Atsushi , Furuya Shinji , Takiguchi Koichi , Sudo Makoto , Shoda Katsutoshi , Akaike Hidenori , Hosomura Naohiro , Kawaguchi Yoshihiko , Amemiya Hidetake , Kawaida Hiromichi , Kono Hiroshi , Ichikawa Daisuke
Published: December 2020

Background

Nodular fasciitis (NF) is a type of rare and rapidly growing tumor that affects the muscular fascial layers. Due to its locally aggressive nature and rapid growth, NF can be mistaken as a malignant process on either clinical or histological grounds.

Case presentation

A 61-year-old man was affected by rectal cancer. We performed a robotic, high-anterior resection with lymph node dissection. According to the 8th edition of Union for International Cancer Control, the diagnosis was stage I pT2N0M0. During a routine follow-up 1.5 years after the robotic surgery, a computed tomography examination revealed a tumor in the upper right abdominal wall, at the site of the surgical port, that measured 45 mm. Magnetic resonance imaging indicated a hypo-intensive mass within the right straight muscle of the abdomen. Port site recurrence following the robotic surgery for rectal cancer was suspected, and an ultrasound-guided fine-needle aspiration was performed; it revealed a low-grade myofibroblastic tumor or benign neoplasm, but was inconclusive. We performed an excision of the lesion, and histopathology confirmed NF, seen as a solid, nodular, spindle-cell lesion. The patient was postoperatively followed for more than 1 year without any sign of recurrence of either cancer or NF.

Conclusions

NF is histologically benign, but local recurrence frequently occurs. We encountered a patient with NF at the port site after robotic surgery for rectal cancer.
Intraoperative responses of motor evoked potentials to the novel intravenous anesthetic remimazolam during spine surgery: a report of two cases
Authors: Kondo Takashi , Toyota Yukari , Narasaki Soshi , Watanabe Tomoyuki , Miyoshi Hirotsugu , Saeki Noboru , Tsutsumi Yasuo M.
Published: December 2020

Background

Remimazolam is a novel short-acting benzodiazepine characterized by metabolism independent from organ function. We report intraoperative MEP responses of two patients who underwent spine surgery under general anesthesia using remimazolam.

Case presentation

In case 1, MEP monitoring was successfully performed with the use of a fixed dose of remimazolam at 0.5 mg/kg/h and remifentanil at 0.2 μg/kg/min. In case 2, an increasing dose of remimazolam from 0.5 to 1.5 mg/kg/h during the operation did not affect MEP signals. In both cases, remimazolam was titrated to maintain the values of entropy electroencephalogram (EEG) monitoring at 40–60.

Conclusions

General anesthesia using remimazolam and remifentanil can be a valuable alternative for spine surgery with MEP monitoring by EEG to assess the optimal dose.
Child dietary diversity and food (in)security as a potential correlate of child anthropometric indices in the context of urban food system in the cases of north-central Ethiopia
Authors: Dinku Amare Molla , Mekonnen Tefera Chane , Adilu Getachew Shumye
Published: December 2020

Objective

To investigate the relation of child dietary diversity and household food insecurity along with other socio-demographic with child anthropometric indices in north-central Ethiopia, an area with a high level of food insecurity and inadequate diet quality.

Design

A community-based cross-sectional study was used.

Settings

The study was conducted in Dessie and Combolcha towns of north-central Ethiopia from April to May 2018.

Participants

Randomly selected 512 mother-child pairs with child’s age range of 6–59 months.

Results

The mean (± SD) scores of weight-for-height/length, height/length-for-age, weight-for-age, and BMI-for-age Z-scores were 1.35 (± 2.03), − 1.89 (± 1.79), 0.05 (± 1.54), and 1.39 (± 2.06), respectively. From all anthropometric indicators, stunting and overweight/obesity remained the severe public issues hitting 43% and 42% of the children, respectively. In the model, mothers’ age and education and child’s age, sex, and dietary diversity were significantly related with child height-for-age Z-score while place of residence, sex of household head, child’s age, and dietary diversity score were the predictors of child BMI-for-age Z-score in the urban contexts of the study area. Nevertheless, food insecurity was not related to any of the child anthropometric indices.

Conclusion

The double burden of malnutrition epidemics (stunting and obesity) coexisted as severe public health concerns in urban settings. Anthropometric statuses of children were affected by multidimensional factors and seek strong integration and immediate intervention of multiple sectors.
The ‘R’ principles in laboratory animal experiments
Authors: Lee Kook Hyun , Lee Dong Won , Kang Byeong Chul
Published: December 2020

Since the Three Rs of replacement, reduction and refinement was proposed by Russel and Birch in 1959, researchers have a moral duty to minimize harm to animals. Even though animal experiments are performed by the Three Rs concept, animal researches which do not comply with international rules and standards are not accepted as well. As animal welfare has been important global issues, the methods to assess animal welfare compromise and distress have been proposed. Humanity is accepted as the goal of the Three Rs, however, another fourth R, ‘Refusal’ of fruitless protocol or ‘Responsibility’ for the experimental animal and social, scientific status of the animal experiments has been proposed. After establishing goals of animal research in a respective society, reliable knowledge can be obtained while improving laboratory animal welfare.
Contributory role of SARS-CoV-2 genomic variations and life expectancy in COVID-19 transmission and low fatality rate in Africa
Authors: Omotoso Olabode E.
Published: December 2020

Background

The novel coronavirus disease (COVID-19) has claimed lots of lives, posing a dire threat to global health. It was predicted that the coronavirus outbreak in the African population would be very lethal and result to economic devastation owing to the prevalence of immune-compromised population, poverty, low lifespan, fragile health care systems, poor economy, and lifestyle factors. Accumulation of mutations gives virus selective advantage for host invasion and adaptation, higher transmissibility of more virulent strains, and drug resistance. The present study determined the severe acute respiratory syndrome-2 (SARS-CoV-2) genomic variability and the contributory factors to the low COVID-19 fatality in Africa. To assess the SARS-CoV-2 mutational landscape, 924 viral sequences from the Africa region with their sociobiological characteristics mined from the Global Initiative on Sharing All Influenza Data (GISAID) database were analyzed.

Results

Mutational analysis of the SARS-CoV-2 sequences revealed highly recurrent mutations in the SARS-CoV-2 spike glycoprotein D614G (97.2%), concurrent R203K, and G204R (65.2%) in the nucleocapsid phosphoprotein, and P4715L (97.2%) in the RNA-dependent RNA polymerase flagging these regions as SARS-CoV-2 mutational hotspots in the African population. COVID-19 is more severe in older people (> 65 years); Africa has a low percentage of people within this age group (4.36%). The average age of the infected patients observed in this study is 46 years with only 47 infected patients (5.1%) above 65 years in Africa in comparison to 13.12% in countries in other continents with the highest prevalence of COVID-19.

Conclusions

Africa’s young generation, the late incidence of the disease, and adherence to public health guidelines are important indicators that may have contributed to the observed low COVID-19 deaths in Africa. However, with the easing of lockdown and regulatory policies, daily increasing incidence in most countries, and low testing and sequencing rate, the epidemiology and the true impact of the pandemic in Africa remain to be unraveled.
Impact of transformational leadership on work performance, burnout and social loafing: a mediation model
Authors: Khan Hira , Rehmat Maryam , Butt Tahira Hassan , Farooqi Saira , Asim Javaria
Published: December 2020

The aim of this research was to study the effect of transformational leadership on employees’ work outcomes which include their work performances and working burnout, and their working behavior such as social loafing at workplace. Also, it studies the impact of intrinsic motivation as a mediator between transformational leadership and other stated variables. A cross-sectional survey was conducted to collect data from 308 employees working in the telecommunication sector. To test the hypotheses, Model 4 of Process Hayes was used to test direct and mediating effects among transformational leadership and employees’ work outcomes and working behavior. The results showed that transformational leadership has a significant positive relationship with mediator intrinsic motivation. The results also concluded that work performance has positive significant relationship with transformational leadership. However, there is indirect and insignificant relationship of transformational leadership with working burnout and social loafing. Therefore, it can be stated that organizational leaders must have transformational attributes by getting informed of their employees well because transformational leader can inspire employees to achieve anticipated or significant outcomes. It gives employees self-confidence over specific jobs, as well as the power to make decisions once they have been trained.
The Character Sketch, the Aesthetics of Representativeness, and Rip Van Winkle’s Electoral Double Vision
Authors: Mansouri Leila
Published: December 2020

This essay examines how a literary genre called the character sketch shaped the ways Americans came to understand electoral representation as representative. Now little known but central to eighteenth- and early-nineteenth-century literary culture in the US and Britain, character sketches and a related aesthetic discourse about how to distinguish “well-drawn characters” from caricature helped to naturalize the notion that meaningful, legitimate representation should be grounded in clearly delineated categories and distinctions that were true to the “Laws of Nature and Nature’s God.” However, this aesthetic and political framework intersected uneasily with the early nineteenth century’s racially and economically diverse electoral public sphere. This public sphere was rife with fear that electoral “combinations” would so badly misrepresent the electorate that the United States would be functionally returned to tyranny. And these abstract fears often became entangled with the embodied discomfort genteel white men like Washington Irving experienced when “beer-barrel” politics brought them into contact with fellow voters whom they considered themselves naturally socially or racially distinct from. As a result, this paper shows, writing for and about early US elections—including Washington Irving’s “Rip Van Winkle” (1819), whose electoral plot is often overlooked—was imbued with a disconcerting sense of double vision. Only by recovering that double vision’s embodied and racialized electoral context can critics fully grapple with the aesthetic and political legacy of American literature’s uneasy foundations.
The Rise of the Conspicuously Young Novelist
Authors: Maguire Michael
Published: December 2020

This essay illuminates the history of what David Foster Wallace dubbed the “conspicuously young” novelist (CYN), drawing on a series of brief case studies (F. Scott Fitzgerald, Raymond Radiguet, Carson McCullers, Truman Capote, Sylvia Plath, and James Baldwin) that demonstrate how certain CYNs were marketed and represented in advertising and journalistic discourse. In the process, it traces the construction of a number of ostensibly meritocratic—but in practice highly inequitable—institutions that functioned to identify, sponsor, and promote young writers. Finally, this essay examines the pervasive critical rhetoric of “promise,” which offers the key to understanding the dynamic of hype and disappointment immanent to each “younger generation” of CY writers.
COVID-19 mimics on chest CT: a pictorial review and radiologic guide
Authors: Hochhegger Bruno , Zanon Matheus , Altmayer Stephan , Mandelli Nicole S , Stüker Guilherme , Mohammed Tan-Lucien , Verma Nupur , Meirelles Gustavo Souza Portes , Marchiori Edson
Published: December 2020

Chest imaging is often used as a complementary tool in the evaluation of coronavirus disease 2019 (COVID-19) patients, helping physicians to augment their clinical suspicion. Despite not being diagnostic for COVID-19, chest CT may help clinicians to isolate high suspicion patients with suggestive imaging findings. However, COVID-19 findings on CT are also common to other pulmonary infections and non-infectious diseases, and radiologists and point-of-care physicians should be aware of possible mimickers. This state-of-the-art review goal is to summarize and illustrate possible etiologies that may have a similar pattern on chest CT as COVID-19. The review encompasses both infectious etiologies, such as non-COVID viral pneumonia, Mycoplasma pneumoniae, Pneumocystis jiroveci, and pulmonary granulomatous infectious, and non-infectious disorders, such as pulmonary embolism, fat embolism, cryptogenic organizing pneumonia, non-specific interstitial pneumonia, desquamative interstitial pneumonia, and acute and chronic eosinophilic pneumonia.
Η αναγκαιότητα του «χρήσιμου ψεύδους» στην πλατωνική Πολιτεία
Authors: Κακλαμάνου Ελένη
Published: December 2020

Ο Πλάτων στην Πολιτεία προβαίνει στη διάκριση ανάμεσα σε «ψεύδη στην ψυχή» και «ψεύδη στα λόγια» και στην ενσωμάτωση των δεύτερων στην ιδανική πολιτεία του μέσα από τις περιπτώσεις της χρήσιμης απάτης. Διευκρινίζει ότι μόνο οι άρχοντες νομιμοποιούνται να κάνουν χρήση του ψεύδους, όταν αυτό αποβλέπει στο όφελος της πόλης, όπως συμβαίνει στην περίπτωση του γενναίου ψεύδους. Η παραχώρηση του δικαιώματος στους άρχοντες να εφευρίσκουν ψεύδη προς όφελος των αρχομένων έχει φαρμακολογικό χαρακτήρα.Ο Popper (1966) κατηγορεί τον Πλάτωνα για πολιτική ανηθικότητα εξαιτίας της χρήσης άνομων μέσων, όπως το ψεύδος, με σκοπό τη διατήρηση της εξουσίας, η οποία είναι συγκεντρωμένη στα χέρια μιας μικρής τάξη ανθρώπων. Σε μια πρόσφατη μελέτη, ο Schofield (2006) ισχυρίζεται οι περιπτώσεις ψεύδους δεν αντιφάσκουν με την προσπάθεια του Πλάτωνα να δημιουργήσει μια δίκαιη πόλη, αλλά αποτελούν μέρος της επιχειρηματολογίας του, ένα είδος πολιτικής ρητορικής, στην απόπειρα να συσταθεί η δίκαιη πόλη.Στόχος της παρούσας έρευνας είναι να εξετάσει διεξοδικά τα «χρήσιμα ψεύδη» στην Πολιτεία, τη διαφορετική φύση τους, αλλά και τις δυσκολίες που δημιουργεί στον Πλάτωνα η συμπερίληψή τους στην ιδανική πολιτεία του. Μέρος της έρευνας είναι η ανάλυση της έννοιας του ψεύδους, της απάτης και άλλων σχετικών εννοιών. Η προσφυγή στην ολοένα αυξανόμενη βιβλιογραφία αναφορικά με την έννοια του ψεύδους και της απάτης συμβάλλει στην αποσαφήνιση των ιδιαιτεροτήτων κάθε είδους ψεύδους. Η έρευνα, λοιπόν, επιχειρεί να καταδείξει ότι το ψεύδος στον Πλάτωνα δεν είναι μόνο ηθικό, αλλά και γνωσιολογικό θέμα. Επιπλέον, εξετάζει παράλληλα τα κείμενα της εποχής (ρητορική, ιστορία, τραγωδία) όσον αφορά στο ερώτημα γιατί προτείνονται τα συγκεκριμένα ψεύδη έναντι κάποιων άλλων. Ένας από τους άξονες της επιχειρηματολογίας είναι ότι ο Πλάτων «δανείζεται» παραδείγματα ψεύδους από την αθηναϊκή ιστορία και τη δημοκρατική καθημερινότητά του και τα επανανοηματοδοτεί, παρουσιάζοντάς τα εντέλει ως περιπτώσεις ψεύδους του κοινού νου.
Rachel A. Epstein - Banking on Markets .The Transformation of Bank-State. Ties in Europe and Beyond
Authors: Καζαντζής Κωνσταντίνος
Published: December 2020

Δεν διατίθεται
Staphylococcus aureus secreted lipases do not inhibit innate immune killing mechanisms
Authors: Sargison Fiona , Alves Joana , Pickering Amy , Fitzgerald J Ross
Published: December 2020

Background: Staphylococcus aureus causes an array of diseases in both humans and livestock. Pathogenesis is mediated by a plethora of proteins secreted by S. aureus, many of which remain incompletely characterised. For example, S. aureus abundantly secretes two isoforms of the enzyme lipase into the extracellular milieu, where they scavenge upon polymeric triglycerides. It has previously been suggested that lipases may interfere with the function of innate immune cells, such as macrophages and neutrophils, but the impact of lipases on phagocytic killing mechanisms remains unknown.

Methods: We employed the epidemic S. aureus clone USA300 strain LAC and its lipase deficient isogenic mutant, along with recombinant lipase proteins, in in vitro experimental infection assays. To determine if lipases can inhibit innate immune killing mechanisms, the bactericidal activity of whole blood, human neutrophils, and macrophages was analysed. In addition, gentamycin protection assays were carried out to examine the influence of lipases on S. aureus innate immune cell escape.

Results: There were no differences in the survival of S. aureus USA300 LAC wild type and its lipase-deficient isogenic mutant after incubation with human whole blood or neutrophils. Furthermore, there was no detectable lipase-dependent effect on phagocytosis, intracellular survival, or escape from both human primary and immortalised cell line macrophages, even upon supplementation with exogenous recombinant lipases.

Conclusions: S. aureus lipases do not inhibit bacterial killing mechanisms of human macrophages, neutrophils, or whole blood. These findings broaden our understanding of the interaction of S. aureus with the innate immune system.