bluuebunny/crossref_metadata_2025 huggingface dataset:
Los judíos en Olisipo (Lisboa). Reflexiones a partir de un posible sello de panadero
Authors: Ávila Ribeiro Ricardo , Neto Nuno , Rebelo Paulo , Bustamante álvarez Macarena
Published: October 2022

Se presenta un sello circular cerámico con iconografía hebraica localizado en Lisboa en un contexto de época tardorromana. En él aparece una menorah esquematizada. En el presente trabajo, además de realizar un análisis iconográfico,  tipológico y funcional del mismo se indaga sobre otros paralelos en clave diacrónica. También el sello ha servido de excusa para reflexionar sobre la presencia de la comunidad judaica en la Hispania romana.
Design and Implementation of Microstrip Array Antenna 2x4 Circular Patch with Defected Ground Structure Dumbbell Hexagonal Head 2.4 GHz Frequency for Wi-Fi Application
Authors: Sholikhah Tania Izza , Koesmarijanto Koesmarijanto , Darmono Hendro
Published: October 2022

Wireless technology is a wireless communication technology that is currently widely used by the public to exchange information. The current information exchange is growing as communication requirements rise. The antenna design needs to be improved in order to boost bandwidth. Microstrip antennas are one kind of antenna that can be used for wireless communication. Meanwhile, to improve the bandwidth value of the antenna can be done using the Defected ground structure or DGS technique. The results of testing the microstrip array circular patch antenna with DGS at 2462 MHz frequency show that it has a maximum gain of 15.7 dBi at a frequency of 2530 MHz and a return loss value of -19.3 dB with a VSWR value of 1,242. There is a type of directional radiation pattern in the antenna of the Microstrip Array with DGS. This study's findings indicate that the Circular Array Microstrip antenna with DGS has a bandwidth of 73 MHz while the Circular Microstrip Array without DGS has a lesser bandwidth of 28 MHz.
Central Bank Digital Currencies: considerations for a not-too-distant future
Authors: Vilela Sampaio Adriano , Centeno Vinicius
Published: October 2022

The central bank digital currencies (CBDC) are subjects of the rising interest of central banks from advanced and emerging economies. Given the relevance and topicality of the subject, this paper seeks to organize the debate that encompasses what is understood as CBDC in the recent international literature, as well as to analyze the possible implications of its implementation. Given that CBDC may assume various forms, there’s still high uncertainty regarding its potential costs and benefits. The decisions concerning the features of the CBDC may have deep implications on various aspects such as the resilience of the domestic financial system, monetary policy effectiveness, functioning of the credit system, and means of payments, among others. Despite the uncertainty associated with the range of possible CBDC architectures, we argue that the strategies of the central banks regarding CBDC may be seen as defensive, as a way to keep up with the technological and cultural changes whilst managing to conduct the process and sustain its central role on the financial system.
Learning beyond formal education in Africa: a selection of contributions to JOPEA 2017-2022
Authors: Nordvall Henrik
Published: October 2022

This volume addresses research on adult learning and the circulation of knowledge beyondthe formal education systems in Sub-Saharan Africa. It is also a volume celebratingthe fact that Journal of Popular Education in Africa (JOPEA), founded in 2017, has existed fora half decade. To draw attention to this anniversary undersigned, together with professoremeritus Staffan Larsson, have been trusted by the editors of this Kenya-based journal toselect for re-publication a few articles published in the journal over the years. Larsson andI are both part of the Division of Education and Adult Learning at Linköping Universityin Sweden, one of the world’s most prominent university settings in the area of adultlearning. Both of us have also for several years been involved in various forms of collaborationswith colleagues in the field of adult education research on the African continent.
The development and use of decision support framework for informing selection of select agent toxins with modelling studies to inform permissible toxin amounts
Authors: Pillai Segaran P. , West Todd , Levinson Rebecca , Fruetel Julia A. , Anderson Kevin , Edwards Donna , Morse Stephen A.
Published: October 2022

Many countries have worked diligently to establish and implement policies and processes to regulate high consequence pathogens and toxins that could have a significant public health impact if misused. In the United States, the Antiterrorism and Effective Death Penalty Act of 1996 (Public Law 104-132, 1996), as amended by the Bioterrorism Preparedness and Response Act of 2002 (Public Law 107-188, 2002) requires that the Department of Health and Human Services (HHS) [through the Centers for Disease Control and Prevention (CDC)] establish a list of bacteria, viruses, and toxins that have the potential to pose a severe threat to public health and safety. Currently, this list is reviewed and updated on a biennial basis using input from subject matter experts (SMEs). We have developed decision support framework (DSF) approaches to facilitate selection of select toxins and, where toxicity data are known, conducted modelling studies to inform selection of toxin amounts that should be excluded from select agent regulations. Exclusion limits allow laboratories to possess toxins under an established limit to support their research or teaching activities without the requirement to register with the Federal Select Agent Program. Fact sheets capturing data from a previously vetted SME workshop convened by CDC, literature review and SME input were developed to assist in evaluating toxins using the DSF approach. The output of the DSF analysis agrees with the current select toxin designations, and no other toxins evaluated in this study were recommended for inclusion on the select agent and toxin list. To inform the selection of exclusion limits, attack scenarios were developed to estimate the amount of toxin needed to impact public health. Scenarios consisted of simulated aerosol releases of a toxin in high-population-density public facilities and the introduction of a toxin into a daily consumable product supply chain. Using published inhalation and ingestion median toxic dose (TD50) and median lethal dose (LD50) values, where available, a range of toxin amounts was examined to estimate the number of people exposed to these amounts in these scenarios. Based on data generated by these models, we proposed toxin exclusion values corresponding to levels below those that would trigger a significant public health response (i.e., amounts estimated to expose up to ten people by inhalation or one hundred people by ingestion to LD50 or TD50 levels of toxin in the modeled scenarios).
Novel biodesign enhancements to at-risk traditional building materials
Authors: Booth Peter , Jankovic Ljubomir
Published: October 2022

Extreme weather conditions increase the frequency of regular maintenance on heritage buildings and cause erosion of traditional materials. Developments in bio-enhanced self-repair materials provide an opportunity to improve building performance and reduce the frequency of costly maintenance schedules. The microbial sequestration of carbon by bacteria, encapsulated and layered into several limewash coats, facilitates capturing atmospheric carbon and reduces carbon-generating maintenance regimes. The use of hydrogels, alginates and biofilm derived biopolymers as novel bacterial encapsulation and nutrient delivery vehicles is discussed and the opportunity to develop self-healing sacrificial limewash as a future research project. Microbial enhanced carbon-fixing limewash may also offer a broader application to improve the performance of sustainable materials such as hemp-lime bio-composites as a fast-forward projection of problems and solutions with these materials in the future.
In a pursuit of optimal glycan fluorescent label for negative MS mode for high-throughput N-glycan analysis
Authors: Šoić Dinko , Mlinarić Zvonimir , Lauc Gordan , Gornik Olga , Novokmet Mislav , Keser Toma
Published: October 2022

Over the past few decades, essential role of glycosylation in protein functioning has become widely recognized, rapidly advancing glycan analysis techniques. Because free glycan’s lack chromophore or fluorophore properties, and do not ionize well, they are often derivatized to facilitate their separation or detection, and to enhance the sensitivity of the analysis. Released glycan’s are usually derivatized using a fluorescent tag, which enables their optical detection in LC profiling. Some fluorescent labels can also promote ionization efficiency, thus facilitating MS detection. For this reason, there is a need to design fluorophores that will contribute more to the fluorescence and ionization of glycan’s and the need to quantify these contributions to improve glycan analysis methods. In this paper we focused on negative MS mode as these methods are more informative than methods involving positive MS mode, allowing for a less ambiguous elucidation of detailed glycan structures. Additionally, traditional glycan labels in negative mode MS usually result with diminished sensitivity compared to positive mode, thus making selection of appropriate label even more important for successful high-throughput analysis. Therefore, eleven fluorescent labels of different chemo-physical properties were chosen to study the influence of label hydrophobicity and presence of a negative charge on glycan ionization in negative MS mode. N-glycans released from IgG sample were labeled with one of the eleven labels, purified with HILIC-SPE and analyzed with HILIC-UPLC-FLR-MS. To make evaluation of studied labels performance more objective, analysis was performed in two laboratories and at two mobile phase pH (4.4 and 7.4). Although there was a notable trend of more hydrophobic labels having bigger signal intensities in one laboratory, we observed no such trend in the other laboratory. The results show that MS parameters and intrinsic configuration of the spectrometer have even bigger effect on the final ESI response of the labeled-glycan ionization in negative MS mode that the labels themselves. With this in mind, further research and development of fluorophores that will be suitable for high-throughput glycan analysis in the negative MS mode are proposed.
Mycobacterium tuberculosis functional genetic diversity, altered drug sensitivity, and precision medicine
Authors: Stanley Sydney , Liu Qingyun , Fortune Sarah M.
Published: October 2022

In the face of the unrelenting global burden of tuberculosis (TB), antibiotics remain our most effective tools to save lives and control the spread of Mycobacterium tuberculosis (Mtb). However, we confront a dual challenge in our use of antibiotics: simplifying and shortening the TB drug regimen while also limiting the emergence and propagation of antibiotic resistance. This task is now more feasible due to the increasing availability of bacterial genomic data at or near the point of care. These resources create an opportunity to envision how integration of bacterial genetic determinants of antibiotic response into treatment algorithms might transform TB care. Historically, Mtb drug resistance studies focused on mutations in genes encoding antibiotic targets and the resulting increases in the minimal inhibitory concentrations (MICs) above a breakpoint value. But recent progress in elucidating the effects of functional genetic diversity in Mtb has revealed various genetic loci that are associated with drug phenotypes such as low-level MIC increases and tolerance which predict the development of resistance and treatment failure. As a result, we are now poised to advance precision medicine approaches in TB treatment. By incorporating information regarding Mtb genetic characteristics into the development of drug regimens, clinical care which tailors antibiotic treatment to maximize the likelihood of success has come into reach.
A rapid One-Pot RNA isolation method for simplified clinical detection of SARS-COV-2 infection in India
Authors: Jain Sonia , Bhowmick Arghya , Pandey Anil Kumar
Published: October 2022

Background

With the rapid increase in COVID-19 cases and the discovery of new viral variants within India over multiple waves, the expensive reagents and time-consuming sample pretreatment required for qPCR analysis have led to slower detection of the disease. The vast Indian population demands an inexpensive and competent sample preparation strategy for rapid detection of the disease facilitating early and efficient containment of the disease.

Methods

In this study, we have surveyed the spread of COVID-19 infection over Faridabad, Haryana, India for 6 months. We also devised a simple single-step method for total RNA extraction using a single tube and compared its efficacy with the commercially available RNA isolation kits.

Findings

Our findings suggest that determining Ct values for samples subjected to the One Pot RNA extraction method was as efficient as the commercially available kits but delivers a subtle advantage in a way, by minimizing the cost, labor and sample preparation time.

Conclusion

This novel crude RNA extraction method is stable and capable of operating in developing countries like India for low resource settings, without the use of expensive reagents and instruments. Additionally, this method can be further adapted to pooling samples strategies owing to its high sensitivity.
Contemporary learning techniques for healthcare professionals: A narrative review
Authors: Pandit Anand S.
Published: October 2022

Background

As medical knowledge continues to expand at an accelerated rate, healthcare professionals face a significant challenge in remaining up-to-date. The goal of this narrative review was to present evidence-based learning strategies that could aid postgraduate clinical education.

Design

Articles were sought for using PubMed, Ovid, PsychINFO, ERIC databases and only included if relevant to the review objective.

Results

A total of 103 articles, chapters, and books were used to compose this narrative review. An additional 135 articles and chapters were examined in full for context. The review is divided into two sections: (1) strategies that can help foster a learning mind-set; and (2) high-yield practical tools that are effective in formal or informal learning domains.

Conclusion

Individual learning is a cornerstone of clinical performance, which influences the quality of care that one can deliver. This review offers a comprehensive set of learning tools for individuals across a variety of settings.
Exploring achievement-level differences in implementing self-regulated learning instruction in a classical Chinese reading intervention program
Authors: Lau Kit Ling
Published: October 2022

Research on self-regulated learning (SRL) instruction typically treats students as a homogeneous group, without considering the possible effects of students’ prior level of SRL competence on the implementation and effectiveness of SRL instruction. To fill this research gap, this study explored the differences in learning outcomes among students with different achievement levels who received an SRL-based classical Chinese reading instruction program. Sixty seven ninth graders from two classes, one with high achievers and the other with moderate achievers, from one secondary school in Hong Kong participated in an intervention program designed by this study’s researchers. The study adopted qualitative methods, including classroom observations, teacher and student interviews, along with supplementary quantitative methods, including reading test and questionnaire, to explore the differences between the two achiever-groups when the intervention program was implemented. The results showed that the two classes differed on students’ SRL performance, the degree of teacher support and student autonomy, and students’ perceptions of SRL instruction. Implications of the findings for SRL research and intervention design are discussed.
Influence analysis of metal foreign objects on the wireless power transmission system
Authors: Li Jiacheng , Huang Yijie
Published: October 2022

The wireless power transmission (WPT) system through magnetic field coupling for energy transmission may have foreign objects in the transmission channel in the practical application process, which brings hidden dangers to the WPT system. In this article, a WPT system without and with foreign objects is constructed. The influence of foreign objects on self-inductance and mutual-inductance of coupling coils is studied from the aspects of foreign object height, radius, transmission distance, and coil turns. Then, by constructing the circuit topology of the series structure, the influence of foreign objects on the transmission efficiency and the phase difference between voltage and current of the system is studied, and finally the influence law of metal foreign objects on the performance of the WPT system is summarized.
Exploring anti-androgen therapies in hormone dependent prostate cancer and new therapeutic routes for castration resistant prostate cancer
Authors: Harris Anna E. , Metzler Veronika M. , Lothion-Roy Jennifer , Varun Dhruvika , Woodcock Corinne L. , Haigh Daisy B. , Endeley Chantelle , Haque Maria , Toss Michael S. , Alsaleem Mansour , Persson Jenny L. , Gudas Lorraine J. , Rakha Emad , Robinson Brian D. , Khani Francesca , Martin Laura M. , Moyer Jenna E. , Brownlie Juliette , Madhusudan Srinivasan , Allegrucci Cinzia , James Victoria H. , Rutland Catrin S. , Fray Rupert G. , Ntekim Atara , de Brot Simone , Mongan Nigel P. , Jeyapalan Jennie N.
Published: October 2022

Androgen deprivation therapies (ADTs) are important treatments which inhibit androgen-induced prostate cancer (PCa) progression by either preventing androgen biosynthesis (e.g. abiraterone) or by antagonizing androgen receptor (AR) function (e.g. bicalutamide, enzalutamide, darolutamide). A major limitation of current ADTs is they often remain effective for limited durations after which patients commonly progress to a lethal and incurable form of PCa, called castration-resistant prostate cancer (CRPC) where the AR continues to orchestrate pro-oncogenic signalling. Indeed, the increasing numbers of ADT-related treatment-emergent neuroendocrine-like prostate cancers (NePC), which lack AR and are thus insensitive to ADT, represents a major therapeutic challenge. There is therefore an urgent need to better understand the mechanisms of AR action in hormone dependent disease and the progression to CRPC, to enable the development of new approaches to prevent, reverse or delay ADT-resistance. Interestingly the AR regulates distinct transcriptional networks in hormone dependent and CRPC, and this appears to be related to the aberrant function of key AR-epigenetic coregulator enzymes including the lysine demethylase 1 (LSD1/KDM1A). In this review we summarize the current best status of anti-androgen clinical trials, the potential for novel combination therapies and we explore recent advances in the development of novel epigenetic targeted therapies that may be relevant to prevent or reverse disease progression in patients with advanced CRPC.
Endogenous GLP-1 levels play an important role in determining the efficacy of DPP-IV Inhibitors in both prediabetes and type 2 diabetes
Authors: Chong Shiau Chin , Sukor Norlela , Robert Sarah Anne , Ng Kim Fong , Kamaruddin Nor Azmi
Published: October 2022

Background

In contrast to Western population, glucagon-like peptide-1 (GLP-1) levels are preserved in some East Asian population with type 2 diabetes (T2D), explaining why dipeptidyl peptidase-IV (DPP-IV) inhibitors are more effective in East Asians. We assessed whether differences in endogenous GLP-1 levels resulted in different treatment responses to DPP-IV inhibitors in prediabetes and T2D.

Methods

A prospective 12-week study using linagliptin 5mg once daily in 50 subjects (28 prediabetes and 22 T2D) who were stratified into high versus low fasting GLP-1 groups. A 75-g oral glucose tolerance test (OGTT) was performed at week 0 and 12. Primary outcomes were changes in HbA1c, fasting and post-OGTT glucose after 12 weeks. Secondary outcomes included changes in insulin resistance and beta cell function indices.

Results

There was a greater HbA1c reduction in subjects with high GLP-1 compared to low GLP-1 levels in both the prediabetes and T2D populations [least-squares mean (LS-mean) change of -0.33% vs. -0.11% and -1.48% vs. -0.90% respectively)]. Linagliptin significantly reduced glucose excursion by 18% in high GLP-1 compared with 8% in low GLP-1 prediabetes groups. The reduction in glucose excursion was greater in high GLP-1 compared to low GLP-1 T2D by 30% and 21% respectively. There were significant LS-mean between-group differences in fasting glucose (-0.95 mmol/L), 2-hour glucose post-OGTT (-2.4 mmol/L) in the high GLP-1 T2D group. Improvement in insulin resistance indices were seen in the high GLP-1 T2D group while high GLP-1 prediabetes group demonstrated improvement in beta cell function indices. No incidence of hypoglycemia was reported.

Conclusions

Linagliptin resulted in a greater HbA1c reduction in the high GLP-1 prediabetes and T2D compared to low GLP-1 groups. Endogenous GLP-1 level play an important role in determining the efficacy of DPP-IV inhibitors irrespective of the abnormal glucose tolerance states.
TCF7L2 gene associated postprandial triglyceride dysmetabolism- a novel mechanism for diabetes risk among Asian Indians
Authors: Madhu Sri Venkata , Mishra Brijesh Kumar , Mannar Velmurugan , Aslam Mohd , Banerjee Basudev , Agrawal Vivek
Published: October 2022

Aim

TCF7L2 gene is believed to increase the risk of T2DM by its effects on insulin secretion. However, the exact mechanism of this enhanced risk is not clearly known. While TCF7L2 gene has been shown to affect lipid metabolism, these effects have remained largely unexplored in the context of diabetes risk.

Methods

Postprandial lipid responses to a standardized fat challenge test were performed in 620 Asian Indian subjects (310 with NGT and 310 with T2DM/prediabetes) and compared between the risk and wild genotypes of the rs7903146 TCF7L2 gene. In 30 subjects scheduled to undergo abdominal surgery (10 each with NGT, Prediabetes and T2DM), adipocyte TCF7L2 gene expression was also performed by real time qPCR and confirmed by protein expression in western blot.

Results

T allele of rs7903146 TCF7L2 gene was confirmed as the risk allele for T2DM (OR=1.8(1.2-2.74), p=0.005). TT+CT genotypes of rs7903146 TCF7L2 gene showed significantly higher 4hrTg (p<0.01), TgAUC (p<0.01), peakTg (p<0.01) as well as higher postprandial plasma glucose (p=.006) levels and HOMA-IR (p=0.03) and significantly lower adiponectin levels (p=0.02) as compared to CC genotype. The expression of TCF7L2 gene in VAT was 11-fold higher in prediabetes group as compared to NGT (P<0.01) and 5.7-fold higher in T2DM group as compared to NGT group(P=0.003) and was significantly associated with PPTg and glucose levels.

Conclusion

There is significant PPTg dysmetabolism associated with the risk allele of rs7903146 polymorphism as well as adipocyte expression of TCF7L2 gene. Significant upregulation of TCF7L2 gene expression in VAT that correlates with PPTg and glycaemia is also seen in Asian Indians with glucose intolerance. Modulation of PPTg metabolism by TCF7L2 gene and the resultant PPHTg may be a novel mechanism that contributes to its diabetes risk in them.
Urban-rural income disparities and atmospheric contamination: Aggravating or restraining?
Authors: Wu Chuanhao , Zhang Zhixin , Elahi Ehsan , Mu Guoting , Zhao Peng
Published: October 2022

This article constructed the local effect and significant interaction model of the urban-rural income disparities with atmospheric contamination and conducted theoretical analysis and empirical tested the urban-rural income disparity influences regional atmospheric contamination. Data were collected from 30 Chinese provinces from 2005 to 2019, and panel regression was employed. The empirical results found that the widening income disparities between urban and rural areas will significantly increase local atmospheric contamination, and there is a significant spatial dependence on regional atmospheric contamination. When the atmospheric contamination in the immediate region is severe, the local atmospheric contamination also worsens. At the same time, the spatial spillover effect of the central area on the surrounding atmospheric contamination is significant and positively affected by the urban-rural income disparities in the central area. Expanding the urban-rural disparities will significantly increase the atmospheric contamination in central and surrounding areas. The regression results were still robust after replacing the core variables and the spatial weight calculation method. Furthermore, results found the income disparities between urban and rural areas to increase agricultural chemicals investment and rural non-agricultural economic output. It significantly and positively influenced atmospheric contamination. The income disparities between urban and rural areas of atmospheric pollution around the region were heterogeneity. The widening income disparities can significantly increase atmospheric contamination levels in less technologically advanced and more polluted areas.
Using Bayesian networks to map winter habitat for mountain goats in coastal British Columbia, Canada
Authors: Wilson Steven F. , Nietvelt Cliff , Taylor Shawn , Guertin Daniel A.
Published: October 2022

The mountain goat (Oreamnos americanus) is an iconic wildlife species of western North America that inhabits steep and largely inaccessible terrain in remote areas. They are at risk from human disturbance, genetic isolation, climate change, and a variety of other stressors. Managing populations is challenging and mountain goats are particularly difficult and expensive to inventory. As a result, biologists often rely on models to estimate the species’ abundance and distribution in remote areas. We used landscape characteristics evident at point locations of mountain goat visual observations, tracks, and telemetry locations, along with random locations, to learn the structure and parameters of a Bayesian network that predicted the suitability of habitats for mountain goats. We then used the model to map habitat suitability across 285,000 km2 of potential habitat in mountain ranges of the south and central Canadian Pacific coast. Steep slopes, forest cover characteristics, and snow depth were the important drivers. Modeling the system as a Bayesian network provided several advantages over more common regression methods because input variables were heterogenous (i.e., a mix of discrete and continuous), autocorrelated, and animals exhibited non-linear responses to landscape conditions. These common characteristics of ecological data routinely violate the assumptions of parametric linear models, which are commonly used to map habitat suitability from animal observations.
RETRACTED: Green finance strategies for mitigating GHG emissions in China: Public spending as a new determinant of green economic development
Authors: Xia Lianfeng , Liu Yujia , Tian Yunqing
Published: October 2022

In order to lessen China’s carbon footprint, the government has turned to environmentally friendly financing. A reduction in CO2 has been reported in some Chinese provinces where green finance has been developed. Numerous regions in China from 2010 to 2020 are selected for this study. Based on a Dynamic Seemingly Uncorrelated, fully modified ordinary least squares and dynamic ordinary least squares regressions model, empirical research is performed with per capita growth in the economy, public spending, and the relationship between economic growth, human resources, and industrial arrangement as core variables to test the influence of green financing on CO2 emission in Chinese provinces. According to the findings, green financing speeds up the reduction of carbon emissions. Moreover, the outcomes present that industrial structure, economic growth per capita, and trade openness increase carbon emissions. Likewise, public expenditures and human capital are significantly contributing to emissions reduction. The findings show that sustainable green environment can only be achieved by boosting the performance of green finance and increasing the level of green finance supported by the Chinese economy. Last but not least, policymakers should promote public health and education spending to fully engage in the protection of the environmental efforts to encourage green consumption while minimizing the structural problems resulting from economic activity.
Role of copper ionophore–induced death in immune microenvironment and clinical prognosis of ccRCC: An integrated analysis
Authors: Xia Shunyao , Jia Haixing , Qian Zhipeng , Xiu Youcheng
Published: October 2022

Background: Clear cell renal cell carcinoma (ccRCC) is a malignancy with a high incidence rate and poor prognosis worldwide. Copper ionophore–induced death (CID) plays an important role in cancer progression.

Methods: One training and three validation datasets were acquired from TCGA, GEO and ArrayExpress. K-means clustering was conducted to identify the CID subtypes. The ESTIMATE and CIBERSORT algorithms were employed to illustrate the immune microenvironment of ccRCC. LASSO Cox regression was applied to construct the CID feature-based prognostic model. The immunotherapy cohort was acquired from the literature to explore the potential risk scores for predicting immunotherapy responsiveness.

Results: Two CID-related cancer subtypes of ccRCC were identified that performed different immune microenvironment characteristics and prognosis. Based on the identified subtypes, we analyzed the biological heterogeneity and constructed a gene prognostic model. The prognostic model performed well in one training dataset, three validation datasets, and different clinical pathological groups. The prognostic model has a good potential for predicting cancer immune features and immunotherapy responsiveness.

Conclusion: CID plays an important role in the tumor microenvironment progression of ccRCC. The robust gene prognostic model developed can help predict cancer prognosis, immune features, and immunotherapy responsiveness.
Revealing prognostic and tumor microenvironment characteristics of cuproptosis in bladder cancer by genomic analysis
Authors: Zhang Shun , Yu Shenggen , Duan Huangqi , Xia Weimin , Wang Chen , Shen Haibo
Published: October 2022

Objectives: Bladder cancer (BLCA) is the most common malignant tumor in the urinary system, while the prognosis of muscle-invasive bladder cancer (MIBC) is poor. Cuproptosis might be a promising therapeutic approach to trigger tumor cell death. This study aimed to figure out the role of cuproptosis in BLCA and constructed a new cuproptosis scoring system to guide clinical diagnosis and individualize treatments.

Methods: Consensus clustering was used to classify 490 patients with BLCA from TCGA and GEO cohorts. Survival outcomes and functional enrichment analyses were performed between the different subtypes. The cuproptosis scoring system was constructed by LASSO-Cox analysis. ESTIMATE, CIBERSORT, and ssGSEA were used to investigate the tumor microenvironment (TME). Drug sensitivity was evaluated with pRRophetic. An immunotherapy cohort was used to investigate the treatment response. The cuproptosis scoring system was verified in our own cohort with quantitative real-time PCR.

Results: An overview of 12 cuproptosis genes (CuGs) in the TCGA database was depicted. Based on the mRNA expression profiles of CuGs, patients were classified into two cuproptosis molecular patterns. Based on the differential genes between the two cuproptosis patterns, the patients were classified into two cuproptosis gene clusters. There were distinct survival outcomes, signaling pathways, and TME between the two subtypes. A 7-gene cuproptosis scoring system was constructed. Patients with high cuproptosis scores showed worse OS and more immunosuppressing TME than those with low cuproptosis scores. The two cuproptosis score groups had distinct mutation profiles. Patients with high cuproptosis scores tended to be sensitive to chemotherapy drugs, but insensitive to immune checkpoint inhibitors (ICIs) treatment.

Conclusion: This study depicted the landscape of cuproptosis in BLCA. We constructed a cuproptosis scoring system to predict the prognosis of BLCA patients. There were significant differences in survival outcomes, TME, mutation profiles, and drug sensitivities in high and low cuproptosis score patients. The cuproptosis scoring system could help oncologists comprehensively understand the tumor characteristic of BLCA and make individualized treatment strategies.
IgA vasculitis update: Epidemiology, pathogenesis, and biomarkers
Authors: Xu Liyun , Li Yongzhen , Wu Xiaochuan
Published: October 2022

Immunoglobulin A vasculitis (IgAV), formerly known as Henoch-Schönlein purpura, is the most common systemic vasculitis in children, characterized by diverse clinical manifestations with a wide spectrum ranging from isolated cutaneous vasculitis to systemic involvement. The incidence of IgAV is geographically and ethnically variable, with a prevalence in autumn and winter, suggesting a driving role that genetic and environmental factors play in the disease. Although IgAV has a certain degree of natural remission, it varies widely among individuals. Some patients can suffer from severe renal involvement and even progress to end-stage renal disease. Its pathogenesis is complex and has not been fully elucidated. The formation of galactose-deficient IgA1 (Gd-IgA1) and related immune complexes plays a vital role in promoting the occurrence and development of IgAV nephritis. In addition, neutrophil activation is stimulated through the binding of IgA to the Fc alpha receptor I expressed on its surface, resulting in systemic vascular inflammation and tissue damage. Starting from the epidemiological characteristics, this article will review the role of immunological factors such as Gd-IgA1, autoantibodies, circulating immune complexes, complement system, cellular immunization, and the contributions of environmental and genetic factors in the pathogenesis of IgAV, and conclude with the major biomarkers for IgAV.
Helminth infection and helminth-derived products: A novel therapeutic option for non-alcoholic fatty liver disease
Authors: Liu Xi , Jiang Yuyun , Ye Jixian , Wang Xuefeng
Published: October 2022

Non-alcoholic fatty liver disease (NAFLD) is closely related to obesity, diabetes, and metabolic syndrome (MetS), and it has become the most common chronic liver disease. Helminths have co-evolved with humans, inducing multiple immunomodulatory mechanisms to modulate the host’s immune system. By using their immunomodulatory ability, helminths and their products exhibit protection against various autoimmune and inflammatory diseases, including obesity, diabetes, and MetS, which are closely associated with NAFLD. Here, we review the pathogenesis of NAFLD from abnormal glycolipid metabolism, inflammation, and gut dysbiosis. Correspondingly, helminths and their products can treat or relieve these NAFLD-related diseases, including obesity, diabetes, and MetS, by promoting glycolipid metabolism homeostasis, regulating inflammation, and restoring the balance of gut microbiota. Considering that a large number of clinical trials have been carried out on helminths and their products for the treatment of inflammatory diseases with promising results, the treatment of NAFLD and obesity-related diseases by helminths is also a novel direction and strategy.
Population structure of the shallow coral Madracis auretenra in the Caribbean Sea
Authors: Ballesteros-Contreras Diana Carolina , Barrios Lina M. , Preziosi Richard
Published: October 2022

The shallow coral Madracis auretenra has an important role in the rich diversity of coral reef ecosystems found in the Caribbean Sea, providing habitat and support to different marine species. Improved understanding of the genetic structure of marine species in the region is needed for the design and management of marine reserves, which are usually created as a biodiversity conservation tool. In this study, seventeen new microsatellite markers were used to examine the population structure of M. auretenra through different areas in the Caribbean Sea (Guatemala, Colombia, Curacao and Barbados), analysing 313 samples from 18 localities. A significant differentiation and a clear clustering were found (k=11), indicating structure in the Caribbean sampled populations with high levels of inbreeding. A pattern of isolation by distance was present in all the localities but not identified in the stratified Mantel test, suggesting a major role of the physical barriers (e.g. currents, upwelling and rivers) in the genetic diversity distribution. Patterns of migration were found for Curacao, Barbados and some areas of Colombia. In contrast, some localities from Colombia (Varadero and Albuquerque) and Guatemala were identified as isolated. The population structure identified here highlights the importance of careful design and monitoring of marine reserves in the region and will help to guide further ecological analysis of shallow Caribbean coral formations.
The potential of functionalized dressing releasing flavonoids facilitates scar-free healing
Authors: Zhang Mengyuan , Chen Xiaohang , Zhang Yuan , Zhao Xiangyu , Zhao Jing , Wang Xing
Published: October 2022

Scars are pathological marks left after an injury heals that inflict physical and psychological harm, especially the great threat to development and aesthetics posed by oral and maxillofacial scars. The differential expression of genes such as transforming growth factor-β, local adherent plaque kinase, and yes-related transcriptional regulators at infancy or the oral mucosa is thought to be the reason of scarless regenerative capacity after tissue defects. Currently, tissue engineering products for defect repair frequently overlook the management of postoperative scars, and inhibitors of important genes alone have negative consequences for the organism. Natural flavonoids have hemostatic, anti-inflammatory, antioxidant, and antibacterial properties, which promote wound healing and have anti-scar properties by interfering with the transmission of key signaling pathways involved in scar formation. The combination of flavonoid-rich drug dressings provides a platform for clinical translation of compounds that aid in drug disintegration, prolonged release, and targeted delivery. Therefore, we present a review of the mechanisms and effects of flavonoids in promoting scar-free regeneration and the application of flavonoid-laden dressings.
Identification and functional characterization of ORF19.5274, a novel gene involved in both azoles susceptibility and hypha development in Candida albicans
Authors: Huang Mingjiao , Yang Longbing , Zhou Luoxiong , Sun Chaoqin , Zhao Wenjing , Peng Jian , Jiao Zhenlong , Tian Chunren , Guo Guo
Published: October 2022

Azole resistance is becoming increasingly serious due to the frequent recurrence of fungal infections and the need for long-term clinical prevention. In our previous study, we discovered ORF19.5274 with an unknown function by TMT™ quantitative proteomics technology after fluconazole (FLC) treatment of Candida albicans. In this study, we created the target gene deletion strain using CRISPR-Cas9 editing technology to see if ORF19.5274 regulates azole sensitivity. The data showed that ORF19.5274 was involved in hyphal development and susceptibility to antifungal azoles. Deleting this gene resulted in defective hyphal growth in solid medium, while only a weak lag in the initiation of hyphal development and restoring hyphal growth during the hyphal maintenance phase under liquid conditions. Moreover, intracellular reactive oxygen species (ROS) assay and propidium iodide staining assays showed increased endogenous ROS levels and membrane permeability, but decreased metabolic activity of biofilm in orf19.5274Δ/Δ after treatment with FLC in comparison with either SC5314 or orf19.5274Δ/Δ::ORF19.5274 strains. More importantly, orf19.5274Δ/Δ significantly enhanced the FLC efficacy against C. albicans in infected Galleria mellonella larvae. The above characteristics were fully or partially restored in the complemented strain indicating that the changes caused by ORF19.5274 deletion were specific. In summary, the ORF19.5274 gene is required for hyphal development of C. albicans, and is correlated with the response to antifungal azoles in vitro and in vivo. The identification of ORF19.5275 is promising to expand the potential candidate targets for azoles.
Oxytocin accelerates tight junction formation and impairs cellular migration in 3D spheroids: evidence from Gapmer-induced exon skipping
Authors: Jurek Benjamin , Denk Lucia , Schäfer Nicole , Salehi Mohammad Saied , Pandamooz Sareh , Haerteis Silke
Published: October 2022

Oxytocin (OXT) is a neuropeptide that has been associated with neurological diseases like autism, a strong regulating activity on anxiety and stress-related behavior, physiological effects during pregnancy and parenting, and various cellular effects in neoplastic tissue. In this study, we aimed to unravel the underlying mechanism that OXT employs to regulate cell-cell contacts, spheroid formation, and cellular migration in a 3D culture model of human MLS-402 cells. We have generated a labeled OXT receptor (OXTR) overexpressing cell line cultivated in spheroids that were treated with the OXTR agonists OXT, Atosiban, and Thr4-Gly7-oxytocin (TGOT); with or without a pre-treatment of antisense oligos (Gapmers) that induce exon skipping in the human OXTR gene. This exon skipping leads to the exclusion of exon 4 and therefore a receptor that lost its intracellular G-protein-binding domain. Sensitive digital PCR (dPCR) provided us with the means to differentiate between wild type and truncated OXTR in our cellular model. OXTR truncation differentially activated intracellular signaling cascades related to cell-cell attachment and proliferation like Akt, ERK1/2-RSK1/2, HSP27, STAT1/5, and CREB, as assessed by a Kinase Profiler Assay. Digital and transmission electron microscopy revealed increased tight junction formation and well-organized cellular protrusions into an enlarged extracellular space after OXT treatment, resulting in increased cellular survival. In summary, OXT decreases cellular migration but increases cell-cell contacts and therefore improves nutrient supply. These data reveal a novel cellular effect of OXT that might have implications for degenerating CNS diseases and tumor formation in various tissues.
Acute invasive mucormycosis rhinosinusitis causing multigroup cranial nerve injury and meningitis—A case report
Authors: Wang Tingting , Cao Duanhua , Han Jingzhe
Published: October 2022

This study reported a case of a Rhino-Orbital-Cerebral Mycosis (ROCM) patient with multiple groups of cranial nerve damage as the primary clinical manifestation, confirmed by histopathology and cerebrospinal fluid metagenomic next-generation sequencing (mNGS) technology. Relying on the MRI3D-SPACE technology, we observed the location and extent of the cranial nerve damage in the patient. The results suggested that fungal meningoencephalitis caused by mucor may enter the skull retrograde along the cranial nerve perineurium. The patient was admitted to the hospital with a preliminary diagnosis of mucormycosis infection after 1.5 days of mouth deviation. We treated the patient immediately with intravenous amphotericin B liposomes. After 21 days of hospitalization, the clinical symptoms of the patient did not improve significantly. The patient was discharged due to financial difficulties and antifungal treatment at home, and his disease had stabilized at the 6-month follow-up.
Motor imagery and action-observation in neurorehabilitation: A study protocol in Parkinson's disease patients
Authors: Rizzi Beatrice , Nuresi Christian , Rovacchi Claudio , Bacchini Massimo , Savi Federica , Falco Lucia , Schianchi Luca , Scaglioni Augusto , Ciracì Chiara , Costantino Cosimo , Buccino Giovanni
Published: October 2022

Introduction

Action Observation Treatment (AOT) and Motor Imagery (MI) represent very promising cognitive strategies in neuro-rehabilitation. This study aims to compare the effectiveness of the two cognitive strategies, taken alone or combined, in Parkinson's disease patients.

Material and methods

This study is designed as a prospective randomized controlled trial, with four arms. We estimated a sample size of 64 patients (16 in each treatment group) to be able to detect an effect size of F = 0.4 with a statistical significance of 0.05. Primary outcomes will be functional gains in the FIM and UPDRS scales. Secondary outcome measure will be functional gain as revealed by kinematic parameters measured at Gait Analysis.

Discussion

The results of this trial will provide insights into the use of AOT and MI, taken alone or combined, in the rehabilitation of Parkinson's disease patients.

Ethics and dissemination

The study protocol was approved by the Ethics Committee of the Don Gnocchi Foundation. The study will be conducted in accordance with the 1996 World Medical Association guidelines and according to good clinical practice. The study has been registered on clinicaltrial.gov under the following code: AOTPRFDG. Dissemination will include both submission of the study to peer-reviewed journals and discussion of the study protocol at conferences.
Therapeutic efficacy of matrix metalloproteinase-12 suppression on neurological recovery after ischemic stroke: Optimal treatment timing and duration
Authors: Challa Siva Reddy , Nalamolu Koteswara Rao , Fornal Casimir A. , Wang Billy C. , Martin Ryan C. , Olson Elsa A. , Ujjainwala Ammar L. , Pinson David M. , Klopfenstein Jeffrey D. , Veeravalli Krishna Kumar
Published: October 2022

We recently showed that the post-ischemic induction of matrix metalloproteinase-12 (MMP-12) in the brain degrades tight junction proteins, increases MMP-9 and TNFα expression, and contributes to the blood-brain barrier (BBB) disruption, apoptosis, demyelination, and infarct volume development. The objectives of this study were to (1) determine the effect of MMP-12 suppression by shRNA-mediated gene silencing on neurological/functional recovery, (2) establish the optimal timing of MMP-12shRNA treatment that provides maximum therapeutic benefit, (3) compare the effectiveness of acute versus chronic MMP-12 suppression, and (4) evaluate potential sex-related differences in treatment outcomes. Young male and female Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion and reperfusion. Cohorts of rats were administered either MMP-12shRNA or scrambled shRNA sequence (control) expressing plasmids (1 mg/kg; i.v.) formulated as nanoparticles. At designated time points after reperfusion, rats from various groups were subjected to a battery of neurological tests to assess their reflex, balance, sensory, and motor functions. Suppression of MMP-12 promoted the neurological recovery of stroke-induced male and female rats, although the effect was less apparent in females. Immediate treatment after reperfusion resulted in a better recovery of sensory and motor function than delayed treatments. Chronic MMP-12 suppression neither enhanced nor diminished the therapeutic effects of acute MMP-12 suppression, indicating that a single dose of plasmid may be sufficient. We conclude that suppressing MMP-12 after an ischemic stroke is a promising therapeutic strategy for promoting the recovery of neurological function.