bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional analysis of bovine interleukin-10 receptor alpha in response to Mycobacterium avium subsp. paratuberculosis lysate using CRISPR/Cas9
Authors: Mallikarjunappa Sanjay , Shandilya Umesh K. , Sharma Ankita , Lamers Kristen , Bissonnette Nathalie , Karrow Niel A. , Meade Kieran G.
Published: November 2020

Background

The interleukin-10 receptor alpha (IL10RA) gene codes for the alpha chain of the IL-10 receptor which binds the cytokine IL-10. IL-10 is an anti-inflammatory cytokine with immunoregulatory function during the pathogenesis of many inflammatory disorders in livestock, including Johne’s disease (JD). JD is a chronic enteritis in cattle caused by Mycobacterium avium subsp. paratuberculosis (MAP) and is responsible for significant economic losses to the dairy industry. Several candidate genes including IL10RA have been found to be associated with JD. The aim of this study was to better understand the functional significance of IL10RA in the context of immune stimulation with MAP cell wall lysate.

Results

An IL10RA knock out (KO) bovine mammary epithelial cell (MAC-T) line was generated using the CRISPR/cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9) gene editing system. These IL10RA KO cells were stimulated with the immune stimulant MAP lysate +/− IL-10, or with LPS as a positive control. In comparison to unedited cells, relative quantification of immune-related genes after stimulation revealed that knocking out IL10RA resulted in upregulation of pro-inflammatory cytokine gene expression (TNFA, IL1A, IL1B and IL6) and downregulation of suppressor of cytokine signaling 3 (SOCS3), a negative regulator of pro-inflammatory cytokine signaling. At the protein level knocking out IL10RA also resulted in upregulation of inflammatory cytokines - TNF-α and IL-6 and chemokines - IL-8, CCL2 and CCL4, relative to unedited cells.

Conclusions

The findings of this study illustrate the broad and significant effects of knocking out the IL10RA gene in enhancing pro-inflammatory cytokine expression and further support the immunoregulatory role of IL10RA in eliciting an anti-inflammatory response as well as its potential functional involvement during the immune response associated with JD.
Label-free quantitative proteomic analysis of alfalfa in response to microRNA156 under high temperature
Authors: Arshad Muhammad , Puri Alpa , Simkovich Aaron J. , Renaud Justin , Gruber Margaret Y. , Marsolais Frédéric , Hannoufa Abdelali
Published: November 2020

Background

Abiotic stress, including heat, is one of the major factors that affect alfalfa growth and forage yield. The small RNA, microRNA156 (miR156), regulates multiple traits in alfalfa during abiotic stress. The aim of this study was to explore the role of miR156 in regulating heat response in alfalfa at the protein level.

Results

In this study, we compared an empty vector control and miR156 overexpressing (miR156OE) alfalfa plants after exposing them to heat stress (40 °C) for 24 h. We measured physiological parameters of control and miR156OE plants under heat stress, and collected leaf samples for protein analysis. A higher proline and antioxidant contents were detected in miR156OE plants than in controls under heat stress. Protein samples were analyzed by label-free quantification proteomics. Across all samples, a total of 1878 protein groups were detected. Under heat stress, 45 protein groups in the empty vector plants were significantly altered (P < 0.05; |log2FC| > 2). Conversely, 105 protein groups were significantly altered when miR156OE alfalfa was subjected to heat stress, of which 91 were unique to miR156OE plants. The identified protein groups unique to miR156OE plants were related to diverse functions including metabolism, photosynthesis, stress-response and plant defenses. Furthermore, we identified transcription factors in miR156OE plants, which belonged to squamosa promoter binding-like protein, MYB, ethylene responsive factors, AP2 domain, ABA response element binding factor and bZIP families of transcription factors.

Conclusions

These results suggest a positive role for miR156 in heat stress response in alfalfa. They reveal a miR156-regulated network of mechanisms at the protein level to modulate heat responses in alfalfa.
Patients’ perception of the practice of anaesthesia in a teaching hospital in Northern Jordan: a survey
Authors: Bataineh Adel M. , Qudaisat Ibraheem Y. , El-Radaideh Khaled , Alzoubi Rawand A. , Abu-Shehab Mohammad I.
Published: November 2020

Background and aim

Despite big leaps of progress in its scope, the practice of anesthesia is still suffering from poor public image, especially in developing countries. Little research investigated the public awareness of anesthesia in the Middle East. This study aimed to examine the perception of the practice of anaesthesia among Jordanian patients.

Methods

A standard questionnaire with 29 questions was administered through personal interview to consenting patients. Questions tested patients’ correct knowledge of the identity of anesthetists, their roles and scope of their practice. Awareness was measured using the frequency of correct answers to each survey question. A total awareness score was calculated as the percentage ratio of the number of correct answers to the total number of questions. We classified this score into: Poor< 50%. Moderate 50–75%, and Good > 75% to reflect patient’s overall perception of anesthetists and their roles. Effects of demographic variables on results were also investigated. Appropriate statistical tests were used to summarize and compare results. A total of 513 patients admitted for elective surgery were sequentially approached for enrolment.

Results

Five hundred and five patients were enrolled. Most patients identified anesthesia as a separate practice from surgery (86%). The anaesthetist was identified as a physician by only 37% of patients. Equal importance to both anaesthetists and surgeons was assumed by 71.5% of patents. Only 15% of patients showed good level of total knowledge of anaesthetist roles, while 51% scored poorly. Highest awareness was of anaesthetist’s preoperative roles (65.1%). Age was the only demographic factor affecting studied awareness (P = 0.009).

Conclusion

Although the importance of anesthetist is well perceived among Jordanian patients, there is still some ignorance in their knowledge of the details of anesthesia practice. Active communication efforts and patient education by anesthetists are needed to improve the public status of the specialty.
Prediction of prognostic signatures in triple-negative breast cancer based on the differential expression analysis via NanoString nCounter immune panel
Authors: Lim Gyeong Back , Kim Young-Ae , Seo Jeong-Han , Lee Hee Jin , Gong Gyungyub , Park Sung Hee
Published: November 2020

Background

Triple-Negative Breast Cancer (TNBC) is an aggressive and complex subtype of breast cancer. The current biomarkers used in the context of breast cancer treatment are highly dependent on the targeting of oestrogen receptor, progesterone receptor, or HER2, resulting in treatment failure and disease recurrence and creating clinical challenges. Thus, there is still a crucial need for the improvement of TNBC treatment; the discovery of effective biomarkers that can be easily translated to the clinics is essential.

Methods

We report an approach for the discovery of biomarkers that can predict tumour relapse and pathologic complete response (pCR) in TNBC on the basis of mRNA expression quantified using the NanoString nCounter Immunology Panel. To overcome the limited sample size, prediction models based on random Forest were constructed using the differentially expressed genes (DEGs) as selected features. We also evaluated the differences between pre- and post-treatment groups aiming for the combinatorial assessment of pCR and relapse using additive models in edgeR.

Results

We identify nine and 13 DEGs strongly associated with pCR and relapse, respectively, from 579 immune genes in a small number of samples (n = 55) using edgeR. An additive model for the comparison of pre- and post-treatment groups via the adjustment of the independent subject in the relapse group revealed associations for 41 genes. Comprehensive analysis indicated that our prediction models outperformed those constructed using features extracted from the existing feature selection model Elastic Net in terms of accuracy. The prediction models were assessed using a randomization test to validate the robustness (empirical P for the model of pCR = 0.015 and empirical P for the model of relapse = 0.018). Furthermore, three DEGs (FCER1A, EDNRB, and TGFBI) in the model of relapse showed prognostic significance for predicting the survival of patients with cancer through Cox proportional hazards regression model-based survival analysis.

Conclusion

Gene expression quantified via the NanoString nCounter Immunology Panel can be seamlessly analysed using edgeR, even considering small sample sizes. Our approach provides a scalable framework that can easily be applied for the discovery of biomarkers based on the NanoString nCounter Immunology Panel.

Data availability

The source code will be available from github at https://github.com/sungheep/nanostring.
Prognostic role of vitamin D receptor in breast cancer: a systematic review and meta-analysis
Authors: Xu Haiyan , Liu Zhenhua , Shi Hongtai , Wang Chunbin
Published: November 2020

Background

A higher vitamin D intake improves the prognosis of early stage breast cancer (BC) patients. We hypothesized that vitamin D intake should refer to vitamin D receptor (VDR) expression. In order to prove this hypothesis, we first intend to evaluate the correlation between VDR expression and prognosis of BC patients using meta-analysis.

Methods

Literatures from PubMed, Embase, and the Cochrane Library (last update by May 20, 2020) were retrieved to find studies assessing the prognostic role of VDR in BC. The hazard ratios (HRs) for patients’ survival were extracted for pooled analyses. Subgroup analysis, sensitivity analysis and meta-regression were performed to explore the sources of heterogeneity.

Results

Seven articles containing eight studies with 2503 patients were enrolled. The results from the pooled analyses showed that the VDR expression generally had no relationship with BC patients’ overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS), and progression-free survival (PFS) (P > 0.05). Because only the number of studies exploring the relationship between VDR expression and OS is greater than five and there is heterogeneity, we explored the sources of heterogeneity of these studies. Subgroup analyses showed that the VDR expression in the nucleus had no relationship with OS, but high total VDR expression in the nucleus and cytoplasm was related to a better OS (pooled HR = 0.41; 95% CI = 0.18–0.95; P = 0.038). In addition, in subgroup of studies using cut-off values other than ‘immunoreactive score (IRS)>5’ and ‘IRS > 25′, high VDR expression was associated with a better OS (pooled HR = 0.47; 95% CI = 0.30–0.74; P = 0.001). Sensitivity analysis showed that the result pattern was not obviously affected by any single study. Meta-regression showed that the source of heterogeneity was not country (P = 0.657), pathological type (P = 0.614), molecular type (P = 0.423), staining location (P = 0.481), or cut-off value (P = 0.509).

Conclusions

The protein expression level of VDR in entire BC cells evaluated by immunohistochemistry is related to the OS of BC patients. It is expected that a more individualized vitamin D intake and a more accurate prognosis assessment can be recommended for BC patients based on the VDR expression. Of course, more preclinical and clinical studies are needed.
An uncertainty estimate of the prevalence of stunting in national surveys: the need for better precision
Authors: Ghosh Santu , Shivakumar Nirupama , Bandyopadhyay Sulagna , Sachdev Harshpal S. , Kurpad Anura V. , Thomas Tinku
Published: November 2020

Background

Stunting is determined by using the World Health Organization (WHO) child growth standard which was developed using precise measurements. However, it is unlikely that large scale surveys maintain the same level of rigour and precision when measuring the height of children. The population measure of stunting in children is sensitive to over-dispersion, and the high prevalence of stunting observed in surveys in low and middle-income countries (LMIC) could partly be due to lower measurement precison.

Objectives

To quantify the incongruence in the dispersion of height-for-age in national surveys of < 5 y children, in relation to the standard WHO Multicenter Growth Reference Study (MGRS), and propose a measure of uncertainty in population measures of stunting.

Methods

An uncertainty factor was proposed and measured from the observed incongruence in dispersion of the height-for-age of < 5 y children in the MGRS against carefully matched populations from the Demographic Health Survey of 17 countries (‘test datasets’, based on the availability of data). This also allowed for the determination of uncertainty-corrected prevalence of stunting (height-for-age Z score < − 2) in < 5 y children.

Results

The uncertainty factor was estimated for 17 LMICs. This ranged from 0.9 to 2.1 for Peru and Egypt respectively (reference value 1). As an explicit country example, the dispersion of height-for-age in the Indian National Family Health Survey-4 test dataset was 39% higher than the MGRS study, with an uncertainty factor of 1.39. From this, the uncertainty-adjusted Indian national stunting prevalence estimate reduced to 18.7% from the unadjusted estimate of 36.2%.

Conclusions

This study proposes a robust statistical method to estimate uncertainty in stunting prevalence estimates due to incongruent dispersions of height measured in national surveys for children < 5 years in relation to the WHO height-for-age standard. The uncertainty is partly due to population heterogeneity, but also due to measurement precision, and calls for better quality in these measurements.
Effect of flipped classroom methodology on the student performance of gastrointestinal and renal physiology entrants and repeaters
Authors: Sánchez Julio C. , López-Zapata Diego F. , Pinzón Óscar A. , García Andrés M. , Morales Martha D. , Trujillo Samuel E.
Published: November 2020

Background

Physiology is a subject that is considered difficult; it is associated with academic failure and causes high levels of stress and anxiety in students.

Methods

This study compared the effectiveness of a traditional lecture-based methodology with that of a flipped classroom scheme focusing on cooperative ludic learning among gastrointestinal and renal physiology students. Two groups were subjected to these two different methods to teach gastrointestinal and renal physiology content divided into 14 topics. Additionally, two subgroups were identified in each group: entrants and repeaters. There were no differences in age or gender between the subgroups.

Results

Levels of self-perceived stress (measured by the SISCO scale), biological stress (measured by awakening salivary cortisol levels), and anxiety (measured by the Zung scale) were high in all of the students; the cortisol levels increased in the entrants and some of the scores in SISCO scale increased in the repeaters, throughout the study. The self-reported study time was longer in the students subjected to the flipped classroom-based method. The final exam results were better only in the new students facing the flipped methodology, but not in the repeaters, who scored lower on the final evaluation. The quantitative and qualitative assessments completed by the participants regarding the different aspects of the flipped-classroom-based methodology were favorable; however, the participants believed that traditional lectures should be maintained for specific topics.

Conclusions

A methodology based on flipped teaching was an effective strategy to improve academic performance ingastrointestinal and renal physiology, but only in new students.
Canine colostrum exosomes: characterization and influence on the canine mesenchymal stem cell secretory profile and fibroblast anti-oxidative capacity
Authors: Villatoro Antonio J. , Martín-Astorga María del Carmen , Alcoholado Cristina , Becerra José
Published: November 2020

Background

Canine colostrum milk (CCM) is a specific secretion of the mammary gland that is fundamental for the survival of the newborn. CCM has many described components (immunoglobulins, proteins or fat), but its small vesicles, named exosomes, are largely unknown.

Results

A characterization of CCM exosomes was performed. Exosomes were abundant in CCM and appeared with the characteristic cup-shaped morphology and well-defined round vesicles. The size distribution of exosomes was between 37 and 140 nm, and western blot analysis showed positive expression of specific exosomal markers. Proteomic analysis revealed a total of 826 proteins in exosome cargo. We also found that exosomes modified the proliferation and secretory profiles in canine mesenchymal stem cells derived from bone marrow (cBM-MSCs) and adipose tissue (cAd-MSCs). Additionally, CCM exosomes demonstrated a potent antioxidant effect on canine fibroblasts in culture.

Conclusions

Our findings highlight, for the first time, the abundant presence of exosomes in CCM and their ability to interact with mesenchymal stem cells (MSCs). The addition of exosomes to two types of MSCs in culture resulted in specific secretory profiles with functions related to angiogenesis, migration and chemotaxis of immune cells. In particular, the cAd-MSCs secretory profile showed higher potential in adipose tissue development and neurogenesis, while cBM-MSC production was associated with immunity, cell mobilization and haematopoiesis. Finally, exosomes also presented antioxidant capacity on fibroblasts against reactive oxygen species activity within the cell, demonstrating their fundamental role in the development and maturation of dogs in the early stages of their life.
Intelligent microbial cell factory with genetic pH shooting (GPS) for cell self-responsive base/acid regulation
Authors: Li Chenyi , Gao Xiaopeng , Peng Xiao , Li Jinlin , Bai Wenxin , Zhong Jiadong , He Mengchao , Xu Ke , Wang Ying , Li Chun
Published: November 2020

Background

In industrial fermentation, pH fluctuation resulted from microbial metabolism influences the strain performance and the final production. The common way to control pH is adding acid or alkali after probe detection, which is not a fine-tuned method and often leads to increased costs and complex downstream processing. Here, we constructed an intelligent pH-sensing and controlling genetic circuits called “Genetic pH Shooting (GPS)” to realize microbial self-regulation of pH.

Results

In order to achieve the self-regulation of pH, GPS circuits consisting of pH-sensing promoters and acid-/alkali-producing genes were designed and constructed. Designed pH-sensing promoters in the GPS can respond to high or low pHs and generate acidic or alkaline substances, achieving endogenously self-responsive pH adjustments. Base shooting circuit (BSC) and acid shooting circuit (ASC) were constructed and enabled better cell growth under alkaline or acidic conditions, respectively. Furthermore, the genetic circuits including GPS, BSC and ASC were applied to lycopene production with a higher yield without an artificial pH regulation compared with the control under pH values ranging from 5.0 to 9.0. In scale-up fermentations, the lycopene titer in the engineered strain harboring GPS was increased by 137.3% and ammonia usage decreased by 35.6%.

Conclusions

The pH self-regulation achieved through the GPS circuits is helpful to construct intelligent microbial cell factories and reduce the production costs, which would be much useful in industrial applications.
Challenging microalgal vitamins for human health
Authors: Del Mondo Angelo , Smerilli Arianna , Sané Elisabet , Sansone Clementina , Brunet Christophe
Published: November 2020

Background

Vitamins’ deficiency in humans is an important threat worldwide and requires solutions. In the concept of natural biofactory for bioactive compounds production, microalgae represent one of the most promising targets filling many biotechnological applications, and allowing the development of an eco-sustainable production of natural bioactive metabolites. Vitamins are probably one of the cutting edges of microalgal diversity compounds.

Main text

Microalgae can usefully provide many of the required vitamins in humans, more than terrestrial plants, for instance. Indeed, vitamins D and K, little present in many plants or fruits, are instead available from microalgae. The same occurs for some vitamins B (B12, B9, B6), while the other vitamins (A, C, D, E) are also provided by microalgae. This large panel of vitamins diversity in microalgal cells represents an exploitable platform in order to use them as natural vitamins’ producers for human consumption. This study aims to provide an integrative overview on vitamins content in the microalgal realm, and discuss on the great potential of microalgae as sources of different forms of vitamins to be included as functional ingredients in food or nutraceuticals for the human health. We report on the biological roles of vitamins in microalgae, the current knowledge on their modulation by environmental or biological forcing and on the biological activity of the different vitamins in human metabolism and health protection.

Conclusion

Finally, we critically discuss the challenges for promoting microalgae as a relevant source of vitamins, further enhancing the interests of microalgal “biofactory” for biotechnological applications, such as in nutraceuticals or cosmeceuticals.
Genetic variations in histidine-rich protein 2 and histidine-rich protein 3 of Myanmar Plasmodium falciparum isolates
Authors: Lê Hương Giang , Kang Jung-Mi , Lee Jinyoung , Yoo Won Gi , Myint Moe Kyaw , Lin Khin , Kim Tong-Soo , Na Byoung-Kuk
Published: November 2020

Background

Malaria rapid diagnostic tests (RDTs) are precious tools to diagnose malaria. Most RDTs used currently are based on the detection of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) in a patient’s blood. However, concern has been raised in recent years that deletion of pfhrp2 in the parasite could affect the accuracy of PfHRP2-based RDTs. In addition, genetic variation in pfhrp2 might influence the accuracy and sensitivity of RDTs. In this study, the genetic variation in pfhrp2 and pfhrp3 in Myanmar P. falciparum isolates was analysed.

Methods

Blood samples were collected from malaria patients who were infected with P. falciparum in Mandalay, Naung Cho, Tha Beik Kyin, and Pyin Oo Lwin, Upper Myanmar between 2013 and 2015. The pfhrp2 and pfhrp3 were amplified by nested polymerase chain reaction (PCR), cloned and sequenced. Genetic variation in Myanmar pfhrp2 and pfhrp3 was analysed using the DNASTAR program. Comparative analysis of Myanmar and global pfhrp2 and pfhrp3 isolates was also performed.

Results

One-hundred and two pfhrp2 and 89 pfhrp3 were amplified from 105 blood samples, of which 84 pfhrp2 and 56 pfhrp3 sequences were obtained successfully. Myanmar pfhrp2 and pfhrp3 showed high levels of genetic variation with different arrangements of distinct repeat types, which further classified Myanmar pfhrp2 and pfhrp3 into 76 and 47 haplotypes, respectively. Novel amino acid changes were also found in Myanmar pfhrp2 and pfhrp3, but their frequencies were very low. Similar structural organization was shared by Myanmar and global pfhrp2 and pfhrp3, and differences in frequencies of repeat types and lengths were also observed between and among global isolates.

Conclusion

Length polymorphisms and amino acid substitutions generated extensive genetic variation in Myanmar pfhrp2 and pfhrp3. Comparative analysis revealed that global pfhrp2 and pfhrp3 share similar structural features, as well as extensive length polymorphisms and distinct organizations of repeat types. These results provide a better understanding of the genetic structure of pfhrp2 and pfhrp3 in global P. falciparum populations and suggest useful information to develop RDTs with improved quality.
Preventing the re-establishment of malaria in Sri Lanka amidst the COVID-19 pandemic
Authors: Ranaweera Prasad , Wickremasinghe Rajitha , Mendis Kamini
Published: November 2020

The COVID-19 pandemic has had a considerable impact on other health programmes in countries, including on malaria, and is currently under much discussion. As many countries are accelerating efforts to eliminate malaria or to prevent the re-establishment of malaria from recently eliminated countries, the COVID-19 pandemic has the potential to cause major interruptions to ongoing anti-malaria operations and risk jeopardizing the gains that have been made so far. Sri Lanka, having eliminated malaria in 2012, was certified by the World Health Organization as a malaria-free country in 2016 and now implements a rigorous programme to prevent its re-establishment owing to the high receptivity and vulnerability of the country to malaria. Sri Lanka has also dealt with the COVID-19 epidemic quite successfully limiting the cumulative number of infections and deaths through co-ordinated efforts between the health sector and other relevant sectors, namely the military, the Police Department, Departments of Airport and Aviation and Foreign Affairs, all of which have been deployed for the COVID-19 epidemic under the umbrella of a Presidential Task Force. The relevance of imported infections and the need for a multi-sectoral response are features common to both the control of the COVID-19 epidemic and the Prevention of Re-establishment (POR) programme for malaria. Sri Lanka’s malaria POR programme has, therefore, creatively integrated its activities with those of the COVID-19 control programme. Through highly coordinated operations the return to the country of Sri Lankan nationals stranded overseas by the COVID-19 pandemic, many from malaria endemic countries, are being monitored for malaria as well as COVID-19 in an integrated case surveillance system under quarantine conditions, to the success of both programmes. Twenty-three imported malaria cases were detected from February to October through 2773 microscopic blood examinations performed for malaria in quarantine centres, this number being not much different to the incidence of imported malaria during the same period last year. This experience highlights the importance of integrated case surveillance and the need for a highly coordinated multi-sectoral approach in dealing with emerging new infections. It also suggests that synergies between the COVID-19 epidemic control programme and other health programmes may be found and developed to the advantage of both.
Do community scorecards improve utilisation of health services in community clinics: experience from a rural area of Bangladesh
Authors: Hanifi S. M. A. , Hossain Aazia , Chowdhury Asiful Haidar , Hoque Shahidul , Selim Mohammad Abdus , Mahmood Shehrin Shaila , Bhuiya Abbas
Published: November 2020

Background

The government of Bangladesh initiated community clinics (CC) to extend the reach of public health services and these facilities were planned to be run through community participation. However, utilisation of CC services is still very low. Evidence indicates community score card is an effective tool to increase utilisation of services from health facility through regular interface meeting between service providers and beneficiary. We investigated whether community scorecards (CSC) improve utilisation of health services provided by CCs in rural area of Bangladesh.

Methods

This study was conducted from December 2017 to November 2018. Three intervention and three control CCs were selected from Chakaria, a rural sub-district of Bangladesh. CSC was introduced with the Community Groups and Community Support Groups in intervention CCs between January to October 2018. Data were collected through observation of CCs during operational hours, key informant interviews, focus group discussions, and from DHIS2. Utilisation of CC services was compared between intervention and control areas, pre and post CSC intervention.

Results

Post CSC intervention, community awareness about CC services, utilisation of clinic operational hours, and accountability of healthcare providers have increased in the intervention CCs. Utilisation of primary healthcare services including family planning services, antenatal care, postnatal care and basic health services have significantly improved in intervention CCs.

Conclusion

CSC is an effective tool to increase the service utilization provided by CCs by ensuring community awareness and participation, and service providers’ accountability. Policy makers and concerned authorities may take necessary steps to integrate community scorecard in the health system by incorporating it in CCs.
Maple syrup urine disease in Brazilian patients: variants and clinical phenotype heterogeneity
Authors: Margutti Ana Vitoria Barban , Silva Wilson Araújo , Garcia Daniel Fantozzi , de Molfetta Greice Andreotti , Marques Adriana Aparecida , Amorim Tatiana , Prazeres Vânia Mesquita Gadelha , Boy da Silva Raquel Tavares , Miura Irene Kazue , Seda Neto João , Santos Emerson de Santana , Santos Mara Lúcia Schmitz Ferreira , Lourenço Charles Marques , Tonon Tássia , Sperb-Ludwig Fernanda , de Souza Carolina Fischinger Moura , Schwartz Ida Vanessa Döederlein , Camelo José Simon
Published: November 2020

Background

Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disease caused by deficient activity of the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by BCKDHA, BCKDHB, DBT, and DLD genes. MSUD is predominantly caused by Variants in BCKDHA, BCKDHB, and DBT genes encoding the E1α, E1β, and E2 subunits of BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD by identifying the point variants in BCKDHA, BCKDHB, and DBT genes in a cohort of Brazilian MSUD patients and to describe their phenotypic heterogeneity. It is a descriptive cross-sectional study with 21 MSUD patients involving molecular genotyping by Sanger sequencing.

Results

Eight new variants predicted as pathogenic were found between 30 variants (damaging and non-damaging) identified in the 21 patients analyzed: one in the BCKDHA gene (p.Tyr120Ter); five in the BCKDHB gene (p.Gly131Val, p.Glu146Glnfs * 13, p.Phe149Cysfs * 9, p.Cys207Phe, and p.Lys211Asn); and two in the DBT gene (p.Glu148Ter and p.Glu417Val). Seventeen pathogenic variants were previously described and five variants showed no pathogenicity according to in silico analysis.

Conclusion

Given that most of the patients received late diagnoses, the study results do not allow us to state that the molecular features of MSUD variant phenotypes are predictive of clinical severity.
Mini-review: advances in 3D bioprinting of vascularized constructs
Authors: Bova Lorenzo , Billi Fabrizio , Cimetta Elisa
Published: November 2020

3D in vitro constructs have gained more and more relevance in tissue engineering and in cancer-modeling. In recent years, with the development of thicker and more physiologically relevant tissue patches, the integration of a vascular network has become pivotal, both for sustaining the construct in vitro and to help the integration with the host tissue once implanted. Since 3D bioprinting is rising to be one of the most versatile methods to create vascularized constructs, we here briefly review the most promising advances in bioprinting techniques.
Assessing the impact of DRS signaling in unlicensed indoor coexistence scenarios
Authors: Baena Eduardo , Fortes Sergio , Barco Raquel
Published: November 2020

The use of unlicensed bands is one of the most promising features envisaged to increase capacity in 5G. However, this poses multiple challenges associated with the operation when coexisting networks are present, such as WiFi. Previous coexistence analyses have been focused on the user-plane data-related transmissions and mainly based on abstract models. Meanwhile, the effects of the shared channel signaling defined by the standards have been mostly disregarded, particularly for ultra-dense scenarios. This paper assesses how the shared data channel signaling mechanisms influence the performance of the coexisting technologies operating unlicensed bands in indoor environments. Based on this analysis, some DRS signaling modifications are envisaged to additionally enhance the service provision and fairness towards WiFi in these scenarios.
Are RGB-based salient object detection methods unsuitable for light field data?
Authors: Liu Yu , Xiao Huaxin , Tan Hanlin , Li Ping
Published: November 2020

Considering the significant progress made on RGB-based deep salient object detection (SOD) methods, this paper seeks to bridge the gap between those 2D methods and 4D light field data, instead of implementing specific 4D methods. We observe that the performance of 2D methods changes dramatically with the input refocusing on different depths. This paper attempts to make the 2D methods available for light field SOD by learning to select the best single image from the 4D tensor. Given a 2D method, a deep model is proposed to explicitly compare pairs of SOD results on one light field sample. Moreover, a comparator module is designed to integrate the features from a pair, which provides more discriminative representations to classify. Experiments over 13 latest 2D methods and 2 datasets demonstrate the proposed method can bring about 24.0% and 5.3% average improvement of mean absolute error and F-measure, and outperform state-of-the-art 4D methods by a large margin.
First detection of F1534C knockdown resistance mutation in Aedes aegypti (Diptera: Culicidae) from Cameroon
Authors: Yougang Aurelie P. , Kamgang Basile , Bahun Theodel A. Wilson , Tedjou Armel N. , Nguiffo-Nguete Daniel , Njiokou Flobert , Wondji Charles S.
Published: November 2020

Background

Aedesborne viral diseases, notably dengue, are increasingly reported in Cameroon withAedes aegyptibeing a major vector. Data on insecticide resistance of this vector and underlying mechanisms needed for outbreak preparedness remain scarce in Cameroon. Here, we present the nationwide distribution of insecticide resistance inAe. aegyptiand investigate the potential resistance mechanisms involved.

Methods

Immature stages ofAe. aegyptiwere collected between March and July 2017 in 13 locations across Cameroon and reared until G1/G2/G3 generation. Larval, adult bioassays, and piperonyl butoxide (PBO) synergist assays were carried out according to World Health Organization guidelines. F1534C mutation was genotyped using allele specific polymerase chain reaction in field collected adults (Go) and the polymorphism of the sodium channel gene was assessed. Theχ2test was used to compare the mortality rate between bioassays with insecticides only and bioassays after preexposure to PBO synergist.

Results

Larval bioassay revealed that all the three populations tested with temephos were susceptible. Adult bioassays showed a good level of susceptibility toward both pyrethroids tested, 0.25% permethrin and 0.05% deltamethrin, with six out of 10 populations susceptible. However, two populations (Douala and Edéa) were resistant (deltamethrin [73.2–92.5% mortality], permethrin [2.6–76.3% mortality]). The resistance to 4% dichlorodiphenyltrichloroethane was observed in four out of 10 populations tested (16.8–87.1% mortality). Resistance was also reported to carbamates including 0.1% propoxur (60.8–87.1% mortality) and to 0.1% bendiocarb (82.9% mortality). All populations tested were fully susceptible to 1% fenitrothion. A partial recovery of susceptibility was observed in the pyrethroid resistant population of Douala after pre-exposed to PBO suggesting the implication of cytochrome P450 monoxygenases permethrin resistance. Genotyping and sequencing detected the F1534Ckdrmutation in the two pyrethroid resistant locations of Edéa and Douala, with allelic frequency of 3.3% and 33.3% respectively. However, the high genetic diversity of the sodium channel gene supports the recent introduction of this mutation in Cameroon.

Conclusions

This study revealed the contrasting resistance profiles to insecticides ofAe. aegyptipopulations in Cameroon suggesting that, instead of a unique nationwide control approach, a regionally adapted strategy will be needed to control this vector. The localised distribution of the F1534Ckdrmutation supports this region-specific control strategy.
Engaging patients and family members to design and implement patient-centered kidney disease research
Authors: Browne Teri , Swoboda Amy , Ephraim Patti L. , Lang-Lindsey Katina , Green Jamie A. , Hill-Briggs Felicia , Jackson George L. , Ruff Suzanne , Schmidt Lana , Woods Peter , Danielson Patty , Bolden Shakur , Bankes Brian , Hauer Chelsie , Strigo Tara , Boulware L. Ebony
Published: November 2020

Plain English summary

We need more research projects that partner and engage with patients and family members as team members. Doing this requires that patients and family members set research priorities and fully participate in research teams. Models for this patient and family member engagement as research partners can help increase patient centered outcomes research. In this article, we describe how we have successfully engaged patients with kidney disease and family members as Co-Investigators on a 5-year research project testing a health system intervention to improve kidney disease care.

Background

This article describes a method for successful engagement of patients and family members in all stages of a 5-year comparative effectiveness research trial to improve transitions of care for patients from chronic kidney disease to end-stage kidney disease.

Methods

This project utilized the Patient-Centered Outcomes Research Institute’s conceptual model for engagement with patients and family members. We conducted a qualitative analysis of grant planning meetings to determine patient and family member Co-Investigators’ priorities for research and to include these engagement efforts in the research design. Patient and family member Co-Investigators partnered in writing this paper.

Results

Patients and family members were successfully engaged in remote and in-person meetings to contribute actively to research planning and implementation stages. Three patient-centered themes emerged from our data related to engagement that informed our research plan: kidney disease treatment decision-making, care transitions from chronic to end-stage kidney disease, and patient-centered outcomes.

Conclusions

The model we have employed represents a new paradigm for kidney disease research in the United States, with patients and family members engaged as full research partners. As a result, the study tests an intervention that directly responds to their needs, and it prioritizes the collection of outcomes data most relevant to patient and family member Co-Investigators.

Trial registration

NCT02722382.
The nexus between education and fertility in six European countries
Authors: Impicciatore Roberto , Tomatis Francesca
Published: November 2020

Given the many linkages between education and family behaviour, the expansion of higher education especially among women in recent decades may have important consequences for fertility in Europe. This is a crucial factor in both the New Home Economics (NHE) theory and the Second Demographic Transition (SDT) that predict a negative association between fertility and education. However, more recently, the Gender Revolution (GR) approach has emphasised the role of gender egalitarianism both in society and within households as a boost for fertility. By adopting a comparative perspective on six European countries, this paper reports our research on the effect of education on the fertility choices in light of the foregoing three different theoretical explanations. Using data from the second wave of Generation and Gender surveys (GGS) for Bulgaria, Czech Republic, France, Germany, and Poland, and the ISTAT survey “Famiglie e Soggetti Sociali” for Italy, we estimated the propensity to have the first and the second child birth on women born between 1940 and 1979 by means of multiprocess hazard models.

For the first childbirth, the influence of education on fertility behaviours not only remains important but also tends to increase among younger cohorts. This result matches the NHE and SDT explanation, suggesting a similar evolution towards an erosion of the family. Conversely, for the second childbirth we found marked differences among countries suggesting an East-West polarisation giving support to the GR approach. However, peculiarities for the Italian case linked to a tempo effect emphasize the need to go beyond the West-East dichotomy.
Effect of cultural conditions on the growth and linamarase production by a local species of Lactobacillus fermentum isolated from cassava effluent
Authors: Fadahunsi Ilesanmi Festus , Busari Nafisat Kemi , Fadahunsi Olumide Samuel
Published: November 2020

Background

This study was designed to investigate the effect of cultural conditions on growth and production of linamarase by a local species ofLactobacillus fermentumisolated from cassava effluent. Isolation and identification of bacteria from cassava effluent were carried out using the culture-dependent method and polyphasic taxonomy, respectively, while screening for cyanide degradation, and the effects of cultural conditions on the growth and linamarase activity ofL. fermentumwere investigated based on standard procedures.

Results

A total of twenty-one bacterial isolates were obtained from cassava effluent, and isolate MA 9 had the highest growth of 2.8 × 1010 cfu/ml in minimum medium, confirmed as safe, identified asLactobacillus fermentumand selected for further study. The highest growth of 2.498 OD and linamarase activity of 2.49 U/ml were observed at inoculums volume of 0.10 ml at 48-h incubation period, while optimum growth of 1.926 OD and linamarase activity of 1.66 U/ml occurred at pH 5.5. At 37 °C, the optimum growth of 0.34 OD was recorded with the highest linamarase activity of 0.81 U/ml at 30 °C. However, the incubation period of 48 h stimulated an optimum growth of 3.091 OD with corresponding linamarase activity of 1.81 U/ml, while the substrate concentration of 400 ppm favours a maximum growth of 2.783 OD with linamarase activity of 1.86 U/ml at 48 h of incubation. The supplemented of 10 mM calcium ions stimulated optimum linamarase activity of 2.65 U/ml.

Conclusion

Lactobacillus fermentumcould be used as starter culture in cassava fermentation for the production cassava-based product with reduced cyanide content.
Monogenic Diabetes in a Child with Cystic Fibrosis: A Case Report and Review of the Literature
Authors: Scully Kevin J , Sawicki Gregory , Kremen Jessica , Putman Melissa S
Published: November 2020

Cystic fibrosis–related diabetes (CFRD) is associated with worsening pulmonary function, lower body mass index, increased infection frequency, and earlier mortality. While the incidence of CFRD is rising, its development in patients under the age of 10 years is uncommon.

We present a 9-year-old girl with cystic fibrosis (CF) who presented with a 5-year history of nonprogressive hyperglycemia, demonstrated by abnormal oral glucose tolerance tests, glycated hemoglobin A1c (HbA1c) levels consistently >6.5%, and negative pancreatic autoantibodies. Subsequent genetic testing revealed a pathogenic heterozygous recessive mutation in the GCK gene at c.667G>A (p.Gly223Ser), consistent with a diagnosis of GCK-MODY.

Significant dysglycemia in young children with CF should raise suspicion for alternative etiologies of diabetes and warrants further investigation. The clinical impact of underlying monogenic diabetes in patients with CF is unclear, and close follow-up is warranted. This case also offers unique insight on the impact of hyperglycemia in the absence of insulin deficiency on CF-specific outcomes.
Against Allegory
Authors: Hung Ruth Y.Y.
Published: November 2020

More than ten years on from the 2008 financial crisis, two trends of global statism remain dominant: Beijing-led “exceptional neoliberalism” and the emerging “illiberal democracy” topped by Trumponomics, with racist populism looming at the back of both. Even though these persistent programs are remnants of the ideological, national, and economic wars of the previous century, the boundary separating them is permeable. Jiang Rong 姜 戎’s prizewinning novel, Wolf Totem 《狼图腾》, helps us see this porosity. Wolf Totem is the first “Chinese Cultural Revolution” (fictional) memoir written explicitly for Chinese nationals and yet goes on to engage the sensibility of readers from a Western historical and ideological context. This essay critically identifies certain acts of reading Wolf Totem and looks at the way these selected readings, all allegorical in their approach, step across the literary subject to build symbolic extensions that stretch thin the wolves for various purposes. Collectively, such acts of reading expose both an important quality of our historical moment and the ideological function of literary intellectuals within it. They show that our era is one of skepticism about the status quo, one in which certain antidemocratic drives commiserate over historical conflicts and strategize for an extended, ongoing, and relentless process of global dominance. The popular reception of Wolf Totem crystallizes the thrust and conduct of these seeming competing drives. In the final analysis, this essay follows through the symptoms of these drives to reveal a kind of energetics or “primitivist social ethos” alive in the unified way humanity makes extinct any life forms unsubscribed to global statisms in their Beijing or “illiberal democratic” forms.
Our Unnamable Present
Authors: Comparini Alberto
Published: November 2020

In this review essay, I take on Roberto Calasso’s Unnamable Present and offer a critical framework to understand his thought after the publication of The Ruin of Kasch in 1983 and his vision of the world of our contemporary society. I argue that, by broadening Zygmunt Bauman’s “liquid modernity” concept, Calasso describes the political and ethical consequences of the loss of the sacred in our unnamed, ominous present. The result of this process is the historical creation of the Homo saecularis in the age of digital culture, whose cultural inconsistency is an expression of the current, unsettling political conditions of Western society, which Calasso directly puts in relation to the equally secular development of Islamism and Christianity.