bluuebunny/crossref_metadata_2025 huggingface dataset:
Public Policy Dilemma of Choosing the Medium of Instruction for School Education: A Case for Questioning Fallacies and Connecting Objectives
Authors: Jha Jyotsna
Published: August 2021

This article focuses on the issue of the public policy choice of the medium of instruction in public schools in India, taking the high demand for English-medium school education into consideration. Building on the available literature and evidence, the article argues against the introduction of English as a singular medium of instruction in school education. The introduction of English in public and private low-cost schools is not helping children in attaining any proficiency in English. The use of English also adversely impacts their capacity to learn other subjects well. The article argues for the adoption of the translanguaging philosophy and multilingual approach to address all objectives that drive the choice of a particular medium of instruction: gaining proficiency in the said languages, ability to communicate well using those languages, using those languages to learn other subjects, making schools inclusive by including diverse home languages present in school education and enabling diverse languages to flourish by promoting their learning and usage in formal schools. This requires a reform in institutional approaches and capacity building but does not necessarily imply additional burden. Certain parts of the world have adopted these approaches successfully and learning from them. Indian states can device their own approaches taking local contexts and realities into account.
The association of Greig syndrome and mastocytosis reveals the involvement of the hedgehog pathway in advanced mastocytosis
Authors: Polivka L. , Parietti V. , Bruneau J. , Soucie E. , Madrange M. , Bayard E. , Rignault R. , Canioni D. , Fraitag S. , Lhermitte L. , Feroul M. , Tissandier M. , Rossignol J. , Frenzel L. , Cagnard N. , Meni C. , Bouktit H. , Collange A.-F. , Gougoula C. , Parisot M. , Bader-Meunier B. , Livideanu C. , Laurent C. , Arock M. , Hadj-Rabia S. , Rüther U. , Dubreuil P. , Bodemer C. , Hermine O. , Maouche-Chrétien L.
Published: August 2021

Mastocytosis is a heterogeneous disease characterized by an abnormal accumulation of mast cells (MCs) in 1 or several organs. Although a somatic KIT D816V mutation is detected in ∼85% of patients, attempts to demonstrate its oncogenic effect alone have repeatedly failed, suggesting that additional pathways are involved in MC transformation. From 3 children presenting with both Greig cephalopolysyndactyly syndrome (GCPS, Mendelian Inheritance in Man [175700]) and congenital mastocytosis, we demonstrated the involvement of the hedgehog (Hh) pathway in mastocytosis. GCPS is an extremely rare syndrome resulting from haploinsufficiency of GLI3, the major repressor of Hh family members. From these familial cases of mastocytosis, we demonstrate that the Hh pathway is barely active in normal primary MCs and is overactive in neoplastic MCs. GLI3 and KIT mutations had a synergistic, tumorigenic effect on the onset of mastocytosis in a GCPS mouse model. Finally, Hh inhibitors suppressed neoplastic MC proliferation in vitro and extend the survival time of mice with aggressive systemic mastocytosis (ASM). This work revealed, for the first time, the involvement of Hh signaling in the pathophysiology of mastocytosis and demonstrated the cooperative effects of the KIT and Hh oncogenic pathways in mice with ASM, leading to the identification of new promising therapeutic targets.
Long non-coding RNAs as the critical regulators of doxorubicin resistance in tumor cells
Authors: Khalili-Tanha Ghazaleh , Moghbeli Meysam
Published: August 2021

Resistance against conventional chemotherapeutic agents is one of the main reasons for tumor relapse and poor clinical outcomes in cancer patients. Various mechanisms are associated with drug resistance, including drug efflux, cell cycle, DNA repair and apoptosis. Doxorubicin (DOX) is a widely used first-line anti-cancer drug that functions as a DNA topoisomerase II inhibitor. However, DOX resistance has emerged as a large hurdle in efficient tumor therapy. Furthermore, despite its wide clinical application, DOX is a double-edged sword: it can damage normal tissues and affect the quality of patients’ lives during and after treatment. It is essential to clarify the molecular basis of DOX resistance to support the development of novel therapeutic modalities with fewer and/or lower-impact side effects in cancer patients. Long non-coding RNAs (lncRNAs) have critical roles in the drug resistance of various tumors. In this review, we summarize the state of knowledge on all the lncRNAs associated with DOX resistance. The majority are involved in promoting DOX resistance. This review paves the way to introducing an lncRNA panel marker for the prediction of the DOX response and clinical outcomes for cancer patients.
Estimation of total mediation effect for high-dimensional omics mediators
Authors: Yang Tianzhong , Niu Jingbo , Chen Han , Wei Peng
Published: August 2021

Background

Environmental exposures can regulate intermediate molecular phenotypes, such as gene expression, by different mechanisms and thereby lead to various health outcomes. It is of significant scientific interest to unravel the role of potentially high-dimensional intermediate phenotypes in the relationship between environmental exposure and traits. Mediation analysis is an important tool for investigating such relationships. However, it has mainly focused on low-dimensional settings, and there is a lack of a good measure of the total mediation effect. Here, we extend an R-squared (R$$^2$$2) effect size measure, originally proposed in the single-mediator setting, to the moderate- and high-dimensional mediator settings in the mixed model framework.

Results

Based on extensive simulations, we compare our measure and estimation procedure with several frequently used mediation measures, including product, proportion, and ratio measures. Our R$$^2$$2-based second-moment measure has small bias and variance under the correctly specified model. To mitigate potential bias induced by non-mediators, we examine two variable selection procedures, i.e., iterative sure independence screening and false discovery rate control, to exclude the non-mediators. We establish the consistency of the proposed estimation procedures and introduce a resampling-based confidence interval. By applying the proposed estimation procedure, we found that 38% of the age-related variations in systolic blood pressure can be explained by gene expression profiles in the Framingham Heart Study of 1711 individuals. An R package “RsqMed” is available on CRAN.

Conclusion

R-squared (R$$^2$$2) is an effective and efficient measure for total mediation effect especially under high-dimensional setting.
A graphical, interactive and GPU-enabled workflow to process long-read sequencing data
Authors: Reddy Shishir , Hung Ling-Hong , Sala-Torra Olga , Radich Jerald P. , Yeung Cecilia CS , Yeung Ka Yee
Published: August 2021

Background

Long-read sequencing has great promise in enabling portable, rapid molecular-assisted cancer diagnoses. A key challenge in democratizing long-read sequencing technology in the biomedical and clinical community is the lack of graphical bioinformatics software tools which can efficiently process the raw nanopore reads, support graphical output and interactive visualizations for interpretations of results. Another obstacle is that high performance software tools for long-read sequencing data analyses often leverage graphics processing units (GPU), which is challenging and time-consuming to configure, especially on the cloud.

Results

We present a graphical cloud-enabled workflow for fast, interactive analysis of nanopore sequencing data using GPUs. Users customize parameters, monitor execution and visualize results through an accessible graphical interface. The workflow and its components are completely containerized to ensure reproducibility and facilitate installation of the GPU-enabled software. We also provide an Amazon Machine Image (AMI) with all software and drivers pre-installed for GPU computing on the cloud. Most importantly, we demonstrate the potential of applying our software tools to reduce the turnaround time of cancer diagnostics by generating blood cancer (NB4, K562, ME1, 238 MV4;11) cell line Nanopore data using the Flongle adapter. We observe a 29x speedup and a 93x reduction in costs for the rate-limiting basecalling step in the analysis of blood cancer cell line data.

Conclusions

Our interactive and efficient software tools will make analyses of Nanopore data using GPU and cloud computing accessible to biomedical and clinical scientists, thus facilitating the adoption of cost effective, fast, portable and real-time long-read sequencing.
Describing global pediatric RSV disease at intensive care units in GAVI-eligible countries using molecular point-of-care diagnostics: the RSV GOLD-III study protocol
Authors: Löwensteyn Yvette N. , Mazur Natalie I. , Nair Harish , Willemsen Joukje E. , van Thiel Ghislaine , Bont Louis ,   the RSV GOLD III—ICU Network study group, Garba Maria Ahuoiza , Giwa Fatima Jumai , Rasooly Mohammad Hafiz , Shirpoor Aminullah , Azizyar Merwais , Makalo Lamin , Nyan Ousman , Mohamed Ali , Osman Khalid , Chapagain Ram Hari , Bista Krishna Prasad , Sharma Arun Kumar , Shrestha Prabina , Goka Bamenla , Osman Kwabena , Obodai Evangeline , Mandi Henshaw , Esong Lucas Esuh , Eposse Charlotte Ekoube , Muando Valéria , Mussá Tufária , Said Yasser Habresh , Shoo Aika Abia , Dor Vanessa Jaelle , Gautier Jacqueline , Abicher Lynda
Published: August 2021

Background

Respiratory syncytial virus (RSV) infection is an important cause of hospitalization and death in young children. The majority of deaths (99%) occur in low- and lower-middle-income countries (LMICs). Vaccines against RSV infection are underway. To obtain access to RSV interventions, LMICs depend on support from Gavi, the Vaccine Alliance. To identify future vaccine target populations, information on children with severe RSV infection is required. However, there is a lack of individual patient-level clinical data on instances of life-threatening RSV infection in LMICs. The RSV GOLD III—ICU Network study aims to describe clinical, demographic and socioeconomic characteristics of children with life-threatening RSV infection in Gavi-eligible countries.

Methods

The RSV GOLD-III—ICU Network study is an international, prospective, observational multicenter study and will be conducted in 10 Gavi-eligible countries at pediatric intensive care units and high-dependency units (PICUs/HDUs) during local viral respiratory seasons for 2 years. Children younger than 2 years of age with respiratory symptoms fulfilling the World Health Organization (WHO) “extended severe acute respiratory infection (SARI)” case definition will be tested for RSV using a molecular point-of-care (POC) diagnostic device. Patient characteristics will be collected through a questionnaire. Mortality rates of children admitted to the PICU and/or HDU will be calculated.

Discussion

This multicenter descriptive study will provide a better understanding of the characteristics and mortality rates of children younger than 2 years with RSV infection admitted to the PICU/HDU in LMICs. These results will contribute to knowledge on global disease burden and awareness of RSV and will directly guide decision makers in their efforts to implement future RSV prevention strategies.

Trial registration number: NL9519, May 27, 2021
A comparison of predictors for mortality and bacteraemia in patients suspected of infection
Authors: Andreassen Steen , Møller Jens Kjølseth , Eliakim-Raz Noa , Lisby Gorm , Ward Logan
Published: August 2021

Background

Stratification by clinical scores of patients suspected of infection can be used to support decisions on treatment and diagnostic workup. Seven clinical scores, SepsisFinder (SF), National Early Warning Score (NEWS), Sequential Orgen Failure Assessment (SOFA), Mortality in Emergency Department Sepsis (MEDS), quick SOFA (qSOFA), Shapiro Decision Rule (SDR) and Systemic Inflammatory Response Syndrome (SIRS), were evaluated for their ability to predict 30-day mortality and bacteraemia and for their ability to identify a low risk group, where blood culture may not be cost-effective and a high risk group where direct-from-blood PCR (dfbPCR) may be cost effective.

Methods

Retrospective data from two Danish and an Israeli hospital with a total of 1816 patients were used to calculate the seven scores.

Results

SF had higher Area Under the Receiver Operating curve than the clinical scores for prediction of mortality and bacteraemia, significantly so for MEDS, qSOFA and SIRS. For mortality predictions SF also had significantly higher area under the curve than SDR. In a low risk group identified by SF, consisting of 33% of the patients only 1.7% had bacteraemia and mortality was 4.2%, giving a cost of € 1976 for one positive result by blood culture. This was higher than the cost of € 502 of one positive dfbPCR from a high risk group consisting of 10% of the patients, where 25.3% had bacteraemia and mortality was 24.2%.

Conclusion

This may motivate a health economic study of whether resources spent on low risk blood cultures might be better spent on high risk dfbPCR.
Metagenomic next-generation sequencing for the early diagnosis of talaromycosis in HIV-uninfected patients: five cases report
Authors: Chen Qiuhua , Qiu Ye , Zeng Wen , Wei Xuan , Zhang Jianquan
Published: August 2021

Background

In recent years, talaromycosis is reportedly on the rise in human immunodeficiency virus (HIV)-uninfected patients. However, the misdiagnosis and mistreatment of talaromycosis is more likely in HIV-uninfected patients than in HIV-infected patients because talaromycosis can be easily mistaken for tuberculosis or any other opportunistic infection. Therefore, we used metagenomic next-generation sequencing (mNGS), a novel gene detection method, for the diagnosis of talaromycosis in HIV-uninfected patients.

Case presentation

We report five cases diagnosed as talaromycosis by mNGS in HIV-uninfected patients, which were further confirmed by tissue culture. There were 3 male and 2 female patients. Two patients had a history of rat contact. The misdiagnosis duration ranged from 88 to 245 days. While the results of tissue culture changed from repeated negative to positive, the mNGS result for Talaromyces marneffei was positive earlier in 4 patients. The reads of Talaromyces marneffei in mNGS ranged from 5 to 414. After antifungal therapy, one of the outcomes was death due to the longest duration of misdiagnosis, and the other outcomes were clinical improvement.

Conclusions

mNGS is perhaps a rapid and effective diagnosis approach for the early confirmation of talaromycosis. Antifungal therapy is recommended once Talaromyces marneffei was revealed by mNGS. mNGS might reduce misdiagnosis duration and improve prognosis. Through these findings, we hope to provide some reference for talaromycosis in HIV-uninfected patients diagnosed early with the help of mNGS.
Diagnostic value of combined pleural interleukin-33, adenosine deaminase and peripheral blood tuberculosis T cell spot detection TB for tuberculous pleurisy
Authors: Fenhua Jin , Daohui Wang , Hui Lin , Xiaodong Xia , Wen Huang
Published: August 2021

Background

To investigate the correlation between pleural fluid interleukin-33 (IL-33) and adenosine deaminase (ADA) and peripheral blood tuberculosis T cell spot detection (T-SPOT.TB), and the combined value of the three tests for the diagnosis of tuberculous pleurisy.

Methods

79 patients with pleural effusion admitted from June 2017 to December 2018 were enrolled. They were divided into tuberculous pleural effusion (TPE) group (57 cases, 72.2%) and malignant pleural effusion group (17 cases, 21.5%), pneumonia-like pleural effusion group (5 cases, 6.3%). Correlation between pleural fluid IL-33, pleural effusion ADA and peripheral blood T-SPOT.TB was analyzed, comparison of the three separate and combined diagnostic efficacy was also performed.

Results

The levels of IL-33, ADA and peripheral blood T-SPOT.TB in patients with TPE were significantly higher than those in non-TPE (P < 0.001). The level of pleural fluid IL-33 was positively correlated with pleural effusion ADA and peripheral blood T-SPOT.TB. The Area under the ROC curve (AUC) of TPE diagnosed by pleural IL-33, ADA and peripheral blood T-SPOT.TB were 0.753, 0.912 and 0.865, respectively. AUC for combined detection of pleural effusion IL-33, ADA and peripheral blood T-SPOT.TB is the largest, with a value of 0.962. Specificity is 100% and sensitivity is 88.5%.

Conclusion

Combined detection of pleural effusion IL-33, ADA and peripheral blood T-SPOT.TB can improve the diagnostic efficacy of tuberculous pleurisy.
A mysterious sensation about sleep and health: the role of interoception
Authors: Arora Teresa , Barbato Mariapaola , Al Hemeiri Shaikha , Omar Omar M. , AlJassmi Maryam A.
Published: August 2021

Background

Interoception is mental awareness, recognition and acknowledgement of physiological body signals. Understanding the role of sleep and interoception may provide a better understanding surrounding the sleep-health connection. Our primary objective was to examine the potential relationships between subjective sleep quality and multiple dimensions of interoceptive abilities in a large sample of young adults, a group who are vulnerable to sleep impairment and its widespread health consequences.

Methods

We conducted an online cross-sectional survey targeting young adults, aged 18–25 years. The Pittsburgh Sleep Quality Index (PSQI) was used to identify subjective sleep quality and the Multidimensional Assessment of Interoceptive Awareness Version 2 was used to assess eight domains of interoception. We conducted a series of Spearman’s bivariate correlations to assess the relationships between global sleep quality as well as the seven PSQI sub-components in relation to the eight interoception outcomes. We then conducted quantile regression to assess if global PSQI score was an independent predictor of interoception. Participants (n = 609) consented and provided data.

Results

After adjustment, the global PSQI was a significant predictor of ‘Non-Distracting’, ‘Emotional Awareness’ and ‘Trusting’, where β = − 0.10 (95% CI: − 0.14, − 0.07), β = 0.05 (0.01, 0.09), and β = − 0.10 (− 0.14, − 0.05), respectively.

Conclusions

Our findings reveal a small, significant relationship between sleep quality and interoceptive abilities amongst young adults. Sleep impairment may inhibit interoceptive skills, thus adding value to the mechanistic explanation of the sleep-health relationship. Experimental and prospective studies are needed to determine temporal associations.
Association between cumulative cigarette and Waterpipe smoking and symptoms of dependence in Lebanese adults
Authors: Malaeb Diana , Akel Marwan , Sacre Hala , Haddad Chadia , Obeid Sahar , Hallit Souheil , Salameh Pascale
Published: August 2021

Background

Waterpipe and cigarette smoking dependence are becoming increasingly prevalent forms of addiction globally. This study examined whether cumulative cigarette smoking and cumulative waterpipe smoking are associated with higher dependence on both cigarettes and waterpipe.

Methods

This cross-sectional study conducted between February and April 2020, enrolled 363 participants drawn from all Lebanese districts. The mean age was 29.51 years, 64.8% were females, and 124 (34.2%) exclusive cigarette smokers, 189 (52.1%) exclusive waterpipe smokers, and 50 (13.8%) dual smokers (waterpipe and cigarette). We used the Hooked on Nicotine Checklist (HONC) as an indicator of decreased autonomy towards nicotine, in addition to the Lebanon Waterpipe Dependence Scale-11 (LWDS11) and the Lebanese Cigarette Dependence scale (LCD). A stepwise linear regression was performed taking the HONC scores due to cigarette and waterpipe smoking, LCD and LWDS-11 scores as dependent variables.

Results

The results showed that in the total sample, higher cumulative cigarette smoking (B = 0.005 with a confidence interval of 0.004, 0.006) was significantly associated with higher HONC cigarette scores, whereas higher cumulative waterpipe smoking (B = -0.006 with a confidence interval of − 0.009, − 0.002) was significantly associated with lower HONC cigarette scores. Moreover, higher cumulative waterpipe smoking (B = 0.012 with a confidence interval of 0.009,0.015) was significantly associated with higher HONC waterpipe scores. The results showed that, in both sexes, higher cumulative cigarette smoking was associated with higher HONC cigarette scores and lower HONC waterpipe scores. Furthermore, higher cumulative waterpipe smoking was significantly associated with higher HONC waterpipe scores in both sexes.

Conclusion

Our study supports the fact that heavy nicotine consumption, related to both the increased frequency and smoking duration, can increase the risk of dependence. It raises the need for strategic plans to minimize and discourage the use of nicotine products in Lebanese community settings.
The impact of graduated compression stockings on calf-vein deformation and blood velocity in patients awaiting total knee arthroplasty
Authors: Zhuang Zaikai , Wang Yexian , Yao Yao , Shen Ying , Chen Dongyang , Jiang Qing
Published: August 2021

Objectives

This study was designed to explore venous deformation of the lower extremities and the changes in venous hemodynamics in supine position before and after wearing graduated elastic stockings in patients awaiting total knee arthroplasty (TKA).

Method

The leg veins of 21 elderly patients awaiting TKA were imaged in the supine position with and without knee-length graduated compression stockings (GCS) according to a fixed protocol. Measured parameters including the lateromedial (LM) diameter, anteroposterior (AP) diameter, and cross-sectional area (CSA) of the great saphenous vein (GSV), gastrocnemius vein (GV), soleus vein (SV), posterior tibial vein (PTV), fibular vein (FV), and anterior tibial vein (ATV). In addition, the mean and maximum velocities of the popliteal vein (PV) and superficial femoral vein (FSV) were measured.

Results

GCS-related compression was observed for all the measured veins. Maximal reduction was observed for the GV and SV, whereas the GSV exhibited the lowest degree of GCS-related compression. The mean cross-sectional area reduction values associated with GCS were 33.1 ± 41.2 % for the GSV, 94.8 ± 11.1 % for the GV, and 85.6 ± 20.3 % for the SV, while the mean reduction of anteroposterior diameter was 18.1 ± 34.5 % for the GSV, 89.0 ± 22.5 % for the GV, and 72.9 ± 35.1 % for the SV, and the mean reduction of the lateromedial diameter was 25.9 ± 36.4 % for the GSV, 89.6 ± 19.6 % for the GV, 78.2 ± 28.3 % for the SV. No significant GCS-related changes in blood velocity in the superficial femoral veins or popliteal veins were detected.

Conclusions

For elderly patients awaiting TKA, knee-length GCS can significantly reduce calf vein dilation while at rest in the supine position, with the greatest reductions being observed for the soleus and gastrocnemius veins. These data might help provide a theoretical basis for the GCS in reducing incidence of deep vein thrombosis in patients undergoing TKA.
Collective forward-looking responsibility of patient advocacy organizations: conceptual and ethical analysis
Authors: Müller Regina , Rach Christoph , Salloch Sabine
Published: August 2021

Background

Patient advocacy organizations (PAOs) have an increasing influence on health policy and biomedical research, therefore, questions about the specific character of their responsibility arise: Can PAOs bear moral responsibility and, if so, to whom are they responsible, for what and on which normative basis? Although the concept of responsibility in healthcare is strongly discussed, PAOs particularly have rarely been systematically analyzed as morally responsible agents. The aim of the current paper is to analyze the character of PAOs’ responsibility to provide guidance to themselves and to other stakeholders in healthcare.

Methods

Responsibility is presented as a concept with four reference points: (1) The subject, (2) the object, (3) the addressee and (4) the underlying normative standard. This four-point relationship is applied to PAOs and the dimensions of collectivity and prospectivity are analyzed in each reference point.

Results

Understood as collectives, PAOs are, in principle, capable of intentionality and able to act and, thus, fulfill one prerequisite for the attribution of moral responsibility. Given their common mission to represent those affected, PAOs can be seen as responsible for patients’ representation and advocacy, primarily towards a certain group but secondarily in a broader social context. Various legal and political statements and the bioethical principles of justice, beneficence and empowerment can be used as a normative basis for attributing responsibility to PAOs.

Conclusions

The understanding of responsibility as a four-point relation incorporating collective and forward-looking dimensions helps one to understand the PAOs’ roles and responsibilities better. The analysis, thus, provides a basis for the debate about PAOs’ contribution and cooperation in the healthcare sector.
Frontline healthcare workers’ experiences in implementing the TB-DM collaborative framework in Northern Ghana
Authors: Salifu Rita Suhuyini , Hlongwana Khumbulani W.
Published: August 2021

Background

Over the past decade, global health policy has increased its focus on measures to halt further increase in tuberculosis (TB) incidence and management of diabetes mellitus (DM). However, the vertical management of these two diseases have not achieved much in addressing the adverse effects of the rising tuberculosis-diabetes co-epidemic. This necessitated the World Health Organisation and the International Union Against Tuberculosis and Lung Disease to develop a framework to manage this dual disease burden.

TB-DM co-epidemic is a public health concern in Ghana, adversely threatening the country’s fragile health systems. Since frontline healthcare workers are critical in health policy implementation, this study used Lipsky’s theoretical framework of street-level bureaucracy to explore their experiences in implementing the collaborative framework at the health facility level in Ghana.

Methods

This qualitative study was conducted between July to September 2019 using an exploratory design. Data was generated using a semi-structured interview guide designed to elicit information on knowledge of TB-DM comorbidity as well as systems for co-management. Twenty-three in-depth interviews were conducted among purposively selected frontline healthcare workers (doctors, nurses, TB task- shifting officers, TB institutional coordinators and hospital managers) from three health facilities in the Northern Region of Ghana. The lead author also conducted observations and document reviews, in order to fully address the study objectives. Thematic analysis was guided by the Lipsky’s theoretical framework of street level bureaucracy.

Results

The findings revealed three main themes and six sub-themes. Main themes were Prioritisation of TB/HIV co-infection while negating TB-DM comorbidity, Poor working conditions, and Coping mechanisms, whereas sub-themes were Low knowledge and awareness of TB-DM comorbidity, Limited awareness of the collaborative framework, High workload in TB & DM Clinics, Multiple roles, Inadequate training, and Space shortage.

Conclusions

Frontline healthcare workers had limited knowledge of TB-DM comorbidity and the collaborative framework, which, in turn adversely affected the effectiveness in implementing the framework. The effective implementation of the framework begins with raising awareness about the framework through in service training amongst the frontline healthcare workers. Additionally, an integrated screening tool to detect both TB and DM would help achieve early detection of TB-DM comorbidity.
Conductive single-wall carbon nanotubes/extracellular matrix hybrid hydrogels promote the lineage-specific development of seeding cells for tissue repair through reconstructing an integrin-dependent niche
Authors: Bai Rui , Liu Jianfeng , Zhang Jiao , Shi Jinmiao , Jin Zhigeng , Li Yi , Ding Xiaoyu , Zhu Xiaoming , Yuan Chao , Xiu Bingshui , Liu Huiliang , Yuan Zengqiang , Liu Zhiqiang
Published: August 2021

Background

The niche of tissue development in vivo involves the growth matrix, biophysical cues and cell-cell interactions. Although natural extracellular matrixes may provide good supporting for seeding cells in vitro, it is evitable to destroy biophysical cues during decellularization. Reconstructing the bioactivities of extracellular matrix-based scaffolds is essential for their usage in tissue repair.

Results

In the study, a hybrid hydrogel was developed by incorporating single-wall carbon nanotubes (SWCNTs) into heart-derived extracellular matrixes. Interestingly, insoluble SWCNTs were well dispersed in hybrid hydrogel solution via the interaction with extracellular matrix proteins. Importantly, an augmented integrin-dependent niche was reconstructed in the hybrid hydrogel, which could work like biophysical cues to activate integrin-related pathway of seeding cells. As supporting scaffolds in vitro, the hybrid hydrogels were observed to significantly promote seeding cell adhesion, differentiation, as well as structural and functional development towards mature cardiac tissues. As injectable carrier scaffolds in vivo, the hybrid hydrogels were then used to delivery stem cells for myocardial repair in rats. Similarly, significantly enhanced cardiac differentiation and maturation(12.5 ± 2.3% VS 32.8 ± 5%) of stem cells were detected in vivo, resulting in improved myocardial regeneration and repair.

Conclusions

The study represented a simple and powerful approach for exploring bioactive scaffold to promote stem cell-based tissue repair.

Graphic abstract
Combination of cell-penetrating peptides with nanomaterials for the potential therapeutics of central nervous system disorders: a review
Authors: Zhang Ying , Guo Pan , Ma Zhe , Lu Peng , Kebebe Dereje , Liu Zhidong
Published: August 2021

Although nanomedicine have greatly developed and human life span has been extended, we have witnessed the soared incidence of central nervous system (CNS) diseases including neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease), ischemic stroke, and brain tumors, which have severely damaged the quality of life and greatly increased the economic and social burdens. Moreover, partial small molecule drugs and almost all large molecule drugs (such as recombinant protein, therapeutic antibody, and nucleic acid) cannot cross the blood–brain barrier. Therefore, it is especially important to develop a drug delivery system that can effectively deliver therapeutic drugs to the central nervous system for the treatment of central nervous system diseases. Cell penetrating peptides (CPPs) provide a potential strategy for the transport of macromolecules through the blood–brain barrier. This study analyzed and summarized the progress of CPPs in CNS diseases from three aspects: CPPs, the conjugates of CPPs and drug, and CPPs modified nanoparticles to provide scientific basis for the application of CPPs for CNS diseases.
Frequency of juvenile idiopathic arthritis and associated uveitis in pediatric rheumatology clinics in Turkey: A retrospective study, JUPITER
Authors: Sahin Sezgin , Acari Ceyhun , Sonmez Hafize Emine , Kilic Fatma Zehra , Sag Erdal , Dundar Hatice Adiguzel , Adrovic Amra , Demir Selcan , Barut Kenan , Bilginer Yelda , Sozeri Betul , Unsal Erbil , Ozen Seza , Kasapcopur Ozgur
Published: August 2021

Background

Juvenile idiopathic arthritis (JIA), is the most common pediatric rheumatologic disorder with unknown etiology. Currently, no population-based data are available regarding the distribution of categories and frequency of uveitis in patients with JIA in Turkey. The purpose of this study was to evaluate the frequency of JIA-associated uveitis (JIAU) and distribution of JIA categories in a Turkish JIA cohort.

Methods

This was a retrospective study of 500 randomized patients in four pediatric rheumatology clinics in Turkey.

Results

Oligoarticular JIA (oJIA) was the most common JIA disease category in this study cohort (38.8%). The frequencies of the other categories were as follows: enthesitis-related arthritis (ERA), 23.2%; rheumatoid factor (RF)–negative polyarthritis, 15.6%; systemic arthritis, 12.2%; juvenile psoriatic arthritis, 5.2%; undifferentiated arthritis, 2.8%; and RF-positive polyarthritis, 2.2%. JIA-associated uveitis was observed in 6.8% of patients at a mean (Standard Deviation, SD) age of 9.1 (3.8) years over a mean JIA disease duration of 4 (1.9) years. Uveitis developed after joint disease, with a mean (SD) duration of 1.8 (1.9) years. Patients with oJIA had the highest rate of uveitis (12.9%) followed by patients with ERA (5.2%) and polyarticular RF-negative disease (3.8%). Compared with persistent oJIA, the extended oJIA category had a > 3-fold higher risk of uveitis (11.3% vs 27.7%; odds ratio, 3.38 [95% Confidence Interval, 1.09–10.4]). The most frequently administered drug after development of uveitis was tumor necrosis factor–alpha inhibitors (38.2%). Five patients (14.7%) had uveitis-related complications that required surgical intervention.

Conclusions

Turkish pediatric patients with JIA experience a lower frequency of oJIA and higher frequency of ERA than their white European counterparts; the occurrence of uveitis is also somewhat lower than expected. Geographic and ethnic factors may affect these differences and need further investigation.
Breast milk to blood lead ratios among women from the West Bank of Palestine: a cross-sectional study of associated factors
Authors: Shawahna Ramzi
Published: August 2021

Background

Infants fed contaminated breast milk are at an increased risk of exposure to lead. Breast milk to blood (M/B) ratios have not been investigated among women in Palestine. The aim of this study was to assess blood, breast milk, and M/B lead ratios in samples collected from Palestinian breastfeeding women. Associations between sociodemographic characteristics with breast milk lead levels and M/B lead ratios were also investigated.

Methods

This study was conducted in a cross-sectional design in the period between October 2017 and April 2018. Breastfeeding women visiting maternity care centers in different regions of the West Bank of Palestine were recruited to the study by the nurses in the maternity care centers. Sociodemographic characteristics, venous blood, and breast milk samples were collected from each participant. Lead concentrations were analyzed using a validated inductively coupled plasma-mass spectrometric method. Mann–Whitney U test, Pearson’s Chi-square, Fisher’s exact, and Spearman’s correlations were used to analyze the data. Odds ratios (OR) were computed using a multivariate logistic regression model.

Results

Matching blood and milk samples were collected from 80 women. Lead concentrations in 11 (13.8%) of the breast milk samples were above the World Health Organization’s recommended levels. Breast milk lead levels were more likely to be ≥5 μg/L in breastfeeding women who lived in urban areas (aOR 4.96; 95% CI 1.10, 22.38) compared to those who lived in rural areas. Breast milk to blood lead ratios were more likely to be ≥25% in breastfeeding women who lived in urban areas (aOR 7.06; 95% CI 1.68, 29.77), used eye kohl (aOR 14.29; 95% CI 1.32, 155.06), and used hair dye (aOR 5.33; 95% CI 1.58, 18.00) compared to those who lived in rural areas, did not use eye kohl, and did not use hair dye, respectively.

Conclusions

Higher M/B lead ratios were predicted by living in urban areas, using eye kohl, and using hair dye. Decision makers in health authorities should address sources of exposure to lead in urban areas. Cosmetics containing lead should be assessed and regulated for lead content.
Bilirubin adsorption versus plasma exchange for hyperbilirubinemia in patients after cardiac surgery: a retrospective study
Authors: Pan Ke , Zhang He , Zhong Kai , Zhang Hai-tao , Li Ze-shi , Chen Zhong , Gu Su-ping , Xie Man , Pan Tuo , Cao Hai-long , Wang Dong-jin
Published: August 2021

Objective

Hyperbilirubinemia after cardiac surgery increases in-hospital mortality and is associated with poor prognosis. Our present study aimed to compare the efficacy of bilirubin adsorption (BA) and plasma exchange (PEX) in patients with hyperbilirubinemia after cardiac surgery.

Methods

We retrospectively included patients who underwent BA treatment or PEX treatment due to severe hyperbilirubinemia after cardiac surgery at our center from 2015 to 2020. We collected results from urine and liver function tests before and after treatment and compared the in-hospital mortality and morbidity between the two treatment groups.

Results

A total of 56 patients were enrolled in this study: 14 patients received BA treatment, and 42 patients received PEX treatment. Compared to the PEX group, the BA group exhibited a statistically significant reduction in total bilirubin (p = 0.016) and direct bilirubin (p = 0.036) levels. The in-hospital mortality was 85.7% (48/56) in the whole group, and the BA group had a lower mortality than the PEX group (71.4% vs. 90.5%, p = 0.078). The BA group showed better circulatory support, including lower risks of IABP (21.4% vs. 52.4%, p = 0.044), ECMO (21.4% vs. 50.0%, p = 0.061), reintubation (64.3% vs. 40.5%, p = 0.122) and ventricular arrhythmias (64.3% vs. 45.2%, p = 0.217). The in-hospital mortality was still lower in the BA treatment group than in the PEX treatment group (71.4% vs. 100%, p = 0.049) in the matched cohort.

Conclusions

Compared to PEX treatment, BA treatment had a higher bilirubin removal ability in patients with hyperbilirubinemia and could reduce the mortality and risks of poor clinical outcomes. BA treatment should be considered an effective treatment method for patients with higher total bilirubin or direct bilirubin levels.
A comprehensive review of the botany, ethnopharmacology, biochemistry, pharmacology, pharmacokinetics and toxicity of Filifolium sibiricum (L.)Kitam
Authors: Lv Shaowa , Qiu Qian , Wang Qiuhong , Kuang Haixue
Published: August 2021

Filifoliumsibiricum (L.)Kitam (F.sibiricum), a compositae plant, is especially used to inhibit drug-resistant bacteria in folk medicine. Modern pharmacological studies also confirmed a variety of pharmacological properties about sedative activities, antibacterial activity, anti-inflammatory activity, analgesic activities, antitussive and asthma relieving. In this paper, the research progress of F.sibiricum in botany, ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and toxicology was reviewed. Prospects for future investigation and application of this herb were also discussed. Information on F.sibiricum was gathered from various sources, including books on traditional Chinese herbal medicine and scientific databases such as PubMed, Google Scholar, Science Direct, Baidu Scholar, CNKI and other professional websites. The results indicate that ~ 66 chemical compounds were isolated and identified from F.sibiricum. Among them, flavonoids are generally considered to be the main bioactive and characteristic ingredients. F.sibiricum is a traditional Chinese medicine with pharmacological activities such as the immune system, nervous system, respiratory system and cardiovascular and cerebrovascular systems. Most importantly, we should concentrate on developing new drugs related to F.sibiricum, so as to exert greater potential for treatment.
INFIMA leverages multi-omics model organism data to identify effector genes of human GWAS variants
Authors: Dong Chenyang , Simonett Shane P. , Shin Sunyoung , Stapleton Donnie S. , Schueler Kathryn L. , Churchill Gary A. , Lu Leina , Liu Xiaoxiao , Jin Fulai , Li Yan , Attie Alan D. , Keller Mark P. , Keleş Sündüz
Published: August 2021

Genome-wide association studies reveal many non-coding variants associated with complex traits. However, model organism studies largely remain as an untapped resource for unveiling the effector genes of non-coding variants. We develop INFIMA, Integrative Fine-Mapping, to pinpoint causal SNPs for diversity outbred (DO) mice eQTL by integrating founder mice multi-omics data including ATAC-seq, RNA-seq, footprinting, and in silico mutation analysis. We demonstrate INFIMA’s superior performance compared to alternatives with human and mouse chromatin conformation capture datasets. We apply INFIMA to identify novel effector genes for GWAS variants associated with diabetes. The results of the application are available at http://www.statlab.wisc.edu/shiny/INFIMA/.
Integrative approach identifies SLC6A20 and CXCR6 as putative causal genes for the COVID-19 GWAS signal in the 3p21.31 locus
Authors: Kasela Silva , Daniloski Zharko , Bollepalli Sailalitha , Jordan Tristan X. , tenOever Benjamin R. , Sanjana Neville E. , Lappalainen Tuuli
Published: August 2021

To date, the locus with the most robust human genetic association to COVID-19 severity is 3p21.31. Here, we integrate genome-scale CRISPR loss-of-function screens and eQTLs in diverse cell types and tissues to pinpoint genes underlying COVID-19 risk. Our findings identify SLC6A20 and CXCR6 as putative causal genes that modulate COVID-19 risk and highlight the usefulness of this integrative approach to bridge the divide between correlational and causal studies of human biology.
Tissue engineering of mouse uterus using menstrual blood stem cells (MenSCs) and decellularized uterine scaffold
Authors: Arezoo Nouri , Mohammad Hajian , Malihezaman Monsefi
Published: August 2021

Background

Uterine tissue engineering can provide the opportunity for curing female infertility. Natural scaffold is a good choice to recapitulate the architecture and functionality of the native tissue. In this study, we purposed the potential of uterine decellularized scaffolds as an adequate natural niche for MenSCs differentiation toward uterus-specific cell lineages.

Methods

Mouse’s uterus was decellularized by immersion of hypo and hypertonic salts or freeze–thaw cycle followed by immersion in Triton X-100 and SDS solutions. MenSCs were isolated from the menstrual blood of 6 healthy women. The decellularized and recellularized samples were prepared for further in vitro and in vivo analyses.

Results

Histochemical studies and Raman spectroscopy revealed uterine ECM was preserved well, and the cells were completely removed after decellularization. Scanning electron microscopy (SEM) showed that the 3D ultrastructure of the uterus remained intact. Flowcytometric examination with CD34, CD44, CD105, CD106, CD144 markers revealed stem cell characters of cells that isolated from menstrual blood. MTT assay confirmed the bioavailability of MenSCs cultured scaffolds after 7 and 10 days.

Conclusion

Histochemical studies, SEM images, and Raman spectra showed MenSCs seeded and growth in uterine scaffolds. Immunostaining using anti-cytokeratin (CK), anti-desmin (Des), anti-vimentin (Vim), and anti-smooth muscle actin (SMA) antibodies showed MenSCs differentiation to epithelial and smooth muscle tissues. The Raman spectroscopy revealed the extracellular matrix (ECM) of decellularized uterine scaffolds was well preserved. The decellularized uterus can be considered a promising vehicle to support cell transplantation and differentiation. MenSCs are a good choice for uterine tissue engineering. The complete decellularization from mice uterine tissue was done by combining chemical agents
Comparative genomic analysis of azasugar biosynthesis
Authors: Beal Hailey E. , Horenstein Nicole A.
Published: August 2021

Azasugars are monosaccharide analogs in which the ring oxygen is replaced with a nitrogen atom. These well-known glycosidase inhibitors are of interest as therapeutics, yet several aspects of azasugars remain unknown including their distribution, structural diversity, and chemical ecology. The hallmark signature of bacterial azasugar biosynthesis is a three gene cluster (3GC) coding for aminotransferase, phosphatase, and dehydrogenase enzymes. Using the bioinformatics platform Enzyme Similarity Tool (EST), we identified hundreds of putative three gene clusters coding for azasugar production in microbial species. In the course of this work, we also report a consensus sequence for the aminotransferase involved in azasugar biosynthesis as being: SGNXFRXXXFPNXXXXXXXLXVPXPYCXRC. Most clusters are found in Bacillus and Streptomyces species which typically inhabit soil and the rhizosphere, but some clusters are found with diverse species representation such as Photorhabdus and Xenorhabdus which are symbiotic with entomopathogenic nematodes; the human skin commensal Cutibacterium acnes, and the marine Bacillus rugosus SPB7, a symbiont to the sea sponge Spongia officinalis. This pan-taxonomic survey of the azasugar 3GC signature may lead to the identification of new azasugar producers, facilitate studies of their natural functions, and lead to new potential therapeutics.
Intracellular proteome compartmentalization: a biotin ligase-based proximity labeling approach
Authors: Durojaye Olanrewaju Ayodeji
Published: August 2021

Specialized biological processes occur in different regions and organelles of the cell. Additionally, the function of proteins correlate greatly with their interactions and subcellular localization. Understanding the mechanism underlying the specialized functions of cellular structures therefore requires a detailed identification of proteins within spatially defined domains of the cell. Furthermore, the identification of interacting proteins is also crucial for the elucidation of the underlying mechanism of complex cellular processes. Mass spectrometry methods have been utilized systematically for the characterization of the proteome of isolated organelles and protein interactors purified through affinity pull-down or following crosslinking. However, the available methods of purification have limited these approaches, as it is difficult to derive intact organelles of high purity in many circumstances. Furthermore, contamination that leads to the identification of false positive is widespread even when purification is possible. Here, we present a highlight of the BioID proximity labeling approach which has been used to effectively characterize the proteomic composition of several cellular compartments. In addition, an observed limitation of this method based on proteomic spatiotemporal dynamics, was also discussed.
Distributed localization using Levenberg-Marquardt algorithm
Authors: Ahmadi Shervin Parvini , Hansson Anders , Pakazad Sina Khoshfetrat
Published: August 2021

In this paper, we propose a distributed algorithm for sensor network localization based on a maximum likelihood formulation. It relies on the Levenberg-Marquardt algorithm where the computations are distributed among different computational agents using message passing, or equivalently dynamic programming. The resulting algorithm provides a good localization accuracy, and it converges to the same solution as its centralized counterpart. Moreover, it requires fewer iterations and communications between computational agents as compared to first-order methods. The performance of the algorithm is demonstrated with extensive simulations in Julia in which it is shown that our method outperforms distributed methods that are based on approximate maximum likelihood formulations.