bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation between TGF-β2/3 promoter DNA methylation and Smad signaling during palatal fusion induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin
Authors: Chen Yao , Liu Xiaozhuan , Liu Xinxin , Cui Lingling , He Zhidong , Gao Zhan , Liu Limin , Li Zhitao , Wan Zhongxiao , Yu Zengli
Published: June 2021

2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) is a persistent organic pollutant that is strongly associated with a number of human diseases and birth defects, including cleft palate. Transforming growth factor (TGF) plays a significant role during mammalian palatogenesis. However, the epigenetic mechanism of transforming growth factors in the process of TCDD-induced cleft palate is unclear. The purpose of this research was to investigate the relationship and potential mechanism between TGF-β2/3 promoter DNA methylation and Smad signaling during TCDD-induced cleft palate. Pregnant C57BL/6N mice were exposed to 64 µg/kg TCDD on gestational day 10 (GD10) to establish the cleft palate model and palatal tissues of embryos were collected on GD13, GD14, and GD15 for subsequent experiments. TGF-β2/3 mRNA expression, TGF-β2/3 promoter methylation, and Smad signaling molecules expression were assessed in the palate of the two groups. The results showed that the incidence of cleft palate was 94.7% in the TCDD-treated group whereas no cleft palate was found in the control group. TCDD-treated group altered specific CpG sites of TGF-β2/3 promoter methylation. Compared to the control group, the proliferation of mouse embryonic palate mesenchymal stromal cells (MEPM), the expressions of TGF-β2/3, p-Smad2, and Smad4 were all reduced, while the expression of Smad7 was significantly increased in the atAR group. Smad signaling was downregulated by TCDD. Therefore, we suggest that TGF-β2/3 promoter methylation and Smad signaling may be involved in TCDD-induced cleft palate formation in fetal mice.
Role of sex hormones in lung cancer
Authors: Fuentes Nathalie , Silva Rodriguez Miguel , Silveyra Patricia
Published: June 2021

Lung cancer represents the world’s leading cause of cancer deaths. Sex differences in the incidence and mortality rates for various types of lung cancers have been identified, but the biological and endocrine mechanisms implicated in these disparities have not yet been determined. While some cancers such as lung adenocarcinoma are more commonly found among women than men, others like squamous cell carcinoma display the opposite pattern or show no sex differences. Associations of tobacco product use rates, susceptibility to carcinogens, occupational exposures, and indoor and outdoor air pollution have also been linked to differential rates of lung cancer occurrence and mortality between sexes. While roles for sex hormones in other types of cancers affecting women or men have been identified and described, little is known about the influence of sex hormones in lung cancer. One potential mechanism identified to date is the synergism between estrogen and some tobacco compounds, and oncogene mutations, in inducing the expression of metabolic enzymes, leading to enhanced formation of reactive oxygen species and DNA adducts, and subsequent lung carcinogenesis. In this review, we present the literature available regarding sex differences in cancer rates, associations of male and female sex hormones with lung cancer, the influence of exogenous hormone therapy in women, and potential mechanisms mediated by male and female sex hormone receptors in lung carcinogenesis. The influence of biological sex on lung disease has recently been established, thus new research incorporating this variable will shed light on the mechanisms behind the observed disparities in lung cancer rates, and potentially lead to the development of new therapeutics to treat this devastating disease.
Multidimensional Phase I Dose Ranging Trials for Stroke Recovery Interventions: Key Challenges and How to Address Them
Authors: Dalton Emily J. , Churilov Leonid , Lannin Natasha A. , Corbett Dale , Campbell Bruce C. V. , Hayward Kathryn S.
Published: June 2021

Despite an increase in the amount of published stroke recovery research, interventions have failed to markedly affect the trajectory of recovery poststroke. We argue that early-phase research to systematically investigate dose is an important contributor to advance the science underpinning stroke recovery. In this article, we aim to ( a) define the problem of insufficient use of a systematic approach to early-phase, multidimensional dose articulation research and ( b) propose a solution that applies this approach to design a multidimensional phase I trial to identify the maximum tolerated dose (MTD). We put forward a design template as a decision support tool to increase knowledge of how to develop a phase I dose-ranging trial for nonpharmaceutical stroke recovery interventions. This solution has the potential to advance the development of efficacious stroke recovery interventions, which include activity-based rehabilitation interventions.
Dose-Dependent Effect of Polystyrene Microplastics on the Testicular Tissues of the Male Sprague Dawley Rats
Authors: Ijaz Muhammad Umar , Shahzadi Sabahat , Samad Abdul , Ehsan Nazia , Ahmed Hussain , Tahir Arfa , Rehman Humaira , Anwar Haseeb
Published: June 2021

Due to the continuous increase in polystyrene microplastics (PS MPs) incorporation in the environment, growing number of adverse effects on living organisms and ecosystem have become a global concern. Therefore, current study was planned to elucidate the impacts of 5 different concentrations control, 2, 20, 200, and 2000 μgL-1 of PS MPs on testicular tissues of rats. PS MPs significantly reduced the activities of antioxidant enzymes (catalase, superoxide dismutase and peroxidase) as well as total protein contents, while elevated the level of lipid peroxidation and reactive oxygen species. Moreover, expressions of steroidogenic enzymes (3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase and steroidogenic acute regulatory protein) as well as the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) in plasma, intra-testicular testosterone and plasma testosterone were reduced and a significant ( P < 0.05) reduction was noticed in the sperm count, motility and viability. Furthermore, PS MPs significantly up-regulated the expressions of Bax and caspase-3, while down-regulated the Bcl-2 expression. The histomorphological assessment revealed significant damages in the testicles as well as decrease in the number of germ cells (spermatogenic, spermatocytes and spermatids). Collectively, PS MPs generated oxidative stress (OS) and caused potential damage to the testicles of rats in a dose-dependent manner.
Carotid artery stenosis in correlation with neck and carotid artery anatomy
Authors: Stula Ivana , Kojundzic Sanja L , Guic Maja M , Novak Katarina
Published: June 2021

Objectives

The purpose of this study was to examine the relationship between neck anatomy, especially its largest muscle – sternocleidomastoid and carotid space, with carotid artery anatomy and stenosis.

Methods

We analysed 102 computed tomography carotid angiograms. The study included the measurement of the neck and sternocleidomastoid length, diameter and volume and the size of the carotid space. Analysis of carotid artery geometry, the length, angle and height of carotid artery bifurcation and the direction of the internal carotid artery origin was also included.

Results

We found a positive correlation only between the neck and carotid length. There was no correlation between other neck characteristics and a carotid anatomy or internal carotid artery stenosis. Direction of internal carotid artery origin was significantly different (p < 0.01) between the left and right sides.

Conclusions

We have not found a correlation between the size of sternocleidomastoid and carotid space and carotid stenosis as a hypothetical factor for atherosclerosis. Also, the degree of carotid artery stenosis did not correlate with other neck and carotid measurements. Neck and carotid anatomy correlated only in their lengths. The left internal carotid artery showed mostly posterolateral origin, and right internal carotid artery had no predominate direction.
Distinct roles of GT1b and CSF-1 in microglia activation in nerve injury-induced neuropathic pain
Authors: Lee Jaesung , Hwang Heehong , Lee Sung Joong
Published: June 2021

Although microglia activation plays an important role in the development of nerve injury-induced neuropathic pain, the molecular mechanisms of spinal cord microglia activation in nerve injury are not completely understood. Recently, two injured sensory neuron-derived molecules, colony stimulating factor-1 (CSF-1) and GT1b, were proposed to trigger spinal cord microglia activation, yet their relationship and relative contribution to microglia activation have not been addressed. In the present study, the role of GT1b and CSF-1 in microglia activation and proliferation was characterized. GT1b stimulation upregulated proinflammatory mediators such as IL-1β, TNF-α, and NADPH oxidase 2 (Nox2), without microglia proliferation. Conversely, CSF-1 stimulation induced microglia proliferation with minimal proinflammatory gene induction. Notably, neither GT1b nor CSF-1 induced mechanical hypersensitivity in female mice; however, they induced similar microglial proliferation in both male and female mice. Taken together, our data indicate that injured sensory neuron-derived GT1b and CSF-1 activate spinal cord microglia in concert through distinct activation pathways.
How does practice change across the season? A descriptive study of the training structures and practice activities implemented by a professional Australian football team
Authors: Tribolet Rhys , Sheehan William Bradshaw , Novak Andrew Roman , Watsford Mark Langley , Fransen Job
Published: June 2021

There is limited research investigating objective practice monitoring in team sports. This observational study examined the practice activities used by eight professional coaches across 72 different practice sessions in one season within a professional Australian football team. This study aimed to evaluate the extent to which these practice types differed from those shown to facilitate skill acquisition in team sports. Across the whole season (pre-season and in-season), coaches implemented seven practice types which were categorised into training-form and playing-form. Practice type frequencies were different between pre- and in-season (χ2 = 109.6, p < 0.001). Significant differences were reported for practice type duration between pre-season and in-season (p = 0.023, d=–0.17), where in-season activities were longer. Coaches implemented a higher percentage of practice time to playing-form activities in-season (62.0 [Formula: see text] 25.4) compared to pre-season (52.4 [Formula: see text] 19.8) [95%CI: –2.35:21.4]. Coaches were more likely to alter the frequency of practice types, rather than the exposure time. Players performed more training-form activities during pre-season than in-season (χ2 = 30.8, p < 0.001). There were no differences in playing-form activities between pre- and in-season. This study provides insights into the practice activities implemented by professional Australian football coaches and discusses the extent to which they represent best practice in the context of skill acquisition.
Is there a relationship between the overhead press and split jerk maximum performance? Influence of sex
Authors: Soriano Marcos A , Haff G Gregory , Comfort Paul , Amaro-Gahete Francisco J , Torres-González Antonio , García-Cifo Angel , Jiménez-Ormeño Ester , de Baranda Pilar Sainz
Published: June 2021

The aims of this study were to (I) determine the differences and relationship between the overhead press and split jerk performance in athletes involved in weightlifting training, and (II) explore the magnitude of these differences in one-repetition maximum (1RM) performances between sexes. Sixty-one men (age: 30.4 ± 6.7 years; height: 1.8 ± 0.5 m; body mass 82.5 ± 8.5 kg; weightlifting training experience: 3.7 ± 3.5 yrs) and 21 women (age: 29.5 ± 5.2 yrs; height: 1.7 ± 0.5 m; body mass: 62.6 ± 5.7 kg; weightlifting training experience: 3.0 ± 1.5 yrs) participated. The 1RM performance of the overhead press and split jerk were assessed for all participants, with the overhead press assessed on two occasions to determine between-session reliability. The intraclass correlation coefficients (ICC) and 95% confidence intervals showed a high reliability for the overhead press ICC = 0.98 (0.97 – 0.99). A very strong correlation and significant differences were found between the overhead press and split jerk 1RM performances for all participants (r = 0.90 [0.93 – 0.85], 60.2 ± 18.3 kg, 95.7 ± 29.3 kg, p ≤ 0.001). Men demonstrated stronger correlations between the overhead press and split jerk 1RM performances (r = 0.83 [0.73-0.90], p ≤ 0.001) compared with women (r = 0.56 [0.17-0.80], p = 0.008). These results provide evidence that 1RM performance of the overhead press and split jerk performance are highly related, highlighting the importance of upper-limb strength in the split jerk maximum performance.
Patient/Consumer Codesign and Coproduction of Medical Curricula: A Possible Path Toward Improved Cultural Competence and Reduced Health Disparity
Authors: Kealy-Bateman Warren , Gorman Georgina M. , Carroll Adam P.
Published: June 2021

There is often a sociocultural distance between medical practitioners and patients. We bridge that gap in the therapeutic alliance via improved cultural competence and an understanding of the person in their context. The traditional approach in medical education has been of learning via expert-designed curricula, which may tend to mirror the knowledge and needs of the experts. This places individuals at risk who come from culturally and linguistically diverse groups (CALD) with known health disparities: minority groups (e.g., African American); First Nations’ people; immigrants and refugees; people who speak nondominant languages; and lesbian, gay, bisexual, transgender people. The authors briefly review the complex area of cultural competency and teaching delivery. The authors survey the Australian population to provide a tangible example of complex cultural diversity amid curriculum challenges. An evidence-based approach that recognizes specific health inequity; the inclusion of CALD stakeholders, students, care professionals, and education professionals; and codesign and coproduction of curriculum components is recommended. This method of people’s own stories and collaboration may be applied in any international context, correctly calibrating the learning experience. The aim is for medical students to improve their knowledge of self, others, others within groups, and recognition of unconscious biases to achieve better health outcomes within their specific communities.
Platform Corporate Social Responsibility and Employee Innovation Performance: A Cross-Layer Study Mediated by Employee Intrapreneurship
Authors: Li Yibin , Zhang Guiqing , Liu Longjun
Published: June 2021

Based on social exchange theory, this research developed a theoretical model on the impact of the internal corporate social responsibility (ICSR) of platform enterprises on employee innovation performance. Based on 414 employee data from 56 platform enterprises, hierarchical linear modeling was employed to test the model at two time points. The results revealed that the ICSR of platform enterprises has a significant positive effect on employee innovation performance, and employee intrapreneurship mediates the relationship; that is, the ICSR of platform enterprises promotes employees’ innovation performance by stimulating their intrapreneurship. Employees’ moral identity can also positively moderate the relationship between the ICSR of platform enterprises and employee intrapreneurship; the stronger the employees’ moral identity is, the stronger the positive impact of the platform’s ICSR is on the employees’ intrapreneurship. The relationship between the ICSR and employee innovation performance was clarified under platform economics. The current conclusions can guide platform enterprises’ innovation and sustainable development efforts.
Exploring the Fundamental Factors of Digital Inequality in Bangladesh
Authors: Islam Muhammad Nazrul , Inan Toki Tahmid
Published: June 2021

Digital inequality is imperative to combat the perpetuation of national development and significantly exists in developing countries. Thus, the purpose of this article is to provide the underlying factors of creating digital inequality in Bangladesh. A mixed-method research approach was followed where both the qualitative and quantitative data were collected using focus group discussion (FGD), semi-structured interviews, and survey. The FGD and interviews were replicated with a total of 60 participants (each study with 30 participants), while 326 respondents participated in the survey study. The content analysis, word cloud, affinity diagram, and descriptive statistics were used to analyze the data. As an outcome, the studies revealed 23 factors that create digital inequality in Bangladesh. The factors were clustered into five groups (referred as elements) of digital inequality through an affinity diagram. The resultant elements of digital inequality were educational, infrastructural, social, economic, and usable design. The results reflect on what factors should consider ensuring the inclusion, adoption, and contributions of information and communications technology in Bangladesh, which in turn contributes to reducing the digital inequality in Bangladesh. As a practical contribution, this research provides an in-depth scenario of digital inclusion and exclusion in Bangladesh, and the underline factors of creating digital inequality, so that nongovernmental organizations and government organizations may take necessary initiatives toward each dimension of digital inequality. The results also include identification of future research agenda toward reducing digital inequality.
Internal GIG Ecosystem in IT/ITeS Organisations for Non-linear Growth
Authors: Dutta Debolina , Mirchandani Prem , Anasha K. P.
Published: June 2021

The Indian IT/ITeS industry is a significant contributor to India’s GDP and has had an impressive growth trajectory. However, it continues to be plagued with talent shortages, managing employee satisfaction, growth aspirations and reducing attrition.

COVID-19 has presented an unprecedented opportunity for IT service organisations to transform the established paradigm of working. The industry has been exploring non-linear growth models that address the talent demand-supply gap. With skilled talent shortage continuing to limit the industry growth, non-linear initiatives of growth are urgently required. We propose a model of ‘Internal Gig’ worker (I-GIG) for the IT services industry. The new I-GIG workforce would be providing non-linear outcomes without increasing costs significantly. We also argue that this model would be motivational for employees who opt for it, with commensurate reward motivations to engage them. Additionally, this model would enable the workanywhere, anytime and leverage talent availability on a global scale.
Sequential Changes in Posterior Tibial Translation After Posterior Cruciate Ligament Reconstruction: Risk Factors for Residual Posterior Sagging
Authors: Tachibana Yuta , Tanaka Yoshinari , Kinugasa Kazutaka , Hamada Masayuki , Horibe Shuji
Published: June 2021

Background:

Residual posterior sagging may occur after posterior cruciate ligament (PCL) reconstruction (PCLR), yet when it mainly occurs is not fully understood.

Purpose:

To elucidate sequential changes in radiographic posterior tibial translation (PTT) after PCLR.

Study Design:

Case-control study; Level of evidence, 3.

Methods:

The authors retrospectively investigated the radiographic findings from 22 patients who underwent bisocket double-bundle PCLR for isolated PCL injury with at least 2 years of follow-up (mean, 4.5 years; range, 2-10 years). Injury severity was assessed using PTT on lateral radiographs with gravity sag views and was stratified according to side-to-side difference in the tibial-femoral stepoff: grade 1 (<5 mm), grade 2 (5 to <10 mm), or grade 3 (≥10 mm). Measurements were taken preoperatively and then immediately, 3 months, 6 months, 1 year, and ≥2 years postoperatively. The authors also investigated the risk factors for residual posterior sagging, indicated when PTT was ≥5 mm (grade ≥2) at the minimum 2-year follow-up.

Results:

Preoperatively, 13 patients had a grade 2 injury, and 9 had grade 3 injury. The PTT, restored immediately after PCLR, significantly increased at 3 months ( P < .001) but remained unchanged thereafter ≥2 years. There were 7 cases of postoperative PTT ≥5 mm on radiographs. Patients with residual posterior sagging had significantly larger mean PTT than did those without residual posterior sagging at all time points except for immediately postoperatively (preoperatively, 9.1 ± 1.6 vs 12.2 ± 2.3 mm; 3-month follow-up, 2.7 ± 1.6 vs 7.0 ± 1.8 mm; ≥2-year follow-up, 3.4 ± 1.0 vs 6.5 ± 1.4 mm; P < .001 for all). Multivariate logistic regression analysis showed that preoperative grade 3 injury was independently associated with residual posterior sagging (OR, 26.809; 95% CI, 1.257-571.963; P < .001).

Conclusion:

The initially reduced postoperative PTT significantly increased within 3 months using conventional rehabilitation protocols, but no progression was observed up to 4.5 years after PCLR. Preoperative grade 3 injury was independently associated with residual posterior sagging.
Diversity Displays and Organizational Messaging: The Case of Historically Black Colleges and Universities
Authors: Okuwobi Oneya , Faulk Deborwah , Roscigno Vincent J.
Published: June 2021

Diversity has simultaneously become a pervasive goal and euphemism for racial differences in higher education. Although discourses within the postsecondary context highlight the positive impact of diversity on learning outcomes, organizational diversity efforts nevertheless warrant interrogation, given their possible obfuscation if not reification of, racial inequality and hierarchy. How do Historically Black Colleges and Universities (HBCUs)—colleges and universities that are, by their very nature, racialized organizations within higher education—express and adapt to the challenges presented by diversity imperatives? In this article, we interrogate this question through systematic content analyses of visual and narrative materials from 31 HBCUs. Results highlight how these institutions often rely on the same mechanisms that characterize diversity within predominately White institutions (PWIs)—commodification of difference and disconnection from issues of racial equity. Consequently, diversity for HBCUs reflects the more general racialized inequality regime in higher education—a regime wherein these organizations largely reinforce ideas, such as racial capitalism, which have implications for racial equity. Our results and discussion hold implications for scholarship on organizational diversity but are also informative with regard to the capacity and constraints of racialized organizations to meet the needs and interests of those they serve.
Safety and Efficacy of Apixaban Following Bioprosthetic Valve Replacements: A Retrospective Evaluation
Authors: Ball Kellie , Covington Elizabeth W.
Published: June 2021

Background: Data on the use of direct oral anticoagulants in the setting of bioprosthetic valve replacements is limited. Objective: The purpose of this study was to describe outcomes among patients who underwent a bioprosthetic valve replacement and were subsequently prescribed apixaban. Methods: A retrospective cohort study was completed for inpatients at a community hospital who were prescribed apixaban following a bioprosthetic valve replacement from 2015 to 2020. Endpoints assessed included incidence of all-cause readmission and emergency visits within 3 months following valvular surgery, incidence of mortality, and all-cause major and minor bleeding. A post hoc analysis was conducted comparing outcomes among patients who underwent mitral versus aortic valve replacement, as well as patients with and without atrial fibrillation. The study was deemed exempt by hospital and university institutional review boards. Results: A total of 54 patients were included for analysis. All-cause readmission or emergency visit occurred in 33% (n = 18) of patients and the mortality rate was 6% (n = 3). A minor bleeding event was reported in 6% (n = 3) of patients and a major bleeding event was reported in 2% (n = 1) of patients. A thrombotic event was reported in 2% (n = 1) of patients. Conclusion: Within this cohort of patients requiring anticoagulation following bioprosthetic valve replacement, apixaban was safe and well-tolerated. However, more prospective data are needed to further correlate the safety and efficacy of apixaban, particularly in the setting of mitral valve replacement.
CD44 loss of function sensitizes AML cells to the BCL-2 inhibitor venetoclax by decreasing CXCL12-driven survival cues
Authors: Yu Xiaobing , Munoz-Sagredo Leonel , Streule Karolin , Muschong Patricia , Bayer Elisabeth , Walter Romina J. , Gutjahr Julia C. , Greil Richard , Concha Miguel L. , Müller-Tidow Carsten , Hartmann Tanja N. , Orian-Rousseau Véronique
Published: June 2021

Acute myeloid leukemia (AML) has a poor prognosis under the current standard of care. In recent years, venetoclax, a BCL-2 inhibitor, was approved to treat patients who are ineligible for intensive induction chemotherapy. However, complete remission rates with venetoclax-based therapies are hampered by minimal residual disease (MRD) in a proportion of patients, leading to relapse. MRD is a result of leukemic stem cells being retained in bone marrow protective environments; activation of the CXCL12-CXCR4 pathway was shown to be relevant to this process. An important role is also played by cell adhesion molecules such as CD44, which has been shown to be crucial for the development of AML. Here we show that CD44 is involved in CXCL12 promotion of resistance to venetoclax-induced apoptosis in human AML cell lines and AML patient samples, which could be abrogated by CD44 knock down, knockout, or blocking with an anti-CD44 antibody. Split-Venus bimolecular fluorescence complementation showed that CD44 and CXCR4 physically associate at the cell membrane upon CXCL12 induction. In the venetoclax-resistant OCI-AML3 cell line, CXCL12 promoted an increase in the proportion of cells expressing high levels of embryonic stem cell core transcription factors (ESC-TFs: Sox2, Oct4, Nanog) abrogated by CD44 knockdown. This ESC-TF–expressing subpopulation which could be selected by venetoclax treatment, exhibited a basally enhanced resistance to apoptosis and expressed higher levels of CD44. Finally, we developed a novel AML xenograft model in zebrafish, which showed that CD44 knockout sensitizes OCI-AML3 cells to venetoclax treatment in vivo. Our study shows that CD44 is a potential molecular target for sensitizing AML cells to venetoclax-based therapies.
Preanalytic depletion of medicinal anti-CD38 antibody from patient plasma for immunohematology testing
Authors: Ehrend Elisabeth , Manns Patricia , Harenkamp Sabine , Seifried Erhard , Geisen Christof , Bonig Halvard
Published: June 2021

Monoclonal antibodies such as daratumumab that target antigens that are also expressed on red blood cells impede blood group typing. The preferred approach to potential transfusion is to do prior extensive antigen typing of patients' red cells; however, this is not always possible. Ehrend et al describe a technique for absorbing the antibodies from serum to allow accurate red cell typing for transfusion.
Leukemia after gene therapy for sickle cell disease: insertional mutagenesis, busulfan, both, or neither
Authors: Jones Richard J. , DeBaun Michael R.
Published: June 2021

Recently, encouraging data provided long-awaited hope for gene therapy as a cure for sickle cell disease (SCD). Nevertheless, the transient suspension of the bluebird bio gene therapy trial (clinicaltrials.gov: NCT02140554) after participants developed acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) raised concerns. Potential possibilities for these cases include busulfan, insertional mutagenesis, both, or neither. Busulfan was considered the cause in the first reported case because the transgene was not present in the AML/MDS. However, busulfan is unlikely to have contributed to the most recent case. The transgene was present in the patient's malignant cells, indicating they were infused after busulfan treatment. Several lines of evidence suggest an alternative explanation for events in the bluebird bio trial, including that SCD population studies show an increased relative, but a low absolute, risk of AML/MDS. We propose a new hypothesis: after gene therapy for SCD, the stress of switching from homeostatic to regenerative hematopoiesis by transplanted cells drives clonal expansion and leukemogenic transformation of preexisting premalignant clones, eventually resulting in AML/MDS. Evidence validating our hypothesis will support prescreening individuals with SCD for preleukemic progenitors before gene therapy. While presumed viable, safe strategy has been implemented to resume gene therapy in adults with severe SCD, reasonable alternative curative therapy should be considered for children and adults with severe SCD. Currently, open multicenter clinical trials are incorporating nonmyeloablative conditioning, related haploidentical donors, and posttransplantation cyclophosphamide. Preliminary results from these trials appear promising, and National Institutes of Health–sponsored trials are ongoing in individuals with SCD using this platform.
CircHYBID regulates hyaluronan metabolism in chondrocytes via hsa-miR-29b-3p/TGF-β1 axis
Authors: Liao Hong-Xing , Zhang Zhi-Hui , Chen Hui-Lin , Huang Ying-Mei , Liu Zhan-Liang , Huang Jian
Published: June 2021

Background

Hyaluronan (HA) metabolism by chondrocytes is important for cartilage development and homeostasis. However, information about the function of circular RNAs (circRNAs) in HA metabolism is limited. We therefore profiled the role of the novel HA-related circRNA circHYBID in the progression of osteoarthritis (OA).

Methods

CircHYBID function in HA metabolism in chondrocytes was investigated using gain-of-function experiments, and circHYBID mechanism was confirmed via bioinformatics analysis and luciferase assays. The expression of circHYBID–hsa-miR-29b-3p–transforming growth factor (TGF)-β1 axis was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. CircHYBID, TGF-β1, and HA levels in cartilage samples were evaluated using qRT-PCR and pathological examination. Enzyme-linked immunosorbent assay was used to assess HA accumulation in chondrocyte supernatant.

Results

CircHYBID expression was significantly downregulated in damaged cartilage samples compared with that in the corresponding intact cartilage samples. CircHYBID expression was positively correlated with alcian blue score. Interleukin-1β stimulation in chondrocytes downregulated circHYBID expression and decreased HA accumulation. Gain-of-function experiments revealed that circHYBID overexpression in chondrocytes increased HA accumulation by regulating HA synthase 2 and HYBID expression. Further mechanism analysis showed that circHYBID upregulated TGF-β1 expression by sponging hsa-miR-29b-3p.

Conclusions

Our results describe a novel HA-related circRNA that could promote HA synthesis and accumulation. The circHYBID–hsa-miR-29b-3p–TGF-β1 axis may play a powerful regulatory role in HA metabolism and OA progression. Thus, these findings will provide new perspectives for studies on OA pathogenesis, and circHYBID may serve as a potential target for OA therapy.
GLEANER: a web server for GermLine cycle Expression ANalysis and Epigenetic Roadmap visualization
Authors: Zeng Shiyang , Hua Yuwei , Zhang Yong , Liu Guifen , Zhao Chengchen
Published: June 2021

Background

Germline cells are important carriers of genetic and epigenetic information transmitted across generations in mammals. During the mammalian germline cell development cycle (i.e., the germline cycle), cell potency changes cyclically, accompanied by dynamic transcriptional changes and epigenetic reprogramming. Recently, to understand these dynamic and regulatory mechanisms, multiomic analyses, including transcriptomic and epigenomic analyses of DNA methylation, chromatin accessibility and histone modifications of germline cells, have been performed for different stages in human and mouse germline cycles. However, the long time span of the germline cycle and material scarcity of germline cells have largely limited the understanding of these dynamic characteristic changes. A tool that integrates the existing multiomics data and visualizes the overall continuous dynamic trends in the germline cycle can partially overcome such limitations.

Results

Here, we present GLEANER, a web server for GermLine cycle Expression ANalysis and Epigenetics Roadmap visualization. GLEANER provides a comprehensive collection of the transcriptome, DNA methylome, chromatin accessibility, and H3K4me3, H3K27me3, and H3K9me3 histone modification characteristics in human and mouse germline cycles. For each input gene, GLEANER shows the integrative analysis results of its transcriptional and epigenetic features, the genes with correlated transcriptional changes, and the overall continuous dynamic trends in the germline cycle. We further used two case studies to demonstrate the detailed functionality of GLEANER and highlighted that it can provide valuable clues to the epigenetic regulation mechanisms in the genetic and epigenetic information transmitted during the germline cycle.

Conclusions

To the best of our knowledge, GLEANER is the first web server dedicated to the analysis and visualization of multiomics data related to the mammalian germline cycle. GLEANER is freely available at http://compbio-zhanglab.org/GLEANER.
Whole-genome resequencing provides insights into the population structure and domestication signatures of ducks in eastern China
Authors: Feng Peishi , Zeng Tao , Yang Hua , Chen Guohong , Du Jinping , Chen Li , Shen Junda , Tao Zhenrong , Wang Ping , Yang Lin , Lu Lizhi
Published: June 2021

Background

Duck is an ancient domesticated animal with high economic value, used for its meat, eggs, and feathers. However, the origin of indigenous Chinese ducks remains elusive. To address this question, we performed whole-genome resequencing to first explore the genetic relationship among variants of these domestic ducks with their potential wild ancestors in eastern China, as well as understand how the their genomes were shaped by different natural and artificial selective pressures.

Results

Here, we report the resequencing of 60 ducks from Chinese spot-billed ducks (Anas zonorhyncha), mallards (Anas platyrhnchos), Fenghua ducks, Shaoxing ducks, Shanma ducks and Cherry Valley Pekin ducks of eastern China (ten from each population) at an average effective sequencing depth of ~ 6× per individual. The results of population and demographic analysis revealed a deep phylogenetic split between wild (Chinese spot-billed ducks and mallards) and domestic ducks. By applying selective sweep analysis, we identified that several candidate genes, important pathways and GO categories associated with artificial selection were functionally related to cellular adhesion, type 2 diabetes, lipid metabolism, the cell cycle, liver cell proliferation, and muscle functioning in domestic ducks.

Conclusion

Genetic structure analysis showed a close genetic relationship of Chinese spot-billed ducks and mallards, which supported that Chinese spot-billed ducks contributed to the breeding of domestic ducks. During the long history of artificial selection, domestic ducks have developed a complex biological adaptation to captivity.
The chloroplast genome evolution of Venus slipper (Paphiopedilum): IR expansion, SSC contraction, and highly rearranged SSC regions
Authors: Guo Yan-Yan , Yang Jia-Xing , Bai Ming-Zhu , Zhang Guo-Qiang , Liu Zhong-Jian
Published: June 2021

Background

Paphiopedilum is the largest genus of slipper orchids. Previous studies showed that the phylogenetic relationships of this genus are not well resolved, and sparse taxon sampling documented inverted repeat (IR) expansion and small single copy (SSC) contraction of the chloroplast genomes of Paphiopedilum.

Results

Here, we sequenced, assembled, and annotated 77 plastomes of Paphiopedilum species (size range of 152,130 – 164,092 bp). The phylogeny based on the plastome resolved the relationships of the genus except for the phylogenetic position of two unstable species. We used phylogenetic and comparative genomic approaches to elucidate the plastome evolution of Paphiopedilum. The plastomes of Paphiopedilum have a conserved genome structure and gene content except in the SSC region. The large single copy/inverted repeat (LSC/IR) boundaries are relatively stable, while the boundaries of the inverted repeat and small single copy region (IR/SSC) varied among species. Corresponding to the IR/SSC boundary shifts, the chloroplast genomes of the genus experienced IR expansion and SSC contraction. The IR region incorporated one to six genes of the SSC region. Unexpectedly, great variation in the size, gene order, and gene content of the SSC regions was found, especially in the subg. Parvisepalum. Furthermore, Paphiopedilum provides evidence for the ongoing degradation of the ndh genes in the photoautotrophic plants. The estimated substitution rates of the protein coding genes show accelerated rates of evolution in clpP, psbH, and psbZ. Genes transferred to the IR region due to the boundary shift also have higher substitution rates.

Conclusions

We found IR expansion and SSC contraction in the chloroplast genomes of Paphiopedilum with dense sampling, and the genus shows variation in the size, gene order, and gene content of the SSC region. This genus provides an ideal system to investigate the dynamics of plastome evolution.
Congenital coronary artery-to-pulmonary fistula with giant aneurysmal dilatation and thrombus formation: a case report and review of literature
Authors: An Xuanqi , Guo Shaoxian , Dong Huawei , Tang Yida , Li Lin , Duan Xuejing , Ye Shaodong
Published: June 2021

Background

Coronary artery-to-pulmonary artery fistula is a rare disorder characterized by abnormal vascular communication between the coronary artery and pulmonary artery. While most patients remain asymptomatic, some might exhibit symptoms of myocardial ischemia, congestive heart failure, or even sudden cardiac death if coronary aneurysm, thrombosis, infective carditis, or other congenital cardiac defects coexist.

Case presentation

We present a 66-year-old male complaining of angina pectoris with a history of hypertension and active smoking. He was diagnosed with a coronary aneurysm based on coronary computed tomography angiography. We subsequently identified a coronary artery-to-pulmonary artery fistula with giant aneurysmal dilation on coronary angiography. Ultimately we conducted surgery ligation and aneurysmorrhaphy. During surgery, we discovered newly formed thrombus within the aneurysmal cavity. Histological analysis of the aneurysmal wall supported the diagnosis of the congenital disorder. Our patient was successfully discharged and remained asymptomatic at two months of follow-up.

Conclusion

We presented a rare and complex combination of congenital coronary artery-to pulmonary artery fistula, giant coronary aneurysmal dilatation, and thrombosis through multi-modality evaluations.
Chronotherapy for morning blood pressure surge in hypertensive patients: a systematic review and meta-analysis
Authors: Xie Ziyan , Zhang Jiahao , Wang Chenyu , Yan Xiaowei
Published: June 2021

Background

The morning blood pressure surge (MBPS) is related to an exaggerated risk of cardiovascular diseases and mortality. With increasing attention on circadian change in blood pressure and extensive use of ambulatory blood pressure monitoring (ABPM), chronotherapy that administration of medication according to biological rhythm, is reported to improve cardiovascular outcomes. The aim of this study is to evaluate the influence of chronotherapy of antihypertensive drugs upon MBPS in hypertensive patients.

Methods

A search strategy was applied in Ovid MEDLINE, EMBASE, Cochrane (Wiley) CENTRAL Register of Controlled Trials, Cochrane Database of Systematic Reviews, and the Chinese Biomedical literature database. No language and date restrictions. Randomized controlled trials (RCT) assessing the efficacy of evening and morning administration of the same medications in adult patients with primary hypertension were included.

Results

A total of ten trials, comprising 1724 participants with a mean age of 61 and 51% female, were included in this study. Combined analysis observed significant reduction of MBPS (− 5.30 mmHg, 95% CI − 8.80 to − 1.80), night-time SBP (− 2.29 mmHg, 95% CI − 4.43 to − 0.15), night-time DBP (− 1.63 mmHg, 95 %CI − 3.23 to − 0.04) and increase in night blood pressure dipping (3.23%, 95% CI 5.37 to 1.10) in evening dosage compared with traditional morning dosage of blood pressure-lowering drugs. No significant difference was found in the incidence of overall adverse effects (RR 0.65, 95% CI 0.30 to 1.41) and withdrawal due to adverse effects (RR 0.95, 95% CI 0.53 to 1.71).

Conclusions

Our study suggested that evening administration of antihypertensive medications exerted better blood pressure-lowering effect on MBPS compared with conventional morning dosage. Safety assessment also indicated that the evening regimen did not increase the risk of adverse events. However, endpoint studies need to be carried out to confirm the significance and feasibility of this treatment regimen in clinical practice.
Identify glioma recurrence and treatment effects with triple-tracer PET/CT
Authors: Li Cong , Yi Chang , Chen Yingshen , Xi Shaoyan , Guo Chengcheng , Yang Qunying , Wang Jian , Sai Ke , Zhang Ji , Ke Chao , Chen Fanfan , Lv Yanchun , Zhang Xiangsong , Chen Zhongping
Published: June 2021

Background

Differential diagnosis of tumour recurrence (TuR) from treatment effects (TrE), mostly induced by radiotherapy and chemotherapy, is still difficult by using conventional computed tomography (CT) or magnetic resonance (MR) imaging. We have investigated the diagnostic performance of PET/CT with 3 tracers, 13N-NH3, 18F-FDOPA, and 18F-FDG, to identify TuR and TrE in glioma patients following treatment.

Methods

Forty-three patients with MR-suspected recurrent glioma were included. The maximum and mean standardized uptake values (SUVmax and SUVmean) of the lesion and the lesion-to-normal grey-matter cortex uptake (L/G) ratio were obtained from each tracer PET/CT. TuR or TrE was determined by histopathology or clinical MR follow-up for at least 6 months.

Results

In this cohort, 34 patients were confirmed to have TuR, and 9 patients met the diagnostic standard of TrE. The SUVmax and SUVmean of 13N-NH3 and 18F-FDOPA PET/CT at TuR lesions were significantly higher compared with normal brain tissue (13N-NH3 0.696 ± 0.558, 0.625 ± 0.507 vs 0.486 ± 0.413; 18F-FDOPA 0.455 ± 0.518, 0.415 ± 0.477 vs 0.194 ± 0.203; both P < 0.01), but there was no significant difference in 18F-FDG (6.918 ± 3.190, 6.016 ± 2.807 vs 6.356 ± 3.104, P = 0.290 and 0.493). L/G ratios of 13N-NH3 and 18F-FDOPA were significantly higher in TuR than in TrE group (13N-NH3, 1.573 ± 0.099 vs 1.025 ± 0.128, P = 0.008; 18F-FDOPA, 2.729 ± 0.131 vs 1.514 ± 0.141, P < 0.001). The sensitivity, specificity and AUC (area under the curve) by ROC (receiver operating characteristic) analysis were 57.7%, 100% and 0.803, for 13N-NH3; 84.6%, 100% and 0.938, for 18F-FDOPA; and 80.8%, 100%, and 0.952, for the combination, respectively.

Conclusion

Our results suggest that although multiple tracer PET/CT may improve differential diagnosis efficacy, for glioma TuR from TrE, 18F-FDOPA PET-CT is the most reliable. The combination of 18F-FDOPA and 13N-NH3 does not increase the diagnostic efficiency, while 18F-FDG is not worthy for differential diagnosis of glioma TuR and TrE.
Resilience and vulnerability of maternity services in Zimbabwe: a comparative analysis of the effect of Covid-19 and lockdown control measures on maternal and perinatal outcomes, a single-centre cross-sectional study at Mpilo Central Hospital
Authors: Shakespeare Clare , Dube Handsome , Moyo Sikhangezile , Ngwenya Solwayo
Published: June 2021

Background

On the 27th of March 2020 the Zimbabwean government declared the Covid-19 pandemic a ‘national disaster’. Travel restrictions and emergency regulations have had significant impacts on maternity services, including resource stock-outs, and closure of antenatal clinics during the lockdown period. Estimates of the indirect impact of Covid-19 on maternal and perinatal mortality was expected it to be considerable, but little data was yet available.

This study aimed to examine the impact of Covid-19 and lockdown control measures on non-Covid outcomes in a government tertiary level maternity unit in Bulawayo, Zimbabwe, by comparing maternal and perinatal morbidity and mortality before, and after the lockdown was implemented.

Methods

This was a retrospective, observational study, using a cross-sectional design to compare routine monthly maternal and perinatal statistics three months before and after Covid-19 emergency measures were implemented at Mpilo Central Hospital.

Results

Between January-March and April-June 2020, the mean monthly deliveries reduced from 747.3 (SD ± 61.3) in the first quarter of 2020 to 681.0 (SD ± 17.6) during lockdown, but this was not statistically significant, p = 0.20. The Caesarean section rates fell from a mean of 29.8% (SD ± 1.7) versus 28.0% (SD ± 1.7), which was also not statistically significant, p = 0.18. During lockdown, the percentage of women delivering at Mpilo Central Hospital who were booked at the hospital fell from a mean of 41.6% (SD ± 1.1) to 35.8% (SD ± 4.3) which was statistically significant, p = 0.03. There was no significant change, however, in maternal mortality or severe maternal morbidity (such as post-partum haemorrhage (PPH), uterine rupture, and severe preeclampsia/eclampsia), stillbirth rate or special care baby unit admission. There was an increase in the mean total number of early neonatal deaths (ENND) (mean 18.7 (SD ± 2.9) versus 24.0 (SD ± 4.6), but this was not statistically significant, p = 0.32.

Conclusions

Overall, maternity services at Mpilo showed resilience during the lockdown period, with no significant change in maternal and perinatal adverse outcomes, with the same number of man-hours worked before and during the lockdown Maternal and perinatal outcomes should continue to be monitored to assess the impact of Covid-19 and the lockdown measures as the pandemic in Zimbabwe unfolds. Further studies would be beneficial to explore women’s experiences and understand how bookings and deliveries at local clinics changed during this time.