bluuebunny/crossref_metadata_2025 huggingface dataset:
Parenting the child with HIV in limited resource communities in South Africa: mothers with HIV’s emotional vulnerability and hope for the future
Authors: Moshoeshoe Malerato , Madiba Sphiwe
Published: November 2021

Introduction:

A diagnosis of HIV does not affect the well-being of mothers alone but also affects how they care for their children. The aim of this study was to explore how mothers who were diagnosed with HIV when pregnant or when their children became ill experience raising children living with HIV. The purpose was to understand how a diagnosis of HIV impacts mothering their children at different points on the mothering journey.

Methods:

Using descriptive phenomenological enquiry, interviews were conducted with 28 mothers recruited via purposeful sampling from clinics in health district in South Africa. The interviews were audiotaped, transcribed verbatim, and analysed following the thematic approach.

Results:

The mothers found mothering a child living with HIV stressful and associated with constant thoughts of death. The burden of mothering was increased for mothers who had to confront emotions of self-blame and guilt for unintentionally infecting the child. They used secrecy to protect their children from the social consequences of a diagnosis of HIV. The thought of living with HIV weighed on them every day and they expressed their experience of intense feelings of chronic worry, anxiety, and sadness. The findings identified high levels of stress, with the mothers expressing emotions suggestive of depression. With time, they accepted living with HIV and embraced motherhood, and became better mothers.

Conclusion:

The negative coping strategies used to deal with the child’s HIV diagnosis and high levels of stress and anxiety identified in the study underscore the need to address the psychosocial needs of mothers living with HIV. There is need to provide psychosocial support and continuous counselling for these mothers post diagnosis and upon a positive HIV diagnosis of the child to women enrolled in the prevention of mother to child transmission of HIV programme.
The Uro-Oncology Multi-disciplinary team (MDT) Clinic – Clinical and Patient-Reported Outcomes From Implementing a New Model of Care
Authors: Lee Alvin Yuanming , Tiwari Raj , Neo Shuhui , Huned Daanesh , Kumaran Arjunan , Lim Chloe Li Wen , Chua Melvin Lee Kiang , Kanesvaran Ravindran , Lee Lui Shiong
Published: November 2021

Introduction

A multi-disciplinary approach has often been advocated to improve the delivery of oncological care, as compared to a mono-disciplinary and linear approach. Our study elucidates the clinical and patient-reported outcomes from a urologic-oncology multi-disciplinary team (MDT) clinic in a regional general hospital.

Materials and Methods

Patients who attended a uro-oncology MDT clinic which was started in January 2019 were identified. This service was specifically catered to patients who were histologically diagnosed with urological cancers. The MDT service comprised a multi-disciplinary tumour board followed by outpatient clinical consults with representatives from urology, medical and radiation oncology. Demographic variables, disease characteristics and treatment rendered were analysed. A survey was administered to assess patient satisfaction.

Results

Fifty patients with a median age of 70 years with complete case records were identified. The cancer types included prostate cancers (46%), urothelial cancers (26%) and renal cell carcinoma (12%) as the most frequent urological cancers. The median time from MDT to therapy initiation was 8 days. Among those with prostate, urothelial, renal and testicular malignancies, 71% (32/45) of our patients received treatment that were in accordance to guideline recommendations. A post-clinic survey showed that patients were satisfied with the information provided during the clinic and this also facilitated decision and time to initiation of therapy.

Conclusion

A multi-disciplinary service comprising a tumour board followed by a one-stop clinic provides patients with multi-disciplinary care, improved access to subsequent therapy, better time efficiency and high patient satisfaction scores. More studies are warranted to demonstrate its oncological outcomes.
Extent of sleep problems and relationship with severity of chronic pain using three validated sleep assessment tools
Authors: Vaughan Rachel , Galley Helen F , Kanakarajan Saravana
Published: November 2021

Objective

Chronic pain can impact on sleep, but the extent and nature of sleep problems in patients with chronic pain are incompletely clear. Several validated tools are available for sleep assessment but they each capture different aspects. We aimed to describe the extent of sleep issues in patients with chronic non-malignant pain using three different validated sleep assessment tools and to determine the relationship of sleep issues with pain severity recorded using the Brief Pain Inventory (BPI), a commonly used self-assessment tool in pain clinics. The BPI has a single question on the interference of pain on sleep and we also compared this with the validated sleep tools.

Design

Prospective, cross-sectional study.

Setting

Pain management clinic at a large teaching hospital in the United Kingdom.

Subjects

Adult patients (with chronic non-malignant pain of at least 3 months’ duration) attending clinic during a 2-month period.

Methods

Participants completed the Pittsburgh Sleep Quality Index (PSQI), the Pain and Sleep Questionnaire-3 (PSQ-3) and the Verran Snyder-Halpern (VSH) sleep scale, plus the BPI. Duration and type of pain, current medications and demographic data were recorded.

Results

We recruited 51 patients and 82% had poor sleep quality as shown by PSQIscores above five. PSQI ( p = 0.0002), PSQ-3 ( p = 0.0032), VSH sleep efficiency ( p = 0.012), sleep disturbance ( p = 0.0014) and waking after sleep onset ( p = 0.0005) scores were associated with worse BPI pain scores. BPI sleep interference scores concurred broadly with the validated sleep tools. Median [range] sleep duration was 5.5 [3.0–10.0] hours and was also related to pain score ( p = 0.0032).

Conclusion

Chronic pain has a marked impact on sleep regardless of the assessment tool used. The sleep interference question in the BPI could be used routinely for initial identification of sleep problems in patients with chronic pain.
Occupational photoallergic contact dermatitis to thiourea in a firefighter
Authors: Pratt Michelle E , Pratt Melanie D
Published: November 2021

Thioureas are a relatively uncommon cause of allergic contact dermatitis and a rare cause of photoallergic contact dermatitis. They are primarily used as vulcanization accelerators in the production of neoprene, and common sources of exposure include gloves, shoe insoles, wet suits, and orthopedic braces. We report a multifactorial case of severe episodic photoallergic contact dermatitis to thiourea in a 29-year-old firefighter. Multiple sources of neoprene exposure were identified, including a firefighting mask, continuous positive airway pressure strap, and hockey helmet.
The effects of yoga on quality of life among postmenopausal women: A systematic review study
Authors: Sharifi Neda , Afshari Fateme , Bahri Narjes
Published: November 2021

Introduction

The quality of life in menopausal women is considered to be an important health issue in different societies and one of the main objectives of health care in this period. This study aimed to investigate the effects of yoga on improving the quality of life in menopausal women.

Method

English databases of Google Scholar, Science Direct, PubMed, Scopus, and Cochrane Library were searched to access related articles using keywords of menopause, quality of life, and yoga. Furthermore, Persian equivalents of the same keywords were searched in databases of Google Scholar, SID, and Magiran, in addition to a combination of the keywords. The search interval was from the inspection to January 2020. The quality of the included studied was assessed based on CONSORT 2017 checklist.

Results

Out of 120 articles found in the databases, six articles entered the study based on the inclusion criteria and were investigated for intervention methods and consequences. The results indicated the positive impact of yoga on the quality of life in menopausal women.

Conclusion

Considering the effects of yoga on the symptoms and quality of life in menopausal women, it is suggested that this low-cost method be used to improve their quality of life and health.
Neonatal Rupture of the Tricuspid Valve and Maternal Lupus: Is There a Correlation?
Authors: Carretero Bellon Juan M. , Brunet-Garcia Laia , Sanchez de Toledo Joan , Congiu Stefano
Published: November 2021

Valve dysfunction is not widely recognized as a feature in newborns born to mothers with positive anti-Ro/SSA antibodies, and only scarce reports have suggested an association between rupture of the atrioventricular valve tensor apparatus and these maternal antibodies. We report the follow-up from fetal life to the time of postnatal surgery of a patient with severe tricuspid regurgitation due to a flail of the anterior tricuspid valve leaflet who was born to an anti-Ro/SSA antibodies positive mother.
Explaining Latinx Youth Delinquency: A Gendered Test of Latinx General Strain Theory
Authors: Zavala Egbert , Perez Graciela , Sabina Chiara
Published: November 2021

Recently, scholars have reintroduced a Latinx general strain theory in which it is suggested that ethnic-specific strains, including acculturation, are driving forces for criminal and delinquent behaviors among the Latinx population. Using data collected from the Dating Violence Among Latino Adolescents (DAVILA) Study, this study investigated whether these ethnic strains influenced delinquency differently based on the respondent's gender. Results indicate that boys engaged in more delinquent behaviors than girls, whereas girls were more acculturated than boys. Depression, anxiety, and social support were more prevalent among girls than among boys. In addition, girls were more likely to be enculturated and perform better in school than boys. Acculturation did not significantly predict delinquency for either boys or girls. In contrast, polyvictimization was the only variable to consistently predict delinquency among boys and girls. Results provided partial support for the hypotheses, in that, while depression and anxiety varied by gender as predicted by the gendered general strain theory, the ethnic-specific strain of acculturation failed to predict delinquent behavior in this sample. Ultimately, this study highlights the need to examine other ethnic-specific strains to better understand delinquent behavior among Latinx youth.
Remote Learning, COVID-19, and Children With Disabilities
Authors: Averett Kate Henley
Published: November 2021

While the COVID-19 pandemic affected the education of nearly all schoolchildren worldwide, pandemic-related school closures did not affect all children in equal ways. Between March and August, 2020, I interviewed 31 parents of children with disabilities as part of a larger interview study of U.S. parents of children in grades K–12. In this article, I analyze these parents’ narratives about their families’ experiences of pandemic-related remote learning to identify the particular challenges children with disabilities and their families faced with remote learning. I find that most, but not all, families struggled with remote learning, both when children’s specific needs while learning at home differed from their needs at school, and when schools failed to provide adequate accommodations and services remotely. These narratives demonstrate how children with disabilities are particularly vulnerable to the type of large-scale systemic shock to U.S. public education that the pandemic has presented.
Promoting a Therapeutic Healing Environment: A Retrospective Examination of HCAHPS “Quiet at Night” Across a Large New York Health System
Authors: Barden Agnes , Loeb Amy E , Giammarinaro Nicole
Published: November 2021

Promoting respite and sleep impacts a patient's health and their inpatient experience. As New York State's largest health system, Northwell Health has been on a journey to create a healing and therapeutic healthcare environment. By establishing leadership accountability, leveraging patient feedback and adopting evidence-based interventions, system and individual adult inpatient hospital improvements have been noted. Between 2017 and 2020, Northwell's overall system HCAHPS “Quiet at Night” Top Box performance increased by 4.7, improving 30 percentile rank points when compared to the Press Ganey national database. This case study outlines Northwell's pragmatic patient-centered strategy and examines the unanticipated impact of limited visitation due to COVID-19 on this HCAHPS measure.
Religious Support for Civil Resistance Movements: When and How Does It Contribute to Regime Change?
Authors: Nepstad Sharon Erickson
Published: November 2021

There is substantial research on the influence of elite defections on civil resistance campaign outcomes. Yet most studies focus on defections among security forces, political leaders, and economic elites. In this article, the author examines religious elite defections. Analyzing 99 civil resistance struggles, the author explores whether religious leaders’ support is associated with regime change in authoritarian contexts. The author also uses qualitative comparative analysis to determine the conditions and pathways that lead to a successful outcome. The author illustrates these pathways with four cases (Ukraine’s orange revolution, Mali’s uprising against General Traoré, the Philippine People Power movement, and Malawi’s struggle against President Banda). The results indicate that religious elite defections are not necessary for civil resistance success. However, religious support can contribute critical resources to movements, create a positive flank effect, facilitate security force defections, provide space for resistance in conditions of indiscriminate repression, and activate international networks that can pressure a regime.
“I Get It Now!”: An Exercise to Highlight Unearned Privilege Using Resource Allocation and Rewards
Authors: Dunn-Jensen Linda M. , Ryan Katherine C. , Bradshaw Christopher C.
Published: November 2021

Individuals who are privileged are often unaware of the unearned advantages that they have. Because of this lack of awareness, individuals with privilege may attribute poor performance of a non-privileged individual to that individual’s lack of effort or ability, rather than recognizing that the non-privileged person may not have had sufficient opportunities or resources. Without fully being aware of such privilege, it can be difficult for students to appreciate the diversity surrounding them, both in the classroom and in the workplace. This experiential exercise and suggested debrief strategies illustrate the concept and consequences of privilege.
Patient and proxies’ attitudes towards deferred consent in randomised trials of acute treatment for stroke: A qualitative survey
Authors: van den Bos Noa , van den Berg Sophie A , Caupain Catalina MM , Pols Jeannette AJ , van Middelaar Tessa , Chalos Vicky , Dippel Diederik WJ , Roos Yvo BWEM , Kappelhof Manon , Nederkoorn Paul J
Published: November 2021

Introduction

Deferral of consent for participation in a clinical study is a relatively novel procedure, in which informed consent is obtained after randomisation and study treatment. Deferred consent can be used in emergency situations, where small therapeutic time windows limit possibilities for patients to provide informed consent. We aimed to investigate patients’ or their proxies’ experiences and opinions regarding deferred consent in acute stroke randomised trials.

Patients and methods

For this qualitative study, Dutch Collaboration for New Treatments of Acute Stroke (CONTRAST) trial participants were selected. Study participants were either patients or their proxies who provided consent and were selected with theoretical sampling based on patient characteristics. Semi-structured interviews were conducted face-to-face or by telephone. Themes and subthemes were iteratively defined.

Results

Twenty of the 23 interviewed participants (16 patients and 7 proxies) considered deferred consent acceptable. The received study treatment and consent conversation were remembered by 18 participations, although the concept of randomisation and treatment comparison were generally not well understood. Sixteen participants felt capable of overseeing the decision to give deferred consent. Distress in the first days after stroke, lack of understanding and neurological deficits were reasons for feeling incapable of providing consent. Four participants would have preferred a different timing of the consent conversation, of whom two prior to treatment.

Conclusion

Our study found that deferred consent was considered acceptable by most study participants who provided consent for acute stroke randomised trials. Though they felt capable, the recall and comprehension of consent were overall limited.
Accuracy of CTA evaluations in daily clinical practice for large and medium vessel occlusion detection in suspected stroke patients
Authors: Duvekot Martijne H. C. , van Es Adriaan C. G. M. , Venema Esmee , Wolff Lennard , Rozeman Anouk D. , Moudrous Walid , Vermeij Frédérique H. , Lingsma Hester F. , Bakker Jeannette , Plaisier Aarnout S. , Hensen Jan-Hein J. , Lycklama à Nijeholt Geert J. , Jan van Doormaal Pieter , Dippel Diederik W.J. , Kerkhoff Henk , Roozenbeek Bob , van der Lugt Aad ,   on behalf of the PRESTO investigators
Published: November 2021

Introduction: Early detection of large vessel occlusion (LVO) is essential to facilitate fast endovascular treatment. CT angiography (CTA) is used to detect LVO in suspected stroke patients. We aimed to assess the accuracy of CTA evaluations in daily clinical practice in a large cohort of suspected stroke patients. Patients and methods: We used data from the PRESTO study, a multicenter prospective observational cohort study that included suspected stroke patients between August 2018 and September 2019. Baseline CTAs were re-evaluated by an imaging core laboratory and compared to the local assessment. LVO was defined as an occlusion of the intracranial internal carotid artery, M1 segment, or basilar artery. Medium vessel occlusion (MeVO) was defined as an A1, A2, or M2 occlusion. We calculated the accuracy, sensitivity, and specificity to detect LVO and LVO+MeVO, using the core laboratory evaluation as reference standard. Results: We included 656 patients. The core laboratory detected 89 LVOs and 74 MeVOs in 155 patients. Local observers missed 6 LVOs (7%) and 28 MeVOs (38%), of which 23 M2 occlusions. Accuracy of LVO detection was 99% (95% CI: 98–100%), sensitivity 93% (95% CI: 86–97%), and specificity 100% (95% CI: 99–100%). Accuracy of LVO+MeVO detection was 95% (95% CI: 93–96%), sensitivity 79% (95% CI: 72–85%), and specificity 99% (95% CI: 98–100%). Discussion and Conclusion: CTA evaluations in daily clinical practice are highly accurate and LVOs are adequately recognized. The detection of MeVOs seems more challenging. The evolving EVT possibilities emphasize the need to improve CTA evaluations in the acute setting.
Micro-embolic signal monitoring in stroke subtypes: A systematic review and meta-analysis of 58 studies
Authors: Sudheer Pachipala , Misra Shubham , Nath Manabesh , Kumar Pradeep , Vibha Deepti , Srivastava M.V.Padma , Tripathi Manjari , Bhatia Rohit , Pandit Awadh Kishor , Singh Rajesh K
Published: November 2021

Introduction

Micro-embolic signals (MESs) detected using transcranial Doppler (TCD) help in risk stratification in stroke patients. A systematic review and meta-analysis were performed to estimate the prevalence of MES and its association with stroke recurrence, functional outcome, and mortality in different stroke subtypes.

Methods

A comprehensive literature search was conducted before 26th January 2021 in PubMed, Embase, Google Scholar, Cochrane Library, and ClinicalTrials.gov . Studies were identified that used TCD to detect MES in stroke/TIA patients. Pooled prevalence and odds ratio (OR) along with 95% confidence interval (95% CI) were calculated for different outcome measures. The entire statistical analysis was conducted in R version 3.6.2.

Findings

Fifty-eight studies involving 5123 patients (1329 MES+, 3794 MES−) were included in our meta-analysis. The pooled prevalence of MES among all acute stroke/TIA patients was 30% (95% CI 25-34%). The pooled prevalence adjusted after the trim-and-fill analysis among all acute stroke/TIA patients was 18% (95% CI 14-23%). The prevalence of MES was high among all stroke subtypes except in patients with small vessel disease (SVD). In patients with new-onset stroke/TIA, the presence of MES was associated with a high risk of recurrence of cerebral ischemia (OR 4.03; 95% CI 2.38-6.82). Although no significant association was observed for the presence of MES with increased mortality (OR 2.37; 95% CI 0.75-7.50) and poor functional outcome (OR 2.11; 95% CI 0.20-22.50) among patients with new-onset stroke/TIA, this could only be determined in a smaller sample size of 477 patients.

Conclusions

Our meta-analysis showed a 30% prevalence of MES following acute stroke/TIA. The presence of MES increased the chance of recurrence of cerebral ischemia but was not associated with poor functional outcomes and mortality in the studied subgroup.
Safety assessment of β-fructofuranosidase from Aspergillus brunneoviolaceus
Authors: Vo Trung Duc , Meetro Jwar , Lynch Barry , Tafazoli Shahrzad , Ichihara Akio , Chikamatsu Go
Published: November 2021

β-Fructofuranosidase (β-D-fructofuranoside fructohydrolase; EC 3.2.1.26) is used in the production of fructo-oligosaccharides that are commonly used by the food industry as prebiotics for their purported health benefits. The β-fructofuranosidase discussed herein is obtained from a novel source organism that is a non-genetically modified strain of Aspergillus brunneoviolaceus, which phylogenetically belongs to the Aspergillus section Nigri. The safety of β-fructofuranosidase was evaluated in a series of toxicology studies as prescribed by Tier 1 toxicity testing by the European Food Safety Authority, including an evaluation of the mutagenicity and genotoxicity potential using the in vitro bacterial reverse mutation and mammalian chromosomal aberration assays, as well as systemic toxicity in a 90-day oral subchronic toxicity study in Sprague-Dawley rats. β-Fructofuranosidase was demonstrated to lack mutagenic or genotoxic potential based on the results of the in vitro assays due to absence of increased revertant colonies in the bacterial reverse mutation test and incidence of chromosome aberrations in the chromosomal aberration assay. Administration of β-fructofuranosidase by gavage at doses up to 1200 mg total organic solids (TOS)/kg body weight/day for 90 days did not elicit any systemic toxic effects in rats based on a lack of adverse effect in any study parameter, and therefore the no-observed-adverse-effect level of β-fructofuranosidase was concluded to be 1200 mg TOS/kg body weight/day, the highest dose tested. The results of the toxicology studies on β-fructofuranosidase from A. brunneoviolaceus demonstrate this species to be a safe and suitable source of enzymes for use by the food industry.
Antibody Response to BNT162b2 Vaccine in Immune Modifiers–Treated Psoriatic Patients
Authors: Pavlotsky Felix , Segal Zvi , Barzilai Aviv
Published: November 2021

Background

Data regarding anti–COVID-19 vaccination efficacy in psoriasis patients treated with immune-modulatory medications are scarce.

Objective

This study aims to examine the rate of positive antibody response following BNT162b2 vaccine in those patients.

Methods

BNT162b2-vaccinated and immune modifier–treated psoriatic patients were assigned to serological testing of IgG antibodies to protein S of SARS-CoV-2 after the second vaccination dose by Abbott Architect or Beckman Coulter. Levels ≥ 1 S1 units/mL (S/ml) and > 150 arbitrary units/ml (AU/ml) are considered a positive antibody response, respectively. The antibody levels further analyzed according to the patient’s characteristics and compared to health workers’ controls.

Results

Forty-nine of the 51 patients had a positive antibody response. Overall, patients treated with immune-modulatory medications had antibody levels similar to the control group.

Conclusions

Immune modifier–treated psoriasis patients seem to develop a positive antibody response to the full BNT162b2 vaccination in the vast majority of cases.
Varieties of post-civil war violence
Authors: Shaw Daniel Odin , Young Enrique Wedgwood
Published: November 2021

Quantitative research on the “durability” of peace following civil wars typically captures the breakdown or survival of “peace” in a binary manner, equating it with the presence or absence of civil war recurrence. In the datasets that underpin such studies, years that do not experience full-scale civil war are implicitly coded as “peaceful.” Yet, post-civil war environments may remain free from war recurrence, while nevertheless experiencing endemic violent crime, state repression, low-intensity political violence, and systematic violence against marginalized groups, all of which are incongruent with the concept of peace. Approaches to assessing post-civil war outcomes which focus exclusively on civil war recurrence risk overestimating the “durability” of peace, implicitly designating as “peaceful” a range of environments which may be anything but. In this article, we discuss the heterogeneity of violent post-civil war outcomes and develop a typology of “varieties of post-civil war violence.” Our typology contributes to the study of post-civil war peace durability, by serving as the basis for an alternative, categorical conceptualization of “peace years” in conflict datasets.
Will failed insurrection lead to terrorism in the United States?
Authors: Crenshaw Martha
Published: November 2021

The following discussion outlines the attractions of a strategy of terrorism and its implications for political order. It also argues that a body of knowledge has been built up over time that provides a foundation for explaining current events. Research has shown that terrorism can be an effective substitute for the mobilization of large numbers when that mobilization is thwarted. Terrorism can sustain an illusion of power, provoke official over-reaction and community counter-mobilization, and deepen political polarization. Studies also suggest that if a broader movement dissolves, the followers who remain strengthen their commitment and become more inclined to violence. The future threat environment is most likely to be multidimensional, with multiple groups cooperating and competing along with individual actors who perceive themselves to be part of an ideological collectivity.
TET2 mutations as a part of DNA dioxygenase deficiency in myelodysplastic syndromes
Authors: Gurnari Carmelo , Pagliuca Simona , Guan Yihong , Adema Vera , Hershberger Courtney E. , Ni Ying , Awada Hassan , Kongkiatkamon Sunisa , Zawit Misam , Coutinho Diego F. , Zalcberg Ilana R. , Ahn Jae-Sook , Kim Hyeoung-Joon , Kim Dennis Dong Hwan , Minden Mark D. , Jansen Joop H. , Meggendorfer Manja , Haferlach Claudia , Jha Babal K. , Haferlach Torsten , Maciejewski Jaroslaw P. , Visconte Valeria
Published: November 2021

Decrease in DNA dioxygenase activity generated by TET2 gene family is crucial in myelodysplastic syndromes (MDS). The general downregulation of 5-hydroxymethylcytosine (5-hmC) argues for a role of DNA demethylation in MDS beyond TET2 mutations, which albeit frequent, do not convey any prognostic significance. We investigated TETs expression to identify factors which can modulate the impact of mutations and thus 5-hmC levels on clinical phenotypes and prognosis of MDS patients. DNA/RNA-sequencing and 5-hmC data were collected from 1665 patients with MDS and 91 controls. Irrespective of mutations, a significant fraction of MDS patients exhibited lower TET2 expression, whereas 5-hmC levels were not uniformly decreased. In searching for factors explaining compensatory mechanisms, we discovered that TET3 was upregulated in MDS and inversely correlated with TET2 expression in wild-type cases. Although TET2 was reduced across all age groups, TET3 levels were increased in a likely feedback mechanism induced by TET2 dysfunction. This inverse relationship of TET2 and TET3 expression also corresponded to the expression of L-2-hydroxyglutarate dehydrogenase, involved in agonist/antagonist substrate metabolism. Importantly, elevated TET3 levels influenced the clinical phenotype of TET2 deficiency whereby the lack of compensation by TET3 (low TET3 expression) was associated with poor outcomes of TET2 mutant carriers.
Antithrombin protects againstPlasmodium falciparumhistidine-rich protein II-mediated inflammation and coagulation
Authors: Biswas Indranil , Panicker Sumith R. , Giri Hemant , Cai Xiaofeng S. , Rezaie Alireza R.
Published: November 2021

Plasmodium falciparum-derived histidine-rich protein II (HRPII) has been shown to inhibit heparin-dependent anticoagulant activity of antithrombin (AT) and induce inflammation in vitro and in vivo. In a recent study, we showed that HRPII interacts with the AT-binding vascular glycosaminoglycans (GAGs) not only to disrupt the barrier-permeability function of endothelial cells but also to inhibit the antiinflammatory signaling function of AT. Here we investigated the mechanisms of the proinflammatory function of HRPII and the protective activity of AT in cellular and animal models. We found that AT competitively inhibits the GAG-dependent HRPII-mediated activation of NF-κB and expression of intercellular cell adhesion molecule 1 (ICAM1) in endothelial cells. Furthermore, AT inhibits HRPII-mediated histone H3 citrullination and neutrophil extracellular trap (NET) formation in HL60 cells and freshly isolated human neutrophils. In vivo, HRPII induced Mac1 expression on blood neutrophils, MPO release in plasma, neutrophil infiltration, and histone H3 citrullination in the lung tissues. HRPII also induced endothelial cell activation as measured by increased ICAM1 expression and elevated vascular permeability in the lungs. AT effectively inhibited HRPII-mediated neutrophil infiltration, NET formation, and endothelial cell activation in vivo. AT also inhibited HRPII-meditated deposition of platelets and fibrin(ogen) in the lungs and circulating level of von Willebrand factor in the plasma. We conclude that AT exerts protective effects against pathogenic effects of P falciparum-derived HRPII in both cellular and animal models.
ADSCs enhance VEGFR3-mediated lymphangiogenesis via METTL3-mediated VEGF-C m6A modification to improve wound healing of diabetic foot ulcers
Authors: Zhou Jie , Wei Tianhong , He Zhiyou
Published: November 2021

Background

Adipose-derived mesenchymal stem cells (ADSCs) are an important focus in regenerative medicine. However, the biological function of ADSCs in the wound repair of diabetic foot ulcers (DFUs) remains unclear. This study aimed to determine the underlying mechanisms of ADSCs involved in the wound healing of DFUs.

Methods

The cell surface markers cluster of differentiation 34 (CD34), stromal cell antigen 1 (Stro-1), cluster of differentiation 90 (CD90) and cluster of differentiation 105 (CD105) on ADSCs were identified by flow cytometry. Oil Red O staining and Alizarin Red S staining were performed to identify the multipotential differentiation of ADSCs into adipocytes and bone. The levels of Methyltransferase-like 3 (METTL3), vascular endothelial growth factor C (VEGF-C) and insulin-like growth factor 2 binding protein 2 (IGF2BP2) were assessed by RT-qPCR. CCK-8, Transwell and tubule formation assays were conducted to assess lymphatic endothelial cell (LEC) viability, migration and tubule formation ability, respectively. RIP and RNA pulldown assays were conducted to assess the interaction between IGF2BP2 and VEGF-C. The levels of VEGF-C, VEGFR3, LYVE-1 and IGF2BP2 proteins were assessed by Western blotting. The levels of VEGF-C in LECs were measured by ELISA.

Results

Our findings illustrated that ADSCs accelerate LEC proliferation, migration and lymphangiogenesis via the METTL3 pathway and regulate VEGF-C expression via the METTL3/IGF2BP2-m6A pathway VEGF-C-mediated lymphangiogenesis via the METTL3/IGF2BP2-m6A pathway in DFU mice.

Conclusion

ADSCs enhance VEGFR3-mediated lymphangiogenesis via METTL3-mediated VEGF-C m6A modification to improve wound healing in DFUs, indicating that ADSCs may be regarded as a promising therapeutic strategy to promote wound healing in DFUs.
Patient-reported results of simultaneous direct anterior approach and posterolateral approach total hip arthroplasties performed in the same patients
Authors: Yang Zhi , Feng Shuo , Guo Kai-Jin , Zha Guo-Chun
Published: November 2021

Background

Several studies have compared clinical results of the direct anterior approach (DAA) and the posterolateral approach (PLA) in total hip arthroplasty (THA); however, the effect of the surgical approach on outcome of THA remains controversial. Most of these studies used two distinct groups of patients, and THAs were performed by different surgeons, using different designs of prosthesis. These confounding factors may limit the strength of the conclusions. The purpose of this prospective, simultaneous bilateral randomized study was to investigate whether patients would perceive the difference between the direct anterior approach (DAA) and the posterolateral approach (PLA) after THA.

Materials and methods

Among 20 patients scheduled to undergo same-day bilateral THA between October 2017 and August 2019, one hip was randomly assigned to DAA and the other to PLA. Patient-reported outcome measures [Hip disability and Osteoarthritis Outcome Score (HOOS), patients’ hip pain on mobilization] and physician-assessed measures [Harris Hip Score (HHS), operative time, intraoperative blood loss, cup abduction, cup anteversion, stem orientation, and incidence of complications (intraoperative fracture, nerve damage, incisional problem, or postoperative dislocation)] were compared.

Results

All patients were followed up for 12 months. Hip pain was significantly less with DAA-THA compared with PLA-THA at postoperative 1, 3, and 7 days (p < 0.05). There was no clinical difference between DAA-THA and PLA-THA in terms of the VAS, HOOS, or HSS at 6 weeks and 3, 6, and 12 months postoperatively (p > 0.05). DAA-THA had a longer operative time and shorter length of incision compared with PLA-THA. There was no statistical difference between DAA-THA and PLA-THA in terms of intraoperative blood loss, cup abduction, cup anteversion, stem orientation, and perioperative complications (p > 0.05).

Conclusions

This study demonstrates that DAA-THA and PLA-THA could provide comparable HHS and HOOS at all follow-ups. Compared with PLA-THA, DAA-THA is associated with less hip pain within postoperative 7 days and shorter incision length, but longer operative time.

Level of evidence

Level I, therapeutic study.

Trial registration Chinese Clinical Trail Registry, ChiCTR1800019816. Registered 30 November 2018—retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=30863
Pleiotropy between language impairment and broader behavioral disorders—an investigation of both common and rare genetic variants
Authors: Nudel Ron , Appadurai Vivek , Buil Alfonso , Nordentoft Merete , Werge Thomas
Published: November 2021

Background

Language plays a major role in human behavior. For this reason, neurodevelopmental and psychiatric disorders in which linguistic ability is impaired could have a big impact on the individual’s social interaction and general wellbeing. Such disorders tend to have a strong genetic component, but most past studies examined mostly the linguistic overlaps across these disorders; investigations into their genetic overlaps are limited. The aim of this study was to assess the potential genetic overlap between language impairment and broader behavioral disorders employing methods capturing both common and rare genetic variants.

Methods

We employ polygenic risk scores (PRS) trained on specific language impairment (SLI) to evaluate genetic overlap across several disorders in a large case-cohort sample comprising ~13,000 autism spectrum disorder (ASD) cases, including cases of childhood autism and Asperger’s syndrome, ~15,000 attention deficit/hyperactivity disorder (ADHD) cases, ~3000 schizophrenia cases, and ~21,000 population controls. We also examine rare variants in SLI/language-related genes in a subset of the sample that was exome-sequenced using the SKAT-O method.

Results

We find that there is little evidence for genetic overlap between SLI and ADHD, schizophrenia, and ASD, the latter being in line with results of linguistic analyses in past studies. However, we observe a small, significant genetic overlap between SLI and childhood autism specifically, which we do not observe for SLI and Asperger’s syndrome. Moreover, we observe that childhood autism cases have significantly higher SLI-trained PRS compared to Asperger’s syndrome cases; these results correspond well to the linguistic profiles of both disorders. Our rare variant analyses provide suggestive evidence of association for specific genes with ASD, childhood autism, and schizophrenia.

Conclusions

Our study provides, for the first time, to our knowledge, genetic evidence for ASD subtypes based on risk variants for language impairment.
Identification of an Elite Core Panel as a Key Breeding Resource to Accelerate the Rate of Genetic Improvement for Irrigated Rice
Authors: Juma Roselyne U. , Bartholomé Jérôme , Thathapalli Prakash Parthiban , Hussain Waseem , Platten John D. , Lopena Vitaliano , Verdeprado Holden , Murori Rosemary , Ndayiragije Alexis , Katiyar Sanjay Kumar , Islam Md Rafiqul , Biswas Partha S. , Rutkoski Jessica E. , Arbelaez Juan D. , Mbute Felister N. , Miano Douglas W. , Cobb Joshua N.
Published: November 2021

Rice genetic improvement is a key component of achieving and maintaining food security in Asia and Africa in the face of growing populations and climate change. In this effort, the International Rice Research Institute (IRRI) continues to play a critical role in creating and disseminating rice varieties with higher productivity. Due to increasing demand for rice, especially in Africa, there is a strong need to accelerate the rate of genetic improvement for grain yield. In an effort to identify and characterize the elite breeding pool of IRRI’s irrigated rice breeding program, we analyzed 102 historical yield trials conducted in the Philippines during the period 2012–2016 and representing 15,286 breeding lines (including released varieties). A mixed model approach based on the pedigree relationship matrix was used to estimate breeding values for grain yield, which ranged from 2.12 to 6.27 t·ha−1. The rate of genetic gain for grain yield was estimated at 8.75 kg·ha−1 year−1(0.23%) for crosses made in the period from 1964 to 2014. Reducing the data to only IRRI released varieties, the rate doubled to 17.36 kg·ha−1 year−1(0.46%). Regressed against breeding cycle the rate of gain for grain yield was 185 kg·ha−1 cycle−1(4.95%). We selected 72 top performing lines based on breeding values for grain yield to create an elite core panel (ECP) representing the genetic diversity in the breeding program with the highest heritable yield values from which new products can be derived. The ECP closely aligns with the indica 1B sub-group ofOryza sativathat includes most modern varieties for irrigated systems. Agronomic performance of the ECP under multiple environments in Asia and Africa confirmed its high yield potential. We found that the rate of genetic gain for grain yield found in this study was limited primarily by long cycle times and the direct introduction of non-improved material into the elite pool. Consequently, the current breeding scheme for irrigated rice at IRRI is based on rapid recurrent selection among highly elite lines. In this context, the ECP constitutes an important resource for IRRI and NAREs breeders to carefully characterize and manage that elite diversity.
Immobilization of mercury in contaminated soils through the use of new carbon foam amendments
Authors: Janeiro-Tato I. , Lopez-Anton M. A. , Baragaño D. , Antuña-Nieto C. , Rodríguez E. , Peláez A. I. , Gallego J. R. , Martínez-Tarazona M. R.
Published: November 2021

Background

Mercury (Hg) is recognized as one of the 10 most toxic elements in nature and is much more persistent in soils than in other environmental compartments. However, an effective, environmentally friendly, economical, and large-scale applicable technology for the remediation of soils contaminated by Hg has not yet been established. This study evaluates the feasibility of a new carbon foam-based product for the remediation of three soils contaminated with Hg, and infers the mobilization or immobilization mechanism through a detailed study of Hg speciation.

Results

Soil treatment with carbon foams, one of them impregnated with goethite, reduced Hg availability by 75–100%. The proportion of mercury associated to humic acids (Hg–HA) determined the mobility and the availability of Hg when soils were treated with carbon foams. The drop of pH promotes changes in the structure of HA, a consequence of which is that Hg–HA becomes part of the unavailable fraction of the soil along with HgS. The carbon foam impregnated with goethite did not mobilize Fe as occurred with zero valence iron nanoparticles. The presence of acidic groups on the surface of the foam (carboxyl, quinone and phenolic groups) can strongly improve the binding of metal cations, enhancing Fe immobilization.

Conclusions

A novel carbon foam-based amendment was efficient in immobilizing Hg in all the soils studied. The carbon foam impregnated with goethite, in addition to not mobilizing Fe, had the additional advantage of its low effect on the electrical conductivity of the soil. This novel approach could be considered as a potential amendment for other industrial and/or abandoned mining areas contaminated with Hg and/or other metal(loid)s.
In depth analysis of Cyprus-specific mutations of SARS-CoV-2 strains using computational approaches
Authors: Oulas Anastasis , Richter Jan , Zanti Maria , Tomazou Marios , Michailidou Kyriaki , Christodoulou Kyproula , Christodoulou Christina , Spyrou George M.
Published: November 2021

Background

This study aims to characterize SARS-CoV-2 mutations which are primarily prevalent in the Cypriot population. Moreover, using computational approaches, we assess whether these mutations are associated with changes in viral virulence.

Methods

We utilize genetic data from 144 sequences of SARS-CoV-2 strains from the Cypriot population obtained between March 2020 and January 2021, as well as all data available from GISAID. We combine this with countries’ regional information, such as deaths and cases per million, as well as COVID-19-related public health austerity measure response times. Initial indications of selective advantage of Cyprus-specific mutations are obtained by mutation tracking analysis. This entails calculating specific mutation frequencies within the Cypriot population and comparing these with their prevalence world-wide throughout the course of the pandemic. We further make use of linear regression models to extrapolate additional information that may be missed through standard statistical analysis.

Results

We report a single mutation found in the ORF1ab gene (nucleotide position 18,440) that appears to be significantly enriched within the Cypriot population. The amino acid change is denoted as S6059F, which maps to the SARS-CoV-2 NSP14 protein. We further analyse this mutation using regression models to investigate possible associations with increased deaths and cases per million. Moreover, protein structure prediction tools show that the mutation infers a conformational change to the protein that significantly alters its structure when compared to the reference protein.

Conclusions

Investigating Cyprus-specific mutations for SARS-CoV-2 can lead to a better understanding of viral pathogenicity. Researching these mutations can generate potential links between viral-specific mutations and the unique genomics of the Cypriot population. This can not only lead to important findings from which to battle the pandemic on a national level, but also provide insights into viral virulence worldwide.
A joint analysis using exome and transcriptome data identifies candidate polymorphisms and genes involved with umbilical hernia in pigs
Authors: Savoldi Igor Ricardo , Ibelli Adriana Mércia Guaratini , Cantão Maurício Egídio , Peixoto Jane de Oliveira , Pires Michele Porto , Mores Marcos Antônio Zanella , Lagos Essamai Brizola , Lopes Jader Silva , Zanella Ricardo , Ledur Mônica Corrêa
Published: November 2021

Background

Umbilical Hernia (UH) is characterized by the passage of part of the intestine through the umbilical canal forming the herniary sac. There are several potential causes that can lead to the umbilical hernia such as bacterial infections, management conditions and genetic factors. Since the genetic components involved with UH are poorly understood, this study aimed to identify polymorphisms and genes associated with the manifestation of umbilical hernia in pigs using exome and transcriptome sequencing in a case and control design.

Results

In the exome sequencing, 119 variants located in 58 genes were identified differing between normal and UH-affected pigs, and in the umbilical ring transcriptome, 46 variants were identified, located in 27 genes. Comparing the two methodologies, we obtained 34 concordant variants between the exome and transcriptome analyses, which were located in 17 genes, distributed in 64 biological processes (BP). Among the BP involved with UH it is possible to highlight cell adhesion, cell junction regulation, embryonic morphogenesis, ion transport, muscle contraction, within others.

Conclusions

We have generated the first exome sequencing related to normal and umbilical hernia-affected pigs, which allowed us to identify several variants possibly involved with this disorder. Many of those variants present in the DNA were confirmed with the RNA-Seq results. The combination of both exome and transcriptome sequencing approaches allowed us to better understand the complex molecular mechanisms underlying UH in pigs and possibly in other mammals, including humans. Some variants found in genes and other regulatory regions are highlighted as strong candidates to the development of UH in pigs and should be further investigated.