bluuebunny/crossref_metadata_2025 huggingface dataset:
The usefulness of 3D printed heart models for medical student education in congenital heart disease
Authors: Karsenty Clement , Guitarte Aitor , Dulac Yves , Briot Jerome , Hascoet Sebastien , Vincent Remi , Delepaul Benoit , Vignaud Paul , Djeddai Camelia , Hadeed Khaled , Acar Philippe
Published: September 2021

Background

Three-dimensional (3D) printing technology enables the translation of 2-dimensional (2D) medical imaging into a physical replica of a patient’s individual anatomy and may enhance the understanding of congenital heart defects (CHD). We aimed to evaluate the usefulness of a spectrum of 3D-printed models in teaching CHD to medical students.

Results

We performed a prospective, randomized educational procedure to teach fifth year medical students four CHDs (atrial septal defect (ASD, n = 74), ventricular septal defect (VSD, n = 50), coarctation of aorta (CoA, n = 118) and tetralogy of Fallot (ToF, n = 105)). Students were randomized into printing groups or control groups. All students received the same 20 min lecture with projected digital 2D images. The printing groups also manipulated 3D printed models during the lecture. Both groups answered an objective survey (Multiple-choice questionnaire) twice, pre- and post-test, and completed a post-lecture subjective survey.

Three hundred forty-seven students were included and both teaching groups for each CHD were comparable in age, sex and pre-test score. Overall, objective knowledge improved after the lecture and was higher in the printing group compared to the control group (16.3 ± 2.6 vs 14.8 ± 2.8 out of 20, p < 0.0001). Similar results were observed for each CHD (p = 0.0001 ASD group; p = 0.002 VSD group; p = 0.0005 CoA group; p = 0.003 ToF group). Students’ opinion of their understanding of CHDs was higher in the printing group compared to the control group (respectively 4.2 ± 0.5 vs 3.8 ± 0.4 out of 5, p < 0.0001).

Conclusion

The use of 3D printed models in CHD lectures improve both objective knowledge and learner satisfaction for medical students. The practice should be mainstreamed.
A framework for the implementation of certification procedures in nurse level: a mixed approach study
Authors: Salma Israa , Waelli Mathias
Published: September 2021

Background

The implementation of certification procedures across healthcare systems is an essential component of the management process. Several promising approaches were developed toward a successful implementation of such policies; however, a precise adaptation and implementation to each local context was essential. Local activities must be considered in order to generate more pragmatic recommendations for managers. In this study, we built a framework for the implementation of certification procedures at nurse activity level. This was developed using two objectives: the identification of key implementation process components, and the integration of these components into a framework which considered the local socio-material context of nurses’ work.

Methods

We used a two-step mixed approach. The first was inductive and consisted of a qualitative case study conducted between April and December 2019. Here, we analyzed the implementation of certification procedures in a French teaching hospital. Data were collected using semi-structured interviews and observations. In the second approach, emerging data were deductively analyzed using the Quality Implementation Tool (QIT) and Translational Mobilization Theory (TMT). Analyses were combined to construct an implementation framework.

Results

Sixteen interviews were conducted with participants from different organizational levels, managers, mid-managers, and nurses. Additionally, 83 observational hours were carried out in two different wards. Our results showed that, (1) All retrieved elements during the process were successfully captured by the QIT components, only one component was not applicable. (2) We identified elements related to the local activity context, with the different interrelationships between actors, actions, and contexts using the TMT. (3) Our analyses were integrated and translated into a framework that presents the implementation of certification procedures in healthcare facilities, with a specific interest to the nurse/mid-manager level. By initially using QIT, the framework components took on a transversal aspect which were then adapted by TMT to the local work context.

Conclusions

We successfully generated a framework that supports the implementation of certification procedures at the activity level. Our approach identified a broader vision of the interactions between proximity managers, teams, and contexts during change mobilization, which were not encompassed by transversal framework only, such as QIT. In the future, more empirical studies are needed to test this framework.
The effects of selected inhibitors on human fetal adrenal steroidogenesis differs under basal and ACTH-stimulated conditions
Authors: Melau Cecilie , Riis Malene Lundgaard , Nielsen John E. , Perlman Signe , Lundvall Lene , Thuesen Lea Langhoff , Hare Kristine Juul , Hammerum Mette Schou , Mitchell Rod T. , Frederiksen Hanne , Juul Anders , Jørgensen Anne
Published: September 2021

Background

Disordered fetal adrenal steroidogenesis can cause marked clinical effects including virilization of female fetuses. In postnatal life, adrenal disorders can be life-threatening due to the risk of adrenal crisis and must be carefully managed. However, testing explicit adrenal steroidogenic inhibitory effects of therapeutic drugs is challenging due to species-specific characteristics, and particularly the impact of adrenocorticotropic hormone (ACTH) stimulation on drugs targeting steroidogenesis has not previously been examined in human adrenal tissue. Therefore, this study aimed to examine the effects of selected steroidogenic inhibitors on human fetal adrenal (HFA) steroid hormone production under basal and ACTH-stimulated conditions.

Methods

This study used an established HFA ex vivo culture model to examine treatment effects in 78 adrenals from 50 human fetuses (gestational weeks 8–12). Inhibitors were selected to affect enzymes critical for different steps in classic adrenal steroidogenic pathways, including CYP17A1 (Abiraterone acetate), CYP11B1/2 (Osilodrostat), and a suggested CYP21A2 inhibitor (Efavirenz). Treatment effects were examined under basal and ACTH-stimulated conditions in tissue from the same fetus and determined by quantifying the secretion of adrenal steroids in the culture media using liquid chromatography-tandem mass spectrometry. Statistical analysis was performed on ln-transformed data using one-way ANOVA for repeated measures followed by Tukey’s multiple comparisons test.

Results

Treatment with Abiraterone acetate and Osilodrostat resulted in potent inhibition of CYP17A1 and CYP11B1/2, respectively, while treatment with Efavirenz reduced testosterone secretion under basal conditions. ACTH-stimulation affected the inhibitory effects of all investigated drugs. Thus, treatment effects of Abiraterone acetate were more pronounced under stimulated conditions, while Efavirenz treatment caused a non-specific inhibition on steroidogenesis. ACTH-stimulation prevented the Osilodrostat-mediated CYP11B1 inhibition observed under basal conditions.

Conclusions

Our results show that the effects of steroidogenic inhibitors differ under basal and ACTH-stimulated conditions in the HFA ex vivo culture model. This could suggest that in vivo effects of therapeutic drugs targeting steroidogenesis may vary in conditions where patients have suppressed or high ACTH levels, respectively. This study further demonstrates that ex vivo cultured HFAs can be used to evaluate steroidogenic inhibitors and thereby provide novel information about the local effects of existing and emerging drugs that targets steroidogenesis.
Molecular detection and genetic characterization of Wenzhou virus in rodents in Guangzhou, China
Authors: Wang Nina , Yang Lichao , Li Guohui , Zhang Xu , Shao Jianwei , Ma Jun , Chen Shouyi , Liu Quan
Published: September 2021

Background

Wenzhou virus (WENV), a newly discovered mammarenavirus in rodents, is associated with fever and respiratory symptoms in humans. This study was aimed to detect and characterize the emerging virus in rodents in Guangzhou, China.

Results

A total of 100 small mammals, including 70 Rattus norvegicus, 22 Suncus murinus, 4 Bandicota indica, 3 Rattus flavipectus, and 1 Rattus losea, were captured in Guangzhou, and their brain tissues were collected and pooled for metagenomic analysis, which generated several contigs targeting the genome of WENV. Two R. norvegicus (2.9%) were further confirmed to be infected with WENV by RT-PCR. The complete genome (RnGZ37-2018 and RnGZ40-2018) shared 85.1–88.9% nt and 83.2–96.3% aa sequence identities to the Cambodian strains that have been shown to be associated with human disease. Phylogenetic analysis showed that all identified WENV could be grouped into four different lineages, and the two Guangzhou strains formed an independent clade. We also analyzed the potential recombinant events occurring in WENV strains.

Conclusions

Our study showed a high genetic diversity of WENV strains in China, emphasizing the relevance of surveillance of this emerging mammarenavirus in both natural reservoirs and humans.
Recent progress in the application of omics technologies in the study of bio-mining microorganisms from extreme environments
Authors: Li Min , Wen Jianping
Published: September 2021

Bio-mining microorganisms are a key factor affecting the metal recovery rate of bio-leaching, which inevitably produces an extremely acidic environment. As a powerful tool for exploring the adaptive mechanisms of microorganisms in extreme environments, omics technologies can greatly aid our understanding of bio-mining microorganisms and their communities on the gene, mRNA, and protein levels. These omics technologies have their own advantages in exploring microbial diversity, adaptive evolution, changes in metabolic characteristics, and resistance mechanisms of single strains or their communities to extreme environments. These technologies can also be used to discover potential new genes, enzymes, metabolites, metabolic pathways, and species. In addition, integrated multi-omics analysis can link information at different biomolecular levels, thereby obtaining more accurate and complete global adaptation mechanisms of bio-mining microorganisms. This review introduces the current status and future trends in the application of omics technologies in the study of bio-mining microorganisms and their communities in extreme environments.
Molecular epidemiology of blaCTX-M gene-producing uropathogenic Escherichia coli among Iranian kidney transplant patients: clonal dissemination of CC131 and CC10
Authors: Halaji Mehrdad , Shahidi Shahrzad , Ataei Behrooz , Atapour Abdolamir , Feizi Awat , Havaei Seyed Asghar
Published: September 2021

Background

This study aimed to investigate the phylogenetic characterization and virulence traits of uropathogenic Escherichia coli (UPEC) isolated from kidney transplant patients (KTPs) as well as non-KTPs and analyze the clonal distribution of Extended spectrum β-lactamases (ESBLs)-producing UPEC containing blaCTX-M gene.

Methods

To this end, we determined virulence marker and the phylogenetic characterization of UPEC in non-KTPs (n = 65) and KTPs (n = 46). The non-KTPs were considered the control group of the study. Also, according to the Achtman scheme, we performed multilocus sequence typing to assess the relationship between twenty-nine of ESBL-producing isolates containing blaCTX-M gene.

Results

According to the results of PCR assay, the prevalence of virulence factor genes ranged from 0% (cnf and papG III) to 93.7% (fimH). Also, KTP isolates significantly differed from non-KTP isolates only in terms of the prevalence of pap GI elements. Moreover, the most frequent UPEC isolates were in phylogenetic group B2, followed by group D (18.9%), and group A (13.5%). Furthermore, except for phylogenetic group C, there was no significant correlation between phylogenetic distribution in KTPs and non-KTPs. Additionally, MLST analysis of blaCTX-M carrying isolates identified 18 unique sequence types (ST) the most common of which was ST131 (24.1%), followed by ST1193 (10.3%), while fourteen STs were detected only once.

Conclusions

The results further revealed significant differences between the UPEC isolates from KTPs and non-KTPs regarding the phylogroups C and PAI gene. Based on MLST analysis, we also observed a relatively high diversity in UPEC isolates obtained from KTPs and non-KTPs. Moreover, clonal complex (CC) 131 and ST131 were found to be the most prevalent clones and ST types, respectively. Besides, for the first time, ST8503 were reported in KTPs. These results suggested regular studies on characterization of UPEC isolates among KTPs.
An ADAR1-dependent RNA editing event in the cyclin-dependent kinase CDK13 promotes thyroid cancer hallmarks
Authors: Ramírez-Moya Julia , Miliotis Christos , Baker Allison R. , Gregory Richard I. , Slack Frank J. , Santisteban Pilar
Published: September 2021

Background

Adenosine deaminases acting on RNA (ADARs) modify many cellular RNAs by catalyzing the conversion of adenosine to inosine (A-to-I), and their deregulation is associated with several cancers. We recently showed that A-to-I editing is elevated in thyroid tumors and that ADAR1 is functionally important for thyroid cancer cell progression. The downstream effectors regulated or edited by ADAR1 and the significance of ADAR1 deregulation in thyroid cancer remain, however, poorly defined.

Methods

We performed whole transcriptome sequencing to determine the consequences of ADAR1 deregulation for global gene expression, RNA splicing and editing. The effects of gene silencing or RNA editing were investigated by analyzing cell viability, proliferation, invasion and subnuclear localization, and by protein and gene expression analysis.

Results

We report an oncogenic function forCDK13in thyroid cancer and identify a new ADAR1-dependent RNA editing event that occurs in the coding region of its transcript.CDK13was significantly over-edited (c.308A > G) in tumor samples and functional analysis revealed that this editing event promoted cancer cell hallmarks. Finally, we show thatCDK13editing increases the nucleolar abundance of the protein, and that this event might explain, at least partly, the global change in splicing produced by ADAR1 deregulation.

Conclusions

Overall, our data support A-to-I editing as an important pathway in cancer progression and highlight novel mechanisms that might be used therapeutically in thyroid and other cancers.
The role of lncRNAs and circRNAs in the PD-1/PD-L1 pathway in cancer immunotherapy
Authors: Jiang Wenxiao , Pan Shuya , Chen Xin , Wang Zhi-wei , Zhu Xueqiong
Published: September 2021

Cancer immunotherapy has recently shown promising antitumor effects in various types of tumors. Among all immune checkpoints, the PD-1/PD-L1 pathway plays an important role in the immune evasion of tumor cells, making it a potent target in antitumor immunity. Accordingly, antibodies targeting the PD-1/PD-L1 pathway have been developed to attack tumor cells; however, resistance to immune therapy remains to be solved. Hence, identification of the underlying modulators of the PD-1/PD-L1 pathway is of significant importance to understand the mechanisms of antitumor immunotherapy. Long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) have been identified to regulate the PD-1/PD-L1 pathway, leading to participation in the immune response and immunotherapy. Therefore, this review focuses on the functions of lncRNAs and circRNAs in regulation of the PD-1/PD-L1 axis in tumorigenesis and tumor progression. We hope this review will stimulate research to supply more precise and effective cancer immune checkpoint therapies for a large number of tumors.
Extracellular vesicles derived from CD73 modified human umbilical cord mesenchymal stem cells ameliorate inflammation after spinal cord injury
Authors: Zhai Xiao , Chen Kai , Yang Huan , Li Bo , Zhou Tianjunke , Wang Haojue , Zhou Huipeng , Chen Shaofeng , Zhou Xiaoyi , Wei Xiaozhao , Bai Yushu , Li Ming
Published: September 2021

Background

Spinal cord injury (SCI) is an inflammatory condition, and excessive adenosine triphosphate (ATP) is released into the extracellular space, which can be catabolized into adenosine by CD73. Extracellular vesicles have been designed as nano drug carriers in many diseases. However, their impacts on delivery of CD73 after SCI are not yet known. We aimed to construct CD73 modified extracellular vesicles and explore the anti-inflammatory effects after SCI.

Methods

CD73 engineered extracellular vesicles (CD73+ hucMSC-EVs) were firstly established, which were derived from human umbilical cord mesenchymal stem cells (hucMSCs) transduced by lentiviral vectors to upregulate the expression of CD73. Effects of CD73+ hucMSC-EVs on hydrolyzing ATP into adenosine were detected. The polarization of M2/M1 was verified by immunofluorescence. Furthermore, A2aR and A2bR inhibitors and A2bR knockdown cells were used to investigate the activated adenosine receptor. Biomarkers of microglia and levels of cAMP/PKA were also detected. Repetitively in vivo study, morphology staining, flow cytometry, cytokine analysis, and ELISA assay, were also applied for verifications.

Results

CD73+ hucMSC-EVs reduced concentration of ATP and promoted the level of adenosine. In vitro experiments, CD73+ hucMSC-EVs increased macrophages/microglia M2:M1 polarization, activated adenosine 2b receptor (A2bR), and then promoted cAMP/PKA signaling pathway. In mice using model of thoracic spinal cord contusion injury, CD73+ hucMSC-EVs improved the functional recovery after SCI through decreasing the content of ATP in cerebrospinal fluid and improving the polarization from M1 to M2 phenotype. Thus, the cascaded pro-inflammatory cytokines were downregulated, such as TNF-α, IL-1β, and IL-6, while the anti-inflammatory cytokines were upregulated, such as IL-10 and IL-4.

Conclusions

CD73+ hucMSC-EVs ameliorated inflammation after spinal cord injury by reducing extracellular ATP, promoting A2bR/cAMP/PKA pathway and M2/M1 polarization. CD73+ hucMSC-EVs might be promising nano drugs for clinical application in SCI therapy.

Graphical Abstract
Development, characteristics and impact of quality improvement casebooks: a scoping review
Authors: Anderson Natalie N. , Gagliardi Anna R.
Published: September 2021

Background

Quality improvement (QI) casebooks, compilations of QI experiences, are one way to share experiential knowledge that healthcare policy-makers, managers and professionals can adapt to their own contexts. However, QI casebook use, characteristics and impact are unknown. We aimed to synthesize published research on QI prevalence, development, characteristics and impact.

Methods

We conducted a scoping review by searching MEDLINE, EMBASE, CINAHL and SCOPUS from inception to 4 February 2021. We extracted data on study characteristics and casebook definitions, development, characteristics (based on the WIDER [Workgroup for Intervention Development and Evaluation Research] framework) and impact. We reported findings using summary statistics, text and tables.

Results

We screened 2999 unique items and included five articles published in Canada from 2011 to 2020 describing three studies. Casebooks focused on promoting positive weight-related conversations with children and parents, coordinating primary care-specialist cancer management, and showcasing QI strategies for cancer management. All defined casebooks similarly described real-world experiences of developing and implementing QI strategies that others could learn from, emulate or adapt. In all studies, casebook development was a multistep, iterative, interdisciplinary process that engages stakeholders in identifying, creating and reviewing content. While casebooks differed in QI topic, level of application and scope, cases featured common elements: setting or context, QI strategy details, impacts achieved, and additional tips for implementing strategies. Cases were described with a blend of text, graphics and tools. One study evaluated casebook impact, and found that it enhanced self-efficacy and use of techniques to improve clinical care. Although details about casebook development and characteristics were sparse, we created a template of casebook characteristics, which others can use as the basis for developing or evaluating casebooks.

Conclusion

Future research is needed to optimize methods for developing casebooks and to evaluate their impact. One approach is to assess how the many QI casebooks available online were developed. Casebooks should be evaluated alone or in combination with other interventions that support QI on a range of outcomes.
Mobility and muscle strength trajectories in old age: the beneficial effect of Mediterranean diet in combination with physical activity and social support
Authors: Saadeh Marguerita , Prinelli Federica , Vetrano Davide L. , Xu Weili , Welmer Anna-Karin , Dekhtyar Serhiy , Fratiglioni Laura , Calderón-Larrañaga Amaia
Published: September 2021

Introduction

Decline in physical function varies substantially across older individuals due to several extrinsic modifiable factors such as dietary patterns, physical activity and social support. We aimed to determine the association of these factors and their interaction with mobility and muscle strength decline.

Methods

We analyzed data from 1686 functionally healthy individuals aged 60 + from the population-based Swedish National study on Aging and Care in Kungsholmen (SNAC-K). The Mediterranean Diet Score (MDS) was calculated based on a validated food frequency questionnaire. Self-reported physical activity was categorized based on current recommendations, and social support was measured according to participants’ perceived material and psychological support from relatives and friends. Participants’ physical function was assessed over 12 years through changes in walking speed (m/s) and chair stand time (s). Linear mixed models adjusted for socio-demographic and clinical factors were used. In order to explore the combined effect of the different exposures, two indicator variables were created by cross-classifying individuals' levels of Mediterranean diet adherence and social support or physical activity.

Results

Participants with a high adherence to Mediterranean diet were primarily < 78 years (82.3%), women (56.1%), married (61.1%), with university education (52.8%), high levels of social support (39.3%) and health-enhancing levels of physical activity (51.5%). A one-point increase in MDS (score range 0–9) was associated with less annual deterioration in walking speed (β*time[year] = 0.001; p = 0.024) and chair-stand time (β*time[year] = -0.014; p = 0.008). The potential protective effect of Mediterranean diet was highest among participants reporting high social support (β*time[year] = -0.065, p = 0.026 for chair stands) and high physical activity (β*time[year] = 0.010, p = 0.001 for walking speed), beyond the effect of each exposure individually.

Conclusion

A higher adherence to Mediterranean diet, especially in combination with recommended levels of physical activity and high social support, may contribute to delay the decline in physical function observed with aging.
Establishment of a novel glycolysis-related prognostic gene signature for ovarian cancer and its relationships with immune infiltration of the tumor microenvironment
Authors: Bi Jianlei , Bi Fangfang , Pan Xue , Yang Qing
Published: September 2021

Background

Glycolysis affects tumor growth, invasion, chemotherapy resistance, and the tumor microenvironment. In this study, we aimed to construct a glycolysis-related prognostic model for ovarian cancer and analyze its relationship with the tumor microenvironment’s immune cell infiltration.

Methods

We obtained six glycolysis-related gene sets for gene set enrichment analysis (GSEA). Ovarian cancer data from The Cancer Genome Atlas (TCGA) database and two Gene Expression Omnibus (GEO) datasets were divided into two groups after removing batch effects. We compared the tumor environments' immune components in high-risk and low-risk groups and analyzed the correlation between glycolysis- and immune-related genes. Then, we generated and validated a predictive model for the prognosis of ovarian cancer using the glycolysis-related genes.

Results

Overall, 27/329 glycolytic genes were associated with survival in ovarian cancer, 8 of which showed predictive value. The tumor cell components in the tumor microenvironment did not differ between the high-risk and low-risk groups; however, the immune score differed significantly between groups. In total, 13/24 immune cell types differed between groups, including 10 T cell types and three other immune cell types. Eight glycolysis-related prognostic genes were related to the expression of multiple immune-related genes at varying degrees, suggesting a relationship between glycolysis and immune response.

Conclusions

We identified eight glycolysis-related prognostic genes that effectively predicted survival in ovarian cancer. To a certain extent, the newly identified gene signature was related to the tumor microenvironment, especially immune cell infiltration and immune-related gene expression. These findings provide potential biomarkers and therapeutic targets for ovarian cancer.
Muscle activation strategies of people with early-stage Parkinson’s during walking
Authors: Keloth Sana M. , Arjunan Sridhar P. , Raghav Sanjay , Kumar Dinesh Kant
Published: September 2021

Introduction

Some people with Parkinson’s disease (PD) frequently have an unsteady gait with shuffling, reduced strength, and increased rigidity. This study has investigated the difference in the neuromuscular strategies of people with early-stage PD, healthy older adults (HOA) and healthy young adult (HYA) during short-distance walking.

Method

Surface electromyogram (sEMG) was recorded from tibialis anterior (TA) and medial gastrocnemius (MG) muscles along with the acceleration data from the lower leg from 72 subjects—24 people with early-stage PD, 24 HOA and 24 HYA during short-distance walking on a level surface using wearable sensors.

Results

There was a significant increase in the co-activation, a reduction in the TA modulation and an increase in the TA-MG lateral asymmetry among the people with PD during a level, straight-line walking. For people with PD, the gait impairment scale was low with an average postural instability and gait disturbance (PIGD) score = 5.29 out of a maximum score of 20. Investigating the single and double support phases of the gait revealed that while the muscle activity and co-activation index (CI) of controls modulated over the gait cycle, this was highly diminished for people with PD. The biggest difference between CI of controls and people with PD was during the double support phase of gait.

Discussion

The study has shown that people with early-stage PD have high asymmetry, reduced modulation, and higher co-activation. They have reduced muscle activity, ability to inhibit antagonist, and modulate their muscle activities. This has the potential for diagnosis and regular assessment of people with PD to detect gait impairments using wearable sensors.
Analysis of intercondylar notch size and shape in patients with cyclops syndrome after anterior cruciate ligament reconstruction
Authors: Ficek Krzysztof , Rajca Jolanta , Cholewiński Jerzy , Racut Agnieszka , Gwiazdoń Paweł , Przednowek Krzysztof , Hajduk Grzegorz
Published: September 2021

Background

Cyclops lesion is the second most common cause of extension loss after anterior cruciate ligament reconstruction. This study focused on the correlation between the anatomy of the intercondylar notch and the incidence of cyclops lesion. To determine whether the size and shape of the intercondylar notch are related to cyclops lesion formation following anterior cruciate ligament reconstruction according to magnetic resonance imaging (MRI) findings.

Methods

One hundred twenty-five (125) patients were retrospectively evaluated. The notch width index (NWI) and notch shape index (NSI) were measured based on coronal and axial MRI sections in patients diagnosed with cyclops syndrome (n = 25), diagnosed with complete anterior cruciate ligament (ACL) tears (n = 50), and without cyclops lesions or ACL ruptures (n = 50).

Results

Imaging analysis results showed that the cyclops and ACL groups had lower mean NWI and NSI values than the control group. Significant between-group differences were found in NSI (p = 0.0140) based on coronal cross-sections and in NWI (p = 0.0026) and NSI (p < 0.0001) based on axial sections.

Conclusions

The geometry of the intercondylar notch was found to be associated with the risk of cyclops lesion formation and ACL rupture.
Risk factor analysis of clinical outcomes of total aortic arch replacement and frozen elephant trunk with aortic balloon occlusion
Authors: Wang Luchen , Li Yunfeng , Dun Yaojun , Sun Xiaogang
Published: September 2021

Background

Total aortic arch replacement (TAR) with frozen elephant trunk (FET) requires hypothermic circulatory arrest (HCA) for 20 min, which increases the surgical risk. We invented an aortic balloon occlusion (ABO) technique that requires 5 min of HCA on average to perform TAR with FET and investigated the possible merit of this new method in this study.

Methods

This retrospective study included consecutive patients who underwent TAR and FET (consisting of 130 cases of ABO group and 230 cases of conventional group) in Fuwai Hospital between August 2017 and February 2019. In addition to the postoperative complications, the alterations of blood routine tests, alanine transaminase (ALT) and aspartate transaminase (AST) during in-hospital stay were also recorded.

Results

The 30-day mortality rates were similar between ABO group (4.6%) and conventional group (7.8%, P = 0.241). Multivariate analysis showed ABO reduced postoperative acute kidney injury (23.1% vs. 35.7%, P = 0.013) and hepatic injury (12.3% vs. 27.8%, P = 0.001), and maintained similar cost to patients (25.5 vs. 24.9 kUSD, P = 0.298). We also found that AST was high during intensive care unit (ICU) stay and recovered to normal before discharge, while ALT was not as high as AST in ICU but showed a rising tendency before discharge. The platelet count showed a rising tendency on postoperative day 3 and may exceed the preoperative value before discharge.

Conclusions

The ABO achieved the surgical goal of TAR with FET with an improved recovery process during the in-hospital stay.
Long-term efficacy of lipoprotein apheresis and lomitapide in the treatment of homozygous familial hypercholesterolemia (HoFH): a cross-national retrospective survey
Authors: D’Erasmo Laura , Gallo Antonio , Cefalù Angelo Baldassare , Di Costanzo Alessia , Saheb Samir , Giammanco Antonina , Averna Maurizio , Buonaiuto Alessio , Iannuzzo Gabriella , Fortunato Giuliana , Puja Arturo , Montalcini Tiziana , Pavanello Chiara , Calabresi Laura , Vigna Giovanni Battista , Bucci Marco , Bonomo Katia , Nota Fabio , Sampietro Tiziana , Sbrana Francesco , Suppressa Patrizia , Sabbà Carlo , Fimiani Fabio , Cesaro Arturo , Calabrò Paolo , Palmisano Silvia , D’Addato Sergio , Pisciotta Livia , Bertolini Stefano , Bittar Randa , Kalmykova Olga , Béliard Sophie , Carrié Alain , Arca Marcello , Bruckert Eric
Published: September 2021

Abstract

Background

Homozygous familial hypercholesterolemia (HoFH) is a rare life-threatening condition that represents a therapeutic challenge. The vast majority of HoFH patients fail to achieve LDL-C targets when treated with the standard protocol, which associates maximally tolerated dose of lipid-lowering medications with lipoprotein apheresis (LA). Lomitapide is an emerging therapy in HoFH, but its place in the treatment algorithm is disputed because a comparison of its long-term efficacy versus LA in reducing LDL-C burden is not available. We assessed changes in long-term LDL-C burden and goals achievement in two independent HoFH patients’ cohorts, one treated with lomitapide in Italy (n = 30) and the other with LA in France (n = 29).

Results

The two cohorts differed significantly for genotype (p = 0.004), baseline lipid profile (p < 0.001), age of treatment initiation (p < 0.001), occurrence of cardiovascular disease (p = 0.003) as well as follow-up duration (p < 0.001). The adjunct of lomitapide to conventional lipid-lowering therapies determined an additional 58.0% reduction of last visit LDL-C levels, compared to 37.1% when LA was added (padj = 0.004).
Yearly on-treatment LDL-C < 70 mg/dl and < 55 mg/dl goals were only achieved in 45.5% and 13.5% of HoFH patients treated with lomitapide. The long-term exposure to LDL-C burden was found to be higher in LA than in Lomitapide cohort (13,236.1 ± 5492.1 vs. 11,656.6 ± 4730.9 mg/dL-year respectively, padj = 0.002). A trend towards fewer total cardiovascular events was observed in the Lomitapide than in the LA cohort.

Conclusions

In comparison with LA, lomitapide appears to provide a better control of LDL-C in HoFH. Further studies are needed to confirm this data and establish whether this translates into a reduction of cardiovascular risk.
Characterization of epidemiological distribution and outcome of COVID-19 in patients with hereditary hemorrhagic telangiectasia: a nationwide retrospective multi-centre study during first wave in Italy
Authors: Suppressa Patrizia , Pagella Fabio , Lenato Gennaro Mariano , Gaetani Eleonora , Serio Ilaria , Masala Maristella Salvatora , Spinozzi Giuseppe , Lizzio Roberta , Matti Elina , De Silvestri Annalisa , Passali Giulio Cesare , Aguglia Maria , Crocione Claudia , Sabbà Carlo
Published: September 2021

Background

Coronavirus Disease 2019 (COVID-19) continues to have a devastating impact across the world. A number of pre-existing common clinical conditions were reported to represent risk factors for more severe COVID-19 outcomes. Hereditary Hemorrhagic Telangiectasia (HHT) is a rare vascular heritable disorders, characterized by complications secondary to visceral Arterio-Venous Malformations. The impact of HHT, as well as for many Rare Diseases (RDs) on infection susceptibility profile and clinical adverse outcome risk is an unresolved issue.

Objectives

The main objectives were: to assess the clinical features and outcomes of HHT patients infected with COVID-19; to compare the relative infection risk in these patients with the Italian general population throughout the first pandemic wave; to investigate the factors potentially associated with severe COVID-19 outcome in HHT patients, and the possible impact of COVID-19 infection on HHT-related symptoms/complications. Finally, we aimed to estimate how the lockdown-associated wearing of personal protective equipment/individual protection devices could affect HHT-related telangiectasia bleeding frequency.

Methods

The study is a nation-wide questionnaire-based survey, with a multi-Center retrospective cross-sectional design, addressed to the whole Italian HHT population. COVID-19 cases, occurring throughout the first pandemic wave, were collected by a questionnaire-based semi-structured interview. Only the cases ascertained by laboratory confirmation (molecular/serological) were included for epidemiological estimates. Information concerning eventual SarS-Cov-2 infection, as well as regarding HHT-related manifestations and HHT-unrelated co-morbidities were collected by the questionnaire. Prevalence data were compared to Italian general population in the same period.

Results

The survey disclosed 9/296 (3.04%) COVID-19 cases, 8/9 of them being resident in Lombardy, the main epidemic epicenter. Pneumonia was reported by 4/9 patients, which prompted hospital admission and intensive care management in 2 cases. No fatal outcome was recorded. After careful refinement of epidemiological analysis, the survey evidenced overlapping infection risk in HHT compared to general population.

Conclusions

COVID-19 infection profile parallels geographical distribution of epidemic foci. COVID-19 in HHT patients can lead to highly variable clinical profile, likely overlapping with that of general population. The HHT disease does not seem to involve a different approach in terms of hospital admission and access to intensive care with respect to general population.
Prevalence and genotype specific concordance of oro-genital and anal human papillomavirus infections among sexually active Nigerian women
Authors: Morhason-Bello Imran O. , Baisley Kathy , Pavon Miquel Angel , Adewole Isaac F. , Bakare Rasheed , de Sanjosé Silvia , Francis Suzanna C. , Watson-Jones Deborah
Published: September 2021

Background

Human papillomavirus (HPV) associated cancers are increasingly reported globally, including in sub-Saharan Africa (SSA). However, with the exception of cervical HPV infection, data from SSA on the epidemiology of oral and genital HPV infections are limited. This study assessed the prevalence and concordance of oro-genital and anal HPV genotype specific infections among women in the general population.

Methods

We conducted a cross-sectional study in sexually active women aged 18–45 years in Ibadan, Nigeria. After a face-to-face interview and clinical examination, oral, cervical, vulvar, and anal samples were collected from participants and tested by the Anyplex II 28 HPV assay. Descriptive and multivariable analyses were used to report prevalence and risk factors associated with HPV infections.

Results

The prevalence of any vulva, cervical, anal, and oral HPV infections was 68.0% (210/309), 59.7% (182/305), 56.8% (172/303), and 16.1% (14/286), respectively. There was an inverse relationship between age-group and HPV prevalence of HPV in all anatomic sites except for the oral HPV infections. HPV 35 was the most prevalent high-risk HPV genotype in the vulva, cervix and oral cavity. Associated risk factors for HPV infection in each of the anatomic sites were reported. Overall, 10.0% (31/310) women had concordance of any HPV type in the four anatomic sites.

Conclusion

There was a high prevalence of oro-genital and anal HPV infections among sexually active Nigerian women, with concordance of HPV types in the cervix, vulva, anus and oral cavity. We advocate large longitudinal studies that will involve sampling of multiple anatomic sites and inclusion of other women in the community for better understanding of HPV epidemiology in this region.
ALKBH5-HOXA10 loop-mediated JAK2 m6A demethylation and cisplatin resistance in epithelial ovarian cancer
Authors: Nie Sipei , Zhang Lin , Liu Jinhui , Wan Yicong , Jiang Yi , Yang Jing , Sun Rui , Ma Xiaolling , Sun Guodong , Meng Huangyang , Xu Mengting , Cheng Wenjun
Published: September 2021

Background

Chemotherapy resistance remains a barrier to improving the prognosis of epithelial ovarian cancer (EOC). ALKBH5 has recently been shown to be one of the RNA N6-methyladenosine (m6A) demethyltransferases associated with various cancers, but its role in cancer therapeutic resistance remains unclear. This study aimed to investigate the role of AlkB homolog 5 (ALKBH5) in cisplatin-resistant EOC.

Methods

Functional assays were performed both in vitro and in vivo. RNA sequencing (RNA-seq), m6A-modified RNA immunoprecipitation sequencing (MeRIP-seq), chromatin immunoprecipitation, RNA immunoprecipitation, and luciferase reporter and actinomycin-D assays were performed to investigate RNA/RNA interaction and m6A modification of the ALKBH5-HOXA10 loop.

Results

ALKBH5 was upregulated in cisplatin-resistant EOC and promoted cancer cell cisplatin resistance both in vivo and in vitro. Notably, HOXA10 formed a loop with ALKBH5 and was found to be the upstream transcription factor of ALKBH5. HOXA10 overexpression also facilitated EOC cell chemoresistance both in vivo and in vitro. Collective results of MeRIP-seq and RNA-seq showed that JAK2 is the m6A-modified gene targeted by ALKBH5. The JAK2/STAT3 signaling pathway was activated by overexpression of the ALKBH5-HOXA10 loop, resulting in EOC chemoresistance. Cell sensitivity to cisplatin was rescued by ALKBH5 and HOXA10 knockdown or inhibition of the JAK2/STAT3 signaling pathway in EOC cells overexpressing ALKBH5-HOXA10.

Conclusions

The ALKBH5-HOXA10 loop jointly activates the JAK2/STAT3 signaling pathway by mediating JAK2 m6A demethylation, promoting EOC resistance to cisplatin. Thus, inhibition of the expression of the ALKBH5-HOXA10 loop may be a potential strategy to overcome cisplatin resistance in EOC.
Beta-blockade is not associated with improved outcomes in isolated severe extracranial injury: an observational cohort study
Authors: Sadi Lin , Sjölin Gabriel , Ahl Hulme Rebecka
Published: September 2021

Background

There is evidence supporting the use of beta-blockade in patients with traumatic brain injury. The reduction in sympathetic drive is thought to underlie the relationship between beta-blockade and increased survival. There is little evidence for similar effects in extracranial injuries. This study aimed to assess the association between beta-blockade and survival in patients suffering isolated severe extracranial injuries.

Methods

Patients treated at an academic urban trauma centre during a 5-year period were retrospectively identified. Adults suffering isolated severe extracranial injury [Injury Severity Score (ISS) ≥ 16 with Abbreviated Injury Score of ≤ 2 for any intracranial injury] were included. Patient characteristics and outcomes were collected from the trauma registry and hospital medical records. Patients were subdivided into beta-blocker exposed and unexposed groups. Patients were matched using propensity score matching. Differences were assessed using McNemar’s or paired Student’s t test. The primary outcome of interest was 90-day mortality and secondary outcome was in-hospital complications.

Results

698 patients were included of whom 10.5% were on a beta-blocker. Most patients suffered blunt force trauma (88.5%) with a mean [standard deviation] ISS of 24.6 [10.6]. Unadjusted mortality was higher in patients receiving beta-blockers (34.2% vs. 9.1%, p < 0.001) as were cardiac complications (8.2% vs. 1.4%, p = 0.002). Patients on beta-blockers were significantly older (69.5 [14.1] vs. 43.2 [18.0] years) and of higher comorbidity. After matching, no statistically significant differences were seen in 90-day mortality (34.2% vs. 30.1%, p = 0.690) or in-hospital complications.

Conclusions

Beta-blocker therapy does not appear to be associated with improved survival in patients with isolated severe extracranial injuries.
Commentary: Pivoting during a pandemic: developing a new recruitment model for a randomised controlled trial in response to COVID-19
Authors: Milton Shakira , McIntosh Jennifer , Boyd Lucy , Karnchanachari Napin , Macrae Finlay , Emery Jon David
Published: September 2021

Background

Many non-COVID-19 trials were disrupted in 2020 and either struggled to recruit participants or stopped recruiting altogether. In December 2019, just before the pandemic, we were awarded a grant to conduct a randomised controlled trial, the Should I Take Aspirin? (SITA) trial, in Victoria, the Australian state most heavily affected by COVID-19 during 2020.

Main body

We originally modelled the SITA trial recruitment method on previous trials where participants were approached and recruited in general practice waiting rooms. COVID-19 changed the way general practices worked, with a significant increase in telehealth consultations and restrictions on in person waiting room attendance. This prompted us to adapt our recruitment methods to this new environment to reduce potential risk to participants and staff, whilst minimising any recruitment bias. We designed a novel teletrial model, which involved calling participants prior to their general practitioner appointments to check their eligibility. We delivered the trial both virtually and face-to-face with similar overall recruitment rates to our previous studies.

Conclusion

We developed an effective teletrial model which allowed us to complete recruitment at a high rate. The teletrial model is now being used in our other primary care trials as we continue to face the impacts of the COVID-19 pandemic.
Detection of Leishmania tarentolae in lizards, sand flies and dogs in southern Italy, where Leishmania infantum is endemic: hindrances and opportunities
Authors: Mendoza-Roldan Jairo Alfonso , Latrofa Maria Stefania , Iatta Roberta , R. S. Manoj Ranju , Panarese Rossella , Annoscia Giada , Pombi Marco , Zatelli Andrea , Beugnet Fred , Otranto Domenico
Published: September 2021

Background

Leishmania tarentolae is a protozoan isolated from geckoes (Tarentola annularis, Tarentola mauritanica), which is considered non-pathogenic and is transmitted by herpetophilic Sergentomyia spp. sand flies. This species occurs in sympatry with Leishmania infantum in areas where canine leishmaniasis is endemic. In the present study, we investigated the circulation of L. tarentolae and L. infantum in sand flies, dogs and lizards in a dog shelter in southern Italy, where canine leishmaniasis by L. infantum is endemic.

Methods

Sheltered dogs (n = 100) negative for Leishmania spp. (March 2020) were screened by immunofluorescence antibody test (IFAT) using promastigotes of both species at two time points (June 2020 and March 2021). Whole blood from dogs, tissues of Podarcis siculus lizards (n = 28) and sand flies (n = 2306) were also sampled and tested by a duplex real-time PCR (dqPCR). Host blood meal was assessed in sand flies by PCR.

Results

Overall, 16 dogs became positive for L. infantum and/or L. tarentolae by IFAT at one or both sampling periods. One canine blood sample was positive for L. infantum, whilst two for L. tarentolae by dqPCR. At the cytology of lizard blood, Leishmania spp. amastigote-like forms were detected in erythrocytes. Twenty-two tissue samples, mostly lung (21.4%), scored molecularly positive for L. tarentolae, corresponding to 10 lizards (i.e., 35.7%). Of the female Sergentomyia minuta sampled (n = 1252), 158 scored positive for L. tarentolae, four for L. infantum, and one co-infected. Two Phlebotomus perniciosus (out of 29 females) were positive for L. tarentolae. Engorged S. minuta (n = 10) fed on humans, and one P. perniciosus, positive for L. tarentolae, on lagomorphs.

Conclusions

Dogs and lacertid lizards (Podarcis siculus) were herein found for the first time infected by L. tarentolae. The detection of both L. tarentolae and L. infantum in S. minuta and P. perniciosus suggests their sympatric circulation, with a potential overlap in vertebrate hosts. The interactions between L. tarentolae and L. infantum should be further investigated in both vectors and vertebrate hosts to understand the potential implications for the diagnosis and control of canine leishmaniasis in endemic areas.

Graphical abstract