bluuebunny/crossref_metadata_2025 huggingface dataset:
Age-specific cut-off levels of anti-Müllerian hormone can be used as diagnostic markers for polycystic ovary syndrome
Authors: Ramezani Tehrani Fahimeh , Rahmati Maryam , Mahboobifard Fatemeh , Firouzi Faezeh , Hashemi Nazanin , Azizi Fereidoun
Published: May 2021

Background

The majority of available studies on the AMH thresholds were not age-specific and performed the receiver operating characteristic curve (ROC) analysis, based on variations in sensitivity and specificity rather than positive and negative predictive values (PPV and NPV, respectively), which are more clinically applicable. Moreover, all of these studies used a pre-specified age categorization to report the age-specific cut-off values of AMH.

Methods

A total of 803 women, including 303 PCOS patients and 500 eumenorrheic non-hirsute control women, were enrolled in the present study. The PCOS group included PCOS women, aged 20–40 years, who were referred to the Reproductive Endocrinology Research Center, Tehran, Iran. The Rotterdam consensus criteria were used for diagnosis of PCOS. The control group was selected among women, aged 20–40 years, who participated in Tehran Lipid and Glucose cohort Study (TLGS). Generalized additive models (GAMs) were used to identify the optimal cut-off points for various age categories. The cut-off levels of AMH in different age categories were estimated, using the Bayesian method.

Main results and the role of chance

Two optimal cut-off levels of AMH (ng/ml) were identified at the age of 27 and 35 years, based on GAMs. The cut-off levels for the prediction of PCOS in the age categories of 20–27, 27–35, and 35–40 years were 5.7 (95 % CI: 5.48–6.19), 4.55 (95 % CI: 4.52–4.64), and 3.72 (95 % CI: 3.55–3.80), respectively. Based on the Bayesian method, the PPV and NPV of these cut-off levels were as follows: PPV = 0.98 (95 % CI: 0.96–0.99) and NPV = 0.40 (95 % CI: 0.30–0.51) for the age group of 20–27 years; PPV = 0.96 (95 % CI: 0.91–0.99) and NPV = 0.82 (95 % CI: 0.78–0.86) for the age group of 27–35 years; and PPV = 0.86 (95 % CI: 0.80–0.94) and NPV = 0.96 (95 % CI: 0.93–0.98) for the age group of 35–40 years.

Conclusions

Application of age-specific cut-off levels of AMH, according to the GAMs and Bayesian method, could elegantly assess the value of AMH in discriminating PCOS patients in all age categories.
Prioritizing guideline recommendations for implementation: a systematic, consumer-inclusive process with a case study using the Australian Clinical Guidelines for Stroke Management
Authors: Lynch Elizabeth A. , Lassig Chris , Turner Tari , Churilov Leonid , Hill Kelvin , Shrubsole Kirstine
Published: May 2021

Background

Implementation of evidence-based care remains a key challenge in clinical practice. Determining “what” to implement can guide implementation efforts. This paper describes a process developed to identify priority recommendations from clinical guidelines for implementation, incorporating the perspectives of both consumers and health professionals. A case study is presented where the process was used to prioritize recommendations for implementation from the Australian Stroke Clinical Guidelines.

Methods

The process was developed by a multidisciplinary group of researchers following consultation with experts in the field of implementation and stroke care in Australia. Use of the process incorporated surveys and facilitated workshops. Survey data were analysed descriptively; responses to ranking exercises were analysed via a graph theory-based voting system.

Results

The four-step process to identify high-priority recommendations for implementation comprised the following: (1) identifying key implementation criteria, which included (a) reliability of the evidence underpinning the recommendation, (b) capacity to measure change in practice, (c) a recommendation–practice gap, (d) clinical importance and (e) feasibility of making the recommended changes; (2) shortlisting recommendations; (3) ranking shortlisted recommendations and (4) reaching consensus on top priorities.

The process was applied to the Australian Stroke Clinical Guidelines between February 2019 and February 2020. Seventy-five health professionals and 16 consumers participated. Use of the process was feasible. Three recommendations were identified as priorities for implementation from over 400 recommendations.

Conclusion

It is possible to implement a robust process which involves consumers, clinicians and researchers to systematically prioritize guideline recommendations for implementation. The process is generalizable and could be applied in clinical areas other than stroke and in different geographical regions to identify implementation priorities. The identification of three clear priority recommendations for implementation from the Australian Stroke Clinical Guidelines will directly inform the development and delivery of national implementation strategies.
Role of the ABL tyrosine kinases in the epithelial–mesenchymal transition and the metastatic cascade
Authors: Luttman Jillian Hattaway , Colemon Ashley , Mayro Benjamin , Pendergast Ann Marie
Published: May 2021

The ABL kinases, ABL1 and ABL2, promote tumor progression and metastasis in various solid tumors. Recent reports have shown that ABL kinases have increased expression and/or activity in solid tumors and that ABL inactivation impairs metastasis. The therapeutic effects of ABL inactivation are due in part to ABL-dependent regulation of diverse cellular processes related to the epithelial to mesenchymal transition and subsequent steps in the metastatic cascade. ABL kinases target multiple signaling pathways required for promoting one or more steps in the metastatic cascade. These findings highlight the potential utility of specific ABL kinase inhibitors as a novel treatment paradigm for patients with advanced metastatic disease.
Annexin A1 protects against cerebral ischemia–reperfusion injury by modulating microglia/macrophage polarization via FPR2/ALX-dependent AMPK-mTOR pathway
Authors: Xu Xin , Gao Weiwei , Li Lei , Hao Jiheng , Yang Bin , Wang Tao , Li Long , Bai Xuesong , Li Fanjian , Ren Honglei , Zhang Meng , Zhang Liyong , Wang Jiyue , Wang Dong , Zhang Jianning , Jiao Liqun
Published: May 2021

Background

Cerebral ischemia–reperfusion (I/R) injury is a major cause of early complications and unfavorable outcomes after endovascular thrombectomy (EVT) therapy in patients with acute ischemic stroke (AIS). Recent studies indicate that modulating microglia/macrophage polarization and subsequent inflammatory response may be a potential adjunct therapy to recanalization. Annexin A1 (ANXA1) exerts potent anti-inflammatory and pro-resolving properties in models of cerebral I/R injury. However, whether ANXA1 modulates post-I/R-induced microglia/macrophage polarization has not yet been fully elucidated.

Methods

We retrospectively collected blood samples from AIS patients who underwent successful recanalization by EVT and analyzed ANXA1 levels longitudinally before and after EVT and correlation between ANXA1 levels and 3-month clinical outcomes. We also established a C57BL/6J mouse model of transient middle cerebral artery occlusion/reperfusion (tMCAO/R) and an in vitro model of oxygen–glucose deprivation and reoxygenation (OGD/R) in BV2 microglia and HT22 neurons to explore the role of Ac2-26, a pharmacophore N-terminal peptide of ANXA1, in regulating the I/R-induced microglia/macrophage activation and polarization.

Results

The baseline levels of ANXA1 pre-EVT were significantly lower in 23 AIS patients, as compared with those of healthy controls. They were significantly increased to the levels found in controls 2–3 days post-EVT. The increased post-EVT levels of ANXA1 were positively correlated with 3-month clinical outcomes. In the mouse model, we then found that Ac2-26 administered at the start of reperfusion shifted microglia/macrophage polarization toward anti-inflammatory M2-phenotype in ischemic penumbra, thus alleviating blood–brain barrier leakage and neuronal apoptosis and improving outcomes at 3 days post-tMCAO/R. The protection was abrogated when mice received Ac2-26 together with WRW4, which is a specific antagonist of formyl peptide receptor type 2/lipoxin A4 receptor (FPR2/ALX). Furthermore, the interaction between Ac2-26 and FPR2/ALX receptor activated the 5’ adenosine monophosphate-activated protein kinase (AMPK) and inhibited the downstream mammalian target of rapamycin (mTOR). These in vivo findings were validated through in vitro experiments.

Conclusions

Ac2-26 modulates microglial/macrophage polarization and alleviates subsequent cerebral inflammation by regulating the FPR2/ALX-dependent AMPK-mTOR pathway. It may be investigated as an adjunct strategy for clinical prevention and treatment of cerebral I/R injury after recanalization. Plasma ANXA1 may be a potential biomarker for outcomes of AIS patients receiving EVT.
Integration of family planning services with HIV treatment for women of reproductive age attending ART clinic in Oromia regional state, Ethiopia
Authors: Demissie Dereje Bayissa , Mmusi-Phetoe Rose
Published: May 2021

Background

In settings where HIV prevalence is high, management of sexual and reproductive health is critical to reducing HIV transmission and maternal mortality. Integration of family planning with HIV services is appropriate for HIV therapy, HIV prevention, and care in a resource-limited country s like Ethiopia. The study aimed at examining the status of integration of family planning services with HIV treatment and factors associated with successful integration of family planning and HIV services for women of reproductive age in Oromia, Ethiopia for better health outcomes.

Methods

The research design of this study was a quantitative survey, non-experimental, explorative and descriptive. A questionnaire was used to collect data from women living with HIV attending ART clinics in the special zone of surrounding Finfinne, Oromia Region in five health centers. Simple random sampling was used to select 654 respondents. Data was analysed through the use of Statistical Package for Social Sciences version 23.0. Bivariate and multivariate logistic regressions were performed to identify factors associated integration of family planning with HIV services with the significant association at an adjusted odds ratio (AOR) with a 95% confidence interval (CI) to controlled effects of possible confounders from the final model.

Result

The response rate of this study was 97.6% (654/670). The ages of those who responded to the administered questionnaires ranged between 18 and 49 years. The mean age of the respondents was 31.86 years with an SD of ± 6.0 years. Most of the respondents in the sample were in the age group 26–35 (n = 374, 57%), and only 96 (14.7%) were in the age group 18–25. This overall integration of FP-HIV services among reproductive-age women living with HIV in Oromia regional state of special zone health centers was found to be 55.8%. Almost all respondents (n = 635, 97.1%) preferred integrated family planning and HIV services from the same facility and the same providers. the study found that 622 (95%) were most satisfied with the utilization of integrated family planning/HIV services.

Conclusion

This study established that in overall, the integration of family planning/HIV services was relatively moderate among women of reproductive age living HIV. The identified factors that affected the integration of family planning with HIV services were the level of education, occupational status, residence, discussion of family planning with healthcare providers, fertility desire and CD4 counts.
LncRNA GAS5 modulates the progression of non-small cell lung cancer through repressing miR-221-3p and up-regulating IRF2
Authors: Ma Juan , Miao Haiyan , Zhang Haiyun , Ren Jingjing , Qu Shengyan , Da Jing , Xu Feifan , Zhao Huan
Published: May 2021

Background

Long non-coding RNA growth arrest specific 5 (GAS5) is a regulator in non-small cell lung cancer (NSCLC) progression. Nonetheless, the mechanism by which GAS5 exerts its biological function in NSCLC cells remains unclear.

Methods

GAS5, miR-221-3p relative expression levels in NSCLC tissues and cells were examined by qPCR. After gain-of-function and loss-of-function models were established, the viability of H1299 and A549 cells were examined by CCK-8 and EdU assays. Cell migration and invasion were examined by the Transwell experiment. The binding sequence of GAS5 for miR-221-3p was confirmed by the dual-luciferase reporter gene experiment. The regulatory function of GAS5 and miR-221-3p on IRF2 was investigated by Western blot.

Results

GAS5 expression was down-modulated in NSCLC tissues and cell lines. GAS5 overexpression restrained the proliferation, migration and invasion of NSCLC cells, while miR-221-3p, which was targeted and negatively modulated by GAS5, worked oppositely. Restoration of miR-221-3p markedly reversed the effects of GAS5 on NSCLC cells. Additionally, GAS5 increased IRF2 expression in NSCLC cells by repressing miR-221-3p.

Conclusions

GAS5 blocks the progression of NSCLC partly via increasing IRF2 expression level via repressing miR-221-3p.
OASI2: a cluster randomised hybrid evaluation of strategies for sustainable implementation of the Obstetric Anal Sphincter Injury Care Bundle in maternity units in Great Britain
Authors: Jurczuk Magdalena , Bidwell Posy , Martinez Dorian , Silverton Louise , Van der Meulen Jan , Wolstenholme Daniel , Thakar Ranee , Gurol-Urganci Ipek , Sevdalis Nick
Published: May 2021

Background

The Obstetric Anal Sphincter Injury (OASI) Care Bundle comprises four primary and secondary prevention practices that target the rising rates of severe perineal tearing during childbirth, which can have severe debilitating consequences for women. The OASI Care Bundle was implemented in 16 maternity units in Britain in the OASI1 project (2017-2018), which demonstrated the care bundle’s effectiveness in reducing OASI rates. In OASI2, the care bundle will be scaled up to 20 additional National Health Service (NHS) maternity units in a hybrid effectiveness-implementation study that will examine the effectiveness of strategies used to introduce, implement and sustain the care bundle.

Methods

OASI2 is a two-arm cluster-randomised control trial (C-RCT) of maternity units in England, Scotland and Wales, with an additional non-randomised study arm. C-RCT arm 1 (peer support, n = 10 units) will be supported by ‘buddy’ units to implement the OASI Care Bundle. C-RCT arm 2 (lean implementation, n = 10 units) will implement without external support. The additional study arm (sustainability, n = 10 units) will include some original OASI1 units to evaluate the care bundle’s sustainability and OASI rates over time, from before OASI1 and through the end of OASI2. Units in all three study arms will receive an Implementation Toolkit with training resources and implementation support. The C-RCT arms will be compared in terms of OASI rate reduction (primary effectiveness outcome) and clinicians’ adoption of the care bundle (primary implementation outcome). Clinical data will be collated from maternity information systems; implementation data will be collected through validated surveys with women and clinicians, supplemented by qualitative methods. Descriptive statistics and regression modelling will be used for analysis. Emergent themes from the qualitative data will be assessed using framework analysis.

Discussion

OASI2 will study the impact of various implementation strategies used to introduce and sustain the OASI Care Bundle, and how these strategies affect the bundle’s clinical effectiveness. The study will generate insights into how to effectively scale-up and sustain uptake and coverage of similar interventions in maternity units. A locally adaptable ‘implementation blueprint’ will be produced to inform development of future guidelines to prevent perineal trauma.

Trial registration

ISRCTN26523605
Non-coding RNAs modulate autophagy in myocardial ischemia-reperfusion injury: a systematic review
Authors: Huang Fuwen , Mai Jingting , Chen Jingwei , He Yinying , Chen Xiaojun
Published: May 2021

The myocardial infarction is the main cause of morbidity and mortality in cardiovascular diseases around the world. Although the timely and complete reperfusion via Percutaneous Coronary Intervention (PCI) or thrombolysis have distinctly decreased the mortality of myocardial infarction, reperfusion itself may lead to supererogatory irreversible myocardial injury and heart function disorders, namely ischemia-reperfusion (I/R) injury. Extensive studies have indicated that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), play important roles in the progress of myocardial I/R injury, which is closely correlative with cardiomyocytes autophagy. Moreover, autophagy plays an important role in maintaining homeostasis and protecting cells in the myocardial ischemia reperfusion and cardiomyocyte hypoxia-reoxygenation (H/R) progress. In this review, we first introduced the biogenesis and functions of ncRNAs, and subsequently summarized the roles and relevant molecular mechanisms of ncRNAs regulating autophagy in myocardial I/R injury. We hope that this review in addition to develop a better understanding of the physiological and pathological roles of ncRNAs, can also lay a foundation for the therapies of myocardial I/R injury, and even for other related cardiovascular diseases.
Towards an ICF-based self-report questionnaire for people with skeletal dysplasia to study health, functioning, disability and accessibility
Authors: Anttila Heidi , Tallqvist Susanna , Muñoz Minna , Leppäjoki-Tiistola Sanna , Mäkitie Outi , Hiekkala Sinikka
Published: May 2021

Background

Little is known about the spectrum of everyday challenges that people with skeletal dysplasia face because of their health and functioning. We aimed to identify factors related to health, functioning and disability in people with skeletal dysplasia, and their challenges with accessibility in order to form a self-reported questionnaire for national data collection. The comprehensive musculoskeletal post-acute core set of the International Classification of Functioning, Disability and Health (ICF) was used as a framework.

Methods

An iterative, participatory and qualitative process was used to formulate a questionnaire. Items were searched from Patient-Reported Outcomes Measurement Information System and from other self-report instruments, additional items were formulated using ICF linking rules. Expert panels from the target population assessed the face and content validity in thematic interviews.

Results

The questionnaire demonstrated its relevance, comprehensiveness and feasibility for people with skeletal dysplasia. The ICF linkages showed the contents’ correspondence to the construct. Expert panels added 15 categories and one on chapter level to the core set and confirmed content validity. The final survey covers 86 ICF categories and 173 ICF-linked items that were grouped to 33 questions.

Conclusions

The content of the questionnaire proved to be sufficiently valid for people with skeletal dysplasia. It can be used to explore their health, functioning, disability and accessibility to develop care and rehabilitation policies, to plan services and to provide information to various parties involved.
Mucopolysaccharidosis VII in Brazil: natural history and clinical findings
Authors: Giugliani Roberto , Barth Anneliese Lopes , Dumas Melissa Rossi Calvão , da Silva Franco José Francisco , de Rosso Giuliani Liane , Grangeiro Carlos Henrique Paiva , Horovitz Dafne Dain Gandelman , Kim Chong Ae , de Araújo Leão Emilia Katiane Embiruçu , de Medeiros Paula Frassinetti Vasconcelos , Miguel Diego Santana Chaves Geraldo , Moreira Maria Espírito Santo Almeida , dos Santos Helena Maria Guimarães Pimentel , da Silva Luiz Carlos Santana , da Silva Luiz Roberto , de Souza Isabel Neves , Nalin Tatiele , Garcia Daniel
Published: May 2021

Background

Mucopolysaccharidosis type VII (MPS VII), also known as Sly syndrome, caused by deficiency of the lysosomal enzyme β-glucuronidase, is an ultra-rare disorder with scarce epidemiological data and few publications about natural history and clinical spectrum.

Methods

We conducted a case series report which included retrospective data from all MPS VII patients diagnosed through the “MPS Brazil Network” who were known to be alive in 2020 in Brazil (N = 13). Clinical data were obtained from a review of the medical records and descriptive statistics and variables were summarized using counts and percentages of the total population.

Results

The majority of the patients were from the Northeast region of Brazil. Among the signs and symptoms that raised the clinical suspicion of MPS, coarse face was the most frequent; 58% of the patients had a history of non-immune hydrops fetalis. All the subjects presented short neck and trunk. The majority presented typical phenotypical signs of MPS disorders. They all presented neurodevelopmental delay and cognitive impairment. About half of this cohort had knees deformities. Dysostosis multiplex was identified in almost all patients and cardiomyopathy was less frequent than observed in other types of MPSs. The mean age at diagnosis was 5 years, ranging from 1 to 14 years. Almost all patients (12/13) were homozygous for the c.526C>T (p.Leu176Phe) mutation. A novel variant of the GUSB gene was found, the c.875T>C (p.Leu292Pro), in a compound heterozygous with the c.526C>T (p.Leu176Phe) variant.

Conclusions

This case series is the biggest data collection of MPS VII patients alive in Latin America. The overall clinical picture of the MPS VII patients is very similar to other MPS disorders, including a spectrum of severity and delayed diagnosis.
Optimization of tetramycin production in Streptomyces ahygroscopicus S91
Authors: Chen Guang , Wang Mengqiu , Ni Xianpu , Xia Huanzhang
Published: May 2021

Background

Tetramycin is a 26-member tetraene antibiotic used in agriculture. It has two components, tetramycin A and tetramycin B. Tetramycin B is obtained by the hydroxylation of tetramycin A on C4. This reaction is catalyzed by the cytochrome P450 monooxygenase TtmD. The two components of tetramycin have different antifungal activities against different pathogenic fungi. Therefore, the respective construction of high-yield strains of tetramycin A and tetramycin B is conducive to more targeted action on pathomycete and has a certain practical value.

Results

Streptomyces ahygroscopicus S91 was used as the original strain to construct tetramycin A high-yield strains by blocking the precursor competitive biosynthetic gene cluster, disrupting tetramycin B biosynthesis, and overexpressing the tetramycin pathway regulator. Eventually, the yield of tetramycin A in the final strain was up to 1090.49 ± 136.65 mg·L− 1. Subsequently, TtmD, which catalyzes the conversion from tetramycin A to tetramycin B, was overexpressed. Strains with 2, 3, and 4 copies of ttmD were constructed. The three strains had different drops in tetramycin A yield, with increases in tetramycin B. The strain with three copies of ttmD showed the most significant change in the ratio of the two components.

Conclusions

A tetramycin A single-component producing strain was obtained, and the production of tetramycin A increased 236.84% ± 38.96% compared with the original strain. In addition, the content of tetramycin B in a high-yield strain with three copies of ttmD increased from 26.64% ± 1.97 to 51.63% ± 2.06%.
Enhanced wound repair ability of arginine-chitosan nanocomposite membrane through the antimicrobial peptides-loaded polydopamine-modified graphene oxide
Authors: Fu Chuan , Qi Zhiping , Zhao Chengliang , Kong Weijian , Li Hongru , Guo Wenlai , Yang Xiaoyu
Published: May 2021

Skin wound healing is a complicated and lengthy process, which is influenced by multiple factors and need a suitable cellular micro-environment. For skin wound, wound dressings remain a cornerstone of dermatologic therapy at present. The dressing material can create an effective protective environment for the wound, and the interactions between the dressing and the wound has a great impact on the wound healing efficiency. An ideal wound dressing materials should have good biocompatibility, moisturizing property, antibacterial property and mechanical strength, and can effectively prevent wound infection and promote wound healing. In this study, in order to design wound dressing materials endowed with excellent antibacterial and tissue repair properties, we attempted to load antimicrobial peptides onto dopmine-modified graphene oxide (PDA@GO) using lysozyme (ly) as a model drug. Then, functionalized GO was used to the surface modification of arginine-modified chitosan (CS-Arg) membrane. To evaluate the potential of the prepared nanocomposite membrane in wound dressing application, the surface morphology, hydrophilic, mechanical properties, antimicrobial activity, and cytocompatibility of the resulting nanocomposite membrane were analyzed. The results revealed that prepared nanocomposite membrane exhibited excellent hydrophilic, mechanical strength and antimicrobial activity, which can effectively promote cell growth and adhesion. In particular, using PDA@GO as drug carrier can effectively maintain the activity of antimicrobial peptides, and can maximize the antibacterial properties of the nanocomposite membrane. Finally, we used rat full-thickness wound models to observe wound healing, and the surface interactions between the prepared nanocomposite membrane and the wound. The results indicated that nanocomposite membrane can obviously accelerated wound closure, and the wounds showed reduced inflammation, improved angiogenesis and accelerated re-epithelialization. Therefore, incorporation of antimicrobial peptides-functionalize graphene oxide (ly-PDA@GO) into CS-Arg membrane was a viable strategy for fabricating excellent wound dressing. Together, this study not only prepared a wound dressing with excellent tissue repair ability, but also provided a novel idea for the development of graphene oxide-based antibacterial dressing.
Optical tissue measurements of invasive carcinoma and ductal carcinoma in situ for surgical guidance
Authors: de Boer Lisanne L. , Kho Esther , Van de Vijver Koen K. , Vranken Peeters Marie-Jeanne T. F. D. , van Duijnhoven Frederieke , Hendriks Benno H. W. , Sterenborg Henricus J. C. M. , Ruers Theo J. M.
Published: May 2021

Background

Although the incidence of positive resection margins in breast-conserving surgery has decreased, both incomplete resection and unnecessary large resections still occur. This is especially the case in the surgical treatment of ductal carcinoma in situ (DCIS). Diffuse reflectance spectroscopy (DRS), an optical technology based on light tissue interactions, can potentially characterize tissue during surgery thereby guiding the surgeon intraoperatively. DRS has shown to be able to discriminate pure healthy breast tissue from pure invasive carcinoma (IC) but limited research has been done on (1) the actual optical characteristics of DCIS and (2) the ability of DRS to characterize measurements that are a mixture of tissue types.

Methods

In this study, DRS spectra were acquired from 107 breast specimens from 107 patients with proven IC and/or DCIS (1488 measurement locations). With a generalized estimating equation model, the differences between the DRS spectra of locations with DCIS and IC and only healthy tissue were compared to see if there were significant differences between these spectra. Subsequently, different classification models were developed to be able to predict if the DRS spectrum of a measurement location represented a measurement location with “healthy” or “malignant” tissue. In the development and testing of the models, different definitions for “healthy” and “malignant” were used. This allowed varying the level of homogeneity in the train and test data.

Results

It was found that the optical characteristics of IC and DCIS were similar. Regarding the classification of tissue with a mixture of tissue types, it was found that using mixed measurement locations in the development of the classification models did not tremendously improve the accuracy of the classification of other measurement locations with a mixture of tissue types. The evaluated classification models were able to classify measurement locations with > 5% malignant cells with a Matthews correlation coefficient of 0.41 or 0.40. Some models showed better sensitivity whereas others had better specificity.

Conclusion

The results suggest that DRS has the potential to detect malignant tissue, including DCIS, in healthy breast tissue and could thus be helpful for surgical guidance.
Including random centre effects in design, analysis and presentation of multi-centre trials
Authors: Edgar Kate , Roberts Ian , Sharples Linda
Published: May 2021

Background

In large multicentre trials in diverse settings, there is uncertainty about the need to adjust for centre variation in design and analysis. A key distinction is the difference between variation in outcome (independent of treatment) and variation in treatment effect. Through re-analysis of the CRASH-2 trial (2010), this study clarifies when and how to use multi-level models for multicentre studies with binary outcomes.

Methods

CRASH-2 randomised 20,127 trauma patients across 271 centres and 40 countries to either single-dose tranexamic acid or identical placebo, with all-cause death at 4 weeks the primary outcome. The trial data had a hierarchical structure, with patients nested in hospitals which in turn are nested within countries. Reanalysis of CRASH-2 trial data assessed treatment effect and both patient and centre level baseline covariates as fixed effects in logistic regression models. Random effects were included to assess where there was variation between countries, and between centres within countries, both in underlying risk of death and in treatment effect.

Results

In CRASH-2, there was significant variation between countries and between centres in death at 4 weeks, but absolutely no differences between countries or centres in the effect of treatment. Average treatment effect was not altered after accounting for centre and country variation in this study.

Conclusions

It is important to distinguish between underlying variation in outcomes and variation in treatment effects; the former is common but the latter is not. Stratifying randomisation by centre overcomes many statistical problems and including random intercepts in analysis may increase power and decrease bias in mean and standard error estimates.

Trial registration

Current Controlled Trials ISRCTN86750102, ClinicalTrials.gov NCT00375258, and South African Clinical Trial Register DOH-27-0607-1919
Comparative efficacy of a single-session “Empowered Relief” videoconference-delivered group intervention for chronic pain: study protocol for a randomized controlled trial
Authors: Ziadni Maisa S. , Anderson Steven R. , Gonzalez-Castro Lluvia , Darnall Beth D.
Published: May 2021

Background

Chronic pain is naturally aversive and often distressing for patients. Pain coping and self-regulatory skills have been shown to effectively reduce pain-related distress and other symptoms. In this trial, the primary goal is to pilot test the comparative efficacy of a single-session videoconference-delivered group pain education class to a waitlist control among patients with chronic pain.

Methods

Our study is a randomized clinical trial pilot testing the superiority of our 2-h single-session videoconference-delivered group pain education class against a waitlist control. We will enroll 120 adult patients with mixed etiology chronic pain and randomize 1:1 to one of the two study arms. We hypothesize superiority for the pain education class for bolstering pain and symptom management. Team researchers masked to treatment assignment will assess the outcomes up to 3 months post-treatment.

Discussion

This study aims to test the utility of a single-session videoconference-delivered group pain education class to improve self-regulation of pain and pain-related outcomes. Findings from our project have the potential to significantly reduce barriers to effective psychological treatment for pain, optimizing the delivery of increasingly vital online and remote-delivered intervention options.

Trial registration

ClinicalTrials.govNCT04546685. Registered on 04 September 2020.
Effects of cycling workstation to get tertiary employee moving on their overall health: study protocol for a REMOVE trial
Authors: Guirado Terry , Metz Lore , Pereira Bruno , Bergouignan Audrey , Thivel David , Duclos Martine
Published: May 2021

Background

Sedentary behaviour (SB) and low levels of physical activity (PA) are predictors of morbidity and mortality. Tertiary employees spend a considerable amount of their daily time seated and new efficient strategies to both reduce sedentary time and increase physical activity are needed. In that context, the REMOVE study aims at evaluating the health effects of a 24-week cycling desk intervention among office workers.

Methods

A prospective, open-label, multicentre, two-arm parallel, randomized controlled trial (RCT) will be conducted in office-sitting desk workers. Office workers (N = 80) who have 0.8 full time equivalent hours (FTE) and 75% of this time in a sitting position will be recruited from tertiary worksites in Clermont-Ferrand, France. Subjects will be randomly assigned to one of the two following interventions: (i) PPM6: performance of two 30 min of cycling desk (using portable pedal exercise machine—PPM) per working day for 6 months or (ii) CTL_PPM3: 3 months with no intervention (control) followed by 3 months during which workers will be asked to complete two 30 min of PPM per working day. At baseline (T0), at 3 months (T1) and at 6 months (T2) after the start of the interventions, primary outcomes; 7-day PA and SB (3D-accelerometers), secondary outcomes; body composition (bioelectrical impedance), physical fitness (aerobic fitness, upper and lower limb strength), metabolic outcomes (fasting blood samples), self-perceived stress, anxiety, quality of life at work and job strain (questionnaires), tertiary outcomes; resting metabolic rate and cycling energy expenditure (indirect calorimetry) and eating behaviours (questionnaires) will be measured. An ergonomic approach based on observations and individual interviews will be used to identify parameters that could determine adherence.

Discussion

The REMOVE study will be the first RCT to assess the effects of cycling workstations on objectively measured PA and SB during working and non-working hours and on key physiological and psychological health outcomes. This study will provide important information regarding the implementation of such cycling workstations in office workers and on the associated potential health benefits.

Trial registration

ClinicalTrials.govNCT04153214. Registered on November 2019, version 1
Identification and characterization of microsatellite markers for population genetic studies of Panstrongylus megistus (Burmeister, 1835) (Triatominae: Reduviidae)
Authors: Ferreira Flávio Campos , Gonçalves Leilane Oliveira , Ruiz Jeronimo Conceição , Koerich Leonardo Barbosa , Pais Fabiano Sviatopolk Mirsky , Diotaiuti Lileia Gonçalves , Belisário Carlota Josefovicz
Published: May 2021

Background

Panstrongylus megistus is the most important vector of Chagas disease in Brazil. Studies show that the principal factor hindering the control of triatomines is reinfestation of houses previously treated with insecticides. Studies at the microgeographic level are therefore necessary to better understand these events. However, an efficient molecular marker is not yet available for carrying out such analyses in this species. The aim of the present study was to identify and characterize microsatellite loci for future population genetic studies of P. megistus.

Methods

This study work consisted of five stages: (i) sequencing of genomic DNA; (ii) assembly and selection of contigs containing microsatellites; (iii) validation of amplification and evaluation of polymorphic loci; (iv) standardization of the polymorphic loci; and (v) verification of cross-amplification with other triatomine species.

Results

Sequencing of males and females generated 7,908,463 contigs with a total length of 2,043,422,613 bp. A total of 2,043,690 regions with microsatellites in 1,441,091 contigs were obtained, with mononucleotide repeats being the most abundant class. From a panel of 96 loci it was possible to visualize polymorphisms in 64.55% of the loci. Of the 20 loci genotyped, the number of alleles varied from two to nine with an average of 4.9. Cross-amplification with other species of triatomines was observed in 13 of the loci.

Conclusions

Due to the high number of alleles encountered, polymorphism and the capacity to amplify from geographically distant populations, the microsatellites described here show promise for utilization in population genetic studies of P. megistus.

Graphical Abstract
Opioid users show worse baseline knee osteoarthritis and faster progression of degenerative changes: a retrospective case-control study based on data from the Osteoarthritis Initiative (OAI)
Authors: Bodden Jannis , Joseph Gabby B. , Schirò Silvia , Lynch John A. , Lane Nancy E. , McCulloch Charles E. , Nevitt Michael C. , Link Thomas M.
Published: May 2021

Background

Opioids are frequently prescribed for pain control in knee osteoarthritis patients, despite recommendations by current guidelines. Previous studies have investigated the chondrotoxicity of different opioid subtypes. However, the impact opioids may have on progression of osteoarthritis in vivo remains unknown. The aim of this study was thus to describe the associations between opioid use and knee structural changes and clinical outcomes, over 4 years.

Methods

Participants with baseline opioid use (n=181) and who continued use for ≥1 year between baseline and 4-year follow-up (n=79) were included from the Osteoarthritis Initiative cohort and frequency matched with non-users (controls) (1:2). Whole-Organ Magnetic Resonance Imaging Scores (WORMS) were obtained, including a total summation score (WORMS total, range 0–96) and subscores for cartilage (0–36), menisci (0–24), and bone marrow abnormalities and subchondral cyst-like lesions (0–18, respectively). Knee Injury Osteoarthritis Outcomes score (KOOS) symptoms, quality of life (QOL), and pain were also obtained at baseline and follow-up (range 0–100; lower scores indicate worse outcomes). Using linear regression models, associations between baseline and longitudinal findings were investigated. As pain may modify observations, a sensitivity analysis was performed for longitudinal findings. All analyses were adjusted for sex, BMI, age, race, and Kellgren-Lawrence grade.

Results

Opioid users had greater structural degeneration at baseline (WORMS total: Coef. [95% CI], P; 7.1 [5.5, 8.8], <0.001) and a greater increase over 4 years (4.7 [2.9, 6.5], <0.001), compared to controls. Cartilage and meniscus scores increased greater in opioid users, compared to controls (P≤0.001), and findings withstood the adjustment for baseline pain (P≤0.002). All baseline KOOS scores were lower in opioid users compared to controls (P<0.001). QOL loss was greater, when adjusted for baseline KOOS pain (QOL −6.9 [−11.6, −2.1], 0.005).

Conclusions

Opioid users had worse baseline knee structural degeneration and faster progression. Opioid use was also associated with worse symptoms, pain, and QOL. Furthermore, QOL loss was greater in opioid users compared to controls, when adjusted for baseline KOOS pain, indicating that opioids may not be suited to prevent subjective disease progression in KOA patients.
Circulating mature granzyme B+ T cells distinguish Crohn’s disease-associated axial spondyloarthritis from axial spondyloarthritis and Crohn’s disease
Authors: Lefferts Adam R. , Regner Emilie H. , Stahly Andrew , O’Rourke Becky , Gerich Mark E. , Fennimore Blair P. , Scott Frank I. , Freeman Alison E. , Jones Ken , Kuhn Kristine A.
Published: May 2021

Background

Axial spondyloarthritis (axSpA) has strong connections with intestinal inflammation as occurs in Crohn’s disease (CD). However, the immunologic mechanisms that distinguish axSpA, CD, and those with features of both diseases (CD-axSpA) are unknown. This study aimed to address this question by initial unbiased single cell RNA-sequencing (scRNAseq) on a pilot cohort followed by validating findings using flow cytometry and ELISA in a larger cohort.

Methods

Two individuals each with CD, axSpA, CD-axSpA, and healthy controls (HC) were recruited for a pilot discovery scRNAseq cohort, and the validation cohort consisted of 18 axSpA, 24 CD, 13 CD-axSpA, and 17 HC that was evaluated by flow cytometry on PBMCs and ELISAs for plasma cytokines.

Results

Uniquely, PBMCs from subjects with CD-axSpA demonstrated a significant increase in granzyme B+ T cells of both CD4+ and CD8+ lineages by both scRNAseq and flow cytometry. T cell maturation was also greater in those with CD-axSpA, particularly the CD4+ granzyme B+ population. Pathway analysis suggested increased interferon response genes in all immune cell populations within CD-axSpA. Although IFN-γ was elevated in the plasma of a subset of subjects with CD-axSpA, IL-6 was also significantly elevated.

Conclusions

Our findings support the presence of a chronic interferonopathy in subjects with CD-axSpA characterized by interferon signaling by pathway analysis and an expansion of mature, cytotoxic T cells. These data indicate fundamental immunological differences between CD-axSpA and both of the putative “parent” conditions, suggesting that it is a distinct disease with unique natural history and treatment needs.
Human biting rhythm of Anopheles gambiae Giles, 1902 (Diptera: Culicidae) and sleeping behaviour of pregnant women in a lagoon area in Southern Benin
Authors: Djènontin Armel , Bouraima Aziz , Soares Christophe , Egbinola Seun , Cottrell Gilles
Published: May 2021

Objective

In the framework of EVALMOUS study aiming to assess the use and effectiveness of mosquito nets by pregnant women and other members of their household in a lagoon area in southern Benin, the behaviour of pregnant women relative to the time they go to bed using the net were recorded. Malaria vectors biting rhythm, Plasmodium falciparum infection and insecticide resistance genes in malaria vectors were also determined.

Results

Overall, 3848 females of Anopheles gambiae s. l were collected and 280 pregnant women responded to the survey. Almost all Anopheles gambiae s. l. tested were Anopheles coluzzi Coetzee and Wilkerson 2013 (Diptera: Culicidae). The CSP index in malaria vector was 1.85% and the allelic frequency of kdr gene was 74.4%. Around 90% of bites and Plasmodium falciparum Welch, 1897 (Haemosporida: Plasmodiidae) transmission occurred between 10 p.m. and 6 a.m., which coincides with the period when more than 80% of pregnant women were under bednet. Despite a slight early evening and early morning biting activity of malaria vectors in the study area, the good use of nets might remain a useful protection tool against mosquito biting and malaria transmission.
Fast-track recovery program after cardiac surgery in a teaching hospital: a quality improvement initiative
Authors: Lloyd-Donald Patryck , Lee Wen-Shen , Hooper James W. , Lee Dong Kyu , Moore Alice , Chandra Nikhil , McCall Peter , Seevanayagam Siven , Matalanis George , Warrillow Stephen , Weinberg Laurence
Published: May 2021

Objective

Fast-track cardiac anesthesia (FTCA) is a technique that may improve patient access to surgery and maximize workforce utilization. However, feasibility and factors impacting FTCA implementation remain poorly explored both locally and internationally. We describe the specific intraoperative and postoperative protocols for our FTCA program, assess protocol compliance and identify reasons for FTCA failure.

Results

We tested the program in 16 patients undergoing elective cardiac surgery requiring cardiopulmonary bypass. There was 100% compliance with the FTCA protocols. Four (25%) patients successfully completed the FTCA protocol (extubated < 4 h postoperatively and discharged from the intensive care unit on the same operative day).
Assessment of changes in genetic transcriptome in nasal epithelial cells exposed to ozone-aged black carbon and pollen allergen by high-throughput transcriptomics
Authors: Ouyang Yuhui , Li Ying , Xu Zhaojun , An Yusan , Zhang Luo
Published: May 2021

Background

Air pollution may be associated with increased airway responsiveness to allergens in allergic rhinitis (AR). Ozone-aged environmental black carbon (O3BC) is an important constituent of atmospheric particulate matter (PM), for which the mechanisms underlying its effects have not been fully elucidated in AR. The objective of the present study was to determine the O3BC and pollen-induced alterations in the transcriptome in human nasal epithelial cells (hNECs) in vitro.

Methods

hNECs from nasal epithelial mucosal samples of healthy individuals undergoing nasal surgery (turbinoplasty or septoplasty) were established as air–liquid interface (ALI) cultures and exposed to O3BC, pollen, or a combination of O3BC+ pollen. Changes in cell viability were analyzed by fluorescence and changes in the transcriptome by high-throughput RNA sequencing (RNA-seq). Several differentially expressed genes were verified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Enrichment analysis, based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database, was performed to determine major biological functions and pathways involved.

Results

Exposure to ≥ 50 μg/ml O3BC or 25 μg/ml O3BC+ 200 μg /ml pollen significantly decreased cell viability of the hNECs compared to control (p < 0.05) or 25 μg/ml O3BC alone (p < 0.05); whereas exposure to pollen alone did not alter cell viability at any concentration investigated. High-throughput RNA sequencing analysis indicated that there was significant difference in gene expression between pollen or O3BC alone and O3BC+ pollen exposed cells. Exposure to 200 μg/ml O3BC was associated with hypoxia stress response GO terms, whereas exposure to 25 μg/ml O3BC+ 200 μg/ml pollen was associated with inflammatory response GO terms; including regulation of neutrophil migration and chemotaxis, macrophage differentiation and chemotaxis, mast cell activation, and phagocytosis. KEGG pathway analysis indicated the top 10 upstream regulators to be IL1B, CSF1, CCL2, TLR2, LPL, IGF8, SPP1, CXCL8, FCER1G and IL1RN; of which expressions of inflammation-related genes IL1B, CSF1 and FCER1G were significantly increased.

Conclusion

O3BC and pollen allergen combined exposure may induce innate immune and allergic inflammation in hNECs, and therefore potentially exacerbate the symptoms of AR in affected individuals.