bluuebunny/crossref_metadata_2025 huggingface dataset:
Deletion of CD36 exhibits limited impact on normal hematopoiesis and the leukemia microenvironment
Authors: Meng Yiting , Pospiech Mateusz , Ali Atham , Chandwani Ritu , Vergel Mary , Onyemaechi Sandra , Yaghmour George , Lu Rong , Alachkar Houda
Published: May 2023

Background

CD36 has been identified as a potential therapeutic target both in leukemic cells and in the tumor immune microenvironment. In acute myeloid leukemia (AML), we found that APOC2 acts with CD36 to promote leukemia growth by activating the LYN-ERK signaling. CD36 also plays a role in lipid metabolism of cancer associated T-cells leading to impaired cytotoxic CD8+ T-cell and enhanced Treg cell function. To establish CD36 as a viable therapeutic target in AML, we investigated whether targeting CD36 has any detrimental impact on normal hematopoietic cells.

Methods

Differential expression data of CD36 during human and mouse normal hematopoiesis were examined and compared. Cd36 knockout (Cd36-KO) mice were evaluated for blood analysis, hematopoietic stem cells and progenitors (HSPCs) function and phenotype analyses, and T cells in vitro expansion and phenotypes in comparison with wild type (WT) mice. In addition, MLL-PTD/FLT3-ITD leukemic cells were engrafted into Cd36-KO and WT mice, and leukemia burden was compared between groups.

Results

RNA-Seq data showed that Cd36 expression was low in HSPCs and increased as cells matured. Phenotypic analysis revealed limited changes in blood count except for a slight yet significantly lower red blood cell count and hemoglobin and hematocrit levels in Cd36-KO mice compared with WT mice (P < 0.05). In vitro cell proliferation assays of splenocytes and HSPCs from Cd36-KO mice showed a similar pattern of expansion to that of cells from WT mice. Characterization of HSPCs showed similar percentages of the different progenitor cell populations between Cd36-KO with WT mice. However, Cd36-KO mice exhibited ~ 40% reduction of the number of colonies developed from HSPCs cells compared with WT mice (P < 0.001). Cd36-KO and WT mice presented comparably healthy BM transplant in non-competitive models and developed similar leukemia burden.

Conclusions

Although the loss of Cd36 affects the hematopoietic stem cell and erythropoiesis, limited detrimental overall impact was observed on normal Hematopoietic and leukemic microenvironments. Altogether, considering the limited impact on normal hematopoiesis, therapeutic approaches to target CD36 in cancer are unlikely to result in toxicity to normal blood cells.
Genome sequence of Ophryocystis elektroscirrha, an apicomplexan parasite of monarch butterflies: cryptic diversity and response to host-sequestered plant chemicals
Authors: Mongue Andrew J. , Martin Simon H. , Manweiler Rachel E. V. , Scullion Helena , Koehn Jordyn L. , de Roode Jacobus C. , Walters James R.
Published: May 2023

Apicomplexa are ancient and diverse organisms which have been poorly characterized by modern genomics. To better understand the evolution and diversity of these single-celled eukaryotes, we sequenced the genome of Ophryocystis elektroscirrha, a parasite of monarch butterflies, Danaus plexippus. We contextualize our newly generated resources within apicomplexan genomics before answering longstanding questions specific to this host-parasite system. To start, the genome is miniscule, totaling only 9 million bases and containing fewer than 3,000 genes, half the gene content of two other sequenced invertebrate-infecting apicomplexans, Porospora gigantea and Gregarina niphandrodes. We found that O. elektroscirrha shares different orthologs with each sequenced relative, suggesting the true set of universally conserved apicomplexan genes is very small indeed. Next, we show that sequencing data from other potential host butterflies can be used to diagnose infection status as well as to study diversity of parasite sequences. We recovered a similarly sized parasite genome from another butterfly, Danaus chrysippus, that was highly diverged from the O. elektroscirrha reference, possibly representing a distinct species. Using these two new genomes, we investigated potential evolutionary response by parasites to toxic phytochemicals their hosts ingest and sequester. Monarch butterflies are well-known to tolerate toxic cardenolides thanks to changes in the sequence of their Type II ATPase sodium pumps. We show that Ophryocystis completely lacks Type II or Type 4 sodium pumps, and related proteins PMCA calcium pumps show extreme sequence divergence compared to other Apicomplexa, demonstrating new avenues of research opened by genome sequencing of non-model Apicomplexa.
Adaptation strategies of leaf traits and leaf economic spectrum of two urban garden plants in China
Authors: Xu Liying , Zhang Nana , Wei Tongchao , Liu Bingyang , Shen Lanyi , Liu Yang , Liu Dounan
Published: May 2023

Background

Previous studies of the relationships between traits have focused on the natural growth conditions of wild plants. Urban garden plants exhibit some differences in plant traits due to environmental interference. It is unknown whether the relationships between the leaf traits of urban garden plants differ under distinct climates. In this study, we revealed the variation characteristics of the leaf functional traits of trees, shrubs, and vines in two urban locations. Two-way ANOVA was used to reveal the response of plant leaf traits to climate and life forms. Pearson correlation analysis and principal component analysis were used to calculate the correlation coefficient between the leaf functional traits of plants at the two locations.

Results

Leaf dry matter content (LDMC) and vein density (VD) of different life forms in Mudanjiang were higher than those in Bozhou (P < 0.05), and the relative water content (RWC) in Bozhou was higher, whereas vein density (VD) of trees and shrubs in the two urban locations was significant (P < 0.05), but the vines were not significant. The photosynthetic pigments of tree and shrub species were larger in Mudanjiang, but the opposite was true for the vines. Both leaf vein density (VD) and stomatal density (SD) showed a very significant positive correlation in the two urban locations (P < 0.01), and both were significantly positively correlated with specific leaf area (SLA) (P < 0.05); and negatively correlated with leaf thickness (LT), and the relationship between pigment content were closer.

Conclusion

The response to climate showed obvious differences in leaf traits of different life forms species in urban area, but the correlations between the traits showed convergence, which reflects that the adaptation strategies of garden plant leaves to different habitats are both coordinated and relatively independent.
Association of MLL3 and TGF-β signaling gene polymorphisms with the susceptibility and prognostic outcomes of Stanford type B aortic dissection
Authors: Yuan Qinghua , Chang Yafei , Jiang Peipei , Sun Ling , Ma Yitong , Ma Xiang
Published: May 2023

Objective

This study aims to investigate the association of lysine methyltransferase 2 C (MLL3) and transforming growth factor β (TGF-β) signaling-related gene polymorphisms with the susceptibility of Stanford type B aortic dissection (AD) and its clinical prognostic outcomes. The methods involved investigating the MLL3 (rs10244604, rs6963460, rs1137721), TGFβ1 (rs1800469), TGFβ2 (rs900), TGFR1 (rs1626340) and TGFR2 (rs4522809) gene polymorphisms. Logistic regression was performed to investigate the association between 7 single nucleotide gene polymorphisms (SNPs) and Stanford type B aortic dissection. The GMDR software was used to analyze gene-gene and gene-environment interactions. The odds ratio (OR) with a 95% confidence interval (CI) was employed to evaluate the association of genes and Stanford type B AD risk.

Results

Genotypes and allele distributions in the case and control groups showed significant differences (P < 0.05). Logistic regression has shown that the Stanford Type B AD risk was highest in individuals with the rs1137721 CT genotype (OR = 4.33, 95% CI = 1.51–12.40). Additionally, WBC, drinking, hypertension, triglycerides (TG), and low-density lipoprotein (LDL-C) were independent risk factors for Stanford Type B AD. Logistic regression showed that the Stanford Type B AD risk was highest in individuals with the MLL3 (rs1137721)-TT + CT and TGFβ1 (rs4522809)-AA genotype (OR = 6.72, 95% CI = 1.56–29.84), and lowest in those with the MLL3 (rs1137721)-CC and TGFβ1 (rs4522809)-AA + GG genotype (OR = 4.38, 95% CI = 0.92–20.83). However, the 55-month median long-term follow-up did not show statistical significance.

Conclusion

Carriers of both TT + CT of MLL3 (rs1137721) and AA of TGFβ1 (rs4522809) polymorphisms may be closely related to the development of Stanford type B AD. MLL3 (rs1137721), WBC, and TG/TC were found to be associated with the morbidity of Stanford type B AD. MLL3 (KMT2C) is associated with the TGF-β signaling pathway protein. The risk of Stanford type B AD is related to the interactions of gene-gene and gene-environment.
Comparison of vasoactive-inotropic score, vasoactive-ventilation-renal score, and modified vasoactive-ventilation-renal score for predicting the poor prognosis after coronary artery bypass grafting
Authors: Du Yanping , Li Wensu , Chen Qingjuan , Shi Haichuan , Li Qiong , Zhang Chunying , Zhuang Yunxu , Li Junying , Tang Li
Published: May 2023

Background

Exploring reliable prediction scoring systems is valuable for the poor prognosis of patients after coronary artery bypass grafting (CABG). Herein, we explored and compared the predictive performance of vasoactive-inotropic score (VIS), vasoactive-ventilation-renal (VVR) score, and modified VVR (M-VVR) score in the poor prognosis of patients undergoing CABG.

Methods

A retrospective cohort study was performed in Affiliated Hospital of Jining Medical University, and data of 537 patients were collected from January 2019 to May 2021. The independent variables were VIS, VVR, and M-VVR. Study endpoint of interest was the poor prognosis. Association between VIS, VVR, M-VVR and poor prognosis was assessed using logistic regression analysis, and odds ratios (OR) and 95% confidence intervals (CIs) were reported. The performance of VIS, VVR, and M-VVR to predict the poor prognosis was assessed by calculating the area under the curve (AUC), and differences of the AUC of the three scoring systems were compared using DeLong test.

Results

After adjusting gender, BMI, hypertension, diabetes, surgery methods, and left ventricular ejection fraction (LVEF), VIS (OR: 1.09, 95%CI: 1.05–1.13) and M-VVR (OR: 1.09, 95%CI: 1.06–1.12) were associated with the increased odds of poor prognosis. The AUC of M-VVR, VVR, and VIS was 0.720 (95%CI: 0.668–0.771), 0.621 (95%CI: 0.566–0.677), and 0.685 (95%CI: 0.631–0.739), respectively. DeLong test displayed that the performance of M-VVR was better than VVR (P = 0.004) and VIS (P = 0.003).

Conclusions

Our study found the good prediction performance of M-VVR for the poor prognosis of patients undergoing CABG, indicating that M-VVR may be a useful prediction index in the clinic.
Temporal changes in characteristics and external validity of randomized controlled trials in older people from 2012 to 2019
Authors: van Eijk Estelle , van der Spek Yanna M. , van Deudekom Floor J. A. , van den Bos Frederiek , Mooijaart Simon P. , Trompet Stella
Published: May 2023

Background

Older individuals are often underrepresented in clinical trials. In 2012 only 7% of RCT’s specifically studied older people and their geriatric characteristics were poorly reported. The aim of this review was to investigate temporal changes in characteristics and external validity of randomized controlled trials in older people from 2012 to 2019.

Methods

PubMed was searched for randomized clinical trials (RCTs) published in 2019. Firstly, the proportion of RCTs specially designed for older people were determined by the following criteria: a reported mean age of ≥ 70 years or a lower age cutoff of ≥ 55. Secondly, the trials with a majority of older people, defined by a reported mean age of ≥ 60 years, were screened for reporting of geriatric assessments. Both parts were compared with identical reviews performed in 2012.

Results

From a 10% random sample, 1446 RCTs were included in this systematic review. First, 8% of trials were specifically designed for older people in 2019 compared to 7% in 2012. Secondly, 25% of the trials included a majority of older people in 2019, compared to 22% in 2012. Thirdly, in 52% of these trials in 2019 one or more of the geriatric assessments were reported compared to 34% in 2012.

Conclusions

Although in 2019 the proportion of published RCTs specifically designed for older people remains low, more characteristics on geriatric assessments were reported compared to 2012. Continued efforts should be paid to increase both the number and the validity of trials for older people.
A back propagation neural network approach to estimate the glomerular filtration rate in an older population
Authors: Jiang Shimin , Li Yetong , Jiao Yuanyuan , Zhang Danyang , Wang Ying , Li Wenge
Published: May 2023

Background

The use of creatinine-based glomerular filtration rate (GFR)-estimating equations to evaluate kidney function in elderly individuals does not appear to offer any performance advantages. We therefore aimed to develop an accurate GFR-estimating tool for this age group.

Methods

Adults aged ≥ 65 years who underwent GFR measurement by technetium-99 m-diethylene triamine pentaacetic acid (99mTc-DTPA) renal dynamic imaging were included. Data were randomly split into a training set containing 80% of the participants and a test set containing the remaining 20% of the subjects. The Back propagation neural network (BPNN) approach was used to derive a novel GFR estimation tool; then we compared the performance of the BPNN tool with six creatinine-based equations (Chronic Kidney Disease-Epidemiology Collaboration [CKD-EPI], European Kidney Function Consortium [EKFC], Berlin Initiative Study-1 [BIS1], Lund-Malmö Revised [LMR], Asian modified CKD-EPI, and Modification of Diet in Renal Disease [MDRD]) in the test cohort. Three equation performance criteria were considered: bias (difference between measured GFR and estimated GFR), precision (interquartile range [IQR] of the median difference), and accuracy P30 (percentage of GFR estimates that are within 30% of measured GFR).

Results

The study included 1,222 older adults. The mean age of both the training cohort (n = 978) and the test cohort (n = 244) was 72 ± 6 years, with 544 (55.6%) and 129 (52.9%) males, respectively. The median bias of BPNN was 2.06 ml/min/1.73 m2, which was smaller than that of LMR (4.59 ml/min/1.73 m2; p = 0.03), and higher than that of the Asian modified CKD-EPI (-1.43 ml/min/1.73 m2; p = 0.02). The median bias between BPNN and each of CKD-EPI (2.19 ml/min/1.73 m2; p = 0.31), EKFC (-1.41 ml/min/1.73 m2; p = 0.26), BIS1 (0.64 ml/min/1.73 m2; p = 0.99), and MDRD (1.11 ml/min/1.73 m2; p = 0.45) was not significant. However, the BPNN had the highest precision IQR (14.31 ml/min/1.73 m2) and the greatest accuracy P30 among all equations (78.28%). At measured GFR < 45 ml/min/1.73 m2, the BPNN has highest accuracy P30 (70.69%), and highest precision IQR (12.46 ml/min/1.73 m2). The biases of BPNN and BIS1 equations were similar (0.74 [-1.55−2.78] and 0.24 [-2.58−1.61], respectively), smaller than any other equation.

Conclusions

The novel BPNN tool is more accurate than the currently available creatinine-based GFR estimation equations in an older population and could be recommended for routine clinical use.
Seasonal mortality trends for hospitalised patients with acute kidney injury across England
Authors: Wong Esther , Peracha Javeria , Pitcher David , Casula Anna , Steenkamp Retha , Medcalf James F , Nitsch Dorothea
Published: May 2023

Background

Incidence of acute kidney injury (AKI) is known to peak in winter months. This is likely influenced by seasonality of commonly associated acute illnesses. We set out to assess seasonal mortality trends for patients who develop AKI across the English National Health Service (NHS) and to better understand associations with patient ‘case-mix’.

Methods

The study cohort included all hospitalised adult patients in England who triggered a biochemical AKI alert in 2017. We modelled the impact of season on 30-day mortality using multivariable logistic regression; adjusting for age, sex, ethnicity, index of multiple deprivation (IMD), primary diagnosis, comorbidity (RCCI), elective/emergency admission, peak AKI stage and community/hospital acquired AKI. Seasonal odds ratios for AKI mortality were then calculated and compared across individual NHS hospital trusts.

Results

The crude 30-day mortality for hospitalised AKI patients was 33% higher in winter compared to summer. Case-mix adjustment for a wide range of clinical and demographic factors did not fully explain excess winter mortality. The adjusted odds ratio of patients dying in winter vs. summer was 1.25 (1.22–1.29), this was higher than for Autumn and Spring vs. Summer, 1.09 (1.06–1.12) and 1.07 (1.04–1.11) respectively and varied across different NHS trusts (9 out of 90 centres outliers).

Conclusion

We have demonstrated an excess winter mortality risk for hospitalised patients with AKI across the English NHS, which could not be fully explained by seasonal variation in patient case-mix. Whilst the explanation for worse winter outcomes is not clear, unaccounted differences including ‘winter-pressures’ merit further investigation.
Identification of immune cell infiltration and effective biomarkers of polycystic ovary syndrome by bioinformatics analysis
Authors: Gao Mengge , Liu Xiaohua , Du Mengxuan , Gu Heng , Xu Hang , Zhong Xingming
Published: May 2023

Background

Patients with polycystic ovary syndrome (PCOS) exhibit a chronic inflammatory state, which is often accompanied by immune, endocrine, and metabolic disorders. Clarification of the pathogenesis of PCOS and exploration of specific biomarkers from the perspective of immunology by evaluating the local infiltration of immune cells in the follicular microenvironment may provide critical insights into disease pathogenesis.

Methods

In this study, we evaluated immune cell subsets and gene expression in patients with PCOS using data from the Gene Expression Omnibus database and single-sample gene set enrichment analysis.

Results

In total, 325 differentially expressed genes were identified, among which TMEM54 and PLCG2 (area under the curve = 0.922) were identified as PCOS biomarkers. Immune cell infiltration analysis showed that central memory CD4+ T cells, central memory CD8+ T cells, effector memory CD4+ T cells, γδ T cells, and type 17 T helper cells may affect the occurrence of PCOS. In addition, PLCG2 was highly correlated with γδ T cells and central memory CD4+ T cells.

Conclusions

Overall, TMEM54 and PLCG2 were identified as potential PCOS biomarkers by bioinformatics analysis. These findings established a basis for further exploration of the immunological mechanisms of PCOS and the identification of therapeutic targets.
The relationship between social determinants of health and fear of contracting infectious diseases in pregnant women presenting to health centers in Kashan, Iran: a path analysis study
Authors: Vakili Fatemeh , Mahmoodi Zohreh , Nasiri Maliheh , Alamolhoda Saiedeh Hanieh
Published: May 2023

Introduction

Pregnancy is one of the most critical times in a woman’s life that is accompanied by a lot of worry, fear, and stress for the mother, and fear of contracting diseases and losing the children are among the most important of them. The present study investigated the relationship between the social determinants of health and fear of contracting infectious diseases in pregnant women using path analysis.

Methods

This cross-sectional study was conducted on 330 pregnant Iranian women in Kashan from September 21th, 2021, to May 25th, 2022, using a multi-stage method. Data were collected through demographic and obstetric details, fear of COVID-19, perceived social support, socioeconomic status, and pregnancy-related anxiety questionnaires. The collected data were then analyzed using SPSS-21 and Lisrel-8 software.

Results

According to the path analysis results, among the variables that have a causal relationship with fear of contracting infectious diseases through only one path, pregnancy anxiety (B = 0.21) had the highest positive relationship and social support had the highest negative relationship (B=-0.18) in the direct path. Among the variables that have a causal relationship with fear of contracting infectious diseases in both paths, socioeconomic status (B=-0.42) had the highest negative causal relationship with fear of contracting infectious diseases.

Conclusion

According to the path analysis results, the fear of contracting infectious diseases in pregnant women in Kashan is moderate and prevalent, which indicates the necessity of screening pregnant women for such problems during epidemics. Moreover, to prevent this fear and its adverse consequences, the following strategies are recommended: helping promote mothers’ and women’s awareness, offering social support through healthcare providers, and taking measures to mitigate pregnancy-related anxiety in high-risk individuals and groups.
A case study of using natural language processing to extract consumer insights from tweets in American cities for public health crises
Authors: Wang Ye , Willis Erin , Yeruva Vijaya K. , Ho Duy , Lee Yugyung
Published: May 2023

Background

The COVID-19 pandemic was a “wake up” call for public health agencies. Often, these agencies are ill-prepared to communicate with target audiences clearly and effectively for community-level activations and safety operations. The obstacle is a lack of data-driven approaches to obtaining insights from local community stakeholders. Thus, this study suggests a focus on listening at local levels given the abundance of geo-marked data and presents a methodological solution to extracting consumer insights from unstructured text data for health communication.

Methods

This study demonstrates how to combine human and Natural Language Processing (NLP) machine analyses to reliably extract meaningful consumer insights from tweets about COVID and the vaccine. This case study employed Latent Dirichlet Allocation (LDA) topic modeling, Bidirectional Encoder Representations from Transformers (BERT) emotion analysis, and human textual analysis and examined 180,128 tweets scraped by Twitter Application Programming Interface’s (API) keyword function from January 2020 to June 2021. The samples came from four medium-sized American cities with larger populations of people of color.

Results

The NLP method discovered four topic trends: “COVID Vaccines,” “Politics,” “Mitigation Measures,” and “Community/Local Issues,” and emotion changes over time. The human textual analysis profiled the discussions in the selected four markets to add some depth to our understanding of the uniqueness of the different challenges experienced.

Conclusions

This study ultimately demonstrates that our method used here could efficiently reduce a large amount of community feedback (e.g., tweets, social media data) by NLP and ensure contextualization and richness with human interpretation. Recommendations on communicating vaccination are offered based on the findings: (1) the strategic objective should be empowering the public; (2) the message should have local relevance; and, (3) communication needs to be timely.
Seminal papers in urology: anticholinergic therapy vs. onabotulinumtoxina for urgency urinary incontinence
Authors: Shugg Nathan , O’Callaghan Michael E.
Published: May 2023

In this critical review, we explore the study design, strengths, and limitations of landmark trial “Anticholinergic therapy vs. onabotulinumtoxinA for urgency urinary incontinence”. This trial was the first to directly compare two key treatment options for urge urinary incontinence – anticholinergic medication and intravesical botox, and still influences clinical guidelines a decade after publication. This non-inferiority, double-blinded, multi-centre randomised controlled trial administered Solifenacin or intra-detrusor botox to women, measuring outcomes six months post-treatment. Non-inferiority of the treatments was established, though Botox had a higher rate of retention and infection, with side effect profile rising as the key discriminator in selecting first-line therapy.
Maxillary anterior segmental distraction osteogenesis to correct maxillary hypoplasia and dental crowding in cleft palate patients: a preliminary study
Authors: Qian Liwen , Qian Yufen , Chen Wener
Published: May 2023

Background

The aim of this study was to present comprehensive skeletal, dental and facial aesthetic outcomes and long-term stability of maxillary anterior segmental distraction osteogenesis (MASDO) for the treatment of maxillary hypoplasia in CLP.

Materials and methods

Six patients with maxillary hypoplasia treated with MASDO by a miniscrew assisted intraoral tooth-borne distractor were included. Cephalometric radiographs were obtained before distraction (T1), after the consolidation period (T2) and after orthodontic treatment or before orthognathic surgery (T3). Thirty-one cephalometric variables (12 skeletal, 9 dental, and 10 soft tissue variables) were used to evaluate changes in the dentofacial structures and the soft tissue profile. Friedman and Wilcoxon tests were applied to identify significant differences in hard and soft tissue changes during the T1–T2, T2–T3, and T1–T3 periods.

Results

All patients successfully underwent MASDO without serious complications. From T1 to T2, forward movements of ANS and A (FH ⊥ N–A, VRL–ANS and VRL–A) were significant (p < 0.05). Significant increases in SNA and ANB were noted. Significant upward movement of points ANS (CFH–ANS) and A (CFH–A) was observed (p < 0.05). After distraction, a significant decrease in overjet and an increase in overbite were obtained (p < 0.05). Anterior tipping of the upper incisors (U1/ANS–PNS and U1/SN) was observed (p < 0.05). The soft tissue points of Pn, Sn, Ss, and ls showed significant anterior movement (p < 0.05). In addition, a significant increase in the nasolabial angle was measured (p < 0.05). All of the above data showed no statistically significant changes between T2 and T3 (p > 0.05).

Conclusion

MASDO using a miniscrew assisted tooth-borne distractor presented significant maxillary advancement and favorable long-term stability in treating CLP patients with maxillary hypoplasia.
Inconsistently reporting post-licensure EPA specifications in different clinical professions hampers fidelity and practice translation: a scoping review
Authors: Moore Sonya J. , Egerton Thorlene , Merolli Mark , Lees Jessica , La Scala Nino , Parry Selina M.
Published: May 2023

Background

Entrustable Professional Activities (EPAs) are defined units of professional practice entrusted to professionals once they have attained the specific competencies required to complete the end-to-end task. They provide a contemporary framework for capturing real-world clinical skillsets and integrating clinical education with practice. Our scoping review question was: how are post-licensure EPAs reported in peer reviewed literature, in different clinical professions?

Method

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) checklist, Arksey and O’Malley and Joanna Briggs Institute (JBI) methodology. Searching ten electronic databases returned 1622 articles, with 173 articles included. Data extracted included demographics, EPA discipline, titles and further specifications.

Results

All articles were published between 2007–2021 across sixteen country contexts. The majority were from North America (n = 162, 73%) describing medical sub-specialty EPAs (n = 126, 94%). There were comparably few EPA frameworks reported in clinical professions other than medicine (n = 11, 6%). Many articles reported only EPA titles without further explanation and limited content validation. The majority did not include information about the EPA design process. Few EPAs and frameworks were reported according to all the recommended EPA attributes. There was unclear distinction between specialty-specific EPAs and those that could be useful across disciplines.

Discussion

Our review highlights the large volume of EPAs reported in post-licensure medicine, including the volume disparity compared to other clinical professions. Basing our enquiry upon existing guidelines for EPA attributes and features, our experience in conducting the review and our primary finding demonstrated heterogeneity of EPA reporting according to these specifications. To promote EPA fidelity, and quality appraisal, and to reduce interpretation subjectivity, we advocate: diligently reporting EPA attributes and features; including reference or citation to EPA design and content validity information; and considering distinguishing EPAs as specialty-specific or transdisciplinary.

Conclusion

A large volume of post-licensure EPAs were identified in medicine relative to other clinical professions. EPA specifications were absent or variously reported in the literature, risking ambiguous interpretation. The authors recommend that future EPAs are reported with reference to established and evolving construct recommendations, which is integral to concept fidelity and translation to practice and education.
Digital communication and virtual reality for extending the behavioural treatment of obesity – the patients’ perspective: results of an online survey in Germany
Authors: Luck-Sikorski Claudia , Hochrein Regine , Döllinger Nina , Wienrich Carolin , Gemesi Kathrin , Holzmann Sophie , Holzapfel Christina , Weinberger Natascha-Alexandra
Published: May 2023

Background

CBT has been found effective for the treatment of EDs and obesity. However not all patients achieve clinically significant weight loss and weight regain is common. In this context, technology-based interventions can be used to enhance traditional CBT but are not yet widespread. This survey therefore explores the status quo of pathways of communication between patients and therapists, the use of digital applications for therapy as well as attitudes towards VR from the perspective of patients with obesity in Germany.

Methods

This cross-sectional online survey was conducted in October 2020. Participants were recruited digitally through social media, obesity associations and self-help groups. The standardized questionnaire included items concerning current treatment, paths of communication with their therapists, and attitudes toward VR. The descriptive analyses were performed with Stata.

Results

The 152 participants were mostly female (90%), had a mean age of 46.5 years (SD = 9.2) and an average BMI of 43.0 kg/m² (SD = 8.4). Face-to-face communication with their therapist was considered of high importance in current treatment (M = 4.30; SD = 0.86) and messenger apps were the most frequently used digital application for communication. Participants were mostly neutral regarding the inclusion of VR methods in obesity treatment (M = 3.27; SD = 1.19). Only one participant had already used VR glasses as part of treatment. Participants considered VR suitable for exercises promoting body image change (M = 3.40; SD = 1.02).

Discussion

Technological approaches in obesity therapy are not widespread. Face-to-face communication remains the most important setting for treatment. Participants had low familiarity with VR but a neutral to positive attitude toward the technology. Further studies are needed to provide a clearer picture of potential treatment barriers or educational needs and to facilitate the transfer of developed VR systems into clinical practice.
Exploring new insights in coronary lesion assessment and treatment in patients with diabetes mellitus: the impact of optical coherence tomography
Authors: Hommels Tobias Michiel , Hermanides Renicus Suffridus , Fabris Enrico , Kedhi Elvin
Published: May 2023

In this review, we summarise new insights into diagnostic approaches and treatment strategies for coronary artery disease (CAD) in patients with diabetes mellitus (DM). Despite the improvements in therapy, the clinical management of DM patients remains challenging as they develop more extensive CAD at a younger age and consistently have worse clinical outcomes than non-DM patients. Current diagnostic modalities as well as revascularisation treatments mainly focus on ischemic lesions. However, the impact of plaque morphology and composition are emerging as strong predictors of adverse cardiac events even in the absence of identified ischemia. In particular, the presence of vulnerable plaques such as thin-cap fibroatheroma (TCFA) lesions has been identified as a very strong predictor of future adverse events. This emphasises the need for an approach combining both functional and morphological methods in the assessment of lesions. In particular, optical coherence tomography (OCT) has proven to be a valuable asset by truly identifying TCFAs. New treatment strategies should consist of individualised and advanced medical regimens and may evolve towards plaque sealing through percutaneous treatment.
Identification of BRAF, CCND1, and MYC mutations in a patient with multiple primary malignant tumors: a case report and review of the literature
Authors: Liu Zheyu , Jin Cheng , Zhang Yi , Jiang Yongquan , Wang Jingshuo , Zheng Luying
Published: May 2023

Background

Multiple primary malignant tumors (MPMTs), usually associated with worse malignant behavior and prognosis comparing to a single primary tumor, and have recently been found to have an increasing incidence globally. However, the pathogenesis of MPMTs remains to be clarified. Here, we report a unique case of the coexistence of malignant melanoma (MM), papillary thyroid carcinoma (PTC), and clear-cell renal cell carcinoma (ccRCC) along with our perceptions on its pathogenesis.

Case presentation

The case reported is of a 59-year-old male patient with unilateral nasal obstruction as well as a renal occupying lesion. Positron emission tomography-computed tomography (PET-CT) revealed a palpable mass of 32 × 30 mm on the posterior and left walls of the nasopharynx. In addition, an isodense nodule was observed in the right superior renal pole, approximately 25 mm in diameter, as well as a slightly hypodense shadow in the right leaf of the thyroid, approximately 13 mm in diameter. Nasal endoscopy and magnetic resonance imaging (MRI) confirmed the existence of a nasopharyngeal neoplasm. Afterward, biopsies of the nasopharyngeal neoplasm, thyroid gland and kidney were performed, and the patient was diagnosed with MM, PTC, and ccRCC according to the pathological and immunohistochemical results. Moreover, mutation of BRAFV600E was detected in bilateral thyroid tissues, and amplification of both CCND1 and MYC oncogenes were detected in the nasopharyngeal melanoma. After chemotherapy, the patient is now in good overall condition.

Conclusions

This is the first reported case of a patient with the co-existence of MM, PTC and ccRCC undergoing chemotherapy with a favorable prognosis. Herein, we suggest that such a combination may be non-random, as for mutation of BRAFV600E might account for the co-occurrence of PTC and MM, while mutations of CCND1 and MYC cause the coexistence of MM and ccRCC. This finding may provide valuable guidance on the diagnosis and treatment of such disease, as well as the prevention of developing a second or third tumor for patients with a single primary.
The effectiveness of spinal manipulative therapy procedures for spine pain: protocol for a systematic review and network meta-analysis
Authors: Nim Casper G. , Aspinall Sasha L. , Cook Chad E. , Corrêa Leticia A. , Donaldson Megan , Downie Aron S. , Harsted Steen , Hartvigsen Jan , Jenkins Hazel J. , McNaughton David , Nyirö Luana , Perle Stephen M. , Roseen Eric J. , Young James J. , Young Anika , Zhao Gong-He , Juhl Carsten B.
Published: May 2023

Background

Spinal manipulative therapy (SMT) is a guideline-recommended treatment option for spinal pain. The recommendation is based on multiple systematic reviews. However, these reviews fail to consider that clinical effects may depend on SMT “application procedures” (i.e., how and where SMT is applied). Using network meta-analyses, we aim to investigate which SMT “application procedures” have the greatest magnitude of clinical effectiveness for reducing pain and disability, for any spinal complaint, at short-term and long-term follow-up. We will compare application procedural parameters by classifying the thrust application technique and the application site (patient positioning, assisted, vertebral target, region target, Technique name, forces, and vectors, application site selection approach and rationale) against: 1. Waiting list/no treatment; 2. Sham interventions not resembling SMT (e.g., detuned ultrasound); 3. Sham interventions resembling SMT; 4. Other therapies not recommended in clinical practice guidelines; and 5. Other therapies recommended in clinical practice guidelines. Secondly, we will examine how contextual elements, including procedural fidelity (whether the SMT was delivered as planned) and clinical applicability (whether the SMT is similar to clinical practice) of the SMT.

Methods

We will include randomized controlled trials (RCT) found through three search strategies, (i) exploratory, (ii) systematic, and (iii) other known sources. We define SMT as a high-velocity low-amplitude thrust or grade V mobilization. Eligibility is any RCT assessing SMT against any other type of SMT, any other active or sham intervention, or no treatment control on adult patients with pain in any spinal region. The RCTs must report on continuous pain intensity and/or disability outcomes. Two authors will independently review title and abstract screening, full-text screening, and data extraction. Spinal manipulative therapy techniques will be classified according to the technique application and choice of application sites. We will conduct a network-meta analysis using a frequentist approach and multiple subgroup and sensitivity analyses.

Discussion

This will be the most extensive review of thrust SMT to date, and will allow us to estimate the importance of different SMT application procedures used in clinical practice and taught across educational settings. Thus, the results are applicable to clinical practice, educational settings, and research studies.

PROSPERO registration: CRD42022375836.
TMT proteomics analysis reveals the mechanism of bleomycin-induced pulmonary fibrosis and effects of Ginseng honeysuckle superfine powdered tea
Authors: Li Xiaoli , Yu Xin , Gao Yuan , Zhao Wenqian , Wang Yajuan , Yu Fei , Fu Chunli , Gao Haiqing , Cheng Mei , Li Baoying
Published: May 2023

Background

Pulmonary fibrosis (PF) is a chronic and potentially fatal lung disease and disorder. Although the active ingredients of ginseng honeysuckle superfine powdered tea (GHSPT) have been proven to have anti-inflammatory and antioxidant effects, the mechanism of GHSPT on PF remains unclear. The present study was to explore the underlying mechanism of GHSPT in treating PF based on proteomics and network pharmacology analysis and to confirm it in vivo.

Materials and methods

We used intratracheal instillation of bleomycin to induce the PF mouse model and GHSPT (640 mg/kg) intragastrically administrated to PF mice for 21 days. The lung tissues were harvested for TMT-based proteomics. The UPLC-Q-Exactive MS/MS analyze the serum migrant compounds of GHSPT in the PF mice. Moreover, components of GHSPT were harvested from the pharmacology database of the TCMSP system. PF-related targets were retrieved using NCBI and GeneCards databases.

Results

Our results showed that GHSPT significantly alleviated PF mice. Proteomics analysis showed that 525 proteins had significantly changed in the lung of untreated PF mice. Among them, 19 differential proteins were back-regulated to normal levels after GHSPT therapy. Moreover, 25 compounds originating from GHSPT were identified in the serum sample. Network analysis showed 159 active ingredients and 92 drug targets against PF. The signaling pathways include apoptosis, ferroptosis, cytokine-cytokine receptor, P53, and PI3K-Akt signaling pathway.

Conclusion

The evidence suggests that GHSPT might play an effective role in the treatment of PF by multi-target interventions against multiple signaling pathways.
Comparison of landiolol and amiodarone for the treatment of new-onset atrial fibrillation after cardiac surgery (FAAC) trial: study protocol for a randomized controlled trial
Authors: Caspersen Edouard , Guinot Pierre-Grégoire , Rozec Bertrand , Oilleau Jean-Ferréol , Fellahi Jean-Luc , Gaudard Philippe , Lorne Emmanuel , Mahjoub Yazine , Besnier Emmanuel , Moussa Mouhamed Djahoum , Mongardon Nicolas , Hanouz Jean-Luc , Briant Anaïs R. , Paul Laure Peyro Saint , Tomadesso Clémence , Parienti Jean-Jacques , Descamps Richard , Denisenko Alina , Fischer Marc-Olivier ,   for the ARCOTHOVA Group
Published: May 2023

Background

Postoperative atrial fibrillation (PoAF) after cardiac surgery has a high incidence of 30%, but its management is controversial. Two strategies are recommended without evidence of a superiority of one against the other: rate control with beta-blocker or rhythm control with amiodarone. Landiolol is a new-generation beta-blocker with fast onset and short half-life. One retrospective, single-center study compared landiolol to amiodarone for PoAF after cardiac surgery with a better hemodynamic stability and a higher rate of reduction to sinus rhythm with landiolol, justifying the need for a multicenter randomized controlled trial. Our aim is to compare landiolol to amiodarone in the setting of PoAF after cardiac surgery with the hypothesis of a higher rate of reduction to sinus rhythm with landiolol during the 48 h after the first episode of POAF.

Methods

The FAAC trial is a multicenter single-blind two parallel-arm randomized study, which planned to include 350 patients with a first episode of PoAF following cardiac surgery. The duration of the study is 2 years. The patients are randomized in two arms: a landiolol group and an amiodarone group.

Randomization (Ennov Clinical®) is performed by the anesthesiologist in charge of the patient if PoAF is persistent for at least 30 min after correction of hypovolemia, dyskalemia, and absence of pericardial effusion on a transthoracic echocardiography done at bedside.

Our hypothesis is an increase of the percentage of patients in sinus rhythm from 70 to 85% with landiolol in less than 48 h after onset of PoAF (alpha risk = 5%, power = 90%, bilateral test).

Discussion

The FAAC trial was approved by the Ethics Committee of EST III with approval number 19.05.08. The FAAC trial is the first randomized controlled trial comparing landiolol to amiodarone for PoAF after cardiac surgery. In case of higher rate of reduction with landiolol, this beta-blocker could be the drug of choice used in this context as to reduce the need for anticoagulant therapy and reduce the risk of complications of anticoagulant therapy for patients with a first episode of postoperative atrial fibrillation after cardiac surgery.

Trial registration

ClinicalTrials.gov NCT04223739. Registered on January 10, 2020.
Software compatibility analysis for quantitative measures of [18F]flutemetamol amyloid PET burden in mild cognitive impairment
Authors: Pemberton Hugh G. , Buckley Christopher , Battle Mark , Bollack Ariane , Patel Vrajesh , Tomova Petya , Cooke David , Balhorn Will , Hegedorn Katherine , Lilja Johan , Brand Christine , Farrar Gill
Published: May 2023

Rationale

Amyloid-β (Aβ) pathology is one of the earliest detectable brain changes in Alzheimer’s disease pathogenesis. In clinical practice, trained readers will visually categorise positron emission tomography (PET) scans as either Aβ positive or negative. However, adjunct quantitative analysis is becoming more widely available, where regulatory approved software can currently generate metrics such as standardised uptake value ratios (SUVr) and individual Z-scores. Therefore, it is of direct value to the imaging community to assess the compatibility of commercially available software packages. In this collaborative project, the compatibility of amyloid PET quantification was investigated across four regulatory approved software packages. In doing so, the intention is to increase visibility and understanding of clinically relevant quantitative methods.

Methods

Composite SUVr using the pons as the reference region was generated from [18F]flutemetamol (GE Healthcare) PET in a retrospective cohort of 80 amnestic mild cognitive impairment (aMCI) patients (40 each male/female; mean age = 73 years, SD = 8.52). Based on previous autopsy validation work, an Aβ positivity threshold of ≥ 0.6 SUVrpons was applied. Quantitative results from MIM Software’s MIMneuro, Syntermed’s NeuroQ, Hermes Medical Solutions’ BRASS and GE Healthcare’s CortexID were analysed using intraclass correlation coefficient (ICC), percentage agreement around the Aβ positivity threshold and kappa scores.

Results

Using an Aβ positivity threshold of ≥ 0.6 SUVrpons, 95% agreement was achieved across the four software packages. Two patients were narrowly classed as Aβ negative by one software package but positive by the others, and two patients vice versa. All kappa scores around the same Aβ positivity threshold, both combined (Fleiss’) and individual software pairings (Cohen’s), were ≥ 0.9 signifying “almost perfect” inter-rater reliability. Excellent reliability was found between composite SUVr measurements for all four software packages, with an average measure ICC of 0.97 and 95% confidence interval of 0.957–0.979. Correlation coefficient analysis between the two software packages reporting composite z-scores was strong (r2 = 0.98).

Conclusion

Using an optimised cortical mask, regulatory approved software packages provided highly correlated and reliable quantification of [18F]flutemetamol amyloid PET with a ≥ 0.6 SUVrpons positivity threshold. In particular, this work could be of interest to physicians performing routine clinical imaging rather than researchers performing more bespoke image analysis. Similar analysis is encouraged using other reference regions as well as the Centiloid scale, when it has been implemented by more software packages.