bluuebunny/crossref_metadata_2025 huggingface dataset:
Using the intervention mapping for adaption framework to adapt an evidence-based sexual health intervention for youth affected by trauma
Authors: Kachingwe Olivia N. , Lewis Quiana , Offiong Asari , Smith Bianca D. , LoVette Ashleigh , Powell Terrinieka W.
Published: June 2023

Background

Children exposed to household challenges (i.e., parental substance use, incarceration, and mental illness) are among the groups most vulnerable to sexual risk-taking in adolescence. These behaviors have been associated with a range of negative outcomes later in life, including substance abuse, low educational attainment, and incarceration. Adapting an evidence-based intervention (EBI) to be suitable for this population is one strategy to address the needs of this group.

Methods

In this study, we describe the use of the Intervention Mapping for Adaption (IM-Adapt) framework to adapt an evidence-based, sexual health intervention (Focus on Youth with Informed Children and Parents). We describe the actions taken at each step of the IM-Adapt process which are to assess needs, search for EBIs, assess fit and plan adaptions, make adaptions, plan for implementation and plan for evaluation.

Results

Key changes of the adapted intervention include the incorporation of trauma-informed principles and gender inclusive language, standardization of the session length, and modernization of the content to be more appropriate for our priority population.

Conclusions

The adapted intervention shows promise toward meeting the behavioral health needs of Black youth exposed to household challenges. Our process and approach can serve as a model for researchers and practitioners aiming to extend the reach of EBIs.
Barriers and enablers to testing for hepatitis C virus infection in people who inject drugs – a scoping review of the qualitative evidence
Authors: Balsom Cathy R. , Farrell Alison , Kelly Deborah V.
Published: June 2023

Background

Injection drug use is the primary mode of transmission of hepatitis C virus (HCV) infection in the developed world and guidelines recommend screening individuals with current or history of injection drug use for HCV; however, the majority of those living with HCV in Canada are not aware of their positive status. This low level of HCV status awareness suggests that screening is not effective with current testing strategies. The aim of this review is to determine what barriers and enablers people who inject drugs (PWID) experience surrounding testing for HCV to help inform the development of an engaging testing strategy.

Methods

Comprehensive literature searches were conducted using Medline, Embase and CINAHL in February 2021. Included studies investigated the barriers and enablers to testing for HCV in PWID and the experiences of PWID in testing for HCV. Studies were included if they were qualitative or mixed-methods design, involved people with current injection drug use or those with a history of injecting drugs, and were written in the English language. Studies were compared and common themes were coded and analyzed.

Results

The literature search resulted in 1554 citations and ultimately nine studies were included. Common barriers included self-perception of low risk for HCV, fear of diagnosis, stigma associated with IV drug use and HCV, antipathy in relation to mainstream health care services, limited knowledge about HCV, lack of rapport with provider, lack of motivation or competing priority of drug use, and limited awareness of new treatment options. Common enablers to testing included increasing awareness of HCV testing and treatment and providing positive narratives around HCV care, positive rapport with provider, accessible testing options and individualized care.

Conclusion

While there has been some qualitative research on barriers and enablers to testing for HCV in PWID more research is needed to focus on this research question as a primary objective in order to provide more understanding from the participant’s perspective.
How personality influences health outcomes and quality of life in adult patients with cystic fibrosis
Authors: Niehammer Ute , Straßburg Svenja , Sutharsan Sivagurunathan , Taube Christian , Welsner Matthias , Stehling Florian , Hirtz Raphael
Published: June 2023

Background

The present study evaluates personality traits in adult patients with cystic fibrosis (CF) and correlates these results with health-related quality of life (HRQoL) and other clinical parameters indicative of disease severity.

Methods

Seventy adults completed the Cystic Fibrosis Questionnaire-Revised (CFQ-R 14+), a CF-specific measure of HRQoL, and a self-administered questionnaire about personality traits and disorders. Mean subscale scores and the prevalence of extreme personality traits on the `Persönlichkeits-Stil- und Störungs-Inventar (PSSI)´ were compared to the norming sample. Moreover, a cluster analysis was conducted to identify personality styles among people with cystic fibrosis (pwCF). The relationship between mean PSSI subscale scores and personality clusters with HRQoL and clinical outcomes, e.g., percent predicted forced expiratory volume in one second (ppFEV1), and body mass index (BMI), was studied by regression analysis considering important confounders.

Results

On several of the subscales of the personality questionnaire, people with cystic fibrosis (pwCF) showed either significantly higher or lower scores than the norm sample. In further analyses, two personality clusters could be identified. PwCF from the cluster with predominantly low scores on the subscales ‘negativistic’, ‘schizoid’, ‘borderline’, ‘depressed’, and ‘paranoid’ showed better HRQoL than pwCF from the other cluster with mainly high normal or elevated scores. The studied health outcomes proved to be independent of the respective personality clusters.

Conclusions

In pwCF, HRQoL is mainly determined by psychological factors, including personality. Since more recent personality theories assume that personality is modifiable, our findings imply that patients with accentuated personality traits may benefit from psychosocial support.
Effect of an app for promoting advance care planning and motivating patients to write their advance directives
Authors: Schöpfer Céline , Bollondi Catherine , Moussa Mohamed Amir , Sommer Johanna , Clavien Christine
Published: June 2023

Background

Accordons-nous, a smartphone app, was developed to support patients in the advance care planning (ACP) process. The app raises awareness and facilitates communication on this sensitive topic. It helps patients express their values and preferences for care and write their advance directives (AD).

Objective

Measure the impact of distributing Accordons-nous on patients’ propensity to engage in the ACP process, compared with the distribution of a leaflet. A secondary objective was to test the effect of socio-demographic factors (age, health status, gender, level of education) on propensity to engage in ACP.

Methods

Pre-post randomized control study. Participants were patients approached in medical waiting rooms. They received the app (treatment) or an information leaflet (control). They responded to two questionnaires: one at recruitment and a second 3–4 weeks later. Improvement on four variables relevant to ACP was measured: reported contemplation of an event relevant to ACP; decision about treatment in case of that event; discussion about it with relatives or health care professionals; writing advance directives. Statistical analysis included between-group comparisons of pre-post differences with 2-sample tests for equality of proportions and logistic regression models.

Results

Four hundred seventy three participants were recruited and full responses obtained from 312. Overall, the intervention (control and treatment together) had a positive effect on the mean reported ACP engagement for all variables: new or renewed contemplation 54%; increase in decision 8%, discussion 11%, and writing 1%, compared to the baseline. Compared to the control (leaflet), the treatment group (app) had a larger effect size for all variables: between-group difference in contemplation + 11% (logistic regression, p = .05), decision + 1% (but p > .05 on this variable), discussion + 5% (p = .05), and writing AD + 5% (p = .03). Moreover, greater age was positively correlated with having written AD at inclusion (21% among retired compared to 2% among young adults) and with the propensity to write AD after our intervention (logistic regression, p = .001). Other factors tested (frequency of consultations, gender, level of education) had no effect on participants’ ACP engagement.

Conclusions

When distributed without specific counselling, the tool increased reported ACP engagement, although effect sizes remain modest. Further studies are needed to investigate whether the app could generate greater ACP engagement if used by professionals in dedicated ACP consultations.
The role of m6A methylation in therapy resistance in cancer
Authors: Zhuang Hengzhao , Yu Bo , Tao Dan , Xu Xiaoyan , Xu Yijun , Wang Jian , Jiao Yang , Wang Lili
Published: June 2023

Cancer therapy resistance is the main cause of cancer treatment failure. The mechanism of therapy resistance is a hot topic in epigenetics. As one of the most common RNA modifications, N6-methyladenosine (m6A) is involved in various processes of RNA metabolism, such as stability, splicing, transcription, translation, and degradation. A large number of studies have shown that m6A RNA methylation regulates the proliferation and invasion of cancer cells, but the role of m6A in cancer therapy resistance is unclear. In this review, we summarized the research progress related to the role of m6A in regulating therapy resistance in cancers.
Evidence synthesis to policy: development and implementation of an impact-oriented approach from the Eastern Mediterranean Region
Authors: El-Jardali Fadi , Fadlallah Racha , Bou Karroum Lama , Akl Elie A.
Published: June 2023

Background

Despite the importance of evidence syntheses in informing policymaking, their production and use remain limited in the Eastern Mediterranean region (EMR). There is a lack of empirical research on approaches to promote and use policy-relevant evidence syntheses to inform policymaking processes in the EMR.

Objective

This study sought to describe the development of an impact-oriented approach to link evidence synthesis to policy, and its implementation through selected case studies in Lebanon, a middle-income country in the EMR.

Methods

This study followed a multifaceted and iterative process that included (i) a review of the literature, (ii) input from international experts in evidence synthesis and evidence-informed health policymaking, and (iii) application in a real-world setting (implementation). We describe four selected case studies of implementation. Surveys were used to assess policy briefs, deliberative dialogues, and post-dialogue activities. Additionally, Kingdon’s stream theory was adopted to further explain how and why the selected policy issues rose to the decision agenda.

Results

The approach incorporates three interrelated phases: (1) priority setting, (2) evidence synthesis, and (3) uptake. Policy-relevant priorities are generated through formal priority setting exercises, direct requests by policymakers and stakeholders, or a focusing event. Identified priorities are translated into focused questions that can be addressed via evidence synthesis (phase 1). Next, a scoping of the literature is conducted to identify existing evidence syntheses addressing the question of interest. Unless the team identifies relevant, up-to-date and high-quality evidence syntheses, it proceeds to conducting SRs addressing the priority questions of interest (phase 2). Next, the team prepares knowledge translation products (e.g., policy briefs) for undertaking knowledge uptake activities, followed by monitoring and evaluation (phase 3). There are two prerequisites to the application of the approach: enhancing contextual awareness and capacity strengthening. The four case studies illustrate how evidence produced from the suites of activities was used to inform health policies and practices.

Conclusions

To our knowledge, this is the first study to describe both the development and implementation of an approach to link evidence synthesis to policy in the EMR. We believe the approach will be useful for researchers, knowledge translation platforms, governments, and funders seeking to promote evidence-informed policymaking and practice.
The choroid plexus acts as an immune cell reservoir and brain entry site in experimental autoimmune encephalomyelitis
Authors: Lazarevic Ivana , Soldati Sasha , Mapunda Josephine A. , Rudolph Henriette , Rosito Maria , de Oliveira Alex Cardoso , Enzmann Gaby , Nishihara Hideaki , Ishikawa Hiroshi , Tenenbaum Tobias , Schroten Horst , Engelhardt Britta
Published: June 2023

The choroid plexus (ChP) has been suggested as an alternative central nervous system (CNS) entry site for CCR6+ Th17 cells during the initiation of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). To advance our understanding of the importance of the ChP in orchestrating CNS immune cell entry during neuroinflammation, we here directly compared the accumulation of CD45+ immune cell subsets in the ChP, the brain and spinal cord at different stages of EAE by flow cytometry. We found that the ChP harbors high numbers of CD45int resident innate but also of CD45hi adaptive immune cell subsets including CCR6+ Th17 cells. With the exception to tissue-resident myeloid cells and B cells, numbers of CD45+ immune cells and specifically of CD4+ T cells increased in the ChP prior to EAE onset and remained elevated while declining in brain and spinal cord during chronic disease. Increased numbers of ChP immune cells preceded their increase in the cerebrospinal fluid (CSF). Th17 but also other CD4+ effector T-cell subsets could migrate from the basolateral to the apical side of the blood-cerebrospinal fluid barrier (BCSFB) in vitro, however, diapedesis of effector Th cells including that of Th17 cells did not require interaction of CCR6 with BCSFB derived CCL20. Our data underscore the important role of the ChP as CNS immune cell entry site in the context of autoimmune neuroinflammation.
Development of a universal, oriented antibody immobilization method to functionalize vascular prostheses for enhanced endothelialization for potential clinical application
Authors: Zhang Qiuwang , Duncan Sebastian , Szulc Daniel A. , de Mestral Charles , Kutryk Michael JB
Published: June 2023

Background

Thrombosis is a common cause of vascular prosthesis failure. Antibody coating of prostheses to capture circulating endothelial progenitor cells to aid endothelialization on the device surface appears a promising solution to prevent thrombus formation. Compared with random antibody immobilization, oriented antibody coating (OAC) increases antibody-antigen binding capacity and reduces antibody immunogenicity in vivo. Currently, few OAC methods have been documented, with none possessing clinical application potential.

Results

Dopamine and the linker amino-PEG8-hydrazide-t-boc were successfully deposited on the surface of cobalt chromium (CC) discs, CC stents and expanded polytetrafluoroethylene (ePTFE) grafts under a slightly basic condition. CD34 antibodies were immobilized through the reaction between aldehydes in the Fc region created by oxidation and hydrazides in the linker after t-boc removal. CD34 antibody-coated surfaces were integral and smooth as shown by scanning electron microscopy (SEM), had significantly reduced or no substrate-specific signals as revealed by X-ray photoelectron spectroscopy, were hospitable for HUVEC growth as demonstrated by cell proliferation assay, and specifically bound CD34 + cells as shown by cell binding testing. CD34 antibody coating turned hydrophobic property of ePTFE grafts to hydrophilic. In a porcine carotid artery interposition model, a confluent monolayer of cobblestone-shaped CD31 + endothelial cells on the luminal surface of the CD34 antibody coated ePTFE graft were observed. In contrast, thrombi and fibrin fibers on the bare graft, and sporadic cells on the graft coated by chemicals without antibodies were seen.

Conclusion

A universal, OAC method was developed. Our in vitro and in vivo data suggest that the method can be potentially translated into clinical application, e.g., modifying ePTFE grafts to mitigate their thrombotic propensity and possibly provide for improved long-term patency for small-diameter grafts.
Metastatic lymph node targeted CTLA4 blockade: a potent intervention for local and distant metastases with minimal ICI-induced pneumonia
Authors: Mishra Radhika , Sukhbaatar Ariunbuyan , Mori Shiro , Kodama Tetsuya
Published: June 2023

Background

Immune checkpoint blockade (ICB) elicits a strong and durable therapeutic response, but its application is limited by disparate responses and its associated immune-related adverse events (irAEs). Previously, in a murine model of lymph node (LN) metastasis, we showed that intranodal administration of chemotherapeutic agents using a lymphatic drug delivery system (LDDS) elicits stronger therapeutic responses in comparison to systemic drug delivery approaches, while minimizing systemic toxicity, due to its improved pharmacokinetic profile at the intended site. Importantly, the LN is a reservoir of immunotherapeutic targets. We therefore hypothesized that metastatic LN-targeted ICB can amplify anti-tumor response and uncouple it from ICB-induced irAEs.

Methods

To test our hypothesis, models of LN and distant metastases were established with luciferase expressing LM8 cells in MXH10/Mo-lpr/lpr mice, a recombinant inbred strain of mice capable of recapitulating ICB-induced interstitial pneumonia. This model was used to interrogate ICB-associated therapeutic response and immune related adverse events (irAEs) by in vivo imaging, high-frequency ultrasound imaging and histopathology. qPCR and flowcytometry were utilized to uncover the mediators of anti-tumor immunity.

Results

Tumor-bearing LN (tbLN)-directed CTLA4 blockade generated robust anti-tumor response against local and systemic metastases, thereby improving survival. The anti-tumor effects were accompanied by an upregulation of effector CD8T cells in the tumor-microenvironment and periphery. In comparison, non-specific CTLA4 blockade was found to elicit weaker anti-tumor effect and exacerbated ICI-induced irAEs, especially interstitial pneumonia. Together these data highlight the importance of tbLN-targeted checkpoint blockade for efficacious response.

Conclusions

Intranodal delivery of immune checkpoint inhibitors to metastatic LN can potentiate therapeutic response while minimizing irAEs stemming from systemic lowering of immune activation threshold.
CREBZF mRNA nanoparticles suppress breast cancer progression through a positive feedback loop boosted by circPAPD4
Authors: Zhou Boxuan , Xue Jinhua , Wu Runxin , Meng Hongyu , Li Ruixi , Mo Zhaohong , Zhai Hang , Chen Xianyu , Liu Rongqiang , Lai Guie , Chen Xiaohong , Li Taiyuan , Zheng Shiyang
Published: June 2023

Background

Breast cancer (BC) negatively impacts the health of women worldwide. Circular RNAs (circRNAs) are a group of endogenous RNAs considered essential regulatory factor in BC tumorigenesis and progression. However, the underlying molecular mechanisms of circRNAs remain unclear.

Methods

Expression levels of circPAPD4, miR-1269a, CREBZF, and ADAR1 in BC cell lines and tissues were measured using bioinformatics analysis, RT-qPCR, ISH, and IHC. Cell proliferation and apoptosis were measured using CCK8, EdU staining, flow cytometry, and TUNEL assays. Pearson correlation analysis, RNA pull-down, dual-luciferase reporter, and co-immunoprecipitation assays were used to explore the correlation among circPAPD4, miR-1269a, CREBZF, STAT3, and ADAR1. Effects of circPAPD4 overexpression on tumor progression were investigated using in vivo assays. Moreover, CREBZF mRNA delivered by polymeric nanoparticles (CREBZF-mRNA-NPs) was used to examine application value of our findings.

Results

CircPAPD4 expression was low in BC tissues and cells. Functionally, circPAPD4 inhibited proliferation and promoted apoptosis in vitro and in vivo. Mechanistically, circPAPD4 biogenesis was regulated by ADAR1. And circPAPD4 promoted CREBZF expression by competitively binding to miR-1269a. More importantly, CREBZF promoted circPAPD4 expression by suppressing STAT3 dimerization and ADAR1 expression, revealing a novel positive feedback loop that curbed BC progression. Systematic delivery of CREBZF-mRNA-NPs effectively induced CREBZF expression and activated the positive feedback loop of circPAPD4/miR-1269a/CREBZF/STAT3/ADAR1, which might suppress BC progression in vitro and in vivo.

Conclusion

Our findings firstly illustrated that circPAPD4/miR-1269a/CREBZF/STAT3/ADAR1 positive feedback loop mediated BC progression, and delivering CREBZF mRNA nanoparticles suppressed BC progression in vitro and in vivo, which might provide novel insights into therapeutic strategies for breast cancer.
Real-life drug retention rate and safety of rituximab when treating rheumatic diseases: a single-centre Swiss retrospective cohort study
Authors: Dumusc Alexandre , Alromaih Fahad , Perreau Matthieu , Hügle Thomas , Zufferey Pascal , Dan Diana
Published: June 2023

Background

In Switzerland, rituximab (RTX) is licenced for the treatment of rheumatoid arthritis (RA) and ANCA-associated vasculitis (AAV) but is frequently used off-label to treat other auto-immune diseases (AID), especially connective tissue diseases (CTD). We aimed to characterise the use of RTX in AID in a real-life Swiss setting and compare RTX retention rates and safety outcomes between patients treated for RA, CTD and AAV.

Methods

A retrospective cohort study of patients who started RTX in the Rheumatology Department for RA or AID. The RTX retention rate was analysed using Kaplan–Meier survival curves. Occurrences of serious adverse events (SAE), low IgG levels and anti-drug antibodies (ADA) were reported.

Results

Two hundred three patients were treated with RTX: 51.7% had RA, 29.6% CTD, 9.9% vasculitis and 8.9% other AIDs. The total observation time was 665 patient-years. RTX retention probability at 2 years (95%CI) was similar for RA and CTD 0.65 (0.55 to 0.73), 0.60 (0.47 to 0.72) and lower for vasculitis 0.25 (0.09 to 0.45). Survival curves for RTX retention matched closely (p = 0.97) between RA and CTD patients but were lower for patients with vasculitis due to a higher percentage of induced remission. Patients with vasculitis (95%) and CTD (75%) had a higher rate of concomitant glucocorticoid use than RA (60%). Moderate to severe hypogammaglobulinaemia was observed more frequently in patients with vasculitis (35%) than with RA (13%) or CTD (9%) and was associated with an increased risk of presenting a first infectious SAE (HR 2.01, 95% CI 1.04 to 3.91). The incidence rate of SAE was 23.3 SAE/100 patient-years (36% were infectious). When searched, ADAs were observed in 18% of the patients and were detected in 63% of infusions-related SAE. 10 patients died during RTX treatment and up to 12 months after the last RTX infusion, 50% from infection.

Conclusion

RTX retention rates are similar for patients with RA and CTD but lower for those with vasculitis due to more frequent remission. Patients treated with RTX for vasculitis present more SAE and infectious SAE than patients with RA and CTD, potentially due to a higher use of concomitant glucocorticoids and the occurrence of hypogammaglobulinaemia.
Higher β cell death in pregnant women, measured by DNA methylation patterns of cell-free DNA, compared to new-onset type 1 and type 2 diabetes subjects: a cross-sectional study
Authors: Linares-Pineda Teresa María , Gutiérrez-Repiso Carolina , Peña-Montero Nerea , Molina-Vega María , Rubio Fuensanta Lima , Arana María Suárez , Tinahones Francisco J. , Picón-César María José , Morcillo Sonsoles
Published: June 2023

Diabetes is a metabolic disorder of glucose homeostasis in which β cell destruction occurs silently and is detected mainly when symptoms appear. In the last few years, it has emerged a great interest in developing markers capable of detecting pancreatic β cell death focused on improving early diagnosis and getting a better treatment response, mainly in type 1 diabetes. But other types of diabetes would also benefit from early detection of β cell death. Differentially methylated circulating DNA is being studied as minimally invasive biomarker of cell death. We aimed to explore whether the unmethylated/methylated ratio of the insulin and amylin genes might be a good biomarker of β cell death in different types of diabetes. A lower index ∆Ct indicates a higher rate of β-cell death. Plasma samples from subjects without diabetes, pregnant women, pregnant with gestational diabetes (GDM), type 1 diabetes and type 2 diabetes were analyzed. A qPCR reaction with specific primers for both methylated and unmethylated fragments of insulin and amylin genes were carried out. Pregnant women, GDM and non- GDM, showed a higher β-cell death for both markers (∆INS = 3.8 ± 2.1 and ∆Amylin = 8.5 ± 3.6), whereas T1D presented lower rate (∆INS = 6.2 ± 2.1 and ∆Amylin = 10.7 ± 2.9) comparable to healthy subjects. The insulin methylation index was associated with the newborn birth weight (r = 0.46; p = 0.033) and with insulin resistance (r = -0.533; p = 0.027) in the GDM group. The higher rate of β-cell death was observed in pregnant women independently of their metabolic status. These indexes could be a good indicator of β cell death in processes caused by defects on insulin secretion, insulin action, or both.
The impact of perceived social support and coping on distress in a sample of Atlantic Canadian health professional students during COVID-19 compared to pre-COVID peers
Authors: Button Pamela , Fallon Laura , Fowler Ken
Published: June 2023

Purpose

Students pursuing higher education and health professional (HP) programs (e.g., nursing, pharmacy, social work, medicine) experience stressors including academic pressures, workload, developing professional competencies, professional socialization, the hidden curriculum, entering clinical practice and navigating relationships with colleagues. Such stress can have detrimental effects on HP students physical and psychological functioning and can adversely affect patient care. This study examined the role of perceived social support and resilience in predicting distress of Atlantic Canadian HP students during the COVID-19 pandemic and compared the findings to a pre-COVID population of age and sex matched Canadians.

Method

Second year HP students (N = 93) completed a survey assessing distress, perceived social support, and resilience and open-ended questions on student awareness of supports and counselling available to them, their use/barriers to the services, and the impact of COVID-19 on their personal functioning. HP student responses were also compared with age and sex matched Canadian peers from data collected prior to COVID-19.

Results

It was found that HP students reported moderate to severe psychological distress, and while they reported high levels of social support on a measure of perceived social support they also reported that the COVID-19 pandemic made them feel isolated and that they lacked social support. It was found that the sample of HP students reported significantly higher psychological distress than the mean scores of the age and sex matched sample of Canadian peers.

Conclusions

These findings call for creation of more tailored interventions and supports for HP students.
Long-term effectiveness of non-surgical open-bite treatment: a systematic review and meta-analysis
Authors: Theodoridou Maria-Zoi , Zarkadi Athanasia-Eirini , Zymperdikas Vasileios F. , Papadopoulos Moschos A.
Published: June 2023

Background

The etiology of open bite is complex, involving various genetic or environmental factors. Several treatment alternatives have been suggested for the correction of open bite, yet their long-term effectiveness remains controversial.

Objective

To assess the long-term effectiveness of open-bite treatment in treated with non-surgical approaches versus untreated patients, through lateral cephalometric radiographs.

Search methods

Unrestricted search of 16 electronic databases and manual searches up to November 2022.

Selection criteria

Randomized or non-randomized controlled trials reporting on the long-term effects of open-bite treatment through angular lateral cephalometric variables.

Data collection and analysis

Only angular variables on lateral cephalometric radiographs were considered as primary outcomes. For each outcome, the mean differences and 95% confidence intervals were calculated using the random-effects model to consider existing heterogeneity. The revised Cochrane risk-of-bias tool (R.o.B. 2.0) and the risk-of-bias tool for non-randomized studies for interventions (ROBINS-I) were utilized for the randomized and non-randomized trials, respectively.

Results

From the initially identified 26,527 hits, only 6 studies (1 randomized and 5 retrospective controlled trials) were finally included in this systematic review reporting on 244 open-bite individuals (134 patients and 110 untreated controls), while five of them were included in the meta-analyses, assessing either the interval ranging from treatment start to post-retention (T3–T1) or from end of treatment to post-retention period (T3–T2). Regarding the vertical plane, for the T3–T2 interval, no significant differences were found for the assessed skeletal measurements, indicating a relative stability of the treatment results. Similarly, with regard to the T3–T1 interval, no significant differences could be identified for the examined skeletal variables, implying that the produced effects are rather minimal and that the correction of the open bite was performed mainly through dentoalveolar rather than skeletal changes. Further, no significant changes could be identified regarding the inclination of the upper and lower incisors. Only the nasolabial angle was significantly reduced in the treated patients in the long term.

Conclusions

According to existing evidence, the influence of non-surgical treatment of open bite on the skeletal tissues and the inclination of the incisors is rather minimal in the long term, while only the nasolabial angle was significantly reduced.
A model of porcine polymicrobial septic shock
Authors: Zurek-Leffers Finnja Marie , Lehmann Florian , Brabenec Laura , Kintrup Sebastian , Hellenthal Katharina E. M. , Mersjann Kira , Kneifel Felicia , Hessler Michael , Arnemann Philip-Helge , Kampmeier Tim-Gerald , Ertmer Christian , Kellner Patrick , Wagner Nana-Maria
Published: June 2023

Background

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Mortality of patients with sepsis is high and largely unchanged throughout the past decades. Animal models have been widely used for the study of sepsis and septic shock, but translation into effective treatment regimes in the clinic have mostly failed. Pigs are considered as suitable research models for human diseases due to their high comparability and similarity to human anatomy, genetics, and the immune system. We here evaluated the previously reported models of septic shock in pigs and established a novel model of polymicrobial sepsis that meets the clinical criteria of septic shock in pigs.

Materials and methods

The literature search was performed using the keywords “pig”, “sepsis” and “septic shock”. For the establishment of septic shock in n = 10 German landrace pigs, mechanical ventilation was initiated, central venous and arterial lines and invasive hemodynamic monitoring via pulse contour cardiac output measurement (PiCCO) established. Peritoneal polymicrobial faecal sepsis was induced by application of 3 g/kg body weight faeces into the abdominal cavity. Septic shock was defined according to the third international consensus definitions (Sepsis-3). Upon shock, pigs underwent the 1-h bundle for the treatment of human sepsis. Cytokine levels were measured by ELISA.

Results

Published porcine sepsis models exhibited high methodological variability and did not meet the clinical criteria of septic shock. In our model, septic shock developed after an average of 4.8 ± 0.29 h and was associated with a reproducible drop in blood pressure (mean arterial pressure 54 ± 1 mmHg) and significant hyperlactatemia (3.76 ± 0.65 mmol/L). Septic shock was associated with elevated levels of interleukin-6 (IL6) and initial cardiac depression followed by a hyperdynamic phase with significant loss of systemic vascular resistance index after initial resuscitation. In addition, organ dysfunction (acute kidney injury) occurred.

Conclusions

We here established a model of septic shock in pigs that meets the clinical criteria of septic shock utilized in human patients. Our model may thus serve as a reference for clinically relevant sepsis research in pigs.
Development of a bespoke phantom to optimize molecular PET imaging of pituitary tumors
Authors: Gillett Daniel , Marsden Daniel , Crawford Rosy , Ballout Safia , MacFarlane James , van der Meulen Merel , Gillett Bethany , Bird Nick , Heard Sarah , Powlson Andrew S. , Santarius Thomas , Mannion Richard , Kolias Angelos , Harper Ines , Mendichovszky Iosif A. , Aloj Luigi , Cheow Heok , Bashari Waiel , Koulouri Olympia , Gurnell Mark
Published: June 2023

Background

Image optimization is a key step in clinical nuclear medicine, and phantoms play an essential role in this process. However, most phantoms do not accurately reflect the complexity of human anatomy, and this presents a particular challenge when imaging endocrine glands to detect small (often subcentimeter) tumors. To address this, we developed a novel phantom for optimization of positron emission tomography (PET) imaging of the human pituitary gland. Using radioactive 3D printing, phantoms were created which mimicked the distribution of 11C-methionine in normal pituitary tissue and in a small tumor embedded in the gland (i.e., with no inactive boundary, thereby reproducing the in vivo situation). In addition, an anatomical phantom, replicating key surrounding structures [based on computed tomography (CT) images from an actual patient], was created using material extrusion 3D printing with specialized filaments that approximated the attenuation properties of bone and soft tissue.

Results

The phantom enabled us to replicate pituitary glands harboring tumors of varying sizes (2, 4 and 6 mm diameters) and differing radioactive concentrations (2 ×, 5 × and 8 × the normal gland). The anatomical phantom successfully approximated the attenuation properties of surrounding bone and soft tissue. Two iterative reconstruction algorithms [ordered subset expectation maximization (OSEM); Bayesian penalized likelihood (BPL)] with a range of reconstruction parameters (e.g., 3, 5, 7 and 9 OSEM iterations with 24 subsets; BPL regularization parameter (β) from 50 to 1000) were tested. Images were analyzed quantitatively and qualitatively by eight expert readers. Quantitatively, signal was the highest using BPL with β = 50; noise was the lowest using BPL with β = 1000; contrast was the highest using BPL with β = 100. The qualitative review found that accuracy and confidence were the highest when using BPL with β = 400.

Conclusions

The development of a bespoke phantom has allowed the identification of optimal parameters for molecular pituitary imaging: BPL reconstruction with TOF, PSF correction and a β value of 400; in addition, for small (< 4 mm) tumors with low contrast (2:1 or 5:1), sensitivity may be improved using a β value of 100. Together, these findings should increase tumor detection and confidence in reporting scans.
NEMA NU 1-2018 performance characterization and Monte Carlo model validation of the Cubresa Spark SiPM-based preclinical SPECT scanner
Authors: Strugari Matthew E. , DeBay Drew R. , Beyea Steven D. , Brewer Kimberly D.
Published: June 2023

Background

The Cubresa Spark is a novel benchtop silicon-photomultiplier (SiPM)-based preclinical SPECT system. SiPMs in SPECT significantly improve resolution and reduce detector size compared to preclinical cameras with photomultiplier tubes requiring highly magnifying collimators. The NEMA NU 1 Standard for Performance Measurements of Gamma Cameras provides methods that can be readily applied or extended to characterize preclinical cameras with minor modifications. The primary objective of this study is to characterize the Spark according to the NEMA NU 1-2018 standard to gain insight into its nuclear medicine imaging capabilities. The secondary objective is to validate a GATE Monte Carlo simulation model of the Spark for use in preclinical SPECT studies.

Methods

NEMA NU 1-2018 guidelines were applied to characterize the Spark’s intrinsic, system, and tomographic performance with single- and multi-pinhole collimators. Phantoms were fabricated according to NEMA specifications with deviations involving high-resolution modifications. GATE was utilized to model the detector head with the single-pinhole collimator, and NEMA measurements were employed to tune and validate the model. Single-pinhole and multi-pinhole SPECT data were reconstructed with the Software for Tomographic Image Reconstruction and HiSPECT, respectively.

Results

The limiting intrinsic resolution was measured as 0.85 mm owing to a high-resolution SiPM array combined with a 3 mm-thick scintillation crystal. The average limiting tomographic resolution was 1.37 mm and 1.19 mm for the single- and multi-pinhole collimators, respectively, which have magnification factors near unity at the center of rotation. The maximum observed count rate was 15,400 cps, and planar sensitivities of 34 cps/MBq and 150 cps/MBq were measured at the center of rotation for the single- and multi-pinhole collimators, respectively. All simulated tests agreed well with measurement, where the most considerable deviations were below 7%.

Conclusions

NEMA NU 1-2018 standards determined that a SiPM detector mitigates the need for highly magnifying pinhole collimators while preserving detailed information in projection images. Measured and simulated NEMA results were highly comparable with differences on the order of a few percent, confirming simulation accuracy and validating the GATE model. Of the collimators initially provided with the Spark, the multi-pinhole collimator offers high resolution and sensitivity for organ-specific imaging of small animals, and the single-pinhole collimator enables high-resolution whole-body imaging of small animals.
Retinal image quality in myopic children undergoing orthokeratology alone or combined with 0.01% atropine
Authors: Tan Qi , Cho Pauline , Ng Alex L. K. , Cheng George P. M. , Woo Victor C. P. , Vincent Stephen J.
Published: June 2023

Background

The retinal image quality derived from lower-order (LOA) and higher-order aberrations (HOA) for fixed 3-mm and photopic pupil diameters, in children undergoing combined 0.01% atropine and orthokeratology (AOK) versus those receiving orthokeratology alone (OK) over two years was evaluated.

Methods

The visual Strehl ratio based on the optical transfer function (VSOTF), derived from 2nd- to 4th-order terms (LOA and HOA combined), 2nd-order terms (LOA only), and 3rd- to 4th-order terms (HOA only) for fixed 3-mm and natural photopic pupil diameters, was compared between the two treatment groups. The individual Zernike coefficients for a fixed 3-mm pupil size of 2nd- to 4th-orders, root mean square (RMS) of LOA ($${Z}_{2}^{0}$$

Z

2

0

, $${Z}_{2}^{-2}$$

Z

2

-
2

, and $${Z}_{2}^{2}$$

Z

2

2

combined), HOA (3rd to 4th orders inclusive), and Coma ($${Z}_{3}^{-1}{\mathrm{and }Z}_{3}^{1}$$

Z

3

-
1

and
Z

3

1

combined) were also compared between the two groups.

Results

Right eye data of 33 AOK and 35 OK participants were analysed. Under photopic conditions, significantly lower VSOTF based on HOA only was observed in the AOK group compared with that in the OK group at all post-treatment visits (all P < 0.05); however, interactions between HOA and LOA resulted in comparable overall retinal image quality (i.e., VSOTF based on LOA and HOA combined) between the two groups at all visits (all P > 0.05). For a fixed 3-mm pupil size, the VSOTF based on HOA only, LOA only, or HOA and LOA combined, were not different between the two groups (all P > 0.05). AOK participants had slower axial elongation (mean ± SD, 0.17 ± 0.19 mm vs. 0.35 ± 0.20 mm, P < 0.001), a larger photopic pupil size (4.05 ± 0.61 mm vs. 3.43 ± 0.41 mm, P < 0.001) than OK participants, over two years.

Conclusions

HOA profile related to an enlarged pupil size may provide visual signal influencing eye growth in the AOK group.
Assessing abnormal corneal endothelial cells from in vivo confocal microscopy images using a fully automated deep learning system
Authors: Qu Jinghao , Qin Xiaoran , Peng Rongmei , Xiao Gege , Gu Shaofeng , Wang Haikun , Hong Jing
Published: June 2023

Background

The goal of this study is to develop a fully automated segmentation and morphometric parameter estimation system for assessing abnormal corneal endothelial cells (CECs) from LASER in vivo confocal microscopy (IVCM) images.

Methods

First, we developed a fully automated deep learning system for assessing abnormal CECs using a previous development set composed of normal images and a newly constructed development set composed of abnormal images. Second, two testing sets, one with 169 normal images and the other with 211 abnormal images, were used to evaluate the clinical validity and effectiveness of the proposed system on LASER IVCM images with different corneal endothelial conditions, particularly on abnormal images. Third, the automatically calculated endothelial cell density (ECD) and the manually calculated ECD were compared using both the previous and proposed systems.

Results

The automated morphometric parameter estimations of the average number of cells, ECD, coefficient of variation in cell area and percentage of hexagonal cells were 257 cells, 2648 ± 511 cells/mm2, 32.18 ± 6.70% and 56.23 ± 8.69% for the normal CEC testing set and 83 cells, 1450 ± 656 cells/mm2, 34.87 ± 10.53% and 42.55 ± 20.64% for the abnormal CEC testing set. Furthermore, for the abnormal CEC testing set, Pearson’s correlation coefficient between the automatically and manually calculated ECDs was 0.9447; the 95% limits of agreement between the manually and automatically calculated ECDs were between 329.0 and − 579.5 (concordance correlation coefficient = 0.93).

Conclusions

This is the first report to count and analyze the morphology of abnormal CECs in LASER IVCM images using deep learning. Deep learning produces highly objective evaluation indicators for LASER IVCM corneal endothelium images and greatly expands the range of applications for LASER IVCM.
Diversification evidence of bitcoin and gold from wavelet analysis
Authors: Bhuiyan Rubaiyat Ahsan , Husain Afzol , Zhang Changyong
Published: June 2023

To measure the diversification capability of Bitcoin, this study employs wavelet analysis to investigate the coherence of Bitcoin price with the equity markets of both the emerging and developed economies, considering the COVID-19 pandemic and the recent Russia-Ukraine war. The results based on the data from January 9, 2014 to May 31, 2022 reveal that compared with gold, Bitcoin consistently provides diversification opportunities with all six representative market indices examined, specifically under the normal market condition. In particular, for short-term horizons, Bitcoin shows favorably low correlation with each index for all years, whereas exception is observed for gold. In addition, diversification between Bitcoin and gold is demonstrated as well, mainly for short-term investments. However, the diversification benefit is conditional for both Bitcoin and gold under the recent pandemic and war crises. The findings remind investors and portfolio managers planning to incorporate Bitcoin into their portfolios as a diversification tool to be aware of the global geopolitical conditions and other uncertainty in considering their investment tools and durations.
A comparative study of the engagement with written corrective feedback of Chinese private college students
Authors: Pan Jie , Chen Huimei , Yuan Surong
Published: June 2023

Previous research has explored how L2 students with one specific level of English proficiency engage with teacher written corrective feedback (WCF) underpinned by a tripartite dimensional construct of student engagement in the context of Chinese public universities. Yet, scant attention has been paid to how students of differing proficiency levels engage with teacher WCF in a Chinese private college context. Based on a quadripartite construct of student engagement, this case study has explored how L2 Chinese students with high proficiency (HP) and with low proficiency (LP) cognitively, affectively, behaviorally and agentically engage with teacher WCF. Data collected from multiple sources were examined, including drafts of student essays, teacher WCF, student immediate self-retrospective verbal reports and semi-structured interviews. The study has found imbalances among the four dimensions of engagement, with relatively high affective engagement and less extensive cognitive, behavioral and agentic engagement, which was mediated by the interplay of individual factors like language proficiency, writing self-efficacy and learner belief and contextual factors like student–teacher relationship. The findings contribute to an understanding of the multifaceted and dynamic nature of HP and LP students’ engagement with teacher WCF and provide some implications for both school administrators and teachers in Chinese private colleges.
Exploring the ideational explanation for pro-immigrant sentiment: evidence from a South Korean survey
Authors: Park Seungbin , Tuxhorn Kim-Lee
Published: June 2023

A consistent finding in the public opinion literature shows that individuals who attain higher levels of education are more likely to express pro-immigrant attitudes. The ideational hypothesis suggests that ideas learned during formal education drive this empirical relationship. In this article, we develop this hypothesis further by asking, "What types of ideas socialize pro-immigrant attitudes?" We argue that exposure to social theories during higher education promotes social inclusivity and tolerance, leading to positive views toward immigrants. This article draws theoretical insights from attitudinal-based theories of immigrant sentiment to construct a mediation model linking ideas from the classroom to attitudes toward immigrants. Using original data from a population-based survey in South Korea, we examine the relationship between respondents’ prior enrollment in different academic courses and their attitudes toward immigrants. We measure exposure to social theories as enrollment in social science and arts & humanities and find that only social science courses are positively associated with pro-immigrant attitudes. We also examine whether enrollment exhibits indirect effects via previously identified attitudinal determinants of immigrant sentiment. Results from our mediation analysis show that enrollment in social science courses is associated with stronger cosmopolitan views and negatively correlates with isolationist attitudes. In contrast, we find that enrollments in courses unrelated to social theories, like math & science and engineering, are not statistically significant predictors of immigrant attitudes. We interpret our results as observational evidence consistent with ideational-based explanations for pro-immigrant attitudes.