bluuebunny/crossref_metadata_2025 huggingface dataset:
Classification of four pitching styles in Japanese baseball players
Authors: Miyanishi Tomohisa , Shimada Kazushi , Kawamura Takashi , Hirayama Daisaku , Takahashi Keizo , Nagahara Ryu
Published: September 2022

This study aimed to provide normative biomechanical data of baseball delivery styles and to verify an appropriate criterion for quantitatively classifying baseball pitches into four delivery styles. In total, 74 pitches were visually identified by seven coaches into 24 overhand (OS), 17 three-quarter (TS), 21 sidearm (SS) and 12 underhand (US) deliveries. The accuracies of the classifications of the pitches using the arm slot angle ( θAS) and using the combination of trunk lateral tilt ( θT) and upper arm elevation ( θA) angles at release were compared. Average values for θAS were 53.9°, 31.5°, 5.8°, and −34.8° in the OS, TS, SS and US; corresponding values for θT were 31.9°, 15.4°, −0.9°, and −40.1°; and for θA were 39.8°, 16.1°, −6.3°, and−43.0°. Both variables ( θAS and the average of θ'T and θ'A, which corresponded to the projection of each point on the regression line) correctly classified the delivery styles, but the accuracy of the classification using θAS (96%) was higher than that using the average of θ'T and θ'A (89%). There were fewer and smaller overlaps of the ranges of pitches classified using θAS (only 6 pitches between TS and SS (14.9° to 23.0°), which can be considered a buffer zone) compared to the average of θ'T and θ'A. Consequently, θAS seems the most appropriate for classifying baseball pitches into the four delivery styles. The separation points between the four styles were marked by θAS values of 45° (between OS and TS), 19° (between TS and SS) and −13° (between SS and US).
The ISIS® prosthesis in 77 cases of trapeziometacarpal arthritis: outcomes and survival at a minimum follow-up of 5 years
Authors: Fauquette Pierre-Jean , Deken-Delannoy Valérie , Chantelot Christophe , Saab Marc
Published: September 2022

The aim of this study was to determine the clinical and radiographic outcomes and survivorship of the ISIS® (Evolutis™, Briennon, France) trapeziometacarpal prosthesis at a minimum follow-up of 5 years. Of the 77 implants (66 patients) reviewed at a mean follow-up of 107.5 months, pain and function had improved significantly. Fourteen cups (19%) and three stems (4%) appeared to have loosened on radiographs. Loosening occurred more often with cemented cups than screwed cups ( p = 0.0342). In five cases, the prosthesis was removed and revised by trapeziectomy and interposition: four were cemented cups (three loosening, one trapezium fracture) and one was a loosened metacarpal stem. A single case of dislocation occurred during the follow-up period. The survival rate was 94% (95% CI: 85 to 97). The ISIS® prosthesis is a reliable implant for treating disabling thumb basal joint arthritis, with a low complication rate and long-lasting clinical and functional improvements. Using a screwed trapezial cup instead of a cemented one appears to prevent loosening and the need for surgical revision.

Level of evidence: IV
Residual flexion deformity after scaphoid nonunion surgery: 7-year follow-up study
Authors: Schriever Thorsten , Wilcke Maria
Published: September 2022

The clinical implication of a residual flexion deformity following surgery for scaphoid nonunion is unclear. Sixty-three patients who underwent scaphoid nonunion surgery were assessed after a mean of 7 years (range 5–10) to analyse the outcomes based on the presence of residual scaphoid deformity. Primary outcome was Disabilities of the Arm, Shoulder and Hand score. Secondary outcomes were Patient-Rated Wrist Evaluation score, wrist range of motion and strength. Patients were dichotomized to residual deformity or no deformity. Scaphoid deformity was calculated from CT scans based on the median difference between the height–length ratio of the operated versus the uninjured scaphoid. There were no differences between residual deformity ( n = 33) and no deformity ( n = 30) in any outcome variables, except for wrist extension which was slightly worse in the deformity group. The deformity group had a greater number of radiographic osteoarthritis, but all cases were mild, and osteoarthritis did not correlate to a worse outcome. We conclude that residual scaphoid deformity has no relevant negative impact on mid-term wrist function.

Level of evidence: IV
Moderate and High Sport Specialization Level in Ice Hockey Athletes Is Associated With Symptomatic Cam Deformity
Authors: Nguyen Mindy , Bixby Sarah , Yen Yi-Meng , Miller Patricia , Stracciolini Andrea
Published: September 2022

Background:

There is a known association between ice hockey and cam deformity in growing athletes. Similarly, the association between sport specialization and overuse injury in youth athletes has been well established. Limited research exists examining the relationship between cam deformity and sport specialization.

Hypothesis/Purpose:

Our hypothesis was that there would be a positive association with cam deformity and sport specialization category.

Study Design:

Retrospective chart review and cross-sectional questionnaire study.

Level of Evidence:

Level 4.

Methods:

Study participants included athletes aged 15 to 25 years with symptomatic femoroacetabular impingement (FAI) and considered ice hockey as their primary sport. All participants had completed Dunn lateral radiographs or hip magnetic resonance imaging as part of their clinical evaluation. All participants completed a survey regarding sport specialization level. Multivariable linear regression analysis controlling for sex was used to analyze the association between degree of sport specialization, age of sport specialization, position played, and level played. Comparisons in radiographic parameters across ice hockey groups were conducted using Student t tests and chi-square tests.

Results:

Sixty-six ice hockey participants made up the cohort. The majority reported high sport specialization (41/66, 62%). The mean age of sport specialization was 10.7 years (SD 3.5). Participants with moderate specialization had 25 times the odds of a cam deformity (odds ratio [OR] 25.2; 95% CI 1.5-410.7; P = 0.02) and those with high specialization had 9 times the odds of cam deformity (OR 9.3; 95% CI 1.2-74.2; P = 0.04) compared with those with a low degree of specialization, controlling for patient sex. No association was detected between the age of specialization and the likelihood of cam deformity when controlling for patient sex.

Conclusion:

Level of sport specialization was associated with a cam deformity in this cohort of youth ice hockey athletes.

Clinical Relevance:

This study suggests that an association exists.
Glitching computational urban subjects
Authors: Pallett Helen
Published: September 2022

This commentary explores the epistemological vector of glitch/glitch proposed by Leszczynski and Elwood for the study of events which are non-performative or 'do not compute' in computational cities. There is a particular focus on the potential for this disposition to foreground more marginalised urban and computational subjects and their experiences. It argues that glitch/glitch can help analysts to identify and draw attention to instances where these subjects are able to more fully embody the role of citizen.
Understanding Student-Run Health Initiatives in the Context of Community-Based Services: A Concept Analysis and Proposed Definitions
Authors: Nagel Daniel A. , Naccarato Taylor T. , Philip Mark T. , Ploszay Victoria K. , Winkler Janice , Sanchez-Ramirez Diana C. , Penner Jamie L.
Published: September 2022

Background:

Student-run health initiatives in the community setting have been utilized to provide practical experience for undergraduate students to develop professional competencies, gain exposure to diverse populations, and to engage in activities of social accountability. There is much literature on student-run health initiatives; however, there is no consensus on a definition of this concept or a comprehensive synthesis of the literature that describes student-run health initiatives offered by students in pre-licensure healthcare education programs.

Purpose:

To provide a concept analysis of, and propose a definition for, student-run health initiatives that provide community-based services for students during pre-licensure health discipline education.

Methods:

A systematic literature search and review process was used to identify and synthesize peer-reviewed articles from 7 academic databases covering a range of pre-licensure health disciplines and education. Walker and Avant’s framework for concept analysis was used to guide exploration of attributes, antecedents and consequences of student-run initiatives, and to inform development of a definition for this concept.

Results:

The review yielded 222 articles for data extraction and represented 17 distinct pre-licensure health disciplines, 18 health-related disciplines, and a range of other baccalaureate and graduate programs. Our analysis revealed 16 definitions, 5 attributes, 6 antecedents, and consequences identified for student-run health initiatives. Attributes were Provision of Service, Service is Free, Target Clientele, Volunteerism, and Student Governance. Antecedents included Purpose/Rationale, Affiliation with Academic Unit, Location and Partnerships, Funding and Resources, Professional Oversight, and Preparation for Student Role. Consequences were improved access to services and outcomes for clients; competency development, personal gains and interprofessional learning for students; and positive outcomes for broader systems, such as decrease of service utilization and cost/benefit.

Conclusions:

There was no clear conceptual definition for student-run health initiatives, but many defining characteristics and well-described exemplars in the literature. Given the variations in purpose and scope of these initiatives, particularly to distinguish degree of students’ roles in operations and the involvement of academic institutions, we propose 3 distinct conceptual definitions: student-run, student-led, and student-infused health initiatives.
Perceived safety of MRI units in the two public hospitals within the central region of South Africa: A pilot study among four MR staff
Authors: Rathebe Phoka C
Published: September 2022

Magnetic resonance scanners are considered safe but comes with substantive safety risks to patients seeking radiological diagnostics and health care professionals. This pilot study aimed to assess the safety compliance of MRI units commonly used in the clinical diagnostic imaging of two public hospitals in South Africa. Structured interviews were conducted with four MRI staff assigned to work in the 1.5 and 3.0 T MRI units. Their responses were benchmarked with ACR MR Safety guideline of 2019 to assess any safety compliance deviations. Thematic analysis was conducted by evaluating responses per themes and further expanding on comments provided on Yes or No options. There were few major shortfalls identified that include outdated safety policies, inadequate screening, nonexistence of demarcations and lack of training of MR and non-MR personnel of MRI safety. These challenges could be eliminated by introducing a comprehensive occupational health and safety program, specific to the MRI units.
Micro-mechanisms and Macro-effects: How Structural Change and Institutional Context Affect Income Inequality in Rich Democracies
Authors: Mahutga Matthew C. , Curran Michaela
Published: September 2022

In this article, the authors develop a taxonomy of the micro-mechanisms by which well-studied macro-level structural changes and institutional contexts distribute income and assess this taxonomy empirically. The authors’ taxonomy explicates five distinct micro-mechanisms that operate inside and outside of the labor market to either increase (premiums) or decrease (penalties) income shares. Their analysis of total household income among over 1 million households across 14 countries and 39 years yields four contributions. First, the findings provide “middle-range” evidence regarding the specific micro-mechanisms of each macro-process. Second, premiums are more common micro-mechanisms than penalties, consistent with the phenomenon of “upper-tail polarization” observed in the literature. Third, workplace authority is the most important micro-mechanism operating in the labor market, but the top-income premium is the most important micro-mechanism overall. Finally, the relative importance of the top-income premium is greater for structural change than institutional context, which portends demands for new forms of redistribution.
When Environmental Inequality Racialized: Historical Evidence from Providence, Rhode Island
Authors: Frickel Scott , Tollefson Jonathan
Published: September 2022

The authors use multiple logistic regression techniques to investigate whether individuals’ occupation, nativity, race, and ethnicity predict residential proximity to large-scale energy infrastructure in Providence, Rhode Island, in 1880 and 1930. Results indicate that in 1880, environmental risks associated with urban energy infrastructure fell most heavily on working-class immigrants; by 1930, those risks disproportionately affected the city’s small population of African American and Latinx residents. Across this 50-year span, environmental inequality racialized such that Providence’s gas lines effectively came to describe the city’s sharpening color line. The article concludes with a discussion of how a historical perspective can help clarify the dynamic relationship between environmental risk and urbanization in the (re)production of racial, ethnic, and economic inequality.
The Perpetuation of Caste: An Exposition of Merleau-Ponty’s Classic Text—Humanism and Terror—to Elaborate Buried Possibilities in the Thought of Ambedkar
Authors: Sampath Rajesh
Published: September 2022

In our investigation into the persistence of caste, we attempt to build a preliminary framework of analysis to set the stage for a reading of Ambedkar’s posthumously published, unfinished manuscript, Buddha or Karl Marx. We see an uncanny resemblance between Ambedkar’s mid-twentieth century context in the newly independent democratic society of post-colonial India and that of French philosopher Maurice Merleau-Ponty’s post-Second World War Western European context and his intriguing attempt to justify communist violence. Ultimately, we argue that although one cannot use one context to understand the other on how to realise a communist revolution within a democratic, industrial capitalist society, there are lessons to be learned from both with regard to problems in the philosophy of history, historical time, and epochal shifts. The ultimate question is whether a new society that has no precedent in either the West or the East and everything in between is imaginable. Ultimately this article sets up the possibility to read Ambedkar’s text while returning to Marx’s (1990) Capital Vol. 1 itself, particularly on the ‘primitive accumulation’. Then we can be in a position to philosophise in the margins and beyond where Ambedkar leaves off on his brief but brilliant essay, Buddha or Karl Marx.
Unequal geographies of urban mining: E-waste management in London, Sao Paulo and Accra
Authors: Lopes dos Santos Kauê
Published: September 2022

E-waste generation has been increasing on a global scale in the past decades, reaching the unprecedented figure of 53.6 million tons (Mt) in 2019 and raising concerns and debates around the risks, challenges and opportunities related to its management. Collecting and recycling this type of waste – activities that are encompassed in the term ‘urban mining’ – should happen under proper environmental and social conditions, to ensure that reverse logistic system and the circular economy become a reality over the globe. Through exploratory qualitative research, this article establishes a comparative analysis among the multiple actors – operating both formal and informally – responsible for e-waste management in London Larger Urban Zone (LLUZ), Sao Paulo Macrometropolis (SPMM) and Greater Accra Region (GAR). These case studies are the most dynamic functional urban areas (FUA) of their respective national territories and integrate the world system with different roles: the United Kingdom representing the core, Brazil the semi-periphery and Ghana the periphery. Findings uncover the broad spectrum of ways in which e-waste can be recycled and confirm the relevance of political economy for understanding the regulatory and technological aspects of its management in different geographic contexts. The article also suggests a reflection on the ‘urban economy recommodization’, a process that is adding new contents to the urban space.
Baclofen-associated neurophysiologic target engagement across species in fragile X syndrome
Authors: Jonak Carrie R. , Pedapati Ernest V. , Schmitt Lauren M. , Assad Samantha A. , Sandhu Manbir S. , DeStefano Lisa , Ethridge Lauren , Razak Khaleel A. , Sweeney John A. , Binder Devin K. , Erickson Craig A.
Published: September 2022

Background

Fragile X syndrome (FXS) is the most common inherited form of neurodevelopmental disability. It is often characterized, especially in males, by intellectual disability, anxiety, repetitive behavior, social communication deficits, delayed language development, and abnormal sensory processing. Recently, we identified electroencephalographic (EEG) biomarkers that are conserved between the mouse model of FXS (Fmr1 KO mice) and humans with FXS.

Methods

In this report, we evaluate small molecule target engagement utilizing multielectrode array electrophysiology in the Fmr1 KO mouse and in humans with FXS. Neurophysiologic target engagement was evaluated using single doses of the GABAB selective agonist racemic baclofen (RBAC).

Results

In Fmr1 KO mice and in humans with FXS, baclofen use was associated with suppression of elevated gamma power and increase in low-frequency power at rest. In the Fmr1 KO mice, a baclofen-associated improvement in auditory chirp synchronization was also noted.

Conclusions

Overall, we noted synchronized target engagement of RBAC on resting state electrophysiology, in particular the reduction of aberrant high frequency gamma activity, across species in FXS. This finding holds promise for translational medicine approaches to drug development for FXS, synchronizing treatment study across species using well-established EEG biological markers in this field.

Trial registration

The human experiments are registered under NCT02998151.
A statistical network pre-processing method to improve relevance and significance of gene lists in microarray gene expression studies
Authors: Agapito Giuseppe , Milano Marianna , Cannataro Mario
Published: September 2022

Background

Microarrays can perform large scale studies of differential expressed gene (DEGs) and even single nucleotide polymorphisms (SNPs), thereby screening thousands of genes for single experiment simultaneously. However, DEGs and SNPs are still just as enigmatic as the first sequence of the genome. Because they are independent from the affected biological context. Pathway enrichment analysis (PEA) can overcome this obstacle by linking both DEGs and SNPs to the affected biological pathways and consequently to the underlying biological functions and processes.

Results

To improve the enrichment analysis results, we present a new statistical network pre-processing method by mapping DEGs and SNPs on a biological network that can improve the relevance and significance of the DEGs or SNPs of interest to incorporate pathway topology information into the PEA. The proposed methodology improves the statistical significance of the PEA analysis in terms of computed p value for each enriched pathways and limit the number of enriched pathways. This helps reduce the number of relevant biological pathways with respect to a non-specific list of genes.

Conclusion

The proposed method provides two-fold enhancements. Network analysis reveals fewer DEGs, by selecting only relevant DEGs and the detected DEGs improve the enriched pathways’ statistical significance, rather than simply using a general list of genes.
Risk stratification and pathway analysis based on graph neural network and interpretable algorithm
Authors: Liang Bilin , Gong Haifan , Lu Lu , Xu Jie
Published: September 2022

Background

Pathway-based analysis of transcriptomic data has shown greater stability and better performance than traditional gene-based analysis. Until now, some pathway-based deep learning models have been developed for bioinformatic analysis, but these models have not fully considered the topological features of pathways, which limits the performance of the final prediction result.

Results

To address this issue, we propose a novel model, called PathGNN, which constructs a Graph Neural Networks (GNNs) model that can capture topological features of pathways. As a case, PathGNN was applied to predict long-term survival of four types of cancer and achieved promising predictive performance when compared to other common methods. Furthermore, the adoption of an interpretation algorithm enabled the identification of plausible pathways associated with survival.

Conclusion

PathGNN demonstrates that GNN can be effectively applied to build a pathway-based model, resulting in promising predictive power.
A pan-cancer analysis of collagen VI family on prognosis, tumor microenvironment, and its potential therapeutic effect
Authors: Li Xiang , Li Zeng , Gu Shanzhi , Zhao Xinhan
Published: September 2022

Background

Collagen VI family (COL6A) is a major member of extracellular matrix protein. There is accumulating evidence that COL6A is involved in tumorigenesis and tumor progression. In this study, we performed a systematic analysis of COL6A in pan-cancer based on their molecular features and clinical significance.

Methods

Based on updated public databases, we integrated several bioinformatics analysis methods to investigate the expression levels of COL6A as well as the relationship between their expression and patient survival, immune subtypes, tumor microenvironment, stemness scores, drug sensitivity, and DNA methylation.

Results

The expression levels of COL6A members varied in different cancers, suggesting their expression was cancer-dependent. Among COL6A members, COL6A1/2/3 were predicted poor prognosis in specific cancers. Furthermore, COL6A1/2/3 expression levels revealed a clear correlation with immune subtypes, and COL6A1/2/3 were associated with tumor purity, that is, gene expression levels were generally higher in tumors with higher stromal scores and immune scores. COL6A1/2/3 had a significantly negative correlation with RNA stemness scores, and meanwhile they were also related to DNA stemness scores in different degrees. In addition, the expression of COL6A1/2/3 was significantly related to drug sensitivity of cancer cells. Finally, our study revealed that COL6A1/2/3 expression was mainly negatively correlated with gene methylation, and the methylation levels showed remarkable differences in various cancers.

Conclusions

These findings highlight both the similarities and differences in the molecular characteristics of COL6A members in pan-cancer, and provide comprehensive insights for further investigation into the mechanism of COL6A.
Genomic distribution and context dependent functionality of novel WRKY transcription factor binding sites
Authors: Arndt Laureen Christin , Heine Susanne , Wendt Lino , Wegele Emilia , Schomerus Jan Titus , Schulze Jutta , Hehl Reinhard
Published: September 2022

Background

The WT-boxes NGACTTTN are novel microbe-associated molecular pattern (MAMP)-responsive cis-regulatory sequences. Many of them are uncommon WRKY transcription factor (TF) binding sites.

Results

To understand their functional relevance, a genomic distribution analysis of the 16 possible WT-boxes and a functional analysis of a WT-box rich promoter was done. The genomic distribution analysis shows an enrichment of specific WT-boxes within 500 bp upstream of all Arabidopsis thaliana genes. Those that harbour a T 5′ to the core sequence GACTTT can also be part of the classic WRKY binding site the W-box TTGACT/C. The MAMP-responsive gene ATEP3, a class IV chitinase, harbours seven WT-boxes within its 1000 bp upstream region. In the context of synthetic promoters, the four proximal WT-boxes confer MAMP responsivity while the three WT-boxes further upstream have no effect. Rendering the nucleotides adjacent and in the vicinity of the WT-box core sequence reveals their functional importance for gene expression. A 158 bp long ATEP3 minimal promoter harbouring the two WT-boxes CGACTTTT, confers WT-box-dependent basal and MAMP-responsive reporter gene expression. The ATEP3 gene is a proposed target of WRKY50 and WRKY70. WRKY50 negatively regulates MAMP responsivity of the two WT-boxes CGACTTTT, while WRKY70 activates gene expression in a WT-box dependent manner. Both WRKY factors bind directly to the WT-box CGACTTTT.

Conclusion

In summary, WT-boxes are enriched in promoter regions and comprise novel and uncommon WRKY binding sites required for basal and MAMP-induced gene expression. WT-boxes not being part of a W-box may be a missing link for WRKY target gene prediction when these genes do not harbour a W-box.
Identification and function analysis of yellow-leaf mutant (YX-yl) of broomcorn millet
Authors: Wang Yushen , Wang Junjie , Chen Liqing , Meng Xiaowei , Zhen Xiaoxi , Liang Yinpei , Han Yuanhuai , Li Hongying , Zhang Bin
Published: September 2022

Background

Broomcorn millet is highly tolerant to drought and barren soil. Changes in chlorophyll content directly affect leaf color, which subsequently leadsleading to poor photosynthetic performance and reduced crop yield. Herein, we isolated a yellow leaf mutant (YX-yl) using a forward genetics approach and evaluated its agronomic traits, photosynthetic pigment content, chloroplast ultrastructure, and chlorophyll precursors. Furthermore, the molecular mechanism of yellowing was explored using transcriptome sequencing.

Results

The YX-yl mutant showed significantly decreased plant height and low yield. The leaves exhibited a yellow-green phenotype and poor photosynthetic capacity during the entire growth period. The content of chlorophyll a, chlorophyll b, and carotenoids in YX-yl leaves was lower than that in wild-type leaves. Chlorophyll precursor analysis results showed that chlorophyll biosynthesis in YX-yl was hindered by the conversion of porphobilinogen to protoporphyrin IX. Examination of chloroplast ultrastructure in the leaves revealed that the chloroplasts of YX-yl accumulated on one side of the cell. Moreover, the chloroplast structure of YX-yl was degraded. The inner and outer membranes of the chloroplasts could not be distinguished well. The numbers of grana and grana thylakoids in the chloroplasts were low. The transcriptome of the yellowing mutant YX-yl was sequenced and compared with that of the wild type. Nine chlorophyll-related genes with significantly different expression profiles were identified: PmUROD, PmCPO, PmGSAM, PmPBDG, PmLHCP, PmCAO, PmVDE, PmGluTR, and PmPNPT. The proteins encoded by these genes were located in the chloroplast, chloroplast membrane, chloroplast thylakoid membrane, and chloroplast matrix and were mainly involved in chlorophyll biosynthesis and redox-related enzyme regulation.

Conclusions

YX-yl is an ideal material for studying pigment metabolism mechanisms. Changes in the expression patterns of some genes between YX-yl and the wild type led to differences in chloroplast structures and enzyme activities in the chlorophyll biosynthesis pathway, ultimately resulting in a yellowing phenotype in the YX-yl mutant. Our findings provide an insight to the molecular mechanisms of leaf color formation and chloroplast development in broomcorn millet.
Health care professionals’ perspectives on the utilisation of a remote surveillance and care tool for patients with COVID-19 in general practice: a qualitative study
Authors: Hoffmann Mariell , Stengel Sandra , Szecsenyi Joachim , Peters-Klimm Frank
Published: September 2022

Background

Most COVID-19 patients with severe symptoms are treated in hospitals. General practices are responsible for assessing most ambulatory patients. However, they face several challenges managing COVID-19 patients, and those with non-COVID-19 conditions. In April of 2020, we designed a software tool for the structured surveillance of high-risk home-quarantined COVID-19 patients in general practice (CovidCare) including several telephone monitorings, in order to support general practices and early identification of severe courses. This study presents the qualitative results of a mixed-methods process evaluation study on CovidCare.

Methods

In a qualitative process evaluation study conducted between March and May 2021, we explored the perspectives of seven general practitioners (GPs) and twelve VERAHs (medical care assistants with special training) on CovidCare using semi-structured interviews based on the RE-AIM framework (reach, effectiveness, adoption, implementation, maintenance). We used deductive qualitative content analysis employing the RE-AIM framework to assess the utilisation and implementation of CovidCare.

Results

Overall, most health care professionals were satisfied with CovidCare. They highlighted 1) a good orientation for the management of COVID-19 patients, especially due to a high level of uncertainty at the beginning of the pandemic, 2) the possibility to gain new knowledge, and 3) the structured data collection as facilitators for the implementation of CovidCare. Moreover, CovidCare reduced the workload for GPs while some VERAHs perceived a higher workload as they were responsible for large parts of the CovidCare management. However, CovidCare positively affected the VERAHs’ job satisfaction as most patients provided positive feedback and felt less anxious about coping with their disease. Previous experience with the software and an easy integration into daily practice were considered to be crucial utilisation drivers. Time and personnel resources were identified as major barriers. To further improve CovidCare, participants suggested a less comprehensive version of CovidCare, the expansion of inclusion criteria as well as an app for the patients’ self-management.

Conclusion

The COVID-19 surveillance and care tool for COVID-19 patients with increased risk was perceived as useful by GPs and VERAHs. Supportive remote health care tools such as CovidCare are a viable means to maintain comprehensive and continuous health care during a pandemic and may strengthen the primary care system.

Trial registration

German Clinical Trials Register DRKS00022054; date of registration: 02/06/2020.
Altered gut microbiota and its metabolites correlate with plasma cytokines in schizophrenia inpatients with aggression
Authors: Deng Hongxin , He Lei , Wang Chong , Zhang Teng , Guo Hua , Zhang Hongwei , Song Yanning , Chen Bangtao
Published: September 2022

Background

The pathophysiological mechanisms of aggression are manifold and they may closely interconnect. Current study aimed to determine the gut microbiota and its metabolites, and clarify their correlations with inflammation, oxidation, leaky gut and clinical profiles underlying aggression in schizophrenia (ScZ).

Methods

Serum and stool specimens from ScZ inpatients with (ScZ-Ag, 25 cases) and without aggression (NScZ-Ag, 25 cases) were collected. Systemic inflammation, oxidation and leaky gut biomarkers were determined by ELISA, gut microbiota by 16S rRNA sequencing, short-chain fatty acids (SCFAs) by gas chromatography-mass spectrometry analysis and neurotransmitters by liquid chromatograph mass spectrometry analysis.

Results

Significantly higher systemic pro-inflammation, pro-oxidation and leaky gut biomarkers were observed in ScZ-Ag than NScZ-Ag group (all P<0.001). Compared to NScZ-Ag group, the alpha-diversity and evenness of fecal bacterial community were much lower, the abundance of fecal genera Prevotella was significantly increased, while that Bacteroides, Faecalibacterium, Blautia, Bifidobacterium,Collinsella and Eubacterium_coprostanoligenes were remarkably reduced in ScZ-Ag group (all corrected P<0.001). Meanwhile, 6 SCFAs and 6 neurotransmitters were much lower in ScZ-Ag group (all P<0.05). Finally, a few strongly positive or negative correlations among altered gut microbiota, SCFAs, systemic pro-inflammation, leaky gut, pro-oxidation and aggression severity were detected.

Conclusions

These results demonstrate that pro-inflammation, pro-oxidation and leaky gut phenotypes relating to enteric dysbacteriosis and microbial SCFAs feature the aggression onset or severity in ScZ individuals.
Country of birth and non-small cell lung cancer incidence, treatment, and outcomes in New South Wales, Australia: a population-based linkage study
Authors: Little Alana , Roder David , Zhao George W. , Challam Sheetal , Malalasekera Ashanya , Currow David
Published: September 2022

Objective

To compare treatment within 12 months of diagnosis, and survival by country of birth for people diagnosed with invasive non-small cell lung cancer (NSCLC) in New South Wales (NSW), Australia.

Design, patients, and setting

A population-based cohort study of NSW residents diagnosed with NSCLC in 2003–2016 using de-identified linked data from the NSW Cancer Registry, NSW Admitted Patient Data collection, Emergency Departments, Medicare Benefits and Pharmaceutical Benefits Scheme, and National Death Index.

Main outcome measures

Odds of receiving any treatment, surgery, systemic therapy, or radiotherapy respectively, in the 12 months following diagnosis were calculated using multivariable logistic regression. The hazard of death (all-cause) at one- and five-years following diagnosis was calculated using multivariable proportional hazards regression.

Results

27,114 People were recorded with NSCLC in the 14-year study period. Higher percentages of older males from European countries applied in the earlier years, with a shift to younger people from South East Asia, New Zealand, and the Middle East. Adjusted analyses indicated that, compared with the Australian born, people from European countries were more likely to receive treatment, and, specifically surgery. Also, people from Asian countries were more likely to receive systemic therapy but less likely to receive radiotherapy. Survival at one- and five-years following diagnosis was higher for people born in countries other than Australia, New Zealand the United Kingdom and Germany.

Conclusions

Variations exist in treatment and survival by country of birth in NSW. This may be affected by differences in factors not recorded in the NSW Registry, including use of general health services, family histories, underlying health conditions, other intrinsic factors, and cultural, social, and behavioural influences.
Color stability and surface roughness of ormocer- versus methacrylate-based single shade composite in anterior restoration
Authors: Ebaya Maha M. , Ali Ashraf I. , El-Haliem Huda Abed , Mahmoud Salah Hasab
Published: September 2022

Background

The blending ability of universal shade composites and their stability in the oral environment are of great concern in restoring anterior teeth. This study aims to evaluate and compare the color stability and surface roughness of two single-shade composite restorations, ormocer-based composite (OBC) and methacrylate resin-based composite (RBC), after storing them in different staining media.

Materials and methods

In this study, two universal shade composite restorative materials were tested: a nanohybrid OBC (Admira fusion X-tra, Voco) and a supra-nanofilled RBC (Omnichroma, Toukyama). In total, 60 cylindrical centralized cavities (diameter: 5 mm, depth: 2 mm) were prepared in sound extracted-human central incisors and divided into two equal groups according to the restorative material used (n = 30). According to the storage media, the teeth of each group were divided into three subgroups (n = 10): artificial saliva, black tea, and cola. The restoration color was evaluated for all teeth at baseline and after four weeks of storage. The color stability (∆E) was measured using a reflective spectrophotometer (X-Rite, model RM200QC, Neu-Isenburg, Germany). The surface roughness (Ra) was evaluated using three-dimensional optical profilometry (Wyko, Model NT 1100, Veeco, Tucson, USA). Additionally, the extracted data were analyzed using two-way analysis of variance (ANOVA), one-way ANOVA and Student’st-test.

Results

In the baseline evaluation, there were no statistically significant differences with respect to color matching or surface roughness results between the two studied restorative materials. However, the differences were statistically significant after storing them in different media.

Conclusion

Universal composites showed satisfactory color matching with different teeth colors and accepted surface smoothness, whereas the aging procedure exerted a negative effect on their color stability and surface characteristics.
Students’ perception and learning experience in the first medical clerkship
Authors: Gottschalk Marc , Albert Christian , Werwick Katrin , Spura Anke , Braun-Dullaeus Ruediger C. , Stieger Philipp
Published: September 2022

Background

The German clerkship (“Famulatur”) is the first phase in medical education, in which students learn from a physician’s perspective. According to the German Licensing Regulations for Physicians, students shall “familiarise” with providing care. However, specific learning objectives for the clerkship are not defined, although the acquisition of different competencies is implicitly demanded. Therefore, an additional understanding of the clerkship students’ learning experience is needed. The goal of this study is to explore the student’s learning perspective and experiences in the clerkship.

Methods

Twelve guideline-based interviews were conducted with third year medical students. All participants completed their first clerkship. A qualitative content analysis was performed. The inductively identified categories were transferred into a quantitative questionnaire using a 5-point Likert-scale to explore their relevance in a validation cohort. The questionnaire was completed by 222 clinical students of the Otto-von-Guericke-Universität Magdeburg.

Results

The qualitative analysis led to 26 individual items assigned to 4 main categories that describe the clerkship experience: 1) “coping with insecurities”, 2) “the clerkship as a social arrangement”, 3) “the clerkship as a learning opportunity” and 4) “the clerkship as a teaching opportunity”. In the quantitative validation cohort, category one yielded a well-balanced result (median 3 = “neither agree nor disagree”; IQR 2–4), items addressed in categories 2–4 were generally supported by the students, predominantly selecting “strongly agree” or “agree” (Median 2; IQR 1–2 for each category). Students rated the role of the clinical team as especially important for their learning success and feared exclusion or negative reactions.

Conclusions

The medical clerkship provides an institutional, professional, and social framework, in which students are learning. Insecurities arose from curricular inconsistencies, a high dependency on the clinical team as well as the absence of specific learning objectives. Therefore, a better curricular integration regarding the semester structure and the learning objectives of the German clerkship is needed.
Using Normalisation Process Theory (NPT) to develop an intervention to improve referral and uptake rates for self-management education for patients with type 2 diabetes in UK primary care
Authors: Turner Jessica , Martin Graham , Hudson Nicky , Shaw Liz , Huddlestone Lisa , Weis Christina , Northern Alison , Schreder Sally , Davies Melanie , Eborall Helen
Published: September 2022

Background

Referral and uptake rates of structured self-management education (SSME) for Type 2 diabetes (T2DM) in the UK are variable and relatively low. Research has documented contributing factors at patient, practitioner and organisational levels. We report a project to develop an intervention to improve referral to and uptake of SSME, involving an integrative synthesis of existing datasets and stakeholder consultation and using Normalisation Process Theory (NPT) as a flexible framework to inform the development process.

Methods

A three-phase mixed-methods development process involved: (1) synthesis of existing evidence; (2) stakeholder consultation; and (3) intervention design. The first phase included a secondary analysis of data from existing studies of T2DM SSME programmes and a systematic review of the literature on application of NPT in primary care. Influences on referral and uptake of diabetes SSME were identified, along with insights into implementation processes, using NPT constructs to inform analysis. This gave rise to desirable attributes for an intervention to improve uptake of SSME. The second phase involved engaging with stakeholders to prioritise and then rank these attributes, and develop a list of associated resources needed for delivery. The third phase addressed intervention design. It involved translating the ranked attributes into essential components of a complex intervention, and then further refinement of components and associated resources.

Results

In phase 1, synthesised analysis of 64 transcripts and 23 articles generated a longlist of 46 attributes of an embedded SSME, mapped into four overarching domains: valued, integrated, permeable and effectively delivered. Stakeholder engagement in phase 2 progressed this to a priority ranked list of 11. In phase 3, four essential components attending to the prioritised attributes and forming the basis of the intervention were identified: 1) a clear marketing strategy for SSME; 2) a user friendly and effective referral pathway; 3) new/amended professional roles; and 4) a toolkit of resources.

Conclusions

NPT provides a flexible framework for synthesising evidence for the purpose of developing a complex intervention designed to increase and reduce variation in uptake to SSME programmes in primary care settings.
Key factors predicting suspected severe malaria case management and health outcomes: an operational study in the Democratic Republic of the Congo
Authors: Okitawutshu Jean , Signorell Aita , Kalenga Jean-Claude , Mukomena Eric , Delvento Giulia , Burri Christian , Mwaluke Fatou , Buj Valentina , Sangare Moulaye , Luketa Sylvie , Brunner Nina , Lee Tristan , Hetzel Manuel , Lengeler Christian , Tshefu Antoinette
Published: September 2022

Background

Evidence suggests that pre-referral Rectal Artesunate (RAS) can be a life-saving intervention for severe malaria in remote settings in Africa. Recognition of danger signs indicative of severe malaria is critical for prompt and appropriate case management.

Methods

This was an observational study conducted in three Health Zones of the Democratic Republic of the Congo to determine the distribution of dangers signs for severe malaria and assess their impact on RAS use, referral completion, injectable treatment and ACT provision, and health outcomes including death. An individual-level analysis was carried out, using multilevel-mixed effects logistic regression models. Severely ill febrile children < 5 years seeking care from community-based healthcare providers were recruited into a patient surveillance system based on the presence of key danger signs. Clinical and case management data were collected comprehensively over a 28 days period. Treatment seeking was elicited and health outcomes assessed during 28 days home visits.

Results

Overall, 66.4% of patients had iCCM general danger signs. Age of 2–5 years and iCCM general danger signs predicted RAS use (aOR = 2.77, 95% CI 2.04–3.77). RAS administration positively affected referral completion (aOR = 0.63, 95% CI 0.44–0.92). After RAS rollout, 161 children died (case fatality ratio: 7.1%, 95% CI 6.1–8.2). RAS improved the health status of the children on Day 28 (aOR = 0.64, 95% CI 0.45–0.92) and there was a non-significant trend that mortality was higher in children not receiving RAS (aOR = 1.50, 95% CI 0.86–2.60). Full severe malaria treatment at the RHF including injectable anti-malarial and a course of ACT was highly protective against death (aOR = 0.26, 95% CI 0.09–0.79).

Conclusions

The main findings point towards the fact that danger signs are reasonably well recognized by health provider at the primary care level, and that RAS could influence positively health outcomes of such severe disease episodes and death. Its effectiveness is hampered by the insufficient quality of care at RHF, especially the provision of a full course of ACT following parenteral treatment. These are simple but important findings that requires urgent action by the health system planners and implementers.
Co-expression IL-15 receptor alpha with IL-15 reduces toxicity via limiting IL-15 systemic exposure during CAR-T immunotherapy
Authors: Zhang Ying , Zhuang Qinghui , Wang Fang , Zhang Can , Xu Chang , Gu Aiqin , Zhong William H. , Hu Yi , Zhong Xiaosong
Published: September 2022

Background

Chimeric antigen receptor (CAR)-T cell therapy is a powerful adoptive immunotherapy against both B-cell malignancies and some types of solid tumors. Interleukin (IL) -15 is an important immune stimulator that may provide ideal long-term persistent CAR-T cells. However, higher base line or peak serum IL-15 levels are also related to severe toxicity, such as cytokine release syndrome (CRS), graft-versus-host disease (GVHD), and neurotoxicity.

Methods

We successfully constructed CD19 specific armored CAR-T cells overexpressing IL-I5 and IL-15 receptor alpha (IL-15Ra). In vitro cell differentiation and viability were monitored by flow cytometry, and an in vivo xenograft mouse models was used to evaluate the anti-tumor efficiency and liver damage of CAR-T cells.

Results

CAR-T cells overexpressing IL-15 alone demonstrated enhanced viability, retarded exhaustion in vitro and superior tumor-inhibitory effects in vivo. However, these tumor-free mice had lower survival rates, with serious liver injuries, as a possible result of toxicity. As expected, CAR-T cells overexpressing IL-15 combined with IL-15Ra had reduced CD132 expression and released fewer cytokines (IFNγ, IL-2 and IL-15) in vitro, as well as had the tendency to improve mouse survival via repressing the growth of tumor cells and keeping livers healthier compared to CAR-IL-15 T cells.

Conclusions

These results indicated the importance of IL-15 in enhancing T cells persistence and IL-15Ra in reducing the adverse effects of IL-15, with superior tumor retardation during CAR-T therapy. This study paves the way for the rapid exploitation of IL-15 in adoptive cell therapy in the future.