bluuebunny/crossref_metadata_2025 huggingface dataset:
Complex multidisciplinary intervention to improve Initial Medication Adherence to cardiovascular disease and diabetes treatments in primary care (the IMA-cRCT study): mixed-methods process evaluation protocol
Authors: Corral-Partearroyo Carmen , Sánchez-Viñas Alba , Gil-Girbau Montserrat , Peñarrubia-María Maria Teresa , Aznar-Lou Ignacio , Gallardo-González Carmen , Olmos-Palenzuela María del Carmen , Rubio-Valera Maria
Published: October 2022

Introduction

Medication non-initiation, or primary non-adherence, is a persistent public health problem that increases the risk of adverse clinical outcomes. The initial medication adherence (IMA) intervention is a complex multidisciplinary intervention to improve adherence to cardiovascular and diabetes treatments in primary care by empowering the patient and promoting informed prescriptions based on shared decision-making. This paper presents the development and implementation strategy of the IMA intervention and the process evaluation protocol embedded in a cluster randomised controlled trial (the IMA-cRCT) to understand and interpret the outcomes of the trial and comprehend the extent of implementation and fidelity, the active mechanisms of the IMA intervention and in what context the intervention is implemented and works.

Methods and analysis

We present the protocol for a mixed-methods process evaluation including quantitative and qualitative methods to measure implementation and fidelity and to explore the active mechanisms and the interactions between the intervention, participants and its context. The process evaluation will be conducted in primary care centres and community pharmacies from the IMA-cRCT, and participants include healthcare professionals (general practitioners, nurses and community pharmacists) as well as patients. Quantitative data collection methods include data extraction from the intervention operative records, patient clinical records and participant feedback questionnaires, whereas qualitative data collection involves semistructured interviews, focus groups and field diaries. Quantitative and qualitative data will be analysed separately and triangulated to produce deeper insights and robust results.

Ethics and dissemination

Ethical approval has been obtained from the Research Ethics Comittee (CEIm) at IDIAP Jordi Gol (codeCEIm 21/051 P). Findings will be disseminated through publications and conferences, as well as presentations to healthcare professionals and stakeholders from healthcare organisations.

Trial registration number

NCT05026775.
Engineered anti-PDL1 with IFNα targets both immunoinhibitory and activating signals in the liver to break HBV immune tolerance
Authors: Meng Chao-Yang , Sun Shiyu , Liang Yong , Xu Hairong , Zhang Chao , Zhang Min , Wang Fu-Sheng , Fu Yang-Xin , Peng Hua
Published: October 2022

Objective

The purpose of this study is to develop an anti-PDL1-based interferon (IFN) fusion protein to overcome the chronic hepatitis B virus (HBV)-induced immune tolerance, and combine this immunotherapy with a HBV vaccine to achieve the functional cure of chronic hepatitis B (CHB) infection.

Design

We designed an anti-PDL1-IFNα heterodimeric fusion protein, in which one arm was derived from anti-PDL1 antibody and the other arm was IFNα, to allow targeted delivery of IFNα into the liver by anti-PDL1 antibody. The effect of the anti-PDL1-IFNα heterodimer on overcoming hepatitis B surface antigen (HBsAg) vaccine resistance was evaluated in chronic HBV carrier mice.

Results

The anti-PDL1-IFNα heterodimer preferentially targeted the liver and resulted in viral suppression, the PD1/PDL1 immune checkpoint blockade and dendritic cell activation/antigen presentation to activate HBsAg-specific T cells, thus breaking immune tolerance in chronic HBV carrier mice. When an HBsAg vaccine was administered soon after anti-PDL1-IFNα heterodimer treatment, we observed strong anti-HBsAg antibody and HBsAg-specific T cell responses for efficient HBsAg clearance in chronic HBV carrier mice that received the combination treatment but not in those that received either single treatment.

Conclusions

Targeting the liver with an engineered anti-PDL1-IFNα heterodimer can break HBV-induced immune tolerance to an HBsAg vaccine, offering a promising translatable therapeutic strategy for the functional cure of CHB.
Rewiring the altered tryptophan metabolism as a novel therapeutic strategy in inflammatory bowel diseases
Authors: Michaudel Chloé , Danne Camille , Agus Allison , Magniez Aurélie , Aucouturier Anne , Spatz Madeleine , Lefevre Antoine , Kirchgesner Julien , Rolhion Nathalie , Wang Yazhou , Lavelle Aonghus , Galbert Chloé , Da Costa Gregory , Poirier Maxime , Lapière Alexia , Planchais Julien , Nádvorník Petr , Illes Peter , Oeuvray Cyriane , Creusot Laura , Michel Marie-Laure , Benech Nicolas , Bourrier Anne , Nion-Larmurier Isabelle , Landman Cecilia , Richard Mathias L , Emond Patrick , Seksik Philippe , Beaugerie Laurent , Arguello Rafael Rose , Moulin David , Mani Sridhar , Dvorák Zdenek , Bermúdez-Humarán Luis G , Langella Philippe , Sokol Harry
Published: October 2022

Objective

The extent to which tryptophan (Trp) metabolism alterations explain or influence the outcome of inflammatory bowel diseases (IBDs) is still unclear. However, several Trp metabolism end-products are essential to intestinal homeostasis. Here, we investigated the role of metabolites from the kynurenine pathway.

Design

Targeted quantitative metabolomics was performed in two large human IBD cohorts (1069 patients with IBD). Dextran sodium sulphate-induced colitis experiments in mice were used to evaluate effects of identified metabolites. In vitro, ex vivo and in vivo experiments were used to decipher mechanisms involved. Effects on energy metabolism were evaluated by different methods including Single Cell mEtabolism by profiling Translation inHibition.

Results

In mice and humans, intestinal inflammation severity negatively correlates with the amount of xanthurenic (XANA) and kynurenic (KYNA) acids. Supplementation with XANA or KYNA decreases colitis severity through effects on intestinal epithelial cells and T cells, involving Aryl hydrocarbon Receptor (AhR) activation and the rewiring of cellular energy metabolism. Furthermore, direct modulation of the endogenous tryptophan metabolism, using the recombinant enzyme aminoadipate aminotransferase (AADAT), responsible for the generation of XANA and KYNA, was protective in rodent colitis models.

Conclusion

Our study identified a new mechanism linking Trp metabolism to intestinal inflammation and IBD. Bringing back XANA and KYNA has protective effects involving AhR and the rewiring of the energy metabolism in intestinal epithelial cells and CD4+T cells. This study paves the way for new therapeutic strategies aiming at pharmacologically correcting its alterations in IBD by manipulating the endogenous metabolic pathway with AADAT.
Identifying opportunities for multisectoral action for drowning prevention: a scoping review
Authors: Scarr Justin-Paul , Jagnoor Jagnoor
Published: October 2022

Background

Drowning is a complex health issue, where global agendas call for greater emphasis on multisectoral action, and engagement with sectors not yet involved in prevention efforts. Here, we explored the conceptual boundaries of drowning prevention in peer-review and grey literature, by reviewing the contexts, interventions, terminologies, concepts, planning models, and sector involvement, to identify opportunities for multisectoral action.

Methods

We applied scoping review method and have reported against Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews checklist. We searched four electronic databases for peer-reviewed articles published on 1 January 2005 and 31 December 2020 and five databases for grey literature published on 1 January 2014 and 31 December 2020. We applied the search term “drowning,” and charted data addressing our research questions.

Results

We included 737 peer-reviewed articles and 68 grey documents. Peer-publications reported situational assessments (n=478, 64.86%) and intervention research (n=259, 35.14%). Drowning was reported in the context of injury (n=157, 21.30%), commonly in childhood injury (n=72, 9.77%), mortality studies (n=60, 8.14%) and in grey documents addressing adolescent, child, environmental, occupational and urban health, refugee and migrant safety and disaster. Intervention research was mapped to World Health Organization recommended actions. The leading sectors in interventions were health, leisure, education and emergency services.

Conclusion

Although drowning is often described as a major health issue, the sectors and stakeholders involved are multifarious. The interventions are more often initiated by non-health sectors, meaning multisectoral action is critical. Framing drowning prevention to reinforce cobenefits for other health and development agendas could strengthen multisectoral action. Greater investment in partnerships with non-health sectors, encouraging joint planning and implementation, and creating systems for increased accountability should be a priority in future years.
Germline mutations inWNK2could be associated with serrated polyposis syndrome
Authors: Soares de Lima Yasmin , Arnau-Collell Coral , Muñoz Jenifer , Herrera-Pariente Cristina , Moreira Leticia , Ocaña Teresa , Díaz-Gay Marcos , Franch-Expósito Sebastià , Cuatrecasas Miriam , Carballal Sabela , Lopez-Novo Anael , Moreno Lorena , Fernàndez Guerau , Díaz de Bustamante Aranzazu , Peters Sophia , Sommer Anna K , Spier Isabel , te Paske Iris B A W , van Herwaarden Yasmijn J , Castells Antoni , Bujanda Luis , Capellà Gabriel , Steinke-Lange Verena , Mahmood Khalid , Joo JiHoon Eric , Arnold Julie , Parry Susan , Macrae Finlay A , Winship Ingrid M , Rosty Christophe , Cubiella Joaquin , Rodríguez-Alcalde Daniel , Holinski-Feder Elke , de Voer Richarda , Buchanan Daniel D , Aretz Stefan , Ruiz-Ponte Clara , Valle Laura , Balaguer Francesc , Bonjoch Laia , Castellvi-Bel Sergi
Published: October 2022

Background

Patients with serrated polyposis syndrome (SPS) have multiple and/or large serrated colonic polyps and higher risk for colorectal cancer. SPS inherited genetic basis is mostly unknown. We aimed to identify new germline predisposition factors for SPS by functionally evaluating a candidate gene and replicating it in additional SPS cohorts.

Methods

After a previous whole-exome sequencing in 39 SPS patients from 16 families (discovery cohort), we sequenced specific genes in an independent validation cohort of 211 unrelated SPS cases. Additional external replication was also available in 297 SPS cases. TheWNK2gene was disrupted in HT-29 cells by gene editing, andWNK2variants were transfected using a lentiviral delivery system. Cells were analysed by immunoblots, real-time PCR and functional assays monitoring the mitogen-activated protein kinase (MAPK) pathway, cell cycle progression, survival and adhesion.

Results

We identified 2 rare germline variants in theWNK2gene in the discovery cohort, 3 additional variants in the validation cohort and 10 other variants in the external cohorts. Variants c.2105C>T (p.Pro702Leu), c.4820C>T (p.Ala1607Val) and c.6157G>A (p.Val2053Ile) were functionally characterised, displaying higher levels of phospho-PAK1/2, phospho-ERK1/2, CCND1, clonogenic capacity and MMP2.

Conclusion

After whole-exome sequencing in SPS cases with familial aggregation and replication of results in additional cohorts, we identified rare germline variants in theWNK2gene. Functional studies suggested germlineWNK2variants affect protein function in the context of the MAPK pathway, a molecular hallmark in this disease.
Micro-guidewire electrocoagulation for the treatment of intracranial aneurysms that are inaccessible by microcatheterization: a case series and review of the literature
Authors: Lu Guang-Dong , Zhao Lin-Bo , Jia Zhen-Yu , Liu Sheng
Published: October 2022

Background

The use of traditional endovascular techniques for aneurysms that are difficult to catheterize is challenging. We present our experience of using micro-guidewire electrocoagulation for the treatment of aneurysms that were inaccessible by a microcatheter.

Methods

Seven consecutive patients who underwent endovascular electrocoagulation for the treatment of aneurysms between January 2020 and May 2022 were retrospectively included. Patient demographics, treatment procedures, and follow-up outcomes were assessed. A review of the literature was also performed.

Results

All of the seven treated aneurysms were ruptured, and micro-guidewire electrocoagulation was only conducted if the microcatheter could not advance into the aneurysm or parent artery. After electrocoagulation for 1–4 min, all seven aneurysms disappeared on contrast angiography. Parent artery occlusion was observed in six cases, and post-procedure infarctions of the operating region were identified in three patients. The 3-month follow-up modified Rankin Scale score was 0 in all except one patient. Follow-up angiography was available in six patients, and complete obliteration of the aneurysm was observed in all of them. With a mean follow-up time of 13.6 months, there was no rebleeding in any of the cases. To date, there are only eight published cases of aneurysms treated using micro-guidewire electrocoagulation, and seven of them achieved total occlusion of the aneurysm without neurological deficits.

Conclusions

Endovascular electrocoagulation is practicable and effective for the treatment of aneurysms that are inaccessible by a microcatheter during short-term observation. Studies on larger populations are needed to further confirm the safety and long-term outcomes for this technique.
Role of small acute hyperintense lesions in long-term progression of cerebral small vessel disease and clinical outcome: a 14-year follow-up study
Authors: Verburgt Esmée , Janssen Esther , Jacob Mina A , Cai Mengfei , ter Telgte Annemieke , Wiegertjes Kim , Kessels Roy P C , Norris David G , Marques Jose , Duering Marco , Tuladhar Anil M , De Leeuw Frank-Erik
Published: October 2022

Background

Small hyperintense lesions are found on diffusion-weighted imaging (DWI) in patients with sporadic small vessel disease (SVD). Their exact role in SVD progression remains unclear due to their asymptomatic and transient nature. The main objective is to investigate the role of DWI+lesions in the radiological progression of SVD and their relationship with clinical outcomes.

Methods

Participants with SVD were included from the Radboud University Nijmegen Diffusion tensor MRI Cohort. DWI+lesions were assessed on four time points over 14 years. Outcome measures included neuroimaging markers of SVD, cognitive performance and clinical outcomes, including stroke, all-cause dementia and all-cause mortality. Linear mixed-effect models and Cox regression models were used to examine the outcome measures in participants with a DWI+lesion (DWI+) and those without a DWI+lesion (DWI−).

Results

DWI+lesions were present in 45 out of 503 (8.9%) participants (mean age: 66.7 years (SD=8.3)). Participants with DWI+lesions and at least one follow-up (n=33) had higher white matter hyperintensity progression rates (β=0.36, 95% CI=0.05 to 0.68, p=0.023), more incident lacunes (incidence rate ratio=2.88, 95% CI=1.80 to 4.67, p<0.001) and greater cognitive decline (β=−0.03, 95% CI=−0.05 to −0.01, p=0.006) during a median follow-up of 13.2 (IQR: 8.8–13.8) years compared with DWI− participants. No differences were found in risk of all-cause mortality, stroke or dementia.

Conclusion

Presence of a DWI+lesion in patients with SVD is associated with greater radiological progression of SVD and cognitive decline compared with patients without DWI+lesions.
Identification of the ideal recruitment situation in pandemic research: learning from the RECOVERY trial in Northern England: a qualitative study
Authors: Coe Dorothy , Dorgan Sharon , Smith Justine , Wroe Caroline
Published: October 2022

Background

In early 2020, little was known about treatments for COVID-19. The UK responded by initiating a call for research, leading to the formation of the National Institute for Health Research (NIHR) Urgent Public Health (UPH) group. Fast-track approvals were initiated and support was offered to research sites via the NIHR. The Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial was designated UPH. High recruitment rates were required for timely results. Recruitment rates were inconsistent across different hospitals and places.

Purpose

The Factors Affecting Recruitment to the RECOVERY trial study was designed to seek out the facilitators and barriers to recruitment across a population of 3 million served by eight different hospitals and suggest recommendations for recruitment to UPH research during a pandemic situation.

Methods

A qualitative grounded theory study using situational analysis was used. This included a contextualisation of each recruitment site containing prepandemic operational status, prior research activity, COVID-19 admission rates and UPH activity. Additionally, one-to-one interviews using topic guides were completed with NHS staff involved in the RECOVERY trial. Analysis sought out the narratives that shaped recruitment activity.

Results

An ideal recruitment situation was identified. The closer sites were able to move towards that ideal situation, the easier they found it to implement the most significant factor on recruitment: embedding research recruitment into standard care. The ability to move to the ideal recruitment situation was mediated by five significant elements: uncertainty, prioritisation, leadership, engagement and communication.

Conclusion

Embedding recruitment into routine clinical care was the most influential factor on recruitment to the RECOVERY trial. To enable this, sites needed to attain the ideal recruitment situation. Prior research activity, size of site and regulator grading did not correlate with high recruitment rates. Research should be at the forefront of prioritisation during future pandemics.
Factors associated with sexually transmitted shigella in men who have sex with men: a systematic review
Authors: Siddiq Mohammed , O'Flanagan Holly , Richardson Daniel , Llewellyn Carrie D
Published: October 2022

Background

Outbreaks of sexually transmitted shigella have been reported in men who have sex with men (MSM) since the 1970s and present a major public health issue. Understanding the factors associated with the sexual transmission of shigella may inform future control strategies.

Methods

We systematically searched four bibliographical databases (January 2000–February 2022) for manuscripts in English. We used a two-stage process to assess eligibility: the primary author conducted an initial screen and then three authors conducted independent full-text reviews to determine the final eligible manuscripts. We only included manuscripts that included MSM diagnosed with sexually transmitted shigella where specific factors associated with transmission were identified.

Results

Thirteen manuscripts met the inclusion criteria that included 547 individuals. Sexually transmitted shigella in MSM was associated with: residing in a capital city/urban region, living with HIV (including engaging in seroadaptive sexual behaviour, having a low CD4 count, having a HIV viral load >100 000 and not engaging with HIV care), using HIV pre-exposure prophylaxis, use of geospatial mobile phone applications to meet sexual partners, visiting sex on premises venues, chemsex and recreational drug use, sexual behaviour (including multiple non-regular sexual partners and oral-anal sexual contact) and concomitant STIs.

Conclusion

We have highlighted some important risk behaviours and factors that are associated with sexually transmitted shigella in MSM that can be used to target future shigella control interventions.
How do New Zealand youth perceive the smoke-free generation policy? A qualitative analysis
Authors: Hoek Janet , Lee Ell , Teddy Lani , Fenton Elizabeth , Ball Jude , Edwards Richard
Published: October 2022

Introduction

Aotearoa New Zealand (NZ) plans to introduce a smoke-free generation (SFG) policy, alongside denicotinisation and reducing the availability of tobacco products. The SFG has a clear rationale, yet we know little about how young people, those the policy targets, perceive it. To inform policy design, communication and implementation, we explored how NZ youth perceived the SFG.

Methods

We undertook in-depth interviews with a sample of 20 youth aged 17 or 18 and explored their knowledge of the SFG, and how they perceived its individual and societal implications. We interpreted the data using a reflexive thematic analysis approach.

Results

We identified two overarching themes. The first theme, ‘societal good and protection from harm’, reflected benefits participants associated with the SFG, which outweighed perceptions of lost freedoms. The second theme, ‘privileging personal choice’, corresponded to two small groups within the sample. The first preferred measures they considered less restrictive, such as increasing the purchase age, and some came to support the SFG as they rationalised their views. The second subgroup expressed more entrenched opposition and felt the SFG deprived them of a choice.

Conclusions

Young people’s deep reflection on the SFG led most to view it as liberating rather than restrictive. Communications that avoid prompting heuristic-based responses could encourage youth to reflect on the policy and elicit strong support from the group the SFG aims to benefit.
MULTIFRACTAL CROSS-CORRELATIONS RISK AMONG WTI AND FINANCIAL ASSETS
Authors: FERNANDES LEONARDO H. S. , SILVA JOSÉ W. L. , QUINTINO DERICK D. , DE ARAUJO FERNANDO H. A. , TABAK BENJAMIN MIRANDA
Published: October 2022

Independent of science branch, scientists have a consensus that peoples lives are highly susceptible to risk, and effectively quantifying risk is a big challenge. This paper assesses the Multifractal Cross-Correlation Measure (MRCC) among West Texas Intermediate (WTI), seven fiat currencies and three foreign exchange rates. Therefore, we use the Multifractal Detrended Cross-Correlation Analysis (MF-DCCA) to examine the volatility dynamics considering the pairs of these financial records. We discover that all these volatility time series pairs [Formula: see text] are characterized by overall persistent behavior based on the values of [Formula: see text]. The MRCC values exhibit that the pairs WTI versus MXN [Formula: see text], WTI versus JPY [Formula: see text] and WTI versus NOK [Formula: see text] are more complex and persistent than the other pairs. Otherwise, the pairs WTI versus AUD [Formula: see text], WTI versus CAD [Formula: see text] and WTI versus EMK [Formula: see text] are less complex and persistent. Thus, our empirical findings shed light on the problem of quantification risk based on a multifractal perspective.
FoodChoices(Q): Exploring the Design of a Serious Game Proxy for Likert-style Survey Questionnaires
Authors: Rogoda Kamil , Daniszewski Piotr , Florowski Kamil , Mathur Rishab , Amouzgar Kourosh , Mackenzie James , Sauvé Kim , Karnik Abhijit
Published: October 2022

Likert-style questionnaires and surveys are commonly used tools for research. To alleviate survey-fatigue, researchers have explored gamification routes to increase engagement and lower drop-outs. However, these attempts still rely on direct use of questionnaire text and focus on creating engagement around the actual activity and do not fully alleviate the challenges of filling survey. In this paper, we explore an alternative approach involving the use of a serious game to capture user responses through in-game activities rather than direct questions. We chose the Food Choice Questionnaire (FCQ) and explored the design challenges of creating a serious game which deploys a sub-sample of the FCQ questions as four mini-game activities. The player actions and decisions are used to compute a result which is compared with their FCQ responses. We demonstrate the method to evaluate the equivalence of game results to the questionnaire responses. We discuss how future serious games can be designed and evaluated to generate similar outcomes while avoiding potential pitfalls through design and analysis.
GazeCues: Exploring the Effects of Gaze-based Visual Cues in Virtual Reality Exploration Games
Authors: Lankes Michael , Ramirez Gomez Argenis
Published: October 2022

This paper examines different gaze-based cue visualization techniques in a Virtual Reality (VR) exploration game. It is argued that gaze could be a valuable design tool for providing cues to players. However, little is known about how these elements could be visually presented and integrated to inform players and fit into the game world. An exploratory study was carried out to investigate four different design approaches (subtle, overlaid-virtual, integrated, emphasized) and their effects on aspects such as clarity, usefulness, and curiosity. In general, the visualizations led to different player impressions on all scales. While players perceived the subtle and emphasized variants as more aesthetically appealing, integrated and virtual-overlaid solutions received more positive ratings regarding tool-related aspects such as ease of extraction and accurateness. We anticipate future work could employ gaze-based cues in various application contexts based on their utility as eye input in VR games continues developing.
NCAlt: Alternatives and Difference Visualizations for Behavior Trees in Game Development Learning
Authors: Hossain Md. Yousuf , Zaman Loutfouz
Published: October 2022

When learning how to develop AI behavior it is common for students to test different ideas before settling on a desired outcome. This functionality is not available in modern behavior tree systems beyond the traditional methods of duplication and conditional execution. We present NCAlt - a visual behavior authoring framework for exploring multiple game AI behaviors. The system also allows selective merging of nodes between multiple behavior tree alternatives and their visual differencing in the game scene and behavior tree views. We present two worked examples which demonstrate how NCAlt can improve the workflow of game development students. We have conducted a user study where NCAlt was compared against NodeCanvas for creating and using alternatives with moderately skilled game development students. Participants rated NCAlt 15% higher than NodeCanvas on the System Usability Scale (SUS). NCAlt was also rated higher on a self-developed questionnaire. We also conducted a semi-structured interview and a detailed longitudinal follow-up and obtained mostly positive feedback for NCAlt. The results suggest NCAlt has a potential to improve the types of workflows with behavior trees that involve exploration for game development students and facilitate learning, as a result. NCAlt was built on top of NodeCanvas - a plugin for the Unity Engine.
The Playful Potential of Digital Commensality: Learning from Spontaneous Playful Remote Dining Practices
Authors: Alhasan Khawla , Ceccaldi Eleonora , Covaci Alexandra , Mancini Maurizio , Altarriba Bertran Ferran , Huisman Gijs , Lemke Mailin , Ang Chee Siang
Published: October 2022

With one-person households being increasingly common and Covid-19 lockdown policies forcing people to stay home, remote dining has become common practice for many, who take it as an opportunity to connect with others in times of loneliness. Sharing meals online, also known as digital commensality, is a rich form of interaction, where people leverage technology to achieve a sense of connectedness and belonging while eating. In this paper, we look at digital commensality and we explore its inherent playful potential with the aim to inspire the design of engaging technologies that can support, enhance and augment this form of interaction. For this, we used a situated play design approach to document and analyze the behavior of 36 people (including pairs of friends and strangers) sharing meals online. Our analysis surfaced a set of play potentials of remote dining -- i.e., playful things people already do and enjoy spontaneously while sharing meals online. We present those play potentials as inspirational material: they can motivate and enrich the design of future digital commensality technologies by responding to people's desire for playful and social interaction with, through, and around food.
Simulating Software Evolution to Evaluate the Reliability of Early Decision-making among Design Alternatives toward Maintainability
Authors: Karanikolas Chris , Dimitroulakos Grigoris , Masselos Konstantinos
Published: October 2022

Critical decisions among design altern seventh atives with regards to maintainability arise early in the software design cycle. Existing comparison models relayed on the structural evolution of the used design patterns are suitable to support such decisions. However, their effectiveness on predicting maintenance effort is usually verified on a limited number of case studies under heterogeneous metrics. In this article, a multi-variable simulation model for validating the decision-making reliability of the derived formal comparison models for the significant designing problem of recursive hierarchies of part-whole aggregations, proposed in our prior work, is introduced. In the absence of a strict validation, the simulation model has been thoroughly calibrated concerning its decision-making precision based on empirical distributions from time-series analysis, approximating the highly uncertain nature of actual maintenance process. The decision reliability of the formal models has been statistically validated on a sample of 1,000 instances of design attributes representing the entire design space of the problem. Despite the limited accuracy of measurements, the results show that the models demonstrate an increasing reliability in a long-term perspective, even under assumptions of high variability. Thus, the modeling theory discussed in our prior work delivers reliable models that significantly reduce decision-risk and relevant maintenance cost.
How windows size and number can influence the schedulability of hierarchically-scheduled time-partitioned distributed real-time systems
Authors: Amurrio A. , Azketa E. , Aldea M. , Gutiérrez J.J.
Published: October 2022

Partitioning techniques are implemented in the development of safety-critical applications to ensure isolation among components. An adequate scheduling of the execution of such partitions is a key challenge so that applications meet the hard deadlines imposed. In this work, we study the effect of different partition window configuration parameters, with the aim of analyzing their impact in the worst-case response times of system tasks. This is the first step in the development of an algorithm for optimizing partition windows in hierarchically-scheduled time partitioned distributed systems.
A Secure and Robust Autoencoder-Based Perceptual Image Hashing for Image Authentication
Authors: Shaik Abdul Subhani , Karsh Ram Kumar , Islam Mohiul , Singh Surendra Pal
Published: October 2022

With the advancement of technology, it has become easier to modify or tamper with digital data effortlessly. In recent times, the image hashing algorithm has gained popularity for image authentication applications. In this paper, a convolutional stacked denoising autoencoder (CSDAE) is utilized for producing hash codes that are robust against different content preserving operations (CPOs). The CSDAE algorithm comprises mapping high-dimensional input data into hash codes while maintaining their semantic similarities. This implies that the images having similar content should have similar hash codes. To demonstrate the effectiveness of the model, the correlation between hash codes of semantically similar images has been evaluated. Subsequently, tampered localization is done by comparing the decoder output of the manipulated image with the hash of the actual image. Then, the localization ability of the model was measured by computing the

f
1

scores between the predicted region and the original tampered region. Based on the comparative performance and receiver-operating characteristics (ROC) curve, we may conclude that the proposed hashing proposed algorithm provides improved performance compared to various state-of-the-art techniques.
Solitary Wave Solutions to the Modified Zakharov–Kuznetsov and the (2 + 1)‐Dimensional Calogero–Bogoyavlenskii–Schiff Models in Mathematical Physics
Authors: Al-Amin M. , Islam M. Nurul , İlhan Onur Alp , Akbar M. Ali , Soybaş Danyal
Published: October 2022

The modified Zakharov–Kuznetsov (mZK) and the (2 + 1)‐dimensional Calogero–Bogoyavlenskii–Schiff (CBS) models convey a significant role to instruct the internal structure of tangible composite phenomena in the domain of two‐dimensional discrete electrical lattice, plasma physics, wave behaviors of deep oceans, nonlinear optics, etc. In this article, the dynamic, companionable, and further broad‐spectrum exact solitary solitons are extracted to the formerly stated nonlinear models by the aid of the recently enhanced auxiliary equation method through the traveling wave transformation. The implication of the soliton solutions attained with arbitrary constants can be substantial to interpret the involuted phenomena. The established soliton solutions show that the approach is broad‐spectrum, efficient, and algebraic computing friendly and it may be used to classify a variety of wave shapes. We analyze the achieved solitons by sketching figures for distinct values of the associated parameters by the aid of the Wolfram Mathematica program.
Patient-Specific Instruments for Forearm Sarcoma Resection and Allograft Reconstruction in Children: Results in 4 Cases
Authors: Paulmier Amaury , Raad Mathieu , Verhelle Charles-Edouard , Paul Laurent , Docquier Pierre-Louis
Published: October 2022

For pediatric malignant bone tumors located in the limbs, limb salvage surgery is the gold standard, but it requires adequate resection margins to avoid local recurrence. Primitive bone sarcomas of the forearm (radius or ulna) are very rare and the reconstruction remains challenging. We describe a method to ensure minimal but adequate resection bone margins with precision in four consecutive patients with primitive bone sarcomas of the forearm. During the preoperative planning, magnetic resonance imaging (MRI) was used to delineate the tumor and the tumor volume was transferred to computerized tomography (CT) by image fusion. A patient-specific instrument (PSI) was manufactured by 3D printing to allow the surgeon to perform the surgical cuts precisely according to the preoperative planning. The first PSI was used for the resection of the tumor, which adopted a unique position at the bony surface. A second PSI was intended for the cutting of the bone allograft so that it fitted perfectly with the bone defect. In all four cases, the safe margin obtained into the bone was free of tumor (R0: microscopically margin-negative resection). The functional result was very good in all four patients. This limb salvage surgical technique can be applied in forearm bone sarcoma and improves surgical precision while maintaining satisfactory local tumor control. It can also reduce the surgical time and allow a stable osteosynthesis.
Association between Extracranial Carotid Artery Plaque and Cognitive Dysfunction: A Systematic Review and Meta-Analysis
Authors: Baradaran Hediyeh , Dahlstrom Kelly A. , Culleton Sinead , Sarrami Amir Hossein , McFarland Mary M. , Romero Jose R.
Published: October 2022

Background: Extracranial carotid atherosclerosis has been variably associated with dementia. Prior studies have focused on the association of carotid intima media thickness or carotid stenosis; however, there is evidence that carotid plaque may contribute to dementia, perhaps via microembolic phenomena. Objectives: We sought to evaluate the role of carotid plaque in contributing to cognitive impairment by performing a systematic review and meta-analysis to summarize the association between extracranial carotid plaque and cognitive dysfunction and dementia. Methods: We performed a comprehensive literature search evaluating the association of extracranial carotid plaque with cognition. We included studies measuring carotid plaque on ultrasound, computed tomography, or MR and also evaluated cognition through neuropsychological testing. Meta-analyses with assessment of study heterogeneity and publication bias were performed. Results were presented in a forest plot and summarized using a random-effects model. Results: After screening 1,674 studies, we included 40 for systematic review and 16 and 7 studies for two meta-analyses with a total of 19,029 and 27,325 patients, respectively. We found a positive relationship between the presence of extracranial carotid plaque and cognitive dysfunction with a pooled random-effects odds ratio (OR) of 1.83 (95% CI, 1.50, 2.24) and a pooled random-effects hazard ratio (HR) of 1.47 (95% CI, 1.15, 1.89), respectively. A sensitivity analysis of only longitudinal studies found a persistent positive association. Measures of heterogeneity showed moderate heterogeneity in each meta-analysis, respectively (I-squared statistic = 57% and 70%). Conclusion: The presence of extracranial carotid plaque is significantly associated with cognitive dysfunction and dementia in both cross-sectional and longitudinal analyses. After further confirmation, our results support carotid plaque being a potentially modifiable risk factor in the development of dementia.
Optimal Choice for Improving the Hearing in Children with Unilateral Microtia and Atresia: Softband or Adhesive Adapter?
Authors: Liu Yujie , Chen Peiwei , Yang Lin , Zhu Jikai , Yang Jinsong , Wang Danni , Ren Ran , Li Ying , Zhao Chunli , Zhao Shouqin
Published: October 2022

Introduction: A nonsurgical bone conduction hearing aid (BCHA) is a well-established treatment for children with congenital unilateral microtia and atresia (UMA). To date, limited studies have evaluated the audiological characteristics of the different wearing modes in the same nonsurgical BCHA. Methods: Eighteen patients with UMA aged 5–24 years were included. Warble tones at frequencies of 0.5, 1, 2, and 4 kHz were presented to determine functional hearing gain (FHG) of hearing thresholds (in dB HL) in the sound field. The speech perception abilities were assessed by the speech discrimination score (SDS, in %) of monosyllables, disyllables, and sentences in quiet and noise using the Chinese Mandarin speech test materials. Hearing outcomes were evaluated with the ADHEAR™ worn on a softband and with an adhesive adapter. A correlational analysis was conducted to analyze the correlations between variables (e.g., age, height, weight, body mass index [BMI], bone conduction pure-tone threshold, and air conduction pure-tone threshold) and the differences in the two wearing modes. Results: The mean FHG (standard deviation, SD) at 0.5–4 kHz was 20.63 (3.94) dB HL with the adhesive adapter and 26.39 (3.15) dB HL with the softband. When aided with the BCHA, significant improvements in SDS were revealed in all Mandarin speech test material lists either in quiet or noise for both wearing modes. Compared with the adapter mode, the softband provided higher aided SDS values. Correctional analyses revealed that higher BMI values were positively associated with larger delta outcomes between the two coupling methods of the softband and adhesive adapter in patients with UMA. Furthermore, a larger delta average FHG of 0.5–4 kHz was consistently associated with larger delta monosyllabic SDS in quiet, disyllabic SDS in quiet, and disyllabic SDS in noise. Discussion: To the best of our knowledge, this is the first study to compare the hearing benefits of coupling methods using novel adhesive adapters and conventional softbands with the same audio processor (ADHEAR™). Under uniform internal settings, softband integration provided more hearing benefits than adhesive adapter integration, and the differences were more obvious in patients with higher BMI values. Besides, a brief measurement of FHG can be utilized to predict individualized speech perception levels.
The Importance of F-Wave Patterns in a Patient with Cerebrovascular Disease Characterized by a Markedly Increased Tone of the Thenar Muscles
Authors: Suzuki Toshiaki , Fukumoto Yuki , Todo Marina , Tani Makiko , Yoshida Sohei
Published: October 2022

F-waves are used to measure the excitability of spinal motor nerve function. This study aimed to investigate the F-wave patterns in a patient with cerebrovascular disease who had no voluntary movement of the hand, particularly the thumb, caused by a considerably increased tone of the thenar muscles. A patient with right hemiplegia caused by left cerebral hemorrhage (putamen) showed a considerably increased tone of the thumb flexors and no voluntary movements. F-waves were recorded from the affected thenar muscles with median nerve stimulation in the supine lying position during the first trial. Exercise therapy that included stretching of the affected thenar muscles was performed twice a week for 20 min for 8 months. Subsequent changes in the F-wave waveform were examined and considered as second trial. The latency and persistence of the F-wave and F-wave conduction velocity did not show any significant change between the two trials. Compared with the first trial, the F/M amplitude ratio in the second trial was increased. Following 8 months of exercise therapy, muscle tone improved slightly, and minimal voluntary movements of the affected thumb were noted. Since motor function of the affected thumb improved with exercise therapy but there was no improvement in F-wave data, it was determined that the main factor underlying the hypertonicity of the thenar muscles in this patient was more likely due to secondary muscle shortening than to spasticity. Unclear waves that possibly were F-waves were also observed approximately 20 ms after the appearance of the M-wave in the first trial but not in the second trial. Because exercise therapy showed muscle tone improvement and did not result in the appearance of unclear waves, F-wave patterns should be monitored for evaluating spasticity, which markedly increases muscle tone in patients with cerebrovascular disease.
Kidney Histopathology Features of Suspected Intra-Kidney Venous Thromboembolism in Patients with Primary Glomerulonephritis
Authors: Lu Hui , Cui Zhao , Xiao Tang-li , Wang Su-xia , Zhao Ming-hui
Published: October 2022

Introduction: Renal vein thromboembolism is a severe complication of nephrotic syndrome. Small thrombus in the intra-kidney venous system cannot be recognized by ultrasonography. The current study was to investigate the kidney pathological features of intra-kidney venous thrombus and their values in clinical practice. Methods: Kidney pathological features of glomerular capillary dilatation and congestion, peritubular capillary dilatation and congestion, and intraglomerular neutrophil infiltration were screened and scored during kidney biopsy information interpretation. Eighty-four consecutive patients with these features and primary glomerulonephritis were analyzed, comparing to another 84 control patients without these features who were matched according to the pathological types of glomerulonephritis. Results: In the patients with pathological features of suspected intra-kidney venous thrombus, the levels of proteinuria (5.2 vs. 3.2 g/24 h, p = 0.005), serum creatinine (80.9 vs. 71.2 μmol/L, p < 0.001), platelet count (274.0 vs. 254.5 ×109/L, p = 0.020), D-dimer (0.2 vs. 0.2 mg/L, p = 0.002), and fibrin degradation products (1.9 vs. 1.0 mg/L, p = 0.003) were significantly higher than those in control patients. The levels of serum albumin (24.2 vs. 28.6 g/L, p = 0.003) and eGFR (92.1 vs. 103.9 mL/min/1.73 m2, p < 0.001) were significantly lower. The scores of these pathological features were positively correlated with the levels of D-dimer (r = 0.21, p = 0.05). During follow-up, 9 (10.7%) patients with pathological features of suspected intra-kidney venous thrombus developed venous thromboembolism, which was significantly more than that of control patients (0%, p = 0.006). Conclusions: Kidney pathological features could indicate intra-kidney venous thromboembolism, and their scores represent the possibility of thrombus. The notice of these features may provide clinical alerts for venous thromboembolism possibility.
Reduction of Missed Diagnosis of G6PD Deficiency in Heterozygous Females by G6PD/6PGD Ratio Assay Combined with Amplification Refractory Mutation System PCR
Authors: Chen Shiguo , Gao Jian , Wu Qunyan , Li Xi , Lin Sheng , Su Jindi , Zheng Kaifeng , Guo Zhaopeng , Yao Jilong , Duan Shan
Published: October 2022

Objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked genetic disorder that results in impaired enzyme activity. The G6PD/6PGD ratio assay was routinely used for G6PD deficiency screening in China, but there is an apparent defect of missed diagnosis in heterozygous females. The study aims to explore the means to improve its accuracy. Methods: A total of 4,161 Chinese females of childbearing age were collected in this retrospective study. All samples were first subjected to G6PD/6PGD ratio assay and then screened by amplification refractory mutation system PCR (ARMS-PCR) for six hotspot mutants in Chinese population (c.1376G>T, c.1388G>A, c.95A>G, c.1024C>T, c.392G>T, and c.871G>A). For the samples with G6PD/6PGD ratio<1.0 and no mutations were found by ARMS-PCR, next-generation sequencing (NGS) was performed. Sanger sequencing was finally used to verify all the variants. Results: The prevalence of G6PD deficiency in Shenzhen females of childbearing age was 7.31%. The proportion of the six hotspot mutations accounted for 98.03% of all 304 G6PD variants carriers. Taking the ARMS-PCR/NGS results as a reference, the missed diagnosis rate of the G6PD/6PGD ratio assay was 33.88%. Using ARMS-PCR to retest the samples with a G6PD/6PGD ratio between 1.00 and ∼1.10 or 1.00 and ∼1.15 could reduce the missed diagnosis rate from the original 33.88% to 18.09% or 12.05% separately. Conclusion: ARMS-PCR is an appropriate supplementary method for discovering most carriers missed by the G6PD/6PGD ratio assay.
On the Variability in Cell and Nucleus Shapes
Authors: Devulapally Anusha , Parekh Varun , Pazhayidam George Clint , Balakrishnan Sreenath
Published: October 2022

Cell morphology is an important regulator of cell function. Many abnormalities in cellular behavior can be discerned from changes in the shape of the cell and its organelles, typically the nucleus. Two major challenges for developing such phenotypic assays are reconstructing 3D surfaces of individual cells and nuclei from confocal images and developing characterizations of these surfaces for comparisons. We demonstrate two algorithms – 3D active contours and 3D condensed-attention UNet – to segment cells and nuclei from confocal images. The cell and nuclear surfaces are then converted into vectors using a reversible, spherical transform – i.e., shapes can be recovered from the vectors. Typical methods for characterizing shapes using size, shape, and image parameters such as area, volume, shape factor, solidity, and pixel intensities are not amenable to such reverse transformation. Our vector representation’s principal component analysis shows that the significant modes of variability among cell and nucleus shapes are scaling and flattening. We benchmark these modes using a known mechanical model for nucleus morphology. Subsequent modes alter the eccentricity of the nucleus and translate and rotate it with respect to the cell. Our vector-space representation of cell and nucleus shape helps physically interpret the variability sources. It may further help to guide mechanical models and identify molecular mechanisms driving cell and nuclear shape changes.