bluuebunny/crossref_metadata_2025 huggingface dataset:
Cannabis use among workers with work-related injuries and illnesses: results from a cross-sectional study of workers’ compensation claimants in Ontario, Canada
Authors: Carnide Nancy , Nadalin Victoria , Mustard Cameron , Severin Colette N , Furlan Andrea D , Smith Peter M
Published: July 2023

Objectives

Little is known about how workers use cannabis following a work-related injury/illness, including whether they receive clinical guidance. The objective was to compare characteristics of workers using and not using cannabis after a work-related injury/illness and describe use patterns.

Design

Cross-sectional study.

Setting and participants

Workers who experienced a work-related physical injury/illness resulting in one or more days of lost time compensated by the workers’ compensation authority in Ontario, Canada (n=1196).

Methods

Participants were interviewed 18 or 36 months after their injury/illness. Participants were asked about their past-year cannabis use, including whether use was for the treatment of their work-related condition. Sociodemographic, work and health characteristics were compared across cannabis groups: no past-year use; use for the work-related condition; use unrelated to the work-related condition. Cannabis use reasons, patterns, perceived impact and healthcare provider engagement were described.

Results

In total, 27.4% of the sample reported using cannabis (14.1% for their work-related condition). Workers using cannabis for their condition were less likely to be working (58.0%) and more likely to have quite a bit/extreme pain interference (48.5%), psychological distress (26.0%) and sleep problems most/all the time (62.1%) compared with those not using cannabis (74.3%, 26.3%, 12.0% and 38.0%, respectively) and those using cannabis for other reasons (74.2%, 19.5%, 12.0% and 37.1%, respectively) (all p<0.0001). No significant differences were observed in medical authorisations for use among those using cannabis for their condition (20.4%) or unrelated to their condition (15.7%) (p=0.3021). Healthcare provider guidance was more common among those using cannabis for their condition (32.7%) compared with those using for other reasons (17.1%) (p=0.0024); however, two-thirds of this group did not receive guidance.

Conclusions

Cannabis may be used to manage the consequences of work-related injuries/illnesses, yet most do not receive clinical guidance. It is important that healthcare providers speak with injured workers about their cannabis use.
Pan-Canadian study of psychiatric care (PCPC): protocol for a mixed-methods study
Authors: Rudoler David , Lavergne M Ruth , Marshall Emily Gard , Zaheer Juveria , Etches Selene , Good Kimberley P , Grudniewicz Agnes , Katz Alan , Kurdyak Paul , Bolton James , Kaoser Ridhwana , Moravac Catherine , Morrison Jason , Mulsant Benoit , Peterson Sandra , Tibbo Phil G
Published: July 2023

Introduction

The Canadian population has poor and inequitable access to psychiatric care despite a steady per-capita supply of psychiatrists in most provinces. There is some quantitative evidence that practice style and characteristics vary substantially among psychiatrists. However, how this compares across jurisdictions and implications for workforce planning require further study. A qualitative exploration of psychiatrists’ preferences for practice style and the practice choices that result is also lacking. The goal of this study is to inform psychiatrist workforce planning to improve access to psychiatric care by: (1) developing and evaluating comparable indicators of supply of psychiatric care across provinces, (2) analysing variations and changes in the characteristics of the psychiatrist workforce, including demographics and practice style and (3) studying psychiatrist practice choices and intentions, and the factors that lead to these choices.

Methods and analysis

A cross-provincial mixed-methods study will be conducted in the Canadian provinces of British Columbia, Manitoba, Ontario and Nova Scotia. We will analyse linked-health administrative data within three of the four provinces to develop comparable indicators of supply and characterise psychiatric services at the regional level within provinces. We will use latent profile analysis to estimate the probability that a psychiatrist is in a particular practice style and map the geographical distribution of psychiatrist practices overlayed with measures of need for psychiatric care. We will also conduct in-depth, semistructured qualitative interviews with psychiatrists in each province to explore their preferences and practice choices and to inform workforce planning.

Ethics and dissemination

This study was approved by Ontario Tech University Research Ethics Board (16637 and 16795) and institutions affiliated with the study team. We built a team comprising experienced researchers, psychiatrists, medical educators and policymakers in mental health services and workforce planning to disseminate knowledge that will support effective human resource policies to improve access to psychiatric care in Canada.
Assessment of knowledge, attitudes and practices towards COVID-19 among rural adolescents in Thakurgaon district, Bangladesh: an interview-based study
Authors: Hossain Md Sobuj , Banik Rajon , Hosen Ismail , Islam Md Zohurul , Kundu Lakshmi Rani
Published: July 2023

Objectives

To evaluate the understanding, opinions and actions concerning COVID-19, referred to as knowledge, attitudes and practices (KAP), among rural adolescents in Bangladesh. Additionally, the study aimed to identify the determinants that may influence adolescents’ KAP.

Design

An interview-based cross-sectional study.

Setting

The study area was the Thakurgaon district, which was located in the northwestern region of Bangladesh.

Participants

A total of 266 rural adolescents were selected using a non-probability (convenience sampling) technique.

Main outcome measures

Sociodemographic characteristics, source of information, COVID-19-related KAP, and their associated factors.

Results

The majority of the respondents were females and reported that mass media (eg, television channels and papers) was the main source of information to learn about COVID-19. The mean score for knowledge was 7.15±3, whereas the scores were 10.5±2.8, and 8.78±2.66 for attitude and practice, respectively. Among the adolescents, only 11% had adequate knowledge, a positive attitude (27%) and good practices (31%). The predictive factors related to adolescents' knowledge and attitude were their religion, educational level and family income. Adolescents who were from the Islamic religion and who had secondary education were more knowledgeable and encompassed more positive attitudes. Besides, poor KAP towards COVID-19 was significantly higher among the participants with the lowest family income (less than 10 000 BDT). Moreover, their knowledge was significantly associated with their attitudes and practices.

Conclusion

The study found that adolescents in rural areas lacked sufficient knowledge of COVID-19 and engaged in unsatisfactory preventative behaviour. Therefore, the development of effective health education programmes that incorporate consideration of KAP-modifying factors is needed. In addition, the result would be helpful for other similar types of pandemics.
A Hybrid Convolutional Bi-Directional Gated Recurrent Unit System for Spoken Languages of JK and Ladakhi
Authors: Thukroo Irshad Ahmad , Bashir Rumaan , Giri Kaiser J.
Published: July 2023

Spoken language identification is the process of recognising language in an audio segment and is the precursor for several technologies such as automatic call routing, language recognition, multilingual conversation, language parsing, and sentimental analysis. Language identification has become a challenging task for low-resource languages like Kashmiri and Ladakhi spoken in the UT’s of Jammu and Kashmir (JK) and Ladakh, India. This is mainly due to speaker variations like duration, moderator, and ambiance particularly when training and testing are done on different datasets whilst analysing the accuracy of language identification system in actual implementation, thus producing low accuracy results. In order to tackle this problem, we propose a hybrid convolutional bi-directional gated recurrent unit (Bi-GRU) utilising the effects of both static and dynamic behaviour of the audio signal in order to achieve better results as compared to state-of-the-art models. The audio signals are first converted into two-dimensional structures called Mel-spectrograms to represent the frequency distribution over time. To investigate the spectral behaviour of audio signals, we employ a convolutional neural network (CNN) that perceives Mel-spectrograms in multiple dimensions. The CNN-learned feature vector serves as input to the Bi-GRU that maintains the dynamic behaviour of the audio signal. Experiments are done on six spoken languages, i.e. Ladakhi, Kashmiri, Hindi, Urdu, English, and Dogri. The data corpora used for experimentation are the International Institute of Information Technology Hyderabad-Indian Language Speech Corpus (IIITH-ILSC) and the self-created data corpus for the Ladakhi language. The model is tested on two datasets, i.e. speaker-dependent and speaker-independent. Results show that when validating the efficiency of our proposed model on both speaker-dependent and speaker-independent datasets, we achieve optimal accuracies of 99% and 91%, respectively, thus achieving promising results in comparison to the state-of-the-art models available.
North Korean Neural Machine Translation through South Korean Resources
Authors: Kim Hwichan , Tosho Hirasawa , Moon Sangwhan , Okazaki Naoaki , Komachi Mamoru
Published: July 2023

South and North Korea both use the Korean language. However, Korean natural language processing (NLP) research has mostly focused on South Korean language. Therefore, existing NLP systems in the Korean language, such as neural machine translation (NMT) systems, cannot properly process North Korean inputs. Training a model using North Korean data is the most straightforward approach to solving this problem, but the data to train NMT models are insufficient. To solve this problem, we constructed a parallel corpus to develop a North Korean NMT model using a comparable corpus. We manually aligned parallel sentences to create evaluation data and automatically aligned the remaining sentences to create training data. We trained a North Korean NMT model using our North Korean parallel data and improved North Korean translation quality using South Korean resources such as parallel data and a pre-trained model. In addition, we propose Korean-specific pre-processing methods, character tokenization, and phoneme decomposition to use the South Korean resources more efficiently. We demonstrate that the phoneme decomposition consistently improves the North Korean translation accuracy compared to other pre-processing methods.
A Systematic Literature Review on Vietnamese Aspect-based Sentiment Analysis
Authors: Van Thin Dang , Hao Duong Ngoc , Nguyen Ngan Luu-Thuy
Published: July 2023

Aspect-based sentiment analysis (ABSA) is one of the principal tasks in the automatic deep understanding of texts, widely applied in a broad range of real-world applications. Many studies have been performed on different tasks and datasets for other languages (e.g., English, Chinese) to address this topic. For Vietnamese language, this topic has been attracting considerable interest in recent years. However, we found that many studies tend to repeat the research instead of inheriting and extending the previous works. Moreover, previous studies’ methods of comparison or evaluation metrics have not shown consistency and connection. This might restrict the development of future studies on this research topic. To the best of our knowledge, no research has been conducted to overview the existing studies for the ABSA research in Vietnamese language. The primary objective of this study is to provide a systematic and comprehensive review of the current Vietnamese ABSA research. More specifically, we analyze the early approaches, evaluation metrics, and available published benchmark datasets used in the Vietnamese ABSA task. We also discuss the challenge and recommend potential future directions for Vietnamese ABSA. This work is expected to provide readers with a wealth of knowledge, the research gap, and the challenges in the Vietnamese ABSA field.
WAD-X: Improving Zero-shot Cross-lingual Transfer via Adapter-based Word Alignment
Authors: Ahmat Ahtamjan , Yang Yating , Ma Bo , Dong Rui , Lu Kaiwen , Wang Lei
Published: July 2023

Multilingual pre-trained language models (mPLMs) have achieved remarkable performance on zero-shot cross-lingual transfer learning. However, most mPLMs implicitly encourage cross-lingual alignment in pre-training stage, making it hard to capture accurate word alignment across languages. In this paper, we propose Word-align ADapters for Cross-lingual transfer (WAD-X) to explicitly align word representations of mPLMs via language-specific subspace. Taking a mPLM as the backbone model, WAD-X constructs subspace for each source-target language pair via adapters. The adapters use statistical alignment as the prior knowledge to guide word-level aligning in the corresponding bilingual semantic subspace. We evaluate our model across a set of target languages on three zero-shot cross-lingual transfer tasks: part-of-speech tagging (POS), dependency parsing (DP), and sentiment analysis (SA). Experimental results demonstrate that our proposed model improves zero-shot cross-lingual transfer on three benchmarks, with improvements of 2.19, 2.50, and 1.61 points in POS, DP, and SA tasks over strong baselines.
Vulnerability Disclosure Considered Stressful
Authors: Moura Giovane C. M. , Heidemann John
Published: July 2023

Vulnerability disclosure is a widely recognized practice in the software industry, but there is a lack of literature detailing the firsthand experiences of researchers who have gone through the process. This work aims to bridge that gap by sharing our personal experience of accidentally discovering a DNS vulnerability and navigating the vulnerability disclosure process for the first time. We document our mistakes and highlight the important lessons we learned, such as the fact that public disclosure can be effective but can also be more time-consuming and emotionally taxing than anticipated. Additionally, we discuss the ethical considerations and potential consequences that may arise during each step of the disclosure process. Lastly, drawing from our own experiences, we identify and discuss issues with the current disclosure process and propose recommendations for its improvement. Our ultimate aim is to provide valuable insights to fellow researchers who may encounter similar challenges in the future and contribute to the enhancement of the overall disclosure process for the benefit of the wider community.
Imaging Neuroscience opening
editorial
Authors: Smith Stephen , Bergmann Til Ole , Forstmann Birte , Dagher Alain , Keilholz Shella , Kennedy Kristen , Kotz Sonja A. , Lustig Cindy , Pike Bruce , Tittgemeyer Marc , Woolrich Mark , Yeo B.T. Thomas , Alexander Andrew , Bijsterbosch Janine , Boonstra Tjeerd , Chakravarty Mallar , Chambers Chris , Chang Catie , Christian Bradley , Dalal Sarang S. , Ding Nai , Duarte Audrey , Fan Audrey P. , Gramfort Alexandre , Hartwigsen Gesa , Jabbi Mbemba , Kochunov Peter , Krämer Ulrike , Lindquist Martin , Mangin Jean-Francois , Murphy Kevin , Polimeni Jonathan , Robinson Emma , Rosenberg Monica , Sadaghiani Sepideh , Seghier Mohamed , Shih Yen-Yu Ian , Thielscher Axel , Uddin Lucina Q. , Van De Ville Dimitri , Vanduffel Wim , Yan Chao-Gan , Yendiki Anastasia
Published: July 2023

In this editorial we introduce a new non-profit open access journal, Imaging Neuroscience. In April 2023, editors of the journals NeuroImage and NeuroImage:Reports resigned, and a month later launched Imaging Neuroscience. NeuroImage had long been the leading journal in the field of neuroimaging. While the move to fully open access in 2020 represented a positive step toward modern academic practices, the publication fee was set to a level that the editors found unethical and unsustainable. The publisher of NeuroImage, Elsevier, was unwilling to reduce the fee after much discussion. This led us to launch Imaging Neuroscience with MIT Press, intended to replace NeuroImage as our field’s leading journal, but with greater control by the neuroimaging academic community over publication fees and adoption of modern and ethical publishing practices.
Nanoparticles Embedded In2O3 Microspheres for Selective and Quantitative Detection of NO2 Gas
Authors: Shah Sufaid , Hussain Shahid , Shaheen Asma , Liu Guiwu , Hashem Mohamed , Alsarani Majed M. , Akhtar M. S. , Tianyan You , Qiao Guanjun , Fouad Hassan
Published: July 2023

Harmful consequences on human health have been caused by the rapidly rising levels of environmentally hazardous gases. It is necessary to detect these polluting gases using a variety of methods. Nanoparticles engraved spherical-shaped indium oxide structures are synthesized via a simple
one-step solvothermal method. The synthesized products were successfully characterized using XRD, SEM, EDS, TEM and XPS analysis. Nanoparticle embedded In2O3 microspheres are prepared for selective, quantitative and low concentration (1–10 ppm) of NO2
gas detection at operating temperature of 75 °C–250 °C. A high sensing response of 29 is observed at 10 ppm with sharp response and recovery times of 44 s and 56 s at 200 °C, respectively. The superior performances towards NO2 gas is attributed to the presence
of plenty of junctions between nanoparticles-microspheres surfaces and high surface area for gas molecules interactions. The fabricated sensors are promised and potential applicants in the environmental pollution detection devices on industrial scale.
Influence of Oxygen Adsorption on Local N-Doped TiO2/p-Si (100) Heterojunction UV-Visible Photodetector
Authors: Tian Gaoqi , Lei Qiumei , Li Wenyao , Su Anna , Hashem Mohamed , Ji Tao
Published: July 2023

TiO2-based devices are known for their responsive behavior to environmental conditions. In this study, we report the fabrication of a locally N-doped TiO2/p-Si (100) heterojunction UV-vis photodetector, achieved through a series of processes including magnetron
sputtering, high-temperature annealing, hydrothermal synthesis, and thermal evaporation. Due to surface oxygen adsorption and partial nitrogen doping in TiO2, the photocurrent of the device was found to be higher in vacuum than in air at low voltage, and lower in vacuum than in
air at higher voltage. Moreover, the photocurrent was more likely to reach saturation under vacuum at low voltage. Under UV light illumination (380 nm), the voltage applied to the device to reach the saturation currents in vacuum and air were approximately −1 V and −1.5 V, respectively,
and these values increased slightly when illuminated by visible light (480 nm). The study of the impact of oxygen adsorption and partial N doping in TiO2 on the hindrance and multiplier effects of carrier movement in photodetectors can be beneficial for the development and application
of wearable, biosensing, and vacuum sensing devices.
Design, Performance Optimization and Application of High-Entropy Alloy Materials in Mechanical Engineering: A Review
Authors: Yi Qiang , Lv Xiyuan
Published: July 2023

High-entropy alloys have multi-scale and complex microstructures, and their properties are highly tunable. They have great potential for development. However, the current development of high-entropy alloys is still dominated by trial and error, lacking effective guidance and low development
efficiency. Machine learning is a data-based material design technology, which has been applied to the prediction of phase composition, prediction and optimization of mechanical properties, and auxiliary simulation calculations in the field of high-entropy alloys. However, the insufficiency
of existing data, unbalanced distribution and the limitation of the model itself lead to great uncertainty in the composition optimization strategy based on machine learning. Based on this, this paper takes the machine learning method as the core, combines the composition design and the material
design idea based on machine learning, and discusses its design idea in the high-entropy alloy system. And summarize their application research status in high entropy alloy composition screening, phase and structure calculation, and performance prediction. Finally, the current problems in
this field are proposed, and solutions and future prospects are provided.
Long Non-Coding RNA Nuclear Paraspeckle Assembly Transcript 1: A Regulator of Trophoblast Cells in the Progression of Gestational Diabetes Mellitus
Authors: Li Wushan , Wang Xiaojuan , Hao Dongdong
Published: July 2023

The potential function of NEAT1 in the progression of Gestational diabetes mellitus (GDM) and the molecular mechanisms are explored. NEAT1 levels in multiple types of cell lines and placental tissues collected from healthy, GDM and preeclampsia pregnancies were detected by quantitative
real-time polymerase chain reaction (qRT-PCR). After intervening NEAT1 level in HTR-8/SVneo cells, proliferative, migratory and apoptotic potentials were examined by cell counting kit-8 (CCK-8), 5-Ethynyl-2′-deoxyuridine (EdU), transwell assay and flow cytometry. The regulatory effect
of NEAT1 on the transcriptional activity of NSD1 was predicted by bioinformatic analysis and further confirmed by dual-luciferase reporter assay. In addition, histone modifications of NEAT1 on NSD1 transcription were examined by chromatin immunoprecipitation (ChIP). NEAT1 was upregulated in
placental tissues collected from GDM patients. Overexpression of NEAT1 stimulated proliferative and migratory potentials, but inhibited apoptosis in HTR-8/SVneo cells. Knockdown of NEAT1 had the opposite outcomes. NEAT1 was able to regulate the transcriptional activity of NSD1 through histone
modifications on H3K27Me3 and H3K27Cro. NEAT1 is upregulated in GDM cases, which triggers proliferative and migratory potentials in trophoblast cells mainly through regulating transcriptional activity of NSD1 via histone modification.
Photobiomodulation Therapy in Mitigating the Risk of SARS CoV-2 Infection by Enhancing Biodiversity of Oral Microbiome-A Conceptual Hypothesis Based on Scoping Review
Authors: Hosmani Jagadish , Alqarni Abdullah , Yavagal Chandrashekar , Abullais Shahabe Saquib , Khalid Imran , Basheer Sulphi Abdul , Ibrahim Mohammed , Alshahrani Mohammad Y. , Alshahrani Abdulrahman Yahya
Published: July 2023

Since March 2020, scientists across the globe are looking for ways to combat COVID-19, a viral disease of recent times which was declared Pandemic by WHO. Mounting an incompetent immune reverberation and the surge in pro-inflammatory cytokines are the main cause for complications. Hence,
it is hypothesized that photobiomodulation therapy (PBMT) using low-level light therapy (LLLT) might be a successful therapeutic treatment for COVID-19 victims since it has been shown to be successful in enhancing immunity, aiding in tissue healing, and reducing pro-inflammatory cytokines.
The goal of this scoping review is to investigate the potential use of PBMT as a promising neo-strategy for an alternative therapy for the treatment of patients with COVID-19 in light of the significance of underlying pathways in the mitigation, therapeutic interventions, and recovery of chronic
diseases like COVID-19. The findings of the review revealed that PBMT using a low-level laser has been proven to be effective in treating COVID-19’s initial stages and prevent the progression to severe form of the disease. This approach needs to be confirmed by clinical trials and larger
studies that include a wider population. Because of its proven effectiveness in reducing inflammation, thrombosis and accelerate wound healing, PBMT may be a promising approach to reduce the severity of COVID-19, especially in the lungs. Based on the findings of the review, we propose a novel
hypothesis of utilizing PBMT to enhance the biodiversity of oral microbiome which will help in extenuating the imperilment of SARS CoV-2 infection.
Mechanism of Triptolide Liposome Nanoparticles on Apoptosis of Multiple Myeloma Cells Induced by Bortezomib
Authors: Xiao Ying , Chang Wei , Jiang Hui , Liu Xiaoqian , Xu Chaoping
Published: July 2023

The aim of this research was to investigated the effects of triptolide (TP) and its liposome nanoparticles (TP-LNP) on the apoptosis of multiple myeloma (MM) cells induced by Bortezomi. The encapsulation rate (ER), drug loading (DL), particle size (PS), and Zeta potential characteristics
of the TP-LNP were evaluated. MMT assay was employed to detect the inhibitory effect of TP single agent and TP-LNP on proliferation of MM cells. MM cells were enrolled into a control group (Ctrl group, no intervention), a Bortezomi group (75 nM Bortezomi intervention 12 h), a Bortezomi +TP
group (Bortezomi combined with TP monotherapy), and a Bortezomi+TP-LNP group (Bortezomi combined with TP-LNP). CCK-8, flow cytometry, and Western blot were utilized to detect the cell survival rate (SR), apoptosis, and MAPK/ERK pathway related protein, respectively. The results revealed that
the shape of TP-LNP was similar to circular and uniformly distributed. Its average PS was (181.2±6.3) nm, the average Zeta potential was −29.15 mV, the average ER was 82.1%, and the average DL was 1.09%. When the drug concentration was 100 nmol/L, the inhibition rates of cell
proliferation of TP and TP-LNP were (66.8±0.5)% and (81.4±0.6)%, respectively; and their median inhibitory concentrations (MICs) after 72 h were (89.5±1.8) nmol/L and (55.3±2.2) nmol/L, respectively. Based on the Ctrl group, the SRs in the Bortezomi, Bortezomi+TP,
and Bortezomi+TP-LNP groups were decreased obviously, while the apoptosis rates were increased, and the comparisons herein exhibited great differences with P <0.05. The SR in the Bortezomi+TP-LNP group was the lowest and the apoptosis rate was the highest, showing great differences
among the three groups (P < 0.05). Based on the Ctrl group, the expressions of P-P38 and P-ErK in the Bortezomi, Bortezomi+TP, and Bortezomi+TP-LNP groups were decreased (P <0.05). The levels of P-P38 and P-Erk in the Bortezomi+TP-LNP group were the lowest, and the differences
in those in this group and the Bortezomi and the Bortezomi+TP groups statistically great (P <0.05). TP-LNP could inhibit the activation of MAPK/ERK pathway, enhance the apoptosis of MM cells induced by Bortezomi, and inhibit the cell proliferation.
A robust quality infrastructure is key to safe and effective delivery of immune effector cells: how FACT-finding can help
Authors: Curran Kevin J. , Nikiforow Sarah , Bachier Carlos , Hsu Yen-Michael , Maloney David , Maus Marcela V. , McCarthy Philip , Porter David , Shi Patricia , Shpall Elizabeth J. , William Basem , Wacker Kara , Warkentin Phyllis , Heslop Helen E.
Published: July 2023

Immune effector cells (IECs) include a broad range of immune cells capable of modulating several disease states, including malignant and nonmalignant conditions. The growth in the use of IECs as both investigational and commercially available products requires medical institutions to develop workflows/processes to safely implement and deliver transformative therapy. Adding to the complexity of this therapy are the variety of targets, diseases, sources, and unique toxicities that a patient experiences following IEC therapy. For over 25 years, the Foundation for the Accreditation of Cellular Therapy (FACT) has established a standard for the use of cellular therapy, initially with hematopoietic cell transplantation (HCT), and more recently, with the development of standards to encompass IEC products such as chimeric antigen receptor (CAR)-T cells. To date, IEC therapy has challenged the bandwidth and infrastructure of the institutions offering this therapy. To address these challenges, FACT has established a programmatic framework to improve the delivery of IEC therapy. In this study, we outline the current state of IEC program development, accreditation, and solutions to the challenges that programs face as they expand their application to novel IEC therapy.
Multi-Round versus Real-Time Delphi survey approach for achieving consensus in the COHESION core outcome set: a randomised trial
Authors: Quirke Fiona A. , Battin Malcolm R. , Bernard Caitlin , Biesty Linda , Bloomfield Frank H. , Daly Mandy , Finucane Elaine , Haas David M. , Healy Patricia , Hurley Tim , Koskei Sarah , Meher Shireen , Molloy Eleanor J. , Niaz Maira , Bhraonáin Elaine Ní , Okaronon Christabell Omukagah , Tabassum Farhana , Walker Karen , Webbe James R. H. , Parkes Matthew J. , Kirkham Jamie J. , Devane Declan
Published: July 2023

Background

Delphi surveys are commonly used to prioritise critical outcomes in core outcome set (COS) development. This trial aims to compare a three-round (Multi-Round) Delphi (MRD) with a Real-Time Delphi (RTD) in the prioritisation of outcomes for inclusion in a COS for neonatal encephalopathy treatments and explore whether ‘feedback’, ‘iteration’, and ‘initial condition’ effects may occur in the two survey methods.

Methods

We recruited 269 participants (parents/caregivers, healthcare providers and researchers/academics) of which 222 were randomised to either the MRD or the RTD. We investigated the outcomes prioritised in each survey and the ‘feedback’, ‘iteration’, and ‘initial condition’ effects to identify differences between the two survey methods.

Results

In the RTD, n = 92 participants (83%) fully completed the survey. In the MRD, n = 60 participants (54%) completed all three rounds. Of the 92 outcomes presented, 26 (28%) were prioritised differently between the RTD and MRD. Significantly fewer participants amended their scores when shown stakeholder responses in the RTD compared to the MRD (‘feedback effect’). The ‘iteration effect’ analysis found most experts appeared satisfied with their initial ratings in the RTD and did not amend their scores following stakeholder response feedback. Where they did amend their scores, ratings were amended substantially, suggesting greater convergence. Variance in scores reduced with subsequent rounds of the MRD (‘iteration effect’). Whilst most participants did not change their initial scores in the RTD, of those that did, later recruits tended to align their final score more closely to the group mean final score than earlier recruits (an ‘initial condition’ effect).

Conclusion

The feedback effect differed between the two Delphi methods but the magnitude of this difference was small and likely due to the large number of observations rather than because of a meaningfully large difference. It did not appear to be advantageous to require participants to engage in three rounds of a survey due to the low change in scores. Larger drop-out through successive rounds in the MRD, together with a lesser convergence of scores and longer time to completion, indicate considerable benefits of the RTD approach.

Trial registration

NCT04471103. Registered on 14 July 2020.
Identification of potential biomarkers related to mesenchymal stem cell response in patients with Alzheimer’s disease
Authors: Choi Yejoo , Shin Sungho , Son Hyo Jin , Lee Na-Hee , Myeong Su Hyeon , Lee Cheolju , Jang Hyemin , Choi Soo Jin , Kim Hee Jin , Na Duk L.
Published: July 2023

Background

Preclinical studies showed that mesenchymal stem cells (MSCs) ameliorate tau phosphorylation, amyloid-beta accumulation, and inflammation in Alzheimer’s disease (AD) mouse models via secretion of neurotrophic factors and cytokines. We aimed to identify CSF biomarkers that can be used to predict or monitor the response to MSCs in patients with AD.

Methods

AD patients were injected with human umbilical cord blood-MSCs (n = 22) or placebo (n = 12). The cerebrospinal fluid (CSF) samples were collected at baseline, one day after the first injection, and one day after the third injection. The patients injected with MSCs were classified into good responder (GR) or poor responder (PR) groups based on the rate of changes in the ratio of total-tau and phosphorylated-tau in the CSF. We selected three typical participants in each group, and their CSF protein levels were analyzed using liquid chromatography/tandem mass spectrometry (LC–MS/MS).

Results

In the LC–MS/MS analysis, 1,667 proteins were identified. Eleven proteins showed significant differences between the typical GR and PR at baseline. Based on their significance level and known functions, two proteins, reticulocalbin-3 (RCN3) and follistatin-related protein 3 (FSTL3), were selected as potential biomarkers to predict MSC response. A total of 173 proteins showed significant change one day after the third injection compared to the baseline in typical GR. We excluded 45 proteins that showed significant change after the third injection compared to the baseline in the typical PR. Based on their significance level and known function, four proteins, scrapie-responsive protein 1 (SCRG1), neural proliferation differentiation and control protein (NPDC1), apolipoprotein E (ApoE), and cystatin C (CysC), were selected as potential biomarker to monitor MSC response. Additionally, functional analysis revealed that the increased CSF proteins after the third injection compared to the baseline in the typical GR were associated with synaptogenesis.

Conclusions

This study identified two proteins (RCN3 and FSTL3) that may be potential biomarkers for predicting MSC response and four proteins (SCRG1, NPDC1, ApoE, CysC) that may be potential biomarkers for monitoring MSC response in patients with AD. Further studies are needed to validate our results.

Trial registration Clinical Trials.gov, NCT02054208. Registered on 4 February 2014. Samsung Medical Center IRB File No.2017-04-025. Registered on 20 June 2017.
Chemical screening links disulfiram with cardiac protection after ischemic injury
Authors: Chen Yuanyuan , Du Jianyong , Zheng Lixia , Wang Zihao , Zhang Zongwang , Wu Zhengyuan , Zhu Xiaojun , Xiong Jing-Wei
Published: July 2023

Ischemia–reperfusion injury occurs after reperfusion treatment for patients suffering myocardial infarction, however the underlying mechanisms are incompletely understood and effective pharmacological interventions are limited. Here, we report the identification and characterization of the FDA-approved drug disulfiram (DSF) as a cardioprotective compound. By applying high-throughput chemical screening, we found that DSF decreased H2O2-induced cardiomyocyte death by inhibiting Gasdermin D, but not ALDH1, in cardiomyocytes. Oral gavage of DSF decreased myocardial infarct size and improved heart function after myocardial ischemia–reperfusion injury in rats. Therefore, this work reveals DSF as a potential therapeutic compound for the treatment of ischemic heart disease.
Antifungal activity of three different varieties of Capsicum annuum against clinical isolates of Candida species
Authors: Moghadam Shaghayegh , Azari Behnam , Rashidi Roghayeh , Bafghi Mahdi Hosseini , Rakhshandeh Hassan , Selman Selman Mohammed , Zarrinfar Hossein
Published: July 2023

Objective

Acquired resistance to antifungal agents is rising among Candida species. Herbal extracts including Capsicum annum extracts have biological profits, which can be employed to overcome drug resistance in fungal species. The present study investigated the efficacy of different varieties of C. annum extracts against Candida species.

Methods

Aqueous and alcoholic extracts of three different varieties of C. annum were prepared using the succulent method. Total values for compound extracts of C. annum var. cayenne, C. annum var. cayenne cultivar sabzevari, and C. annum var. cerasiforme were 43, 42, and 38 g, respectively. The clinical Candida isolates including C. albicans (n = 13), C. dubliniensis (n = 2), C. parapsilosis (n = 2), and C. tropicalis (n = 1); and reference strains of C. albicans (TIMML 1292 and TIMML 183), C. krusei (TIMML 1321), C. parapsilosis (TIMML 2201), and C. tropicalis (TIMML 731) were examined based on the M27-A3 guideline.

Results

Aqueous and alcoholic extracts of Capsicum annum showed a minimum inhibitory concentration (MIC) range of more than 512 µg/ml against clinical and reference strains of Candida. There was no justifiable difference between the effects of these extracts on Candida species.

Conclusion

Both aqueous and alcoholic extracts of Capsicum annum could not exert a significant effective impact on clinical and reference strains of Candida. The difference in pepper spiciness did not show a significant role against Candida isolates. However, their possible effects might be different among other yeasts or filamentous fungi.
Designing a survey framework to collect port stakeholders’ insight regarding AI implementation: results from the Flemish context
Authors: Farzadmehr Mehran , Carlan Valentin , Vanelslander Thierry
Published: July 2023

Today, several research/initiatives exist in AI technology at the port operation. They mainly focus on solution development in a particular port and shipping industry domain. This scattered implementation leads to an unstructured overview of the port sector regarding AI innovation in use. Equally, this study aims to structure this overview for aligning stakeholders and AI providers toward implementation. In doing so, the first step would be collecting the port stakeholders' insight regarding AI implementation. This study develops a structured framework to collect the port stakeholders’ insight through both desk and empirical research. Besides, an online survey is built based on the framework and sent to a target group of port stakeholders to collect their insight. The survey results show that a huge effort is needed to establish a structure for data exchange to increase the quality of data. Additionally, by highlighting the importance of data from specific stakeholders, developers can effectively convey the value proposition to these stakeholders. They can emphasize how utilizing this vital data can result in operational enhancements, cost reductions, improved decision-making, and competitive advantages. As an implication, alignment between port stakeholders and AI providers enhances the maturity level of the market in AI solutions by fostering collaboration, addressing industry-specific challenges, tailoring solutions, and garnering support for implementation.
Qualitative exploration of the visual function impairments and impacts on vision-dependent activities of daily living in Retinitis Pigmentosa and Leber Congenital Amaurosis: content validation of the ViSIO-PRO and ViSIO-ObsRO measures
Authors: Kay Christine , Audo Isabelle , Naujoks Christel , Spera Claudio , Fischer M. Dominik , Green Jane , Durham Todd , Williamson Nicola , Bradley Helena , Barclay Melissa , Sims Joel , Banhazi Judit , Patalano Francesco
Published: July 2023

Background

Retinitis Pigmentosa (RP) and Leber Congenital Amaurosis (LCA) are rare inherited retinal degenerative disorders. The associated visual impairments have significant impacts on patients’ vision-dependent activities of daily living (ADL), mobility, and distal health-related quality of life (HRQoL). To adequately capture patient and caregiver perspectives in clinical trials, patient and observer-reported outcome instruments must demonstrate sufficient evidence of content validity in the target population. This study aimed to explore the patient experience of RP/LCA and assess the content validity of the Visual Symptom and Impact Outcomes PRO (ViSIO-PRO) and ObsRO (ViSIO-ObsRO) instruments in RP/LCA.

Methods

A total of 66 qualitative, combined concept elicitation (CE) and cognitive debriefing (CD) interviews were conducted (33 adults, 10 adolescents, 8 children and 15 caregivers of children) in the US, France, Germany, and Canada. Patients had a clinical and genetic diagnosis of RP/LCA from a range of genotypes. CE results were used to further inform the development of a conceptual model and CD interviews assessed the relevance and understanding of the 44-item ViSIO-PRO and 26-item ViSIO-ObsRO instruments. Interviews were conducted across two iterative rounds to allow item modifications.

Results

Findings were consistent across RP/LCA genotypes. Night blindness, reduced peripheral vision, vision in very bright lighting and light/dark adaptation were the most frequently reported visual function symptoms impacting vision-dependent ADL and mobility. Impacts on distal HRQoL domains were also reported. The ViSIO-PRO and ObsRO items were well understood by participants and relevant across genotypes. The instructions, 7-day recall period and response scales were well understood and endorsed. Participant and expert clinician feedback supported modifications to item wording, the addition of six new ViSIO-PRO items and one new ViSIO-ObsRO item, and the removal of one ViSIO-PRO item due to lack of relevance.

Conclusions

Findings support the content validity of the ViSIO-PRO and ViSIO-ObsRO instruments for use across RP/LCA genotypes. Ongoing research to evaluate the psychometric validity of the instruments will support future use of the instruments as efficacy endpoints in clinical trials and in general clinical practice to track disease severity and impact of disease on functioning.
Extraction of biosurfactant from pseudomonas aeruginosa inhabiting oil-spilled soils
Authors: Yagoo Alex , Vilvest Jelin
Published: July 2023

Background

Screening for biosurfactant-producing microbes involves the process of sampling and isolating bacteria from various environmental sources. Hydrocarbon-contaminated locations are considered ideal sources for isolating bacteria that produce biosurfactants. This is because these microbes have adapted to living in oil-contaminated environments and have developed mechanisms to produce biosurfactants as a means of survival. Therefore, screening microbes from such locations increases the likelihood of finding bacteria capable of producing biosurfactants.

Results

This investigation aimed to isolate bisurfactant-producing bacteria from oil-contaminated soil samples, with a particular focus on Pseudomonas aeruginosa. Out of the 10 samples collected, four were confirmed to be P. aeruginosa, and all strains showed positive results for antagonistic, hemolytic, and emulsification tests. The strains were effective against B. subtilis, S. aureus, and E. coli but less effective against A. hydrophila. The PS10 strain exhibited the highest emulsification index, while PS08 showed the lowest. Based on microscopic and biochemical examination, P. aeruginosa was identified as the most effective isolate.

Conclusion

These findings highlight the potential of P. aeruginosa as a biosurfactant producer for industrial and environmental applications. However, further studies are needed to fully understand the biosurfactant production potential of these strains and to optimize the conditions for biosurfactant production.
Longitudinal Monitoring of Circulating Tumor DNA to Assess the Efficacy of Immune Checkpoint Inhibitors in Patients With Advanced Genitourinary Malignancies
Authors: Jang Albert , Lanka Sree M. , Jaeger Ellen B. , Lieberman Alexandra , Huang Minqi , Sartor A. Oliver , Mendiratta Prateek , Brown Jason R. , Garcia Jorge A. , Farmer Tiffany , Sudhaman Sumedha , Mahmood Tamara , Pajak Natalia , Calhoun Mark , Dutta Punashi , ElNaggar Adam , Liu Minetta C. , Barata Pedro C.
Published: July 2023

PURPOSE

Circulating tumor DNA (ctDNA) detection in blood has emerged as a prognostic and predictive biomarker demonstrating improved assessment of treatment response in patients receiving immune checkpoint inhibitors (ICIs). Here, we performed a pilot study to support the role of ctDNA for longitudinal treatment response monitoring in patients with advanced genitourinary (GU) malignancies receiving ICIs.

MATERIALS AND METHODS

Patients with histologically confirmed advanced GU malignancies were prospectively enrolled. All eligible patients received ICI treatment for at least 12 weeks, followed by serial collection of blood samples every 6-8 weeks and conventional scans approximately every 12 weeks until disease progression. ctDNA analysis was performed using Signatera, a tumor-informed multiplex-polymerase chain reaction next-generation sequencing assay. Overall, the objective response rate (ORR) was reported and its association with ctDNA status was evaluated. Concordance rate between ctDNA dynamics and conventional imaging was also assessed.

RESULTS

ctDNA analysis was performed on 98 banked plasma samples from 20 patients (15 renal, four urothelial, and one prostate). The median follow-up from the time of initiation of ICI to progressive disease (PD) or data cutoff was 67.7 weeks (range, 19.6-169.6). The ORR was 70% (14/20). Eight patients ultimately developed PD. The overall concordance between ctDNA dynamics and radiographic response was observed in 83% (15/18) of patients. Among the three patients with discordant results, two developed CNS metastases and one progressed with extracranial systemic disease while ctDNA remained undetectable.

CONCLUSION

In this pilot study, longitudinal ctDNA analysis for monitoring response to ICI in patients with advanced GU tumors was feasible. Larger prospective studies are warranted to validate the utility of ctDNA as an ICI response monitoring tool in patients with advanced GU malignancies.
Age-related Changes in the Adrenal Cortex: Insights and Implications
Authors: Warde Kate M , Smith Lorenzo J , Basham Kaitlin J
Published: July 2023

Aging is characterized by a gradual decline in physiological function. This process affects all organs including the adrenal cortex, which normally functions to produce essential steroid hormones including mineralocorticoids, glucocorticoids, and androgens. With increasing age, features such as reduced adrenal cortex size, altered zonation, and increased myeloid immune cell infiltration substantially alter the structure and function of the adrenal cortex. Many of these hallmark features of adrenal cortex aging occur both in males and females, yet are more enhanced in males. Hormonally, a substantial reduction in adrenal androgens is a key feature of aging, which is accompanied by modest changes in aldosterone and cortisol. These hormonal changes are associated with various pathological consequences including impaired immune responses, decreased bone health, and accelerated age-related diseases. One of the most notable changes with adrenal aging is the increased incidence of adrenal tumors, which is sex dimorphic with a higher prevalence in females. Increased adrenal tumorigenesis with age is likely driven by both an increase in genetic mutations as well as remodeling of the tissue microenvironment. Novel antiaging strategies offer a promising avenue to mitigate adrenal aging and alleviate age-associated pathologies, including adrenal tumors.