bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of an artificial intelligence system to identify hypoglycaemia via ECG in adults with type 1 diabetes: protocol for data collection under controlled and free-living conditions
Authors: Cisuelo Owain , Stokes Katy , Oronti Iyabosola B , Haleem Muhammad Salman , Barber Thomas M , Weickert Martin O , Pecchia Leandro , Hattersley John
Published: April 2023

Introduction

Hypoglycaemia is a harmful potential complication in people with type 1 diabetes mellitus (T1DM) and can be exacerbated in patients receiving treatment, such as insulin therapies, by the very interventions aiming to achieve optimal blood glucose levels. Symptoms can vary greatly, including, but not limited to, trembling, palpitations, sweating, dry mouth, confusion, seizures, coma, brain damage or even death if untreated. A pilot study with healthy (euglycaemic) participants previously demonstrated that hypoglycaemia can be detected non-invasively with artificial intelligence (AI) using physiological signals obtained from wearable sensors. This protocol provides a methodological description of an observational study for obtaining physiological data from people with T1DM. The aim of this work is to further improve the previously developed AI model and validate its performance for glycaemic event detection in people with T1DM. Such a model could be suitable for integrating into a continuous, non-invasive, glucose monitoring system, contributing towards improving surveillance and management of blood glucose for people with diabetes.

Methods and analysis

This observational study aims to recruit 30 patients with T1DM from a diabetes outpatient clinic at the University Hospital Coventry and Warwickshire for a two-phase study. The first phase involves attending an inpatient protocol for up to 36 hours in a calorimetry room under controlled conditions, followed by a phase of free-living, for up to 3 days, in which participants will go about their normal daily activities unrestricted. Throughout the study, the participants will wear wearable sensors to measure and record physiological signals (eg, ECG and continuous glucose monitor). Data collected will be used to develop and validate an AI model using state-of-the-art deep learning methods.

Ethics and dissemination

This study has received ethical approval from National Research Ethics Service (ref: 17/NW/0277). The findings will be disseminated via peer-reviewed journals and presented at scientific conferences.

Trial registration number

NCT05461144.
Impact of slack resources on healthcare costs in tertiary and secondary hospitals: a panel data study of public hospitals in Beijing from 2015 to 2019
Authors: Chen Chen , Song Xinrui , Zhu Junli
Published: April 2023

Objective

This study aims to explore the relationship between slack resources and cost consumption index in tertiary and secondary hospitals and to provide targeted healthcare resource utilisation recommendations for tertiary and secondary hospital managers.

Design

This is a panel data study of 51 public hospitals in Beijing from 2015 to 2019.

Setting

Tertiary and secondary public hospitals in Beijing. Data envelope analysis was used to calculate the slack resources. Regression models were used to explore the relationship between slack resources and healthcare costs.

Participants

A total of 255 observations were collected from 33 tertiary hospitals and 18 secondary hospitals.

Outcome measures

Slack resources and healthcare costs in tertiary and secondary public hospitals in Beijing from 2015 to 2019. Linear or curve relationship between slack resources and healthcare costs in tertiary and secondary hospitals.

Results

The cost of healthcare in tertiary hospitals has always been higher than in secondary hospitals, and the slack resources in secondary hospitals have always been worse than in tertiary hospitals. For tertiary hospitals, the cubic coefficient of slack resources is significant (β=−12.914, p<0.01) and the R2of cubic regression is increased compared with linear and quadratic regression models, so there is a transposed S-shaped relationship between slack resources and cost consumption index. For secondary hospitals, only the first-order coefficient of slack resources in the linear regression was significant (β=0.179, p<0.05), so slack resources in secondary hospitals were positively related to the cost consumption index.

Conclusions

This study shows that slack resources’ impact on healthcare costs differs in tertiary and secondary public hospitals. For tertiary hospitals, slack should be kept within a reasonable range to control excessive growth in healthcare costs. In secondary hospitals, keeping too many slack resources is not ideal, so managers should adopt strategies to improve competitiveness and service transformation.
Views of leaders in under-represented and equity-denied communities on organ and tissue donation in Nova Scotia, Canada, in light of the Human Organ and Tissue Donation Act: a qualitative descriptive study
Authors: Urquhart Robin , Kendell Cynthia , Weiss Matthew , Kureshi Nelofar , Dirk Jade , Cordoba Wendy , Beed Stephen
Published: April 2023

Objective

To explore the views of underserved and equity-denied communities in Nova Scotia, Canada, regarding organ and tissue donation and deemed consent legislation.

Design

A qualitative descriptive study was undertaken, employing both interviews and focus groups.

Setting

The province of Nova Scotia, Canada—the first jurisdiction in North America to implement deemed consent legislation for organ and tissue donation.

Participants

Leaders of African Nova Scotian, Lesbian, Gay, Bisexual, Trans, Queer, Two Spirit (LGBTQ2S+) and Faith-based communities (Islam and Judaism) were invited to participate (n=11). Leaders were defined as persons responsible for community organisations or in other leadership roles, and were purposively recruited by the research team.

Results

Through thematic analysis, four main themes were identified: (1) alignment with personal values as well as religious beliefs and perspectives; (2) trust and relationships, which need to be acknowledged and addressed in the context of deemed consent legislation; (3) cultural competence, which is essential to the roll-out of the new legislation and (4) communication and information to combat misconceptions and misinformation, facilitate informed decision-making, and mitigate conflict within families.

Conclusions

Leaders of African Nova Scotian, LGBTQ2S+ and Faith-based communities in Nova Scotia are highly supportive of deemed consent legislation. Despite this, many issues exemplify the need for cultural competence at all levels. These findings should inform ongoing implementation of the legislation and other jurisdictions considering a deemed consent approach to organ and tissue donation.
Seroprevalence of antibodies to herpes simplex virus 1 and 2 in patients with HIV positive from Ebonyi State, Nigeria: a cross-sectional study
Authors: Onu Euslar Nnenna , Ekuma Uchechukwu Onyeukwu , Judi Hawraa K , Ogbu Ogbonnaya , Okoro Nworie , Ajugwo Gloria C , Akrami Sousan , Okoli Chukwudum S , Anyanwu Chioma Ngozi , Saki Morteza , Edeh Peter Anyigor
Published: April 2023

Objectives

To assess the seroprevalence of herpes simplex virus (HSV) types 1 and 2 in patients infected with HIV in Nigeria.

Design

Cross-sectional design from January to June 2019.

Setting

Federal Teaching Hospital, Ebonyi State, Nigeria.

Participants

A total of 276 patients with HIV were analysed using ELISA method for the presence of HSV-1 and HSV-2 specific IgG antibodies.

Outcomes

Fisher’s exact test was used to determine the association between the seroprevalence of HSV and demographic variables (statistically significant=p value ≤0.05).

Results

Totally, 212 (76.8%) and 155 (56.2%) patients with HIV were seropositive for HSV-1 and HSV-2 IgG antibodies, respectively. The seroprevalence of HSV-1 was significantly higher than the HSV-2 in patients with HIV (p value <0.0001). HSV-1 and HSV-2 seroprevalence were higher in patients aged more than 30 years. The seroprevalence of HSV-1 was significantly higher (p=0.01) in females (82.4%, 131/159) than males (69.2%, 81/117), but there was no significant difference in seroprevalence of HSV-2 in females (57.9%, 92/159) compared with males (53.8%, 63/117) (p=0.51). Professional drivers had a higher seroprevalence of HSV-1 and HSV-2 and there was a significant association between the occupation and the HSV-1 and HSV-2 seropositivity (p>0.05). The seroprevalence of HSV-1 was significantly higher in the singles (87.4%, 90/103) than the married patients with HIV (p=0.001). However, HSV-2 seroprevalence was significantly higher in the married patients with HIV (63.6%, 110/173) (p=0.001).

Conclusions

Prevalence of 76.8% for HSV-1 and 56.2% for HSV-2 among patients with HIV was seen. The HSV-1 was significantly higher in the singles while HSV-2 seroprevalence was significantly higher in the married patients with HIV with HSV-1 and HSV-2 coinfection rate of 7.6%. This study became very imperative to provide an important insight into the hidden dynamics of HSV infections.
Longitudinal faculty development to improve interprofessional collaboration and practice: a multisite qualitative study at five US academic health centres
Authors: Rider Elizabeth A , Chou Calvin , Abraham Corrine , Weissmann Peter , Litzelman Debra K , Hatem David , Branch William
Published: April 2023

Objectives

Interprofessional (IP) collaboration and effective teamwork remain variable in healthcare organisations. IP bias, assumptions and conflicts limit the capacity of healthcare teams to leverage the expertise of their members to meet growing complexities of patient needs and optimise healthcare outcomes. We aimed to understand how a longitudinal faculty development programme, designed to optimise IP learning, influenced its participants in their IP roles.

Design

In this qualitative study, using a constructivist grounded theory approach, we analysed participants’ anonymous narrative responses to open-ended questions about specific knowledge, insights and skills acquired during our IP longitudinal faculty development programme and applications of this learning to teaching and practice.

Setting

Five university-based academic health centres across the USA.

Participants

IP faculty/clinician leaders from at least three different professions completed small group-based faculty development programmes over 9 months (18 sessions). Site leaders selected participants from applicants forecast as future leaders of IP collaboration and education.

Interventions

Completion of a longitudinal IP faculty development programme designed to enhance leadership, teamwork, self-knowledge and communication.

Results

A total of 26 programme participants provided 52 narratives for analysis. Relationships and relational learning were the overarching themes. From the underlying themes, we developed a summary of relational competencies identified at each of three learning levels: (1) Intrapersonal (within oneself): reflective capacity/self-awareness, becoming aware of biases, empathy for self and mindfulness. (2) Interpersonal (interacting with others): listening, understanding others’ perspectives, appreciation and respect for colleagues and empathy for others. (3) Systems level (interacting within organisation): resilience, conflict engagement, team dynamics and utilisation of colleagues as resources.

Conclusions

Our faculty development programme for IP faculty leaders at five US academic health centres achieved relational learning with attitudinal changes that can enhance collaboration with others. We observed meaningful changes in participants with decreased biases, increased self-reflection, empathy and understanding of others’ perspectives and enhanced IP teamwork.
Reporting of retrospective registration in clinical trial publications: a cross-sectional study of German trials
Authors: Haslberger Martin , Gestrich Stefanie , Strech Daniel
Published: April 2023

Objective

Prospective registration has been widely implemented and accepted as a best practice in clinical research, but retrospective registration is still commonly found. We assessed to what extent retrospective registration is reported transparently in journal publications and investigated factors associated with transparent reporting.

Design

We used a dataset of trials registered in ClinicalTrials.gov or Deutsches Register Klinischer Studien, with a German University Medical Center as the lead centre, completed in 2009–2017, and with a corresponding peer-reviewed results publication. We extracted all registration statements from results publications of retrospectively registered trials and assessed whether they mention or justify the retrospective registration. We analysed associations of retrospective registration and reporting thereof with registration number reporting, International Committee of Medical Journal Editors (ICMJE) membership/-following and industry sponsorship using χ2or Fisher exact test.

Results

In the dataset of 1927 trials with a corresponding results publication, 956 (53.7%) were retrospectively registered. Of those, 2.2% (21) explicitly report the retrospective registration in the abstract and 3.5% (33) in the full text. In 2.1% (20) of publications, authors provide an explanation for the retrospective registration in the full text. Registration numbers were significantly underreported in abstracts of retrospectively registered trials compared with prospectively registered trials. Publications in ICMJE member journals did not have statistically significantly higher rates of both prospective registration and disclosure of retrospective registration, and publications in journals claiming to follow ICMJE recommendations showed statistically significantly lower rates compared with non-ICMJE-following journals. Industry sponsorship of trials was significantly associated with higher rates of prospective registration, but not with transparent registration reporting.

Conclusions

Contrary to ICMJE guidance, retrospective registration is disclosed and explained only in a small number of retrospectively registered studies. Disclosure of the retrospective nature of the registration would require a brief statement in the manuscript and could be easily implemented by journals.
Healthcare utilisation and costs associated with adherence to antipsychotics among people living with HIV/AIDS and schizophrenia: a population-based cohort study in British Columbia, Canada
Authors: Subedi Sony , Nanditha Ni Gusti Ayu , Tafessu Hiwot M , Nathani Hasan , St-Jean Martin , Elefante Julius , Patterson Thomas L , Honer William G , Montaner Julio S G , Lima Viviane D
Published: April 2023

Objectives

Non-adherence to antipsychotics is the greatest obstacle to treating schizophrenia. We assessed the economic and clinical impacts of adherence to antipsychotics among people living with HIV/AIDS (PLWH) and schizophrenia in British Columbia, Canada.

Design and setting

A population-based cohort study in British Columbia, Canada.

Methods

Eligible PLWH were enrolled in the Seek and Treat for Optimal Prevention HIV/AIDS population-based cohort during 2001–2016, diagnosed with schizophrenia, on antipsychotics for ≥1 day, and followed for ≥1 year from schizophrenia diagnosis date or 1 January 2001, whichever occurred last.

Primary and secondary outcome measures

A two-part model assessed the marginal effect of adherence on healthcare costs (in 2016 Canadian dollar), while logistic regression examined the effect on virological failure, and generalised linear mixed models examined the effect on hospital readmissions within 30 days and length of hospital stay.

Results

Among 726 PLWH with schizophrenia, ≥80% adherence to antipsychotics increased from 25% (50/198) in 2001 to 41% (225/554) in 2016. In most years, we observed no difference in adherence to antipsychotics among those who used only injectables, only non-injectables, and a combination of both, or among those who have ever consumed typical/first-generation antipsychotics and who consumed only atypical/second-generation antipsychotics. Overall healthcare costs were higher in the non-adherent group ($C2185), driven by the average annual hospitalisation costs ($C5517), particularly among women ($C8806) and people who ever injected drugs (PWID) ($C5985). Non-adherent individuals also experienced higher hospital readmissions (adjusted odds ratio (aOR) 1.48, 95% CI 1.23 to 1.77), and longer hospital stays (adjusted mean ratio 1.23, 95% CI 1.13 to 1.35) in comparison to adherent individuals. We found no difference in virological failure by adherence groups, except when we stratified by gender where the aOR for women was 2.48 (95% CI 1.06 to 5.82).

Conclusions

Our results showed that implementing strategies and interventions to increase antipsychotic adherence, particularly among women and PWID, will be critical in addressing this public health challenge.
Prevalence and incidence of alcohol dependence: cross-sectional primary care analysis in Liverpool, UK
Authors: Montgomery Catharine , Schoetensack Christine , Saini Pooja , Owens Lynn , Van Ginneken Nadja , Rice Melissa , Young Ryan , Jones Andrew
Published: April 2023

Objectives

Liverpool has high prevalence of alcohol use disorders (AUDs) compared with the rest of the UK. Early identification and referral in primary care would improve treatment for people with AUD. This study aimed to identify changes in prevalence and incidence of AUD in primary care in Liverpool, to identify local need for specialist services.

Design

Cross-sectional retrospective analysis of electronic health records.

Setting

National Health Service (NHS) Liverpool Clinical Commissioning Group (CCG) primary care. In total, 62 of the 86 general practitioner (GP) practices agreed to share their anonymised Egton Medical Information Systems (EMIS) data from 1 January 2017 to 31 December 2021.

Participants

Patients aged over 18 years with a SNOMED code for alcohol dependence (AD) or hazardous drinking (N=4936). Patients were excluded if they had requested that their data was not to be shared, and practices were excluded if they opted out (N=2) or did not respond to the data sharing request (N=22).

Primary and secondary outcomes

Prevalence and incidence of AUD diagnoses in primary care over the 5-year period; demographic profile of patients (sex, age, ethnicity, occupation); GP postcode; alcohol-related medications; and psychiatric and physical comorbidities.

Results

There were significant decreases in incidence of AD and hazardous drinking diagnoses over the 5 years (p<0.001 in all cases). Prevalence showed less change over time. Diagnoses were significantly higher in more deprived areas (Indices of Multiple Deprivation decile 1 vs 2–10). Overall pharmacotherapy prescriptions were lower than national estimates.

Conclusions

There are low levels of identification of AUDs in primary care in Liverpool, and this is decreasing year on year. There was weak evidence to suggest patients in the most deprived areas are less likely to receive pharmacotherapy once diagnosed. Future research should seek to investigate practitioner and patient perspectives on barriers and facilitators to management of AUDs in primary care.
Verbal autopsy analysis of maternal mortality in Bong County, Liberia: a retrospective mixed methods study
Authors: Lee Haeun , Perosky Joseph , Horton Madison , Reynolds Christopher , Nyanplu Aloysius , Lori Jody R
Published: April 2023

Background

While the medical contributors to maternal mortality are well known, the contextual contributors are less known and understudied. Liberia has one of the highest maternal mortality rates in sub-Saharan Africa, with recent increases in maternal deaths in rural Bong County. The purpose of this study was to better classify the contextual factors leading up to maternal deaths and to develop a list of recommendations to prevent future similar deaths.

Methods

A retrospective mixed method study was conducted examining 35 maternal deaths in Bong County, Liberia using verbal autopsy reports from 2019. An interdisciplinary death audit team reviewed and analysed the maternal deaths to determine the contextual causes of the maternal death.

Findings

This study identified three contextual causes: limited resources (materials, transportation, facility, staff), inadequate skills and knowledge (staff, community, family, patient), and ineffective communication (between providers, between health facilities and hospitals, and between provider and patient/family). Of these, inadequate patient education (54.28%), inadequate staff education and training (51.42%), ineffective communication between health facilities and hospitals (31.42%), and inadequate materials (28.57%) were most frequently mentioned.

Conclusion

Maternal mortality remains an issue in Bong County, Liberia, due to addressable contextual causes. Interventions to ameliorate these preventable deaths include ensuring availability of resources and transportation through improved supply chain and health system accountability. Recurring training should be provided to healthcare workers which involves husbands, families and communities. Innovative means for providers and facilities to communicate clearly and consistently should also be prioritised to prevent future maternal deaths in Bong County, Liberia.
Limited caffeine consumption as first-line treatment in managing primary monosymptomatic enuresis in children: how effective is it? A randomised clinical trial
Authors: Rezakhaniha Sadra , Rezakhaniha Bijan , Siroosbakht Soheila
Published: April 2023

Objective

Evidence about the negative caffeine effect on enuresis in children remains understudied or poorly understood. The study aimed to investigate the effect of caffeine restriction on the improvement and severity of primary monosymptomatic nocturnal enuresis (PMNE).

Design

Randomised clinical trial.

Setting

Two referral hospitals in Tehran, Iran, from 2021 to 2023.

Patients

Five hundred and thirty-four PMNE children aged 6–15 years (each group 267).

Interventions

Amount of caffeine consumption was recorded by the feed frequency questionnaire and was estimated by Nutrition 4 software. Caffeine consumption per day in the intervention group was <30 mg, and in the control group, 80–110 mg. All children were asked to return 1 month later to check the recorded data. The ordinal logistic regression analysis was used to assay the effects of caffeine restriction on PMNE by relative risk (RR) at a 95% CI.

Main outcome measures

The effect of limited caffeine consumption on the improvement and severity of PMNE.

Results

The mean age of the intervention and control groups was 10.9±2.3 and 10.5±2.5 years, respectively. The mean number of bed-wetting before caffeine restriction in the intervention and control group was 3.5 (SD 1.7) times/week and 3.4 (SD 1.9) times/week (p=0.91) and 1 month after intervention were 2.3 (SD 1.8) times/week and 3.2 (SD 1.9) times/week, respectively (p=0.001). Caffeine restriction significantly reduced the severity of enuresis in the intervention group. Fifty-four children (20.2%) improved (dry at night) in caffeine restriction and 18 children (6.7%) in the control group with RR 0.615 at 95% CI 0.521 to 0.726, p=0.001. The caffeine restriction significantly reduced the enuresis in children with a number-needed-to-treat benefit 7.417. It means you must treat 7.417 PMNE children with caffeine limitation to improve one child with enuresis (become dry).

Conclusion

Caffeine restriction can be helpful in reducing PMNE or its severity. Constructive limitation of caffeine is suggested as one of the first-line treatments in the management of PMNE.

Trial registration number

IRCT20180401039167N3.
Position statement of the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) onAPCI1307K and cancer risk
Authors: Valle Laura , Katz Lior H , Latchford Andrew , Mur Pilar , Moreno Victor , Frayling Ian M , Heald Brandie , Capellá Gabriel
Published: April 2023

While constitutional pathogenic variants in theAPCgene cause familial adenomatous polyposis,APCc.3920T>A; p.Ile1307Lys (I1307K) has been associated with a moderate increased risk of colorectal cancer (CRC), particularly in individuals of Ashkenazi Jewish descent. However, published data include relatively small sample sizes, generating inconclusive results regarding cancer risk, particularly in non-Ashkenazi populations. This has led to different country/continental-specific guidelines regarding genetic testing, clinical management and surveillance recommendations for I1307K. A multidisciplinary international expert group endorsed by the International Society for Gastrointestinal Hereditary Tumours (InSiGHT), has generated a position statement on theAPCI1307K allele and its association with cancer predisposition. Based on a systematic review and meta-analysis of the evidence published, the aim of this document is to summarise the prevalence of theAPCI1307K allele and analysed the evidence of the associated cancer risk in different populations. Here we provide recommendations on the laboratory classification of the variant, define the role of predictive testing for I1307K, suggest recommendations for cancer screening in I1307K heterozygous and homozygous individuals and identify knowledge gaps to be addressed in future research studies. Briefly, I1307K, classified as pathogenic, low penetrance, is a risk factor for CRC in individuals of Ashkenazi Jewish origin and should be tested in this population, offering carriers specific clinical surveillance. There is not enough evidence to support an increased risk of cancer in other populations/subpopulations. Therefore, until/unless future evidence indicates otherwise, individuals of non-Ashkenazi Jewish descent harbouring I1307K should be enrolled in national CRC screening programmes for average-risk individuals.
Granulocyte activation markers in cerebrospinal fluid differentiate acute neuromyelitis spectrum disorder from multiple sclerosis
Authors: Leppert David , Watanabe Mitsuru , Schaedelin Sabine , Piehl Fredrik , Furlan Roberto , Gastaldi Matteo , Lambert Jeremy , Evertsson Björn , Fink Katharina , Matsushita Takuya , Masaki Katsuhisa , Isobe Noriko , Kira Jun-ichi , Benkert Pascal , Maceski Aleksandra , Willemse Eline , Oechtering Johanna , Orleth Annette , Meier Stephanie , Kuhle Jens
Published: April 2023

Background

Granulocyte invasion into the brain is a pathoanatomical feature differentiating neuromyelitis optica spectrum disorder (NMOSD) from multiple sclerosis (MS). We aimed to determine whether granulocyte activation markers (GAM) in cerebrospinal fluid (CSF) can be used as a biomarker to distinguish NMOSD from MS, and whether levels associate with neurological impairment.

Methods

We quantified CSF levels of five GAM (neutrophil elastase, myeloperoxidase, neutrophil gelatinase-associated lipocalin, matrixmetalloproteinase-8, tissue inhibitor of metalloproteinase-1), as well as a set of inflammatory and tissue-destruction markers, known to be upregulated in NMOSD and MS (neurofilament light chain, glial fibrillary acidic protein, S100B, matrix metalloproteinase-9, intercellular adhesion molecule-1, vascular cellular adhesion molecule-1), in two cohorts of patients with mixed NMOSD and relapsing-remitting multiple sclerosis (RRMS).

Results

In acute NMOSD, GAM and adhesion molecules, but not the other markers, were higher than in RRMS and correlated with actual clinical disability scores. Peak GAM levels occurred at the onset of NMOSD attacks, while they were stably low in MS, allowing to differentiate the two diseases for ≤21 days from onset of clinical exacerbation. Composites of GAM provided area under the curve values of 0.90–0.98 (specificity of 0.76–1.0, sensitivity of 0.87–1.0) to differentiate NMOSD from MS, including all anti-aquaporin-4 protein (aAQP4)-antibody-negative patients who were untreated.

Conclusions

GAM composites represent a novel biomarker to reliably differentiate NMOSD from MS, including in aAQP4−NMOSD. The association of GAM with the degree of concurrent neurological impairment provides evidence for their pathogenic role, in turn suggesting them as potential drug targets in acute NMOSD.
Free academic discourse and the law: the case of liposomal bupivacaine
Authors: Poeran Jashvant , Hong Genewoo , Memtsoudis Stavros G
Published: April 2023

Liposomal bupivacaine has been the topic of intense academic debate over the past years culminating in an industry-initiated libel lawsuit against the American Society of Anesthesiologists and various other defendants. In this Daring Discourse, we first aim to provide a general overview of main themes in the ongoing controversy: (1) between-study heterogeneity, (2) the high number of negative high-quality reviews and meta-analyses, (3) publication bias in the context of an active role of industry and (4) difference between statistical and clinical significance. We then discuss the contents of the lawsuit, its potential implications and what the recent resolution of this lawsuit means for the future of research and the academic discourse on liposomal bupivacaine.
Dexmedetomidine and clonidine in palliative medicine: multicentric qualitative evaluation
Authors: Prod'homme Chloé , Werbrouck Xavier , Pierrat Magali , Chevalier Luc , Lesaffre Helene , Pasqualini Claire , Touzet Licia
Published: April 2023

Objectives

Alpha-2 agonists have analgesic and sedative properties that can prove interesting in palliative care. The main objective of this study was to describe the use of clonidine and dexmedetomidine in palliative care units (PCU). The secondary objective was to identify physicians’ perspectives and attitudes toward alpha-2-agonists.

Methods

International multicentric qualitative survey of prescribing characteristics and attitudes towards alpha-2 agonist. All 159 PCUs in France, Belgium and French-speaking Switzerland were contacted, and 142 physicians answered the questionnaire (31% participation).

Results

20% of the practitioners surveyed prescribe these molecules are mainly for analgesic and sedative indications. There was considerable heterogeneity in the modalities and dosages of administration. The use of clonidine is more frequent and common in Belgium, while dexmedetomidine is only used in France. There is a high level of satisfaction among practitioners who use these molecules, with the desire of the majority of respondents to obtain additional studies and information on alpha-2-agonists.

Conclusion

Alpha-2 agonists are little known and little prescribed by French-speaking palliative care physicians but are of interest because of their potential in this field. Phase 3 studies could justify the use of these molecules in palliative situations and would contribute to harmonising professional practices.
Group 2 innate lymphoid cells resolve neuroinflammation following cerebral ischaemia
Authors: Zheng Pei , Xiu Yuwhen , Chen Zhili , Yuan Meng , Li Yan , Wang Ningning , Zhang Bohao , Zhao Xin , Li Minshu , Liu Qiang , Shi Fu-Dong , Jin Wei-Na
Published: April 2023

Background

Acute brain ischaemia elicits pronounced inflammation, which aggravates neural injury. However, the mechanisms governing the resolution of acute neuroinflammation remain poorly understood. In contrast to regulatory T and B cells, group 2 innate lymphoid cells (ILC2s) are immunoregulatory cells that can be swiftly mobilised without antigen presentation; whether and how these ILC2s participate in central nervous system inflammation following brain ischaemia is still unknown.

Methods

Leveraging brain tissues from patients who had an ischaemic stroke and a mouse model of focal ischaemia, we characterised the presence and cytokine release of brain-infiltrating ILC2s. The impact of ILC2s on neural injury was evaluated through antibody depletion and ILC2 adoptive transfer experiments. Using Rag2−/−γc−/−mice receiving passive transfer of IL-4−/−ILC2s, we further assessed the contribution of interleukin (IL)-4, produced by ILC2s, in ischaemic brain injury.

Results

We demonstrate that ILC2s accumulate in the areas surrounding the infarct in brain tissues of patients with cerebral ischaemia, as well as in mice subjected to focal cerebral ischaemia. Oligodendrocytes were a major source of IL-33, which contributed to ILC2s mobilisation. Adoptive transfer and expansion of ILC2s reduced brain infarction. Importantly, brain-infiltrating ILC2s reduced the magnitude of stroke injury severity through the production of IL-4.

Conclusions

Our findings revealed that brain ischaemia mobilises ILC2s to curb neuroinflammation and brain injury, expanding the current understanding of inflammatory networks following stroke.
SomaticGJA4mutation in intracranial extra-axial cavernous hemangiomas
Authors: Huo Ran , Yang Yingxi , Xu Hongyuan , Zhao Shaozhi , Song Dong , Weng Jiancong , Ma Ruochen , Sun Yingfan , Wang Jie , Jiao Yuming , Zhang Junze , He Qiheng , Wu Ruolei , Wang Shuo , Zhao Ji-Zong , Zhang Junting , Wang Jiguang , Cao Yong
Published: April 2023

Objective

Extra-axial cavernous hemangiomas (ECHs) are sporadic and rare intracranial occupational lesions that usually occur within the cavernous sinus. The aetiology of ECHs remains unknown.

Methods

Whole-exome sequencing was performed on ECH lesions from 12 patients (discovery cohort) and droplet digital polymerase-chain-reaction (ddPCR) was used to confirm the identified mutation in 46 additional cases (validation cohort). Laser capture microdissection (LCM) was carried out to capture and characterise subgroups of tissue cells. Mechanistic and functional investigations were carried out in human umbilical vein endothelial cells and a newly established mouse model.

Results

We detected somaticGJA4mutation (c.121G>T, p.G41C) in 5/12 patients with ECH in the discovery cohort and confirmed the finding in the validation cohort (16/46). LCM followed by ddPCR revealed that the mutation was enriched in lesional endothelium. In vitro experiments in endothelial cells demonstrated that theGJA4mutation activated SGK-1 signalling that in turn upregulated key genes involved in cell hyperproliferation and the loss of arterial specification. Compared with wild-type littermates, mice overexpressing theGJA4mutation developed ECH-like pathological morphological characteristics (dilated venous lumen and elevated vascular density) in the retinal superficial vascular plexus at the postnatal 3 weeks, which were reversed by an SGK1 inhibitor, EMD638683.

Conclusions

We identified a somaticGJA4mutation that presents in over one-third of ECH lesions and proposed that ECHs are vascular malformations due toGJA4-induced activation of the SGK1 signalling pathway in brain endothelial cells.
Enhanced heat transmission in conical slip flow of Walter’s-B nanofluid
Authors: Sandeep N. , Babu R. Suresh , Nanda P. , Ashwinkumar G. P.
Published: April 2023

This paper examines the thermal transfer attributes of ZnO-H2O Walter’s-B nanoliquid flow alongside an upright cone in the bearing of slip mechanism, radiative heat flux, and non-uniform heat source. We adopted suitable similarities to convert the nonlinear PDEs into ODEs and solved the transformed governing system by employing the bvp5c solver package in Matlab software. The prime novelty of this research is to compute the effective thermal diffusivity of the nanoliquid via the Maxwell and Xue nanomodels. Further, simultaneous results are deliberated for Maxwell and Xue cases via pictorial outcomes under various controlling limitations, such as velocity slip, radiative heat flux, buoyancy, viscoelastic, and volume fraction of nanomaterial. The thermal transmission rate of nanoliquid reported by the Xue nanomodel is higher than the Maxwell nanomodel. Therefore, the Xue nanomodel effectively works to enhance the thermal conductivity of the liquids with viscoelastic nature. Further, this study is helpful in industrial processing, where control over heat transport is required.
Nonlocal reduced integrable mKdV-type equations from a vector integrable hierarchy
Authors: Chen Shou-Ting , Ma Wen-Xiu
Published: April 2023

This paper aims to present two hierarchies of nonlocal reduced integrable mKdV-type equations from a vector integrable hierarchy associated with a matrix Lie algebra, not being A type. The key point is to make similarity transformations for the spectral matrix, which keep the associated zero curvature equations invariant and then there follow reduced nonlocal integrable mKdV-type equations. The success lies in determining a Laurent series solution to the corresponding reduced stationary zero curvature equation, which generates temporal matrix spectral problems in the zero curvature formation.
China’s Belt and Road Initiative: The Economic Footprints in the Middle East vs. Geopolitical Dimensions with the United States
Authors: CHEUNG Gordon C K
Published: April 2023

China’s economic rise in global economic platform empowered by the go-out strategy is its attempt to establish a global presence, through which it develops economic relations by launching China-led development and economic projects. This article focuses on China’s Belt and Road Initiative, in particular the political significance of China’s economic footprints in the Middle East, with a view of understanding the geopolitical tensions between China and the United States.
The Impact of Russia’s Invasion of Ukraine on East Asia
Authors: PURI Samir
Published: April 2023

Although unfolding a continent away, Russia’s invasion of Ukraine is detrimental to the strategic stability of East Asia, which is already riven by its own unresolved conflicts and territorial control disputes. The degradation of global security norms, the disruption to global energy supplies and the need to pick sides for or against Russia have each contributed to making East Asia’s security a more complex Rubik’s cube to manage. This article examines the implications of Russia’s invasion of Ukraine on Russia–China relations; Taiwan Strait’s stability; Japan’s defence policy; and the Korean peninsula. How and on what terms Russia’s invasion ends will carry another set of impacts and lessons for East Asia. In closing, the lessons of freezing conflicts in East Asia are applied to the emerging situation in Eastern Europe: of an unresolveable and unwinnable war that may become a lasting feature of European security, in the way that unresolved wars over Korea and Taiwan have become enduring realities in East Asia.
Japan and Australia: Strengthening Partnership in the Indo-Pacific Era
Authors: JAIN Purnendra
Published: April 2023

After many decades of a relationship defined primarily by commercial ties, Japan and Australia now have a robust security and defence partnership. While making their bilateral relations more all-rounded in the Indo-Pacific era, they also aim to promote a regional order where the United States remains engaged and like-minded nations come together to manage the ever-volatile strategic environment in the wake of China’s rise and US–China strategic rivalry. These tasks are not easy due to strategic complexities; how the two key Indo-Pacific nations respond to each other and to their partners in managing the China challenge while ensuring US commitment to the region will be of deep interest to policymakers and analysts alike.
Framing Machine Learning Opportunities for Hypotension Prediction in Perioperative Care: A Socio-technical Perspective
Authors: Ghosh Pratik , Posner Karen L. , Hyland Stephanie L. , van Cleve Wil , Bristow Melissa , Long Dustin R. , Palla Konstantina , Nair Bala , Fong Christine , Pauldine Ronald , Vavilala Monica S. , O'Hara Kenton
Published: April 2023

Hypotension during perioperative care, if undetected or uncontrolled, can lead to serious clinical complications. Predictive machine learning models, based on routinely collected EHR data, offer potential for early warning of hypotension to enable proactive clinical intervention. However, while research has demonstrated the feasibility of such machine learning models, little effort is made to ground their formulation and development in socio-technical context of perioperative care work. To address this, we present a study of collaborative work practices of clinical teams during and after surgery with specific emphasis on the organisation of hypotension management. The findings highlight where predictive insights could be usefully deployed to reconfigure care and facilitate more proactive management of hypotension. We further explore how the socio-technical insights help define key parameters of machine learning prediction tasks to align with the demands of collaborative clinical practice. We discuss more general implications for the design of predictive machine learning in hospital care.
A Method for Animating Children’s Drawings of the Human Figure
Authors: Smith Harrison Jesse , Zheng Qingyuan , Li Yifei , Jain Somya , Hodgins Jessica K.
Published: April 2023

Children’s drawings have a wonderful inventiveness, creativity, and variety to them. We present a system that automatically animates children’s drawings of the human figure, is robust to the variance inherent in these depictions, and is simple and straightforward enough for anyone to use. We demonstrate the value and broad appeal of our approach by building and releasing the Animated Drawings Demo, a freely available public website that has been used by millions of people around the world. We present a set of experiments exploring the amount of training data needed for fine-tuning, as well as a perceptual study demonstrating the appeal of a novel
twisted perspective
retargeting technique. Finally, we introduce the Amateur Drawings Dataset, a first-of-its-kind annotated dataset, collected via the public demo, containing over 178,000 amateur drawings and corresponding user-accepted character bounding boxes, segmentation masks, and joint location annotations.
A Decidable Fragment of First Order Modal Logic: Two Variable Term Modal Logic
Authors: Padmanabha Anantha , Ramanujam R.
Published: April 2023

First order modal logic (𝖥𝖮𝖬𝖫)
is built by extending
First Order Logic (𝖥𝖮)
with modal operators. A typical formula is of the form

\(\forall x \exists y \Box P(x,y)\)

. Not only is 𝖥𝖮𝖬𝖫 undecidable, even simple fragments like that of restriction to unary predicate symbols, guarded fragment and two variable fragment, which are all decidable for 𝖥𝖮 become undecidable for 𝖥𝖮𝖬𝖫. In this paper we study
Term Modal logic (𝖳𝖬𝖫)
which allows modal operators to be indexed by terms. A typical formula is of the form

\(\forall x \exists y~\Box _x P(x,y)\)

. There is a close correspondence between 𝖳𝖬𝖫 and 𝖥𝖮𝖬𝖫 and we explore this relationship in detail in the paper.

In contrast to 𝖥𝖮𝖬𝖫, we show that the two variable fragment (without constants, equality) of 𝖳𝖬𝖫 is decidable. Further, we prove that adding a single constant makes the two variable fragment of 𝖳𝖬𝖫 undecidable. On the other hand, when equality is added to the logic, it loses the finite model property.
An Insight into the Mechanisms of Energy Storage in a Double Layer Capacitor with ILs and a Microporous Carbon: Experimental Evidences of Ion-Swapping by Electrochemical Impedance Spectroscopy
Authors: Quintanal Noemí , Barreda Daniel , Blanco Clara , González Zoraida , Álvarez Patricia , Granda Marcos , Sevilla Marta , Santamaría Ricardo
Published: April 2023

The energy storage mechanism operating in carbon-based supercapacitors using ionic liquids as electrolytes is not yet fully understood. In this paper, the interactions of ions of two widely used ionic liquids, i.e. EMImTFSI and EMImBF4, with a high specific surface area microporous carbon are investigated. Galvanostatic cycling experiments performed on each electrode and in the full cell demonstrate that a specific energy close to 46 Wh kg−1 can be achieved with this carbon. More interestingly, impedance spectroscopy studies reveal the presence of some unusual behavior, such as the presence of inductive elements in some of the electrodes, either in the positive or in the negative electrode. These inductive elements are identified, for the first time, as another type of possible experimental evidences of some phenomena previously proposed, such as ion-swapping or co-ions desorption, both phenomena leading to the formation of the superionic state.
A novel conceptual framework for the functionality of the glymphatic system
Authors: Astara Kyriaki , Pournara Christina , de Natale Edoardo Rosario , Wilson Heather , Vavougios George D. , Lappas Andreas S. , Politis Marios , Christodoulou Nikos G.
Published: April 2023

The glymphatic system is responsible for the clearance of the potentially harmful metabolic waste of the central nervous system. The prevalent theory is that the cerebrospinal fluid (CSF) circulates in the perivascular space (PVS) and through the astrocytes’ aquaporin-4 channels (AQ-4), and it is then drained by the lymphatic vessels after mixing with interstitial fluid (ISF). However, there is little evidence supporting this hypothesis. A deeper understanding of the physiology of the glymphatic system could transform the way we understand neuropathology and our approach to treating neurological and neuropsychiatric disorders. In this review, we introduce a new conceptual framework for the functionality of the glymphatic system, offering new directions for future research. We propose that CSF and ISF exchange flow depends on arterial pulsation, respiration, posture, and sleep. PVS changes due to disrupted cerebral autoregulation, alternations of intrathoracic pressure, venous flow, and body position can also influence the glymphatic flow. The role of respiration remains controversial due to the variety of parameters that interfere with glymphatic functionality. Slow-wave sleep is important for glymphatic clearance due to neuronal electromagnetic synchronization and expansion of the interstitial space. Therefore, sleep and vascular disorders, as well as aging, may hinder glymphatic flow and induce a noxious milieu of susceptibility to neurodegenerative disorders because of metabolic waste accumulation. We lastly introduce a new idea postulating that electromagnetic induction may constitute one of the propelling forces for the convectional current and mixing of CSF and ISF.
Spike timing-dependent plasticity alters electrosensory neuron synaptic strength in vitro but does not consistently predict changes in sensory tuning in vivo
Authors: Lube Adalee J. , Ma Xiaofeng , Carlson Bruce A.
Published: April 2023

We replicated behaviorally relevant temporal patterns of synaptic activity in vitro and used the same patterns during sensory stimulation in vivo. There was a Hebbian spike timing-dependent plasticity (STDP) pattern in vitro, but sensory responses in vivo did not shift according to STDP predictions. Analysis suggests that this disparity is influenced by differences in polysynaptic activity, including inhibitory interneurons. These results suggest that STDP rules at synapses in vitro do not necessarily apply to circuits in vivo.
Effect of Olive Pomace Fiber on the Baking Properties of Wheat Flour and Flat Bread (Barbari Bread) Quality
Authors: Azadfar Elham , Elhami Rad Amir Hossein , Sharifi Akram , Armin Mohammad
Published: April 2023

The current study is aimed at fortifying Barbari bread with different levels (

T

Co

: 0,

T

5
%

: 5%,

T

10
%

: 10%, and

T

15
%

: 15) of olive pomace dietary fiber (ODF) and investigating the quality properties of enriched bread. The fiber of the defatted olive pomace powder was extracted by an enzymatic process as a green extraction method (α-amylase, protease, amyloglucosidase, and cellulase; incubation time: 4.5 h, 40°C). The effect of ODF addition on the thermal (based on differential scanning calorimetry (DSC)), rheological, physical, textural, and sensory properties of samples was investigated. The DSC curves of samples were a broad endothermic transition peak (

T

onset

~
43

 °C and

T

peak

=
123.58
−
125.74

 °C). By increasing the ODF level, the water absorption rate of the dough increased while softening degree reduced. There was a negative significant correlation between baking loss and crumb moisture (

R
>
−
0.94

) and aw (

R
=
−
0.769

). By increasing ODF, sample porosity and specific volume decreased. There was a significant difference between hardness and springiness of

T

15
%

and

T

Co

. Replacement of wheat flour with 10% ODF had no significant effect on the sensory parameters of Barbari bread.