bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of transitioning to adult mental health services and associated costs: a cross-country comparison
Authors: Appleton Rebecca , Canaway Alastair , Tuomainen Helena , Dieleman Gwen , Gerritsen Suzanne , Overbeek Mathilde , Maras Athanasios , van Bodegom Larissa , Franić Tomislav , de Girolamo Giovanni , Madan Jason , McNicholas Fiona , Purper-Ouakil Diane , Schulze Ulrike M E , Tremmery Sabine , Singh Swaran P
Published: October 2023

Background

Young people are at risk of falling through the care gap after leaving child and adolescent mental health services (CAMHS) despite an ongoing need for mental health support. Currently, little is known about the predictors of transitioning to adult mental health services (AMHS), and associated healthcare and societal costs as young people cross the transition boundary.

Objective

To conduct a secondary data analysis exploring predictors of transitioning or falling through the gap and associated costs.

Methods

Data were used from a longitudinal study, which followed young people from seven European countries for 2 years after reaching their CAMHS boundary. Predictors of transitioning (including sociodemographic and clinical variables) and longitudinal resource use were compared for 488 young people who transitioned to AMHS versus those who fell through the gap.

Findings

Young people were more likely to transition to AMHS if they were severely ill. Those from Italy, the Netherlands and the UK were more likely to fall through the gap than transition to AMHS. Healthcare costs fell for all young people over the study, with a sharper decrease for those who fell through the gap.

Conclusions

Total healthcare costs fell for all participants, indicating that the intensity of mental health support reduces for all young people as they cross the CAMHS boundary, regardless of clinical need.

Clinical implications

It is important that alternative forms of mental health support are available for young people who do not meet the AMHS care threshold but still have mental health needs after leaving CAMHS.
Proportion of medical admissions that may be hospitalised at home and their service utilisation patterns: a single-centre, descriptive retrospective cohort study in Singapore
Authors: Ko Stephanie Q , Wang Zhemin , Goh Samuel Li Earn , Soong John T Y
Published: October 2023

Objectives

For eligible patient groups, hospital-at-home (HaH) programmes have been shown to deliver equivalent patient outcomes with cost reduction compared with standard care. This study aims to establish a benchmark of inpatient admissions that could potentially be substituted by HaH services.

Design

Descriptive retrospective cohort study.

Setting

Academic tertiary hospital in Singapore.

Participants

124 253 medical admissions over 20 months (January 2016 to August 2017).

Primary and secondary outcome measures

The primary measure was the proportion of hospitalised patients who may be eligible for HaH, based on eligibility criteria adapted for the Singapore context. The secondary measures were the utilisation patterns and outcomes of these patients.

Results

Applying generalised eligibility criteria to the retrospective dataset showed that 53.0% of 124 253 medical admissions fitted the eligibility criteria for HaH based on administrative data. 46.8% of such patients had a length of stay <48 hours (‘short-stay’) and 53.1% had a length of stay ≥48 hours (‘medium-stay’). The mortality rate and the 30-day readmission rate were lower in the ‘short-stay’ cohort (0.6%, 12.8%) compared with the ‘medium-stay’ cohort (0.7%, 20.3%). The key services used by both groups were: parenteral drug administration, blood investigations, imaging procedures and consultations with allied health professionals.

Conclusions

Up to 53.0% of medical admissions receive care elements that HaH programmes could provide. Applying estimates of functional limitations and patient preferences, we propose a target of ~18% of inpatient medical admissions to be substituted by HaH services. The methodology adopted in this paper is a reproducible approach to characterise potential patients and service utilisation requirements when developing such programmes.
Study protocol of LANTana: a phase Ib study to investigate epigenetic modification of somatostatin receptor-2 with ASTX727 to improve therapeutic outcome with [177Lu]Lu-DOTA-TATE in patients with metastatic neuroendocrine tumours, UK
Authors: Murphy Ravindhi , Chander Gurvin , Martinez Maria , Ward Caroline , Khan Sairah R , Naik Mitesh , Barwick Tara , Aboagye Eric , Sharma Rohini
Published: October 2023

Introduction

Suitability for peptide receptor radionuclide therapy (PRRT) for neuroendocrine neoplasia (NENs) depends on presence of somatostatin receptor-2 (SSTR2) determined by [68Ga]Ga-DOTA-peptide-positron emission tomography (PET). Some patients have low or no uptake on [68Ga]Ga-DOTA-peptide-PET, precluding PRRT. The upstream promoter region of SSRT2 is methylated, with percentage of methylation correlating with SSTR2 expression. Demethylating agents increase uptake on PET imaging in vivo such that tumours previously negative on PET become positive, correlating with a dose dependent increase in tumorous SSTR2 expression. LANTana will determine whether treatment with the demethylating agent, ASTX727, results in re-expression of SSTR2 using [68Ga]Ga-DOTA-peptide-PET to image epigenetic modification of the SSTR2 locus, allowing subsequent PRRT.

Methods and analysis

27 participants with a histological diagnosis of NEN (Ki67<55%) with no or low uptake on baseline [68Ga]Ga-DOTA-TATE-PET/CT will be recruited. Patients will receive 5 days of ASTX727 (fixed dose 35 mg decitabine+100 mg cedazuridine). [68Ga]Ga-DOTA-peptide-PET/CT will be repeated day 8±2; where there is significant uptake greater than liver in most lesions, PRRT will be administered. Primary objective is to determine re-expression of SSTR2 on PET imaging. Tolerability, progression-free survival, overall response and quality of life will be assessed. Methylation in peripheral blood mononuclear cells and tumorous methylation will be evaluated.

Ethics and dissemination

LANTana has ethical approval from Leeds West Research Ethics Committee (REC Reference: 21/YH/0247).

Sponsored by Imperial College London and funded by Advanced Accelerator Applications pharmaceuticals. Results will be presented at conferences and submitted to peer-reviewed journals for publication and will be available on ClinicalTrials.gov.

Trial registration numbers

EUDRACT number: 2020-003800-15,NCT05178693.
Prognostic prediction models for clinical outcomes in patients diagnosed with visceral leishmaniasis: protocol for a systematic review
Authors: Wilson James , Chowdhury Forhad , Hassan Shermarke , Harriss Elinor K , Alves Fabiana , Dahal Prabin , Stepniewska Kasia , Guérin Philippe J
Published: October 2023

Introduction

Visceral leishmaniasis (VL) is a neglected tropical disease responsible for many thousands of preventable deaths each year. Symptomatic patients often struggle to access effective treatment, without which death is the norm. Risk prediction tools support clinical teams and policymakers in identifying high-risk patients who could benefit from more intensive management pathways. Investigators interested in using their clinical data for prognostic research should first identify currently available models that are candidates for validation and possible updating. Addressing these needs, we aim to identify, summarise and appraise the available models predicting clinical outcomes in VL patients.

Methods and analysis

We will include studies that have developed, validated or updated prognostic models predicting future clinical outcomes in patients diagnosed with VL. Systematic reviews and meta-analyses that include eligible studies are also considered for review. Conference abstracts and educational theses are excluded. Data extraction, appraisal and reporting will follow current methodological guidelines. Ovid Embase; Ovid MEDLINE; the Web of Science Core Collection, SciELO and LILACS are searched from database inception to 1 March 2023 using terms developed for the identification of prediction models, and with no language restriction. Screening, data extraction and risk of bias assessment will be performed in duplicate with discordance resolved by a third independent reviewer. Risk of bias will be assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). Tables and figures will compare and contrast key model information, including source data, participants, model development and performance measures, and risk of bias. We will consider the strengths, limitations and clinical applicability of the identified models.

Ethics and dissemination

Ethics approval is not required for this review. The systematic review and all accompanying data will be submitted to an open-access journal. Findings will also be disseminated through the research group’s website (www.iddo.org/research-themes/visceral-leishmaniasis) and social media channels.

PROSPERO registration number

CRD42023417226.
Estimating the prevalence of diagnosed Alzheimer disease in England across deprivation groups using electronic health records: a clinical practice research datalink study
Authors: Leahy Thomas Patrick , Simpson Alex , Sammon Cormac , Ballard Clive , Gsteiger Sandro
Published: October 2023

Objective

Estimate the prevalence of diagnosed Alzheimer’s disease (AD) and early Alzheimer’s disease (eAD) overall and stratified by age, sex and deprivation and combinations thereof in England on 1 January 2020.

Design

Cross-sectional.

Setting

Primary care electronic health record data, the Clinical Practice Research database linked with secondary care data, Hospital Episode Statistics (HES) and patient-level deprivation data, Index of Multiple Deprivation (IMD).

Outcome measures

The prevalence per 100 000 of the population and corresponding 95% CIs for both diagnosed AD and eAD overall and stratified by covariates. Sensitivity analyses were conducted to assess the sensitivity of the population definition and look-back period.

Results

There were 448 797 patients identified in the Clinical Practice Research Datalink that satisfied the study inclusion criteria and were eligible for HES and IMD linkage. For the main analysis of AD and eAD, 379 763 patients are eligible for inclusion in the denominator. This resulted in an estimated prevalence of diagnosed AD of 378.39 (95% CI, 359.36 to 398.44) per 100 000 and eAD of 292.81 (95% CI, 276.12 to 310.52) per 100 000. Prevalence estimates across main and sensitivity analyses for the entire AD study population were found to vary widely with estimates ranging from 137.48 (95% CI, 127.05 to 148.76) to 796.55 (95% CI, 768.77 to 825.33). There was significant variation in prevalence of diagnosed eAD when assessing the sensitivity with the look-back periods, as low as 120.54 (95% CI, 110.80 to 131.14) per 100 000, and as high as 519.01 (95% CI, 496.64 to 542.37) per 100 000.

Conclusions

The study found relatively consistent patterns of prevalence across both AD and eAD populations. Generally, the prevalence of diagnosed AD increased with age and increased with deprivation for each age category. Women had a higher prevalence than men. More granular levels of stratification reduced patient numbers and increased the uncertainty of point prevalence estimates. Despite this, the study found a relationship between deprivation and prevalence of AD.
Is disease activity associated with social support and psychological distress in Crohn’s disease patients? Results of a cross-sectional study in a Chinese hospital population
Authors: Huang Mengting , Tu Lei , Wu Linxia , Zou Yan , Li Xin , Yue Xiaofei , Huang Chen , Lei Ping , Li Qian , Han Ping , Yang Lian , Zhu Liangru
Published: October 2023

Objectives

This study aims to assess the relative of social support and psychological distress in disease activity among patients with Crohn’s disease (CD) in China, and explore whether sex moderates the relationship between disease activity and social support and psychological distress in CD.

Design

Our study has a cross-sectional design.

Setting

This was a single-centre study, which was conducted in Wuhan, China.

Participants

A total of 184 patients with CD at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were enrolled in this study; of these,162 patients were included in the final analysis.

Primary and secondary outcome measures

The main study outcome was the CD patients’ clinical and questionnaire data. The association of disease activity, social support and psychological distress with patients with CD was also evaluated based on the collected data.

Results

A total of 162 patients with CD were enrolled. Compared with patients with CD in remission (CD-R), the patients with CD in activity (CD-A) had higher C reactive protein (CRP) (p=0.001), anaemia (p<0.001) and relapse rates in the last year (p<0.001). Independent samples t-tests indicated that the CD-A group reported lower Social Support Rating Scale scores and higher Symptom Checklist-90 scores than the CD-R group. Moreover, men with CD had lower somatisation (p=0.030) and anxiety (p=0.050) scores than women. In binary logistic regression models, the subjective support (beta=0.903, p=0.013), the clinical factors of CRP (beta=1.038, p=0.001) and psychological distress factors of anxiety (beta=1.443, p=0.008) and other (beta=1.235, p=0.042) were disease activity predictors.

Conclusion

The findings highlight the importance of the psychological distress and social support factors that may play a role in CD patients’ health. Interventions to address these issues should be part of management in CD.
Interventions for treating umbilical granuloma: a protocol for a systematic review and meta-analysis of randomised controlled trials
Authors: Namba Fumihiko , Miyahara Naoyuki , Haga Mitsuhiro , Ota Erika , Ikuta Yasuhisa , Mamahit Citra Gabriella
Published: October 2023

Introduction

The most frequent umbilical abnormality in infancy period is umbilical granuloma. Although umbilical granuloma treatment with silver nitrate is practised worldwide, silver nitrate cauterisation is high in cost and if silver nitrate comes into contact with healthy tissues, it might cause injury. This systematic review aims to look for evidence concerning the safety and efficacy of all interventions for treating umbilical granuloma in neonates.

Methods and analysis

Individual and cluster randomised controlled trials will be included in our study. The direct comparisons between two of any interventions for treating umbilical granuloma, including silver nitrate cauterisation, dry care, common salt, alcoholic wipes, topical doxycycline, topical steroid ointment, ligatures, cryosurgery, electrocautery, surgical excision and no intervention will be investigated. Primary outcomes will be the healing rate after 2 weeks of treatment and the incidence of cord-related adverse events. We will search CENTRAL, Embase and MEDLINE.

Ethics and dissemination

Ethical approval is not applicable in this study since we will retrieve and analyse data from previous published studies. The results of this systematic review are expected to be published in a scientific journal and presented at medical conferences.

PROSPERO registration number

CRD42022369915.
CURATE.AI COR-Tx platform as a digital therapy and digital diagnostic for cognitive function in patients with brain tumour postradiotherapy treatment: protocol for a prospective mixed-methods feasibility clinical trial
Authors: Remus Alexandria , Tadeo Xavier , Kai Grady Ng Shi , Blasiak Agata , Kee Theodore , Vijayakumar Smrithi , Nguyen Le , Raczkowska Marlena N , Chai Qian Yee , Aliyah Fatin , Rusalovski Yaromir , Teo Kejia , Yeo Tseng Tsai , Wong Andrea Li Ann , Chia David , Asplund Christopher L , Ho Dean , Vellayappan Balamurugan A
Published: October 2023

Introduction

Conventional interventional modalities for preserving or improving cognitive function in patients with brain tumour undergoing radiotherapy usually involve pharmacological and/or cognitive rehabilitation therapy administered at fixed doses or intensities, often resulting in suboptimal or no response, due to the dynamically evolving patient state over the course of disease. The personalisation of interventions may result in more effective results for this population. We have developed the CURATE.AI COR-Tx platform, which combines a previously validated, artificial intelligence-derived personalised dosing technology with digital cognitive training.

Methods and analysis

This is a prospective, single-centre, single-arm, mixed-methods feasibility clinical trial with the primary objective of testing the feasibility of the CURATE.AI COR-Tx platform intervention as both a digital intervention and digital diagnostic for cognitive function. Fifteen patient participants diagnosed with a brain tumour requiring radiotherapy will be recruited. Participants will undergo a remote, home-based 10-week personalised digital intervention using the CURATE.AI COR-Tx platform three times a week. Cognitive function will be assessed via a combined non-digital cognitive evaluation and a digital diagnostic session at five time points: preradiotherapy, preintervention and postintervention and 16-weeks and 32-weeks postintervention. Feasibility outcomes relating to acceptability, demand, implementation, practicality and limited efficacy testing as well as usability and user experience will be assessed at the end of the intervention through semistructured patient interviews and a study team focus group discussion at study completion. All outcomes will be analysed quantitatively and qualitatively.

Ethics and dissemination

This study has been approved by the National Healthcare Group (NHG) DSRB (DSRB2020/00249). We will report our findings at scientific conferences and/or in peer-reviewed journals.

Trial registration number

NCT04848935.
Child health valuation protocol for a discrete choice experiment comparing paired comparison and kaizen tasks and estimating US EQ-5D-Y-3L values on an experience scale
Authors: Jumamyradov Maksat , Craig Benjamin Matthew , Rivero-Arias Oliver , Jakubczyk Michał
Published: October 2023

Introduction

A decade ago, the first national valuation study of the EQ-5D-Y-3L (Y-3L) involved a discrete choice experiment (DCE) that asked 4155 US adult respondents to complete 40 paired comparisons, choosing between two dying children. Instead of choosing between dying children, the respondents in this novel protocol are asked whether ‘being in a coma’ is better or worse than experiencing ‘health problems’ (ie, experience scale) and how they would relieve health problems (ie, kaizen tasks). Our aims are to compare the preference evidence of the paired comparison and kaizen tasks and to conduct a DCE for the valuation of Y-3L profiles on an experience scale.

Methods and analysis

Under this protocol, we will conduct an online survey that collects preference evidence from 600 US adult respondents on the health of a 10-year-old child for a week. Across all scenarios, each child will be described as either being ‘in a coma’ or having ‘health problems’, namely five three-level attributes (Y-3L). In this DCE, each respondent will be randomly assigned to one of four D-efficient blocks, including five coma comparisons (ie, Y-3L vs coma), 10 paired comparisons (Y-3L vs Y-3L) and 10 kaizen tasks (preference paths). In addition to comparing evidence by task (aim 2), the analysis plan includes the estimation of main-effects conditional logit models to create a Y-3L value set on an ‘experience scale’ where positive (negative) experiences have positive (negative) values (0 is ‘being in a coma’ and 1 is full health).

Ethics and dissemination

The institutional review board (IRB) (Advarra) determined that this project (Pro00072276) is exempt from IRB oversight based on DHHS 45 CFR 46.104(d)(2) and is not subject to requirements for continuing review. The results will be prepared for publication in peer-reviewed journals and presented at scientific meetings. The data and code will be made available on reasonable request.
Quality of refractive error care in Pakistan: an unannounced standardised patient study
Authors: Lee Ling , Javaid Muhammed Iqbal , Riaz Farah , Awan Farooq , Varga Beatrice , Ho Suit May , McGuinness Myra Beth , Burnett Anthea
Published: October 2023

Objective

Undercorrected refractive errors are the primary cause of vision impairment worldwide, including in Pakistan. However, limited data exist on the quality of refractive error care. Our study assessed the quality of refractive error care in Punjab, Pakistan by estimating the proportion of spectacles that were optimally prescribed.

Methods and analysis

In this cross-sectional study, 12 unannounced standardised patients (USPs) from Jhang, Khanewal and Sahiwal districts were recruited. USPs underwent baseline subjective refraction and were trained to attend optical services, observe consultations, request spectacles and obtain prescriptions. The spectacles received were compared with baseline refraction to determine quality. We also examined the associations between spectacle quality, service and patient characteristics.

Results

Out of 276 attempted visits to 69 optical services, 241 pairs of spectacles were dispensed. A population size-weighted percentage of 42.7% (95% CI 36.4% to 49.3%) of spectacles were optimal quality, with the range varying from 13.8% in Jhang to 67.0% in Khanewal. Half the suboptimal quality spectacles had horizontal prism deviations outside of tolerance limits. Optimal spectacles were associated with performing focimetry (unadjusted OR=7.15, 95% CI (3.02 to 16.94), p<0.001) and good communication (OR=2.23, 95% CI (1.06 to 4.67), p=0.03). Hyperopic USPs were less likely to receive optimal spectacles (OR=0.01 95% CI (0.00 to 0.11), p<0.001).

Conclusion

The quality of refractive error care in Pakistan requires improvement, particularly in the Jhang district. Key areas for enhancing refractive error care in Pakistan include refining dispensing and refraction skills for hyperopic prescriptions, providing training on the risks of using previous spectacles, and emphasising the importance of effective communication skills.
Semaglutide: a new drug for the treatment of obesity
Authors: Lexchin Joel , Mintzes Barbara
Published: October 2023

Semaglutide (▼Ozempic solution for injection, ▼Rybelsus tablets—Novo Nordisk) was initially granted market authorisation for the treatment of type 2 diabetes as an adjunct to diet and exercise. In 2021 and 2022, regulatory agencies in the USA and Europe licensed semaglutide (▼Wegovy solution for injection—Novo Nordisk) for the treatment of individuals who are obese, or overweight and who have at least one weight-related comorbidity. Manufacturer-sponsored randomised controlled trials have shown a loss of almost 12% of body weight over a 68-week period, however, once the medication is stopped people regain most of their pretreatment weight. Gastrointestinal adverse events occur commonly with semaglutide, and pancreatitis, diabetic retinopathy and severe allergic reactions have also been reported. Extensive hype in social and general media has resulted in increased demand for semaglutide leading to supply problems across the various licensed products including those used for treatment of diabetes. In the UK, the National Institute for Health and Care Excellence has recommended semaglutide as an option for weight management for a maximum treatment duration of 2 years. Further studies are underway to assess the effect of semaglutide on longer-term health benefits.
Opportunities and challenges for hepatitis B cure
Authors: Roca Suarez Armando Andres , Zoulim Fabien
Published: October 2023

In spite of the fact that safe and effective vaccines have been available for over 40 years, hepatitis B virus (HBV) remains a major public health problem, as there are 296 million chronically HBV-infected individuals worldwide and 820 000 HBV-related deaths taking place every year. Achieving the goal of HBV cure remains a challenge due to the particularities of the HBV cycle underlying viral persistence. The new understanding of HBV biology and antiviral immune responses has allowed to identify novel drug targets. This has led to a renewed interest in developing new curative strategies and combinations for HBV. In the present review, we aim to summarise the biological and clinical challenges associated with chronic HBV infection. Moreover, we consider the lessons that have been learnt in the past years regarding the preclinical and clinical evaluation of compounds against HBV and how this is driving the field to explore new directions.
Quantification of circulating HBV RNA expressed from intrahepatic cccDNA in untreated and NUC treated patients with chronic hepatitis B
Authors: Testoni Barbara , Scholtès Caroline , Plissonnier Marie-Laure , Paturel Alexia , Berby Françoise , Facchetti Floriana , Villeret François , Degasperi Elisabetta , Scott Beth , Hamilton Aaron , Heil Marintha , Lampertico Pietro , Levrero Massimo , Zoulim Fabien
Published: October 2023

Objective

A convenient, reproducible biomarker of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) transcriptional activity is lacking. We measured circulating HBV RNA (cirB-RNA) in untreated and nucleos(t)ide analogues (NUC) treated chronic hepatitis B (CHB) patients to define its correlation with intrahepatic viral markers and HBV core-related antigen (HBcrAg).

Design

Paired liver biopsy and serum samples were collected from 122 untreated and 30 NUC-treated CHB patients. We measured cirB-RNA, HBV DNA, hepatitis B surface antigen (HBsAg), HBcrAg and alanine aminotransferase levels. cirB-RNA was quantified using an investigational HBV RNA assay for use on the cobas 6800 system. The test detects a region spanning the HBV canonical polyadenylation site. cccDNA and 3.5 kb RNA in liver tissue were assessed by quantitative PCR and droplet digital PCR.

Results

cirB-RNA was detectable in 100% of HBeAg(+) chronic hepatitis (CH), 57% and 14% of HBeAg(−) CH and chronic infection untreated patients and 47% of NUC-treated patients. cirB-RNA undetectability was associated with lower intrahepatic cccDNA transcriptional activity, as well as serum HBcrAg, but no significant differences in HBsAg, in both untreated and treated patients. In untreated HBeAg(−) patients, cirB-RNA correlated with intrahepatic 3.5 kb RNA and cccDNA transcriptional activity, serum HBV DNA and HBcrAg, but not with HBsAg or total cccDNA levels. Combined undetectability of both cirB-RNA and HBcrAg detection in untreated HBeAg(−) patients identified a subgroup with the lowest levels of intrahepatic transcriptionally active cccDNA.

Conclusion

Our results support the usefulness of quantification of circulating HBV RNA expressed from cccDNA as an indicator of intrahepatic active viral reservoir in both untreated and NUC-treated CHB patients.

Trial registration number

NCT02602847.
Coronary physiology thresholds associated with microvascular obstruction in myocardial infarction
Authors: Benenati Stefano , Montorfano Matteo , Pica Silvia , Crimi Gabriele , Ancona Marco , Montone Rocco A , Rinaldi Riccardo , Gramegna Mario , Esposito Antonio , Palmisano Anna , Tavano Davide , Monizzi Giovanni , Bartorelli Antonio , Porto Italo , Ambrosio Giuseppe , Camici Paolo Guido
Published: October 2023

Objectives

To ascertain whether invasive assessment of coronary physiology soon after recanalisation of the culprit artery by primary percutaneous coronary intervention is associated with the development of microvascular obstruction by cardiac magnetic resonance in patients with ST-segment elevation myocardial infarction (STEMI).

Methods

Between November 2020 and December 2021, 102 consecutive patients were prospectively enrolled in five tertiary centres in Italy. Coronary flow reserve (CFR) and index of microvascular resistance (IMR) were measured in the culprit vessel soon after successful primary percutaneous coronary intervention. Optimal cut-off points of IMR and CFR to predict the presence of microvascular obstruction were estimated, stratifying the population accordingly in four groups. A comparison with previously proposed stratification models was carried out.

Results

IMR>31 units and CFR≤1.25 yielded the best accuracy. Patients with IMR>31 and CFR≤1.25 exhibited higher microvascular obstruction prevalence (83% vs 38%, p<0.001) and lower left ventricular ejection fraction (45±9% vs 52±9%, p=0.043) compared with those with IMR≤31 and CFR>1.25, and lower left ventricular ejection fraction compared with patients with CFR≤1.25 and IMR≤31 (45±9% vs 54±7%, p=0.025). Infarct size and area at risk were larger in the former, compared with other groups.

Conclusions

IMR and CFR are associated with the presence of microvascular obstruction in STEMI. Patients with an IMR>31 units and a CFR≤1.25 have higher prevalence of microvascular obstruction, lower left ventricular ejection fraction, larger infarct size and area at risk.

Trial registration number

NCT04677257.
Consent to testing for brain death
Authors: Lyons Barry , Donnelly Mary
Published: October 2023

Canada has recently published a new Clinical Practice Guideline on the diagnosis and management of brain death. It states that consent is not necessary to carry out the interventions required to make the diagnosis. A supporting article not only sets out the arguments for this but also contends that ‘UK laws similarly carve out an exception, excusing clinicians from a prima facie duty to get consent’. This is supplemented by the claim that recent court decisions in the UK similarly confirm that consent is not required, referencing two judgements inBattersbee. We disagree with the authors’ interpretation of the law on consent in the UK and argue that there is nothing inBattersbeeto support the conclusion that consent to testing is not necessary. Where there is a disagreement about testing for brain death in the UK, court authorisation is required.
Are patients with GBA–Parkinson disease good candidates for deep brain stimulation? A longitudinal multicentric study on a large Italian cohort
Authors: Avenali Micol , Zangaglia Roberta , Cuconato Giada , Palmieri Ilaria , Albanese Alberto , Artusi Carlo Alberto , Bozzali Marco , Calandra-Buonaura Giovanna , Cavallieri Francesco , Cilia Roberto , Cocco Antoniangela , Cogiamanian Filippo , Colucci Fabiana , Cortelli Pietro , Di Fonzo Alessio , Eleopra Roberto , Giannini Giulia , Imarisio Alberto , Imbalzano Gabriele , Ledda Claudia , Lopiano Leonardo , Malaguti Maria Chiara , Mameli Francesca , Minardi Raffaella , Mitrotti Pierfrancesco , Monfrini Edoardo , Spagnolo Francesca , Tassorelli Cristina , Valentino Francesca , Valzania Franco , Pacchetti Claudio , Valente Enza Maria
Published: October 2023

Background

GBAvariants increase the risk of developing Parkinson disease (PD) and influence its outcome. Deep brain stimulation (DBS) is a recognised therapeutic option for advanced PD. Data on DBS long-term outcome inGBAcarriers are scarce.

Objective

To elucidate the impact ofGBAvariants on long-term DBS outcome in a large Italian cohort.

Methods

We retrospectively recruited a multicentric Italian DBS-PD cohort and assessed: (1)GBAprevalence; (2) pre-DBS clinical features; and (3) outcomes of motor, cognitive and other non-motor features up to 5 years post-DBS.

Results

We included 365 patients with PD, of whom 73 (20%) carriedGBAvariants. 5-year follow-up data were available for 173 PD, including 32 mutated subjects. GBA-PD had an earlier onset and were younger at DBS than non-GBA-PD. They also had shorter disease duration, higher occurrence of dyskinesias and orthostatic hypotension symptoms.

At post-DBS, both groups showed marked motor improvement, a significant reduction of fluctuations, dyskinesias and impulsive-compulsive disorders (ICD) and low occurrence of most complications. Only cognitive scores worsened significantly faster in GBA-PD after 3 years. Overt dementia was diagnosed in 11% non-GBA-PD and 25% GBA-PD at 5-year follow-up.

Conclusions

Evaluation of long-term impact ofGBAvariants in a large Italian DBS-PD cohort supported the role of DBS surgery as a valid therapeutic strategy in GBA-PD, with long-term benefit on motor performance and ICD. Despite the selective worsening of cognitive scores since 3 years post-DBS, the majority of GBA-PD had not developed dementia at 5-year follow-up.
Proximity extension assay-based discovery of biomarkers for disease activity in chronic inflammatory demyelinating polyneuropathy
Authors: Wieske Luuk , Michael Milou R , in 't Veld Sjors G J G , Visser Allerdien , van Schaik Ivo N , Eftimov Filip , Teunissen Charlotte E
Published: October 2023

Background

Objective disease activity biomarkers are lacking in chronic inflammatory demyelinating polyneuropathy (CIDP), impacting treatment decisions in clinical care and outcomes in clinical trials. Using a proximity extension assay, we aimed to identify candidate serum protein biomarkers for disease activity in CIDP.

Method

We collected clinical data and serum of 106 patients with CIDP. Patients starting induction treatment (n=53) and patients on maintenance treatment starting treatment withdrawal (n=40) were assessed at baseline and at 6 months (or at relapse). Patients in remission (n=13) were assessed once. Clinical disease activity was defined based on improvement or deterioration by the minimal clinically important difference on the inflammatory Rasch-built Overall Disability Scale in combination with either grip strength or the Medical Research Council sum score. Using a proximity extension assay (Olink Explore platform), 1472 protein levels were analysed in serum. Candidate proteins were selected based on fold change>0.5 or <−0.5 and p<0.05 between clinically active and inactive disease. Longitudinal changes of candidate proteins between baseline and follow-up were analysed.

Results

We identified 48 candidate proteins that differed between clinically active and inactive disease on cross-sectional comparison. Five of these proteins (SUGT1, IRAK4, DCTN1, 5'-nucleotidase cytosolic IIIA (NT5C3A), glutaredoxin (GLRX)) also showed longitudinal changes consistent with disease activity changes. IRAK4 was also identified in a sensitivity analysis, using another definition for disease activity.

Conclusion

Our results indicate that IRAK4 and possibly SUGT1, DCTN1, NT5C3A and GLRX are candidate biomarkers for monitoring clinical disease activity in CIDP.
Microvascular C5b-9 deposition in non-lesional skin in patients with SLE and its correlation with active lupus nephritis: a prospective observational study
Authors: Anderson Meghan , Magro Cynthia , Belmont H Michael
Published: October 2023

Objective

Tissue damage in lupus nephritis (LN) is mediated by activation of the classical complement pathway. Complement-mediated upregulation of endothelial cell adhesion molecules is seen in dermal blood vessels of non-lesional skin of patients with active lupus. In diseases with systemic complement activation, extensive microvascular C5b-9 deposition is seen in non-lesional skin. In this study, we assess the presence of systemic complement pathway activation as determined by non-lesional skin microvascular C5b-9 deposition in patients with LN.

Methods

Eight patients with active LN and eight patients without active LN underwent non-lesional skin biopsies. Using a diaminobenzidine technique, specimens were evaluated for microvascular C5b-9 consistent with systemic complement pathway activation.

Results

Five of eight patients with active LN and one of eight patients without active LN demonstrated positive C5b-9 staining in non-lesional skin (p=0.04). Positive non-lesional C5b-9 staining has greater specificity, 87.5%, for active LN than pyuria, low complements, elevated double-stranded DNA (dsDNA) and proteinuria. Urine protein creatinine ratio was significantly higher in patients with positive non-lesional C5b-9 deposition (5.18 vs 1.20; p=0.04). C5b-9 deposition was not associated with a higher NIH Activity Index, interstitial fibrosis, dsDNA or lower complements.

Conclusion

This is the first study to demonstrate evidence in non-lesional skin of microvascular C5b-9 indicative of systemic complement pathway activation in LN. C5b-9 deposition is statistically more common and demonstrated greater specificity than most historical biomarkers for active LN. The findings support a potential role for microvascular C5b-9 assessment in non-lesional skin as a biomarker for LN activity.
Quantum entanglement patterns in the structure of atomic nuclei within the nuclear shell model
Authors: Pérez-Obiol A. , Masot-Llima S. , Romero A. M. , Menéndez J. , Rios A. , García-Sáez A. , Juliá-Díaz B.
Published: October 2023

Quantum entanglement offers a unique perspective into the underlying structure of strongly-correlated systems such as atomic nuclei. In this paper, we use quantum information tools to analyze the structure of light and medium-mass berillyum, oxygen, neon and calcium isotopes within the nuclear shell model. We use different entanglement metrics, including single-orbital entanglement, mutual information, and von Neumann entropies for different equipartitions of the shell-model valence space and identify mode-entanglement patterns related to the energy, angular momentum and isospin of the nuclear single-particle orbitals. We observe that the single-orbital entanglement is directly related to the number of valence nucleons and the energy structure of the shell, while the mutual information highlights signatures of proton–proton and neutron–neutron pairing, as well as nuclear deformation. Proton and neutron orbitals are weakly entangled by all measures, and in fact have the lowest von Neumann entropies among all possible equipartitions of the valence space. In contrast, orbitals with opposite angular momentum projection have relatively large entropies, especially in spherical nuclei. This analysis provides a guide for designing more efficient quantum algorithms for the noisy intermediate-scale quantum era.
Relations between basis sets of fields in the renormalization procedure
Authors: Draukšas Simonas
Published: October 2023

It seems that the literature suggests to go in two opposing directions simultaneously. On the one hand, many papers construct basis-independent quantities, since exactly these quantities appear in the expressions for observables. This means that the mixing angles such as $$\tan \beta $$

tan
β

in the generic Two Higgs Doublet Model must drop out when calculating anything physical. On the other hand, there are many attempts to renormalize such mixing angles – this is in the opposite direction to basis-independence. This basis-dependent approach seems to bring gauge-dependence and singular behaviour, both of which are required to be absent in mixing renormalization. Most importantly, mixing angle counterterms single out a preferred basis and further basis rotations lead to inconsistencies. In contrast, we argue that the bare mixing angles should be identified with the renormalized ones – this is the basis-independent approach – such that all the mixing renormalization requirements are fulfilled in a trivial and consistent manner.
Spreadsheets on Interactive Surfaces: Breaking through the Grid with the Pen
Authors: Cavez Vincent , Appert Caroline , Pietriga Emmanuel
Published: October 2023

Spreadsheet programs for interactive surfaces have limited manipulations capabilities and are often frustrating to use. One key reason is that the spreadsheet grid creates a layer that intercepts most user input events, making it difficult to reach the cell values that lie underneath. We conduct an analysis of commercial spreadsheet programs and an elicitation study to understand what users can do and what they would like to do with spreadsheets on interactive surfaces. Informed by these, we design interaction techniques that leverage the precision of the pen to mitigate friction between the different layers. These enable more operations by direct manipulation on and through the grid, targeting not only cells and groups of cells, but values and substrings within and across cells as well. We prototype these interaction techniques and conduct a qualitative study with information workers who perform a variety of spreadsheet operations on their own data.
Hierarchical Synergy-Enhanced Multimodal Relational Network for Video Question Answering
Authors: Peng Min , Shao Xiaohu , Shi Yu , Zhou Xiangdong
Published: October 2023

Video question answering (VideoQA) is challenging as it requires reasoning about natural language and multimodal interactive relations. Most existing methods apply attention mechanisms to extract interactions between the question and the video or to extract effective spatio-temporal relational representations. However, these methods neglect the implication of relations between intra- and inter-modal interactions for multimodal learning, and they fail to fully exploit the synergistic effect of multiscale semantics in answer reasoning. In this article, we propose a novel hierarchical synergy-enhanced multimodal relational network (HMRNet) to address these issues. Specifically, we devise (i) a compact and unified relation-oriented interaction module that explores the relation between intra- and inter-modal interactions to enable effective multimodal learning; and (ii) a hierarchical synergistic memory unit that leverages a memory-based interaction scheme to complement and fuse multimodal semantics at multiple scales to achieve synergistic enhancement of answer reasoning. With careful design of each component, our HMRNet has fewer parameters and is computationally efficient. Extensive experiments and qualitative analyses demonstrate that the HMRNet is superior to previous state-of-the-art methods on eight benchmark datasets. We also demonstrate the effectiveness of the different components of our method.
Data Refusal from Below: A Framework for Understanding, Evaluating, and Envisioning Refusal as Design
Authors: Zong Jonathan , Matias J. Nathan
Published: October 2023

Amidst calls for public accountability over large data-driven systems, feminist and indigenous scholars have developed
refusal
as a practice that challenges the authority of data collectors. However, because data affect so many aspects of daily life, it can be hard to see seemingly different refusal strategies as part of the same repertoire. Furthermore, conversations about refusal often happen from the standpoint of designers and policymakers rather than the people and communities most affected by data collection. In this article, we introduce a framework for
data refusal from below
—writing from the standpoint of people who refuse, rather than the institutions that seek their compliance. Because refusers work to reshape socio-technical systems, we argue that refusal is an act of design and that design-based frameworks and methods can contribute to refusal. We characterize refusal strategies across four constituent facets common to all refusal, whatever strategies are used:
autonomy
, or how refusal accounts for individual and collective interests;
time
, or whether refusal reacts to past harm or proactively prevents future harm;
power
, or the extent to which refusal makes change possible; and
cost
, or whether or not refusal can reduce or redistribute penalties experienced by refusers. We illustrate each facet by drawing on cases of people and collectives that have refused data systems. Together, the four facets of our framework are designed to help scholars and activists describe, evaluate, and imagine new forms of refusal.
Understanding Embodied Emissions
Authors: Irwin David , Shenoy Prashant
Published: October 2023

Decarbonizing societal infrastructure, including computing, has emerged as a grand challenge for the 21st century, and thus has seen increasing research attention in recent years. Reducing the carbon emissions of societal infrastructure, whether it be a commercial building or cloud datacenter, generally has two important aspects: reducing operational emissions---the carbon emissions from day-to-day operations---and reducing embodied emissions---the carbon emissions from construction and deployment. These different types of emissions are formally defined for companies in the Greenhouse Gas Protocol (GHG) as (i) Scope 1 emissions, which represent a company's direct emissions, e.g., from directly burning fossil fuels, (ii) Scope 2 emissions, which represent a company's indirect emissions from purchasing and using energy, primarily in the form of electricity, and (iii) Scope 3 emissions, which are indirect emissions that result from all other upstream and downstream activities, such as from purchased goods and services. Collectively, Scopes 1 and 2 capture a company's operational emissions, while Scope 3 captures its embodied emissions.
Toward Carbon-Aware Networking
Authors: Zilberman Noa , Schooler Eve M. , Cummings Uri , Manohar Rajit , Nafus Dawn , Soulé Robert , Taylor Rick
Published: October 2023

Data transmission tends to be neglected when considering the carbon efficiency of systems, even though the electricity usage of data networks as a whole is as large, or larger, than that of data centers. Accounting for carbon cost of the movement of data is hard, and is often assumed to be the responsibility of the receiver or an intermediate provider.

To be able to account for the carbon footprint of networks, mutually agreed metrics are required, covering the end-to-end environmental cost of data transmission and up-the-stack network software costs of data processing, rather than merely the independent network devices.

Beyond discussing the considerations for defining these metrics, this paper suggests building upon existing practices, such as network telemetry, programmable network elements and cost-aware routing to enable carbon-intelligent networking, a concept that goes beyond network energy efficiency and considers the impact of energy decarbonization on the routing and scheduling of data transmission.
The Sky is Not the Limit: Untapped Opportunities for Green Computing
Authors: Josephson Colleen , Peill-Moelter Nicola , Pan Zhelong , Pfaff Ben , Firoiu Victor
Published: October 2023

The Information and Communications Technology (ICT) industry emits as much carbon as the aviation industry [11], and if we continue business as usual our share of emissions will grow manyfold in the coming decade [30]. At the same time, more and more businesses are making commitments to be zero carbon or carbon neutral by 2050 or sooner. The path to zero carbon ICT has four key pillars: prioritizing renewable energy, using resources like power and water more efficiently, addressing embodied carbon, and removing institutional barriers. We discuss from a broad industry perspective the challenges and opportunities within each pillar, as well as the role ICT can play in helping other industries achieve zero carbon goals.
Metrics for Sustainability in Data Centers
Authors: Gandhi Anshul , Lee Dongyoon , Liu Zhenhua , Mu Shuai , Zadok Erez , Ghose Kanad , Gopalan Kartik , Liu Yu David , Hussain Syed Rafiul , Mcdaniel Patrick
Published: October 2023

Despite several calls from the community for improving the sustainability of computing, sufficient progress is yet to be made on one of the key prerequisites of sustainable computing---the ability to define and measure computing sustainability holistically. This position paper proposes metrics that aim to measure the end-to-end sustainability footprint in data centers. To enable useful sustainable computing efforts, these metrics can track the sustainability footprint at various granularities---from a single request to an entire data center. The proposed metrics can also broadly influence sustainable computing practices by incentivizing end-users and developers to participate in sustainable computing efforts in data centers.