bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular diversity and evolution of neuron types in the amniote brain
Authors: Hain David , Gallego-Flores Tatiana , Klinkmann Michaela , Macias Angeles , Ciirdaeva Elena , Arends Anja , Thum Christina , Tushev Georgi , Kretschmer Friedrich , Tosches Maria Antonietta , Laurent Gilles
Published: September 2022

The existence of evolutionarily conserved regions in the vertebrate brain is well established. The rules and constraints underlying the evolution of neuron types, however, remain poorly understood. To compare neuron types across brain regions and species, we generated a cell type atlas of the brain of a bearded dragon and compared it with mouse datasets. Conserved classes of neurons could be identified from the expression of hundreds of genes, including homeodomain-type transcription factors and genes involved in connectivity. Within these classes, however, there are both conserved and divergent neuron types, precluding a simple categorization of the brain into ancestral and novel areas. In the thalamus, neuronal diversification correlates with the evolution of the cortex, suggesting that developmental origin and circuit allocation are drivers of neuronal identity and evolution.
A mosaic of new and old cell types
Authors: Faltine-Gonzalez Dylan Z. , Kebschull Justus M.
Published: September 2022

Comparative transcriptomics could reveal patterns of cell type evolution in the tetrapod brain
Omicron shots are coming—with lots of questions
Authors: Vogel Gretchen
Published: September 2022

Decisions on boosters targeting subvariants will be based on limited data
Deoxygenation and organic carbon sequestration in the Tethyan realm associated with the middle Eocene climatic optimum
Authors: Cramwinckel Margot J. , van der Ploeg Robin , van Helmond Niels A.G.M. , Waarlo Niels , Agnini Claudia , Bijl Peter K. , van der Boon Annique , Brinkhuis Henk , Frieling Joost , Krijgsman Wout , Mather Tamsin A. , Middelburg Jack J. , Peterse Francien , Slomp Caroline P. , Sluijs Appy
Published: September 2022

The middle Eocene climatic optimum (ca. 40 Ma) stands out as a transient global warming phase of ∼400 k.y. duration that interrupted long-term Eocene cooling; it has been associated with a rise in atmospheric CO2 concentrations that has been linked to a flare-up in Arabia-Eurasia continental arc volcanism. Increased organic carbon burial in the Tethys Ocean has been proposed as a carbon sequestration mechanism to bring the middle Eocene climatic optimum to an end. To further test these hypotheses, we assessed the sedimentary and geochemical expression of the middle Eocene climatic optimum in the northern Peri-Tethys, specifically, the organic-rich Kuma Formation of the Belaya River section, located on the edge of the Scythian Platform in the North Caucasus, Russia. We constructed an age-depth model using nannofossil chronobiostratigraphy. Throughout the studied middle Eocene interval (41.2−39.9 Ma), we documented sea-surface temperatures of 32−36 °C based on the tetraether index of tetraethers consisting of 86 carbons (TEX86), depending on proxy calibration, and during the early middle Eocene climatic optimum, we observed sea-surface warming of 2−3 °C. Despite the proximity of the section to the Arabia-Eurasia volcanic arc, the hypothesized source of volcanic CO2, we found no evidence for enhanced regional volcanism in sedimentary mercury concentrations. Sedimentary trace-element concentrations and iron speciation indicate reducing bottom waters throughout the middle Eocene, but the most reducing, even euxinic, conditions were reached during late middle Eocene climatic optimum cooling. This apparent regional decoupling between ocean warming and deoxygenation hints at a role for regional tectonics in causing basin restriction and anoxia. Associated excess organic carbon burial, extrapolated to the entire regional Kuma Formation, may have been ∼8.1 Tg C yr−1, comprising ∼450 Pg C over this ∼55 k.y. interval. Combined with evidence for enhanced organic carbon drawdown in the western Peri-Tethys, this supports a quantitatively significant role for the basin in the termination of the middle Eocene climatic optimum by acting as a large organic carbon sink, and these results collectively illustrate that the closing Tethys Ocean might have affected global Paleogene climate. Moreover, this study highlights the importance of the interplay between global climate and regional oceanic gateway evolution in determining local climate and oceanographic change.
Cardiac AL amyloidosis presenting as recurrent dyspnoea in a patient with cancer: an important clinical clue to an early diagnosis
Authors: Suero-Abreu Giselle Alexandra , Lim Phillip , Patel Brijesh , Thomas Renjit
Published: September 2022

Cardiac amyloidosis (CA) is challenging to diagnose due to its non-specific clinical manifestations early in the disease process. We report the case of a patient who presented with dyspnoea, abdominal distension and leg swelling. Medical history was notable for hypertension, recurrent vulvar squamous cell carcinoma and polysubstance abuse. Over 1 year before the official diagnosis of CA, the patient had multiple hospital readmissions for dyspnoea. Our case illustrates the importance of having a high index of clinical suspicion for an early diagnosis of CA. Furthermore, it highlights the need to re-evaluate a presumed diagnosis when a patient’s symptoms recur or do not respond to appropriate treatment and to consider the influence of social factors on diagnostic processes.
In vivo assessment of associations between photoreceptors structure and macular perfusion in type 1 diabetes
Authors: Viggiano Pasquale , Costanzo Eliana , Giannini Daniela , Fragiotta Serena , De Geronimo Daniele , Giorno Paola , Picconi Fabiana , Frontoni Simona , Varano Monica , Parravano Mariacristina
Published: September 2022

Purpose

To explore the potential relationships between macular vascular network and different adaptive optics (AO) metrics in patients with type 1 diabetes mellitus (DM1) with no signs (NoDR) or mild non-proliferative diabetic retinopathy (NPDR).

Design

Observational cross-sectional study.

Methods

Forty eyes of consecutive patients with DM1 (12 NoDR and 28 NPDR) and 10 healthy age-matched control subjects were included. All patients and controls were imaged using AO retinal camera and PLEX Elite 9000 optical coherence tomography (OCT) angiography (OCTA). The AO outcome measures to evaluate the cone photoreceptor mosaic characteristics were as follows: (1) Cone density (CD); (2) Linear Dispersion Index (LDi) and (3) Heterogeneity Packing Index (HPi). The OCTA outcome measures included: (1) superficial capillary plexus (SCP) perfusion density (PD); (2) deep capillary plexus (DCP) PD and (3) the choriocapillaris (CC) flow deficit percentage (FD%).

Results

NPDR group exhibited a close relationship between cone metrics and CC FD. Notably, CC FD% increase along with LDi (p=0.035), while the increasing CC FD% were associated with reducing CD (p=0.042) and the HPi (p=0.017). Furthermore, the OCTA parameters, including PD SCP and DCP, showed a significant negative correlation with CD.

Conclusions

Our results demonstrated the relationship between macular perfusion at both retinal and choroidal levels and the cone mosaic in patients with DM1 interpolating swept-source-OCTA and AO metrics. In NPDR eyes, the photoreceptor damage was accompanied by CC insufficiency since the early stages of the disease.
Efficacy and safety of tai chi for hyperlipidaemia: a protocol for systematic review and meta-analysis
Authors: Dong Weitao , Zhang Feng , Lian Daoshi , Chen Xingliang , Zhou Hongchi , Gong Tingting , Wang Chao
Published: September 2022

Introduction

The prevalence of hyperlipidaemia is increasing, and patients with hyperlipidaemia are at increased risk of cardiovascular disease and atherosclerosis. In recent years, there has been a growing number of studies on tai chi for hyperlipidaemia. However, a systematic review on its efficacy and safety is not available. Therefore, this study aims to evaluate the efficacy and safety of tai chi for hyperlipidaemia.

Methods and analysis

Four English databases and four Chinese databases will be searched from their inception to May 2021: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Database and Wanfang Database. Chinese and English randomised controlled trials related to tai chi for hyperlipidaemia will be included. Two reviewers should independently carry out study selection, data extraction and risk assessment of bias. The risk of bias in the study will be assessed by the Cochrane risk of bias tool. RevMan (V.5.4) statistical software will be applied for meta-analysis. The Grading of Recommendations Assessment, Development and Evaluation system approach will be employed to assess the quality of evidence.

Ethics and dissemination

Ethical approval is not required because this protocol will not involve patients’ individual information and jeopardise the rights of patients. The meta-analysis result will be reported in peer-reviewed journals or disseminated at related conferences.

OSF registration number

DOI 10.17605/OSF.IO/79D2S.
Economic impact of the first pass effect in mechanical thrombectomy for acute ischaemic stroke treatment in Spain: a cost-effectiveness analysis from the national health system perspective
Authors: González Diaz Eva , Rodríguez-Paz Carlos , Fernandez-Prieto Andres , Martínez-Galdámez Mario , Martínez-Moreno Rosa , Ortega Quintanilla Joaquín , Tomasello Alejandro , Zamarro Joaquín , Liebeskind David , Zaidat Osama O , Mueller-Kronast Nils H
Published: September 2022

Objective

The mechanical thrombectomy (MT) benefit is related to the degree of reperfusion achieved. First pass effect (FPE) is defined as complete/near revascularisation of the large-vessel occlusion (modified Thrombolysis in Cerebral Infarction (mTICI) 2c-3) after a single device pass. This study assessed the health benefit and economic impact of achieving FPE for acute ischaemic stroke (AIS) patients from the Spanish National Health System (NHS) perspective.

Design

A lifetime Markov model was used to estimate incremental costs and health outcomes (measured in quality-adjusted life-years (QALYs)) of patients that achieve FPE. A subanalysis of the Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischaemic Stroke (STRATIS) registry was performed to obtain clinical outcomes. The base case included all patients that achieved at least a final mTICI ≥2 b, while the alternative scenario included all patients regardless of their final mTICI (0–3). Treatment costs were updated to reflect current practice based on expert panel consensus, while other acute and long-term costs were obtained from a previous cost-effectiveness analysis of MT performed in Spain. Sensitivity analyses were performed to assess the model’s robustness.

Setting

Spanish healthcare perspective.

Participants

AIS patients in Spain.

Interventions

FPE following MT.

Outcome measures

The model estimated QALYs, lifetime costs and net monetary benefit for the FPE and non-FPE group, depending on the inclusion of reperfusion groups and formal care costs.

Results

STRATIS subanalysis estimated significantly better clinical outcomes at 90 days for the FPE group in all scenarios. In the base case, the model estimated lifetime cost saving per patient of €16 583 and an incremental QALY gain of 1.2 years of perfect health for the FPE group. Cost savings and QALY gains were greater in the alternative scenario (-€44 289; 1.75). In all scenarios, cost savings were driven by the long-term cost reduction.

Conclusion

Achieving FPE after MT can lead to better health outcomes per AIS patient and important cost savings for the Spanish NHS.
Bidirectional relationship between cognitive function and loss hierarchy of activities of daily living among older adults with disabilities in urban China: a cross-lagged analysis
Authors: Sun Qian , Jiang Nan , Lu Nan , Lou Vivian W Q
Published: September 2022

Objectives

The present study aimed to determine the bidirectional relationship between cognitive function and the loss hierarchy of activities of daily living (ADL) among older adults in China.

Design

Data were derived from the Longitudinal Study on Family Caregivers for Frail Older Adults Aged 75 or Above in Shanghai (2010–2013).

Setting

Community-dwelling older adults and their primary caregivers were invited to participate in this research.

Participants

The inclusion criteria for the older adults were as follows: (a) have a Shanghai urban household registration status, (b) be 75 years old or older, (c) have no fewer than two limitations in ADLs or equivalent, and (d) have one primary caregiver aged 18 years or older. 469 older adults cared by their spouses or children were included in the final analytical sample of this research.

Primary and secondary outcome measures

Cognitive function was assessed using the Chinese version of the Short Portable Mental Status Questionnaire and ADLs were measured by self-reports of having difficulty or needing help with basic daily activities.

Results

Cognitive function in 2010 was a significant predictor of intermediate loss of ADLs in 2013 (β=−0.13, p<0.05) and late loss of ADLs in 2013 (β=−0.17, p<0.01). The loss hierarchy of ADLs among older adults was not shown to be significant as a risk factor of cognitive function in 2013.

Conclusions

Practitioners are encouraged to adopt the ADL loss hierarchy as a supplementary needs assessment tool to make the social service delivery process more effective, economical and tailored. Cognitive function change monitoring programmes and services providing education on nutrition and encouraging social participation of older individuals were also helpful in promoting the quality of life of the older adults.
Microbiome Characteristics in Early Threatened Miscarriage Study (MCETMS): a study protocol for a prospective cohort investigation in China
Authors: Chen Xiaofeng , Guo Yinan , Zhang Yingxuan , Si Chen , Zhang Huimin , Huang Xuge , Luo Songping , Deng Gaopi , Gao Jie
Published: September 2022

Introduction

Studies have suggested that the vaginal microbiome and gut microbiome are involved in pregnancy-related diseases, but little exploration of the link with early miscarriage or threatened miscarriage (TM) has been done. Whether the characteristics of the vaginal microbiome and gut microbiome in early pregnancy are related to TM and early pregnancy outcomes remains unclear.

Methods and analysis

The Microbiome Characteristics in Early Threatened Miscarriage Study (MCETMS) is a prospective investigation that will recruit 326 pregnant women with early TM. Pregnant women will be enrolled at 4–8 weeks of gestation, and their vaginal secretions, faecal samples, clinical data and sociodemographic characteristics will be collected prospectively. Pregnant women with TM will be followed up to 12 weeks of gestation to determine the early pregnancy outcomes (ongoing pregnancy or pregnancy loss). DNA will be extracted from the collected samples and will be analysed by 16S rRNA gene sequencing.

Ethics and dissemination

The MCETMS study protocol has been approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Traditional Chinese Medical University (ZYYECK[2020]051). Dissemination of study findings will occur through peer-reviewed journals, conferences and presentations.

Trial registration number

ChiCTR2000041172.
Purchasing high-cost medical devices and equipment in hospitals: a systematic review
Authors: Hinrichs-Krapels Saba , Ditewig Bor , Boulding Harriet , Chalkidou Anastasia , Erskine Jamie , Shokraneh Farhad
Published: September 2022

Objectives

To systematically review academic literature for studies on any processes, procedures, methods or approaches to purchasing high-cost medical devices and equipment within hospitals in high-income countries.

Methods

On 13 August 2020, we searched the following from inception: Cost-Effectiveness Analysis Registry, EconLit and ProQuest Dissertations & Theses A&I via ProQuest, Embase, MEDLINE, and MEDLINE in Process via Ovid SP, Google and Google Scholar, Health Management and Policy Database via Ovid SP, IEEE Xplore Digital Library, International HTA Database, NHS EED via CRD Web, Science Citation Index-Expanded, Conference Proceedings Citation Index-Science, and Emerging Sources Citation Index via Web of Science, Scopus, and Zetoc conference search. Studies were included if they described the approach to purchasing (also known as procurement or acquisition) of high-cost medical devices and/or equipment conducted within hospitals in high-income countries between 2000 and 2020. Studies were screened, data extracted and results summarised in tables under themes identified.

Results

Of 9437 records, 24 were included, based in 12 different countries and covering equipment types including surgical robots, medical imaging equipment, defibrillators and orthopaedic implants. We found heterogeneity in methods and approaches; including descriptions of processes taking place within or across hospitals (n=14), out of which three reported cost savings; empirical studies in which hospital records or participant data were analysed (n=8), and evaluations or pilots of proposed purchasing processes (n=2). Studies emphasise the importance of balancing technical, financial, safety and clinical requirements for device selection through multidisciplinary involvement (especially clinical engineers and clinicians) in decision-making, and the potential of increasing evidence-based purchasing decisions using approaches such as hospital-based health technology assessments, ergonomics and device ‘user trials’.

Conclusions

We highlight the need for more empirical work that evaluates purchasing approaches or interventions, and greater specificity in study reporting (eg, equipment type, evaluation outcomes) to build the evidence base required to influence policy and practice for medical equipment purchasing.

Protocol registration

This review was registered in Open Science Framework: Shokraneh F, Hinrichs-Krapels S, Chalkidou Aet al. Purchasing high-cost medical equipment in hospitals in OECD countries: A systematic review. Open Science Framework 2021; doi:10.17605/OSF.IO/GTXN8. Available at:https://osf.io/gtxn8/(accessed 12 February 2022).
Developing digital contact tracing tailored to haulage in East Africa to support COVID-19 surveillance: a protocol
Authors: Muwonge Adrian , Mpyangu Christine Mbabazi , Nsangi Allen , Mugerwa Ibrahim , Bronsvoort Barend M deC , Porphyre Thibaud , Ssebaggala Emmanuel Robert , Kiayias Aggelos , Mwaka Erisa Sabakaki , Joloba Moses
Published: September 2022

Introduction

At the peak of Uganda’s first wave of SARS-CoV-2 in May 2020, one in three COVID-19 cases was linked to the haulage sector. This triggered a mandatory requirement for a negative PCR test result at all ports of entry and exit, resulting in significant delays as haulage drivers had to wait for 24–48 hours for results, which severely crippled the regional supply chain.

To support public health and economic recovery, we aim to develop and test a mobile phone-based digital contact tracing (DCT) tool that both augments conventional contact tracing and also increases its speed and efficiency.

Methods and analysis

To test the DCT tool, we will use a stratified sample of haulage driver journeys, stratified by route type (regional and local journeys).

We will include at least 65% of the haulage driver journeys ~83 200 on the network through Uganda. This allows us to capture variations in user demographics and socioeconomic characteristics that could influence the use and adoption of the DCT tool. The developed DCT tool will include a mobile application and web interface to collate and intelligently process data, whose output will support decision-making, resource allocation and feed mathematical models that predict epidemic waves.

The main expected result will be an open source-tested DCT tool tailored to haulage use in developing countries.

This study will inform the safe deployment of DCT technologies needed for combatting pandemics in low-income countries.

Ethics and dissemination

This work has received ethics approval from the School of Public Health Higher Degrees, Research and Ethics Committee at Makerere University and The Uganda National Council for Science and Technology. This work will be disseminated through peer-reviewed publications, our websiteshttps://project-thea.org/and Github for the open source codehttps://github.com/project-thea/.
Postnatal maternal depressive symptoms and behavioural outcomes in term-born and preterm-born toddlers: a longitudinal UK community cohort study
Authors: Kleine Ira , Vamvakas George , Lautarescu Alexandra , Falconer Shona , Chew Andrew , Counsell Serena , Pickles Andrew , Edwards David , Nosarti Chiara
Published: September 2022

Objectives

To examine the association between maternal depressive symptoms in the immediate postnatal period and offspring’s behavioural outcomes in a large cohort of term-born and preterm-born toddlers.

Design and participants

Data were drawn from the Developing Human Connectome Project. Maternal postnatal depressive symptoms were assessed at term-equivalent age, and children’s outcomes were evaluated at a median corrected age of 18.4 months (range 17.3–24.3).

Exposure and outcomes

Preterm birth was defined as <37 weeks completed gestation. Maternal depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale (EPDS). Toddlers’ outcome measures were parent-rated Child Behaviour Checklist 11/2–5 Total (CBCL) and Quantitative Checklist for Autism in Toddlers (Q-CHAT) scores. Toddlers’ cognition was assessed with the Bayley Scales of Infant and Toddler Development—Third Edition (Bayley-III).

Results

Higher maternal EPDS scores were associated with toddlers’ higher CBCL (B=0.93, 95% CI 0.43 to 1.44, p<0.001, f2=0.05) and Q-CHAT scores (B=0.27, 95% CI 0.03 to 0.52, p=0.031, f2=0.01). Maternal EPDS, toddlers’ CBCL and Q-CHAT scores did not differ between preterm (n=97; 19.1% of the total sample) and term participants. Maternal EPDS score did not disproportionately affect preterm children with respect to CBCL or Q-CHAT scores.

Conclusions

Our findings indicate that children whose mothers reported increased depressive symptoms in the early postnatal period, including subclinical symptoms, exhibit more parent-reported behavioural problems in toddlerhood. These associations were independent of gestational age. Further research is needed to confirm the clinical significance of these findings.
Antimicrobial prescribing for children in China: data from point prevalence surveys in 18 tertiary centres in China in 2016–2017
Authors: Zhang Jiaosheng , Zhang Wenshuang , Ma Xiang , Tang Lanfang , Tian Daiyin , Wu Keye , Zheng Yuejie , Shen Kunling , Deng Jikui , Yang Yonghong
Published: September 2022

Objectives

The reports on evaluating the classification of antibiotic agents prescribed for Chinese children by combining WHO’s and China’s administrative categories were rare. This study aimed to investigate the pattern of antimicrobial agents prescribing for Chinese children in 2016.

Settings

18 tertiary centres from nine provinces located in northern, southern, eastern and western China.

Participants

The antimicrobial prescribing data from the children admitted in medical wards, surgical wards and intensive care units were collected and analysed. A total of 3680 antibiotic prescriptions for Chinese children were included in the analysis.

Primary and secondary outcome measures

One-day point-prevalence surveys (PPSs) on antimicrobial prescribing were conducted among hospitalised children in China between 1 February 2016 and 28 February 2017. Five hospitals participated in the first PPS, 13 hospitals in the second PPS, 17 hospitals in the third PPS and 18 hospitals in the fourth PPS. Patterns of antibiotic use with a drug utilisation of 90%, Anatomical Therapeutical Chemical Classification, WHO Access, Watch and Reserve (AWaRe) (version 2019) and antibiotic classification in China were described retrospectively.

Results

A total of 4442 children and 3680 antibiotic prescriptions for Chinese children were included in the analysis. 2900 (65.3%) children received at least one ongoing antibiotic during the survey days. On the basis of WHO AWaRe classification, the proportion of antibiotics in the Watch group was 76.5% (2814/3680). According to the Management of Antibiotic Classification in China, 56.8% (2089/3680) and 16.1% (594/3680) of antibiotic prescriptions in the Restricted group and the Special group, respectively, were included into broad-spectrum antibiotics. The most common indication for antibiotics was bacterial lower respiratory tract infection (2044/3680, 55.5%).

Conclusions

The use of broad-spectrum antibiotics was frequent and excessive in hospitalised children in China in 2016.
Effect on diagnostic accuracy of cognitive reasoning tools for the workplace setting: systematic review and meta-analysis
Authors: Staal Justine , Hooftman Jacky , Gunput Sabrina T G , Mamede Sílvia , Frens Maarten A , Van den Broek Walter W , Alsma Jelmer , Zwaan Laura
Published: September 2022

Background

Preventable diagnostic errors are a large burden on healthcare. Cognitive reasoning tools, that is, tools that aim to improve clinical reasoning, are commonly suggested interventions. However, quantitative estimates of tool effectiveness have been aggregated over both workplace-oriented and educational-oriented tools, leaving the impact of workplace-oriented cognitive reasoning tools alone unclear. This systematic review and meta-analysis aims to estimate the effect of cognitive reasoning tools on improving diagnostic performance among medical professionals and students, and to identify factors associated with larger improvements.

Methods

Controlled experimental studies that assessed whether cognitive reasoning tools improved the diagnostic accuracy of individual medical students or professionals in a workplace setting were included. Embase.com, Medline ALL via Ovid, Web of Science Core Collection, Cochrane Central Register of Controlled Trials and Google Scholar were searched from inception to 15 October 2021, supplemented with handsearching. Meta-analysis was performed using a random-effects model.

Results

The literature search resulted in 4546 articles of which 29 studies with data from 2732 participants were included for meta-analysis. The pooled estimate showed considerable heterogeneity (I2=70%). This was reduced to I2=38% by removing three studies that offered training with the tool before the intervention effect was measured. After removing these studies, the pooled estimate indicated that cognitive reasoning tools led to a small improvement in diagnostic accuracy (Hedges’g=0.20, 95% CI 0.10 to 0.29, p<0.001). There were no significant subgroup differences.

Conclusion

Cognitive reasoning tools resulted in small but clinically important improvements in diagnostic accuracy in medical students and professionals, although no factors could be distinguished that resulted in larger improvements. Cognitive reasoning tools could be routinely implemented to improve diagnosis in practice, but going forward, more large-scale studies and evaluations of these tools in practice are needed to determine how these tools can be effectively implemented.

PROSPERO registration number

CRD42020186994.
Fluid biomarkers and risk of neurodegenerative disease in retired athletes with multiple concussions: results from the International Concussion and Head Injury Research Foundation Brain health in Retired athletes Study of Ageing and Impact-Related Neurodegenerative Disease (ICHIRF-BRAIN study)
Authors: Swann Owen James , Turner Michael , Heslegrave Amanda , Zetterberg Henrik
Published: September 2022

Objectives

To investigate the association and utility of blood plasma markers of neurodegeneration in a population of retired athletes self-reporting multiple concussions throughout a sporting career. It is hypothesised that this type of athletic history would cause an increased prevalence of neurodegenerative disease, as detected by biomarkers for neurodegenerative disease processes.

Methods

One hundred and fifty-nine participants were recruited (90 males, 69 females, mean age 61.3±9.13 years), including 121 participants who had retired from playing professional or semiprofessional sports and self-reported ≥1 concussion during their careers (range 1–74; mean concussions=10.7). The control group included 38 age-matched and sex-matched controls, with no history of concussion. We measured neurofilament light (NfL) and tau (neurodegeneration markers), glial fibrillar acidic protein (GFAP) (astrocytic activation marker) and 40 and 42 amino acid-long amyloid beta (Aβ40 and Aβ42) (Alzheimer-associated amyloid pathology markers) concentrations using ultrasensitive single molecule array technology.

Results

We found retired athletes reporting one or more concussions throughout an athletic career showed no significant changes in NfL, tau, GFAP and Aβ40 and Aβ42 concentrations in comparison to a control group. No correlations were found between biomarkers and number of concussions (mean=10.7). A moderate correlation was found between NfL concentration and age.

Conclusion

No difference in blood concentrations of neurodegeneration markers NfL, tau, GFAP and Aβ40 and Aβ42 was found in retired athletes with a history of concussion compared with controls. An increased prevalence of neurodegenerative diseases is not detected by biomarkers in a population self-reporting multiple concussions.

Trial registration number

ISRCTN 11312093
Context of boat drowning in Ghana: a mixed qualitative research study
Authors: Kushitor Mawuli Komla , Bour Helen , Nyame Prince , Yabila Solomon
Published: September 2022

Background

Drowning is a significant public health challenge globally. In Africa and Ghana, drowning has remained a silent epidemic among poor communities. Limited evidence has challenged advances in drowning knowledge and prevention. While drowning deaths are often widely circulated in the newspapers, drowning data are not systematically organised to constitute a body of evidence sufficient for scientific exploration. Although drowning was frequent, they were poorly understood. We explore the context of drowning from multiple perspectives from the Volta-basin where the largest man-made lake in the world has become a hotspot for drowning.

Method

This study adopts a sequential-mix-qualitative study comprising content analysis of newspaper reports on drowning, structured-observations and in-depth interviews with boaters and fisherfolk. We first explored, the content of newspapers over a 10-year period. This information provided the context of drowning. We followed up with extensive observation of activities on the lake by a team of five. Photovoice qualitative interviews were conducted with 22 boaters, fishers and community members. Thematic content analysis was applied to both the newspaper reports and the in-depth interviews.

Results

Drowning was attributed to both proximate and distal causes. Distal causes were the reasons for movement, while proximate causes were the immediate cause of the drowning. Travelling to farm, market, hospital, church, sell were important distal causes of drowning. Proximate determinants included strong winds, tree stumps, overcrowding, no-adherence to safety procedures, spiritual reasons and high tides. Four types of boat accidents were observed: boat-capsizing, boat-sinking, boat-splitting and boat-catching-fire. Ideas converged and diverged in comparing the newspaper content analysis to the photovoice interviews.
Feasibility and acceptability of a paeārahi (Indigenous Whānau Ora navigator) intervention for unintentional injury prevention for older Māori: non-randomised, non-comparator trial study protocol
Authors: Hikaka Joanna , Ihimaera Louise , Kool Bridget , Kerse Ngaire , Parsons John , Maxwell-Crawford Kirsty , Vercoe Hariata , Merito Parehuia , Cavadino Alana , Te Ao Braden , Aramoana-Arlidge Brooke
Published: September 2022

Background

Māori (the Indigenous population of Aotearoa New Zealand) experience increased burden of unintentional injury and reduced access to publicly funded injury prevention and rehabilitation services, compared with non-Māori. Māori-led models of care have been shown to improve outcomes for Māori. Paeārahi navigate across sectors (including health, education, housing and employment) to advocate for the best possible outcomes for individuals and families. This study aims to (1) test the acceptability and feasibility and (2) undertake exploratory efficacy analysis of a paeārahi injury intervention for Māori older adults.

Methods

A prospective non-randomised, non-comparator study with preintervention and postintervention measurements of predefined outcomes. Eligible participants who consented to participate (Māori, 55+ years, community-dwelling and enrolled in one of three study general practices) will undergo a multivisit paeārahi intervention. The intervention includes home-hazard assessment, basic health screening, teaching of strength and balance exercises, education relating to injury prevention and access to injury-related, referral and connection to other health and social services) and participants can choose to have whānau (family) involved in the intervention.

Outcomes

The primary outcome of interest is participant, whānau and paeārahi acceptability of the intervention. Secondary outcomes include intervention feasibility, cost-effectiveness and exploratory efficacy (including preintervention and postintervention unintentional injury-related hospitalisation, primary care access and public injury-related claims).

Discussion

The findings of this intervention research will be used to inform injury care models for older Māori and process for Māori-led health intervention development more generally.

Trial registration number

ACTRN12621001691831p.
Effects of Wisconsin’s handgun waiting period repeal on suicide rates
Authors: Oliphant Stephen N
Published: September 2022

Objective

To estimate the effect of a handgun purchase waiting period repeal on handgun and firearm suicides in Wisconsin.

Methods

Data for outcome and predictor variables were obtained for the 1999–2020 study period. Synthetic controls were used to assess the impact of Wisconsin’s waiting period repeal on mean-centred suicide rates. Placebo tests, difference-in-differences regression and augmented synthetic controls supplemented the synthetic control analyses.

Results

Postrepeal suicides were more likely to involve handguns than those in the 5 years immediately preceding the repeal (χ² (1, N=8269) = 49.25, p<0.001). The waiting period repeal resulted in an estimated annual increase of 1.1 handgun suicides per 100 000, or roughly 65 handgun suicide deaths per year. Estimates from difference-in-differences regression and augmented synthetic control analyses indicated similar treatment effects. Relative to the synthetic control, firearm suicides increased 6.5% following the repeal.

Conclusion

The waiting period repeal in Wisconsin was associated with increases in both handgun and firearm suicides. The findings suggest that waiting periods may be effective means restriction policies to reduce suicide. Additionally, the synthetic control’s ability to closely approximate preintervention handgun suicide trends despite a limited donor pool has implications for future policy analyses.
Comparison of laboratory methods for the detection of neoplastic plasma cells in plasma cell dyscrasias
Authors: Dietz Robin , Lollie Trang K , Goh Tracie , Rao Nagesh , Pullarkat Sheeja
Published: September 2022

Aims

To compare the ability of immunohistochemistry (IHC), multiparameter flow cytometry (MFC) and fluorescence in situ hybridisation (FISH) to detect clonal plasma cells. We also attempted to outline a testing strategy for monitoring multiple myeloma patients.

Methods

A retrospective review was performed on 278 CD138+sorted FISH studies from November 2019 to December 2020 along with their concurrent IHC and MFC results. A p value was computed using McNemar’s test for paired data. Association was calculated using the non-parametric Spearman correlation coefficient.

Results

Using the Mc Nemar’s test for paired data, CD138+sorted FISH studies achieved the highest proportion of positive results and was significantly greater than MFC (63% vs 53%, p=0.01). FISH had more positive results than IHC, although this did not reach statistical significance (60% vs 57%, p=0.34). IHC and MFC had high correlation and high agreement (90.3% agreement, kappa=0.805, p<0.0001). CD138+sorted FISH studies achieved the highest proportion of positive results relative to IHC and MFC, indicating that it may be a reliable marker for clonal plasma cell detection.

Conclusions

While CD138+sorted FISH is primarily used for prognostication, it may be employed as a single test for detection and monitoring clonality in certain scenarios. Further studies are needed to monitor the outcomes of patients with positive FISH and negative IHC and MFC. Additionally, there was high agreement between IHC and MFC, suggesting that performing both tests may not be necessary.
Chromatin remodeling (SWI/SNF) complexes, cancer, and response to immunotherapy
Authors: Krishnamurthy Nithya , Kato Shumei , Lippman Scott , Kurzrock Razelle
Published: September 2022

Chromatin regulation involves four subfamilies composed of ATP-dependent multifunctional protein complexes that remodel the way DNA is packaged. The SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex subfamily mediates nucleosome reorganization and hence activation/repression of critical genes. The SWI/SNF complex is composed of the BRG-/BRM-associated factor and Polybromo-associated BAF complexes, which in turn have multiple subunits. Significantly, ~20% of malignancies harbor alterations in >1 of these subunits, making the genes encoding SWI/SNF family members among the most vulnerable to genomic aberrations in cancer. ARID1A is the largest subunit of the SWI/SNF complex and is altered in ~40%–50% of ovarian clear cell cancers and ~15%–30% of cholangiocarcinomas, in addition to a variety of other malignancies. Importantly, outcome was improved after immune checkpoint blockade (ICB) in patients withARID1A-altered versuss wild-type tumors, and this result was independent of microsatellite instability or tumor mutational burden. Another subunit—PBRM1—is mutated in ~40% of clear cell renal cell carcinomas and ~12% of cholangiocarcinomas; there are contradictory reports regarding ICB responsiveness. Two other SWI/SNF subunits of interest are SMARCA4 and SMARCB1. SMARCA4 loss is the hallmark of small cell carcinoma of the ovary hypercalcemic type (and is found in a variety of other malignancies);SMARCA4germline alterations lead to rhabdoid tumor predisposition syndrome-2;SMARCB1germline alterations, rhabdoid tumor predisposition syndrome-1. Remarkable, although anecdotal, responses to ICB have been reported in bothSMARCA4-aberrant andSMARCB1-aberrant advanced cancers. This review focuses on the role that SWI/SNF chromatin remodeling subunits play in carcinogenesis, the immune microenvironment, and in immunotherapy responsiveness.
Shift work is associated with 10-year incidence of atrial fibrillation in younger but not older individuals from the general population: results from the Tromsø Study
Authors: Zwartkruis Victor W , Sharashova Ekaterina , Wilsgaard Tom , de Boer Rudolf A , Løchen Maja-Lisa , Rienstra Michiel
Published: September 2022

Objectives

Shift work is associated with myocardial infarction and stroke. We studied if shift work is also associated with incident atrial fibrillation (AF) and if this association differs, depending on sex and age.

Methods

We studied 22 339 participants (age 37.0±9.8 years, 49% women) with paid work from the third (1986–1987), fourth (1994–1995), fifth (2001) and sixth (2007–2008) surveys of the population-based Tromsø Study, Norway. Participants were followed up for ECG-confirmed AF through 2016. Shift work was assessed by questionnaire at each survey. We used unadjusted and multivariable-adjusted Cox regression models to study the association of shift work with 10-year incident AF and incident AF during extensive follow-up up to 31 years. Interactions with sex and age were tested in the multivariable model.

Results

Shift work was reported by 21% of participants at the first attended survey. There was an interaction between shift work and age for 10-year incident AF (p=0.069). When adjusted for AF risk factors, shift work was significantly associated with 10-year incident AF in participants <40 years (HR 2.90, 95% CI 1.12 to 7.49) but not≥40 years of age (HR 0.90, 95% CI 0.53 to 1.51). Shift work was not associated with incident AF during extensive follow-up (HR 1.03, 95% CI 0.89 to 1.20). There was no interaction between shift work and sex.

Conclusions

Shift work was associated with 10-year incident AF in individuals <40 years but not ≥40 years of age. Shift work was not associated with incident AF during extensive follow-up up to 31 years, and there were no sex differences.
The role of multi-parton interactions in doubly-heavy hadron production
Authors: Egede U. , Hadavizadeh T. , Singla M. , Skands P. , Vesterinen M.
Published: September 2022

Beauty and charm quarks are ideal probes of pertubative Quantum Chromodymanics in proton–proton collisions, owing to their large masses. In this paper the role of multi-parton interactions in the production of doubly-heavy hadrons is studied using simulation samples generated with Pythia, a Monte Carlo event generator. Comparisons are made to the stand-alone generators BcVegPy and GenXicc. New methods of speeding up Pythia simulations for events containing heavy quarks are described, enabling the production of large samples with multiple heavy-quark pairs. We show that significantly higher production rates of doubly-heavy hadrons are predicted in models that allow heavy quarks originating from different parton–parton interactions (within the same hadron–hadron collision) to combine to form such hadrons. Quantitative predictions are sensitive to the modelling of colour reconnections. We suggest a set of experimental measurements capable of differentiating these additional contributions.
Annihilation-to-nothing: DeWitt boundary condition inside a black hole
Authors: Brahma Suddhasattwa , Chen Che-Yu , Yeom Dong-han
Published: September 2022

In canonical quantum gravity, the wave function for a hypersurface inside a Schwarzschild black hole can be obtained by solving the Wheeler–DeWitt equation. What is of prime importance is the behavior of the wave function for the future boundary near the singularity, and the DeWitt boundary condition implies that it should vanish here. In this paper, we provide several generalizations, and new interpretations, of the DeWitt boundary condition. First, we summarize existing works on the wave function inside the black hole to justify the DeWitt boundary condition. Next, we investigate the wave function for the collapsing null shell to show that due to the reflection symmetry in space and time, there exists a destructive interference near the singularity and hence a vanishing boundary condition can be natural. If we extend this point of view to the black hole spacetime itself, then the DeWitt boundary condition is equivalent to saying that there exists a symmetric anti-black hole contribution, such that eventually these two geometries are annihilated-to-nothing near the quantum transition surface. This symmetric model can be realized within black hole models of loop quantum gravity with a novel interpretation for the arrow(s) of time.
Determining some pseudoscalar meson masses from axial anomaly
Authors: Liu Chang-Yong
Published: September 2022

Following our previous work [C. Y. Liu, Mod. Phys. Lett. A 36, 2150080 (2021), doi:10.1142/S0217732321500802], we investigate the masses of some pseudoscalar mesons which have the anomalous decays from axial anomaly (the Adler–Bell–Jackiw anomaly). We apply a non-perturbative mass formula to study the neutral single flavor pseudoscalar meson [Formula: see text]. We find the mass of pseudoscalar meson [Formula: see text] which can solve the problem of double [Formula: see text] production in [Formula: see text] annihilation at [Formula: see text] and obtain the mass of pseudoscalar meson [Formula: see text] which is the same as the invariant mass of [Formula: see text] pairs produced in association with [Formula: see text] jet in [Formula: see text]-collisions at the LHC. We generalize this formula to three flavors pseudoscalar mesons, we obtain the mass of [Formula: see text] meson [Formula: see text] which is almost the same as the experimental value [Formula: see text].
Inapproximability of Counting Hypergraph Colourings
Authors: Galanis Andreas , Guo Heng , Wang Jiaheng
Published: September 2022

Recent developments in approximate counting have made startling progress in developing fast algorithmic methods for approximating the number of solutions to constraint satisfaction problems (CSPs) with large arities, using connections to the Lovász Local Lemma. Nevertheless, the boundaries of these methods for CSPs with non-Boolean domain are not well-understood. Our goal in this article is to fill in this gap and obtain strong inapproximability results by studying the prototypical problem in this class of CSPs, hypergraph colourings.

More precisely, we focus on the problem of approximately counting
q
-colourings on
K
-uniform hypergraphs with bounded degree Δ. An efficient algorithm exists if

\({{\Delta \lesssim \frac{q^{K/3-1}}{4^KK^2}}}\)

[Jain et al.
25
; He et al.
23
]. Somewhat surprisingly however, a hardness bound is not known even for the easier problem of finding colourings. For the counting problem, the situation is even less clear and there is no evidence of the right constant controlling the growth of the exponent in terms of
K
.

To this end, we first establish that for general
q
computational hardness for finding a colouring on simple/linear hypergraphs occurs at Δ ≳
Kq

K

, almost matching the algorithm from the Lovász Local Lemma. Our second and main contribution is to obtain a far more refined bound for the counting problem that goes well beyond the hardness of finding a colouring and which we conjecture is asymptotically tight (up to constant factors). We show in particular that for all even
q
≥ 4 it is
NP
-hard to approximate the number of colourings when Δ ≳
q

K/2

. Our approach is based on considering an auxiliary weighted binary CSP model on graphs, which is obtained by “halving” the
K
-ary hypergraph constraints. This allows us to utilise reduction techniques available for the graph case, which hinge upon understanding the behaviour of random regular bipartite graphs that serve as gadgets in the reduction. The major challenge in our setting is to analyse the induced matrix norm of the interaction matrix of the new CSP which captures the most likely solutions of the system. In contrast to previous analyses in the literature, the auxiliary CSP demonstrates both symmetry and asymmetry, making the analysis of the optimisation problem severely more complicated and demanding the combination of delicate perturbation arguments and careful asymptotic estimates.