bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of p38α MAPK restores neuronal p38γ MAPK and ameliorates synaptic degeneration in a mouse model of DLB/PD
Authors: Iba Michiyo , Kim Changyoun , Kwon Somin , Szabo Marcell , Horan-Portelance Liam , Peer Cody J. , Figg William D. , Reed Xylena , Ding Jinhui , Lee Seung-Jae , Rissman Robert A. , Cookson Mark R. , Overk Cassia , Wrasidlo Wolf , Masliah Eliezer
Published: May 2023

Alterations in the p38 mitogen-activated protein kinases (MAPKs) play an important role in the pathogenesis of dementia with Lewy bodies (DLB) and Parkinson’s disease (PD). Activation of the p38α MAPK isoform and mislocalization of the p38γ MAPK isoform are associated with neuroinflammation and synaptic degeneration in DLB and PD. Therefore, we hypothesized that p38α might be associated with neuronal p38γ distribution and synaptic dysfunction in these diseases. To test this hypothesis, we treated in vitro cellular and in vivo mouse models of DLB/PD with SKF-86002, a compound that attenuates inflammation by inhibiting p38α/β, and then investigated the effects of this compound on p38γ and neurodegenerative pathology. We found that inhibition of p38α reduced neuroinflammation and ameliorated synaptic, neurodegenerative, and motor behavioral deficits in transgenic mice overexpressing human α-synuclein. Moreover, treatment with SKF-86002 promoted the redistribution of p38γ to synapses and reduced the accumulation of α-synuclein in mice overexpressing human α-synuclein. Supporting the potential value of targeting p38 in DLB/PD, we found that SKF-86002 promoted the redistribution of p38γ in neurons differentiated from iPS cells derived from patients with familial PD (carrying the A53T α-synuclein mutation) and healthy controls. Treatment with SKF-86002 ameliorated α-synuclein–induced neurodegeneration in these neurons only when microglia were pretreated with this compound. However, direct treatment of neurons with SKF-86002 did not affect α-synuclein–induced neurotoxicity, suggesting that SKF-86002 treatment inhibits α-synuclein–induced neurotoxicity mediated by microglia. These findings provide a mechanistic connection between p38α and p38γ as well as a rationale for targeting this pathway in DLB/PD.
Broadly neutralizing antibodies against sarbecoviruses generated by immunization of macaques with an AS03-adjuvanted COVID-19 vaccine
Authors: Feng Yupeng , Yuan Meng , Powers John M. , Hu Mengyun , Munt Jennifer E. , Arunachalam Prabhu S. , Leist Sarah R. , Bellusci Lorenza , Kim JungHyun , Sprouse Kaitlin R. , Adams Lily E. , Sundaramurthy Sumana , Zhu Xueyong , Shirreff Lisa M. , Mallory Michael L. , Scobey Trevor D. , Moreno Alberto , O’Hagan Derek T. , Kleanthous Harry , Villinger Francois J. , Veesler David , King Neil P. , Suthar Mehul S. , Khurana Surender , Baric Ralph S. , Wilson Ian A. , Pulendran Bali
Published: May 2023

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has placed an imperative on the development of countermeasures that provide broad protection against SARS-CoV-2 and related sarbecoviruses. Here, we identified extremely potent monoclonal antibodies (mAbs) that neutralized multiple sarbecoviruses from macaques vaccinated with AS03-adjuvanted monovalent subunit vaccines. Longitudinal analysis revealed progressive accumulation of somatic mutation in the immunoglobulin genes of antigen-specific memory B cells (MBCs) for at least 1 year after primary vaccination. Antibodies generated from these antigen-specific MBCs at 5 to 12 months after vaccination displayed greater potency and breadth relative to those identified at 1.4 months. Fifteen of the 338 (about 4.4%) antibodies isolated at 1.4 to 6 months after the primary vaccination showed potency against SARS-CoV-2 BA.1, despite the absence of serum BA.1 neutralization. 25F9 and 20A7 neutralized authentic clade 1 sarbecoviruses (SARS-CoV, WIV-1, SHC014, SARS-CoV-2 D614G, BA.1, and Pangolin-GD) and vesicular stomatitis virus–pseudotyped clade 3 sarbecoviruses (BtKY72 and PRD-0038). 20A7 and 27A12 showed potent neutralization against all SARS-CoV-2 variants and multiple Omicron sublineages, including BA.1, BA.2, BA.3, BA.4/5, BQ.1, BQ.1.1, and XBB. Crystallography studies revealed the molecular basis of broad and potent neutralization through targeting conserved sites within the RBD. Prophylactic protection of 25F9, 20A7, and 27A12 was confirmed in mice, and administration of 25F9 particularly provided complete protection against SARS-CoV-2, BA.1, SARS-CoV, and SHC014 challenge. These data underscore the extremely potent and broad activity of these mAbs against sarbecoviruses.
Variation in Temperature Dependences across Europe Reveals the Climate Sensitivity of Soil Microbial Decomposers
Authors: Cruz-Paredes Carla , Tájmel Dániel , Rousk Johannes
Published: May 2023

One of the largest uncertainties of global warming is if the microbial decomposer feedback will strengthen or weaken soil C-climate feedback. Despite decades of research effort, the strength of this feedback to warming remains unknown.
p38MAPK- and GSK3-Mediated Phosphorylation of Snakehead Vesiculovirus Phosphoprotein at Threonine 160 Facilitates Viral Replication
Authors: Qin Xiangmou , Zhang Yong-An , Tu Jiagang
Published: May 2023

Phosphorylation of viral proteins plays important roles in viral replication. Currently, the role of phosphorylation of phosphoprotein (P) in the replication of single-stranded negative-sense RNA viruses is far from clear.
Structurally distinct mitoviruses: are they an ancestral lineage of the
Mitoviridae
exclusive to arbuscular mycorrhizal fungi (Glomeromycotina)?
Authors: Ezawa Tatsuhiro , Silvestri Alessandro , Maruyama Hayato , Tawaraya Keitaro , Suzuki Mei , Duan Yu , Turina Massimo , Lanfranco Luisa
Published: May 2023

Mitoviruses in the family
Mitoviridae
are the mitochondria-replicating “naked RNA viruses” with genomes encoding only the replicase RNA-dependent RNA polymerase (RdRp) and prevalent across fungi, plants, and invertebrates. Arbuscular mycorrhizal fungi in the subphylum Glomeromycotina are obligate plant symbionts that deliver water and nutrients to the host. We discovered distinct mitoviruses in glomeromycotinian fungi, namely “large duamitovirus,” encoding unusually large RdRp with a unique N-terminal motif that is endogenized in some host genomes. More than 400 viral sequences similar to the large duamitoviruses are present in metatranscriptome databases. They are globally distributed in soil ecosystems, consistent with the cosmopolitan distribution of glomeromycotinian fungi, and formed the most basal clade of the
Mitoviridae
in phylogenetic analysis. Given that glomeromycotinian fungi are the only confirmed hosts of these viruses, we propose the hypothesis that large duamitoviruses are the most ancestral lineage of the
Mitoviridae
that have been maintained exclusively in glomeromycotinian fungi.
Microbiome Analysis of Sugarcane Juices and Biofilms from Louisiana Raw Sugar Factories
Authors: Qi Yunci , Bruni Gillian O. , Klasson K. Thomas
Published: May 2023

Amplicon-based sequencing was utilized to address long-ignored gaps in microbiological knowledge about the diversity of microbes present in processing streams at Louisiana sugarcane raw sugar factories. These results support an emerging model where diverse organisms contribute to sugarcane juice degradation, help to contextualize microbial contamination problems faced by raw sugar factories, and will guide future studies on biocontrol measures to mitigate sucrose losses and operational challenges due to exopolysaccharide production.
Comparison of injury patterns and interventions between adolescent, adult and paediatric trauma cases: a cross-sectional review of TARN data
Authors: Mullen Stephen , Tolson Amy , Bouamra Omar , Watson Ben , Lyttle Mark David , Roland Damian , James David
Published: May 2023

Objectives

The aim is to compare adolescent (10–24.99 years) trauma patterns and interventions to adult (≥25) and paediatric cases (<10) and to identify any transition points.

Design and setting

Data were collected from the Trauma and Audit Research Network (TARN) over a 10-year period. We conducted a retrospective cross-sectional analysis.

Participants

After exclusions there were 505 162 TARN eligible cases.

Primary and secondary outcome measures

To compare adolescent trauma patterns and interventions to those in paediatric and adult cohorts. Identify transition points for mechanism of injury (MOI) and interventions by individual year over the adolescent age range (10–24.99).

Results

Road traffic accidents are the most common MOI in the adolescent group, in contrast to both the paediatric and adult group where falls <2 m are most common. Violence-related injury (shootings and stabbings) are more common in the adolescent group, 9.4% compared with 0.3% and 1.5% in the paediatric and adult groups, respectively. The adolescent grouping had the highest median Injury Severity Score (ISS) and the highest proportion of interventions. The proportion of cases due to stabbing peaked at age 17 (11.8%) becoming the second most common MOI. The median ISS peaked at 13 at age 18. The percentage of cases that fulfil the definition of polytrauma enters double figures (11.8%) at age 15 reaching a peak of 17.6% at age 18. The use of blood products within the first 6 hours remains around 2% (1.6%–2.8%) until age 15 (3.4%), increasing to 4.7% at age 16.

Conclusions

Trauma patterns are more closely aligned between adult and paediatric cohorts than adolescence. The highest proportion of trauma interventions occur in the adolescent population. Analysing the adolescent cohort by year of age identified some common points for when descriptors or outcomes altered in frequency, predominantly between the ages of 15–17 years.
Readiness for transfer: a mixed-methods study on ICU transfers of care
Authors: Lee Soo-Hoon , Wee Clarice , Phan Phillip , Kowitlawakul Yanika , Tan Chee-Kiat , Mukhopadhyay Amartya
Published: May 2023

Objective

Past studies on intensive care unit (ICU) patient transfers compare the efficacy of using standardised checklists against unstructured communications. Less studied are the experiences of clinicians in enacting bidirectional (send/receive) transfers. This study reports on the differences in protocols and data elements between receiving and sending transfers in the ICU, and the elements constituting readiness for transfer.

Methods

Mixed-methods study of a 574-bed general hospital in Singapore with a 74-bed ICU for surgical and medical patients. Six focus group discussions (FGDs) with 34 clinicians comprising 15 residents and 19 nurses, followed by a structured questionnaire survey of 140 clinicians comprising 21 doctors and 119 nurses. FGD transcripts were analysed according to the standard qualitative research guidelines. Survey data were analysed using Student’s t-test with Bonferroni corrections.

Results

General ward (GW) clinicians are more likely to receive ICU patients with complete discharge summaries while ICU clinicians receiving GW patients get significantly less data. Emergency department (ED), GW and operating theatre physicians accompany their patients to the ICU while ICU nurses accompany their patients to the GW. Not all units, such as the ED, experience bidirectional transfers.

Conclusion

The protocols and supporting data elements of an ICU transfer vary by the type of transfer and transferring unit. Readiness for transfer means that sending unit protocols affirmatively consider the needs of the receiving unit’s data needs and resource constraints.
Diagnostic performance of deep learning in infectious keratitis: a systematic review and meta-analysis protocol
Authors: Ong Zun Zheng , Sadek Youssef , Liu Xiaoxuan , Qureshi Riaz , Liu Su-Hsun , Li Tianjing , Sounderajah Viknesh , Ashrafian Hutan , Ting Daniel Shu Wei , Said Dalia G , Mehta Jodhbir S , Burton Matthew J , Dua Harminder Singh , Ting Darren Shu Jeng
Published: May 2023

Introduction

Infectious keratitis (IK) represents the fifth-leading cause of blindness worldwide. A delay in diagnosis is often a major factor in progression to irreversible visual impairment and/or blindness from IK. The diagnostic challenge is further compounded by low microbiological culture yield, long turnaround time, poorly differentiated clinical features and polymicrobial infections. In recent years, deep learning (DL), a subfield of artificial intelligence, has rapidly emerged as a promising tool in assisting automated medical diagnosis, clinical triage and decision-making, and improving workflow efficiency in healthcare services. Recent studies have demonstrated the potential of using DL in assisting the diagnosis of IK, though the accuracy remains to be elucidated. This systematic review and meta-analysis aims to critically examine and compare the performance of various DL models with clinical experts and/or microbiological results (the current ‘gold standard’) in diagnosing IK, with an aim to inform practice on the clinical applicability and deployment of DL-assisted diagnostic models.

Methods and analysis

This review will consider studies that included application of any DL models to diagnose patients with suspected IK, encompassing bacterial, fungal, protozoal and/or viral origins. We will search various electronic databases, including EMBASE and MEDLINE, and trial registries. There will be no restriction to the language and publication date. Two independent reviewers will assess the titles, abstracts and full-text articles. Extracted data will include details of each primary studies, including title, year of publication, authors, types of DL models used, populations, sample size, decision threshold and diagnostic performance. We will perform meta-analyses for the included primary studies when there are sufficient similarities in outcome reporting.

Ethics and dissemination

No ethical approval is required for this systematic review. We plan to disseminate our findings via presentation/publication in a peer-reviewed journal.

PROSPERO registration number

CRD42022348596.
Intersection of reproductive coercion and intimate partner violence: cross-sectional influences on women’s contraceptive use in Burkina Faso, Côte d’Ivoire and Kenya
Authors: Wood Shannon N , Thomas Haley L , Thiongo Mary , Guiella Georges , Bazié Fiacre , Onadja Yentéma , Mosso Rosine , Fassassi Raimi , Gichangi Peter , Decker Michele R
Published: May 2023

Objectives

Among nationally representative cross-sections of women in need of contraception from Burkina Faso, Côte d'Ivoire and Kenya, we aimed to: (1) examine the intersection of past-year physical/sexual intimate partner violence (IPV), emotional IPV and reproductive coercion (RC) and (2) assess the impact of physical/sexual IPV, emotional IPV and RC on women’s contraceptive use outcomes, including current contraceptive use, method type and covert use.

Design

The present analysis uses cross-sectional female data collected in Burkina Faso (December 2020–March 2021), Côte d'Ivoire (October–November 2021) and Kenya (November–December 2020).

Settings

Burkina Faso, Côte d'Ivoire and Kenya

Participants

Analytical samples were restricted to partnered women with contraceptive need who completed a violence module (Burkina Faso n=1863; Côte d'Ivoire n=1105; Kenya n=3390).

Primary and secondary outcome measures

The exposures of interest—past-year emotional IPV, physical/sexual IPV and RC—were assessed using abridged versions of the Revised Conflict and Tactics Scale-2 and Reproductive Coercion Scale, respectively. Outcomes of interest included current contraceptive use, contraceptive method type (female controlled vs male compliant), and covert contraceptive use, and used standard assessments.

Results

Across sites, 6.4% (Côte d'Ivoire) to 7.8% (Kenya) of women in need of contraception experienced RC; approximately one-third to one-half of women experiencing RC reported no other violence forms (31.7% in Burkina Faso to 45.8% in Côte d'Ivoire), whereas physical/sexual IPV largely occurred with emotional IPV. In multivariable models, RC was consistently associated with covert use (Burkina Faso: aOR 2.84 (95% CI 1.21 to 6.64); Côte d'Ivoire: aOR 4.45 (95% CI 1.76 to 11.25); Kenya: aOR 5.77 (95% CI 3.51 to 9.46)). Some IPV in some settings was also associated with covert use (emotional IPV, Burkina Faso: aOR 2.99 (95% CI 1.56 to 5.74); physical/sexual, Kenya: aOR 2.35 (95% CI 1.33 to 4.17)).

Conclusions

Across settings, covert use is a critical strategy for women experiencing RC. Country policies must recognise RC as a unique form of violence with profound implications for women’s reproductive health.
Rabies in Southeast Asia: a systematic review of its incidence, risk factors and mortality
Authors: Jane Ling Miaw Yn , Halim Ahmad Farid Nazmi Abdul , Ahmad Dzulfitree , Ramly Nurfatehar , Hassan Mohd Rohaizat , Syed Abdul Rahim Syed Sharizman , Saffree Jeffree Mohammad , Omar Azizan , Hidrus Aizuddin
Published: May 2023

Objective

Rabies is a neglected zoonotic disease that can infect all mammals, including humans. We aimed to summarise the current knowledge of the incidence, risk factors and mortality of rabies in Southeast Asia.

Design

Systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020.

Data sources

Scopus, Web of Science and PubMed were searched from 1 January 2012 to 21 February 2023.

Eligibility criteria

Original English language articles published between 2012 and 2023 were included.

Data extraction and synthesis

Nine independent reviewers extracted data and assessed the risk of bias. The quality appraisal of included articles was carried out using the Mixed Methods Appraisal Tool.

Results

A total of eight articles were included in this analysis. In Vietnam, the incidence of rabies ranged from 1.7 to 117.2 per 100 000 population. The cumulative incidence in Sarawak was estimated at 1.7 per 100 000 population. In Indonesia, 104 human rabies cases were reported from 2008 to 2010, while in Thailand, a total of 46 rabies cases were reported in Thailand from 2010 to 2015. In the Philippines, the incidence of rabies ranged from 0.1 to 0.3 per 100 000 population. An increased risk of rabies virus infection was associated with a high population density, illiteracy, seasonal patterns and dog butchers. The case fatality rate was 100%.

Conclusion

This study included research from Southeast Asia, which may not represent rabies infection in other regions or continents. In addition, the role of publication bias should be acknowledged as grey literature was not included. The occurrence of rabies in Southeast Asia is due to the high number of unvaccinated stray and pet dogs, working hazards (dog butchers in Vietnam), the unavailability of the rabies vaccine in rural regions and misinformation about the significance of seeking treatment after dog bites.

PROSPERO registration number

CRD42022311654.
Cohort profile: Bangladesh Cook Stove Pregnancy Cohort Study (CSPCS)
Authors: Jabin Nusrat , Rahman Md Mostafijur , Salam Muhammad T , Sharna Tasnia Ishaque , Franklin Meredith , Bailey Maximilian J , Alderete Tanya L. , Ahmed Anisuddin , Quaiyum MA , Islam Talat
Published: May 2023

Purpose

The Cook Stove Pregnancy Cohort Study (CSPCS) was designed to assess the effects of biomass fuel use on household air pollution (HAP) as well as the effects of HAP (fine particulate matter, PM2.5) on birth outcomes and acute lower respiratory infection (ALRI) among infants in Bangladesh.

Participants

We recruited 903 women within 18 weeks of pregnancy from rural and semiurban areas of Bangladesh between November 2016 and March 2017. All women and their infants (N=831 pairs) were followed until 12 months after delivery and a subset have undergone respiratory and gut microbiota analysis.

Methods

Questionnaires were administered to collect detailed sociodemographic, medical, nutritional and behavioural information on the mother–child dyads. Anthropometric measurements and biological samples were also collected, as well as household PM2.5concentrations.

Findings to date

Published work in this cohort showed detrimental effects of biomass fuel and health inequity on birth outcomes. Current analysis indicates high levels of household PM2.5being associated with cooking fuel type and infant ALRI. Lastly, we identified distinct gut and respiratory microbial communities at 6 months of age.

Future plans

This study provides an economical yet effective framework to conduct pregnancy cohort studies determining the health effects of adverse environmental exposures in low-resource countries. Future analyses in this cohort include assessing the effect of indoor PM2.5levels on (1) physical growth, (2) neurodevelopment, (3) age of first incidence and frequency of ALRI in infants and (4) the development of the respiratory and gut microbiome. Additional support has allowed us to investigate the effect of in utero exposure to metals on infant neurodevelopment in the first year of life.
Feasibility and efficacy of ultrasound in the diagnosis of discoid lateral meniscus and its classification in children: protocol for a prospective, multicentre, diagnostic test study
Authors: Yang ShunJie , Zhang MingZhi , Wang LingCheng , You Mingke , Li Jian , Chen Gang
Published: May 2023

Introduction

Although ultrasound can reportedly diagnose discoid lateral meniscus (DLM) in children, its widespread application is challenging because the diagnostic criteria are based on qualitative descriptions of DLM morphology rather than quantitative parameters. Additionally, no studies have applied ultrasound in classifying DLM. Therefore, this study aims to establish the quantitative ultrasound parameters that reflect DLM morphology, evaluate the feasibility and validity of these parameters for identifying DLM and their classification, and develop the quantitative ultrasound diagnostic criteria for DLM and their classification in children.

Methods and analysis

Patients will be recruited from the outpatient clinics of the orthopaedics department at West China Hospital, Sichuan University, the Fourth Medical Center of the Chinese People’s Liberation Army General Hospital, Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine, Yibin Hospital affiliated with West China Hospital Sichuan University, Suining Central Hospital and the Third Hospital of Mianyang from August 2022 to July 2024. Eligible patients are those aged ≤14 years, with knee symptoms such as pain, locking and limited extension, and who planned to undergo arthroscopic surgery. Exclusion criteria are patients with contraindications to ultrasound examination, such as severe skin damage or fracture around the knee. The sample size is estimated to be 576 cases with a power of 0.9 for hypothesis testing, a two-sided α of 0.05, and an expected sensitivity and specificity of 95%. Three days before surgery, ultrasound will be used to observe the morphology of the lateral meniscus and measure its width, angle α formed by the chord of upper and lower arc-shaped articular surface at the free edge, and the movement distance of the peripheral rim. Participants will be categorised according to the arthroscopy results for the DLM and its classification. The diagnostic performance of each parameter will be assessed and compared in terms of the area under the curve, sensitivity, specificity, and positive and negative predictive values.

Ethics and dissemination

This study was approved by the Ethics Committee of West China Hospital, Sichuan University (approval no. 2022-923), and this approval covers all study hospitals. Written informed consent is required from all participants before enrolment in the study. The study’s findings will be disseminated through peer-reviewed publications and conference presentations.

Trial registration number

Chinese Clinical Trial Registry (ChiCTR2200062000).
Multimodal individualised intervention to prevent functional decline after stroke: protocol of a randomised controlled trial on long-term follow-up after stroke (LAST-long)
Authors: Askim Torunn , Hokstad Anne , Bergh Elin , Døhl Øystein , Ellekjær Hanne , Ihle-Hansen Haakon , Indredavik Bent , Leer Anne Silja Mäkitalo , Lydersen Stian , Saltvedt Ingvild , Seljeseth Yngve , Thommessen Bente
Published: May 2023

Introduction

Multimodal interventions have emerged as new approaches to provide more targeted intervention to reduce functional decline after stroke. Still, the evidence is contradictory. The main objective of the Life After Stroke (LAST)-long trial is to investigate if monthly meetings with a stroke coordinator who offers a multimodal approach to long-term follow-up can prevent functional decline after stroke.

Methods and analysis

LAST-long is a pragmatic single-blinded, parallel-group randomised controlled trial recruiting participants living in six different municipalities, admitted to four hospitals in Norway. The patients are screened for inclusion and recruited into the trial 3 months after stroke. A total of 300 patients fulfilling the inclusion criteria will be randomised to an intervention group receiving monthly follow-up by a community-based stroke coordinator who identifies the participants’ individual risk profile and sets up an action plan based on individual goals, or to a control group receiving standard care. All participants undergo blinded assessments at 6-month, 12-month and 18-month follow-up. Modified Rankin Scale at 18 months is primary outcome. Secondary outcomes are results of blood tests, blood pressure, adherence to secondary prophylaxis, measures of activities of daily living, cognitive function, physical function, physical activity, patient reported outcome measures, caregiver’s burden, the use and costs of health services, safety measures and measures of adherence to the intervention. Mixed models will be used to evaluate differences between the intervention and control group for all endpoints across the four time points, with treatment group, time as categorical covariates and their interaction as fixed effects, and patient as random effect.

Ethics and dissemination

This trial was approved by the Regional Committee of Medical and Health Research Ethics, REC no. 2018/1809. The main results will be published in international peer-reviewed open access scientific journals and to policy-makers and end users in relevant channels.

Trial registration number

ClincalTrials.gov Identifier:NCT03859063, registered on 1 March 2019.
Evaluation of the usability, content, readability and cultural appropriateness of online alcohol and other drugs resources for Aboriginal and Torres Strait Islander Peoples in New South Wales, Australia
Authors: Amanda Rebecca , Rana Kritika , Saunders Paul , Tracy Marguerite , Bridges Nicole , Poudel Prakash , Arora Amit
Published: May 2023

Objectives

This study aimed to analyse the usability, content, readability and cultural appropriateness of alcohol and other drugs (AODs) resources for Aboriginal and Torres Strait Islander Peoples in New South Wales (NSW), Australia.

Outcome measures

The content of 30 AOD resources for Aboriginal and Torres Strait Islander Peoples was analysed according to the following criteria: general characteristics; elements of graphical design and written communication; thoroughness and content; readability (Flesch-Kincaid grade level (FKGL), Gunning Fog index (Fog), Simplified Measure of Gobbledygook and Flesch Reading Ease); and cultural appropriateness.

Results

Most resources displayed good usability, depicted by the use of headings and subheadings (n=27), superior writing style (n=19), relevant visuals (n=19) and use of colour support (n=30). However, some resources used at least one professional jargon (n=13), and many did not provide any peer-reviewed references (n=22). During content analysis, 12 resources were categorised into the alcohol group and 18 resources in the other drugs group. Impact of alcohol during pregnancy and breast feeding (n=12) was the most common included topics in the resources related to alcohol, while the physical impact of drugs (n=15) was the most discussed topics among the other drugs group. Based on the FKGL readability score, 83% of resources met the recommended reading grade level of 6–8 by NSW Health. Many resources (n=21) met at least half of the cultural appropriateness elements of interest. However, less than one-third were developed in collaboration with the local community (n=9), used local terms (n=5), targeted the local community (n=3), included an Aboriginal voice (n=2) and addressed the underlying cause (n=1).

Conclusions

Many AOD resources are developed specifically for Aboriginal and Torres Strait Islander Peoples, but their usability, content and readability differed, and they were not culturally appropriate for all communities. Development of a standardised protocol for resource development is suggested.
A protocol for a single-arm interventional study assessing the effects of a home-based joystick-operated ride-on-toy navigation training programme to improve affected upper extremity function and spontaneous use in children with unilateral cerebral palsy (UCP)
Authors: Shahane Vaishnavi , Kumavor Patrick , Morgan Kristin , Friel Kathleen M , Srinivasan Sudha Madhav
Published: May 2023

Introduction

Children with unilateral cerebral palsy (UCP) face significant limitations in upper extremity (UE) function and require effective interventions that promote intensive goal-directed practice while maximising motivation and adherence with therapy. This study builds on our past work and will assess the effects of a 6-week researcher-caregiver codelivered, home-based ride-on-toy navigation training (RNT) programme in young children with UCP. We hypothesise that the RNT programme will be acceptable, feasible to implement, and lead to greater improvements in unimanual and bimanual function when combined with conventional therapy, compared with conventional therapy provided alone.

Methods and analysis

15 children with UCP between 3 and 8 years will be recruited. During the 6-week control phase, participants will receive treatement-as-usual alone. During the subsequent 6-week intervention phase, in addition to conventional therapy, RNT will be provided 4–5 times/week (2 times by researchers, 2–3 times by caregivers), 30–45 min/session. We will assess UE function using standardised tests (Quality of Upper Extremity Skills Test and Shriner’s Hospital Upper Extremity Evaluation), reaching kinematics, wrist-worn accelerometry, caregiver-rated ABILHAND-Kids questionnaire, and training-specific measures of movement control during RNT. Programme feasibility and acceptance will be assessed using device use metrics, child and caregiver exit questionnaires, training-specific measures of child engagement, and the Physical Activity Enjoyment Scale. All assessments will be conducted at pretest, following the control phase (midpoint), and after completion of the intervention phase (post-test).

Ethics and dissemination

The study is approved by the Institutional Review Board of the University of Connecticut (# H22-0059). Results from this study will be disseminated through peer-reviewed manuscripts in scientific journals in the field, through national and international conferences, and through presentations to parent advocacy groups and other support organisations associated with CP.

Trial registration number

NCT05559320.
“It’s probably an STI because you’re gay”: a qualitative study of diagnostic error experiences in sexual and gender minority individuals
Authors: Wiegand Aaron A , Sheikh Taharat , Zannath Fateha , Trudeau Noah M , Dukhanin Vadim , McDonald Kathryn M
Published: May 2023

Background

There is a critical need to identify specific causes of and tailored solutions to diagnostic error in sexual and gender minority (SGM) populations.

Purpose

To identify challenges to diagnosis in SGM adults, understand the impacts of patient-reported diagnostic errors on patients’ lives and elicit solutions.

Methods

Qualitative study using in-depth semistructured interviews. Participants were recruited using convenience and snowball sampling. Recruitment efforts targeted 22 SGM-focused organisations, academic centres and clinics across the USA. Participants were encouraged to share study details with personal contacts. Interviews were analysed using codebook thematic analysis.

Results

Interviewees (n=20) ranged from 20 to 60 years of age with diverse mental and physical health symptoms. All participants identified as sexual minorities, gender minorities or both. Thematic analysis revealed challenges to diagnosis. Provider-level challenges included pathologisation of SGM identity; dismissal of symptoms due to anti-SGM bias; communication failures due to providers being distracted by SGM identity and enforcement of cis-heteronormative assumptions. Patient-level challenges included internalised shame and stigma. Intersectional challenges included biases around factors like race and age. Patient-reported diagnostic error led to worsening relationships with providers, worsened mental and physical health and increased self-advocacy and community-activism. Solutions to reduce diagnostic disparities included SGM-specific medical education and provider training, using inclusive language, asking questions, avoiding assumptions, encouraging diagnostic coproduction, upholding high care standards and ethics, involving SGM individuals in healthcare improvement and increasing research on SGM health.

Conclusions

Anti-SGM bias, queerphobia, lack of provider training and heteronormative attitudes hinder diagnostic decision-making and communication. As a result, SGM patients report significant harms. Solutions to mitigate diagnostic disparities require an intersectional approach that considers patients’ gender identity, sexual orientation, race, age, economic status and system-level changes.
Factors associated with lower limb tendinopathy in a large cohort of runners: a survey with a particular focus on nutrition
Authors: Baart A Mireille , Terink Rieneke , Naeff Mannes , Naeff Eelke , Mensink Marco , Alsma Jelmer , Witteman Ben J M , Zwerver Johannes
Published: May 2023

Objectives

Lower limb tendinopathy (LLT) is highly prevalent in runners. Treatment can be challenging, and knowledge of risk factors may be valuable to develop preventive or treatment interventions for LLT. The aims of this study were (1) to assess the prevalence of three common LLTs (Achilles tendinopathy (AT), patellar tendinopathy and plantar fasciopathy) in a large cohort of Dutch and Belgian runners and (2) to investigate its association with potential risk factors, with a particular focus on nutritional factors in the habitual diet.

Methods

A total of 1993 runners were included in the study. They completed two online questionnaires: a general questionnaire on running habits and injuries and a Food Frequency Questionnaire. Runners with and without LLT were compared regarding personal characteristics, running characteristics and nutritional factors.

Results

The point prevalence for the three LLTs was 6%; 33% of the runners reported LLT in the past and 35% had either a current or past LLT. AT was the most prevalent type of LLT, and prevalence rates for all types of LLT were higher in men than women. Positive associations with LLT were observed for age and running years (men and women), running level and running distance (men). No associations between LLT and nutritional factors were observed.

Conclusion

One-third of this population of runners had ever experienced an LLT. These tendinopathies were associated with gender, age and running load, but not with nutritional factors.
Likelihood reclassification by an acoustic-based score in suspected coronary artery disease
Authors: Rasmussen Laust Dupont , Winther Simon , Karim Salma Raghad , Westra Jelmer , Kirk Johansen Jane , Søndergaard Hanne Maare , Hammid Osama , Sevestre Emelyne , Onuma Yoshinobu , Nyegaard Mette , Ejlersen June Anita , Høj Christiansen Evald , Eftekhari Ashkan , Holm Niels Ramsing , Schmidt Samuel Emil , Bøttcher Morten
Published: May 2023

Objective

Validation studies of the 2019 European Society of Cardiology pretest probability model (ESC-PTP) for coronary artery disease (CAD) report that 35%–40% of patients have low pretest probability (ESC-PTP 5% to <15%). Acoustic detection of coronary stenoses could potentially improve clinical likelihood stratification. Aims were to (1) investigate the diagnostic performance of an acoustic-based CAD score and (2) study the reclassification potential of a dual likelihood strategy by the ESC-PTP and a CAD score.

Methods

Consecutive patients (n=1683) with stable angina symptoms referred for coronary CT angiography (CTA) underwent heart sound analyses by an acoustic CAD-score device. All patients with ≥50% luminal stenosis in any coronary segment at coronary CTA were referred to investigation with invasive coronary angiography (ICA) with fractional flow reserve (FFR).

A predefined CAD-score cut-off ≤20 was used to rule out obstructive CAD.

Results

In total, 439 patients (26%) had ≥50% luminal stenosis on coronary CTA. The subsequent ICA with FFR showed obstructive CAD in 199 patients (11.8%). Using the ≤20 CAD-score cut-off for obstructive CAD rule-out, sensitivity was 85.4% (95% CI 79.7 to 90.0), specificity 40.4% (95% CI 37.9 to 42.9), positive predictive value 16.1% (95% CI 13.9 to 18.5) and negative predictive value 95.4% (95% CI 93.4 to 96.9) in all patients. Applying the cut-off in ESC-PTP 5% to <15% patients, 316 patients (48%) were down-classified to very-low likelihood. The obstructive CAD prevalence was 3.5% in this group.

Conclusion

In a large contemporary cohort of patients with low CAD likelihood, the additional use of an acoustic rule-out device showed a clear potential to downgrade likelihood and could supplement current strategies for likelihood assessment to avoid unnecessary testing.

Trial registration number

NCT03481712.
Aortic sodium [18F]fluoride uptake following endovascular aneurysm repair
Authors: Debono Samuel , Nash Jennifer , Fletcher Alexander J , Syed Maaz , van Beek Edwin J R , Williams Michelle Claire , Falah Orwa , Tambyraja Andrew , Dweck Marc R , Newby David E , Forsythe Rachael O
Published: May 2023

Objective

In patients with abdominal aortic aneurysms, sodium [18F]fluoride positron emission tomography identifies aortic microcalcification and disease activity. Increased uptake is associated with aneurysm expansion and adverse clinical events. The effect of endovascular aneurysm repair (EVAR) on aortic disease activity and sodium [18F]fluoride uptake is unknown. This study aimed to compare aortic sodium [18F]fluoride uptake before and after treatment with EVAR.

Methods

In a preliminary proof-of-concept cohort study, preoperative and post-operative sodium [18F]fluoride positron emission tomography-computed tomography angiography was performed in patients with an infrarenal abdominal aortic aneurysm undergoing EVAR according to current guideline-directed size treatment thresholds. Regional aortic sodium [18F]fluoride uptake was assessed using aortic microcalcification activity (AMA): a summary measure of mean aortic sodium [18F]fluoride uptake.

Results

Ten participants were recruited (76±6 years) with a mean aortic diameter of 57±2 mm at time of EVAR. Mean time from EVAR to repeat scan was 62±21 months. Prior to EVAR, there was higher abdominal aortic AMA when compared with the thoracic aorta (AMA 1.88 vs 1.2; p<0.001). Following EVAR, sodium [18F]fluoride uptake was markedly reduced in the suprarenal (ΔAMA 0.62, p=0.03), neck (ΔAMA 0.72, p=0.02) and body of the aneurysm (ΔAMA 0.69, p=0.02) while it remained unchanged in the thoracic aorta (ΔAMA 0.11, p=0.41).

Conclusions

EVAR is associated with a reduction in AMA within the stented aortic segment. This suggests that EVAR can modify aortic disease activity and aortic sodium [18F]fluoride uptake is a promising non-invasive surrogate measure of aneurysm disease activity.
AR-A014418 regulates intronic polyadenylation and transcription of PD-L1 through inhibiting CDK12 and CDK13 in tumor cells
Authors: Zhang Ganggang , Lan Bin , Zhang Xin , Lin Mengyao , Liu Yi , Chen Junsong , Guo Fang
Published: May 2023

Background

Immune checkpoint molecules, especially programmed death 1 (PD-1) and its ligand, programmed death ligand 1 (PD-L1), protect tumor cells from T cell-mediated killing. Immune checkpoint inhibitors, designed to restore the antitumor immunosurveillance, have exhibited significant clinical benefits for patients with certain cancer types. Nevertheless, the relatively low response rate and acquisition of resistance greatly limit their clinical applications. A deeper understanding of the regulatory mechanisms of PD-L1 protein expression and activity will help to develop more effective therapeutic strategies.

Methods

The effects of AR-A014418 and THZ531 on PD-L1 expression were detected by western blot, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and flow cytometry. In vitro kinase assays with recombinant proteins were performed to confirm that AR-A014418 functioned as a CDK12 and CDK13 dual inhibitor. The roles of CDK12 and CDK13 in intronic polyadenylation (IPA) and transcription of PD-L1 were determined via RNA interference or protein overexpression. T-cell cytotoxicity assays were used to validate the activation of antitumor immunity by AR-A014418 and THZ531.

Results

AR-A014418 inhibits CDK12 to enhance the IPA, and inhibits CDK13 to repress the transcription of PD-L1. IPA generates a secreted PD-L1 isoform (PD-L1-v4). The extent of IPA was not enough to reduce full-length PD-L1 expression obviously. Only the superposition of enhancing IPA and repressing transcription (dual inhibition of CDK12 and CDK13) dramatically suppresses full-length PD-L1 induction by interferon-γ. AR-A014418 and THZ531 could potentiate T-cell cytotoxicity against tumor cells.

Conclusions

Our work identifies a new regulatory pathway for PD-L1 expression and discovers CDK12 and CDK13 as promising drug targets for immune modulation and combined therapeutic strategies.
Australian Defence Force Global Health Engagement through malaria and other vectorborne disease programmes in the Pacific and Southeast Asia
Authors: Reade Michael Charles , Auliff A , McPherson B , Edstein M
Published: May 2023

Global Health Engagement is one method employed by the Australian Defence Force (ADF) in pursuit of its objectives to shape Australia’s strategic environment and to deter actions against Australia’s interests. Two recent examples of such engagements are malaria mitigation programmes led by the ADF Malaria and Infectious Disease Institute in partnership with the Vietnam People’s Army and the Papua New Guinea Defence Force. Both programmes were designed with extensive collaboration with host nation stakeholders, empowered local institutions and governance systems, built the capacity of the host nation with the aim of achieving independence from Australian support and met the strategic policy requirements of all nations involved. Process and outcome measures were built into both programmes, providing partner nations with the necessary assurance that funding was being used effectively. The long-term nature of each programme engendered personal trust between individuals and cultural understanding between military units. Recognising the value of formal education in the design and conduct of such programmes, ADF officers participate as students and instructors in the US Uniformed University of the Health Sciences course in Global Health and Global Health Engagement. Critically, this educational opportunity is afforded to future leaders in all professions related to health, including clinicians, military health planners and commanders. While an essential prerequisite to Global Health Engagement Programmes is their technical viability and validity, the most important key to success in the military context is a widespread understanding of how they achieve desired strategic effects for all involved.
Bilateral swelling of the salivary glands and sicca symptoms: an unusual differential diagnosis—Kimura’s disease, a rare allergic condition with a high IgE serum level—a case report and review of the literature
Authors: Braun Jüergen , Mairinger Thomas , Kaschke Oliver , Behrendt Kai , Ramsbacher Josef , Karberg Kirsten
Published: May 2023

A 68-year-old woman presented with bilateral swelling of the salivary glands, sicca symptoms of eyes and mouth, itching, fatigue and weight gain of about 5 kg in the last 2–3 years. As part of a careful diagnostic work up including lab tests for antinuclear antibodies (ANA), antibodies to extractable nuclear antigens (ENA), anti-neutrophilic cytoplasmatic antiobodies (ANCA), immunoglobulin (Ig)G4, a whole body computed tomography (CT) and a parotid biopsy several rheumatic diseases such as Sjoegren’s syndrome, IgG4-related disease and sarcoidosis were ruled out and, considering a very high titre of IgE, Kimura’s disease was diagnosed. The case and a short review of the literature are presented.
Effects of biodiesel ratio and nozzle diameter on combustion and emissions of a biodiesel–DME-fueled engine
Authors: Hou Junxing , Xi Shuanghui , Wang Zhenghe , Li Shuhao
Published: May 2023

This paper compares the combustion behavior and emission of a turbocharged compression ignition engine fueled with biodiesel BD100, dimethyl ether DME100, low-proportioned biodiesel blends BD30, and medium-proportioned biodiesel blends BD50. The impacts of biodiesel ratio and nozzle diameter on combustion and emissions characteristics were determined. The findings show that BD100 with a nozzle 6 × 0.24 mm has the highest value of maximum pressure, maximum pressure rise rate, maximum heat release rate, and NOx emissions. DME100 with a nozzle of 6 × 0.40 mm has the lowest values. CO emissions and HC emissions of BD100 with a nozzle 6 × 0.24 mm and DME100 with nozzles 6 × 0.40 mm and 6 × 0.35 mm gradually decrease. Among biodiesel blends, BD30 and BD50 with two types of nozzles, BD30 with a nozzle 6 × 0.40 mm has the lowest value of maximum pressure, maximum pressure rise rate, NOx emissions, and soot emissions. Compared with BD50, BD30 with nozzles 6 × 0.35 mm and 6 × 0.40 mm has lower CO emissions, HC emissions, and smoke emissions.
Predicting compressive strength of geopolymer concrete using machine learning
Authors: Gupta Priyanka , Gupta Nakul , Saxena Kuldeep K.
Published: May 2023

The anaconda software required python code in order to run the utilized individual K-nearest neighbor (KNN), random forest regression (RFR), and linear regression (LR) models. The results show that RFR machine learning (ML) technique out of the other utilized models shows the best performance for a used dataset. The findings of this article indicate that the dataset utilized proposed model provides an acceptable algorithm for FACC design and optimization. In the current study of preparation of geopolymer concrete (GPC), relevant variables such as curing, fly ash, calcined clay, added water, super plasticizer, coarse aggregate, quarry stone dust, caustic soda, and water glass were used as input parameters. The ranges, mode, median, standard deviation, and other identifying details were checked using descriptive statistical analysis for the input parameters. The strength due to the compression of FACC GPC was predicted using RFR, LR, and KNN ML techniques, all based on Python coding. The ensemble ML technique, RFR outperformed the individual ML technique, KNN, in terms of prediction. The RFR indicates that the maximum amount of [Formula: see text] is 0.92, and LR provides 0.58, although the KNN was less accurate, with a coefficient of determination of 0.56. The RFR technique’s lower values of errors, mean absolute error (MAE), MSE, and root mean square error (RMSE) yield 1.99, 7.17, and 2.67[Formula: see text]MPa, respectively. The excellent accuracy of the RFR methodology is confirmed by a statistical analysis of errors. Curing temperature, curing hours, molarity of NaOH, and FACC ratio significantly affect the compressive strength (CS) of FACC GPC. The findings indicate that the proposed model provides an acceptable algorithm for FACC design and optimization using RFR among the three combinations of ML methods for a given dataset.