bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain iron acquisition depends on age and sex in iron‐deficient mice
Authors: Palsa Kondaiah , Neely Elizabeth B. , Baringer Stephanie L. , Helmuth Timothy B. , Simpson Ian A. , Connor James R.
Published: November 2023

Adequate and timely delivery of iron is essential for brain development. The uptake of transferrin‐bound (Tf) iron into the brain peaks at the time of myelination, whereas the recently discovered H‐ferritin (FTH1) transport of iron into the brain continues to increase beyond the peak in myelination. Here, we interrogate the impact of dietary iron deficiency (ID) on the uptake of FTH1‐ and Tf‐bound iron. In the present study, we used C57BL/6J male and female mice at a developing (post‐natal day (PND) 15) and adult age (PND 85). In developing mice, ID results in increased iron delivery from both FTH1 and Tf for both males and females. The amount of iron uptake from FTH1 was higher than the Tf and this difference between the iron delivery was much greater in females. In contrast, in the adult model, ID was associated with increased brain iron uptake by both FTH1 and Tf but only in the males. There was no increased uptake from either protein in the females. Moreover, transferrin receptor expression on the microvasculature as well as whole brain iron, and H and L ferritin levels revealed the male brains became iron deficient but not the female brains. Last, under normal dietary conditions, 55Fe uptake was higher in the developing group from both delivery proteins than in the adult group. These results indicate that there are differences in iron acquisition between the developing and adult brain for FTH1 and Tf during nutritional ID and demonstrate a level of regulation of brain iron uptake that is age and sex‐dependent.
Does the OTA Open Fracture Classification Align With the Gustilo-Anderson Classification? A Study of 2215 Open Fractures
Authors: Kovvur Murali , Turner Kristin E. , Lawrence Joshua E. , O’Toole Robert V. , O’Hara Nathan N. , Slobogean Gerard P.
Published: November 2023

OBJECTIVES:

To characterize the Orthopaedic Trauma Association Open Fracture Classification (OTA-OFC) and Gustilo-Anderson classification of open extremity fractures and determine if there is meaningful alignment between these grading systems.

METHODS:

Design
: Retrospective case series.

Setting
: Level I academic trauma center.

Patient Selection Criteria
: Adult patients with at least one operatively treated open extremity fracture and surgeon-assigned OTA-OFC and Gustilo-Anderson classification.

Outcome Measures and Comparisons
: Frequency, distribution, and association measures of OTA-OFC category scores and Gustilo-Anderson classification types.

RESULTS:

2027 patients (mean age, 43.1 ± 17.5 years) with 2215 fractures were included. Gustilo-Anderson Type I or II fractures (n = 961; 43%) most frequently had the least severe scores for all OTA-OFC categories. Type IIIA fractures (n = 978; 44%) were most often assigned intermediate scores for OTA-OFC Bone Loss (n = 564; 58%). Type IIIB fractures (n = 204, 9%) were most often assigned intermediate OTA-OFC Skin scores (n = 120; 59%). Type IIIC fractures (n = 72; 3%) were most often assigned the most severe OTA-OFC Arterial score (n = 60; 83%). In the multivariable model, OTA-OFC Contamination scores showed little association (β = 0.05; 95% confidence interval [CI], 0.01–0.09) with Gustilo-Anderson classification severity. Conversely, higher OTA-OFC Arterial (β = 0.50; 95% CI, 0.44–0.56) and Skin (β = 0.46; 95% CI, 0.40–0.51) scores were strongly associated with more severe Gustilo-Anderson classifications.

CONCLUSIONS:

OTA-OFC Contamination scores were weakly associated with Gustilo-Anderson classification severity for open fractures. The study findings suggest the current Gustilo-Anderson classification does not adequately account for injury contamination, a known predictor of infection.
Open versus Closed Geriatric Ankle Fractures
Authors: Bowers Mathew , Ta Canhnghi , Vasudevan Rajiv Siddhartha , Trimm Conner Dean , Kent William T
Published: November 2023

OBJECTIVES

To determine if open (O) or closed (C) geriatric ankle fractures had different patient characteristics or outcomes.

METHODS

Design: Retrospective cohort study

Setting: Urban level 1 trauma center

Patient Selection Criteria: Patients, age 60 years and older, who underwent operative fixation of a rotational ankle fracture (OTA/AO 44A-C) between January 2012 and September 2021.

Outcome Measures and Comparisons: Morbidity, defined as 90-day reoperation, 90-day readmission, or loss of mobility, as well as 1-year mortality compared between patients with closed and open fractures.

RESULTS

The open cohort was older (75 years vs 68 years; p=.003) but had similar Charlson Comorbidity Indices (CCI) (4.6 O vs 4.0 C; p=.323) and pre-injury rates of independent ambulation (70.4% O vs 80.9% C; p=.363). There were higher rates of 1-year mortality (11% vs 0%; p<0.001), deep infection (14.8% vs 3.9%; p=.019), and loss of mobility (64.7% vs 23.0%; p<0.001) in the open cohort. Multivariate regression identified open fracture as an independent predictor of 90-day reoperation (OR: 20.6; p=.022) and loss of mobility (OR: 5.1; p=.011).

CONCLUSION

Despite having comorbidities and pre-injury function similar to the closed geriatric ankle fracture cohort, open ankle fracture was independently predictive of greater loss of mobility. Nearly two-thirds of geriatric patients with open ankle fractures experienced a decline in functional independence, compared with 1 in 4 of those with closed fractures. Open fracture was associated with higher rates of deep infection, reoperation, and 1-year mortality.

LEVEL OF EVIDENCE:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Improved Patient-reported Outcomes in Patients Aged 16 and Younger at Two Years After Anterior Cruciate Ligament Reconstruction Despite Relatively High Rates of Reinjury and Repeat Surgery
Authors: Doxey Stephen A. , Kleinsmith Rebekah M. , Huyke-Hernández Fernando A. , Schweitzer Adam , Only Arthur J. , Tompkins Marc , Kweon Christopher Y. , Cunningham Brian P.
Published: November 2023

Background:

Anterior cruciate ligament reconstruction (ACLR) in adolescent patients, particularly those aged 16 and under, are increasingly common procedure that lacks robust clinical and patient-reported outcome (PRO) data. The purpose of this study was to report 2-year PROs of patients receiving ACLR aged 16 or younger using the single assessment numerical evaluation (SANE) and knee injury and osteoarthritis outcome score (KOOS). Secondary aims included characterizing treatment characteristics, return to sport (RTS), and clinical outcomes.

Methods:

The institutional PRO database was queried for patients receiving ACLR from 2009 to 2020. Patients aged older than 16, revision procedures, concomitant ligament repairs/reconstructions, and patients without full outcome data at 2 years were excluded. Outcomes over 2 years after ACLR included SANE, KOOS, reinjuries, reoperations, and time to RTS.

Results:

A total of 98 patients were included with an average age of 15.0 years. Most patients were females (77.6%). Bone-tendon-bone autograft (69.4%) was the most used. Average RTS was 8.7 months (range: 4.8 to 24.0 mo), with 90% of patients eventually returning to sport. A total of 23 patients (23.5%) experienced a reinjury and 24.5% (n = 24) underwent reoperation. Timing to RTS was not associated with reinjury, but patients who returned between 9.5 and 13.7 months did not sustain reinjuries. Mean KOOS and SANE scores at 2 years were 87.1 and 89.1, respectively, with an average improvement of +18.4 and +22.9, respectively. Change in KOOS was negatively impacted by reinjury to the anterior cruciate ligament graft and reoperation (anterior cruciate ligament failure: +10.0 vs 19.3, P = 0.081, respectively; reoperation: +13.2 vs +20.1, P = 0.051, respectively), though these did not reach statistical significance.

Conclusion:

Patients experienced improved SANE and KOOS scores after ACLR. Rates of reinjury and reoperation were relatively high and negatively impacted PRO scores but were not associated with the timing of RTS. Adolescent patients should be counseled regarding the risk of subsequent ipsilateral and contralateral knee injury after ACLR.

Level of Evidence:

Level IV—case series.
Postoperative Sclerotic Modic Changes after Transforaminal Lumbar Interbody Fusion
Authors: Xiao Yang , Zhu Ce , Xiu Peng , Wang Liang , Zhang Zhuang , Deng Zhipeng , Song Yueming , Yang Xi
Published: November 2023

Study Design.

A retrospective cohort study.

Objective.

This study aimed to assess postoperative sclerotic Modic changes (MCs) following transforaminal lumbar interbody fusion (TLIF) for lumbar degenerative disc disease (LDD), investigating their prevalence, risk factors and association with clinical outcomes.

Summary of Background Data.

Sclerotic MCs may occur in patients with LDD after lumbar interbody fusion. The incidence and characteristics of postoperative sclerotic MCs, as well as their clinical impact, are unknown.

Methods.

The study included 467 patients (510 levels) who underwent single or two-level TLIF surgery, divided into a postoperative sclerotic MC group (60 patients, 66 levels) and non-MC group (407 patients, 444 levels). The time of development and location of postoperative sclerotic MCs, fusion rate, cage subsidence, bilateral process decompression, and cross-link usage were recorded. Preoperative, postoperative, and follow-up VAS and ODI scores were collected. Multivaraible logistic regression was used to evaluate factors associated with the development of postoperative sclerotic MCs.

Results.

The prevalence of postoperative sclerotic MCs was 12.8%. The postoperative sclerotic MC group had higher BMI. The postoperative sclerotic MC group demonstrated a fusion rate of 47%, significantly lower than that of the non-MC group (71%) at 6 months post-operation. At final follow-up, the fusion rate in the postoperative sclerotic MC group was 62%, significantly lower than that of the non-MC group (86%). Post-operative VAS and ODI scores were significantly higher in the group with postoperative sclerotic MCs. BMI and osteoporosis were significantly associated with the development of postoperative sclerotic MCs.

Conclusion.

Postoperative sclerotic MCs generally appear within the first year after surgery, with a prevalence of 12.8%. The presence of postoperative sclerotic MCs can adversely impact post-operative outcomes. To prevent postoperative sclerotic MCs, we postulate extending the immobilization period with external bracing and improving the management of BMI and osteoporosis in the peri-operative time window.
Impact of Body Mass Index on Cardiac Arrest Outcomes: A Systematic Review and Meta-Analysis
Authors: Xie Wangmin , Zhou Jie , Zhou Huifei
Published: November 2023

The influence of an individual’s body mass index (BMI) on cardiac arrest outcomes remains uncertain. The aim of this study is to evaluate the impact of BMI categories (underweight, normal BMI, overweight, and obese) on mortality and neurological outcomes in patients experiencing cardiac arrest. We comprehensively searched standard electronic databases (PubMed, EMBASE, and Scopus) for relevant observational studies published in peer-reviewed journals written in English. We calculated pooled effect estimates using random-effects models and reported them as odds ratios (ORs) with 95% confidence intervals (CIs). We included 20 studies in our meta-analysis. Individuals with normal BMIs and those who were underweight had similar risks of in-hospital mortality (OR, 1.20; 95% CI, 0.90–1.60), mortality within 6 months of discharge (OR, 0.92; 95% CI, 0.59–1.42), mortality after the 1-year follow-up (OR, 2.42; 95% CI, 0.96–6.08), and odds of favorable neurological outcomes at hospital discharge (OR, 0.86; 95% CI, 0.53–1.39) and at the 6-month follow-up (OR, 0.73; 95% CI, 0.47–1.13). The risks of in-hospital mortality and mortality within 6 months of discharge in overweight and obese individuals were similar to those in individuals with normal BMIs. However, overweight (OR, 0.57; 95% CI, 0.35–0.92) and obese individuals (OR, 0.67; 95% CI, 0.51–0.89) had lower risks of mortality after their 1-year follow-ups. For overweight and obese subjects, the reduced risk of mortality after the 1 year of follow-up was noted only for those with in-hospital cardiac arrest and not for those with out-of-hospital cardiac arrest. The odds of favorable neurological outcomes in both overweight and obese individuals were similar to those with normal BMIs. BMI does not significantly impact short-term mortality or neurological outcomes. Overweight and obese individuals appear to have a lower risk of long-term mortality, but this differed by the place of arrest and needs to be confirmed by others.
Dapagliflozin Suppresses Isoprenaline-Induced Cardiac Hypertrophy Through Inhibition of Mitochondrial Fission
Authors: Yang Zhuo-Jing , Guo Chun-Ling , Gong Yu-Xin , Li Long , Wang Li-li , Liu Hui-Min , Cao Ji-Min , Lu Zhao-Yang
Published: November 2023

Dapagliflozin (DAPA) is a novel oral hypoglycemic agent, and there is increasing evidence that DAPA has a protective effect against cardiovascular disease. The study aimed to investigate how DAPA inhibits cardiac hypertrophy and explore its potential mechanisms. By continuously infusing isoprenaline (ISO) for 2 weeks using a subcutaneous osmotic pump, a cardiac hypertrophic model was established in male C57BL/6 mice. On day 14 after surgery, echocardiography showed that left ventricle mass (LV mass), interventricular septum, left ventricle posterior wall diastole, and left ventricular posterior wall systole were significantly increased, and ejection fraction was decreased compared with control mice. Masson and Wheat Germ Agglutinin staining indicated enhanced myocardial fibrosis and cell morphology compared with control mice. Importantly, these effects were inhibited by DAPA treatment in ISO-induced mice. In H9c2 cells and neonatal rat cardiomyocytes, we found that mitochondrial fragmentation and mitochondrial oxidative stress were significantly augmented in the ISO-induced group. However, DAPA rescued the cardiac hypertrophy in ISO-induced H9c2 cells and neonatal rat cardiomyocytes. Mechanistically, we found that DAPA restored the PIM1 activity in ISO-induced H9c2 cells and subsequent increase in dynamin-associated protein 1 (Drp1) phosphorylation at S616 and decrease in Drp1 phosphorylation at S637 in ISO-induced cells. We found that DAPA mitigated ISO-induced cardiac hypertrophy by suppressing Drp1-mediated mitochondrial fission in a PIM1-dependent fashion.
Effect of Glucosamine on Intraocular Pressure and Risk of Developing Glaucoma
Authors: Lehrer Steven , Morello Timothy , Karrasch Charles , Rheinstein Peter H. , Danias John
Published: November 2023

Précis:

Glucosamine supplementation is common but can be associated with increased intraocular pressure (IOP) and could contribute to the pathogenesis of glaucoma. It may be prudent for ophthalmologists to elicit any history of glucosamine use from their patients and advise them accordingly. Further studies on the role of glucosamine in glaucoma are warranted.

Background:

The most frequently recommended slow-acting medication for osteoarthritis symptoms is glucosamine, although its effectiveness is questionable. Widely used glucosamine sulfate supplements may increase IOP.

Methods:

In the current study, we analyzed online databases such as UK Biobank, MedWatch, and FinnGen to evaluate the relationship between glucosamine and IOP and glaucoma. We included budesonide and fluticasone in the analysis for comparison since these drugs are associated with increased IOP.

Results:

In UK Biobank subjects, glucosamine use was associated with increased corneal compensated IOP (P=0.002, 2-tailed t test). This was also true in subjects without glaucoma (P=0.002, 2-tailed t test). However, no significant association between glucosamine and IOP was detected in subjects with a diagnosis of glaucoma. In MedWatch, 0.21% of subjects taking glucosamine reported glaucoma, 0.29% of subjects using budesonide reported glaucoma, and 0.22% of subjects using fluticasone reported glaucoma. In contrast, 0.08% of subjects using any other drug reported glaucoma. This variability is significant (P<0.001, 2-tailed Fisher exact test). Data from FinnGen on the risk of primary open angle glaucoma or glaucoma in subjects using glucosamine before the diagnosis of the disease revealed a significantly increased risk for both primary open angle glaucoma (hazard ratio: 2.35) and glaucoma (hazard ratio: 1.95).

Conclusion:

Glucosamine supplementation is common but can be associated with increased IOP and could contribute to the pathogenesis of glaucoma. It may be prudent for ophthalmologists to elicit any history of glucosamine use from their patients and advise them accordingly. Further studies on the role of glucosamine in glaucoma are warranted.
Association of Postural Blood Pressure Response With Disease Severity in Primary Open Angle Glaucoma
Authors: Ameen Ismail Ahmed , Sadek Sherin Hassan , Kamal Mahmoud Ahmed , Hatata Ragai Magdy
Published: November 2023

Précis:

Patients with primary open angle glaucoma (POAG) demonstrated exaggerated postural blood pressure dip in recumbency that was positively correlated with the severity of glaucomatous optic neuropathy (GON). Postural dip testing can be used clinically as a marker of systemic vascular dysregulation in GON risk assessment.

Objective:

To investigate whether patients with POAG demonstrated abnormal postural blood pressure response to recumbency and whether such abnormal postural response correlated with GON severity.

Patients and Methods:

This is a prospective observational study where 47 patients with POAG underwent intraocular pressure and systemic arterial blood pressure, systolic blood pressure (SBP) and diastolic blood pressure (DBP), measurement in seated and after 20-minute recumbency positions. Mean arterial blood pressure (MABP) was calculated for seated and recumbent positions. The percentage difference between seated and recumbent SBP, DBP, and MABP was calculated according to which participants were divided into 3 groups, that is, nondippers, normal dippers, and exaggerated dippers with percentage dips of <10%, ≥10%≤20%, >20%, respectively. Participants underwent optical coherence tomography of optic nerve head to measure retinal nerve fiber layer thickness (RNFLT) which was used as a structural biomarker of GON.

Results:

RNFLT was lower in exaggerated dippers than in nondippers and normal dippers. There was a negative correlation between postural dip and average RNFLT. Linear regression showed that postural dip was associated with lower RNFLT independent of age and intraocular pressure. The χ2 independence test demonstrated a strong relation among corresponding dip groups for SBP, DBP, and MABP. However, it showed no significant relation between hypertension and postural dip. Fisher exact test showed no relation between antihypertensive medication and postural dip.

Conclusions:

Patients with POAG demonstrated abnormal postural blood pressure response comprising exaggerated recumbent dip which was positively correlated with disease severity. Postural dip assessment may serve as a simple clinic-based test of systemic vascular dysregulation as part of GON risk evaluation.
Treatment Strategies and Outcomes of Right Ventricular Failure Post Left Ventricular Assist Device Implantation: An INTERMACS Analysis
Authors: Chamogeorgakis Themistokles , Toumpoulis Ioannis , Bonios Michael J. , Lanfear David , Williams Celeste , Koliopoulou Antigoni , Cowger Jennifer
Published: November 2023

Right heart failure (RHF) management after left ventricular assist device (LVAD) implantation includes inotropes, right ventricular mechanical support, and heart transplantation. The purpose of this study is to compare different RHF treatment strategies in patients with a magnetically levitated centrifugal LVAD. A total of 6,632 Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) patients from 2013 to 2020 were included. Of which, 769 (69.6%) patients (group 1) were supported with inotropes (≥14 days post-LVAD implantation), 233 (21.1%) patients (group 2) were supported with temporary right ventricular assist device (RVAD) that was implanted during LVAD implant, 77 (7.0%) patients (group 3) with durable centrifugal RVAD implanted during the LVAD implant, and 26 (2.4%) patients (group 4) were supported with RVAD (temporary or permanent), which was implanted at a later stage. Groups 1 and 4 had higher survival rates in comparison with group 2 (hazard ratio [HR] = 0.513, 95% confidence intervals [CIs] = 0.402–0.655,p< 0.001,versusgroup 1) and group 3 (HR = 0.461, 95% CIs = 0.320–0.666,p< 0.001,versusgroup 1). Patients in group 3 showed higher heart transplantation rates at 12 and 36 months as compared with group 1 (40.4% and 46.6%vs.21.9% and 37.4%, respectively), group 2 (40.4% and 46.6%vs.25.8% and 39.3%, respectively), and group 4 (40.4% and 46.6%vs.3.8% and 12.0%, respectively). Severe RHF post-LVAD is associated with poor survival. Patients with LVAD who during the perioperative period are in need of right ventricular temporary or durable mechanical circulatory support constitute a group at particular risk. Improvement of devices tailored for right ventricular support is mandatory for further evolution of the field.
School-Based Therapists' Perspectives of Wheelchair Use in US Schools: A Survey Study
Authors: Kenyon Lisa K. , Straw Lindsay , Wassermann Maura , Yasick Erin L. , Kiger Angela L.
Published: November 2023

Purpose:

To gather information concerning the current state of students' wheelchair (WC) use in US schools from the perspective of school-based therapists.

Methods:

This descriptive study used a Web-based survey to gather information regarding factors that facilitated or hindered student WC use at school, the frequency at which various tasks related to WC provision were performed, and factors that would facilitate students' independence with WC use.

Results:

A dependent manual WC was the most common type of WC mobility used at school. Various student and nonstudent factors were reported as a facilitator or a barrier to students' WC use at school.

Conclusions:

Although most respondents reported working with a student who used a WC, few reported active engagement in tasks related to WC service provision. Future research exploring potential attitudinal issues influencing students' WC use at school and ways to optimally support students' independent WC use is indicated.
A Spatial Comparison of Molecular Features Associated with Resistance to Pembrolizumab in BCG Unresponsive Bladder Cancer
Authors: Meghani Khyati , Frydenlund Noah , Yu Yanni , Choy Bonnie , Meeks Joshua J.
Published: November 2023

Background

Intravenous immune checkpoint inhibition achieves a 40% three-month response in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS). Yet only half of early responders will continue to be disease free by 12 months, and resistance mechanisms are poorly defined.

Objective

We assessed the molecular features associated with response to immunotherapy in BCG unresponsive non-muscle invasive bladder cancers treated with pembrolizumab.

Design, Setting, and Participants

We performed digital spatial profiling (DSP) of BCG unresponsive NMIBC tumors before and after IV pembrolizumab therapy.

Intervention

Pembrolizumab was administered intravenously in patients with NMIBC at the time of recurrence after BCG therapy. Biopsies were obtained before starting IV pembrolizumab and three months post-treatment.

Outcomes and Statistical Analysis

Spatial gene expression profiling of the tumor niche pre- and post IV pembrolizumab.

Results and Limitations

We evaluated 119 regions of interest (ROIs) from five patients, which included 60 epithelial (PanCK+) and 59 stromal segments (PanCK-). ROIs from responders had distinct expression signatures from non-responders for both the tumor and TME. Responders were more likely to have a dynamic change in expression after pembrolizumab than non-responders. A major limitation of this study was the number of patients evaluated.

Conclusion

For the first time, we have identified distinct expression signatures associated with response and resistance to IV pembrolizumab in NMIBCs. Further research with more patients and alternative checkpoint inhibitors is essential to validate our findings.

Patient Summary

We identify the molecular features of tumors associated with response to pembrolizumab for patients with BCG unresponsive NMIBCs.
Copy-number variants and polygenic risk for intelligence confer risk for autism spectrum disorder irrespective of their effects on cognitive ability
Authors: Schmilovich Zoe , Bourque Vincent-Raphaël , Douard Elise , Huguet Guillaume , Poulain Cécile , Ross Jay P. , Alipour Paria , Castonguay Charles-Étienne , Younis Nadine , Jean-Louis Martineau , Saci Zohra , Pausova Zdenka , Paus Tomas , Schuman Gunter , Porteous David , Davies Gail , Redmond Paul , Harris Sarah E. , Deary Ian J. , Whalley Heather , Hayward Caroline , Dion Patrick A. , Jacquemont Sébastien , Rouleau Guy A.
Published: November 2023

Rare copy number variants (CNVs) and polygenic risk for intelligence (PRS-IQ) both confer risk for autism spectrum disorder (ASD) but have opposing effects on cognitive ability. The field has struggled to disentangle the effects of these two classes of genomic variants on cognitive ability from their effects on ASD risk, in part because previous studies did not include controls with cognitive measures. We aim to investigate the impact of these genomic variants on ASD risk while adjusting for their known effects on cognitive ability. In a cohort of 8,426 subjects with ASD and 169,804 controls with cognitive assessments, we found that rare coding CNVs and PRS-IQ increased ASD risk, even after adjusting for their effects on cognitive ability. Bottom decile PRS-IQ and CNVs both decreased cognitive ability but had opposing effects on ASD risk. Models combining both classes of variants showed that the effects of rare CNVs and PRS-IQ on ASD risk and cognitive ability were largely additive, further suggesting that risk for ASD is conferred independently from its effects on cognitive ability. Despite imparting mostly additive effects on ASD risk, rare CNVs and PRS-IQ showed opposing effects on core and associated features and developmental history among subjects with ASD. Our findings suggest that cognitive ability itself may not be the factor driving the underlying risk for ASD conferred by these two classes of genomic variants. In other words, ASD risk and cognitive ability may be two distinct manifestations of CNVs and PRS-IQ. This study also highlights the challenge of understanding how genetic risk for ASD maps onto its dimensional traits.
Craniofacial phenotyping with fetal MRI: A feasibility study of 3D visualisation, segmentation, surface-rendered and physical models
Authors: Matthew Jacqueline , Uus Alena , De Souza Leah , Wright Robert , Fukami-Gartner Abi , Priego Gema , Saija Carlos , Deprez Maria , Collado Alexia Egloff , Hutter Jana , Story Lisa , Malamateniou Christina , Rhode Kawal , Hajnal Jo , Rutherford Mary A.
Published: November 2023

This study explores the potential of 3D Slice-to-Volume Registration (SVR) motion-corrected fetal MRI for craniofacial assessment, traditionally used only for fetal brain analysis. In addition, we present the first description of an automated pipeline based on 3D Attention UNet trained for 3D fetal MRI craniofacial segmentation, followed by surface refinement. Results of 3D printing of selected models are also presented.

Qualitative analysis of multiplanar volumes based on the SVR output and surface segmentations outputs, assessed with computer and printed models, were based on standardised protocols that we developed for evaluating image quality and visibility of diagnostic craniofacial features. A test set of 25, postnatally confirmed, Trisomy 21 fetal cases (24-36 weeks gestational age), revealed that 3D reconstructed T2 SVR images provided 66-100% visibility of relevant craniofacial and head structures in the SVR output, and 20-100% and 60-90% anatomical visibility was seen for the baseline and refined 3D computer surface model outputs respectively. Furthermore, 12 of 25 cases, 48%, of refined surface models demonstrated good or excellent overall quality with a further 9 cases, 36% demonstrating moderate quality to include facial, scalp and external ears. Additional 3D printing of 12 physical real-size models (20-36 weeks gestational age) revealed good/excellent overall quality in all cases and distinguishable features between healthy control cases and cases with confirmed anomalies, with only minor manual adjustments required before 3D printing.

Despite varying image quality and data heterogeneity, 3D T2w SVR reconstructions and models provided sufficient resolution for the subjective characterisation of subtle craniofacial features. We also contributed a publicly accessible online 3D T2w MRI atlas of the fetal head, validated for accurate representation of normal fetal anatomy.

Future research will focus on quantitative analysis, optimizing the pipeline, and exploring diagnostic, counselling, and educational applications in fetal craniofacial assessment.
Profiling the genome and proteome of metabolic dysfunction-associated steatotic liver disease identifies potential therapeutic targets
Authors: Liu Jun , Hu Sile , Chen Lingyan , Daly Charlotte , Medina Cesar Augusto Prada , Richardson Tom G , Traylor Matthew , Dempster Niall J , Mbasu Richard , Monfeuga Thomas , Vujkovic Marijana , Tsao Philip S , Lynch Julie A , Voight Benjamin F. , Chang Kyong-Mi ,   VA Million Veteran Program, Cobbold Jeremy F , Tomlinson Jeremy W , van Duijn Cornelia M , Howson Joanna M M
Published: November 2023

BACKGROUND & AIMS

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects over 25% of the population and currently has no effective treatments. Plasma proteins with causal evidence may represent promising drug targets. We aimed to identify plasma proteins in the causal pathway of MASLD and explore their interaction with obesity.

METHODS

We analysed 2,941 plasma proteins in 43,978 European participants from UK Biobank. We performed genome-wide association study (GWAS) for all MASLD-associated proteins and created the largest MASLD GWAS (109,885 cases/1,014,923 controls). We performed Mendelian Randomization (MR) and integrated proteins and their encoding genes in MASLD ranges to identify candidate causal proteins. We then validated them through independent replication, exome sequencing, liver imaging, bulk and single-cell gene expression, liver biopsies, pathway, and phenome-wide data. We explored the role of obesity by MR and multivariable MR across proteins, body mass index, and MASLD.

RESULTS

We found 929 proteins associated with MASLD, reported five novel genetic loci associated with MASLD, and identified 17 candidate MASLD protein targets. We identified four novel targets for MASLD (CD33, GRHPR, HMOX2, and SCG3), provided protein evidence supporting roles of AHCY, FCGR2B, ORM1, and RBKS in MASLD, and validated nine previously known targets. We found that CD33, FCGR2B, ORM1, RBKS, and SCG3 mediated the association of obesity and MASLD, and HMOX2, ORM1, and RBKS had effect on MASLD independent of obesity.

CONCLUSIONS

This study identified new protein targets in the causal pathway of MASLD, providing new insights into the multi-omics architecture and pathophysiology of MASLD. These findings advise further therapeutic interventions for MASLD.
The mediating role of organisational learning capabilities between workplace happiness and organisational citizenship behaviour
Authors: Goel Preeti , Singh Animesh
Published: November 2023

Purpose

This paper aims to examine whether happiness at workplace (HAW) impacts organisational citizenship behaviour (OCB) and whether this impact can be further improved by promoting learning capabilities in organisations, thus investigating the mediating role of organisational learning capabilities (OLC).

Design/methodology/approach

This study was conducted on knowledge-intensive workers (employees of EdTech companies) in India. Responses were collected via questionnaire in online mode, and after discarding the incomplete responses, 500 replies were considered for data analysis with PLS-SEM technique.

Findings

The outcomes reveal that the HAW has a significant influence on OCB. The outcomes also reveal that this impact is further enhanced with the presence of OLC, thus confirming that OLC operates as a mediator in the link connecting HAW and OCB.

Originality/value

This study makes a distinctive contribution by bringing out the significance of workplace learning in the connection between the workplace happiness and citizenship behaviour of employees that will provide impetus to the practitioners to formulate strategies in such a manner that the employees voluntarily perform the actions beyond their designated roles.
Do ESG ratings and COVID-19 severity score predict stock behavior and market perception? Evidence from emerging markets
Authors: Said Mai T. , ElBannan Mona A.
Published: November 2023

Purpose

The purpose of this study is to examine the impact of firm environmental, social and governance (ESG) rating scores on market perception and stock behavior from 2017 to 2021 while controlling for COVID-19 severity score.

Design/methodology/approach

The authors used panel regression models with robust standard errors based on cross-country and cross-industry sample of 1,324 ESG firms from 25 emerging countries across four regions. Four separate regression analyses are used. Hausman test is used to determine whether fixed-effect (FE) or random-effect approaches should be used in regression models. Lagrange multiplier test is used to test for time FEs, and F-test for individual effects to choose between pooled ordinary least squares model and FE. Two-unit root tests are conducted to check stationarity. Heteroskedasticity and serial correlation were controlled through a robust covariance matrix estimation.

Findings

The authors provide evidence that the stakeholder theory persists in emerging countries. Overall, the results suggest that firms’ stock behavior is positively associated with the level of environmental and social performance in the region. However, the results do not provide empirical evidence to support the link between ESG performance and stock market perception proxied by the price-to-sales ratio. The results suggest that Refinitiv and Bloomberg ESG rating scores have a positive impact on stock performance in emerging markets, albeit the Bloomberg rating score is insignificant.

Practical implications

Favorable impact of environmental and social performance on stock performance suggests that policymakers should take initiatives to raise awareness toward investments in ESG projects. Evidence shows that ESG stock performance in emerging markets does not insulate firms from the COVID-19 severity. Furthermore, this study highlights the inconsistency in calculating the ESG ratings, therefore, a more standardized approach is recommended to support investors seeking sustainable investments.

Social implications

The findings have social implications for investors with proenvironmental preferences and nonpecuniary motives for ethical investments. Asset fund managers should develop ESG investment strategies to promote investor preferences that are linked to the proenvironmental and prosocial attitudes by increasing their investments in stocks of firms that behave ethically and support the environment. Furthermore, the findings show that investors pay a price for ethical and socially responsible investments as they are evaluating the environmental and social activities, hence, the firm ESG profile influences equity valuation and risk assessment.

Originality/value

The study extends the literature and provides evidence from the unique setting of emerging markets by analyzing the relationship between ESG rating scores and the COVID-19 severity scores on one hand, and stock behavior and market perception on the other.
Characterization of cotton woven compression bandages with different structures
Authors: Seddik Khaled Mohamed , Ali Marwa Atif
Published: November 2023

Purpose

Nowadays, textiles play a striking role in various medical applications. Compression bandages are the most essential medical fabrics that help treat venous flow and edema. This study aims to investigate the characteristics of different woven compressive bandage structures produced using compact cotton and cotton/lycra.

Design/methodology/approach

Four samples were weaved by matt-plain2/2, twill2/2, stripe-stain4 and mock-leno structures. Several properties were tested that related to structural performance. Tensile strength, elastic and sub-bandage pressure are considered the main functional properties. Three different analysis tools were performed: chart-diagram, one-factor ANOVA and radar chart area.

Findings

The woven structures critically affected the performance of woven compression bandage samples as well as their classifications.

Originality/value

The woven structures critically affected the performance of woven compression bandage samples as well as their classifications.
Managerial capture of sustainability assurance. Empirical evidence and capital market reactions
Authors: Sánchez-Sancho Marta , Martínez-Ferrero Jennifer , Perote-Peña Javier
Published: November 2023

Purpose

This paper aims to investigate the potential influence of managers on sustainability assurance. When the quality of sustainability reporting is questionable because of subsequent restatements, the authors explore whether assurance is used to enhance its credibility as a legitimization tool or as an impression management strategy. Additionally, the authors analyze how capital markets react to this potential managerial capture and, particularly, whether investors penalize this practice through the cost of capital.

Design/methodology/approach

Using an international sample from 2012 to 2016 and panel data regressions, this study relies on DICTION’s master variables of optimism and certainty to examine the impact of managers on assurance and the market’s reaction to these practices.

Findings

The study shows that some managers might use assurance as a legitimization tool rather than as a means of reinforcing the credibility of sustainability reporting. In such cases, the results reveal that investors penalize (reward) managerial influence (no influence) on assurance.

Practical implications

The new findings help companies understand that they will not improve their financing terms if investors perceive that managers have influenced assurance. Moreover, these findings emphasize the need for standardization to clarify assurance criteria and prevent managerial influence.

Social implications

Managerial influence on assurance raises doubts about its value in terms of reducing information asymmetry and especially improving investors’ decision-making.

Originality/value

The present study represents the first evidence of the potential use of assurance for non-informative purposes. The authors provide clear evidence of how investors penalize managerial influence on assurance, in contrast to the mainstream literature, which shows that this practice always improves investors’ decision-making and is rewarded.
Immune checkpoint inhibitor‐induced epidermal necrolysis: A narrative review evaluating demographics, clinical features, and culprit medications
Authors: Satoh Takashi K. , Neulinger Matthias Munoz , Stadler Pia‐Charlotte , Aoki Rui , French Lars E.
Published: November 2023

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but can cause immune‐related adverse events (irAEs). Severe cutaneous irAEs, including epidermal necrolysis, are rare but potentially life‐threatening. There is limited understanding of the clinical features and management of ICI‐induced Stevens‐Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), so we aimed to analyze 95 cases of ICI‐induced SJS/TEN (35 cases of SJS, 26 cases of TEN, two cases of SJS/TEN overlap, and 32 cases of unspecified) to increase knowledge of this condition among oncologists and dermatologists. We conducted a comprehensive search of PubMed for all relevant case reports published until the end of December 2022, and collected data on patient demographics, cancer type, ICI regimen, time to onset of SJS/TEN, clinical presentation, management strategies, and outcomes. PD‐1 inhibitors were the most common ICIs associated with SJS/TEN (58.9%), followed by the combination of PD‐1 and CTLA‐4 inhibitors (11.6%), and PD‐L1 inhibitors (6.3%). Lung cancer and melanoma were the most frequent malignancies treated (35.8% and 25.4%, respectively). SJS/TEN occurred most frequently within the first 4 weeks (51.7%), and corticosteroid monotherapy was the most commonly chosen systemic treatment (56.4%). The overall mortality rate of ICI‐induced SJS/TEN was 30.8%. Our findings highlight the frequency and severity of ICI‐induced SJS/TEN and the urgent need for predictive molecular biomarkers aimed at preventive measures and early intervention.
Influence of WC addition on mechanical properties of (HfNbTaZrTiMo)C‐Co cermet
Authors: Deng Xiao‐Chun , Kang Xiao‐Dong , Zhang Guo‐Hua
Published: November 2023

(HfNbTaZrTiMo)C‐Co high entropy carbide cermet was fabricated by conventional vacuum sintering. The effect of WC addition on the mechanical properties of cermets was also investigated. For cermets without WC addition, with the extension of sintering time, the hardness of cermets first rose and then fell, while the fracture toughness showed a decreasing trend. The increase in sintering temperature led to a decline in hardness and an enhancement of fracture toughness. The (HfNbTaZrTiMo)C‐15 wt. % Co cermet sintered at 1450°C for 2 h had the best comprehensive properties, with the hardness and fracture toughness of 16.36 ± 0.17 GPa and 7.19 MPa·m1/2, respectively. After adding WC, there was a typical black core (undissolved (HfNbTaZrTiMo)C phase)‐gray rim (seven‐component (HfNbTaZrTiMoW)C solid solutions) structure in the cermets. Meanwhile, Mo diffused into WC to form (Mo, W)C solid solutions. The formations of (HfTaZrNbMoTiW)C and (Mo, W)C solid solutions resulted in an improvement in hardness. In addition, since the addition of WC enhanced the wettability between carbides phase and Co phase, the comprehensive properties of cermets were improved. The hardness and fracture toughness of the (HfNbTaZrTiMo)C‐42.5 wt. % WC‐15 wt.% Co cermet sintered at 1450°C for 2 h were 17.42 ± 0.06 GPa and 8.22 MPa·m1/2, respectively.
Effects of pore size on electrical and thermal properties of porous SiC ceramics
Authors: Das Dulal , Lucio Maria Dolores Sosa , Kultayeva Shynar , Kim Young‐Wook
Published: November 2023

Porous SiC ceramics with three different pore sizes (∼7, ∼45, and ∼98 μm) and two different porosities (∼54% and ∼63%) were prepared to investigate the effects of pore size on electrical and thermal properties of the porous ceramics. With an increase in pore size from ∼7 to ∼98 μm at the same porosity (∼54%), the electrical and thermal conductivities of the porous ceramics increased from ∼1.01 to ∼2.30 Ω−1·cm−1 and ∼14.3 to ∼26.2 W·m−1K−1, respectively. Similar trends have been obtained in the ceramics with ∼63% porosity. The porous SiC ceramic with larger pore size has smaller pore/strut interface area at the same porosity, which leads to less carrier scattering and phonon‐pore scattering at the pore/strut interfaces, resulting in higher electrical and thermal conductivities, respectively. These results suggest that the electrical and thermal properties of porous SiC ceramics can be successfully tuned by adjusting the pore size and porosity depending on the application.
Parental supporter in pediatric resuscitation: A mixed‐method study with Delphi and analytic hierarchy process
Authors: Ghavi Arezoo , Hassankhani Hadi , Meert Kathleen L.
Published: November 2023

Introduction

Providing support to parents is an evidence‐based practice and a crucial part of family‐centered nursing care. However, it is not clear who and how to provide the best support to parents during and after their child's resuscitation attempts.

Purpose

This study was conducted to explore the characteristics and roles of parental supporters responsible for caring for parents during and after their child's resuscitation.

Methods

This is a mixed‐method study combining the Delphi technique and the Analytic Hierarchy Process. A list of potentially important items describing the characteristics and roles of parental supporters caring for parents during and after pediatric resuscitation was developed through qualitative interviews with parents and members of the resuscitation team, and a thorough literature search. Then, the Delphi round was conducted with key experts. In the final step, the Analytic Hierarchy Process was used for ranking items in the order of their importance.

Results

A list with 69 items describing the characteristics and roles of parental supporters was developed. 15 items (21.74%) were related to the “Characteristics of parental supporter” category; 8 items (11.59%) were related to the “Roles of a parental supporter during resuscitation” category; 13 items (18.84%) were related to the “Roles of a parental supporter after successful resuscitation” category; 23 items (33.34%) were related to the “Roles of a parental supporter after unsuccessful resuscitation” category; and 10 items (14.49%) were related to the “Roles of a parental supporter after unsuccessful resuscitation with help of other staff of the hospital” category.

Conclusion

The findings of this study can be used to develop guidelines that include parental supporter characteristics and roles to support parents during and after their child's resuscitation according to family‐centered care practices in pediatric settings.

Clinical Relevance

Study findings indicate the need for the presence of a parental supporter during and after pediatric resuscitation, whether witnessed by the parents or not. Knowledge regarding the characteristics and roles of parental supporters can be used in practice to uphold family‐centered nursing care during critical situations.
Forest understorey flowering phenology responses to experimental warming and illumination
Authors: Lorer Eline , Verheyen Kris , Blondeel Haben , De Pauw Karen , Sanczuk Pieter , De Frenne Pieter , Landuyt Dries
Published: November 2023

Species are altering their phenology to track warming temperatures. In forests, understorey plants experience tree canopy shading resulting in light and temperature conditions, which strongly deviate from open habitats. Yet, little is known about understorey phenology responses to forest microclimates.

We recorded flowering onset, peak, end and duration of 10 temperate forest understorey plant species in two mesocosm experiments to understand how phenology is affected by sub‐canopy warming and how this response is modulated by illumination, which is related to canopy change. Furthermore, we investigated whether phenological sensitivities can be explained by species' characteristics, such as thermal niche.

We found a mean advance of flowering onset of 7.1 d per 1°C warming, more than previously reported in studies not accounting for microclimatic buffering. Warm‐adapted species exhibited greater advances. Temperature sensitivity did not differ between early‐ and later‐flowering species. Experimental illumination did not significantly affect species' phenological temperature sensitivities, but slightly delayed flowering phenology independent from warming.

Our study suggests that integrating sub‐canopy temperature and light availability will help us better understand future understorey phenology responses. Climate warming together with intensifying canopy disturbances will continue to drive phenological shifts and potentially disrupt understorey communities, thereby affecting forest biodiversity and functioning.