bluuebunny/crossref_metadata_2025 huggingface dataset:
Daily living skill support for autistic people through a neurodiversity‐affirming practice lens
Authors: Morrison Chelsea , Cashin Andrew , Foley Kitty‐Rose
Published: October 2024

Introduction

Supporting daily living skill (DLS) development for autistic people is a component of occupational therapy practice. DLSs are essential for an increased quality of life (QoL), independent living, and community participation. Autistic young people experience poorer outcomes in terms of QoL and independent living than non‐autistic peers. Finding a balance between targeted DLS support to maximise independent living and improve QoL, while avoiding attempts to ‘normalise’ or ‘change’ autistic people, presents as a dilemma for therapists striving to align with neurodiversity‐affirming practice.

Methods

This theoretical paper explored literature pertaining to DLS and the neurodiversity movement in the context of occupational therapy values and the Canadian Model of Occupational Participation. Consideration of whether targeted DLS support is neurodiversity‐affirming or whether occupational therapists are compelling autistic people to mimic behavioural norms perceived by society was discussed.

Results

DLSs are an important factor for maximising QoL, regardless of neurotype. Occupational therapy values align with the core tenets of the neurodiversity movement, and occupational therapists are equipped with the values and skills to support the development of DLSs utilising affirming practice.

Conclusion

Occupational therapists should critically reflect on their practice to ensure alignment with the professions core values and recent occupational therapy models, to ensure affirming practice. Further research investigating DLS and neurodiversity‐affirming practice would benefit occupational therapists striving to align with neurodiversity‐affirming practice.

Consumer and Community Involvement

No consumer or community involvement. Consumers have been considered throughout the development of this paper through their representation in the literature. This involved a process of reviewing the literature and considering it in the scope of the questions and how occupational therapy sits within the neurodiversity movement.

PLAIN LANGUAGE SUMMARY

It is important to help autistic people to learn to do everyday things. Everyday things include activities like showering, cleaning, and cooking. These things are important so that autistic people can live on their own. It has shown that autistic young people are less likely to be able to do everyday activities on their own. It is important that therapists help autistic people learn how to do everyday things; however, do not try and change who they are. This is because completing everyday activities is an important part of QoL for all people.
Altered tubulin detyrosination due to SVBP malfunction induces cytokinesis failure and senescence, underlying a complex hereditary spastic paraplegia
Authors: Launay Nathalie , Espinosa‐Alcantud Maria , Verdura Edgard , Fernández‐Eulate Gorka , Ondaro Jon , Iruzubieta Pablo , Marsal Maria , Schlüter Agatha , Ruiz Montserrat , Fourcade Stephane , Rodríguez‐Palmero Agustí , Zulaica Miren , Sistiaga Andone , Labayru Garazi , Loza‐Alvarez Pablo , Vaquero Alejandro , Lopez de Munain Adolfo , Pujol Aurora
Published: October 2024

Senescence, marked by permanent cell cycle arrest may contribute to the decline in regenerative potential and neuronal function, thereby promoting neurodegenerative disorders. In this study, we employed whole exome sequencing to identify a previously unreported biallelic missense variant in SVBP (p.Leu49Pro) in six patients from three unrelated families. These affected individuals present with a complex hereditary spastic paraplegia (HSP), peripheral neuropathy, verbal apraxia, and intellectual disability, exhibiting a milder phenotype compared to patients with nonsense SVBP mutations described previously. Consistent with SVBP's primary role as a chaperone necessary for VASH‐mediated tubulin detyrosination, both patient fibroblasts with the p.Leu49Pro mutation, and HeLa cells harboring an SVBP knockdown exhibit microtubule dynamic instability and alterations in pericentriolar material (PCM) component trafficking and centrosome cohesion. In patient fibroblasts, structural abnormalities in the centrosome trigger mitotic errors and cellular senescence. Notably, premature senescence characterized by elevated levels of p16INK4, was also observed in patient peripheral blood mononuclear cells (PBMCs). Taken together, our findings underscore the critical role of SVBP in the development and maintenance of the central nervous system, providing novel insights associating cytokinesis failure with cortical motor neuron disease and intellectual disability.
Ketogenic β‐hydroxybutyrate regulates β‐hydroxybutyrylation of TCA cycle‐associated enzymes and attenuates disease‐associated pathologies in Alzheimer's mice
Authors: Han Wanhong , Zhang Bingchang , Zhao Wenpeng , Zhao Wentao , He Jiawei , Qiu Xiansheng , Zhang Liang , Wang Xiuyan , Wang Yong , Lu Hanwen , Zhang Yaya , Xie Yuanyuan , Geng Yanyan , Zhao Wujie , Huang Qionghui , Zhang Yun‐wu , Wang Zhanxiang
Published: October 2024

Lysine β‐hydroxybutyrylation (Kbhb) is a post‐translational modification that has recently been found to regulate protein functions. However, whether and how protein Kbhb modification participates in Alzheimer's disease (AD) remains unknown. Herein, we carried out 4D label‐free β‐hydroxybutylation quantitative proteomics using brain samples of 8‐month‐old and 2‐month‐old APP/PS1 AD model mice and wild‐type (WT) controls. We identified a series of tricarboxylic acid (TCA) cycle‐associated enzymes including citrate synthase (CS) and succinate‐CoA ligase subunit alpha (SUCLG1), whose Kbhb modifications were decreased in APP/PS1 mice at pathological stages. Sodium β‐hydroxybutyrate (Na‐β‐OHB) treatment markedly increased Kbhb modifications of CS and SUCLG1 and their enzymatic activities, leading to elevated ATP production. We further found that Kbhb modifications at lysine 393 site in CS and at lysine 81 site in SUCLG1 were crucial for their enzymatic activities. Finally, we found that β‐OHB levels were decreased in the brain of APP/PS1 mice at pathological stages. While ketogenic diet not only significantly increased β‐OHB levels, Kbhb modifications and enzymatic activities of CS and SUCLG1, and ATP production, but also dramatically attenuated β‐amyloid plaque pathologies and microgliosis in APP/PS1 mice. Together, our findings indicate the importance of protein Kbhb modification for maintaining normal TCA cycle and ATP production and provide a novel molecular mechanism underlying the beneficial effects of ketogenic diet on energy metabolism and AD intervention.
Quantitative Modeling to Characterize Maternal Inflammatory Response of Histologic Chorioamnionitis in Placental Membranes
Authors: Chou Teresa , Senkow Karolina J. , Nguyen Megan B. , Patel Payal V. , Sandepudi Kirtana , Cooper Lee A. , Goldstein Jeffery A.
Published: October 2024

Problem

The placental membranes are a key barrier to fetal and uterine infection. Inflammation of the membranes, diagnosed as maternal inflammatory response (MIR) or alternatively as acute chorioamnionitis, is associated with adverse maternal‐fetal outcomes. MIR is staged 1–3, with higher stages indicating more hazardous inflammation. However, the diagnosis relies upon subjective evaluation and has not been deeply characterized. The goal of this work is to develop a cell classifier for eight placental membrane cells and quantitatively characterize MIR1–2.

Method of Study

Hematoxylin and eosin (H&E)‐stained placental membrane slides were digitized. A convolutional neural network was trained on a dataset of hand‐annotated and machine learning‐identified cells. Overall cell class‐level metrics were calculated. The model was applied to 20 control, 20 MIR1, and 23 MIR2 placental membrane cases. MIR cell composition and neutrophil distribution were assessed via density and Ripley's cross K‐function. Clinical data were compared to neutrophil density and distribution.

Results

The classification model achieved a test‐set accuracy of 0.845, with high precision and recall for amniocytes, decidual cells, endothelial cells, and trophoblasts. Using this model to classify 53 073 cells from healthy and MIR1–2 placental membranes, we found that (1) MIR1–2 have higher neutrophil density and fewer decidual cells and trophoblasts, (2) Neutrophils colocalize heavily around decidual cells in healthy placental membranes and around trophoblasts in MIR1, (3) Neutrophil density impacts distribution in MIR, and (4) Neutrophil metrics correlate with features of clinical chorioamnionitis.

Conclusions

This paper introduces cell classification into the placental membranes and quantifies cell composition and neutrophil spatial distributions in MIR.
Evaluating the Prognostic Significance of Cystatin C Level Variations Pre‐ and Post‐Radiofrequency Catheter Ablation in the Recurrence of Persistent Atrial Fibrillation
Authors: Zhang Yu‐Yan , Ge Ji‐Yong , Ji Yuan , Zhu Yi , Zhu Zhen‐Yan , Wang Fang‐Fang
Published: October 2024

Objective

To investigate the correlation between persistent atrial fibrillation (AF) recurrence and alterations in cystatin C levels pre‐ and post‐radiofrequency catheter ablation (RFCA).

Methods

This study encompassed 114 patients diagnosed with persistent AF. Their serum cystatin C levels were assessed both prior to and 3 months after undergoing an RFCA procedure. The variance in cystatin C levels before and after RFCA is represented as ΔCystatin C. Subsequently, we compared these values between two groups: patients who did not experience a recurrence of AF (n = 79) and those who did experience a recurrence (n = 35).

Results

A significant reduction in cystatin C levels post‐RFCA in both groups, with a more pronounced decrease observed in the non‐recurrence group. Moreover, the recurrence group exhibited larger left atrial diameter and volume before RFCA compared to the non‐recurrence group. Cox regression analysis indicated that smaller reductions in serum cystatin C levels and greater left atrial volumes before RFCA were associated with an increased risk of recurrence, after adjusting for covariates. The receiver operating characteristic curve indicated an elevated probability of clinical recurrence of AF post‐RFCA in patients with a cystatin C decline < 0.08 mg/L (AUC 0.64). The Kaplan–Meier survival analysis revealed that patients with a cystatin C decline > 0.08 mg/L exhibited significantly higher rates of remaining free from recurrence following RFCA across a 24‐month follow‐up period (Log‐rank test p = 0.003).

Conclusions

Alterations in ΔCystatin C levels pre and post‐RFCA in the initial phase could independently predict the recurrence of AF.
A review of emergency laparoscopic cholecystectomies in Far North Queensland
Authors: Sawyer Emily , Buschel Helen , Tang Hannah , Mouline Omar , Wu Roxanne
Published: October 2024

Background

Access to laparoscopic cholecystectomy is more limited for remote communities and Indigenous patients internationally. To date, studies exploring the incidence of gallstone disease and access to laparoscopic cholecystectomy in Australian regional communities are limited. This study examined the rates and outcomes of emergency laparoscopic cholecystectomy (EMLC) in Far North Queensland, specifically in Indigenous and remote populations.

Aims

We retrospectively examined all patients who underwent an EMLC at Cairns Hospital between 2016 and 2021.

Results

Over the study period, 634 EMLCs were undertaken. The average annual rate of 56 cases per 100 000 was considerably lower than national estimates. However, rates of EMLC were significantly higher in remote communities and Indigenous patients compared with the remaining cohort. Patients from remote communities were more likely to have pre‐existing gallstone disease but were less likely to have been seen in a surgical outpatient clinic prior to admission. Despite this, surgical outcomes for EMLC were comparable to national and international standards.

Conclusion

This study highlights the challenges in surgical healthcare provision for gallstone disease in a regional centre. The requirement for EMLC disproportionately effects geographically isolated communities and Australian Indigenous people. Addressing the healthcare barriers to management of GD in regional Australia should be a priority.
A genome‐wide association study reveals fetal genetic factor for gestation length on chromosome 21 in Japanese Black cattle
Authors: Kurose‐Iwanaga Marina , Muraki Eiji , Sasaki Shinji
Published: October 2024

Gestation length (GL) in cattle is associated with neonatal health and the subsequent reproductive performance of dams. We performed a genome‐wide association study (GWAS) using 25,144 single nucleotide polymorphisms (SNPs) in 4373 animals to detect genetic variants associated with GL as a fetal trait in Japanese Black cattle in Gifu Prefecture. We identified four significant SNPs on chromosome 21 in moderate linkage disequilibrium (LD). The minor allele of the most significant SNP has the effect on −2.47 days GL with a 0.019 allele frequency. Of the 4373 animals, 140 heterozygotes and one homozygote with the minor allele were traced back to a heterozygous sire. The 7.2 Mb LD region harbors three genes: gamma‐aminobutyric acid type A receptor subunit beta3 (GABRB3), arrestin domain containing 4 (ARRDC4), and nuclear receptor subfamily 2 group F member 2 (NR2F2, also known as COUP‐TFII). RNA expression analysis and its functions suggest that GABRB3, ARRDC4, and NR2F2 (COUP‐TFII) are involved in glucose production via the hypothalamic–pituitary–adrenal axis during the fetal stress response at gestation period termination. These results suggest that an increase in the allele frequency of the associated SNPs has an impact on genetic improvement by shortening the GL in the population.
Nicotinamide enhances Treg differentiation by promoting Foxp3 acetylation in immune thrombocytopenia
Authors: Li Ju , Zhang Cheng , Hu Yuefen , Peng Jun , Feng Qi , Hu Xiang
Published: October 2024

Imbalanced nicotinamide adenine dinucleotide (NAD+) homeostasis has been reported in multiple autoimmune diseases and supplementation with NAD+ precursors has consistently demonstrated positive therapeutic benefits for these conditions. Immune thrombocytopenia (ITP) is an acquired autoimmune disease, in which the decreased number and impaired function of regulatory T cells (Tregs) contribute to the main pathogenesis. Here we found NAD+ level was decreased in the plasma and CD4+ T cells of ITP patients. Supplementation with NAD+ precursor nicotinamide (NAM), but not nicotinamide mononucleotide (NMN), increased Treg frequency and ameliorated thrombocytopenia in an ITP murine model. Moreover, whilst both NAM and NMN restored cytosolic NAD+ level in the CD4+ T cells from ITP patients, only NAM promoted Treg differentiation. Mechanistically, Sirtuin1 (Sirt1), a major consumer of NAD+, was highly expressed in the CD4+ T cells of ITP patients, potentially contributing to the low level of NAD+. NAM, which could act as Sirt1 inhibitor, promoted Foxp3 acetylation and stability in induced Tregs derived from naïve CD4+ T cells of ITP patients. These findings suggest that NAM holds promise as a novel therapeutic strategy for restoring immune balance in ITP.
Baseline characteristics of Ghanaian children and adults enrolled in PIVOT, a randomised clinical trial of hydroxyurea in HbSC disease in sub‐Saharan Africa
Authors: Segbefia Catherine I. , Smart Luke R. , Stuber Susan E. , Amissah‐Arthur Kwesi N. , Dzefi‐Tettey Klenam , Ekpale Priscilla , Mensah Enoch , Lane Adam C. , Ghunney William , Tagoe Lily Gloria , Oteng Alpha , Amoako Emmanuella , Latham Teresa S. , Dei‐Adomakoh Yvonne A. , Ware Russell E.
Published: October 2024

HbSC disease is a common form of sickle cell disease with significant morbidity and early mortality. Whether hydroxyurea is beneficial for HbSC disease is unknown. Prospective Identification of Variables as Outcomes for Treatment (PIVOT, Trial ID PACTR202108893981080) is a double‐blind, randomised, placebo‐controlled phase II trial of hydroxyurea for people with HbSC, age 5–50 years, in Ghana. After screening, participants were randomised to placebo (standard of care) or hydroxyurea. The primary outcome is the cumulative incidence of haematological toxicities during 12 months of blinded treatment; secondary outcomes include multiple laboratory and clinical assessments. Between April 2022 and June 2023, 112 children and 102 adults were randomised, including 44% females and average age 21.6 ± 14.5 years. Participants had substantial morbidity including previous hospitalisations (93%), vaso‐occlusive events (86%), malaria (79%), often received transfusions (20%), with baseline haemoglobin 11.0 ± 1.2 g/dL and foetal haemoglobin 1.8% ± 1.5%. The spleen was palpable in six children and one adult, and ultrasonographic volumes were collected. Proliferative sickle retinopathy was common (30% children, 75% adults), but proteinuria was less common (3% children, 8% adults). Whole blood viscosity, ektacytometry, point‐of‐sickling, transcranial Doppler, near‐infrared spectrometry (NIRS), 6‐minute walk, and quality of life were also measured. Now fully enrolled, PIVOT will document the safety and potential benefits of hydroxyurea on clinical and laboratory outcomes in HbSC disease.
CDK8/19 inhibition triggers a switch from mitosis to endomitosis in cord blood megakaryocytes
Authors: Liu Zhi‐Jian , Thom Christopher , Nitulescu Ioana I. , Pelish Henry E. , Rimsza Lisa M. , Teruel‐Montoya Raul , Ferrer‐Marin Francisca , Shair Matthew D. , Sola‐Visner Martha
Published: October 2024

Neonatal and adult megakaryocytes differ in proliferative capacity and ploidy levels, and neonatal and adult platelets differ in function, gene expression, and protein content. The mechanisms underlying these differences are incompletely understood. CDK8 and CDK19 are transcriptional kinases part of the CDK‐mediator complex, which regulates gene transcription in a cell‐specific manner. We discovered that cortistatin A, a potent highly selective inhibitor of CDK8/CDK19, significantly reduced cell expansion and increased ploidy in cord blood‐derived megakaryocytes. These phenotypic changes were associated with gene expression changes that partially overlapped developmentally regulated genes. These findings might have relevance for the management of developmental megakaryocyte disorders.
A novel hypothesis‐generating computational workflow utilizing reverse pharmacophore mapping—A drug repurposing perspective of istradefylline towards major depressive disorder
Authors: van der Walt Mietha Magdalena , Smith Arnold Petrus
Published: October 2024

Background and Purpose

Drug repurposing (DR) offers a compelling alternative to traditional drug discovery's lengthy, resource‐intensive process. DR is the process of identifying alternative clinical applications for pre‐approved drugs as a low‐risk and low‐cost strategy. Computational approaches are crucial during the early hypothesis‐generating stage of DR. However, ‘large‐scale’ data retrieval remains a significant challenge. A computational workflow addressing such limitations might improve hypothesis generation, ultimately benefit patients and advance DR research.

Experimental Approach

We introduce a novel computational workflow (combining free‐accessible computational platforms) to provide ‘proof‐of‐concept’ of the pre‐approved drug's suitability for repurposing. Three key phases are included: target fishing (via reverse pharmacophore mapping), target identification (via disease‐ and drug‐target pathway identification) and retrospective literature and drug‐like analysis (via in silico ADMET properties determination). Istradefylline is a Parkinson's disease‐approved drug with literature‐attributed antidepressant properties remaining unclear. Practically applied, istradefylline's antidepressant activity was assessed in the context of major depressive disorder (MDD).

Key Results

Data mining aided by target identification resulted in istradefylline potentially representing a novel antidepressant drug class. Retrieved drug targets (KYNU, MAO‐B, ALOX12 and PLCB2) associated with selected MDD pathways (tryptophan metabolism and serotonergic synapse) generated a hypothesis that istradefylline increased extracellular 5‐HT levels (MAO‐B inhibition) and reduced inflammation (KYNU, ALOX12 and PLCB2 inhibition).

Conclusion and Implications

The practically applied workflow's generated hypothesis aligns with known experimental data, validating the effectiveness of this novel computational workflow. It is a low‐risk and low‐cost DR computational tool providing a bird's‐eye view for exploring alternative clinical applications of pre‐approved drugs.
Reduction in mutualistic ant aggressive behavior upon sugar supplementation
Authors: Hoffman Sarah G. , Benson Luke R. , Philson Conner S. , Chock Rachel Y. , Curti Joseph N. , Flores‐Negrón César F. , Grether Gregory F.
Published: October 2024

Mutualistic interactions between species are widespread and important for community structure and ecosystem function. In a changing environment, the proximate mechanisms that maintain mutualisms affect their stability and susceptibility to perturbation. In ant‐plant mutualisms, ants defend their host plants against herbivores or competing plants in exchange for housing or food. While the phenomenon of species exchanging services for resources is well documented, how such arrangements are maintained is not. There are at least four hypothesized mechanisms through which plants use sugar to induce ant defense against herbivores. Three such hypotheses (“deficit”, “fuel for foraging”, “predictable rewards”) predict that the appearance of a new sugar source near the host plant would increase the rate of ant attacks against herbivores, but the fourth hypothesis (“attract and distract”) predicts the opposite. To examine how the mutualism between Triplaris americana and Pseudomyrmex dendroicus would be affected, we simulated the appearance of a novel sugar source at a random half of 34 T. americana trees with P. dendroicus colonies. Compared to control colonies, those with access to the sugar source were less likely to attack herbivorous insects (Nasutitermes sp. termites). Thus, our findings support the “attract and distract” hypothesis. We infer that this ant‐plant mutualism could be destabilized by the appearance of an alternative sugar source, such as a nectar‐producing plant or honeydew‐excreting insect. More broadly, we conclude that the mechanisms responsible for maintaining mutualistic relationships are relevant for understanding how ecological communities are affected by environmental change.

Abstract in Spanish is available with online material.
Tyramine Derivatives as Versatile Pharmacophores With Potent Biological Properties: Sex Hormone–Binding Globulin Inhibition, Colon Cancer Antimigration, and Antimicrobial Activity
Authors: Marjanović Jovana S. , Arsenijević Dejan , Kosanić Marijana , Matić Jovana , Bogdanović Goran A. , Kostić Marina D. , Divac Vera M.
Published: October 2024

Guided by the idea that the presence of a heterocyclic aromatic core and tyramine moiety, under the umbrella of a single molecular scaffold could bring interesting biological properties, herein we present synthesis, characterization, with two crystal structures reported, and biological evaluation of some tyramine derivates. Cytotoxic and antimigratory potential was addressed by using a colorectal cancer cell line as a model system. Although possessing no cytotoxic effects, two compounds have shown strong antimigratory potential in low doses, with no effect on healthy MRC‐5 cells. Evaluation of their antimicrobial activities suggested prominent antimicrobial activity, where Compound 4 outperformed streptomycin against Escherichia coli and Proteus mirabilis. Hormone‐dependent types of cancer, such as prostate, ovary, and breast, are highly dependent on human sex hormone–binding globulin (SHBG) blood levels. A molecular docking study has shown that 1 has high affinity to bind and therefore compete with natural steroids for the SHBG steroid‐binding site. DNA‐binding study have shown that 4 interacts with CT‐DNA in a groove‐binding mode. In silico ADME/T study revealed that all compounds have suitable physicochemical properties for oral bioavailability and druglikeness, while toxicity tests for 1, 4, and 6 suggested potential for mutagenicity (4, 6), hepatotoxicity (6), and skin sensation (1).
Insulin‐Like Growth Factor Binding Protein 2 Drives Neurodegeneration in Parkinson's Disease: Insights From In Vivo and In Vitro Studies
Authors: An Jing , Wen Lulu , Yu Haiyang , Bu Zhongqi , Feng Juan
Published: October 2024

Aims

Insulin‐like growth factor binding protein 2 (IGFBP2) is implicated in various neurodegenerative diseases. However, its role in Parkinson's disease (PD) is unclear.

Methods

PD rat model was established by 6‐OHDA injection. After 3 weeks, mRNA‐seq was conducted. Rats received rIGFBP2 via intra‐MFB injection 6 h prior to 6‐OHDA infusion, and the effect of IGFBP2 in PD rats was investigated by western blotting, IHC, specific kits, JC‐1 staining, and TUNEL analysis. In vitro, PC12 cells were treated with 6‐OHDA, and CCK‐8, specific kits, Hoechst 33258 staining, Western blotting, and JC‐1 staining were performed to assess the IGFBP2's role.

Results

mRNA‐seq revealed DEGs in PD, with attention to downregulated IGFBP2. rIGFBP2 treatment aggravated neurobehavioral deficits, decreased TH expression, Ψm, ATP level and SOD, GSH‐Px activities but increased α‐synuclein, ROS, MDA, mitochondrial cytochrome c contents, cell apoptosis in 6‐OHDA‐lesioned rats, which might be mediated through inactivating IGF‐1R/AKT pathway. In 6‐OHDA‐treated PC12 cells, rIGFBP2 aggravated cell injury, demonstrated by decreased cell viability and increased apoptosis, oxidative stress, and mitochondrial dysfunction. Co‐treatment with rIGFBP2 and rIGF‐1 partially reversed the effect of rIGFBP2 on cell damage.

Conclusion

IGFBP2 exacerbates neurodegeneration in PD through increasing oxidative stress, mitochondrial dysfunction, and apoptosis via inhibiting IGF‐1R/AKT pathway.
Progress in Noninvasive Surveillance for Acute Rejection in Pediatric Heart Transplant Recipients: A Real‐World Analysis of Donor‐Derived Cell‐Free DNA‐Based Surveillance Protocol
Authors: Akabas Leor , Bravo Stephen A. , Zhang Yun , Simonelli Anna , Zuckerman Warren A. , Richmond Marc E. , Lytrivi Irene D.
Published: October 2024

Purpose

Acute cellular (ACR) and antibody‐mediated (AMR) rejection are risk factors for allograft loss in heart transplant (HT) recipients. Endomyocardial biopsy (EMB), although considered the gold standard for rejection surveillance, is invasive and has high interobserver variability. Noninvasive donor‐derived cell‐free DNA (dd‐cfDNA) sampling has a high negative predictive value (NPV) for rejection in adults and is increasingly used in pediatrics. This single center study aimed to test the performance of dd‐cfDNA in screening for acute rejection (AR) and donor‐specific antibodies (DSAs) in pediatric HT recipients.

Methods

Blood samples for dd‐cfDNA were obtained per clinical protocol for all eligible HT recipients in our center from July 1, 2022 to December 31, 2023. Primary endpoints were episodes of AR, pathology grading of EMBs temporally related to ddcfDNA sampling (0–150 days), and presence of DSAs.

Results

There were 471 interpretable samples, in 192 unique patients. Of those, 199 dd‐cfDNA tests were paired with EMB ± DSA in 152 patients. Abnormal dd‐cfDNA (> 0.2%) was found in 77 samples (median 0.48%, range 0.21%–11%) and led to EMB, where one sample was positive for ACR (grade 2R), 13 for AMR, yielding an NPV of 97% for AMR. After excluding abnormal ddcfDNA testing associated with AR, 65 abnormal dd‐cfDNA tests were paired with DSA testing. The NPV of the test for detection of DSAs was 93%.

Conclusion

Implementation of noninvasive rejection surveillance with dd‐cfDNA in a pediatric cohort demonstrates high NPV for AR and high DSAs, making it an ideal screening tool for long‐term monitoring of allograft health in pediatrics.
The impact of Scotland's minimum unit pricing for alcohol policy on people accessing services for alcohol dependence: A difference‐in‐difference structured interview study
Authors: Buykx Penny , Perkins Andy , Hughes Jane , Livingston Wulf , Boyd Jennifer , Perman‐Howe Parvati , Johnston Allan , McCarthy Trevor , McLean Alex , Wright Alex , Little Simon , Holmes John
Published: October 2024

Introduction

A minimum unit price (MUP) for alcohol of £0.50 per unit (1 UK unit = 10 mL/8 g alcohol) was introduced in Scotland in May 2018. Few previous studies have examined the impact of alcohol pricing policies on people who are alcohol dependent. This study aimed to evaluate the effect of MUP on people who are alcohol dependent including changes in alcohol consumption and health status, as well as potential unintended consequences.

Methods

Three waves of cross‐sectional data were collected in Scotland (intervention) and Northern England (control) at 0–6 months pre‐implementation then 3–9 months and 18–22 months post‐implementation. The sample was N = 706 people receiving treatment related to their alcohol use. We collected structured interview data including recent drinking information via a 7‐day timeline‐follow‐back drinking diary. Difference‐in‐difference analyses estimated change in indicators in Scotland compared to England at both post‐implementation timepoints.

Results

The proportion of participants consuming alcohol costing on average <£0.50 per unit in Scotland decreased from 60.6% at 0–6 months prior to MUP implementation to 6.3% at 3–9 months post‐implementation (p < 0.0004). There was no significant change in the indicators for alcohol consumption, severity of dependence, health status, other substance use, deprivation level or parenting.

Discussion and Conclusions

The introduction of MUP in Scotland was associated with increases in the prices paid for alcohol by people with dependence and presenting to treatment services. There was no evidence of changes in their alcohol consumption or health status. There was also no evidence of harmful unintended consequences for this population.
In vitro diagnostics of drug allergies
Authors: Glässner Andreas , Weßollek Katharina , Yazdi Amir S. , Sachs Bernhardt
Published: October 2024

In vitro diagnostics for drug hypersensitivity reactions distinguish between serological and cellular‐based tests. A serological test used for the diagnosis of immediate type reactions is the detection of specific IgE antibodies. The cellular tests include the basophil activation test for immediate type reactions and the lymphocyte transformation test, which is mainly used to detect delayed type hypersensitivity reactions. Further cellular‐based tests are the CAST‐ELISA and the mast cell activation test. None of the above‐mentioned tests can definitively exclude an allergy if the result is negative. In addition, it is important to note that even a positive test result is not necessarily associated with an allergy but has to be interpreted in the clinical context.
Thermal Tolerance and Species Distributions: Interactions Between Latitude, Elevation and Arboreality in Ants
Authors: Camara Talita , N. Andersen Alan , Nascimento Geraldo , Arnan Xavier
Published: October 2024

Aim

Global warming has highlighted the importance of understanding the role of thermal tolerance as a driver of species distributions, especially for ectotherms. Here we analyse interactions between latitude, elevation and arboreality as predictors of geographic patterns of thermal tolerance in ants.

Location

The collected data are distributed globally.

Methods

We first tested the effect of latitude, elevation and its interactive effect on ant CTmax and CTmin. Second, we tested whether CTmax and CTmin are phylogenetic clustering. Finally, we tested whether CTmax and CTmin can be explained by nesting microhabitat (ground vs. tree‐nesting species) and whether the probability of occurrence of tree‐nesting species along thermal gradients helps explain the global pattern in ant CTmax.

Results

CTmax and CTmin displayed high and low phylogenetic signals respectively and therefore showed different responses to geographic gradients. Notably, we found that CTmax was higher in higher latitudes. This was explained by a lack of elevational turnover at high latitudes among tree‐nesting species, which are exposed to warmer microclimates and have higher CTmax compared with ground‐nesting species. CTmin decreased with elevation at low latitudes, but did not vary with elevation at higher latitudes.

Main Conclusions

Our findings highlight the important influence of arboreality on the macroecology of thermal tolerance, substantially modifying traditional notions of variation along latitudinal and elevation gradients.
More Than Just Treats? Effects of Grandparental Support for Children Growing up in Adversity
Authors: Riem Madelon M. E. , Hasselman Fred , Psyllou Constantina , van Harmelen Anne‐Laura , Pearce Anna , Minnis Helen , Lodder Paul , Cima Maaike
Published: October 2024

This study examined whether grandparental support is a protective factor for children's socio‐emotional development in the context of adversity. Using longitudinal data from the Millennium Cohort Study, we investigated the effects of grandparental support across development in children with and without adverse childhood experiences (ACEs). Socio‐emotional development was assessed with the Strengths and Difficulties Questionnaire when children were aged 3 years (N = 10,186), 5 years (N = 10,412) and 7 years (N = 10,551). Parent‐reported grandparental childcare, coresidence and financial help were assessed and parents reported on the occurrence of five ACEs: physical and emotional abuse assessed with the Straus’ Conflict Tactics Scale, parental mental illness assessed with the Kessler scale, domestic violence and parental separation. We found that children with relatively higher levels of ACEs showed more prosocial behaviour and less externalizing problems when they received grandparental care compared to non‐grandparental (in)formal care, but only at age 3. By age 7, children with higher levels of ACEs receiving grandparental care showed less prosocial behaviour and more externalizing problems. In addition, grandparental financial support at age 3 was related to more externalizing problems. Post‐hoc analyses showed that internalizing and externalizing behaviours at age 5 were related to an increased probability of grandparental childcare at age 7, indicating that children's socio‐emotional problems trigger grandparental support. Our findings point to a protective effect of grandparental care on children's socio‐emotional development at age 3. Our results highlight the importance of going beyond the nuclear family towards the impact of the wider family network when examining children's socio‐emotional development.

Research Highlights

Three‐year‐old children with high levels of adverse childhood experiences (ACEs) show more prosocial behaviour and less externalizing behaviour when they receive grandparental care.

Grandparental care has therefore protective effects on young children's socio‐emotional development in the context of family adversity.

Grandparents respond to children's socio‐emotional problems and family adversity by increasing financial support and involvement in care.

These findings underscore the importance of going beyond the nuclear family towards the impact of the wider family network when examining children's socio‐emotional development.
Transmitral Pressure Gradients in Patients With Degenerative Mitral Regurgitation After Robotic Mitral Valve Repair With Leaflet Preservation Techniques
Authors: Goldberger Madison I. , Pollak Angela , Fuller Matthew , Sun Katherine , Alenezi Fawaz , Glower Donald , Nicoara Alina
Published: October 2024

Introduction

The hemodynamic effects of mitral valve repair (MVr) with respect to transmitral pressure gradients (TMPGs) have not been described well in patients undergoing leaflet preservation techniques. In a population of patients undergoing robotic MVr with leaflet preservation, we investigate the expected change of the postrepair intraoperative TMPG in the postoperative follow‐up period.

Methods

We retrospectively studied 144 adult patients who underwent robotic MVr. Demographic, clinical, procedural, and echocardiographic data were collected and analyzed.

Results

We found a slight increase in the mean TMPG from the intraoperative postrepair to the immediate postoperative period (intraoperative 3.3 ± 1.4 mmHg vs. first postoperative transthoracic echocardiography [TTE] follow‐up 3.6 ± 1.9 mmHg, p = 0.016) with a gradual decline in the long‐term follow‐up (mean TMPG at last follow‐up TTE 2.4+2.1 mmHg). When dichotomizing the patient population using a cutoff of 3 mmHg for the intraoperative mean TMPG, patients with an intraoperative mean TMPG > 3 mmHg had higher mean TMPG gradients at first TTE (4.5 ± 2.4 vs. 3.1 ± 1.3 mmHg, p < 0.001) as well as at last TTE (3.0± 2.2 vs. 2.1 ± 2.0 mmHg, p = 0.01) when compared with patients with an intraoperative mean TMPG ≤ 3 mmHg. There was no difference in clinical outcomes.

Conclusions

Although the hemodynamic effect of MVr seems to be small, patients with an intraoperative TMPG > 3 mmHg have a higher mean TMPG at follow‐up. The hemodynamic effect does not seem to have an impact on clinical outcome.
Microbial Evolution Drives Adaptation of Substrate Degradation on Decadal to Centennial Time Scales Relevant to Global Change
Authors: Abs Elsa , Coulette David , Ciais Philippe , Allison Steven D.
Published: October 2024

Understanding microbial adaptation is crucial for predicting how soil carbon dynamics and global biogeochemical cycles will respond to climate change. This study employs the DEMENT model of microbial decomposition, along with empirical mutation and dispersal rates, to explore the roles of mutation and dispersal in the adaptation of soil microbial populations to shifts in litter chemistry, changes that are anticipated with climate‐driven vegetation dynamics. Following a change in litter chemistry, mutation generally allows for a higher rate of litter decomposition than dispersal, especially when dispersal predominantly introduces genotypes already present in the population. These findings challenge the common idea that mutation rates are too low to affect ecosystem processes on ecological timescales. These results demonstrate that evolutionary processes, such as mutation, can help maintain ecosystem functioning as the climate changes.
Vagus nerve stimulation for epilepsy: A narrative review of factors predictive of response
Authors: Clifford Harry J. , Paranathala Menaka P. , Wang Yujiang , Thomas Rhys H. , da Silva Costa Tiago , Duncan John S. , Taylor Peter N.
Published: October 2024

Vagus nerve stimulation (VNS) is an established therapy for drug‐resistant epilepsy. However, there is a lack of reliable predictors of VNS response in clinical use. The identification of factors predictive of VNS response is important for patient selection and stratification as well as tailored stimulation programming. We conducted a narrative review of the existing literature on prognostic markers for VNS response using clinical, demographic, biochemical, and modality‐specific information such as from electroencephalography (EEG), magnetoencephalography, and magnetic resonance imaging (MRI). No individual marker demonstrated sufficient predictive power for individual patients, although several have been suggested, with some promising initial findings. Combining markers from underresearched modalities such as T1‐weighted MRI morphometrics and EEG may provide better strategies for treatment optimization.
Biochar Production From Plastic‐Contaminated Biomass
Authors: Hilber Isabel , Hagemann Nikolas , de la Rosa José María , Knicker Heike , Bucheli Thomas D. , Schmidt Hans‐Peter
Published: October 2024

Anaerobic digestion and composting of biowastes are vital pathways to recycle carbon and nutrients for agriculture. However, plastic contamination of soil amendments and fertilizers made from biowastes is a relevant source of (micro‐) plastics in (agricultural) ecosystems. To avoid this contamination, plastic containing biowastes could be pyrolyzed to eliminate the plastic, recycle most of the nutrients, and create carbon sinks when the resulting biochar is applied to soil. Literature suggests plastic elimination mainly by devolatilization at co‐pyrolysis temperatures of > 520°C. However, it is uncertain if the presence of plastic during biomass pyrolysis induces the formation of organic contaminants or has any other adverse effects on biochar properties. Here, we produced biochar from wood residues (WR) obtained from sieving of biowaste derived digestate. The plastic content was artificially enriched to 10%, and this mixture was pyrolyzed at 450°C and 600°C. Beech wood (BW) chips and the purified, that is, (macro‐) plastic‐free WR served as controls. All biochars produced were below limit values of the European Biochar Certificate (EBC) regarding trace element content and organic contaminants. Under study conditions, pyrolysis of biowaste, even when contaminated with plastic, can produce a biochar suitable for agricultural use. However, thermogravimetric and nuclear magnetic resonance spectroscopic analysis of the WR + 10% plastics biochar suggested the presence of plastic residues at pyrolysis temperatures of 450°C. More research is needed to define minimum requirements for the pyrolysis of plastic containing biowaste and to cope with the automated identification and determination of plastic types in biowaste at large scales.
Gender diversity in top management teams and corporate reputation: Evidence from Spanish listed companies
Authors: Martín‐Zamora María‐Pilar , Borralho João Miguel Capela , Hernández‐Linares Remedios
Published: October 2024

Companies gain significant advantages from having a favorable corporate reputation (CR), so researchers have analyzed the factors that contribute to the formation and maintenance of this intangible asset. One of these variables could be gender diversity in management. This study drew on stakeholder, signaling, and critical mass theories to explore how women in firms' top management teams (TMTs) can influence these organizations' CR. A sample of data on Spanish listed companies were collected for the period of 2017–2022. The results reveal that a positive relationship exists between gender diversity in TMTs and CR and that this relationship is moderated by women on boards of directors and by board independence. The findings contribute to the literature by providing evidence of top management's influence on CR. This empirical research also expands the literature on gender diversity in organizations by demonstrating that the positive impact of gender diversity on CR extends beyond boards of directors.
Autoethnographical Research on the Experience of Identity Change as an Artist, Teacher and Teaching Artist
Authors: Jeong Ok‐Hee
Published: October 2024

An autoethnographic exploration of identity formation raises the question of how individuals inhabit, negotiate, accommodate and resist the social groups to which they belong, continually coming to terms with who and what they are. This paper discusses, through this researcher's autobiographical exploration, the ways in which pedagogical discourse and practice produce identities that are constructed within the broader sociocultural context of arts education. As an art educator who has been learning and teaching in the Korean sociocultural context since the 1970s, I have experienced the struggle between my identity as an artist and my identity as a teacher amidst the changes in educational ideology reflected in the Korean national curriculum, which is a set of pedagogical discourses and practices that are constructed within a particular sociocultural context. It can be said that my autobiographical narration has important implications for the practice of art education in connecting individuals and society in an ambiguous and complex future society by enhancing theoretical understanding of wider social phenomena. In this paper, the narrative interpretation of my changing identity as an artist, an art teacher and a teaching artist provides a timely insight into identity shifts in how the artwork we encounter and our perceptions of art are shaped and transformed by our own cultural experiences and recollections of our own personal experiences within the interconnectedness of art and education across time.
Oxidative state is associated with migration distance, but not traits linked to flight energetics
Authors: László Pap Péter , Vincze Orsolya , Vágási Csongor I.
Published: October 2024

Flight can be highly energy demanding, but its efficiency depends largely on flight style, wing shape and wing loading, and a range of morphological and lifestyle adaptations that can modify the cost of sustained flight. Such behavioural and morphological adaptations can also influence the physiological costs associated with migration. For instance, during intense flight and catabolism of reserves, lipid damage induced by pro‐oxidants increases, and to keep oxidative physiological homeostasis under control, the antioxidant machinery can be upregulated. Studies on the oxidative physiology of endurance flight have produced contradictory results, making generalization difficult, especially because multispecies studies are missing. Therefore, to explore the oxidative cost of flight and migration, we used samples collected during the breeding season from 113 European bird species and explored the associations of measures of antioxidant capacity (total antioxidant status, uric acid and glutathione concentration) and oxidative damage of lipids (malondialdehyde) with variables reflecting flight energetics (year‐round or specifically during migration) using a phylogenetic framework. We found that none of the traits predicting year‐round flight energy expenditure (flight style, wing morphology and flight muscle morphology) explained any measures of oxidative state. Our results suggest that birds endure their everyday flight exercise without or with low oxidative cost. However, oxidative damage to lipids and one component of the endogenous antioxidant system (uric acid), measured after the end of spring migration on breeding adult birds, increased with migration distance. Our results suggest that migration could have oxidative consequences that might be carried over to subsequent life‐history stages (breeding).
Interest rate liberalization and corporate innovation: Evidence from natural experiments in China
Authors: Yu Shuangli , Ke Yun , Quan Xiaofeng , Ding Wenhong
Published: October 2024

We examine whether and how interest rate liberalization affects corporate innovation in China. Using the removal of the interest rate ceiling and floor as exogenous shocks, and the numbers of granted patents to proxy for corporate innovation, we find that corporate innovation increases after interest rate liberalization. Our finding holds through several robustness tests. Furthermore, we show that state‐owned enterprises (SOEs) and non‐SOEs benefit from interest rate liberalization differently: Non‐SOEs benefit more from interest rate ceiling removal, whereas SOEs benefit more from interest rate floor removal. Cross‐sectional analyses also show that the effect is more pronounced when bank competition is higher and when firms rely more on external finance. Exploring potential channels through which interest rate liberalization spurs innovation, we find that although ceiling removal mitigates firms’ financial constraints, floor removal lowers corporate loan costs. Our study provides evidence of how financial reform benefits the real economy.