bluuebunny/crossref_metadata_2025 huggingface dataset:
RIPK1 deficiency prevents thymic NK1.1 expression and subsequent iNKT cell development
Authors: Hägglöf Thomas , Parthasarathy Raksha , Liendo Nathaniel , Dudley Elizabeth A. , Leadbetter Elizabeth A.
Published: October 2023

Receptor Interacting Protein Kinase 1 (RIPK1) and caspase-8 (Casp8) jointly orchestrate apoptosis, a key mechanism for eliminating developing T cells which have autoreactive or improperly arranged T cell receptors. Mutations in the scaffolding domain of Ripk1 gene have been identified in humans with autoinflammatory diseases like Cleavage Resistant RIPK1 Induced Autoinflammatory (CRIA) and Inflammatory Bowel Disease. RIPK1 protein also contributes to conventional T cell differentiation and peripheral T cell homeostasis through its scaffolding domain in a cell death independent context. Ripk1 deficient mice do not survive beyond birth, so we have studied the function of this kinase in vivo against a backdrop Ripk3 and Casp8 deficiency which allows the mice to survive to adulthood. These studies reveal a key role for RIPK1 in mediating NK1.1 expression, including on thymic iNKT cells, which is a key requirement for thymic stage 2 to stage 3 transition as well as iNKT cell precursor development. These results are consistent with RIPK1 mediating responses to TcR engagement, which influence NK1.1 expression and iNKT cell thymic development. We also used in vivo and in vitro stimulation assays to confirm a role for both Casp8 and RIPK1 in mediating iNKT cytokine effector responses. Finally, we also noted expanded and hyperactivated iNKT follicular helper (iNKTFH) cells in both DKO (Casp8-, Ripk3- deficient) and TKO mice (Ripk1-, Casp8-, Ripk3- deficient). Thus, while RIPK1 and Casp8 jointly facilitate iNKT effector function, RIPK1 uniquely influenced thymic iNKT cell development most likely by regulating molecular responses to T cell receptor engagement. iNKT developmental and functional aberrances were not evident in mice expressing a kinase-dead version of RIPK1 (RIPK1kd), indicating that the scaffolding function of this protein exerts the critical regulation of iNKT cells. Our findings suggest that small molecule inhibitors of RIPK1 could be used to regulate iNKT cell development and effector function to alleviate autoinflammatory conditions in humans.
In the skin lesions of patients with mycosis fungoides, the number of MRGPRX2-expressing cells is increased and correlates with mast cell numbers
Authors: Hu Man , Pyatilova Polina , Altrichter Sabine , Sheng Caibin , Liu Nian , Terhorst-Molawi Dorothea , Lohse Katharina , Ginter Katharina , Puhl Viktoria , Maurer Marcus , Metz Martin , Kolkhir Pavel
Published: October 2023

Background

Mycosis fungoides (MF) is an indolent T-cell lymphoma that mainly affects the skin and presents with itch in more than half of the patients. Recently, the expression of Mas-related G protein-coupled receptor X2 (MRGPRX2), a receptor of mast cell (MC) responsible for the IgE-independent non-histaminergic itch, has been shown in lesional skin of patients with pruritic skin diseases, including chronic urticaria, prurigo, and mastocytosis. As of yet, limited knowledge exists regarding the MRGPRX2 expression in the skin of patients with MF.

Objectives

To investigate the number of MRGPRX2-expressing (MRGPRX2+) cells in the skin of patients with MF and its correlation with clinical and laboratory characteristics of the disease.

Methods

MRGPRX2 was analyzed in lesional and non-lesional skin of MF patients and healthy skin tissues by immunohistochemistry. Co-localization of MRGPRX2 with the MC marker tryptase was assessed by immunofluorescence. Public single-cell RNAseq data was reanalyzed to identify the MRGPRX2 expression on the distinct cell types.

Results

In lesional skin of MF patients, MRGPRX2+ cell number was higher than in non-lesional skin and healthy control skin (mean:15.12 vs. 6.84 vs. 5.51 cells/mm2, p=0.04), and correlated with MC numbers (r=0.73, p=0.02). MC was the primary cell type expressing MRGPRX2 in MF patients. The ratio of MRGPRX2+ MCs to MRGPRX2+ cells in lesional and non-lesional skin correlated with the severity of disease (r=0.71, p=0.02 and r=0.67, p=0.03, respectively).

Conclusions

Our findings point to the role of MRGPRX2 and MC in the pathogenesis of MF that should be investigated in further studies.
CAR-T cells and CAR-Tregs targeting conventional type-1 dendritic cell suppress experimental autoimmune encephalomyelitis
Authors: Moorman Cody D. , Yu Sherman , Briseno Carlos G. , Phee Hyewon , Sahoo Anupama , Ramrakhiani Ambika , Chaudhry Ashutosh
Published: October 2023

Conventional type 1 dendritic cells (DC1) contribute to the development of pathogenic T helper type 1 (Th1) cells in part via the production of the proinflammatory cytokine interleukin-12. Thus, depletion of DC1 has the potential to dampen autoimmune responses. Here, we developed X-C motif chemokine receptor 1 (XCR1)-specific chimeric antigen receptor (CAR)-T cells and CAR-Tregs that specifically targeted DC1. XCR1 CAR-T cells were successfully generated as CD4+ and CD8+ T cells, expressed XCR1 CAR efficiently, and induced XCR1-dependent activation, cytokine production and proliferation. XCR1 CAR-T cells selectively depleted DC1 when transferred into RAG2−/− mice with a compensatory increase in conventional type 2 DC (DC2) and plasmacytoid DC (pDC). XCR1 CAR-T cell-mediated depletion of DC1 modestly suppressed the onset of Th1-driven experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Diphtheria toxin-mediated DC1 depletion in XCR1-diphtheria toxin receptor mice also suppressed EAE, suggesting that DC1 depletion was responsible for EAE suppression. XCR1 CAR-Tregs were successfully generated and suppressed effector T cells in the presence of XCR1+ cells. Therapeutic treatment with XCR1 CAR-Tregs suppressed Th1-driven EAE. Therefore, we conclude that depletion of DC1 with XCR1 CAR-T cells or immune suppression with XCR1 CAR-Tregs can modestly suppress Th1-driven EAE.
Targeting regulatory T cells by E7777 enhances CD8 T-cell–mediated anti-tumor activity and extends survival benefit of anti-PD-1 in solid tumor models
Authors: Mahdi Haider S. , Woodall-Jappe Mary , Singh Preeti , Czuczman Myron S.
Published: October 2023

Introduction

Regulatory T cell (Treg)-targeting cancer immunotherapy aims to transiently deplete Treg cells in the tumor microenvironment, without affecting effector T cells (Teff), thus both enhancing anti-tumor activity and avoiding autoimmunity. This study evaluated whether adding E7777 (a new formulation of denileukin diftitox [DD]) improved the efficacy of anti-PD-1 antibody therapy. DD is a recombinant protein containing the hydrophobic and catalytic portions of diphtheria toxin fused to full-length human IL-2. E7777 has the same amino acid sequence and brief circulatory half-life as DD, but with greater purity and potency.

Methods

Subcutaneous syngeneic murine solid tumor models (colon cancer CT-26 and liver cancer H22) were used to evaluate safety, efficacy, and overall survival with E7777 and anti-PD-1 antibodies, each administered as monotherapy or in concurrent or sequential combination. In Experiment 1, treatments were compared to assess anti-tumor activity at various time points, with tumors excised and dissociated and tumor leukocytes characterized. In Experiment 2, tumor growth, response, and overall survival were characterized for 100 days following a 3-week treatment.

Results

E7777 administered in combination with anti-PD-1 led to significantly increased anti-tumor activity and durable, extended overall survival compared to either treatment alone. In both tumor models, the Treg cell infiltration induced by anti-PD-1 treatment was counterbalanced by co-treatment with E7777, suggesting potential synergistic activity. Combination therapy showed the most favorable results. Treatment with E7777 was safe and well-tolerated.

Discussion

Combined E7777 and anti-PD-1 therapy was well tolerated and more effective than monotherapy with either drug.
Experimental procedures for flow cytometry of wild-type mouse brain: a systematic review
Authors: Sharp Robert C. , Guenther Dylan T. , Farrer Matthew J.
Published: October 2023

Objective

The aim of this study was to systematically review the neuroimmunology literature to determine the average immune cell counts reported by flow cytometry in wild-type (WT) homogenized mouse brains.

Background

Mouse models of gene dysfunction are widely used to study age-associated neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease. The importance of the neuroimmune system in these multifactorial disorders has become increasingly evident, and methods to quantify resident and infiltrating immune cells in the brain, including flow cytometry, are necessary. However, there appears to be no consensus on the best approach to perform flow cytometry or quantify/report immune cell counts. The development of more standardized methods would accelerate neuroimmune discovery and validation by meta-analysis.

Methods

There has not yet been a systematic review of ‘neuroimmunology’ by ‘flow cytometry’ via examination of the PROSPERO registry. A protocol for a systematic review was subsequently based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) using the Studies, Data, Methods, and Outcomes (SDMO) criteria. Literature searches were conducted in the Google Scholar and PubMed databases. From that search, 900 candidate studies were identified, and 437 studies were assessed for eligibility based on formal exclusion criteria.

Results

Out of the 437 studies reviewed, 58 were eligible for inclusion and comparative analysis. Each study assessed immune cell subsets within homogenized mouse brains and used flow cytometry. Nonetheless, there was considerable variability in the methods, data analysis, reporting, and results. Descriptive statistics have been presented on the study designs and results, including medians with interquartile ranges (IQRs) and overall means with standard deviations (SD) for specific immune cell counts and their relative proportions, within and between studies. A total of 58 studies reported the most abundant immune cells within the brains were TMEM119+ microglia, bulk CD4+ T cells, and bulk CD8+ T cells.

Conclusion

Experiments to conduct and report flow cytometry data, derived from WT homogenized mouse brains, would benefit from a more standardized approach. While within-study comparisons are valid, the variability in methods of counting of immune cell populations is too broad for meta-analysis. The inclusion of a minimal protocol with more detailed methods, controls, and standards could enable this nascent field to compare results across studies.
Quantifying N2 fixation and its contribution to export production near the Tonga-Kermadec Arc using nitrogen isotope budgets
Authors: Forrer Heather J. , Bonnet Sophie , Thomas Rachel K. , Grosso Olivier , Guieu Cecile , Knapp Angela N.
Published: October 2023

The spatial distribution of marine di-nitrogen (N2) fixation informs our understanding of the sensitivities of this process as well as the potential for this new nitrogen (N) source to drive export production, influencing the global carbon (C) cycle and climate. Using geochemically-derived δ15N budgets, we quantified rates of N2 fixation and its importance for supporting export production at stations sampled near the southwest Pacific Tonga-Kermadec Arc. Recent observations indicate that shallow (<300 m) hydrothermal vents located along the arc provide significant dissolved iron to the euphotic zone, stimulating N2 fixation. Here we compare measurements of water column δ15NNO3+NO2 with sinking particulate δ15N collected by short-term sediment traps deployed at 170 m and 270 m at stations in close proximity to subsurface hydrothermal activity, and the δ15N of N2 fixation. Results from the δ15N budgets yield high geochemically-based N2 fixation rates (282 to 638 µmol N m-2 d-1) at stations impacted by hydrothermal activity, supporting 64 to 92% of export production in late spring. These results are consistent with contemporaneous 15N2 uptake rate estimates and molecular work describing high Trichodesmium spp. and other diazotroph abundances associated with elevated N2 fixation rates. Further, the δ15N of sinking particulate N collected at 1000 m over an annual cycle revealed sinking fluxes peaked in the summer and coincided with the lowest δ15N, while lower winter sinking fluxes had the highest δ15N, indicating isotopically distinct N sources supporting export seasonally, and aligning with observations from most other δ15N budgets in oligotrophic regions. Consequently, the significant regional N2 fixation input to the late spring/summer Western Tropical South Pacific results in the accumulation of low-δ15NNO3+NO2 in the upper thermocline that works to lower the elevated δ15NNO3+NO2 generated in the oxygen deficient zones in the Eastern Tropical South Pacific.
Development and validation of a diagnostic model for the identification of chronic ocular graft-versus-host disease (oGVHD)
Authors: Shen Zhan , Hu Bohao , Tao Liyuan , Ma Jiao , Peng Rongmei , Zhao Yinghan , Hong Jing
Published: October 2023

Purpose

To verify the International Chronic Ocular Graft-Versus-Host Disease (ICCGVHD) Group diagnostic criteria and establish an easy-to-use and reliable diagnosis model for quick identification of chronic oGVHD.

Methods

This study included 180 patients (355 eyes) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and visited the Peking University Third Hospital Cornea and Ocular Surface Disease Specialist Clinic from July 2020 to February 2021. The proportion of chronic oGVHD was 76.06% (279/355).

Results

Five complaints, including eye dryness, photophobia, foreign body sensation, eye redness, and burning sensation; six ophthalmic examinations, including Ocular Surface Disease Index (OSDI) score, corneal fluorescein staining (CFS), tear break-up time (TBUT), Schirmer’s test score without anesthesia, conjunctival score, tear meniscus height, and non-ocular GVHD-involved organs were significantly different between patients with chronic oGVHD and control group (p < 0.05). Binary logistic regression (backward LR algorithm) selection demonstrated that three variables retained diagnostic significance for chronic oGVHD: CFS (OR = 2.71 (1.92–3.81), p < 0.001), Schirmer’s test score without anesthesia (OR = 0.83 (0.76–0.91), p < 0.001), and conjunctival score (OR = 1.96 (1.13–3.42), p = 0.031). A nomogram for the identification of chronic oGVHD was developed, and its performance was examined using an internal validation cohort (118 eyes). The areas under the curve (AUCs) for the three-variable-based nomogram were 0.976 (95% CI (0.959–0.992), p < 0.01) and 0.945 (95% CI (0.904–0.986), p < 0.01) in the development and internal validation cohorts, respectively.

Conclusion

This concise three-variable-based nomogram based on ICCGVHD criteria could serve as an easy-to-use and reliable tool for rapid screening of chronic oGVHD.
Fungicides and insecticides can alter the microbial community on the cuticle of honey bees
Authors: Reiß Fabienne , Schuhmann Antonia , Sohl Leon , Thamm Markus , Scheiner Ricarda , Noll Matthias
Published: October 2023

Honey bees are crucial for our ecosystems as pollinators, but the intensive use of plant protection products (PPPs) in agriculture poses a risk for them. PPPs do not only affect target organisms but also affect non-targets, such as the honey bee Apis mellifera and their microbiome. This study is the first of its kind, aiming to characterize the effect of PPPs on the microbiome of the cuticle of honey bees. We chose PPPs, which have frequently been detected in bee bread, and studied their effects on the cuticular microbial community and function of the bees. The effects of the fungicide Difcor® (difenoconazole), the insecticide Steward® (indoxacarb), the combination of both (mix A) and the fungicide Cantus® Gold (boscalid and dimoxystrobin), the insecticide Mospilan® (acetamiprid), and the combination of both (mix B) were tested. Bacterial 16S rRNA gene and fungal transcribed spacer region gene-based amplicon sequencing and quantification of gene copy numbers were carried out after nucleic acid extraction from the cuticle of honey bees. The treatment with Steward® significantly affected fungal community composition and function. The fungal gene copy numbers were lower on the cuticle of bees treated with Difcor®, Steward®, and PPP mix A in comparison with the controls. However, bacterial and fungal gene copy numbers were increased in bees treated with Cantus® Gold, Mospilan®, or PPP mix B compared to the controls. The bacterial cuticular community composition of bees treated with Cantus® Gold, Mospilan®, and PPP mix B differed significantly from the control. In addition, Mospilan® on its own significantly changed the bacterial functional community composition. Cantus® Gold significantly affected fungal gene copy numbers, community, and functional composition. Our results demonstrate that PPPs show adverse effects on the cuticular microbiome of honey bees and suggest that PPP mixtures can cause stronger effects on the cuticular community than a PPP alone. The cuticular community composition was more diverse after the PPP mix treatments. This may have far-reaching consequences for the health of honey bees.
Role of carotid duplex in the assessment of carotid artery restenosis after endarterectomy or stenting
Authors: Szegedi István , Potvorszki Fanni , Mészáros Zsófia Réka , Daniel Cecilia , Csiba László , Oláh László
Published: October 2023

Introduction

Redo carotid endarterectomy (CEA) and carotid stenting (CAS) are often performed when there is evidence of post-procedural restenosis. The incidence of restenosis after carotid reconstruction is not negligible, ranging from 5 to 33%. The diagnosis of significant internal carotid artery (ICA) restenosis is usually based on duplex ultrasound (US) criteria, mostly on peak-systolic flow velocity (PSV). However, there have been no generally accepted duplex US criteria for carotid restenosis after CAS or CEA.

Methods

In this systematic review, the PubMed/ Medline and Scopus databases were screened to find trials that reported duplex US criteria for significant restenosis after CEA and/or CAS. Only those reports were analyzed in which the restenoses were also assessed by CT/MR or digital subtraction angiography as comparators for duplex US.

Results

Fourteen studies met the predetermined search criteria and were included in this review. In most studies, PSV thresholds for significant in-stent ICA restenosis after CAS were higher than those for significant stenosis in non-procedurally treated (native) ICA. Many fewer studies investigated the US criteria for ICA restenosis after CEA. Despite the heterogeneous data, there is a consensus to use higher flow velocity thresholds for assessment of stenosis in stented ICA than in native ICA; however, there have been insufficient data about the flow velocity criteria for significant restenosis after CEA. Although the flow velocity thresholds for restenosis after CAS and CEA seem to be different, the large studies used the same duplex criteria to define restenosis after the two procedures. Moreover, different studies used different flow velocity thresholds to define ICA restenosis, leading to variable restenosis rates.

Discussion

We conclude that (1) further examinations are warranted to determine appropriate duplex US criteria for restenosis after CAS and CEA, (2) single duplex US parameter cannot be used to reliably determine the degree of ICA restenosis, (3) inappropriate US criteria used in large studies may have led to false restenosis rates, and (4) studies are required to determine if there is a benefit from redo carotid artery procedure, such as redo-CEA or redo-CAS, starting with prospective risk stratification studies using current best practice non-invasive care alone.
A Chinese patient with POLR3A-related leukodystrophy: a case report and literature review
Authors: Sun Lei , Lin Weihong , Meng Hongmei , Zhang Wuqiong , Hou Shuai
Published: October 2023

Background

Leukodystrophies are hereditary white matter diseases characterized by genetic polymorphisms and considerable phenotypic variability. They can be classified into myelin and non-myelin malformations. These diseases are rare, affecting 1 out of 250,000–500,000 individuals and can manifest at any age. A subtype of leukodystrophy, associated with missense mutations in the RNA polymerase subunit III (POLR3A) gene, is inherited in an autosomal recessive manner.

Case report

We report and analyse a case of a 34-year-old female who presented with ataxia. Magnetic Resonance Imaging (MRI) of the brain revealed demyelinating lesions in the white matter. Genetic testing identified the c.4044C > G and c.1186-2A > G variants in the POLR3A gene. The patient was diagnosed with hypomyelinating leukodystrophy type 7 and received neurotrophic and symptomatic supportive therapy. However, after 1 month of follow-up, there was no improvement in her symptoms.

Conclusion

POLR3A-induced leukodystrophy is relatively rare and not well understood, making it challenging to diagnose and easy to overlook. The prognosis for this disease is generally poor, significantly impacting the quality of life of affected individuals. Currently, no cure is available for this condition, and treatment is limited to managing symptoms. Further research into new treatment methods for POLR3A-induced leukodystrophy is imperative to improve the quality of life and potentially extend the life expectancy of patients.
Rehabilitation of cognition and psychosocial well-being – a better life with epilepsy (ReCaP-ABLE): a protocol for a randomized waitlist-controlled trial
Authors: Puteikis Kristijonas , Jakonienė Asta , Jasionis Arminas , Wolf Peter , Mameniškienė Rūta
Published: October 2023

Despite advances in the understanding of cognitive dysfunction among people with epilepsy (PWE), evidence for cognitive rehabilitation in epilepsy (CoRE) remains scarce. We present the protocol of a randomized waitlist-controlled trial (ClinicalTrials.gov ID NCT05934786) of a psychological-behavioral intervention aiming to ameliorate quality of life as well as cognitive functioning in a mixed PWE sample. The study is set at Vilnius University Hospital Santaros Klinikos and will offer adult PWE six individual and two group sessions led by a certified psychologist and directed toward improving memory, attention, self-regulation, mood and quality of life. The trial is expected to address major gaps in the literature by providing novel evidence on the effectiveness of CoRE in patients with genetic generalized epilepsies, the importance of epilepsy-specific factors for the response to CoRE, the impact of CoRE on long-term memory as well as its maintenance effects.
The autism spectrum disorder risk gene NEXMIF over-synchronizes hippocampal CA1 network and alters neuronal coding
Authors: Mount Rebecca A. , Athif Mohamed , O’Connor Margaret , Saligrama Amith , Tseng Hua-an , Sridhar Sudiksha , Zhou Chengqian , Bortz Emma , San Antonio Erynne , Kramer Mark A. , Man Heng-Ye , Han Xue
Published: October 2023

Mutations in autism spectrum disorder (ASD) risk genes disrupt neural network dynamics that ultimately lead to abnormal behavior. To understand how ASD-risk genes influence neural circuit computation during behavior, we analyzed the hippocampal network by performing large-scale cellular calcium imaging from hundreds of individual CA1 neurons simultaneously in transgenic mice with total knockout of the X-linked ASD-risk gene NEXMIF (neurite extension and migration factor). As NEXMIF knockout in mice led to profound learning and memory deficits, we examined the CA1 network during voluntary locomotion, a fundamental component of spatial memory. We found that NEXMIF knockout does not alter the overall excitability of individual neurons but exaggerates movement-related neuronal responses. To quantify network functional connectivity changes, we applied closeness centrality analysis from graph theory to our large-scale calcium imaging datasets, in addition to using the conventional pairwise correlation analysis. Closeness centrality analysis considers both the number of connections and the connection strength between neurons within a network. We found that in wild-type mice the CA1 network desynchronizes during locomotion, consistent with increased network information coding during active behavior. Upon NEXMIF knockout, CA1 network is over-synchronized regardless of behavioral state and fails to desynchronize during locomotion, highlighting how perturbations in ASD-implicated genes create abnormal network synchronization that could contribute to ASD-related behaviors.
Chronic intermittent hypoxia due to obstructive sleep apnea slightly alters nutritional status: a pre-clinical study
Authors: Breuillard Charlotte , Moulin Sophie , Bouyon Sophie , Couchet Morgane , Moinard Christophe , Belaidi Elise
Published: October 2023

Obstructive sleep apnea syndrome (OSAS) is associated with chronic intermittent hypoxia (cIH) that causes disturbances in glucose and lipid metabolism. Animals exposed to cIH show lower body weight and food intake, but the protein-energy metabolism has never been investigated. Here, to address the gap, we studied the impact of cIH on nutritional status in rats. A total of 24 male Wistar rats were randomized into 3 groups (n = 8): a control group (Ctrl), a cIH group (cIH) exposed to cIH (30 s 21–30 s 5% fraction of inspired oxygen, 8 h per day, for 14 days), and a pair-fed group (PF) exposed to normoxia with food intake adjusted to the intake of the cIH group rats with anorexia. Body weight and food intake were measured throughout the study. After 14 days, the rats were euthanized, the organs were collected, weighed, and the liver, intestine mucosa, and muscles were snap-frozen to measure total protein content. Food intake was decreased in the cIH group. Body weight was significantly lower in the cIH group only (−11%, p < 0.05). Thymus and liver weight as well as EDL protein content tended to be lower in the cIH group than in the Ctrl and PF groups. Jejunum and ileum mucosa protein contents were lower in the cIH group compared to the PF group. cIH causes a slight impairment of nutritional status and immunity. This pre-clinical work argues for greater consideration of malnutrition in care for OSAS patients. Further studies are warranted to devise an adequate nutritional strategy.
Ultrasound radiomics models based on multimodal imaging feature fusion of papillary thyroid carcinoma for predicting central lymph node metastasis
Authors: Dai Quan , Tao Yi , Liu Dongmei , Zhao Chen , Sui Dong , Xu Jinshun , Shi Tiefeng , Leng Xiaoping , Lu Man
Published: October 2023

Objective

This retrospective study aimed to establish ultrasound radiomics models to predict central lymph node metastasis (CLNM) based on preoperative multimodal ultrasound imaging features fusion of primary papillary thyroid carcinoma (PTC).

Methods

In total, 498 cases of unifocal PTC were randomly divided into two sets which comprised 348 cases (training set) and 150 cases (validition set). In addition, the testing set contained 120 cases of PTC at different times. Post-operative histopathology was the gold standard for CLNM. The following steps were used to build models: the regions of interest were segmented in PTC ultrasound images, multimodal ultrasound image features were then extracted by the deep learning residual neural network with 50-layer network, followed by feature selection and fusion; subsequently, classification was performed using three classical classifiers—adaptive boosting (AB), linear discriminant analysis (LDA), and support vector machine (SVM). The performances of the unimodal models (Unimodal-AB, Unimodal-LDA, and Unimodal-SVM) and the multimodal models (Multimodal-AB, Multimodal-LDA, and Multimodal-SVM) were evaluated and compared.

Results

The Multimodal-SVM model achieved the best predictive performance than the other models (P < 0.05). For the Multimodal-SVM model validation and testing sets, the areas under the receiver operating characteristic curves (AUCs) were 0.910 (95% CI, 0.894-0.926) and 0.851 (95% CI, 0.833-0.869), respectively. The AUCs of the Multimodal-SVM model were 0.920 (95% CI, 0.881-0.959) in the cN0 subgroup-1 cases and 0.828 (95% CI, 0.769-0.887) in the cN0 subgroup-2 cases.

Conclusion

The ultrasound radiomics model only based on the PTC multimodal ultrasound image have high clinical value in predicting CLNM and can provide a reference for treatment decisions.
Validation of the Chinese version of PedsQL™ brain tumor module
Authors: Wang Juan , Li Jin , Jiang Xiaofan , Sun Pei , Li Xia , Wang Guanyi
Published: October 2023

Background

The study introduced the Pediatric Quality of Life Inventory™ (PedsQL™) brain tumor module for the first time in China. Further, the Chinese version of the PedsQL™ brain tumor module was developed and its feasibility, reliability, and validity were investigated.

Methods

A total 129 cases completed the assessment. Feasibility was evaluated according to the percentage of missing items and the time required to complete the questionnaire. Internal consistency, retest reliability, and split-half reliability were tested to confirm reliability. We evaluated validity by testing content validity, construct validity, and criterion-related validity. The consistency between the child-self and parent-proxy reports was analyzed by calculating the correlation coefficient (r value) between them.

Results

The Cronbach's alpha values for all subscales were above 0.7 and many subscales scored more than 0.9. The intra-class correlation coefficients of retest reliability were higher than 0.9. The split-half reliability scores for all subscales were higher than 0.6. The factor-item correlations ranged between 0.575–0.922 in the child report and 0.492–0.949 in the parent report. Exploratory factor analyses produced five factors corresponding to each subscale in the child report and six factors in the parent report.

Conclusion

The feasibility, reliability, and validity of the Chinese PedsQL™ brain tumor module were ascertained through this study. This module can be used to effectively monitor children with brain tumors and conduct descriptive or exploratory studies to determine the risk factors affecting their quality of life. This would help develop a new basis for formulating measures to improve patient prognosis and quality of life.
Evaluating the impact of modeling the family effect for clonal selection in potato-breeding programs
Authors: Martins Vinicius Samuel , Andrade Mario Henrique Murad Leite , Padua Leticia Novais , Miguel Luciana Aparecida , Fernandes Filho Claudio Carlos , Guedes Marcio Lisboa , Nunes Jose Airton Rodrigues , Hoffmann Leo Jr , Zotarelli Lincoln , Resende Márcio Fernando Ribeiro de Jr , Carneiro Pedro Crescêncio Souza , Marçal Tiago de Souza
Published: October 2023

Because of its wide distribution, high yield potential, and short cycle, the potato has become essential for global food security. However, the complexity of tetrasomic inheritance, the high level of heterozygosity of the parents, the low multiplication rate of tubers, and the genotype-by-environment interactions impose severe challenges on tetraploid potato–breeding programs. The initial stages of selection take place in experiments with low selection accuracy for many of the quantitative traits of interest, for example, tuber yield. The goal of this study was to investigate the contribution of incorporating a family effect in the estimation of the total genotypic effect and selection of clones in the initial stage of a potato-breeding program. The evaluation included single trials (STs) and multi-environment trials (METs). A total of 1,280 clones from 67 full-sib families from the potato-breeding program at Universidade Federal de Lavras were evaluated for the traits total tuber yield and specific gravity. These clones were distributed in six evaluated trials that varied according to the heat stress level: without heat stress, moderate heat stress, and high heat stress. To verify the importance of the family effect, models with and without the family effect were compared for the analysis of ST and MET data for both traits. The models that included the family effect were better adjusted in the ST and MET data analyses for both traits, except when the family effect was not significant. Furthermore, the inclusion of the family effect increased the selective efficiency of clones in both ST and MET analyses via an increase in the accuracy of the total genotypic value. These same models also allowed the prediction of clone effects more realistically, as the variance components associated with family and clone effects within a family were not confounded. Thus, clonal selection based on the total genotypic value, combining the effects of family and clones within a family, proved to be a good alternative for potato-breeding programs that can accommodate the logistic and data tracking required in the breeding program.
Physiological and molecular mechanisms of Acacia melanoxylon stem in response to boron deficiency
Authors: Chen Zhaoli , Bai Xiaogang , Zeng Bingshan , Fan Chunjie , Li Xiangyang , Hu Bing
Published: October 2023

Boron is an essential micronutrient for plant growth as it participates in cell wall integrity. The growth and development of Acacia melanoxylon stem can be adversely affected by a lack of boron. To explore the mechanism of boron deficiency in A. melanoxylon stem, the changes in morphological attributes, physiological, endogenous hormone levels, and the cell structure and component contents were examined. In addition, the molecular mechanism of shortened internodes resulting from boron deficiency was elucidated through transcriptome analysis. The results showed that boron deficiency resulted in decreased height, shortened internodes, and reduced root length and surface area, corresponding with decreased boron content in the roots, stems, and leaves of A. melanoxylon. In shortened internodes of stems, oxidative damage, and disordered hormone homeostasis were induced, the cell wall was thickened, hemicellulose and water-soluble pectin contents decreased, while the cellulose content increased under boron deficiency. Furthermore, plenty of genes associated with cell wall metabolism and structural components, including GAUTs, CESAs, IRXs, EXPs, TBLs, and XTHs were downregulated under boron deficiency. Alterations of gene expression in hormone signaling pathways comprising IAA, GA, CTK, ET, ABA, and JA were observed under boron deficiency. TFs, homologous to HD1s, NAC10, NAC73, MYB46s, MYB58, and ERF92s were found to interact with genes related to cell wall metabolism, and the structural components were identified. We established a regulatory mechanism network of boron deficiency-induced shortened internodes in A. melanoxylon based on the above results. This research provides a theoretical basis for understanding the response mechanism of woody plants to boron deficiency.
“It was too much for me”: mental load, mothers, and working from home during the COVID-19 pandemic
Authors: Delaney Caitriona , Bobek Alicja , Clavero Sara
Published: October 2023

This study analyses the experiences of working from home (WfH) during the COVID-19 pandemic and the impact it has on working mothers through the lens of “mental load.” Remote study, often lauded as a way to reduce work/life conflicts, can bring new multifaceted challenges for working mothers and, as this study shows, suddenly shifting to remote work led to the boundaries among work, care, and domestic labour becoming blurred. The data used here are from narrative interviews collected as part of the RESpondIng to outbreakS through co-creaTIve inclusive equality stRatEgies (RESISTIRÉ) Horizon 2020 project, which analyses the impact of COVID-19 policies on gendered inequalities across the EU27 and Türkiye, Serbia, UK, and Iceland. We draw on 12 narratives from working mothers in Austria, Bulgaria, Czechia, Denmark, Ireland, Estonia, Greece, Portugal, Netherlands, the United Kingdom, and Slovakia. Employing thematic analysis, the analysis of these narratives, illuminates the challenges and opportunities of WfH and highlights its impact on mental load. While adding to the research on WfH and working mothers, the analysis also illustrates the lessons to be taken forward as well as underscoring the importance of mental load both theoretically and empirically.
Mental health and post-traumatic stress disorder in firefighters: an integrated analysis from an action research study
Authors: Oliveira Joana , Aires Dias Joana , Duarte Isabel Catarina , Caldeira Salomé , Marques António Reis , Rodrigues Vítor , Redondo João , Castelo-Branco Miguel
Published: October 2023

Introduction

The presence of post-traumatic stress disorder (PTSD) symptomatology in firefighters is an ever-pressing issue that requires close attention for adequate interventions. The present study investigated PTSD and global psychopathology prevalence in a sample of highly risk-exposed Portuguese firefighters, collected after the widespread deadly wildfires in 2017 that ravaged the country. Following an action research approach, the aim of this study was to depict this sample and examine the impact of cumulative adverse experiences on their mental health, which is a phenomenon worth attention.

Method

From an initial sample of 283 firefighters who manifested interest in participating, a total of 139 firefighters from the Coimbra District, of whom 130 unequivocally experienced a potentially traumatic/adverse event as a firefighter, completed BSI (to obtain indicators on psychopathology), QEPAT (an inventory of adverse events possibly experienced as a firefighter), and PCL-5 (a measure of PTSD symptomatology) through an online survey during the year 2018 by the Regional Medical Organization, as proposed and supervised by the local Centre for Prevention and Treatment of Psychological Trauma (CPTTP).

Results

We found a global prevalence of 8.6% of possible PTSD and 14.4% of possible psychopathology (n = 139). When considering only firefighters who unequivocally reported a potentially traumatic/adverse event as a firefighter (n = 130), 9.2% present possible PTSD, and 13.8% present possible global psychopathology. This sample experienced a mean of 28 adverse events during firefighting work. Linear regressions (n = 118) demonstrated that the perceived severity of the most traumatic event reported and the experience of more adverse events were both related to an increase in PTSD symptomatology. Global psychopathology was associated with PCL-5 scores, with an emphasis on paranoid ideation, hostility, depression, anxiety, and phobic anxiety.

Discussion

The severe wildfires of 2017 did not impact PTSD scores in this sample (collected the year after), suggesting that cumulative adverse events are more important than particular episodes. However, the number of reported events was related to PTSD scores. These results can be used to develop interventions that target all firefighters by addressing risk and protective factors. This action research study motivated specialized aid for firefighters involved in this study.
Late preterm and very preterm infants differ in the acquisition time and quantity of reaches with grasping at reaching onset: an exploratory study
Authors: França Andressa Lagoa Nascimento , Teruia Priscila Maier , de Oliveira Arguelho Amanda , Tudella Eloisa , Soares-Marangoni Daniele Almeida
Published: October 2023

Introduction

The onset of manual reaching allows the expansion of the infant’s interaction with the environment. When born preterm, infants become vulnerable to problems in the development of reaching. However, it is still unknown whether there are differences in reaching according to the degree of prematurity.

Objective

This study aimed to explore the differences in reaching acquisition and behavior between late preterm and very preterm infants, as well as whether age and clinical variables influence the results.

Method

This is an exploratory, comparative, observational study. In total, 24 infants were included soon after reaching onset; 12 infants were born late preterm (35.55 ± 0.67 gestational weeks) and 12 very preterm (30.60 ± 0.05 gestational weeks). Infants were placed in a baby seat, and a toy was placed at a reachable distance for 2 min. Reaching behavior was the primary variable; birth weight and length of hospital stay were secondary variables.

Results

The age of reaching onset was higher in the very preterm group. The proportion of reaches with grasping was higher in the late preterm group. These differences were affected by the lower birth weight and longer length of hospital stay in the very preterm group. The proportions of proximal and distal adjustments did not differ between groups.

Conclusion

Very preterm infants presented disadvantages in the acquisition time and the number of reaches with grasping, but not in the proportions of proximal and distal adjustments of reaching, relative to late preterm infants. Group differences were influenced by clinical variables.
Health surveillance for SARS-CoV-2: infection spread and vaccination coverage in the schools of Modena province, Italy
Authors: Paduano Stefania , Facchini Maria Chiara , Borsari Lucia , D’Alterio Alessandra , Iacuzio Laura , Greco Antonella , Fioretti Elisabetta , Creola Giacomo , Kahfian Zaynalabedin , Zona Stefano , Bargellini Annalisa , Filippini Tommaso
Published: October 2023

Introduction

In Italy, over 4.8 million individuals aged 0–19 years have been infected with SARS-CoV-2. This study aims to evaluate the spread of SARS-CoV-2 within schools in Modena province and the influence of anti-SARS-CoV-2 vaccination coverage.

Methods

We performed a survey in the period 1 September-15 December 2021, involving student population aged 0–19 years and related teachers screened for SARS-CoV-2 infection using nasopharyngeal swab after the detection of an index case within their class. During the study period, vaccination against SARS-CoV-2 was actively offered to all subjects aged ≥12 years.

Results

A total of 13,934 subjects were tested, 12,534 students and 1,400 teachers (594 classes). We identified a total of 594 and 779 index and secondary cases, respectively. We found that 9.8% of students and 10.6% of teachers were positive for SARS-CoV-2. Overall at the test time, 32.5% were vaccinated with at least one dose of anti-SARS-CoV-2 vaccine. Among secondary cases, 7.8% were vaccinated compared to 34.9% among negative tested subjects. A higher secondary attack rate was for non-vaccinated subjects rather than vaccinated ones (8.1% vs. 1.4%). Higher secondary attack rates were reported for subjects attending infant and primary school (5.9 and 9.6%, respectively). Lower secondary attack rates were for those who attended middle school (4.9%) and especially high school (1.7%).

Conclusion

Our results highlight the differential spread of the infection within various educational settings and that the vaccination, available in the study period for the population aged ≥12, have mitigated SARS-CoV-2 spread in high and middle schools.
Prevalence of COVID-19 fear and its association with quality of life and network structure among Chinese mental health professionals after ending China’s dynamic zero-COVID policy: a national survey
Authors: Lam Mei Ieng , Chen Pan , Zhang Qinge , Sha Sha , An Feng-Rong , Su Zhaohui , Cheung Teris , Ungvari Gabor S. , Ng Chee H. , Xiang Yu-Tao , Feng Yuan
Published: October 2023

Background

China recorded a massive COVID-19 pandemic wave after ending its Dynamic Zero-COVID Policy on January 8, 2023. As a result, mental health professionals (MHPs) experienced negative mental health consequences, including an increased level of fear related to COVID-19. This study aimed to explore the prevalence and correlates of COVID-19 fear among MHPs following the end of the Policy, and its association with quality of life (QoL) from a network analysis perspective.

Methods

A cross-sectional national study was conducted across China. The correlates of COVID-19 fear were examined using both univariate and multivariate analyses. An analysis of covariance (ANCOVA) was conducted to determine the relationship between fear of COVID-19 and QoL. Central symptoms were identified using network analysis through the “Expected Influence” of the network model while specific symptoms directly correlated with QoL were identified through the “flow function.”

Results

A total of 10,647 Chinese MHPs were included. The overall prevalence of COVID-19 fear (FCV-19S total score ≥ 16) was 60.8% (95% CI = 59.9–61.8%). The binary logistic regression analysis found that MHPs with fear of COVID-19 were more likely to be married (OR = 1.198; p < 0.001) and having COVID-19 infection (OR = 1.235; p = 0.005) and quarantine experience (OR = 1.189; p < 0.001). Having better economic status (good vs. poor: OR = 0.479; p < 0.001; fair vs. poor: OR = 0.646; p < 0.001) and health status (good vs. poor: OR = 0.410; p < 0.001; fair vs. poor: OR = 0.617; p < 0.001) were significantly associated with a lower risk of COVID-19 fear. The ANCOVA showed that MHPs with fear of COVID-19 had lower QoL [F = 228.0, p < 0.001]. “Palpitation when thinking about COVID-19” was the most central symptom in the COVID-19 fear network model, while “Uncomfortable thinking about COVID-19” had the strongest negative association with QoL (average edge weight = −0.048).

Conclusion

This study found a high prevalence of COVID-19 fear among Chinese MHPs following the end of China’s Dynamic Zero-COVID Policy. Developing effective prevention and intervention measures that target the central symptoms as well as symptoms correlated with QoL in our network structure would be important to address COVID-19 fear and improve QoL.
The use of Zuckerkandl's tubercle as an anatomical landmark in identifying recurrent laryngeal nerve and superior parathyroid gland during total thyroidectomy: a prospective single-surgeon study
Authors: Gurluler Ercument
Published: October 2023

Objective

To determine the incidence and characteristics of Zuckerkandl's tubercle (ZT), and its relationship with recurrent laryngeal nerve (RLN) and the superior parathyroid gland (SPG) in the setting of total thyroidectomy.

Methods

A total of 421 patients (mean (min-max) age: 45.6 (18–78) years, 76.2% were females) who had total thyroidectomy were included in this prospective single-surgeon thyroidectomy series study. Patient demographics and thyroidectomy indications (benign and malignant) were recorded in each patient. The presence, grade and laterality of ZT, and its relationship with RLN and SPG were recorded during surgery.

Results

Most of the thyroidectomy indications (69.1%) were related to a malignant disease. The ZT was unrecognizable in 41(9.7%) of 421 patients. In 380 patients with identifiable ZT, the grade 2 (46.3%) ZT was the most common finding. Majority of ZTs (92.9%) were unilaterally located (right-sided: 64.9%; left-sided: 35.1%). In majority of the cases (83.2%), the RLN was found to lie medial to ZT. Overall, SPG was identified in close proximity to ZT in 66.6% of patients (Class 2 [0.5–1 cm from ZT] in 46.6% and Class 3 [<0.5 cm from ZT] in 20.0%). SPG was more likely to be identified in close proximity to ZT when the grade of ZT was higher, which was found to be located 0.5–1 cm from the ZT in 56.9% and 42.7% of grade 2 and grade 3 ZTs, respectively, and <0.5 cm from the ZT in 46.1% of grade 3 ZTs.

Conclusion

In conclusion, this prospective single-surgeon thyroidectomy series study indicates the likelihood of localizing the RLN medial to ZT, and the SPG in close proximity to ZT during total thyroidectomy operations. Hence, the ZT can be used as a reliable and constant landmark to localize both the RLN and the SPG during thyroid surgery, which enables minimizing the risk of iatrogenic injury to RLN, while ensuring a parathyroid-sparing thyroidectomy. The thyroid surgeon should have complete knowledge of thyroid gland anatomy and embryogenesis and should follow a careful and meticulous approach particularly for dissections around larger ZTs, given the increased likelihood of SPG and RLN to be in close proximity.