bluuebunny/crossref_metadata_2025 huggingface dataset:
A unique expression pattern of LAG3 distinct from that of other immune checkpoints in diffuse large B‐cell lymphoma
Authors: Lee Hyunjee , Yoon Sang Eun , Kim Seok Jin , Kim Won Seog , Cho Junhun
Published: June 2023

Background

Although some patients with diffuse large B‐cell lymphoma (DLBCL) show a response to immunotherapy, there are still many who do not respond. This suggests that various immune checkpoints are complicatedly intertwined in the composition of the tumor microenvironment of DLBCL.

Patients and Methods

To comprehensively understand the expression of various immune checkpoint genes in DLBCL, we performed NanoString assay in 98 patients to investigate 579 genes. In addition, we performed immunohistochemistry for LAG‐3 and PD‐L1 to compare the results with expression in NanoString assay.

Results

As a result of hierarchical clustering of NanoString assay, 98 DLBCLs were classified into three tumor immune microenvironment clusters. Most immune checkpoint genes showed the highest expression in cluster A and the lowest in cluster C. However, the expression of LAG3 was the highest in cluster C and the lowest in cluster A, showing an expression pattern opposite to that of other immune checkpoint genes. In Cluster A, the expression of genes related to T‐cell activity such as CD8A and GZMB was increased. In Cluster C, the expression of genes related to major histocompatibility complex molecules was the highest. Immunohistochemical stains showed modest agreement with the NanoString results but did not help clustering.

Conclusion

Our results show that the unique expression pattern of LAG3 in DLBCL contrasts with that of other immune checkpoints. We suggest that the combination of anti‐PD‐1/PD‐L1 and anti‐LAG‐3 blockades in the immunotherapy of DLBCL patients can have a synergistic effect, improving the immunotherapy efficacy and outcome in DLBCL patients.
Recurring nodular scleritis following inactivated vaccination for COVID‐19
Authors: Peyman Alireza , Pourazizi Mohsen , Dehghani Shakiba , Ghorbani Sarah
Published: June 2023

Key Clinical Message

Though COVID‐19 vaccination saved many lives all around the world, it has had many adverse effects including ophthalmologic side effects. It is important to report such adverse effects to provide timely diagnosis and management.

Since the COVID‐19 global outbreak, many types of vaccines have been introduced. These vaccines have been associated with some adverse effects including ocular manifestations. Herein, we report a case of a patient who developed nodular scleritis shortly after receiving the first and second doses of the inactivated COVID‐19 vaccine, Sinopharm.
Neonatal rhizomelic chondrodysplasia punctata type 2 caused by a novel homozygous variant in the GNPAT gene
Authors: Sayed Jamal , Gamal Ahmed , Theyab Abdulrahman , Algahtani Mohamed , Aldaadi Banan Bakheet
Published: June 2023

Key Clinical Message

Rhizomelic chondrodysplasia punctata (RCDP) is a rare disorder (~1 in 100,000 live births) of faulty plasmalogen biosynthesis and defective peroxisomal metabolism. RCDP type 2 is specifically caused by glyceronephosphate O‐acyltransferase (GNPAT) gene mutations and is inherited as an autosomal recessive trait. The disorder is characterized by skeletal abnormalities, distinctive facial features, intellectual disability, and respiratory distress. The case report describes a newborn baby with a dysmorphic facial appearance and skeletal abnormalities who was admitted to neonatal intensive care with respiratory distress. His parents were first cousins. The whole exome sequencing for this patient identified an interesting homozygous variant in the GNPAT gene [GNPAT (NM_014236.4):c.1602+1G>A (p.?), Chr1 (GRCh37):g.231408138G>A]. This case report aims to highlight the patient's clinical presentation with the variant and the whole exome sequencing, indicating the identification of a novel mutation in the GNPAT gene causing RCDP type 2.
A case of intradural lumbar disc herniation
Authors: Bhattarai Utsav , Gurung Pritam , Shrestha Janam , Dhakal Sudan , Acharya Samir , Pant Basant
Published: June 2023

Key Clinical Message

MRI remains the best tool in the diagnosis of this disease entity however preoperative diagnosis remains a difficult task. A high degree of suspicion is raised when intraoperative findings and preoperative image description become incompatible.

Lumbar disc herniation into the dural space is a rare phenomenon of lumbar disc degeneration with an unclear remaining pathogenesis. Intraoperative ultrasonography and histopathological examination of resected specimen help in the diagnosis of intradural disc herniation. Prompt surgery is recommended due to the high incidence of cauda equina syndrome.
Bronchobiliary fistulae as a complication of untreated pulmonary hydatid cyst presenting with bilioptysis: A report of two cases
Authors: Mardani Parviz , Kamran Hooman , Khosravi Fateme , Shahriarirad Reza , Shahabinejad Pardis , Geramizadeh Bita , Soleimani Neda , Amirian Armin
Published: June 2023

Key Clinical Message

We reported two patients, a 45‐year‐old lady and a 48‐year‐old man, known cases of untreated liver and lung hydatid cysts complicated with bronchobiliary fistulae. Surgery was performed, and bronchobiliary fistulae were diagnosed intraoperatively. Lobectomy was done on the lobe, which was chronically infected. Symptoms resolved after surgery in both cases. Green‐colored sputum in a patient with a history of echinococcosis should raise the physician's attention to the probability of a connection between the bronchial tree and the biliary tract. Surgery in advanced cases is a suitable therapeutic option.
Robotic‐assisted percutaneous pelvis fixation: A case report
Authors: Smith Austin F. , Carlson Jon B.
Published: June 2023

Key Clinical Message

It may be possible to extend the use of the robotic arm to pelvic and acetabular surgery leading to safe, repeatable screw placement, and less radiation exposure for patients, surgeons and OR staff.

In this case, a novel, robotic‐assisted technique was used to place a sacroiliac screw in a patient with unstable injuries of the pelvic ring. Intraoperative and postoperative fluoroscopic, radiographic, and CT imaging demonstrated a safely positioned 6.5 mm cannulated screw without unplanned cortical violation or impingement on neurovascular structures. To our knowledge, this is the first such reported case using a robot widely available in the Americas or Europe.
Energy‐efficient Electrochemical Hydrogen Production Combined with Biomass Oxidation Using Polyoxometalate and Metal Salts
Authors: Xu Weizhuo , Zhou Bingjie , Wang Qing , Xu Guohao , Li Ning , Liu Wei , Zhang Z. Conrad
Published: June 2023

Biomass oxidation in anode electrolyte solution is investigated for energy‐efficient hydrogen production. The redox of polyoxometalate (POM) as both biomass oxidation catalyst in the solution and charge carrier through regeneration at the graphite electrode promotes hydrogenation generation at the cathode, but suffers from a limited rate of biomass degradation due to the complex structure of solid lignocellulosic biomass. Herein, transition metal salts (CuCl2, CrCl3 and FeCl3) are studied as the synergistic catalysts with POM to promote the degradation of raw biomass. Notably, FeCl3 has the most significant effect in promoting the hydrolysis of cellulose by coordinating with the oxygen donor groups of carbohydrates and helps re‐oxidize reduced POM to maintain high oxidation ability of the solution. As a result, the faraday efficiency of hydrogen production at the cathode could reach 90 %. Coupling oxidation of biomass by contiguously recharged metal salts and POM with electrochemical hydrogen evolution, pure hydrogen source with improved economics is obtained at low energy consumption.
Radical Covalent Catalysis: Recent Advances and Future Developments
Authors: Xiao Wei , Wu Jie
Published: June 2023

Radical covalent catalysis, namely radical catalysis via a radical catalyst addition and elimination process, has emerged in the past few decades. This review is aimed to summarize the recent advances of radical covalent catalysis by highlighting some outstanding challenges and confirming potential areas of improvement, which may offer inspiration for future studies.
Computational modelling of explosions caused by failed Li‐ion batteries
Authors: Simancas Nicolás Santiago Navarro , Méndez Juliana Puello , Vianna Sávio Souza Venâncio
Published: June 2023

The implementation rate of renewable energy sources such as lithium‐ion batteries has grown over the last decade. Consequently, the number of explosion occurrences associated with these batteries has also increased. Such events are due to a process called thermal runaway (TR). The flamelet combustion approach has been widely used to model premixed combustion. However, its applicability for modelling accidental explosions from lithium‐ion batteries remains limited. Moreover, the effects and contributions from stress, strain, and wrinkling on the flame front in gas mixtures from Li‐ion batteries are not fully understood. As far as computational modelling is concerned, the same effects require further investigation. The current research investigates the performance of the flamelet approach for modelling premixed combustion scenarios caused by the gases ejected by a fully charged lithium‐ion‐phosphate (LFP) battery. A new laminar burning velocity correlation is proposed based on experimental data to calculate overpressure, flame position, and flame velocity in a semi‐confined geometry. Promising results are presented resorted by good agreement with experimental data.
Outcomes and predictors of patients with moderate or severe functional mitral regurgitation and nonischemic dilated cardiomyopathy
Authors: Li Jiangtao , Wei Xiang
Published: June 2023

Background

Patients with functional mitral regurgitation (FMR) and nonischemic dilated cardiomyopathy (DCM) are associated with high mortality.

Objectives

Our study aimed to compare the clinical outcomes between different treatment strategies and identify predictors associated with the adverse outcomes.

Methods

A total of 112 patients with moderate or severe FMR and nonischaemic DCM were included in our study. The primary composite outcome was all‐cause death or unplanned hospitalization for heart failure. The secondary outcomes were individual components of the primary outcome and the cardiovascular death.

Results

In this study, the primary composite outcome occurred in 26 patients (44.8%) in mitral valve repair (MVr) group and 37 patients (68.5%) in medical group (hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.14–0.55; p < .001). The 1‐, 3‐, and 5‐year survival rates for patients with MVr were 96.6%, 91.8%, and 77.4%, respectively, which were significantly higher than that of medical group: 81.2%, 71.9%, and 65.1%, respectively (HR, 0.32; 95% CI, 0.12–0.87; p = .03). Left ventricular ejection fraction (LVEF) < 41.5% (p < .001) and atrial fibrillation (p = .02) were independently associated with the primary outcome. LVEF < 41.5% (p = .007), renal insufficiency (p = .003), and left ventricular end‐diastolic diameter > 66.5 mm (p < .001) were independently associated with heightened risk for all‐cause death.

Conclusion

Compared with medical therapy, MVr was associated with a better prognosis in patients with moderate or severe FMR and nonischemic DCM. We observed that LVEF < 41.5% was the only independent predictor of the primary outcome and all individual components of secondary outcomes.
Low‐cost Photoactive Hybrid Materials: From Green Synthesis to Multi‐technique Analytical Characterization
Authors: Conterosito Eleonora , Toson Valentina , Boccaleri Enrico , Antonioli Diego , Milanesio Marco , Palin Luca , Barolo Claudia , Barbero Nadia , Galliano Simone , Gianotti Valentina
Published: June 2023

Low‐cost photoactive hybrid materials for light management, based on neutral organic molecules intercalated into saponite, were prepared by facile green methods and characterized. TPBI (2‐(2’‐tosylaminophenyl)benzimidazole) was chosen as an organic host dye, envisioning its application as a downconverter in silicon or dye‐sensitized photovoltaic modules. Mixed with a cationic surfactant, the neutral molecule was intercalated with a sort of “trojan horse” approach by an easy, almost solvent‐free method, thus limiting its aggregation. The obtained material was characterized by combining spectroscopic, diffractometric, and microscopic techniques. Moreover, the intercalation of the dye, the species present in the interlayer, their stability and mutual interactions were assessed by TGA‐GC‐MS. We obtained a material containing a fluorescent dye in the solid state and stabilized by intercalation and dispersion into saponite. At last, this material was used to prepare a photoactive polymer by melt blending, obtaining materials with the desired optical properties, with Stokes shifts larger than 100 nm and an emission yield above 50%.
LINC01116 affects patient survival differently and is dissimilarly expressed in ER+ and ER− breast cancer samples
Authors: Karimi Taheri Mohammadjavad , Ghanbari Sogol , Gholipour Akram , Givi Taraneh , Sadeghizadeh Majid
Published: June 2023

Background

Breast cancer is the most commonly detected cancer and one of the leading causes of cancer mortality. Emerging evidence supports that aberrant expression of lncRNAs is correlated with tumor progression and various aspects of tumor development.

Aim

This study aimed to evaluate the expression pattern of LINC01116 in breast cancer tissues and investigate the impact of LINC01116 on patients' survival.

Methods and Results

Microarray and qRT‐PCR data analysis were performed, and the KM‐plotter database was used in this study. In addition, the gain of function approach was performed to examine the effect of LINC01116 on breast cancer cells in‐vitro. The results exhibited that LINC01116 is meaningfully upregulated in the ER+ tumor specimens compared to the ER– ones. Also, relative to normal tissues, the expression of LINC01116 in ER+ and ER– tumor tissues significantly increased and decreased, respectively. ROC curve analysis revealed the power of LINC01116 in distinguishing ER+ from ER– samples. Additionally, the Kaplan‐Meier survival analysis showed that the LINC01116 expression positively correlates with survival probability in all as well as ER+ patients. However, this correlation was negative in ER– patients. Furthermore, our results showed that the overexpression of LINC01116 induces TGF‐β signaling in ER– cells (MDA‐MB‐231), and microarray data analysis revealed that LINC01116 is significantly upregulated in 17β‐Estradiol treated MCF7 cells.

Conclusion

In conclusion, our results suggest that LINC01116 can be a potential biomarker in distinguishing ER+ and ER– tissues and has different effects on patients' survival based on ER status by affecting TGF‐β and ER signaling.
Methotrexate Polyglutamates Exposure – Response Modeling in a Large Cohort of Rheumatoid Arthritis Patients Starting Methotrexate
Authors: Hebing Renske C. F. , Bartelink Imke H. , Gosselt Helen R. , Heil Sandra G. , de Rotte Mauritis C. F. J. , de Jong Pascal H. P. , Nurmohamed Mike T. , de Jonge Robert , Mathôt Ron A. A.
Published: June 2023

Methotrexate polyglutamates (MTX‐PG) concentrations in red blood cells (RBCs) have been suggested as a biomarker of response in patients with rheumatoid arthritis (RA) receiving low‐dose MTX therapy. We investigated the association and interpatient variability between RBC‐MTX‐PG3‐5‐exposure and response in patients with RA starting MTX. Data of three prospective cohorts were available. The relationship between exposure and Disease Activity Score in 28 joints (DAS28) was analyzed using a population pharmacokinetic‐pharmacodynamic model. Relevant covariates were tested using full covariate modeling and backward elimination. From 395 patients, 3,401 MTX‐PG concentrations and 1,337 DAS28 measurements were available between 0 and 300 days after MTX treatment onset. The developed model adequately described the time course of MTX‐PG3‐5 and DAS28. The median MTX‐PG3‐5 level at month 1 was 30.9 nmol/L (interquartile range (IQR): 23.6–43.7; n = 41) and at month 3: 69.3 nmol/L (IQR: 17.9–41.2; n = 351). Clearance of MTX‐PG3‐5 from RBCs was 28% lower (95% confidence interval (CI): 23.6–32.8%) in a woman and 10% lower (95% CI: 7.7–12.4%) in a 65‐year‐old compared with a 35‐year‐old patient. MTX‐PG3‐5 concentrations associated with DAS28: half‐maximal effective concentration (EC50) was 9.14 nmol/L (95% CI: 4.2 nmol/L‐14.1 nmol/L). EF at 80% (EC80) above 47 nmol/L was regarded as the optimal response. Independent of the MTX‐PG 3–5 – response association, co‐administration of disease‐modifying antirheumatic drugs and corticosteroids improved response (additive effect on maximum effect (Emax)), whereas smoking, high body mass index and low albumin decreased Emax. In patients with RA starting MTX, RBC‐MTX‐PG3‐5 was associated with clinical response. A dose increase is suggested when MTX‐PG3‐5 at month 1 is below 9.15 nmol/L, continued with the same dose when the concentration is above 47 nmol/L, and consider other treatment options above 78 nmol/L from 3 months onwards.
Directing the Selectivity of Oxygen Reduction to Water by Confining a Cu Catalyst in a Metal Organic Framework
Authors: Hoefnagel Marlene E. , Rademaker Dana , Hetterscheid Dennis G. H.
Published: June 2023

Electrocatalysis is to play a key role in the transition towards a sustainable chemical and energy industry and active, stable and selective redox catalysts are much needed. Porous structures such as metal organic frameworks (MOFs) are interesting materials as these may influence selectivity of chemical reactions through confinement effects. In this work, the oxygen reduction catalyst Cu‐tmpa was incorporated into the NU1000 MOF. Confinement of the catalyst within NU1000 steers the selectivity of the oxygen reduction reaction (ORR) towards water rather than peroxide. This is attributed to retention of the obligatory H2O2 intermediate in close proximity to the catalytic center. Moreover, the resulting NU1000|Cu‐tmpa MOF shows an excellent activity and stability in prolonged electrochemical studies, illustrating the potential of this approach.
Linear Scaling Relationships for Furan Hydrodeoxygenation over Transition Metal and Bimetallic Surfaces
Authors: Kanchan Dipika Rajendra , Banerjee Arghya
Published: June 2023

Brønsted‐Evans‐Polanyi (BEP) and transition‐state‐scaling (TSS) relationships have become valuable tools for the rational design of catalysts for complex reactions like hydrodeoxygenation (HDO) of bio‐oil (containing heterocyclic and homocyclic molecules). In this work, BEP and TSS relationships are developed for all the elementary steps of furan activation (C and O hydrogenation and CHx−OHy scission, for both ring and open‐ring intermediates) to oxygenates, ring‐saturated compounds and deoxygenated products on the most stable facets of Ni, Co, Rh, Ru, Pt, Pd, Fe and Ir surfaces using Density Functional Theory (DFT) calculations. Furan ring opening barriers were found to be facile and strongly dependent on carbon and oxygen binding strength on the investigated surfaces. Our calculations suggest linear chain oxygenates form on Ir, Pt, Pd and Rh surfaces due to their low hydrogenation and high CHx−OHy scission barriers, while deoxygenated linear products are favoured on Fe and Ni surfaces due to their low CHx−OHy scission and moderate hydrogenation barriers. Bimetallic alloy catalysts were also screened for their potential HDO activity and PtFe catalysts were found to significantly lower the ring opening and deoxygenation barriers relative to the corresponding pure metals. The developed BEPs for monometallic surfaces can be extended to estimate the barriers on bimetallic surfaces for ring opening and ring hydrogenation reactions but fails to predict the barriers for open‐ring activation reactions due to the change in transition state binding sites on the bimetallic surface. The obtained BEP and TSS relationships can be used to develop microkinetic models for facilitating accelerated catalyst discovery for HDO.
Interplay Between Particle Size and Hierarchy of Zeolite ZSM‐5 During the CO2‐to‐aromatics Process
Authors: Liu Kun , Ramirez Adrian , Zhang Xin , Çağlayan Mustafa , Gong Xuan , Gascon Jorge , Chowdhury Abhishek Dutta
Published: June 2023

The CO2‐to‐aromatics process is a chemical reaction that converts carbon dioxide (CO2) into valuable petrochemical, i. e., aromatics (especially, benzene, toluene, and xylene) over the metal/zeolite bifunctional catalytic systems. These aromatics are used in producing plastics, fibers, and other industrial products, which are currently exclusively sourced from fossil‐derived feedstocks. The significance of this process lies in its potential to mitigate climate change by reducing greenhouse gas emissions and simultaneously producing valuable chemicals. Consequently, these CO2‐derived aromatics can reduce the reliance on fossil fuels as a source of feedstocks, which can help to promote a more sustainable and circular economy. Owing to the existence of a wider straight channel favoring the aromatization process, zeolite ZSM‐5 is extensively used to yield aromatics during CO2 hydrogenation over bifunctional (metal/zeolite) catalytic systems. To provide a better understanding of this unique property of zeolite ZSM‐5, this work investigates the impact of particle size and hierarchy of the zeolite and how these govern the reaction performance and the overall selectivity. As a result, an improved understanding of the zeolite‐catalyzed hydrocarbon conversion process has been obtained.
Sustained increase in physical fitness independently predicts improvements in cardiometabolic risk profile in type 2 diabetes
Authors: Balducci Stefano , Haxhi Jonida , Vitale Martina , Mattia Lorenza , Sacchetti Massimo , Orlando Giorgio , Cardelli Patrizia , Iacobini Carla , Bollanti Lucilla , Conti Francesco , Zanuso Silvano , Nicolucci Antonio , Pugliese Giuseppe ,   for the Italian Diabetes and Exercise Study 2 (IDES_2) Investigators
Published: June 2023

Aims

To investigate the relationship between changes in physical fitness and cardiovascular risk factors and scores in patients with type 2 diabetes receiving either a behavioural counselling intervention to increase moderate‐to‐vigorous‐intensity physical activity (MVPA) and decrease sedentary‐time (SED‐time) or standard care.

Materials and Methods

This is a pre‐specified ancillary analysis of the Italian Diabetes and Exercise Study_2, a 3‐year randomized clinical trial in which 300 physically inactive and sedentary patients were randomized 1:1 to receive either a one‐month theoretical and practical counselling each year or standard care. Mean changes from baseline throughout the 3‐year period in MVPA, SED‐time, cardiorespiratory fitness (VO2max), muscle strength, flexibility, cardiovascular risk factors and scores were calculated for study completers (n = 267) and considered irrespective of study arm.

Results

Haemoglobin (Hb) A1c and coronary heart disease (CHD) risk scores decreased with quartiles of VO2max and lower body muscle strength changes. Multivariable linear regression analysis showed that increases in VO2max independently predicted decreases in HbA1c, blood glucose, diastolic blood pressure (BP), CHD and total stroke 10‐year risk and increases in HDL cholesterol, whereas increases in lower body muscle strength independently predicted decreases in body mass index (BMI), waist circumference, triglycerides, systolic BP, CHD and fatal stroke 10‐year risk. These associations remained after including changes in BMI, waist circumference, fat mass and fat‐free mass, or MVPA and SED‐time as covariates.

Conclusions

Improvement in physical fitness predicts favourable changes in cardiometabolic risk profile, independent of changes not only in (central) adiposity or body composition but also in MVPA and SED‐time.

Trial Registration

ClinicalTrials.gov; NCT01600937; URL https://clinicaltrials.gov/ct2/show/NCT01600937.
Addressing Uncertainties in Potential Human Dietary Exposure to Mercury in the Watershed of the South River, Virginia, USA
Authors: McCue Dana , Mancini Ceil , Liberati Michael R. , Stahl Ralph G.
Published: June 2023

Much has been published about the harmful effects to humans when they are exposed to mercury (Hg) in environmental media including their diet. Numerous health advisories around the world, including for the South River, Virginia, USA, warn against consumption of Hg-contaminated fish species. Fewer studies have focused on other dietary sources of Hg and how to advise humans potentially exposed by this route. In undertaking a human health risk assessment for the former DuPont facility in Waynesboro, Virginia, USA, and the nearby South River and surrounding watershed, the available published information on Hg exposure through dietary consumption of nonfish items proved unsuitable for extrapolation purposes. In response, an evaluation of potential Hg exposure to residents who might consume livestock, poultry, and wildlife raised or collected in the South River watershed was conducted to inform the risk-assessment process. The newly collected data on Hg in these dietary items filled an important data gap, suggesting that there was little concern about limiting dietary consumption for most items. These results were communicated to the public through print and electronic platforms, in the form of “fact sheets.” We describe the studies and actions taken to better explain the potential for human exposures to Hg in nonfish dietary items from a portion of the watershed of the South River. Environ Toxicol Chem 2023;42:2237–2252. © 2023 SETAC
Cryptic Species in Ecotoxicology
Authors: Jourdan Jonas , Bundschuh Mirco , Copilaș-Ciocianu Denis , Fišer Cene , Grabowski Michał , Hupało Kamil , Jemec Kokalj Anita , Kabus Jana , Römbke Jörg , Soose Laura J. , Oehlmann Jörg
Published: June 2023

The advent of genetic methods has led to the discovery of an increasing number of species that previously could not be distinguished from each other on the basis of morphological characteristics. Even though there has been an exponential growth of publications on cryptic species, such species are rarely considered in ecotoxicology. Thus, the particular question of ecological differentiation and the sensitivity of closely related cryptic species is rarely addressed. Tackling this question, however, is of key importance for evolutionary ecology, conservation biology, and, in particular, regulatory ecotoxicology. At the same time, the use of species with (known or unknown) cryptic diversity might be a reason for the lack of reproducibility of ecotoxicological experiments and implies a false extrapolation of the findings. Our critical review includes a database and literature search through which we investigated how many of the species most frequently used in ecotoxicological assessments show evidence of cryptic diversity. We found a high proportion of reports indicating overlooked species diversity, especially in invertebrates. In terrestrial and aquatic realms, at least 67% and 54% of commonly used species, respectively, were identified as cryptic species complexes. The issue is less prominent in vertebrates, in which we found evidence for cryptic species complexes in 27% of aquatic and 6.7% of terrestrial vertebrates. We further exemplified why different evolutionary histories may significantly determine cryptic species' ecology and sensitivity to pollutants. This in turn may have a major impact on the results of ecotoxicological tests and, consequently, the outcome of environmental risk assessments. Finally, we provide a brief guideline on how to deal practically with cryptic diversity in ecotoxicological studies in general and its implementation in risk assessment procedures in particular. Environ Toxicol Chem 2023;42:1889–1914. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Experimental testing on timber connections considering the influence of gap size and intumescent sealants
Authors: du Plessis Marika , Sulon Darren , Streicher Dirk , Walls Richard
Published: June 2023

This paper investigates the influence of gap size (openings/spaces between two structural members) and the presence of intumescent sealants on the development of temperature when timber connections are exposed to fire conditions. The experimental results of 21 samples representing a concealed steel‐to‐timber connection configuration that was exposed with a 0, 3, 6, and 10 mm gap to the ISO834 standard fire for 120 min are presented. Half of the samples in each sample group were protected with an intumescent fire protection sealant. The temperatures in the timber were measured at various locations around the gap and directly next to the steel component. The experimental results show that the presence of a gap increases the temperature of the timber more than predicted by the thermal penetration models available, with current code guidelines (e.g., Eurocode 5) possibly being non‐conservative. The use of an intumescent fire protection sealant in the gap is shown to be an effective protection method, but that the application configuration is important to ensure effective protection, especially as the gap becomes smaller. The results also show that the use of an intumescent fire protection sealant in a gap increases the predictability of the temperatures in the timber in longer duration fires. Unprotected samples and 0 mm gap samples exhibited large variability in the thermal development outcomes over time.
Sex analysis in marine biological systems: insights and opportunities
Authors: Gissi Elena , Schiebinger Londa , Santoleri Rosalia , Micheli Fiorenza
Published: June 2023

The ocean is facing unprecedented challenges due to the escalating impacts of climate change and other pressures threatening ecosystems and the many benefits they provide. Effective strategies for reversing the loss of biodiversity rely on knowledge of how marine organisms, populations, and communities respond to environmental change. A fundamental but often overlooked biological characteristic of organisms is sex, which is distinct from sociocultural gender. Here, we examined how sex influences marine organisms, populations, and communities, through a review of sex analysis applications in marine biological research. We found that sex broadly affects the morphology, physiology, behavior, and distribution of organisms and populations across taxa, with evidence of sex‐specific differences in survival to thermal stress, timing of biological mechanisms, and energetics. To facilitate further integration of sex into marine biological research, we synthesize current approaches, discuss methodological and logistical challenges, and lay out guidelines for future research.
In their own words: An exploration of primary children's participation in a dementia education program
Authors: Pawlicka Nataszia , Eady Michelle J. , Green Corinne A. , Harris Penny , Traynor Victoria , Barkley Carinya , Primmer Jennine , Baker Jess R , Burns Pippa
Published: June 2023

Issue Addressed

As the population ages the prevalence of dementia increases and children are increasingly experiencing family members and older friends living with dementia. Unfortunately, stigma about living with dementia is common. Increasing understanding about dementia among children has the potential to reduce this stigma. This paper reports on the qualitative findings of Project DARE (dementia knowledge, art, research and education), a school‐based, multi‐modal, arts program designed to increase understanding about dementia among children aged 8–10 years.

Methods

A constructivist grounded theory approach was used to understand students' experience of the intervention. Thematic analysis was used to identify key themes emerging from interviews with randomly selected students (n = 40) who had taken part in the program.

Results

The data analysis generated three themes related to students' awareness of dementia and experiences of the program: (1) nurturing empathy, (2) memory loss is complex, (3) learning about dementia through the arts to promote resilience. These themes show that the intervention increased students' awareness of dementia, and empathy towards people who are both directly and indirectly affected by dementia.

Conclusions

Although dementia education can be viewed as too sensitive for primary aged students, the current study demonstrates that such initiatives are feasible and can be effectively implemented with this age group.

So What?

Changing student's beliefs about dementia can positively impact their relationships with people living with dementia.
Th17/Treg balance is regulated by myeloid‐derived suppressor cells in experimental autoimmune myocarditis
Authors: Xiong Xin , Yu Mengjia , Wang Dinghang , Wang Yange , Cheng Longxian
Published: June 2023

Objective

Autoimmune myocarditis is caused by both innate and adaptive immune responses. Many studies have found that myeloid‐derived suppressor cells (MDSCs) suppress T‐cell responses and reduce immune tolerance, while MDSCs may serve as a key player in inflammatory responses and pathogenesis in variety of autoimmune diseases. However, research into the role of MDSCs in experimental autoimmune myocarditis (EAM) remains lacking.

Methods and Results

We discovered that the expansion of MDSCs in EAM was closely related to the severity of myocardial inflammation. At an early stage of EAM, both adoptive transfer (AT) and selective depletion of MDSCs could inhibit the expression of IL‐17 in CD4+ cells and downregulate the Th17/Treg ratio, alleviating excessive inflammation of EAM myocarditis. In another experiment, in addition, MDSCs transferred after selective depletion could increase IL‐17 and Foxp3 expressions in CD4+ cells, as well as the Th17/Treg ratio, contributing to the aggravation of myocardial inflammation. MDSCs promoted the Th17 cell induction under Th17‐polarizing conditions in vitro but suppressed Treg expansion.

Conclusion

These findings suggest that MDSCs play a plastic role in sustaining mild inflammation in EAM by shifting Th17/Treg balance.
Clinical features and prognostic factors of anti‐melanoma differentiation‐associated gene 5 antibody‐positive dermatomyositis with rapidly progressive interstitial lung disease in Chinese patients
Authors: Lian Li , Tong Jing‐jing , Xu Sheng‐qian
Published: June 2023

Objective

The objective of this study is to investigate clinical features and prognostic factors of antimelanoma differentiation‐associated gene 5 (anti‐MDA5)‐positive dermatomyositis with rapidly progressive interstitial lung disease (RP‐ILD) in Chinese patients.

Methods

Clinical features and prognostic factors of patients with newly diagnosed or recurrent dermatomyositis patients were retrospectively analyzed. All patients were divided into the anti‐MDA5‐positive or negative dermatomyositis, and with or without RP‐ILD groups. Clinical features and prognostic factors were statistically compared among different groups.

Results

The serum ferritin (SF) levels (1500.0 [658.80, 1844.0]) and γ‐glutamyl transpeptidase (γ‐GT) (125.5 [61.0, 232.0] vs. 28 [16.0, 41.0],Z = 5.528;p < .001) were markedly higher, and phosphocreatine myoenzyme (CK) (73.0 [42.0, 201.0] vs. 1333.0 [79.0, 8000.0],Z = −2.739,p = .006), serum albumin level (32.51 ± 5.23 vs. 35.81 ± 5.88,t = −2.542,p = .013), and lymphocyte count (0.80 ± 0.36 vs. 1.45 ± 0.77,t = −4.717,p < .001) were lower than those in anti‐MDA5‐negative counterparts. Among patients with anti‐MDA5 antibody (Ab) with RP‐ILD, the SF level (1531.0 [1163.8, 2016.5] vs. 584.9 [564.8, 1042.5],Z = 2.664,p = .008), γ‐GT (134.0 [81.0, 204.5] vs. 123.0 [76.0, 189.0],Z = 3.136,p = .002) and positive rate of anti‐RO‐52 Ab (90.9% vs. 50.0%,χ2 = 7.222,p = .013) were higher and lymphocyte count (0.79 ± 0.38 vs. 1.32 ± 0.74,t = −3.025,p = .029) was lower than those in their counterparts without RP‐ILD. The SF level of anti‐MDA5 nonsurvivors (1544 [1447.32, 2089.0] vs. 584.9 [515.7, 1500.0],Z = 2.096,p = .030), anti‐RO‐52 Ab‐positive rate ([16/18, 88.9%] vs. [9/16, 56.2%],χ2 = 4.636,p = .031) were higher than those in survivors. Lymphocytopenia was a risk factor for RP‐ILD and death of patients with anti‐MDA5‐positive dermatomyositis. The area under receiver operating characteristic curve was 0.888 (95% confidence interval: 0.756, 1.000;p < .001), the sensitivity was 85.7%, the specificity was 93.8%, and Youden's index was 0.795.

Conclusions

Anti‐MDA5‐positive dermatomyositis patients are prone to developing RP‐ILD. Declined lymphocyte count is a critical risk factor for RP‐ILD, probably acting as a simple and effective predictor for Chinese patients with anti‐MDA5‐positive dermatomyositis.
IL‐38 attenuates myocardial ischemia–reperfusion injury by inhibiting macrophage inflammation
Authors: Wei Yuzhen , Xing Junhui , Su Xin , Li Xiangrao , Yan Xiaofei , Zhao Jiangtao , Tao Hailong
Published: June 2023

Background

Reperfusion therapy is the most effective approach to resolve coronary occlusion, but myocardial injury caused by excessive inflammation during myocardial ischemia–reperfusion will also pose a new threat to health. Our prior study revealed the expression pattern of interleukin‐38 (IL‐38) in the peripheral blood serum of patients with ischemic cardiomyopathy and the role of IL‐38 in acute myocardial infarction in mice. However, its role and potential mechanisms in myocardial ischemia/reperfusion injury (MIRI) remain to be determined.

Methods and Results

The left anterior descending artery of C57BL/6 mice was transiently ligated to induce the MIRI model. We found that MIRI induced the expression of endogenous IL‐38, which was mainly produced by locally infiltrating macrophages. Overexpression of IL‐38 in C57BL/6 mice attenuated inflammatory injury and decreased myocardial apoptosis after myocardial ischemia–reperfusion. Furthermore, IL‐38 inhibited lipopolysaccharide‐induced macrophage inflammation in vitro. Cardiomyocytes cocultured with the supernatant of IL‐38‐ and troponin I‐treated macrophages showed a lower rate of apoptosis than controls.

Conclusions

IL‐38 attenuates MIRI by inhibiting macrophage inflammation. This inhibitory effect may be partially achieved by inhibiting the activation of NOD‐like receptor pyrin domain‐related protein 3 inflammasome, resulting in decreased expression of inflammatory factors and reduced cardiomyocyte apoptosis.
Melatonin regulates microglial polarization to M2 cell via RhoA/ROCK signaling pathway in epilepsy
Authors: Li Pingping , Ji Xuefei , Shan Ming , Wang Yi , Dai Xingliang , Yin Mengyuan , Liu Yunlong , Guan Liao , Ye Lei , Cheng Hongwei
Published: June 2023

Background

Melatonin (MEL), an endogenous hormone, has been widely investigated in neurological diseases. Microglia (MG), a resident immunocyte localizing in central nervous system is reported to play important functions in the animal model of temporal lobe epilepsy (TLE). Some evidence showed that MEL influenced activation of MG, but the detailed model of action that MEL plays in remains uncertain.

Methods

In this study, we established a model of TLE in mice by stereotactic injection of kainic acid (KA). We treated the mice with MEL. Lipopolysaccharide, ROCK2‐knockdown (ROCK‐KD) and ‐overexpression (ROCK‐OE) of lentivirus‐treated cells were used in cell experiments to simulate an in vitro inflammatory model.

Results

The results of electrophysiological tests showed that MEL reduced frequency and severity of seizure. The results of behavioral tests indicated MEL improved cognition, learning, and memory ability. Histological evidences demonstrated a significant reduction of neuronal death in the hippocampus. In vivo study showed that MEL changed the polarization status of MG from a proinflammatory M1 phenotype to an anti‐inflammatory M2 phenotype by inversely regulating the RhoA/ROCK signaling pathway. In cytological study, we found that MEL had a significant protective effect in LPS‐treated BV‐2 cells and ROCK‐KD cells, while the protective effect of MEL was significantly attenuated in ROCK‐OE cells.

Conclusion

MEL played an antiepileptic role in the KA‐induced TLE modeling mice both in behavioral and histological levels, and changed MG polarization status by regulating the RhoA/ROCK signaling pathway.
Characterization of SARS‐CoV‐2 humoral immune response in a subject with unique sampling: A case report
Authors: Walker Melanie R. , Idorn Manja , Bennett Anja , Søgaard Max , Salanti Ali , Ditlev Sisse B. , Barfod Lea
Published: June 2023

Background

The development of vaccine candidates for COVID‐19, and the administration of booster vaccines, has meant a significant reduction in COVID‐19 related deaths world‐wide and the easing of global restrictions. However, new variants of SARS‐CoV‐2 have emerged with less susceptibility to vaccine induced immunity leading to breakthrough infections among vaccinated people. It is generally acknowledged that immunoglobulins play the major role in immune‐protection, primarily through binding to the SARS‐COV‐2 receptor binding domain (RBD) and thereby inhibiting viral binding to the ACE2 receptor. However, there are limited investigations of anti‐RBD isotypes (IgM, IgG, IgA) and IgG subclasses (IgG1–4) over the course of vaccination and breakthrough infection.

Method

In this study, SARS‐CoV‐2 humoral immunity is examined in a single subject with unique longitudinal sampling. Over a two year period, the subject received three doses of vaccine, had two active breakthrough infections and 22 blood samples collected. Serological testing included anti‐nucleocapsid total antibodies, anti‐RBD total antibodies, IgG, IgA, IgM and IgG subclasses, neutralization and ACE2 inhibition against the wildtype (WT), Delta and Omicron variants.

Results

Vaccination and breakthrough infections induced IgG, specifically IgG1 and IgG4 as well as IgM and IgA. IgG1 and IgG4 responses were cross reactive and associated with broad inhibition.

Conclusion

The findings here provide novel insights into humoral immune response characteristics associated with SARS‐CoV‐2 breakthrough infections.
A balancing act: Non‐directive communication, risk perceptions, and meeting patient needs in genetic counseling: A South African case study
Authors: Scott Megan , Watermeyer Jennifer , Wessels Tina‐Marie
Published: June 2023

Genetic counseling (GC) traditionally follows a non‐directive counseling approach. Although a cornerstone of GC teaching and theory, there has been debate on whether GC is, can be, or should be a patient‐led service due to challenges in practice, as well as the advancement and complexity of genetic testing. Personal risk perceptions and patient expectations within particular contexts may further affect how genetic counselors discuss risk information, even while attempting to remain neutral. Less is known about the process of GC communication in non‐Western settings. This paper presents empirical evidence from a South African prenatal GC consultation where tensions become apparent due to differing risk perceptions and expectations between a genetic counselor and a patient, which ultimately impacts non‐directive communication practice. The case study forms part of a larger qualitative study focusing on risk and uncertainty communication within GC consultations in Cape Town, South Africa. A blended sociolinguistic approach drawing on principles of conversation analysis (CA) and theme‐orientated discourse analysis (TODA) provides evidence of the complexity of imparting risk information and challenging patients to reflect on their decision‐making, whilst refraining from sharing personal risk perceptions during everyday practice. The case study demonstrates how a genetic counselor may become implicitly and explicitly directive in their communication approach within the same consult which may reveal their personal risk perceptions on the matter discussed. In addition, the case study reveals how a genetic counselor may grapple with the dilemma of honoring the non‐directive guidelines of the profession, whilst simultaneously supporting a patient who requests advice. The ongoing debate on non‐directive counseling, decision‐making, and patient care in GC is important for the reflection and development of the profession to understand how to assist and support patients facing sensitive and difficult decisions, in a meaningful, and contextually‐tailored manner.
Diffusion‐Weighted MRI of the Fetal Brain in Fetal Growth Restriction With Maternal Preeclampsia or Gestational Hypertension
Authors: Zheng Weizeng , Yan Guohui , Jiang Ying , Bao Zhongkun , Li Kui , Deng Meixiang , Li Baohua , Zou Yu
Published: June 2023

Background

The fetal neurodevelopmental microstructural alterations of intrauterine exposure to preeclampsia (PE) or gestational hypertension (GH) remain unknown.

Purpose

To evaluate the differences in diffusion‐weighted imaging (DWI) of the fetal brain between normotensive pregnancies and PE/GH pregnancies, with a focus on PE/GH pregnancies with fetal growth restriction (FGR).

Study Type

Retrospective matched case–control study.

Population

40 singleton pregnancies with PE/GH complicated by FGR, and 3 paired control groups (PE/GH without FGR, normotensive FGR, normotensive pregnancies) (28–38 gestational weeks).

Field Strength/Sequence

DWI with single‐shot echo‐planar imaging at 1.5 Tesla.

Assessment

The apparent diffusion coefficient (ADC) values were calculated in the centrum semi‐ovale (CSO), parietal white matter (PWM), frontal white matter (FWM), occipital white matter (OWM), temporal white matter (TWM), basal ganglia, thalamus (THAL), pons, and cerebellar hemisphere.

Statistical Tests

Student t test or Wilcoxon matched test was used to reveal the difference of ADC values among the investigated brain regions. A correlation between gestational age (GA) and ADC values was determined by linear regression analysis.

Results

Compared with fetuses in PE/GH without FGR and those with normotensive pregnancies, fetuses in the PE/GH with FGR group had significantly lower average ADC measurements of supratentorial regions (1.65 ± 0.09 vs. 1.71 ± 0.10 10−3 mm2/sec; vs. 1.73 ± 0.11 10−3 mm2/sec, respectively). Regions of significantly decreased ADC values in the fetal brain included CSO, FWM, PWM, OWM, TWM and THAL in cases of PE/GH with FGR. ADC values from supratentorial regions in PE/GH pregnancies were not significantly correlated with GA (P = 0.12, 0.26); however, this trend was statistically significant in the normotensive groups.

Data Conclusion

ADC values may indicate fetal brain developmental alterations in PE/GH with FGR fetuses but more microscopic and morphological studies are necessary to provide additional evidence to offer a different interpretation of this trend in fetal brain.

Level of Evidence

4

Technical Efficacy Stage

3
Broadband PA design using Bayesian algorithms with different covariance functions
Authors: Huang Jiajun , Qu Yan , Hao Zefang , Cai Jialin
Published: June 2023

This article examines the effects of Bayesian optimization (BO) with different covariance functions on the optimization of a radio frequency power amplifier (RFPA). An initial PA is designed based on a Chebyshev low‐pass topology using a 10 W Gallium Nitride (GaN) transistor. The objective function is established in a novel manner. The performance of the initially designed PA was optimized by using various BO algorithms, including two different acquisition functions and five different covariance functions. Both simulation and measurement results indicate that the kernel squared exponential (KSE) and Matérn32 covariance functions provide the best option for optimizing PA by BO. A broadband power amplifier (PA) operating at a frequency range from 2.5 GHz to 3.5 GHz has been developed with an output power (Pout) greater than 40.8 dBm and a power‐added efficiency (PAE) greater than 65%.