bluuebunny/crossref_metadata_2025 huggingface dataset:
Usefulness of FAPα assessment in bronchoalveolar lavage as a marker of fibrogenesis: results of a preclinical study and first report in patients with idiopathic pulmonary fibrosis
Authors: Lavis Philomène , Pingitore Julien , Doumont Gilles , Garabet Ani , Van Simaeys Gaetan , Lacroix Simon , Passon Nicolas , Van Heymbeek Christophe , De Maeseneire Coraline , Allard Justine , Collin Amandine , Huaux François , Decaestecker Christine , Salmon Isabelle , Goldman Serge , Cardozo Alessandra Kupper , Bondue Benjamin
Published: October 2023

Background

Fibroblast activation protein-α (FAPα) is a marker of activated fibroblasts that can be selectively targeted by an inhibitor (FAPI) and visualised by PET/CT imaging. We evaluated whether the measurement of FAPα in bronchoalveolar lavage fluids (BALF) and the uptake of FAPI by PET/CT could be used as biomarkers of fibrogenesis.

Methods

The dynamics of lung uptake of18F-labeled FAPI ([18F]FAPI-74) was assessed in the bleomycin mouse model at various time points and using different concentrations of bleomycin by PET/CT. FAPα was measured in BALFs from these bleomycin-treated and control mice. FAPα levels were also assessed in BALFs from controls and patients with idiopathic pulmonary fibrosis (IPF).

Results

Bleomycin-treated mice presented a significantly higher uptake of [18F]FAPI-74 during lung fibrinogenesis (days 10 and 16 after instillation) compared to control mice. No significant difference was observed at initial inflammatory phase (3 days) and when fibrosis was already established (28 days). [18F]FAPI-74 tracer was unable to show a dose-response to bleomycin treatment. On the other hand, BALF FAPα levels were steeply higher in bleomycin-treated mice at day 10 and a significant dose-response effect was observed. Moreover, FAPα levels were strongly correlated with lung fibrosis as measured by the modified Aschroft histological analysis, hydroxyproline and the percentage of weight loss. Importantly, higher levels of FAPα were observed in IPF patients where the disease was progressing as compared to stable patients and controls. Moreover, patients with FAPα BALF levels higher than 192.5 pg/mL presented a higher risk of progression, transplantation or death compared to patients with lower levels.

Conclusions

Our preclinical data highlight a specific increase of [18F]FAPI-74 lung uptake during the fibrotic phase of the bleomycin murine model. The measurement of FAPα in BALF appears to be a promising marker of the fibrotic activity in preclinical models of lung fibrosis and in IPF patients. Further studies are required to confirm the role of FAPα in BALF as biomarker of IPF activity and assess the relationship between FAPα levels in BALF and [18F]FAPI-74 uptake on PET/CT in patients with fibrotic lung disease.
Study on the intracellular adaptative mechanism of Acidithiobacillus caldus MTH-04 to NaCl stress
Authors: Li Min , Wen Jianping
Published: October 2023

To understand the adaptive mechanism of bioleaching microorganism Acidithiobacillus caldus MTH-04, its physiology and metabolic changes at the transcriptional level were systemically studied. The results of growth curves, SO42− content, pH and flow cytometry analyses indicated that the higher the NaCl concentration, the more the strain was inhibited. The transcriptome response of A. caldus to elevated NaCl concentrations included changes in carbon flux, elevated glutathione synthesis, alterations in cell wall and membrane composition, the down-regulation in genes involved in flagellar synthesis and rotation, the reduced energy generation through sulfur oxidation, and the up-regulation in genes involved in DNA and protein repair. Based on the transcriptome results, the effects of proline and glutathione on NaCl adaptation in A. caldus were analyzed separately. We found that either the exogenous addition of proline and glutathione or the intracellular overexpression of the enzymes responsible for the synthesis of these two substances contributed to the enhancement of the adaptive capacity of A. caldus under NaCl stress. The findings offer insight into the design of chloride-based techniques for the bioprocessing of minerals.
How to improve research capacity strengthening efforts: learning from the monitoring and evaluation of four research consortia in Africa
Authors: Kasprowicz Victoria O. , Jeffery Caroline , Mbuvi Dorcas , Bukirwa Victoria , Ouattara Karim , Kirimi Florence , Heitz-Tokpa Kathrin , Gorrethy Mary , Chopera Denis , Nakanjako Damalie , Bonfoh Bassirou , Elliott Alison , Kinyanjui Samson , Bates Imelda , Ndung’u Thumbi
Published: October 2023

Recent efforts to shift the control and leadership of health research on African issues to Africa have led to increased investments for scientific research capacity strengthening (RCS) on the continent and a greater demand for accountability, value for money and demonstration of return on investment. There is limited literature on monitoring and evaluation (M&E) of RCS systems and there is a clear need to further explore whether the M&E frameworks and approaches that are currently used are fit for purpose. The M&E approaches taken by four African RCS consortia funded under the Developing Excellence in Leadership, Training and Science in Africa (DELTAS) I initiative were assessed using several methods, including a framework comparison of the M&E approaches, semi-structured interviews and facilitated discussion sessions. The findings revealed a wide range in the number of indicators used in the M&E plans of individual consortium, which were uniformly quantitative and at the output and outcome levels. Consortia revealed that additional information could have been captured to better evaluate the success of activities and measure the ripple effects of their efforts. While it is beneficial for RCS consortia to develop and implement their own M&E plans, this could be strengthened by routine engagement with funders/programme managers to further align efforts. It is also important for M&E plans to consider qualitative data capture for assessment of RCS efforts. Efforts could be further enhanced by supporting platforms for cross-consortia sharing, particularly when trying to assess more complex effects. Consortia should make sure that processes for developmental evaluation, and capturing and using the associated learning, are in place. Sharing the learning associated with M&E of RCS efforts is vital to improve future efforts. Investing and improving this aspect of RCS will help ensure tracking of progress and impact of future efforts, and ensure accountability and the return on investment. The findings are also likely applicable well beyond health research.
Cat eye syndrome caused by 22q11.1q11.21 duplication: case report in a Chinese family
Authors: Wang Yanan , Zhang Pai , Chai Yuqiong , Zang Weiwei
Published: October 2023

Purpose

 This paper presents a report on two uncommon instances of cat eye syndrome in a Chinese family.

Case presentation

The proband, a 23-year-old female, exhibited a diminutive cornea and complete blindness in her right eye, and the uncorrected distance visual acuity of her left eye was 0.7 LogMAR. Peripheral blood chromosome karyotyping reveal a karyotype of 47, XX, + mar. Subsequent analysis of chromosome copy number variation unveiled a 1.5 Mb duplication in the 22q11.1q11.21 region of the proband. The proband's mother,aged 49, displayed small eyes, wide-set eyes, downward slanting eyelids, and congenital heart disease. Chromosome copy number variation analysis also showed a 1.55 Mb duplication in the 22q11.1q11.21 region of chromosome 22 in the proband's mother. Ultimately, both members of this family were diagnosed with cat eye syndrome.

Conclusion

 Cat eye syndrome is a rare genetic disorder that greatly affects patients' lives and requires personalized treatment. This study provides new evidence for a better understanding of the diagnosis of cat eye syndrome and emphasizes the importance of genetic counseling and supervision.
Reprogramming T cell differentiation and exhaustion in CAR-T cell therapy
Authors: Bulliard Yannick , Andersson Borje S. , Baysal Mehmet A. , Damiano Jason , Tsimberidou Apostolia M.
Published: October 2023

T cell differentiation is a highly regulated, multi-step process necessary for the progressive establishment of effector functions, immunological memory, and long-term control of pathogens. In response to strong stimulation, as seen in severe or chronic infections or cancer, T cells acquire a state of hypo-responsiveness known as exhaustion, limiting their effector function. Recent advances in autologous chimeric antigen receptor (CAR)-T cell therapies have revolutionized the treatment of hematologic malignancies by taking advantage of the basic principles of T cell biology to engineer products that promote long-lasting T cell response. However, many patients’ malignancies remain unresponsive to treatment or are prone to recur. Discoveries in T cell biology, including the identification of key regulators of differentiation and exhaustion, offer novel opportunities to have a durable impact on the fate of CAR-T cells after infusion. Such next-generation CAR-T cell therapies and their clinical implementation may result in the next leap forward in cancer treatment for selected patients. In this context, this review summarizes the foundational principles of T cell differentiation and exhaustion and describes how they can be utilized and targeted to further improve the design and efficacy of CAR-T cell therapies.
Taxonomic and molecular characterization of a new entomopathogenic nematode species, Heterorhabditis casmirica n. sp., and whole genome sequencing of its associated bacterial symbiont
Authors: Bhat Aashaq Hussain , Machado Ricardo A. R. , Abolafia Joaquín , Ruiz-Cuenca Alba N. , Askary Tarique Hassan , Ameen Fuad , Dass Wasim Muzamil
Published: October 2023

Background

Nematodes of the genus Heterorhabditis are important biocontrol agents as they form a lethal combination with their symbiotic Photorhabdus bacteria against agricultural insect pests. This study describes a new species of Heterorhabditis.

Methods

Six Heterorhabditis nematode populations were recovered from agricultural soils in Jammu and Kashmir, India. An initial examination using mitochondrial and nuclear genes showed that they belong to a new species. To describe this new species, a variety of analyses were conducted, including reconstructing phylogenetic relationships based on multiple genes, characterizing the nematodes at the morphological and morphometric levels, performing self-crossing and cross-hybridization experiments, and isolating and characterizing their symbiotic bacteria.

Results

The newly discovered species, Heterorhabditis casmirica n. sp., shares 94% mitochondrial cytochrome C oxidase subunit I gene (COI) sequence identity with Heterorhabditis bacteriophora and Heterorhabditis ruandica, and 93% with Heterorhabditis zacatecana. Morphologically, it differs from H. bacteriophora in its infective juvenile phasmids (present vs. inconspicuous) and bacterial pouch visibility in the ventricular portion of the intestine (invisible vs. visible); genital papilla 1 (GP1) position (at manubrium level vs. more anterior), and in its b ratio (body length/neck length), c ratio (tail length/bulb width), and D% [(excretory pore/neck length) × 100]. Other morphological differences include anterior end to the nerve ring distance (77–100 vs. 121–130 μm), V% [(anterior end of vulva/body length) × 100] (46–57 vs. 41–47) in hermaphroditic females; rectum size (slightly longer than the anal body diameter vs. about three times longer), phasmids (smaller vs. inconspicuous), body length (0.13–2.0 vs. 0.32–0.39 mm), body diameter (73–150 vs. 160–220 μm), anterior end to the excretory pore distance (135–157 vs. 174–214 μm), and demanian ratios in amphimictic females. Morphological differences with H. ruandica and H. zacatecana were also observed. Furthermore, H. casmirica n. sp. did not mate or produce fertile progeny with other Heterorhabditis nematodes reported from India. It was also discovered that H. casmirica n. sp. is associated with 'Photorhabdus laumondii subsp. clarkei symbiotic bacteria.

Conclusions

The discovery of H. casmirica n. sp. provides novel insights into the diversity and evolution of Heterorhabditis nematodes and their symbiotic bacteria. This new species adds to the catalog of entomopathogenic nematodes in India.

Graphical Abstract
Fatal eosinophilic myocarditis and submassive hepatic necrosis in lamotrigine induced DRESS syndrome
Authors: Doan Khanh Duy , Akinsanya Adeyinka , Kuhar Matthew , Mesa Hector
Published: October 2023

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a rare but severe and sometimes fatal adverse drug reaction that is known to occur with a number of antiepileptic drugs. It often follows a prolonged clinical course, which can worsen even after discontinuing the causative drug and administering steroid treatment. Failure to promptly identify the delayed involvement of vital organs, such as the heart and liver, may result in irreversible organ failure and death. We report a case of a presumed sudden death of a young woman who had a documented history of a protracted intermittent hypersensitivity reaction to lamotrigine. Postmortem examination revealed the presence of eosinophilic myocarditis and submassive hepatic necrosis diagnostic of fatal DRESS syndrome that progressed despite early discontinuation of the medication and improvement of dermatologic and hematologic symptoms following steroid therapy.
Translatome analysis of tuberous sclerosis complex 1 patient-derived neural progenitor cells reveals rapamycin-dependent and independent alterations
Authors: Aksoylu Inci S. , Martin Pauline , Robert Francis , Szkop Krzysztof J. , Redmond Nicholas E. , Bhattacharyya Srirupa , Wang Jennifer , Chen Shan , Beauchamp Roberta L. , Nobeli Irene , Pelletier Jerry , Larsson Ola , Ramesh Vijaya
Published: October 2023

Background

Tuberous sclerosis complex (TSC) is an inherited neurocutaneous disorder caused by mutations in the TSC1 or TSC2 genes, with patients often exhibiting neurodevelopmental (ND) manifestations termed TSC-associated neuropsychiatric disorders (TAND) including autism spectrum disorder (ASD) and intellectual disability. Hamartin (TSC1) and tuberin (TSC2) proteins form a complex inhibiting mechanistic target of rapamycin complex 1 (mTORC1) signaling. Loss of TSC1 or TSC2 activates mTORC1 that, among several targets, controls protein synthesis by inhibiting translational repressor eIF4E-binding proteins. Using TSC1 patient-derived neural progenitor cells (NPCs), we recently reported early ND phenotypic changes, including increased cell proliferation and altered neurite outgrowth in TSC1-null NPCs, which were unaffected by the mTORC1 inhibitor rapamycin.

Methods

Here, we used polysome profiling, which quantifies changes in mRNA abundance and translational efficiencies at a transcriptome-wide level, to compare CRISPR-edited TSC1-null with CRISPR-corrected TSC1-WT NPCs generated from one TSC donor (one clone/genotype). To assess the relevance of identified gene expression alterations, we performed polysome profiling in postmortem brains from ASD donors and age-matched controls. We further compared effects on translation of a subset of transcripts and rescue of early ND phenotypes in NPCs following inhibition of mTORC1 using the allosteric inhibitor rapamycin versus a third-generation bi-steric, mTORC1-selective inhibitor RMC-6272.

Results

Polysome profiling of NPCs revealed numerous TSC1-associated alterations in mRNA translation that were largely recapitulated in human ASD brains. Moreover, although rapamycin treatment partially reversed the TSC1-associated alterations in mRNA translation, most genes related to neural activity/synaptic regulation or ASD were rapamycin-insensitive. In contrast, treatment with RMC-6272 inhibited rapamycin-insensitive translation and reversed TSC1-associated early ND phenotypes including proliferation and neurite outgrowth that were unaffected by rapamycin.

Conclusions

Our work reveals ample mRNA translation alterations in TSC1 patient-derived NPCs that recapitulate mRNA translation in ASD brain samples. Further, suppression of TSC1-associated but rapamycin-insensitive translation and ND phenotypes by RMC-6272 unveils potential implications for more efficient targeting of mTORC1 as a superior treatment strategy for TAND.
Quantitative and clinical implications of the EARL2 versus EARL1 [18F]FDG PET-CT performance standards in head and neck squamous cell carcinoma
Authors: Cox Maurice C. , Jurcka Tijn , Arens Anne I. J. , van Rijk Maartje C. , Kaanders Johannes H. A. M. , van den Bosch Sven
Published: October 2023

Background

The EANM Research Ltd. (EARL) guidelines give recommendations for harmonization of [18F]FDG PET-CT image acquisition and reconstruction, aiming to ensure reproducibility of quantitative data between PET scanners. Recent technological advancements in PET-CT imaging resulted in an updated version of the EARL guidelines (EARL2). The aim of this study is to compare quantitative [18F]FDG uptake metrics of the primary tumor and lymph nodes in patients with head and neck squamous cell carcinoma (HNSCC) on EARL2 versus EARL1 reconstructed images and to describe clinical implications for nodal staging and treatment.

Methods

Forty-nine consecutive patients with HNSCC were included. For all, both EARL1 and EARL2 images were reconstructed from a singular [18F]FDG PET-CT scan. Primary tumors and non-necrotic lymph nodes ≥ 5 mm were delineated on CT-scan. In the quantitative analysis, maximum standardized uptake values (SUVmax) and standardized uptake ratios (SURmax, i.e., SUVmax normalized to cervical spinal cord uptake) were calculated for all lesions on EARL1 and EARL2 reconstructions. Metabolic tumor volume (MTV) and total lesion glycolysis were compared between EARL1 and EARL2 using different segmentation methods (adaptive threshold; SUV2.5/3.5/4.5; SUR2.5/3.5/4.5; MAX40%/50%). In the qualitative analysis, each lymph node was scored independently by two nuclear medicine physicians on both EARL1 and EARL2 images on different occasions using a 4-point scale.

Results

There was a significant increase in SUVmax (16.5%) and SURmax (9.6%) of primary tumor and lymph nodes on EARL2 versus EARL1 imaging (p < 0.001). The proportional difference of both SUVmax and SURmax between EARL2 and EARL1 decreased with increasing tumor volume (p < 0.001). Absolute differences in MTVs between both reconstructions were small (< 1.0 cm3), independent of the segmentation method. MTVs decreased on EARL2 using relative threshold methods (adaptive threshold; MAX40%/50%) and increased using static SUV or SUR thresholds. With visual scoring of lymph nodes 38% (11/29) of nodes with score 2 on EARL1 were upstaged to score 3 on EARL2, which resulted in an alteration of nodal stage in 18% (6/33) of the patients.

Conclusions

Using the EARL2 method for PET image reconstruction resulted in higher SUVmax and SURmax compared to EARL1, with nodal upstaging in a significant number of patients.
Comparative effectiveness and cost-effectiveness of cardioprotective glucose-lowering therapies for type 2 diabetes in Brazil: a Bayesian network model
Authors: Nogueira Ana Claudia Cavalcante , Barreto Joaquim , Moura Filipe A. , Luchiari Beatriz , Abuhab Abrão , Bonilha Isabella , Nadruz Wilson , Gaziano J. Michael , Gaziano Thomas , de Carvalho Luiz Sergio F. , Sposito Andrei C. ,   on behalf of the Brazilian Heart Study Group
Published: October 2023

Background

The escalating prevalence of type 2 diabetes (T2DM) poses an unparalleled economic catastrophe to developing countries. Cardiovascular diseases remain the primary source of costs among individuals with T2DM, incurring expenses for medications, hospitalizations, and surgical interventions. Compelling evidence suggests that the risk of cardiovascular outcomes can be reduced by three classes of glucose-lowering therapies (GLT), including SGLT2i, GLP-1A, and pioglitazone. However, an evidence-based and cost-effective protocol is still unavailable for many countries. The objective of the current study is to compare the effectiveness and cost-effectiveness of GLT in individuals with T2DM in Brazil.

Methods

We employed Bayesian Networks to calculate the incremental cost-effectiveness ratios (ICER), expressed in international dollars (Int$) per disease-adjusted life years [DALYs] averted. To determine the effectiveness of GLT, we conducted a systematic review with network meta-analysis (NMA) to provide insights for our model. Additionally, we obtained cardiovascular outcome incidence data from two real-world cohorts comprising 851 and 1337 patients in primary and secondary prevention, respectively. Our cost analysis took into account the perspective of the Brazilian public health system, and all values were converted to Int$.

Results

In the NMA, SGLT2i [HR: 0.81 (95% CI 0.69–0.96)], GLP-1A [HR: 0.79 (95% CI 0.67–0.94)], and pioglitazone [HR: 0.73 (95% CI 0.59–0.91)] demonstrated reduced relative risks of non-fatal cardiovascular events. In the context of primary prevention, pioglitazone yielded 0.2339 DALYs averted, with an ICER of Int$7,082 (95% CI 4,521–10,770) per DALY averted when compared to standard care. SGLT2i and GLP-1A also increased effectiveness, resulting in 0.261 and 0.259 DALYs averted, respectively, but with higher ICERs of Int$12,061 (95% CI: 7,227–18,121) and Int$29,119 (95% CI: 23,811–35,367) per DALY averted. In the secondary prevention scenario, all three classes of treatments were deemed cost-effective at a maximum willingness-to-pay threshold of Int$26,700. Notably, pioglitazone consistently exhibited the highest probability of being cost-effective in both scenarios.

Conclusions

In Brazil, pioglitazone presented a higher probability of being cost-effective both in primary and secondary prevention, followed by SGLT2i and GLP-1A. Our findings support the use of cost-effectiveness models to build optimized and hierarchical therapeutic strategy in the management of T2DM.

Trial registration

CRD42020194415.
An improved wavelet threshold denoising approach for surface electromyography signal
Authors: Ouyang Chuanyun , Cai Liming , Liu Bin , Zhang Tianxiang
Published: October 2023

Background

The surface electromyography (sEMG) signal presents significant challenges for the dynamic analysis and subsequent examination of muscle movements due to its low signal energy, broad frequency distribution, and inherent noise interference. However, the conventional wavelet threshold filtering techniques for sEMG signals are plagued by the Gibbs-like phenomenon and an overall decrease in signal amplitude, leading to signal distortion.

Purpose

This article aims to establish an improved wavelet thresholding method that can filter various types of signals, with a particular emphasis on sEMG signals, by adjusting two independent factors. Hence, it generates the filtered signal with a higher signal-to-noise ratio (SNR), a lower mean square error (MSE), and better signal quality.

Results

After denoising Doppler and Heavysine signals, the filtered signal exhibits a higher SNR and lower MSE than the signal generated from traditional filtering algorithms. The filtered sEMG signal has a lower noise baseline while retaining the peak sEMG signal strength.

Conclusion

The empirical evaluation results show that the quality of the signal processed by the new noise reduction algorithm is better than the traditional hard thresholding, soft thresholding, and Garrote thresholding methods. Moreover, the filtering performance on the sEMG signal is improved significantly, which enhances the accuracy and reliability of subsequent experimental analyses.
New inertial self-adaptive algorithms for the split common null-point problem: application to data classifications
Authors: Promkam Ratthaprom , Sunthrayuth Pongsakorn , Kesornprom Suparat , Tanprayoon Ekapak
Published: October 2023

In this paper, we propose two inertial algorithms with a new self-adaptive step size for approximating a solution of the split common null-point problem in the framework of Banach spaces. The step sizes are adaptively updated over each iteration by a simple process without the prior knowledge of the operator norm of the bounded linear operator. Under suitable conditions, we prove the weak-convergence results for the proposed algorithms inp-uniformly convex and uniformly smooth Banach spaces. Finally, we give several numerical results in both finite- and infinite-dimensional spaces to illustrate the efficiency and advantage of the proposed methods over some existing methods. Also, data classifications of heart diseases and diabetes mellitus are presented as the applications of our methods.
Adaptive neural-domain refinement for solving time-dependent differential equations
Authors: Schneidereit Toni , Breuß Michael
Published: October 2023

A classic approach for solving differential equations with neural networks builds upon neural forms, which employ the differential equation with a discretisation of the solution domain. Making use of neural forms for time-dependent differential equations, one can apply the recently developed method of domain segmentation. That is, the domain may be split into several subdomains, on which the optimisation problem is solved.

In classic adaptive numerical methods, the mesh as well as the domain may be refined or decomposed, in order to improve the accuracy. Also, the degree of approximation accuracy may be adapted. Therefore, it is desirable to transfer such important and successful strategies to the field of neural-network-based solutions. In the presented work, we propose a novel adaptive neural approach to meet this aim for solving time-dependent problems.

To this end, each subdomain is reduced in size until the optimisation is resolved up to a predefined training accuracy. In addition, while the neural networks employed are by default small, we propose a means to adjust also the number of neurons in an adaptive way. We introduce conditions to automatically confirm the solution reliability and optimise computational parameters whenever it is necessary. Results are provided for several initial-value problems that illustrate important computational properties of the method.
SAM protects against alveolar septal cell apoptosis in autoimmune emphysema rats
Authors: Li Dan , Li Ben-xue , Zhang Ye , Li Xia , Li Jia-yi , Zhang Xiang-yan , Ye Xian-wei , Zhang Cheng
Published: October 2023

Background

Hypomethylation of the perforin gene promoter in CD4 + T cells, inflammation and oxidative stress, might be involved in alveolar septal cell apoptosis associated with emphysema in rats. This study aimed to investigate the effects of S-adenosylmethionine (SAM) on this kind of apoptosis in rats with autoimmune emphysema.

Methods

Twenty-four rats were randomly divided into three groups: a normal control group, a model group, and a SAM group. Pathological changes in lung tissues were observed, and the mean linear intercept (MLI) and mean alveolar number (MAN) were measured. The levels of anti-endothelial cell antibodies (AECA) in serum, alveolar septal cell apoptosis, perforin gene promotor methylation in CD4 + T cells in the spleen, and the levels of cytokines, malondialdehyde (MDA), and glutathione (GSH) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in bronchoalveolar lavage fluid (BALF) were investigated.

Results

The MLI, apoptosis index (AI) of alveolar septal cells, levels of AECA in serum, and levels of tumour necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9) and MDA in BALF were increased, while the MAN, methylation levels, and the activities of GSH, SOD and GSH-Px in BALF were decreased in the model group compared with those in the normal control group and the SAM group (all P < 0.05). The levels of interleukin-8 (IL-8) in BALF were greater in the model group than in the normal control group (P < 0.05).

Conclusions

SAM protects against alveolar septal cell apoptosis, airway inflammation and oxidative stress in rats with autoimmune emphysema possibly by partly reversing the hypomethylation of the perforin gene promoter in CD4 + T cells.
Crosstalk between autophagy and insulin resistance: evidence from different tissues
Authors: Sadeghi Asie , Niknam Maryam , Momeni-Moghaddam Mohammad Amin , Shabani Maryam , Aria Hamid , Bastin Alireza , Teimouri Maryam , Meshkani Reza , Akbari Hamed
Published: October 2023

Insulin is a critical hormone that promotes energy storage in various tissues, as well as anabolic functions. Insulin resistance significantly reduces these responses, resulting in pathological conditions, such as obesity and type 2 diabetes mellitus (T2DM). The management of insulin resistance requires better knowledge of its pathophysiological mechanisms to prevent secondary complications, such as cardiovascular diseases (CVDs). Recent evidence regarding the etiological mechanisms behind insulin resistance emphasizes the role of energy imbalance and neurohormonal dysregulation, both of which are closely regulated by autophagy. Autophagy is a conserved process that maintains homeostasis in cells. Accordingly, autophagy abnormalities have been linked to a variety of metabolic disorders, including insulin resistance, T2DM, obesity, and CVDs. Thus, there may be a link between autophagy and insulin resistance. Therefore, the interaction between autophagy and insulin function will be examined in this review, particularly in insulin-responsive tissues, such as adipose tissue, liver, and skeletal muscle.
A novel serum calprotectin (MRP8/14) particle-enhanced immuno-turbidimetric assay (sCAL turbo) helps to differentiate systemic juvenile idiopathic arthritis from other diseases in routine clinical laboratory settings
Authors: Foell Dirk , Saers Melanie , Park Carolin , Brix Ninna , Glerup Mia , Kessel Christoph , Wittkowski Helmut , Hinze Claas , Berntson Lillemor , Fasth Anders , Myrup Charlotte , Nordal Ellen , Rygg Marite , Hasle Henrik , Albertsen Birgitte Klug , Herlin Troels , Holzinger Dirk , Niederberger Christian , Schlüter Bernhard
Published: October 2023

Background

Differential diagnosis in children with signs of unprovoked inflammation can be challenging. In particular, differentiating systemic juvenile idiopathic arthritis (SJIA) from other diagnoses is difficult. We have recently validated the complex of myeloid-related proteins 8/14 (MRP8/14, also known as S100A8/A9 complex or serum calprotectin) as a helpful biomarker supporting the diagnosis of SJIA. The results were subsequently confirmed with a commercial ELISA. However, further optimization of the analytical technology is important to ensure its feasibility for large-scale use in routine laboratory settings.

Methods

To evaluate the accuracy in identifying children with SJIA, the performance of a particle-enhanced immuno-turbidimetric assay for serum calprotectin (sCAL turbo) on an automated laboratory instrument was analyzed. Samples from 615 children were available with the diagnoses SJIA (n = 99), non-systemic JIA (n = 169), infections (n = 51), other inflammatory diseases (n = 126), and acute lymphoblastic leukemia (ALL,n = 147). In addition, samples from 23 healthy controls were included.

Results

The sCAL turbo assay correlated well with the MRP8/14 ELISA used in previous validation studies (r = 0.99,p < 0.001). It could reliably differentiate SJIA from all other diagnoses with significant accuracy (cutoff at 10,500 ng/ml, sensitivity 84%, specificity 94%, ROC area under curve 0.960,p < 0.001).

Conclusions

Serum calprotectin analyses are a helpful tool supporting the diagnosis of SJIA in children with prolonged fever or inflammatory disease. Here, we show that an immuno-turbidimetric assay for detection of serum calprotectin on an automated laboratory instrument can be implemented in clinical laboratory settings to facilitate its use as a diagnostic routine test in clinical practice.
An evaluation of Substance Painter and Mari as visualisation methods using the Piraeus Lion and its runic inscriptions as a case study
Authors: Potter Rich , Rönnlund Robin , Wallensten Jenny
Published: October 2023

This paper explores the effectiveness in the use of texture painting software packages, which are more commonly used in the film and game industries, as a method for detecting and recording carvings on non-planar surfaces. This new approach is demonstrated through a case study of the Piraeus Lion, a sculpture in Venice which has documented engravings that are subtle and have proven difficult to fully recorded and interpret using traditional approaches. Through the creation of a new digital documentation of the Piraeus Lion using Structure from Motion, the model was processed using existing methods and other experimental visualisation techniques. The outputs from these were then compared to the those from two software, Substance Painter and Mari. These software packages helped to visualise the carvings and showed that the method has potential for a wide range of uses, both within epigraphy and other fields of study relating to carvings on stone including rock art and runology. The presented method is intended to be used alongside existing digital and analogue methods as a tool for annotating, evaluating, and discovering new carvings in their original context. In particular, Substance Painter offers a repeatable, easy to use, and intuitive solution to creating easily distributable visualisations and annotated models.
Using open educational resources in studio-based flipped classrooms: action research in video production learning
Authors: Chan Yuet Kai , Oh Jae-Eun , Ma Henry
Published: October 2023

This study explores the use of open educational resources (OERs) in studio-based learning and their influence on learning experiences. The research team conducted action research with 30 bachelor of arts students who were completing a video production subject. Students were required to learn from a website containing open online learning resources under a flipped classroom approach. A teaching schedule and website were designed according to several criteria. Research data were collected through observation, reflective journals, and interviews and were analyzed via thematic analysis. Participating students expressed their perceptions of benefits and hesitation in utilizing OERs in learning. They agreed that the use of OERs as flipped classroom learning materials could positively affect their learning, primarily through competence and learning autonomy as indicated in self-determination theory. This investigation provides teachers with valuable experience and suggestions for teaching and learning approaches that incorporate OERs into studio-based education. Students learn from OERs in which they can gain the most up-to-date technical knowledge in an autonomous environment. This experience indicates that this pedagogy greatly and positively influences students’ subject-learning experiences, learning outcomes, and self-learning skills.
SARS-CoV-2 spike protein S1 activates Cx43 hemichannels and disturbs intracellular Ca2+ dynamics
Authors: Prieto-Villalobos Juan , Lucero Claudia M. , Rovegno Maximiliano , Gómez Gonzalo I. , Retamal Mauricio A. , Orellana Juan A.
Published: October 2023

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the ongoing coronavirus disease 2019 (COVID-19). An aspect of high uncertainty is whether the SARS-CoV-2 per se or the systemic inflammation induced by viral infection directly affects cellular function and survival in different tissues. It has been postulated that tissue dysfunction and damage observed in COVID-19 patients may rely on the direct effects of SARS-CoV-2 viral proteins. Previous evidence indicates that the human immunodeficiency virus and its envelope protein gp120 increase the activity of connexin 43 (Cx43) hemichannels with negative repercussions for cellular function and survival. Here, we evaluated whether the spike protein S1 of SARS-CoV-2 could impact the activity of Cx43 hemichannels.

Results

We found that spike S1 time and dose-dependently increased the activity of Cx43 hemichannels in HeLa-Cx43 cells, as measured by dye uptake experiments. These responses were potentiated when the angiotensin-converting enzyme 2 (ACE2) was expressed in HeLa-Cx43 cells. Patch clamp experiments revealed that spike S1 increased unitary current events with conductances compatible with Cx43 hemichannels. In addition, Cx43 hemichannel opening evoked by spike S1 triggered the release of ATP and increased the [Ca2+]i dynamics elicited by ATP.

Conclusions

We hypothesize that Cx43 hemichannels could represent potential pharmacological targets for developing therapies to counteract SARS-CoV-2 infection and their long-term consequences.
Energy metaverse: the conceptual framework with a review of the state-of-the-art methods and technologies
Authors: Ma Zheng
Published: October 2023

The transition to green energy systems is vital for addressing climate change, with a focus on renewable sources like wind and solar. This change requires substantial investment, societal adaptations, and managing a complex energy ecosystem. However, no existing evaluation methods support this purpose. The "energy metaverse" is proposed as a digital platform that mirrors the energy ecosystem, enabling the design, trial, and assessment of new technologies, business models, and value chains before real-world deployment. Drawing from State-of-the-Art technologies and methodologies, this paper introduces a conceptual framework for the energy metaverse, comprising five essential components: a versatile energy ecosystem data space, an interoperable virtual ecosystem living lab, an energy system models and artificial intelligent algorithms sandbox, a circular value chain co-design toolbox, and an ecosystem lifecycle evaluation software tool. This paper also suggests specific methods and technologies to develop each of these five components of the energy metaverse.
Highly efficient flexible structured metasurface by roll-to-roll printing for diurnal radiative cooling
Authors: Lin Keng-Te , Nian Xianbo , Li Ke , Han Jihong , Zheng Nan , Lu Xiaokang , Guo Chunsheng , Lin Han , Jia Baohua
Published: October 2023

An ideal radiative cooler requires accurate spectral control capability to achieve efficient thermal emission in the atmospheric transparency window (8–13 μm), low solar absorption, good stability, scalability, and a simple structure for effective diurnal radiative cooling. Flexible cooling films made from polymer relying on polymer intrinsic absorbance represent a cost-effective solution but lack accuracy in spectral control. Here, we propose and demonstrate a metasurface concept enabled by periodically arranged three-dimensional (3D) trench-like structures in a thin layer of polymer for high-performance radiative cooling. The structured polymer metasurface radiative cooler is manufactured by a roll-to-roll printing method. It exhibits superior spectral breadth and selectivity, which offers outstanding omnidirectional absorption/emission (96.1%) in the atmospheric transparency window, low solar absorption (4.8%), and high stability. Impressive cooling power of 129.8 W m−2 and temperature deduction of 7 °C on a clear sky midday have been achieved, promising broad practical applications in energy saving and passive heat dispersion fields.
Severe mental illness, race/ethnicity, multimorbidity and mortality following COVID-19 infection: nationally representative cohort study
Authors: Das-Munshi Jayati , Bakolis Ioannis , Bécares Laia , Dyer Jacqueline , Hotopf Matthew , Ocloo Josephine , Stewart Robert , Stuart Ruth , Dregan Alex
Published: October 2023

Background

The association of COVID-19 with death in people with severe mental illness (SMI), and associations with multimorbidity and ethnicity, are unclear.

Aims

To determine all-cause mortality in people with SMI following COVID-19 infection, and assess whether excess mortality is affected by multimorbidity or ethnicity.

Method

This was a retrospective cohort study using primary care data from the Clinical Practice Research Database, from February 2020 to April 2021. Cox proportional hazards regression was used to estimate the effect of SMI on all-cause mortality during the first two waves of the COVID-19 pandemic.

Results

Among 7146 people with SMI (56% female), there was a higher prevalence of multimorbidity compared with the non-SMI control group (n = 653 024, 55% female). Following COVID-19 infection, the SMI group experienced a greater risk of death compared with controls (adjusted hazard ratio (aHR) 1.53, 95% CI 1.39–1.68). Black Caribbean/Black African people were more likely to die from COVID-19 compared with White people (aHR = 1.22, 95% CI 1.12–1.34), with similar associations in the SMI group and non-SMI group (P for interaction = 0.73). Following infection with COVID-19, for every additional multimorbidity condition, the aHR for death was 1.06 (95% CI 1.01–1.10) in the SMI stratum and 1.16 (95% CI 1.15–1.17) in the non-SMI stratum (P for interaction = 0.001).

Conclusions

Following COVID-19 infection, patients with SMI were at an elevated risk of death, further magnified by multimorbidity. Black Caribbean/Black African people had a higher risk of death from COVID-19 than White people, and this inequity was similar for the SMI group and the control group.
Deconstructing the English Major in Senior Capstone Courses
Authors: Stewart Jennifer
Published: October 2023

This article offers a rationale and model for a reflective capstone course for English majors. Rooted in the SoTL concepts of active transfer and project-based experiential learning, this course asks students to reflect on and analyze their undergraduate work while developing a toolkit to articulate the value of their humanities degrees. Toward that end, students create scaffolded professional projects in multiple genres that help them highlight the soft skills they have developed in their academic career.
Teaching Amos Tutuola's The Palm-Wine Drinkard as Part of a Decolonial Literature Syllabus
Authors: Fyfe Alexander
Published: October 2023

This essay argues that The Palm-Wine Drinkard ([1952] 2014), a tale of a quest through the African bush by the Nigerian writer Amos Tutuola, does important decolonial work and is therefore an excellent candidate for inclusion on a literature syllabus that aims to introduce students to decolonial thinking. After introducing Tutuola's work and considering some of the issues at stake for a decolonial pedagogy, it argues that Drinkard provides an active reading experience that creates powerful opportunities in the classroom to challenge students’ assumptions about how colonialism was experienced by colonized populations, the valences of the human, and uses of the English language. In so doing, the essay highlights potential teachable moments in the text that may be useful to instructors who wish to adopt a decolonial approach in their literature courses.
Hidden in Plain Sight (and Hearing)
Authors: Glixon Jonathan
Published: October 2023

Jacopo de’ Barbari’s View reveals much about Venice at the turn of the sixteenth century; however, by its nature as a bird’s-eye view, it also conceals some essential aspects of the city. One of these is purely visual: for anybody viewing Venice at sea level, in 1500 or today, the image of the city would be defined by an element that fades into the broader picture: the bell towers, about a hundred of which dominate the skyline. As chapter 14 makes clear, bringing the bell towers back into focus also makes us aware of another way a bird’s-eye view obscures reality. From high in the air, Venice is quiet and serene, but at ground level, it was occupied by over 100,000 people and filled with sounds, none of them louder or more ubiquitous than those produced by the three hundred or so bells that rang out from their towers.
“Both by Sea and Land”
Authors: DeLancey Julia A.
Published: October 2023

Writing some hundred years after the publication of Jacopo de’ Barbari and Anton Kolb’s celebrated View of Venice, Thomas Coryat stated of the Venetian empire: “All these territories both by sea and land do yield them . . . exceeding great revenue.” Chapter 21 explores how the View illuminates a variety of aspects of the lucrative mercantile activity for which Venice was so famous. This stunning print maps the vessels, buildings, and waterways essential for Venetian mercantile activity: it shows a variety of types of ships and boats, many of which would have been used in the movement of goods into, out of, and around Venice; it reveals the ways in which Venetian waterways aided not only in the movement of goods but also in trade and networks; and it lays out the built fabric of the city and how that built fabric fostered interconnections between merchants, goods, and families.
Cosmopolitanism in Venice and State Strategies
Authors: Massaro Martina
Published: October 2023

Jacopo de’ Barbari’s View depicts a cosmopolitan state that visually communicates the symbolic and economic function of the city and its principal sites before the noteworthy urban interventions of the sixteenth century. This includes the transformation of Piazza San Marco into a sociopolitical stage, delimiting its original economic purpose; early in the sixteenth century, the Rialto becomes the city’s economic core. To make way for new architectural structures, physical modification within Piazza San Marco included the removal of guesthouses, apartments for wealthy foreign merchants who resided in the city, and osterie (hostelries) for those who came temporarily to Venice for business transactions. In conjunction with its political agenda, the state relocated foreign communities to specific areas within the city; the Jews obtained a permanent, unified, and clearly demarcated presence within the Ghetto, established in 1516. In this way, the state simultaneously welcomed non-Venetian communities and managed and controlled their presence.
Dynamic metabolism during early mammalian embryogenesis
Authors: Zhao Jing , Wang Wenjie , Zhang Ling , Zhang Jia , Sturmey Roger , Zhang Jin
Published: October 2023

Dynamic metabolism is exhibited by early mammalian embryos to support changing cell fates during development. It is widely acknowledged that metabolic pathways not only satisfy cellular energetic demands, but also play pivotal roles in the process of cell signalling, gene regulation, cell proliferation and differentiation. Recently, various new technological advances have been made in metabolomics and computational analysis, deepening our understanding of the crucial role of dynamic metabolism during early mammalian embryogenesis. In this Review, we summarize recent studies on oocyte and embryo metabolism and its regulation, with a particular focus on its association with key developmental events such as fertilization, zygote genome activation and cell fate determination. In addition, we discuss the mechanisms of certain metabolites that, in addition to serving as energy sources, contribute to epigenetic modifications.