bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the effect of a mild cycling heating period on leukocyte coping capacity in growing pigs
Authors: Byrd Christopher J. , Young Jennifer M.
Published: April 2023

This study evaluated whether leukocyte coping capacity (LCC) could be an effective method for detecting physiological stress in growing pigs who are exposed to a mild cycling heating period. We hypothesized that whole blood samples collected from pigs exposed to high environmental temperatures would exhibit a reduced respiratory burst response [measured in relative light units (RLU) using chemiluminescence, where reduced RLU levels indicate a smaller respiratory burst size] compared to pigs that were only exposed to thermoneutral temperatures. A secondary objective was to determine the time required for LCC whole blood samples to reach their maximal RLU value following in vitro challenge using phorbol-12-myristate 13-acetate (PMA) to induce a respiratory burst. Forty growing pigs (mean 66.7 kg; range: 54.9 – 87.5 kg) were assigned to 1 of 2 treatments: 1) heat stress (HS; n = 20), or 2) thermoneutral (TN; n = 20). The HS pigs experienced a cycling mild heat stress period over 48 h (range: 19.5-28.6°C), while TN pigs were exposed to thermoneutral temperatures (range: 18.9-23.7°C). Whole-blood samples were collected via jugular venipuncture at 0, + 4, +8, +24, and +48 h relative to the start of the cycling heating period and were artificially challenged using PMA. Samples were measured at 0, + 15, and +30 min relative to in vitro challenge. No differences were observed between HS and TN treatments (P = 0.67) and no treatment by hour interaction was detected (P = 0.48). Maximal RLU values were obtained at 15 min post-PMA challenge (P < 0.05).
Decellularized rat submandibular gland as an alternative scaffold for dental pulp regeneration
Authors: Shi Yuanyuan , Wang Yingxin , Shan Zhaochen , Gao Zhenhua
Published: April 2023

Introduction: Decellularized extracellular matrix has been recognized as an optimal scaffold for dental pulp regeneration. However, the limited amount of native dental pulp tissue restricts its clinical applications. The submandibular gland shares some basic extracellular matrix components and characteristics with dental pulp. However, whether decellularized submandibular gland extracellular matrix (DSMG) can be used as an alternative scaffold for dental pulp regenerative medicine is unclear.

Methods: Thus, we successfully decellularized the whole rat submandibular gland and human dental pulp, and then conducted in vitro and in vivo studies to compare the properties of these two scaffolds for dental pulp regeneration.

Results: Our results showed that extracellular matrix of the submandibular gland had great similarities in structure and composition with that of dental pulp. Furthermore, it was confirmed that the DSMG could support adhesion and proliferation of dental pulp stem cells in vitro. In vivo findings revealed that implanted cell-seeded DSMG formed a vascularized dental pulp-like tissue and expressed markers involved in dentinogenesis and angiogenesis.

Discussion: In summary, we introduced a novel accessible biological scaffold and validated its effectiveness as an extracellular matrix-based tissue engineering scaffold for dental pulp regenerative therapy.
Empowering trusted data sharing for data analytics in a federated environment: A blockchain-based approach
Authors: Plebani Pierluigi , Rossetto Davide , Tiezzi Francesco
Published: April 2023

As data analytics is used in business to increase profits, organizations use it to pursue their goals. Even if enterprise data could be already valuable on its own, in many cases, combining it with external data sources would boost the value of the output, making data sharing a need in data analytics. At the same time, organizations are reluctant to share data, as they are scared of disclosing critical information. This calls for solutions that are able to safeguard data holders by regulating how data can be shared to ensure the so-called data sovereignty. This paper focuses on the usage of data lakes as well-established technology across enterprises for data analytics where internal or publicly available data are considered. The goal is to extend data lakes with functionalities that, respecting the data sovereignty, enable a data lake also to be ingested with data shared by other organizations and to share data to external organizations. Notable, the purpose of this work is to face this issue by defining an architecture that, inserted in a federated environment: restricts data access and enables monitoring that the actual usage of data respects the data sovereignty expressed in the policies agreed upon by the involved parties; makes use of Blockchain technology as a means for guaranteeing the traceability of data sharing; and allows for balancing computation movement and data movement. The proposed approach has been applied to a healthcare scenario where several institutions (e.g., hospitals and clinics, research institutes, and medical universities) produce and collect clinical data in local data lakes.
The KDM5B and KDM1A lysine demethylases cooperate in regulating androgen receptor expression and signalling in prostate cancer
Authors: Metzler Veronika M. , de Brot Simone , Haigh Daisy B. , Woodcock Corinne L. , Lothion-Roy Jennifer , Harris Anna E. , Nilsson Emeli M. , Ntekim Atara , Persson Jenny L. , Robinson Brian D. , Khani Francesca , Laursen Kristian B. , Gudas Lorraine J. , Toss Michael S. , Madhusudan Srinivasan , Rakha Emad , Heery David M. , Rutland Catrin S. , Mongan Nigel P. , Jeyapalan Jennie N.
Published: April 2023

Histone H3 lysine 4 (H3K4) methylation is key epigenetic mark associated with active transcription and is a substrate for the KDM1A/LSD1 and KDM5B/JARID1B lysine demethylases. Increased expression of KDM1A and KDM5B is implicated in many cancer types, including prostate cancer (PCa). Both KDM1A and KDM5B interact with AR and promote androgen regulated gene expression. For this reason, there is great interested in the development of new therapies targeting KDM1A and KDM5B, particularly in the context of castrate resistant PCa (CRPC), where conventional androgen deprivation therapies and androgen receptor signalling inhibitors are no longer effective. As there is no curative therapy for CRPC, new approaches are urgently required to suppress androgen signalling that prevent, delay or reverse progression to the castrate resistant state. While the contribution of KDM1A to PCa is well established, the exact contribution of KDM5B to PCa is less well understood. However, there is evidence that KDM5B is implicated in numerous pro-oncogenic mechanisms in many different types of cancer, including the hypoxic response, immune evasion and PI3/AKT signalling. Here we elucidate the individual and cooperative functions of KDM1A and KDM5B in PCa. We show that KDM5B mRNA and protein expression is elevated in localised and advanced PCa. We show that the KDM5 inhibitor, CPI-455, impairs androgen regulated transcription and alternative splicing. Consistent with the established role of KDM1A and KDM5B as AR coregulators, we found that individual pharmacologic inhibition of KDM1A and KDM5 by namoline and CPI-455 respectively, impairs androgen regulated transcription. Notably, combined inhibition of KDM1A and KDM5 downregulates AR expression in CRPC cells. Furthermore, combined KDM1A and KDM5 inhibition impairs PCa cell proliferation and invasion more than individual inhibition of KDM1A and KDM5B. Collectively our study has identified individual and cooperative mechanisms involving KDM1A and KDM5 in androgen signalling in PCa. Our findings support the further development of KDM1A and KDM5B inhibitors to treat advanced PCa. Further work is now required to confirm the therapeutic feasibility of combined inhibition of KDM1A and KDM5B as a novel therapeutic strategy for targeting AR positive CRPC.
Intensified biodiesel production from waste cooking oil and flow pattern evolution in small-scale reactors
Authors: Tsaoulidis Dimitrios , Garciadiego-Ortega Eduardo , Angeli Panagiota
Published: April 2023

In this paper, the transesterification reaction of waste cooking oil (WCO) with methanol using KOH as catalyst to produce biodiesel was performed in a micro-reactor (1 mm ID) using a cross-flow inlet configuration. The effects of different variables such as, methanol-to-oil molar ratio, temperature, catalyst concentration, and residence time on biodiesel yield, as well as the associated flow patterns during the transesterification reaction were investigated and the relationship between flow characteristics and mass transfer performance of the system was examined. The work reveals important aspects and the links between the hydrodynamic behaviour and the mass transfer performance of the intensified reactors. It was found that high yield (>90%) of biodiesel can be achieved in one-stage reaction using cross-flow micro-reactors for a wide range of conditions, i.e., methanol-to-oil molar ratio: 8–14, catalyst concentration: 1.4%–1.8% w/w, temperature: 55°C–60°C, and residence times: 55–75 s.
Case report: Early acute myocarditis after radiation therapy for breast cancer: A case presentation and review of literature
Authors: Sharifkazemi Mohammadbagher , Elahi Mahsa , Sayad Masoud
Published: April 2023

Breast cancer is the most commonly diagnosed cancer in women worldwide, and with the increased survival of patients by novel treatments, the frequency of complications of cancer treatments rises. Radiotherapy, especially on the chest wall, can damage different cardiac structures. Radiotherapy-induced cardiomyopathy mainly occurs over 10 years after breast cancer treatment; however, there is a gap in the literature on acute myocarditis following radiotherapy. Here, we present a 54-year-old woman who developed acute myocarditis shortly after 25 sessions of radiotherapy with 50 Gy of radiation, successfully diagnosed with the use of speckle tracking echocardiography (STE) and cardiac magnetic resonance (CMR), and responded to the medical treatment with relative clinical improvement until the final follow-up. This case suggests the necessity of detailed examination of patients after radiotherapy, not only for chronic occurrence of cardiomyopathy but also for acute myocarditis. Although STE and CMR resulted in accurate diagnosis, in this case, further studies are required to determine the diagnostic accuracy of these two imaging methods compared with other imaging modalities in such patients and investigate the best diagnostic tool and therapeutic approach for these patients.
Transcatheter heart valve commissural alignment: an updated review
Authors: Akodad Mariama , Lounes Youcef , Meier David , Sanguineti Francesca , Hovasse Thomas , Blanke Philipp , Sathananthan Janarthanan , Tzimas Georgios , Leipsic Jonathon , Wood David A. , Webb John , Chevalier Bernard
Published: April 2023

Transcatheter aortic valve replacement (TAVR) indications recently extended to lower surgical risk patients with longer life expectancy. Commissural alignment (CA) is one of the emerging concepts and is becoming one of the cornerstones of the TAVR procedure in a patient with increased longevity. Indeed, CA may improve transcatheter heart valve (THV) hemodynamics, future coronary access, and repeatability. The definition of CA has been recently standardized by the ALIGN-TAVR consortium using a four-tier scale based on CT analysis. Progress has been made during the index TAVR procedure to optimize CA, especially with self-expandable platforms. Indeed, specific delivery catheter orientation, THV rotation, and computed-tomography-derived views have been proposed to achieve a reasonable degree of CA. Recent data demonstrate feasibility, safety, and a significant reduction in coronary overlap using these techniques, especially with self-expandable platforms. This review provides an overview of THV CA including assessment methods, alignment techniques during the index TAVR procedure with different THV platforms, the clinical impact of commissural misalignment, and challenging situations for CA.
Experimental study on the evolution characteristics of gas pressure field for true triaxial cyclic mining
Authors: Geng Jiabo , Liu Jiangtong , Zeng Gaoxiong , Zhang Dongming , Guo Zhigguo , Xu Jiang
Published: April 2023

The evolution characteristics of coal seam strain and gas pressure in circular mining were explored by conducting physical simulation tests on the influence of cyclic stress on coal seam parameters under different initial gas pressures using a large true triaxial physical simulation test rig. The evolution characteristics of gas pressure and coal seam strain with the number of cycles and gas pressure were discussed. The test results showed that during cyclic loading and unloading, the coal seam is cracked under stress and new cracks are generated, and the new fractures cause the overall pressure of the coal seam methane to decrease by adsorbing more free gas. In the loading stage, the coal skeleton is squeezed by stress, which causes the space of coal seam pores and cracks to shrink, the free gas in the pores and fractures of the coal seam is extruded, and the strain and gas pressure of the coal seam increase with the increase of stress. In the unloading stage, the reduction of stress leads to the coal skeleton tending to return to its initial state, the free gas in the pores is transported and enriched into the fractures of the coal seam, and the strain and gas pressure of the coal seam are gradually reduced. With the increase of the number of cycles, the damage of the coal seam increases and deformation occurs, the increasing amplitude of gas pressure gradually increases during loading, and the decreasing amplitude of gas pressure gradually decreases when unloading, and the closer the distance from the pressurized boundary, the greater the amplitude change. Under different initial gas pressure conditions, the greater the initial gas pressure, the greater the increasing amplitude of gas pressure and the smaller the decreasing amplitude.
Decreased macular choriocapillaris in thyroid-associated ophthalmopathy: focusing on chorioretinal folds with and without optic disc edema
Authors: Zeng Peng , Liang Jia-qi , Peng Yuan-yu , Fan Shu-xian , Wang Jing , Zhou Shi-you , Tian Peng , Wang Mei
Published: April 2023

Purpose

The aim of this study was to evaluate the vessel density (VD) of the macular choriocapillaris (CC) and retina in thyroid-associated ophthalmopathy (TAO) patients with chorioretinal folds (CRFs) with and without optic disc edema (ODE) and the correlations of these characteristics with visual function.

Method

This was a cross-sectional study. Twenty TAO patients with CRFs (35 eyes) and 20 normal subjects (normal group, 40 eyes) were recruited at the Ophthalmology Department of the Sun Yat-sen Memorial Hospital from March 2018 to October 2022. Then, CRF patients were divided into two groups, the ODE and non-ODE groups (NODE), based on the presence or absence of ODE. All the patients underwent optical coherence tomography angiography (OCTA) and the VD of the macular CC and retina was computed. The correlation of VD and visual function was analyzed.

Results

Compared with the normal group, the macular whole-image VD in the retinal superficial layer (SLR-mwiVD: 49.82 ± 3.38 in the normal group, 42.44 ± 5.40 in the NODE group, and 42.51 ± 5.37 in the ODE group), deep layer (DLR-mwiVD: 51.05 ± 6.23 in the normal group, 45.71 ± 6.66 in the NODE group, and 46.31 ± 5.48 in the ODE group), and CC (CC-mwiVD: 70.23 ± 2.47 in the normal group, 68.04 ± 3.73 in the NODE group, and 63.09 ± 6.51 in the ODE group) was decreased in the NODE (all p < 0.05) and ODE group (all p < 0.01). There was no difference in these parameters except CC-mwiVD between the ODE and NODE groups. The CC-mwiVD in the ODE group (63.09 ± 6.51) was significantly reduced compared with that in the NODE group (68.04 ± 3.73, p = 0.004). All these VD parameters were negatively correlated with BCVA, VF-PSD, and P100 latency and positively associated with VF-MD, P100 amplitude, and HRR scores (all p < 0.05).

Conclusions

There was a significant decrease in the VD of the macular CC and retina of patients with CRFs with or without ODE, which was correlated with visual dysfunction. The VD of the macular CC in CRF patients with ODE was significantly reduced compared with that in the NODE group, but similar results were not observed in the retina.
Functional brain alterations in Cushing’s syndrome
Authors: Papakokkinou Eleni , Ragnarsson Oskar
Published: April 2023

Cognitive impairment and affective disorders are common in patients with Cushing’s syndrome (CS). In fact, as an effect of prolonged cortisol excess on the brain, patients with CS often have memory problems, concentration difficulties, impaired attention and executive function, that are not always reversible following successful treatment. Neuroimaging is essential for understanding the deleterious effects of hypercortisolism on the brain. In CS, structural alterations have been observed, including reduction of hippocampal volume, amygdala and the prefrontal cortex. The aim of this article is to summarize results from studies that have used functional magnetic resonance imaging (fMRI) to study functional brain alterations in patients with CS. In these studies, alterations in brain areas and networks essential for cognitive function, emotional processing, and executive function have been observed, both in patients with active CS as well as following treatment. Nevertheless, longitudinal studies with a comprehensive evaluation of functional brain alterations and neurocognitive evaluation are still needed to determine whether the apparent deleterious effects of hypercortisolism on the brain are reversible or not.
Role of ADMA in the pathogenesis of microvascular complications in type 2 diabetes mellitus
Authors: Guo Xinyang , Xing Yiqiao , Jin Wei
Published: April 2023

Diabetic microangiopathy is a typical and severe problem in diabetics, including diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, and diabetic cardiomyopathy. Patients with type 2 diabetes and diabetic microvascular complications have significantly elevated levels of Asymmetric dimethylarginine (ADMA), which is an endogenous inhibitor of nitric oxide synthase (NOS). ADMA facilitates the occurrence and progression of microvascular complications in type 2 diabetes through its effects on endothelial cell function, oxidative stress damage, inflammation, and fibrosis. This paper reviews the association between ADMA and microvascular complications of diabetes and elucidates the underlying mechanisms by which ADMA contributes to these complications. It provides a new idea and method for the prevention and treatment of microvascular complications in type 2 diabetes.
Comparative transcriptome analysis of the mechanism difference in heat stress response between indica rice cultivar “IR64” and japonica cultivar “Koshihikari” at the seedling stage
Authors: Wang Yingfeng , Wang Yubo , Chen Wenjuan , Dong Yating , Zhang Guilian , Deng Huabing , Liu Xiong , Lu Xuedan , Wang Feng , Chen Guihua , Xiao Yunhua , Tang Wenbang
Published: April 2023

Heat stress (HS) has become a major abiotic stress in rice, considering the frequency and intensity of extreme hot weather. There is an urgent need to explore the differences in molecular mechanisms of HS tolerance in different cultivars, especially in indica and japonica. In this study, we investigated the transcriptome information of IR64 (indica, IR) and Koshihikari (japonica, Kos) in response to HS at the seedling stage. From the differentially expressed genes (DEGs) consistently expressed at six time points, 599 DEGs were identified that were co-expressed in both cultivars, as well as 945 and 1,180 DEGs that were specifically expressed in IR and Kos, respectively. The results of GO and KEGG analysis showed two different HS response pathways for IR and Kos. IR specifically expressed DEGs were mainly enriched in chloroplast-related pathways, whereas Kos specifically expressed DEGs were mainly enriched in endoplasmic reticulum and mitochondria-related pathways. Meanwhile, we highlighted the importance of NO biosynthesis genes, especially nitrate reductase genes, in the HS response of IR based on protein-protein interaction networks. In addition, we found that heat shock proteins and heat shock factors play very important roles in both cultivars. This study not only provides new insights into the differences in HS responses between different subspecies of rice, but also lays the foundation for future research on molecular mechanisms and breeding of heat-tolerant cultivars.
Modulating sphingosine 1-phosphate receptor signaling skews intrahepatic leukocytes and attenuates murine nonalcoholic steatohepatitis
Authors: Liao Chieh-Yu , Barrow Fanta , Venkatesan Nanditha , Nakao Yasuhiko , Mauer Amy S. , Fredrickson Gavin , Song Myeong Jun , Sehrawat Tejasav S. , Dasgupta Debanjali , Graham Rondell P. , Revelo Xavier S. , Malhi Harmeet
Published: April 2023

Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid associated with nonalcoholic steatohepatitis (NASH). Immune cell-driven inflammation is a key determinant of NASH progression. Macrophages, monocytes, NK cells, T cells, NKT cells, and B cells variably express S1P receptors from a repertoire of 5 receptors termed S1P1 – S1P5. We have previously demonstrated that non-specific S1P receptor antagonism ameliorates NASH and attenuates hepatic macrophage accumulation. However, the effect of S1P receptor antagonism on additional immune cell populations in NASH remains unknown. We hypothesized that S1P receptor specific modulation may ameliorate NASH by altering leukocyte recruitment. A murine NASH model was established by dietary feeding of C57BL/6 male mice with a diet high in fructose, saturated fat, and cholesterol (FFC) for 24 weeks. In the last 4 weeks of dietary feeding, the mice received the S1P1,4,5 modulator Etrasimod or the S1P1 modulator Amiselimod, daily by oral gavage. Liver injury and inflammation were determined by histological and gene expression analyses. Intrahepatic leukocyte populations were analyzed by flow cytometry, immunohistochemistry, and mRNA expression. Alanine aminotransferase, a sensitive circulating marker for liver injury, was reduced in response to Etrasimod and Amiselimod treatment. Liver histology showed a reduction in inflammatory foci in Etrasimod-treated mice. Etrasimod treatment substantially altered the intrahepatic leukocyte populations through a reduction in the frequency of T cells, B cells, and NKT cells and a proportional increase in CD11b+ myeloid cells, polymorphonuclear cells, and double negative T cells in FFC-fed and control standard chow diet (CD)-fed mice. In contrast, FFC-fed Amiselimod-treated mice showed no changes in the frequencies of intrahepatic leukocytes. Consistent with the improvement in liver injury and inflammation, hepatic macrophage accumulation and the gene expression of proinflammatory markers such as Lgals3 and Mcp-1 were decreased in Etrasimod-treated FFC-fed mice. Etrasimod treated mouse livers demonstrated an increase in non-inflammatory (Marco) and lipid associated (Trem2) macrophage markers. Thus, S1P1,4,5 modulation by Etrasimod is more effective than S1P1 antagonism by Amiselimod, at the dose tested, in ameliorating NASH, likely due to the alteration of leukocyte trafficking and recruitment. Etrasimod treatment results in a substantial attenuation of liver injury and inflammation in murine NASH.
Nafamostat has anti-asthmatic effects associated with suppressed pro-inflammatory gene expression, eosinophil infiltration and airway hyperreactivity
Authors: Allam Venkata Sita Rama Raju , Waern Ida , Taha Sowsan , Akula Srinivas , Wernersson Sara , Pejler Gunnar
Published: April 2023

Introduction

Asthma is characterized by an imbalance between proteases and their inhibitors. Hence, an attractive therapeutic option could be to interfere with asthma-associated proteases. Here we exploited this option by assessing the impact of nafamostat, a serine protease inhibitor known to neutralize mast cell tryptase.

Methods

Nafamostat was administered in a mouse model for asthma based on sensitization by house dust mite (HDM) extract, followed by the assessment of effects on airway hyperreactivity, inflammatory parameters and gene expression.

Results

We show that nafamostat efficiently suppressed the airway hyperreactivity in HDM-sensitized mice. This was accompanied by reduced infiltration of eosinophils and lymphocytes to the airways, and by lower levels of pro-inflammatory compounds within the airway lumen. Further, nafamostat had a dampening impact on goblet cell hyperplasia and smooth muscle layer thickening in the lungs of HDM-sensitized animals. To obtain deeper insight into the underlying mechanisms, a transcriptomic analysis was conducted. This revealed, as expected, that the HDM sensitization caused an upregulated expression of numerous pro-inflammatory genes. Further, the transcriptomic analysis showed that nafamostat suppressed the levels of multiple pro-inflammatory genes, with a particular impact on genes related to asthma.

Discussion

Taken together, this study provides extensive insight into the ameliorating effect of nafamostat on experimental asthma, and our findings can thereby provide a basis for the further evaluation of nafamostat as a potential therapeutic agent in human asthma.
The magic of small-molecule drugs during ex vivo expansion in adoptive cell therapy
Authors: Zhang Hanwen , Passang Tenzin , Ravindranathan Sruthi , Bommireddy Ramireddy , Jajja Mohammad Raheel , Yang Lily , Selvaraj Periasamy , Paulos Chrystal M. , Waller Edmund K.
Published: April 2023

In the past decades, advances in the use of adoptive cellular therapy to treat cancer have led to unprecedented responses in patients with relapsed/refractory or late-stage malignancies. However, cellular exhaustion and senescence limit the efficacy of FDA-approved T-cell therapies in patients with hematologic malignancies and the widespread application of this approach in treating patients with solid tumors. Investigators are addressing the current obstacles by focusing on the manufacturing process of effector T cells, including engineering approaches and ex vivo expansion strategies to regulate T-cell differentiation. Here we reviewed the current small-molecule strategies to enhance T-cell expansion, persistence, and functionality during ex vivo manufacturing. We further discussed the synergistic benefits of the dual-targeting approaches and proposed novel vasoactive intestinal peptide receptor antagonists (VIPR-ANT) peptides as emerging candidates to enhance cell-based immunotherapy.
Three doses of a recombinant conjugated SARS-CoV-2 vaccine early after allogeneic hematopoietic stem cell transplantation: predicting indicators of a high serologic response—a prospective, single-arm study
Authors: Barkhordar Maryam , Chahardouli Bahram , Biglari Alireza , Ahmadvand Mohammad , Bahri Tanaz , Alaeddini Farshid , Sharifi Aliabadi Leyla , Noorani Seied Saeid , Bagheri Amiri Fahimeh , Biglari Mohammad , Shemshadi Mohammad Reza , Ghavamzadeh Ardeshir , Vaezi Mohammad
Published: April 2023

Background

Allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients must be vaccinated against SARS-CoV-2 as quickly as possible after transplantation. The difficulty in obtaining recommended SARS-CoV-2 vaccines for allo-HSCT recipients motivated us to utilize an accessible and affordable SARS-CoV-2 vaccine with a recombinant receptor-binding domain (RBD)–tetanus toxoid (TT)-conjugated platform shortly after allo-HSCT in the developing country of Iran.

Methods

This prospective, single-arm study aimed to investigate immunogenicity and its predictors following a three-dose SARS-CoV-2 RBD–TT-conjugated vaccine regimen administered at 4-week (± 1-week) intervals in patients within 3–12 months post allo-HSCT. An immune status ratio (ISR) was measured at baseline and 4 weeks (± 1 week) after each vaccine dose using a semiquantitative immunoassay. Using the median ISR as a cut-off point for immune response intensity, we performed a logistic regression analysis to determine the predictive impact of several baseline factors on the intensity of the serologic response following the third vaccination dose.

Results

Thirty-six allo-HSCT recipients, with a mean age of 42.42 years and a median time of 133 days between hematopoietic stem cell transplant (allo-HSCT) and the start of vaccination, were analyzed. Our findings, using the generalized estimating equation (GEE) model, indicated that, compared with the baseline ISR of 1.55 [95% confidence interval (CI) 0.94 to 2.17], the ISR increased significantly during the three-dose SARS-CoV-2 vaccination regimen. The ISR reached 2.32 (95% CI 1.84 to 2.79; p = 0.010) after the second dose and 3.87 (95% CI 3.25 to 4.48; p = 0.001) after the third dose of vaccine, reflecting 69.44% and 91.66% seropositivity, respectively. In a multivariate logistic regression analysis, the female sex of the donor [odds ratio (OR) 8.67; p = 0.028] and a higher level donor ISR at allo-HSCT (OR 3.56; p = 0.050) were the two positive predictors of strong immune response following the third vaccine dose. No serious adverse events (i.e., grades 3 and 4) were observed following the vaccination regimen.

Conclusions

We concluded that early vaccination of allo-HSCT recipients with a three-dose RBD–TT-conjugated SARS-CoV-2 vaccine is safe and could improve the early post-allo-HSCT immune response. We further believe that the pre-allo-HSCT SARS-CoV-2 immunization of donors may enhance post-allo-HSCT seroconversion in allo-HSCT recipients who receive the entire course of the SARS-CoV-2 vaccine during the first year after allo-HSCT.
MicroRNAs reshape the immunity of insects in response to bacterial infection
Authors: Abbas Muhammad Nadeem , Kausar Saima , Asma Bibi , Ran Wenhao , Li Jingui , Lin Zini , Li Tiejun , Cui Hongjuan
Published: April 2023

The interaction between bacteria and insects can significantly impact a wide range of different areas because bacteria and insects are widely distributed around the globe. The bacterial-insect interactions have the potential to directly affect human health since insects are vectors for disease transmission, and their interactions can also have economic consequences. In addition, they have been linked to high mortality rates in economically important insects, resulting in substantial economic losses. MicroRNAs (miRNAs) are types of non-coding RNAs involved in regulating gene expression post-transcriptionally. The length of miRNAs ranges from 19 to 22 nucleotides. MiRNAs, in addition to their ability to exhibit dynamic expression patterns, have a diverse range of targets. This enables them to govern various physiological activities in insects, like innate immune responses. Increasing evidence suggests that miRNAs have a crucial biological role in bacterial infection by influencing immune responses and other mechanisms for resistance. This review focuses on some of the most recent and exciting discoveries made in recent years, including the correlation between the dysregulation of miRNA expression in the context of bacterial infection and the progression of the infection. Furthermore, it describes how they profoundly impact the immune responses of the host by targeting the Toll, IMD, and JNK signaling pathways. It also emphasizes the biological function of miRNAs in regulating immune responses in insects. Finally, it also discusses current knowledge gaps about the function of miRNAs in insect immunity, in addition to areas that require more research in the future.
Surviving the cold: a review of the effects of cold spells on bivalves and mitigation measures
Authors: Masanja Fortunatus , Xu Yang , Yang Ke , Mkuye Robert , Deng Yuewen , Zhao Liqiang
Published: April 2023

Cold spells, characterized by prolonged periods of low temperature, have become increasingly frequent, intense, and prolonged due to the ongoing effects of climate change, resulting in devastating consequences for marine ecosystems and significant socio-economic impacts. As ectothermic organisms, bivalves are dependent on their environment for regulating body temperature, and thus, cold spells can disrupt their normal functioning, leading to mass mortalities. This review comprehensively summarizes the effects of cold spells on bivalves and proposes mitigation measures to be considered in future bivalve farming and management plans. Scientific evidence has indicated that cold spells can alter bivalve metabolism, leading to an increase in stress protein production and a decrease in the activity of energy metabolism-related enzymes, which can negatively impact the bivalve immune system and increase the risk of disease. To mitigate the effects of cold spells on bivalves, a number of strategies can be employed, including the use of thermal shelters such as floating covers, selective breeding of more cold-tolerant bivalves, and genetic engineering to enhance the expression of heat-shock proteins in bivalves. The impacts of cold spells on bivalves are significant, affecting both their physiological and molecular processes. Through the implementation of thermal shelters, selective breeding, and genetic engineering, the effects of cold spells on bivalves can be reduced, improving their survival and growth. Further research is required to fully understand cold spells’ impacts on bivalves and develop effective mitigation measures.
Spatial distribution and temporal trends of cyclic and linear siloxanes in sediment from semi-enclosed and industrialized bays of Korea, in 2013 and 2021
Authors: Chen Wenming , Kang Yujin , Lee Hyun-Kyung , Lim Jae-Eun , Lee Moonjin , Moon Hyo-Bang
Published: April 2023

Although siloxanes are contaminants of emerging concerns, limited studies have been conducted on contamination and time trends in siloxanes from aquatic environments worldwide. To date, most previous studies have focused on the environmental relevance of cyclic siloxanes in coastal environments. In the present study, cyclic and linear siloxanes were measured in sediment collected from semi-enclosed bays in Korea in 2013 and 2021 to assess occurrence, spatial distribution, temporal trends, and ecological risks. Almost all siloxanes were detected in all sediment samples, indicating continuous contamination for the last decade. The concentrations of cyclic siloxanes in sediment were approximately two times higher than those of linear siloxanes. Decamethylcyclopentasiloxane (D5) and dodecamethylcyclohexasiloxane (D6) were predominantly detected in all sediment samples, possibly due to their high consumption and strong resistance. The overall concentrations of siloxanes in sediment gradually decreased from inner to outer parts of the bays, suggesting that industrial activities largely contributed to siloxane contamination. Moreover, the highest concentrations of siloxanes in both sampling years were observed in sediment near the outfall of wastewater treatment plant, implying a potential source in the coastal environment. Siloxane concentrations in sediment were significantly correlated with sedimentary organic carbon. The concentrations of siloxanes in sediment were not significantly different between 2013 and 2021, indicating ongoing contamination. The concentrations of D5 and D6 in our sediment samples showed a limited potential to pose a threat to benthic organisms.
Finite element simulation of bonding defects in cementing casing based on circumferential SH guided waves
Authors: Gong Rui , Lyu Yan , Song Guorong , Gao Jie , He Cunfu
Published: April 2023

The circumferential guide wave can effectively evaluate the damage of pipe or the cementation quality between pipe and peripheral medium. In this research, the state matrix method is applied to derive the circumferential SH waves dispersion equation of semi-infinite domain cement clad hollow circular pipe of steel matrix in cylindrical coordinate system. By combining the orthogonal basis of Legendre and Laguerre polynomial series, the circumferential SH waves dispersion curve of semi-infinite domain clad hollow circular pipe is numerically calculated. To investigate the interaction between circumferential SH waves and various cement bonding defects, a simulation model of the cemented casing structure was established using the finite element software ABAQUS. The model was designed to vary the defect parameters, providing a comprehensive understanding of cementing quality in cementing casing. Based on the numerical calculation results, it is concluded that the amplitude of the circumferential SH wave increases with the increase of the circumferential angle of the cement bonding defect. This approach serves as a basis for evaluating the effectiveness of circumferential SH waves in identifying cement bonding defects.
Overexpression of plastid lipid-associated protein in marine diatom enhances the xanthophyll synthesis and storage
Authors: Jiang Er-Ying , Fan Yong , Phung Nghi-Van , Xia Wan-Yue , Hu Guang-Rong , Li Fu-Li
Published: April 2023

Plastoglobules, which are lipoprotein structures surrounded by a single hydrophobic phospholipid membrane, are subcellular organelles in plant chromoplasts and chloroplasts. They contain neutral lipids, tocopherols, quinones, chlorophyll metabolites, carotenoids and their derivatives. Proteomic studies indicated that plastoglobules are involved in carotenoid metabolism and storage. In this study, one of the plastid lipid-associated proteins (PAP), the major protein in plastoglobules, was selected and overexpressed in Phaeodactylum tricornutum. The diameter of the plastoglobules in mutants was decreased by a mean of 19.2% versus the wild-type, while the fucoxanthin level was increased by a mean of 51.2%. All mutants exhibited morphological differences from the wild-type, including a prominent increase in the transverse diameter. Moreover, the unsaturated fatty acid levels were increased in different mutants, including an 18.9–59.3% increase in eicosapentaenoic acid content. Transcriptomic analysis revealed that PAP expression and the morphological changes altered xanthophyll synthesis and storage, which affected the assembly of the fucoxanthin chlorophyll a/c-binding protein and expression of antenna proteins as well as reduced the non-photochemical quenching activity of diatom cells. Therefore, metabolic regulation at the suborganelle level can be achieved by modulating PAP expression. These findings provide a subcellular structural site and target for synthetic biology to modify pigment and lipid metabolism in microalgae chassis cells.
Systems biology of autophagy in leishmanial infection and its diverse role in precision medicine
Authors: Guhe Vrushali , Ingale Prajakta , Tambekar Anil , Singh Shailza
Published: April 2023

Autophagy is a contentious issue in leishmaniasis and is emerging as a promising therapeutic regimen. Published research on the impact of autophagic regulation on Leishmania survival is inconclusive, despite numerous pieces of evidence that Leishmania spp. triggers autophagy in a variety of cell types. The mechanistic approach is poorly understood in the Leishmania parasite as autophagy is significant in both Leishmania and the host. Herein, this review discusses the autophagy proteins that are being investigated as potential therapeutic targets, the connection between autophagy and lipid metabolism, and microRNAs that regulate autophagy and lipid metabolism. It also highlights the use of systems biology to develop novel autophagy-dependent therapeutics for leishmaniasis by utilizing artificial intelligence (AI), machine learning (ML), mathematical modeling, network analysis, and other computational methods. Additionally, we have shown many databases for autophagy and metabolism in Leishmania parasites that suggest potential therapeutic targets for intricate signaling in the autophagy system. In a nutshell, the detailed understanding of the dynamics of autophagy in conjunction with lipids and miRNAs unfolds larger dimensions for future research.
Developmental exposure to corn grown on Lake Erie dredged material: a preliminary analysis
Authors: Flanigan Kaylyn A. S. , Czuba Madelyn I. , Riesgo Victoria R. , Rúa Megan A. , Stevenson Louise M. , Willing Jari
Published: April 2023

While corn is considered to be a healthy food option, common agricultural practices, such as the application of soil amendments, might be introducing contaminants of concern (COC) into corn plants. The use of dredged material, which contain contaminants such as heavy metals, polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs), as a soil amendment is increasing. Contaminants from these amendments can accumulate in corn kernels harvested from plants grown on these sediments and potentially biomagnify in organisms that consume them. The extent to which secondary exposure to such contaminants in corn affect the mammalian central nervous system has been virtually unexplored. In this preliminary study, we examine the effects of exposure to corn grown in dredge amended soil or a commercially available feed corn on behavior and hippocampal volume in male and female rats. Perinatal exposure to dredge-amended corn altered behavior in the open-field and object recognition tasks in adulthood. Additionally, dredge-amended corn led to a reduction in hippocampal volume in male but not female adult rats. These results suggest the need for future studies examining how dredge-amended crops and/or commercially available feed corn may be exposing animals to COC that can alter neurodevelopment in a sex-specific manner. This future work will provide insight into the potential long-term consequences of soil amendment practices on the brain and behavior.
An artificial intelligence-based approach for identifying rare disease patients using retrospective electronic health records applied for Pompe disease
Authors: Lin Simon , Nateqi Jama , Weingartner-Ortner Rafael , Gruarin Stefanie , Marling Hannes , Pilgram Vinzenz , Lagler Florian B. , Aigner Elmar , Martin Alistair G.
Published: April 2023

Objective

We retrospectively screened 350,116 electronic health records (EHRs) to identify suspected patients for Pompe disease. Using these suspected patients, we then describe their phenotypical characteristics and estimate the prevalence in the respective population covered by the EHRs.

Methods

We applied Symptoma's Artificial Intelligence-based approach for identifying rare disease patients to retrospective anonymized EHRs provided by the “University Hospital Salzburg” clinic group. Within 1 month, the AI screened 350,116 EHRs reaching back 15 years from five hospitals, and 104 patients were flagged as probable for Pompe disease. Flagged patients were manually reviewed and assessed by generalist and specialist physicians for their likelihood for Pompe disease, from which the performance of the algorithms was evaluated.

Results

Of the 104 patients flagged by the algorithms, generalist physicians found five “diagnosed,” 10 “suspected,” and seven patients with “reduced suspicion.” After feedback from Pompe disease specialist physicians, 19 patients remained clinically plausible for Pompe disease, resulting in a specificity of 18.27% for the AI. Estimating from the remaining plausible patients, the prevalence of Pompe disease for the greater Salzburg region [incl. Bavaria (Germany), Styria (Austria), and Upper Austria (Austria)] was one in every 18,427 people. Phenotypes for patient cohorts with an approximated onset of symptoms above or below 1 year of age were established, which correspond to infantile-onset Pompe disease (IOPD) and late-onset Pompe disease (LOPD), respectively.

Conclusion

Our study shows the feasibility of Symptoma's AI-based approach for identifying rare disease patients using retrospective EHRs. Via the algorithm's screening of an entire EHR population, a physician had only to manually review 5.47 patients on average to find one suspected candidate. This efficiency is crucial as Pompe disease, while rare, is a progressively debilitating but treatable neuromuscular disease. As such, we demonstrated both the efficiency of the approach and the potential of a scalable solution to the systematic identification of rare disease patients. Thus, similar implementation of this methodology should be encouraged to improve care for all rare disease patients.
Time estimation during motor activity
Authors: D’Agostino Ottavia , Castellotti Serena , Del Viva Maria Michela
Published: April 2023

Several studies on time estimation showed that the estimation of temporal intervals is related to the amount of attention devoted to time. This is explained by the scalar timing theory, which assumes that attention alters the number of pulses transferred by our internal clock to an accumulator that keeps track of the elapsed time. In a previous study, it was found that time underestimation during cognitive-demanding tasks was more pronounced while walking than while sitting, whereas no clear motor-induced effects emerged without a concurrent cognitive task. What remains unclear then is the motor interference itself on time estimation. Here we aim to clarify how the estimation of time can be influenced by demanding motor mechanisms and how different motor activities interact with concurrent cognitive tasks during time estimation. To this purpose, we manipulated simultaneously the difficulty of the cognitive task (solving arithmetic operations) and the motor task. We used an automated body movement that should require no motor or mental effort, a more difficult movement that requires some motor control, and a highly demanding movement requiring motor coordination and attention. We compared the effects of these three types of walking on time estimation accuracy and uncertainty, arithmetic performance, and reaction times. Our findings confirm that time estimation is affected by the difficulty of the cognitive task whereas we did not find any evidence that time estimation changes with the complexity of our motor task, nor an interaction between walking and the concurrent cognitive tasks. We can conclude that walking, although highly demanding, does not have the same effects as other mental tasks on time estimation.
Endoplasmic reticulum stress and ubiquitin-proteasome system impairment in natural scrapie
Authors: Lozada Ortiz Jenny , Betancor Marina , Pérez Lázaro Sonia , Bolea Rosa , Badiola Juan J. , Otero Alicia
Published: April 2023

Chronic accumulation of misfolded proteins such as PrPSc can alter the endoplasmic reticulum homeostasis triggering the unfolded protein response (UPR). In this pathogenic event, the molecular chaperones play an important role. Several reports in humans and animals have suggested that neurodegeneration is related to endoplasmic reticulum stress in diseases caused by the accumulation of misfolded proteins. In this study, we investigated the expression of three endoplasmic reticulum stress markers: PERK (protein kinase R-like endoplasmic reticulum kinase), BiP (binding immunoglobulin protein), and PDI (Protein Disulfide Isomerase). In addition, we evaluated the accumulation of ubiquitin as a marker for protein degradation mediated by the proteasome. These proteins were studied in brain tissues of sheep affected by scrapie in clinical and preclinical stages of the disease. Results were compared with those observed in healthy controls. Scrapie-infected sheep showed significant higher levels of PERK, BiP/Grp78 and PDI than healthy animals. As we observed before in models of spontaneous prion disease, PDI was the most altered ER stress marker between scrapie-infected and healthy sheep. Significantly increased intraneuronal and neuropil ubiquitinated deposits were observed in certain brain areas in scrapie-affected animals compared to controls. Our results suggest that the neuropathological and neuroinflammatory phenomena that develop in prion diseases cause endoplasmic reticulum stress in brain cells triggering the UPR. In addition, the significantly higher accumulation of ubiquitin aggregates in scrapie-affected animals suggests an impairment of the ubiquitin-proteasome system in natural scrapie. Therefore, these proteins may contribute as biomarkers and/or therapeutic targets for prion diseases.