bluuebunny/crossref_metadata_2025 huggingface dataset:
ExaTN: Scalable GPU-Accelerated High-Performance Processing of General Tensor Networks at Exascale
Authors: Lyakh Dmitry I. , Nguyen Thien , Claudino Daniel , Dumitrescu Eugene , McCaskey Alexander J.
Published: July 2022

We present ExaTN (Exascale Tensor Networks), a scalable GPU-accelerated C++ library which can express and process tensor networks on shared- as well as distributed-memory high-performance computing platforms, including those equipped with GPU accelerators. Specifically, ExaTN provides the ability to build, transform, and numerically evaluate tensor networks with arbitrary graph structures and complexity. It also provides algorithmic primitives for the optimization of tensor factors inside a given tensor network in order to find an extremum of a chosen tensor network functional, which is one of the key numerical procedures in quantum many-body theory and quantum-inspired machine learning. Numerical primitives exposed by ExaTN provide the foundation for composing rather complex tensor network algorithms. We enumerate multiple application domains which can benefit from the capabilities of our library, including condensed matter physics, quantum chemistry, quantum circuit simulations, as well as quantum and classical machine learning, for some of which we provide preliminary demonstrations and performance benchmarks just to emphasize a broad utility of our library.
Constructing Injectable Bone-Forming Units by Loading a Subtype of Osteoprogenitors on Decellularized Bone Matrix Powders for Bone Regeneration
Authors: Xu Yan , Yan Shaohang , Chen Can , Lu Bangbao , Zhao Ruibo
Published: July 2022

Bone defects resulting from trauma or tumor are one of the most challenging problems in clinical settings. Current tissue engineering (TE) strategies for managing bone defects are insufficient, owing to without using optimal osteoconductive material and seeding cells capable of superior osteogenic potential; thus their efficacy is instable. Herein, a novel TE strategy was developed for treating bone defects. First, the decellularized bone matrix (DBM) was manufactured into powders, and these DBM powders preserved the ultrastructural and compositional properties of native trabecular bone, are non-cytotoxic and low-immunogenic, and are capable of inducing the interacted stem cells differentiating into osteogenic lineage. Then, a subtype of osteoprogenitors was isolated from mouse long bones, and its high osteogenic potential was identified in vitro. After that, we constructed a “bone-forming unit” by seeding the special subtype of osteoprogenitors onto the DBM powders. In vivo performance of the “bone-forming units” was determined by injecting into the defect site of a mouse femoral epiphysis bone defect model. The results indicated that the “bone-forming unit” was capable of enhancing bone defect healing by regulating new bone formation and remodeling. Overall, the study establishes a protocol to construct a novel “bone-forming unit,” which may be an alternative strategy in future bone TE application.
Activated Platelets and Platelet-Derived Extracellular Vesicles Mediate COVID-19-Associated Immunothrombosis
Authors: Ebeyer-Masotta Marie , Eichhorn Tanja , Weiss René , Lauková Lucia , Weber Viktoria
Published: July 2022

Activated platelets and platelet-derived extracellular vesicles (EVs) have emerged as central players in thromboembolic complications associated with severe coronavirus disease 2019 (COVID-19). Platelets bridge hemostatic, inflammatory, and immune responses by their ability to sense pathogens via various pattern recognition receptors, and they respond to infection through a diverse repertoire of mechanisms. Dysregulated platelet activation, however, can lead to immunothrombosis, a simultaneous overactivation of blood coagulation and the innate immune response. Mediators released by activated platelets in response to infection, such as antimicrobial peptides, high mobility group box 1 protein, platelet factor 4 (PF4), and PF4+ extracellular vesicles promote neutrophil activation, resulting in the release of neutrophil extracellular traps and histones. Many of the factors released during platelet and neutrophil activation are positively charged and interact with endogenous heparan sulfate or exogenously administered heparin via electrostatic interactions or via specific binding sites. Here, we review the current state of knowledge regarding the involvement of platelets and platelet-derived EVs in the pathogenesis of immunothrombosis, and we discuss the potential of extracorporeal therapies using adsorbents functionalized with heparin to deplete platelet-derived and neutrophil-derived mediators of immunothrombosis.
Emerging Roles of Non-proteolytic Ubiquitination in Tumorigenesis
Authors: Yin Xiu , Liu Qingbin , Liu Fen , Tian Xinchen , Yan Tinghao , Han Jie , Jiang Shulong
Published: July 2022

Ubiquitination is a critical type of protein post-translational modification playing an essential role in many cellular processes. To date, more than eight types of ubiquitination exist, all of which are involved in distinct cellular processes based on their structural differences. Studies have indicated that activation of the ubiquitination pathway is tightly connected with inflammation-related diseases as well as cancer, especially in the non-proteolytic canonical pathway, highlighting the vital roles of ubiquitination in metabolic programming. Studies relating degradable ubiquitination through lys48 or lys11-linked pathways to cellular signaling have been well-characterized. However, emerging evidence shows that non-degradable ubiquitination (linked to lys6, lys27, lys29, lys33, lys63, and Met1) remains to be defined. In this review, we summarize the non-proteolytic ubiquitination involved in tumorigenesis and related signaling pathways, with the aim of providing a reference for future exploration of ubiquitination and the potential targets for cancer therapies.
Loop-Mediated Isothermal Amplification Coupled With Nanoparticle-Based Biosensor: A Rapid and Sensitive Method to Detect Mycoplasma pneumoniae
Authors: Xiao Fei , Zhou Juan , Sun Chunrong , Huang Xiaolan , Zheng Baoying , Fu Jin , Jia Nan , Xu Zheng , Cui Xiaodai , Wang Yi
Published: July 2022

Mycoplasma pneumoniae (MP), the causative agent of MP pneumonia (MPP), has posed a substantial burden to public health owing to a lack of rapid and effective diagnostic methods. Here, we designed a loop-mediated isothermal amplification (LAMP)-based assay, termed LAMP, combined with a nanoparticle-based lateral flow biosensor (LAMP-LFB) for rapid and sensitive diagnosis of MP.-LAMP-LFB included a set of six primers targeting the community-acquired respiratory distress syndrome (CARDS) toxin gene and was performed optimally at 63°C for only 30 min. The resulting LAMP products could be visually indicated by LFB within 2 min, thus the whole process could be accomplished within an hour. MP-LAMP-LFB’s sensitivity was 50 fg per reaction, which was in complete accordance with these results obtained from real-time turbidity and visual detection reagent (VDR). MP-LAMP-LFB had no cross-reactivity with other pathogens that had similar clinical presentations. Our assay was further validated using 100 nasopharyngeal swab samples collected from children suspected of MPP, and the result was compared with the real-time PCR method. With a positive rate of 50%, the data indicated that MP-LAMP-LFB is a sensitive test for MP detection in clinical settings. Collectively, the MP-LAMP-LFB assay targeting the CARDS toxin gene was a rapid, highly sensitive, and specific test that could be widely applied in point-of-care settings and basic medical facilities in rural areas.
A Phenotype and Genotype Case Report of a Neonate With Congenital Bilateral Coronary Artery Fistulas and Multiple Collateral Arteries
Authors: Su Shixin , Xia Shuliang , He Ye , Li Jianbin , Ma Li , Chen Xinxin , Li Jia
Published: July 2022

We report a unique case of an 18-day-old girl with three coronary artery fistulas to the right atrium and right ventricle, respectively: three collateral arteries arising from the descending aorta and one from the right subclavian artery draining through a sac to the top of the right atrium, patent ductus arteriosus, and atrial septal defect. She presented symptoms of acute congestive heart failure. Cardiac catheterization and surgical interventions were performed to repair the defects. The patient recovered uneventfully and grew up well at 3 years of follow-up. Whole-genome sequencing (WES) in the patient, compared to her parents, showed 17 variants within 11 genes. Among these, only compound heterozygous mutation, c.T470G (p.L157R) and c.A1622G (p.D541G), in the DRC1 gene have been reportedly related to congenital heart disease and are the most likely causative in our patient.
A Personalized Management Approach of OHSS: Development of a Multiphase Prediction Model and Smartphone-Based App
Authors: Cao Mingzhu , Liu Zhi , Lin Yanshan , Luo Yiqun , Li Sichen , Huang Qing , Liu Haiying , Liu Jianqiao
Published: July 2022

Objective

This study aimed to develop multiphase big-data-based prediction models of ovarian hyperstimulation syndrome (OHSS) and a smartphone app for risk calculation and patients’ self-monitoring.

Methods

Multiphase prediction models were developed from a retrospective cohort database of 21,566 women from January 2017 to December 2020 with controlled ovarian stimulation (COS). There were 17,445 women included in the final data analysis. Women were randomly assigned to either training cohort (n = 12,211) or validation cohort (n = 5,234). Their baseline clinical characteristics, COS-related characteristics, and embryo information were evaluated. The prediction models were divided into four phases: 1) prior to COS, 2) on the day of ovulation trigger, 3) after oocyte retrieval, and 4) prior to embryo transfer. The multiphase prediction models were built with stepwise regression and confirmed with LASSO regression. Internal validations were performed using the validation cohort and were assessed by discrimination and calibration, as well as clinical decision curves. A smartphone-based app “OHSS monitor” was constructed as part of the built-in app of the IVF-aid platform. The app had three modules, risk prediction module, symptom monitoring module, and treatment monitoring module.

Results

The multiphase prediction models were developed with acceptable distinguishing ability to identify OHSS at-risk patients. The C-statistics of the first, second, third, and fourth phases in the training cohort were 0.628 (95% CI 0.598–0.658), 0.715 (95% CI 0.688–0.742), 0.792 (95% CI 0.770–0.815), and 0.814 (95% CI 0.793–0.834), respectively. The calibration plot showed the agreement of predictive and observed risks of OHSS, especially at the third- and fourth-phase prediction models in both training and validation cohorts. The net clinical benefits of the multiphase prediction models were also confirmed with a clinical decision curve. A smartphone-based app was constructed as a risk calculator based on the multiphase prediction models, and also as a self-monitoring tool for patients at risk.

Conclusions

We have built multiphase prediction models based on big data and constructed a user-friendly smartphone-based app for the personalized management of women at risk of moderate/severe OHSS. The multiphase prediction models and user-friendly app can be readily used in clinical practice for clinical decision-support and self-management of patients.
Pan-Cancer Analysis of OLFML2B Expression and Its Association With Prognosis and Immune Infiltration
Authors: Hu Pengbo , Zhang Xiuyuan , Li Yiming , Xu Liang , Qiu Hong
Published: July 2022

Background: The function of olfactomedin-like 2B (OLFML2B), as a member of the olfactomedin domain-containing protein family, remains ambiguous, especially in tumors. The current study explores the possible correlation between OLFML2B, prognosis, and immune infiltration in pan-cancer.

Methods: We applied a number of bioinformatics techniques to probe the prospective function of OLFML2B, consisting of its association with prognosis, clinicopathology, alteration, GSEA, tumor microenvironment (TME), immune-associated genes, immune infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), and drug sensitivity in several cancer types. qPCR and immunohistochemistry were used to identify OLFML2B expression in LIHC cell lines and liver cancer tissues.

Results: We discovered that OLFML2B was overexpressed in 14 cancers and positively related to several cancer type prognoses. The expression of OLFML2B was further validated in the LIHC cell lines. OLFML2B expression was bound up with TMB in 13 cancers, MSI in 10 cancers, and TME in almost all cancers. Furthermore, OLFML2B was highly co-expressed with genes encoding immune activators and immune suppressors. We further found that OLFML2B played a role in infiltrating different types of immune cells, such as macrophages and cancer-associated fibroblasts. OLFML2B may influence various cancer and immune-related pathways, such as the PI3K-Akt signaling pathway, ECM–receptor interaction, focal adhesion, and leukocyte transendothelial migration. In addition, OLFML2B may increase drug resistance of binimetinib, cobimentinib, and trametinib.

Conclusion: Our outcomes reveal that OLFML2B may act as a prognostic marker and a potential target in immunotherapy for diverse tumors due to its oncogenesis function and immune infiltration.
Three Variants Affecting Exon 1 of Ectodysplasin A Cause X-Linked Hypohidrotic Ectodermal Dysplasia: Clinical and Molecular Characteristics
Authors: Wang Yupei , Zhang Chuan , Zhou Bingbo , Hui Ling , Zheng Lei , Chen Xue , Wang Shifan , Yang Lan , Hao Shengju , Zhang Qinghua
Published: July 2022

Background: Ectodysplasin A (EDA) variations are major pathogenic factors for hypohidrotic ectodermal dysplasia (HED), the most common form of ectodermal dysplasia (ED), characterized by hypotrichosis, hypohidrosis, hypodontia, and other oral features.

Methods: Molecular genetic defects in three HED families were detected by whole-exome sequencing and confirmed by Sanger sequencing or multiplex ligation-dependent probe amplification. The effect of splicing variant was further verified by EDA minigene in vitro analysis. De novo deletion was confirmed by chromosomal microarray analysis.

Results: Three variants (c.396 + 1 G > C, c.171-173 del GTT, and exon 1 deletion) were identified, all affecting exon 1 of the EDA gene. Variants c.396 + 1 G > C and c.171-173 del GTT were first identified. Minigene analysis of the splicing variant (c.396 + 1 G > C) displayed a prolonged EDA-A1 transcript containing extra 699 bp at the start of intron 1, representing a functional cryptic splice site formation in vitro. Combining the results of chromosomal microarray analysis and whole-exome sequencing, the deletion variant was over 87 kb. Three variants were predicted to affect protein function to differing degrees, and were responsible for X-linked HED with varying phenotype.

Conclusion: Investigating the clinical and molecular characteristics of these variations broadens our understanding of EDA gene variants, supporting clinical diagnosis, genetic counseling, and prenatal diagnosis of HED.
Occult Hepatitis B Virus Infection Among Blood Donors in the Capital City of Addis Ababa, Ethiopia: Implications for Blood Transfusion Safety
Authors: Gemechu Gizachew , Abagez Woldearegay Erku , Alemayehu Dawit Hailu , Tesfaye Abebech , Tadesse Demewoz , Kinfu Abiy , Mihret Adane , Mulu Andargachew
Published: July 2022

Background

Occult hepatitis B virus infection (OBI) remains a potential threat to blood safety in developing countries. Nevertheless, there is no data available on the magnitude of occult hepatitis among blood donors in Ethiopia. Therefore, this study aimed to estimate the magnitude of OBI among blood donors in Ethiopia.

Objectives

The aim of this study is to determine the magnitude of OBI and associated risk factors among blood donors at the National Blood Bank, Addis Ababa, Ethiopia.

Methods

A total of 973 HBsAg-negative plasma samples were tested for anti-HBc antibody using an ELISA and viral DNA using automated ABBOTT real-time PCR. Along with plasma samples, demographic data were retrieved from the database with respect to donors. Both descriptive and inferential statistics were employed for the analysis of data by SPSS 20. p-values less than 0.05 were considered as statistically significant.

Results

Of the total of 973 study participants, 445 (45.7%) were female with a mean age of 26.5 years. A total of 144 (14.8%) blood samples were anti-HBc antibody reactive. Four (0.41% of all samples, and 2.8% of anti-HBc-positive samples) samples were confirmed to have OBI by DNA detection. The mean viral load among the confirmed OBI samples was 31 IU/ml with ±12 SD, suggesting true occult hepatitis BV infections. Age was found to be a risk factor for anti-core positivity and was statically significant at p = 0.0001.

Conclusion

About four out of 1,000 blood donors screened negative with HBsAg had occult HBV infection. This shows that there could be a risk of HBV transmission through blood transfusion in Ethiopia. Therefore, there is a need for further investigation and action to revise the existing blood screening strategy by including anti-HBc and HBV nucleic acid testing.
Comprehensive Flow Cytometric Characterization of Bronchoalveolar Lavage Cells Indicates Comparable Phenotypes Between Asthmatic and Healthy Horses But Functional Lymphocyte Differences
Authors: Gressler A. Elisabeth , Lübke Sabrina , Wagner Bettina , Arnold Corinna , Lohmann Katharina L. , Schnabel Christiane L.
Published: July 2022

Equine asthma (EA) is a highly relevant disease, estimated to affect up to 20% of all horses, and compares to human asthma. The pathogenesis of EA is most likely immune-mediated, yet incompletely understood. To study the immune response in the affected lower airways, mixed leukocytes were acquired through bronchoalveolar lavage (BAL) and the cell populations were analyzed on a single-cell basis by flow cytometry (FC). Samples of 38 horses grouped as respiratory healthy or affected by mild to moderate (mEA) or severe EA (sEA) according to their history, clinical signs, and BAL cytology were analyzed. Using FC, BAL cells and PBMC were comprehensively characterized by cell surface markers ex vivo. An increased percentage of DH24A+ polymorphonuclear cells, and decreased percentages of CD14+ macrophages were detected in BAL from horses with sEA compared to healthy horses or horses with mEA, while lymphocyte proportions were similar between all groups. Independently of EA, macrophages in BAL were CD14+CD16+, which contrasts the majority of CD14+CD16- classical monocytes in PBMC. Percentages of CD16-expressing BAL macrophages were reduced in BAL from horses with sEA compared to healthy horses. While PBMC lymphocytes predominantly contain CD4+ T cells, B cells and few CD8+ T cells, BAL lymphocytes comprised mainly CD8+ T cells, fewer CD4+ T cells and hardly any B cells. These lymphocyte subsets’ distributions were similar between all groups. After PMA/ionomycin stimulation in vitro, lymphocyte activation (CD154 and T helper cell cytokine expression) was analyzed in BAL cells of 26 of the horses and group differences were observed (p=0.01–0.11). Compared to healthy horses’ BAL, CD154+ lymphocytes from horses with mEA, and CD4+IL-17A+ lymphocytes from horses with sEA were increased in frequency. Activated CD4+ T helper cells were more frequent in asthmatics’ (mEA, sEA) compared to healthy horses’ PBMC lymphocytes. In summary, FC analysis of BAL cells identified increased polymorphonuclear cells frequencies in sEA as established, while macrophage percentages were mildly reduced, and lymphocyte populations remained unaffected by EA. Cytokine production differences of BAL lymphocytes from horses with sEA compared to healthy horses’ cells point towards a functional difference, namely increased local type 3 responses in sEA.
Omicron Booster in Ancestral Strain Vaccinated Mice Augments Protective Immunities Against Both Delta and Omicron Variants
Authors: Jia Liqiu , Zhou Yang , Li Shaoshuai , Zhang Yifan , Yan Dongmei , Wang Wanhai , Zhang Wenhong , Wan Yanmin , Qiu Chao
Published: July 2022

A booster vaccination is called for constraining the evolving epidemic of SARS-CoV-2. However, the necessity of a new COVID-19 vaccine is currently unclear. To compare the effect of an Omicron-matched S DNA vaccine and an ancestral S DNA vaccine in boosting cross-reactive immunities, we firstly immunized mice with two-dose of a DNA vaccine encoding the spike protein of the ancestral Wuhan strain. Then the mice were boosted with DNA vaccines encoding spike proteins of either the Wuhan strain or the Omicron variant. Specific antibody and T cell responses were measured at 4 weeks post boost. Our data showed that the Omicron-matched vaccine efficiently boosted RBD binding antibody and neutralizing antibody responses against both the Delta and the Omicron variants. Of note, antibody responses against the Omicron variant elicited by the Omicron-matched vaccine were much stronger than those induced by the ancestral S DNA vaccine. Meanwhile, CD8+ T cell responses against both the ancestral Wuhan strain and the Omicron strain also tended to be higher in mice boosted by the Omicron-matched vaccine than those in mice boosted with the ancestral S DNA vaccine, albeit no significant difference was observed. Our findings suggest that an Omicron-matched vaccine is preferred for boosting cross-protective immunities.
CAR T-Cell Therapy Predictive Response Markers in Diffuse Large B-Cell Lymphoma and Therapeutic Options After CART19 Failure
Authors: Caballero Ana Carolina , Escribà-Garcia Laura , Alvarez-Fernández Carmen , Briones Javier
Published: July 2022

Immunotherapy with T cells genetically modified with chimeric antigen receptors (CARs) has shown significant clinical efficacy in patients with relapsed/refractory B-cell lymphoma. Nevertheless, more than 50% of treated patients do not benefit from such therapy due to either absence of response or further relapse. Elucidation of clinical and biological features that would predict clinical response to CART19 therapy is of paramount importance and eventually may allow for selection of those patients with greater chances of response. In the last 5 years, significant clinical experience has been obtained in the treatment of diffuse large B-cell lymphoma (DLBCL) patients with CAR19 T cells, and major advances have been made on the understanding of CART19 efficacy mechanisms. In this review, we discuss clinical and tumor features associated with response to CART19 in DLBCL patients as well as the impact of biological features of the infusion CART19 product on the clinical response. Prognosis of DLBCL patients that fail CART19 is poor and therapeutic approaches with new drugs are also discussed.
NKG7 Enhances CD8+ T Cell Synapse Efficiency to Limit Inflammation
Authors: Lelliott Emily J. , Ramsbottom Kelly M. , Dowling Mark R. , Shembrey Carolyn , Noori Tahereh , Kearney Conor J. , Michie Jessica , Parish Ian A. , Jordan Margaret A. , Baxter Alan G. , Young Neil D. , Brennan Amelia J. , Oliaro Jane
Published: July 2022

Cytotoxic lymphocytes are essential for anti-tumor immunity, and for effective responses to cancer immunotherapy. Natural killer cell granule protein 7 (NKG7) is expressed at high levels in cytotoxic lymphocytes infiltrating tumors from patients treated with immunotherapy, but until recently, the role of this protein in cytotoxic lymphocyte function was largely unknown. Unexpectedly, we found that highly CD8+ T cell-immunogenic murine colon carcinoma (MC38-OVA) tumors grew at an equal rate in Nkg7+/+ and Nkg7-/- littermate mice, suggesting NKG7 may not be necessary for effective CD8+ T cell anti-tumor activity. Mechanistically, we found that deletion of NKG7 reduces the ability of CD8+ T cells to degranulate and kill target cells in vitro. However, as a result of inefficient cytotoxic activity, NKG7 deficient T cells form a prolonged immune synapse with tumor cells, resulting in increased secretion of inflammatory cytokines, including tumor necrosis factor alpha (TNF). By deleting the TNF receptor, TNFR1, from MC38-OVA tumors, we demonstrate that this hyper-secretion of TNF compensates for reduced synapse-mediated cytotoxic activity against MC38-OVA tumors in vivo, via increased TNF-mediated tumor cell death. Taken together, our results demonstrate that NKG7 enhances CD8+ T cell immune synapse efficiency, which may serve as a mechanism to accelerate direct cytotoxicity and limit potentially harmful inflammatory responses.
Beneficial Effect of Heat-Killed Lactiplantibacillus plantarum L-137 on Skin Functions in Healthy Participants: A Randomized, Placebo-Controlled, Double-Blind Study
Authors: Yoshitake Rieko , Nakai Hiroko , Ebina Manato , Kawasaki Kengo , Murosaki Shinji , Hirose Yoshitaka
Published: July 2022

To determine whether consuming heat-killedLactiplantibacillus plantarumL-137 (HK L-137) influences skin functions, we performed a randomized, placebo-controlled, double-blind study in healthy participants who were conscious of dry skin. A total of 80 healthy participants (20 men, 60 women; mean age, 47.3 years) were assigned to receive a tablet containing HK L-137 or a placebo tablet daily for 12 weeks. Every 4 weeks, the skin water content and transepidermal water loss (TEWL) were measured at the forearm and face, and participants completed two skin-related questionnaires, the Dermatology Life Quality Index and a self-evaluation. The HK L-137 group tended to show greater increases from baseline of water content at the forearm and larger decreases of TEWL at the face. The total scores of both questionnaires improved significantly more in the HK L-137 group. Water content and TEWL improved significantly in participants in the HK L-137 group who were above the median age of study participants or had relatively dry skin. These findings suggest that daily HK L-137 intake can improve dry skin, thereby contributing to skin satisfaction.
Multiple Adaptive Strategies of Himalayan Iodobacter sp. PCH194 to High-Altitude Stresses
Authors: Kumar Vijay , Kashyap Prakriti , Kumar Subhash , Thakur Vikas , Kumar Sanjay , Singh Dharam
Published: July 2022

Bacterial adaption to the multiple stressed environments of high-altitude niches in the Himalayas is intriguing and is of considerable interest to biotechnologists. Previously, we studied the culturable and unculturable metagenome microbial diversity from glacial and kettle lakes in the Western Himalayas. In this study, we explored the adaptive strategies of a unique Himalayan eurypsychrophile Iodobacter sp. PCH194, which can synthesize polyhydroxybutyrate (PHB) and violacein pigment. Whole-genome sequencing and analysis of Iodobacter sp. PCH194 (4.58 Mb chromosome and three plasmids) revealed genetic traits associated with adaptive strategies for cold/freeze, nutritional fluctuation, defense against UV, acidic pH, and the kettle lake's competitive environment. Differential proteome analysis suggested the adaptive role of chaperones, ribonucleases, secretion systems, and antifreeze proteins under cold stress. Antifreeze activity inhibiting the ice recrystallization at −9°C demonstrated the bacterium's survival at subzero temperature. The bacterium stores carbon in the form of PHB under stress conditions responding to nutritional fluctuations. However, violacein pigment protects the cells from UV radiation. Concisely, genomic, proteomic, and physiological studies revealed the multiple adaptive strategies of Himalayan Iodobacter to survive the high-altitude stresses.
Euendolithic Cyanobacteria and Proteobacteria Together Contribute to Trigger Bioerosion in Aquatic Environments
Authors: Wu Guimei , Huang Aiyou , Wen Yanhong , Wang Hongxia , Wang Jiangxin , Luo Fuguang , Wu Mingcan
Published: July 2022

Shellfish, mussels, snails, and other aquatic animals, which assimilate limestone (calcium carbonate, CaCO3) to build shells and skeletons, are effective carbon sinks that help mitigate the greenhouse effect. However, bioerosion, the dissolution of calcium carbonate and the release of carbon dioxide, hinders carbon sequestration process. The bioerosion of aquatic environments remains to be elucidated. In this study, the bioerosion of Bellamya spp. shells from the aquatic environment was taken as the research object. In situ microbial community structure analysis of the bioerosion shell from different geographical locations, laboratory-level infected culture, and validated experiments were conducted by coupling traditional observation and 16S rRNA sequencing analysis method. Results showed that bioeroders can implant into the CaCO3 layer of the snail shell, resulting in the formation of many small holes in the shell, which reduced the shell’s density and made the shell fragile. Results also showed that bioeroders were distributed in two major phyla, namely, Cyanobacteria and Proteobacteria. Cluster analysis showed that Cyanobacteria sp. and two unidentified genera (Burkholderiaceae and Raistonia) were the key bioeroders. Moreover, results suggested that the interaction of Cyanobacteria and other bacteria promoted the biological function of “shell bioerosion.” This study identified the causes of “shell bioerosion” in aquatic environments and provided some theoretical basis for preventing and controlling it in the aquatic industry. Results also provided new insights of cyanobacterial bioerosion of shells and microalgae carbon sequestration.
New Insights in the Interplay Between African Swine Fever Virus and Innate Immunity and Its Impact on Viral Pathogenicity
Authors: Ayanwale Abraham , Trapp Sascha , Guabiraba Rodrigo , Caballero Ignacio , Roesch Ferdinand
Published: July 2022

The continuous spread of African swine fever virus (ASFV) in Europe and Asia represents a major threat to livestock health, with billions of dollars of income losses and major perturbations of the global pig industry. One striking feature of African swine fever (ASF) is the existence of different forms of the disease, ranging from acute with mortality rates approaching 100% to chronic, with mild clinical manifestations. These differences in pathogenicity have been linked to genomic alterations present in attenuated ASFV strains (and absent in virulent ones) and differences in the immune response of infected animals. In this mini-review, we summarized current knowledge on the connection between ASFV pathogenicity and the innate immune response induced in infected hosts, with a particular focus on the pathways involved in ASFV detection. Indeed, recent studies have highlighted the key role of the DNA sensor cGAS in ASFV sensing. We discussed what other pathways may be involved in ASFV sensing and inflammasome activation and summarized recent findings on the viral ASFV genes involved in the modulation of the interferon (IFN) and nuclear factor kappa B (NF-κB) pathways.
The Multi-Functional Roles of CCR7 in Human Immunology and as a Promising Therapeutic Target for Cancer Therapeutics
Authors: Alrumaihi Faris
Published: July 2022

An important hallmark of the human immune system is to provide adaptive immunity against pathogens but tolerance toward self-antigens. The CC-chemokine receptor 7 (CCR7) provides a significant contribution in guiding cells to and within lymphoid organs and is important for acquiring immunity and tolerance. The CCR7 holds great importance in establishing thymic architecture and function and naïve and regulatory T-cell homing in the lymph nodes. Similarly, the receptor is a key regulator in cancer cell migration and the movement of dendritic cells. This makes the CCR7 an important receptor as a drug and prognostic marker. In this review, we discussed several biological roles of the CCR7 and its importance as a drug and prognostic marker.
Toward Precision Medicine in ADHD
Authors: Buitelaar Jan , Bölte Sven , Brandeis Daniel , Caye Arthur , Christmann Nina , Cortese Samuele , Coghill David , Faraone Stephen V. , Franke Barbara , Gleitz Markus , Greven Corina U. , Kooij Sandra , Leffa Douglas Teixeira , Rommelse Nanda , Newcorn Jeffrey H. , Polanczyk Guilherme V. , Rohde Luis Augusto , Simonoff Emily , Stein Mark , Vitiello Benedetto , Yazgan Yanki , Roesler Michael , Doepfner Manfred , Banaschewski Tobias
Published: July 2022

Attention-Deficit Hyperactivity Disorder (ADHD) is a complex and heterogeneous neurodevelopmental condition for which curative treatments are lacking. Whilst pharmacological treatments are generally effective and safe, there is considerable inter-individual variability among patients regarding treatment response, required dose, and tolerability. Many of the non-pharmacological treatments, which are preferred to drug-treatment by some patients, either lack efficacy for core symptoms or are associated with small effect sizes. No evidence-based decision tools are currently available to allocate pharmacological or psychosocial treatments based on the patient's clinical, environmental, cognitive, genetic, or biological characteristics. We systematically reviewed potential biomarkers that may help in diagnosing ADHD and/or stratifying ADHD into more homogeneous subgroups and/or predict clinical course, treatment response, and long-term outcome across the lifespan. Most work involved exploratory studies with cognitive, actigraphic and EEG diagnostic markers to predict ADHD, along with relatively few studies exploring markers to subtype ADHD and predict response to treatment. There is a critical need for multisite prospective carefully designed experimentally controlled or observational studies to identify biomarkers that index inter-individual variability and/or predict treatment response.
Spatiotemporal Dynamics of Covert vs. Overt Emotional Face Processing in Dysphoria
Authors: Jaspers-Fayer Fern , Maffei Antonio , Goertzen Jennifer , Kleffner Killian , Coccaro Ambra , Sessa Paola , Liotti Mario
Published: July 2022

People at risk of developing clinical depression exhibit attentional biases for emotional faces. To clarify whether such effects occur at an early, automatic, or at a late, deliberate processing stage of emotional processing, the present study used high-density electroencephalography during both covert and overt processing of sad, fearful, happy, and neutral expressions in healthy participants with high dysphoria (n = 16) and with low dysphoria (n = 19). A state-of-the-art non-parametric permutation-based statistical approach was then used to explore the effects of emotion, attentional task demands, and group. Behaviorally, participants responded faster and more accurately when overtly categorizing happy faces and they were slower and less accurate when categorizing sad and fearful faces, independent of the dysphoria group. Electrophysiologically, in an early time-window (N170: 140–180 ms), there was a significant main effect for the dysphoria group, with greater negative voltage for the high vs. low dysphoria group over the left-sided temporo-occipital scalp. Furthermore, there was a significant group by emotional interaction, with the high dysphoria group displaying greater negative amplitude N170 for happy than fearful faces. Attentional task demands did not influence such early effects. In contrast, in an intermediate time-window (EPN: 200–400 ms) and in a late time-window (LPP: 500–750 ms) there were no significant main effects nor interactions involving the dysphoria Group. The LPP results paralleled the behavioral results, with greater LPP voltages for sad and fearful relative to happy faces only in the overt task, but similarly so in the two dysphoria groups. This study provides novel evidence that alterations in face processing in dysphoric individuals can be seen at the early stages of face perception, as indexed by the N170, although not in the form of a typical pattern of mood-congruent attentional bias. In contrast, intermediate (EPN) and late (LPP) stages of emotional face processing appear unaffected by dysphoria. Importantly, the early dysphoria effect appears to be independent of the top-down allocation of attention, further supporting the idea that dysphoria may influence a stage of automatic emotional appraisal. It is proposed that it may be a consequence of a shift from holistic to feature-based processing of facial expressions, or may be due to the influence of negative schemas acting as a negative context for emotional facial processing.
Composition and Organization of Acute Ischemic Stroke Thrombus: A Wealth of Information for Future Thrombolytic Strategies
Authors: Desilles Jean-Philippe , Di Meglio Lucas , Delvoye Francois , Maïer Benjamin , Piotin Michel , Ho-Tin-Noé Benoît , Mazighi Mikael
Published: July 2022

During the last decade, significant progress has been made in understanding thrombus composition and organization in the setting of acute ischemic stroke (AIS). In particular, thrombus organization is now described as highly heterogeneous but with 2 preserved characteristics: the presence of (1) two distinct main types of areas in the core—red blood cell (RBC)-rich and platelet-rich areas in variable proportions in each thrombus—and (2) an external shell surrounding the core composed exclusively of platelet-rich areas. In contrast to RBC-rich areas, platelet-rich areas are highly complex and are mainly responsible for the thrombolysis resistance of these thrombi for the following reasons: the presence of platelet-derived fibrinolysis inhibitors in large amounts, modifications of the fibrin network structure resistant to the tissue plasminogen activator (tPA)-induced fibrinolysis, and the presence of non-fibrin extracellular components, such as von Willebrand factor (vWF) multimers and neutrophil extracellular traps. From these studies, new therapeutic avenues are in development to increase the fibrinolytic efficacy of intravenous (IV) tPA-based therapy or to target non-fibrin thrombus components, such as platelet aggregates, vWF multimers, or the extracellular DNA network.
Novel miRNA Biomarkers for Patients With Duchenne Muscular Dystrophy
Authors: Meng Qi , Zhang Jiapeng , Zhong Jingzi , Zeng Dan , Lan Dan
Published: July 2022

Creatine kinase (CK) as a biomarker has long been expected to be replaced by other fluid biomarkers for Duchenne muscular dystrophy (DMD) because it is independent of disease severity. Growing evidence has demonstrated that muscle-specific microRNAs, known as myomiRs, can act as biomarkers for monitoring muscle pathology and disease severity of DMD patients. To gain insights into the relationship between serum myomiRs and clinical assessment, we measured serum levels of miR-1, miR-133a, miR-133b, miR-206, miR-208a, miR-208b, and miR-499 in 48 DMD patients by using real-time quantitative reverse transcription polymerase chain reaction. These were then compared with age, muscle strength, muscle functions, CK levels, cardiac manifestations, and mutation types (deletions, duplications, and small mutations). When compared to 53 controls, the expression levels of myomiRs were all significantly elevated (p < 0.05). The receiver operating characteristic curves of all seven myomiRs reflected marked differences between DMD patients and healthy controls (p < 0.05). We also showed that serum levels of myomiRs were positively correlated with lower limb distal muscle strength in patients of all age groups. The levels of miR-499, miR-208b, miR-133a, and miR-133b had significant negative correlations with the time to be upright from the supine position (Gowers' time) and the time taken to climb four stairs in DMD patients older than 7 years. Serum levels of miR-1, miR-133a, miR-133b, and miR-499 in patients with cardiac involvement were remarkably higher than those in non-cardiac-involved patients. There was no significant difference in levels of myomiRs between the different mutation groups. Our results indicated that serum myomiRs could be considered as novel biomarkers for monitoring pathology/pathophysiology of DMD patients. In particular, miR-499, miR-208b, miR-133a, and miR-133b might have the ability to reflect the extent of muscle impairment.
G2019S LRRK2 Mutation Enhances MPP+-Induced Inflammation of Human Induced Pluripotent Stem Cells-Differentiated Dopaminergic Neurons
Authors: Chen Ying , Yin Qing , Cheng Xiao-Yu , Zhang Jin-Ru , Jin Hong , Li Kai , Mao Cheng-Jie , Wang Fen , Bei Hong-Zhe , Liu Chun-Feng
Published: July 2022

Induced pluripotent stem cells (iPSCs) offer an unprecedented opportunity to mimic human diseases of related cell types, but it is unclear whether they can successfully mimic age-related diseases such as Parkinson’s disease (PD). We generated iPSCs lines from three patients with familial PD associated with the G2019S mutation in the LRRK2 gene and one age-matched healthy individual (control). During long-term culture, dopaminergic (DA) neurons differentiated from iPSCs of G2019S LRRK2 PD patients exhibited morphological changes, including a reduced number of neurites and neurite arborization, which were not evident in DA neurons differentiated from control iPSCs. To mimic PD pathology in vitro, we used 1-methyl-4-phenylpyridium (MPP+) to damage DA neurons and found that DA neurons differentiated from patients with G2019S LRRK2 mutation significantly reduced the survival rate and increased apoptosis compared with the controls. We also found that the mRNA level of inflammatory factors [interleukin (IL)-1β, tumor necrosis factor-α, cyclooxygenase-2, IL-6, and inducible NO synthase] with G2019S LRRK2 mutation were higher than control group after exposure to MPP+. Our study provides an in vitro model based on iPSCs that captures the patients’ genetic complexity and investigates the pathogenesis of familial PD cases in a disease-associated cell type.
A Meta-Analysis on Vitamin D Supplementation and Asthma Treatment
Authors: Liu Meiqi , Wang Jun , Sun Xinrong
Published: July 2022

Background

Vitamin D, as an immunomodulator, may be related to the therapeutic effect of asthma patients, but the research in this area is still controversial. The aim of this meta-analysis was to analyze the role of vitamin D supplementation in the treatment of asthma patients.

Materials and Methods

Randomized Controlled Trials (RCTs) of vitamin D supplementation in asthma were searched in PubMed, EMBASE, and the Cochrane library. Primary outcomes were forced expiratory volume in one second (FEV1), asthma exacerbations, Asthma Control Test scores (ACT scores), and fractional exhaled nitric oxide (FENO).

Results

A total of 10 RCTs were included, including 1,349 patients. Vitamin D supplementation didn’t affect the ACT scores (SMD = 0.04, 95% CI = −0.13 to 0.21, P = 0.87), FEV1 (SMD = 0.04, 95% CI = −0.35 to 0.43, P < 0.01) and FENO (SMD = −0.01, 95% CI = −0.22 to 0.20, P = 0.27), but reduced the rate of asthma exacerbations (RR = 0.69, 95% CI = 0.41 to 0.88, P < 0.01), especially in subgroups of children (RR = 0.46, 95% CI = 0.30 to 0.70, P = 0.83) and follow up time less than 6 months (RR = 0.45, 95% CI = 0.32 to 0.63, P = 0.95). Additionally, though there was only one study included in the subgroup, it significantly enhanced FEV1 at the last visit for patients whose FEV1 baseline value was less than 70% (SMD = 0.94, 95% CI = 0.47 to 1.41).

Conclusion

Vitamin D supplementation can reduce asthma exacerbations, especially in children, and within 6 months of follow up time. In addition, vitamin D has a positive effect on improving FEV1 of patients whose FEV1 baseline value is less than 70%, but more RCTs are still needed to support this conclusion.

Systematic Review Registration

[https://inplasy.com], identifier [10.37766/inplasy20 22.6.0049].
Effects of Quercetin Glycoside Supplementation Combined With Low-Intensity Resistance Training on Muscle Quantity and Stiffness: A Randomized, Controlled Trial
Authors: Otsuka Yuta , Miyamoto Naokazu , Nagai Akitoshi , Izumo Takayuki , Nakai Masaaki , Fukuda Masahiro , Arimitsu Takuma , Yamada Yosuke , Hashimoto Takeshi
Published: July 2022

Objective

Aging of skeletal muscle is characterized not only by a decrease of muscle quantity but also by changes in muscle quality, such as an increase in muscle stiffness. The present study aimed to investigate the effects of supplementation with quercetin glycosides (QGs), well-known polyphenolic flavonoids, combined with resistance exercise on muscle quantity and stiffness.

Materials and Methods

A randomized, controlled trial was conducted in community-dwelling, Japanese people aged 50–74 years who were randomly allocated to exercise with placebo or 200 or 500 mg of QG supplementation. All participants performed low-intensity resistance training mainly targeting thigh muscles with 40% of 1-repetition maximum, 3 days per week for 24 weeks. Muscle cross-sectional area (CSA), lean mass, and vastus lateralis (VL) muscle stiffness were measured before and after the 24-week intervention.

Results

Forty-eight subjects completed the 24-week intervention. There were no significant group × time interactions in thigh CSA for primary outcome, as well as lean mass. VL muscle stiffness in the stretched position was significantly lower in both the 200 mg and 500 mg QG groups than in the placebo group after the 24-week intervention (p < 0.05). No significant correlation was observed between changes of VL muscle CSA and stiffness during the 24-week intervention.

Conclusion

Quercetin glycoside supplementation combined with low-intensity resistance exercise improved passive muscle stiffness independently of muscle quantity.

Clinical Trial Registration

[www.umin.ac.jp/ctr/], identifier [UMIN000037633].
Pre-Procedural Anxiety and Associated Factors Among Women Seeking for Cervical Cancer Screening Services in Shenzhen, China: Does Past Screening Experience Matter?
Authors: Lin Wei , Huang Weikang , Mei Chaofan , Zhong Chuyan , Zhu Leilei , Liu Peiyi , Yuan Shixin , Liu Zhihua , Wang Yueyun
Published: July 2022

Background

Research gaps exist in addressing the psychological harm related to the cervical cancer screening. Anxiety is the most common distress driven by the screening procedures, which may be affected by past screening experience (PSE) but with uncertainty. This study aimed to evaluate the pre-procedural anxiety in cervical cancer screening and to identify the influence attributed to PSE.

Methods

A cross-sectional survey targeted women seeking for cervical cancer screening services was conducted from June 5th to December 31st, 2020 in Shenzhen. The 20-item state anxiety scale of the State-Trait Anxiety Inventory (STAI-S) was applied to measure pre-procedural anxiety, in which a score of 40 or higher was regarded with anxiety symptom. Logistic regression models were established to explore potential associated factors of pre-procedural anxiety both for women with and without PSE.

Results

Overall, 3,651 women were enrolled, in which 36.1% had never been screened and the remaining 63.9% had been screened at least once before. Women without PSE demonstrated more prevalent pre-procedural anxiety (74.5% vs. 67.8%, P <0.001) than their experienced counterparts. Among women without PSE, having heard of cervical cancer screening was associated with a lower likelihood of pre-procedural anxiety (OR: 0.37, 95%CI: 0.25~0.56). Among experienced women, participating three or more times screening was negatively associated with anxiety symptom (OR: 0.67, 95%CI: 0.53~0.84), however, both receiving screening within three years (OR: 1.58, 95%CI: 1.27~1.97) and unknowing previous screening results (OR: 1.42, 95%CI: 1.11~1.82) increased the susceptibility of pre-procedural anxiety.

Conclusions

Women participating in cervical cancer screening commonly present pre-procedural anxiety. The association between PSE and pre-procedural anxiety may be influenced by past screening times, interval, and results. Psychological counseling according to women’s PSE before cervical cancer screening is warranted of necessity.