bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiomics Analysis of Computed Tomography for Prediction of Thyroid Capsule Invasion in Papillary Thyroid Carcinoma: A Multi-Classifier and Two-Center Study
Authors: Wu Xinxin , Yu Pengyi , Jia Chuanliang , Mao Ning , Che Kaili , Li Guan , Zhang Haicheng , Mou Yakui , Song Xicheng
Published: May 2022

Objective

To investigate the application of computed tomography (CT)-based radiomics model for prediction of thyroid capsule invasion (TCI) in papillary thyroid carcinoma (PTC).

Methods

This retrospective study recruited 412 consecutive PTC patients from two independent institutions and randomly assigned to training (n=265), internal test (n=114) and external test (n=33) cohorts. Radiomics features were extracted from non-contrast (NC) and artery phase (AP) CT scans. We also calculated delta radiomics features, which are defined as the absolute differences between the extracted radiomics features. One-way analysis of variance and least absolute shrinkage and selection operator were used to select optimal radiomics features. Then, six supervised machine learning radiomics models (k-nearest neighbor, logistic regression, decision tree, linear support vector machine [L-SVM], Gaussian-SVM, and polynomial-SVM) were constructed. Univariate was used to select clinicoradiological risk factors. Combined models including optimal radiomics features and clinicoradiological risk factors were constructed by these six classifiers. The prediction performance was evaluated using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA).

Results

In the internal test cohort, the best combined model (L-SVM, AUC=0.820 [95% CI 0.758–0.888]) performed better than the best radiomics model (L-SVM, AUC = 0.733 [95% CI 0.654–0.812]) and the clinical model (AUC = 0.709 [95% CI 0.649–0.783]). Combined-L-SVM model combines 23 radiomics features and 1 clinicoradiological risk factor (CT-reported TCI). In the external test cohort, the AUC was 0.776 (0.625–0.904) in the combined-L-SVM model, showing that the model is stable. DCA demonstrated that the combined model was clinically useful.

Conclusions

Our combined model based on machine learning incorporated with CT radiomics features and the clinicoradiological risk factor shows good predictive ability for TCI in PTC.
Spexin and Galanin in Metabolic Functions and Social Behaviors With a Focus on Non-Mammalian Vertebrates
Authors: Mohd Zahir Izzati , Ogawa Satoshi , Dominic Nisha Angela , Soga Tomoko , Parhar Ishwar S.
Published: May 2022

Spexin (SPX) and galanin (GAL) are two neuropeptides that are phylogenetically related and have descended from a common ancestral gene. Considerable attention has been given to these two multifunctional neuropeptides because they share GAL receptors 1,2, and 3. Since GAL and SPX-synthesizing neurons have been detected in several brain areas, therefore, it can be speculated that SPX and GAL are involved in various neurophysiological functions. Several studies have shown the functions of these two neuropeptides in energy regulation, reproduction, and response to stress. SPX acts as a satiety factor to suppress food intake, while GAL has the opposite effect as an orexigenic factor. There is evidence that SPX acts as an inhibitor of reproductive functions by suppressing gonadotropin release, while GAL modulates the activity of gonadotropin-releasing hormone (GnRH) neurons in the brain and gonadotropic cells in the pituitary. SPX and GAL are responsive to stress. Furthermore, SPX can act as an anxiolytic factor, while GAL exerts anti-depressant and pro-depressive effects depending on the receptor it binds. This review describes evidence supporting the central roles of SPX and GAL neuropeptides in energy balance, reproduction, stress, and social behaviors, with a particular focus on non-mammalian vertebrate systems.
Necroptosis is Related to Anti-PD-1 Treatment Response and Influences the Tumor Microenvironment in Head and Neck Squamous Cell Carcinoma
Authors: Wang Qiwei , Wang Fang , Zhao Yinan , Tan Guolin
Published: May 2022

The latest research suggesting that necroptosis plays a vital role in immune response. However, the influence of necroptosis on tumor microenvironment (TME) remodeling and immunotherapy is still unclear. We analyzed the variations in the expression of 26 necroptosis-related molecules in HNSCC and the influence of genome changes. We investigated HNSCC samples and determined that there are two necroptosis phenotypes in HNSCC cancer, and there are significant differences in cell infiltration characteristics and survival in different necroptosis phenotypes. We used the single‐sample gene set enrichment analysis to measure the level of necroptosis in patients with NecroticScore, we confirmed that the NecroticScore can predict the prognosis of HNSCC patients and the response to immunotherapy. Patients with a high NecroticScore are more sensitive to immunotherapy and have a better prognosis. Our study suggests a significant correlation between the expression imbalance of necroptosis-related molecules and suggests necroptosis plays an important role in modeling the TME. In addition, we construct a risk prediction model which could stratify patients with HNSCC and predict patient prognosis according to this necroptosis-related molecules. In conclusion, evaluating necroptosis modification patterns contributes to enhancing our understanding of TME and can guide more effective immunotherapy strategies.
Repetitive Elements, Sequence Turnover and Cyto-Nuclear Gene Transfer in Gymnosperm Mitogenomes
Authors: Liu Hui , Zhao Wei , Zhang Ren-Gang , Mao Jian-Feng , Wang Xiao-Ru
Published: May 2022

Among the three genomes in plant cells, the mitochondrial genome (mitogenome) is the least studied due to complex recombination and intergenomic transfer. In gymnosperms only ∼20 mitogenomes have been released thus far, which hinders a systematic investigation into the tempo and mode of mitochondrial DNA evolution in seed plants. Here, we report the complete mitogenome sequence of Platycladus orientalis (Cupressaceae). This mitogenome is assembled as two circular-mapping chromosomes with a size of ∼2.6 Mb and which contains 32 protein-coding genes, three rRNA and seven tRNA genes, and 1,068 RNA editing sites. Repetitive sequences, including dispersed repeats, transposable elements (TEs), and tandem repeats, made up 23% of the genome. Comparative analyses with 17 other mitogenomes representing the five gymnosperm lineages revealed a 30-fold difference in genome size, 80-fold in repetitive content, and 230-fold in substitution rate. We found dispersed repeats are highly associated with mitogenome expansion (r = 0.99), and most of them were accumulated during recent duplication events. Syntenic blocks and shared sequences between mitogenomes decay rapidly with divergence time (r = 0.53), with the exceptions of Ginkgo and Cycads which retained conserved genome structure over long evolutionary time. Our phylogenetic analysis supports a sister group relationship of Cupressophytes and Gnetophytes; both groups are unique in that they lost 8–12 protein-coding genes, of which 4–7 intact genes are likely transferred to nucleus. These two clades also show accelerated and highly variable substitution rates relative to other gymnosperms. Our study highlights the dynamic and enigmatic evolution of gymnosperm mitogenomes.
Neuron-Specific Deletion of Scrib in Mice Leads to Neuroanatomical and Locomotor Deficits
Authors: Ezan Jerome , Moreau Maité M. , Mamo Tamrat M. , Shimbo Miki , Decroo Maureen , Sans Nathalie , Montcouquiol Mireille
Published: May 2022

Scribble (Scrib) is a conserved polarity protein acting as a scaffold involved in multiple cellular and developmental processes. Recent evidence from our group indicates that Scrib is also essential for brain development as early global deletion of Scrib in the dorsal telencephalon induced cortical thickness reduction and alteration of interhemispheric connectivity. In addition, Scrib conditional knockout (cKO) mice have behavioral deficits such as locomotor activity impairment and memory alterations. Given Scrib broad expression in multiple cell types in the brain, we decided to determine the neuronal contribution of Scrib for these phenotypes. In the present study, we further investigate the function of Scrib specifically in excitatory neurons on the forebrain formation and the control of locomotor behavior. To do so, we generated a novel neuronal glutamatergic specific Scrib cKO mouse line called Nex-Scrib−/− cKO. Remarkably, cortical layering and commissures were impaired in these mice and reproduced to some extent the previously described phenotype in global Scrib cKO. In addition and in contrast to our previous results using Emx1-Scrib−/− cKO, the Nex-Scrib−/− cKO mutant mice exhibited significantly reduced locomotion. Altogether, the novel cKO model described in this study further highlights an essential role for Scrib in forebrain development and locomotor behavior.
Identification of Biomarkers for Predicting Ovarian Reserve of Primordial Follicle via Transcriptomic Analysis
Authors: Liu Li , Liu Biting , Li Ke , Wang Chunyan , Xie Yan , Luo Ning , Wang Lian , Sun Yaoqi , Huang Wei , Cheng Zhongping , Liu Shupeng
Published: May 2022

Ovarian reserve (OR) is mainly determined by the number of primordial follicles in the ovary and continuously depleted until ovarian senescence. With the development of assisted reproductive technology such as ovarian tissue cryopreservation and autotransplantation, growing demand has arisen for objective assessment of OR at the histological level. However, no specific biomarkers of OR can be used effectively in clinic nowadays. Herein, bulk RNA-seq datasets of the murine ovary with the biological ovarian age (BOA) dynamic changes and single-cell RNA-seq datasets of follicles at different stages of folliculogenesis were obtained from the GEO database to identify gene signature correlated to the primordial follicle pool. The correlations between gene signature expression and OR were also validated in several comparative OR models. The results showed that genes including Lhx8, Nobox, Sohlh1, Tbpl2, Stk31, and Padi6 were highly correlated to the OR of the primordial follicle pool, suggesting that these genes might be used as biomarkers for predicting OR at the histological level.
A RE-AIM Framework Analysis of DNA-Based Population Screening: Using Implementation Science to Translate Research Into Practice in a Healthcare System
Authors: Jones Laney K. , Strande Natasha T. , Calvo Evan M. , Chen Jingheng , Rodriguez Gabriela , McCormick Cara Z. , Hallquist Miranda L. G. , Savatt Juliann M. , Rocha Heather , Williams Marc S. , Sturm Amy C. , Buchanan Adam H. , Glasgow Russell E. , Martin Christa L. , Rahm Alanna Kulchak
Published: May 2022

Introduction: DNA-based population screening has been proposed as a public health solution to identify individuals at risk for serious health conditions who otherwise may not present for medical care. The clinical utility and public health impact of DNA-based population screening is a subject of active investigation. Geisinger, an integrated healthcare delivery system, was one of the first healthcare systems to implement DNA screening programs (MyCode Community Health Initiative (MyCode) and clinical DNA screening pilot) that leverage exome data to identify individuals at risk for developing conditions with potential clinical actionability. Here, we demonstrate the use of an implementation science framework, RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance), to conduct a post-hoc evaluation and report outcomes from these two programs to inform the potential impact of DNA-based population screening.

Methods: Reach and Effectiveness outcomes were determined from the MyCode research program, while Adoption and Implementation outcomes were measured using the clinical DNA screening pilot. Reach was defined as the number of patients who were offered and consented to participate in MyCode. Effectiveness of DNA screening was measured by reviewing MyCode program publications and synthesizing findings from themes. Adoption was measured by the total number of DNA screening tests ordered by clinicians at the clinical pilot sites. Implementation was assessed by interviewing a subset of clinical pilot clinicians about the deployment of and recommended adaptations to the pilot that could inform future program dissemination.

Results:Reach: As of August 2020, 68% (215,078/316,612) of individuals approached to participate in the MyCode program consented. Effectiveness: Published evidence reported from MyCode demonstrates that DNA screening identifies at-risk individuals more comprehensively than clinical ascertainment based on phenotypes or personal/family history. Adoption: From July 2018 to June 2021, a total of 1,026 clinical DNA screening tests were ordered by 60 clinicians across the three pilot clinic sites. Implementation: Interviews with 14 clinicians practicing at the pilot clinic sites revealed motivation to provide patients with DNA screening results and yielded future implementation strategies.

Conclusion: The RE-AIM framework offers a pragmatic solution to organize, analyze, and report outcomes across differently resourced and designed precision health programs that include genomic sequencing and return of clinically actionable genomic information.
Presence of Circulatory Autoantibodies Against ROS-Modified Histone H1 Protein in Lymphoma Patients
Authors: Binsaleh Naif K. , Eltayeb Reem , Qanash Husam , Aziz Mohammad Azhar , Albaradie Raid , Khan Mohd Wajid Ali
Published: May 2022

Lymphoma is a chronic inflammatory disease in which the immune system is highly affected. Increased oxidative stress is one of the common conditions of cancer and affects macromolecules. Histone modifications affect the chromatin structure and functions. In this study, histone H1 (His-H1) protein was modified by reactive oxygen species (ROS), and structural and chemical changes were studied. Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients were selected, and oxidative stress markers, inflammatory cytokines, and serum autoantibodies were analyzed using biochemical and immunological assays. Furthermore, the formation of antigen-antibody immune complexes was assessed by the Langmuir plot. ROS-modified His-H1 (ROS-His-H1) showed substantial structural perturbation in protein (UV-hyperchromicity and increased intrinsic fluorescence) compared to the native His-H1 protein. A possible explanation for the changes is suggested by the exposure of the aromatic chromophore to the solvent. In-depth structural analysis by circular dichroism (CD) exhibited major changes in α-helix (−21.43%) and turns (+33%), reflecting changes in the secondary structure of histone H1 protein after ROS exposure. ELISA and competitive ELISA findings revealed high recognitions of serum autoantibodies to ROS-His-H1 from NHL, followed by HL subjects. Healthy controls showed negligible binding. Non-modified His-H1 did not show any binding with serum samples from either cohort. High apparent association constants (ACCs) were calculated for ROS-His-H1 using purified IgGs from NHL (1.46 × 10–6 M) compared to HL (1.33 × 10–6 M) patients. Non-modified His-H1 exhibited a hundred times less ACC for NHL (2.38 × 10–8 M) and HL (2.46 × 10–8 M) patients. Thus, ROS modifications of histone H1 cause structural changes and expose cryptic neo-epitopes on the protein against which autoantibodies were generated. These perturbations might affect the histone DNA interaction dynamics and potentially be correlated with gene dysregulation. These subtle molecular changes with an immune imbalance might further aggravate the disease.
Sentence vs. Word Perception by Young Healthy Females: Toward a Better Understanding of Emotion in Spoken Language
Authors: Sinvani Rachel-Tzofia , Sapir Shimon
Published: May 2022

Expression and perception of emotions by voice are fundamental for basic mental health stability. Since different languages interpret results differently, studies should be guided by the relationship between speech complexity and the emotional perception. The aim of our study was therefore to analyze the efficiency of speech stimuli, word vs. sentence, as it relates to the accuracy of four different categories of emotions: anger, sadness, happiness, and neutrality. To this end, a total of 2,235 audio clips were presented to 49 females, native Hebrew speakers, aged 20–30 years (M = 23.7; SD = 2.13). Participants were asked to judge audio utterances according to one of four emotional categories: anger, sadness, happiness, and neutrality. Simulated voice samples were consisting of words and meaningful sentences, provided by 15 healthy young females Hebrew native speakers. Generally, word vs. sentence was not originally accepted as a means of emotional recognition of voice; However, introducing a variety of speech utterances revealed a different perception. Thus, the emotional conveyance provided new, even higher precision to our findings: Anger emotions produced a higher impact to the single word (χ2 = 10.21, p < 0.01) as opposed to the sentence, while sadness was identified more accurately with a sentence (χ2 = 3.83, p = 0.05). Our findings resulted in a better understanding of how speech types can interpret perception, as a part of mental health.
Asthma and the Missing Heritability Problem: Necessity for Multiomics Approaches in Determining Accurate Risk Profiles
Authors: Augustine Tracy , Al-Aghbar Mohammad Ameen , Al-Kowari Moza , Espino-Guarch Meritxell , van Panhuys Nicholas
Published: May 2022

Asthma is ranked among the most common chronic conditions and has become a significant public health issue due to the recent and rapid increase in its prevalence. Investigations into the underlying genetic factors predict a heritable component for its incidence, estimated between 35% and 90% of causation. Despite the application of large-scale genome-wide association studies (GWAS) and admixture mapping approaches, the proportion of variants identified accounts for less than 15% of the observed heritability of the disease. The discrepancy between the predicted heritable component of disease and the proportion of heritability mapped to the currently identified susceptibility loci has been termed the ‘missing heritability problem.’ Here, we examine recent studies involving both the analysis of genetically encoded features that contribute to asthma and also the role of non-encoded heritable characteristics, including epigenetic, environmental, and developmental aspects of disease. The importance of vertical maternal microbiome transfer and the influence of maternal immune factors on fetal conditioning in the inheritance of disease are also discussed. In order to highlight the broad array of biological inputs that contribute to the sum of heritable risk factors associated with allergic disease incidence that, together, contribute to the induction of a pro-atopic state. Currently, there is a need to develop in-depth models of asthma risk factors to overcome the limitations encountered in the interpretation of GWAS results in isolation, which have resulted in the missing heritability problem. Hence, multiomics analyses need to be established considering genetic, epigenetic, and functional data to create a true systems biology-based approach for analyzing the regulatory pathways that underlie the inheritance of asthma and to develop accurate risk profiles for disease.
Metabolic Reprogramming Mediates Delayed Apoptosis of Human Neutrophils Infected With Francisella tularensis
Authors: Krysa Samantha J. , Allen Lee-Ann H.
Published: May 2022

Neutrophils (polymorphonuclear leukocytes, PMNs) have a distinctively short lifespan, and tight regulation of cell survival and death is imperative for their normal function. We demonstrated previously that Francisella tularensis extends human neutrophil lifespan, which elicits an impaired immune response characterized by neutrophil dysfunction. Herein, we extended these studies, including our transcriptional profiling data, and employed Seahorse extracellular flux analysis, gas chromatography-mass spectrometry metabolite analysis, flow cytometry and several other biochemical approaches to demonstrate that the delayed apoptosis observed in F. tularensis-infected neutrophils is mediated, in part, by metabolic reprogramming. Specifically, we show that F. tularensis-infected neutrophils exhibited a unique metabolic signature characterized by increased glycolysis, glycolytic flux and glucose uptake, downregulation of the pentose phosphate pathway, and complex glycogen dynamics. Glucose uptake and glycolysis were essential for cell longevity, although glucose-6-phosphate translocation into the endoplasmic reticulum was not, and we identify depletion of glycogen as a potential trigger of apoptosis onset. In keeping with this, we also demonstrate that ablation of apoptosis with the pan-caspase inhibitor Q-VD-OPh was sufficient to profoundly increase glycolysis and glycogen stores in the absence of infection. Taken together, our data significantly advance understanding of neutrophil immunometabolism and its capacity to regulate cell lifespan.
Extracellular Vesicles: Recent Insights Into the Interaction Between Host and Pathogenic Bacteria
Authors: Zou Chaoyu , Zhang Yige , Liu Huan , Wu Yu , Zhou Xikun
Published: May 2022

Extracellular vesicles (EVs) are nanosized lipid particles released by virtually every living cell. EVs carry bioactive molecules, shuttle from cells to cells and transduce signals, regulating cell growth and metabolism. Pathogenic bacteria can cause serious infections via a wide range of strategies, and host immune systems also develop extremely complex adaptations to counteract bacterial infections. As notable carriers, EVs take part in the interaction between the host and bacteria in several approaches. For host cells, several strategies have been developed to resist bacteria via EVs, including expelling damaged membranes and bacteria, neutralizing toxins, triggering innate immune responses and provoking adaptive immune responses in nearly the whole body. For bacteria, EVs function as vehicles to deliver toxins and contribute to immune escape. Due to their crucial functions, EVs have great application potential in vaccines, diagnosis and treatments. In the present review, we highlight the most recent advances, application potential and remaining challenges in understanding EVs in the interaction between the host and bacteria.
Pyroptosis and Its Role in Autoimmune Disease: A Potential Therapeutic Target
Authors: You Ruixuan , He Xinglan , Zeng Zhuotong , Zhan Yi , Xiao Yangfan , Xiao Rong
Published: May 2022

Autoimmune diseases are a group of heterogeneous diseases with diverse clinical manifestations that can be divided into systemic and organ-specific. The common etiology of autoimmune diseases is the destruction of immune tolerance and the production of autoantibodies, which attack specific tissues and/or organs in the body. The pathogenesis of autoimmune diseases is complicated, and genetic, environmental, infectious, and even psychological factors work together to cause aberrant innate and adaptive immune responses. Although the exact mechanisms are unclear, recently, excessive exacerbation of pyroptosis, as a bond between innate and adaptive immunity, has been proven to play a crucial role in the development of autoimmune disease. Pyroptosis is characterized by pore formation on cell membranes, as well as cell rupture and the excretion of intracellular contents and pro-inflammatory cytokines, such as IL-1β and IL-18. This overactive inflammatory programmed cell death disrupts immune system homeostasis and promotes autoimmunity. This review examines the molecular structure of classical inflammasomes, including NLRP3, AIM2, and P2X7-NLRP3, as the switches of pyroptosis, and their molecular regulation mechanisms. The sophisticated pyroptosis pathways, including the canonical caspase-1-mediated pathway, the noncanonical caspase-4/5/11-mediated pathway, the emerging caspase-3-mediated pathway, and the caspase-independent pathway, are also described. We highlight the recent advances in pyroptosis in autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Sjögren’s syndrome and dermatomyositis, and attempt to identify its potential advantages as a therapeutic target or prognostic marker in these diseases.
Associations Between Serum Fatty Acids and Immunological Markers in Children Developing Islet Autoimmunity—The TRIGR Nested Case–Control Study
Authors: Niinistö Sari , Miettinen Maija E. , Cuthbertson David , Honkanen Jarno , Hakola Leena , Autio Reija , Erlund Iris , Arohonka Petra , Vuorela Arja , Härkönen Taina , Hyöty Heikki , Krischer Jeffrey P. , Vaarala Outi , Knip Mikael , Virtanen Suvi M. ,   TRIGR Investigators
Published: May 2022

Aims

Altered immune functions as well as fatty acid intake and status have been associated with the development of type 1 diabetes. We aimed to study the relationship between fatty acids and immunological markers in young children with increased genetic risk for type 1 diabetes in order to define putative mechanisms related to development of islet autoimmunity.

Methods

Serum samples for fatty acid and immunological marker measurements were obtained in the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) ancillary study (Divia) from children born between 2002 and 2007 in 15 countries. Case children (n = 95) were defined as having repeated positivity for at least two out of four diabetes-associated autoantibodies. For each case child, control children were selected matched for country and date of birth (n = 173). Serum fatty acids and immunological markers were measured from cord serum and at the age of 6 and 12 months. Spearman correlation coefficients were calculated between fatty acids and immunological markers.

Results

Correlations between circulating fatty acids and immunological markers were different in case children who developed islet autoimmunity than in control children already at birth continuing across the first year of life. In case children, saturated fatty acids (SFAs) showed stronger correlations with immunological markers, while in controls, polyunsaturated fatty acids (PUFAs) showed stronger correlations.

Conclusions

In cases, SFAs were associated with several immunological markers (CXCL10, IL-6, IL-9, IL-17, and CM-CSF) previously linked to the type 1 diabetes disease process. Findings indicate that fatty acids could have immunomodulatory potential in the early phase of the disease development, although causality between fatty acids and the immunological pathways remains to be explored.

Trial registry number

NCT00179777
Epigenetics Regulates Antitumor Immunity in Melanoma
Authors: Chen Yuhan , Yi Xiuli , Sun Ningyue , Guo Weinan , Li Chunying
Published: May 2022

Melanoma is the most malignant skin cancer, which originates from epidermal melanocytes, with increasing worldwide incidence. The escape of immune surveillance is a hallmark of the tumor, which is manifested by the imbalance between the enhanced immune evasion of tumor cells and the impaired antitumor capacity of infiltrating immune cells. According to this notion, the invigoration of the exhausted immune cells by immune checkpoint blockades has gained encouraging outcomes in eliminating tumor cells and significantly prolonged the survival of patients, particularly in melanoma. Epigenetics is a pivotal non-genomic modulatory paradigm referring to heritable changes in gene expression without altering genome sequence, including DNA methylation, histone modification, non-coding RNAs, and m6A RNA methylation. Accumulating evidence has demonstrated how the dysregulation of epigenetics regulates multiple biological behaviors of tumor cells and contributes to carcinogenesis and tumor progression in melanoma. Nevertheless, the linkage between epigenetics and antitumor immunity, as well as its implication in melanoma immunotherapy, remains elusive. In this review, we first introduce the epidemiology, clinical characteristics, and therapeutic innovations of melanoma. Then, the tumor microenvironment and the functions of different types of infiltrating immune cells are discussed, with an emphasis on their involvement in antitumor immunity in melanoma. Subsequently, we systemically summarize the linkage between epigenetics and antitumor immunity in melanoma, from the perspective of distinct paradigms of epigenetics. Ultimately, the progression of the clinical trials regarding epigenetics-based melanoma immunotherapy is introduced.
A Roadmap for Investigating Preclinical Autoimmunity Using Patient-Oriented and Epidemiologic Study Designs: Example of Rheumatoid Arthritis
Authors: Kowalski Emily N. , Qian Grace , Vanni Kathleen M.M. , Sparks Jeffrey A.
Published: May 2022

Background & Aims

Rheumatoid arthritis (RA) is a prototypic autoimmune disease causing inflammatory polyarthritis that affects nearly 1% of the population. RA can lead to joint destruction and disability along with increased morbidity and mortality. Similar to other autoimmune diseases, RA has distinct preclinical phases corresponding to genetic risk, lifestyle risk factors, autoantibody development, and non-specific symptoms prior to clinical diagnosis. This narrative review will detail observational studies for RA risk and clinical trials for RA prevention as a roadmap to investigating preclinical autoimmunity that could be applied to other diseases.

Methods

In this narrative review, we summarized previous and ongoing research studies investigating RA risk and prevention, categorizing them related to their design and preclinical phases.

Results

We detailed the following types of studies investigating RA risk and prevention: retrospective population-based and administrative datasets; prospective studies (case-control and cohort; some enrolling based on genetics, first-degree relative status, elevated biomarkers, or early symptoms/arthritis); and randomized clinical trials. These correspond to all preclinical RA phases (genetic, lifestyle, autoimmunity, early signs/symptoms). Previous and ongoing randomized controlled trials have enrolled individuals at very elevated risk for RA based on biomarkers, symptoms, imaging abnormalities, or early signs/symptoms.

Conclusion

We detailed the rich variety of study designs that is necessary to investigate distinct preclinical phases of an autoimmune disease such as RA. However, further progress is needed to fully elucidate the pathogenesis of RA that may ultimately lead to prevention or delay of disease onset.
Prussian Blue Scavenger Ameliorates Hepatic Ischemia-Reperfusion Injury by Inhibiting Inflammation and Reducing Oxidative Stress
Authors: Huang Yongxin , Xu Qinyuan , Zhang Jiang , Yin Yanze , Pan Yixiao , Zheng Yuanyi , Cai Xiaojun , Xia Qiang , He Kang
Published: May 2022

Oxidative stress and excessive inflammatory responses are the two critical mechanisms of hepatic ischemia-reperfusion injury (HIRI) encountered in many clinical settings, including following hepatectomy and liver transplantation. Effective anti-inflammatory and anti-oxidative pharmacological interventions are urgently needed to counter HIRI. The present study showed that a biocompatible Prussian blue (PB) scavenger with reactive oxygen species (ROS) scavenging and anti-inflammatory properties might be used a promising treatment for HIRI. Following intravenous administration, PB scavenger was mainly distributed in the liver, where it showed excellent ability to alleviate apoptosis, tissue injury and organ dysfunction after HIRI. PB scavenger was found to protect liver tissue by scavenging ROS, reducing neutrophil infiltration and promoting macrophage M2 polarization. In addition, PB scavenger significantly reduced oxidative stress in primary hepatocytes, restoring cell viability under oxidative stress condition. PB scavenger effectively reduced lipopolysaccharide-stimulated inflammation in RAW 264.7 cells. These findings indicate that PB scavenger may be a potential therapeutic agent for the treatment of HIRI, providing an alternative treatment for ROS-associated and inflammatory liver diseases.
Nanodrugs Targeting T Cells in Tumor Therapy
Authors: Haist Maximilian , Mailänder Volker , Bros Matthias
Published: May 2022

In contrast to conventional anti-tumor agents, nano-carriers allow co-delivery of distinct drugs in a cell type-specific manner. So far, many nanodrug-based immunotherapeutic approaches aim to target and kill tumor cells directly or to address antigen presenting cells (APC) like dendritic cells (DC) in order to elicit tumor antigen-specific T cell responses. Regulatory T cells (Treg) constitute a major obstacle in tumor therapy by inducing a pro-tolerogenic state in APC and inhibiting T cell activation and T effector cell activity. This review aims to summarize nanodrug-based strategies that aim to address and reprogram Treg to overcome their immunomodulatory activity and to revert the exhaustive state of T effector cells. Further, we will also discuss nano-carrier-based approaches to introduce tumor antigen-specific chimeric antigen receptors (CAR) into T cells for CAR-T cell therapy which constitutes a complementary approach to DC-focused vaccination.
Twin Growth Discordance and Risk of Postpartum Hemorrhage: A Retrospective Cohort Study
Authors: Cao Xiuhong , Luo Ye , Zhou Shuangqiong , Zhao Qingsong , Qin Xuewei , Liu Zhiqiang , Xu Zhendong
Published: May 2022

Background

In recent years, the incidence of postpartum hemorrhage has increased globally. Multiple pregnancies and cesarean sections are well-known risk factors for postpartum hemorrhage. No studies have evaluated the associations between fetal growth anomalies and postpartum hemorrhage in women with twin pregnancies undergoing cesarean section. This study aimed to identify the relationship between fetal growth anomalies and postpartum hemorrhage in women with twin pregnancies undergoing cesarean section.

Methods

This retrospective single-center study included 3,180 women with twin pregnancies at a tertiary hospital between August 2013 and July 2020. Singleton reference charts were used to assess fetal growth restriction at birth. Discordant growth was defined as an intertwin birth weight difference of ≥20%. Logistic regression analyses were used to evaluate the association between fetal growth anomalies and postpartum hemorrhage. Additionally, sensitivity analysis of abnormal placenta and stratification by twin chorionicity were conducted.

Results

The overall incidence of postpartum hemorrhage was 4.3%. Twin growth discordance, especially with fetal growth restriction, was associated with an increased risk of postpartum hemorrhage (adjusted odds ratio [AOR] = 1.62, 95% confidence interval [CI], 1.05–2.51, P = 0.031; AOR = 1.71; 95% CI, 1.08–2.70, P = 0.022; AOR = 1.98, 95% CI, 1.21–3.25, P = 0.006, respectively). After stratification, this relationship persisted in dichorionic twins (OR = 1.71, 95% CI, 1.04–2.82, P = 0.036; OR = 1.90, 95% CI, 1.13–3.21, P = 0.016; OR = 2.48, 95% CI, 1.41–4.38, P = 0.002, respectively). However, no significant association was observed in monochorionic twin pregnancies.

Conclusion

Growth discordance, especially complicated by fetal growth restriction, was associated with an increased risk of postpartum hemorrhage in women with twin pregnancies undergoing cesarean section, and was more evident in patients with dichorionic twins.
Establishment of Genome Based Criteria for Classification of the Family Desulfovibrionaceae and Proposal of Two Novel Genera, Alkalidesulfovibrio gen. nov. and Salidesulfovibrio gen. nov.
Authors: Park Mi-Jeong , Kim Yun Jae , Park Myeongkyu , Yu Jihyun , Namirimu Teddy , Roh Yoo-Rim , Kwon Kae Kyoung
Published: May 2022

Bacteria in the Desulfovibrionaceae family, which contribute to S element turnover as sulfate-reducing bacteria (SRB) and disproportionation of partially oxidized sulfoxy anions, have been extensively investigated since the importance of the sulfur cycle emerged. Novel species belonging to this taxon are frequently reported, because they exist in various environments and are easy to culture using established methods. Due to the rapid expansion of the taxon, correction and reclassification have been conducted. The development of high-throughput sequencing facilitated rapid expansion of genome sequence database. Genome-based criteria, based on these databases, proved to be potential classification standard by overcoming the limitations of 16S rRNA-based phylogeny. Although standards methods for taxogenomics are being established, the addition of a novel genus requires extensive calculations with taxa, including many species, such as Desulfovibrionaceae. Thus, the genome-based criteria for classification of Desulfovibrionaceae were established and validated in this study. The average amino-acid identity (AAI) cut-off value, 63.43 ± 0.01, was calculated to be an appropriate criterion for genus delineation of the family Desulfovibrionaceae. By applying the AAI cut-off value, 88 genomes of the Desulfovibrionaceae were divided into 27 genera, which follows the core gene phylogeny results. In this process, two novel genera (Alkalidesulfovibrio and Salidesulfovibrio) and one former invalid genus (“Psychrodesulfovibrio”) were officially proposed. Further, by applying the 95–96% average nucleotide identity (ANI) standard and the 70% digital DNA–DNA hybridization standard values for species delineation of strains that were classified as the same species, five strains have the potential to be newly classified. After verifying that the classification was appropriately performed through relative synonymous codon usage analysis, common characteristics were listed by group. In addition, by detecting metal resistance related genes via in silico analysis, it was confirmed that most strains display metal tolerance.
Thermophilic Geobacillus WSUCF1 Secretome for Saccharification of Ammonia Fiber Expansion and Extractive Ammonia Pretreated Corn Stover
Authors: Bhalla Aditya , Arce Jessie , Ubanwa Bryan , Singh Gursharan , Sani Rajesh K. , Balan Venkatesh
Published: May 2022

A thermophilic Geobacillus bacterial strain, WSUCF1 contains different carbohydrate-active enzymes (CAZymes) capable of hydrolyzing hemicellulose in lignocellulosic biomass. We used proteomic, genomic, and bioinformatic tools, and genomic data to analyze the relative abundance of cellulolytic, hemicellulolytic, and lignin modifying enzymes present in the secretomes. Results showed that CAZyme profiles of secretomes varied based on the substrate type and complexity, composition, and pretreatment conditions. The enzyme activity of secretomes also changed depending on the substrate used. The secretomes were used in combination with commercial and purified enzymes to carry out saccharification of ammonia fiber expansion (AFEX)-pretreated corn stover and extractive ammonia (EA)-pretreated corn stover. When WSUCF1 bacterial secretome produced at different conditions was combined with a small percentage of commercial enzymes, we observed efficient saccharification of EA-CS, and the results were comparable to using a commercial enzyme cocktail (87% glucan and 70% xylan conversion). It also opens the possibility of producing CAZymes in a biorefinery using inexpensive substrates, such as AFEX-pretreated corn stover and Avicel, and eliminates expensive enzyme processing steps that are used in enzyme manufacturing. Implementing in-house enzyme production is expected to significantly reduce the cost of enzymes and biofuel processing cost.
Comparison of Microbial Populations in the Blood of Patients With Myocardial Infarction and Healthy Individuals
Authors: Khan Ikram , Khan Imran , Kakakhel Mian Adnan , Xiaowei Zhang , Ting Mao , Ali Ikram , Fei Yu , Jianye Zhou , Zhiqiang Li , Lizhe An
Published: May 2022

Increased bacterial translocation in the gut and bloodstream infections are both major comorbidities of heart failure and myocardial infarction (MI). However, the alterations in the microbiome of the blood of patients with MI remain unclear. To test this hypothesis, we conducted this case-control study to explore the microbiota compositions in the blood of Chinese patients with MI. Using high-throughput Illumina HiSeq sequencing targeting the V3–V4 region of the 16S ribosomal RNA (rRNA) gene, the microbiota communities in the blood of 29 patients with MI and 29 healthy controls were examined. In addition, the relationship between the blood microbiome and clinical features of MI was investigated. This study revealed a significant reduction in alpha diversity (Shannon index) in the MI group compared with the healthy controls. Also, a significant difference was detected in the structure and richness between the patients with MI and healthy controls. The members of the phylum Actinobacteria, class Actinobacteria, order Bifdobacteriales, family Bifidobacteriaceae, and genus Bifidobacterium were significantly abundant in the MI group, while the members of the phylum Bacteroidetes, class Bacteroidia, and order Bacteroidales were significantly enriched in the healthy controls (p < 0.05). Moreover, the functional analysis revealed a significant variation between both groups. For instance, the enrichment of genes involved in the metabolism pathways of three amino acids decreased, that is, nucleotide transport and metabolism, coenzyme transport and metabolism, and lipid transport and metabolism, among others. Our study will contribute to a better knowledge of the microbiota of blood, which will further lead to improved MI diagnosis and therapy. Further study is needed to determine the role of the blood microbiota in human health and disease.
Modeling Bacterial Flagellar Motor With New Structure Information: Rotational Dynamics of Two Interacting Protein Nano-Rings
Authors: Cao Yuansheng , Li Tairan , Tu Yuhai
Published: May 2022

In this article, we develop a mathematical model for the rotary bacterial flagellar motor (BFM) based on the recently discovered structure of the stator complex (MotA5MotB2). The structure suggested that the stator also rotates. The BFM is modeled as two rotating nano-rings that interact with each other. Specifically, translocation of protons through the stator complex drives rotation of the MotA pentamer ring, which in turn drives rotation of the FliG ring in the rotor via interactions between the MotA ring of the stator and the FliG ring of the rotor. Preliminary results from the structure-informed model are consistent with the observed torque-speed relation. More importantly, the model predicts distinctive rotor and stator dynamics and their load dependence, which may be tested by future experiments. Possible approaches to verify and improve the model to further understand the molecular mechanism for torque generation in BFM are also discussed.
A Comprehensive Roadmap Towards the Generation of an Influenza B Reporter Assay Using a Single DNA Polymerase-Based Cloning of the Reporter RNA Construct
Authors: Kedia Nandita , Banerjee Saptarshi , Mondal Arindam
Published: May 2022

The mini-genome reporter assay is a key tool for conducting RNA virus research. However, procedural complications and the lack of adequate literature pose a major challenge in developing these assay systems. Here, we present a novel, yet generic and simple, cloning strategy for the construction of an influenza B virus reporter RNA template and describe an extensive standardization of the reporter RNP/polymerase activity assay for monitoring viral RNA synthesis in an infection-free setting. Using this assay system, we showed for the first time the effect of viral protein NS1 and host protein kinase C delta (PKCD) on influenza B virus RNA synthesis. In addition, the assay system showed promising results in evaluating the efficacy of antiviral drugs targeting viral RNA synthesis and virus propagation. Together, this work offers a detailed protocol for the standardization of the influenza virus minigenome assay and an excellent tool for screening of host factors and antivirals in a fast, user-friendly, and high-throughput manner.
NLRP6 Serves as a Negative Regulator of Neutrophil Recruitment and Function During Streptococcus pneumoniae Infection
Authors: Tao Qi , Xu Dongyi , Jia Kaixiang , Cao Xinrui , Ye Chao , Xie Sanlei , Hu Dong-Liang , Peng Lianci , Fang Rendong
Published: May 2022

Streptococcus pneumoniae is an invasive pathogen with high morbidity and mortality in the immunocompromised children and elderly. NOD-like receptor family pyrin domain containing 6 (NLRP6) plays an important role in the host innate immune response against pathogen infections. Our previous studies have shown that NLRP6 plays a negative regulatory role in host defense against S. pneumoniae, but the underlying mechanism is still unclear. The further negative regulatory role of NLRP6 in the host was investigated in this study. Our results showed that NLRP6−/− mice in the lung had lower bacterial burdens after S. pneumoniae infection and expressed higher level of tight junction (TJ) protein occludin compared to WT mice, indicating the detrimental role of NLRP6 in the host defense against S. pneumoniae infection. Transcriptome analysis showed that genes related to leukocytes migration and recruitment were differentially expressed between wild-type (WT) and NLRP6 knockout (NLRP6−/−) mice during S. pneumoniae infection. Also, NLRP6−/− mice showed higher expression of chemokines including C-X-C motif chemokine ligand 1 (CXCL1) and 2 (CXCL2) and lower gene expression of complement C3a receptor 1 (C3aR1) and P-selectin glycoprotein ligand-1 (PSGL-1) which are the factors that inhibit the recruitment of neutrophils. Furthermore, NLRP6−/− neutrophils showed increased intracellular bactericidal ability and the formation of neutrophil extracellular traps (NETs) during S. pneumoniae infection. Taken together, our study suggests that NLRP6 is a negative regulator of neutrophil recruitment and function during S. pneumoniae infection. Our study provides a new insight to develop novel strategies to treat invasive pneumococcal infection.
Biosynthesis of Phenolic Compounds and Antioxidant Activity in Fresh-Cut Fruits and Vegetables
Authors: Hu Wenzhong , Sarengaowa  , Guan Yuge , Feng Ke
Published: May 2022

Phenolic compounds are secondary metabolites and widely distributed in higher plants. When plants are subjected to injury stress, the rapid synthesis of more phenols is induced to result in injury defense response for wound healing and repair. Fresh-cut fruits and vegetables undergo substantial mechanical injury caused by pre-preparations such as peeling, coring, cutting and slicing. These processing operations lead to activate the biosynthesis of phenolic compounds as secondary metabolite. Phenolic compounds are important sources of antioxidant activity in fresh-cut fruits and vegetables. The wound-induced biosynthesis and accumulation of phenolic compounds in fresh-cut fruits and vegetables have been widely reported in recent years. This article provides a brief overview of research published over the last decade on the phenolic compounds and antioxidant activity in fresh-cut fruits and vegetables. It is suggested that fresh-cut processing as mechanical wounding stress can be used as an effective way to improve the nutritional composition and function of fresh-cut produces.