bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishment and Validation of a Ferroptosis-Related Gene Signature to Predict Overall Survival in Lung Adenocarcinoma
Authors: Wang Su , Xie Zhen , Wu Zenghong
Published: January 2022

Background: Lung adenocarcinoma (LUAD) is the most common and lethal subtype of lung cancer. Ferroptosis, an iron-dependent form of regulated cell death, has emerged as a target in cancer therapy. However, the prognostic value of ferroptosis-related genes (FRGs)x in LUAD remains to be explored.

Methods: In this study, we used RNA sequencing data and relevant clinical data from The Cancer Genome Atlas (TCGA) dataset and Gene Expression Omnibus (GEO) dataset to construct and validate a prognostic FRG signature for overall survival (OS) in LUAD patients and defined potential biomarkers for ferroptosis-related tumor therapy.

Results: A total of 86 differentially expressed FRGs were identified from LUAD tumor tissues versus normal tissues, of which 15 FRGs were significantly associated with OS in the survival analysis. Through the LASSO Cox regression analysis, a prognostic signature including 11 FRGs was established to predict OS in the TCGA tumor cohort. Based on the median value of risk scores calculated according to the signature, patients were divided into high-risk and low-risk groups. Kaplan–Meier analysis indicated that the high-risk group had a poorer OS than the low-risk group. The area under the curve of this signature was 0.74 in the TCGA tumor set, showing good discrimination. In the GEO validation set, the prognostic signature also had good predictive performance. Functional enrichment analysis showed that some immune-associated gene sets were significantly differently enriched in two risk groups.

Conclusion: Our study unearthed a novel ferroptosis-related gene signature for predicting the prognosis of LUAD, and the signature may provide useful prognostic biomarkers and potential treatment targets.
Case Report: Unmanipulated Matched Sibling Donor Hematopoietic Cell Transplantation In TBX1 Congenital Athymia: A Lifesaving Therapeutic Approach When Facing a Systemic Viral Infection
Authors: Chitty-Lopez Maria , Duff Carla , Vaughn Gretchen , Trotter Jessica , Monforte Hector , Lindsay David , Haddad Elie , Keller Michael D. , Oshrine Benjamin R. , Leiding Jennifer W.
Published: January 2022

Congenital athymia can present with severe T cell lymphopenia (TCL) in the newborn period, which can be detected by decreased T cell receptor excision circles (TRECs) on newborn screening (NBS). The most common thymic stromal defect causing selective TCL is 22q11.2 deletion syndrome (22q11.2DS). T-box transcription factor 1 (TBX1), present on chromosome 22, is responsible for thymic epithelial development. Single variants in TBX1 causing haploinsufficiency cause a clinical syndrome that mimics 22q11.2DS. Definitive therapy for congenital athymia is allogeneic thymic transplantation. However, universal availability of such therapy is limited. We present a patient with early diagnosis of congenital athymia due to TBX1 haploinsufficiency. While evaluating for thymic transplantation, she developed Omenn Syndrome (OS) and life-threatening adenoviremia. Despite treatment with anti-virals and cytotoxic T lymphocytes (CTLs), life threatening adenoviremia persisted. Given the imminent need for rapid establishment of T cell immunity and viral clearance, the patient underwent an unmanipulated matched sibling donor (MSD) hematopoietic cell transplant (HCT), ultimately achieving post-thymic donor-derived engraftment, viral clearance, and immune reconstitution. This case illustrates that because of the slower immune recovery that occurs following thymus transplantation and the restricted availability of thymus transplantation globally, clinicians may consider CTL therapy and HCT to treat congenital athymia patients with severe infections.
Tumor Flare Reaction in a Classic Hodgkin Lymphoma Patient Treated With Brentuximab Vedotin and Tislelizumab: A Case Report
Authors: Zhu Chunting , Zhao Yi , Yu Fang , Huang Weijia , Wu Wenjun , He Jingsong , Cai Zhen , He Donghua
Published: January 2022

Background

Tumor flare reaction (TFR) is a clinical syndrome, which is mainly associated with painful and swollen lymph nodes or splenomegaly, slight fever, bone pain, and skin rash during treatment with immune-related drugs, causing difficulty in distinguishing TFR from disease progression. Brentuximab vedotin (BV) and programmed death 1 (PD-1) inhibitor are two ideal drugs used for the treatment of classic Hodgkin lymphoma, but few studies have reported their adverse effects in association with TFR. The efficacy and safety of monotherapy or combination therapy with these drugs needs to be further evaluated. It is essential to determine whether treated patients can develop TFR, thus enabling more accurate diagnosis and treatment.

Case presentation

A 26-year-old female patient, diagnosed with classic Hodgkin lymphoma, had received 2 + 3 cycles of ABVD chemotherapy (a combination of adriamycin, bleomycin, vinblastine, and dacarbazine) and 4 cycles of PD-1 inhibitor (tislelizumab) therapy but exhibited poor efficacy. Subsequently, she was given combination therapy of BV (100 mg) + tislelizumab (200 mg). However, a slight fever, painful and swollen axillary lymph nodes, multiple skin rashes with pruritus, joint pain, and fatigue with poor appetite appeared during the treatment. Ultrasound (US) scans revealed that multiple lymph nodes were significantly enlarged. After treatment with low-dose dexamethasone and cetirizine, the symptoms were alleviated. A biopsy of the left axillary lymph node revealed that lymphoid tissue exhibited proliferative changes, without tumor cell infiltration. These findings were consistent with the clinical and pathological manifestations of TFR.

Conclusion

Combination therapy with BV and PD-1 inhibitor was effective in the treatment of relapsed or refractory classic Hodgkin lymphoma. The results suggest that the combination therapy may cause TFR, and biopsy and also continuous imaging observation are important to determine the disease stage. This approach allows clinicians to decide whether to continue the current treatment plan, and alerts them to the occurrence of excessive activation of the immune system.
TRPM2 Is Not Required for T-Cell Activation and Differentiation
Authors: Lory Niels C. , Nawrocki Mikolaj , Corazza Martina , Schmid Joanna , Schumacher Valéa , Bedke Tanja , Menzel Stephan , Koch-Nolte Friedrich , Guse Andreas H. , Huber Samuel , Mittrücker Hans-Willi
Published: January 2022

Antigen recognition by the T-cell receptor induces a cytosolic Ca2+signal that is crucial for T-cell function. The Ca2+channel TRPM2 (transient receptor potential cation channel subfamily M member 2) has been shown to facilitate influx of extracellular Ca2+through the plasma membrane of T cells. Therefore, it was suggested that TRPM2 is involved in T-cell activation and differentiation. However, these results are largely derived fromin vitrostudies using T-cell lines and non-physiologic means of TRPM2 activation. Thus, the relevance of TRPM2-mediated Ca2+signaling in T cells remains unclear. Here, we use TRPM2-deficient mice to investigate the function of TRPM2 in T-cell activation and differentiation. In response to TCR stimulationin vitro,Trpm2-/-and WT CD4+and CD8+T cells similarly upregulated the early activation markers NUR77, IRF4, and CD69. We also observed regular proliferation ofTrpm2-/-CD8+T cells and unimpaired differentiation of CD4+T cells into Th1, Th17, and Treg cells under specific polarizing conditions.In vivo,Trpm2-/-and WT CD8+T cells showed equal specific responses toListeria monocytogenesafter infection of WT andTrpm2-/-mice and after transfer of WT andTrpm2-/-CD8+T cells into infected recipients. CD4+T-cell responses were investigated in the model of anti-CD3 mAb-induced intestinal inflammation, which allows analysis of Th1, Th17, Treg, and Tr1-cell differentiation. Here again, we detected similar responses of WT andTrpm2-/-CD4+T cells. In conclusion, our results argue against a major function of TRPM2 in T-cell activation and differentiation.
Atypical Ataxia Presentation in Variant Ataxia Telangiectasia: Iranian Case-Series and Review of the Literature
Authors: Moeini Shad Tannaz , Yazdani Reza , Amirifar Parisa , Delavari Samaneh , Heidarzadeh Arani Marzieh , Mahdaviani Seyed Alireza , Sadeghi-Shabestari Mahnaz , Aghamohammadi Asghar , Rezaei Nima , Abolhassani Hassan
Published: January 2022

Ataxia-telangiectasia (AT) is a rare autosomal recessive neurodegenerative multisystem disorder. A minority of AT patients can present late-onset atypical presentations due to unknown mechanisms. The demographic, clinical, immunological and genetic data were collected by direct interview and examining the Iranian AT patients with late-onset manifestations. We also conducted a systematic literature review for reported atypical AT patients. We identified three Iranian AT patients (3/249, 1.2% of total registry) with later age at ataxia onset and slower neurologic progression despite elevated alpha-fetoprotein levels, history of respiratory infections, and immunological features of the syndrome. Of note, all patients developed autoimmunity in which a decrease of naïve T cells and regulatory T cells were observed. The literature searches also summarized data from 73 variant AT patients with atypical presentation indicating biallelic mild mutations mainly lead to an atypical phenotype with an increased risk of cancer. Variant AT patients present with milder phenotype or atypical form of classical symptoms causing under- or mis- diagnosis. Although missense mutations are more frequent, an atypical presentation can be associated with deleterious mutations due to unknown modifying factors.
Implementation of Early Next-Generation Sequencing for Inborn Errors of Immunity: A Prospective Observational Cohort Study of Diagnostic Yield and Clinical Implications in Dutch Genome Diagnostic Centers
Authors: Elsink Kim , Huibers Manon M. H. , Hollink Iris H. I. M. , Simons Annet , Zonneveld-Huijssoon Evelien , van der Veken Lars T. , Leavis Helen L. , Henriet Stefanie S. V. , van Deuren Marcel , van de Veerdonk Frank L. , Potjewijd Judith , Berghuis Dagmar , Dalm Virgil A. S. H. , Vermont Clementien L. , van de Ven Annick A. J. M. , Lambeck Annechien J. A. , Abbott Kristin M. , van Hagen P. Martin , de Bree Godelieve J. , Kuijpers Taco W. , Frederix Geert W. J. , van Gijn Mariëlle E. , van Montfrans Joris M. ,   the Genetics First for Primary Immunodeficiency Disorders Consortium
Published: January 2022

Objective

Inborn errors of immunity (IEI) are a heterogeneous group of disorders, affecting different components of the immune system. Over 450 IEI related genes have been identified, with new genes continually being recognized. This makes the early application of next-generation sequencing (NGS) as a diagnostic method in the evaluation of IEI a promising development. We aimed to provide an overview of the diagnostic yield and time to diagnosis in a cohort of patients suspected of IEI and evaluated by an NGS based IEI panel early in the diagnostic trajectory in a multicenter setting in the Netherlands.

Study Design

We performed a prospective observational cohort study. We collected data of 165 patients with a clinical suspicion of IEI without prior NGS based panel evaluation that were referred for early NGS using a uniform IEI gene panel. The diagnostic yield was assessed in terms of definitive genetic diagnoses, inconclusive diagnoses and patients without abnormalities in the IEI gene panel. We also assessed time to diagnosis and clinical implications.

Results

For children, the median time from first consultation to diagnosis was 119 days versus 124 days for adult patients (U=2323; p=0.644). The median turn-around time (TAT) of genetic testing was 56 days in pediatric patients and 60 days in adult patients (U=1892; p=0.191). A definitive molecular diagnosis was made in 25/65 (24.6%) of pediatric patients and 9/100 (9%) of adults. Most diagnosed disorders were identified in the categories of immune dysregulation (n=10/25; 40%), antibody deficiencies (n=5/25; 20%), and phagocyte diseases (n=5/25; 20%). Inconclusive outcomes were found in 76/165 (46.1%) patients. Within the patient group with a genetic diagnosis, a change in disease management occurred in 76% of patients.

Conclusion

In this cohort, the highest yields of NGS based evaluation for IEI early in the diagnostic trajectory were found in pediatric patients, and in the disease categories immune dysregulation and phagocyte diseases. In cases where a definitive diagnosis was made, this led to important disease management implications in a large majority of patients. More research is needed to establish a uniform diagnostic pathway for cases with inconclusive diagnoses, including variants of unknown significance.
Chitosan Protects Immunosuppressed Mice Against Cryptosporidium parvum Infection Through TLR4/STAT1 Signaling Pathways and Gut Microbiota Modulation
Authors: Rahman Sajid Ur , Gong Haiyan , Mi Rongsheng , Huang Yan , Han Xiangan , Chen Zhaoguo
Published: January 2022

Cryptosporidium parvum infection is very common in infants, immunocompromised patients, or in young ruminants, and chitosan supplementation exhibits beneficial effects against the infection caused by C. parvum. This study investigated whether chitosan supplementation modulates the gut microbiota and mediates the TLR4/STAT1 signaling pathways and related cytokines to attenuate C. parvum infection in immunosuppressed mice. Immunosuppressed C57BL/6 mice were divided into five treatment groups. The unchallenged mice received a basal diet (control), and three groups of mice challenged with 1 × 106 C. parvum received a basal diet, a diet supplemented with 50 mg/kg/day paromomycin, and 1 mg/kg/day chitosan, and unchallenged mice treated with 1 mg/kg/day chitosan. Chitosan supplementation regulated serum biochemical indices and significantly (p < 0.01) reduced C. parvum oocyst excretion in infected mice treated with chitosan compared with the infected mice that received no treatment. Chitosan-fed infected mice showed significantly (p < 0.01) decreased mRNA expression levels of interferon-gamma (IFN-γ) and tumor necrosis factor-α (TNF-α) compared to infected mice that received no treatment. Chitosan significantly inhibited TLR4 and upregulated STAT1 protein expression (p < 0.01) in C. parvum-infected mice. 16S rRNA sequencing analysis revealed that chitosan supplementation increased the relative abundance of Bacteroidetes/Bacteroides, while that of Proteobacteria, Tenericutes, Defferribacteres, and Firmicutes decreased (p < 0.05). Overall, the findings revealed that chitosan supplementation can ameliorate C. parvum infection by remodeling the composition of the gut microbiota of mice, leading to mediated STAT1/TLR4 up- and downregulation and decreased production of IFN-γ and TNF-α, and these changes resulted in better resolution and control of C. parvum infection.
Levels of Breast Milk MicroRNAs and Other Non-Coding RNAs Are Impacted by Milk Maturity and Maternal Diet
Authors: Hicks Steven D. , Confair Alexandra , Warren Kaitlyn , Chandran Desirae
Published: January 2022

There is emerging evidence that non-coding RNAs (ncRNAs) within maternal breast milk (MBM) impart unique metabolic and immunologic effects on developing infants. Most studies examining ncRNAs in MBM have focused on microRNAs. It remains unclear whether microRNA levels are related to other ncRNAs, or whether they are impacted by maternal characteristics. This longitudinal cohort study examined 503 MBM samples from 192 mothers to: 1) identify the most abundant ncRNAs in MBM; 2) examine the impact of milk maturity on ncRNAs; and 3) determine whether maternal characteristics affect ncRNAs. MBM was collected at 0, 1, and 4 months post-delivery. High throughput sequencing quantified ncRNAs within the lipid fraction. There were 3069 ncRNAs and 238 microRNAs with consistent MBM presence (≥10 reads in ≥10% samples). Levels of 17 ncRNAs and 11 microRNAs accounted for 80% of the total RNA content. Most abundant microRNAs displayed relationships ([R]>0.2, adj p< 0.05) with abundant ncRNAs. A large proportion of ncRNAs (1269/3069; 41%) and microRNAs (206/238; 86%) were affected by MBM maturity. The majority of microRNAs (111/206; 54%) increased from 0-4 months. Few ncRNAs and microRNAs were affected (adj p < 0.05) by maternal age, race, parity, body mass index, gestational diabetes, or collection time. However, nearly half of abundant microRNAs (4/11) were impacted by diet. To our knowledge this is the largest study of MBM ncRNAs, and the first to demonstrate a relationship between MBM microRNAs and maternal diet. Such knowledge could guide nutritional interventions aimed at optimizing metabolic and immunologic microRNA profiles within MBM.
In Silico Studies on Psilocybin Drug Derivatives Against SARS-CoV-2 and Cytokine Storm of Human Interleukin-6 Receptor
Authors: Khan Faez Iqbal , Hassan Fakhrul , Lai Dakun
Published: January 2022

Various metabolites identified with therapeutic mushrooms have been found from different sources and are known to have antibacterial, antiviral, and anticancer properties. Over thousands soil growth-based mushroom metabolites have been discovered, and utilized worldwide to combat malignancy. In this study, psilocybin-mushroom that contains the psychedelic compounds such as psilacetin, psilocin, and psilocybine were screened and found to be inhibitors of SARS-CoV-2 Mprotease. It has been found that psilacetin, psilocin, and psilocybine bind to Mprotease with −6.0, −5.4, and −5.8 kcal/mol, respectively. Additionally, the psilacetin was found to inhibit human interleukin-6 receptors to reduce cytokine storm. The binding of psilacetin to Mprotease of SARS-CoV-2 and human interleukin-6 receptors changes the structural dynamics and Gibbs free energy patterns of proteins. These results suggested that psilocybin-mushroom could be utilized as viable potential chemotherapeutic agents for SARS-CoV-2.
Neoadjuvant PD-1 Blockade Combined With Chemotherapy Followed by Concurrent Immunoradiotherapy in Locally Advanced Anal Canal Squamous Cell Carcinoma Patients: Antitumor Efficacy, Safety and Biomarker Analysis
Authors: Xiao WeiWei , Yuan Yan , Wang SuiHai , Liao Zhidong , Cai PeiQiang , Chen BaoQing , Zhang Rong , Wang Fang , Zeng ZhiFan , Gao YuanHong
Published: January 2022

Background

Anal canal squamous cell carcinoma (ACSCC) is an exceedingly rare malignant neoplasm with challenges in sphincter preservation, treatment toxicities and long-term survival. Little is known concerning the activity of PD-1 antibodies in locally advanced ACSCC. This study reports on the efficacy and toxicities of a neoadjuvant PD-1 blockade combined with chemotherapy followed by concurrent immunoradiotherapy in ACSCC patients, and describes biomarkers expression and mutation signatures.

Methods

In this cohort study, patients were treated as planned, including four cycles of neoadjuvant PD-1 antibody toripalimab combined with docetaxol and cisplatin, followed by radiotherapy and two cycles of concurrent toripalimab. Multiplex immunofluorescence staining (mIHC) with PD-L1, CD8, CD163, Pan-Keratin and DAPI was performed with the pretreatment tumor tissue. Whole exome sequencing was performed for the primary tumor and peripheral blood mononuclear cells. The primary endpoint was the complete clinical response (cCR) rate at 3 months after overall treatment. Acute and late toxicities graded were assessed prospectively.

Results

Five female patients with a median age of 50 years old (range, 43-65 years old), finished treatment as planned. One patient had grade 3 immune related dermatitis. Two patients had grade 3 myelosuppression during neoadjuvant treatment. No severe radiation-related toxicities were noted. Four patients with PD-L1 expression >1% achieved a cCR after neoadjuvant treatment. and the other patient with negative PD-L1 expression also achieved a cCR at 3 months after radiotherapy. All the patients were alive and free from disease and had a normal quality of life, with 19.6-24 months follow up. Inconsistent expression of PD-L1 and CD163 was detected in 3 and 5 patients, respectively. TTN, POLE, MGAM2 were the top mutation frequencies, and 80 significant driver genes were identified. Pathway analysis showed enrichment of apoptosis, Rap1, Ras, and pathways in cancer signaling pathways. Eight significantly deleted regions were identified.

Conclusions

This small cohort of locally advanced ACSCC patients had quite satisfactory cCR and sphincter preservation rate, after neoadjuvant PD-1 antibody toripalimab combined with chemotherapy followed by concurrent immunoradiotherapy, with mild acute and long-term toxicities.
Mitochondrial Dysfunction Associates With Acute T Lymphocytopenia and Impaired Functionality in COVID-19 Patients
Authors: Mo Yufei , To Kelvin Kai-Wang , Zhou Runhong , Liu Li , Cao Tianyu , Huang Haode , Du Zhenglong , Lim Chun Yu Hubert , Yim Lok-Yan , Luk Tsz-Yat , Chan Jacky Man-Chun , Chik Thomas Shiu-Hong , Lau Daphne Pui-Ling , Tsang Owen Tak-Yin , Tam Anthony Raymond , Hung Ivan Fan-Ngai , Yuen Kwok-Yung , Chen Zhiwei
Published: January 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in rapid T lymphocytopenia and functional impairment of T cells. The underlying mechanism, however, remains incompletely understood. In this study, we focused on characterizing the phenotype and kinetics of T-cell subsets with mitochondrial dysfunction (MD) by multicolor flow cytometry and investigating the association between MD and T-cell functionality. While 73.9% of study subjects displayed clinical lymphocytopenia upon hospital admission, a significant reduction of CD4 or CD8 T-cell frequency was found in all asymptomatic, symptomatic, and convalescent cases. CD4 and CD8 T cells with increased MD were found in both asymptomatic and symptomatic patients within the first week of symptom onset. Lower proportion of memory CD8 T cell with MD was found in severe patients than in mild ones at the stage of disease progression. Critically, the frequency of T cells with MD in symptomatic patients was preferentially associated with CD4 T-cell loss and CD8 T-cell hyperactivation, respectively. Patients bearing effector memory CD4 and CD8 T cells with the phenotype of high MD exhibited poorer T-cell responses upon either phorbol 12-myristate-13-acetate (PMA)/ionomycin or SARS-CoV-2 peptide stimulation than those with low MD. Our findings demonstrated an MD-associated mechanism underlying SARS-CoV-2-induced T lymphocytopenia and functional impairment during the acute phase of infection.
Current Understanding of Exosomal MicroRNAs in Glioma Immune Regulation and Therapeutic Responses
Authors: Peng Jinwu , Liang Qiuju , Xu Zhijie , Cai Yuan , Peng Bi , Li Jianbo , Zhang Wenqin , Kang Fanhua , Hong Qianhui , Yan Yuanliang , Zhang Mingyu
Published: January 2022

Exosomes, the small extracellular vesicles, are released by multiple cell types, including tumor cells, and represent a novel avenue for intercellular communication via transferring diverse biomolecules. Recently, microRNAs (miRNAs) were demonstrated to be enclosed in exosomes and therefore was protected from degradation. Such exosomal miRNAs can be transmitted to recipient cells where they could regulate multiple cancer-associated biological processes. Accumulative evidence suggests that exosomal miRNAs serve essential roles in modifying the glioma immune microenvironment and potentially affecting the malignant behaviors and therapeutic responses. As exosomal miRNAs are detectable in almost all kinds of biofluids and correlated with clinicopathological characteristics of glioma, they might be served as promising biomarkers for gliomas. We reviewed the novel findings regarding the biological functions of exosomal miRNAs during glioma pathogenesis and immune regulation. Furthermore, we elaborated on their potential clinical applications as biomarkers in glioma diagnosis, prognosis and treatment response prediction. Finally, we summarized the accessible databases that can be employed for exosome-associated miRNAs identification and functional exploration of cancers, including glioma.
Gallic Acid Alleviates Gut Dysfunction and Boosts Immune and Antioxidant Activities in Puppies Under Environmental Stress Based on Microbiome–Metabolomics Analysis
Authors: Yang Kang , Deng Xiaolin , Jian Shiyan , Zhang Meiyu , Wen Chaoyu , Xin Zhongquan , Zhang Limeng , Tong Aorigeile , Ye Shibin , Liao Pinfeng , Xiao Zaili , He Shansong , Zhang Fan , Deng Jinping , Zhang Lingna , Deng Baichuan
Published: January 2022

Early-life exposure to environmental stress disrupts the gut barrier and leads to inflammatory responses and changes in gut microbiota composition. Gallic acid (GA), a natural plant polyphenol, has received significant interest for its antioxidant, anti-inflammatory, and antimicrobial properties that support the maintenance of intestinal health. To assess whether dietary supplementation of GA alleviates environmental stress, a total of 19 puppies were randomly allocated to the following three dietary treatments for 2 weeks: 1) basal diet (control (CON)); 2) basal diet + transportation (TS); and 3) basal diet with the addition of 500 mg/kg of GA + transportation (TS+GA). After a 1-week supplementation period, puppies in the TS and TS+GA groups were transported from a stressful environment to another livable location, and puppies in the CON group were then left in the stressful environment. Results indicated that GA markedly reduced the diarrhea rate in puppies throughout the trial period and caused a moderate decline of serum cortisol and HSP-70 levels after transportation. Also, GA alleviated the oxidative stress and inflammatory response caused by multiple environmental stressors. Meanwhile, puppies fed GA had a higher abundance of fecal Firmicutes and Lactobacillus and lower Proteobacteria, Escherichia–Shigella, and Clostridium_sensu_stricto_1 after transportation. As a result, the TS+GA group had the highest total short-chain fatty acids and acetic acid. Also, the fecal and serum metabolomics analyses revealed that GA markedly reversed the abnormalities of amino acid metabolism, lipid metabolism, carbohydrate metabolism, and nucleotide metabolism caused by stresses. Finally, Spearman’s correlation analysis was carried out to explore the comprehensive microbiota and metabolite relationships. Overall, dietary supplementation of GA alleviates oxidative stress and inflammatory response in stressed puppies by causing beneficial shifts on gut microbiota and metabolites that may support gut and host health.
Microbiome Development of Seawater-Incubated Pre-production Plastic Pellets Reveals Distinct and Predictive Community Compositions
Authors: Ward Christopher S. , Diana Zoie , Ke Kate Meicong , Orihuela Beatriz , Schultz Thomas P. , Rittschof Daniel
Published: January 2022

Plastics of various chemistries pollute global water bodies. Toxic chemicals leach with detrimental and often unpredictable impacts on the surrounding ecosystems. We found that seawater leachates of plastic pre-production pellets from 7 recycle categories are acutely toxic to stage II barnacle nauplii; lethal concentration 50 (LC50s) were observed in 24-h leachates from dilutions ranging from 0.007 to 2.1 mg/mL of seawater. Based on previous observations that macro-organismal settlement on fouling management coatings of various toxicities can be used to predict the toxicity of the coating, we hypothesized that interaction of plastic pre-production pellets with emerging microbiomes would exhibit patterns indicative of the chemistry at the pellet surface. We used amplicon sequencing of bacterial 16S ribosomal RNA genes to characterize the microbiomes that developed from 8 through 70 days on pellets exposed to the same flowing ambient seawater. Diversity and composition of the microbiomes colonizing plastic pellets changed over time and varied with plastic type. Microbial taxa belong to taxonomic groups known to consume hydrocarbons, to be prevalent following marine oil spills, or to live on fouling management surfaces. Microbiomes were still distinct between plastic types at Day 70, suggesting that differences in the physicochemical characteristics of the underlying plastics continue to exert variable selection of surface microbial communities. A random forest-based sample classifier correctly predicted 93% of plastic types using microbiome compositions. Surface microbiomes have promise for use in forensically identifying plastic types and potential toxicities.
Review on Applications of Lignin in Pavement Engineering: A Recent Survey
Authors: Yao Hui , Wang Yiran , Liu Junfu , Xu Mei , Ma Pengrui , Ji Jie , You Zhanping
Published: January 2022

Lignin is the second-largest plant polymer on Earth after cellulose. About 98% of lignin produced in the papermaking and pulping industry is used for combustion heating or power generation. Less than 2% of lignin is used in more valuable fields, mainly in the formulation of dispersants, adhesives, and surfactants. Asphalt is one of the most important materials in pavement engineering. It is a dark brown complex mixture composed of hydrocarbons with different molecular weights and their non-metallic derivatives. Because the chemical structure of lignin is similar to that of asphalt, it is a carbon-based hydrocarbon material. More researchers studied the application of lignin in pavement engineering. In this paper, the structure, application, and extraction technology of lignin were summarized. This is a review article describing the different applications of lignin in pavement engineering and exploring the prospects of the application. There are three main types of pavement materials that can be used for lignin in pavement engineering, which are asphalt, asphalt mixture, and roadbed soil. In asphalt, lignin can be used as a modifier, extender, emulsifier, antioxidant, and coupling agent. In asphalt mixtures, lignin can be used as an additive. In road base soils, lignin can be used as a soil stabilizer. Furthermore, the article analyzed the application effects of lignin from the life cycle assessment. The conclusions suggest that lignin-modified asphalt exhibits more viscosity and hardness, and its high-temperature resistance and rutting resistance can be significantly improved compared with conventional asphalt. In addition, some lignin-modified asphalt binders exhibit reduced low-temperature crack resistance and fatigue resistance, which can be adjusted and selected according to the climate change in different regions. The performance of lignin as an asphalt mixture additive and asphalt extender has been proved to be feasible. Lignin can also produce good mechanical properties as well as environmental benefits as a soil stabilizer. In summary, lignin plays an important role in asphalt pavement and roadbed soil, and it is likely to be a development trend in the future due to its environmental friendliness and low cost. More research is needed to generalize the application of lignin in pavement engineering.
Potential Association Between Changes in Microbiota Level and Lung Diseases: A Meta-Analysis
Authors: Chai Lan , Wang Qi , Si Caijuan , Gao Wenyan , Zhang Lun
Published: January 2022

Objective:

Lung microbiota is increasingly implicated in multiple types of respiratory diseases. However, no study has drawn a consistent conclusion regarding the relationship between changes in the microbial community and lung diseases. This study verifies the association between microbiota level and lung diseases by performing a meta-analysis.

Methods:

Literature databases, including PubMed, ISI Web of Science, Embase, Google Scholar, PMC, and CNKI, were used to collect related articles published before March 20, 2021. The standard mean deviation (SMD) and related 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup, sensitivity, and publication bias analyses were also conducted.

Results:

Six studies, comprising 695 patients with lung diseases and 176 healthy individuals, were included in this meta-analysis. The results indicated that the microbiota level was higher in patients with lung diseases than in healthy individuals (SMD = 0.39, 95% CI = 0.22–0.55, I2 = 91.5%, P < 0.01). Subgroup analysis based on country demonstrated that the microbiota level was significantly higher in Chinese (SMD = 1.90, 95% CI = 0.87–2.93, I2 = 62.3%, P < 0.01) and Korean (SMD = 0.24, 95% CI = 0.13–0.35, I2 = 78.7%, P < 0.01) patients with lung diseases. The microbiota level of patients with idiopathic pulmonary fibrosis (IPF) (SMD = 1.40, 95% CI = 0.42–2.38, I2 = 97.3%, P = 0.005), chronic obstructive pulmonary disease (COPD) (SMD = 0.30, 95% CI = 0.09–0.50, I2 = 83.9%, P = 0.004), and asthma (SMD = 0.19, 95% CI = 0.06–0.32, I2 = 69.4%, P = 0.004) were significantly higher than those of the healthy group, whereas a lower microbiota level was found in patients with chronic hypersensitivity pneumonitis (CHP). The microbiota level significantly increased when the disease sample size was >50. Subgroup analysis based on different microbiota genera, indicated that Acinetobacter baumannii and Pseudomonas aeruginosa were significantly increased in COPD and asthma diseases.

Conclusion:

We observed that patients with IPF, COPD, and asthma had a higher microbiota level, whereas patients with CHP had a lower microbiota level compared to the healthy individuals. The level of A. baumannii and P. aeruginosa were significantly higher in patients with COPD and asthma, and thus represented as potential microbiota markers in the diagnosis and treatment of lung diseases.
Patient Survival Between Hemodialysis and Peritoneal Dialysis Among End-Stage Renal Disease Patients Secondary to Myeloperoxidase-ANCA-Associated Vasculitis
Authors: Wu Xueqin , Zhong Yong , Meng Ting , Ooi Joshua Daniel , Eggenhuizen Peter J. , Tang Rong , Nie Wannian , Xiao Xiangcheng , Sun Jian , Ao Xiang , Zhang Hao
Published: January 2022

Background

A significant proportion of anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis eventually progresses to end-stage renal disease (ESRD) thus requiring long-term dialysis. There is no consensus about which dialysis modality is more recommended for those patients with associated vasculitis (AAV-ESRD). The primary objective of this study was to compare patient survival in patients with AAV-ESRD treated with hemodialysis (HD) or peritoneal dialysis (PD).

Methods

This double-center retrospective cohort study included dialysis-dependent patients who were treated with HD or PD. Clinical data were collected under standard format. The Birmingham vasculitis activity score (BVAS) was used to evaluate disease activity at diagnosis and organ damage was assessed using the vasculitis damage index (VDI) at dialysis initiation.

Results

In total, 85 patients were included: 64 with hemodialysis and 21 with peritoneal dialysis. The patients with AAV-PD were much younger than the AAV-HD patients (48 vs. 62, P < 0.01) and more were female (76.2 vs. 51.6%, P = 0.05). The laboratory data were almost similar. The comorbidities, VDI score, and immuno-suppressive therapy at dialysis initiation were almost no statistical difference. Patient survival rates between HD and PD at 1 year were 65.3 vs. 90% (P = 0.062), 3 year were 59.6 vs. 90% (P < 0.001), and 5 years were 59.6 vs. 67.5% (P = 0.569). The overall survival was no significant difference between the two groups (P = 0.086) and the dialysis modality (HD or PD) was not shown to be an independent predictor for all-cause death (hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.31–1.7; P = 0.473). Cardio-cerebrovascular events were the main cause of death among AAV-HD patients while infection in patients with AAV-PD.

Conclusion

These results provide real-world data that the use of either hemodialysis or peritoneal dialysis modality does not affect patient survival for patients with AAV-ESRD who need long-term dialysis.
Liquid Biopsy as a Prognostic and Theranostic Tool for the Management of Pancreatic Ductal Adenocarcinoma
Authors: Osei-Bordom Daniel C. , Sachdeva Gagandeep , Christou Niki
Published: January 2022

Pancreatic ductal adenocarcinomas (PDAC) represent one of the deadliest cancers worldwide. Survival is still low due to diagnosis at an advanced stage and resistance to treatment. Herein, we review the main types of liquid biopsy able to help in both prognosis and adaptation of treatments.
Medication Errors in Pediatrics: Proposals to Improve the Quality and Safety of Care Through Clinical Risk Management
Authors: D'Errico Stefano , Zanon Martina , Radaelli Davide , Padovano Martina , Santurro Alessandro , Scopetti Matteo , Frati Paola , Fineschi Vittorio
Published: January 2022

Medication errors represent one of the most common causes of adverse events in pediatrics and are widely reported in the literature. Despite the awareness that children are at increased risk for medication errors, little is known about the real incidence of the phenomenon. Most studies have focused on prescription, although medication errors also include transcription, dispensing, dosage, administration, and certification errors. Known risk factors for therapeutic errors include parenteral infusions, oral fluid administration, and tablet splitting, as well as the off-label use of drugs with dosages taken from adult literature. Emergency Departments and Intensive Care Units constitute the care areas mainly affected by the phenomenon in the hospital setting. The present paper aims to identify the risk profiles in pediatric therapy to outline adequate preventive strategies. Precisely, through the analysis of the available evidence, solutions such as standardization of recommended doses for children, electronic prescribing, targeted training of healthcare professionals, and implementation of reporting systems will be indicated for the prevention of medication errors.
Gut Microbiome in Retina Health: The Crucial Role of the Gut-Retina Axis
Authors: Scuderi Gianluca , Troiani Emidio , Minnella Angelo Maria
Published: January 2022

The term microbiome means not only a complex ecosystem of microbial species that colonize our body but also their genome and the surrounding environment in which they live. Recent studies support the existence of a gut-retina axis involved in the pathogenesis of several chronic progressive ocular diseases, including age-related macular disorders. This review aims to underline the importance of the gut microbiome in relation to ocular health. After briefly introducing the characteristics of the gut microbiome in terms of composition and functions, the role of gut microbiome dysbiosis, in the development or progression of retinal diseases, is highlighted, focusing on the relationship between gut microbiome composition and retinal health based on the recently investigated gut-retina axis.
Fatal Pneumonia Associated With a Novel Genotype of Human Coronavirus OC43
Authors: Lau Susanna Kar Pui , Li Kenneth Sze Ming , Li Xin , Tsang Ka-Yan , Sridhar Siddharth , Woo Patrick Chiu Yat
Published: January 2022

Since its first discovery in 1967, human coronavirus OC43 (HCoV-OC43) has been associated with mild self-limiting upper respiratory infections worldwide. Fatal primary pneumonia due to HCoV-OC43 is not frequently described. This study describes a case of fatal primary pneumonia associated with HCoV-OC43 in a 75-year-old patient with good past health. The viral loads of the respiratory tract specimens (bronchoalveolar lavage and endotracheal aspirate) from diagnosis to death were persistently high (3.49 × 106–1.10 × 1010 copies/ml). HCoV-OC43 at a 6.46 × 103 copies/ml level was also detected from his pleural fluid 2 days before his death. Complete genome sequencing and phylogenetic analysis showed that the present HCoV-OC43 forms a distinct cluster with three other HCoV-OC43 from United States, with a bootstrap value of 100% and sharing 99.9% nucleotide identities. Pairwise genetic distance between this cluster and other HCoV-OC43 genotypes ranged from 0.27 ± 0.02% to 1.25 ± 0.01%. In contrast, the lowest pairwise genetic distance between existing HCoV-OC43 genotypes was 0.26 ± 0.02%, suggesting that this cluster constitutes a novel HCoV-OC43 genotype, which we named genotype I. Unlike genotypes D, E, F, G, and H, no recombination event was observed for this novel genotype. Structural modeling revealed that the loop with the S1/S2 cleavage site was four amino acids longer than other HCoV-OC43, making it more exposed and accessible to protease, which may have resulted in its possible hypervirulence.
Exploiting Beneficial Pseudomonas spp. for Cannabis Production
Authors: Balthazar Carole , Joly David L. , Filion Martin
Published: January 2022

Among the oldest domesticated crops, cannabis plants (Cannabis sativa L., marijuana and hemp) have been used to produce food, fiber, and drugs for thousands of years. With the ongoing legalization of cannabis in several jurisdictions worldwide, a new high-value market is emerging for the supply of marijuana and hemp products. This creates unprecedented challenges to achieve better yields and environmental sustainability, while lowering production costs. In this review, we discuss the opportunities and challenges pertaining to the use of beneficial Pseudomonas spp. bacteria as crop inoculants to improve productivity. The prevalence and diversity of naturally occurring Pseudomonas strains within the cannabis microbiome is overviewed, followed by their potential mechanisms involved in plant growth promotion and tolerance to abiotic and biotic stresses. Emphasis is placed on specific aspects relevant for hemp and marijuana crops in various production systems. Finally, factors likely to influence inoculant efficacy are provided, along with strategies to identify promising strains, overcome commercialization bottlenecks, and design adapted formulations. This work aims at supporting the development of the cannabis industry in a sustainable way, by exploiting the many beneficial attributes of Pseudomonas spp.
Structure Determination of Microtubules and Pili: Past, Present, and Future Directions
Authors: Garnett James A. , Atherton Joseph
Published: January 2022

Historically proteins that form highly polymeric and filamentous assemblies have been notoriously difficult to study using high resolution structural techniques. This has been due to several factors that include structural heterogeneity, their large molecular mass, and available yields. However, over the past decade we are now seeing a major shift towards atomic resolution insight and the study of more complex heterogenous samples and in situ/ex vivo examination of multi-subunit complexes. Although supported by developments in solid state nuclear magnetic resonance spectroscopy (ssNMR) and computational approaches, this has primarily been due to advances in cryogenic electron microscopy (cryo-EM). The study of eukaryotic microtubules and bacterial pili are good examples, and in this review, we will give an overview of the technical innovations that have enabled this transition and highlight the advancements that have been made for these two systems. Looking to the future we will also describe systems that remain difficult to study and where further technical breakthroughs are required.
Low-Frequency vs. Theta Burst Transcranial Magnetic Stimulation for the Treatment of Chronic Non-fluent Aphasia in Stroke: A Proof-of-Concept Study
Authors: Chou Ting-Yu , Wang Jia-Chi , Lin Mu-Yun , Tsai Po-Yi
Published: January 2022

Background

Although low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) has shown promise in the treatment of poststroke aphasia, the efficacy of high-frequency rTMS (HF-rTMS) has yet to be determined.

Purpose

We investigated the efficacy of intermittent theta burst stimulation (iTBS) in ameliorating chronic non-fluent aphasia and compared it with that of LF-rTMS.

Methods

We randomly assigned patients with poststroke non-fluent aphasia to an ipsilesional iTBS (n = 29), contralesional 1-Hz rTMS (n = 27), or sham (n = 29) group. Each group received the rTMS protocol executed in 10 daily sessions over 2 weeks. We evaluated language function before and after the intervention by using the Concise Chinese Aphasia Test (CCAT).

Results

Compared with the sham group, the iTBS group exhibited significant improvements in conversation, description, and expression scores (P = 0.0004–0.031), which characterize verbal production, as well as in auditory comprehension, reading comprehension, and matching scores (P < 0.01), which characterize language perception. The 1-Hz group exhibited superior improvements in expression, reading comprehension, and imitation writing scores compared with the sham group (P < 0.05). The iTBS group had significantly superior results in CCAT total score, matching and auditory comprehension (P < 0.05) relative to the 1-Hz group.

Conclusion

Our study findings contribute to a growing body of evidence that ipsilesional iTBS enhances the language recovery of patients with non-fluent aphasia after a chronic stroke. Auditory comprehension was more preferentially enhanced by iTBS compared with the 1-Hz protocol. Our findings highlight the importance of ipsilesional modulation through excitatory rTMS for the recovery of non-fluent aphasia in patients with chronic stroke.

Clinical Trial Registration:

[www.ClinicalTrials.gov], identifier [NCT03059225].
Relationship Between the Pyroptosis Pathway and Epilepsy: A Bioinformatic Analysis
Authors: Xia Lu , Liu Lu , Wang Qiang , Ding Jing , Wang Xin
Published: January 2022

Purpose

This study aimed to analyse the correlation between the pyroptosis pathway and epilepsy using bioinformatics analysis technology. We analyzed the expression of gasdermin D (GSDMD) and gasdermin E (GSDME), the key molecules of pyroptosis, in kainic acid-induced epileptic mice.

Methods

Weighted gene co-expression network analysis (WGCNA) was used to construct a signed co-expression network from expression data to screen gene sets closely related to epilepsy. The correlation between the module and epilepsy was verified through module conservative analysis, gene ontology (GO) annotation analysis, and correlation analysis with known epilepsy genes. We obtained currently recognized pyroptosis-related molecules through literature review, and correlation analysis was used to evaluate their correlation with epilepsy. Differentially expressed gene (DEG) analysis was used to analyse expression changes of pyroptosis-related molecules at the transcriptome level, compared to the sham group. We subsequently established a kainic acid-induced status epilepticus (SE) model in mice and validated the mRNA and protein expression of GSDMD and GSDME, the key molecules of pyroptosis, by quantitative reverse transcription PCR (qRT-PCR) and western blotting (WB).

Results

Using WGCNA, module conservative analysis, and correlation analysis with known epilepsy genes, we screened out a module (a gene set of interest) closely related to epilepsy that was prominently enriched in immune and inflammatory-related biological processes. Correlation analysis results suggest that pyroptosis-related molecules are closely related to this module, but have no obvious correlation with others. DEG analysis of molecules associated with pyroptosis suggests that most of the pyroptosis-related molecules had significantly increased expression after SE, such as IL1b, Casp1, Casp4, Pycard, Gsdmd, Nlrp3, Aim2, Mefv, Tlr2, Tlr3, and Tlr4. qRT-PCR and WB analysis confirmed that the mRNA and protein levels of GSDMD in the mouse hippocampus were significantly upregulated after SE. The mRNA expression of GSDME was not different between the epilepsy group and sham group. However, the WB results showed that the expression of full-length GSDME was decreased and GSDME-N-terminus were significantly increased after SE.

Conclusions

Our study highlights that the pyroptosis pathway may be closely related to epilepsy. GSDMD and GSDME, the key executive molecules of pyroptosis, will help to understand the pathogenesis of epilepsy and aid in discovering new targets for anti-epileptic drug treatments.