bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishment and Validation of a Genetic Label Associated With M2 Macrophage Infiltration to Predict Survival in Patients With Colon Cancer and to Assist in Immunotherapy
Authors: Xu Boyang , Peng Ziqi , Yan Guanyu , Wang Ningning , Chen Moye , Yao Xue , Sun Mingjun , An Yue
Published: September 2021

Background

Colon cancer is a malignant tumor with high morbidity and mortality. Researchers have tried to interpret it from different perspectives and divided it into different subtypes to facilitate individualized treatment. With the rise in the use of immunotherapy, its value in the field of tumor has begun to emerge. From the perspective of immune infiltration, this study classified colon cancer according to the infiltration of M2 macrophages in patients with colon cancer and further explored the same.

Methods

Cibersort algorithm was used to analyze the level of immune cell infiltration in patients with colon cancer in The Cancer Genome Atlas (TCGA) database. Weighted gene co-expression network analysis (WGCNA), Consensus Clustering analysis, Lasso analysis, and univariate Kaplan–Meier analysis were used to screen and verify the hub genes associated with M2 macrophages. Principal component analysis (PCA) was used to establish the M2 macrophage-related score (M2I Score). The correlation between M2I Score and somatic cell variation and microsatellite instability (MSI) were analyzed. Furthermore, the correlation between M2 macrophage score and differences in immunotherapy sensitivity was also explored.

Results

M2 macrophage infiltration was associated with poor prognosis. Four hub genes (ANKS4B, CTSD, TIMP1, and ZNF703) were identified as the progression-related genes associated with M2 macrophages. A stable and accurate M2I Score for M2 macrophages used in colon adenocarcinoma was determined based on four hub genes. The M2I Score was positively correlated with the tumor mutation load (TMB). The M2I Score of the group with high instability of microsatellites was higher than that of the group with low instability of microsatellites and microsatellite-stable group. Combined with the Cancer Immunome Atlas database, we concluded that patients with high M2I Scores were more sensitive to programmed cell death protein 1 (PD-1) inhibitors and PD-1 inhibitors combined with cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitors. The low-rating group may have better efficacy without immune checkpoint inhibitors or with CTLA4 inhibitors alone.

Conclusion

Four prognostic hub genes associated with M2 macrophages were screened to establish the M2I Score. Patients were divided into two subgroups: high M2I Score group and low M2I Score group. TMB, MSI, and sensitivity to immunotherapy were higher in the high-rated group. PD-1 inhibitors or PD-1 combined with CTLA-4 inhibitors are preferred for patients in the high-rated group who are more sensitive to immunotherapy.
Established and Emerging Regulatory Roles of Eukaryotic Translation Initiation Factor 5B (eIF5B)
Authors: Chukka Prakash Amruth Raj , Wetmore Stacey D. , Thakor Nehal
Published: September 2021

Translational control (TC) is one the crucial steps that dictate gene expression and alter the outcome of physiological process like programmed cell death, metabolism, and proliferation in a eukaryotic cell. TC occurs mainly at the translation initiation stage. The initiation factor eIF5B tightly regulates global translation initiation and facilitates the expression of a subset of proteins involved in proliferation, inhibition of apoptosis, and immunosuppression under stress conditions. eIF5B enhances the expression of these survival proteins to allow cancer cells to metastasize and resist chemotherapy. Using eIF5B as a biomarker or drug target could help with diagnosis and improved prognosis, respectively. To achieve these goals, it is crucial to understand the role of eIF5B in translational regulation. This review recapitulates eIF5B’s regulatory roles in the translation initiation of viral mRNA as well as the cellular mRNAs in cancer and stressed eukaryotic cells.
The Immune Landscape of Chinese Head and Neck Adenoid Cystic Carcinoma and Clinical Implication
Authors: Dou Shengjin , Li Rongrong , He Ning , Zhang Menghuan , Jiang Wen , Ye Lulu , Yang Yining , Zhao Guodong , Yang Yadong , Li Jiang , Chen Di , Zhu Guopei
Published: September 2021

Novel systemic agents and effective treatment strategies for recurrence adenoid cystic carcinoma (ACC) of the head and neck are still worthy of further exploration. Here, we analyzed the mutations and expression profiles of 75 Chinese ACC patients, characterized the prognostic value of the immune signature for recurrence or distant metastasis, and explored the potential of immunotherapeutic biomarkers in ACC. In general, MYB fusion and somatic mutations accounted for a high proportion, which was 46.7% (35/75). ACCs displayed an overall low mutation burden and lack of programmed cell death ligand-1 (PD-L1) expression. The antigen-presenting machinery (APM) expression score and immune infiltration score (IIS) were the lowest among ACC patients, compared with other cancer types. For 61 primary cases, the locoregional recurrence-free survival (LRRFS) was statistically significantly correlated with the IIS [univariate analysis; hazard ratio (HR) = 0.32; 95% CI, 0.11–0.92; p = 0.035] and T-cell infiltration score (TIS) (univariate analysis; HR = 0.33; 95% CI, 0.12–0.94; p = 0.037]. Patients with lower IIS (log-rank p = 0.0079) or TIS (log-rank p = 0.0079) had shorter LRRFS. Additionally, solid pattern was also a prognostic factor related to locoregional recurrence, whereas postoperative radiotherapy (PORT) exerted its beneficial effects. We further evaluated the pretreatment immune profile of five ACC patients treated with PD-1 inhibitors. Patients who responded to camrelizumab or pembrolizumab observed elevated APM and TIS, compared with patients with progressive disease. Our study highlights the immune infiltration pattern and messenger RNA (mRNA) signatures of Chinese ACC patients, which has the potential value for prognosis and immunotherapy.
Prevention of Diabetes-Associated Cognitive Dysfunction Through Oral Administration of Lipopolysaccharide Derived From Pantoea agglomerans
Authors: Mizobuchi Haruka , Yamamoto Kazushi , Yamashita Masashi , Nakata Yoko , Inagawa Hiroyuki , Kohchi Chie , Soma Gen-Ichiro
Published: September 2021

Diabetes-related cognitive dysfunction (DRCD) is a serious complication induced by diabetes. However, there are currently no specific remedies for DRCD. Here, we show that streptozotocin-induced DRCD can be prevented without causing side effects through oral administration of lipopolysaccharide (LPS) derived from Pantoea agglomerans. Oral administration of LPS (OAL) prevented the cerebral cortex atrophy and tau phosphorylation induced by DRCD. Moreover, we observed that neuroprotective transformation of microglia (brain tissue-resident macrophages) is important for preventing DRCD through OAL. These findings are contrary to the general recognition of LPS as an inflammatory agent when injected systemically. Furthermore, our results strongly suggest that OAL promotes membrane-bound colony stimulating factor 1 (CSF1) expression on peripheral leukocytes, which activates the CSF1 receptor on microglia, leading to their transformation to the neuroprotective phenotype. Taken together, the present study indicates that controlling innate immune modulation through the simple and safe strategy of OAL can be an innovative prophylaxis for intractable neurological diseases such as DRCD. In a sense, for modern people living in an LPS-depleted environment, OAL is like a time machine that returns microglia to the good old LPS-abundant era.
Infants Younger Than 90 Days Admitted for Late-Onset Sepsis Display a Reduced Abundance of Regulatory T Cells
Authors: Fortmann Ingmar , Dammann Marie-Theres , Siller Bastian , Humberg Alexander , Demmert Martin , Tüshaus Ludger , Lindert Judith , van Zandbergen Vera , Pagel Julia , Rupp Jan , Herting Egbert , Härtel Christoph
Published: September 2021

Objective

To provide epidemiological data of infants < 90 days of age with suspected late-onset sepsis (LOS) and evaluate distinct immunological specificities. We hypothesized that previously healthy infants < 3 months of age with sepsis have a yet undefined immunological predisposition; e.g. differences in lymphocyte subsets including regulatory T cells.

Methods

We performed an exploratory, single center study between January 1st, 2019 and June 1st, 2021. Routine diagnostics included conventional culture (blood, cerebrospinal fluid, urine), PCR and inflammatory markers in infants < 90 days of age with suspected sepsis. We additionally analyzed lymphocyte subsets and CD4+ CD25+ forkhead box protein (FoxP3)+ Tregs at admission for sepsis workup as compared to age-matched controls.

Results

A convenience sample cohort of n= 51 infants with sepsis workup was enrolled. Invasive bacterial infection (IBI) was diagnosed in 25 (49.0%) patients including two infants with a rhinovirus co-infection and viral infection in 14 (27.5%) neonates. No infectious cause was found in 12 cases. Infants with suspected LOS displayed a decreased abundance of CD4+ FoxP3+ T cells as compared to controls, which was most pronounced in the subgroup of infants with IBI. We also noticed elevated HLA-DR-positive CD3+ cells in infants with LOS and a higher CD4/CD8-ratio in infants with viral infection as compared to healthy controls. Infants with viral infections had a higher number of natural killer cells as compared to infants with IBI.

Conclusion

Our exploratory data support the concept of a potential immaturity state and failed immune tolerance development for young infants with LOS. Future large-scale studies are needed to elucidate pre-sepsis conditions and to target the microbiome-immunity interplay as a potential risk pattern.
The Ability of Zika virus Intravenous Immunoglobulin to Protect From or Enhance Zika Virus Disease
Authors: Pinto Amelia K. , Hassert Mariah , Han Xiaobing , Barker Douglas , Carnelley Trevor , Branche Emilie , Steffen Tara L. , Stone E. Taylor , Geerling Elizabeth , Viramontes Karla M. , Nykiforuk Cory , Toth Derek , Shresta Sujan , Kodihalli Shantha , Brien James D.
Published: September 2021

The closely related flaviviruses, dengue and Zika, cause significant human disease throughout the world. While cross-reactive antibodies have been demonstrated to have the capacity to potentiate disease or mediate protection during flavivirus infection, the mechanisms responsible for this dichotomy are still poorly understood. To understand how the human polyclonal antibody response can protect against, and potentiate the disease in the context of dengue and Zika virus infection we used intravenous hyperimmunoglobulin (IVIG) preparations in a mouse model of the disease. Three IVIGs (ZIKV-IG, Control-Ig and Gamunex®) were evaluated for their ability to neutralize and/or enhance Zika, dengue 2 and 3 virusesin vitro. The balance between virus neutralization and enhancement provided by thein vitroneutralization data was used to predict the IVIG concentrations which could protect or enhance Zika, and dengue 2 diseasein vivo. Using this approach, we were able to define the uniquein vivodynamics of complex polyclonal antibodies, allowing for both enhancement and protection from flavivirus infection. Our results provide a novel understanding of how polyclonal antibodies interact with viruses with implications for the use of polyclonal antibody therapeutics and the development and evaluation of the next generation flavivirus vaccines.
Novel Discoveries in Immune Dysregulation in Inborn Errors of Immunity
Authors: Ren Anwen , Yin Wei , Miller Heather , Westerberg Lisa S. , Candotti Fabio , Park Chan-Sik , Lee Pamela , Gong Quan , Chen Yan , Liu Chaohong
Published: September 2021

With the expansion of our knowledge on inborn errors of immunity (IEI), it gradually becomes clear that immune dysregulation plays an important part. In some cases, autoimmunity, hyperinflammation and lymphoproliferation are far more serious than infections. Thus, immune dysregulation has become significant in disease monitoring and treatment. In recent years, the wide application of whole-exome sequencing/whole-genome sequencing has tremendously promoted the discovery and further studies of new IEI. The number of discovered IEI is growing rapidly, followed by numerous studies of their pathogenesis and therapy. In this review, we focus on novel discovered primary immune dysregulation diseases, including deficiency of SLC7A7, CD122, DEF6, FERMT1, TGFB1, RIPK1, CD137, TET2 and SOCS1. We discuss their genetic mutation, symptoms and current therapeutic methods, and point out the gaps in this field.
PD-1 Blockade Restores the Proliferation of Peripheral Blood Lymphocyte and Inhibits Lymphocyte Apoptosis in a BALB/c Mouse Model of CP BVDV Acute Infection
Authors: Liu Yu , Wu Chenhua , Chen Nannan , Li Yang , Fan Chunling , Zhao Shangqi , Bai Tongtong , Zhao Zhibo , Chen Jinwei , Su Siyu , Zhang Zecai , Zhou Yulong , Zhu Zhanbo
Published: September 2021

Acute infection of bovine viral diarrhea virus (BVDV) is associated with immune dysfunction and can cause peripheral blood lymphopenia and lymphocyte apoptosis. Our previous study has confirmed that programmed death-1 (PD-1) blockade inhibits peripheral blood lymphocytes (PBL) apoptosis and restores proliferation and anti-viral immune functions of lymphocytes after BVDV infection in vitro. However, the situation in vivo remains to be further studied and confirmed. Therefore, in this study, we established a BALB/c mouse model of acute BVDV infection with cytopathic (CP) BVDV (strain NADL) and non-cytopathic (NCP) BVDV (strain NY-1). Then, we examined the mRNA and protein levels of PD-1 and programmed death-ligand 1 (PD-L1) in peripheral blood mononuclear cells (PBMC) from BVDV-infected mice and analyzed the effects of PD-1 blockade on the proportions of CD3+, CD4+, and CD8+ T cell subsets, the apoptosis and proliferation of PBL, and the production of IL-2 and IFN-γ. We found that leukopenia, lymphocytopenia, and thrombocytopenia were developed in both CP and NCP BVDV-infected mice at day 7 of post-infection. The mRNA and protein expression of PD-1 and PD-L1 were significantly upregulated in CP and NCP BVDV-infected mice. Moreover, PD-1/PD-L1 upregulation was accompanied by leukopenia and lymphopenia. Additionally, PD-1 blockade inhibited PBL apoptosis and virus replication, restored the proportions of CD3+, CD4+, and CD8+ T cell subsets, and increased IFN-γ production and p-ERK expression in BVDV-infected mice. However, blocking PD-1 did not significantly affect PBL proliferation and IL-2 production in NCP BVDV-infected mice. Our findings further confirmed the immunomodulatory role of PD-1 in peripheral blood lymphocytopenia in vivo and provided a scientific basis for exploring the molecular mechanism of immune dysfunction caused by acute BVDV infection.
IFNβ Is a Potent Adjuvant for Cancer Vaccination Strategies
Authors: Audsley Katherine M. , Wagner Teagan , Ta Clara , Newnes Hannah V. , Buzzai Anthony C. , Barnes Samantha A. , Wylie Ben , Armitage Jesse , Kaisho Tsuneyasu , Bosco Anthony , McDonnell Alison , Cruickshank Mark , Fear Vanessa S. , Foley Bree , Waithman Jason
Published: September 2021

Cancer vaccination drives the generation of anti-tumor T cell immunity and can be enhanced by the inclusion of effective immune adjuvants such as type I interferons (IFNs). Whilst type I IFNs have been shown to promote cross-priming of T cells, the role of individual subtypes remains unclear. Here we systematically compared the capacity of distinct type I IFN subtypes to enhance T cell responses to a whole-cell vaccination strategy in a pre-clinical murine model. We show that vaccination in combination with IFNβ induces significantly greater expansion of tumor-specific CD8+T cells than the other type I IFN subtypes tested. Optimal expansion was dependent on the presence of XCR1+dendritic cells, CD4+T cells, and CD40/CD40L signaling. Therapeutically, vaccination with IFNβ delayed tumor progression when compared to vaccination without IFN. When vaccinated in combination with anti-PD-L1 checkpoint blockade therapy (CPB), the inclusion of IFNβ associated with more mice experiencing complete regression and a trend in increased overall survival. This work demonstrates the potent adjuvant activity of IFNβ, highlighting its potential to enhance cancer vaccination strategies alone and in combination with CPB.
Health Risks and Benefits Among Surfers After Exposure to Seawater in Monterey Bay, Santa Cruz County, California, United States
Authors: O’Halloran Chris , Silver Mary
Published: September 2021

We investigated the health risks and benefits among surfers in Monterey Bay, Santa Cruz County, California, United States after seawater exposure. A total of 47 surfers enrolled and completed an online survey on the effect of the ocean environment on their well-being, physical and mental health, and provided their perspectives on ocean conservation. The majority of the surfers were white males, with a median age of 40 years, and a mean of 21 years surfing experience. Most of the participants spent over 5 h/week in the ocean. The most common health problems reported were adverse effects due to red tide exposure, surfer’s ear, back and neck problems, and allergies. A total of 41% reported upper respiratory symptoms, and 8% of the participants reported gastrointestinal symptoms. All participants reported that the ocean benefited their emotional health, and 45/47 (>96%) reported that the ocean increased their life satisfaction, happiness, and decreased their stress level. All participants reported being engaged in ocean stewardship. This study suggests surfers were significantly more likely to report upper respiratory symptoms when they had experienced adverse health effects while surfing during a “red tide” and during a bloom of the microscopic, single-celled phytoplankter,Akashiwo sanguinea.
Non-uniform Segmental Range of Motion of the Thoracic Spine During Maximal Inspiration and Exhalation in Healthy Subjects
Authors: Burgos Jesús , Barrios Carlos , Mariscal Gonzalo , Lorente Alejandro , Lorente Rafael
Published: September 2021

Background and Objective:To analyse the range of motion of the thoracic spine by radiographically measuring changes in the sagittal profile of different thoracic segments during maximal inspiration and exhalation. The starting hypothesis was that forced deep breathing requires an active, but non-uniform widening of the lordotic–kyphotic range of motion of the different thoracic segments.

Methods:Cross-sectional study. Participants were 40 healthy volunteers aged 21–60. Conventional anteroposterior and functional sagittal chest radiographs were performed during maximal inspiration and exhalation. The range of motion of each spinal thoracic functional segment, global T1–T12 motion, and the sagittal displacement of the thoracic column during breathing were measured. Considering the different type of ribs and their attachment the spine and sternum, thoracic segments were grouped in T1–T7, T7–T10, and T10–T12. The displacement of the thoracic spine with respect to the sternum and manubrium was also recorded.

Results:The mean difference from inspiration to exhalation in the T1–T12 physiologic kyphosis was 15.9° ± 4.6°, reflecting the flexibility of the thoracic spine during deep breathing (30.2%). The range of motion was wider in the caudal hemicurve than in the cranial hemicurve, indicating more flexibility of the caudal component of the thoracic kyphosis. A wide range of motion from inspiration to exhalation was found at T7–T10, responsible for 73% of T1–T12 sagittal movement. When the sample was stratified according to age ranges (20–30, 30–45, and 45–60 yr.), none of the measurements for inspiration or exhalation showed statistically significant differences.

Only changes at this level showed a positive correlation with changes in the global thoracic kyphosis (r= 0.794,p<0.001).

Conclusion:The range of motion of the thoracic spine plays a relevant role in respiration dynamics. Maximal inspiration appears to be highly dependent on the angular movements of the T7–T10 segment.
Real-Life Experience With First-Line Therapy Bortezomib Plus Melphalan and Prednisone in Elderly Patients With Newly Diagnosed Multiple Myeloma Ineligible for High Dose Chemotherapy With Autologous Stem-Cell Transplantation
Authors: Buda Gabriele , Del Giudice Maria Livia , Antonioli Elisabetta , Ghio Francesco , Orciuolo Enrico , Morganti Riccardo , Martini Francesca , Staderini Michela , Galimberti Sara , Petrini Mario
Published: September 2021

Introduction: Currently, the regimen with bortezomib plus melphalan and prednisone (VMP) is a standard treatment for multiple myeloma and it is recommended as the first-line therapy for patients with multiple myeloma (MM) ineligible for high-dose chemotherapy with autologous stem-cell transplantation.

Objectives: Participants of the clinical trial are highly selected populations; therefore, the aim of this study was to present observations from real practice that can provide important information for practitioners and to investigate clinical outcomes of VMP regimen in elderly patients with newly diagnosed MM.

Patients and Methods: We retrospectively analyzed the data on the efficacy and survival parameters, such as overall survival (OS) and event-free survival (EFS), with attention to the effect of gender, age and International Staging System (ISS) stage, of VMP regimen in 164 patients with newly diagnosed MM not eligible for high-dose chemotherapy with autologous stem-cell transplantation (median age, 75 years; range, 60–86 years).

Results: Patients aged 75 years or older constituted 50.6% of the study cohort. Frail patients were 10.36%, according to the clinical frailty scale of geriatric assessment (GA). A total of 1203 courses of VMP regimen (mainly VMP 1–29, 99.16 %) were administered. The median cumulative delivered dose of bortezomib was 46.8 mg/m2. The overall response rate (ORR), including all patients with a partial response or better, was 81.7% and the complete response rate (CRR) was 10.36 %. After a median 38.51 months of follow-up, the median overall survival (OS) was 34.33 months; the median event-free survival (EFS) after VMP and second-line therapy (mainly Rd, 56.31%) were 18.51 and 10.75 months, respectively. In the subgroup of patients with 75 years or older the median OS was 29.76 months; the median EFS after first and second-line therapy were 17.76 and 8.93 months, respectively. The hazard ratio for OS was 2.276 (p-value 0.046) and for EFS was 1.507 (p-value 0.055) for the ISS stage II and III group. Age and gender were not negative predictors of survival.

Conclusions: VMP treatment is highly effective in the first-line therapy of elderly patients with multiple myeloma ineligible for HDT with auto-SCT.
HIV Viremia Is Associated With APOL1 Variants and Reduced JC-Viruria
Authors: Kruzel-Davila Etty , Sankofi Barbara Mensah , Kubi Amos-Abanyie Ernestine , Ghansah Anita , Nyarko Alexander , Agyemang Seth , Awandare Gordon A. , Szwarcwort-Cohen Moran , Reiner-Benaim Anat , Hijazi Basem , Ulasi Ifeoma , Raji Yemi Raheem , Boima Vincent , Osafo Charlotte , May Adabayeri Victoria , Matekole Michael , Olanrewaju Timothy O. , Ajayi Samuel , Mamven Manmak , Antwi Sampson , Ademola Adebowale D. , Plange-Rhule Jacob , Arogundade Fatiu , Akyaw Priscilla Abena , Winkler Cheryl A. , Salako Babatunde L. , Ojo Akinlolu , Skorecki Karl , Adu Dwomoa
Published: September 2021

Variants in the Apolipoprotein L1 (APOL1) gene (G1-rs60910145, rs73885319, G2-rs71785313) are common in Africans and in individuals of recent African ancestry and are associated with an increased risk of non-diabetic chronic kidney disease (CKD) and in particular of HIV associated nephropathy (HIVAN). In light of the significantly increased risk of HIVAN in carriers of two APOL1 risk alleles, a role in HIV infectivity has been postulated in the mechanism of APOL1 associated kidney disease. Herein, we aim to explore the association between HIV viremia and APOL1 genotype. In addition, we investigated interaction between BK and JC viruria, CKD and HIV viremia. A total of 199 persons living with HIV/AIDS (comprising 82 CKD cases and 117 controls) from among the participants in the ongoing Human Heredity and Health in Africa (H3Africa) Kidney Disease Research Network case control study have been recruited. The two APOL1 renal risk alleles (RRA) genotypes were associated with a higher risk of CKD (OR 12.6, 95% CI 3.89–40.8, p < 0.0001). Even a single APOL1 RRA was associated with CKD risk (OR 4.42, 95% CI 1.49–13.15, p = 0.007). The 2 APOL1 RRA genotypes were associated with an increased probability of having HIV viremia (OR 2.37 95% CI 1.0–5.63, p = 0.05). HIV viremia was associated with increased CKD risk (OR 7.45, 95% CI 1.66–33.35, P = 0.009) and with a significant reduction of JC virus urine shedding (OR 0.35, 95% CI 0.12–0.98, p = 0.046). In contrast to prior studies, JC viruria was not associated with CKD but was restricted in patients with HIV viremia, regardless of CKD status. These findings suggest a role of APOL1 variants in HIV infectivity and emphasize that JC viruria can serve as biomarker for innate immune system activation.
Psoriatic Arthritis and Metabolic Syndrome: Is There a Role for Disease Modifying Anti-Rheumatic Drugs?
Authors: Atzeni Fabiola , Gerratana Elisabetta , Francesco Masala Ignazio , Bongiovanni Sara , Sarzi-Puttini Piercarlo , Rodríguez-Carrio Javier
Published: September 2021

Although psoriatic arthritis (PsA) primarily leads to joint and skin damage, it is associated with higher prevalence of metabolic syndrome (MetS) and its components, namely hypertension, dyslipidemia, obesity, and type II diabetes. Additionally, chronic inflammation is known to aggravate these cardiometabolic factors, thus explaining the enhanced cardiovascular (CV) morbidity and mortality in RA. Furthermore, emerging evidence suggest that some risk factors can fuel inflammation, thus pointing to a bidirectional crosstalk between inflammation and cardiometabolic factors. Therefore, dampening inflammation by disease-modifying anti-rheumatic drugs (DMARDs) may be thought to ameliorate MetS burden and thus, CV risk and disease severity. In fact, recommendations for PsA management emphasize the need of considering comorbidities to guide the treatment decision process. However, the existing evidence on the impact of approved DMARDs in PsA on MetS and MetS components is far from being optimal, thus representing a major challenge for the clinical setting. Although a beneficial effect of some DMARDs such as methotrexate, TNF inhibitors and some small molecules is clear, no head-to-head studies are published and no evidence is available for other therapeutic approaches such as IL-23 or IL-17 inhibitors. This narrative review summarizes the main evidence related to the effect of DMARDs on MetS outcomes in PsA patients and identify the main limitations, research needs and future perspectives in this scenario.
Genetic Diversity of Multidrug-Resistant Pseudomonas aeruginosa Isolates Carrying blaVIM–2 and blaKPC–2 Genes That Spread on Different Genetic Environment in Colombia
Authors: Rada Ana M. , De La Cadena Elsa , Agudelo Carlos A. , Pallares Christian , Restrepo Eliana , Correa Adriana , Villegas María V. , Capataz Cesar
Published: September 2021

Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen with an increase in the frequency of infections caused by multidrug resistant (MDR) and extensively drug resistant (XDR) strains, limiting the available therapeutic options. The most troublesome resistance is the acquisition and production of carbapenemases such as Verona integron-encoded metallo-β-lactamases (VIM), the most frequent and widespread, and the Klebsiella pneumoniae carbapenemases (KPC), which has continuously spread in the last decade. Its dissemination is linked to their location on mobile genetic elements (MGEs). In Colombia, VIM and KPC have been increasing in its frequency showing major successful dissemination. In this article, we molecularly characterized and analyzed the genetic context of blaVIM and blaKPC in carbapenem-resistant P. aeruginosa (CRPA) isolates from infected and colonized patients in two tertiary-care hospitals, one in Medellín and the other in a municipality close to Medellín, both areas with high carbapenemase endemicity in Colombia (2013–2015). Using whole-genome sequencing (WGS), we identified a remarkable variety of genetic backgrounds in these MDR P. aeruginosa isolates carrying blaKPC–2 and blaVIM–2. There were a diversity of class 1 integron and variations in the gene cassettes associated to blaVIM–2, as well as a possible event of spread of blaKPC–2 mediated by a plasmid that contained part of Tn4401b in one infection case. The dissemination of blaVIM–2 and blaKPC–2 in P. aeruginosa in this area in Colombia has been strongly influenced by successful international clones, carrying these genes and additional determinants of resistance on MGEs, accompanied by gene rearrangement under an antimicrobial selection pressure. These findings emphasize the need to implement control strategies based on rational antibiotic use.
Ultra-Rapid Drug Susceptibility Testing for Klebsiella pneumoniae Clinical Isolates in 60 Min by SYBR Green I/Propidium Iodide Viability Assay
Authors: Chen Jiazhen , Wang Xuyang , Wang Shiyong , Chen Chen , Zhang Wenhong , Zhang Ying
Published: September 2021

Background

We aimed to optimize and validate the drug susceptibility test (DST) assay by SYBR Green I/PI (SG-PI) method using a panel of 89 Klebsiella pneumoniae clinical isolates in comparison with the conventional DST method to three most important antibiotics used for treatment of this bacterial infection, including imipenem, cefmetazole, and gentamicin.

Methods

By staining with SYBR Green I and PI dyes, green fluorescence and red fluorescence, which linearly correlated with the percentages of live and dead or membrane damaged cells, respectively, were used to produce two standard curves to calculate the relative cell membrane impermeable rates for each log and stationary phase cultures. Stationary phase K. pneumoniae cells were used in imipenem and cefmetazole SG-PI DST assay whereas log phase cells were used in the gentamicin assay. The conventional broth microdilution method was used as a gold standard for DST for comparison.

Results

Data showed that after antibiotic treatment for 30–60 min, the antibiotic-resistant K. pneumoniae strains had significantly higher numbers of surviving cells than the susceptible strains at different concentrations of imipenem, cefmetazole, and gentamicin, where the average relative membrane impermeable rates were 88.5, 92.5, and 103.8% for resistant clinical strains, respectively, and 9.1, 49.3, and 71.5% for susceptible strains, respectively. Overall, the total concordances between the ultra-rapid SG-PI method and conventional minimal inhibitory concentration assay in diagnosing imipenem, cefmetazole and gentamicin resistance were high and were 96.6% (86/89), 95.4% (83/87), and 95.5% (85/89), respectively.

Conclusion

We demonstrate that our novel SG-PI assay can accurately and stably detect resistance to different antibiotics in clinical isolates of K. pneumoniae in an ultra-fast manner in 60–90 min.
Biochar and Intercropping With Potato–Onion Enhanced the Growth and Yield Advantages of Tomato by Regulating the Soil Properties, Nutrient Uptake, and Soil Microbial Community
Authors: He Xingjia , Xie Hua , Gao Danmei , Khashi U. Rahman M. , Zhou Xingang , Wu Fengzhi
Published: September 2021

The application of biochar stimulates the activities of microorganisms that affect soil quality and plant growth. However, studies on the impacts of biochar mainly focus on a monoculture, its effects on interspecific interactions are rarely reported. Here, we investigated the impacts of biochar on tomato/potato–onion intercropped (TO) in a pot experiment. Tomato monoculture (T) and TO were treated with no, 0.3, 0.6, and 1.2% biochar concentrations in a pot experiment. Microbial communities from tomato rhizosphere soil were analyzed by quantitative PCR and Illumina MiSeq. The results showed that compared with the tomato monoculture, 0.6%TO and 1.2%TO significantly increased tomato yield in 2018. TO and 1.2%TO significantly increased plant height and dry weight in 2018 and 2019. Biochar treatments increased soil pH, decreased NO3--N and bulk density, and increased the absorption of N, P, and K by tomato. Bacterial and fungal abundances increased with an increase in biochar concentration, while Bacillus spp. and Pseudomonas spp. abundances showed an “increase-decrease-increase” trend. Biochar had a little effect on bacterial diversities but significantly lowered fungal diversities. TO, 0.6%TO, and 1.2%TO increased the potentially beneficial organisms (e.g., Pseudeurotium and Solirubrobacter) and lowered the potentially pathogenic organisms (e.g., Kribbella and Ilyonectria). Different concentrations of biochar affected the bacterial and fungal community structures. Redundancy analysis indicated that the bacterial community was strongly correlated with soil pH, NO3--N, and EC, while the fungal community was closely related to soil NO3--N and moisture. The network analysis showed that biochar and intercropping affected the symbiosis pattern of the microorganisms and increased the proportion of positive interactions and nitrifying microorganisms (Nitrospirae) in the microbial community. Overall, our results indicated that monoculture and intercropping with biochar improved soil physicochemical states and plant nutrient absorption, and regulated soil microbial communities, these were the main factors to promote tomato growth and increase tomato productivity.
The Toxins of Beauveria bassiana and the Strategies to Improve Their Virulence to Insects
Authors: Wang Haiyang , Peng Hui , Li Wenjuan , Cheng Peng , Gong Maoqing
Published: September 2021

The long-term and excessive usage of pesticides is an enormous burden on the environment, which also increases pest resistance. To overcome this problem, research and application of entomopathogenic fungi, which are both environmentally friendly and cause lower resistance, have gained great momentum. Entomopathogenic fungi have a wide range of prospects. Apart from Bacillus thuringiensis, Beauveria bassiana is the most studied biopesticide. After invading insect hosts, B. bassiana produces a variety of toxins, which are secondary metabolites such as beauvericin, bassianin, bassianolide, beauverolides, tenellin, oosporein, and oxalic acid. These toxins help B. bassiana to parasitize and kill the hosts. This review unequivocally considers beauveria toxins highly promising and summarizes their attack mechanism(s) on the host insect immune system. Genetic engineering strategies to improve toxin principles, genes, or virulent molecules of B. bassiana have also been discussed. Lastly, we discuss the future perspective of Beauveria toxin research, including newly discovered toxins.
Isolation, Characterization, and Evaluation of Native Rhizobacterial Consortia Developed From the Rhizosphere of Rice Grown in Organic State Sikkim, India, and Their Effect on Plant Growth
Authors: Sherpa Mingma Thundu , Sharma Laxuman , Bag Niladri , Das Sayak
Published: September 2021

Eight rhizospheric bacteria were isolated from the organic paddy fields of Sikkim, India, and identified asPseudomonas kribbensisKSB,Burkholderia cenocepaciaSRD,Kosakonia oryzendophyticaYMA7,Pseudomonas rhodesiaeSRB,Bacillussp. ARA,Paenibacillus polymyxaCOW3,Bacillus aryabhattaiPSB2, andBacillus megateriumPSB1. They showed plant growth-promoting attributes in rice and have bio-control potential against phytopathogenColletotrichum gloeosporioidesof large cardamom (Amomum subulatum).Burkholderia cenocepaciaSRD showed production of indole acetic acid and ammonia and solubilization of phosphate and potassium and also possessed nitrogen fixation potential. It showed antagonistic activity against two other plant pathogens of large cardamom, viz.,Curvularia eragrostidisandPestalotiopsissp., underin vitroconditions. The liquid bacterial consortium was prepared using the bacterial strains SRB, PSB1, and COW3 (Consortia-1); PSB2, SRD, and COW3 (Consortia-2); and COW3, KSB, and YMA7 (Consortia-3) to increase the growth and yield of rice plants under organic farming conditions. Greenhouse and field studies showed that the Consortia-3 had the highest plant growth-promoting activity. Consortia-3 demonstrated better agronomic performance in terms of root length (9.5 cm),number of leaflets per plant (5.3), grains per panicle (110.6), test grain weight (27.4 g), dry root weight per plant (0.73 g), and total dry biomass per plant (8.26 g).
Fungi-Bacteria Associations in Wilt Diseased Rhizosphere and Endosphere by Interdomain Ecological Network Analysis
Authors: Tan Lin , Zeng Wei-ai , Xiao Yansong , Li Pengfei , Gu Songsong , Wu Shaolong , Zhai Zhengguang , Feng Kai , Deng Ye , Hu Qiulong
Published: September 2021

In the plant rhizosphere and endosphere, some fungal and bacterial species regularly co-exist, however, our knowledge about their co-existence patterns is quite limited, especially during invasion by bacterial wilt pathogens. In this study, the fungal communities from soil to endophytic compartments were surveyed during an outbreak of tobacco wilt disease caused byRalstonia solanacearum. It was found that the stem endophytic fungal community was significantly altered by pathogen invasion in terms of community diversity, structure, and composition. The associations among fungal species in the rhizosphere and endosphere infected byR. solanacearumshowed more complex network structures than those of healthy plants. By integrating the bacterial dataset, associations between fungi and bacteria were inferred by Inter-Domain Ecological Network (IDEN) approach. It also revealed that infected samples, including both the rhizosphere and endosphere, had more complex interdomain networks than the corresponding healthy samples. Additionally, the bacterial wilt pathogenicRalstoniamembers were identified as the keystone genus within the IDENs of both root and stem endophytic compartments.Ralstoniamembers was negatively correlated with the fungal generaPhoma, Gibberella, andAlternariain infected roots, as well asPhoma, Gibberella, andDiaporthein infected stems. This suggested that those endophytic fungi may play an important role in resisting the invasion ofR. solanacearum.
Mindfulness Training Improves Cognition and Strengthens Intrinsic Connectivity Between the Hippocampus and Posteromedial Cortex in Healthy Older Adults
Authors: Sevinc Gunes , Rusche Johann , Wong Bonnie , Datta Tanya , Kaufman Robert , Gutz Sarah E. , Schneider Marissa , Todorova Nevyana , Gaser Christian , Thomalla Götz , Rentz Dorene , Dickerson Bradford D. , Lazar Sara W.
Published: September 2021

Maintaining optimal cognitive functioning throughout the lifespan is a public health priority. Evaluation of cognitive outcomes following interventions to promote and preserve brain structure and function in older adults, and associated neural mechanisms, are therefore of critical importance. In this randomized controlled trial, we examined the behavioral and neural outcomes following mindfulness training (n = 72), compared to a cognitive fitness program (n = 74) in healthy, cognitively normal, older adults (65–80 years old). To assess cognitive functioning, we used the Preclinical Alzheimer Cognitive Composite (PACC), which combines measures of episodic memory, executive function, and global cognition. We hypothesized that mindfulness training would enhance cognition, increase intrinsic functional connectivity measured with magnetic resonance imaging (MRI) between the hippocampus and posteromedial cortex, as well as promote increased gray matter volume within those regions. Following the 8-week intervention, the mindfulness training group showed improved performance on the PACC, while the control group did not. Furthermore, following mindfulness training, greater improvement on the PACC was associated with a larger increase in intrinsic connectivity within the default mode network, particularly between the right hippocampus and posteromedial cortex and between the left hippocampus and lateral parietal cortex. The cognitive fitness training group did not show such effects. These findings demonstrate that mindfulness training improves cognitive performance in cognitively intact older individuals and strengthens connectivity within the default mode network, which is particularly vulnerable to aging affects.

Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT02628548], identifier [NCT02628548].
Dopamine D1 and D2 Receptors Are Important for Learning About Neutral-Valence Relationships in Sensory Preconditioning
Authors: Roughley Stephanie , Marcus Abigail , Killcross Simon
Published: September 2021

Dopamine neurotransmission has been ascribed multiple functions with respect to both motivational and associative processes in reward-based learning, though these have proven difficult to tease apart. In order to better describe the role of dopamine in associative learning, this series of experiments examined the potential of dopamine D1- and D2-receptor antagonism (or combined antagonism) to influence the ability of rats to learn neutral valence stimulus-stimulus associations. Using a sensory preconditioning task, rats were first exposed to pairings of two neutral stimuli (S2-S1). Subsequently, S1 was paired with a mild foot-shock and resulting fear to both S1 (directly conditioned) and S2 (preconditioned) was examined. Initial experiments demonstrated the validity of the procedure in that measures of sensory preconditioning were shown to be contingent on pairings of the two sensory stimuli. Subsequent experiments indicated that systemic administration of dopamine D1- or D2-receptor antagonists attenuated learning when administered prior to S2-S1 pairings. However, the administration of a more generic D1R/D2R antagonist was without effect. These effects remained constant regardless of the affective valence of the conditioning environment and did not differ between male and female rats. The results are discussed in the context of recent suggestions that dopaminergic systems encode more than a simple reward prediction error, and provide potential avenues for future investigation.
Exploring the Embodiment of a Virtual Hand in a Spatially Augmented Respiratory Biofeedback Setting
Authors: Barresi Giacinto , Marinelli Andrea , Caserta Giulia , de Zambotti Massimiliano , Tessadori Jacopo , Angioletti Laura , Boccardo Nicolò , Freddolini Marco , Mazzanti Dario , Deshpande Nikhil , Frigo Carlo Albino , Balconi Michela , Gruppioni Emanuele , Laffranchi Matteo , De Michieli Lorenzo
Published: September 2021

Enhancing the embodiment of artificial limbs—the individuals' feeling that a virtual or robotic limb is integrated in their own body scheme—is an impactful strategy for improving prosthetic technology acceptance and human-machine interaction. Most studies so far focused on visuo-tactile strategies to empower the embodiment processes. However, novel approaches could emerge from self-regulation techniques able to change the psychophysiological conditions of an individual. Accordingly, this pilot study investigates the effects of a self-regulated breathing exercise on the processes of body ownership underlying the embodiment of a virtual right hand within a Spatially Augmented Respiratory Biofeedback (SARB) setting. This investigation also aims at evaluating the feasibility of the breathing exercise enabled by a low-cost SARB implementation designed for upcoming remote studies (a need emerged during the COVID-19 pandemic). Twenty-two subjects without impairments, and two transradial prosthesis users for a preparatory test, were asked (in each condition of a within-group design) to maintain a normal (about 14 breaths/min) or slow (about 6 breaths/min) respiratory rate to keep a static virtual right hand “visible” on a screen. Meanwhile, a computer-generated sphere moved from left to right toward the virtual hand during each trial (1 min) of 16. If the participant's breathing rate was within the target (slow or normal) range, a visuo-tactile event was triggered by the sphere passing under the virtual hand (the subjects observed it shaking while they perceived a vibratory feedback generated by a smartphone). Our results—mainly based on questionnaire scores and proprioceptive drift—highlight that the slow breathing condition induced higher embodiment than the normal one. This preliminary study reveals the feasibility and potential of a novel psychophysiological training strategy to enhance the embodiment of artificial limbs. Future studies are needed to further investigate mechanisms, efficacy and generalizability of the SARB techniques in training a bionic limb embodiment.
Generation of Direct-, Retrograde-, and Source-Wave Gaits in Multi-Legged Locomotion in a Decentralized Manner via Embodied Sensorimotor Interaction
Authors: Ambe Yuichi , Aoi Shinya , Tsuchiya Kazuo , Matsuno Fumitoshi
Published: September 2021

Multi-legged animals show several types of ipsilateral interlimb coordination. Millipedes use a direct-wave gait, in which the swing leg movements propagate from posterior to anterior. In contrast, centipedes use a retrograde-wave gait, in which the swing leg movements propagate from anterior to posterior. Interestingly, when millipedes walk in a specific way, both direct and retrograde waves of the swing leg movements appear with the waves' source, which we call the source-wave gait. However, the gait generation mechanism is still unclear because of the complex nature of the interaction between neural control and dynamic body systems. The present study used a simple model to understand the mechanism better, primarily how local sensory feedback affects multi-legged locomotion. The model comprises a multi-legged body and its locomotion control system using biologically inspired oscillators with local sensory feedback, phase resetting. Each oscillator controls each leg independently. Our simulation produced the above three types of animal gaits. These gaits are not predesigned but emerge through the interaction between the neural control and dynamic body systems through sensory feedback (embodied sensorimotor interaction) in a decentralized manner. The analytical description of these gaits' solution and stability clarifies the embodied sensorimotor interaction's functional roles in the interlimb coordination.