bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Phylogeography of Birds Across the Tocantins–Araguaia Interfluve Reveals a New Biogeographic Suture in the Amazon Far East
Authors: Dornas Tulio , Dantas Sidnei Melo , Araújo-Silva Lucas Eduardo , Morais Fernando , Aleixo Alexandre
Published: June 2022

Few phylogeographic studies have focused on understanding the role of the Tocantins–Araguaia Interfluve (TAI) in the diversification of Amazonian biodiversity. Herein we evaluate the phylogeographic relationships of 14 avian lineages present in the TAI and its two neighboring Amazonian Areas of Endemism: the Xingu (XAE) and Belém (BAE). Four alternative scenarios coupling degree of genetic differentiation and area relationships were tested: (1) populations distributed in TAI, BAE, and XAE are not genetically differentiated from each other (assumed as the null hypothesis); (2) populations from TAI are more closely related to those from BAE; (3) populations from TAI are more closely related to those from XAE; and (4) TAI populations represent independent or endemic lineages not present in either the BAE or XAE. Molecular analyses considered Bayesian Inference methods and Bayesian Information Criterion (BIC) evolutionary models, haplotype sharing and genetic differentiation estimates. We found three distinct phylogeographic patterns: (i) four lineages presented no population structure across XAE, TAI and BAE; (ii) six lineages were represented in the TAI with distinct phylogroups replacing each other between XAE and BAE, but with varying degrees of contact and evidence of gene-flow within the TAI; and (iii) for four lineages, the Tocantins River acted as a barrier isolating BAE phylogroups from those inhabiting both TAI and XAE. These different patterns demonstrate a heterogeneous response to the barrier effects posed by both the Tocantins and Araguaia rivers on the local fauna. Historical geomorphological and hydromorphological factors, such as the presence and absence of paleochannels and anastomosed channel stretches and variations in sedimentation rates support a dynamic history for the Araguaia-Tocantins floodplains, likely accounting for the observed heterogeneity in species’ specific responses. Finally, the scenario of phylogeographic breaks and population subdivision recovered herein along the Tocantins and Araguaia rivers, associated with the existence of contact zones and the occurrence of gene flow, define the TAI as hitherto unknown biogeographic suture zone, localized in southeasternmost Amazonia.
Dissecting Immunosuppressive Cell Communication Patterns Reveals JunB Proto-Oncogene (JUNB) Shaping a Non-Inflamed Tumor Microenvironment
Authors: Chen Hualin , Chen Gang
Published: June 2022

Background:Immunosuppressive cell interactions are responsible for tumor progression and metastasis, as well as anti-tumor immune dysfunction. However, the communication pattern remains unclear.

Methods:We first integrated two single-cell RNA-seq datasets (GSE72056 and GSE103322) of different tumor types to increase the diversity of immunosuppressive cells. Then, based on the analysis results of the communication network, gene regulatory network (GRN), and highly activated pathways, we identified the hub gene in the immunosuppressive tumor microenvironment (TME). To further explore the molecular features of the identified gene, we performed severalin silicoanalysis andin vitroexperiments including qRT-PCR and CCK-8 assay.

Results:Four types of immunosuppressive cells were identified, including cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), and regulatory T cells (Tregs). Based on GRNs and the interactions of immunosuppressive cells and tumor cells, we constructed an intercellular communication signature that divided the pan-cancer TME into two clusters with distinct immunological features and different responses to immunotherapy. In combination with pathway analysis, JunB proto-oncogene (JUNB) was identified as the hub gene of the immunosuppressive TME, and it designed a non-inflamed TME of bladder cancer according to evidence that JUNB was negatively correlated with immunomodulators, chemokines, major histocompatibility complex molecules, immune cell infiltration abundances, anti-cancer immune response, and immune checkpoint inhibitors. Moreover, JUNB may predict an unfavorable response to immunotherapy. The signaling network of the four types of cells demonstrated the dominant roles of CAFs and TAMs in the TME. Further investigation uncovered that the complement signal was highly activated in the interactions between subpopulations of the inflammatory phenotype of CAFs and TAMs. Functional experiment results demonstrated the upregulated JUNB in bladder cancer tissues and low-immunity-score tissues. In addition, CAFs showed a pro-tumor proliferation effectviaJUNB.

Conclusion:Our findings gave insights into the immunosuppressive TME communication network and provided potential therapeutic targets.
Mothers and Babies Online Course: Participant Characteristics and Behaviors in a Web-Based Prevention of Postpartum Depression Intervention
Authors: Barrera Alinne Z. , Morris Sydney Y. , Ruiz Adriana
Published: June 2022

Despite the availability of evidence-based postpartum depression (PPD) prevention and treatment interventions, perinatal persons continue to suffer. eHealth and mHealth tools to address mental health issues have grown exponentially, especially given the ubiquity of technology and the increased demand for telemental health resources. The Mothers and Babies Online Course (eMB), an 8-lesson prevention of PPD intervention, was digitally adapted to expand the reach of evidence-based interventions to perinatal persons with limited access to maternal mental health resources. This report describes the characteristics, behaviors, and feedback provided by users of the updated eMB website. Two hundred eight predominantly English-speaking U.S. residents enrolled in the eMB. Thirty-seven percent were either pregnant (n = 38) or postpartum (n = 39) women interested in learning skills to manage changes in their mood during and after pregnancy; 63% were health providers (n = 131) interested in learning how to support their patient communities. Seventy-six percent (n = 159) viewed at least one of the eight eMB lessons, with 50.9% exclusively viewing Lesson 1. Few (4.4%) viewed all eight lessons. The lessons were rated favorably on usefulness and understanding. Perinatal women engaged with interactive content at higher rates than health providers. Examining user behaviors and feedback is an essential developmental step before empirically testing the efficacy of digital tools. Future iterations of the eMB will incorporate these preliminary findings to provide perinatal persons with accessible web-based interventions that will hopefully reduce the incidence and negative consequences of postpartum depression.
What Level of Migration Is Required to Achieve Zero Population Growth in the Shortest Possible Time? Asian Examples
Authors: McDonald Peter , Hosseini-Chavoshi Meimanat
Published: June 2022

Sustained below replacement fertility leads to declining population size. Several countries in Asia have experienced below replacement fertility for many years. The paper applies a novel approach to examining the viability of using immigration to achieve zero population growth in six Asian countries: China, Japan, Republic of Korea, Thailand, Singapore and Australia. The novel approach is to estimate the level of immigration that would be required to maintain a constant annual number of births in the long term. Maintaining the number of births at the current level is the fastest way to achieve eventual zero population growth. A population with a constant annual number of births, labeled as a quasi-stationary population, also has a near-to constant age structure that is not excessively old. The study concludes that, for all countries except Australia, no reasonable level of immigration could produce a quasi-stationary population if fertility remains at the country's 2020 level. The constraining factors are the current population size and level of fertility and the extent to which there is acceptance of permanent immigrants in the country. If fertility were to increase over 15–20 years to 1.7 births per woman and the country was accepting of relatively large numbers of permanent immigrants, the quasi-stable outcome becomes potentially viable for all countries except China.
The Immune Subtype Contributes to Distinct Overall Survival for Ovarian Cancer Patients With Platinum-Based Adjuvant Therapy
Authors: Li Yueyi , Wang Hang , Chen Ming , Ma Xuelei
Published: June 2022

Objective

Nowadays, platinum-based therapy has been widely used as the first-line therapy of ovarian cancer. However, the effect of the tumor microenvironment on platinum-based therapy remains unclear. In this study, we aim to investigate the relationship between immune microenvironment subtypes and the prognosis of platinum-based therapy in ovarian cancer.

Methods

We integrated 565 ovarian cancer samples from two datasets and obtained the immune subtypes (ISs) by consistent clustering of 1190 immune-related gene expressions. The proportional hazards regression model was used to assess the relationship between ISs and the prognosis of platinum-based adjuvant therapy including progression-free survival (PFS) and overall survival (OS). The prognostic contribution of ISs was validated in three additional cohorts. Non-parametric tests were used to assess genomic characteristics, the proportion of immune cells, and immune-related signature differences among ISs.

Results

We identified and validated five ISs associated with different clinical outcomes of the platinum-based adjuvant therapy in ovarian cancer patients. These differences were only found in OS rather than PFS. An immune subtype had the worst OS. Those patients mainly derived from the mesenchymal subtype had the lowest tumor purity with a high leukocyte fraction as well as stromal fraction and had the highest TGF-β response signaling. By contrast, an immune subtype characterized by immunoreactive status with the highest CD8+T cell infiltration and elevated IFN-γ response signaling had the best prognosis. Other subtypes with more diverse immunologic features such as lowest macrophage regulation signaling showed intermediate prognoses. Notably, the contribution of ISs to OS was independent of the clinical response to platinum-based drugs.

Conclusion

Our analysis revealed the association between different immune characteristics and platinum-based adjuvant therapy, indicating the combination of ISs and chemotherapy could optimize the treatment strategy of OC patients.
Immune Dysfunction Mediated by the ceRNA Regulatory Network in Human Placenta Tissue of Intrahepatic Cholestasis Pregnancy
Authors: Wang Yuya , Tang Yan , Yang Xianli , Xu Jie , Chen Yanjie , Xu Jing , Hu Shan , Yi Ping
Published: June 2022

Pregnancy-related intrahepatic cholestasis (ICP) is a serious complication with adverse perinatal outcomes of preterm labor, fetal distress, or stillbirth. As a result, it is important to investigate and identify the potential critical pathogenic mechanisms of ICP. First, we collected the placental tissues from the ICP with placental weight and fetal birth weight loss for the whole transcriptome sequencing. Then we analyzed the differentially expressed (DE) circRNAs (DEcircRNAs) by SRPBM, DElncRNAs by FRKM, DEmiRNAs by TPM, and DEmRNAs by TPM and RSEM. Based on differential expression of term pregnancy placental tissues from pregnancies impacted by ICP (n=7) as compared to gestational aged matched control tissues (n=5), the circ/lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) regulatory networks were constructed. The ceRNA regulatory networks covered 3,714 events, including 21 DEmiRNAs, 36 DEcircRNAs, 146 DElncRNAs, and 169 DEmRNAs. According to the functional analysis, ICP complications were linked to the immune system, signal transduction, endocrine system, cell growth and death, and transport and catabolism. Further evidence suggested that the expression of immune-related genes KLRD1, BRAF, and NFATC4 might have a potential ceRNA mechanism by individual lncRNA sponging miR372-3p, miR-371a-3p, miR-7851-3p, and miR-449a to control downstream the level of TNF-α, IFN-γ, and IL-10, thereby regulating the pathophysiology of ICP. Furthermore, our results were validated by the qRT-PCR, western blotting and ELISA assays. In conclusion, this study is the first to evaluate placental ceRNA networks in pregnancies affected by ICP, showing alterations in immune regulatory networks which may impact fetal and placental growth. Overall our these data suggest that the ceRNA regulatory network may refine biomarker predictions for developing novel therapeutic approaches in ICP.
Case Report: A Pediatric Case of Familial Mediterranean Fever Concurrent With Autoimmune Hepatitis
Authors: Aoki Mariko , Izawa Kazushi , Tanaka Takayuki , Honda Yoshitaka , Shiba Takeshi , Maeda Yukako , Miyamoto Takayuki , Okamoto Keisuke , Nishitani-Isa Masahiko , Nihira Hiroshi , Imai Kohsuke , Takita Junko , Nishikomori Ryuta , Hiejima Eitaro , Yasumi Takahiro
Published: June 2022

Familial Mediterranean fever (FMF) is a hereditary, autoinflammatory disease that causes recurrent fever, arthritis, and serositis. The diagnosis of FMF is based on the presentation of typical clinical symptoms and the Mediterranean fever gene (MEFV) test. However, the challenge lies in diagnosing atypical cases. In this report, we have described a pediatric patient with complex FMF whose diagnosis required trio-whole exome sequencing (WES) and functional validation of a rare MEFV variant. A 3-year-old boy presented with recurrent episodes of elevated liver enzymes and arthralgia. He was diagnosed with autoimmune hepatitis (AIH), and his liver enzymes improved rapidly with steroid treatment. However, he exhibited recurrent arthralgia and severe abdominal attacks. Trio-WES identified compound heterozygous mutations in MEFV (V726A and I692del). Ex vivo functional assays of the patient’s monocytes and macrophages, which had been pre-treated with Clostridium difficile toxin A (TcdA) and colchicine, were comparable to those of typical FMF patients, thereby confirming the diagnosis of FMF. Although he was intolerant to colchicine because of liver toxicity, subsequent administration of canakinumab successfully ameliorated his abdominal attacks. However, it was ineffective against liver injury, which recurred after steroid tapering. Therefore, in this case, the pathogenesis of AIH was probably interleukin-1β (IL-1β)-independent. In fact, AIH might have been a concurrent disease with FMF, rather than being one of its complications. Nevertheless, further studies are necessary to determine whether FMF-induced inflammasome activation contributes to AIH development. Moreover, we must consider the possibility of mixed phenotypes in such atypical patients who present distinct pathologies simultaneously.
Case Report: Novel STIM1 Gain-of-Function Mutation in a Patient With TAM/STRMK and Immunological Involvement
Authors: de la Fuente-Munoz Eduardo , Van Den Rym Ana , García-Solis Blanca , Ochoa Grullón Juliana , Guevara-Hoyer Kissy , Fernández-Arquero Miguel , Galán Dávila Lucía , Matías-Guiú Jorge , Sánchez-Ramón Silvia , Pérez de Diego Rebeca
Published: June 2022

Gain-of-function (GOF) mutations in STIM1 are responsible for tubular aggregate myopathy and Stormorken syndrome (TAM/STRMK), a clinically overlapping multisystemic disease characterised by muscle weakness, miosis, thrombocytopaenia, hyposplenism, ichthyosis, dyslexia, and short stature. Several mutations have been reported as responsible for the disease. Herein, we describe a patient with TAM/STRMK due to a novel L303P STIM1 mutation, who not only presented clinical manifestations characteristic of TAM/STRMK but also manifested immunological involvement with respiratory infections since childhood, with chronic cough and chronic bronchiectasis. Despite the seemingly normal main immunological parameters, immune cells revealed GOF in calcium signalling compared with healthy donors. The calcium flux dysregulation in the immune cells could be responsible for our patient’s immune involvement. The patient’s mother carried the mutation but did not exhibit TAM/STRMK, manifesting an incomplete penetrance of the mutation. More cases and evidence are necessary to clarify the dual role of STIM1 in immune system dysregulation and myopathy.
Immunosuppression Reversal Nanovaccines Substituting Dendritic Cells for Personalized Cancer Immunotherapy
Authors: Chen Hu , Cheng Hongwei , Liang Xiaoliu , Cai Shundong , Liu Gang
Published: June 2022

Although immunotherapy has paved a new avenue for cancer treatment, inadequate immune response often executes suboptimal therapeutic effects. In general, an effective immune response undergoes presentation of antigen by antigen-presenting cells, proliferation and differentiation of lymphocytes, and attack of cancer cells by cytotoxic T lymphocytes (CTLs). The antigen self-presentation and immunosuppression reversal (ASPIRE) nanovaccine derived from dendritic cells provides a simplified and immune deregulated procedure for immunotherapy profiting from its orientable peculiarity. By integrating major histocompatibility complex class I (MHC-I) molecules into present specific epitopes and co-delivering anti-PD-1 antibody and B7 costimulatory molecules through the programmed biomimetic synthesis, the ASPIRE nanovaccine demonstrates a milestone in personalized cancer immunotherapy.
The Sargasso Sea High Seas EBSA After Ten Years: Is It Still Relevant and How Has It Helped Conservation Efforts?
Authors: Roe Howard S. J. , Freestone David , Sapsford Fae
Published: June 2022

The Sargasso Sea is a high seas ecosystem located within the North Atlantic Subtropical Gyre. The floating Sargassum macroalgae for which it is named support a diverse and productive ocean ecosystem. The floating mats and windrows of Sargassum house distinct communities of animals including endemic species, and provide shelter, nursery areas and food for many others including juvenile turtles, fish, and birds. A decade ago, in 2012, the two million square mile core area of the Sargasso Sea was “described” by the parties to the Convention on Biological Diversity (CBD) as an Ecologically or Biologically Significant Marine Area (EBSA), having scored highly on six of the seven designated criteria. At the time it was the largest high seas EBSA to be so described. This paper reviews the scientific evidence supporting the finding that it meets the rigorous criteria for an EBSA and assesses whether there have been major changes in the decade since. It puts this in the context of the work of the Sargasso Sea Commission and the Hamilton Declaration Signatories to “conserve the Sargasso Sea for the benefit of present and future generations” and assesses the extent to which being an EBSA has assisted with these conservation efforts.
Construction and Validation of a Chloroplast Expression Vector for the Production of Recombinant Proteins in Chlorella vulgaris
Authors: Bolaños-Martínez Omayra C. , Malla Ashwini , Rosales-Mendoza Sergio , Vimolmangkang Sornkanok
Published: June 2022

Microalgae constitute a diverse group of photosynthetic unicellular microorganisms that have gained immense attention for biotechnological applications. They are promising platforms for the production of high-value metabolites and biopharmaceuticals for commercial and therapeutic applications because of their physiological properties and capability to grow easily in natural and artificial environments. Although the proof-of-concept for some applications have been achieved for model species, such as Chlamydomonas reinhardtii, the genetic engineering methods for microalgae are still in their infancy. Thus, an expansion of this field is required. Chlorella vulgaris is an important algal species with a high protein content and requires focus for the development of an efficient nuclear and chloroplast transformation process. This research aimed to establish a chloroplast transformation method for the freshwater green-algae species C. vulgaris based on a specific expression vector (pCMCC, which was named after Chula Mexico Chlorella chloroplast) constructed with endogenous recombination regions, namely, 16S–trn I (left) and trn A–23S (right), and the Prrn promoter. Human basic fibroblast growth factor (bFGF) was adopted as a target biopharmaceutical to establish the chloroplast expression approach. The plasmid pCMCC:bFGF was transformed into C. vulgaris via electroporation using simple carbohydrate-based buffers, which aided in the transfer of the transgene into the chloroplast genome. Cells transformed with the pCMCC:bFGF vector were selected using kanamycin, and resistant colonies were analyzed by polymerase chain reaction and Western blotting to confirm the presence of the transgene and the recombinant bFGF, respectively. The bFGF that accumulated in the transplastomic C. vulgaris clones ranged from 0.26 to 1.42 ng/g fresh weight of biomass, and it was quantified by enzyme-linked immunosorbent assay. Therefore, the designed expression vector, in combination with an optimized electroporation protocol, constitutes a viable approach to successfully develop transplastomic lines of C. vulgaris for the potential low-cost production of biopharmaceuticals using this algal species. This study paves the way for the establishment of chloroplast biotechnology in microalgae other than the model organism C. reinhardtii.
Nutrient-Loading Mitigation by Shellfish Aquaculture in Semi-Enclosed Estuaries
Authors: Guyondet Thomas , Filgueira Ramón , Pearce Christopher M. , Tremblay Réjean , Comeau Luc A.
Published: June 2022

Bivalve aquaculture may provide a variety of ecosystem services including nitrogen extraction from estuaries, which are often subject to excess nutrient loading from various land activities, causing eutrophication. This nitrogen extraction may be affected by a combination of various non-linear interactions between the cultured organisms and the receiving ecosystem. The present study used a coupled hydro-biogeochemical model to examine the interactive effects of various factors on the degree of estuarine nutrient mitigation by farmed bivalves. These factors included bay geomorphology (leaky, restricted and choked systems), river size (small and large rivers leading to moderate (105.9 Mt N yr-1) and high (529.6 Mt N yr-1) nutrient discharges), bivalve species (blue mussel (Mytilus edulis) and eastern oyster (Crassostrea virginica)), farmed bivalve area (0, 10, 25 and 40% of estuarine surface area) and climate change (water temperature, sea level and precipitation reflecting either present or future (Horizon 2050) conditions). Model outputs indicated that bivalve culture was associated with the retention of nitrogen within estuaries, but that this alteration of nitrogen exchange between estuaries and the open ocean was not uniform across all tested variables and it depended on the nature of their interaction with the bivalves as well as their own dynamics. When nitrogen extraction resulting from harvest was factored in, however, bivalve culture was shown to provide a net nitrogen removal in the majority of the tested model scenarios. Mussels provided more nutrient mitigation than oysters, open systems were more resilient to change than closed ones, and mitigation potential was shown to generally increase with increasing bivalve biomass. Under projected future temperature conditions, nutrient mitigation from mussel farms was predicted to increase, while interactions with the oyster reproductive cycle led to both reduced harvested biomass and nutrient mitigation potential. This study presents the first quantification of the effects of various biological, physical, geomorphological and hydrodynamical processes on nutrient mitigation by bivalve aquaculture and will be critical in addressing questions related to eutrophication mitigation by bivalves and prediction of possible nutrient trading credits.
“Debriefing and Organizational Lessons Learned” (DOLL): A Qualitative Study to Develop a Classification Framework for Reporting Clinical Debriefing Results
Authors: Paquay Méryl , Dubois Nadège , Diep Anh Nguyet , Graas Gwennaëlle , Sassel Tamara , Piazza Justine , Servotte Jean-Christophe , Ghuysen Alexandre
Published: June 2022

Background

The COVID-19 crisis has radically affected our healthcare institutions. Debriefings in clinical settings provide a time for the clinicians to reflect on the successes (pluses) and difficulties (deltas) encountered. Debriefings tend to be well-received if included in the broader management of the unit. The goal of this study was to develop a framework to categorize these debriefings and to assess its worthiness.

Methods

A qualitative approach based on a grounded theory research method was adopted resulting in the “Debriefing and Organizational Lessons Learned” (DOLL) framework. Debriefings were conducted within two Emergency Departments of a Belgian University Hospital during an 8-week period. In the first step, three researchers used debriefing transcripts to inductively develop a tentative framework. During the second step, these three researchers conducted independent categorizations of the debriefings using the developed framework. In step 3, the team analyzed the data to understand the utility of the framework. Chi-square was conducted to examine the associations between the item types (pluses and deltas) and the framework's dimensions.

Results

The DOLL is composed of seven dimensions and 13 subdimensions. Applied to 163 debriefings, the model identified 339 items, including 97 pluses and 242 deltas. Results revealed that there was an association between the frequency of pluses and deltas and the dimensions (p < 0.001). The deltas were mainly related to the work environment (equipment and maintenance) (p < 0.001) while the pluses identified tended to be related to the organization of the unit (communication and roles) (p < 0.001). With leadership's support and subsequent actions, clinicians were more enthusiastic about participating and the researchers anecdotally detected a switch toward a more positive organizational learning approach.

Conclusion

The framework increases the potential value of clinical debriefings because it organizes results into actionable areas. Indeed, leadership found the DOLL to be a useful management tool. Further research is needed to investigate how DOLL may work in non-crisis circumstances and further apply the DOLL into incident reporting and risk management process of the unit.
IL-6 Autoantibodies Predict Lower Platelet Counts and Altered Plasma Cytokine Profiles in Healthy Blood Donors: Results From the Danish Blood Donor Study
Authors: von Stemann Jakob Hjorth , Pedersen Ole Birger Vesterager , Hjalgrim Henrik , Erikstrup Christian , Ullum Henrik , Dowsett Joseph , Thørner Lise Wegner , Larsen Margit Anita Hørup , Sørensen Erik , Hansen Morten Bagge , Ostrowski Sisse Rye
Published: June 2022

Cytokine-specific autoantibodies (c-aAb) represent a novel type of immune dysfunction. Though they have been detected in both patient cohorts and healthy individuals, and have immunomodulatory properties, the full extent of their influence remains unknown. Based on the critical role of several cytokines in thrombopoiesis, we investigated if there is an association between c-aAb and platelet variables in healthy individuals, with a specific focus on c-aAb against a known thrombopoietic cytokine, IL-6. Using platelet count and mean platelet volume in 3,569 healthy participants of the Danish Blood Donor Study as dependent variables, we performed a series of multivariate regression analyses using five cytokine autoantibodies, including IL-6 c-aAb, as independent variables. In men, high titers of IL-6 c-aAb were negatively associated with platelet counts (β = −24 *109/l (95% confidence interval −43 to −6), p = 0.008) and positively associated with mean platelet volume (β = 0.4 fL (95% confidence interval 0.0–0.7) p = 0.043). These associations were exacerbated when adjusting for undetectable C-reactive protein levels, which we used as a proxy for c-aAb mediated IL-6 inhibition in vivo. Furthermore, in a smaller subgroup, individuals with high vs. low titer IL-6 c-aAb had different profiles of plasma IL-6, IL-10, TNFα and TPO, further suggesting a functional inhibition of IL-6 by high titers of circulating IL-6 c-aAb. We therefore speculate that in addition to their immunomodulatory potential IL-6 c-aAb may interfere with thrombopoiesis – directly or indirectly – under normal physiological conditions. This study is the first to suggest an influence of c-aAb on platelets in healthy individuals, beyond their apparent effects on immune competence.
Spatial Variation of the Microbial Community Structure of On-Site Soil Treatment Units in a Temperate Climate, and the Role of Pre-treatment of Domestic Effluent in the Development of the Biomat Community
Authors: Criado Monleon Alejandro Javier , Knappe Jan , Somlai Celia , Betancourth Carolina Ospina , Ali Muhammad , Curtis Thomas P. , Gill Laurence William
Published: June 2022

The growth of microbial mats or “biomats” has been identified as an essential component in the attenuation of pollutants within the soil treatment unit (STU) of conventional on-site wastewater treatment systems (OWTSs). This study aimed to characterize the microbial community which colonizes these niches and to determine the influence of the pre-treatment of raw-domestic wastewater on these communities. This was achieved through a detailed sampling campaign of two OWTSs. At each site, the STU areas were split whereby half received effluent directly from septic tanks, and half received more highly treated effluents from packaged aerobic treatment systems [a coconut husk media filter on one site, and a rotating biodisc contactor (RBC) on the other site]. Effluents from the RBC had a higher level of pre-treatment [~90% Total Organic Carbon (TOC) removal], compared to the media filter (~60% TOC removal). A total of 92 samples were obtained from both STU locations and characterized by 16S rRNA gene sequencing analysis. The fully treated effluent from the RBC resulted in greater microbial community richness and diversity within the STUs compared to the STUs receiving partially treated effluents. The microbial community structure found within the STU receiving fully treated effluents was significantly different from its septic tank, primary effluent counterpart. Moreover, the distance along each STU appears to have a greater impact on the community structure than the depth in each STU. Our findings highlight the spatial variability of diversity, Phylum- and Genus-level taxa, and functional groups within the STUs, which supports the assumption that specialized biomes develop around the application of effluents under different degrees of treatment and distance from the source. This research indicates that the application of pre-treated effluents infers significant changes in the microbial community structure, which in turn has important implications for the functionality of the STU, and consequently the potential risks to public health and the environment.
Gene Expression Subtyping Reveals Immune alterations:TCGA Database for Prognosis in Ovarian Serous Cystadenocarcinoma
Authors: Feng Chunxia , Xu Yan , Liu Yuanyuan , Zhu Lixia , Wang Le , Cui Xixi , Lu Jingjing , Zhang Yan , Zhou Lina , Chen Minbin , Zhang Zhiqin , Li Ping
Published: June 2022

Serous ovarian cancer is the most common and primary death type in ovarian cancer. In recent studies, tumor microenvironment and tumor immune infiltration significantly affect the prognosis of ovarian cancer. This study analyzed the four gene expression types of ovarian cancer in TCGA database to extract differentially expressed genes and verify the prognostic significance. Meanwhile, functional enrichment and protein interaction network analysis exposed that these genes were related to immune response and immune infiltration. Subsequently, we proved these prognostic genes in an independent data set from the GEO database. Finally, multivariate cox regression analysis revealed the prognostic significance of TAP1 and CXCL13. The genetic alteration and interaction network of these two genes were shown. Then, we established a nomogram model related to the two genes and clinical risk factors. This model performed well in Calibration plot and Decision Curve Analysis. In conclusion, we have obtained a list of genes related to the immune microenvironment with a better prognosis for serous ovarian cancer, and based on this, we have tried to establish a clinical prognosis model.
Mastoparans: A Group of Multifunctional α-Helical Peptides With Promising Therapeutic Properties
Authors: de Santana Carlos José Correia , Pires Júnior Osmindo Rodrigues , Fontes Wagner , Palma Mário Sérgio , Castro Mariana S.
Published: June 2022

Biologically active peptides have been attracting increasing attention, whether to improve the understanding of their mechanisms of action or in the search for new therapeutic drugs. Wasp venoms have been explored as a remarkable source for these molecules. In this review, the main findings on the group of wasp linear cationic α-helical peptides called mastoparans were discussed. These compounds have a wide variety of biological effects, including mast cell degranulation, activation of protein G, phospholipase A2, C, and D activation, serotonin and insulin release, and antimicrobial, hemolytic, and anticancer activities, which could lead to the development of new therapeutic agents.
Pharmacological Responses of the G542X-CFTR to CFTR Modulators
Authors: Fang Xinxiu , Yeh Jiunn-Tyng , Hwang Tzyh-Chang
Published: June 2022

Cystic fibrosis (CF) is a lethal hereditary disease caused by loss-of-function mutations of the chloride channel cystic fibrosis transmembrane conductance regulator (CFTR). With the development of small-molecule CFTR modulators, including correctors that facilitate protein folding and expression and potentiators that promote channel activity, about 90% of the CF patients are now receiving efficacious target therapies. G542X-CFTR, a premature termination codon (PTC) mutation, is the most common disease-associated mutation found in the remaining 10% of patients that await effective drugs to rectify the fundamental defects caused by PTC. In this study, we employed biophysical and biochemical techniques to characterize the pharmacological responses of the translational products of G542X-CFTR to a range of new CFTR modulators. Specifically, we identified two different proteins translated from the G542X-CFTR cDNA using western blotting: the C-terminus truncated protein that responds to the C1 corrector which binds to the N-terminal part of the protein and a full-length CFTR protein through the read-through process. Electrophysiological data suggest that the read-through protein, but not the C-terminus truncated one, is functional and responds well to CFTR potentiators despite a lower open probability compared to wild-type CFTR. As the expression of the read-through products can be increased synergistically with the read-through reagent G418 and C1 corrector, but not with combinations of different types of correctors, we concluded that an efficacious read-through reagent is a prerequisite for mitigating the deficits of G542X-CFTR. Moreover, the CFTR potentiators may help improve the effectiveness of future combinational therapy for patients carrying PTCs such as G542X.
Meta-Analysis of the Association Between Asthma and the Risk of Stroke
Authors: Fang Zheng-Hua , Li Zhi-Fei , An Zhuo-Yu , Huang Si-Cheng , Hao Meng-Di , Zhang Wei-Xing
Published: June 2022

Introduction

Asthma and stroke share many risk factors. Previous meta-analysis has indicated that asthma is associated with an increased risk of stroke. However, this study were limited by the small number of articles included and the lack of subgroup analyses of different stroke types and different populations. This meta-analysis aimed to synthesize evidence systematically to investigate the impact of asthma on stroke.

Methods

We searched Medline (via PubMed), Web of Science and EMBASE databases and manually identified eligible studies (inception dates to December 25, 2021) that analyzed the association between asthma and stroke. We conducted quality assessment to evaluate the risk of bias of studies and sensitivity analyses to test the robustness of results.

Results

We included 8 cohort studies and 10 cross-sectional studies comprised 3,011,016 participants. We found patients with asthma had a higher risk of stroke than patients without asthma [relative risk (RR): 1.34, 95% confidence interval (CI): 1.21–1.47]. Moreover, asthma significantly increased the risk of ischemic stroke (RR: 1.25, 95% CI: 1.06–1.47) without increasing the risk of hemorrhagic stroke (RR: 1.08, 95% CI: 0.87–1.34). Asthma increased the risk of stroke in both men (RR: 1.20, 95% CI: 1.10–1.32) and women (RR: 1.29, 95% CI: 1.12–1.48) with no significant difference between the sexes. We also found that patients with inactive asthma, child-onset asthma, or no smoking history did not have an increased risk of stroke.

Conclusions

These results supported the finding that asthma could significantly increase the risk of stroke, but this impact was not consistent in different populations.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=290745, identifier: CRD42021290745.
Chiral Determination of Naringenin by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry and Application in Citrus Peel and Pulp
Authors: Yao Zhoulin , Wu Shaohui , Zhang Hu , Feng Xianju , Wang Zhen , Lin Mei
Published: June 2022

A chiral separation method of naringenin in citrus pulp and peel was established using ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) in this study. The liquid-phase conditions for separation were Chiralpak IG-3 column at 40°C, mobile phase of methanol, and 0.1% formic acid solution (85/15; v/v). Isovolumetric elution can complete the detection within 5 min. Considering the matrix effect, the matrix standard calibration curve was used for sample quantification. Quantitation was achieved by fitting a calibration curve using a standard matrix. The mean overall recoveries of the two enantiomers from orange pulp were 91.0–110.0% and orange peel were 85.3–110.3%, with relative standard deviations of 1.5–3.8 and 0.9–3.6% at the 0.5, 2.5, 50, and 250 μg/kg levels, respectively. The limit of quantification for all enantiomers in the citrus matrix did not exceed 0.5 μg/kg. Furthermore, the absolute configuration of the naringenin enantiomer was determined by combining experimental and predicted electron circular dichroism spectroscopy, and it was confirmed on a Chiralpak IG-3 column that the first eluting enantiomer was (S)-naringenin. The determination of chiral naringenin content in actual citrus samples showed that the naringenin content in hybrid citrus and citrus pulp was significantly higher than that in pomelo. The method established in this study can be used for the determination of naringenin enantiomers in citrus, which is beneficial to variety selection.
Lifestyle and Dietary Habits Affect Plasma Levels of Specific Cytokines in Healthy Subjects
Authors: D'Esposito Vittoria , Di Tolla Michele Francesco , Lecce Manuela , Cavalli Francesco , Libutti Michele , Misso Saverio , Cabaro Serena , Ambrosio Maria Rosaria , Parascandolo Alessia , Covelli Bianca , Perruolo Giuseppe , Sansone Mario , Formisano Pietro
Published: June 2022

Low-grade chronic inflammation (LGCI) is a common feature of non-communicable diseases. Cytokines play a crucial role in LGCI. This study aimed to assess how LGCI risk factors [e.g., age, body mass index (BMI), smoke, physical activity, and diet] may impact on specific cytokine levels in a healthy population. In total, 150 healthy volunteers were recruited and subjected to questionnaires about the last 7-day lifestyle, including smoking habit, physical activity, and food frequency. A panel of circulating cytokines, chemokines, and growth factors was analyzed by multiplex ELISA. BMI showed the heaviest impact on the correlation between LGCI-related risk factors and cytokines and was significantly associated with CRP levels. Aging was characterized by an increase in IL-1b, eotaxin, MCP-1, and MIP-1α. Smoking was related to higher levels of IL-1b and CCL5/RANTES, while physical activity was related to MIP-1α. Within the different eating habits, CRP levels were modulated by eggs, red meat, shelled fruits, and greens consumption; however, these associations were not confirmed in a multivariate model after adjusting for BMI. Nevertheless, red meat consumption was associated with an inflammatory pattern, characterized by an increase in IL-6 and IL-8. IL-8 levels were also increased with the frequent intake of sweets, while a higher intake of shelled fruits correlated with lower levels of IL-6. Moreover, IL-6 and IL-8 formed a cluster that also included IL-1b and TNF-α. In conclusion, age, BMI, smoke, physical activity, and dietary habits are associated with specific cytokines that may represent potential markers for LGCI.
Prediction Model for Lung Cancer in High-Risk Nodules Being Considered for Resection: Development and Validation in a Chinese Population
Authors: Xia Chunqiu , Liu Minghui , Li Xin , Zhang Hongbing , Li Xuanguang , Wu Di , Ren Dian , Hua Yu , Dong Ming , Liu Hongyu , Chen Jun
Published: June 2022

Background

Determining benign and malignant nodules before surgery is very difficult when managing patients with pulmonary nodules, which further makes it difficult to choose an appropriate treatment. This study aimed to develop a lung cancer risk prediction model for predicting the nature of the nodule in patients’ lungs and deciding whether to perform a surgical intervention.

Methods

This retrospective study included patients with pulmonary nodules who underwent lobectomy or sublobectomy at Tianjin Medical University General Hospital between 2017 and 2020. All subjects were further divided into training and validation sets. Multivariable logistic regression models with backward selection based on the Akaike information criterion were used to identify independent predictors and develop prediction models.

Results

To build and validate the model, 503 and 260 malignant and benign nodules were used. Covariates predicting lung cancer in the current model included female sex, age, smoking history, nodule type (pure ground-glass and part-solid), nodule diameter, lobulation, margin (smooth, or spiculated), calcification, intranodular vascularity, pleural indentation, and carcinoembryonic antigen. The final model of this study showed excellent discrimination and calibration with a concordance index (C-index) of 0.914 (0.890–0.939). In an independent sample used for validation, the C-index for the current model was 0.876 (0.825–0.927) compared with 0.644 (0.559–0.728) and 0.681 (0.605–0.757) for the Mayo and Brock models. The decision curve analysis showed that the current model had higher discriminatory power for malignancy than the Mayo and the Brock models.

Conclusions

The current model can be used in estimating the probability of lung cancer in nodules requiring surgical intervention. It may reduce unnecessary procedures for benign nodules and prompt diagnosis and treatment of malignant nodules.
Application of Single-Port Laparoscopic Surgery in Myomectomy
Authors: Jiang Lili , Tong Deming , Li Yan , Liu Qifang , Liu Kuiran
Published: June 2022

Research Question

The use of a power morcellator in laparoscopic myomectomy is a controversial topic. The application of single-port laparoscopy solves this problem, but its safety, efficacy and prognosis are also challenges. The purpose of this study was to compare the clinical application of single-port laparoscopy and traditional three-port laparoscopy in myomectomy.

Design

This is a retrospective review of a total of 120 patients who underwent single-port laparoscopic myomectomy (n=60) or traditional three-port laparoscopic myomectomy (n=60), performed between January 2019 to December 2020. The operation time, intraoperative blood loss, specimen removal time, hemoglobin change after operation, postoperative ambulation time, first exhaust time after surgery, the length of hospital stay, pain score on the day, the first day after operation and the satisfaction of abdominal wall scar were evaluated for the surgical outcomes.

Results

Compared with the traditional three-port laparoscopic group, the specimen removal time, postoperative ambulation time, first exhaust time after surgery, the length of hospital stay were all shorter, the satisfaction of abdominal wall scar were higher in single-port laparoscopic group. The duration of surgery was longer in single-port laparoscopic group significantly. The differences were statistically significant (P<0.05). The intraoperative blood loss, hemoglobin change after operation, pain score on the day of operation and the first day after operation of the two groups had no differences (P>0.05).

Conclusions

The clinical effect of single-port laparoscopic myomectomy is satisfactory and can be popularized in clinic.
Diagnostic Performance of Diffusion-Weighted Imaging for Colorectal Cancer Detection: An Updated Systematic Review and Meta-Analysis
Authors: Xiao Yunfei , Li Juan , Zhong Jiamei , Chen Dequan , Shi Jianbo , Jin Hongrui
Published: June 2022

Background

Magnetic resonance imaging (MRI), which uses strong magnetic fields and radio waves (radiofrequency energy) to make images, is one of the best imaging methods for soft tissues and can clearly display unique anatomical structures. Diffusion-weighted imaging (DWI) has been developed for identifying various malignant tumors.

Aim

To investigate the diagnostic value of DWI-MRI quantitative analysis in colorectal cancer detection.

Methods

The PubMed, Cochrane Library, and Embase databases were searched from inception to May 29, 2020. Studies published in English that used DWI-MRI for diagnosing colorectal cancer were included. Case reports, letters, reviews, and studies conducted in non-humans or in-vitro experiments were excluded. The pooled diagnostic odds ratio (DOR) and hierarchical summary receiver operating characteristic (HSROC) curves were computed for DWI, and the area under the curve (AUC) and associated standard error (SE) and 95% confidence intervals (CIs) were also used.

Results

In total, 15 studies with 1,655 participants were finally included in this meta-analysis. There were four prospective studies and 11 retrospective studies. Eight studies focused on rectal cancer, six on colorectal cancer, and one on colonic cancer. The performance of DWI-MRI for diagnosing colorectal cancer was accurate, with pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of 0.88 (95% CI = 0.85–0.91), 0.92 (95% CI = 0.91–0.94), 30.36 (95% CI = 11.05–83.43), and 0.44 (95% CI = 0.30–0.64), respectively. The DOR and HSROC curves were 121 (95% CI = 56–261) and 0.92 (λ: 4.79), respectively.

Conclusion

DWI showed high diagnostic accuracy for colorectal cancer detection. Further studies with large sample sizes and prospective design are needed to confirm these results.