bluuebunny/crossref_metadata_2025 huggingface dataset:
Complement membrane attack complex is an immunometabolic regulator of NLRP3 activation and IL-18 secretion in human macrophages
Authors: Jimenez-Duran Gisela , Kozole Joseph , Peltier-Heap Rachel , Dickinson Eleanor R. , Kwiatkowski Christopher R. , Zappacosta Francesca , Annan Roland S. , Galwey Nicholas W. , Nichols Eva-Maria , Modis Louise K. , Triantafilou Martha , Triantafilou Kathy , Booty Lee M.
Published: September 2022

The complement system is an ancient and critical part of innate immunity. Recent studies have highlighted novel roles of complement beyond lysis of invading pathogens with implications in regulating the innate immune response, as well as contributing to metabolic reprogramming of T-cells, synoviocytes as well as cells in the CNS. These findings hint that complement can be an immunometabolic regulator, but whether this is also the case for the terminal step of the complement pathway, the membrane attack complex (MAC) is not clear. In this study we focused on determining whether MAC is an immunometabolic regulator of the innate immune response in human monocyte-derived macrophages. Here, we uncover previously uncharacterized metabolic changes and mitochondrial dysfunction occurring downstream of MAC deposition. These alterations in glycolytic flux and mitochondrial morphology and function mediate NLRP3 inflammasome activation, pro-inflammatory cytokine release and gasdermin D formation. Together, these data elucidate a novel signalling cascade, with metabolic alterations at its center, in MAC-stimulated human macrophages that drives an inflammatory consequence in an immunologically relevant cell type.
miR-aculous new avenues for cancer immunotherapy
Authors: Tang William W. , Bauer Kaylyn M. , Barba Cindy , Ekiz Huseyin Atakan , O’Connell Ryan M.
Published: September 2022

The rising toll of cancer globally necessitates ingenuity in early detection and therapy. In the last decade, the utilization of immune signatures and immune-based therapies has made significant progress in the clinic; however, clinical standards leave many current and future patients without options. Non-coding RNAs, specifically microRNAs, have been explored in pre-clinical contexts with tremendous success. MicroRNAs play indispensable roles in programming the interactions between immune and cancer cells, many of which are current or potential immunotherapy targets. MicroRNAs mechanistically control a network of target genes that can alter immune and cancer cell biology. These insights provide us with opportunities and tools that may complement and improve immunotherapies. In this review, we discuss immune and cancer cell–derived miRNAs that regulate cancer immunity and examine miRNAs as an integral part of cancer diagnosis, classification, and therapy.
Association between immune-related adverse events and the efficacy of PD-1 inhibitors in advanced esophageal cancer
Authors: Qin Wenru , Yang Linlin , Fan Bingjie , Zou Bing , Duan Yanan , Li Butuo , Wang Linlin
Published: September 2022

Introduction

Recent developments in immune checkpoint inhibitors (ICIs) have improved the treatment outcomes of esophageal cancer (EC); however, it may initiate immune-related adverse events (irAEs) in some patients. The ICIs’ therapeutic efficacy is associated with irAEs in patients with non-small cell lung cancer or renal cell carcinoma, although this association is unknown in EC. The purpose of this study was to explore the association between irAEs and the efficacy of programmed death 1 (PD-1) inhibitors in EC patients.

Patients and methods

This study included patients with advanced EC treated with PD-1 inhibitors. The patients were divided into two groups according to the occurrence of irAEs. Afterward, the efficacy was compared between the irAE-negative and irAE-positive groups, and we analyzed the predictive factors of irAEs and survival.

Results

Overall, 295 patients were included in this study. Baseline characteristics were balanced in the irAE-negative and irAE-positive groups. In total, 143 (48.47%) patients experienced irAEs. The most frequent irAEs were anemia (49, 16.61%), hyperthyroidism (45, 15.25%), and pneumonitis (44, 14.92%). In total, 33 (11.19%) patients had grade ≥ 3 irAEs and pneumonitis have 15 (5.08%). No grade 5 adverse events were observed. A total of 52 (17.63%) and 91 (30.85%) patients had single and multiple irAEs, respectively. Compared with patients without irAEs, those with irAEs had significantly higher objective response rate (ORR) (37.76% vs. 25.00%, p = 0.018) and disease control rate (DCR) (92.31% vs. 83.55%, p = 0.022). Univariate Cox analyses indicated the significant association between irAEs and improved median progression-free survival (PFS) (10.27 vs. 6.2 months, p < 0.001) and overall survival (OS) (15.4 vs. 9.2 months, p < 0.001). In multivariate analyses, irAEs were independently associated with longer PFS (p = 0.011) and OS (p = 0.002). Moreover, multivariate analysis revealed that cycles > 8, radiation, as well as antiangiogenic therapy were strongly associated with irAEs development (p < 0.001, p = 0.002, and p = 0.025, respectively).

Conclusion

In advanced EC, patients with irAEs showed markedly better efficacy in ORR, DCR, PFS, and OS compared with patients without irAEs.
Innate immune checkpoint inhibitor resistance is associated with melanoma sub-types exhibiting invasive and de-differentiated gene expression signatures
Authors: Hossain Sultana Mehbuba , Gimenez Gregory , Stockwell Peter A. , Tsai Peter , Print Cristin G. , Rys Janusz , Cybulska-Stopa Bozena , Ratajska Magda , Harazin-Lechowska Agnieszka , Almomani Suzan , Jackson Christopher , Chatterjee Aniruddha , Eccles Michael R.
Published: September 2022

Melanoma is a highly aggressive skin cancer, which, although highly immunogenic, frequently escapes the body’s immune defences. Immune checkpoint inhibitors (ICI), such as anti-PD1, anti-PDL1, and anti-CTLA4 antibodies lead to reactivation of immune pathways, promoting rejection of melanoma. However, the benefits of ICI therapy remain limited to a relatively small proportion of patients who do not exhibit ICI resistance. Moreover, the precise mechanisms underlying innate and acquired ICI resistance remain unclear. Here, we have investigated differences in melanoma tissues in responder and non-responder patients to anti-PD1 therapy in terms of tumour and immune cell gene-associated signatures. We performed multi-omics investigations on melanoma tumour tissues, which were collected from patients before starting treatment with anti-PD1 immune checkpoint inhibitors. Patients were subsequently categorized into responders and non-responders to anti-PD1 therapy based on RECIST criteria. Multi-omics analyses included RNA-Seq and NanoString analysis. From RNA-Seq data we carried out HLA phenotyping as well as gene enrichment analysis, pathway enrichment analysis and immune cell deconvolution studies. Consistent with previous studies, our data showed that responders to anti-PD1 therapy had higher immune scores (median immune score for responders = 0.1335, median immune score for non-responders = 0.05426, p-value = 0.01, Mann-Whitney U two-tailed exact test) compared to the non-responders. Responder melanomas were more highly enriched with a combination of CD8+ T cells, dendritic cells (p-value = 0.03) and an M1 subtype of macrophages (p-value = 0.001). In addition, melanomas from responder patients exhibited a more differentiated gene expression pattern, with high proliferative- and low invasive-associated gene expression signatures, whereas tumours from non-responders exhibited high invasive- and frequently neural crest-like cell type gene expression signatures. Our findings suggest that non-responder melanomas to anti-PD1 therapy exhibit a de-differentiated gene expression signature, associated with poorer immune cell infiltration, which establishes a gene expression pattern characteristic of innate resistance to anti-PD1 therapy. Improved understanding of tumour-intrinsic gene expression patterns associated with response to anti-PD1 therapy will help to identify predictive biomarkers of ICI response and may help to identify new targets for anticancer treatment, especially with a capacity to function as adjuvants to improve ICI outcomes.
Coagulation parameters predict COVID-19-related thrombosis in a neural network with a positive predictive value of 98%
Authors: de Laat-Kremers Romy , De Jongh Raf , Ninivaggi Marisa , Fiolet Aernoud , Fijnheer Rob , Remijn Jasper , de Laat Bas
Published: September 2022

Thrombosis is a major clinical complication of COVID-19 infection. COVID-19 patients show changes in coagulation factors that indicate an important role for the coagulation system in the pathogenesis of COVID-19. However, the multifactorial nature of thrombosis complicates the prediction of thrombotic events based on a single hemostatic variable. We developed and validated a neural net for the prediction of COVID-19-related thrombosis. The neural net was developed based on the hemostatic and general (laboratory) variables of 149 confirmed COVID-19 patients from two cohorts: at the time of hospital admission (cohort 1 including 133 patients) and at ICU admission (cohort 2 including 16 patients). Twenty-six patients suffered from thrombosis during their hospital stay: 19 patients in cohort 1 and 7 patients in cohort 2. The neural net predicts COVID-19 related thrombosis based on C-reactive protein (relative importance 14%), sex (10%), thrombin generation (TG) time-to-tail (10%), α2-Macroglobulin (9%), TG curve width (9%), thrombin-α2-Macroglobulin complexes (9%), plasmin generation lag time (8%), serum IgM (8%), TG lag time (7%), TG time-to-peak (7%), thrombin-antithrombin complexes (5%), and age (5%). This neural net can predict COVID-19-thrombosis at the time of hospital admission with a positive predictive value of 98%-100%.
Preoperative systemic inflammatory response index predicts long-term outcomes in type B aortic dissection after endovascular repair
Authors: Zhao Yufei , Hong Xiang , Xie Xinsheng , Guo Daqiao , Chen Bin , Fu Weiguo , Wang Lixin
Published: September 2022

Objectives

Inflammation is a hallmark of the initial development and progression of aortic dissection. This study aimed to investigate the value of preoperative inflammatory biomarkers in predicting aorta-related adverse events (AAEs) after thoracic endovascular aortic repair (TEVAR) for type B aortic dissection.

Methods

We included all patients who underwent TEVAR for type B aortic dissection between November 2016 and November 2020 in this single-center, retrospective cohort study. Patients were divided into two groups: the AAEs group (n = 75) and the non-AAEs group (n = 126). Preoperative inflammatory biomarkers were recorded, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), and systemic inflammatory response index (SIRI). Patients were followed-up for the development of AAEs. Prediction accuracy of inflammatory biomarkers for AAEs were evaluated using the area under the receiver operating characteristic curves.

Results

This study included 201 patients, of whom 80.0% were men, with a mean age of 59.1 ± 12.5 years. A total of 75 patients developed AAEs after TEVAR. The AUCs of NLR, MLR, PLR, SII, and SIRI for AAEs were.746,.782,.534,.625 and.807, respectively. Age and SIRI were independent risk factors for the AAEs after TEVAR (HR 3.264, p <.001; HR 4.281, p <.001, respectively). Survival analysis revealed significantly lower AAE-free status in patients with preoperative SIRI > = 4 (p <.001).

Conclusion

Increased preoperative SIRI and age are independent risk factors for AAEs after TEVAR in type B aortic dissection.
Dietary sodium butyrate administration alleviates high soybean meal-induced growth retardation and enteritis of orange-spotted groupers (Epinephelus coioides)
Authors: Ke Liner , Qin Yingmei , Song Tao , Wang Kun , Ye Jidan
Published: September 2022

An 8-week feeding trial was conducted to investigate whether dietary sodium butyrate (SB) administration alleviates growth reduction and enteritis of orange-spotted grouper (Epinephelus coioides) caused by high soybean meal (SBM) feeding. The control diet (FM diet) was formulated to contain 48% protein and 11% fat. Soybean meal was used to replace 60% FM protein in FM diet to prepare a high SBM diet (HSBM diet). Sodium butyrate (SB) at 0.1%, 0.2%, and 0.3% were added to HSBM diets to prepare three diets. Triplicate groups of 30 groupers (initial weight: 33.0 ± 0.3 g) were fed one of the diets twice daily, to apparent satiety. HSBM diets had lowered growth rate and feed efficiency vs FM diets (P <0.05). Growth rate and feed efficiency were improved by dietary SB administration and were in a dose-dependent manner (P <0.05). A similar pattern to the growth rate was observed for plasma LDL-C and gut digestive activity of lipase, trypsin, and protease, but the opposite trend was observed for intestinal contents of D-lactic acid and endotoxin, in response to dietary SB inclusion levels (P >0.05). The muscular thickness in the middle and distal intestines in SB-treated diets were higher than that in HSBM diets (P <0.05). The mRNA levels of intestinal pro-inflammatory cytokines IL-8, IL-1β, IL-12 and TNF-α had a decreasing trend, and the mRNA level of intestinal anti-inflammatory cytokine TGF-β1 had the opposite trend, with increasing SB inclusion levels (P < 0.05). The above results indicate that dietary SB intervention could enhance growth and feed utilization of groupers with SBM-induced enteritis by promoting intestinal digestive enzyme activities, reducing mucosa permeability, maintaining the integrity of intestinal morphology and attenuating the intestinal inflammatory response.
Effects of coastal marsh conversion to shrimp aquaculture ponds on sediment nitrogen fixation
Authors: Liu Cheng , Li Niu , Shao Xuexin , Gao Dengzhou , Xia Jiangbao , Cui Qian , Zhang Dongjie
Published: September 2022

As a common reclamation practice in global estuaries and coasts, conversion of natural wetlands to aquaculture ponds for food demand had significant effects on nitrogen (N) cycling processes. However, the response of sedimemt N fixation process on this conversion remains poorly understood. Here, slury incubation experiment combined with 15N isotope tracing method and molecular analysis technique were used to investigate the influences of conversion of natural marshland to shrimp ponds on sediemt N fixation process. The results showed that conversion of natural marshland to shrimp ponds significantly promoted sediment N fixation rate. The increasing of sediment N fixation rate may be mainly attributed to the change of sediment EC, TOC and Fe2+/Fe3+ rather than the change of N fixation gene abundance. In addition, there was no obvious difference in sediment N fixation rate between 5-year-old shrimp ponds and 18-year-old shrimp ponds, which may be ascribed to the increasing inhibiting effect of inorganic N concentration with reclamation time. Overall, our findings highlighted that conversion of natural wetlands to aquaculture ponds can affect the N budgets in estuarine and coastal regions by altering the sediment N fixation process.
Basin-wide estimates of loggerhead turtle abundance in the Mediterranean Sea derived from line transect surveys
Authors: DiMatteo Andrew , Cañadas Ana , Roberts Jason , Sparks Laura , Panigada Simone , Boisseau Olivier , Moscrop Anna , Fortuna Caterina Maria , Lauriano Giancarlo , Holcer Draško , Peltier Hélène , Ridoux Vincent , Raga Juan Antonia , Tomás Jesús , Broderick Annette C. , Godley Brendan J. , Haywood Julia , March David , Snape Robin , Sagarminaga Ricardo , Hochscheid Sandra
Published: September 2022

Loggerhead turtles are a globally vulnerable species of marine turtle. Broad-scale patterns of distribution and abundance can provide regional managers a tool to effectively conserve and manage this species at basin and sub-basin scales. In this study, combined aerial and shipboard line transect survey data collected between 2003 and 2018 were used to estimate distribution and abundance throughout the Mediterranean Sea. Approximately 230,000 linear kilometers of survey effort, from seven different surveying organizations were incorporated into a generalized additive model to relate loggerhead density on survey segments to environmental conditions. Two spatial density models estimating loggerhead density, abundance, and distribution were generated – one a long-term annual average covering 2003-2018 and another covering the summer of 2018, when a basin-wide aerial survey, the Agreement on the Conservation of Cetaceans of the Black Sea, Mediterranean Sea and Contiguous Atlantic Area Survey Initiative, was performed. Both models were adjusted for availability bias using dive data from loggerhead turtles tagged with time depth recorders. Mean abundance for the long-term average model was estimated as 1,201,845 (CV=0.22). The summer 2018 abundance estimate was 789,244 turtles and covered a smaller area than the long-term average. These estimates represent the first basin-wide estimates of abundance for loggerhead turtles in the Mediterranean not based on demographic models. Both models predicted similar distributions, with higher abundance predicted in the northern Adriatic Sea, central Mediterranean basin, Tyrrhenian Sea, and south of the Balearic Islands. Lower densities were predicted in the eastern Mediterranean Sea and the Aegean Sea. The highest density areas generally did not coincide with previously established adult loggerhead turtle foraging areas, which are typically neritic, indicating the models are predominantly predicting oceanic distributions, where most of the survey effort occurred. Juvenile loggerhead turtles are predominantly oceanic and comprise most of the population, but care must be taken when using these models as they may not accurately predict distribution of neritic foraging areas, where subadult and adult loggerheads can often be found. Despite this limitation, these models represent a major step forward for conservation planning and understanding basin-wide distribution and abundance patterns of this species.
Influence of doubly-hydrogenated oxygen vacancy on the TID effect of MOS devices
Authors: Lu Guangbao , Liu Jun , Zheng Qirong , Li Yonggang
Published: September 2022

The total ionizing dose (TID) effect is one of the main causes of the performance degradation/failure of semiconductor devices under high-energy γ-ray irradiation. In special, the concentration of doubly-hydrogenated oxygen vacancy (a case study of VoγH2) in the oxide layer seriously exacerbates the TID effect. Therefore, we developed a dynamic model of mobile particles and fixed defects by solving the rate equations and Poisson’s equation simultaneously, to reveal the contribution and influence mechanisms of VoγH2 on the TID effect of MOS devices. We found that VoγH2 can directly and indirectly promote the formation of Voγ+ and VoγH+, respectively, which can increase the electric field near the Si/SiO2 interface and reduce the threshold voltage of silicon MOS devices accordingly. Controlling VoγH2 with a concentration below 1014 cm−3 can suppress the adverse TID effects. The results are much helpful for analyzing the microscopic mechanisms of the TID effect and designing new MOS devices with high radiation-hardening.
Prospects and challenges of the electrochemical reduction of iron oxides in alkaline media for steel production
Authors: Lopes Daniela V. , Quina Margarida J. , Frade Jorge R. , Kovalevsky Andrei V.
Published: September 2022

Steelmaking industries have been facing strict decarbonization guidelines. With a net zero carbon emissions target, European policies are expected to be accomplished before 2050. Traditional steelmaking industry still operates by the carbothermic reduction of iron ores for steel production. Consequently, the steel sector is responsible for a large amount of CO2emissions, accounting for up to 9% of the CO2worldwide emissions. In this scope, the electrochemical reduction or electrolysis of iron oxides into metallic iron in alkaline media arises as a promising alternative technology for ironmaking. Significant advantages of this technology include the absence of CO2emissions, non-polluting by-products such as hydrogen and oxygen gases, lower temperature against the conventional approach (∼100°Cversus2000°C) and lower electric energy consumption, where around 6 GJ per ton of iron manufactured can be spared. The present minireview discusses the progress on the electrochemical reduction of iron oxides in alkaline media as a green steelmaking route. A historical overview of the global steelmaking against recent developments and challenges of the novel technology is presented, and the fundamental mechanisms of iron oxide reduction to iron and alternative iron feedstocks are discussed. Factors affecting the Faradaic efficiencies of the alkaline electroreduction of iron oxide suspensions or iron oxide bulk ceramics are also explored, focusing on the concurrent hydrogen evolution reaction. Overall, if scrutinized, this technology may become a breaking point for the steel industry sector.
Molecular characterization of a new SARS-CoV-2 recombinant cluster XAG identified in Brazil
Authors: Silva Thaís de Souza , Salvato Richard Steiner , Gregianini Tatiana Schäffer , Gomes Ighor Arantes , Pereira Elisa Cavalcante , de Oliveira Eneida , de Menezes André Luiz , Barcellos Regina Bones , Godinho Fernanda Marques , Riediger Irina , Debur Maria do Carmo , de Oliveira Cristina Mendes , Ribeiro-Rodrigues Rodrigo , Miyajima Fabio , Dias Fernando Stehling , Abbud Adriano , Monte-Neto Rubens do , Calzavara-Silva Carlos Eduardo , Siqueira Marilda Mendonça , Wallau Gabriel Luz , Resende Paola Cristina , Fernandes Gabriel da Rocha , Alves Pedro
Published: September 2022

Recombination events have been described in the Coronaviridae family. Since the beginning of the SARS-CoV-2 pandemic, a variable degree of selection pressure has acted upon the virus, generating new strains with increased fitness in terms of viral transmission and antibody scape. Most of the SC2 variants of concern (VOC) detected so far carry a combination of key amino acid changes and indels. Recombination may also reshuffle existing genetic profiles of distinct strains, potentially giving origin to recombinant strains with altered phenotypes. However, co-infection and recombination events are challenging to detect and require in-depth curation of assembled genomes and sequencing reds. Here, we present the molecular characterization of a new SARS-CoV-2 recombinant between BA.1.1 and BA.2.23 Omicron lineages identified in Brazil. We characterized four mutations that had not been previously described in any of the recombinants already identified worldwide and described the likely breaking points. Moreover, through phylogenetic analysis, we showed that the newly named XAG lineage groups in a highly supported monophyletic clade confirmed its common evolutionary history from parental Omicron lineages and other recombinants already described. These observations were only possible thanks to the joint effort of bioinformatics tools auxiliary in genomic surveillance and the manual curation of experienced personnel, demonstrating the importance of genetic, and bioinformatic knowledge in genomics.
Immunological imprint on peripheral blood in kidney transplant recipients after two doses of SARS-CoV-2 mRNA vaccination in Japan
Authors: Takiguchi Shinya , Tomita Yusuke , Uehara Saeko , Tateishi Koichiro , Yamamoto Norio , Nakamura Michio
Published: September 2022

The immunological imprint after two doses of severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) mRNA vaccination for patients after kidney transplantation (KTx) remain unclear. This study included KTx recipients and volunteer healthy controls (HCs) who received two doses of SARS-CoV-2 mRNA vaccine (Pfizer BioNTech) from January 2021 to December 2021. We analyzed safety within 21 days after each vaccination dose and compared the immune response in peripheral blood mononuclear cells (PBMCs) between the two groups. No graft rejection was observed throughout this study. Adverse events were generally observed within 5 days. The KTx group exhibited a significantly lower degree of symptoms between doses 1 and 2 (P < 0.001). Increases in activated subsets of T and B cells expressing human leukocyte antigen (HLA)-DR and/or CD38 were observed in the HC group after dose 2 (both P < 0.001), with the greatest increases in HLA-DR+CD8+ T cells and CD38+CD19+ B cells (P = 0.042 and P = 0.031, respectively). In addition, PD1+CD8+ T cells—but not PD1+CD4+ T cells—increased significantly in the HC group (P = 0.027). In the KTx group, however, activated HLA-DR+, CD38+, and PD1+ cells remained at baseline levels. Immunoglobulin (Ig)G against SARS-CoV-2 was detected in only four KTx recipients (13.3%) after dose 2 (P < 0.001). Multivariate logistic regression analyses revealed that ΔHLA-DR+CD8+ T cells and ΔCD38+CD19+ B cells were significantly associated with IgG formation (both P = 0.02). SARS-CoV-2 mRNA vaccine generates impaired cellular and humoral immunity for KTx recipients. Results indicate the need for modified vaccination strategies in immunocompromised KTx recipients.
Medical decision support system using weakly-labeled lung CT scans
Authors: Murillo-González Alejandro , González David , Jaramillo Laura , Galeano Carlos , Tavera Fabby , Mejía Marcia , Hernández Alejandro , Rivera David Restrepo , Paniagua J. G. , Ariza-Jiménez Leandro , Garcés Echeverri José Julián , Diaz León Christian Andrés , Serna-Higuita Diana Lucia , Barrios Wayner , Arrázola Wiston , Mejía Miguel Ángel , Arango Sebastián , Marín Ramírez Daniela , Salinas-Miranda Emmanuel , Quintero O. L.
Published: September 2022

Purpose

Determination and development of an effective set of models leveraging Artificial Intelligence techniques to generate a system able to support clinical practitioners working with COVID-19 patients. It involves a pipeline including classification, lung and lesion segmentation, as well as lesion quantification of axial lung CT studies.

Approach

A deep neural network architecture based on DenseNet is introduced for the classification of weakly-labeled, variable-sized (and possibly sparse) axial lung CT scans. The models are trained and tested on aggregated, publicly available data sets with over 10 categories. To further assess the models, a data set was collected from multiple medical institutions in Colombia, which includes healthy, COVID-19 and patients with other diseases. It is composed of 1,322 CT studies from a diverse set of CT machines and institutions that make over 550,000 slices. Each CT study was labeled based on a clinical test, and no per-slice annotation took place. This enabled a classification into Normal vs. Abnormal patients, and for those that were considered abnormal, an extra classification step into Abnormal (other diseases) vs. COVID-19. Additionally, the pipeline features a methodology to segment and quantify lesions of COVID-19 patients on the complete CT study, enabling easier localization and progress tracking. Moreover, multiple ablation studies were performed to appropriately assess the elements composing the classification pipeline.

Results

The best performing lung CT study classification models achieved 0.83 accuracy, 0.79 sensitivity, 0.87 specificity, 0.82 F1 score and 0.85 precision for the Normal vs. Abnormal task. For the Abnormal vs COVID-19 task, the model obtained 0.86 accuracy, 0.81 sensitivity, 0.91 specificity, 0.84 F1 score and 0.88 precision. The ablation studies showed that using the complete CT study in the pipeline resulted in greater classification performance, restating that relevant COVID-19 patterns cannot be ignored towards the top and bottom of the lung volume.

Discussion

The lung CT classification architecture introduced has shown that it can handle weakly-labeled, variable-sized and possibly sparse axial lung studies, reducing the need for expert annotations at a per-slice level.

Conclusions

This work presents a working methodology that can guide the development of decision support systems for clinical reasoning in future interventionist or prospective studies.
Bitter friends are not always toxic: The loss of acetic acid bacteria and the absence of Komagataeibacter in the gut microbiota of the polyphagous fly Anastrepha ludens could inhibit its development in Psidium guajava in contrast to A. striata and A. fraterculus that flourish in this host
Authors: Ochoa-Sánchez Manuel , Cerqueda-García Daniel , Moya Andrés , Ibarra-Laclette Enrique , Altúzar-Molina Alma , Desgarennes Damaris , Aluja Martín
Published: September 2022

The gut microbiota is key for the homeostasis of many phytophagous insects, but there are few studies comparing its role on host use by stenophagous or polyphagous frugivores. Guava (Psidium guajava) is a fruit infested in nature by the tephritids Anastrepha striata and A. fraterculus. In contrast, the extremely polyphagous A. ludens infests guava only under artificial conditions, but unlike A. striata and the Mexican A. fraterculus, it infests bitter oranges (Citrus x aurantium). We used these models to analyze whether the gut microbiota could explain the differences in host use observed in these flies. We compared the gut microbiota of the larvae of the three species when they developed in guava and the microbiota of the fruit pulp larvae fed on. We also compared the gut microbiota of A. ludens developing in C. x aurantium with the pulp microbiota of this widely used host. The three flies modified the composition of the host pulp microbiota (i.e., pulp the larvae fed on). We observed a depletion of Acetic Acid Bacteria (AAB) associated with a deleterious phenotype in A. ludens when infesting P. guajava. In contrast, the ability of A. striata and A. fraterculus to infest this fruit is likely associated to a symbiotic interaction with species of the Komagataeibacter genus, which are known to degrade a wide spectrum of tannins and polyphenols. The three flies establish genera specific symbiotic associations with AABs. In the case of A. ludens, the association is with Gluconobacter and Acetobacter, but importantly, it cannot be colonized by Komagataeibacter, a factor likely inhibiting its development in guava.
Characterization of a Bacillus velezensis strain isolated from Bolbostemmatis Rhizoma displaying strong antagonistic activities against a variety of rice pathogens
Authors: Zhou Jianping , Xie Yunqiao , Liao Yuhong , Li Xinyang , Li Yiming , Li Shuping , Ma Xiuguo , Lei Shimin , Lin Fei , Jiang Wei , He Yong-Qiang
Published: September 2022

Biological control is an effective measure in the green control of rice diseases. To search for biocontrol agents with broad-spectrum and high efficiency against rice diseases, in this study, a strain of antagonistic bacterium BR-01 with strong inhibitory effect against various rice diseases was isolated from Bolbostemmatis Rhizoma by plate confrontation method. The strain was identified as Bacillus velezensis by morphological observation, physiological and biochemical identification, and molecular characterization by 16S rDNA and gyrB gene sequencing analysis. The confrontation test (dual culture) and Oxford cup assays demonstrated that B. velezensis BR-01 had strong antagonistic effects on Magnaporthe oryzae, Ustilaginoidea virens, Fusarium fujikuroi, Xanthomonas oryzae pv. Oryzicola, and Xanthomonas oryzae pv. oryzae, the major rice pathogens. The genes encoding antimicrobial peptides (ituA, ituD, bmyB, bmyC, srfAA, fenB, fenD, bacA, and bacD) were found in B. velezensis BR-01 by PCR amplification with specific primers. B. velezensis BR-01 could produce protease, cellulase, β-1,3-glucanase, chitinase, indoleacetic acid, siderophore, and 1-aminocyclopropane-1-carboxylate (ACC) deaminase, and might produce three lipopeptide antibiotics, surfactin, iturin, and fengycin based on Liquid chromatography–mass spectrometry (LC-MS) results. Furthermore, the plant assays showed that B. velezensis BR-01 had significant control effects on rice bacterial blight and bacterial leaf streak by pot experiments in greenhouse. In conclusion, B. velezensis BR-01 is a broad-spectrum antagonistic bacterium and has the potential as the ideal biocontrol agent in controlling multiple rice diseases with high efficiency.
Machine learning models identify ferroptosis-related genes as potential diagnostic biomarkers for Alzheimer’s disease
Authors: Deng Yanyao , Feng Yanjin , Lv Zhicheng , He Jinli , Chen Xun , Wang Chen , Yuan Mingyang , Xu Ting , Gao Wenzhe , Chen Dongjie , Zhu Hongwei , Hou Deren
Published: September 2022

Alzheimer’s disease (AD) is a complex, and multifactorial neurodegenerative disease. Previous studies have revealed that oxidative stress, synaptic toxicity, autophagy, and neuroinflammation play crucial roles in the progress of AD, however, its pathogenesis is still unclear. Recent researches have indicated that ferroptosis, an iron-dependent programmed cell death, might be involved in the pathogenesis of AD. Therefore, we aim to screen correlative ferroptosis-related genes (FRGs) in the progress of AD to clarify insights into the diagnostic value. Interestingly, we identified eight FRGs were significantly differentially expressed in AD patients. 10,044 differentially expressed genes (DEGs) were finally identified by differential expression analysis. The following step was investigating the function of DEGs using gene set enrichment analysis (GSEA). Weight gene correlation analysis was performed to explore ten modules and 104 hub genes. Subsequently, based on machine learning algorithms, we constructed diagnostic classifiers to select characteristic genes. Through the multivariable logistic regression analysis, five features (RAF1, NFKBIA, MOV10L1, IQGAP1, FOXO1) were then validated, which composed a diagnostic model of AD. Thus, our findings not only developed genetic diagnostics strategy, but set a direction for further study of the disease pathogenesis and therapy targets.
Computational modeling of trans-synaptic nanocolumns, a modulator of synaptic transmission
Authors: Li Xiaoting , Hémond Gabriel , Godin Antoine G. , Doyon Nicolas
Published: September 2022

Understanding synaptic transmission is of crucial importance in neuroscience. The spatial organization of receptors, vesicle release properties and neurotransmitter molecule diffusion can strongly influence features of synaptic currents. Newly discovered structures coined trans-synaptic nanocolumns were shown to align presynaptic vesicles release sites and postsynaptic receptors. However, how these structures, spanning a few tens of nanometers, shape synaptic signaling remains little understood. Given the difficulty to probe submicroscopic structures experimentally, computer modeling is a useful approach to investigate the possible functional impacts and role of nanocolumns. In our in silico model, as has been experimentally observed, a nanocolumn is characterized by a tight distribution of postsynaptic receptors aligned with the presynaptic vesicle release site and by the presence of trans-synaptic molecules which can modulate neurotransmitter molecule diffusion. In this work, we found that nanocolumns can play an important role in reinforcing synaptic current mostly when the presynaptic vesicle contains a small number of neurotransmitter molecules. Our work proposes a new methodology to investigate in silico how the existence of trans-synaptic nanocolumns, the nanometric organization of the synapse and the lateral diffusion of receptors shape the features of the synaptic current such as its amplitude and kinetics.
Sevoflurane exposure may cause dysplasia of dendritic spines and result in fine motor dysfunction in developing mouse through the PI3K/AKT/mTOR pathway
Authors: Zhong Linhong , Ma Xiaofan , Niu Yixuan , Zhang Lei , Xue Zhenyu , Yan Jia , Jiang Hong
Published: September 2022

Sevoflurane has become one of the most widely used volatile anesthetics in pediatric surgery. However, sevoflurane exposure may interfere with dendritic development and synaptogenesis, resulting in brain function impairment. The PI3K/AKT/mTOR pathway plays an important role in dendritic development and synaptic plasticity. Here we investigated whether sevoflurane exposure would affect the morphological proportions of dendritic spines in developing mouse and explored the role of the change of plasticity of dendritic spines in sevoflurane-induced neurodevelopmental toxicity. The related signaling pathway was also examined. C57BL/6 mice at postnatal day (PND) 7 were exposed to 2% sevoflurane for 3 h. The PI3k/AKT/mTOR agonist IGF-1 or the mTOR phosphorylation inhibitor KU0063794 was intraperitoneally injected 30 min before sevoflurane or O2 exposure at PND7. Hippocampi were harvested 6 h after sevoflurane exposure. Western blotting was applied to measure the protein expression of PI3K/AKT/mTOR pathway phosphorylation. At PND14, brains from all groups were harvested for Golgi staining, and the morphology of dendritic spines of hippocampal neurons was observed by an oil immersion lens. When the mice grew to adolescence (PND48), fine motor function was measured by the Beam walking test. Here we showed that exposure to 2% sevoflurane for 3 h decreased the proportion of thin dendritic spines and increased the proportion of mushroom dendritic spines, but not changed the density of the dendritic spines. Sevoflurane exposure also suppressed the phosphorylation of the PI3K/AKT/mTOR pathway in immature mice hippocampi, and eventually led to long-term fine motor dysfunction. Meanwhile, IGF-1 pretreatment could rescue and KU0063794 pretreatment could aggravate the impairment induced by sevoflurane. In conclusion, sevoflurane exposure may cause a change of proportions of the types of dendritic spines through impacting the phosphorylation expression of the PI3K/AKT/mTOR pathway, and eventually led to long-term fine motor dysfunction in developing mouse.
Efficacy of nGVS to improve postural stability in people with bilateral vestibulopathy: A systematic review and meta-analysis
Authors: McLaren Ruth , Smith Paul F. , Taylor Rachael L. , Ravindran Shobika , Rashid Usman , Taylor Denise
Published: September 2022

Objective

Noisy galvanic vestibular stimulation (nGVS) has been used to boost vestibular afferent information to the central nervous system. This has the potential to improve postural control for people for whom vestibular signals are weak, such as in bilateral vestibulopathy (BVP). The aim of this systematic review and meta-analysis is to investigate the evidence for nGVS as a modality to improve postural control in people with BVP.

Methods

A comprehensive systematic search was conducted of five databases up to July 2022 to find studies applying nGVS to people with BVP, with the aim of improving postural control. Two independent reviewers screened and identified eligible studies, completed a risk of bias evaluation (Cochrane) and extracted relevant data. The standardized mean difference (SMD) based on Hedges' g was calculated as a measure of effect size for the primary outcome measure that best identified postural control, and a forest plot generated.

Results

Seven studies met the eligibility criteria, with five being suitable for meta-analysis. Meta-analysis revealed a moderate effect in favor of nGVS improving postural control during standing and walking [pooled SMD = 0.47 95% CI (0.25, 0.7)]. nGVS-mediated improvements in postural control were most evident in observations of reduced sway velocity when standing on a firm surface with eyes closed, and in the reduced variability of gait parameters, particularly those measuring lateral stability.

Conclusions

Coincident nGVS in people with BVP improves postural control during standing and walking. This improvement appears to be context specific, in that vestibular augmentation is most effective in situations where visual inputs are limited, and where reliable context specific proprioceptive cues are available. Further research is warranted investigating additional circumstances in which nGVS improves postural control, including investigating the residual, and sustained effects of nGVS.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=342147, identifier: 342147.
New insights on single-neuron selectivity in the era of population-level approaches
Authors: Vaccari Francesco Edoardo , Diomedi Stefano , Filippini Matteo , Hadjidimitrakis Kostas , Fattori Patrizia
Published: September 2022

In the past, neuroscience was focused on individual neurons seen as the functional units of the nervous system, but this approach fell short over time to account for new experimental evidence, especially for what concerns associative and motor cortices. For this reason and thanks to great technological advances, a part of modern research has shifted the focus from the responses of single neurons to the activity of neural ensembles, now considered the real functional units of the system. However, on a microscale, individual neurons remain the computational components of these networks, thus the study of population dynamics cannot prescind from studying also individual neurons which represent their natural substrate. In this new framework, ideas such as the capability of single cells to encode a specific stimulus (neural selectivity) may become obsolete and need to be profoundly revised. One step in this direction was made by introducing the concept of “mixed selectivity,” the capacity of single cells to integrate multiple variables in a flexible way, allowing individual neurons to participate in different networks. In this review, we outline the most important features of mixed selectivity and we also present recent works demonstrating its presence in the associative areas of the posterior parietal cortex. Finally, in discussing these findings, we present some open questions that could be addressed by future studies.
Effects of gliadin and glutenin on the hygroscopicity of freeze-dried apple powders
Authors: Yang Xiaotong , Wei Yujie , Liu Jing , Liang Hongshan , Li Bin , Li Jing
Published: September 2022

Wheat gluten addition in freeze-dried apple powders can effectively prevent their undesirable moisture adsorption and caking during long-term storage, but the working mechanism of wheat gluten had not been expounded. Therefore, such anti-hygroscopicity effects were systematically investigated from the perspective of wheat gluten major components: gliadin and glutenin. Herein, moisture adsorption curve/isotherm, morphology, and moisture migration law of the protein-added apple powders were analyzed at varied storage humidities. Results showed that Peleg, GAB, and Ferro-Fontan models could describe the moisture adsorption process of gliadin-added and glutenin-added freeze-dried apple powder. By comparing the model fitting results, it was found that the fitting degree of moisture adsorption isotherm of the sample increased with the increase of water activity, and the imitative effect of the Ferro-Fontan model was the best. According to the result of the fitting prediction, the equilibrium moisture content of glutenin-added apple powder was 4.7% lower than that of gliadin-added apple powder at 25°C and 75% relative humidity (RH). Type III moisture adsorption isotherms were observed for gliadin-added apple powder, while that of glutenin-added apple powder was type II. In addition, the gliadin-added apple powder demonstrated better fluidity and lower water migration when the relative humidity (RH) of the environment was lower than 58%. Once above this RH value, the protecting effect of glutenin was more obvious. These findings not only elucidate the anti-hygroscopic mechanism of wheat gluten in the processing of apple powder, but also provide a new idea for improving the quality of apple powder and the development of new anti-hygroscopic agents.
Infodemiology on diet and weight loss behavior before and during COVID-19 pandemic in Indonesia: Implication for public health promotion
Authors: Ramadhani Ira Dewi , Latifah Leny , Prasetyo Andjar , Khairunnisa Marizka , Wardhani Yurika Fauzia , Yunitawati Diah , Fahlevi Mochammad
Published: September 2022

Objective

This study set out to explore public interest through information search trends on diet and weight loss before and during the COVID-19 pandemic in Indonesia.

Methods

The Google Trends database was evaluated for the relative internet search popularity on diet-related search terms, including top and rising diet-related terms. The search range was before and during the COVID-19 pandemic (April 2018 to January 2022) in the Indonesia region. We analyzed the Relative Search Volume (RSV) data using line charts, correlation, and comparison tests.

Results

Search queries of “lose weight” was higher during the pandemic (58.34 ± 9.70 vs. 68.69 ± 7.72; p<0.05). No difference was found in diet-related searches before and after the pandemic. Public interest in the diet was higher after Eid al-Fitr (Muslims break fasting celebration day) and after the new year. Many fad diet (FD) terms were found on the top and rising terms.

Conclusion

After Eid al-Fitr and the new year were susceptible times for promoting a healthy diet in Indonesia. Potential need found before those times for education in inserting healthy food among fatty and sugary menus related to holidays and celebrations. Higher interest in “lose weight” was relevant to heightened obesity risk during the social restriction and heightened COVID-19 morbidity and mortality due to obesity. The high interest for rapid weight loss through FD needs to be resolved by promoting healthy diets with a more captivating message and messenger, like consistently using top terms in the keywords of the official healthy diet guidance. Future research could explore the relationship between diet and other behavior or with non-communicable diseases.
The combination of sarcopenia and biochemical factors can predict the survival of hepatocellular carcinoma patients receiving transarterial chemoembolization
Authors: Chien Tzu-Ping , Huang Song-Fong , Chan Wen-Hui , Pan Kuang-Tse , Yu Ming-Chin , Lee Wei-Chen , Tsai Hsin-I , Lin Po-Ting , Chen Hsing-Yu , Chen Jui-Hsuan , Lee Chao-Wei
Published: September 2022

Background

Transarterial chemoembolization(TACE) is the suggested treatment for hepatocellular carcinoma (HCC) not amenable to curative treatments. We investigated the role of sarcopenia on overall survival in HCC patients receiving TACE and proposed a new prognostic scoring system incorporating sarcopenia.

Materials and methods

We retrospectively analyzed 260 HCC patients who received TACE between 2010 and 2015. Total psoas muscle was measured on a cross-sectional CT image before the first TACE session. Sarcopenia was defined by the pre-determined sex-specific cutoff value. We assessed the impact of sarcopenia and other biochemical factors on the overall survival and compared the new scoring system with other prognostic scoring systems.

Results

One hundred and thirty patients (50%) were classified as sarcopenia before the first TACE. They were older with a higher male tendency and a significantly lower body mass index (BMI). Cox regression multivariate analysis demonstrated that sarcopenia, multiple tumors, maximal tumor diameter≥ 5cm, major venous thrombosis, sarcopenia, AFP ≥ 200 ng/ml, and albumin<3.5mg/dL were independent poor prognostic factors for overall survival in HCC patients receiving TACE. Our scoring system comprising these factors outperformed other major scoring systems in terms of predicting survival after TACE.

Conclusion

The current study demonstrated that sarcopenia was an independent prognostic factor for HCC undergoing TACE therapy. Our newly developed scoring system could effectively predict patient survival after TACE. Physicians could, based on the current score model, carefully select candidate patients for TACE treatment in order to optimize their survival. Further studies are warranted to validate our findings.