bluuebunny/crossref_metadata_2025 huggingface dataset:
The prospect of universal coronavirus immunity: characterization of reciprocal and non-reciprocal T cell responses against SARS-CoV2 and common human coronaviruses
Authors: Soni Mithil K. , Migliori Edoardo , Fu Jianing , Assal Amer , Chan Hei Ton , Pan Jian , Khatiwada Prabesh , Ciubotariu Rodica , May Michael S. , Pereira Marcus R. , De Giorgi Valeria , Sykes Megan , Mapara Markus Y. , Muranski Pawel J.
Published: October 2023

T cell immunity plays a central role in clinical outcomes of Coronavirus Infectious Disease 2019 (COVID-19) and T cell-focused vaccination or cellular immunotherapy might provide enhanced protection for some immunocompromised patients. Pre-existing T cell memory recognizing SARS-CoV-2 antigens antedating COVID-19 infection or vaccination, may have developed as an imprint of prior infections with endemic non-SARS human coronaviruses (hCoVs) OC43, HKU1, 229E, NL63, pathogens of “common cold”. In turn, SARS-CoV-2-primed T cells may recognize emerging variants or other hCoV viruses and modulate the course of subsequent hCoV infections. Cross-immunity between hCoVs and SARS-CoV-2 has not been well characterized. Here, we systematically investigated T cell responses against the immunodominant SARS-CoV-2 spike, nucleocapsid and membrane proteins and corresponding antigens from α- and β-hCoVs among vaccinated, convalescent, and unexposed subjects. Broad T cell immunity against all tested SARS-CoV-2 antigens emerged in COVID-19 survivors. In convalescent and in vaccinated individuals, SARS-CoV-2 spike-specific T cells reliably recognized most SARS-CoV-2 variants, however cross-reactivity against the omicron variant was reduced by approximately 47%. Responses against spike, nucleocapsid and membrane antigens from endemic hCoVs were significantly more extensive in COVID-19 survivors than in unexposed subjects and displayed cross-reactivity between α- and β-hCoVs. In some, non-SARS hCoV-specific T cells demonstrated a prominent non-reciprocal cross-reactivity with SARS-CoV-2 antigens, whereas a distinct anti-SARS-CoV-2 immunological repertoire emerged post-COVID-19, with relatively limited cross-recognition of non-SARS hCoVs. Based on this cross-reactivity pattern, we established a strategy for in-vitro expansion of universal anti-hCoV T cells for adoptive immunotherapy. Overall, these results have implications for the future design of universal vaccines and cell-based immune therapies against SARS- and non-SARS-CoVs.
The oesophageal adenocarcinoma tumour immune microenvironment dictates outcomes with different modalities of neoadjuvant therapy – results from the AGITG DOCTOR trial and the cancer evolution biobank
Authors: Lonie James M. , Brosda Sandra , Bonazzi Vanessa F. , Aoude Lauren G. , Patel Kalpana , Brown Ian , Sharma Sowmya , Lampe Guy , Addala Venkateswar , Koufariotis Lambros T. , Wood Scott , Waddell Nicola , Dolcetti Riccardo , Barbour Andrew P.
Published: October 2023

A plateau in treatment effect can be seen for the current ‘one-size-fits-all’ approach to oesophageal adenocarcinoma (OAC) management using neoadjuvant chemoradiotherapy (nCRT) or chemotherapy (nCT). In OAC, the tumour microenvironment (TME) is largely immunosuppressed, however a subgroup of patients with an immune-inflamed TME exist and show improved outcomes. We aimed to understand the overall immune-based mechanisms underlying treatment responses and patient outcomes in OAC, and in relation to neoadjuvant therapy modality. This study included 107 patients; 68 patients were enrolled in the Australian Gastro-Intestinal Trials Group sponsored DOCTOR Trial, and 38 patients were included from the Cancer Evolution Biobank. Matched pre-treatment and post-treatment tumour biopsies were used to perform multi-modality analysis of the OAC TME including NanoString mRNA expression analysis, multiplex and single colour immunohistochemistry (IHC), and peripheral blood mononuclear cell analysis of tumour-antigen specific T cell responses. Patients with the best clinicopathological outcomes and survival had an immune-inflamed TME enriched with anti-tumour immune cells and pathways. Those with the worst survival showed a myeloid T regulatory cell enriched TME, with decreased CD8+ cell infiltration and increased pro-tumour immune cells. Multiplex IHC analysis identified that high intra-tumoural infiltration of CD8+ cells, and low infiltration with CD163+ cells was associated with improved survival. High tumour core CD8+ T cell infiltration, and a low tumour margin infiltration of CD163+ cells was also associated with improved survival. nCRT showed improved survival compared with nCT for patients with low CD8+, or high CD163+ cell infiltration. Poly-functional T cell responses were seen with tumour-antigen specific T cells. Overall, our study supports the development of personalised therapeutic approaches based on the immune microenvironment in OAC. Patients with an immune-inflamed TME show favourable outcomes regardless of treatment modality. However, in those with an immunosuppressed TME with CD163+ cell infiltration, treatment with nCRT can improve outcomes. Our findings support previous studies into the TME of OAC and with more research, immune based biomarker selection of treatment modality may lead in improved outcomes in this deadly disease.
Sulindac sulfide as a non-immune suppressive γ-secretase modulator to target triple-negative breast cancer
Authors: Hossain Fokhrul , Ucar Deniz A. , Monticone Giulia , Ran Yong , Majumder Samarpan , Larter Kristina , Luu Hanh , Wyczechowska Dorota , Heidari Soroor , Xu Keli , Shanthalingam Sudarvili , Matossian Margarite , Xi Yaguang , Burow Matthew , Collins-Burow Bridgette , Del Valle Luis , Hicks Chindo , Zabaleta Jovanny , Golde Todd , Osborne Barbara , Miele Lucio
Published: October 2023

Introduction

Triple-negative breast cancer (TNBC) comprises a heterogeneous group of clinically aggressive tumors with high risk of recurrence and metastasis. Current pharmacological treatment options remain largely limited to chemotherapy. Despite promising results, the efficacy of immunotherapy and chemo-immunotherapy in TNBC remains limited. There is strong evidence supporting the involvement of Notch signaling in TNBC progression. Expression of Notch1 and its ligand Jagged1 correlate with poor prognosis. Notch inhibitors, including g-secretase inhibitors (GSIs), are quite effective in preclinical models of TNBC. However, the success of GSIs in clinical trials has been limited by their intestinal toxicity and potential for adverse immunological effects, since Notch plays key roles in T-cell activation, including CD8 T-cells in tumors. Our overarching goal is to replace GSIs with agents that lack their systemic toxicity and ideally, do not affect tumor immunity. We identified sulindac sulfide (SS), the active metabolite of FDA-approved NSAID sulindac, as a potential candidate to replace GSIs.

Methods

We investigated the pharmacological and immunotherapeutic properties of SS in TNBC models in vitro, ex-vivo and in vivo.

Results

We confirmed that SS, a known γ-secretase modulator (GSM), inhibits Notch1 cleavage in TNBC cells. SS significantly inhibited mammosphere growth in all human and murine TNBC models tested. In a transplantable mouse TNBC tumor model (C0321), SS had remarkable single-agent anti-tumor activity and eliminated Notch1 protein expression in tumors. Importantly, SS did not inhibit Notch cleavage in T- cells, and the anti-tumor effects of SS were significantly enhanced when combined with a-PD1 immunotherapy in our TNBC organoids and in vivo.

Discussion

Our data support further investigation of SS for the treatment of TNBC, in conjunction with chemo- or -chemo-immunotherapy. Repurposing an FDA-approved, safe agent for the treatment of TNBC may be a cost-effective, rapidly deployable therapeutic option for a patient population in need of more effective therapies.
Mitochondrial antiviral signaling protein: a potential therapeutic target in renal disease
Authors: Wu Meng , Pei Zhiyin , Long Guangfeng , Chen Hongbing , Jia Zhanjun , Xia Weiwei
Published: October 2023

Mitochondrial antiviral signaling protein (MAVS) is a key innate immune adaptor on the outer mitochondrial membrane that acts as a switch in the immune signal transduction response to viral infections. Some studies have reported that MAVS mediates NF-κB and type I interferon signaling during viral infection and is also required for optimal NLRP3 inflammasome activity. Recent studies have reported that MAVS is involved in various cancers, systemic lupus erythematosus, kidney diseases, and cardiovascular diseases. Herein, we summarize the structure, activation, pathophysiological roles, and MAVS-based therapies for renal diseases. This review provides novel insights into MAVS’s role and therapeutic potential in the pathogenesis of renal diseases.
Mesothelin expression remodeled the immune-matrix tumor microenvironment predicting the risk of death in patients with malignant pleural mesothelioma
Authors: Qualiotto Aline Nery , Baldavira Camila Machado , Balancin Marcelo , Ab’Saber Alexandre , Takagaki Teresa , Capelozzi Vera Luiza
Published: October 2023

Background

The combination of immunobiological agents with immune checkpoint proteins is a promising treatment for malignant pleural mesothelioma (MPM). Mesothelin and anti-PD-L1 antibody-drug conjugates specifically target malignant neoplastic cells, inhibit the migration and invasion of neoplastic cells, and restore the immune landscape. In this study, we confirmed the importance of mesothelin and examined the relationship between mesothelin and the immune landscape of the tumor microenvironment (TME) in two MPM cohorts.

Methods

The discovery cohort included 82 MPM cases. Tissue microarray slides were generated, and samples were processed for hematoxylin & eosin staining, immunohistochemistry, and immunofluorescence assays. The relationship between mesothelin, biomarkers of histogenesis, histological aggressiveness, PD-L1, immune cells (CD4, CD8, CD20, CD68), and collagen type I and type V fibers was evaluated by quantitative digital analyses. The outcome was the survival time until death from disease recurrence. The exploratory cohort included 87 malignant mesothelioma (MESO) patients from The Cancer Genome Atlas database.

Results

Most patients were male (70.7%) with a history of asbestos exposure (53.7%) and with the epithelioid subtype (89%). Surgical resection was performed in 85.4% of patients, and 14.6% received chemotherapy; 59.8% of patients died from disease extension to the mediastinum. Low tumor mesothelin expression was associated with tumor necrosis and nuclear grade 1, whereas high mesothelin expression was significantly associated with the epithelioid histotype and high density of T cells CD8+, macrophages CD68+, and collagen type I fibers. Cox multivariate analysis showed a high risk of death for non-operated patients [hazard ratio (HR), 3.42 (1.15–10.16)] with low tumor mesothelin levels [HR, 2.58 (1.09–6.10)] and high PD-L1 and low infiltration of T cells CD4+ [HR, 3.81 (1.58–9.18)]. In the exploratory cohort, low mesothelin and high COL1A1 and COL5A1 expression were associated with poor overall survival.

Conclusion

Tumor mesothelin expression associated with the TME immune landscape predicts the risk of death for patients with MPM and could be a new target for immunotherapy in MPM.
Analysis of mangrove dynamics and its protection effect in the Guangdong-Hong Kong-Macao Coastal Area based on the Google Earth Engine platform
Authors: Zeng Jiali , Ai Bin , Jian Zhuokai , Ye Mingzhen , Zhao Jun , Sun Shaojie
Published: October 2023

Mangroves are rapidly disappearing in several places of the world, and mangrove dynamics are becoming important evidence of ecological restoration and protection along the coast. Mangrove populations in the Guangdong-Hong Kong-Macao Coastal Area (GCA) have experienced a substantial impact of anthropogenic pressure in the 20th century. Monitoring its spatio-temporal variation and protection effect has been regarded as an important task in coastal management. In this study, we provided the comprehensive assessment of mangrove dynamics in the GCA and typical sites from 1988 to 2020 at eight-year intervals. At this time interval, mangrove ecosystems changed significantly as a result of global warming and human impacts. The geographical distribution of mangroves was obtained by applying the Random Forest (RF) classifier on Landsat images with a 30 m spatial resolution on the Google Earth Engine (GEE) platform, based on relevant indices such as Normalized Difference Mangrove Index (NDMI), Normalized Difference Vegetation Index (NDVI), Normalized Difference Suspended Sediment Index (NDSSI), Normalized Difference Built-up Index (NDBI) and Soil Adjusted Vegetation Index (SAVI). Quantitative evaluation indicated that overall accuracy of over 88% was achieved with RF classifier for mangrove extraction. In the GCA, mangrove area was 95.4 km2 in 1988, dropped to 71.4 km2 in 1996, then expanded to 127.5 km2 in 2020, with an overall dynamic rate of 1.02%. In typical sites, mangroves show a similar trend to the overall area. The subsequent mangrove growth is attributed to reserve establishment, accompanied by the expansion of replanted mangrove areas. In the GCA, provincial-level and county-level reserves show a high rate of mangrove dynamic, while national-level reserves display a low rate of mangrove dynamic. The dynamic rate in reserves of the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) is higher than other parts of the GCA, indicating that the effect of mangrove protection is better in the GBA. The results of this study will provide scientific foundations for the sustainable management and conservation of mangrove ecosystem, the quantification of ecosystem services (such as coastal protection and carbon storage), as well as the formulation of strategies for mitigating and adapting to climate change.
The effect of multiple outgrowths from bronchial tissue explants on progenitor/stem cell number in primary bronchial epithelial cell cultures from smokers and patients with COPD
Authors: Bostancieri Nuray , Bakir Kemal , Kul Seval , Eralp Ayhan , Kayalar Ozgecan , Konyalilar Nur , Rajabi Hadi , Yuncu Mehmet , Yildirim Ali Önder , Bayram Hasan
Published: October 2023

Background

Although studies suggest a deficiency in stem cell numbers in chronic airway diseases such as chronic obstructive pulmonary disease (COPD), the role of bronchial epithelial progenitor/stem (P/S) cells is not clear. The objectives of this study were to investigate expression of progenitor/stem (P/S) cell markers, cytokeratin (CK) 5, CK14 and p63 in bronchial epithelial explants and cell cultures obtained from smokers with and without COPD following multiple outgrowths, and to study this effect on bronchial epithelial cell (BEC) proliferation.

Methods

Bronchial epithelial explants were dissected from lung explants and cultured on coverslips. Confluent cultures were obtained after 3–4 weeks’ (transfer, Tr1), explants were then transferred and cultured for a second (Tr2) and third (Tr3) time, respectively. At each stage, expression of CK5, CK14 and p63 in explants and BEC were determined by immunostaining. In parallel experiments, outgrowing cells from explants were counted after 4wks, and explants subsequently transferred to obtain new cultures for a further 3 times.

Results

As the transfer number advanced, CK5, CK14 and p63 expression was decreased in both explants and BEC from both smokers without COPD and patients with COPD, with a more pronounced decrease in BEC numbers in the COPD group. Total cell numbers cultured from explants were decreased with advancing outgrowth number in both groups. Smoking status and lung function parameters were correlated with reduced P/S marker expression and cell numbers.

Conclusion

Our findings suggest that the number of P/S cells in airway epithelium may play a role in the pathogenesis of COPD, as well as a role in the proliferation of airway epithelial cells, in vitro.
Interaction between intratumoral microbiota and tumor mediates the response of neoadjuvant therapy for rectal cancer
Authors: Sun Lejia , Qu Jiangming , Ke Xindi , Zhang Yue , Xu Hengyi , Lv Ning , Leng Jingze , Zhang Yanbin , Guan Ai , Feng Yifei , Sun Yueming
Published: October 2023

Background

Previous observations have demonstrated that the response to neoadjuvant chemoradiotherapy (nCRT) is highly variable in patients with locally advanced rectal cancer (LARC). Recent studies focusing on the intratumoral microbiota of colorectal cancer have revealed its role in oncogenesis and tumor progression. However, limited research has focused on the influence of intratumoral microbiota on the nCRT of LARC.

Methods

We explored the microbial profiles in the tumor microenvironment of LARC using RNA-seq data from a published European cohort. Microbial signatures were characterized in pathological complete response (pCR) and non-pCR groups. Multi-omics analysis was performed between intratumor microbiomes and transcriptomes.

Results

Microbial α and β diversity were significantly different in pCR and non-pCR groups. Twelve differential microbes were discovered between the pCR and non-pCR groups, six of which were related to subclusters of cancer-associated fibroblasts (CAFs) associated with extracellular matrix formation. A microbial risk score based on the relative abundance of seven differential microbes had predictive value for the nCRT response (AUC = 0.820, p < 0.001).

Conclusion

Our study presents intratumoral microbes as potential independent predictive markers for the response of nCRT to LARC and demonstrates the underlying mechanism by which the interaction between intratumoral microbes and CAFs mediates the response to nCRT.
Organic vs. conventional: impact of cultivation treatments on the soil microbiota in the vineyard
Authors: Colautti Andrea , Civilini Marcello , Contin Marco , Celotti Emilio , Iacumin Lucilla
Published: October 2023

The aim of this study was to compare the effects of two vineyard management practices on the soil and its associated microbiota. The experiments were conducted in two adjacent plots, one completely organically managed and the other conventionally managed in terms of phytosanitary treatments but fertilized with organic amendments. The chemical soil analyses were correlated to the prokaryotic and fungal communities, which were studied using the metabarcoding technique. The main difference between the two treatments was a significantly higher amount of Cu in the organic managed vineyard soil, while conventional managed soil presented higher concentration of Na and Mg and was also associated with higher pH values. Despite these differences, no significant diversities were observed on soil biodiversity and microbial composition considering alpha and beta diversity metrics. However, the percentages of some phyla analyzed individually differed significantly between the two managements. Analyzing the metabolisms of these phyla, it was discovered an increment of species correlated to soils with higher organic matter content or land not used for agricultural purposes in the organic treated soil. The findings indicate that, despite the use of copper-based phytosanitary products, there was no degradation and loss of biodiversity in the organic soil microbial population compared to conventional management with the same type of fertilization, and the observed microbial population was more similar to that of natural soils.
Metabolism-linked methylotaxis sensors responsible for plant colonization in Methylobacterium aquaticum strain 22A
Authors: Tani Akio , Masuda Sachiko , Fujitani Yoshiko , Iga Toshiki , Haruna Yuuki , Kikuchi Shiho , Shuaile Wang , Lv Haoxin , Katayama Shiori , Yurimoto Hiroya , Sakai Yasuyoshi , Kato Junichi
Published: October 2023

Motile bacteria take a competitive advantage in colonization of plant surfaces to establish beneficial associations that eventually support plant health. Plant exudates serve not only as primary growth substrates for bacteria but also as bacterial chemotaxis attractants. A number of plant-derived compounds and corresponding chemotaxis sensors have been documented, however, the sensors for methanol, one of the major volatile compounds released by plants, have not been identified. Methylobacterium species are ubiquitous plant surface-symbiotic, methylotrophic bacteria. A plant-growth promoting bacterium, M. aquaticum strain 22A exhibits chemotaxis toward methanol (methylotaxis). Its genome encodes 52 methyl-accepting chemotaxis proteins (MCPs), among which we identified three MCPs (methylotaxis proteins, MtpA, MtpB, and MtpC) responsible for methylotaxis. The triple gene mutant of the MCPs exhibited no methylotaxis, slower gathering to plant tissues, and less efficient colonization on plants than the wild type, suggesting that the methylotaxis mediates initiation of plant-Methylobacterium symbiosis and engages in proliferation on plants. To examine how these MCPs are operating methylotaxis, we generated multiple gene knockouts of the MCPs, and Ca2+-dependent MxaFI and lanthanide (Ln3+)-dependent XoxF methanol dehydrogenases (MDHs), whose expression is regulated by the presence of Ln3+. MtpA was found to be a cytosolic sensor that conducts formaldehyde taxis (formtaxis), as well as methylotaxis when MDHs generate formaldehyde. MtpB contained a dCache domain and exhibited differential cellular localization in response to La3+. MtpB expression was induced by La3+, and its activity required XoxF1. MtpC exhibited typical cell pole localization, required MxaFI activity, and was regulated under MxbDM that is also required for MxaF expression. Strain 22A methylotaxis is realized by three independent MCPs, two of which monitor methanol oxidation by Ln3+-regulated MDHs, and one of which monitors the common methanol oxidation product, formaldehyde. We propose that methanol metabolism-linked chemotaxis is the key factor for the efficient colonization of Methylobacterium on plants.
Host genetic background rather than diet-induced gut microbiota shifts of sympatric black-necked crane, common crane and bar-headed goose
Authors: Wang Yeying , Long Zhengmin , Zhang Yu , Li Xianyu , Zhang Xu , Su Haijun
Published: October 2023

Introduction

Gut microbiota of wild birds are affected by many factors, and host genetic background and diet are considered to be two important factors affecting their structure and function.

Methods

In order to clarify how these two factors influence the gut microbiota, this study selected the sympatric and closely related and similar-sized Black-necked Crane (Grus nigricollis) and Common Crane (Grus grus), as well as the distantly related and significantly different-sized Bar-headed Goose (Anser indicus). The fecal samples identified using sanger sequencing as the above three bird species were subjected to high-throughput sequencing of rbcL gene and 16S rRNA gene to identify the feeding types phytophagous food and gut microbiota.

Results

The results showed significant differences in food diversity between black-necked cranes and Common Cranes, but no significant differences in gut microbiota, Potatoes accounted for approximately 50% of their diets. Bar-headed Geese mainly feed on medicinal plants such as Angelica sinensis, Alternanthera philoxeroides, and Ranunculus repens. Black-necked cranes and Common Cranes, which have a high-starch diet, have a similar degree of enrichment in metabolism and synthesis functions, which is significantly different from Bar-headed Geese with a high-fiber diet. The differences in metabolic pathways among the three bird species are driven by food. The feeding of medicinal plants promotes the health of Bar-headed Geese, indicating that food influences the functional pathways of gut microbiota. Spearman analysis showed that there were few gut microbiota related to food, but almost all metabolic pathways were related to food.

Conclusion

The host genetic background is the dominant factor determining the composition of the microbiota. Monitoring the changes in gut microbiota and feeding types of wild birds through bird feces is of great reference value for the conservation of other endangered species.
Unraveling the functional instability of bacterial consortia in crude oil degradation via integrated co-occurrence networks
Authors: Li Ping , Liang Xiaolong , Shi Rongjiu , Wang Yongfeng , Han Siqin , Zhang Ying
Published: October 2023

Introduction

Soil ecosystems are threatened by crude oil contamination, requiring effective microbial remediation. However, our understanding of the key microbial taxa within the community, their interactions impacting crude oil degradation, and the stability of microbial functionality in oil degradation remain limited.

Methods

To better understand these key points, we enriched a crude oil-degrading bacterial consortium generation 1 (G1) from contaminated soil and conducted three successive transfer passages (G2, G3, and G4). Integrated Co-occurrence Networks method was used to analyze microbial species correlation with crude oil components across G1-G4.

Results and discussion

In this study, G1 achieved a total petroleum hydrocarbon (TPH) degradation rate of 32.29% within 10 days. Through three successive transfer passages, G2-G4 consortia were established, resulting in a gradual decrease in TPH degradation to 23.14% at the same time. Specifically, saturated hydrocarbon degradation rates ranged from 18.32% to 14.17% among G1-G4, and only G1 exhibited significant aromatic hydrocarbon degradation (15.59%). Functional annotation based on PICRUSt2 and FAPROTAX showed that functional potential of hydrocarbons degradation diminished across generations. These results demonstrated the functional instability of the bacterial consortium in crude oil degradation. The relative abundance of the Dietzia genus showed the highest positive correlation with the degradation efficiency of TPH and saturated hydrocarbons (19.48, 18.38, p < 0.05, respectively), Bacillus genus demonstrated the highest positive correlation (21.94, p < 0.05) with the efficiency of aromatic hydrocarbon degradation. The key scores of Dietzia genus decreased in successive generations. A significant positive correlation (16.56, p < 0.05) was observed between the Bacillus and Mycetocola genera exclusively in the G1 generation. The decline in crude oil degradation function during transfers was closely related to changes in the relative abundance of key genera such as Dietzia and Bacillus as well as their interactions with other genera including Mycetocola genus. Our study identified key bacterial genera involved in crude oil remediation microbiome construction, providing a theoretical basis for the next step in the construction of the oil pollution remediation microbiome.
Genetic background influences the 5XFAD Alzheimer's disease mouse model brain proteome
Authors: Hurst Cheyenne D. , Dunn Amy R. , Dammer Eric B. , Duong Duc M. , Shapley Sarah M. , Seyfried Nicholas T. , Kaczorowski Catherine C. , Johnson Erik C. B.
Published: October 2023

There is an urgent need to improve the translational validity of Alzheimer's disease (AD) mouse models. Introducing genetic background diversity in AD mouse models has been proposed as a way to increase validity and enable the discovery of previously uncharacterized genetic contributions to AD susceptibility or resilience. However, the extent to which genetic background influences the mouse brain proteome and its perturbation in AD mouse models is unknown. In this study, we crossed the 5XFAD AD mouse model on a C57BL/6J (B6) inbred background with the DBA/2J (D2) inbred background and analyzed the effects of genetic background variation on the brain proteome in F1 progeny. Both genetic background and 5XFAD transgene insertion strongly affected protein variance in the hippocampus and cortex (n = 3,368 proteins). Protein co-expression network analysis identified 16 modules of highly co-expressed proteins common across the hippocampus and cortex in 5XFAD and non-transgenic mice. Among the modules strongly influenced by genetic background were those related to small molecule metabolism and ion transport. Modules strongly influenced by the 5XFAD transgene were related to lysosome/stress responses and neuronal synapse/signaling. The modules with the strongest relationship to human disease—neuronal synapse/signaling and lysosome/stress response—were not significantly influenced by genetic background. However, other modules in 5XFAD that were related to human disease, such as GABA synaptic signaling and mitochondrial membrane modules, were influenced by genetic background. Most disease-related modules were more strongly correlated with AD genotype in the hippocampus compared with the cortex. Our findings suggest that the genetic diversity introduced by crossing B6 and D2 inbred backgrounds influences proteomic changes related to disease in the 5XFAD model, and that proteomic analysis of other genetic backgrounds in transgenic and knock-in AD mouse models is warranted to capture the full range of molecular heterogeneity in genetically diverse models of AD.
Research on deep reinforcement learning basketball robot shooting skills improvement based on end to end architecture and multi-modal perception
Authors: Zhang Jun , Tao Dayong
Published: October 2023

Introduction

In the realm of basketball, refining shooting skills and decision-making levels using intelligent agents has garnered significant interest. This study addresses the challenge by introducing an innovative framework that combines multi-modal perception and deep reinforcement learning. The goal is to create basketball robots capable of executing precise shots and informed choices by effectively integrating sensory inputs and learned strategies.

Methods

The proposed approach consists of three main components: multi-modal perception, deep reinforcement learning, and end-to-end architecture. Multi-modal perception leverages the multi-head attention mechanism (MATT) to merge visual, motion, and distance cues for a holistic perception of the basketball scenario. The deep reinforcement learning framework utilizes the Deep Q-Network (DQN) algorithm, enabling the robots to learn optimal shooting strategies over iterative interactions with the environment. The end-to-end architecture connects these components, allowing seamless integration of perception and decision-making processes.

Results

The experiments conducted demonstrate the effectiveness of the proposed approach. Basketball robots equipped with multi-modal perception and deep reinforcement learning exhibit improved shooting accuracy and enhanced decision-making abilities. The multi-head attention mechanism enhances the robots' perception of complex scenes, leading to more accurate shooting decisions. The application of the DQN algorithm results in gradual skill improvement and strategic optimization through interaction with the environment.

Discussion

The integration of multi-modal perception and deep reinforcement learning within an end-to-end architecture presents a promising avenue for advancing basketball robot training and performance. The ability to fuse diverse sensory inputs and learned strategies empowers robots to make informed decisions and execute accurate shots. The research not only contributes to the field of robotics but also has potential implications for human basketball training and coaching methodologies.
Angiotensin-converting enzyme insertion/deletion gene polymorphism and the progression of cerebral microbleeds
Authors: Yoon Cindy W. , Kim Jonguk , Suh Young Ju , Kim Byeong C. , Youn Young Chul , Jeong Jee Hyang , Han Hyun Jeong , Choi Seong Hye
Published: October 2023

Background and purpose

The angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism has been studied as a genetic candidate for cerebral small vessel disease (CSVD). However, no previous study has evaluated the relationship between the ACE I/D polymorphism and cerebral microbleed (CMB), an important CSVD marker. We evaluated the association between ACE I/D polymorphisms and 2-year changes in CMBs.

Methods

The CHALLENGE (Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes) database was analyzed. Of 256 subjects, 186 participants who underwent a 2-year follow-up brain scan and ACE genotyping were included. Our analysis was conducted by dividing the ACE genotype into two groups (DD vs. ID/II) under the assumption of the recessive effects of the D allele. A linear mixed-effect model was used to compare the 2-year changes in the number of CMBs between the DD and combined ID/II genotypes.

Results

Among 186 patients included in this study, 24 (12.9%) had the DD genotype, 91 (48.9%) had the ID genotype, and 71 (38.2%) had the II genotype. Baseline clinical characteristics and cerebral small vessel disease markers were not different between the two groups (DD vs. ID/II) except for the prevalence of hypertension (DD 66.7% vs. ID/II 84.6%; p = 0.04). A multivariate linear mixed-effects model showed that the DD carriers had a greater increase in total CMB counts than the ID/II carriers after adjusting for the baseline number of CMBs, age, sex, and hypertension (estimated mean of difference [standard error (SE)] = 1.33 [0.61]; p = 0.03). When we performed an analysis of cases divided into deep and lobar CMBs, only lobar CMBs were significantly different between the two groups (estimated mean of difference [SE] = 0.94 [0.42]; p = 0.02).

Conclusion

The progression of CMBs over 2 years was greater in the ACE DD carriers compared with the combined II/ID carriers. The results of our study indicate a possible association between the ACE I/D polymorphism and CMB. A study with a larger sample size is needed to confirm this association.
Antineutrophil cytoplasmic antibody-associated vasculitis with predominant truncal muscle weakness: a retrospective case series
Authors: Nemoto Joe , Nishihara Hideaki , Yasuhi Taro , Sato Ryota , Koga Michiaki , Kanda Takashi , Nakamori Masayuki
Published: October 2023

Introduction

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) frequently leads to mononeuritis multiplex, which are characterized by distal weakness associated with sensory disturbances. Although AAV has also been reported to be associated with myopathy, the pathogenesis and characteristics remain unclear. We aimed to show the clinical and laboratory findings in AAV-associated myopathy.

Methods

This retrospective single-center study included patients with the diagnosis of AAV who had been admitted to the neurology department and had biopsy specimens of muscle and/or nerve tissue.

Results

We identified four patients with a distinct clinical presentation of muscle weakness in the trunk and proximal limbs. The weakness resembled that of inflammatory muscle disease. These patients denied symptoms associated with neuropathy, and had normal serum creatine kinase (CK) levels. Needle electromyography (needle EMG) showed spontaneous electrical activity at rest, and results of magnetic resonance imaging (MRI) suggested inflammatory myopathy. Muscle biopsy specimens from all four patients revealed vasculitis and inflammation in proximity to the affected vessels, without any discernible characteristics of other myopathies. The patients also complained of symptoms affecting other organs, such as the ears and kidneys, which is typical of AAV cases. Remission induction therapy, such as cyclophosphamide pulse therapy in addition to oral prednisolone, were effective for all four patients. However, relapses occurred in two patients during maintenance therapy and two patients died of aspiration pneumonia.

Discussion

The clinical course of our patients might represent a subtype of AAV that is characterized by muscle weakness of the trunk and proximal extremities and arises from vasculitis within the muscles. The clinical manifestations of our patients were similar to those of patients with inflammatory myopathy with regard to the distribution of muscle weakness, MRI and needle EMG findings. However, there are notable differences between AAV associated myopathy vs. inflammatory myositis like dermatomyositis; (1) the absence of elevated CK levels, (2) the presence of complications in other organs, (3) distinct pathological findings, and (4) severe outcomes. Awareness that AAV patients with muscle involvement could have a subtype of AAV that seriously affects various organs is critical for an accurate diagnosis and effective therapeutic management.
Changes in alpha, theta, and gamma oscillations in distinct cortical areas are associated with altered acute pain responses in chronic low back pain patients
Authors: Kenefati George , Rockholt Mika M. , Ok Deborah , McCartin Michael , Zhang Qiaosheng , Sun Guanghao , Maslinski Julia , Wang Aaron , Chen Baldwin , Voigt Erich P. , Chen Zhe Sage , Wang Jing , Doan Lisa V.
Published: October 2023

Introduction

Chronic pain negatively impacts a range of sensory and affective behaviors. Previous studies have shown that the presence of chronic pain not only causes hypersensitivity at the site of injury but may also be associated with pain-aversive experiences at anatomically unrelated sites. While animal studies have indicated that the cingulate and prefrontal cortices are involved in this generalized hyperalgesia, the mechanisms distinguishing increased sensitivity at the site of injury from a generalized site-nonspecific enhancement in the aversive response to nociceptive inputs are not well known.

Methods

We compared measured pain responses to peripheral mechanical stimuli applied to a site of chronic pain and at a pain-free site in participants suffering from chronic lower back pain (n = 15) versus pain-free control participants (n = 15) by analyzing behavioral and electroencephalographic (EEG) data.

Results

As expected, participants with chronic pain endorsed enhanced pain with mechanical stimuli in both back and hand. We further analyzed electroencephalographic (EEG) recordings during these evoked pain episodes. Brain oscillations in theta and alpha bands in the medial orbitofrontal cortex (mOFC) were associated with localized hypersensitivity, while increased gamma oscillations in the anterior cingulate cortex (ACC) and increased theta oscillations in the dorsolateral prefrontal cortex (dlPFC) were associated with generalized hyperalgesia.

Discussion

These findings indicate that chronic pain may disrupt multiple cortical circuits to impact nociceptive processing.
The utility of algae as sources of high value nutritional ingredients, particularly for alternative/complementary proteins to improve human health
Authors: Wu Jia Yee , Tso Rachel , Teo Hwee Sze , Haldar Sumanto
Published: October 2023

As the global population continues to grow, the demand for dietary protein is rapidly increasing, necessitating the exploration of sustainable and nutritious protein sources. Algae has emerged as a promising food source due to their high value ingredients such as proteins, as well as for their environmental sustainability and abundance. However, knowledge gaps surrounding dietary recommendations and food applications restrict algae’s utilization as a viable protein source. This review aims to address these gaps by assessing the suitability of both microalgae and macroalgae as alternative/complementary protein sources and exploring their potential applications in food products. The first section examines the potential suitability of algae as a major food source by analyzing the composition and bioavailability of key components in algal biomass, including proteins, lipids, dietary fiber, and micronutrients. Secondly, the biological effects of algae, particularly their impact on metabolic health are investigated with an emphasis on available clinical evidence. While evidence reveals protective effects of algae on glucose and lipid homeostasis as well as anti-inflammatory properties, further research is required to understand the longer-term impact of consuming algal protein, protein isolates, and concentrates on metabolic health, including protein metabolism. The review then explores the potential of algal proteins in food applications, including ways to overcome their sensory limitations, such as their dark pigmentation, taste, and odor, in order to improve consumer acceptance. To maximize algae’s potential as a valuable protein source in the food sector, future research should prioritize the production of more acceptable algal biomass and explore new advances in food sciences and technology for improved consumer acceptance. Overall, this paper supports the potential utility of algae as a sustainable and healthy ingredient source for widespread use in future food production.
Mapping the landscape of artificial intelligence in skin cancer research: a bibliometric analysis
Authors: Liu Qianwei , Zhang Jie , Bai Yanping
Published: October 2023

Objective

Artificial intelligence (AI), with its potential to diagnose skin cancer, has the potential to revolutionize future medical and dermatological practices. However, the current knowledge regarding the utilization of AI in skin cancer diagnosis remains somewhat limited, necessitating further research. This study employs visual bibliometric analysis to consolidate and present insights into the evolution and deployment of AI in the context of skin cancer. Through this analysis, we aim to shed light on the research developments, focal areas of interest, and emerging trends within AI and its application to skin cancer diagnosis.

Methods

On July 14, 2023, articles and reviews about the application of AI in skin cancer, spanning the years from 1900 to 2023, were selected from the Web of Science Core Collection. Co-authorship, co-citation, and co-occurrence analyses of countries, institutions, authors, references, and keywords within this field were conducted using a combination of tools, including CiteSpace V (version 6.2. R3), VOSviewer (version 1.6.18), SCImago, Microsoft Excel 2019, and R 4.2.3.

Results

A total of 512 papers matching the search terms and inclusion/exclusion criteria were published between 1991 and 2023. The United States leads in publications with 149, followed by India with 61. Germany holds eight positions among the top 10 institutions, while the United States has two. The most prevalent journals cited were Cancer, the European Journal of Cancer, and Sensors. The most frequently cited keywords include “skin cancer”, “classification”, “artificial intelligence”, and “deep learning”.

Conclusions

Research into the application of AI in skin cancer is rapidly expanding, and an increasing number of scholars are dedicating their efforts to this field. With the advancement of AI technology, new opportunities have arisen to enhance the accuracy of skin imaging diagnosis, treatment based on big data, and prognosis prediction. However, at present, the majority of AI research in the field of skin cancer diagnosis is still in the feasibility study stage. It has not yet made significant progress toward practical implementation in clinical settings. To make substantial strides in this field, there is a need to enhance collaboration between countries and institutions. Despite the potential benefits of AI in skin cancer research, numerous challenges remain to be addressed, including developing robust algorithms, resolving data quality issues, and enhancing results interpretability. Consequently, sustained efforts are essential to surmount these obstacles and facilitate the practical application of AI in skin cancer research.
Acral cutaneous malignant melanoma treated with linear accelerator-based boron neutron capture therapy system: a case report of first patient
Authors: Igaki Hiroshi , Nakamura Satoshi , Yamazaki Naoya , Kaneda Tomoya , Takemori Mihiro , Kashihara Tairo , Murakami Naoya , Namikawa Kenjiro , Nakaichi Tetsu , Okamoto Hiroyuki , Iijima Kotaro , Chiba Takahito , Nakayama Hiroki , Nagao Ayaka , Sakuramachi Madoka , Takahashi Kana , Inaba Koji , Okuma Kae , Nakayama Yuko , Shimada Kazuaki , Nakagama Hitoshi , Itami Jun
Published: October 2023

This study reports the first patient treatment for cutaneous malignant melanoma using a linear accelerator-based boron neutron capture therapy (BNCT) system. A single-center open-label phase I clinical trial had been conducted using the system since November 2019. A patient with a localized node-negative acral malignant melanoma and the largest diameter of the tumor ≤ 15 cm who refused primary surgery and chemotherapy was enrolled. After administering boronophenylalanine (BPA), a single treatment of BNCT with the maximum dose of 18 Gy-Eq delivered to the skin was performed. The safety and efficacy of the accelerator-based BNCT system for treating localized cutaneous malignant melanoma were evaluated. The first patient with cutaneous malignant melanoma in situ on the second finger of the left hand did not develop dose-limiting toxicity in the clinical trial. After BNCT, the treatment efficacy was gradually observed, and the patient achieved PR within 6 months and CR within 12 months. Moreover, during the follow-up period of 12 months after BNCT, the patient did not exhibit a recurrence without any treatment-related grade 2 or higher adverse events. Although grade 1 adverse events of dermatitis, dry skin, skin hyperpigmentation, edema, nausea, and aching pain were noted in the patient, those adverse events were relieved without any treatment. This case report shows that the accelerator-based BNCT may become a promising treatment modality for cutaneous malignant melanoma. We expect further clinical trials to reveal the efficacy and safety of the accelerator-based BNCT for cutaneous malignant melanoma.
Hepatitis C virus infection is associated with high risk of breast cancer: a pooled analysis of 68,014 participants
Authors: Chen Haiping , Du Pei , Yang Tianyao , Xu Xueyuan , Cui Tianyang , Dai Yuhang
Published: October 2023

Introduction

Breast cancer is the most common malignancy among women. Previous studies had shown that hepatitis C virus (HCV) infection might serve as a risk factor for breast cancer, while some studies failed to find such an association.

Methods

In this study, we presented a first attempt to capture and clarify this clinical debate via a cumulative analysis (registration ID: CRD42023445888).

Results

After systematically searching and excluding the irrelevant publications, five case-control or cohort studies were finally included. The synthetic effect from the eligible studies showed that patients with HCV infection had a significantly higher prevalence of breast cancer than non-HCV infected general population (combined HR= 1.382, 95%CI: 1.129 to 1.692, P=0.002). There was no evidence of statistical heterogeneity during this pooled analysis (I2 = 13.2%, P=0.33). The sensitivity analyses confirmed the above findings. No significant publication bias was observed among the included studies. The underlying pathophysiological mechanisms for this relationship might be associated with persistent infection/inflammation, host immune response, and the modulation of HCV-associated gene expression.

Discussion

Though the causal association between HCV infection and breast cancer did not seem quite as strong, screening for HCV might enable the early detection of breast cancer and help to prevent the progression of the disease. Since the topic of this study remains a matter of clinical debate, further studies are still warranted to validate this potential association.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023445888