bluuebunny/crossref_metadata_2025 huggingface dataset:
A pyroptosis-related gene model and its correlation with the microenvironment of lung adenocarcinoma: A bioinformatics analysis and experimental verification
Authors: Dong Yi , Yi Lina , Song Qibin , Yao Yi
Published: November 2022

Background: Non-small cell lung cancer, comprising lung adenocarcinoma (LUAD) and lung squamous cell carcinoma, is one of the leading causes of cancer-related mortality. Pyroptosis is a new form of programmed cell death involved in cancer development. The relationship between LUAD and pyroptosis is unclear. This research aims to investigate this relationship and develop a stratified clinical model based on pyroptosis-related genes (PRGs).

Methods: We analyzed the data of LUAD from The Cancer Genome Atlas (TCGA) and evaluated the expression of 48 PRGs to identify the differentially expressed genes. Then, constructing the risk model using the least absolute shrinkage and selection operator and the Cox regression method to find the gene signatures. The functional enrichment, immune cell infiltration, tumor mutational burden (TMB), and expression of immune checkpoints were compared to investigate the potential mechanism. The IC50 of common drugs was evaluated and compared. The inflammasome activation assay and lactate dehydrogenase (LDH) assay of NLR-family CARD-containing protein 4 (NLRC4) were also performed to confirm the role of pyroptosis in LUAD.

Results: The pyroptosis-related model accurately predicted the prognosis of patients with LUAD, with the low-risk group exhibiting a higher survival probability. The risk score was an independent prognostic factor for survival. The stratified patients exhibited distinct tumor microenvironments, TMB, and drug sensitivity. The validation experiments of NLRC4 confirmed its role in inducing pyroptosis via promoting IL-1 maturation.

Conclusion: PRGs regulated the tumor microenvironment and influenced the outcome of LUAD. NLRC4 may function as a hub gene in the process of LUAD.
The multidimensional legal nature of personal genomic sequence data: A South African perspective
Authors: Thaldar Donrich W. , Townsend Beverley A. , Donnelly Dusty-Lee , Botes Marietjie , Gooden Amy , van Harmelen Joanne , Shozi Bonginkosi
Published: November 2022

This article provides a comprehensive analysis of the various dimensions in South African law applicable to personal genomic sequence data. This analysis includes property rights, personality rights, and intellectual property rights. Importantly, the under-investigated question of whether personal genomic sequence data are capable of being owned is investigated and answered affirmatively. In addition to being susceptible of ownership, personal genomic sequence data are also the object of data subjects’ personality rights, and can also be the object of intellectual property rights: whether on their own qua trade secret or as part of a patented invention or copyrighted dataset. It is shown that personality rights constrain ownership rights, while the exploitation of intellectual property rights is constrained by both personality rights and ownership rights. All of these rights applicable to personal genomic sequence data should be acknowledged and harmonized for such data to be used effectively.
Granzyme B in circulating CD8+ T cells as a biomarker of immunotherapy effectiveness and disability in neuromyelitis optica spectrum disorders
Authors: Shi Ziyan , Du Qin , Wang Xiaofei , Wang Jianchen , Chen Hongxi , Lang Yanling , Kong Lingyao , Luo Wenqin , Yang Mu , Zhou Hongyu
Published: November 2022

Background and objective

Neuromyelitis optica spectrum disorders (NMOSD) are chronical inflammatory demyelinating diseases of the central nervous system (CNS) and the underlying mechanism remains unclear. Several recent studies have demonstrated that T cells play a pivotal role in the pathogenesis of NMOSD.In this study, we investigated CD8+ T cell phenotypes and levels of the cytotoxic protein granzyme B (GzmB), as well as their potential clinical application in NMOSD.

Methods

In this study, 90 peripheral blood samples were collected from 59 NMOSD patients with seropositive anti-aquaporin-4 (AQP4) antibodies and 31 sex- and age-matched healthy donors (HDs). Flow cytometry was used to detect circulating levels of GzmB and CD8+ T cell subpopulations, including naïve (TN, CCD7+CD45RA+), central memory (TCM, CCD7+CD45RA-), effector memory (TEM, CCD7-CD45RA-), terminal differentiation effector memory cells (TEMRA, CCD7-CD45RA+) in both groups. The associations between GzmB levels in CD8+T cells and clinical characteristics of NMOSD were evaluated.

Results

NMOSD patients exhibited significantly decreased proportions of CD8+TN cells and increased proportions of highly differentiated CD8+T cells (TEMRA) compared with HDs. In addition, levels of GzmB in CD8+ T cells were markedly higher in NMOSD patients than in HDs. Moreover, we observed that high proportions of GzmB-expressing CD8+ T cells were more common in patients with a poor response to immunotherapies, and showed a good potential to distinguish poor responders from responders (ACU=0.89). Clinical correlation analysis indicated that high levels of GzmB in CD8+ T cells were not only related to severe disability but also significantly associated with increased serum levels of neurofilament light (NFL) and glial fibrillary acidic protein (GFAP). Multivariate linear regression analyses further suggested that GzmB expression in CD8+ T cells was predominantly associated with disability and immunotherapy effectiveness in NMOSD, independent of the sex, age, and disease phase. Transcription factor T-bet in CD8+ T cells were also significantly elevated in NMOSD and were associated with increasing number of circulating CD8+TEMRA cells and GzmB-expressing CD8+T cells.

Conclusions

Our study support the involvement of GzmB-expressing CD8+ T cells in the inflammatory response in patients with NMOSD and provide a potential biomarker for disease immunotherapy effectiveness and disability progression.
Viral tropism for the testis and sexual transmission
Authors: Wang Fei , Zhang Jing , Wang Yu , Chen Yongmei , Han Daishu
Published: November 2022

The mammalian testis adopts an immune privileged environment to protect male germ cells from adverse autoimmune reaction. The testicular immune privileged status can be also hijacked by various microbial pathogens as a sanctuary to escape systemic immune surveillance. In particular, several viruses have a tropism for the testis. To overcome the immune privileged status and mount an effective local defense against invading viruses, testicular cells are well equipped with innate antiviral machinery. However, several viruses may persist an elongated duration in the testis and disrupt the local immune homeostasis, thereby impairing testicular functions and male fertility. Moreover, the viruses in the testis, as well as other organs of the male reproductive system, can shed to the semen, thus allowing sexual transmission to partners. Viral infection in the testis, which can impair male fertility and lead to sexual transmission, is a serious concern in research on known and on new emerging viruses. To provide references for our scientific peers, this article reviews research achievements and suggests future research focuses in the field.
Targeting matrix metalloproteases: A promising strategy for herbal medicines to treat rheumatoid arthritis
Authors: Li Ruo-Lan , Duan Hu-Xinyue , Liang Qi , Huang Yong-Liang , Wang Ling-Yu , Zhang Qing , Wu Chun-Jie , Liu Shu-Qin , Peng Wei
Published: November 2022

As a type of metalloproteinase, matrix metalloproteinases (MMPs) can be divided into collagenase, gelatinase, stromelysins, membrane-type (MT)-MMPs and heterogeneous subgroups according to their structure and function. MMP contents in the human body are strictly regulated, and their synthesis, activation and inhibition processes should be kept in a certain balance; otherwise, this would result in the occurrence of various diseases. Rheumatoid arthritis (RA) is a known immune-mediated systemic inflammatory disease that is affected by a variety of endogenous and exogenous factors. In RA development, MMPs act as important mediators of inflammation and participate in the degradation of extracellular matrix substrates and digestion of fibrillar collagens, leading to the destruction of joint structures. Interestingly, increasing evidence has suggested that herbal medicines have many advantages in RA due to their multitarget properties. In this paper, literature was obtained through electronic databases, including the Web of Science, PubMed, Google Scholar, Springer, and CNKI (Chinese). After classification and analysis, herbal medicines were found to inhibit the inflammatory process of RA by regulating MMPs and protecting joint structures. However, further preclinical and clinical studies are needed to support this view before these herbal medicines can be developed into drugs with actual application to the disease.
The relation of the frequency and functional molecules expression on plasmacytoid dendritic cells to postpartum hepatitis in women with HBeAg-positive chronic hepatitis B virus infection
Authors: Wang Fuchuan , Song Meiying , Hu Yuhong , Yang Liu , Bi Xiaoyue , Lin Yanjie , Jiang Tingting , Deng Wen , Wang Shiyu , Sun Fangfang , Zeng Zhan , Lu Yao , Shen Ge , Liu Ruyu , Chang Min , Wu Shuling , Gao Yuanjiao , Hao Hongxiao , Xu Mengjiao , Chen Xiaoxue , Hu Leiping , Wan Gang , Zhang Lu , Li Minghui , Xie Yao
Published: November 2022

Objective

To explore the correlation between postpartum hepatitis and changes of plasmacytoid dendritic cells’ (pDC) function and frequency in hepatitis B e antigen (HBeAg)-positive pregnant women with chronic hepatitis B virus (HBV) infection.

Methods

Pregnant women with chronic HBV infection receiving antiviral treatment (treated group) or not receiving antiviral treatment (untreated group) were enrolled and demographic information was collected before delivery. Clinical biochemical, virological serology, pDC frequency and functional molecular expression were tested before delivery and at 6, 12, 24 weeks after delivery.

Results

90 eligible pregnant women were enrolled, 36 in the untreated group and 54 in the treated group. 36 patients developed postpartum hepatitis, including 17 (17/36, 47.2%) in the untreated group and 19 (19/54, 35.2%) in the treated group (χ2 = 1.304 p=0.253), and 22 cases of hepatitis occurred at 6 weeks postpartum, 12 at 12 weeks postpartum, and 2 at 24 weeks postpartum. The alanine transaminase (ALT) levels at any time postpartum were significantly higher than that of the antepartum, especially at 6 weeks and 12 weeks postpartum. However, the frequencies of pDCs, CD83+ pDCs and CD86+ pDCs antepartum had no significant difference from any time postpartum. The frequencies of CD83+ pDCs, CD86+ pDCs in the treated group antepartum were significantly higher than those in the untreated group [12.70 (9.46, 15.08) vs. 10.20 (7.96, 11.85), p=0.007; 22.05 (19.28, 33.03) vs. 18.05 (14.33, 22.95), p=0.011], and the same at 12 weeks postpartum [12.80 (10.50, 15.50) vs. 9.38 (7.73, 12.60), p=0.017; 22.50 (16.80, 31.20) vs. 16.50 (12.65, 20.80), p=0.001]. The frequency of CD86+ pDCs in the treated group was significantly higher than that in the untreated group at 24 weeks postpartum [22.10 (16.70, 30.00) vs. 17.10 (13.70, 20.05), p=0.006].

Conclusions

Postpartum hepatitis in HBV infected women mainly occurs at 6-12 weeks postpartum. Antiviral treatment during pregnancy can significantly increase the frequencies of CD83+ pDCs and CD86+ pDCs in pregnant women with chronic HBV infection.
Chromomycin A5 induces bona fide immunogenic cell death in melanoma
Authors: Florêncio Katharine Gurgel Dias , Edson Evelline Araújo , Fernandes Keilla Santana da Silva , Luiz João Paulo Mesquita , Pinto Francisco das Chagas Lima , Pessoa Otília Deusdênia Loiola , Cunha Fernando de Queiroz , Machado-Neto João Agostinho , Wilke Diego Veras
Published: November 2022

Purpose

Some first-line cytotoxic chemotherapics, e.g. doxorubicin, paclitaxel and oxaliplatin, induce activation of the immune system through immunogenic cell death (ICD). Tumor cells undergoing ICD function as a vaccine, releasing damage-associated molecular patterns (DAMPs), which act as adjuvants, and neoantigens of the tumor are recognized as antigens. ICD induction is rare, however it yields better and long-lasting antitumor responses to chemotherapy. Advanced metastatic melanoma (AMM) is incurable for more than half of patients. The discovery of ICD inducers against AMM is an interesting drug discovery strategy with high translational potential. Here we evaluated ICD induction of four highly cytotoxic chromomycins A (CA5-8).

Methods

ICD features and DAMPs were evaluated using several in vitro techniques with metastatic melanoma cell line (B16-F10) exposed to chromomcins A5-8 such as flow cytometry, western blot, RT-PCR and luminescence. Additionally in vivo vaccination assays with CA5-treated cells in a syngeneic murine model (C57Bl/6) were performed to confirm ICD evaluating the immune cells activation and their antitumor activity.

Results

B16-F10 treated with CA5-8 and doxorubicin exhibited ICD features such as autophagy and apoptosis, externalization of calreticulin, and releasing of HMGB1. However, CA5-treated cells had the best profile, also inducing ATP release, ERp57 externalization, phosphorylation of eIF2α and altering expression of transcription of genes related to autophagy, endoplasmic reticulum stress, and apoptosis. Bona fide ICD induction by CA5 was confirmed by vaccination of C57BL/6 mice with CA5-treated cells which activated antigen-presenting cells and T lymphocytes and stimulated antitumor activity.

Conclusion

CA5 induces bona fide immunogenic cell death on melanoma.
Development and evaluation of low-volume tests to detect and characterize antibodies to SARS-CoV-2
Authors: Halliday Alice , Long Anna E. , Baum Holly E. , Thomas Amy C. , Shelley Kathryn L. , Oliver Elizabeth , Gupta Kapil , Francis Ore , Williamson Maia Kavanagh , Di Bartolo Natalie , Randell Matthew J. , Ben-Khoud Yassin , Kelland Ilana , Mortimer Georgina , Ball Olivia , Plumptre Charlie , Chandler Kyla , Obst Ulrike , Secchi Massimiliano , Piemonti Lorenzo , Lampasona Vito , Smith Joyce , Gregorova Michaela , Knezevic Lea , Metz Jane , Barr Rachael , Morales-Aza Begonia , Oliver Jennifer , Collingwood Lucy , Hitchings Benjamin , Ring Susan , Wooldridge Linda , Rivino Laura , Timpson Nicholas , McKernon Jorgen , Muir Peter , Hamilton Fergus , Arnold David , Woolfson Derek N. , Goenka Anu , Davidson Andrew D. , Toye Ashley M. , Berger Imre , Bailey Mick , Gillespie Kathleen M. , Williams Alistair J. K. , Finn Adam
Published: November 2022

Low-volume antibody assays can be used to track SARS-CoV-2 infection rates in settings where active testing for virus is limited and remote sampling is optimal. We developed 12 ELISAs detecting total or antibody isotypes to SARS-CoV-2 nucleocapsid, spike protein or its receptor binding domain (RBD), 3 anti-RBD isotype specific luciferase immunoprecipitation system (LIPS) assays and a novel Spike-RBD bridging LIPS total-antibody assay. We utilized pre-pandemic (n=984) and confirmed/suspected recent COVID-19 sera taken pre-vaccination rollout in 2020 (n=269). Assays measuring total antibody discriminated best between pre-pandemic and COVID-19 sera and were selected for diagnostic evaluation. In the blind evaluation, two of these assays (Spike Pan ELISA and Spike-RBD Bridging LIPS assay) demonstrated >97% specificity and >92% sensitivity for samples from COVID-19 patients taken >21 days post symptom onset or PCR test. These assays offered better sensitivity for the detection of COVID-19 cases than a commercial assay which requires 100-fold larger serum volumes. This study demonstrates that low-volume in-house antibody assays can provide good diagnostic performance, and highlights the importance of using well-characterized samples and controls for all stages of assay development and evaluation. These cost-effective assays may be particularly useful for seroprevalence studies in low and middle-income countries.
Immune mechanisms associated with cardiovascular disease in systemic lupus erythematosus: A path to potential biomarkers
Authors: Guzmán-Martínez Gabriela , Marañón Concepción ,   CYTED RIBLES Network
Published: November 2022

Systemic lupus erythematosus (SLE) patients display an increased risk of cardiovascular disease (CVD). With the improved clinical management of other classical severe manifestation of the disease, CVD is becoming one of the most relevant complications of SLE, and it is an important factor causing morbidity and mortality. Several immune constituents have been shown to be involved in the pathogenesis of atherosclerosis and endothelial damage in SLE patients, including specific circulating cell populations, autoantibodies, and inflammatory mediators. In this review, we summarize the presentation of CVD in SLE and the role of the autoimmune responses present in SLE patients in the induction of atherogenesis, endothelial impairment and cardiac disease. Additionally, we discuss the utility of these immune mediators as early CVD biomarkers and targets for clinical intervention in SLE patients.
Immune-profiling of SARS-CoV-2 viremic patients reveals dysregulated innate immune responses
Authors: Sun Xiaoming , Gao Ce , Zhao Ke , Yang Yanhui , Rassadkina Yelizaveta , Fajnzylber Jesse , Regan James , Li Jonathan Z. , Lichterfeld Mathias , Yu Xu G.
Published: November 2022

SARS-CoV-2 plasma viremia has been associated with severe disease and death in COVID-19. However, the effects of viremia on immune responses in blood cells remain unclear. The current study comprehensively examined transcriptional signatures of PBMCs involving T cells, B cells, NK cells, monocytes, myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs) respectively, from three different groups including individuals with moderate (nM), or severe disease with (vS) or without (nS) detectable plasma viral load. Whole transcriptome analysis demonstrated that all seven immune cell subsets were associated with disease severity regardless of cell type. Supervised clustering analysis demonstrated that mDCs and pDCs gene signatures could distinguish disease severity. Notably, transcriptional signatures of the vS group were enriched in pathways related to DNA repair, E2F targets, and G2M checkpoints; in contrast, transcriptional signatures of the nM group were enriched in interferon responses. Moreover, we observed an impaired induction of interferon responses accompanied by imbalanced cell-intrinsic immune sensing and an excessive inflammatory response in patients with severe disease (nS and vS). In sum, our study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in seven major immune cells in COVID-19 patients.
SILAC-based quantitative proteomics and microscopy analysis of cancer cells treated with the N-glycolyl GM3-specific anti-tumor antibody 14F7
Authors: Bousquet Paula A. , Manna Dipankar , Sandvik Joe A. , Arntzen Magnus Ø. , Moreno Ernesto , Sandvig Kirsten , Krengel Ute
Published: November 2022

Cancer immunotherapy represents a promising approach to specifically target and treat cancer. The most common mechanisms by which monoclonal antibodies kill cells include antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity and apoptosis, but also other mechanisms have been described. 14F7 is an antibody raised against the tumor-associated antigen NeuGc GM3, which was previously reported to kill cancer cells without inducing apoptotic pathways. The antibody was reported to induce giant membrane lesions in tumor cells, with apparent changes in the cytoskeleton. Here, we investigated the effect of humanized 14F7 on HeLa cells using stable isotope labeling with amino acids in cell culture (SILAC) in combination with LC-MS and live cell imaging. 14F7 did not kill the HeLa cells, however, it caused altered protein expression (MS data are available via ProteomeXchange with identifier PXD024320). Several cytoskeletal and nucleic-acid binding proteins were found to be strongly down-regulated in response to antibody treatment, suggesting how 14F7 may induce membrane lesions in cells that contain higher amounts of NeuGc GM3. The altered expression profile identified in this study thus contributes to an improved understanding of the unusual killing mechanism of 14F7.
CARD9 in host immunity to fungal, bacterial, viral, and parasitic infections: An update
Authors: Hu Ang , Hu Zeming , Zou Haohong , Zhang Jiankang , Zhang Dongliang , Wang Hao , Zhong Jianing , Chen Bin
Published: November 2022

Microbial infection, caused by fungi, bacteria, viruses, and parasites, significantly contributes to the global death burden and health costs. The innate and adaptive immune systems orchestrate a multifaceted signaling response to invading pathogens as the human antimicrobial system. In this process, caspase recruitment domain-containing protein 9 (CARD9) emerges as a critical intermediary adaptor molecule to participate in regulating a series of antimicrobial immune reactions. Previous publications have confirmed that CARD9 plays a crucial role in fungal, bacterial, viral, and parasitic infections. In this study, we aim to provide an update on the recent clinical and basic studies where the mechanism and function of CARD9 have been further studied and understood. In addition, we summarize the latest treatment and prevention strategies based on CARD9 and discuss the current perspectives and future direction of CARD9.
Directed evolution engineering to improve activity of glucose dehydrogenase by increasing pocket hydrophobicity
Authors: Hua Li , Qianqian Bao , Jianfeng Zhao , Yinbiao Xu , Shengyu Yang , Weishi Xue , Yang Sun , Yupeng Liu
Published: November 2022

Glucose dehydrogenase (GDH) is a NAD(P)+ dependent oxidoreductase, which is useful in glucose determination kits, glucose biosensors, cofactor regeneration, and biofuel cells. However, the low efficiency of the catalysis hinders the use of GDH in industrial applications. In this study, an analysis of interactions between eight GDH mutants and NADP+ is powered by AlphaFold2 and Discovery Studio 3.0. The docking results showed that more hydrogen bonds formed between mutants, such as P45A and NADP+, which indicated that these mutants had the potential for high catalytic efficiency. Subsequently, we verified all the mutants by site-directed mutagenesis. It was notable that the enzyme activity of mutant P45A was 1829 U/mg, an improvement of 28-fold compared to wild-type GDH. We predicted the hydrophobicity of the protein-ligand complexes, which was confirmed by an 8-anilino-1-naphthalenesulphonic acid fluorescent probe. The following order of increasing hydrophobicity index was deduced: GDH < N46E < F155Y < P45A, which suggested that the enzyme activity of GDH is positively related to its pocket hydrophobicity. Furthermore, P45A still showed better catalytic ability in organic solvents, reaching 692 U/mg in 10% isopropanol, which was 19-fold that of the wild-type GDH. However, its substrate affinity was affected by organic solvents. This study provides a good theoretical foundation for further improving the catalytic efficiency of GDH.
The mitochondrial Cu+ transporter PiC2 (SLC25A3) is a target of MTF1 and contributes to the development of skeletal muscle in vitro
Authors: McCann Cat , Quinteros Michael , Adelugba Ifeoluwa , Morgada Marcos N. , Castelblanco Aida R. , Davis Emily J. , Lanzirotti Antonio , Hainer Sarah J. , Vila Alejandro J. , Navea Juan G. , Padilla-Benavides Teresita
Published: November 2022

The loading of copper (Cu) into cytochrome c oxidase (COX) in mitochondria is essential for energy production in cells. Extensive studies have been performed to characterize mitochondrial cuproenzymes that contribute to the metallation of COX, such as Sco1, Sco2, and Cox17. However, limited information is available on the upstream mechanism of Cu transport and delivery to mitochondria, especially through Cu-impermeable membranes, in mammalian cells. The mitochondrial phosphate transporter SLC25A3, also known as PiC2, binds Cu+and transports the ion through these membranes in eukaryotic cells, ultimately aiding in the metallation of COX. We used the well-established differentiation model of primary myoblasts derived from mouse satellite cells, wherein Cu availability is necessary for growth and maturation, and showed that PiC2 is a target of MTF1, and its expression is both induced during myogenesis and favored by Cu supplementation. PiC2 deletion using CRISPR/Cas9 showed that the transporter is required for proliferation and differentiation of primary myoblasts, as both processes are delayed upon PiC2 knock-out. The effects of PiC2 deletion were rescued by the addition of Cu to the growth medium, implying the deleterious effects of PiC2 knockout in myoblasts may be in part due to a failure to deliver sufficient Cu to the mitochondria, which can be compensated by other mitochondrial cuproproteins. Co-localization and co-immunoprecipitation of PiC2 and COX also suggest that PiC2 may participate upstream in the copper delivery chain into COX, as verified byin vitroCu+-transfer experiments. These data indicate an important role for PiC2 in both the delivery of Cu to the mitochondria and COX, favoring the differentiation of primary myoblasts.
Metabolomics-driven strain improvement: A mini review
Authors: Iman Marvin Nathanael , Herawati Elisa , Fukusaki Eiichiro , Putri Sastia Prama
Published: November 2022

In recent years, mass spectrometry-based metabolomics has been established as a powerful and versatile technique for studying cellular metabolism by comprehensive analysis of metabolites in the cell. Although there are many scientific reports on the use of metabolomics for the elucidation of mechanism and physiological changes occurring in the cell, there are surprisingly very few reports on its use for the identification of rate-limiting steps in a synthetic biological system that can lead to the actual improvement of the host organism. In this mini review, we discuss different strategies for improving strain performance using metabolomics data and compare the application of metabolomics-driven strain improvement techniques in different host microorganisms. Finally, we highlight several success stories on the use of metabolomics-driven strain improvement strategies, which led to significant bioproductivity improvements.
Development of an age-dependent cognitive index: relationship between impaired learning and disturbances in circadian timekeeping
Authors: Souza Karienn A. , Powell Andrew , Allen Gregg C. , Earnest David J.
Published: November 2022

Preclinical quantitative models of cognitive performance are necessary for translation from basic research to clinical studies. In rodents, non-cognitive factors are a potential influence on testing outcome and high variability in behavior requires multiple time point testing for better assessment of performance in more sophisticated tests. Thus, these models have limited translational value as most human cognitive tests characterize cognition using single digit scales to distinguish between impaired and unimpaired function. To address these limitations, we developed a cognitive index for learning based on previously described scores for strategies used by mice to escape the Barnes maze. We compared the cognitive index and circadian patterns of light-dark entrainment in young (4–6 months), middle-aged (13–14 months), and aged (18–24 months) mice as cognitive changes during aging are often accompanied by pronounced changes in sleep-wake cycle. Following continuous analysis of circadian wheel-running activity (30–40 days), the same cohorts of mice were tested in the Barnes maze. Aged mice showed significant deficits in the learning and memory portions of the Barnes maze relative to young and middle-aged animals, and the cognitive index was positively correlated to the memory portion of the task (probe) in all groups. Significant age-related alterations in circadian entrainment of the activity rhythm were observed in the middle-aged and aged cohorts. In middle-aged mice, the delayed phase angle of entrainment and increased variability in the daily onsets of activity preceded learning and memory deficits observed in aged animals. Interestingly, learning-impaired mice were distinguished by a positive relationship between the extent of Barnes-related cognitive impairment and variability in daily onsets of circadian activity. While it is unclear whether changes in the sleep-wake cycle or other circadian rhythms play a role in cognitive impairment during aging, our results suggest that circadian rhythm perturbations or misalignment may nevertheless provide an early predictor of age-related cognitive decline.
High precision visual localization method of UAV based on feature matching
Authors: Xue Bayang , Yang Zhong , Liao Luwei , Zhang Chi , Xu Hao , Zhang Qiuyan
Published: November 2022

In this paper, the precision hovering problem of UAV operation is studied. Aiming at the diversity and complexity of the UAV operating environment, a high-precision visual positioning and orientation method based on image feature matching was proposed. The image feature matching based on the improved AKAZE algorithm is realized, and the optimal matching point pair screening method based on the fusion of Hamming distance and matching line angle is innovatively proposed, which greatly improves the robustness of the algorithm without affecting the performance of the algorithm. The real-time image is matched with the benchmark image for image feature matching. By reducing the deviation of image feature, the pose state correction of UAV hovering is achieved, and the precision hovering of the UAV is realized. Both simulation and real UAV tests verify the effectiveness of the proposed UAV high-precision visual positioning and orientation method.
Mechanisms underlying acupuncture therapy in chronic kidney disease: A narrative overview of preclinical studies and clinical trials
Authors: Liu Xinyin , Wang Xiaoran , Ma Hongzhen , Zhang Wen
Published: November 2022

Chronic kidney disease (CKD) is associated with high incidence, low awareness, and high disability rates among the population. Moreover, the disease significantly affects the physical and mental health of patients. Approximately 25% of patients with CKD develop end-stage renal disease (ESRD) within 20 years of diagnosis and have to rely on renal replacement therapy, which is associated with high mortality, heavy economic burden, and symptoms including fatigue, pain, insomnia, uremia pruritus, and restless leg syndrome. Currently, the means to delay the progress of CKD are insufficient; therefore, developing strategies for delaying CKD progression has important practical implications. In recent years, more and more people are accepting the traditional Chinese medical technique “acupuncture.” Acupuncture has been shown to improve the uncomfortable symptoms of various diseases through stimulation (needling, medicinal moxibustion, infrared radiation, and acupressure) of acupoints. Its application has been known for thousands of years, and its safety and efficacy have been verified. As a convenient and inexpensive complementary therapy for CKD, acupuncture has recently been gaining interest among clinicians and scientists. Nevertheless, although clinical trials and meta-analysis findings have demonstrated the efficacy of acupuncture in reducing albuminuria, improving glomerular filtration rate, relieving symptoms, and improving the quality of life of patients with CKD, the underlying mechanisms involved are still not completely understood. Few studies explored the correlation between acupuncture and renal pathological diagnosis. The aim of this study was to conduct a literature review summarizing the currently known mechanisms by which acupuncture could delay the progress of CKD and improve symptoms in patients with ESRD. This review help provide a theoretical basis for further research regarding the influence of acupuncture on renal pathology in patients with CKD, as well as the differences between specific therapeutic mechanisms of acupuncture in different renal pathological diagnosis. The evidence in this review indicates that acupuncture may produce marked effects on blocking and reversing the critical risk factors of CKD progression (e.g., hyperglycemia, hypertension, hyperlipidemia, obesity, aging, and anemia) to improve the survival of patients with CKD via mechanisms including oxidative stress inhibition, reducing inflammatory effects, improving hemodynamics, maintaining podocyte structure, and increasing energy metabolism.
Fertility preferences and unmet need for family planning in women with multiple sclerosis
Authors: López-Reyes Lorena , Guío-Sánchez Claudia , González-Uribe Catalina , Cárdenas-Robledo Simón
Published: November 2022

Background

Most women with multiple sclerosis (MS) have childbearing potential. Although fertility and pregnancy are not affected by MS, the fertility preferences of women with MS can change due to the risk of complications for the mother and/or adverse pregnancy outcomes resulting from the disease or its treatment.

Objectives

To describe fertility preferences (FPs) and their associated factors, to estimate the Unmet Need for Family Planning (UNFP), use of contraceptives, and history of exposure to disease-modifying therapies (DMTs) during pregnancy in women with MS.

Methods

In a cross-sectional observational study, a random sample of women with MS were surveyed with the FP subset of the Demographic and Health Survey of Colombia. Factors associated with FP were evaluated through bivariate and logistic regression analysis. The proportion of pregnancies exposed to DMTs, UNFP, and use of contraceptives was estimated.

Results

Of the 141 women interviewed, 101 women had childbearing potential, of whom 49 did not want to have children, 38 were sterilized, 33 wanted to have more children, 19 were undecided, and 2 stated they were unable to bear children (menopause or hysterectomy). No MS-related variables were associated with the preference to have more children. Age (OR 0.91; 95% CI 0.84–0.98) and the number of children (OR 0.23; 95% CI 0.09–0.58) decreased the likelihood of desire for children. Of 116 sexually active women, 87.06 % (101) were using contraceptives, and among them, four were using fertility awareness methods and withdrawal. The UNFP was estimated at 6.03% and was not significantly different from the general population. Eighty-two pregnancies were identified, of which 48 occurred after diagnosis, and 25 were exposed to DMTs.

Conclusion

Fertility preference in women with MS is not associated with clinical variables. A large proportion of women choose not to have children and prefer to use permanent contraceptive methods. Although the frequency of contraceptive use was high, some women have the UNFP and use low-efficacy contraceptive methods, which may result in unplanned pregnancies.
Retrospective behavioral sampling (RBS): A method to effectively track the cognitive fluctuations driven by naturalistic stimulation
Authors: Brandman Talia , Malach Rafael , Simony Erez
Published: November 2022

Everyday experiences are dynamic, driving fluctuations across simultaneous cognitive processes. A key challenge in the study of naturalistic cognition is to disentangle the complexity of these dynamic processes, without altering the natural experience itself. Retrospective behavioral sampling (RBS) is a novel approach to model the cognitive fluctuations corresponding to the time-course of naturalistic stimulation, across a variety of cognitive dimensions. We tested the effectiveness and reliability of RBS in a web-based experiment, in which 53 participants viewed short movies and listened to a story, followed by retrospective reporting. Participants recalled their experience of 55 discrete events from the stimuli, rating their quality of memory, magnitude of surprise, intensity of negative and positive emotions, perceived importance, reflectivity state, and mental time travel. In addition, a subset of the original cohort re-rated their memory of events in a follow-up questionnaire. Results show highly replicable fluctuation patterns across distinct cognitive dimensions, thereby revealing a stimulus-driven experience that is substantially shared among individuals. Remarkably, memory ratings more than a week after stimulation resulted in an almost identical time-course of memorability as measured immediately following stimulation. In addition, idiosyncratic response patterns were preserved across different stimuli, indicating that RBS characterizes individual differences that are stimulus invariant. The current findings highlight the potential of RBS as a powerful tool for measuring dynamic processes of naturalistic cognition. We discuss the promising approach of matching RBS fluctuations with dynamic processes measured via other testing modalities, such as neuroimaging, to study the neural manifestations of naturalistic cognitive processing.
Transfer learning in hand movement intention detection based on surface electromyography signals
Authors: Soroushmojdehi Rahil , Javadzadeh Sina , Pedrocchi Alessandra , Gandolla Marta
Published: November 2022

Over the past several years, electromyography (EMG) signals have been used as a natural interface to interact with computers and machines. Recently, deep learning algorithms such as Convolutional Neural Networks (CNNs) have gained interest for decoding the hand movement intention from EMG signals. However, deep networks require a large dataset to train appropriately. Creating such a database for a single subject could be very time-consuming. In this study, we addressed this issue from two perspectives: (i) we proposed a subject-transfer framework to use the knowledge learned from other subjects to compensate for a target subject’s limited data; (ii) we proposed a task-transfer framework in which the knowledge learned from a set of basic hand movements is used to classify more complex movements, which include a combination of mentioned basic movements. We introduced two CNN-based architectures for hand movement intention detection and a subject-transfer learning approach. Classifiers are tested on the Nearlab dataset, a sEMG hand/wrist movement dataset including 8 movements and 11 subjects, along with their combination, and on open-source hand sEMG dataset “NinaPro DataBase 2 (DB2).” For the Nearlab database, the subject-transfer learning approach improved the average classification accuracy of the proposed deep classifier from 92.60 to 93.30% when classifier was utilizing 10 other subjects’ data via our proposed framework. For Ninapro DB2 exercise B (17 hand movement classes), this improvement was from 81.43 to 82.87%. Moreover, three stages of analysis in task-transfer approach proved that it is possible to classify combination hand movements using the knowledge learned from a set of basic hand movements with zero, few samples and few seconds of data from the target movement classes. First stage takes advantage of shared muscle synergies to classify combined movements, while second and third stages take advantage of novel algorithms using few-shot learning and fine-tuning to use samples from target domain to further train the classifier trained on the source database. The use of information learned from basic hand movements improved classification accuracy of combined hand movements by 10%.
Characteristics and predictors of breast milk iodine in exclusively breastfed infants: Results from a repeated-measures study of iodine metabolism
Authors: Guo Wenxing , Wu Wen , Gao Min , Yang Ying , Pearce Elizabeth N. , Li Shaohan , Ren Zhiyuan , Zhang Naifan , Zhang Kexin , Pan Ziyun , Zhang Wanqi
Published: November 2022

Background

The iodine supply of exclusively breastfed infants entirely depends upon breast milk. Changes in breast milk iodine affect infants’ iodine nutritional status. This study aimed to comprehensively assess the characteristics and predictors of breast milk iodine concentration (BMIC).

Materials and methods

This 7-day iodine metabolism experiment was conducted in 25 exclusively breastfed mother-infant pairs. The duplicate portion method was used to measure the mother’s daily iodine intake from foods and water, and maternal 24-h urine excretion was assessed. We recorded the number of breastfeeds per mother per day and collected breast milk samples before and after each feeding.

Results

The median [quartile (Q)1–Q3 range] of BMIC was 115 (86.7, 172) μg/L. The BMIC before breastfeeding was generally higher than that after breastfeeding. Time-sequential analysis found that morning BMIC was most highly correlated with the prior day’s iodine intake. Breast milk samples taken in the afternoon or after midnight are closer to the median level of BMIC throughout the day. The number of breast milk samples needed to estimate the iodine level with 95% CI within precision ranges of ± 20% was 83 for a population, 9 for an individual, and 2 for an individual’s single day. Maternal total iodine intake (TII) and urine iodine were significantly associated with BMIC. 24-h urinary iodine excretion (24-h UIE) was found to be the best predictive indicator for the BMIC (β = 0.71, 95% CI: 0.64, 0.79).

Conclusion

BMIC is a constantly changing indicator and trended downward during each breastfeeding. Breast milk samples taken in the afternoon or after midnight are most representative. BMIC was significantly associated with recent iodine intake. Maternal 24-h UIE was the best predictor of BMIC.
Food preference acquired by social transmission is altered by the absence of the olfactory marker protein in mice
Authors: de Vallière Aurélie , Lopes Ana Catarina , Addorisio Andrea , Gilliand Noah , Nenniger Tosato Monique , Wood Dean , Brechbühl Julien , Broillet Marie-Christine
Published: November 2022

Food preference is conserved from the most primitive organisms to social animals including humans. A continuous integration of olfactory cues present both in food and in the different environmental and physiological contexts favors the intake of a given source of food or its avoidance. Remarkably, in mice, food preference can also be acquired by olfactory communication in-between conspecifics, a behavior known as the social transmission of food preference (STFP). STFP occurs when a mouse sniffs the breath of a conspecific who has previously eaten a novel food emitting specific odorants and will then develop a preference for this never encountered food. The efficient discrimination of odorants is performed by olfactory sensory neurons (OSNs). It is essential and supports many of the decision-making processes. Here, we found that the olfactory marker protein (OMP), an enigmatic protein ubiquitously expressed in all mature olfactory neurons, is involved in the fine regulation of OSNs basal activity that directly impacts the odorant discrimination ability. Using a previously described Omp null mouse model, we noticed that although odorants and their hedonic-associated values were still perceived by these mice, compensatory behaviors such as a higher number of sniffing events were displayed both in the discrimination of complex odorant signatures and in social-related contexts. As a consequence, we found that the ability to differentiate the olfactory messages carried by individuals such as those implicated in the social transmission of food preference were significantly compromised in Omp null mice. Thus, our results not only give new insights into the role of OMP in the fine discrimination of odorants but also reinforce the fundamental implication of a functional olfactory system for food decision-making.
Isolation and characterization of a novel human intestinal Enterococcus faecium FUA027 capable of producing urolithin A from ellagic acid
Authors: Zhang Xiaomeng , Fang Yaowei , Yang Guang , Hou Xiaoyue , Hai Yang , Xia Mengjie , He Fuxiang , Zhao Yaling , Liu Shu
Published: November 2022

Urolithin A (UA) has received considerable research attention because of its health benefits. However, only a few strains have been reported to produce UA from ellagic acid (EA), and the molecular mechanisms underlying the gut microbiota-mediated transformation of ellagic acid into urolithin A is limited. In the present study, a single strain FUA027 capable of converting ellagic acid into UA in vitro was isolated from the fecal samples. The strain was identified as Enterococcus faecium through the morphological, physiological, biochemical and genetic tests. UA was produced at the beginning of the stationary phase and its levels peaked at 50 h, with the highest concentration being 10.80 μM. The strain Enterococcus faecium FUA027 is the first isolated strain of Enterococcus sp. producing urolithin A from ellagic acid, which may be developed as probiotics and used to explore molecular mechanisms underlying the biotransformation of ellagic acid into UA.
Palladium encapsulated nanofibres for scavenging ethylene from sapota fruits
Authors: Gundewadi Gajanan , Rudra Shalini Gaur , Prasanna Radha , Banerjee Tirthankar , Singh Sanjay Kumar , Dhakate Sanjay R. , Gupta Ashish , Anand Anjali
Published: November 2022

Scavenging ethylene is a useful intervention during the transportation and storage of tropical climacteric fruits like sapota. Sapota (Manilkara achras Mill.) is a delicious tropical fruit with a very high respiration rate and poor shelf life. To prolong its post-harvest shelf life, the use of palladium chloride in electrospun nanomats was evaluated at a concentration varying from 1 to 4% levels. Encapsulation of 1–2% PdCl2 in nanomats increased the ethylene scavenging capacity (ESC) by 47–68%. Although, upon encapsulation, both PdCl2 and potassium permanganate showed significantly the same ethylene scavenging activity, the efficacy of PdCl2 was found better in presence of sapota fruits. The PdCl2 nanomats were brighter (L* > 73) in colour compared to the potassium permanganate mat. The placement of nanomats (2 cm2 × 9 cm2) in corrugated fibre board boxes in which the sapota was packed showed higher quality indices (firmness, TSS, ascorbic acid, and phenolics) along with lower PLW and respiration rate during the 8 days of storage period. Compared to control (8.35%), physiological loss in weight of 4.47% was recorded in fruits stored with ethylene scavenging nanomats. PdCl2 encapsulated PVA nanomats can emerge as a promising option for the retention of quality in fruits during storage and transit.
Repurposing live attenuated trivalent MMR vaccine as cost-effective cancer immunotherapy
Authors: Zhang Yuguo , Gabere Musa , Taylor Mika A. , Simoes Camila C. , Dumbauld Chelsae , Barro Oumar , Tesfay Mulu Z. , Graham Alicia L. , Ferdous Khandoker Usran , Savenka Alena V. , Chamcheu Jean Christopher , Washam Charity L. , Alkam Duah , Gies Allen , Byrum Stephanie D. , Conti Matteo , Post Steven R. , Kelly Thomas , Borad Mitesh J. , Cannon Martin J. , Basnakian Alexei , Nagalo Bolni M.
Published: November 2022

It has long been known that oncolytic viruses wield their therapeutic capability by priming an inflammatory state within the tumor and activating the tumor immune microenvironment, resulting in a multifaceted antitumor immune response. Vaccine-derived viruses, such as measles and mumps, have demonstrated promising potential for treating human cancer in animal models and clinical trials. However, the extensive cost of manufacturing current oncolytic viral products makes them far out of reach for most patients. Here by analyzing the impact of intratumoral (IT) administrations of the trivalent live attenuated measles, mumps, and rubella viruses (MMR) vaccine, we unveil the cellular and molecular basis of MMR-induced anti-cancer activity. Strikingly, we found that IT delivery of low doses of MMR correlates with tumor control and improved survival in murine hepatocellular cancer and colorectal cancer modelsviaincreased tumor infiltration of CD8+ granzyme B+ T-cells and decreased macrophages. Moreover, our data indicate that MMR activates key cellular effectors of the host’s innate and adaptive antitumor immunity, culminating in an immunologically coordinated cancer cell death. These findings warrant further work on the potential for MMR to be repurposed as safe and cost-effective cancer immunotherapy to impact cancer patients globally.