bluuebunny/crossref_metadata_2025 huggingface dataset:
Decreased CD57 expression of natural killer cells enhanced cytotoxicity in patients with primary sclerosing cholangitis
Authors: Liu Bin , Yang Guo-Xiang , Sun Ying , Tomiyama Takashi , Zhang Weici , Leung Patrick S. C. , He Xiao-Song , Dhaliwal Sandeep , Invernizzi Pietro , Gershwin M. Eric , Bowlus Christopher L.
Published: August 2022

Background/aims

Primary sclerosing cholangitis (PSC) is a chronic inflammatory biliary disease for which the immunopathological basis remains an enigma. Natural killer (NK) cells are key components of innate immunity and seemingly play diversified roles in different autoimmune disorders (AIDs). The aim of this study was to determine the role of NK cells in the pathogenesis of PSC.

Methods

The frequency and phenotype of circulating NK cells in a large cohort of patients with PSC and healthy controls (HCs) were systematically examined. In addition, the functional capacity of NK cells including cytotoxicity and cytokine production was studied.

Results

The frequency of CD3−CD56dimCD16+ (defined as CD56dim) NK cells in PSC patients was significantly lower in comparison to HCs. CD56dim NK cells from PSC displayed a more immature phenotype including high expression of the natural killing receptor NKp46 and downregulation of the highly differentiated NK cell marker CD57. Interestingly, the reduction of CD57 expression of NK cells was associated with the disease severity of PSC. In addition, PSC CD56dim NK cells exhibited increased CD107a degranulation and cytolytic activity toward target cells compared with HCs. Further analysis demonstrated that CD57−CD56dim NK cells from PSC had elevated expression of NKp46, NKp30, IL-2 receptor, and KLRG1 and higher cytotoxic capacity as compared to CD57+CD56dim NK cells.

Conclusions

Our data demonstrate that the differentiation of PSC NK cells is dysregulated with enhanced cytotoxic activity. This change is likely to be functionally involved in pathogenesis and disease progression, deducing the potential of NK-directed immunotherapy for PSC.
Identification of key genes and pathways in chronic rhinosinusitis with nasal polyps and asthma comorbidity using bioinformatics approaches
Authors: Wang Mingming , Tang Shuangmei , Yang Xiaoqi , Xie Xinyu , Luo Yang , He Shaojuan , Li Xuezhong , Feng Xin
Published: August 2022

Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma comorbidity (ACRSwNP) present severe symptoms and are more likely to relapse. However, the pathogenesis of ACRSwNP is not fully understood. The aim of this study was to explore the underlying pathogenesis of ACRSwNP using bioinformatics approaches. ACRSwNP-related differentially expressed genes (DEGs) were identified by the analysis of the GSE23552 dataset. The clusterProfiler R package was used to carry out functional and pathway enrichment analysis. A protein–protein interaction (PPI) network was built using the STRING database to explore key genes in the pathogenesis of ACRSwNP. The bioinformatics analysis results were verified through qRT-PCR. The Connectivity Map (CMap) database was used to predict potential drugs for the treatment of ACRSwNP. A total of 36 DEGs were identified, which were mainly enriched in terms of regulation of immune response and detection sensory perception of taste. Thirteen hub genes including AZGP1, AQP9, GAPT, PIP, and PRR4 were identified as potential hub genes in ACRSwNP from the PPI network. Analysis of the GSE41861 dataset showed that upregulation of CST1 in nasal mucosa was associated with asthma. qRT-PCR detection confirmed the bioinformatics analysis results. Tacrolimus and spaglumic acid were identified as potential drugs for the treatment of ACRSwNP from the CMap database. The findings of this study provide insights into the pathogenesis of ACRSwNP and may provide a basis for the discovery of effective therapeutic modalities for ACRSwNP.
The association between antibiotic use and outcomes of HCC patients treated with immune checkpoint inhibitors
Authors: Zhang Lilong , Chen Chen , Chai Dongqi , Li Chunlei , Guan Yongjun , Liu Li , Kuang Tianrui , Deng Wenhong , Wang Weixing
Published: August 2022

Objective

Recently, immune checkpoint inhibitor (ICI) treatment has shown encouraging performance in improving the prognosis of hepatocellular carcinoma (HCC) patients. The gut microbiome plays a vital role in altering the efficacy of ICIs, which may be impacted by antibiotics. The aim of the meta-analysis is to estimate the influence of antibiotic use on the survival of HCC patients treated with ICIs.

Methods

The literature review was conducted using databases like PubMed, EMBASE, Cochrane Library, CNKI, WANFANG DATA, VIP, Google Scholar, and ClinicalTrials.gov before May 15, 2022. The primary endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR).

Results

A total of six retrospective studies met the inclusion criteria. 1056 patients were included in the study, of which 352 (33.33%) received antibiotic treatment. The meta-analysis results revealed antibiotic use did not affect the OS (HR: 1.41, 95% CI: 0.96-2.08, P = 0.088) and PFS (HR: 1.21, 95% CI: 0.73-2.00, P = 0.459) in HCC patients treated with ICIs. Besides, the use of antibiotics did not reduce the ORR (OR: 1.06, 95% CI: 0.69-1.64, P = 0.784) and DCR (OR: 0.42, 95% CI: 0.09-2.06, P = 0.286) in HCC patients treated with ICIs.

Conclusion

Current evidence reveals that antibiotic use does alter the therapeutic efficacy of ICIs in HCC patients.

Systematic Review Registration

https://www.crd.york.ac.uk/, identifier CRD42022311948.
Immunosuppressant exposure confounds gene expression analysis in systemic lupus erythematosus
Authors: Northcott Melissa , Gearing Linden J. , Bonin Julie , Koelmeyer Rachel , Hoi Alberta , Hertzog Paul J. , Morand Eric F.
Published: August 2022

Objectives

The analysis of gene module expression in SLE is emerging as a tool to identify active biological pathways, with the aim of developing targeted therapies for subsets of patients. Detailed information on the effect of immunosuppressants on gene module expression is lacking. We aimed to examine the impact of medication exposure on gene module expression.

Methods

A set of commercially available disease-relevant gene modules were measured in 730 whole blood samples from a dedicated lupus clinic on whom prospectively collected, contemporaneous clinical data including medication exposure were available.

Results

Compared to heathy controls, SLE patients showed over-expression of IFN and under-expression of B cell, T cell and pDC modules. Neutrophil module over-expression and under-expression of B and T cell modules were observed in patients with active lupus nephritis or highly active disease (SLEDAI-2K > 8), while Lupus Low Disease Activity State (LLDAS) had inverse associations. Disease activity in other organ domains was not associated with specific gene modules. In contrast, medications were associated with multiple effects. Glucocorticoid use was associated with under-expression of T cell, B cell and plasmablast modules, and over-expression of neutrophil modules. Mycophenolate and azathioprine exposure were associated with plasmablast module and B cell module under-expression respectively. Disease activity associations with neutrophil over-expression and lymphocyte module under-expression were attenuated by multivariable adjustment for medication exposure.

Conclusion

Medications have significant effect on gene module expression in SLE patients. These findings emphasize the need to control for medications in studies of gene expression in SLE.
Involvement of Fusobacterium nucleatum in malignancies except for colorectal cancer: A literature review
Authors: He Zhixing , Tian Wei , Wei Qichun , Xu Jing
Published: August 2022

Fusobacterium nucleatum (F. nucleatum) is originally an oral opportunistic pathogen and accumulating evidence links the presence of F. nucleatum with the pathogenicity, development, and prognosis of colorectal cancer (CRC). However, only limited preliminary data is available dealing with the role of F. nucleatum in other malignancies except for CRC. The present review aims to update and systematize the latest information about the mechanisms of F. nucleatum-mediating carcinogenesis, together with the detection rates, clinicopathological, and molecular features in F. nucleatum-associated malignancies. Comparing with adjacent non-tumorous tissue, previous studies have shown an overabundance of intratumoural F. nucleatum. Although the prognostic role of F. nucleatum is still controversial, a higher prevalence of F. nucleatum was usually associated with a more advanced tumor stage and a worse overall survival. Preliminary evidence have shown that epithelial-to-mesenchymal transition (EMT) and relevant inflammation and immune response aroused by F. nucleatum may be the probable link between F. nucleatum infection and the initiation of oral/head and neck cancer. Further studies are needed to elucidate the etiologic role of the specific microbiota and the connection between the extent of periodontitis and carcinogenesis in different tumor types. The mechanisms of how the antibiotics exerts the critical role in the carcinogenesis and antitumor effects in malignancies other than CRC need to be further explored.
Regulatory T cells regulate blastemal proliferation during zebrafish caudal fin regeneration
Authors: Hui Subhra P. , Sugimoto Kotaro , Sheng Delicia Z. , Kikuchi Kazu
Published: August 2022

The role of T cells in appendage regeneration remains unclear. In this study, we revealed an important role for regulatory T cells (Tregs), a subset of T cells that regulate tolerance and tissue repair, in the epimorphic regeneration of zebrafish caudal fin tissue. Upon amputation, fin tissue-resident Tregs infiltrate into the blastema, a population of progenitor cells that produce new fin tissues. Conditional genetic ablation of Tregs attenuates blastemal cell proliferation during fin regeneration. Blastema-infiltrating Tregs upregulate the expression of igf2a and igf2b, and pharmacological activation of IGF signaling restores blastemal proliferation in Treg-ablated zebrafish. These findings further extend our understandings of Treg function in tissue regeneration and repair.
Cellular and humoral immune responses and breakthrough infections after three SARS-CoV-2 mRNA vaccine doses
Authors: Almendro-Vázquez Patricia , Chivite-Lacaba Marta , Utrero-Rico Alberto , González-Cuadrado Cecilia , Laguna-Goya Rocio , Moreno-Batanero Miguel , Sánchez-Paz Laura , Luczkowiak Joanna , Labiod Nuria , Folgueira María Dolores , Delgado Rafael , Paz-Artal Estela
Published: August 2022

Background

SARS-CoV-2 vaccination has proven the most effective measure to control the COVID-19 pandemic. Booster doses are being administered with limited knowledge on their need and effect on immunity.

Objective

To determine the duration of specific T cells, antibodies and neutralization after 2-dose vaccination, to assess the effect of a third dose on adaptive immunity and to explore correlates of protection against breakthrough infection.

Methods

12-month longitudinal assessment of SARS-CoV-2-specific T cells, IgG and neutralizing antibodies triggered by 2 BNT162b2 doses followed by a third mRNA-1273 dose in a cohort of 77 healthcare workers: 17 with SARS-CoV-2 infection prior to vaccination (recovered) and 60 naïve.

Results

Peak levels of cellular and humoral response were achieved 2 weeks after the second dose. Antibodies declined thereafter while T cells reached a plateau 3 months after vaccination. The decline in neutralization was specially marked in naïve individuals and it was this group who benefited most from the third dose, which resulted in a 20.9-fold increase in neutralization. Overall, recovered individuals maintained higher levels of T cells, antibodies and neutralization 1 to 6 months post-vaccination than naïve. Seventeen asymptomatic or mild SARS-CoV-2 breakthrough infections were reported during follow-up, only in naïve individuals. This viral exposure boosted adaptive immunity. High peak levels of T cells and neutralizing antibodies 15 days post-vaccination associated with protection from breakthrough infections.

Conclusion

Booster vaccination in naïve individuals and the inclusion of viral antigens other than spike in future vaccine formulations could be useful strategies to prevent SARS-CoV-2 breakthrough infections.
A system of marine animal bioconstructions in the mesophotic zone along the Southeastern Italian coast
Authors: Cardone Frine , Corriero Giuseppe , Longo Caterina , Pierri Cataldo , Gimenez Guadalupe , Gravina Maria Flavia , Giangrande Adriana , Lisco Stefania , Moretti Massimo , De Giosa Francesco , Mercurio Maria , Marzano Carlotta Nonnis
Published: August 2022

A widespread and diversified mesophotic system of carbonate bioconstructions along the Southern Adriatic and Ionian Italian coasts is described, providing new data on the distribution, structure and associated megabenthic assemblages of mesophotic Mediterranean bioconstructions. The bioconstructions were detected at six different sites off the coasts of Apulia, in presence of marked morphological escarpments, developing on a basal substrate consisting of meso-Cenozoic carbonate rocks. Two biogenic structure types were observed, one mainly built by the nonsymbiotic scleractinians Phyllangia americana mouchezii and Polycyathus muellerae, at depths between approximately 35 and 55 m, and the other by the oyster Neopycnodonte cochlear, at depths from approximately 40 to 70 m. A total of 52 taxa of megabenthic invertebrates, belonging to 6 phyla, were found on the surface of the mesophotic bioconstructions, thus confirming the role of biodiversity hotspots of these carbonate structures. Megabenthic assemblages showed a remarkable heterogeneity both in pattern of species and abundance, probably depending on both the morphological differences of the seabed and the life traits of the single species. Primary bioconstructors seemed to influence the associated community pattern. This peculiar system deserves sound conservation measures in the light of the holistic ecosystem approach for the management of coastal marine areas.
Sarcoid-like reaction in patients with malignant tumors: Long-term clinical course and outcomes
Authors: Huh Jin-Young , Moon Do Sik , Song Jin Woo
Published: August 2022

Background

The development of non-caseating epithelioid cell granulomas in cancer patients who do not fulfill the systemic sarcoidosis criteria is termed sarcoid-like reaction (SLR). Little is known about this condition's natural course and impact on the prognosis of malignancy. We aimed to investigate the natural course and prognostic value of cancer-associated SLR.

Methods

Clinical data were retrospectively analyzed in 32 patients with biopsy-proven cancer-associated SLR. Among patients with non-small cell lung cancer (NSCLC), SLR cases (n = 8) were matched with non-SLR cases (n = 78) for survival analysis.

Results

Among the included patients, the mean age was 59.7 years, and 68.8% were female. The median follow-up period was 35.6 months [interquartile range (IQR): 14.0–61.4 months]. Of all the included malignancies (n = 32), breast cancer (25.0%) and NSCLC (25.0%) were the most common, with stage I being the most frequent tumor stage (59.4%). During follow-up, SLR progression to overt sarcoidosis was not observed. In the 28 patients with available follow-up computed tomography images (median interval: 24.9 months; IQR: 14.4–41.7), 4 patients received corticosteroids (n = 4), resulting to a decrease of SLR lesions. Meanwhile, among those who did not receive treatment (n = 24), the extent of SLR decreased or did not change in 85.7% of them, whereas 3.6% had increased SLR extent. Furthermore, among patients with NSCLC, SLR was not associated with overall survival [hazard ratio (HR) = 1.28, 95% confidence interval (CI): 0.02–67.71, P = 0.882] and recurrence of malignancy (HR = 1.27, 95% CI 0.21–7.51, P = 0.793) in the Cox proportional hazard regression model.

Conclusions

During the follow-up of cancer-related SLR, we found no further evidence for systemic sarcoidosis, and most of the lesions decreased or did not change. Development of SLR was also not associated with overall survival or disease-free survival in patients with NSCLC.
Elevated serum TLR4 level as a potential marker for postsurgical chronic pain in pediatric patients with different approaches to analgesia
Authors: Semkovych Yaroslav , Dmytriiev Dmytro
Published: August 2022

Introduction

The perioperative period of any surgery is accompanied by immune suppression. The level of Toll-like receptor 4 (TLR4) is known to increase in inflammation and after nerve injury and contributes to the development of neuropathic pain. The interaction of TLRs in response to the effect of opioids results in paradoxical hyperalgesia. Regional anesthesia techniques are the standard of care for perioperative pain management in children.

Aim

The aim of the study was to determine and evaluate the indicators of TLR4 for different methods of pain relief in anesthetic management of hernia repair in children and their effect on pain chronification.

Materials and methods

There were examined 60 children with inguinal hernia during 2020–2022. Children were divided into 3 groups: Group I included 20 children who underwent surgery under general anesthesia using the block of the anterior abdominal wall—transversalis fascia plane block (TFPB), combined with the quadratus lumborum block (QLB-4) via a single intramuscular injection; Group II included 20 children who underwent surgery under general anesthesia using the TFPB; Group III comprised 20 children who underwent surgery under general anesthesia using opioid analgesics. The levels of TLR4 were evaluated at a discharge from the hospital, 3 and 6 months after surgery.

Results

There was no difference in age and body weight among all groups. In Group II, boys prevailed. In Group III, the length of hospital stay was the longest (3.28 ± 0.24 days, p < 0.05, t = 4.09) as compared to children of Group II and Group I (3.0 ± 0.30 (p < 0.05, t = 2.647) and 2.1 ± 0.16 days, respectively). While staying in the surgical department, children of Group III demonstrated significantly higher FLACC and VAS scores. The prevalence of chronic pain was the highest among children of Group III (35%) as compared to those in Group II and Group I (20 and 15%, respectively). The highest increase in the level of TLR4 was found in the group of opioid analgesia on the third and sixth months after surgery (68.86 + 10.31 pg/ml and 143.15 + 18.77 pg/ml (p < 0.05, t = 6.33), respectively) as compared to patients who received regional anesthesia.

Conclusions

There were confirmed the following advantages of the transversalis fascia plane block combined with the quadratus lumborum block (QLB + TFPB) via a single intramuscular injection: ease of use; adequate perioperative pain control as evidenced by the FLACC and VAS pain assessment scales; reduced perioperative use of opioid analgesics; shortening the length of hospital stay.
Calculating intraocular lens power in anterior megalophthalmos: A case report
Authors: Mu Jiancheng , Yang Yu , Xiong Tianxu , Fan Wei
Published: August 2022

Introduction

We report a case of a man with cataract and anterior megalophthalmos (AM), in which some myopia was retained when calculating intraocular lens (IOL) power using the Haigis formula to avoid postoperative farsightedness.

Case description

A 59-year-old Chinese man was referred to our clinic for cataract surgery in his right eye. He had strong bilateral megalocornea, and his left eye had undergone surgery four times. After complete preoperative examinations and repeated biometry, the Haigis formula was used, and a 3-piece IOL was implanted with a target power of −1.97 D. At 1-year follow-up, the patient showed the best-corrected distance vision of 20/20 with the refraction of −1.50 DC × 160°, and the IOL was stable.

Conclusion

Our patient with anterior megalophthalmos showed postoperative hyperopia drift even though the Haigis formula was used as suggested in previous studies. To prevent farsightedness after surgery, some myopia should be retained when calculating IOL power. The Kane, Holladay II with AL adjustment, and Barrett Universal II formulas may be more accurate for calculating IOL power in such patients.
Survival characteristics and transcriptome profiling reveal the adaptive response of the Brucella melitensis 16M biofilm to osmotic stress
Authors: Guo Jia , Zhu Jiale , Zhao Tianyi , Sun Zhihua , Song Shengnan , Zhang Yu , Zhu Dexin , Cao Shuzhu , Deng Xingmei , Chai Yingjin , Sun Yongxue , Maratbek Suleimenov , Chen Chuangfu , Liu Liangbo , Zhang Hui
Published: August 2022

Brucella can inhabit hostile environments, including osmotic stress. How Brucella responds collectively to osmotic stress is largely unexplored, particularly in spatially structured communities such as a biofilm. To gain insight into this growth mode, we set out to characterize the Brucella melitensis 16M biofilm, describe its phenotype, and carry out a comparative transcriptomic analysis between biofilms under osmotic stress and control conditions. We determined that the bacteria challenged with 1.5 M NaCl had a reduced ability to aggregate and form clumps and develop a biofilm; however, the salt stress promoted the release of the outer membrane vesicles from the biofilm. Together with the genotypical response to osmotic stress, we identified 279 differentially expressed genes in B. melitensis 16M grown under osmotic conditions compared with control conditions; 69 genes were upregulated and 210 downregulated. Under osmotic stress, the main changed genes of biofilm were predicted to be involved in flagellar assembly, cell envelope, translation, small RNA regulation, transport and binding proteins, and energy metabolism. In addition, the ABC transporter was enriched in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. We highlight 12 essential ABC transporter genes associated with a bacterial response to osmotic stress at the biofilm stage, including one specific locus, BME_RS12880, mediating betaine accumulation in biofilms to eliminate osmotic stress. The current study results can help researchers gain insights into B. melitensis 16M biofilm adaptation to osmotic stress and provide information for developing intervention strategies to control Brucella.
Sustainable citric acid production from CO2 in an engineered cyanobacterium
Authors: Zhang Lifang , Bryan Samantha J. , Selão Tiago Toscano
Published: August 2022

Citric acid is one of the most widely used organic acids in the world, with applications ranging from acidity regulation in food and beverages to metal chelation in hydrometallurgical processes. Most of its production is currently derived from fermentative processes, using plant-derived carbon feedstocks. While these are currently dominant, there is an increasing need to develop closed-loop production systems that reduce process carbon footprint. In this work, we demonstrate for the first time that an engineered marine cyanobacterium Synechococcus sp. PCC 7002 can be used as a sustainable chassis for the photosynthetic conversion of CO2 to citric acid. Decreased citric acid cycle flux, through the use of a theophylline-responsive riboswitch, was combined with improved flux through citrate synthase and enhanced citric acid excretion, resulting in a significant improvement to citric acid production. While allowing citrate production, this strategy induces a growth defect which can be overcome by glutamate supplementation or by fine-tuning aconitase levels, resulting in an increase in production relative to WT of over 100-fold. This work represents a first step toward sustainable production of a commodity organic acid from CO2.
Folic acid restricts SARS-CoV-2 invasion by methylating ACE2
Authors: Zhang Yuanzhou , Pang Yechun , Xu Baiyin , Chen Xingshi , Liang Shunshun , Hu Jingying , Luo Xiaoying
Published: August 2022

The current COVID-19 pandemic is motivating us to elucidate the molecular mechanism of SARS-CoV-2 invasion and find methods for decreasing its transmissibility. We found that SARS-CoV-2 could increase the protein level of ACE2 in mice. Folic acid and 5-10-methylenetetrahydrofolate reductase (MTHFR) could promote the methylation of the ACE2 promoter and inhibit ACE2 expression. Folic acid treatment decreased the binding ability of Spike protein, pseudovirus and inactivated authentic SARS-CoV-2 to host cells. Thus, folic acid treatment could decrease SARS-CoV-2 invasion and SARS-CoV-2-neutralizing antibody production in mice. These data suggest that increased intake of folic acid may inhibit ACE2 expression and reduce the transmissibility of SARS-CoV-2. Folic acid could play an important role in SARS-CoV-2 infection prevention and control.
A cuproptosis-related lncRNAs signature for prognosis, chemotherapy, and immune checkpoint blockade therapy of low-grade glioma
Authors: Yan Xiuwei , Wang Nan , Dong Jiawei , Wang Fang , Zhang Jiheng , Hu Xueyan , Zhao Hongtao , Gao Xin , Liu Zhihui , Li Yongzhe , Hu Shaoshan
Published: August 2022

Cuproptosis is a new type of cell death that is associated with mitochondrial respiration of the tricarboxylic acid cycle. Previous studies showed that long non-coding RNAs (lncRNAs) regulated low-grade glioma (LGG) progression. However, the potential applications of cuproptosis-related lncRNAs (CRLs) in LGG were not explored. A comprehensive analysis was performed in The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) cohorts. We first screened two distinct cuproptosis subtypes based on prognostic CRLs using consensus clustering. To facilitate individualized survival prediction in LGG, we constructed a prognostic signature (including CRNDE, HAR1A, and FAM181A-AS1) in the TCGA dataset. The prognostic signature exhibited excellent predictive ability and reliability, which was validated in the CGGA_325 and CGGA_693 datasets. Notably, patients in the high-risk group had increased immune cell infiltration and expression of immune checkpoints, which indicated that they may benefit more from immune checkpoint blockade (ICB) therapy. Finally, the prognostic signature screened the population with sensitivity to chemotherapy and ICB therapy. In summary, this study initially explored the mechanism of CRLs in LGG and provides some insights into chemotherapy and ICB therapy of LGG.
Contrasting Effects of Sleep Restriction, Total Sleep Deprivation, and Sleep Timing on Positive and Negative Affect
Authors: Groeger John A. , Lo June C-Y. , Santhi Nayantara , Lazar Alpar S. , Dijk Derk-Jan
Published: August 2022

Laboratory-based sleep manipulations show asymmetries between positive and negative affect, but say little about how more specific moods might change. We report extensive analyzes of items from the Positive and Negative Affect Scale (PANAS) during days following nights of chronic sleep restriction (6 h sleep opportunity), during 40 h of acute sleep deprivation under constant routine conditions, and during a week-long forced desynchrony protocol in which participants lived on a 28-h day. Living in the laboratory resulted in medium effects sizes on all positive moods (Attentiveness, General Positive Affect, Joviality, Assuredness), with a general deterioration as the days wore on. These effects were not found with negative moods. Sleep restriction reduced some positive moods, particularly Attentiveness (also General Positive), and increased Hostility. A burden of chronic sleep loss also led to lower positive moods when participants confronted the acute sleep loss challenge, and all positive moods, as well as Fearfulness, General Negative Affect and Hostility were affected. Sleeping at atypical circadian phases resulted in mood changes: all positive moods reduced, Hostility and General Negative Affect increased. Deteriorations increased the further participants slept from their typical nocturnal sleep. In most cases the changes induced by chronic or acute sleep loss or mistimed sleep waxed or waned across the waking day, with linear or various non-linear trends best fitting these time-awake-based changes. While extended laboratory stays do not emulate the fluctuating emotional demands of everyday living, these findings demonstrate that even in controlled settings mood changes systematically as sleep is shortened or mistimed.
Anthropomorphic or non-anthropomorphic? Effects of biological sex in observation of actions in a digital human model and a gantry robot model
Authors: Abel Miriam , Kuz Sinem , Patel Harshal Jayeshkumar , Petruck Henning , Klann Juliane , Schlick Christopher M. , Schüppen André , Pellicano Antonello , Binkofski Ferdinand C.
Published: August 2022

Robots are ever more relevant for everyday life, such as healthcare or rehabilitation, as well as for modern industrial environment. One important issue in this context is the way we perceive robots and their actions. From our previous study, evidence exists that sex can affect the way people perceive certain robot's actions. In our fMRI study, we analyzed brain activations of female and male participants, while they observed anthropomorphic and robotic movements performed by a human or a robot model. While lying in the scanner, participants rated the perceived level of anthropomorphic and robotic likeness of movements in the two models. The observation of the human model and the anthropomorphic movements similarly activated the biological motion coding areas in posterior temporal and parietal areas. The observation of the robot model activated predominantly areas of the ventral stream, whereas the observation of robotic movements activated predominantly the primary and higher order motor areas. To note, this later activation originated mainly from female participants, whereas male participants activated, in both robot model and robotic movements contrasts, areas in the posterior parietal cortex. Accordingly, the general contrast of sex suggests that men tend to use the ventro-dorsal stream most plausibly to rely on available previous knowledge to analyze the movements, whereas female participants use the dorso-dorsal and the ventral streams to analyze online the differences between the movement types and between the different models. The study is a first step toward the understanding of sex differences in the processing of anthropomorphic and robotic movements.
Multi-type RFC1 repeat expansions as the most common cause of hereditary sensory and autonomic neuropathy
Authors: Yuan Jun-Hui , Higuchi Yujiro , Ando Masahiro , Matsuura Eiji , Hashiguchi Akihiro , Yoshimura Akiko , Nakamura Tomonori , Sakiyama Yusuke , Mitsui Jun , Ishiura Hiroyuki , Tsuji Shoji , Takashima Hiroshi
Published: August 2022

Non-coding repeat expansions within RFC1 and NOTCH2NLC genes have lately been linked to multisystem neurodegenerative diseases, which also shed light on yet undiagnosed patients with inherited peripheral neuropathies. The aim of this study was to identify the genetic basis of patients with hereditary sensory and autonomic neuropathy (HSAN). We collected 79 unrelated DNA samples clinically suspected with HSAN from multiple regions of Japan. Mutation screening was first performed using gene panel sequencing and whole-exome sequencing. Pathogenic/likely pathogenic variants were identified from genes of WNK1/HSN2 (6 cases), SCN9A (3 cases), NTRK1 (3 cases), and DNMT1 (2 cases). Subsequently, long-range flanking PCR and repeat-primed PCR were applied to analyze repeat expansions in RFC1 and NOTCH2NLC. Bi-allelic RFC1 repeat expansions were detected from 20 adult-onset HSAN patients, consisting of [(AAGGG)exp/(AAGGG)exp] (8 cases), [(ACAGG)exp/(ACAGG)exp] (8 cases), and [(AAGGG)exp/(ACAGG)exp] (4 cases). GGC repeat expansion in NOTCH2NLC was found in 1 case. Single-nucleotide variant-based haplotype analysis of patients harboring disease-associated repeat expansions in RFC1 revealed distinguishable haplotypes among subgroups with different repeat genotypes. These findings substantially redefine the genetic spectrum of HSAN, where multi-type RFC1 repeat expansions account for 25.3% of all patients, highlighting the necessity of genetic screening, particularly for adult-onset patients.
Altered dynamic intrinsic brain activity of the default mode network in Alzheimer’s disease: A resting-state fMRI study
Authors: Liao Zhengluan , Sun Wangdi , Liu Xiaozheng , Guo Zhongwei , Mao Dewang , Yu Enyan , Chen Yan
Published: August 2022

Objective

Static regional homogeneity (ReHo) based on the resting-state functional magnetic resonance imaging (rs-fMRI) has been used to study intrinsic brain activity (IBA) in Alzheimer’s disease (AD). However, few studies have examined dynamic ReHo (dReHo) in AD. In this study, we used rs-fMRI and dReHo to investigate the alterations in dynamic IBA in patients with AD to uncover dynamic imaging markers of AD.

Method

In total, 111 patients with AD, 29 patients with mild cognitive impairment (MCI), and 73 healthy controls (HCs) were recruited for this study ultimately. After the rs-fMRI scan, we calculated the dReHo values using the sliding window method. ANOVA and post hoc two-sample t-tests were used to detect the differences among the three groups. We used the mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA) to evaluate the cognitive function of the subjects. The associations between the MMSE score, MoCA score, and dReHo were assessed by the Pearson correlation analysis.

Results

Significant dReHo variability in the right middle frontal gyrus (MFG) and right posterior cingulate gyrus (PCG) was detected in the three groups through ANOVA. In post hoc analysis, the AD group exhibited significantly greater dReHo variability in the right MFG than the MCI group. Compared with the HC group, the AD group exhibited significantly increased dReHo variability in the right PCG. Furthermore, dReHo variability in the right PCG was significantly negatively correlated with the MMSE and MoCA scores of patients with AD.

Conclusion

Disrupted dynamic IBA in the DMN might be an important characteristic of AD and could be a potential biomarker for the diagnosis or prognosis of AD.
Training Spiking Neural Networks for Reinforcement Learning Tasks With Temporal Coding Method
Authors: Wu Guanlin , Liang Dongchen , Luan Shaotong , Wang Ji
Published: August 2022

Recent years witness an increasing demand for using spiking neural networks (SNNs) to implement artificial intelligent systems. There is a demand of combining SNNs with reinforcement learning architectures to find an effective training method. Recently, temporal coding method has been proposed to train spiking neural networks while preserving the asynchronous nature of spiking neurons to preserve the asynchronous nature of SNNs. We propose a training method that enables temporal coding method in RL tasks. To tackle the problem of high sparsity of spikes, we introduce a self-incremental variable to push each spiking neuron to fire, which makes SNNs fully differentiable. In addition, an encoding method is proposed to solve the problem of information loss of temporal-coded inputs. The experimental results show that the SNNs trained by our proposed method can achieve comparable performance of the state-of-the-art artificial neural networks in benchmark tasks of reinforcement learning.
Dietary assessment training: The Italian IV SCAI study on 10–74 year-old individuals’ food consumption
Authors: Le Donne Cinzia , Piccinelli Raffaela , Sette Stefania , Martone Deborah , Catasta Giovina , Censi Laura , Comendador Azcarraga Francisco Javier , D’Addezio Laura , Ferrari Marika , Mistura Lorenza , Pettinelli Antonella , Saba Anna , Barbina Donatella , Guerrera Debora , Carbone Pietro , Mazzaccara Alfonso , Turrini Aida
Published: August 2022

Dietary surveys are conducted to examine the population’s dietary patterns that require a complex system of databases, and rules for constructing the data matrix (precision, coding, deriving new variables, e.g., body mass index from individual’s height and weight, classes, e.g., age-class, socio-economic status, physical activity, etc.). Management of the data collection requires specialized fieldworkers to allow for the collection of harmonized and standardized data. In this way, only statistical variability is envisaged and any eventual biases are due to probabilistic distribution but data are not affected by inaccuracy. Training the fieldworkers is a crucial part of each dietary survey. The idea to provide constant training throughout the whole survey period, from the preparatory phase to the data collection phase, relies on the necessity to train fieldworkers and monitor the skills acquired during the study, in addition to helping fieldworkers to gain the necessary experience. This study aims to relate the experience in conducting the course path to high specialized interviewers who carried out the cycle devoted to the 10–74 age class of the fourth nationwide food consumption study in Italy (IV SCAI ADULT) according to the European Food Safety Authority (EFSA) guide. A course path was structured in three steps corresponding to the preparation, pilot, and collection phases. The whole path achieved the goal of collecting data related to 12 individuals by each participant, with an overall success rate (successful trainees/total participants) of 16.8% (84 out of an initial 500). The study aimed to provide good quality data in the short term and a highly specialized community in the long term. Surveillance nutritional systems can count on a highly skilled community, so decision-making in public health nutrition and a sustainable and healthy food system can rely on this infrastructure.
Metabolic protection by the dietary flavonoid 7,8-dihydroxyflavone requires an intact gut microbiome
Authors: Sharma Priyanka , Silva Camila , Pfreundschuh Sarah , Ye Hong , Sampath Harini
Published: August 2022

Background

7,8-dihydroxyflavone (DHF) is a naturally occurring flavonoid found in Godmania, Tridax, and Primula species that confers protection against high-fat diet (HFD) induced metabolic pathologies selectively in female mice. We have previously reported that this metabolic protection is associated with early and stable remodeling of the intestinal microbiome, evident in female but not male DHF-supplemented mice. Early changes in the gut microbiome in female DHF-fed mice were highly predictive of subsequent metabolic protection, suggesting a causative association between the gut microbiome and the metabolic effects of DHF.

Objective

To investigate a causal association between the gut microbiome and the metabolic effects of DHF using a model of antibiotic-induced gut microbiome ablation.

Materials and methods

Age-matched male and female C57Bl6/J mice were given ad libitum access to HFD and drinking water containing vehicle or DHF for 12 weeks. For antibiotic (Abx) treatment, female mice were given drinking water containing a cocktail of antibiotics for 2 weeks prior to HFD feeding and throughout the feeding period. Metabolic phenotyping consisted of longitudinal assessments of body weights, body composition, food, and water intake, as well as measurement of energy expenditure, glucose tolerance, and plasma and hepatic lipids. Protein markers mediating the cellular effects of DHF were assessed in brown adipose tissue (BAT) and skeletal muscle.

Results

Metabolic protection conferred by DHF in female HFD-fed mice was only apparent in the presence of an intact gut microbiome. Abx-treated mice were not protected from HFD-induced obesity by DHF administration. Further, tissue activation of the tropomyosin-related kinase receptor B (TrkB) receptor, which has been attributed to the biological activity of DHF, was lost upon gut microbiome ablation, indicating a requirement for microbial “activation” of DHF for its systemic effects. In addition, we report for the first time that DHF supplementation significantly activates TrkB in BAT of female, but not male, mice uncovering a novel target tissue of DHF. DHF supplementation also increased uncoupling protein 1 (UCP1) and AMP-activated protein kinase (AMPK) protein in BAT, consistent with protection from diet-induced obesity.

Conclusion

These results establish for the first time a requirement for the gut microbiome in mediating the metabolic effects of DHF in female mice and uncover a novel target tissue that may mediate these sexually-dimorphic protective effects.
Navigating preemptive and therapeutic donor lymphocyte infusions in advanced myeloid malignancies by high-sensitivity chimerism analysis
Authors: Stadler Michael , Venturini Letizia , Bünting Ivonne , Dammann Elke , Weissinger Eva M. , Schwarzer Adrian , Schultze-Florey Christian , Ehrlich Steve , Markel Dominik , Lueck Catherina , Gladysz Alexandra , Fröhlich Tabea , Damrah Nouraldin , Beutel Gernot , Eder Matthias , Ganser Arnold , Hambach Lothar
Published: August 2022

Preemptive and therapeutic donor lymphocyte infusions (preDLI and tDLI) are widely used in relapsing and relapsed hematopoietic malignancies after allogeneic stem cell transplantation (alloSCT) to enhance the graft-versus-malignancy effect. However, in advanced myeloid malignancies, long-term survival after preDLI and tDLI remains low, reflecting our inability to master the double-edged sword of alloreactivity, balancing anti-neoplastic activity versus graft-versus-host disease (GvHD). We previously evaluated a quantitative PCR-based high-sensitivity chimerism (hs-chimerism) based on insertion/deletion polymorphisms instead of short tandem repeats, where increasing host chimerism in peripheral blood predicts relapse more than a month before clinical diagnosis, and declining host chimerism signals anti-host alloreactivity. Here we report 32 consecutive patients with advanced myeloid malignancies receiving preDLI or tDLI “navigated” by hs-chimerism (“navigated DLI”). We compared them to a historical cohort of 110 consecutive preDLI or tDLI recipients, prior to implementation of hs-chimerism at our institution (“controls”). Both groups were comparable regarding age, gender, conditioning, donor type, and time to DLI. With longer median follow-up of the navigated DLI group (8.5 versus 5 months), their landmark overall (64%) and disease-free survival (62%) at 2 years from first DLI compared favorably with controls (23% and 21%, respectively). Improved survival of navigated DLI was due to both reduced relapse incidence (38% versus 60%) and non-relapse mortality (17% versus 44%) at 2 years. Early relapse prediction by hs-chimerism allowed a preemptive approach in 28% of navigated DLI versus 7% in controls. Our results confirm hs-chimerism as a highly valuable tool for monitoring and steering immune interventions after alloSCT.
Evolutions in the management of non-small cell lung cancer: A bibliometric study from the 100 most impactful articles in the field
Authors: Chen Siyuan , Qiao Yu , Chen Juan , Li Yanan , Xie Jianlian , Cui Pengfei , Huang Ziwei , Huang Di , Gao Yiming , Hu Yi , Liu Zhefeng
Published: August 2022

Objective

The study was designed to explore the evolution of non-small cell lung cancer (NSCLC) management in the last 20 years.

Methods

The top 100 most-cited papers on NSCLC treatment were retrieved from the Web of Science Core Collection database. R and VOSviewer were used to extract bibliographic information, including the year of publication, countries/regions, institutions, authors, journals, keywords, impact factor, and total citations. The topic and type of papers were checked independently by authors. Bibliometric analysis was conducted and visualized with R, CiteSpace, Excel and VOSviewer to identify output dynamics, research forces, topics, hotspots, and frontiers in the field.

Results

The average citation of each retrieved top 100 most-cited NSCLC management papers was 1,725 (range: 615-7,340). Fifty-seven corresponding authors were from the United States. This country contributed the most papers (n=76), followed by Germany (n=34), France (n=33), and South Korea (n=32). The top contributors were Paz-Ares L. (n=12) and Reck M. (n=12). The Memorial Sloan Kettering Cancer Center published the largest number of papers (n=20). There were two significant citation paths, indicating publications in medicine/medical/clinical journals primarily cited journals in molecular/biology/genetics fields, partly cited health/nursing/medicine fields. Top-cited papers mainly came from the New England Journal of Medicine (n=33, citations=80,427), followed closely by the Journal of Clinical Oncology (n=28, citations=32,408). “Chemotherapy” (n=36) was the keyword with the greatest frequency of co-occurrence. “Open-label” was the keyword with the strongest burst strength (=4.01), followed by “nivolumab” (=3.85), “blockade” (=2.86), and “efficacy” (=2.85).

Conclusions

The United States as a nation and the Memorial Sloan Kettering Cancer Center as an institute contributed the most to this field. The New England Journal of Medicine is the most eye-catching journal. Hotspots of NSCLC management have almost undergone an evolution from chemotherapy and radiotherapy to targeted therapy to immunotherapy. Molecular/biological/genetic fields become the main research base for NSCLC treatment. Immunotherapy and combination therapy are research frontiers.
Machine learning-featured Secretogranin V is a circulating diagnostic biomarker for pancreatic adenocarcinomas associated with adipopenia
Authors: Jo Yunju , Yeo Min-Kyung , Dao Tam , Kwon Jeongho , Yi Hyon‐Seung , Ryu Dongryeol
Published: August 2022

Background

Pancreatic cancer is one of the most fatal malignancies of the gastrointestinal cancer, with a challenging early diagnosis due to lack of distinctive symptoms and specific biomarkers. The exact etiology of pancreatic cancer is unknown, making the development of reliable biomarkers difficult. The accumulation of patient-derived omics data along with technological advances in artificial intelligence is giving way to a new era in the discovery of suitable biomarkers.

Methods

We performed machine learning (ML)-based modeling using four independent transcriptomic datasets, including GSE16515, GSE62165, GSE71729, and the pancreatic adenocarcinoma (PAC) dataset of the Cancer Genome Atlas. To find candidates for circulating biomarkers, we exported expression profiles of 1,703 genes encoding secretory proteins. Integrating three transcriptomic datasets into either a training or test set, ML-based modeling distinguishing PAC from normal was carried out. Another ML-model classifying long-lived and short-lived patients with PAC was also built to select prognosis-associated features. Finally, circulating level of SCG5 in the plasma was determined from the independent cohort (non-tumor = 25 and pancreatic cancer = 25). We also investigated the impact of SCG5 on adipocyte biology using recombinant protein.

Results

Three distinctive ML-classifiers selected 29-, 64- and 18-featured genes, recognizing the only common gene, SCG5. As per the prediction of ML-models, the SCG5 transcripts was significantly reduced in PAC and decreased further with the progression of the tumor, indicating its potential as a diagnostic as well as prognostic marker for PAC. External validation of SCG5 using plasma samples from patients with PAC confirmed that SCG5 was reduced significantly in patients with PAC when compared to controls. Interestingly, plasma SCG5 levels were correlated with the body mass index and age of donors, implying pancreas-originated SCG5 could regulate energy metabolism systemically. Additionally, analyses using publicly available Genotype-Tissue Expression datasets, including adipose tissue histology and pancreatic SCG5 expression, further validated the association between pancreatic SCG5 expression and the size of subcutaneous adipocytes in humans. However, we could not observe any definite effect of rSCG5 on the cultured adipocyte, in 2D in vitro culture.

Conclusion

Circulating SCG5, which may be associated with adipopenia, is a promising diagnostic biomarker for PAC.