bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired quality of life, but not cognition, is linked to a history of chronic hypercortisolism in patients with Cushing’s disease in remission
Authors: Pupier Emilie , Santos Alicia , Etchamendy Nicole , Lavielle Aurélie , Ferriere Amandine , Marighetto Aline , Resmini Eugenia , Cota Daniela , Webb Susan M. , Tabarin Antoine
Published: August 2022

Context

Impaired cognition and altered quality of life (QoL) may persist despite long-term remission of Cushing’s disease (CD). Persistent comorbidities and treatment modalities may account for cognitive impairments. Therefore, the role of hypercortisolism per se on cognitive sequelae remains debatable.

Objective

To investigate whether memory and QoL are impaired after long-term remission of CD in patients with no confounding comorbidity.

Design and Setting

Cross-sectional case-control study in two tertiary referral centers

Patients

25 patients (44.5 ± 2.4 years) in remission from CD for 102.7 ± 19.3 Mo and 25 well-matched controls, without comorbidity or treatment liable to impair cognition.

Main Outcome Measure(s)

Hippocampus- and prefrontal cortex-dependent memory, including memory flexibility and working memory, were investigated using multiple tests including sensitive locally-developed computerized tasks. Depression and anxiety were evaluated with the MADRS and HADS questionnaires. QoL was evaluated with the SF-36 and CushingQoL questionnaires. The intensity of CD was assessed using mean urinary free cortisol and a score for clinical symptoms.

Results

CD patients displayed similar performance to controls in all cognitive tests. In contrast, despite the absence of depression and a minimal residual clinical Cushing score, patients had worse QoL. Most of the SF36 subscales and the CushingQoL score were negatively associated only with the duration of exposure to hypercortisolism (p≤ 0.01 to 0.001).

Conclusions

Persistent comorbidities can be a primary cause of long-lasting cognitive impairment and should be actively treated. Persistently altered QoL may reflect irreversible effects of hypercortisolism, highlighting the need to reduce its duration.

Clinical Trial Registration number

https://clinicaltrials.gov, identifier NCT02603653
PV/WT Integrated System Using the Gray Wolf Optimization Technique for Power Quality Improvement
Authors: Goud B. Srikanth , Rami Reddy Ch. , Naga Sai kalyan Ch. , Udumula Ramanjaneya Reddy , Bajaj Mohit , Abdul Samad Bdereddin , Shouran Mokhtar , Kamel Salah
Published: August 2022

This paper presents the integration of renewable energy sources such as photovoltaics, wind, and batteries to the grid. The hybrid shunt active power filter (HSHAPF) is optimized with the Gray wolf optimization (GWO) and fractional order proportional integral controller (FOPI) for harmonic reduction under nonlinear and unbalanced load conditions. With the use of GWO, the parameters of FOPI are tuned, which effectively minimizes the harmonics. The proposed model has effectively compensated the total harmonic distortions when compared with without the filter and with the passive filter, the active power filter with a PI controller, and the GWO-FOPI-based controller. The performance of the proposed controller is tested under nonlinear and unbalanced conditions. The parameters of the FOPI controller are better tuned with the GWO technique. The comparative results reflect the best results of GWO-FOPI-based HSHAPF. The suggested controller is built in the MATLAB/Simulink Platform.
Capacity value analysis of interruptible loads in regional power systems with intermittent renewable energy
Authors: Fan Hengjian , Wang Hongliang , Xu Yang , Hu Jiahua , Zhang Weiwei , Xiao Xuanyi
Published: August 2022

The proportion of renewable energy is increasing rapidly to develop low-carbon power systems and the intermittence nature of renewable energy harms the security operation of power systems. The participation of interruptible loads is an effective means to handle the intermittence of renewable energy. However, the capacity value of interruptible loads has not been fully recognized, which results in limited involvement of interruptible loads in power system operations. Hence, it is urgent to analyze the capacity value of interruptible loads. In this paper, a capacity value calculation method of interruptible loads is proposed. A joint optimal operation model of interruptible loads and multiple power sources including thermal power units, hydropower units, and wind turbines is established to realize the application paradigm of power system operations with interruptible loads. Case analysis based on the operation data of the power system in a particular area verifies that the proposed method can effectively recognize the capacity value of interruptible loads and reduce the installed capacity of thermal power units. It thereby lays the theoretical foundation for analyzing the role of interruptible loads in the low-carbon transition of the electric energy industry.
Synergetic use of unmanned aerial vehicle and satellite images for detecting non-native tree species: An insight into Acacia saligna invasion in the Mediterranean coast
Authors: Marzialetti Flavio , Di Febbraro Mirko , Frate Ludovico , De Simone Walter , Acosta Alicia Teresa Rosario , Carranza Maria Laura
Published: August 2022

Invasive alien plants (IAPs) are increasingly threatening biodiversity worldwide; thus, early detection and monitoring tools are needed. Here, we explored the potential of unmanned aerial vehicle (UAV) images in providing intermediate reference data which are able to link IAP field occurrence and satellite information. Specifically, we used very high spatial resolution (VHR) UAV maps of A. saligna as calibration data for satellite-based predictions of its spread in the Mediterranean coastal dunes. Based on two satellite platforms (PlanetScope and Sentinel-2), we developed and tested a dedicated procedure to predict A. saligna spread organized in four steps: 1) setting of calibration data for satellite-based predictions, by aggregating UAV-based VHR IAP maps to satellite spatial resolution (3 and 10 m); 2) selection of monthly multispectral (blue, green, red, and near infra-red bands) cloud-free images for both satellite platforms; 3) calculation of monthly spectral variables depicting leaf and plant characteristics, canopy biomass, soil features, surface water and hue, intensity, and saturation values; 4) prediction of A. saligna distribution and identification of the most important spectral variables discriminating IAP occurrence using a fandom forest (RF) model. RF models calibrated for both satellite platforms showed high predictive performances (R2 > 0.6; RMSE <0.008), with accurate spatially explicit predictions of the invaded areas. While Sentinel-2 performed slightly better, the PlanetScope-based model effectively delineated invaded area edges and small patches. The summer leaf chlorophyll content followed by soil spectral variables was regarded as the most important variables discriminating A. saligna patches from native vegetation. Such variables depicted the characteristic IAP phenology and typically altered leaf litter and soil organic matter of invaded patches. Overall, we presented new evidence of the importance of VHR UAV data to fill the gap between field observation of A. saligna and satellite data, offering new tools for detecting and monitoring non-native tree spread in a cost-effective and timely manner.
RETRACTED: Carbon pricing and environmental response: A way forward for China’s carbon and energy market
Authors: Wang Yuchen , Zhou Xiaoming , Ali Anis , Omar Abdullah Bin , Rahman Zia Ur
Published: August 2022

Addressing the conflict between fossil fuel exploitation, usage, and greenhouse gas emissions is a top priority for China’s low-carbon socioeconomic development. Scalable Axisymmetric Matrix “a computerized general equilibrium model” is used to assess the impact of carbon tax policies on energy usage, carbon pollution, and macroeconomic drivers at reduction levels of 10%, 20%, and 30% of emissions. In the meantime, we examine the impact of various carbon tax recycling schemes in line with the tax neutrality concept. Although the carbon tax successfully reduces carbon emissions, we conclude that it will have a detrimental effect on the economy and social well-being. To cope with China’s increasing pollution emissions and ecological imbalances, the Chinese government promulgated the environmental protection tax law of the people’s Republic of China, which was officially implemented in 2018. Although carbon dioxide is not included in the Taxable Pollutants and Single Quantity Table attached to this law, China has almost reached a consensus on taxing carbon emissions. In 2021, the State Council of China issued the opinions on completely, accurately, and comprehensively implementing the new development concept and doing a good job in carbon peak and carbon neutralization, which made a comprehensive deployment to achieve the “double carbon” goal and improved the carbon tax policy and legal system, which is an essential part of it. Therefore, based on fiscal neutrality, an effective carbon tax recycling scheme can mitigate the adverse effects of its adoption. However, due to the current development in China’s energy-generating and transportation sectors, even minor steps can have huge effects on emissions with marginal economic implications.
Energy consumption and pollution control from the perspective of industrial economic activity: An empirical study of China’s coastal provinces
Authors: Lu Qing
Published: August 2022

From the perspective of production performance, energy supply are the basic material conditions. However, greenhouse gas, air pollution and waste water are also produced in the process of production. If the undesired characteristics are ignored in the process of performance evaluation, the production efficiency will be misestimated. Based on this, this study uses Data Envelopment Analysis (DEA) to evaluate the undesired output, and discusses the production efficiency with thermal consumption in Chinese port cities, especially with severe shipping emissions, during 2015–2019. The empirical results show that the efficiency declines first (2015–2017) and then increases (2018–2019) when considering the undesired output of wastewater and SO2 generated by thermal consumption.
Time-series transcriptome analysis identified differentially expressed genes in broiler chicken infected with mixed Eimeria species
Authors: Kim Minjun , Chung Yoonji , Manjula Prabuddha , Seo Dongwon , Cho Sunghyun , Cho Eunjin , Ediriweera Thisarani Kalhari , Yu Myunghwan , Nam Sunju , Lee Jun Heon
Published: August 2022

Coccidiosis caused by the Eimeria species is a highly problematic disease in the chicken industry. Here, we used RNA sequencing to observe the time-dependent host responses of Eimeria-infected chickens to examine the genes and biological functions associated with immunity to the parasite. Transcriptome analysis was performed at three time points: 4, 7, and 21 days post-infection (dpi). Based on the changes in gene expression patterns, we defined three groups of genes that showed differential expression. This enabled us to capture evidence of endoplasmic reticulum stress at the initial stage of Eimeria infection. Furthermore, we found that innate immune responses against the parasite were activated at the first exposure; they then showed gradual normalization. Although the cytokine-cytokine receptor interaction pathway was significantly operative at 4 dpi, its downregulation led to an anti-inflammatory effect. Additionally, the construction of gene co-expression networks enabled identification of immunoregulation hub genes and critical pattern recognition receptors after Eimeria infection. Our results provide a detailed understanding of the host-pathogen interaction between chicken and Eimeria. The clusters of genes defined in this study can be utilized to improve chickens for coccidiosis control.
Harnessing the potential of bulk segregant analysis sequencing and its related approaches in crop breeding
Authors: Majeed Aasim , Johar Prerna , Raina Aamir , Salgotra R. K. , Feng Xianzhong , Bhat Javaid Akhter
Published: August 2022

Most plant traits are governed by polygenes including both major and minor genes. Linkage mapping and positional cloning have contributed greatly to mapping genomic loci controlling important traits in crop species. However, they are low-throughput, time-consuming, and have low resolution due to which their efficiency in crop breeding is reduced. In this regard, the bulk segregant analysis sequencing (BSA-seq) and its related approaches, viz., quantitative trait locus (QTL)-seq, bulk segregant RNA-Seq (BSR)-seq, and MutMap, have emerged as efficient methods to identify the genomic loci/QTLs controlling specific traits at high resolution, accuracy, reduced time span, and in a high-throughput manner. These approaches combine BSA with next-generation sequencing (NGS) and enable the rapid identification of genetic loci for qualitative and quantitative assessments. Many previous studies have shown the successful identification of the genetic loci for different plant traits using BSA-seq and its related approaches, as discussed in the text with details. However, the efficiency and accuracy of the BSA-seq depend upon factors like sequencing depth and coverage, which enhance the sequencing cost. Recently, the rapid reduction in the cost of NGS together with the expected cost reduction of third-generation sequencing in the future has further increased the accuracy and commercial applicability of these approaches in crop improvement programs. This review article provides an overview of BSA-seq and its related approaches in crop breeding together with their merits and challenges in trait mapping.
Identification of CXCL10 and CXCL11 as the candidate genes involving the development of colitis-associated colorectal cancer
Authors: Lu Can , Zhang Xiaopeng , Luo Yang , Huang Jingang , Yu Minhao
Published: August 2022

Background: Ulcerative colitis (UC) is a well-known risk factor for developing colitis-associated colorectal cancer (CAC). However, the molecular mechanism of the pathogenesis of CAC remains unclear. This study aimed to explore candidate genes involved in the tumorigenesis of CAC.

Methods: GSE75214 and the Cancer Genome Atlas Program (TCGA) dataset were used to analyze the differentially expressed genes (DEGs) in UC and colorectal cancer (CRC), respectively. Survival-hub genes were identified from these DEGs by sequentially constructing a protein–protein interaction network, selecting hub genes, and conducting survival analysis. Regulatory signatures were also predicted on these genes through the online database. Apcmin/+ and UC mice models were used to validate the expression of the above-predicted molecules. Gene set enrichment analysis and CIBERSORT were performed to explore the enriched molecular pathways and associated tissue-infiltrating immune cells of genes.

Results: Here, 376 common DEGs were identified from the GSE75214 and TCGA datasets. Through survival-hub gene selection and in vivo experiments, we confirmed that CXCL10 and CXCL11 were significantly upregulated in UC and CRC. We also proved that miR-34a-5p and miR-203a-5p were potential regulators of CXCL10 and CXCL11. Meanwhile, CXCL10 and CXCL11 may activate the JAK–STAT signaling pathway via the interaction with cytokine receptors in UC. Furthermore, CXCL10 and CXCL11 were positively associated with the tissue infiltration of proinflammatory M1 macrophages in UC and CRC.

Conclusion: CXCL10 and CXCL11 may act as the candidate genes involved in the tumorigenesis of CAC and potential therapeutic targets to prevent the development of CAC from UC.
Human leukocyte antigen class II gene diversity tunes antibody repertoires to common pathogens
Authors: Khan Taushif , Rahman Mahbuba , Ahmed Ikhlak , Al Ali Fatima , Jithesh Puthen Veettil , Marr Nico
Published: August 2022

Allelic diversity of human leukocyte antigen (HLA) class II genes may help maintain humoral immunity against infectious diseases. In this study, we investigated germline genetic variation in classical HLA class II genes and employed a systematic, unbiased approach to explore the relative contribution of this genetic variation in the antibody repertoire to various common pathogens. We leveraged a well-defined cohort of 800 adults representing the general Arab population in which genetic material is shared because of the high frequency of consanguineous unions. By applying a high-throughput method for large-scale antibody profiling to this well-defined cohort, we were able to dissect the overall effect of zygosity for classical HLA class II genes, as well as the effects associated with specific HLA class II alleles, haplotypes and genotypes, on the antimicrobial antibody repertoire breadth and antibody specificity with unprecedented resolution. Our population genetic studies revealed that zygosity of the classical HLA class II genes is a strong predictor of antibody responses to common human pathogens, suggesting that classical HLA class II gene heterozygosity confers a selective advantage. Moreover, we demonstrated that multiple HLA class II alleles can have additive effects on the antibody repertoire to common pathogens. We also identified associations of HLA-DRB1 genotypes with specific antigens. Our findings suggest that HLA class II gene polymorphisms confer specific humoral immunity against common pathogens, which may have contributed to the genetic diversity of HLA class II loci during hominine evolution.
Microbiome in cancer: An exploration of carcinogenesis, immune responses and immunotherapy
Authors: Zhou Pei , Hu Yawen , Wang Xiaoyan , Shen Luxuan , Liao Xinghao , Zhu Yajuan , Yu Jiadong , Zhao Fulei , Zhou Yi , Shen Hengshui , Li Jiong
Published: August 2022

Cancer is a major disease endangering human health. More and more studies have shown that microorganisms play an extremely important role in the occurrence, development and treatment of tumors. As a very promising tumor treatment strategy, immunotherapy has also been proved to have a great relationship with microorganisms. Here, the authors review the contribution of the microbiota to cancer and the research on its impact on cancer immunotherapy. We also highlight the possible mechanism of their interaction and outlined the potential application of microbiota in tumor immunotherapy.
The soluble CD83 protein prevents bone destruction by inhibiting the formation of osteoclasts and inducing resolution of inflammation in arthritis
Authors: Royzman Dmytro , Andreev Darja , Stich Lena , Peckert-Maier Katrin , Wild Andreas B. , Zinser Elisabeth , Mühl-Zürbes Petra , Jones Evan , Adam Susanne , Frey Silke , Fuchs Maximilian , Kunz Meik , Bäuerle Tobias , Nagel Lisa , Schett Georg , Bozec Aline , Steinkasserer Alexander
Published: August 2022

Here we show that soluble CD83 induces the resolution of inflammation in an antigen-induced arthritis (AIA) model. Joint swelling and the arthritis-related expression levels of IL-1β, IL-6, RANKL, MMP9, and OC-Stamp were strongly reduced, while Foxp3 was induced. In addition, we observed a significant inhibition of TRAP+ osteoclast formation, correlating with the reduced arthritic disease score. In contrast, cell-specific deletion of CD83 in human and murine precursor cells resulted in an enhanced formation of mature osteoclasts. RNA sequencing analyses, comparing sCD83- with mock treated cells, revealed a strong downregulation of osteoclastogenic factors, such as Oc-Stamp, Mmp9 and Nfatc1, Ctsk, and Trap. Concomitantly, transcripts typical for pro-resolving macrophages, e.g., Mrc1/2, Marco, Klf4, and Mertk, were upregulated. Interestingly, members of the metallothionein (MT) family, which have been associated with a reduced arthritic disease severity, were also highly induced by sCD83 in samples derived from RA patients. Finally, we elucidated the sCD83-induced signaling cascade downstream to its binding to the Toll-like receptor 4/(TLR4/MD2) receptor complex using CRISPR/Cas9-induced knockdowns of TLR4/MyD88/TRIF and MTs, revealing that sCD83 acts via the TRIF-signaling cascade. In conclusion, sCD83 represents a promising therapeutic approach to induce the resolution of inflammation and to prevent bone erosion in autoimmune arthritis.
A Pan-Pneumovirus vaccine based on immunodominant epitopes of the fusion protein
Authors: Huang Jiachen , Miller Rose J. , Mousa Jarrod J.
Published: August 2022

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two leading causes of severe respiratory infections in children, the elderly, and immunocompromised patients. The fusion (F) protein is the major target of neutralizing antibodies. Recent developments in stabilizing the pre-fusion conformation of the F proteins, and identifying immunodominant epitopes that elicit potent neutralizing antibodies have led to the testing of numerous pre-fusion RSV F-based vaccines in clinical trials. We designed and tested the immunogenicity and protective efficacy of a chimeric fusion protein that contains immunodominant epitopes of RSV F and hMPV F (RHMS-1). RHMS-1 has several advantages over vaccination with pre-fusion RSV F or hMPV F, including a focus on recalling B cells to the most important protective epitopes and the ability to induce protection against two viruses with a single antigen. RHMS-1 was generated as a trimeric recombinant protein, and analysis by negative-stain electron microscopy demonstrated the protein resembles the pre-fusion conformation. Probing of RHMS-1 antigenicity using a panel of RSV and hMPV F-specific monoclonal antibodies (mAbs) revealed the protein retains features of both viruses, including the pre-fusion site Ø epitope of RSV F. Mice immunized with RHMS-1 generated neutralizing antibodies to both viruses and were completely protected from RSV or hMPV challenge. Overall, this study demonstrates protection against two viruses with a single antigen and supports testing of RHMS-1 in additional pre-clinical animal models.
EST12 regulates Myc expression and enhances anti-mycobacterial inflammatory response via RACK1-JNK-AP1-Myc immune pathway
Authors: Wu Jian , Luo Feng-Ling , Xie Yan , Xiong Huan , Gao Yadong , Liu Guanghui , Zhang Xiao-Lian
Published: August 2022

c-Myc (Myc) is a well-known transcription factor that regulates many essential cellular processes. Myc has been implicated in regulating anti-mycobacterial responses. However, its precise mechanism in modulating mycobacterial immunity remains elusive. Here, we found that a secreted Rv1579c (early secreted target with molecular weight 12 kDa, named EST12) protein, encoded by virulentMycobacterium tuberculosis(M.tb) H37Rv region of deletion (RD)3, induces early expression and late degradation of Myc protein. Interestingly, EST12-induced Myc was further processed by K48 ubiquitin proteasome degradation in E3 ubiquitin ligase FBW7 dependent manner. EST12 protein activates JNK-AP1-Myc signaling pathway, promotes Myc binding to the promoters of IL-6, TNF-α and iNOS, then induces the expression of pro-inflammatory cytokines (IL-6 and TNF-α)/inducible nitric oxide synthase (iNOS)/nitric oxide (NO) to increase mycobacterial clearance in a RACK1 dependent manner, and these effects are impaired by both Myc and JNK inhibitors. Macrophages infected with EST12-deficiency strain (H37RvΔEST12) displayed less production of iNOS, IL-6 and TNF-α. In conclusion, EST12 regulates Myc expression and enhances anti-mycobacterial inflammatory responseviaRACK1-JNK-AP1-Myc immune pathway. Our finding provides new insights intoM.tb-induced immunity through Myc.
Electroacupuncture attenuates surgical pain-induced delirium-like behavior in mice via remodeling gut microbiota and dendritic spine
Authors: Yang Liuyue , Ding Weihua , Dong Yuanlin , Chen Cynthia , Zeng Yanru , Jiang Zhangjie , Gan Shuyuan , You Zerong , Zhao Yilin , Zhang Yiying , Ren Xinghua , Wang Shiyu , Dai Jiajia , Chen Zhong , Zhu Shengmei , Chen Lucy , Shen Shiqian , Mao Jianren , Xie Zhongcong
Published: August 2022

Surgical pain is associated with delirium in patients, and acupuncture can treat pain. However, whether electroacupuncture can attenuate the surgical pain-associated delirium via the gut–brain axis remains unknown. Leveraging a mouse model of foot incision-induced surgical pain and delirium-like behavior, we found that electroacupuncture stimulation at specific acupoints (e.g., DU20+KI1) attenuated both surgical pain and delirium-like behavior in mice. Mechanistically, mice with incision-induced surgical pain and delirium-like behavior showed gut microbiota imbalance, microglia activation in the spinal cord, somatosensory cortex, and hippocampus, as well as an enhanced dendritic spine elimination in cortex revealed by two-photon imaging. The electroacupuncture regimen that alleviated surgical pain and delirium-like behavior in mice also effectively restored the gut microbiota balance, prevented the microglia activation, and reversed the dendritic spine elimination. These data demonstrated a potentially important gut–brain interactive mechanism underlying the surgical pain-induced delirium in mice. Pending further studies, these findings revealed a possible therapeutic approach in preventing and/or treating postoperative delirium by using perioperative electroacupuncture stimulation in patients.
Detailed spatial immunophenotyping of primary melanomas reveals immune cell subpopulations associated with patient outcome
Authors: Attrill Grace H. , Lee Hansol , Tasker Annie T. , Adegoke Nurudeen A. , Ferguson Angela L. , da Silva Ines Pires , Saw Robyn P. M. , Thompson John F. , Palendira Umaimainthan , Long Georgina V. , Ferguson Peter M. , Scolyer Richard A. , Wilmott James S.
Published: August 2022

While the tumor immune microenvironment (TIME) of metastatic melanoma has been well characterized, the primary melanoma TIME is comparatively poorly understood. Additionally, although the association of tumor-infiltrating lymphocytes with primary melanoma patient outcome has been known for decades, it is not considered in the current AJCC melanoma staging system. Detailed immune phenotyping of advanced melanoma has revealed multiple immune biomarkers, including the presence of CD8+ T-cells, for predicting response to immunotherapies. However, in primary melanomas, immune biomarkers are lacking and CD8+ T-cells have yet to be extensively characterized. As recent studies combining immune features and clinicopathologic characteristics have created more accurate predictive models, this study sought to characterize the TIME of primary melanomas and identify predictors of patient outcome. We first phenotyped CD8+ T cells in fresh stage II primary melanomas using flow cytometry (n = 6), identifying a CD39+ tumor-resident CD8+ T-cell subset enriched for PD-1 expression. We then performed Opal multiplex immunohistochemistry and quantitative pathology-based immune profiling of CD8+ T-cell subsets, along with B cells, NK cells, Langerhans cells and Class I MHC expression in stage II primary melanoma specimens from patients with long-term follow-up (n = 66), comparing patients based on their recurrence status at 5 years after primary diagnosis. A CD39+CD103+PD-1- CD8+ T-cell population (P2) comprised a significantly higher proportion of intratumoral and stromal CD8+ T-cells in patients with recurrence-free survival (RFS) ≥5 years vs those with RFS <5 years (p = 0.013). Similarly, intratumoral B cells (p = 0.044) and a significantly higher B cell density at the tumor/stromal interface were associated with RFS. Both P2 and B cells localized in significantly closer proximity to melanoma cells in patients who remained recurrence-free (P2 p = 0.0139, B cell p = 0.0049). Our results highlight how characterizing the TIME in primary melanomas may provide new insights into how the complex interplay of the immune system and tumor can modify the disease outcomes. Furthermore, in the context of current clinical trials of adjuvant anti-PD-1 therapies in high-risk stage II primary melanoma, assessment of B cells and P2 could identify patients at risk of recurrence and aid in long-term treatment decisions at the point of primary melanoma diagnosis.
Morphology and molecular phylogeny of two new Aspidisca species (Ciliophora, Spirotrichea, Euplotida) collected from subtropical coastal waters in China
Authors: Zheng Bohan , Zhao Xuetong , Ye Tingting , Huang Jie , Vallesi Adriana , Jiang Yaohan , Chen Xiangrui
Published: August 2022

Ciliates are morphologically diverse and highly specialized unicellular eukaryotes that constitute an important component of the microbial food web. Aspidisca Ehrenberg, 1830, is a highly speciose genus that plays key ecological roles in a wide range of environments, and its species diversity has always been a hot spot in protozoan research. In this study, we investigate the living morphology, infraciliature, silverline system, and ribosomal small subunit (SSU rRNA) gene sequences of two new Aspidisca species collected from subtropical coastal waters of China using standard methods. Aspidisca spina sp. n. is characterized by having an obvious peristomial spur, two transparent posterior protrusions, seven frontoventral cirri in “polystyla-arrangement”, and six dorsal ridges. It can be distinguished from the most similar congener, A. magna Kahl, 1932, by the presence of posterior protrusions, more membranelles in the posterior part of adoral zone (AZM2), and different SSU rRNA gene sequences. A. shini sp. n. is smaller in body size, only 35–40 × 25–30 µm in vivo, with four prominent ridges on the arched dorsal side, very similar with the “well-known” species A. steini Buddenbrock, 1920, in morphological characteristics, but it can be distinguished by the arrangement of frontoventral cirri and 121 nucleotide difference in the SSU rRNA gene sequences. Phylogenetic analyses based on the SSU rRNA gene sequences revealed the systematic positions of two new taxa and supported the validity of them as distinct species.
The Burden of Living With Cutaneous Lupus Erythematosus
Authors: Drenkard Cristina , Barbour Kamil E. , Greenlund Kurt J. , Lim S. Sam
Published: August 2022

Cutaneous lupus erythematosus (CLE) is a group of heterogeneous autoimmune disorders primarily affecting the skin. Patients with these conditions are mostly young women when they become sick and often suffer from recurrent skin symptoms or longstanding changes in their physical appearance. CLE disorders lead to different levels of morbidity and can impact profoundly patients' quality of life, particularly in the psychological and social health domains. This review provides a summary of recent research investigating the psychosocial burden of living with CLE and the intersect amongst the disease characteristics, patient factors, and social determinants of health. Furthermore, this review provides insight into patient care and research needs that remain unmet to improve the quality of life of patients living with CLE.
Association between sleep-disordered breathing and periodontal diseases: A systematic review protocol
Authors: Chen Danyan , Meng Ziyan , Zhao Tingting , Yu Xueqian , He Hong , Hua Fang , Dong Weili
Published: August 2022

Background

Sleep-disordered breathing (SDB) is a chronic sleep-related breathing disorder, considered associated with increased risk of cardiovascular disorders, metabolic disorders, cognitive dysfunction and behavior changes. Periodontal diseases are chronic infectious diseases that are also believed to be associated with cardiovascular diseases, metabolic syndrome and cognitive dysfunction. Several studies have indicated that SDB may be associated with periodontal diseases through certain mechanisms such as inflammation response, oxidative stress and oral dryness. The aim of this systematic review is to explore the association between SDB and periodontal diseases in an integrated approach.

Materials and Methods

This systematic review will include cohort studies, cross-sectional studies and case-control studies that are identified by electronic and manual searches. Electronic searches will be conducted in the following databases: PubMed, Embase, Scopus and Web of Science. Our search will cover articles published from inception of databases to March 2022 without restrictions in language and settings. Pre-determined eligibility criteria include: participants (participants without a history of respiratory diseases, history of periodontal treatment within the past 6 months and history of medication that is known to influence SDB or periodontal diseases); exposure (participants who have been diagnosed with SDB or at high-risk for SDB); comparison (participants without SDB); and outcome (periodontal parameters, such as probing depth, clinical attachment level, bleeding on probing, radiographic bone loss). Two authors will perform study screening and data extraction independently and in duplicate. All discrepancies will be solved by discussion. The methodological quality of included studies will be assessed using the Newcastle-Ottawa Scale.

Discussion

This systematic review will summarize the existing evidence on the association between SDB and periodontal diseases, a topic of controversy and clinical significance. Its findings can provide evidence for the development of relevant prevention and treatment strategies. The results will be disseminated through peer-reviewed journals.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022313024. Registered on March 28th 2022.
Clinical relevance of circulating autoantibodies in idiopathic pulmonary fibrosis; A NAt hard to break
Authors: Kirgou Paraskevi , Sinis Sotirios I. , Dimeas Ilias E. , Papanikolaou Ilias C. , Tatsis Konstantinos , Gogali Athena , Gourgoulianis Konstantinos I. , Bogdanos Dimitrios P. , Daniil Zoe
Published: August 2022

Patients with idiopathic pulmonary fibrosis are screened for circulating autoantibodies as part of the initial interstitial lung disease workup. Management of seropositive idiopathic pulmonary fibrosis is currently considered no different than that of lone idiopathic pulmonary fibrosis. Emerging data however suggest that the former may possess distinct characteristics in terms of pathophysiology, histopathology, prognosis and amenability to immunomodulation. In that context, the aim of our study was to evaluate the influence of autoantibody status on: (i) the decline of forced vital capacity; (ii) the decline of diffusing capacity of lung for carbon monoxide; and (iii) 3-year survival; in a cohort of 102 idiopathic pulmonary fibrosis patients. In a pilot sub-study, we also sought to evaluate whether changes in antibody status during disease course affect the aforementioned parameters by potentially reflecting activity of the autoimmunity component of the pro-fibrotic mechanism.
Potential roles of synaptotagmin family members in cancers: Recent advances and prospects
Authors: Suo Huandan , Xiao Nan , Wang Kewei
Published: August 2022

With the continuous development of bioinformatics and public database, more and more genes that play a role in cancers have been discovered. Synaptotagmins (SYTs) are abundant, evolutionarily conserved integral membrane proteins composed of a short N-terminus, a variable linker domain, a single transmembrane domain, and two C2 domains, and they constitute a family of 17 isoforms. The synaptotagmin family members are known to regulate calcium-dependent membrane fusion events. Some SYTs play roles in hormone secretion or neurotransmitter release or both, and much evidence supports SYTs as Ca2+ sensors of exocytosis. Since 5 years ago, an increasing number of studies have found that SYTs also played important roles in the occurrence and development of lung cancer, gastric cancer, colon cancer, and other cancers. Down-regulation of SYTs inhibited cell proliferation, migration, and invasion of cancer cells, but promoted cell apoptosis. Growth of peritoneal nodules is inhibited and survival is prolonged in mice administrated with siSYTs intraperitoneally. Therefore, most studies have found SYTs serve as an oncogene after overexpression and may become potential prognostic biomarkers for multiple cancers. This article provides an overview of recent studies that focus on SYT family members’ roles in cancers and highlights the advances that have been achieved.
Heme oxygenase-independent bilin biosynthesis revealed by a hmox1 suppressor screening in Chlamydomonas reinhardtii
Authors: Zhang Weiqing , Deng Rui , Shi Weida , Li Zheng , Larkin Robert M. , Fan Qiuling , Duanmu Deqiang
Published: August 2022

Bilins are open-chain tetrapyrroles synthesized in phototrophs by successive enzymic reactions catalyzed by heme oxygenases (HMOXs/HOs) and ferredoxin-dependent biliverdin reductases (FDBRs) that typically serve as chromophore cofactors for phytochromes and phycobiliproteins. Chlamydomonas reinhardtii lacks both phycobiliproteins and phytochromes. Nonetheless, the activity and stability of photosystem I (PSI) and the catalytic subunit of magnesium chelatase (MgCh) named CHLH1 are significantly reduced and phototropic growth is significantly attenuated in a hmox1 mutant that is deficient in bilin biosynthesis. Consistent with these findings, previous studies on hmox1 uncovered an essential role for bilins in chloroplast retrograde signaling, maintenance of a functional photosynthetic apparatus, and the direct regulation of chlorophyll biosynthesis. In this study, we generated and screened a collection of insertional mutants in a hmox1 genetic background for suppressor mutants with phototropic growth restored to rates observed in wild-type 4A+ C. reinhardtii cells. Here, we characterized a suppressor of hmox1 named ho1su1 with phototrophic growth rates and levels of CHLH1 and PSI proteins similar to 4A+. Tetrad analysis indicated that a plasmid insertion co-segregated with the suppressor phenotype of ho1su1. Results from TAIL-PCR and plasmid rescue experiments demonstrated that the plasmid insertion was located in exon 1 of the HMOX1 locus. Heterologous expression of the bilin-binding reporter Nostoc punctiforme NpF2164g5 in the chloroplast of ho1su1 indicated that bilin accumulated in the chloroplast of ho1su1 despite the absence of the HMOX1 protein. Collectively, our study reveals the presence of an alternative bilin biosynthetic pathway independent of HMOX1 in the chloroplasts of Chlamydomonas cells.
Expanding the chemical diversity of M13 bacteriophage
Authors: Allen Grace L. , Grahn Ashley K. , Kourentzi Katerina , Willson Richard C. , Waldrop Sean , Guo Jiantao , Kay Brian K.
Published: August 2022

Bacteriophage M13 virions are very stable nanoparticles that can be modified by chemical and genetic methods. The capsid proteins can be functionalized in a variety of chemical reactions without loss of particle integrity. In addition, Genetic Code Expansion (GCE) permits the introduction of non-canonical amino acids (ncAAs) into displayed peptides and proteins. The incorporation of ncAAs into phage libraries has led to the discovery of high-affinity binders with low nanomolar dissociation constant (KD) values that can potentially serve as inhibitors. This article reviews how bioconjugation and the incorporation of ncAAs during translation have expanded the chemistry of peptides and proteins displayed by M13 virions for a variety of purposes.
Suboptimal states and frontoparietal network-centered incomplete compensation revealed by dynamic functional network connectivity in patients with post-stroke cognitive impairment
Authors: Rao Bo , Wang Sirui , Yu Minhua , Chen Linglong , Miao Guofu , Zhou Xiaoli , Zhou Hong , Liao Weijing , Xu Haibo
Published: August 2022

Background

Neural reorganization occurs after a stroke, and dynamic functional network connectivity (dFNC) pattern is associated with cognition. We hypothesized that dFNC alterations resulted from neural reorganization in post-stroke cognitive impairment (PSCI) patients, and specific dFNC patterns characterized different pathological types of PSCI.

Methods

Resting-state fMRI data were collected from 16 PSCI patients with hemorrhagic stroke (hPSCI group), 21 PSCI patients with ischemic stroke (iPSCI group), and 21 healthy controls (HC). We performed the dFNC analysis for the dynamic connectivity states, together with their topological and temporal features.

Results

We identified 10 resting-state networks (RSNs), and the dFNCs could be clustered into four reoccurring states (modular, regional, sparse, and strong). Compared with HC, the hPSCI and iPSCI patients showed lower standard deviation (SD) and coefficient of variation (CV) in the regional and modular states, respectively (p < 0.05). Reduced connectivities within the primary network (visual, auditory, and sensorimotor networks) and between the primary and high-order cognitive control domains were observed (p < 0.01).

Conclusion

The transition trend to suboptimal states may play a compensatory role in patients with PSCI through redundancy networks. The reduced exploratory capacity (SD and CV) in different suboptimal states characterized cognitive impairment and pathological types of PSCI. The functional disconnection between the primary and high-order cognitive control network and the frontoparietal network centered (FPN-centered) incomplete compensation may be the pathological mechanism of PSCI. These results emphasize the flexibility of neural reorganization during self-repair.
Prevalence and risk factors of stroke-related sarcopenia at the subacute stage: A case control study
Authors: Yao Ruihong , Yao Liqing , Rao Amin , Ou Jibing , Wang Wenli , Hou Qinzhi , Xu Chunyan , Gao Bu-Lang
Published: August 2022

Purpose

To investigate the prevalence and risk factors of stroke-related sarcopenia (SRS) in hospitalized patients receiving rehabilitation treatment.

Methods

Approximately, 259 patients with stroke that satisfied the inclusion and exclusion criteria were consecutively recruited between June 2020 and July 2022. The epidemiologic data, history, clinical data, and measured data of the skeletal muscle index were collected. The patients were divided into the sarcopenia and non-sarcopenia group for comparison and analysis with the univariate and multivariate analysis.

Results

SRS was presented in 121 (46.7%) patients with a mean age of 59.6 ± 9.7 years, including 42 women and 79 men. Multivariate logistic regression analysis revealed the following parameters to be significant (p < 0.05) risk factors for SRS: college degree or above (OR, 2.1, 95% CI, 1.1–4.1), ICU stay (OR, 1.7, 95% CI, 1.06–2.8), pneumonia (OR, 1.9, 9% CI, 1.1–3.6), walking ability (OR, 2.6, 95% CI, 1.5–4.6), cognitive impairment (OR, 1.8, 95%, 1.1–2.9), aphasia (OR, 2.1, 95% CI, 1.2–3.5), nasogastric feeding (OR, 3.7, 95%, 1.9–7.3), age (OR, 1.04, 95% CI, 1–1.1), and creatine kinase (OR, 1.1, 95% CI,0.9–1.2).

Conclusions

Older age, light weight, severer clinical conditions, cognitive impairment, and significantly decreased levels of albumin, RAG, creatinine, uric acid, red blood cell count, hemoglobin, prealbumin, iron, and creatine kinase are more significantly present in patients with SRS compared with those without SRS.
Usability of serum annexin A7 as a biochemical marker of poor outcome and early neurological deterioration after acute primary intracerebral hemorrhage: A prospective cohort study
Authors: Wang Chuan-Liu , Xu Yan-Wen , Yan Xin-Jiang , Zhang Cheng-Liang
Published: August 2022

Objective

Annexin A7 (ANXA7), a calcium-dependent phospholipid-binding protein, may act to aggravate brain injury. This study aimed to assess the clinical utility of serum ANXA7 as a predictor of severity, early neurological deterioration (END), and prognosis after intracerebral hemorrhage (ICH).

Methods

A total of 126 ICH patients and 126 healthy controls were enrolled. Symptomatic severity was evaluated utilizing the National Institutes of Health Stroke Scale (NIHSS) score. The lesion volume of ICH was measured according to the ABC/2 method. END was referred to as an increase of 4 or greater points in the NIHSS score or death at post-stroke 24 h. The unfavorable functional outcome was a combination of death and major disability at post-stroke 90 days.

Results

Serum ANXA7 levels were significantly higher in patients than in controls (median, 46.5 vs. 9.7 ng/ml; P < 0.001). Serum ANXA7 levels were independently correlated with NIHSS score [beta: 0.821; 95% confidence interval (CI): 0.106–1.514; variance inflation factor: 5.180; t = 2.573; P = 0.014] and hematoma volume (beta: 0.794; 95% CI: 0.418–1.173; variance inflation factor: 5.281; t = 2.781; P = 0.007). Serum ANXA7 levels were significantly elevated with increase in modified Rankin scale scores (P < 0.001). Also, serum ANXA7, which was identified as a categorical variable, independently predicted END and an unfavorable outcome with odds ratio values of 3.958 (95% CI: 1.290–12.143; P = 0.016) and 2.755 (95% CI: 1.051–7.220; P = 0.039), respectively. Moreover, serum ANXA7 levels efficiently differentiated END (area under the curve: 0.781; 95% CI: 0.698–0.849) and an unfavorable outcome (area under the curve: 0.776; 95% CI: 0.693–0.846).

Conclusion

Serum ANXA7 may represent a useful blood-derived biomarker for assessing the severity, END, and prognosis of ICH.
Automating provision of feedback to stroke patients with and without information on compensatory movements: A pilot study
Authors: Fruchter Daphne , Feingold Polak Ronit , Berman Sigal , Levy-Tzedek Shelly
Published: August 2022

Providing effective feedback to patients in a rehabilitation training program is essential. As technologies are being developed to support patient training, they need to be able to provide the users with feedback on their performance. As there are various aspects on which feedback can be given (e.g., task success and presence of compensatory movements), it is important to ensure that users are not overwhelmed by too much information given too frequently by the assistive technology. We created a rule-based set of guidelines for the desired hierarchy, timing, and content of feedback to be used when stroke patients train with an upper-limb exercise platform which we developed. The feedback applies to both success on task completion and to the execution of compensatory movements, and is based on input collected from clinicians in a previous study. We recruited 11 stroke patients 1–72 months from injury onset. Ten participants completed the training; each trained with the rehabilitation platform in two configurations: with motor feedback (MF) and with no motor feedback (control condition) (CT). The two conditions were identical, except for the feedback content provided: in both conditions they received feedback on task success; in the MF condition they also received feedback on making undesired compensatory movements during the task. Participants preferred the configuration that provided feedback on both task success and quality of movement (MF). This pilot experiment demonstrates the feasibility of a system providing both task-success and movement-quality feedback to patients based on a decision tree which we developed.