bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of the Intestinal Microbiota in Nonalcoholic Steatohepatitis
Authors: Xiang Hui , Sun Dating , Liu Xin , She Zhi-Gang , Chen Yonghong
Published: February 2022

Nonalcoholic steatohepatitis (NASH) is a serious disease threatening public health, and its pathogenesis remains largely unclear. Recent scientific research has shown that intestinal microbiota and its metabolites have an important impact on the development of NASH. A balanced intestinal microbiota contributes to the maintenance of liver homeostasis, but when the intestinal microbiota is disequilibrated, it serves as a source of pathogens and molecules that lead to NASH. In this review, we mainly emphasize the key mechanisms by which the intestinal microbiota and its metabolites affect NASH. In addition, recent clinical trials and animal studies on the treatment of NASH by regulating the intestinal microbiota through prebiotics, probiotics, synbiotics and FMT have also been briefly elaborated. With the increasing understanding of interactions between the intestinal microbiota and liver, accurate and personalized detection and treatment methods for NASH are expected to be established.
Limited Role of Hair Cortisol and Cortisone Measurement for Detecting Cortisol Autonomy in Patients With Adrenal Incidentalomas
Authors: Puglisi Soraya , Leporati Marta , Amante Eleonora , Parisi Alice , Pia Anna Rosa , Berchialla Paola , Terzolo Massimo , Vincenti Marco , Reimondo Giuseppe
Published: February 2022

Several studies demonstrated the diagnostic accuracy of hair glucocorticoid measurement in patients with overt Cushing syndrome, but few data are available for patients with adrenal incidentaloma (AI) and cortisol autonomy. The aim of our study was to assess whether measurement of 5 corticosteroid hormones with the ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method in the keratin matrix is useful to stratify patients with AI by the presence of autonomous cortisol secretion [ACS] (defined as serum cortisol after 1 mg dexamethasone suppression test (DST) > 138 nmol/l) or possible ACS [PACS] (defined as serum cortisol after 1 mg DST > 50 nmol/l but ≤138 nmol/l). We analysed data of 67 AI patients (32 with cortisol autonomy) and 81 healthy subjects. We did not find any significant statistical difference comparing hair cortisol, cortisone, and 20β-dihydrocortisol concentrations between healthy controls and AI patients, while 6β-hydroxycortisol and 11-deoxycortisol were undetectable. Moreover, no significant difference was found in hair cortisol, cortisone, and 20β-dihydrocortisol levels of AI patients with or without cortisol autonomy. Finally, we did not find any correlation in patients with AI between hormonal concentrations in the keratin matrix and serum, salivary, and urinary cortisol levels, or with body mass index. In conclusion, our findings suggest that hair glucocorticoid measurement is not suitable as a diagnostic test for cortisol autonomy (ACS and PACS).
circEPS15 Overexpression in Hepatocellular Carcinoma Modulates Tumor Invasion and Migration
Authors: Jiang Bin , Tian Maolin , Li Gang , Sadula Abuduhaibaier , Xiu Dianrong , Yuan Chunhui , Bing Yuntao
Published: February 2022

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Recent evidence has shown that circular RNAs (circRNAs) play important roles in tissue development, gene transcription, signal regulation and tumorigenesis. However, whether circRNAs are involved in HCC progression and encode functional proteins remains largely unknown. In the present study, we aimed to explore the function and molecular mechanism of circRNAs in HCC. First, many circRNAs were found to be differentially expressed in HCC samples and paired adjacent normal liver tissues. The validation of dysregulated circRNAs by qRT-PCR revealed that circEPS15 expression was downregulated in HCC tissues, and the survival curves showed that low circEPS15 levels were associated with poor overall survival in HCC patients. Then, the overexpression of circEPS15 suppressed tumor cell invasion and migration by inhibiting the TJP1/CDH2/VIM signaling pathway and retarded cell cycle progression, which was confirmed by the Transwell culture system, wound healing assays, flow cytometry and western blot assays. After that, the spanning junction open reading frame in circEPS15 driven by IRES was shown to encode a novel protein, which was verified by western blotting with full-length, mutated, and truncated sequences of circEPS15 with a FLAG tag. Moreover, ceRNA analysis and qRT-PCR results suggest a possible circRNA (circEPS15)-miRNA-mRNA network in HCC. Collectively, our study reveals that endogenous circEPS15 plays a novel role in repressing HCC through the ceRNA network and encodes a functional protein.
Immune Regulatory 1 Cells: A Novel and Potent Subset of Human T Regulatory Cells
Authors: Krause Nicolas , Mengwasser Jörg , Phithak Elpida , Beato Francisca , Appis Marc , Milford Edgar Louis , Pratschke Johan , Sauer Igor , Kuehl Anja , Vogel Arndt , Goodyear Michael , Hammerich Linda , Tacke Frank , Haas Johanna Faith , Müller Tobias , Utku Nalan
Published: February 2022

A subset of T regulatory cells (Tregs), identified by TIRC7 (T cell immune response cDNA 7) expression is designated as Immune Regulatory 1 Cells (IR1 cells). TIRC7 is an immune checkpoint inhibitor, co-localized with the T- cell receptor, HLA-DR and CTLA-4 during T-cell activation, which delivers regulatory signals via binding to its ligand, HLA-DR α2 domain. IR1 cells express FOXP3, and multiple other markers associated with immune suppression. They constitute as much as 10% of Tregs. IR1 cells strongly inhibit proliferation in mixed lymphocyte reactions, where they express high levels of IL-10. Ex vivo expansion of Tregs over 2 weeks in the presence of an agonist TIRC7 antibody disproportionately expands the IR1 Treg subset, while maintaining high expression of suppressive markers including CD39, IL-10, LAP and GARP. Ex vivo expanded IR1 cells are a potent, homogeneous, stable set of suppressor Tregs with the potential to modulate immune dysregulation. The characteristics of IR1 cells suggest a therapeutic advantage over polyclonal Tregs for therapeutic interventions. Early restoration of immune homeostasis using IR1 cells has the potential to fundamentally alter the natural history of conditions characterized by abnormalities in the T regulatory cell compartment.
Are There Hidden Genes in DNA/RNA Vaccines?
Authors: Beaudoin Christopher A. , Bartas Martin , Volná Adriana , Pečinka Petr , Blundell Tom L.
Published: February 2022

Due to the fast global spreading of the Severe Acute Respiratory Syndrome Coronavirus – 2 (SARS-CoV-2), prevention and treatment options are direly needed in order to control infection-related morbidity, mortality, and economic losses. Although drug and inactivated and attenuated virus vaccine development can require significant amounts of time and resources, DNA and RNA vaccines offer a quick, simple, and cheap treatment alternative, even when produced on a large scale. The spike protein, which has been shown as the most antigenic SARS-CoV-2 protein, has been widely selected as the target of choice for DNA/RNA vaccines. Vaccination campaigns have reported high vaccination rates and protection, but numerous unintended effects, ranging from muscle pain to death, have led to concerns about the safety of RNA/DNA vaccines. In parallel to these studies, several open reading frames (ORFs) have been found to be overlapping SARS-CoV-2 accessory genes, two of which, ORF2b and ORF-Sh, overlap the spike protein sequence. Thus, the presence of these, and potentially other ORFs on SARS-CoV-2 DNA/RNA vaccines, could lead to the translation of undesired proteins during vaccination. Herein, we discuss the translation of overlapping genes in connection with DNA/RNA vaccines. Two mRNA vaccine spike protein sequences, which have been made publicly-available, were compared to the wild-type sequence in order to uncover possible differences in putative overlapping ORFs. Notably, the Moderna mRNA-1273 vaccine sequence is predicted to contain no frameshifted ORFs on the positive sense strand, which highlights the utility of codon optimization in DNA/RNA vaccine design to remove undesired overlapping ORFs. Since little information is available on ORF2b or ORF-Sh, we use structural bioinformatics techniques to investigate the structure-function relationship of these proteins. The presence of putative ORFs on DNA/RNA vaccine candidates implies that overlapping genes may contribute to the translation of smaller peptides, potentially leading to unintended clinical outcomes, and that the protein-coding potential of DNA/RNA vaccines should be rigorously examined prior to administration.
Negative Regulation of the IL-1 System by IL-1R2 and IL-1R8: Relevance in Pathophysiology and Disease
Authors: Supino Domenico , Minute Luna , Mariancini Andrea , Riva Federica , Magrini Elena , Garlanda Cecilia
Published: February 2022

Interleukin-1 (IL-1) is a primary cytokine of innate immunity and inflammation. IL-1 belongs to a complex family including ligands with agonist activity, receptor antagonists, and an anti-inflammatory cytokine. The receptors for these ligands, the IL-1 Receptor (IL-1R) family, include signaling receptor complexes, decoy receptors, and negative regulators. Agonists and regulatory molecules co-evolved, suggesting the evolutionary relevance of a tight control of inflammatory responses, which ensures a balance between amplification of innate immunity and uncontrolled inflammation. IL-1 family members interact with innate immunity cells promoting innate immunity, as well as with innate and adaptive lymphoid cells, contributing to their differentiation and functional polarization and plasticity. Here we will review the properties of two key regulatory receptors of the IL-1 system, IL-1R2, the first decoy receptor identified, and IL-1R8, a pleiotropic regulator of different IL-1 family members and co-receptor for IL-37, the anti-inflammatory member of the IL-1 family. Their complex impact in pathology, ranging from infections and inflammatory responses, to cancer and neurologic disorders, as well as clinical implications and potential therapeutic exploitation will be presented.
The Effect of Hypoxia and Hypoxia-Associated Pathways in the Regulation of Antitumor Response: Friends or Foes?
Authors: Abou Khouzam Raefa , Zaarour Rania Faouzi , Brodaczewska Klaudia , Azakir Bilal , Venkatesh Goutham Hassan , Thiery Jerome , Terry Stéphane , Chouaib Salem
Published: February 2022

Hypoxia is an environmental stressor that is instigated by low oxygen availability. It fuels the progression of solid tumors by driving tumor plasticity, heterogeneity, stemness and genomic instability. Hypoxia metabolically reprograms the tumor microenvironment (TME), adding insult to injury to the acidic, nutrient deprived and poorly vascularized conditions that act to dampen immune cell function. Through its impact on key cancer hallmarks and by creating a physical barrier conducive to tumor survival, hypoxia modulates tumor cell escape from the mounted immune response. The tumor cell-immune cell crosstalk in the context of a hypoxic TME tips the balance towards a cold and immunosuppressed microenvironment that is resistant to immune checkpoint inhibitors (ICI). Nonetheless, evidence is emerging that could make hypoxia an asset for improving response to ICI. Tackling the tumor immune contexture has taken on an in silico, digitalized approach with an increasing number of studies applying bioinformatics to deconvolute the cellular and non-cellular elements of the TME. Such approaches have additionally been combined with signature-based proxies of hypoxia to further dissect the turbulent hypoxia-immune relationship. In this review we will be highlighting the mechanisms by which hypoxia impacts immune cell functions and how that could translate to predicting response to immunotherapy in an era of machine learning and computational biology.
Toward Exploring Topographic Effects on Evolution and Propagation of Ocean Mesoscale Eddies Through Life Cycle Across Izu-Ogasawara Ridge in Northwestern Pacific Ocean
Authors: Nian Rui , Geng Xue , Zhang Zhengguang , Yuan Minghan , Fu Zhen , Xu Hengfu , Yang Hua , Lai Qi , He Hui , Su Chi Wei , Zang Lina , Yuan Qiang , He Bo
Published: February 2022

Ocean mesoscale eddies contribute significantly to water transport on a global scale, constituting the ubiquitous, irregular, discrete, nonlinear components. In this manuscript, we propose to explore whether and how the topographic effect of one meridional ridge, could exert considerable influences on the evolution and propagation of mesoscale eddies through their life cycle, directly from the perspectives of real observation statistics. We systematically investigate the known variability of mesoscale eddy trajectories, derived by multimission satellite altimetry from 1993 to 2018, of a life cycle more than 6 months, over the Izu-Ogasawara Ridge, and quantitatively examined the eddy-ridge interaction by observation statistics and wavelet coherence map, with respect to the intrinsic attributes, namely, the amplitude, the rotation speed, the radius. Due to the spatial-temporal diversity, a series of correlative steps have been particularly designed along time-frequency domain to trace back mesoscale eddy trajectories in a variety of origins, location, lifespan, polarity, either completely or partially passing over the ridge, and to facilitate the standardization in statistics across three phases of their life cycle, i.e., before, during and after the interaction with the ridge. It has been revealed in our experiment that three intrinsic attributes of mesoscale eddies within 25 years, all demonstrated noticeable correlation with the variation of topographic relief over the ridge. We observed that most of the cyclonic eddies obviously tended to begin to decay or even demise, while on the contrary, some of the anticyclonic eddies preferred to intensify slightly, or making no significant difference when encountering the upslope until climbing across the top, basically consistent with the expectation of potential vorticity (PV) conservation. The drifting velocity agreed with the tendency that the direction would be more probably modified toward equatorward or poleward by forcing to meridional component, with zonal component reduced at the beginning. The mesoscale eddies with the passage over the ridge exhibited the relatively high average horizontal scales, amplitude, rotation speed on the whole, compared to those with only partially passage. The developed scheme could integrate more evidences on how mesoscale eddies response to the topographic effects during their time-varying evolution and propagation process, and help provide opportunities to potentially identify and predict the underlying dynamic patterns and mechanisms that mesoscale eddies engage in ocean dynamics when proceeding toward meridional ridges on a global scale, with the promise of the end-to-end data-driven solution, such as deep learning architecture involved in the future.
Artisanal Fisher Association Leaders’ Estimates of Poaching in Their Exclusive Access Management Areas
Authors: Romero Pedro , Estévez Rodrigo A. , Romero Pablo , Gelcich Stefan
Published: February 2022

In marine environments, poaching can become a key threat to marine ecosystem conservation. Poaching can occur in marine protected areas and/or in fishery management areas. Unfortunately, understanding the magnitude and characteristics of poaching under community based and co-management governance schemes in coastal and marine environments, has not received the attention it deserves. In Chile, a system of Territorial Users Rights for Fisheries (TURF) has been recognized as one of the largest experiences of small-scale fisheries co-management at a global scale. Currently, poaching is one of the main threats to the TURF system in Chile. In this article, we assessed poaching of a highly valuable benthic resource (Concholepas concholepas) from TURF management areas. We estimated artisanal fisher association leaders’ perceptions of poaching within their TURFs and explore determinants of poaching for Concholepas concholepas. Poaching of Concholepas concholepas showed differences along the studied sites. As expected, the greater abundance of Concholepas concholepas in the management areas generates an increased incentive to poach. Areas that make the greatest investment in surveillance are those most affected by poaching. However, our study cannot determine the effectiveness of current levels of surveillance on illegal extraction. Results show older areas tend to reduce the levels of illegal extraction, which could indicate a greater capacity and experience to control poaching. Supporting fisher associations in enforcing TURFs and following up on sanctions against perpetrators are conditioning factors, highlighted by fisher leaders, for TURF sustainability. The approach used in this study provides insights to prioritize geographies and opportunities to address poaching in small-scale co-managed fisheries.
Green and Highly Efficient Wool Keratin Extraction by Microwave Induction Method
Authors: Du Wenqian , Zhang Liran , Zhang Changhuan , Cao Jianwei , Wang Dongmin , Li Hongwei , Li Wenxia , Zeng Jinling
Published: February 2022

Keratin is a plentiful and renewable fibrous protein resource found in nature, but a great deal of keratin-containing waste causes environmental problems, especially wool waste, which accounts for the majority. A green and efficient extraction method of keratin based on microwave induction method was studied. Compared with traditional thermal induction, the extraction time was shortened by half, and the dissolution rate of the wool was improved. The effects of the above two methods on the size, structure, crystallinity, and thermal stability of wool keratin were studied by a series of analysis methods [e.g., attenuated total reflectance Fourier transform infrared spectrometry (ATR-FTIR), Raman spectroscopy, X-ray diffraction spectroscopy (XRD), dynamic light scattering (DLS), thermogravimetric analysis (TG), and so on]. The results showed that under microwave irradiation, the disulfide bonds were destroyed greatly, and the secondary structure changed significantly, which was beneficial to obtain wool keratin with low crystallinity and small particle size.
Gut Mucosal Microbiome Signatures of Colorectal Cancer Differ According to BMI Status
Authors: Shaw Sophie , Berry Susan , Thomson John , Murray Graeme I. , El-Omar Emad , Hold Georgina L.
Published: February 2022

Background

Carrying excess body weight is a strong risk factor for colorectal cancer (CRC) development with ~11% of CRC cases in Europe linked to being overweight. The mechanisms through which excess body weight influences CRC development are not well understood but studies suggest the involvement of the presence of chronic low-grade inflammation and changes in the gut microbiota are involved.

Aim

To compare the mucosal associated microbiota of patients with CRC to understand whether carrying excess body weight was associated with a unique CRC microbial signature.

Methods

Microbiota signatures from colonic mucosal biopsies of CRC lesions and adjacent normal mucosal samples from 20 patients with overt CRC were compared with 11 healthy controls to see if having a BMI of >25 kg/m2 influenced colonic microbial composition.

Results

Colonic mucosa samples from patients with CRC confirmed previously reported over-abundance of Fusobacteria associated with CRC but also an increase in Fusobacteria and Prevotella were associated with a BMI of >25 kg/m2. Correlation analysis of bacterial taxa indicated co-exclusive relationships were more common in CRC patients with a BMI >25 kg/m2 with an increase in transphylum relationships also seen in this patient group.

Conclusions

The findings suggest that gut microbiota composition in patients with CRC is influenced by BMI status. Further understanding/defining these differences will provide valuable information in terms of developing novel pre-onset screening and providing post-manifestation therapeutic intervention.
Prevalence and Impact of Rheumatologic Pain in Cystic Fibrosis Adult Patients
Authors: Schmoll Axelle , Launois Claire , Perotin Jeanne-Marie , Ravoninjatovo Bruno , Griffon Muriel , Carré Sophie , Mulette Pauline , Ancel Julien , Hagenburg Jean , Lebargy François , Deslée Gaëtan , Salmon Jean-Hugues , Dury Sandra
Published: February 2022

Background

With the improvement of cystic fibrosis (CF) patient survival, the prevalence of long-term complications increased, among them rheumatologic disorders.

Methods

The aim of this prospective study was to evaluate the prevalence of spinal and joint pain, and their impact on disability, anxiety, depression, and quality of life in CF adult patients.

Results

Forty-seven patients were analyzed, 72% of men, mean aged 28 years, with a mean body mass index of 22 kg/m2 and a mean FEV1% of 63%. Twenty-two patients (47%) described rheumatologic pain either spinal (n = 15, 32%) and/or joint pain (n = 14, 30%). Patients with spinal and/or joint pain were shorter (p = 0.023), more frequently colonized with Staphylococcus aureus (p < 0.008), had more frequent ΔF508 homozygous mutations (p = 0.014), and a trend for more impairment of the 6-min walking distance (p = 0.050). The presence of rheumatologic pain tended to be associated with disability according to the Health Assessment Questionnaire (HAQ) and anxiety. Compared with patients with no pain patients with both spinal and joint pain exhibited a more pronounced impact on the St George's Respiratory Questionnaire (SGRQ).

Conclusion

Rheumatologic pain is frequent in CF adult patients, and may affect daily living, anxiety and quality of life. Systematic assessment of rheumatologic pain should be included in the management of CF patients.
First Characterization of a Hafnia Phage Reveals Extraordinarily Large Burst Size and Unusual Plaque Polymorphism
Authors: Pan Lingting , Li Dengfeng , Sun Zhitong , Lin Wei , Hong Binxin , Qin Weinan , Xu Lihua , Liu Wencai , Zhou Qin , Wang Fei , Cai Ruqian , Qian Minhua , Tong Yigang
Published: February 2022

A unique lytic phage infecting Hafnia paralvei was isolated and identified. Hafnia phage Ca belongs to the family Autographiviridae, possessing an icosahedral head with a diameter of 55 nm and a short non-contractile tail. Unusually, the burst size of Hafnia phage Ca of 10,292 ± 1,097 plaque-forming units (PFUs)/cell is much larger than other dsDNA phages reported before. Compared to the genome of the related phage, Hafnia phage Ca genome contains extra genes including DNA mimic ocr, dGTP triphosphohydrolase inhibitor, endonuclease, endonuclease VII, and HNH homing endonuclease gene. Extraordinarily, the phage developed different sizes of plaques when a single plaque was picked out and inoculated on a double-layer Luria broth agar plate with its host. Furthermore, varied packaging tightness for the tails of Hafnia phage Ca was observed (tail length: 4.35–45.92 nm). Most of the tails appeared to be like a cone with appendages, some were dot-like, bun-like, table tennis racket handle-like, and ponytail-like. Although the complete genome of Hafnia phage Ca is 40,286 bp, an incomplete genome with a deletion of a 397-bp fragment, containing one ORF predicted as HNH homing endonuclease gene (HEG), was also found by high throughput sequencing. Most of the genome of the virus particles in large plaques is complete (>98%), while most of the genome of the virus particles in small plaques is incomplete (>98%), and the abundance of both of them in medium-sized plaques is similar (complete, 40%; incomplete, 60%). In an experiment to see if the phage could be protective to brocade carps intramuscularly injected with H. paralvei LY-23 and phage Ca, the protection rate of Hafnia phage Ca to brocade carp (Cyprinus aka Koi) against H. paralvei was 33.38% (0.01 < p < 0.05). This study highlights some new insights into the peculiar biological and genomic characteristics of phage.
T1SEstacker: A Tri-Layer Stacking Model Effectively Predicts Bacterial Type 1 Secreted Proteins Based on C-Terminal Non-repeats-in-Toxin-Motif Sequence Features
Authors: Chen Zewei , Zhao Ziyi , Hui Xinjie , Zhang Junya , Hu Yixue , Chen Runhong , Cai Xuxia , Hu Yueming , Wang Yejun
Published: February 2022

Type 1 secretion systems play important roles in pathogenicity of Gram-negative bacteria. However, the substrate secretion mechanism remains largely unknown. In this research, we observed the sequence features of repeats-in-toxin (RTX) proteins, a major class of type 1 secreted effectors (T1SEs). We found striking non-RTX-motif amino acid composition patterns at the C termini, most typically exemplified by the enriched “[FLI][VAI]” at the most C-terminal two positions. Machine-learning models, including deep-learning ones, were trained using these sequence-based non-RTX-motif features and further combined into a tri-layer stacking model, T1SEstacker, which predicted the RTX proteins accurately, with a fivefold cross-validated sensitivity of ∼0.89 at the specificity of ∼0.94. Besides substrates with RTX motifs, T1SEstacker can also well distinguish non-RTX-motif T1SEs, further suggesting their potential existence of common secretion signals. T1SEstacker was applied to predict T1SEs from the genomes of representative Salmonella strains, and we found that both the number and composition of T1SEs varied among strains. The number of T1SEs is estimated to reach 100 or more in each strain, much larger than what we expected. In summary, we made comprehensive sequence analysis on the type 1 secreted RTX proteins, identified common sequence-based features at the C termini, and developed a stacking model that can predict type 1 secreted proteins accurately.
Decreased Expression of circ_0000160 in Breast Cancer With Axillary Lymph Node Metastasis
Authors: Wang Ya-Wen , Chen Xu , Tian Yaru , Liu Long , Su Peng
Published: February 2022

Background: Circular RNAs (circRNAs) have been shown to play important roles in the development and progression of human cancers. Emerging evidence shows that circRNAs have the potential to be promising biomarkers for cancer diagnosis and prognosis. However, the roles of circRNAs in breast cancer axillary lymph node metastasis (ALNM) remain to be determined.

Methods: Transcriptome sequencing was utilized to screen the differentially expressed circRNAs in three breast cancer tissues with ALNM and three without ALNM. Differentially expressed circRNAs were further verified by quantitative real-time PCR. Moreover, receiver operating characteristic (ROC) curve analysis was performed to calculate the value of circRNAs to distinguish breast cancer tissues with ALNM and those without ALNM. To explore the potential mechanism of the circRNAs, a circRNA–miRNA–mRNA network was constructed based on the CircInteractome, circBank, and mirDIP online software.

Results: In total, 31 differentially expressed circRNAs were identified by transcriptome sequencing; among them, 21 were upregulated and 10 were downregulated in breast cancer with ALNM compared to those without ALNM. Circ_0000160 was validated to be downregulated in breast cancer tissues with ALNM compared with those without ALNM. The ROC curve showed the ability of circ_0000160 to distinguish breast cancer tissues with ALNM and those without ALNM, with an area under the curve of 0.7435. Furthermore, bioinformatics analysis revealed that the predicted mRNAs for circ_0000160 may be related to lymph node metastasis. The predicted mRNAs for circ_0000160 may be involved in many cancer-related pathways.

Conclusion: A decreased expression of circ_0000160 was found in breast cancer with axillary lymph node metastasis. Circ_0000160 may have the potential to distinguish breast cancer with axillary lymph node metastasis from those without axillary lymph node metastasis.
A Role of Socioeconomic Status in Cognitive Impairment Among Older Adults in Macau: A Decomposition Approach
Authors: Zhang Zhuo , Zhao Yonghua , Bian Ying
Published: February 2022

Background

To explore the prevalence and inequality of cognitive impairment among older adults in Macau and the contributions of influencing factors to inequality in cognitive impairment.

Methods

The Montreal Cognitive Assessment (MoCA) was used to measure the prevalence of cognitive impairment. Socioeconomic status scores were used to describe economic level of the subjects. The concentration index was applied to measure the inequality of cognitive impairment associated with socioeconomic status (SES) and decomposed into its influencing factors.

Results

The prevalence of cognitive impairment was 44.35% in Macau. The concentration index of cognitive impairment among the elderly was −0.165 (95% CI: −0.232 to −0.098), indicating that the prevalence of cognitive impairment was concentrated in households with poor SES. Older age, poor SES, long or short sleep duration, other marital status, poor appetite, no tea/coffee drinking, no religious belief, and depression contributed positively to the inequality of cognitive impairment. Among these factors, SES made the largest contribution to inequality, accounting for 76.74%.

Conclusion

In Macau, the prevalence of cognitive impairment among people aged 65 years and older is concentrated among those who are in poor economic conditions. Reducing the gap between the rich and the poor at the source, increasing educational level of low SES population and improving their access to healthcare services will help to improve the inequity of cognitive impairment.
The Effect of Melatonin and Exercise on Social Isolation-Related Behavioral Changes in Aged Rats
Authors: Alghamdi Badrah Saeed
Published: February 2022

Social isolation (SI) is well established as an environmental factor that negatively influences different behavioral parameters, including cognitive function, anxiety, and social interaction, depending on the age of isolation. Aging is a physiological process that is associated with changes in cognitive function, locomotor activity, anxiety and emotional responses. Few studies have investigated the effect of SI in senescence, or possible interventions. In the current study, we investigated the possible complementary effects of melatonin (MLT) and exercise (Ex) in improving SI-related behavioral changes in aged rats. Forty aged Wistar rats (24 months old) were randomly divided into five groups (n = 8 per group): Control (group housing), SI (individual housing for 7 weeks), SI + MLT (SI rats treated with 0.4 mg MLT/ml in drinking water), SI + Ex (SI rats treated with 60 min of swimming), and SI + MLT + Ex (SI rats treated with both MLT and Ex). Different behavioral tasks were conducted in the following sequence: open field test, elevated plus maze test, sucrose preference test, Y maze test, and Morris water maze test. Locomotor activities measured by total distance moved and velocity revealed that SI + Ex (P = 0.0038; P = 0.0015) and SI + MLT + Ex (P = 0.0001; P = 0.0003) significantly improved the locomotor activity compared with SI rats but SI + MLT (P = 0.0599; P = 0.0627) rats showed no significant change. Anxiety index score was significantly improved in SI + MLT + Ex (P = 0.0256) compared with SI rats while SI + MLT (P > 0.9999) and SI + Ex (P = 0.2943) rats showed no significant change. Moreover, latency to reach the platform in Morris water maze was significantly reduced at day 5 in SI + MLT + Ex (P = 0.0457) compared with SI rats but no change was detected in SI + MLT (P = 0.7314) or SI + Ex (P = 0.1676) groups. In conclusion, this study supports the possible potential of MLT in combination with Ex in improving physical activity, anxiety, and cognitive functions in aging population.
Predicting Multiple Sclerosis: Challenges and Opportunities
Authors: Hone Luke , Giovannoni Gavin , Dobson Ruth , Jacobs Benjamin Meir
Published: February 2022

Determining effective means of preventing Multiple Sclerosis (MS) relies on testing preventive strategies in trial populations. However, because of the low incidence of MS, demonstrating that a preventive measure has benefit requires either very large trial populations or an enriched population with a higher disease incidence. Risk scores which incorporate genetic and environmental data could be used, in principle, to identify high-risk individuals for enrolment in preventive trials. Here we discuss the concepts of developing predictive scores for identifying individuals at high risk of MS. We discuss the empirical efforts to do so using real cohorts, and some of the challenges-both theoretical and practical-limiting this work. We argue that such scores could offer a means of risk stratification for preventive trial design, but are unlikely to ever constitute a clinically-helpful approach to predicting MS for an individual.
Efficacy and Safety of Tirofiban in Clinical Patients With Acute Ischemic Stroke
Authors: Han Bin , Ma Teng , Liu Zhendong , Wu Yiqun , Tan Weiwei , Sun Shaoyang , Li Xuemei , Shao Changyan , Tang Duyong , Sun Jinping
Published: February 2022

Background

Intravenous thrombolysis and endovascular thrombectomy have been approved for acute ischemic stroke (AIS). However, only a minority of patients received these treatments in China. We aimed to evaluate the efficacy and safety of tirofiban in patients with AIS who were not undergoing early recanalization treatments.

Methods

Patients with mild-to-moderate stroke [National Institutes of Health Stroke Scale (NIHSS) score, 4–15] were enrolled in this study. Patients due to cardiogenic embolism were excluded. Eligible patients within 12 h from symptom onset were randomly assigned (1:1) to receive tirofiban (a loading dose of 0.4 μg/kg/min over 30 min and a maintenance dose of 0.1 μg/kg/min up to 48 h) followed by regular treatment or to receive regular treatment (aspirin at a dose of 100 mg per day for 90 days) (control). The primary outcome was the proportion of favorable functional outcomes at 90 days [defined as the modified Rankin Scale (mRS) score of 0–2]. The secondary outcomes included a shift in the distribution of the mRS scores at 90 days and the NIHSS score at 24 h and 7 days. The primary safety outcome was symptomatic intracranial hemorrhage (sICH) within 7 days after tirofiban treatment.

Results

A total of 380 eligible patients were randomly assigned to the tirofiban group (n = 190) or the control group (n = 190). The proportion of favorable functional outcomes was higher in the tirofiban group (79.1%) than that in the control group (67.8%) at 90 days [odds ratio (OR), 1.80; 95% CI, 1.12–2.90; p = 0.0155]. An improvement was also observed in the overall distribution of the 90-day mRS scores (adjusted common OR, 2.31; 95% CI, 1.58–3.39; p < 0.0001). Additionally, the median NIHSS score was lower in the tirofiban group than in the control group at 7 days (3 vs. 5, p < 0.0001). Next, we observed that the occurrence of sICH did not differ between the two groups.

Conclusion

Our trial supports that tirofiban was safe and effective and might be a remedial treatment for patients with AIS who did not receive recanalization treatments.

Clinical Trial Registration

http://www.chictr.org.cn/, identifier: ChiCTR2000031297.
Bibliometric Analysis Reveals a 20-Year Research Trend for Chemotherapy-Induced Peripheral Neuropathy
Authors: Gu Jialin , Hu Miao , Gu Zhancheng , Yu Jialin , Ji Yi , Li Lingchang , Hu Canhong , Wei Guoli , Huo Jiege
Published: February 2022

Objective

A lot of research has focused on the field of chemotherapy-induced peripheral neuropathy (CIPN). In this study, we performed a bibliometric analysis of CIPN-related publications to identify the key research areas and trends over the last 20 years.

Methods

We searched the Web of Science core collection for publications related to CIPN that were published between January 2001 and September 2021. We then performed bibliometric analysis and visualization using Microsoft Excel 2019, VOSviewer, and the Bibliometric online analysis platform (https://bibliometric.com/).

Results

In total, we identified 2,188 eligible publications in the field of CIPN, with an increasing trend in the annual number of publications. The United States and Italy were dominant in the CIPN field. Supportive Care in Cancer was the most productive journal. G. Cavaletti and A.A. Argyriou published the largest number of papers. Of all institutions, the University of Milano-Bicocca, Italy, published the highest number of papers. Analysis of the co-occurrence of keywords revealed the specific characteristics relating to the four main clusters: oxaliplatin, paclitaxel, pain management, and quality of life (QOL). Newly emerging research focusses predominantly on neuroinflammatory mechanisms and non-pharmacological interventions for CIPN.

Conclusion

This bibliometric study reviewed the evolutionary trends in CIPN research and identified current research hotspots and research trends. In addition, we identified journals, institutions, and authors, with the highest levels of impact to enhance the collaboration and learning.
Clinical and Molecular Correlates of Abnormal Changes in the Cerebellum and Globus Pallidus in Fragile X Premutation
Authors: Wang Jun Yi , Grigsby Jim , Placido Diego , Wei Hongjiang , Tassone Flora , Kim Kyoungmi , Hessl David , Rivera Susan M. , Hagerman Randi J.
Published: February 2022

Background

Fragile X premutation carriers (55–200 CGG triplets) may develop a progressive neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS), after the age of 50. The neuroradiologic markers of FXTAS are hyperintense T2-signals in the middle cerebellar peduncle—the MCP sign. We recently noticed abnormal T2-signals in the globus pallidus in male premutation carriers and controls but the prevalence and clinical significance were unknown.

Methods

We estimated the prevalence of the MCP sign and pallidal T2-abnormalities in 230 male premutation carriers and 144 controls (aged 8–86), and examined the associations with FXTAS symptoms, CGG repeat length, and iron content in the cerebellar dentate nucleus and globus pallidus.

Results

Among participants aged ≥45 years (175 premutation carriers and 82 controls), MCP sign was observed only in premutation carriers (52 vs. 0%) whereas the prevalence of pallidal T2-abnormalities approached significance in premutation carriers compared with controls after age-adjustment (25.1 vs. 13.4%,p= 0.069). MCP sign was associated with impaired motor and executive functioning, and the additional presence of pallidal T2-abnormalities was associated with greater impaired executive functioning. Among premutation carriers, significant iron accumulation was observed in the dentate nucleus, and neither pallidal or MCP T2-abnormalities affected measures of the dentate nucleus. While the MCP sign was associated with CGG repeat length >75 and dentate nucleus volume correlated negatively with CGG repeat length, pallidal T2-abnormalities did not correlate with CGG repeat length. However, pallidal signal changes were associated with age-related accelerated iron depletion and variability and having both MCP and pallidal signs further increased iron variability in the globus pallidus.

Conclusions

Only the MCP sign, not pallidal abnormalities, revealed independent associations with motor and cognitive impairment; however, the occurrence ofcombinedMCP and pallidal T2-abnormalities may present a risk for greater cognitive impairment and increased iron variability in the globus pallidus.
The Effects of a Single Transcranial Direct Current Stimulation Session on Impulsivity and Risk Among a Sample of Adult Recreational Cannabis Users
Authors: Patel Herry , Naish Katherine , Soreni Noam , Amlung Michael
Published: February 2022

Individuals with substance use disorders exhibit risk-taking behaviors, potentially leading to negative consequences and difficulty maintaining recovery. Non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) have yielded mixed effects on risk-taking among healthy controls. Given the importance of risk-taking behaviors among substance-using samples, this study aimed to examine the effects of tDCS on risk-taking among a sample of adults using cannabis. Using a double-blind design, 27 cannabis users [M(SD) age = 32.48 (1.99), 41% female] were randomized, receiving one session of active or sham tDCS over the bilateral dorsolateral prefrontal cortex (dlPFC). Stimulation parameters closely followed prior studies with anodal right dlPFC and cathodal left dlPFC stimulation. Risk-taking—assessed via a modified Cambridge Gambling Task—was measured before and during tDCS. Delay and probability discounting tasks were assessed before and after stimulation. No significant effects of stimulation on risk-taking behavior were found. However, participants chose the less risky option ∼86% of the trials before stimulation which potentially contributed to ceiling effects. These results contradict one prior study showing increased risk-taking among cannabis users following tDCS. There was a significant increase in delay discounting of a $1000 delayed reward during stimulation for the sham group only, but no significant effects for probability discounting. The current study adds to conflicting and inconclusive literature on tDCS and cognition among substance-using samples. In conclusion, results suggest the ineffectiveness of single session dlPFC tDCS using an established stimulation protocol on risk-taking, although ceiling effects at baseline may have also prevented behavior change following tDCS.
Reconfiguration of Brain Network Dynamics in Autism Spectrum Disorder Based on Hidden Markov Model
Authors: Lin Pingting , Zang Shiyi , Bai Yi , Wang Haixian
Published: February 2022

Autism spectrum disorder (ASD) is a group of complex neurodevelopment disorders characterized by altered brain connectivity. However, the majority of neuroimaging studies for ASD focus on the static pattern of brain function and largely neglect brain activity dynamics, which might provide deeper insight into the underlying mechanism of brain functions for ASD. Therefore, we proposed a framework with Hidden Markov Model (HMM) analysis for resting-state functional MRI (fMRI) from a large multicenter dataset of 507 male subjects. Specifically, the 507 subjects included 209 subjects with ASD and 298 well-matched health controls across 14 sites from the Autism Brain Imaging Data Exchange (ABIDE). Based on the HMM, we can identify the recurring brain function networks over time across ASD and healthy controls (HCs). Then we assessed the dynamical configuration of the whole-brain networks and further analyzed the community structure of transitions across the brain states. Based on the 19 HMM states, we found that the global temporal statistics of the specific HMM states (including fractional occupancies and lifetimes) were significantly altered in ASD compared to HCs. These specific HMM states were characterized by the activation pattern of default mode network (DMN), sensory processing networks [including visual network, auditory network, and sensory and motor network (SMN)]. Meanwhile, we also find that the specific modules of transitions between states were closely related to ASD. Our findings indicate the temporal reconfiguration of the brain network in ASD and provide novel insights into the dynamics of the whole-brain networks for ASD.
Implications of Malnutrition on Contrast-Associated Acute Kidney Injury in Young and Old Patients Undergoing Percutaneous Coronary Intervention: A Multicenter Prospective Cohort
Authors: Liang Jingjing , Zhang Lingyu , Huang Zhidong , He Yibo , Ling Yihang , Chen Kai , Ying Ming , Lin Mengfei , Li Guode , Liu Jin , Liu Yong , Liang Yan , Chen Shiqun , Hu Yunzhao
Published: February 2022

Background

The relationship between malnutrition and the risk of contrast-associated acute kidney injury (CA-AKI) and the resulting prognosis in patients undergoing percutaneous coronary intervention (PCI) is still not well known.

Methods

Patients undergoing PCI were consecutively enrolled in a multicenter study in China (NCT01402232), categorized by nutritional status (non-malnutrition, malnutrition) based on two different cut-off values (i.e., traditional threshold and the best cut-off value based on the receiver operating characteristic (ROC) curve) for the controlling nutritional status (CONUT) score. The primary endpoint was CA-AKI, diagnosed as a rise in serum creatinine >0.3 mg/dl or >50% than the baseline level occurring within 48 h after the intervention. The secondary endpoint was all-cause mortality. The relationships of malnutrition, CA-AKI, and all-cause mortality were examined using multivariate-adjusted logistic and Cox regression analyses, respectively.

Results

Among 2,083 patients undergoing PCI (age: 62.8 ± 11.1 years; 79.0% men), 1,258 (60.4%) were malnourished. During hospitalization, 80 (3.8%) patients developed CA-AKI events. The incidence of CA-AKI in patients who did not have malnutrition (the non-malnutrition group) and those who did have malnutrition (the malnutrition group) was 1.7% and 5.25%, respectively. Patients with malnutrition had a 2-fold increased adjusted risk of CA-AKI compared to those with no malnutrition [adjusted odds ratio (aOR) (95% confidence interval CI): 2.41 (1.22 to 5.22)]. Malnutrition was associated with a 3-fold increased adjusted risk of CA-AKI in patients aged ≤ 75 years [N = 1,791, aOR (95% CI): 3.39 (1.46–9.25)]. Malnourished patients with CA-AKI had a higher risk of all-cause mortality than the others. Similar results were observed in the grouping of Supplemental Analyses based on the optimal cut-off value of the CONUT score identified by the ROC curve.

Conclusions

Malnutrition is strongly associated with an increased risk of CA-AKI in both young and old patients undergoing PCI. Malnourished patients with CA-AKI had a significantly higher risk of all-cause mortality. Further studies are needed to prospectively assess the efficacy of nutritional interventions on outcomes in patients undergoing PCI.