bluuebunny/crossref_metadata_2025 huggingface dataset:
Roles of BTLA in Immunity and Immune Disorders
Authors: Ning Zhaochen , Liu Keyan , Xiong Huabao
Published: March 2021

B and T lymphocyte attenuator (BTLA) is one of the most important cosignaling molecules. It belongs to the CD28 superfamily and is similar to programmed cell death-1 (PD-1) and cytotoxic T lymphocyte associated antigen-4 (CTLA-4) in terms of its structure and function. BTLA can be detected in most lymphocytes and induces immunosuppression by inhibiting B and T cell activation and proliferation. The BTLA ligand, herpesvirus entry mediator (HVEM), does not belong to the classic B7 family. Instead, it is a member of the tumor necrosis factor receptor (TNFR) superfamily. The association of BTLA with HVEM directly bridges the CD28 and TNFR families and mediates broad and powerful immune effects. Recently, a large number of studies have found that BTLA participates in numerous physiopathological processes, such as tumor, inflammatory diseases, autoimmune diseases, infectious diseases, and transplantation rejection. Therefore, the present work aimed to review the existing knowledge about BTLA in immunity and summarize the diverse functions of BTLA in various immune disorders.
Case Report: Metagenomic Next-Generation Sequencing in Diagnosis of Talaromycosis of an Immunocompetent Patient
Authors: Shi Jiejun , Yang Naibin , Qian Guoqing
Published: March 2021

Background: Talaromycosis is a serious fungal infection which is rare in immunocompetent people. Since its clinical manifestations lack specificity, it is easy to escape diagnosis or be misdiagnosed leading to high mortality and poor prognosis. It is necessary to be alert to the disease when broad-spectrum antibiotics do not work well in immunocompetent patients.

Case Presentation: A 79-year-old man was admitted to our Infectious Diseases Department for recurrent fever and cough. Before admission he has been treated with piperacillin-tazobactam, moxifloxacin followed by antituberculous agents in other hospitals while his symptoms were not thoroughly eased. During the first hospitalization in another hospital, he has been ordered a series of examination including radionuclide whole body bone imaging, transbronchial needle aspiration for subcarinal nodes. However, the results were negative showing no neoplasm. After being admitted to our hospital, he underwent various routine examinations. The initial diagnosis was bacterial pneumonia, and he was given meropenem injection and tigecycline injection successively, but there were no improvement of symptoms and inflammatory indicators. In the end, the main pathogen Talaromyces marneffei was confirmed using Metagenomic Next-Generation Sequencing (mNGS), and his clinical symptoms gradually relieved after targeted antifungal treatment using voriconazole.

Conclusion: When empirical anti-infective treatment is ineffective, it is necessary to consider the possibility of opportunistic fungal infections on immunocompetent patients. mNGS, as a new generation of pathogenic testing methods, can often detect pathogenic bacteria faster than traditional methods, providing important help for clinical decision-making.
Antimicrobial Resistance Profiles, Virulence Genes, and Genetic Diversity of Thermophilic Campylobacter Species Isolated From a Layer Poultry Farm in Korea
Authors: Gahamanyi Noel , Song Dae-Geun , Yoon Kye-Yoon , Mboera Leonard E. G. , Matee Mecky I. , Mutangana Dieudonné , Amachawadi Raghavendra G. , Komba Erick V. G. , Pan Cheol-Ho
Published: March 2021

ThermophilicCampylobacterspecies are among the major etiologies of bacterial enteritis globally. This study aimed at assessing the antimicrobial resistance (AMR) profiles, virulence genes, and genetic diversity of thermophilicCampylobacterspecies isolated from a layer poultry farm in South Korea. One hundred fifty-three chicken feces were collected from two layer poultry farms in Gangneung, South Korea. TheCampylobacterspecies were isolated by cultural techniques, while PCR and sequencing were used for species confirmation. Antimicrobial susceptibility testing for six antimicrobials [ciprofloxacin (CIP), nalidixic acid (NAL), sitafloxacin (SIT), erythromycin (ERY), tetracycline (TET), and gentamicin (GEN)] was carried out by broth microdilution. Three AMR and nine virulence genes were screened by PCR. Genotyping was performed byflaA-restriction fragment length polymorphism (RFLP) and multilocus sequence typing (MLST). Of the 153 samples,Campylobacterspp. were detected in 55 (35.9%), withCampylobacter jejuniandCampylobacter colibeing 49 (89.1%) and six (10.9%), respectively. High-level resistance was observed for CIP (100%), NAL (100%), and TET (C. jejuni, 93.9%;C. coli: 83.3%). No resistance was observed for SIT. The missense mutation (C257T) ingyrA gene was confirmed by sequencing, while thetet(O) gene was similar to known sequences in GenBank. The rate of multidrug-resistant (MDR) strains was 8.2%, and they all belonged toC. jejuni. AllCampylobacterisolates possessed five virulence genes (cdtB,cstII,flaA,cadF, anddnaJ), but none possessedggt, while the rates for other genes (csrA,ciaB, andpldA) ranged between 33.3 and 95.9%. TheflaA-RFLP yielded 26flaA types (C. jejuni: 21 andC. coli: five), while the MLST showed 10 sequence types (STs) forC. jejuniand three STs forC. coli, with CC-607 (STs 3611) and CC-460 (ST-460) being predominant. Among the 10 STs ofC. jejuni, three were newly assigned. The findings of this study highlight the increased resistance to quinolones and TET, the virulence potential, and the diverse genotypes amongCampylobacterstrains isolated from the layer poultry farm.
Cottonseed Press Cake as a Potential Diet for Industrially Farmed Black Soldier Fly Larvae Triggers Adaptations of Their Bacterial and Fungal Gut Microbiota
Authors: Tegtmeier Dorothee , Hurka Sabine , Klüber Patrick , Brinkrolf Karina , Heise Philipp , Vilcinskas Andreas
Published: March 2021

Black soldier fly larvae (Hermetia illucens, Diptera: Stratiomyidae) are used for the bioconversion of organic side products into valuable compounds such as proteins, lipids and chitin. However, the economic competitiveness of farmed insects compared to conventional protein production systems in agriculture and aquaculture depends on the availability of large quantities of inexpensive insect feed. Cottonseed press cake (CPC) is a side-stream of cotton production that is rich in proteins and lipids but unsuitable as feed for several farmed animals, except ruminants, due to the presence of the anti-nutritional sesquiterpenoid gossypol. Here, we tested CPC as a feed for black soldier fly larvae and studied the impact of this diet on the gut microbiome. Larvae reared on CPC developed normally and even showed a shorter life-cycle, but were smaller at the end of larval development than control larvae reared on chicken feed. The adaptability of the larvae to different diets is mediated by their versatile gut microbiome, which facilitates digestion and detoxification. We therefore used amplicon sequencing to analyze the bacterial and fungal communities associated with larvae reared on each diet, revealing differences between the larval guts and frass (residual feed substrate) as well as differences between the two diet groups. For example, Actinomycetaceae and Aspergillaceae were significantly enriched in guts of the CPC diet group and may help to metabolize compounds such as gossypol. Potentially probiotic yeasts and beneficial Enterobacteriaceae, which presumably belong to the core microbiota, were detected in high relative abundance in the gut and frass, indicating a functional role of these microbes, especially the protection against pathogens. We conclude that CPC may be suitable as an inexpensive and environmentally sustainable feed for the industrial rearing of black soldier flies.
Potential Role and Utilization of Plant Growth Promoting Microbes in Plant Tissue Culture
Authors: Soumare Abdoulaye , Diédhiou Abdala G. , Arora Naveen Kumar , Tawfeeq Al-Ani Laith Khalil , Ngom Mariama , Fall Saliou , Hafidi Mohamed , Ouhdouch Yedir , Kouisni Lamfeddal , Sy Mame Ourèye
Published: March 2021

Plant growth promoting microbes (PGPMs) play major roles in diverse ecosystems, including atmospheric nitrogen fixation, water uptake, solubilization, and transport of minerals from the soil to the plant. Different PGPMs are proposed as biofertilizers, biostimulants, and/or biocontrol agents to improve plant growth and productivity and thereby to contribute to agricultural sustainability and food security. However, little information exists regarding the use of PGPMs in micropropagation such as thein vitroplant tissue culture. This review presents an overview of the importance of PGPMs and their potential application in plant micropropagation. Our analysis, based on published articles, reveals that the process ofin vitroclassical tissue culture techniques, under strictly aseptic conditions, deserves to be reviewed to allow vitroplants to benefit from the positive effect of PGPMs. Furthermore, exploiting the potential benefits of PGPMs will lead to lessen the cost production of vitroplants during micropropagation process and will make the technique of plant tissue culture more efficient. The last part of the review will indicate where research is needed in the future.
Interplay Between CMGC Kinases Targeting SR Proteins and Viral Replication: Splicing and Beyond
Authors: Pastor Florentin , Shkreta Lulzim , Chabot Benoit , Durantel David , Salvetti Anna
Published: March 2021

Protein phosphorylation constitutes a major post-translational modification that critically regulates the half-life, intra-cellular distribution, and activity of proteins. Among the large number of kinases that compose the human kinome tree, those targeting RNA-binding proteins, in particular serine/arginine-rich (SR) proteins, play a major role in the regulation of gene expression by controlling constitutive and alternative splicing. In humans, these kinases belong to the CMGC [Cyclin-dependent kinases (CDKs), Mitogen-activated protein kinases (MAPKs), Glycogen synthase kinases (GSKs), and Cdc2-like kinases (CLKs)] group and several studies indicate that they also control viral replicationviadirect or indirect mechanisms. The aim of this review is to describe known and emerging activities of CMGC kinases that share the common property to phosphorylate SR proteins, as well as their interplay with different families of viruses, in order to advance toward a comprehensive knowledge of their pro- or anti-viral phenotype and better assess possible translational opportunities.
Butyrate Suppresses Glucose Metabolism of Colorectal Cancer Cells via GPR109a-AKT Signaling Pathway and Enhances Chemotherapy
Authors: Geng Hong-Wei , Yin Feng-Yi , Zhang Zhi-Fa , Gong Xu , Yang Yun
Published: March 2021

Glycolysis inhibitors are promising therapeutic drugs for tumor treatment, which target the uniquely elevated glucose metabolism of cancer cells. Butyrate is a critical product of beneficial microbes in the colon, which exerts extraordinary anti-cancer activities. In particular, butyrate shows biased inhibitory effects on the cell growth of cancerous colonocytes, whereas it is the major energy source for normal colonocytes. Besides its roles as the histone deacetylases (HDACs) inhibitor and the ligand for G-protein coupled receptor (GPR) 109a, the influence of butyrate on the glucose metabolism of cancerous colonocytes and the underlying molecular mechanism are not fully understood. Here, we show that butyrate markedly inhibited glucose transport and glycolysis of colorectal cancer cells, through reducing the abundance of membrane GLUT1 and cytoplasmic G6PD, which was regulated by the GPR109a-AKT signaling pathway. Moreover, butyrate significantly promoted the chemotherapeutical efficacy of 5-fluorouracil (5-FU) on cancerous colonocytes, with exacerbated impairment of DNA synthesis efficiency. Our findings provide useful information to better understand the molecular basis for the impact of butyrate on the glucose metabolism of colorectal cancer cells, which would promote the development of beneficial metabolites of gut microbiota as therapeutical or adjuvant anti-cancer drugs.
Blepharospasm, Oromandibular Dystonia, and Meige Syndrome: Clinical and Genetic Update
Authors: Ma Hongying , Qu Jian , Ye Liangjun , Shu Yi , Qu Qiang
Published: March 2021

Meige syndrome (MS) is cranial dystonia characterized by the combination of upper and lower cranial involvement and including binocular eyelid spasms (blepharospasm; BSP) and involuntary movements of the jaw muscles (oromandibular dystonia; OMD). The etiology and pathogenesis of this disorder of the extrapyramidal system are not well-understood. Neurologic and ophthalmic examinations often reveal no abnormalities, making diagnosis difficult and often resulting in misdiagnosis. A small proportion of patients have a family history of the disease, but to date no causative genes have been identified to date and no cure is available, although botulinum toxin A therapy effectively mitigates the symptoms and deep brain stimulation is gaining increasing attention as a viable alternative treatment option. Here we review the history and progress of research on MS, BSP, and OMD, as well as the etiology, pathology, diagnosis, and treatment.
Clopidogrel Plus Aspirin in Patients With Different Types of Single Small Subcortical Infarction
Authors: Wang Guangyao , Yang Xiaomeng , Jing Jing , Zhao Xingquan , Liu Liping , Wang Chunxue , Wang David , Wang Anxin , Meng Xia , Wang Yongjun , Wang Yilong
Published: March 2021

Background: We aim to investigate the effects and safety of clopidogrel plus aspirin in patients with different types of single small subcortical infarction (SSSI) in the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial.

Methods: SSSI was defined as single DWI lesion of ≤2.0 cm. Patients with SSSI were divided into SSSI + PAD (parent artery disease) and SSSI – PAD, according to the stenosis of the parent artery. The efficacy outcome was stroke recurrence during 90-day follow-up. Cox proportional hazards models or logistic regression models were used to assess the interaction of the treatment effects of clopidogrel plus aspirin vs. aspirin alone among patients with and without PAD.

Results: Among 338 patients with SSSI included in the subanalysis, 105 were with PAD and 233 without. The efficacy of clopidogrel plus aspirin compared with aspirin alone on any stroke was consistent between patients with [adjusted hazard ratio (HR) 0.84; 95% confidence interval (CI), 0.25–2.75] and without PAD (adjusted HR 1.03; 95% CI, 0.40–2.68, interaction P = 0.83). In patients with SSSI + PAD, the rate of stroke recurrence in those treated with dual antiplatelet therapy and mono antiplatelet therapy was not significantly different (10.9 vs. 13.6%, P = 0.77). The number of bleeding events was similar between the clopidogrel-aspirin group and aspirin group regardless of SSSI + PAD or SSSI – PAD.

Conclusions: There was no significant difference in the efficacy of clopidogrel plus aspirin compared with aspirin alone between patients with SSSI + PAD and SSSI – PAD in the CHANCE trial. Studies in other populations and with adequate power are needed to further verify such findings.
The Neurobiology of Zika Virus: New Models, New Challenges
Authors: Moura Luciana Monteiro , Ferreira Vinicius Leati de Rossi , Loureiro Rafael Maffei , de Paiva Joselisa Péres Queiroz , Rosa-Ribeiro Rafaela , Amaro Edson , Soares Milena Botelho Pereira , Machado Birajara Soares
Published: March 2021

The Zika virus (ZIKV) attracted attention due to one striking characteristic: the ability to cross the placental barrier and infect the fetus, possibly causing severe neurodevelopmental disruptions included in the Congenital Zika Syndrome (CZS). Few years after the epidemic, the CZS incidence has begun to decline. However, how ZIKV causes a diversity of outcomes is far from being understood. This is probably driven by a chain of complex events that relies on the interaction between ZIKV and environmental and physiological variables. In this review, we address open questions that might lead to an ill-defined diagnosis of CZS. This inaccuracy underestimates a large spectrum of apparent normocephalic cases that remain underdiagnosed, comprising several subtle brain abnormalities frequently masked by a normal head circumference. Therefore, new models using neuroimaging and artificial intelligence are needed to improve our understanding of the neurobiology of ZIKV and its true impact in neurodevelopment.
One Month of Classic Therapeutic Ketogenic Diet Decreases Short Chain Fatty Acids Production in Epileptic Patients
Authors: Ferraris Cinzia , Meroni Erika , Casiraghi Maria Cristina , Tagliabue Anna , De Giorgis Valentina , Erba Daniela
Published: March 2021

Ketogenic diet (KD), a high fat and very low carbohydrates diet, is used worldwide for the treatment of drug resistant epilepsy but, due to its composition, it might exert an impact on gut health. Even though data of KD effects on intestinal microbiota changes are recently emerging, its influence on the gut environment has been scarcely addressed so far. The aim of this study was to investigate whether 1 month of KD affects the gut environment in epileptic patients, by analyzing short chain fatty acids (SCFA) production and fecal water toxicity. A total of seven patients were enrolled. Stool samples were collected before (T0) and after 1 month of KD (4:1 ketogenic ratio) (T1). SCFA were determined by GC-FID and fecal water toxicity in Caco-2 cell culture by comet assay. Concentrations of SCFA significantly decreased after KD (p < 0.05): in particular, we found a 55% reduction of total SCFA level, a 64% reduction of acetate, 33% of propionate, and 20% of butyrate (p < 0.05). Cytotoxicity of fecal water extracted from stool samples was not significantly altered by diet, while genotoxicity was slightly decreased after KD (p < 0.05). Genotoxicity values were consistent with data previously obtained from a healthy Italian population. The present study suggests that 1 month of KD significantly reduce SCFA production. Since SCFA produced by gut microbiota exert many health promoting effects on either the gut environment or human metabolism, these results open a new branch of investigation into KD effects.
Colloidal Particles in Tuna Head Soup: Chemical Localization, Structural Change, and Antioxidant Property
Authors: Ma Chenchen , Liu Pingping , Tao Ningping , Wang Xichang , Deng Shanggui
Published: March 2021

In this work, chemical localization, structural changes, and antioxidant properties of tuna colloidal particles (TCPs) in boiling tuna head soup were examined. The results demonstrated that TCPs might be core–shell colloidal spherical structures. The hydrophobic core consisted of triglycerides and chloride ions. The hydrophilic shell layer consisted of chloride ions, sodium ions, phospholipids, protein, and glycosyl molecules. Coalescence of TCPs occurred during the boiling process, and water may enter the hydrophobic core of TCPs after the boiling time of 60 min. TCPs had excellent antioxidant properties against H2O2-induced human umbilical vein endothelial cell injury. It might be resulted from that TCPs could decrease cell apoptosis proportion and downregulate mRNA levels of endoplasmic reticulum-bounded chaperone protein glucose-related protein (GRP78), C/EBP homologous protein (CHOP), and activating transcription factor-4 (ATF4). This work can provide useful basic information to understand the colloidal system in foods, especially in soup. In addition, it may also promote the potential high-value-added utilization of aquatic by-products.
Immunotherapy for Hepatocellular Carcinoma: Current Limits and Prospects
Authors: Zhong Cheng , Li Yirun , Yang Jing , Jin Shengxi , Chen Guoqiao , Li Duguang , Fan Xiaoxiao , Lin Hui
Published: March 2021

Although many approaches have been used to treat hepatocellular carcinoma (HCC), the clinical benefits remain limited, particularly for late stage HCC. In recent years, studies have focused on immunotherapy for HCC. Immunotherapies have shown promising clinical outcomes in several types of cancers and potential therapeutic effects for advanced HCC. In this review, we summarize the immune tolerance and immunotherapeutic strategies for HCC as well as the main challenges of current therapeutic approaches. We also present alternative strategies for overcoming these limitations.
Automatic Detection of Gastric Wall Structure Based on Oral Contrast-Enhanced Ultrasound and Its Application on Tumor Screening
Authors: Sui An , Hu Zhaoyu , Xie Xuan , Deng Yinhui , Wang Yuanyuan , Yu Jinhua , Shen Li
Published: March 2021

Gastric cancer is the second most lethal type of malignant tumor in the world. Early diagnosis of gastric cancer can reduce the transformation to advanced cancer and improve the early treatment rate. As a cheap, real-time, non-invasive examination method, oral contrast-enhanced ultrasonography (OCUS) is a more acceptable way to diagnose gastric cancer than interventional diagnostic methods such as gastroscopy. In this paper, we proposed a new method for the diagnosis of gastric diseases by automatically analyzing the hierarchical structure of gastric wall in gastric ultrasound images, which is helpful to quantify the diagnosis information of gastric diseases and is a useful attempt for early screening of gastric cancer. We designed a gastric wall detection network based on U-net. On this basis, anisotropic diffusion technology was used to extract the layered structure of the gastric wall. A simple and useful gastric cancer screening model was obtained by calculating and counting the thickness of the five-layer structure of the gastric wall. The experimental results showed that our model can accurately identify the gastric wall, and it was found that the layered parameters of abnormal gastric wall is significantly different from that of normal gastric wall. For the screening of gastric disease, a statistical model based on gastric wall stratification can give a screening accuracy of 95% with AUC of 0.92.
TRPC1 Inhibits Cell Proliferation/Invasion and Is Predictive of a Better Prognosis of Esophageal Squamous Cell Carcinoma
Authors: Zeng Yun-Zhu , Zhang Yong-Qu , Chen Jiong-Yu , Zhang Li-Ying , Gao Wen-Liang , Lin Xue-Qiong , Huang Shao-Min , Zhang Fan , Wei Xiao-Long
Published: March 2021

Background and Objectives

In China, over 90% of esophageal cancer (EC) cases are esophageal squamous cell carcinoma (ESCC). ESCC is a frequently malignant tumor with poor prognosis despite the development of comprehensive therapeutic strategies, for which there is still a lack of effective prognostic factors. Previous studies found that the abnormal expression of TRPC1 is closely related to the proliferation, invasion, metastasis, and differentiation of various tumors. However, the relationship between TRPC1 and ESCC is currently unclear. The present study aimed to clarify the clinical significance of TRPC1 and to preliminarily assess the molecular mechanism by which TRPC1 regulates cell proliferation, migration, and invasion in ESCC.

Materials and Methods

Immunohistochemistry (IHC) was used to determine the expression of TRPC1 and Ki-67 in 165 cases of ESCC. The correlations between TRPC1 expression and clinicopathological characteristics were determined, and both univariate and multivariate analyses were utilized to quantify the impact of TRPC1 expression on patient survival. Cell Counting Kit-8, scratch wound healing, and transwell assays were used to determine the effects of TRPC1 on proliferation, migration, and invasion in ESCC in vitro, respectively.

Results

The positive expression rate of TRPC1 showed significantly decreased in ESCC (45.50%) compared with the levels in normal esophageal mucosa (NEM; 80.80%) and high-grade intraepithelial neoplasia (HGIEN; 63.20%) (P<0.001). Higher expression rate of TRPC1 was associated with low lymph node metastasis (P<0.001), high differentiation (rs= 0.232, P=0.003), and low Ki-67 (rs = −0.492, P<0.001). We further revealed that low expression of TRPC1 was associated with poor prognosis (Disease-free survival, DFS: 95% CI=0.545–0.845, P=0.001; Overall survival, OS: 95% CI=0.553–0.891, P=0.004). Furthermore, we showed that downregulation of TRPC1 promoted the proliferation, migration, and invasion of human esophageal squamous cell carcinoma cell line EC9706 in vitro. In contrast, overexpression of TRPC1 inhibited the proliferation, migration, and invasion of human esophageal squamous cell carcinoma cell line KYSE150 (P<0.01), in a manner at least in part mediated through the AKT/p27 pathway.

Conclusion

TRPC1 inhibited the proliferation, migration, and invasion of EC9706 and KYSE150 cells, at least, in part mediated through the AKT/p27 pathway in vitro. The downregulation of TRPC1 may be one of the most important molecular events in the malignant progression of ESCC. TRPC1 could be a new candidate tumor suppressor gene and a new prognostic factor of ESCC.
IDH1/IDH2 Inhibition in Acute Myeloid Leukemia
Authors: Cerchione Claudio , Romano Alessandra , Daver Naval , DiNardo Courtney , Jabbour Elias Joseph , Konopleva Marina , Ravandi-Kashani Farhad , Kadia Tapan , Martelli Maria Paola , Isidori Alessandro , Martinelli Giovanni , Kantarjian Hagop
Published: March 2021

Recently, the discovery of biological and clinical properties of mutated isoforms 1 and 2 mutations of isocitrate dehydrogenases (IDH) 1 and 2, affecting approximately 20% of patients with acute myeloid leukemia (AML), lead to the development of an individualized treatment strategy. Promoting differentiation and maturation of the malignant clone targeting IDH is an emerging strategy to promote clinical responses in AML. Phase I/II trials have shown evidence of safety, tolerability, and encouraging evidence of efficacy of two small molecule inhibitors targeting IDH2 and IDH1 gene mutations, respectively enasidenib and ivosidenib. In this review, the contribution of IDH1/IDH2 mutations in leukemogenesis and progress of targeted therapeutics in AML will be highlighted.
Diagnosis and Treatment of Male Accessory Breast Cancer: A Comprehensive Systematic Review
Authors: Pang Liwei , Cui Meiying , Dai Wanlin , Wu Shuodong , Kong Jing
Published: March 2021

Background

Accessory breast cancer is extremely rare, especially in male patients, and only a few cases have been reported in the literature. To date, no specific guidelines regarding its diagnosis and treatment are available.

Objectives

This study aimed to investigate the guidelines for the diagnosis and treatment of male accessory breast cancer by reviewing the available literature on this disease.

Methods

The Web of Science, Cochrane, PubMed, and CNKI databases were systematically searched (last search: 30 November 2020) to identify studies on male axillary accessory breast cancer. The following data were extracted: author names, number of patients, country, patient age, tumor location, tumor size, pathologic diagnosis, and treatment.

Results

There were 16 studies included (6 in Chinese and 10 in English), corresponding to 16 cases of male axillary accessory breast cancer. Primary surgical resection is currently the main procedure, followed by comprehensive treatment including chemotherapy, radiotherapy, and endocrine therapy. Patient age ranged from 51–87 years, and the average age was 67.1 years. The main clinical features of the patients were pain, the portion of the skin covering the mass was either reddish or purplish, and the mass could show swelling and erosion on the surface, with purulent exudate.

Conclusions

Once male accessory breast cancer is diagnosed, we can follow the latest guidelines for the diagnosis and treatment of breast cancer. Tumor biopsy and resection seems the treatment of first choice, combined with comprehensive treatment including chemotherapy, radiotherapy, and endocrine therapy.
Myeloid-Derived Suppressor Cells in Immune Microenvironment Promote Progression of Esophagogastric Junction Adenocarcinoma
Authors: Wang Ying , Sun Haiyan , Zhu Ningning , Wu Xianxian , Sui Zhilin , Gong Lei , Yu Zhentao
Published: March 2021

Adenocarcinoma of the esophagogastric junction (AEG) is a fatal disease. Accumulating evidence indicates that, for a comprehensive understanding of AEG, studies should be conducted not only to investigate tumor cells, but also the tumor microenvironment (TME). In this study, we collected AEG patient data from The Cancer Genome Atlas, and used the CIBERSORT algorithm to analyze tumor-infiltrating immune cell profiles. The levels of CD8+ T cells and M0 and M2 macrophages were relatively high in AEG tissues. M2 macrophages were abundant in G3 tumors, and neutrophils were associated with poor prognosis. Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immunosuppressive cells which share a similar origin to neutrophils and macrophages. We further analyzed the levels of MDSCs in AEG patients and healthy donors (HD) using flow cytometry. MDSC levels were elevated at tumor sites, with polymorphonuclear MDSCs (PMN-MDSCs) being the predominant subtype. Circulating MDSCs partly represented cells at the tumor site. We observed that PMN-MDSC levels at tumor sites were positively correlated with advanced staging, low grade, lymph node metastasis, and HER2− status. Immunohistochemistry and immunofluorescence analyses indicated that activation of the STAT3 and NF-κB pathways in MDSCs may be a potential mechanism for cancer progression. Our studies provided a comprehensive perspective involving tumor-infiltrating immune cells, and detailed insights into the proportion of MDSCs in AEG and their clinical significance. Together, these findings may improve our current understanding of cancer progression involving tumor-infiltrating immune cells in the TME.
Personalized Survival Prediction of Patients With Acute Myeloblastic Leukemia Using Gene Expression Profiling
Authors: Mosquera Orgueira Adrián , Peleteiro Raíndo Andrés , Cid López Miguel , Díaz Arias José Ángel , González Pérez Marta Sonia , Antelo Rodríguez Beatriz , Alonso Vence Natalia , Bao Pérez Laura , Ferreiro Ferro Roi , Albors Ferreiro Manuel , Abuín Blanco Aitor , Fontanes Trabazo Emilia , Cerchione Claudio , Martinnelli Giovanni , Montesinos Fernández Pau , Mateo Pérez Encinas Manuel , Luis Bello López José
Published: March 2021

Acute Myeloid Leukemia (AML) is a heterogeneous neoplasm characterized by cytogenetic and molecular alterations that drive patient prognosis. Currently established risk stratification guidelines show a moderate predictive accuracy, and newer tools that integrate multiple molecular variables have proven to provide better results. In this report, we aimed to create a new machine learning model of AML survival using gene expression data. We used gene expression data from two publicly available cohorts in order to create and validate a random forest predictor of survival, which we named ST-123. The most important variables in the model were age and the expression of KDM5B and LAPTM4B, two genes previously associated with the biology and prognostication of myeloid neoplasms. This classifier achieved high concordance indexes in the training and validation sets (0.7228 and 0.6988, respectively), and predictions were particularly accurate in patients at the highest risk of death. Additionally, ST-123 provided significant prognostic improvements in patients with high-risk mutations. Our results indicate that survival of patients with AML can be predicted to a great extent by applying machine learning tools to transcriptomic data, and that such predictions are particularly precise among patients with high-risk mutations.
Association of Routinely Measured Proinflammatory Biomarkers With Abnormal MRI Findings in Asphyxiated Neonates Undergoing Therapeutic Hypothermia
Authors: Ruhfus Maria , Giannakis Stamatios , Markus Mona , Stein Anja , Hoehn Thomas , Felderhoff-Mueser Ursula , Sabir Hemmen
Published: March 2021

Background: The neuroprotective treatment effect of therapeutic hypothermia (TH) following perinatal asphyxia may be negatively influenced by neonatal sepsis and concomitant inflammation. We aimed to correlate routinely used blood biomarkers for perinatal sepsis in cooled asphyxiated newborns with MRI findings.

Methods: Perinatal data was retrospectively collected from 67 cooled asphyxiated newborns. Levels of C-reactive protein (CRP), white blood cells and platelets were analyzed before, during and after TH. Interleukin-6 blood levels were analyzed before initiation of TH. Magnetic resonance imaging (MRI) on postnatal day 5–7 was used defining short-term outcome. Adverse outcome was defined as death or adverse MRI findings. Amplitude-integrated electroencephalography (aEEG) was additionally analyzed and correlated with short-term MRI outcome.

Results: Forty-nine newborns had favorable short-term MRI outcome. Perinatal data referring to perinatal sepsis did not differ significantly between groups. IL-6 levels before initiation of TH and CRP levels on day three and after TH were significantly higher in newborns with adverse short-term MRI outcome. Males with adverse short-term MRI outcome had significantly increased CRP values at the end of the cooling phase. aEEG strongly correlated with short-term MRI outcome.

Conclusion: Routinely used blood biomarkers may be helpful early identifying newborns at high risk of unfavorable outcome and in need of close neurodevelopmental follow-up.
How the Management of Children With Congenital Central Hypoventilation Syndrome Has Changed Over Time: Two Decades of Experience From an Italian Center
Authors: Porcaro Federica , Paglietti Maria Giovanna , Cherchi Claudio , Schiavino Alessandra , Chiarini Testa Maria Beatrice , Cutrera Renato
Published: March 2021

Background:Congenital central hypoventilation syndrome (CCHS) is a rare disorder whose clinical phenotype is closely related to genotype.

Methods:A retrospective analysis has been conducted on 22 patients with CCHS, who were referred to the Pediatric Pulmonology and Respiratory Intermediate Care Unit of Bambino Gesù Children's Hospital (Italy) for a multidisciplinary follow-up program between 2000 and 2020.

Results:Apnea and cyanosis were the most frequent symptoms at onset (91%). Overall, 59% of patients required tracheostomy and invasive mechanical ventilation (IMV) in the first months of life. Thirty-two percent of patients had Hirschsprung disease (HSCR) that was associated with longer polyalanine repetitions or non-polyalanine repeat expansion mutations (NPARMs). Polyalanine repeat expansion mutations (PARMs) were more frequent and two novel NPARMs (c.780dupT and C.225–256delCT) were described in 14% of patients. Focal epilepsy was first described in 14% of patients and neurocognitive and neuromotor impairment involved 27% and 23% of children, respectively. Symptoms due to autonomic nervous system dysfunction/dysregulation (ANSD)—including strabismus (27%), dysphagia (27%), abnormal heart rhythm (10%), breath-holding spells (9%), and recurrent seizures due to hypoglycemia (9%)—were associated with an increased number of polyalanine repetitions of exon 3 or NPARMs of PHOX2B gene. Overall, the number of patients with moderate to severe phenotype initially treated with non-invasive ventilation (NIV) increased over time, and the decannulation program was concluded with 3 patients who started with IMV.

Conclusions:Our study confirms that more severe phenotypes of CCHS are related to the number of polyalanine repetitions or to NPARMs. Although invasive ventilation is often required by patients with severe genotype/phenotype, gradual acquisition of specific skills in the management of patients with CCHS and technological improvements in mechanical ventilation allowed us to improve our therapeutic approach in this population.
A Systematic Review of the Preventive and Therapeutic Effects of Naringin Against Human Malignancies
Authors: Ghanbari-Movahed Maryam , Jackson Gloria , Farzaei Mohammad Hosein , Bishayee Anupam
Published: March 2021

Background: Natural product-based cancer preventive and therapeutic entities, such as flavonoids and their derivatives, are shown to have a noticeable capability to suppress tumor formation and cancer cell growth. Naringin, a natural flavanone glycoside present in various plant species, has been indicated to modulate different signaling pathways and interact with numerous cell signaling molecules, which allows for an extensive variety of pharmacological actions, such as amelioration of inflammation, oxidative stress, metabolic syndromes, bone disorders, and cancer. The purpose of this systematic review is to present a critical and comprehensive assessment of the antitumor ability of naringin and associated molecular targets in various cancers.

Methods: Studies were identified through systematic searches of Science Direct, PubMed, and Scopus as well as eligibility checks according to predefined selection criteria.

Results: Eighty-seven studies were included in this systematic review. There was strong evidence for the association between treatment with naringin alone, or combined with other drugs and antitumor activity. Additionally, studies showed that naringin-metal complexes have greater anticancer effects compared to free naringin. It has been demonstrated that naringin employs multitargeted mechanisms to hamper cancer initiation, promotion, and progression through modulation of several dysregulated signaling cascades implicated in cell proliferation, autophagy, apoptosis, inflammation, angiogenesis, metastasis, and invasion.

Conclusion: The results of our work show that naringin is a promising candidate for cancer prevention and treatment, and might offer substantial support for the clinical application of this phytocompound in the future. Nevertheless, further preclinical and clinical studies as well as drug delivery approaches are needed for designing novel formulations of naringin to realize the full potential of this flavonoid in cancer prevention and intervention.
Work Extraction and Performance of Colloidal Heat Engines in Viscoelastic Baths
Authors: Gomez-Solano Juan Ruben
Published: March 2021

A colloidal particle embedded in a fluid can be used as a microscopic heat engine by means of a sequence of cyclic transformations imposed by an optical trap. We investigate a model for the operation of such kind of Brownian engines when the surrounding medium is viscoelastic, which endows the particle dynamics with memory friction. We analyze the effect of the relaxation time of the fluid on the performance of the colloidal engine under finite-time Stirling cycles. We find that, due to the frequency-dependence of the friction in viscoelastic fluids, the mean power delivered by the engine and its efficiency can be highly enhanced as compared to those in a viscous environment with the same zero-shear viscosity. In addition, with increasing fluid relaxation time the interval of cycle times at which positive power output can be delivered by the engine broadens. Our results reveal the importance of the transient behavior of the friction experienced by a Brownian heat engine in a complex fluid, which cannot be neglected when driven by thermodynamic cycles of finite duration.
Autofocusing Algorithm for Pixel-Super-Resolved Lensfree On-Chip Microscopy
Authors: Wu Yumin , Lu Linpeng , Zhang Jialin , Li Zhuoshi , Zuo Chao
Published: March 2021

In recent years, lensfree on-chip microscopy has developed into a promising and powerful computational optical microscopy technique that allows for wide-field, high-throughput microscopic imaging without using any lenses. However, due to the limited pixel size of the state-of-the-art image sensors, lens-free on-chip microscopy generally suffers from low imaging resolution, which is far from enough to meet the current demand for high-resolution microscopy. Many pixel super-resolution techniques have been developed to solve or at least partially solve this problem by acquiring a series of low-resolution holograms with multiple lateral sub-pixel shifting or axial distances. However, the prerequisite of these pixel super-resolution techniques is that the propagation distance of each low-resolution hologram can be obtained precisely, which faces two major challenges. On the one hand, the captured hologram is inherent pixelated and of low resolution, making it difficult to determine the focal plane by evaluating the image sharpness accurately. On the other hand, the twin-image is superimposed on the backpropagated raw hologram, further exacerbating the difficulties in accurate focal plane determination. In this study, we proposed a high-precision autofocusing algorithm for multi-height pixel-super-resolved lensfree on-chip microscopy. Our approach consists of two major steps: individual preliminary estimation and global precise estimation. First, an improved critical function that combines differential critical function and frequency domain critical function is proposed to obtain the preliminary focus distances of different holograms. Then, the precise focus distances can be determined by further evaluating the global offset of the averaged, low-noise reconstruction from all backpropagated holograms with preliminary focus distances. Simulations and experimental results verified the validity and effectiveness of the proposed algorithm.
Mineralocorticoid Receptor in Myeloid Cells Mediates Angiotensin II-Induced Vascular Dysfunction in Female Mice
Authors: Manrique-Acevedo Camila , Padilla Jaume , Naz Huma , Woodford Makenzie L. , Ghiarone Thaysa , Aroor Annayya R. , Hulse Jack L. , Cabral-Amador Francisco J. , Martinez-Diaz Vanesa , Hans Chetan P. , Whaley-Connell Adam , Martinez-Lemus Luis A. , Lastra Guido
Published: March 2021

Enhanced mineralocorticoid receptor (MR) signaling is critical to the development of endothelial dysfunction and arterial stiffening. However, there is a lack of knowledge about the role of MR-induced adipose tissue inflammation in the genesis of vascular dysfunction in women. In this study, we hypothesize that MR activation in myeloid cells contributes to angiotensin II (Ang II)-induced aortic stiffening and endothelial dysfunction in femalesviaincreased pro-inflammatory (M1) macrophage polarization. Female mice lacking MR in myeloid cells (MyMRKO) were infused with Ang II (500 ng/kg/min) for 4 weeks. This was followed by determinations of aortic stiffness and vasomotor responses, as well as measurements of markers of inflammation and macrophage infiltration/polarization in different adipose tissue compartments. MyMRKO mice were protected against Ang II-induced aortic endothelial stiffening, as assessedviaatomic force microscopy in aortic explants, and vasorelaxation dysfunction, as measured by aortic wire myography. In alignment, MyMRKO mice were protected against Ang II-induced macrophage infiltration and M1 polarization in visceral adipose tissue (VAT) and thoracic perivascular adipose tissue (tPVAT). Collectively, this study demonstrates a critical role of MR activation in myeloid cells in the pathogenesis of vascular dysfunction in females associated with pro-inflammatory macrophage polarization in VAT and tPVAT. Our data have potential clinical implications for the prevention and management of cardiovascular disease in women, who are disproportionally at higher risk for poor outcomes.
Alteration of DNA Damage Response Causes Cleft Palate
Authors: Yamaguchi Hiroyuki , Kitami Kohei , Wu Xiao , He Li , Wang Jianbo , Wang Bin , Komatsu Yoshihiro
Published: March 2021

Cleft palate is one of the most common craniofacial birth defects, however, little is known about how changes in the DNA damage response (DDR) cause cleft palate. To determine the role of DDR during palatogenesis, the DDR process was altered using a pharmacological intervention approach. A compromised DDR caused by a poly (ADP-ribose) polymerase (PARP) enzyme inhibitor resulted in cleft palate in wild-type mouse embryos, with increased DNA damage and apoptosis. In addition, a mouse genetic approach was employed to disrupt breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2), known as key players in DDR. An ectomesenchymal-specific deletion ofBrca1orBrca2resulted in cleft palate due to attenuation of cell survival. This was supported by the phenotypes of the ectomesenchymal-specificBrca1/Brca2double-knockout mice. The cleft palate phenotype was rescued by superimposing p53 null alleles, demonstrating that the BRCA1/2–p53 DDR pathway is critical for palatogenesis. Our study highlights the importance of DDR in palatogenesis.
Infodemic Pathways: Evaluating the Role That Traditional and Social Media Play in Cross-National Information Transfer
Authors: Bridgman Aengus , Merkley Eric , Zhilin Oleg , Loewen Peter John , Owen Taylor , Ruths Derek
Published: March 2021

The COVID-19 pandemic has occurred alongside a worldwide infodemic where unprecedented levels of misinformation have contributed to widespread misconceptions about the novel coronavirus. Conspiracy theories, poorly sourced medical advice, and information trivializing the virus have ignored national borders and spread quickly. This information spread has occurred despite generally strong preferences for domestic national media and social media networks that tend to be geographically bounded. How, then, is (mis)information crossing borders so rapidly? Using social media and survey data, we evaluate the extent to which consumption and propagation patterns of domestic and international traditional news and social media can help inform theorizing about cross-national information spread. In a detailed case study of Canada, we employ a large multi-wave survey and a massive data set of Canadian Twitter users. We show that the majority of misinformation circulating on Twitter that is shared by Canadian accounts is retweeted from U.S.-based accounts. Moreover, exposure to U.S.-based media outlets is associated with COVID-19 misperceptions and increased exposure to U.S.-based information on Twitter is associated with an increased likelihood to post misinformation. We thus theorize and empirically identify a key globalizing infodemic pathway: disregard for national origin of social media posting.
Variable Speed Across Dimensions of Ability in the Joint Model for Responses and Response Times
Authors: Zhan Peida , Jiao Hong , Man Kaiwen , Wang Wen-Chung , He Keren
Published: March 2021

Working speed as a latent variable reflects a respondent’s efficiency to apply a specific skill, or a piece of knowledge to solve a problem. In this study, the common assumption of many response time models is relaxed in which respondents work with a constant speed across all test items. It is more likely that respondents work with different speed levels across items, in specific when these items measure different dimensions of ability in a multidimensional test. Multiple speed factors are used to model the speed process by allowing speed to vary across different domains of ability. A joint model for multidimensional abilities and multifactor speed is proposed. Real response time data are analyzed with an exploratory factor analysis as an example to uncover the complex structure of working speed. The feasibility of the proposed model is examined using simulation data. An empirical example with responses and response times is presented to illustrate the proposed model’s applicability and rationality.