bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuronal Correlates of Cognitive Control Are Altered in Women With Endometriosis and Chronic Pelvic Pain
Authors: Steiner Genevieve Z. , Barry Robert J. , Wassink Katherine , De Blasio Frances M. , Fogarty Jack S. , Cave Adele E. , Love Sapphire , Armour Mike
Published: January 2021

Endometriosis is a debilitating women's health condition and is the most common cause of chronic pelvic pain. Impaired cognitive control is common in chronic pain conditions, however, it has not yet been investigated in endometriosis. The aim of this study was to explore the neuronal correlates of cognitive control in women with endometriosis. Using a cross-sectional study design with data collected at a single time-point, event-related potentials were elicited during a cued continuous performance test from 20 women with endometriosis (mean age = 28.5 ± 5.2 years) and 20 age- and gender-matched controls (mean age = 28.5 ± 5.2 years). Event-related potential components were extracted and P3 component amplitudes were derived with temporal principal components analysis. Behavioral and ERP outcomes were compared between groups and subjective pain severity was correlated with ERP component amplitudes. No significant behavioral differences were seen in task performance between the groups (all p > 0.094). Target P3b (all p < 0.034) and SW (all p < 0.040), and non-target early P3a (eP3a; all p < 0.023) and late P3a (lP3a; all p < 0.035) amplitudes were smaller for the endometriosis compared to the healthy control group. Lower non-target eP3a (p < 0.001), lP3a (p = 0.013), and SW (p = 0.019) amplitudes were correlated with higher pain severity scores. Findings suggest that endometriosis-associated chronic pelvic pain is linked to alterations in stimulus-response processing and inhibitory control networks, but not impaired behavioral performance, due to compensatory neuroplastic changes in overlapping cognitive control and pain networks.
The Stability, Microstructure, and Microrheological Properties of Monascus Pigment Double Emulsions Stabilized by Polyglycerol Polyricinoleate and Soybean Protein Isolate
Authors: Xu Duoxia , Zheng Boyan , Che Yixin , Liu Guorong , Yuan Yingmao , Wang Shaojia , Cao Yanping
Published: January 2021

Monascus pigment is a natural food pigment and is commonly used for coloring and as antiseptic of cured meat products, confectionery, cakes, and beverages. However, Monascus pigment is sensitive to environmental conditions. The main aim of this study was to investigate the effect of polyglycerol polyricinoleate (PGPR) and soy protein isolate (SPI) on the particle size, zeta potential, physical stability, microstructure, and microrheological properties of Monascus pigment double emulsions. The effects of ionic strength, heating, and freeze thawing treatment on the stabilities of Monascus pigment double emulsions were also characterized. It was found that the optimum PGPR and SPI concentrations for fabricating Monascus pigment double emulsion were 3.6 and 3.0 wt%, respectively. The fabricated Monascus pigment double emulsion was composed of fine particles with narrow and uniform size distributions. Microrheological property results suggested that the elastic characteristic of the Monascus pigment double emulsion was dominated with increasing PGPR and SPI contents. It was mainly due to the increased collision and interaction between the droplets during the movement resulting in force increasing. Monascus pigment double emulsions with <5 mM CaCl2 prevented calcium to destroy the physical stability of emulsions, while Monascus pigment double emulsions with more than 10 mM CaCl2 formed creaming. After freeze thawing treatment, creaming occurred in Monascus pigment double emulsion. However, it was stable against heating treatment due to heating leading to a dense network structure. It could be contributed to the practical applications of Monascus pigment double emulsions in food products.
Metabolite Fingerprinting of Kersting's Groundnut [Macrotyloma geocarpum (Harms) Maréchal & Baudet] Seeds Using UPLC-qTOF-MS Reveals the Nutraceutical and Antioxidant Potentials of the Orphan Legume
Authors: Tsamo Armelle Tontsa , Mohammed Mustapha , Dakora Felix Dapare
Published: January 2021

The identification and subsequent quantification of phenolic compounds in plants is the first step toward harnessing their associated nutritional and health benefits. Due to their diverse phenolic compound compositions, grain legumes are known for their high nutritional and health values. The aim of this study was to assess the inter-variations in chemical composition, phytochemical content, and antioxidant capacity of seed extracts from eight Kersting's groundnut [Macrotyloma geocarpum(Harms) Marechal & Baudet] landraces. The chemical profiles were evaluated using UPLC-qTOF-MS. Total phenolics and flavonoids content were determined by the Folin-Ciocalteu and aluminum chloride methods, respectively. The antioxidant capacities in the forms of DPPH and ABTS were evaluated using spectrophotometric methods. Principal component analysis was used to define similarities/differences between the landraces. Based on untargeted metabolomics analysis, 57 metabolites were identified, with phenolics, triterpenes, fatty acids, and sphingolipids being the most predominant. The results showed that the black seeded KG1 (Puffeun) had the highest total phenolic (9.44 mg GAE/g) and flavonoid (3.01 mg QE/g) contents, as well as antioxidant capacity (9.17 μg/mL and 18.44 μg/mL based on DDPH and ABTS assays, respectively). The concentrations of ferulic acid hexoside, procyanidin B2, eryodictyiol-7-rutinoside and quercetin pentoside ranged from 51.78–441.31, 1.86–18.25, 3.26–13.95 to 5.44–63.85 μg/mg, respectively. This study presents a useful report on the phytochemical characterization of Kersting's groundnuts and shows that the grains can be used as a source of nutraceuticals for human consumption.
The Nutritional Potential of the Native Australian Green Plum (Buchanania obovata) Compared to Other Anacardiaceae Fruit and Nuts
Authors: Fyfe Selina , Smyth Heather E. , Schirra Horst Joachim , Rychlik Michael , Sultanbawa Yasmina
Published: January 2021

The native Australian green plum (Buchanania obovata) is a small fruit that grows in the northern parts of the Northern Territory and Western Australia. The fruit belongs to the family Anacardiaceae, which includes the other agriculturally important fruit mangoes, pistachios and cashew nuts. The green plum is a favored species of fruit for the Aboriginal communities and an important bush food in the Northern Territory. To date, only minimal scientific studies have been performed on the green plum as a food. This review is about plant foods in the family Anacardiaceae and the key nutritional compounds that occur in these fruit and nuts. It looks at the more traditional nutrient profiles, some key health metabolites, allergens and anti-nutrients that occur, and the role these foods play in the health of populations. This provides a guide for future studies of the green plum to show what nutritional and anti-nutritional properties and compounds should be analyzed and if there are areas where future studies should focus. This review includes an update on studies and analysis of the green plum and how its nutritional properties give it potential as a food for diet diversification in Australia.
Dysregulation of the Immune Microenvironment Contributes to Malignant Progression and Has Prognostic Value in Bladder Cancer
Authors: Zheng Zongtai , Mao Shiyu , Zhang Wentao , Liu Ji , Li Cheng , Wang Ruiliang , Yao Xudong
Published: January 2021

Objective

The malignant progression from non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) is common and has detrimental effect on patients. We aimed to elucidate the underlying mechanisms of the malignant progression from an immunological perspective and establish a reliable signature for prognostic prediction and immunotherapeutic strategies.

Methods

The Cell Type Identification by Estimating Relative Subsets of RNA Transcripts algorithm was applied to the GSE32894 data set to identify the different tumor-infiltrating immune cells involved in NMIBC and MIBC. Using weighted gene correlation network analysis, survival analysis and least absolute shrinkage and selection operator Cox analysis, we established an immune prognostic signature (IPS) based on 14 overall survival-associated immune genes in The Cancer Genome Atlas (TCGA). Functional enrichment analyses and nomogram were performed to explore the potential effects and prognostic performance of the IPS. Furthermore, the RNA-sequence data from our center were used to validate the expression levels of the selected immune genes in BLCA samples.

Results

Diverse proportions of macrophage subtypes were observed between NMIBC and MIBC. Patients with high risk scores had a worse prognosis than patients with low risk scores in training (TCGA) and validation data sets (GSE32894, GSE13507, and GSE48277). The IPS was a useful prognostic factor for patients treated with immunotherapy in the IMvigor210 trial. Hallmarks of multiple oncogenic pathways were significantly enriched in the high risk group. A novel nomogram model was established for prognostic predictions. The dysregulated expression of the selected immune genes between NMIBC and MIBC was also validated in BLCA samples.

Conclusion

Dysregulation of the immune microenvironment promoted the malignant progression from NMIBC to MIBC. The IPS can stratify patients into different risk groups with distinct prognoses and immunotherapeutic susceptibility, thus facilitating personalized immunotherapy.
Silencing SAPCD2 Represses Proliferation and Lung Metastasis of Fibrosarcoma by Activating Hippo Signaling Pathway
Authors: Zhu Bowen , Wu Yanqin , Niu Lizhi , Yao Wang , Xue Miao , Wang Hongyu , Yang Jianyong , Li Jiaping , Fan Wenzhe
Published: January 2021

The primary problem associated with fibrosarcoma is its high potential to metastasize to the lung. Aberrant expression of SAPCD2 has been widely reported to be implicated in the progression and metastasis in multiple cancer types. However, the clinical significance and biological roles of SAPCD2 in fibrosarcoma remain unknown. Here, we reported that SAPCD2 expression was markedly elevated in fibrosarcoma tissues, and its expression was differentially upregulated in fibrosarcoma cell lines compared with that in several primary fibroblast cell lines. Kaplan-Meier survival analysis revealed that SAPCD2 overexpression was significantly correlated with early progression and metastasis, and poor prognosis in fibrosarcoma patients. Our results further showed that silencing SAPCD2 inhibited the proliferation and increased the apoptosis of fibrosarcoma cells in vitro. Importantly, silencing SAPCD2 repressed lung metastasis of fibrosarcoma cells in vivo. Mechanistic investigation further demonstrated that silencing SAPCD2 inhibited the proliferation and lung metastasis of fibrosarcoma cells by activating the Hippo signaling pathway, as evidenced by the finding that constitutively active YAP1, YAP1-S127A, significantly reversed the inhibitory effect of SAPCD2 downregulation on the colony formation and anchorage-independent growth capabilities of fibrosarcoma cells, as well as the stimulatory effect on the apoptotic ratio of fibrosarcoma cells. In conclusion, SAPCD2 promotes the proliferation and lung metastasis of fibrosarcoma cells by regulating the activity of Hippo signaling, and this mechanism represents a potential therapeutic target for the treatment of lung metastatic fibrosarcoma.
Long Non-Coding RNA LINC00355 Promotes the Development and Progression of Colorectal Cancer by Elevating Guanine Nucleotide Exchange Factor T Expression via RNA Binding Protein lin-28 Homolog A
Authors: Wang Yuanyuan , Zhang Bing , Gao Ge , Zhang Yinping , Xia Qingxin
Published: January 2021

Background

Our previous study showed that guanine nucleotide exchange factor T (GEFT) was highly expressed in colorectal cancer (CRC) tissues and CRC patients with high GEFT expression had a poor prognosis, and suggested the close link of GEFT expression and CRC tumorigenesis/metastasis. In this text, the roles and upstream regulatory mechanisms of GEFT in the development and progression of CRC were further investigated.

Methods

Expression levels of GEFT mRNA and LINC00355 was measured by RT-qPCR assay. Protein levels of lin-28 homologue A (LIN28A) and GEFT were determined by western blot assay. Cell proliferative, migratory, and invasive capacities were assessed by CCK-8, Transwell migration and invasion assays, respectively. The effect of GEFT knockdown on CRC tumorigenesis was examined by mouse xenograft experiments in vivo. GEFT mRNA stability was examined by actinomycin D assay. The relationships of LINC000355, LIN28A, and GEFT were explored by RNA pull down and RIP assays.

Results

GEFT was highly expressed in CRC tissues and cell lines. GEFT knockdown inhibited CRC cell proliferation, migration, and invasion, and hindered CRC xenograft tumor growth. GEFT overexpression alleviated the detrimental effects of LINC00355 loss on CRC cell proliferation, migration, and invasion. LINC00355 promoted GEFT expression and enhanced GEFT mRNA stability via LIN28A. LIN28A knockdown weakened the promotive effect of LINC00355 on CRC cell proliferation, migration, and invasion.

Conclusion

LINC00355 facilitated CRC tumorigenesis and progression by increasing GEFT expression via LIN28A, deepening our understanding on roles and upstream regulatory mechanisms of GEFT in CRC development and progression.
The Implications of PDK1–4 on Tumor Energy Metabolism, Aggressiveness and Therapy Resistance
Authors: Atas Emine , Oberhuber Monika , Kenner Lukas
Published: January 2021

A metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis—known as the Warburg effect—is characteristic for many cancers. It gives the cancer cells a survival advantage in the hypoxic tumor microenvironment and protects them from cytotoxic effects of oxidative damage and apoptosis. The main regulators of this metabolic shift are the pyruvate dehydrogenase complex and pyruvate dehydrogenase kinase (PDK) isoforms 1–4. PDK is known to be overexpressed in several cancers and is associated with bad prognosis and therapy resistance. Whereas the expression of PDK1–3 is tissue specific, PDK4 expression is dependent on the energetic state of the whole organism. In contrast to other PDK isoforms, not only oncogenic, but also tumor suppressive functions of PDK4 have been reported. In tumors that profit from high OXPHOS and high de novo fatty acid synthesis, PDK4 can have a protective effect. This is the case for prostate cancer, the most common cancer in men, and makes PDK4 an interesting therapeutic target. While most work is focused on PDK in tumors characterized by high glycolytic activity, little research is devoted to those cases where PDK4 acts protective and is therefore highly needed.
EBV-Positive Gastric Cancer: Current Knowledge and Future Perspectives
Authors: Sun Keran , Jia Keqi , Lv Huifang , Wang Sai-Qi , Wu Yan , Lei Huijun , Chen Xiaobing
Published: January 2021

Gastric cancer is the fifth most common malignant tumor and second leading cause of cancer-related deaths worldwide. With the improved understanding of gastric cancer, a subset of gastric cancer patients infected with Epstein–Barr virus (EBV) has been identified. EBV-positive gastric cancer is a type of tumor with unique genomic aberrations, significant clinicopathological features, and a good prognosis. After EBV infects the human body, it first enters an incubation period in which the virus integrates its DNA into the host and expresses the latent protein and then affects DNA methylation through miRNA under the action of the latent protein, which leads to the occurrence of EBV-positive gastric cancer. With recent developments in immunotherapy, better treatment of EBV-positive gastric cancer patients appears achievable. Moreover, studies show that treatment with immunotherapy has a high effective rate in patients with EBV-positive gastric cancer. This review summarizes the research status of EBV-positive gastric cancer in recent years and indicates areas for improvement of clinical practice.
Detection of ESR1 Mutations Based on Liquid Biopsy in Estrogen Receptor-Positive Metastatic Breast Cancer: Clinical Impacts and Prospects
Authors: Liao Hao , Huang Wenfa , Pei Wendi , Li Huiping
Published: January 2021

Endocrine therapy is the main treatment option for estrogen receptor-positive (ER+) breast cancer (BC). Compared with other clinical subtypes, ER+ BC patients usually have a more favorable prognosis. However, almost all ER+ BCpatients develop endocrine resistance and disease progression eventually. A large number of studies based on liquid biopsy suggest that ESR1 mutations may play a key role in this process. For patients with ER+ metastatic BC (MBC), ESR1 is an important prognostic factor and may associate with the resistance to endocrine therapy, like aromatase inhibitors. The advances of sequencing technologies allow us to conduct longitudinal monitoring of disease and unveil the clinical implications of each ESR1 sub-clone in ER+ MBC. Moreover, since the ESR1-related endocrine resistance has not been fully addressed by existing agents, more potent cornerstone drugs should be developed as soon as possible. Herein, we reviewed the recent progress of detecting ESR1 mutations based on liquid biopsy and different sequencing technologies in ER+ MBC and discussed its clinical impacts and prospects.
Long-Term Outcomes of Treosulfan- vs. Busulfan-Based Conditioning Regimen for Patients With Myelodysplastic Syndrome and Acute Myeloid Leukemia Before Hematopoietic Cell Transplantation: A Systematic Review and Meta-Analysis
Authors: Zhu Sheng , Liu Gang , Liu Jing , Chen Qiuying , Wang Zhiqiang
Published: January 2021

Background

Many studies aimed to evaluate the efficacy and safety of treosulfan-based conditioning regimens for allogeneic hematopoietic cell transplantation (allo-HCT) compared with other regimens, but different outcomes were reported across studies.

Aim

To determine the long-term survival outcomes of treosulfan-based vs. busulfan-based conditioning regimens in myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) patients.

Methods

PubMed, Embase, and Cochrane library were searched for studies published prior to December 6, 2019. The fixed-effects model was applied for overall survival (OS), leukemia-free survival (LFS), non-relapse mortality (NRM), acute and chronic graft versus host disease (GvHD). Relapse incidence (RI) was pooled by the use of the random-effects model.

Results

Six studies were included (3,982 patients; range, 57–1,956). The pooled HR for OS favored treosulfan (HR=0.80, 95%CI: 0.71–0.90). There was no significant difference in NRM between the two regimens (HR=0.84, 95%CI=0.71–1.01). There was no significant difference in LFS between the two regimens (HR=0.98, 95%CI=0.87–1.12). Treosulfan-based regimens showed a lower risk of aGvHD (HR=0.70, 95%CI=0.59–0.82), but there was no difference for cGvHD (HR=0.94, 95%CI=0.81–1.09). There was no significant difference in RI between the two regimens (HR=0.96, 95%CI=0.71–1.31). There was no publication bias among these studies.

Conclusion

The current meta-analysis determined that treosulfan-based conditioning regimens could improve the OS in patients with MDS and AML, with lower acute graft-versus-host disease incidence, compared with busulfan-based regimens.
Prognostic Importance of the Preoperative Naples Prognostic Score for Patients With Adenocarcinoma of the Esophagogastric Junction
Authors: Xiong Jianping , Wang Yaqin , Kang Wenzhe , Ma Fuhai , Liu Hao , Ma Shuai , Li Yang , Jin Peng , Hu Haitao , Tian Yantao
Published: January 2021

Background

The naples prognostic score (NPS) is established according to nutritional or inflammatory state, and it is identified as the new prognostic score for a variety of malignant tumors. However, its significance in cases suffering from adenocarcinoma of esophagogastric junction (AEJ) who receive surgery remains unclear so far.

Methods

In this study, patients receiving surgery without preoperative therapy were examined between June 2007 and August 2017 in a retrospective way. Typically, the serum albumin level, total cholesterol level, neutrophil-to-lymphocyte ratio, together with the lymphocyte-to-monocyte ratio, was determined to calculate the NPS. The prognostic impact of NPS was evaluated using survival analyses. Time-dependent receiver operating characteristic curve (t-ROC) analysis was also carried out for comparing prognostic impacts of those scoring systems.

Results

Altogether 231 cases were enrolled in this study. A higher NPS showed positive correlation with perineural invasion. Upon multivariate analysis, NPS was identified to be the independent prognostic factor to predict overall survival (OS) along with relapse-free survival (RFS) (both P< 0.05), and an especially strong correlation was observed at advanced pTNM stages based on NPS system. As for subgroup analyses on adjuvant chemotherapy or surgery only, NPS still independently predicted the OS as well as RFS (both P< 0.05) in both groups. Furthermore, t-ROC analysis showed that NPS was more accurate than the systemic inflammation score in predicting OS and RFS.

Conclusions

The NPS represents the simple and useful rating system, which can independently predict the survival for AEJ cases undergoing surgery.
Case Report: First in Human Online Adaptive MR Guided SBRT of Peritoneal Carcinomatosis Nodules: A New Therapeutic Approach for the Oligo-Metastatic Patient
Authors: Boldrini Luca , Romano Angela , Placidi Lorenzo , Mattiucci Gian Carlo , Chiloiro Giuditta , Cusumano Davide , Pollutri Veronica , Antonelli Marco Valerio , Indovina Luca , Gambacorta Maria Antonietta , Valentini Vincenzo
Published: January 2021

Peritoneal carcinosis (PC) is characterized by poor prognosis. PC is currently treated as a locoregional disease and the possibility to perform very precise treatments such as stereotactic body radiation therapy (SBRT) has opened up new therapeutic perspectives. More recently, the introduction of Magnetic Resonance-guided Radiation Therapy (MRgRT) allowed online adaptation (OA) of treatment plan to optimize daily dose distribution based on patient’s anatomy. The aim of this study is the evaluation of the effectiveness of SBRT OA workflow in an oligometastatic patient affected by PC. We report the clinical case of a patient affected by PC originating from colon cancer, previously treated with chemotherapy and surgery, addressed to OA SBRT treatment on a single chemoresistant PC nodule, delivered with a 0.35 T MR Linac. Treatment was delivered using gating approach in deep inspiration breath hold condition in order to reduce intrafraction variability. Prescription dose was 35 Gy in 5 fractions. The PTV V95% of the original plan was 96.6%, while the predicted values for the following fractions were 11.9, 56.4, 0, 0, and 61%. Similarly, the small bowel V19.5 Gy of the original plan was 4.63 cc, while the predicted values for the following fractions were 3.7, 8.6, 10.7, 1.96, 3.7 cc. Thanks to the OA approach, the re-optimized PTV V95% coverage improved to 96.1, 89.0, 85.5, 94.5, and 94%; while the small bowel V19.5 Gy to 3.36; 3.28; 1.84; 2.62; 2.6 cc respectively. After the end of RT, the patient was addressed to follow-up, and the re-evaluation 18F-FDG PET-CT was performed after 10 months from irradiation showed complete response. No acute or late toxicities were recorded. MRgRT with OA approach in PC patients is technically and clinically feasible with clean toxicity result. Online adaptive SBRT for oligometastases opens up new therapeutic scenarios in the management of this category of patients.
Development of a Web-Based Supportive Care Program for Patients With Head and Neck Cancer
Authors: Fang Carolyn Y. , Galloway Thomas J. , Egleston Brian L. , Bauman Jessica R. , Ebersole Barbara , Chwistek Marcin , Bühler Janice G. , Longacre Margaret L. , Ridge John A. , Manne Sharon L. , Manning Cheri
Published: January 2021

Patients undergoing radiation treatment for head and neck cancer experience significant side-effects that can impact a wide range of daily activities. Patients often report receiving insufficient information during and after treatment, which could impede rehabilitation efforts; they may also encounter practical and logistical barriers to receipt of supportive care. Thus, we developed a web-based program, My Journey Ahead, to provide information and strategies for managing symptom-focused concerns, which may be easily accessed from the patient’s home. The purpose of this study was to evaluate patient acceptability and satisfaction with the My Journey Ahead program. In Phase 1, five patients with head and neck squamous cell carcinoma (HNSCC) reviewed the web-based program and provided initial feedback, which informed program modifications. In Phase 2, 55 patients were recruited to evaluate the program. Patient assessments were obtained prior to and after use of the web-based program, and included measures of psychological distress, self-efficacy in coping with cancer-related issues, and satisfaction with the website. Among the 55 patients enrolled, 44 logged in and viewed the web-based program. Participants reported high levels of satisfaction with the information received, and indicated that the website was interesting and easy to use. Older age and higher levels of self-efficacy in coping were each associated with higher levels of satisfaction with the website. In summary, the web-based program was well-received by patients, the majority of whom found it to be informative and useful. An easy-to-use web-based program, particularly for older patients who may have difficulty locating reliable evidence-based information on the internet, may be helpful in addressing survivors’ needs in symptom management and coping with cancer.

Clinical Trial Registration

https://clinicaltrials.gov/, NCT02442336
Challenges in Maintaining the Hemostatic Balance in Children Undergoing Extracorporeal Membrane Oxygenation: A Systematic Literature Review
Authors: Drop Joppe G. F. , Wildschut Enno D. , Gunput Sabrina T. G. , de Hoog Matthijs , van Ommen C. Heleen
Published: January 2021

Background:Despite advances in technology and clinical experience, the incidence of hemostatic complications, including bleeding and thrombosis, remains high in children supported with extracorporeal membrane oxygenation (ECMO). These hemostatic complications are important to prevent, since they are associated with increased morbidity and mortality. This systematic literature review aims to outline the most important risk factors for hemostatic complications in children undergoing ECMO treatment, to summarize the reported alternative anticoagulant drugs used in pediatric ECMO and to describe studied associations between coagulation tests and hemostatic complications.

Methods:A literature search was performed in Embase, Medline, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and Google Scholar in February 2020. Included studies were studies evaluating children (<18 years old) treated with ECMO, and studies evaluating risk factors for hemostatic complications, alternative anticoagulants, or the association between coagulation tests and hemostatic complications.

Results:Out of 1,152 articles, 35 studies were included. Thirteen out of 49 risk factors were investigated in three or more studies. Most consistent results were found regarding ECMO duration and pH. However, evidence for risk factors was equivocal in the majority of studies, which is explained by the variability of populations studied, definitions of hemostatic complications, ECMO circuits, anticoagulation protocols, transfusion triggers and monitoring of anticoagulation. Five studies described alternative anticoagulants, including bivalirudin (n= 3), argatroban (n= 1) and FUT (n= 1). Higher anti-factor Xa levels were associated with less clotting events in one of nine studies, investigating the association between tests and hemostatic complications. Two studies revealed an association between anti-factor Xa assay-based protocols and a decreased number of transfusions, bleedings and need for circuit change.

Conclusion:Studies regarding risk factors showed conflicting results and a few retrospective studies reported the use of new anticoagulants and data on coagulation tests in relation to hemostatic complications. To decrease hemostatic complications in ECMO children, prospective multicenter studies are needed with clear bleeding and thrombotic definitions, and the best possible standardization of ECMO circuits used, anticoagulation protocols, and transfusion triggers.
Multisystem Inflammatory Syndrome in Children (MIS-C), a Post-viral Myocarditis and Systemic Vasculitis—A Critical Review of Its Pathogenesis and Treatment
Authors: McMurray Jeremy C. , May Joseph W. , Cunningham Madeleine W. , Jones Olcay Y.
Published: January 2021

MIS-C is a newly defined post-viral myocarditis and inflammatory vasculopathy of children following COVID-19 infection. This review summarizes the literature on diagnosis, parameters of disease severity, and current treatment regimens. The clinical perspective was analyzed in light of potential immunopathogenesis and compared to other post-infectious and inflammatory illnesses of children affecting the heart. In this paradigm, the evidence supports the importance of endothelial injury and activation of the IL-1 pathway as a common determinant among MIS-C, Kawasaki disease, and Acute Rheumatic fever.
Enhanced Bioavailability of Boswellic Acid by Piper longum: A Computational and Pharmacokinetic Study
Authors: Vijayarani K. Reeta , Govindarajulu Manoj , Ramesh Sindhu , Alturki Mansour , Majrashi Mohammed , Fujihashi Ayaka , Almaghrabi Mohammed , Kirubakaran N. , Ren Jun , Babu R. Jayachandra , Smith Forrest , Moore Timothy , Dhanasekaran Muralikrishnan
Published: January 2021

Chronic inflammation is a key culprit factor in the onset and progression of several diseases. Novel and pharmacologically effective therapeutic approaches are needed for new treatment remedy or improved pharmacokinetics and pharmacodynamics for existing synthetic drugs, in particular natural products. Boswellic acids are well-known natural products, with capacity to effectively retard inflammation without severe adverse effects. However, the therapeutic use of Boswellic acids are greatly hindered by its poor pharmacokinetic properties. Co-administration strategies that facilitate the oral absorption and distribution of Boswellic acids should lead to a safe and more effective use of this product prophylactically and therapeutically in inflammatory disorders. In this study, we examined the effect of Piper longum extract on the absorption and bioavailability of Boswellic acid in rabbits. In addition, we further explored computational pharmacodynamic interactions between Piper longum and Boswellic acid. Piper longum extract at 2.5 and 10 mg/kg, increased the bioavailability of Boswellic acid (p < 0.05). Based on our drug-based computational modeling, cytochrome P450 (CYP450)-mediated mechanism was involved in increased bioavailability. These findings confirmed that Piper longum with Boswellic acid may be administered orally together for effective therapeutic efficacy. Thus, our studies support the application of Piper longum with Boswellic acid as a novel therapeutic avenue in diseases associated with inflammation.
Repurposing Approved Drugs for Guiding COVID-19 Prophylaxis: A Systematic Review
Authors: Andrade Bruno Silva , Rangel Fernanda de Souza , Santos Naiane Oliveira , Freitas Andria dos Santos , Soares Wagner Rodrigues de Assis , Siqueira Sérgio , Barh Debmalya , Góes-Neto Aristóteles , Birbrair Alexander , Azevedo Vasco Ariston de Carvalho
Published: January 2021

The SARS-CoV-2 outbreak originally appeared in China in December 2019 and became a global pandemic in March 2020. This infectious disease has directly affected public health and the world economy. Several palliative therapeutic treatments and prophylaxis strategies have been used to control the progress of this viral infection, including pre-(PrEP) and post-exposure prophylaxis. On the other hand, research groups around the world are still studying novel drug prophylaxis and treatment using repurposing approaches, as well as vaccination options, which are in different pre-clinical and clinical testing phases. This systematic review evaluated 1,228 articles from the PubMed and Scopus indexing databases, following the Kitchenham bibliographic searching protocol, with the aim to list drug candidates, potentially approved to be used as new options for SARS-CoV-2 prophylaxis clinical trials and medical protocols. In searching protocol, we used the following keywords: “Covid-19 or SARS-CoV-2” or “Coronavirus or 2019 nCoV,” “prophylaxis,” “prophylactic,” “pre-exposure,” “COVID-19 or SARS-CoV-2 Chemoprophylaxis,” “repurposed,” “strategies,” “clinical,” “trials,” “anti-SARS-CoV-2,” “anti-covid-19,” “Antiviral,” “Therapy preventionin vitro,” in cells “and” human testing. After all protocol steps, we selected 60 articles that included: 15 studies with clinical data, 22 studies that usedin vitroexperiments, seven studies using animal models, and 18 studies performed with in silico experiments. Additionally, we included more 22 compounds between FDA approved drugs and drug-like like molecules, which were tested in large-scale screenings, as well as those repurposed approved drugs with new mechanism of actions. The drugs selected in this review can assist clinical studies and medical guidelines on the rational repurposing of known antiviral drugs for COVID-19 prophylaxis.
Role of PRDM1 in Tumor Immunity and Drug Response: A Pan-Cancer Analysis
Authors: Shen Lujun , Chen Qifeng , Yang Changsheng , Wu Ying , Yuan Hui , Chen Shuanggang , Ou Shunling , Jiang Yiquan , Huang Tao , Ke Liangru , Mo Jinqing , Feng Ziqing , Zhou Penghui , Fan Weijun
Published: January 2021

Background: PR domain zinc finger protein 1 (PRDM1) is a regulator of both B cell and T cell differentiation and plays a critical role in immunosuppression. Its role in tumor immunity and correlation with drug response remain unknown.

Methods: This work comprehensively analyzed the transcriptional expression pattern of the PRDM1 among 33 types of malignancies from The Cancer Genome Atlas and the Genotype-Tissue Expression projects. Besides, correlation of the PRDM1 with cancer prognosis, immune infiltrates, checkpoint markers, cancer stemness and drug response were explored.

Results: High expression level of PRDM1 were observed in ACC, COAD, LAML, LGG, LUAD, OV, PAAD, STAD, TGCT. Cox regression model showed high expression of PRDM1 in tumor samples correlates with poor prognosis in LGG, PAAD, UVM while favorable prognosis in KIRC, SKCM and THCA. PRDM1 expression positively correlates with the expression of LAG3, CTLA4, PDCD1 (PD-1), CD274 (PD-L1), PDCD1LG2 (PD-L2), TIGIT in the majority of 33 cancer types. PRDM1 positively correlated with TNFRSF14 in LGG and UVM among cancers with unfavorable prognosis; this correlation were weak or even negative in cancers with favorable prognosis. The top negatively enriched KEGG terms in high PRDM1 subgroup were B cell receptor signaling, T cell receptor signaling, and the top negatively enriched HALLMARK terms included IL-2-STAT5 signaling and allograft rejection. The expression of PRDM1 was found positively correlated with cancer stemness in CHOL, KIRP, TGCT, THYM and UVM. A series of targeted drugs and small-molecule drugs with promising efficacy predicted by PRDM1 level were identified.

Conclusion: The clinical significance and biological impact of high transcriptional expression of PRDM1 differs across different cancers. Inhibiting the PRDM1-dependent signaling could be a novel and promising strategy of immunotherapy in cancers including LGG, PAAD and UVM.
Current Evidence of Interleukin-6 Signaling Inhibitors in Patients With COVID-19: A Systematic Review and Meta-Analysis
Authors: Han Qi , Guo Mingyue , Zheng Yue , Zhang Ying , De Yanshan , Xu Changchang , Zhang Lin , Sun Ruru , Lv Ying , Liang Yan , Xu Feng , Pang Jiaojiao , Chen Yuguo
Published: January 2021

Background: Interleukin-6 (IL-6) is known to be detrimental in coronavirus disease 2019 (COVID-19) because of its involvement in driving cytokine storm. This systematic review and meta-analysis aimed to assess the safety and efficacy of anti-IL-6 signaling (anti-IL6/IL-6R/JAK) agents on COVID-19 based on the current evidence.

Methods: Studies were identified through systematic searches of PubMed, EMBASE, ISI Web of Science, Cochrane library, ongoing clinical trial registries (clinicaltrials.gov), and preprint servers (medRxiv, ChinaXiv) on August 10, 2020, as well as eligibility checks according to predefined selection criteria. Statistical analysis was performed using Review Manager (version 5.3) and STATA 12.0.

Results: Thirty-one studies were included in the pooled analysis of mortality, and 12 studies were identified for the analysis of risk of secondary infections. For mortality analysis, 5630 COVID-19 cases including 2,132 treated patients and 3,498 controls were analyzed. Anti-IL-6 signaling agents plus standard of care (SOC) significantly decreased the mortality rate compared to SOC alone (pooled OR = 0.61, 95% CI 0.45–0.84, p = 0.002). For the analysis of secondary infection risk, 1,624 patients with COVID-19 including 639 treated patients and 985 controls were included, showing that anti-IL-6 signaling agents did not increase the rate of secondary infections (pooled OR = 1.21, 95% CI 0.70–2.08, p = 0.50). By contrast, for patients with critical COVID-19 disease, anti-IL-6 signaling agents failed to reduce mortality compared to SOC alone (pooled OR = 0.75, 95% CI 0.42–1.33, p = 0.33), but they tended to increase the risk of secondary infections (pooled OR = 1.85, 95% CI 0.95–3.61, p = 0.07). A blockade of IL-6 signaling failed to reduce the mechanical ventilation rate, ICU admission rate, or elevate the clinical improvement rate.

Conclusion: IL-6 signaling inhibitors reduced the mortality rate without increasing secondary infections in patients with COVID-19 based on current studies. For patients with critical disease, IL-6 signaling inhibitors did not exhibit any benefit.
Bone Chemical Composition Analysis Using Photoacoustic Technique
Authors: Feng Ting , Xie Yejing , Xie Weiya , Ta Dean , Cheng Qian
Published: January 2021

Photoacoustic (PA) signal analysis based on ultrasonic wave detection can provide both high-sensitivity optical contrast information and micro-architectural information which is highly related with the chemical composition of tissue. In this study, the feasibility assessment of bone composition assessment was investigated using the multi-wavelength PA analysis (MWPA) method which could reflect the molecular information. By illuminating a bone specimen using a laser light with wavelength over an optical spectrum ranging from 680 to 950 nm, the optical absorption spectrum of the bone was acquired. Then, with the optical absorption spectra of all optical absorption chemical components in the known bone, a spectral unmixing procedure was performed to quantitatively assess the relative content of each chemical component. The experimental results from rabbit bones show that MWPA method can be used to assess chemical components related to bone metabolism. Our study confirmed that PA technique can be used as a novel bone diagnostic technique by providing new information about the quantity of bone and identifying biomarkers of bone that can improve the current diagnostic imaging techniques.
A Dual-Band Dual-Polarized Omnidirectional Antenna
Authors: Gu Hui , Ge Lei , Zhang Jihong
Published: January 2021

A dual-band dual-polarized omnidirectional antenna is investigated. The two bands are generated by a lower circular patch and an upper circular patch, respectively. A set of conductive vias and a coupled ring are utilized to widen the antenna bandwidth. Curved branches are introduced to contribute to circularly polarized radiation. A prototype was designed, fabricated and measured to demonstrate the performance of the antenna. Measured results show that an overlapped bandwidth of 15% from 2.22 to 2.58 GHz for both S11 ≤ −10 dB and axial ratio ≤3 dB is obtained in the low band, and an impedance bandwidth of 11.1% from 5.63 to 6.29 GHz is achieved in the high band. Measured peak gains are approximately 4.3 dBic and 5.4 dBi at two bands. Moreover, omnidirectional radiation patterns are also obtained within the operating band.
The Mysteries of Capsaicin-Sensitive Afferents
Authors: Fischer Michael J. M. , Ciotu Cosmin I. , Szallasi Arpad
Published: January 2021

A fundamental subdivision of nociceptive sensory neurons is named after their unique sensitivity to capsaicin, the pungent ingredient in hot chili peppers: these are the capsaicin-sensitive afferents. The initial excitation by capsaicin of these neurons manifested as burning pain sensation is followed by a lasting refractory state, traditionally referred to as “capsaicin desensitization,” during which the previously excited neurons are unresponsive not only to capsaicin but a variety of unrelated stimuli including noxious heat. The long sought-after capsaicin receptor, now known as TRPV1 (transient receptor potential cation channel, subfamily V member 1), was cloned more than two decades ago. The substantial reduction of the inflammatory phenotype of Trpv1 knockout mice has spurred extensive efforts in the pharmaceutical industry to develop small molecule TRPV1 antagonists. However, adverse effects, most importantly hyperthermia and burn injuries, have so far prevented any compounds from progressing beyond Phase 2. There is increasing evidence that these limitations can be at least partially overcome by approaches outside of the mainstream pharmaceutical development, providing novel therapeutic options through TRPV1. Although ablation of the whole TRPV1-expressing nerve population by high dose capsaicin, or more selectively by intersectional genetics, has allowed researchers to investigate the functions of capsaicin-sensitive afferents in health and disease, several “mysteries” remain unsolved to date, including the molecular underpinnings of “capsaicin desensitization,” and the exact role these nerves play in thermoregulation and heat sensation. This review tries to shed some light on these capsaicin mechanisms.
Cocoon-Spinning Behavior and 20-Hydroxyecdysone Regulation of Fibroin Genes in Plutella xylostella
Authors: Shi Yan , Lin Gan-Lin , Fu Xiu-Lian , Keller Mike , Smagghe Guy , Liu Tong-Xian
Published: January 2021

The diamondback moth Plutella xylostella is a serious pest of crucifers. It has high reproductive potential and is resistant to many insecticides. Typically, the last-instar larvae of P. xylostella, before pupation, move to the lower or outer plant leaves to make a loose silk cocoon and pupate inside for adult formation. To better understand this pivotal stage we studied the cocoon-spinning behavior of P. xylostella and measured three successive phases by video-recording, namely the selection of a pupation site, spinning a loose cocoon and padding the scaffold cocoon. Subsequently, we cloned three fibroin genes related to cocoon production, i.e., fibroin light chain (Fib-L), fibroin heavy chain (Fib-H), and glycoprotein P25. A spatio-temporal study of these three fibroin genes confirmed a high expression in the silk glands during the final larval instar silk-producing stage. In parallel, we did an exogenous treatment of the insect molting hormone 20-hydroxyecdysone (20E), and this suppressed fibroin gene expression, reduced the normal time needed for cocoon spinning, and we also observed a looser cocoon structure under the scanning electron microscope. Hence, we demonstrated that the expression levels of key genes related to the synthesis of 20E [the three Halloween genes Spook (Spo), Shadow (Sad), and Shade (Shd)] decreased significantly during spinning, the expression of the 20E receptor (EcR and USP) was significantly lower during spinning than before spinning, and that the expression levels of CYP18-A1 related to 20E degradation were significantly up-regulated during spinning. The significance of the cocoon and the effects of 20E on the cocoon-spinning behavior of P. xylostella are discussed.
Impact of Left Atrial Bipolar Electrogram Voltage on First Pass Pulmonary Vein Isolation During Radiofrequency Catheter Ablation
Authors: Garg Lohit , Pothineni Naga Venkata K. , Daw J. Michael , Hyman Matthew C. , Arkles Jeffrey , Tschabrunn Cory M. , Santangeli Pasquale , Marchlinski Francis E.
Published: January 2021

Background

First pass pulmonary vein isolation (PVI) is associated with durable isolation and reduced recurrence of atrial fibrillation (AF).

Objective

We sought to investigate the relationship between left atrial electrogram voltage using multielectrode fast automated mapping (ME-FAM) and first pass isolation with radiofrequency ablation.

Methods

We included consecutive patients (pts) undergoing first time ablation for paroxysmal AF (pAF), and compared the voltage characteristics between patients with and without first pass isolation. Left atrium (LA) adjacent to PVs was divided into 6 regions, and mean voltages obtained with ME-FAM (Pentaray, Biosense Webster) in each region and compared. LA electrograms with marked low voltage (<0.5 mV) were identified and the voltage characteristics at the site of difficult isolation was compared to the voltage in adjacent region.

Results

Twenty consecutive patients (10 with first pass and 10 without) with a mean age of 63.3 ± 6.2 years, 65% males, were studied. Difficult isolation occurred on the right PVs in eight pts and left PVs in three pts. The mean voltage in pts without first pass isolation was lower in all 6 regions; posterior wall (1.93 ± 1.46 versus 2.99 ± 2.19; p < 0.001), roof (1.83 ± 2.29 versus 2.47 ± 1.99; p < 0.001), LA-LPV posterior (1.85 ± 3.09 versus 2.99 ± 2.19, p < 0.001), LA-LPV ridge (1.42 ± 1.04 versus 1.91 ± 1.61; p < 0.001), LA-RPV posterior (1.51 ± 1.11 versus 2.30 ± 1.77, p < 0.001) and LA-RPV septum (1.55 ± 1.23 versus 2.31 ± 1.40, p < 0.001). Patients without first pass isolation also had a larger percentage of signal with an amplitude of <0.5 mV for each of the six regions (12.8% versus 7.5%). In addition, the mean voltage at the site of difficult isolation was lower at 8 out of 11 sites compared to mean voltage for remaining electrograms in that region.

Conclusion

In patients undergoing PVI for paroxysmal AF, failure in first pass isolation was associated with lower global LA voltage, more marked low amplitude signal (<0.5 mV) and lower local signal voltage at the site with difficult isolation. The results suggest that a greater degree of global and segmental fibrosis may play a role in ease of PV isolation with radiofrequency energy.
COVID-19-Associated Hyper-Fibrinolysis: Mechanism and Implementations
Authors: Jacob Giris , Aharon Anat , Brenner Benjamin
Published: January 2021

The emerging novel coronavirus disease (COVID-19), which is caused by the SARS-CoV-2 presents with high infectivity, morbidity and mortality. It presenting a need for immediate understanding of its pathogenicity. Inflammation and coagulation systems are over-activated in COVID-19. SARS-CoV-2 damages endothelial cell and pneumocyte, resulting in hemostatic disorder and ARDS. An influential biomarkers of poor outcome in COVID-19 are high circulating cytokines and D-dimer level. This latter is due to hyper-fibrinolysis and hyper-coagulation. Plasmin is a key player in fibrinolysis and is involved in the cleavage of many viruses envelop proteins, including SARS-CoV. This function is similar to that of TMPRSS2, which underpins the entry of viruses into the host cell. In addition, plasmin is involved in the pathophysiology of ARDS in SARS and promotes secretion of cytokine, such as IL-6 and TNF, from activated macrophages. Here, we suggest an out-of-the-box treatment for alleviating fibrinolysis and the ARDS of COVID-19 patients. This proposed treatment is concomitant administration of an anti-fibrinolytic drug and the anticoagulant.