bluuebunny/crossref_metadata_2025 huggingface dataset:
Habitat, Snow-Cover and Soil pH, Affect the Distribution and Diversity of Mortierellaceae Species and Their Associations to Bacteria
Authors: Telagathoti Anusha , Probst Maraike , Peintner Ursula
Published: July 2021

Mortierellaceae species are among the most frequent and globally distributed soil fungi. However, the factors shaping their diversity and distribution remain obscure. Several species have been reported to be associated to bacteria, but the kind and frequency of such associations were not addressed up to now. We hypothesized that such associations could be important for Mortierellaceae ecology. Therefore, our aim was to understand the driving factors responsible for the Mortierellaceae diversity, community composition and bacterial associations in alpine and subalpine habitats. For answering our question, we collected both snow-free and snow-covered soil at sampling sites from different habitats: bare alpine soil in a glacier forefield, alpine dwarf-willow habitats, and high-altitude Pinus cembra forests. The isolations were carried out by direct cultivation without any antibiotics to the isolation media. Altogether, we obtained 389 Mortierellaceae isolates representing 29 operational taxonomic units (OTUs). Many OTUs could be placed to the genera Mortierella sensu stricto, Dissophora, Entomortierella, Gamsiella, Linnemannia, and Podila, but others could not unambiguously be assigned to a genus. Our results demonstrate that both, the distribution as well as the diversity of the Mortierellaceae species, were significantly influenced by habitat, soil pH, and snow-cover. We noticed that >30% of our isolates were associated to a non-contaminant bacterium. The bacteria associated to our Mortierellaceae isolates belonged to seven different genera. Pseudomonas was the most frequently detected genus associated to the isolated Mortierellaceae species and it was found to be species-specific. Mortierellaceae–bacteria pairs, including those with Pseudomonas, were influenced by location, habitat, and snow-cover. The majority of the fungus–bacterium associations were potentially epihyphal, but we also detected potential endohyphal bacterial species belonging to Mycoavidus, Burkholderiaceae, and Paraburkholderia. Taken together, the non-random associations we detected suggest that fungus–bacterium associations are ecologically meaningful – an interesting path that needs to be investigated further.
Characterization of BisI Homologs
Authors: Xu Shuang-yong , Zemlyanskaya Elena V. , Gonchar Danila A. , Sun Zhiyi , Weigele Peter , Fomenkov Alexey , Degtyarev Sergey Kh , Roberts Richard J.
Published: July 2021

BisI is a sequence-specific and 5-methylcytosine (m5C)-dependent restriction endonuclease (REase), that cleaves the modified DNA sequence Gm5CNGC (G indicates that the cytosine opposite to G is modified). We expressed and purified a number of BisI homologs from sequenced bacterial genomes and used Illumina sequencing to determine the Pam7902I (Esp638I-like) cleavage sites in phage Xp12 DNA. One BisI homolog KpnW2I is EcoBLMcrX-like, cleaving GCNGC/RCNGY/RCNRC sites with m5C. We also cloned and expressed three BisI homologs from metagenome sequences derived from thermophilic sources. One enzyme EsaTMI is active at 37 to 65°C. EsaHLI cleaves GCNGC sites with three to four m5C and is active up to 50°C. In addition, we determined the number and position of m5C in BisI sites for efficient cleavage. BisI cleavage efficiency of GCNGC site is as following: Gm5CNGC (two internal m5C) > Gm5CNGC (one internal m5C) > GCNGm5C (one external m5C) > > GCNGC (unmodified). Three or four m5C in GCNGC site also supports BisI cleavage although partial inhibition was observed on duplex oligos with four m5C. BisI can be used to partially cleave a desired GCNGC site targeted with a complementary oligonucleotide (hemi-methylated). The m5C-dependent BisI variants will be useful for epigenetic research.
Metabolism-Relevant Molecular Classification Identifies Tumor Immune Microenvironment Characterization and Immunotherapeutic Effect in Cervical Cancer
Authors: Li Luyi , Gao Hui , Wang Danhan , Jiang Hao , Wang Hongzhu , Yu Jiajian , Jiang Xin , Huang Changjiang
Published: July 2021

Cervical cancer (CESC) is a gynecologic malignant tumor associated with high incidence and mortality rates because of its distinctive management complexity. Herein, we characterized the molecular features of CESC based on the metabolic gene expression profile by establishing a novel classification system and a scoring system termed as METAscore. Integrative analysis was performed on human CESC samples from TCGA dataset. Unsupervised clustering of RNA sequencing data on 2,752 formerly described metabolic genes identified three METAclusters. These METAclusters for overall survival time, immune characteristics, metabolic features, transcriptome features, and immunotherapeutic effectiveness existed distinct differences. Then we analyzed 207 DEGs among the three METAclusters and as well identified three geneclusters. Correspondingly, these three geneclusters also differently expressed among the aforementioned features, supporting the reliability of the metabolism-relevant molecular classification. Finally METAscore was constructed which emerged as an independent prognostic biomarker, related to CESC transcriptome features, metabolic features, immune characteristics, and linked to the sensitivity of immunotherapy for individual patient. These findings depicted a new classification and a scoring system in CESC based on the metabolic pattern, thereby furthering the understanding of CESC genetic signatures and aiding in the prediction of the effectiveness to anticancer immunotherapies.
Serum Extracellular Vesicle–Derived miR-124-3p as a Diagnostic and Predictive Marker for Early-Stage Acute Ischemic Stroke
Authors: Qi Zheng , Zhao Yingying , Su Yu , Cao Bin , Yang Jian-Jun , Xing Qinghe
Published: July 2021

Background: A delay in the diagnosis of acute ischemic stroke (AIS) reduces the eligibility and outcome of patients for thrombolytic therapy. Therefore, early diagnosis and treatment of AIS are crucial. The present study evaluated the sensitivity and accuracy of serum extracellular vesicle (EV)-derived miR-124-3p in the diagnosis and prediction of AIS.

Methods: An miRNA expression profile was downloaded from Gene Expression Omnibus (GEO) database and analyzed by R software. EVs were harvested from the serum of AIS patients using a total exosome isolation kit and characterized by Western blotting, a transmission electron microscope, and the nanoparticle tracking analysis. BV2 microglia were pre-stimulated with lipopolysaccharide (LPS), followed by miR-124-3p treatment for 24 h and subsequent analysis of viability, apoptosis, and migration (scratch assay), and Western blotting. The relative expression of the selected genes was assessed by qRT-PCR. The phosphorylation of Erk1/2, PI3K/Akt, and p38MAPK in BV2 microglia cells was evaluated by Western blotting, while the luciferase reporter gene assay detected the correlation between key genes involved in the pro-inflammatory signaling pathways and miR-124-3p.

Results:hsa-miR-124-3p was downregulated in AIS serum compared to the non-AIS serum (p < 0.05), and the gene expression of has-miR-124-3p in EVs was negatively correlated with serum pro-inflammatory cytokines and the NIHSS (p < 0.05). In addition, miR-124-3p promoted the viability and inhibited the apoptosis of LPS-induced BV2 microglia. Furthermore, miR-124-3p reduced the phosphorylation of Erk1/2, PI3K/Akt, and p38MAPK, and promoted the migration in LPS-induced BV2 microglia (p < 0.05).

Conclusion: Serum EV-derived miR-124-3p serves as a diagnostic and predictive marker for early-stage AIS.
PPI-MASS: An Interactive Web Server to Identify Protein-Protein Interactions From Mass Spectrometry-Based Proteomics Data
Authors: González-Avendaño Mariela , Zúñiga-Almonacid Simón , Silva Ian , Lavanderos Boris , Robinson Felipe , Rosales-Rojas Roberto , Durán-Verdugo Fabio , González Wendy , Cáceres Mónica , Cerda Oscar , Vergara-Jaque Ariela
Published: July 2021

Mass spectrometry-based proteomics methods are widely used to identify and quantify protein complexes involved in diverse biological processes. Specifically, tandem mass spectrometry methods represent an accurate and sensitive strategy for identifying protein-protein interactions. However, most of these approaches provide only lists of peptide fragments associated with a target protein, without performing further analyses to discriminate physical or functional protein-protein interactions. Here, we present the PPI-MASS web server, which provides an interactive analytics platform to identify protein-protein interactions with pharmacological potential by filtering a large protein set according to different biological features. Starting from a list of proteins detected by MS-based methods, PPI-MASS integrates an automatized pipeline to obtain information of each protein from freely accessible databases. The collected data include protein sequence, functional and structural properties, associated pathologies and drugs, as well as location and expression in human tissues. Based on this information, users can manipulate different filters in the web platform to identify candidate proteins to establish physical contacts with a target protein. Thus, our server offers a simple but powerful tool to detect novel protein-protein interactions, avoiding tedious and time-consuming data postprocessing. To test the web server, we employed the interactome of the TRPM4 and TMPRSS11a proteins as a use case. From these data, protein-protein interactions were identified, which have been validated through biochemical and bioinformatic studies. Accordingly, our web platform provides a comprehensive and complementary tool for identifying protein-protein complexes assisting the future design of associated therapies.
Intermittent Hypoxia Training Prevents Deficient Learning-Memory Behavior in Mice Modeling Alzheimer's Disease: A Pilot Study
Authors: Ryou Myoung-Gwi , Chen Xiaoan , Cai Ming , Wang Hong , Jung Marianna E. , Metzger Daniel B. , Mallet Robert T. , Shi Xiangrong
Published: July 2021

In mouse models of Alzheimer's disease (AD), normobaric intermittent hypoxia training (IHT) can preserve neurobehavioral function when applied before deficits develop, but IHT's effectiveness after onset of amyloid-β (Aβ) accumulation is unclear. This study tested the hypothesis that IHT improves learning-memory behavior, diminishes Aβ accumulation in cerebral cortex and hippocampus, and enhances cerebrocortical contents of the neuroprotective trophic factors erythropoietin and brain-derived neurotrophic factor (BDNF) in mice manifesting AD traits. Twelve-month-old female 3xTg-AD mice were assigned to untreated 3xTg-AD (n = 6), AD+IHT (n = 6), and AD+sham-IHT (n = 6) groups; 8 untreated wild-type (WT) mice also were studied. AD+IHT mice alternately breathed 10% O2 for 6 min and room air for 4 min, 10 cycles/day for 21 days; AD+sham-IHT mice breathed room air. Spatial learning-memory was assessed by Morris water maze. Cerebrocortical and hippocampal Aβ40 and Aβ42 contents were determined by ELISA, and cerebrocortical erythropoietin and BDNF were analyzed by immunoblotting and ELISA. The significance of time (12 vs. 12 months + 21 days) and treatment (IHT vs. sham-IHT) was evaluated by two-factor ANOVA. The change in swimming distance to find the water maze platform after 21 d IHT (−1.6 ± 1.8 m) differed from that after sham-IHT (+5.8 ± 2.6 m). Cerebrocortical and hippocampal Aβ42 contents were greater in 3xTg-AD than WT mice, but neither time nor treatment significantly affected Aβ40 or Aβ42 contents in the 3xTg-AD mice. Cerebrocortical erythropoietin and BDNF contents increased appreciably after IHT as compared to untreated 3xTg-AD and AD+sham-IHT mice. In conclusion, moderate, normobaric IHT prevented spatial learning-memory decline and restored cerebrocortical erythropoietin and BDNF contents despite ongoing Aβ accumulation in 3xTg-AD mice.
Identifying Mild Cognitive Impairment in Parkinson’s Disease With Electroencephalogram Functional Connectivity
Authors: Cai Min , Dang Ge , Su Xiaolin , Zhu Lin , Shi Xue , Che Sixuan , Lan Xiaoyong , Luo Xiaoguang , Guo Yi
Published: July 2021

Objective

Cognitive impairment occurs frequently in Parkinson’s disease (PD) and negatively impacts the patient’s quality of life. However, its pathophysiological mechanism remains unclear, hindering the development of new therapies. Changes in brain connectivity are related to cognitive impairment in patients with PD, with the dorsolateral prefrontal cortex (DLPFC) being considered the essential region related to PD cognitive impairment. Nevertheless, few studies have focused on the global connectivity responsible for communication with the DLPFC node, the posterior division of the middle frontal gyrus (PMFG) in patients with PD; this was the focus of this study.

Methods

We applied resting-state electroencephalography (EEG) and calculated a reliable functional connectivity measurement, the debiased weighted phase lag index (dWPLI), to examine inter-regional functional connectivity in 68 patients with PD who were classified into two groups according to their cognitive condition.

Results

We observed that altered left and right PMFG-based functional connectivity associated with cognitive impairment in patients with PD in the theta frequency bands under the eyes closed condition (r = −0.426, p < 0.001 and r = −0.437, p < 0.001, respectively). Exploratory results based on the MoCA subdomains indicated that poorer visuospatial function was associated with higher right PMFG-based functional connectivity (r = −0.335, p = 0.005), and poorer attention function was associated with higher left and right PMFG-based functional connectivity (r = −0.380, p = 0.001 and r = −0.256, p = 0.035, respectively). Further analysis using logistic regression and receiver operating characteristic (ROC) curves found that this abnormal functional connectivity was an independent risk factor for cognitive impairment [odds ratio (OR): 2.949, 95% confidence interval (CI): 1.294–6.725, p = 0.01 for left PMFG; OR: 11.278, 95% CI: 2.578–49.335, p = 0.001 for right PMFG, per 0.1 U], and provided moderate classification power to discriminate between cognitive abilities in patients with PD [area under the ROC curve (AUC) = 0.770 for left PMFG; AUC = 0.809 for right PMFG].

Conclusion

These preliminary findings indicate that abnormal PMFG-based functional connectivity patterns associated with cognitive impairment in the theta frequency bands under the eyes closed condition and altered functional connectivity patterns have the potential to act as reliable biomarkers for identifying cognitive impairment in patients with PD.
High Neutrophil–Lymphocyte Ratio Predicts Post-stroke Cognitive Impairment in Acute Ischemic Stroke Patients
Authors: Lee Minwoo , Lim Jae-Sung , Kim Chul-Ho , Lee Sang-Hwa , Kim Yerim , Hun Lee Ju , Jang Min Uk , Sun Oh Mi , Lee Byung-Chul , Yu Kyung-Ho
Published: July 2021

Background and Aims: Systemic inflammation is associated with an increased risk of cognitive impairment and dementia, but the associations between them in stroke patients are less clear. We examined the impact of systemic inflammation represented as the neutrophil-lymphocyte ratio (NLR) on the development of post-stroke cognitive impairment (PSCI) and domain-specific cognitive outcomes 3-month after ischemic stroke.

Methods: Using prospective stroke registry data, we consecutively enrolled 345 participants with ischemic stroke whose cognitive functions were evaluated 3-month after stroke. Their cognition was assessed with the Korean version of the Vascular Cognitive Impairment Harmonization Standards and the Korean-Mini Mental Status Examination. PSCI was defined as a z-score of < -2 standard deviations for age, sex, and education adjusted means in at least one cognitive domain. The participants were categorized into five groups according to the quintiles of NLR (lowest NLR, Q1). The cross-sectional association between NLR and PSCI was assessed using multiple logistic regression, adjusting for age, sex, education, vascular risk factors, and stroke type.

Results: A total of 345 patients were enrolled. The mean age was 63.0 years and the median NIHSS score and NLR were 2 [1–4] and 2.26 [1.65–2.91], respectively. PSCI was identified in 71 (20.6%) patients. NLR was a significant predictor for PSCI both as a continuous variable (adjusted OR, 1.14; 95% CI, 1.00–1.31) and as a categorical variable (Q5, adjusted OR, 3.26; 95% CI, 1.17–9.08). Patients in the Q5 group (NLR ≥ 3.80) showed significantly worse performance in global cognition and in visuospatial and memory domains.

Conclusions: NLR in the acute stage of ischemic stroke was independently associated with PSCI at 3 months after stroke, and high NLR was specifically associated with cognitive dysfunction in the memory and visuospatial domains. Thus, systemic inflammation may be a modifiable risk factor that may influence cognitive outcomes after stroke.
Probing the Pre-diagnostic Phase of Parkinson's Disease in Population-Based Studies
Authors: Dommershuijsen Lisanne J. , Boon Agnita J. W. , Ikram M. Kamran
Published: July 2021

Parkinson's disease covers a wide spectrum of symptoms, ranging from early non-motor symptoms to the characteristic bradykinesia, tremor and rigidity. Although differences in the symptomatology of Parkinson's disease are increasingly recognized, there is still a lack of insight into the heterogeneity of the pre-diagnostic phase of Parkinson's disease. In this perspective, we highlight three aspects regarding the role of population-based studies in providing new insights into the heterogeneity of pre-diagnostic Parkinson's disease. First we describe several specific advantages of population-based cohort studies, including the design which overcomes some common biases, the broad data collection and the high external validity. Second, we draw a parallel with the field of Alzheimer's disease to provide future directions to uncover the heterogeneity of pre-diagnostic Parkinson's disease. Finally, we anticipate on the emergence of prevention and disease-modification trials and the potential role of population-based studies herein. In the coming years, bridging gaps between study designs will be essential to make vital advances in elucidating the heterogeneity of pre-diagnostic Parkinson's disease.
Role of the Preoptic Area in Sleep and Thermoregulation
Authors: Rothhaas Rebecca , Chung Shinjae
Published: July 2021

Sleep and body temperature are tightly interconnected in mammals: warming up our body helps to fall asleep and the body temperature in turn drops while falling asleep. The preoptic area of the hypothalamus (POA) serves as an essential brain region to coordinate sleep and body temperature. Understanding how these two behaviors are controlled within the POA requires the molecular identification of the involved circuits and mapping their local and brain-wide connectivity. Here, we review our current understanding of how sleep and body temperature are regulated with a focus on recently discovered sleep- and thermo-regulatory POA neurons. We further discuss unresolved key questions including the anatomical and functional overlap of sleep- and thermo-regulatory neurons, their pathways and the role of various signaling molecules. We suggest that analysis of genetically defined circuits will provide novel insights into the mechanisms underlying the coordinated regulation of sleep and body temperature in health and disease.
Effect of Home Enteral Nutrition on Nutritional Status, Body Composition and Quality of Life in Patients With Malnourished Intestinal Failure
Authors: Gao Xuejin , Zhang Yupeng , Zhang Li , Liu Sitong , Liu Hao , Zhou Da , Li Jieshou , Wang Xinying
Published: July 2021

Background: The ultimate goal of intestinal failure (IF) management is to maintain optimal nutritional status, improve the quality of life (QoL), and promote intestinal adaptation. Enteral nutrition support is safe and effective in patients with IF and plays a central role in the management of patients with IF. The purpose of this study was to evaluate the effect of home enteral nutrition on nutritional status, body composition (BC), QoL and other clinical outcomes in malnourished patients with intestinal failure.

Methods: This prospective observational study included 166 malnourished patients with intestinal failure presented to Jinling Hospital from January 2016 to October 2018. All patients were supported with home enteral nutrition after discharge. We evaluated clinical outcomes, including nutritional status, BC, phase angle (PhA), QoL, mortality, gastrointestinal complications related to enteral feeding, and other clinical outcomes at 1, 3, and 6 months after discharge.

Results: Body weight, BC, and other nutritional parameters were maintained or significantly increased during the period of home enteral nutrition after discharge (p < 0.01). Especially, the quality of skeletal muscle mass in body composition was significantly improved (p < 0.01). SF-36 quality of life scores was significantly improved (discharged at 6 months: reported health transition 40.7 ± 12.1 vs. 69.3 ± 16.3, p < 0.01). There were no differences between hospital and out of hospital with respect to tube-related or gastrointestinal complications. Advanced age, disease type, and poor nutritional status were risk factors for poor clinical outcomes.

Conclusions: Home enteral nutrition support is effective for malnourished patients with intestinal failure. It improves nutritional status, BC, PhA, and QoL.

Clinical Trial Registration: identifier: ChiCTR2000035145.
Personality Traits and Weight Loss Maintenance: A Cross-Sectional Study
Authors: Koutras Yiannis , Chrysostomou Stavri , Giannakou Konstantinos , Kosmidis Mary H. , Yannakoulia Mary
Published: July 2021

Purpose: This cross-sectional study was based on the Cypriot cohort of the MedWeight study and examined differences between maintainers and regainers regarding personality traits.

Methods: Participants were men and women who reported being at least overweight and experienced an intentional weight loss of ≥10% of their maximum weight, at least 1 year before participation. Assessment of personality, diet and physical activity was conducted through validated questionnaires and with 24 h recalls.

Results: Findings from logistic regression analysis indicated that the odds of maintaining weight loss increased to 50% for agreeableness and decreased to 20 and 7% for perseverance and motor impulsiveness, respectively.

Conclusion: Specific aspects of personality and impulsivity are relevant to weight loss maintenance and need to be considered when developing weight management interventions.
Comprehensive Characterization of Immune Landscape Based on Epithelial-Mesenchymal Transition Signature in OSCC: Implication for Prognosis and Immunotherapy
Authors: Zhang Si-yuan , Ren Xian-yue , Wang Chun-yang , Chen Xi-juan , Cao Ruo-yan , Liu Qin , Pan Xue , Zhou Jia-ying , Zhang Wei-lin , Tang Xin-Ran , Cheng Bin , Wu Tong
Published: July 2021

Current anatomic TNM stage classification fails to capture the immune heterogeneity of oral squamous cell carcinoma (OSCC). Increasing evidence indicates the strong association between epithelial-mesenchymal transition (EMT) and tumor immune response. In this study, we employed an EMT signature to classify OSCC patients into epithelial- (E-) and mesenchymal- (M-) phenotypes using TCGA and GSE41613 transcriptome data. The ESTIMATE and CIRBERSORT analyses implied that the EMT signature genes originated from the stroma of the bulk tissue. The M-subtype tumors were characterized as “immune-hot” with more immune cell infiltration than the E-subtype ones. The low infiltration of active immune cells, the high infiltration of inactive immune cells, and the high expressions of immune checkpoints demonstrated an immunosuppressive characteristic of the M-subtype tumors. Moreover, we developed and validated a novel prognostic classifier based on the EMT score, the expressions of seven immune checkpoints, and the TNM stages, which could improve the prediction efficiency of the current clinical parameter. Together, our findings provide a better understanding of the tumor immune heterogeneity and may aid guiding immunotherapy in OSCC.
FDG-PET/CT in the Radiotherapy Treatment Planning of Locally Advanced Anal Cancer: A Monoinstitutional Experience
Authors: Di Carlo Clelia , di Benedetto Maika , Vicenzi Lisa , Costantini Sara , Cucciarelli Francesca , Fenu Francesco , Arena Eleonora , Mariucci Cristina , Montisci Maria , Panni Valeria , Patani Fabiola , Valenti Marco , Palucci Andrea , Burroni Luca , Mantello Giovanna
Published: July 2021

Aims

Radiotherapy with concurrent 5-fluorouracil/mitomycin-C based chemotherapy has been established as definitive standard therapy approach for anal cancer. Intensity Modulated Radiotherapy (IMRT) leads to a precise treatment of the tumor, allowing dose escalation on Gross Tumor Volume (GTV), with a surrounding healthy tissues sparing. Our study assessed the impact of 18-Fluorodeoxyglucose positron emission tomography (18FDG-PET/CT) on the radiotherapy contouring process and its contribution to lymphatic spread detection, resulting to a personalization of Clinical Target Volume (CTV) and dose prescription.

Methods

Thirty-seven patients, with histologically proven squamous cell carcinoma of the anal canal (SCCAC) were analyzed. All patients were evaluated with history and physical examination, trans-anal endoscopic ultrasound, pelvis magnetic resonance imaging (MRI), computed tomography (CT) scans of the chest, abdomen and pelvis and planning 18FDG-PET/CT. The GTV and CTV were drawn on CT, MRI and 18FDG-PET/CT fused images.

Results

Thirty-four (91%) out of 37 patients presented lymph nodes involvement, in one or more areas, detected on 18FDG-PET/CT and/or MRI. The 18FDG-PET/CT showed positive lymph nodes not detected on MRI imaging (PET+, MRI−) in 14/37 patients (38%). In 14 cases, 18FDG-PET/CT allowed to a dose escalation in the involved nodes. The 18FDG-PET/CT fused images led to change the stage in 5/37(14%) cases: four cases from N0 to N1 (inguinal lymph nodes) and in one case from M0 to M1 (common iliac lymph nodes).

Conclusions

The 18FDG-PET/CT has a potentially relevant impact in staging and target volume delineation/definition in patients affected by anal cancer. In our experience, clinical stage variation occurred in 14% of cases. More investigations are needed to define the role of 18FDG-PET/CT in the target volume delineation of anal cancer.
Neuropilin-1: A Key Protein to Consider in the Progression of Pediatric Brain Tumors
Authors: Douyère Manon , Chastagner Pascal , Boura Cédric
Published: July 2021

Neuropilins are transmembrane glycoproteins that play important roles in cardiovascular and neuronal development, as well as in immunological system regulations. NRP1 functions as a co-receptor, binding numerous ligands, such as SEMA 3 or VEGF and, by doing so, reinforcing their signaling pathways and can also interface with the cytoplasmic protein synectin. NRP1 is expressed in many cancers, such as brain cancers, and is associated with poor prognosis. The challenge today for patients with pediatric brain tumors is to improve their survival rate while minimizing the toxicity of current treatments. The aim of this review is to highlight the involvement of NRP1 in pediatric brain cancers, focusing essentially on the roles of NRP1 in cancer stem cells and in the regulation of the immune system. For this purpose, recent literature and tumor databases were analyzed to show correlations between NRP1 and CD15 (a stem cancer cells marker), and between NRP1 and PDL1, for various pediatric brain tumors, such as high- and low-grade gliomas, medulloblastomas, and ependymomas. Finally, this review suggests a relevant role for NRP1 in pediatric brain tumors progression and identifies it as a potential diagnostic or therapeutic target to improve survival and life quality of these young patients.
Case Report: Squamous Cell Carcinoma of Pancreas With High PD-L1 Expression: A Rare Presentation
Authors: Yang Baohong , Ren Haipeng , Yu Guohua
Published: July 2021

Primary pancreatic squamous cell carcinoma is sporadic. The diagnosis is usually made following surgery or needle biopsy and requires a thorough workup to exclude metastatic squamous cell carcinoma. Squamous cell carcinoma of the pancreas often has a very poor prognosis. There is no treatment guideline for this type of cancer, and to date, no therapeutic regimen has been proven effective. Here, we report the effectiveness of immunotherapy in combination with chemotherapy against locally advanced squamous cell carcinoma of the pancreas with high programmed cell death ligand 1 (PD-L1) expression. Regional intra-arterial infusion chemotherapy consisting of nab-Paclitaxel followed by gemcitabine infused via gastroduodenal artery every three weeks for two cycles. This therapy resulted in the depletion of carcinoma, and the patient continues to lead a high-quality life with no symptoms for more than 16 months.
HBV Reactivation During the Treatment of Non-Hodgkin Lymphoma and Management Strategies
Authors: Cao Xing , Wang Yafei , Li Panyun , Huang Wei , Lu Xiaojuan , Lu Hongda
Published: July 2021

Hepatitis B virus reactivation (HBV-R), which can lead to HBV-related morbidity and mortality, is a common and well-known complication that occurs during the treatment of non-Hodgkin lymphoma (NHL) patients with current or past exposure to HBV infection. HBV-R is thought to be closely associated with chemotherapeutic or immunosuppressive therapies. However, immunosuppressive agents such as anti-CD20 antibodies (e.g., rituximab and ofatumumab), glucocorticoids, and hematopoietic stem cell transplantation (HSCT) administered to NHL patients during treatment can cause deep immunodepression and place them at high risk of HBV-R. In this review, we explore the current evidence, the guidelines of several national and international organizations, and the recommendations of expert panels relating to the definition, risk factors, screening and monitoring strategies, whether to use prophylaxis or pre-emptive therapy, and the optimal antiviral agent and duration of antiviral therapy for HBV-R.
Unnecessity of Routine Dissection of Right Central Lymph Nodes in cN0 Papillary Thyroid Carcinoma Located at the Left Thyroid Lobe
Authors: Zhang Songtao , Zhang Runfang , Wang Chao , Gong Wenbo , Zheng Chen , Fang Qigen , Dai Liyuan
Published: July 2021

Objective

The lymph node posterior to the right recurrent laryngeal nerve (LN-prRLN) is an important part of the central lymph nodes (LNs). We aimed to explore the rate and predictors of LN-prRLN metastasis in cN0 papillary thyroid carcinoma (PTC) located at the left thyroid lobe.

Methods

Patients with surgically treated primary left lobe PTC were retrospectively enrolled. The metastatic distribution of LN-prRLN and postoperative complications were assessed. The association between LN-prRLN metastasis and clinicopathological variables was evaluated by univariate and multivariate analyses.

Results

A total of 857 patients were included for the analysis. Central LN metastasis was noted in 310 (35.3%) cases. The most (27.6%) and least (1.7%) commonly involved LNs were the left paratracheal LN and the LN-prRLN. In the univariate analysis, the tumor size, multifocality, the extent of extrathyroidal extension (none vs. macroscopic vs. macroscopic maximal), and perineural invasion were associated with positive LN-prRLN. In the multivariate analysis, tumor size of >40.0 mm and macroscopic maximal invasion were found as the only two independent predictors. Transient and permanent hypoparathyroidism were noted in 90 (10.2%) and 13 (1.5%) patients, respectively. Voice change was noted in 40 (4.6%) patients, and 20 patients recovered.

Conclusions

In cN0 PTC located at the left lobe, LN-prRLN metastasis was very uncommon. We found that LN-prRLN dissection is not required routinely, but should be performed if the tumor size is >40.0 mm and macroscopic maximal extrathyroidal extension is present.
Identification of Prognostic miRNAs Associated With Immune Cell Tumor Infiltration Predictive of Clinical Outcomes in Patients With Non-Small Cell Lung Cancer
Authors: Zhang Yuepeng , Mi Kai , Li Zhiheng , Qiang Lixia , Lv Meiyu , Wu Yushan , Yuan Ligong , Jin Shoude
Published: July 2021

Background

A detailed means of prognostic stratification in patients with non-small cell lung cancer (NSCLC) is urgently needed to support individualized treatment plans. Recently, microRNAs (miRNAs) have been used as biomarkers due to their previously reported prognostic roles in cancer. This study aimed to construct an immune-related miRNA signature that effectively predicts NSCLC patient prognosis.

Methods

The miRNAs and mRNA expression and mutation data of NSCLC was obtained from The Cancer Genome Atlas (TCGA). Immune-associated miRNAs were identified using immune scores calculated by the ESTIMATE algorithm. LASSO-penalized multivariate survival models were using for development of a tumor immune-related miRNA signature (TIM-Sig), which was evaluated in several public cohorts from the Gene Expression Omnibus (GEO) and the CellMiner database. The miRTarBase was used for constructing the miRNA-target interactions.

Results

The TIM-Sig, including 10 immune-related miRNAs, was constructed and successfully predicted overall survival (OS) in the validation cohorts. TIM-Sig score negatively correlated with CD8+ T cell infiltration, IFN-γ expression, CYT activity, and tumor mutation burden. The correlation between TIM-Sig score and genomic mutation and cancer chemotherapeutics was also evaluated. A miRNA-target network of 10 miRNAs in TIM-Sig was constructed. Further analysis revealed that these target genes showed prognostic value in both lung squamous cell carcinoma and adenocarcinoma.

Conclusions

We concluded that the immune-related miRNAs demonstrated a potential value in clinical prognosis.
Spontaneous, Voluntary, and Affective Behaviours in Rat Models of Pathological Pain
Authors: Draxler Peter , Moen Aurora , Galek Karolina , Boghos Ani , Ramazanova Dariga , Sandkühler Jürgen
Published: July 2021

In pain patients affective and motivational reactions as well as impairment of daily life activities dominate the clinical picture. In contrast, many rodent pain models have been established on the basis of mechanical hypersensitivity testing. Up to today most rodent studies on pain still rely on reflexive withdrawal responses only. This discrepancy has likely contributed to the low predictive power of preclinical pain models for novel therapies. Here, we used a behavioural test array for rats to behaviourally evaluate five aetiologically distinct pain models consisting of inflammatory-, postsurgical-, cephalic-, neuropathic- and chemotherapy-induced pain. We assessed paralleling clinical expressions and comorbidities of chronic pain with an array of behavioural tests to assess anxiety, social interaction, distress, depression, and voluntary/spontaneous behaviours. Pharmacological treatment of the distinct pain conditions was performed with pathology-specific and clinically efficacious analgesics as gabapentin, sumatriptan, naproxen, and codeine. We found that rats differed in their manifestation of symptoms depending on the pain model and that pathology-specific analgesics also reduced the associated behavioural parameters. Based on all behavioural test performed, we screened for tests that can discriminate experimental groups on the basis of reflexive as well as non-sensory, affective parameters. Together, we propose a set of non-evoked behaviours with a comparable predictive power to mechanical threshold testing for each pain model.
Blood Pressure Variability and Baroreflex Sensitivity in Premature Newborns—An Effect of Postconceptional and Gestational Age
Authors: Javorka Kamil , Haskova Katarina , Czippelova Barbora , Zibolen Mirko , Javorka Michal
Published: July 2021

Introduction: Cardiovascular system is the vitally important system in the dynamical adaptation process of the newborns to the extrauterine environment. To reliably detect immaturity in the given organ system, it is crucial to study the development of the organ functions in relation to maturation process.

Objectives: The objective was to determine the changes in the spontaneous short-term blood pressure variability (BPV) and baroreflex sensitivity (BRS) reflecting various aspects of cardiovascular control during the process of maturation in preterm babies and to separate effects of gestational age and postnatal age.

Methods: Thirty-three prematurely born infants without any signs of cardio-respiratory disorders (gestational age: 31.8, range: 27–36 weeks; birth weight: 1,704, range: 820–2,730 grams) were enrolled. Continuous peripheral blood pressure signal was obtained by non-invasive volume-clamp photoplethysmography method during supine rest. The recordings of 250 continuous beat-to-beat blood pressure values were processed by spectral analysis of BPV (assessed measures: total power, low frequency and high frequency powers of systolic BPV) and BRS calculation. For each infant we also assessed systolic, diastolic and mean blood pressures, heart rate and respiratory rate.

Results: With the postconceptional age, BPV measures decreased (for total power: Spearman correlation coefficient rs = −0.345, P = 0.049; for low frequency power: rs = −0.365, P = 0.037; for high frequency power rs = −0.349; P = 0.046); and BRS increased significantly (rs = 0.448, P = 0.009). The further analysis demonstrated that these effects were more attributable to gestational age than to postnatal age. BRS correlated negatively with BPV magnitude (rs = −0.479 to −0.592, P = 0.001–0.005). Mean blood pressure and diastolic blood pressure increased during maturation (rs = 0.517 and 0.537, P = 0.002 and 0.001, respectively) while heart rate and respiratory rate decreased (rs = −0.366 and −0.516, P = 0.036 and 0.002, respectively).

Conclusion: We conclude that maturation process is accompanied by an increased involvement of baroreflex buffering of spontaneous short-term blood pressure oscillations. Gestational age plays a dominant role not only in BPV changes but also in BRS, mean blood pressure, diastolic blood pressure and heart rate changes.
Benefits and Safety of Chinese Herbal Medicine in Treating Psoriasis: An Overview of Systematic Reviews
Authors: Zhang Jie , Yu Qianying , Peng Li , Qin Yuesi , Jing Mingyi , Huang Dan , Guo Jing , Xiao Min , Chen Mingling
Published: July 2021

Background: In recent years, systematic reviews/meta-analyses (SRs/MAs) of Chinese herbal medicine (CHM) for psoriasis have continuously emerged. Their methods and evidence quality, however, are yet to be evaluated, and whether their conclusions can provide clinicians with reliable evidence is still debatable.

Objectives: This overview aims to evaluate the methodological quality, risk of bias, and reporting quality of relevant SRs/MAs, as well as the current evidence of CHM for treating psoriasis.

Methods: We searched nine electronic databases from their respective time of establishment to January 20, 2021, as well as the reference lists of the included SRs/MAs, protocol registries, and gray literature. Two reviewers independently used the following: A Measurement Tool to Assess Systematic Reviews (AMSTAR) 2, Risk of Bias in Systematic Reviews (ROBIS), the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and Grades of Recommendations, Assessment, Development and Evaluation (GRADE) to evaluate the methodological quality, risk of bias, reporting quality, and evidence quality of the included SRs/MAs.

Results: This review included 14 SRs/MAs involving 45 outcomes, of which 12 (85.71%) SRs/MAs had a very low quality evaluated by AMSTAR 2 and 7 (50.00%) SRs/MAs had a high risk of bias assessed by ROBIS. The protocol and registration and funding statements were the major reporting flaws according to the PRISMA checklist. The evaluation with the GRADE system demonstrated no outcome of high-quality evidence, and inconsistent efficacy evaluations were found in this overview. Only 15 (33.33%) outcomes were moderate-quality evidence, supporting the claim that CHM plus Western medicine (WM) was superior to WM. Generally low quality of evidence showed no difference in the incidence of adverse events between the combined therapy and WM. However, the conclusion that CHM was superior to WM cannot be drawn due to the inconsistent results.

Conclusion: Despite that CHM has the potential benefit and safety in the adjuvant treatment of psoriasis, the conclusion should be treated with caution because of the generally low quality of methodology and evidence. In the future, high-quality randomized controlled trials (RCTs) should be carried out, and the quality of relevant SRs should also be improved to promote their clinical application.
Evidence of Omics, Immune Infiltration, and Pharmacogenomic for SENP1 in the Pan-Cancer Cohort
Authors: Taghvaei Somayye , Sabouni Farzaneh , Minuchehr Zarrin
Published: July 2021

Sentrin specific-protease 1 (SENP1) is a protein involved in deSUMOylation that is almost overexpressed in cancer. SENP1 has a determinative role in the activation of transcription programs in the innate immune responses and the development B of and C lymphocytes. We found, SENP1 possibly plays a critical role in immune infiltration and acts as an expression marker in PAAD, ESCA, and THYM. CD4+ T cells, CD8+ T cells, and macrophages were more key-related immune cells, indicating that SENP1 might be introduced as a potential target for cancer immunotherapy. We further showed that dysregulation of SENP1 is powerfully associated with decreased patient survival and clinical stage. Total SENP1 protein also increases in cancer. SENP1 is also controlled by transcription factors (TFs) CREB1, KDM5A, REST, and YY1 that regulates apoptosis, cell cycle, cell proliferation, invasion, tumorigenesis, and metastasis. These TFs were in a positive correlation with SENP1. MiR-138–5p, miR-129-1-3p, and miR-129-2-3p also inhibit tumorigenesis through targeting of SENP1. The SENP1 expression level positively correlated with the expression levels of UBN1, SP3, SAP130, NUP98, NUP153 in 32 tumor types. SENP1 and correlated and binding genes: SAP130, NUP98, and NUP153 activated cell cycle. Consistent with this finding, drug analysis was indicated SENP1 is sensitive to cell cycle, apoptosis, and RTK signaling regulators. In the end, SENP1 and its expression-correlated and functional binding genes were enriched in cell cycle, apoptosis, cellular response to DNA damage stimulus. We found that the cell cycle is the main way for tumorigenesis by SENP1. SENP1 attenuates the effect of inhibitory drugs on the cell cycle. We also introduced effective FDA-Approved drugs that can inhibit SENP1. Therefore in the treatments in which these drugs are used, SENP1 inhibition is a suitable approach. This study supplies a wide analysis of the SENP1 across The Cancer Genome Atlas (CGA) cancer types. These results suggest the potential roles of SENP1 as a biomarker for cancer. Since these drugs and the drugs that cause to resistance are applied to cancer treatment, then these two class drugs can use to inhibition of SENP1.
Leismanicidal Activity of Propolis Collected in the Semiarid Region of Brazil
Authors: Cavalcante Giani Maria , Camara Celso Amorim , Silva Eva Monica Sarmento Da , Santos Mariana Silva , Leite Anderson Brandão , Queiroz Aline Cavalcanti , Evelyn Da Silva Amanda , Araújo Morgana Vital , Alexandre-Moreira Magna Suzana , Silva Tania Maria Sarmento
Published: July 2021

Objective: The aim of the current study is to investigate the chemical composition, cytotoxic effect, and leishmanicidal activity of propolis collected in the semi-arid region of Bahia, Brazil.

Methods: EtOH extract, hexane, EtOAc and MeOH fractions from propolis were analyzed by ultra-performance liquid chromatography coupled with diode array detector and quadrupole time-of-flight mass spectrometry. The identification was based on the exact mass, general fragmentation behaviors and UV absorption of the flavonoids. The in vitro cytotoxic effect and leishmanicidal activity of ethanolic extract, hexane, ethyl acetate, and methanolic fractions of propolis were evaluated.

Results: Five triterpenes and twenty-four flavonoids were identified. The propolis did not present toxicity to the host cell up to the maximum concentration tested. In addition, all tested samples showed statistically significant activity against promastigotes of Leishmania chagasi and Leishmania amazonensis. Regarding the activity against amastigote forms of L. amazonensis, the hexane fraction, presented statistically significant activity with IC50 of 1.3 ± 0.1 μg/ml.

Conclusion: The results support the idea that propolis can be used for future antileishmania studies.
High Dose Lopinavir/Ritonavir Does Not Lead to Sufficient Plasma Levels to Inhibit SARS-CoV-2 in Hospitalized Patients With COVID-19
Authors: Karolyi Mario , Omid Sara , Pawelka Erich , Jilma Bernd , Stimpfl Thomas , Schoergenhofer Christian , Laferl Hermann , Seitz Tamara , Traugott Marianna , Wenisch Christoph , Zoufaly Alexander
Published: July 2021

Background: Despite lopinavir/ritonavir (LPV/RTV) demonstrating in-vitro activity against SARS-CoV-2, large trials failed to show any net clinical benefit. Since SARS-CoV-2 has an EC50 of 16.4 μg/ml for LPV this could be due to inadequate dosing.

Methods: COVID-19 positive patients admitted to the hospital who received high dose LPV/RTV were included. High dose (HD) LPV/RTV 200/50 mg was defined as four tablets bid as loading dose, then three tablets bid for up to 10 days. Trough plasma concentrations were measured after the loading dose and on day 5–7 in steady state (SS). Post loading dose (PLD) and SS plasma trough levels were compared with SS trough levels from COVID-19 patients who received normal dose (ND) LPV/RTV (2 tablets bid) at the beginning of the pandemic.

Results: Fifty patients (30% female) with a median age of 59 years (interquartile range 49–70.25) received HD LPV/RTV. Median HD-PLD concentration was 24.9 μg/ml (IQR 15.8–30.3) and significantly higher than HD-SS (12.9 μg/ml, IQR 7.2–19.5, p < 0.001) and ND-SS (13.6 μg/ml, IQR 10.1–22.2, p = 0.013). HD-SS and ND-SS plasma levels did not differ significantly (p = 0.507). C-reactive-protein showed a positive correlation with HD-SS (Spearman correlation-coefficient rS = 0.42, p = 0.014) and ND-SS (rS = 0.81, p = 0.015) but not with HD-PLD (rS = 0.123, p = 0.43).

Conclusion: HD-PLD plasma trough concentration was significantly higher than HD-SS and ND-SS concentration, but no difference was detected between HD-SS and ND-SS trough levels. Due to the high EC50 of SARS-CoV-2 and the fact that LPV/RTV is highly protein bound, it seems unlikely that LPV/RTV exhibits a relevant antiviral effect against SARS-CoV-2 in vivo.