bluuebunny/crossref_metadata_2025 huggingface dataset:
Replication Region Analysis Reveals Non-lambdoid Shiga Toxin Converting Bacteriophages
Authors: Llarena Ann-Katrin , Aspholm Marina , O’Sullivan Kristin , Wêgrzyn Grzegorz , Lindbäck Toril
Published: March 2021

Shiga toxin is the major virulence factor of enterohemorrhagicEscherichia coli(EHEC), and the gene encoding it is carried within the genome of Shiga toxin-converting phages (Stx phages). Numerous Stx phages have been sequenced to gain a better understanding of their contribution to the virulence potential of EHEC. The Stx phages are classified into the lambdoid phage family based on similarities in lifestyle, gene arrangement, and nucleotide sequence to the lambda phages. This study explores the replication regions of non-lambdoid Stx phages that completely lack theOandPgenes encoding the proteins involved in initiating replication in the lambdoid phage genome. Instead, they carry sequences encoding replication proteins that have not been described earlier, here referred to aserugenes (afterEHEC phagereplicationunit genes). This study identified three different types of Eru-phages, where the Eru1-type is carried by the highly pathogenic EHEC strains that caused the Norwegian O103:H25 outbreak in 2006 and the O104:H4 strain that caused the large outbreak in Europe in 2011. We show that Eru1-phages exhibit a less stable lysogenic state than the classical lambdoid Stx phages. As production of phage particles is accompanied by production of Stx toxin, the Eru1-phage could be associated with a high-virulence phenotype of the host EHEC strain. This finding emphasizes the importance of classifying Stx phages according to their replication regions in addition to their Stx-type and could be used to develop a novel strategy to identify highly virulent EHEC strains for improved risk assessment and management.
Control of Microbial Opsin Expression in Stem Cell Derived Cones for Improved Outcomes in Cell Therapy
Authors: Garita-Hernandez Marcela , Chaffiol Antoine , Guibbal Laure , Routet Fiona , Khabou Hanen , Riancho Luisa , Toualbi Lyes , Picaud Serge , Sahel José-Alain , Goureau Olivier , Duebel Jens , Dalkara Deniz
Published: March 2021

Human-induced pluripotent stem cell (hiPSC) derived organoids have become increasingly used systems allowing 3D-modeling of human organ development, and disease. They are also a reliable source of cells for transplantation in cell therapy and an excellent model to validate gene therapies. To make full use of these systems, a toolkit of genetic modification techniques is necessary to control their activity in line with the downstream application. We have previously described adeno-associated viruse (AAV) vectors for efficient targeting of cells within human retinal organoids. Here, we describe biological restriction and enhanced gene expression in cone cells of such organoids thanks to the use of a 1.7-kb L-opsin promoter. We illustrate the usefulness of implementing such a promoter to enhance the expression of the red-shifted opsin Jaws in fusion with a fluorescent reporter gene, enabling cell sorting to enrich the desired cell population. Increased Jaws expression after transplantation improved light responses promising better therapeutic outcomes in a cell therapy setting. Our results point to the importance of promoter activity in restricting, improving, and controlling the kinetics of transgene expression during the maturation of hiPSC retinal derivatives. Differentiation requires mechanisms to initiate specific transcriptional changes and to reinforce those changes when mature cell states are reached. By employing a cell-type-specific promoter we put transgene expression under the new transcriptional program of mature cells.
Establishment of Long-Term Primary Cortical Neuronal Cultures From Neonatal Opossum Monodelphis domestica
Authors: Petrović Antonela , Ban Jelena , Tomljanović Ivana , Pongrac Marta , Ivaničić Matea , Mikašinović Sanja , Mladinic Miranda
Published: March 2021

Primary dissociated neuronal cultures have become a standard model for studying central nervous system (CNS) development. Such cultures are predominantly prepared from the hippocampus or cortex of rodents (mice and rats), while other mammals are less used. Here, we describe the establishment and extensive characterization of the primary dissociated neuronal cultures derived from the cortex of the gray South American short-tailed opossums,Monodelphis domestica. Opossums are unique in their ability to fully regenerate their CNS after an injury during their early postnatal development. Thus, we used cortex of postnatal day (P) 3–5 opossum to establish long-surviving and nearly pure neuronal cultures, as well as mixed cultures composed of radial glia cells (RGCs) in which their neurogenic and gliogenic potential was confirmed. Both types of cultures can survive for more than 1 monthin vitro. We also prepared neuronal cultures from the P16–18 opossum cortex, which were composed of astrocytes and microglia, in addition to neurons. The long-surviving opossum primary dissociated neuronal cultures represent a novel mammalianin vitroplatform particularly useful to study CNS development and regeneration.
Local Neuronal Synchronization in Frequent Nightmare Recallers and Healthy Controls: A Resting-State Functional Magnetic Resonance Imaging Study
Authors: Marquis Louis-Philippe , Julien Sarah-Hélène , Daneault Véronique , Blanchette-Carrière Cloé , Paquette Tyna , Carr Michelle , Soucy Jean-Paul , Montplaisir Jacques , Nielsen Tore
Published: March 2021

Nightmares are highly dysphoric dreams that are well-remembered upon awakening. Frequent nightmares have been associated with psychopathology and emotional dysregulation, yet their neural mechanisms remain largely unknown. Our neurocognitive model posits that nightmares reflect dysfunction in a limbic-prefrontal circuit comprising medial prefrontal and anterior cingulate cortices, hippocampus, and amygdala. However, there is a paucity of studies that used brain imaging to directly test the neural correlates of nightmares. One such study compared the regional homogeneity (ReHo) of resting-state functional magnetic resonance imaging blood-oxygen level-dependent signals between frequent nightmare recallers and controls. The main results were greater regional homogeneity in the left anterior cingulate cortex and right inferior parietal lobule for the nightmare recallers than for the controls. In the present study, we aimed to document the ReHo correlates of frequent nightmares using several nightmare severity measures. We acquired resting-state functional magnetic resonance imaging data from 18 frequent nightmare recallers aged 18–35 (3 males and 15 females) and 18 age- and sex-matched controls, as well as retrospective and prospective disturbed dreaming frequency estimates and scores on the Nightmare Distress Questionnaire. While there were inconsistent results for our different analyses (group comparisons, correlational analyses for frequency estimates/Nightmare Distress scores), our results suggest that nightmares are associated with altered ReHo in frontal (medial prefrontal and inferior frontal), parietal, temporal and occipital regions, as well as some subcortical regions (thalamus). We also found a positive correlation between retrospective disturbed dreaming frequency estimates and ReHo values in the hippocampus. These findings are mostly in line with a recent SPECT study from our laboratory. Our results point to the possibility that a variety of regions, including but not limited to the limbic-prefrontal circuit of our neurocognitive model, contribute to nightmare formation.
Clinical Implications of Psychophysical Olfactory Testing: Assessment, Diagnosis, and Treatment Outcome
Authors: Su Baihan , Bleier Benjamin , Wei Yongxiang , Wu Dawei
Published: March 2021

Purpose of Review

Olfactory dysfunction dramatically impairs quality of life with a prevalence of 20% in the general adult population. Psychophysical olfactory testing has been widely used to evaluate the ability to smell due to its validated utility and feasibility in clinic. This review summarizes the current literature regarding psychophysical olfactory testing and the clinical relevance of the olfactory testing with different components. Furthermore, the review highlights the diagnosis and treatment value of olfactory subtests in patients with olfactory dysfunction.

Recent Findings

With the accumulation of studies of psychophysical olfactory testing in olfactory disorders, the clinical relevance of olfactory testing with different components is expanding. Different olfactory domains present with distinct olfactory processing and cortical activity. Psychophysical assessment of olfaction with three domains reveals different levels of olfactory processing and might assist with analyzing the pathophysiologic mechanism of the various olfactory disorders. Furthermore, olfactory thresholds provided the largest amount of non-redundant information to the olfactory diagnosis. Sinonasal olfactory dysfunction and non-sinonasal-related olfactory dysfunction are emerging classifications of smell disorders with certain characteristics of olfactory impairment and different responses to the therapy including steroids, sinus surgery, and olfactory training.

These recent advancements should promote the understanding of psychophysical olfactory testing, the association between individual subcomponents and neurophysiological processes, and pave the way for precision assessment and treatment of the olfactory dysfunction.
Targeted Quantification of Detergent-Insoluble RNA-Binding Proteins in Human Brain Reveals Stage and Disease Specific Co-aggregation in Alzheimer’s Disease
Authors: Guo Qi , Dammer Eric B. , Zhou Maotian , Kundinger Sean R. , Gearing Marla , Lah James J. , Levey Allan I. , Shulman Joshua M. , Seyfried Nicholas T.
Published: March 2021

Core spliceosome and related RNA-binding proteins aggregate in Alzheimer’s disease (AD) brain even in early asymptomatic stages (AsymAD) of disease. To assess the specificity of RNA-binding protein aggregation in AD, we developed a targeted mass spectrometry approach to quantify broad classes of RNA-binding proteins with other pathological proteins including tau and amyloid beta (Aβ) in detergent insoluble fractions from control, AsymAD, AD and Parkinson’s disease (PD) brain. Relative levels of specific insoluble RNA-binding proteins across different disease groups correlated with accumulation of Aβ and tau aggregates. RNA-binding proteins, including splicing factors with homology to the basic-acidic dipeptide repeats of U1-70K, preferentially aggregated in AsymAD and AD. In contrast, PD brain aggregates were relatively depleted of many RNA-binding proteins compared to AsymAD and AD groups. Correlation network analyses resolved 29 distinct modules of co-aggregating proteins including modules linked to spliceosome assembly, nuclear speckles and RNA splicing. Modules related to spliceosome assembly and nuclear speckles showed stage-specific enrichment of insoluble RBPs from AsymAD and AD brains, whereas the RNA splicing module was reduced specifically in PD. Collectively, this work identifies classes of RNA-binding proteins that distinctly co-aggregate in detergent-insoluble fractions across the specific neurodegenerative diseases we examined.
Leveraging Online Learning to Promote Systems Thinking for Sustainable Food Systems Training in Dietetics Education
Authors: Spiker Marie , Hege Amanda , Giddens Janice , Cummings Joanna , Steinmetz Jasia , Tagtow Angie , Bergquist Erin , Burns Lauren , Campbell Christina , Stadler Diane , Combs Elizabeth , Prange Nancy , Schwartz Aaron , Brown Katie , Sauer Kevin
Published: March 2021

Educating and training a multisectoral food systems workforce is a critical part of developing sustainable, resilient, and healthy food and water systems. This paper shares perspectives from a working group of educators, learners, and food systems subject matter experts that collaborated over the course of a year to develop, pilot test, and evaluate two interactive webinar series with a multi-site cohort of dietetics interns and graduate students. The three-part webinar series format included a training webinar, a practice activity, and a synthesis webinar. In reflecting on the effectiveness of this format, we provide direct assessments of student learning from subject matter experts alongside indirect assessments from pre- and post-surveys fielded with learners. Learners who participated in an interactive webinar series demonstrated skills in several dimensions of systems thinking and gained confidence in food systems learning outcomes. Learners also shared valuable feedback on the opportunities and challenges of using online platforms for this experience. As online learning opportunities become more common, it will become increasingly important for educators to prioritize strategies that effectively equip students with the higher-order thinking skills, such as systems thinking, needed to address the complexities of sustainable food systems. The interactive webinar series format described here provides an opportunity to leverage didactic webinars in combination with interactive experiences that enable learners to deepen their knowledge through practice with peers and subject matter experts. Though this format was piloted within dietetics education programs, many of the lessons learned are transferable to other food systems educational contexts.
Immune Check Point Inhibitors and Immune-Related Adverse Events in Small Cell Lung Cancer
Authors: Hou Wanting , Zhou Xiaohan , Yi Cheng , Zhu Hong
Published: March 2021

Small cell lung cancer (SCLC) is a malignant solid tumor. In recent years, although immune check point inhibitors (ICIs) have achieved important advances in the treatment of SCLC, immune-related adverse events (irAEs) have occurred at the same time during the therapeutic period. Some irAEs lead to dose reduction or treatment rejection. The immune microenvironment of SCLC is complicated, therefore, understanding irAEs associated with ICIs is of great importance and necessity for the clinical management of SCLC. However, the lack of comprehensive understanding of irAEs in patients with SCLC remains remarkable. This review aims to provide an up-to-date overview of ICIs and their associated irAEs in patients with SCLC based on present clinical data.
Case Report: Efficacy of Pyrotinib in ERBB2 Amplification Pulmonary Adenoid Cystic Carcinoma
Authors: Tang Zhongben , Lin Feng , Xiao Jiarong , Du Xiaojun , Zhang Jian , Li Sini , Tang Gongshun , Chen Chen , Li Jian
Published: March 2021

Primary pulmonary adenoid cystic carcinomas are salivary tumors that are low-grade malignant and prone to recurrence and metastasis. Surgery is currently the main treatment, but there is no standard with regard to postoperative adjuvant therapy. Adenoid cystic carcinoma is more sensitive to radiotherapy and patients benefit less from chemotherapy, but few studies have focused on targeted therapy, and their conclusions are inconsistent. With respect to primary pulmonary adenoid cystic carcinoma, large-scale studies cannot be conducted due to its low incidence, and studies on the targeted therapy of it are very scarce. A few case reports indicate that targeted therapy can be effective however, suggesting that it may be a good option. The current report is the first on the occurrence of human epidermal growth factor receptor 2 amplification in pulmonary adenoid cystic carcinoma. The patient was treated with pyrotinib for 6 months and achieved stable disease.
Computed Tomography Features of Gastric Cancer Patients With DNA Mismatch Repair Deficiency
Authors: Cao Qian , Lai Sheng-Yuan , Xu Nan , Lu Yang , Chen Shuai , Zhang Xin-Sheng , Li Xiang
Published: March 2021

Objective

To explore the computed tomography (CT) features of gastric cancer (GC) patients with DNA mismatch repair deficiency (dMMR).

Materials and Methods

This study reviewed the clinical and CT features of GC patients with dMMR, confirmed by the postoperative results, between September 2017 and December 2019. The expression pattern of MMR major proteins (MLH1, MSH2, MSH6, and PMS2) in immunohistochemistry was used to confirm the MMR status in GC tissues. The correlation between pre-treatment CT features and MMR status was statistically analyzed.

Results

A total of 28 patients with GC were diagnosed as dMMR in our study, and 49 patients were MMR-proficient (pMMR). The tumor locations were significantly different between the dMMR and pMMR groups (p = 0.006). The CT tumor thickness, CT long and short diameters of the largest lymph node, and the number of lymph nodes on CT of the dMMR group were significantly different from the pMMR group.

Conclusion

The dMMR GC exhibited a lower stomach location, smaller tumor thickness and lymph node diameter, and fewer lymph nodes on CT imaging.
Impact of Postoperative Radiotherapy on Survival of Patients With de novo Stage IV Breast Cancer: A Population-Based Study From the SEER Database
Authors: Zhang Jie , Luo Shiping , Qiu Zhaozhen , Lin Yuxiang , Song Chuangui
Published: March 2021

Purpose: In our study, we aimed to evaluate the role of postoperative radiotherapy for patents with de novo stage IV breast cancer.

Patients and Methods: Patients diagnosed with stage IV breast cancer from 2010 to 2016 were selected from the Surveillance, Epidemiology, and End Result (SEER) database. Those patients who received both chemotherapy and surgery and lived longer than 6 months were divided into radiotherapy and non-radiotherapy groups. Kaplan-Meier analysis and multivariate Cox proportional hazards models were used to estimate the survival outcomes before and after being 1:1 propensity score matched (PSM). Subgroup analyses stratified by age, subtype, status of distant metastasis, and surgery type were also performed.

Results: Among 1,935 patients, 52% (1006) underwent radiotherapy while the non-radiotherapy group contained 48% (929). After PSM, a total of 1,520 patients in two groups of 760 patients were enrolled in this analysis. Kaplan-Meier and the multivariate survival analysis demonstrated that the radiotherapy group presented with a better prognosis compared to the non-radiotherapy group (after PSM, BCSS: Hazard Ratio, 0.697; 95% confidence interval, 0.59–0.823; P < 0.001; OS: Hazard Ratio, 0.707; 95% confidence interval, 0.601–0.831; P < 0.001). Further subgroup analyses showed the Luminal subtype (HR+/HER2–), triple-negative breast cancer (TNBC), and bone-only metastasis patients presented with the most promising survival in the radiotherapy group.

Conclusions: Postoperative radiotherapy is associated with a significant survival advantages in BCSS and OS. It can be an optimal supplementary treatment for stage IV patients after surgery, especially for Luminal subtype, TNBC, and patients with a low metastatic burden.
Potential Mechanism Underlying the Role of Mitochondria in Breast Cancer Drug Resistance and Its Related Treatment Prospects
Authors: Li Yuefeng , Li Zhian
Published: March 2021

Breast cancer incidence and mortality rates have been consistently high among women. The use of diverse therapeutic strategies, including chemotherapy, endocrine therapy, targeted therapy, and immunotherapy, has improved breast cancer prognosis. However, drug resistance has become a tremendous obstacle in overcoming breast cancer recurrence and metastasis. It is known that mitochondria play an important role in carcinoma cell growth, invasion and apoptosis. Recent studies have explored the involvement of mitochondrial metabolism in breast cancer prognosis. Here, we will provide an overview of studies that investigated mitochondrial metabolism pathways in breast cancer treatment resistance, and discuss the application prospects of agents targeting mitochondrial pathways against drug-resistant breast cancer.
CMPK1 Regulated by miR-130b Attenuates Response to 5-FU Treatment in Gastric Cancer
Authors: Chu Huaizhu , Han Nahui , Xu Jianguo
Published: March 2021

Gastric cancer (GC) remains a major world-wide challenge, especially in Asian countries. Chemotherapy with 5-fluorouracil (5-FU) and cisplatin is used as the first-line treatment and development of chemoresistance is a major cause of progression. UMP/CMP kinase is responsible for the phosphorylation of the ribonucleotide metabolite 5-fluoro-5′-monophosphate (FUMP) in 5-FU metabolic process, and recognized as a key step in the conversion of 5-FU to cytotoxic metabolites. Our bioinformatics analysis and molecular experiments demonstrated that high expression of CMPK1 was associated with prolonged survival and response to 5-FU treatment in GC samples. Further analysis demonstrated that miR-130b as a key epigenetic regulator of CMPK1, and miR-130b-mediated attenuation of CMPK1 resulted in resistance of gastric cancer cells to DNA damage and cell death after treatment with 5-FU. Rescue experiments with augmented CMPK1 expression abolished the effect of miR-130b demonstrating the key function of this miRNA in this pathway. Thus, this newly identified miR-130b-CMPK1 axis suggests a potentially new chemotherapeutic strategy for improved response to 5-FU therapy.
Relating Gut Microbiome and Its Modulating Factors to Immunotherapy in Solid Tumors: A Systematic Review
Authors: Huang Chengliang , Li Meizhang , Liu Ben , Zhu Huanbo , Dai Qun , Fan Xianming , Mehta Kathan , Huang Chao , Neupane Prakash , Wang Fen , Sun Weijing , Umar Shahid , Zhong Cuncong , Zhang Jun
Published: March 2021

Background: Gut microbiome is proved to affect the activity of immunotherapy in certain tumors. However, little is known if there is universal impact on both the treatment response and adverse effects (AEs) of immune checkpoint inhibitors (ICIs) across multiple solid tumors, and whether such impact can be modulated by common gut microbiome modifiers, such as antibiotics and diet.

Methods: A systematic search in PubMed followed by stringent manual review were performed to identify clinical cohort studies that evaluated the relevance of gut microbiome to ICIs (response and/or AEs, 12 studies), or association of antibiotics with ICIs (17 studies), or impact of diet on gut microbiome (16 studies). Only original studies published in English before April 1st, 2020 were used. Qualified studies identified in the reference were also included.

Results: At the phylum level, patients who had enriched abundance in Firmicutes and Verrucomicrobia almost universally had better response from ICIs, whereas those who were enriched in Proteobacteria universally presented with unfavorable outcome. Mixed correlations were observed for Bacteroidetes in relating to treatment response. Regarding the AEs, Firmicutes correlated to higher incidence whereas Bacteroidetes were clearly associated with less occurrence. Interestingly, across various solid tumors, majority of the studies suggested a negative association of antibiotic use with clinical response from ICIs, especially within 1-2 month prior to the initiation of ICIs. Finally, we observed a significant correlation of plant-based diet in relating to the enrichment of “ICI-favoring” gut microbiome (P = 0.0476).

Conclusions: Gut microbiome may serve as a novel modifiable biomarker for both the treatment response and AEs of ICIs across various solid tumors. Further study is needed to understand the underlying mechanism, minimize the negative impact of antibiotics on ICIs, and gain insight regarding the role of diet so that this important lifestyle factor can be harnessed to improve the therapeutic outcomes of cancer immunotherapy partly through its impact on gut microbiome.
The Long Non-coding RNA TMPO-AS1 Promotes Bladder Cancer Growth and Progression via OTUB1-Induced E2F1 Deubiquitination
Authors: Zhang Yeyu , Zhu Yuxing , Xiao Mengqing , Cheng Yaxin , He Dong , Liu Jianye , Xiang Liang , Gong Lian , Wang Zhanwang , Deng Liping , Cao Ke
Published: March 2021

Background: Increasing evidence indicates that long non-coding RNAs (lncRNAs) play crucial roles in cancer tumorigenesis and progression. TMPO antisense RNA 1 (TMPO-AS1) has been found to be involved in several cancers by acting as a competing endogenous RNA. However, the potential roles of TMPO-AS1 in bladder cancer (BC) and the potential interactions with proteins remain poorly understood.

Methods: The expression of the lncRNA TMPO-AS1 was evaluated via bioinformatic analysis and further validated by quantitative real-time PCR (qRT-PCR). Loss- and gain-of-function assays were performed to determine the biological functions of TMPO-AS1 in BC cell proliferation, migration, and invasion. Moreover, chromatin immunoprecipitation, Western blotting, and fluorescence in situ hybridization, as well as RNA pull-down, RNA immunoprecipitation, and luciferase reporter assays, were conducted to explore the upstream and downstream molecules interacting with TMPO-AS1.

Results: TMPO-AS1 is upregulated in BC. Functional experiments demonstrated that TMPO-AS1 promotes cell proliferation, migration, and invasion in BC and inhibits cell apoptosis in vivo and in vitro. Mechanically, E2F1 is responsible for TMPO-AS1 upregulation. Additionally, TMPO-AS1 facilitates the interaction of E2F1 with OTU domain-containing ubiquitin aldehyde binding 1 (OTUB1), leading to E2F1 deubiquitination and stabilization; therefore, TMPO-AS1 promotes BC malignant phenotypes. Furthermore, rescue experiments showed that TMPO-AS1 promotes BC growth in an E2F1-dependent manner.

Conclusions: Our study is the first to uncover the novel TMPO-AS1/E2F1 positive regulatory loop important for the promotion of BC malignant behaviors. The TMPO-AS1/E2F1 loop should be considered in the quest for new BC therapeutic options.
Therapeutic Efficacy of Nasoenteric Tube Feeding in Children Needing Enteral Nutrition
Authors: Chen Mi-Chi , Chao Hsun-Chin , Yeh Pai-Jui , Lai Ming-Wei , Chen Chien-Chang
Published: March 2021

Background: There is limited information on therapeutic benefits and tube-related complications of pediatric nasoenteric (NE) tube feeding. We viewed, from different clinical aspects, NE tube feeding in children who are under intolerable conditions.

Methods: A 10-years retrospective study enrolled 77 pediatric patients who underwent an endoscopic-guided placement of the NE tube for enteral nutrition. The evaluated data, including growth parameters, feeding volume, parenteral nutrition (PN) dependence, and nutritional markers [serum hemoglobin (Hb) and albumin] before and after NE tube feeding were compared. Tube-related complications and major adverse events were also recorded.

Results: A total of 77 patients (including 50 males) underwent 176 endoscopic-guided placements of the NE tube with an average duration of 133.7 (6.0–1,847.3) days. The gastroesophageal reflux disease-related symptoms (vomiting, desaturations, and aspiration pneumonia) improved in 71.4% of patients. Feeding volume increased significantly after intervention, especially in patients with delayed gastric emptying, from 144.8 ± 28.5 to 1,103.1 ± 524.7 ml/days (p < 0.001). Weaning from PN was successfully achieved in 84.3% of patients with an average of 9.33 ± 7.30 days. About 16 patients (20.8%) were subsequently highly compatible with oral feeding after NE tube placement for an average of 24.7 ± 14.1 days. Patients either without neurologic dysfunction or with no ventilator-dependent status had a higher chance of shifting to oral feeding. Weight-for-age z-scores increased by 0.15 ± 1.33 after NE tube intervention. One NE tube-related adverse event, which caused bowel perforation at 6 days post-insertion, was recorded. No direct tube-related mortality was observed.

Conclusions: Endoscopic-guided NE tube placement is a relatively safe, non-invasive procedure for pediatric patients who require enteral nutrition. Feeding via NE tube showed beneficial effects such as improvement in symptoms, PN weaning, and maintenance of body growth without major tube-related complications.
A Matched Case Control Study of Surgically and Non-surgically Treated Patent Ductus Arteriosus in Extremely Pre-term Infants
Authors: Olsson Karl Wilhelm , Youssef Sawin , Kjellberg Mattias , Raaijmakers Renske , Sindelar Richard
Published: March 2021

Introduction: There are still uncertainties about the timing and indication for surgical ligation of patent ductus arteriosus (PDA) in pre-term infants, where lower gestational age (GA) usually is predictive for surgical treatment.

Objective: Our aim was to assess differences in clinical characteristics and outcomes between surgically treated and matched non-surgically treated PDA in extremely pre-term infants.

Methods: All extremely pre-term infants born 2010–2016 with surgically treated PDA (Ligated group; n = 44) were compared to non-surgically treated infants (Control group; n = 44) matched for gestational age (+/−1 week) and time of birth (+/−1 month). Perinatal parameters, echocardiographic variables, details of pharmacological PDA treatment, morbidity, and mortality were assessed.

Result: Mean GA and birthweight were similar between the Ligated group (24+5 ± 1+3 weeks and 668 ± 170 g) and the Control group (24+5 ± 1+3 weeks and 704 ± 166 g; p = 1.000 and p = 0.319, respectively). Infants in the Ligated group had larger ductal diameters prior to pharmacological treatment, and lack of diameter decrease and PDA closure after treatment (p = 0.022, p = 0.043 and 0.006, respectively). Transfusions, post-natal steroids and invasive respiratory support were more common in the Ligated group. Except for a higher incidence of severe bronchopulmonary dysplasia (BPD) in the Ligated group there were no other differences in outcomes or mortality between the groups.

Conclusion: Early large ductal diameter and reduced responsiveness to pharmacological treatment predicted the need for future surgical ligation in this matched cohort study of extremely pre-term infants where the effect of GA and differences in treatment strategies were excluded. Besides an increased incidence of severe BPD in the Ligated group, no other differences in morbidity or mortality were detected.
Clofazimine: A Promising Inhibitor of Rabies Virus
Authors: Wu Jiajing , Cao Shouchun , Lei Shan , Liu Qiang , Li Yinghong , Yu Yueyang , Xie Hui , Li Qianqian , Zhao Xiaoqiang , Chen Ruifeng , Huang Weijin , Xiao Xinyue , Yu Yongxin , Song Danqing , Li Yuhua , Wang Youchun
Published: March 2021

With an almost 100% mortality rate, rabies virus (RABV) infection is a global concern. Limited post-exposure prophylaxis and lack of an effective treatment necessitate novel antiviral therapies against RABV. Here, using a high-throughput screening (HTS) method developed in our lab, 11 candidates with anti-RABV activity were identified from a library of 767 clinical drugs. Clofazimine (CFZ), an anti-leprosy drug, displayed an EC50 of 2.28 μM, and SI over 967 against RABV. Investigations into the underlying mechanisms revealed that CFZ targeted viral membrane fusion at the early stages of virus replication. Moreover, CFZ and Clofazimine salicylates (CFZS) exhibited elevated survival rates in vivo, compared with the positive control T-705. Thus, this study revealed CFZ as a promising drug against RABV infection.
The Protection of Crocin Against Ulcerative Colitis and Colorectal Cancer via Suppression of NF-κB-Mediated Inflammation
Authors: Teng Shanshan , Hao Jie , Bi Hui , Li Congcong , Zhang Yongfeng , Zhang Yaqin , Han Weiwei , Wang Di
Published: March 2021

Background: In China, the incidence of ulcerative colitis (UC) is increasing every year, but the etiology of UC remains unclear. UC is known to increase the risk of colorectal cancer (CRC). The aim of this study was to investigate the protective effects of crocin against UC and CRC in mouse models.

Methods: Crocin was used to treat the dextran sodium sulfate (DSS)-induced UC mice for 3 weeks, and ApcMinC/Gpt mice with colorectal cancer for 8 weeks. Proteomics screening was used to detect changes in the protein profiles of colon tissues of UC mice. Enzyme-linked immunosorbent assays and western blot were used to verify these changes.

Results: Crocin strongly reduced the disease activity index scores of UC mice, and improved the pathological symptoms of the colonic epithelium. The anti-inflammatory effects of crocin were indicated by its regulation of the activity of various cytokines, such as interleukins, via the modulation of nuclear factor kappa-B (NF-κB) signaling. Crocin significantly suppressed tumor growth in ApcMinC/Gpt mice and ameliorated pathological alterations in the colon and liver, but had no effects on spleen and kidney. Additionally, crocin significantly decreased the concentrations of interleukins and tumor necrosis factor-α in the sera and colon tissues, suggesting its anti-inflammatory effects related to NF-κB signaling. Finally, 12-h incubation of SW480 cells with crocin caused cell cycle arrest, enhanced the apoptotic rate, promoted the dissipation of mitochondrial membrane potential, and the over-accumulation of reactive oxygen species. From the theoretical analyses, phosphorylated residues on S536 may enhance the protein-protein interactions which may influence the conformational changes in the secondary structure of NF-κB.

Conclusion: The protective effects of crocin on UC and CRC were due to its suppression of NF-κB-mediated inflammation.
Absence of Rgs5 Influences the Spatial and Temporal Fluctuation of Cardiac Repolarization in Mice
Authors: Song Zi-liang , Liu Yang , Liu Xu , Qin Mu
Published: March 2021

Aims

This study investigated the contribution of the regulator of G-protein signaling 5 (Rgs5) knockout to the alteration of the action potential duration (APD) restitution and repolarizing dispersion in ventricle.

Methods and Results

The effects of Rgs5–/– were investigated by QT variance (QTv) and heart rate variability analysis of Rgs5–/– mice. Monophasic action potential analysis was investigated in isolated Rgs5–/– heart. Rgs5–/– did not promote ventricular remodeling. The 24-h QTv and QT variability index (QTVI) of the Rgs5–/– mice were higher than those of wild-type (WT) mice (P < 0.01). In WT mice, a positive correlation was found between QTv and the standard deviation of all NN intervals (r = 0.62; P < 0.01), but not in Rgs5–/– mice (R = 0.01; P > 0.05). The absence of Rgs5 resulted in a significant prolongation of effective refractory period and APD in isolated ventricle. In addition, compared with WT mice, the knockout of Rgs5 significantly deepened the slope of the APD recovery curve at all 10 sites of the heart (P < 0.01) and increased the spatial dispersions of Smax (COV-Smax) (WT: 0.28 ± 0.03, Rgs5–/–: 0.53 ± 0.08, P < 0.01). Compared with WT heart, Rgs5–/– increased the induced S1–S2 interval at all sites of heart and widened the window of vulnerability of ventricular tachyarrhythmia (P < 0.05).

Conclusion

Our findings indicate that Rgs5–/– is an important regulator of ventricular tachyarrhythmia in mice by prolonging ventricular repolarization and increasing spatial dispersion in ventricle.
Isokinetic Muscle Strength and Postural Sway of Recreationally Active Older Adults vs. Master Road Runners
Authors: Taveira Henrique V. , de Lira Claudio A. B. , Andrade Marilia S. , Viana Ricardo B. , Tanaka Hirofumi , Hill Lee , Nikolaidis Pantelis T. , Knechtle Beat , Rosemann Thomas , Vancini Rodrigo L.
Published: March 2021

Trunk muscle strength and control is an important prerequisite for everyday activities among elderly people decreasing the predisposition to falls. High levels of physical exercise performed by older athletes could offer benefits to core/trunk muscle strength and postural control compared with recreational physical activities and among elderly people with lower levels of physical activity. The present study aimed to compare trunk muscle strength and postural control of older running athletes vs. older physically active adults. Participants were master road runners (RUN, n = 15, six women, 64.3 ± 3.6 years) and physically active elderly (control group, CON, n = 15, six women, 65.4 ± 5.0 years) people that were submitted to the evaluations: esthesiometer, posturography (force plate), and isokinetic test (Biodex dynamometer) of trunk muscle extension and flexion. RUN presented higher values for relative peak torque of trunk extensor muscles at 60°/s (p = 0.046) and 180°/s (p = 0.007) and relative average power during trunk extension at 60°/s (p = 0.008) and 180°/s (p = 0.004) compared to CON. CON had a higher medial-lateral oscillation speed of the center of pressure in the stable condition with eyes closed (p = 0.004) compared to RUN. RUN presented higher isokinetic torque of extensor trunk muscles and better postural control than CON. This supposedly could help with postural control and balance and contribute to the prevention of falls among the elderly. The practice of running systematically by master athletes may partially explained our findings.
Comparative Analysis of Adelphocoris suturalis Jakovlev (Hemiptera: Miridae) Immune Responses to Fungal and Bacterial Pathogens
Authors: Ma Meiqi , Guo Libin , Tu Chengjie , Wang Aoli , Xu Letian , Luo Jing
Published: March 2021

The wide-spread culture of transgenic Bt cotton resisting the infamous cotton bollworms has reduced the adoption of broad-spectrum insecticides to a large extent. Consequently, the non-targeted insect Adelphocoris suturalis Jakovlev has become a major cotton pest in China. Entomopathogenic microbes show promising results for controlling this pest in the future, but A. suturalis innate immune responses to these pathogens are poorly understood. Here, we used the entomopathogenic fungus Beauveria bassiana and the Gram-negative pathogenic bacteria Enterobactor cloacae to infect A. suturalis nymphs, followed by high throughput RNA-seq to analyze the immune transcriptomes of A. suturalis in response to the two pathogens. A total of 150 immunity-related genes were identified, including pattern recognition receptors, extracellular signal modulators, signal pathways (Toll, IMD, JNK, and JAK/STAT), and response effectors. Further quantitative real-time PCR analysis demonstrated that B. bassiana and E. cloacae were recognized by different receptors (GNBP and PGRP, respectively); activated Toll pathway and IMD pathway respectively; and both induced expression of the effector gene Defensin. However, melanization is suppressed in B. bassiana-infected nymphs. Collectively, this study provides a transcriptomic snapshot of the A. suturalis immune system, and at the genetic level, gains multifaceted insights of the immune response to fungal and Gram-negative bacterial pathogens. Ultimately this work pioneers the study of molecular mechanisms underlying immune interactions between A. suturalis and its pathogens and assists in the development of novel mitigation strategies to control this pest.
Sex-Dependent Association Between Early Morning Ambulatory Blood Pressure Variations and Acute Mountain Sickness
Authors: Chen Renzheng , Yang Jie , Liu Chuan , Sun Mengjia , Ke Jingbin , Yang Yuanqi , Shen Yang , Yuan Fangzhengyuan , He Chunyan , Cheng Ran , Lv Hailin , Tan Hu , Gao Xubin , Zhang Jihang , Huang Lan
Published: March 2021

Background

Acute high altitude (HA) exposure elicits blood pressure (BP) responses in most subjects, and some of them suffer from acute mountain sickness (AMS). However, a 24-h ambulatory BP (ABP) change and the correlation with the occurrence of AMS in different sexes are still unclear.

Objectives

This prospective study aimed to investigate HA induced BP responses in males and females and the relationship between AMS and 24-h ABP.

Methods

Forty-six subjects were matched according to demographic parameters by propensity score matching with a ratio of 1:1. All the subjects were monitored by a 24-h ABP device; the measurement was one period of 24 h BP. 2018 Lake Louise questionnaire was used to evaluate AMS.

Results

Both the incidence of AMS (14 [60.9%] vs. 5 [21.7%], P = 0.007) and headache (18 [78.3%] vs. 8 [34.8%], P = 0.003) were higher in females than in males. All subjects showed an elevated BP in the early morning [morning systolic BP (SBP), 114.72 ± 13.57 vs. 120.67 ± 11.10, P = 0.013]. The elevation of morning SBP variation was more significant in females than in males (11.95 ± 13.19 vs. −0.05 ± 14.49, P = 0.005), and a higher morning BP surge increase (4.69 ± 18.09 vs. −9.66 ± 16.96, P = 0.005) was observed after acute HA exposure in the female group. The increase of morning SBP was associated with AMS occurrence (R = 0.662, P < 0.001) and AMS score (R = 0.664, P = 0.001). Among the AMS symptoms, we further revealed that the incidence (R = 0.786, P < 0.001) and the severity of headache (R = 0.864, P < 0.001) are closely correlated to morning SBP.

Conclusions

Our study demonstrates that females are more likely to suffer from AMS than males. AMS is closely associated with elevated BP in the early morning period, which may be correlated to higher headache incidence in subjects with higher morning SBP.
Novel Effects of Leonardite-Based Applications on Sugar Beet
Authors: Della Lucia Maria C. , Bertoldo Giovanni , Broccanello Chiara , Maretto Laura , Ravi Samathmika , Marinello Francesco , Sartori Luigi , Marsilio Giovanni , Baglieri Andrea , Romano Alessandro , Colombo Mauro , Magro Francesco , Campagna Giovanni , Concheri Giuseppe , Squartini Andrea , Stevanato Piergiorgio
Published: March 2021

The present study aimed to explore the effects of foliar application of a leonardite-based product on sugar beet (Beta vulgaris L.) plants grown in the field. The approach concerned the evaluation of the community compositional structure of plant endophytic bacteria through a metabarcoding approach, the expression level of a gene panel related to hormonal metabolism and signaling, and the main sugar beet productivity traits. Results indicated that plants treated with leonardite (dosage of 2,000 ml ha–1, dilution 1:125, 4 mg C l–1) compared with untreated ones had a significant increase (p < 0.05) in (i) the abundance of Oxalicibacterium spp., recognized to be an endophyte bacterial genus with plant growth-promoting activity; (ii) the expression level of LAX2 gene, coding for auxin transport proteins; and (iii) sugar yield. This study represents a step forward to advance our understanding of the changes induced by leonardite-based biostimulant in sugar beet.
Italian Community Psychology in the COVID-19 Pandemic: Shared Feelings and Thoughts in the Storytelling of University Students
Authors: Di Napoli Immacolata , Guidi Elisa , Arcidiacono Caterina , Esposito Ciro , Marta Elena , Novara Cinzia , Procentese Fortuna , Guazzini Andrea , Agueli Barbara , Gonzáles Leone Florencia , Meringolo Patrizia , Marzana Daniela
Published: March 2021

This study investigated how young Italian people experienced the period of peak spread of COVID-19 in their country by probing their emotions, thoughts, events, and actions related to interpersonal and community bonds. This approach to the pandemic will highlight social dimensions that characterized contextual interactions from the specific perspective of Community Psychology. The aim was to investigate young people's experiences because they are the most fragile group due to their difficulty staying home and apart from their peers and because they are, at the same time, the most potentially dangerous people due to their urge to gather in groups. The research involved 568 university students, 475 females, and 93 males, with an average age of 21.82 years (SD = 4.836). The collected data were analyzed with the Grounded Theory Methodology, using the Atlas 8.0 software. From the textual data, representative codes were defined and grouped into 10 categories, which reflect the individuals' prosocial attitudes, behaviors, and values. These categories formed three macro-categories, called: “Collective Dimensions,” which includes Connectedness, Solidarity, Italian-ness, Social Problems, and Collective Mourning; “Prosocial Orientation,” which includes Trust and Hope; and “Collective Values,” which includes Values of Freedom, Respect of Social Rules, and Civic-Mindedness. All these macro-categories are indicative of the shared feelings experienced by Italians during the first time of the pandemic. Further practical implications of these results will be discussed, including a consideration of the risk of developing distress and improving well-being, as well as promoting preventive behaviors.
Communication of Diagnosis of Infertility: A Systematic Review
Authors: Mosconi Laura , Crescioli Giada , Vannacci Alfredo , Ravaldi Claudia
Published: March 2021

Background: When infertility is diagnosed, physicians have the difficult task to break bad news. Their communication skills play a central role in improving patients' coping abilities and adherence to infertility treatments. However, specific guidelines and training courses on this topic are still lacking. The aim of the present study is to provide some practical advice for improving breaking bad news in infertility diagnosis through a systematic literature review of qualitative and quantitative studies.

Methods: Electronic searches were performed in the MEDLINE, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Psychology and Behavioral Sciences Collection databases. All articles focusing on the communication of the diagnosis of infertility were included. The main findings of each included article were then summarized.

Results: Literature search identified 11,838 references that were screened for eligibility. Full texts of 81 articles were retrieved, and their analysis led to the inclusion of 4 articles, which treated the theme of communication of infertility only partially. The main addressed aspects concerning the communication of the infertility diagnosis were the following: (i) the value that patients give to healthcare professionals' communication skills; (ii) the importance of giving clear information on diagnostic procedures and treatments in order to decrease patients' anxiety; and (iii) the importance of involving both partners.

Conclusions: This review pointed out that the communication of the infertility diagnosis is still underinvestigated. Specific guidelines are currently not available, but other protocols could be used. Taking into account the principal aspects of communication highlighted with this review, in this study, we suggested an adaptation of the original SPIKES protocol that could be used by healthcare professionals for the communication of the infertility status.