bluuebunny/crossref_metadata_2025 huggingface dataset:
Follistatin-Like 3 Correlates With Lymph Node Metastasis and Serves as a Biomarker of Extracellular Matrix Remodeling in Colorectal Cancer
Authors: Yang Chao , Cao Fengyu , Huang Shuoyang , Zheng Yongbin
Published: July 2021

Background

As a heterogeneous disease, colorectal cancer (CRC) presents a great challenge to individualized treatment due to its lymph node metastasis (LNM). Existing studies have shown that immune and stromal components in extracellular matrix (ECM) act as important part in tumorigenicity and progression, while their roles in LNM have not been fully elucidated. Here, crucial ECM-related genes responsible for LNM in CRC were selected by multi-omics analysis.

Methods

Firstly, we characterized the immune infiltration landscape of CRC samples from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases by using ssGSEA algorithm. The CRC patients were divided into several immune subgroups by hierarchical clustering analyses. Then, differential genes were identified among immune subgroups and CRC vs. normal tissues in TCGA and GEO GSE39582 cohorts, respectively. Next, weighted correlation network analysis (WGCNA) was employed to construct a co-expression network to find LNM-related modules and hub genes. Subsequently, we evaluated the clinical value of hub gene in prognostic prediction and chemotherapy/immunotherapy. Besides, the protein level of key gene was verified in an external cohort from our center. Finally, we explored the underlying mechanism of FSTL3-mediated LNM by Gene function annotation and correlation analysis.

Results

Two immune subgroups, namely Immunity_High and Immunity_Low, were defined among the two CRC cohorts using ssGSEA algorithm, respectively. Based on the two immune subgroups, 2,635 overlapping differentially expressed genes were obtained from two cohorts, which were sequentially subjected to WGCNA and univariate Cox regression analysis. Ultimately, FSTL3 was selected as the key gene. Here, we first confirmed that overexpression of FSTL3 correlated with LNM and worse prognosis in CRC and was verified at the protein level in the external validation cohort. Moreover, FSTL3 expression showed strongly positive correlation with immune and stromal components in ECM. We furthermore found that FSTL3 may accelerate LNM through the formation of inhibitory immune microenvironment via promoting macrophage and fibroblast polarization and T cell exhaustion. Interestingly, high FSTL3 expression is linked to chemoresistance, but immunotherapy-sensitive.

Conclusion

FSTL3 is identified as a biomarker for ECM remodeling and worse clinical outcomes for the first time in CRC and is also a potential immunotherapeutic target to block LNM for CRC.
The Impact of Regional Industrial Structure Upgrading on the Economic Growth of Marine Fisheries in China—The Perspective of Industrial Structure Advancement and Rationalization
Authors: Wang Bo , Han Limin , Zhang Hongzhi
Published: July 2021

From the perspective of industrial structure advancement and rationalization, this paper studied the impact of regional industrial structure upgrading on the economic growth of marine fisheries through theoretical analysis and empirical tests. The results show the effects of different industrial structure upgrading on the economic growth of marine fisheries is varied. The advancement evolution has a “suppression effect,” while rationalization evolution has a “promotion effect.” The adverse impact of advancement evolution is greater than the favorable impact of rationalization evolution. Therefore, the development of marine fisheries reduces this unfavorable impact from advancement evolution by accelerating the transformation of innovation-driven internal combustion and creating new kinetic energy and fostering new business forms; it is also necessary to coordinate regional structure upgrading and industrial internal structure adjustment, promote the effect of structural rationalization, strengthen internal and external linkages, and improve the overall effectiveness of marine fisheries.
Physiological and Genomic Characterization of a Hyperthermophilic Archaeon Archaeoglobus neptunius sp. nov. Isolated From a Deep-Sea Hydrothermal Vent Warrants the Reclassification of the Genus Archaeoglobus
Authors: Slobodkina Galina , Allioux Maxime , Merkel Alexander , Cambon-Bonavita Marie-Anne , Alain Karine , Jebbar Mohamed , Slobodkin Alexander
Published: July 2021

Hyperthermophilic archaea of the genus Archaeoglobus are the subject of many fundamental and biotechnological researches. Despite their significance, the class Archaeoglobi is currently represented by only eight species obtained as axenic cultures and taxonomically characterized. Here, we report the isolation and characterization of a new species of Archaeoglobus from a deep-sea hydrothermal vent (Mid-Atlantic Ridge, TAG) for which the name Archaeoglobus neptunius sp. nov. is proposed. The type strain is SE56T (=DSM 110954T = VKM B-3474T). The cells of the novel isolate are motile irregular cocci growing at 50–85°C, pH 5.5–7.5, and NaCl concentrations of 1.5–4.5% (w/v). Strain SE56T grows lithoautotrophically with H2 as an electron donor, sulfite or thiosulfate as an electron acceptor, and CO2/HCO3− as a carbon source. It is also capable of chemoorganotrophic growth by reduction of sulfate, sulfite, or thiosulfate. The genome of the new isolate consists of a 2,115,826 bp chromosome with an overall G + C content of 46.0 mol%. The whole-genome annotation confirms the key metabolic features of the novel isolate demonstrated experimentally. Genome contains a complete set of genes involved in CO2 fixation via reductive acetyl-CoA pathway, gluconeogenesis, hydrogen and fatty acids oxidation, sulfate reduction, and flagellar motility. The phylogenomic reconstruction based on 122 conserved single-copy archaeal proteins supported by average nucleotide identity (ANI), average amino acid identity (AAI), and alignment fraction (AF) values, indicates a polyphyletic origin of the species currently included into the genus Archaeoglobus, warranting its reclassification.
Hyper-Aerotolerant Campylobacter coli From Swine May Pose a Potential Threat to Public Health Based on Its Quinolone Resistance, Virulence Potential, and Genetic Relatedness
Authors: Guk Jae-Ho , Song Hyokeun , Yi Saehah , An Jae-Uk , Lee Soomin , Kim Woo-Hyun , Cho Seongbeom
Published: July 2021

Campylobacter, a major foodborne pathogen, is susceptible to oxygen. Recently, aerotolerant Campylobacter with enhanced tolerance to aerobic stress has become a major concern in food safety. However, the aerotolerance of Campylobacter coli from pigs has not been studied extensively. Here, we sought to investigate the prevalence of C. coli across multiple swine groups in farms, including weaning, growing, and fattening pigs in production stages and pregnant sows. Additionally, we analyzed C. coli aerotolerance, quinolone resistance, virulence potential, and multilocus sequence typing (MLST) genotypes. Finally, we compared the characteristics of C. coli according to the aerotolerance levels. In total, we obtained 124 (66.3%) C. coli isolates from 187 swine fecal samples across six swine farms. The pathogen was prevalent in weaning (45.5%), growing (68.3%), and fattening (75.4%) pigs, and pregnant sows (66.7%). Hyper-aerotolerant HAT C. coli (13.7% of 124 isolates) was present in all swine groups, with the highest proportion in the pregnant sows (27.3%). All HAT isolates possessed diverse virulence-related genes such as flaA, cadF, pldA, ceuE, and cdtA. All C. coli isolates were resistant to quinolones, and 12 (10%) presented high-level ciprofloxacin resistance (MIC ≥ 32 μg/mL). The proportion of C. coli isolates with a high-level ciprofloxacin resistance was the highest in HAT C. coli (18.8%). Furthermore, six MLST sequence types (STs) (ST827, ST830, ST854, ST1016, ST1068, and ST1096) of swine-derived C. coli were in common with human-derived C. coli (PubMLST). The proportion of C. coli belonging to such shared STs at each aerotolerance level was the highest in HAT C. coli (HAT vs. oxygen-sensitive; OR = 3.13). In conclusion, quinolone resistance of C. coli may be distributed throughout in all swine groups in farms. HAT C. coli is likely to remain in pig farms and re-infect other pigs in the farms. Furthermore, swine-derived HAT C. coli could be transmitted to humans easily through the food chain owing to its aerotolerance, and it could pose a threat to public health owing to its high-level ciprofloxacin resistance and virulence. This study highlights the need to develop management practices that prevent the transmission of swine-derived HAT C. coli to humans.
Phylogeny of the Varidnaviria Morphogenesis Module: Congruence and Incongruence With the Tree of Life and Viral Taxonomy
Authors: Woo Anthony C. , Gaia Morgan , Guglielmini Julien , Da Cunha Violette , Forterre Patrick
Published: July 2021

Double-stranded DNA viruses of the realm Varidnaviria (formerly PRD1-adenovirus lineage) are characterized by homologous major capsid proteins (MCPs) containing one (kingdom: Helvetiavirae) or two β-barrel domains (kingdom: Bamfordvirae) known as the jelly roll folds. Most of them also share homologous packaging ATPases (pATPases). Remarkably, Varidnaviria infect hosts from the three domains of life, suggesting that these viruses could be very ancient and share a common ancestor. Here, we analyzed the evolutionary history of Varidnaviria based on single and concatenated phylogenies of their MCPs and pATPases. We excluded Adenoviridae from our analysis as their MCPs and pATPases are too divergent. Sphaerolipoviridae, the only family in the kingdom Helvetiavirae, exhibit a complex history: their MCPs are very divergent from those of other Varidnaviria, as expected, but their pATPases groups them with Bamfordvirae. In single and concatenated trees, Bamfordvirae infecting archaea were grouped with those infecting bacteria, in contradiction with the cellular tree of life, whereas those infecting eukaryotes were organized into three monophyletic groups: the Nucleocytoviricota phylum, formerly known as the Nucleo-Cytoplasmic Large DNA Viruses (NCLDVs), Lavidaviridae (virophages) and Polintoviruses. Although our analysis mostly supports the recent classification proposed by the International Committee on Taxonomy of Viruses (ICTV), it also raises questions, such as the validity of the Adenoviridae and Helvetiavirae ranking. Based on our phylogeny, we discuss current hypotheses on the origin and evolution of Varidnaviria and suggest new ones to reconcile the viral and cellular trees.
Alternative Splicing of MoPTEN Is Important for Growth and Pathogenesis in Magnaporthe oryzae
Authors: Wang Shaowei , Liang Hao , Wei Yi , Zhang Penghui , Dang Yuejia , Li Guihua , Zhang Shi-Hong
Published: July 2021

Human PTEN, a dual-phosphatase tumor suppressor, is frequently dysregulated by alternative splicing. Fungi harbor PTEN homologs, but alternative splicing of fungal PTENs has not been reported as far as we know. Here, we described an alternative splicing case in the PTEN homolog of Magnaporthe oryzae (MoPTEN). Two splice variants of MoPTEN were detected and identified, which are resulted from an intron retention and exclusion (MoPTEN-1/2). Both proteins were different in lipid and protein phosphatase activity and in expression patterns. The MoPTEN deletion mutant (ΔMoPTEN) showed the defects in conidiation, appressorium formation, and pathogenesis. ΔMoPTEN could be completely restored by MoPTEN, but rescued partially by MoPTEN-1 in the defect of conidium and appressorium formation, and by MoPTEN-2 in the defect of invasive development. Assays to assess sensitivity to oxidative stress reveal the involvement of MoPTEN-2 in scavenging exogenous and host-derived H2O2. Taken together, MoPTEN undergoes alternative splicing, and both variants cooperatively contribute to conidium and appressorium development, and invasive hyphae growth in plant cells, revealing a novel disease development pathway in M. oryzae.
A Daytime Nap Does Not Enhance the Retention of a First-Order or Second-Order Motor Sequence
Authors: Barham Michael P. , Lum Jarrad A. G. , Conduit Russell , Fernadez Lara , Enticott Peter G. , Clark Gillian M.
Published: July 2021

This study examined the effects of a daytime nap on the retention of implicitly learnt “first-order conditional” (FOC) and “second-order conditional” (SOC) motor sequences. The implicit learning and retention of a motor sequence has been linked to the neural processes undertaken by the basal ganglia and primary motor cortex (i.e., procedural memory system). There is evidence, however, suggesting that SOC learning may further rely on the hippocampus-supported declarative memory system. Sleep appears to benefit the retention of information processed by the declarative memory system, but not the procedural memory system. Thus, it was hypothesized that sleep would benefit the retention of a SOC motor sequence but not a FOC sequence. The implicit learning and retention of these sequences was examined using the Serial Reaction Time Task. In this study, healthy adults implicitly learnt either a FOC (n = 20) or a SOC sequence (n = 20). Retention of both sequences was assessed following a daytime nap and period of wakefulness. Sleep was not found to improve the retention of the SOC sequence. There were no significant differences in the retention of a FOC or a SOC sequence following a nap or period of wakefulness. The study questions whether the declarative memory system is involved in the retention of implicitly learnt SOC sequences.
Case Report: Improving Verbal Retrieval Deficits With High Definition Transcranial Direct Current Stimulation Targeting the Pre-Supplementary Motor Area in a Patient With Chronic Traumatic Brain Injury
Authors: Chiang Hsueh-Sheng , Shakal Scott , Vanneste Sven , Kraut Michael , Hart John
Published: July 2021

We report a patient who has cognitive sequalae including verbal retrieval deficits after severe traumatic brain injury (TBI). The cortico-caudate-thalamic circuit involving the pre-Supplementary Motor Area (pre-SMA) has been proposed to underlie verbal retrieval functions. We hypothesized that High Definition-transcranial Direct Current Stimulation (HD-tDCS) targeting the pre-SMA would selectively modulate this circuit to remediate verbal retrieval deficits. After the patient underwent 10 sessions of 20 min of 1 mA HD-tDCS targeting the pre-SMA, we documented significant improvements for verbal fluency and naming, and for working memory and executive function tasks that involve the frontal lobes. The effects persisted for up to 14 weeks after completion of HD-tDCS treatment. We also demonstrated normalization of the event-related potentials suggesting modulation of the underlying neural circuit. Our study implicates that region-specific non-invasive brain stimulation, such as HD-tDCS, serves as a potential individualized therapeutic tool to treat cognitive deficits by inducing longer-lasting neuroplasticity even in the chronic phase of TBI.
Determination of Dynamic Brain Connectivity via Spectral Analysis
Authors: Robinson Peter A. , Henderson James A. , Gabay Natasha C. , Aquino Kevin M. , Babaie-Janvier Tara , Gao Xiao
Published: July 2021

Spectral analysis based on neural field theory is used to analyze dynamic connectivity via methods based on the physical eigenmodes that are the building blocks of brain dynamics. These approaches integrate over space instead of averaging over time and thereby greatly reduce or remove the temporal averaging effects, windowing artifacts, and noise at fine spatial scales that have bedeviled the analysis of dynamical functional connectivity (FC). The dependences of FC on dynamics at various timescales, and on windowing, are clarified and the results are demonstrated on simple test cases, demonstrating how modes provide directly interpretable insights that can be related to brain structure and function. It is shown that FC is dynamic even when the brain structure and effective connectivity are fixed, and that the observed patterns of FC are dominated by relatively few eigenmodes. Common artifacts introduced by statistical analyses that do not incorporate the physical nature of the brain are discussed and it is shown that these are avoided by spectral analysis using eigenmodes. Unlike most published artificially discretized “resting state networks” and other statistically-derived patterns, eigenmodes overlap, with every mode extending across the whole brain and every region participating in every mode—just like the vibrations that give rise to notes of a musical instrument. Despite this, modes are independent and do not interact in the linear limit. It is argued that for many purposes the intrinsic limitations of covariance-based FC instead favor the alternative of tracking eigenmode coefficients vs. time, which provide a compact representation that is directly related to biophysical brain dynamics.
Therapeutic Potential of Neoechinulins and Their Derivatives: An Overview of the Molecular Mechanisms Behind Pharmacological Activities
Authors: Sharifi-Rad Javad , Bahukhandi Amit , Dhyani Praveen , Sati Priyanka , Capanoglu Esra , Docea Anca Oana , Al-Harrasi Ahmed , Dey Abhijit , Calina Daniela
Published: July 2021

Neoechinulins are diketopiperazine type indole alkaloids that demonstrate radical scavenging, anti-inflammatory, antiviral, anti-neurodegenerative, neurotrophic factor-like, anticancer, pro-apoptotic, and anti-apoptotic properties. An array of neoechinulins such as neoechinulins A-E, isoechinulins A-C, cryptoechunilin have been isolated from various fungal sources like Aspergillus sp., Xylaria euglossa, Eurotium cristatum, Microsporum sp., etc. Besides, neoechinulin derivatives or stereoisomers were also obtained from diverse non-fungal sources viz. Tinospora sagittata, Opuntia dillenii, Cyrtomium fortunei, Cannabis sativa, and so on. The main purpose of this review is to provide update information on neoechinulins and their analogues about the molecular mechanisms of the pharmacological action and possible future research. The recent data from this review can be used to create a basis for the discovery of new neoechinulin-based drugs and their analogues in the near future. The online databases PubMed, Science and Google scholar were researched for the selection and collection of data from the available literature on neoechinulins, their natural sources and their pharmacological properties. The published books on this topic were also analysed. In vitro and in vivo assays have established the potential of neoechinulin A as a promising anticancer and anti-neuroinflammatory lead molecule. Neoechinulin B was also identified as a potential antiviral drug against hepatitis C virus. Toxicological and clinical trials are needed in the future to improve the phyto-pharmacological profile of neoquinolines. From the analysis of the literature, we found that neoechinulins and their derivatives have special biological potential. Although some modern pharmacological analyzes have highlighted the molecular mechanisms of action and some signalling pathways, the correlation between these phytoconstituents and pharmacological activities must be validated in the future by preclinical toxicological and clinical studies.
Ketogenic Diets and Chronic Disease: Weighing the Benefits Against the Risks
Authors: Crosby Lee , Davis Brenda , Joshi Shivam , Jardine Meghan , Paul Jennifer , Neola Maggie , Barnard Neal D.
Published: July 2021

Very-low-carbohydrate ketogenic diets have been long been used to reduce seizure frequency and more recently have been promoted for a variety of health conditions, including obesity, diabetes, and liver disease. Ketogenic diets may provide short-term improvement and aid in symptom management for some chronic diseases. Such diets affect diet quality, typically increasing intake of foods linked to chronic disease risk and decreasing intake of foods found to be protective in epidemiological studies. This review examines the effects of ketogenic diets on common chronic diseases, as well as their impact on diet quality and possible risks associated with their use. Given often-temporary improvements, unfavorable effects on dietary intake, and inadequate data demonstrating long-term safety, for most individuals, the risks of ketogenic diets may outweigh the benefits.
Refractory Head and Neck Lymphatic Malformation in Infants Treated With Sirolimus: A Case Series
Authors: Wu Changhua , Song Dan , Guo Lei , Wang Liang
Published: July 2021

Background

Extensive and complex head and neck lymphatic malformations (LMs) are challenging to manage through traditional therapy. The purpose of this retrospective study was to assess the efficacy and safety of sirolimus in infants with refractory head and neck LMs.

Methods

Sirolimus was administered orally on a continuous dosing schedule. Patients were seen every month for the first three months and then subsequently every three months. The primary endpoints were safety and efficacy based on clinical and radiological evaluations.

Results

Eight patients, refractory to standard care, were enrolled and received sirolimus continuously. After 12 months of follow-up, the response and safety to medication was evaluated: all patients experienced reductions in LMs bulk, ranging from modest to significant. Some minor adverse effects were reported: mouth sores, eczema, gastrointestinal reaction, dyslipidemia, and neutropenia.

Conclusion

Sirolimus was efficient in children with refractory head and neck LMs and was well tolerated.
Prediction of Survival and Analysis of Prognostic Factors for Patients With Combined Hepatocellular Carcinoma and Cholangiocarcinoma: A Population-Based Study
Authors: Wang Jitao , Li Zhi , Liao Yong , Li Jinlong , Dong Hui , Peng Hao , Xu Wenjing , Fan Zhe , Gao Fengxiao , Liu Chengyu , Liu Dengxiang , Zhang Yewei
Published: July 2021

Background

Combined hepatocellular carcinoma and cholangiocarcinoma (CHC) is an uncommon subtype of primary liver cancer. Because of limited epidemiological data, prognostic risk factors and therapeutic strategies for patients with CHC tend to be individualized. This study aimed to identify independent prognostic factors and develop a nomogram-based model for predicting the overall survival (OS) of patients with CHC.

Methods

We recruited eligible individuals from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 and randomly divided them into the training or verification cohort. Univariate and multivariate analyses were performed to identify independent variables associated with OS. Based on multivariate analysis, the nomogram was established, and its prediction performance was evaluated using the consistency index (C-index) and calibration curve.

Results

In total, 271 patients with CHC were included in our study. The median OS was 14 months, and the 1-, 3-, and 5-year OS rates were 52.3%, 27.1%, and 23.3%, respectively. In the training cohort, multivariate analysis showed that the pathological grade (hazard ratio [HR], 1.26; 95% confidence interval [CI]: 0.96–1.66), TNM stage (HR, 1.21; 95% CI: 1.02 - 1.44), and surgery (HR, 0.26; 95% CI: 0.17 - 0.40) were independent indicators of OS. The nomogram-based model related C-indexes were 0.76 (95% CI: 0.72 - 0.81) and 0.72 (95% CI: 0.66 - 0.79) in the training and validation cohorts, respectively. The calibration of the nomogram showed good consistency of 1-, 3-, and 5-year OS rates between the actual observed survival and predicted survival in both cohorts. The TNM stage (HR, 1.23; 95% CI: 1.01 - 1.49), and M stage (HR, 1.87; 95% CI: 1.14 3.05) were risk factors in the surgical treatment group. Surgical resection and liver transplantation could significantly prolong the survival, with no statistical difference observed.

Conclusions

The pathological grade, TNM stage, and surgery were independent prognostic factors for patients with CHC. We developed a nomogram model, in the form of a static nomogram or an online calculator, for predicting the OS of patients with CHC, with a good predictive performance.
Application Research of Individualized Conditional Reprogramming System to Guide Treatment of Gastric Cancer
Authors: Zhao Weizhu , Liu Kai , Sun Zhikun , Wang Longgang , Liu Bing , Liu Luguang , Qu Xianlin , Cao Zhixiang , Sun Jujie , Chai Jie
Published: July 2021

Background

Gastric cancer (GC) is one of the most common causes of malignant tumors in the world. Due to the high heterogeneity of GC and lack of specificity of available chemotherapy regimens, these tumors are prone to resistance, recurrence, and metastasis. Here, we formulated an individualized chemotherapy regimen for GC using a modified individual conditional reprogramming (i-CR) system. We established a primary tumor cell bank of GC cells and completed drug screening in order to realize individualized and accurate GC treatment.

Methods

We collected specimens from 93 surgical or gastroscopy GC cases and established a primary tumor cell bank using the i-CR system and PDX models. We also completed in vitro culture and drug sensitivity screening of the GC cells using the i-CR system. Whole-exome sequencing (WES) of the i-CR cells was performed using P0 and P5. We then chose targeted chemotherapy drugs based on the i-CR system results.

Results

Of the 72 cases that were collected from surgical specimens, 26 cases were successfully cultured with i-CR system, and of the 21 cases collected from gastroscopy specimens, seven were successfully cultured. Among these, 20 cases of the PDX model were established. SRC ± G3 had the highest culture success rate. The i-CR cells of P0 and P5 appeared to be highly conserved. According to drug sensitivity screening, we examined the predictive value of responses of GC patients to chemotherapeutic agents, especially in neoadjuvant patients.

Conclusion

The i-CR system does not only represent the growth characteristics of tumors in vivo, but also provides support for clinical drug use. Drug susceptibility results were relatively consistent with clinical efficacy.
Case Report: Long-Term Tolvaptan Treatment in a Child With SIADH and Suprasellar Arachnoid Cyst
Authors: Puma Andrea , Brugnara Milena , Cavarzere Paolo , Zaffanello Marco , Piacentini Giorgio , Gaudino Rossella
Published: July 2021

Suprasellar arachnoid cysts represent a rare occurrence in the pediatric population and usually cause symptoms related to mass effect and can occasionally cause endocrine dysfunctions. The association between SAC and the syndrome of inappropriate antidiuretic hormone (SIADH) in the pediatric population has rarely been described previously. In most cases, SIADH is temporary and resolves by treating the underlying cause. The first-line treatment consists of fluid restriction in asymptomatic children. Oral urea and demeclocycline are other effective treatment options. Vaptans are a new class of medication for the management of SIADH. These agents are a nonpeptide vasopressin V2 receptor antagonist that selectively antagonizes the antidiuretic effect of AVP, resulting in excretion of diluted urine or “aquaresis.” Their efficacy has been shown in adult patients with euvolemic or hypervolemic hyponatremia. However, evidence is lacking in pediatric patients with SIADH. We report the case of a 9-year-old female child with a SAC, who underwent endoscopic fenestration at the age of 2 years. After surgery she developed chronic hyponatremia due to SIADH. Hyponatremia was refractory to treatment with fluid restriction, oral sodium, and urea. In order to normalize serum sodium levels, tolvaptan treatment was started on a compassionate-use basis; 24–48 h later serum sodium levels returned to normal. To date, tolvaptan has been used regularly for 6 years with no side effects occurring during the treatment period. This is the first case of a child with chronic SIADH secondary to SAC successfully treated with tolvaptan. Further studies are needed to demonstrate its usefulness on a broader case series.
Honeymoon Period in Newborn Rats With CDH Is Associated With Changes in the VEGF Signaling Pathway
Authors: Miura da Costa Karina , Fabro Alexandre Todorovic , Becari Christiane , Figueira Rebeca Lopes , Schmidt Augusto F. , Ruano Rodrigo , Sbragia Lourenço
Published: July 2021

Background: Patients with congenital diaphragmatic hernia (CDH) have a short postnatal period of ventilatory stability called the honeymoon period, after which changes in pulmonary vascular reactivity result in pulmonary hypertension. However, the mechanisms involved are still unknown. The aim of this study was to evaluate mechanical ventilation's effect in the honeymoon period on VEGF, VEGFR-1/2 and eNOS expression on experimental CDH in rats.

Materials and Methods: Neonates whose mothers were not exposed to nitrofen formed the control groups (C) and neonates with left-sided defects formed the CDH groups (CDH). Both were subdivided into non-ventilated and ventilated for 30, 60, and 90 min (n = 7 each). The left lungs (n = 4) were evaluated by immunohistochemistry of the pulmonary vasculature (media wall thickness), VEGF, VEGFR-1/2 and eNOS. Western blotting (n = 3) was performed to quantify the expression of VEGF, VEGFR-1/2 and eNOS.

Results: CDH had lower biometric parameters than C. Regarding the pulmonary vasculature, C showed a reduction in media wall thickness with ventilation, while CDH presented reduction with 30 min and an increase with the progression of the ventilatory time (honeymoon period). CDH and C groups showed different patterns of VEGF, VEGFR-1/2 and eNOS expressions. The receptors and eNOS findings were significant by immunohistochemistry but not by western blotting, while VEGF was significant by western blotting but not by immunohistochemistry.

Conclusion: VEGF, its receptors and eNOS were altered in CDH after mechanical ventilation. These results suggest that the VEGF-NO pathway plays an important role in the honeymoon period of experimental CDH.
Case Report: Two Distinct Focal Congenital Hyperinsulinism Lesions Resulting From Separate Genetic Events
Authors: Rosenfeld Elizabeth , Mitteer Lauren , Boodhansingh Kara , Becker Susan A. , McKnight Heather , Boyajian Linda , Ackermann Amanda M. , Kalish Jennifer M. , Bhatti Tricia R. , States Lisa J. , Adzick N. Scott , Lord Katherine , De León Diva D.
Published: July 2021

Focal hyperinsulinism (HI) comprises nearly 50% of all surgically treated HI cases and is cured if the focal lesion can be completely resected. Pre-operative localization of the lesion is thus critical. Few cases of hyperinsulinism with multiple focal lesions have been reported, and assessment of the molecular mechanisms driving this rare occurrence has been limited. We present two cases of multifocal HI, each resulting from two independent, pancreatic focal lesions. 18Fluoro-dihydroxyphenylalanine positron emission tomography/computed tomography detected both lesions preoperatively in one patient, whereas identification of the second lesion was an incidental finding during surgical exploration in the other. Complete resection of the focal lesions resulted in cure of the HI in both cases. In each patient, genetic testing of the individual focal lesions revealed different regions of loss of heterozygosity for the maternal 11p15 allele, confirming that each lesion arose from independent somatic events in the setting of a paternally inherited germline ABCC8 mutation. These cases highlight the importance of a multidisciplinary and personalized approach to the management of infants with HI.
Potentials of Antitussive Traditional Persian Functional Foods for COVID-19 Therapy†
Authors: Mosleh Ghazaleh , Badr Parmis , Zaeri Meysam , Mohagheghzadeh Abdolali
Published: July 2021

Coronavirus disease 2019 is a worldwide pandemic resulting in a severe acute respiratory syndrome. Remdesivir is the only FDA-approved drug for hospitalized patients older than age 12. It shows the necessity of finding new therapeutic strategies. Functional foods (FFs) could have co-therapeutic and protective effects against COVID-19 infection. Traditional Persian medicine (TPM), one of the safest and most popular schools of medicine for hundreds of years, has recommended potential FF candidates to manage such a global pandemic. To reveal the potential of TPM in terms of antitussive FFs, traditional Persian pharmacopoeia “Qarabadin-e-Salehi” was searched using the keywords “Soaal” and “Sorfeh.” Also, a search of MEDLINE, PubMed Central, Google Scholar, and Science Direct was performed for the relevant literature published from the inception up to March 2021. A combination of search terms including “cough, antitussive, antioxidant, anti-inflammation, antiviral, COVID-19, mucoactive, mucolytic, expectorant, and mucoregulatory” was also applied. The potential mechanism of action in SARS-CoV-2 infection was discussed. Twelve TPM FFs were found including Laooqs, Morabbas, a Saviq, a soup, and a syrup. They are combinations of two to seven ingredients. Natural compounds of mentioned formulations have the main pharmacological mechanisms including antiviral, anti-inflammatory, antioxidant, antihistamine, bronchodilator, immunomodulatory, and mucoactive effects as well as central or peripheral antitussive activities. FFs are cost-effective, easily accessible, and safe options for both treatment and prevention of COVID-19. They might have positive psychological effects along with their pharmacological effects and nutritional virtues. They could also manage persistent respiratory discomforts after recovery from COVID-19.
Large-Scale Transcriptome Analysis Identified a Novel Cancer Driver Genes Signature for Predicting the Prognostic of Patients With Hepatocellular Carcinoma
Authors: Li Gao , Du Xiaowei , Wu Xiaoxiong , Wu Shen , Zhang Yufei , Xu Jing , Wang Hao , Chen Tingsong
Published: July 2021

Background: Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality and heterogeneity. Genetic mutations caused by driver genes are important contributors to the formation of the tumor microenvironment. The purpose of this study is to discuss the expression of cancer driver genes in tumor tissues and their clinical value in predicting the prognosis of HCC.

Methods: All data were sourced from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and Gene Expression Omnibus (GEO) public databases. Differentially expressed and prognostic genes were screened by the expression distribution of the cancer driver genes and their relationship with survival. Candidate genes were subjected to functional enrichment and transcription factor regulatory network. We further constructed a prognostic signature and analyzed the survival outcomes and immune status between different risk groups.

Results: Most cancer driver genes are specifically expressed in cancer tissues. Driver genes may influence HCC progression through processes such as transcription, cell cycle, and T-cell receptor-related pathways. Patients in different risk groups had significant survival differences (p < 0.05), and risk scores showed high predictive efficacy (AUC>0.69). Besides, risk subgroups were also associated with multiple immune functions and immune cell content.

Conclusion: We confirmed the critical role of cancer driver genes in mediating HCC progression and the immune microenvironment. Risk subgroups contribute to the assessment of prognostic value in different patients and explain the heterogeneity of HCC.
The Efficacy and Safety of Chinese Herbal Medicine Xianling Gubao Capsule Combined With Alendronate in the Treatment of Primary Osteoporosis: A Systematic Review and Meta-Analysis of 20 Randomized Controlled Trials
Authors: Chen Jiaru , Zheng Junju , Chen Mangmang , Lin Shenglei , Lin Zhou
Published: July 2021

Objective: Herein, we purposed to evaluate the efficacy along with the safety of Xianling Gubao capsule (XLGB) combined with alendronate (ALE) for primary osteoporosis (POP) from the current literature.

Materials and Methods: We carried out a search for electronic literature in the PubMed, Chinese National Knowledge Infrastructure, EMBASE, Wanfang Web of Science, Chinese Biomedical Literature Database, Cochrane Library, as well as Chinese VIP databases targeting articles published from inception to December 2020. Only randomized controlled trials (RCTs) were enrolled into the study. Alkaline phosphatase (ALP), visual analogue scale (VAS), serum phosphorus (S-P), bone gla protein (BGP), serum calcium (S-Ca) and bone mineral density (BMD) were the primary outcome variable. The total clinical effective rate along with the adverse drug reaction (ADR) were the secondary outcome variables. The meta-analysis was conducted using RevMan 5.3 and STATA 12.0. GRADE pro3.6.1 software was used for the assessment of evidence quality.

Results: Overall, 20 RCTs focusing on 1911 patients were enrolled into the study. Our meta-analysis demonstrated that XLGB combined with ALE remarkably increased BMD (p < 0.001), BGP (p < 0.001), S-Ca (p < 0.001), S-P (p < 0.001) and effective rate (p < 0.001) than ALE alone in patients with POP. Moreover, ALP (p < 0.001) and VAS (p < 0.001) were overtly by decreased XLGB. However, XLGB combined with ALE would not markedly increase the rate of ADR in contrast with ALE alone (p = 0.499).

Conclusion: The results of our study demonstrated that XLGB is a potential candidate for OP treatment. We recommend that rigorous, as well as high-quality trials involving large samples sizes should be conducted to confirm our findings.
The Role of High-Density Lipoprotein in COVID-19
Authors: Wang Guyi , Deng Jiayi , Li Jinxiu , Wu Chenfang , Dong Haiyun , Wu Shangjie , Zhong Yanjun
Published: July 2021

The current Coronavirus disease 2019 (COVID-19) pandemic has become a global challenge. Managing a large number of acutely ill patients in a short time, whilst reducing the fatality rate and dealing with complications, brings unique difficulties. The most striking pathophysiological features of patients with severe COVID-19 are dysregulated immune responses and abnormal coagulation function, which can result in multiple-organ failure and death. Normally metabolized high-density lipoprotein (HDL) performs several functions, including reverse cholesterol transport, direct binding to lipopolysaccharide (LPS) to neutralize LPS activity, regulation of inflammatory response, anti-thrombotic effects, antioxidant, and anti-apoptotic properties. Clinical data shows that significantly decreased HDL levels in patients with COVID-19 are correlated with both disease severity and mortality. However, the role of HDL in COVID-19 and its specific mechanism remain unclear. In this analysis, we review current evidence mainly in the following areas: firstly, the pathophysiological characteristics of COVID-19, secondly, the pleiotropic properties of HDL, thirdly, the changes and clinical significance of HDL in COVID-19, and fourthly the prospect of HDL-targeting therapy in COVID-19 to clarify the role of HDL in the pathogenesis of COVID-19 and discuss the potential of HDL therapy in COVID-19.
Review of Driving Waveform for Electrowetting Displays
Authors: Yi Zichuan , Zhang Hu , Zeng Wenjun , Feng Haoqiang , Long Zhengxing , Liu Liming , Hu Yunfeng , Zhou Xichen , Zhang Chongfu
Published: July 2021

Electrowetting display (EWD) is the most potential technology among new electronic paper technologies. It not only has the advantages of electrophoretic display (EPD) technology but also can realize color video playback. Therefore, this technology has been widely studied in recent years. Driving waveform is a voltage sequence which can drive pixels to display gray scales in EWDs. As one of the key technologies, it directly affects the display effect of pixels. In this paper, we give a review of the display principle of EWDs and the research status of driving waveforms. At the same time, the contact angle hysteresis, charge trapping, and oil splitting are also reviewed, which can provide a reference value for designing driving waveforms.
A Contemporary View of Natriuretic Peptides in the SARS-CoV-2 Era
Authors: Rubattu Speranza , Gallo Giovanna , Volpe Massimo
Published: July 2021

The heart releases natriuretic peptides (NPs) which represent an important hormonal axis with cardiorenal protective effects. In view of their properties, NPs have pathophysiologic, diagnostic and prognostic implications in several cardiovascular diseases (CVDs). Severe pulmonary inflammation, as induced by the SARS-COV2, may increase pulmonary pressure with potential influence on NPs release, whereby normal cardiovascular integrity becomes impaired. Moreover, pre-existing CVDs are strong negative prognostic factors since they exacerbate the effects of the viral infection and lead to worse outcomes. In this context, it may be expected that NPs exert a key protective role toward the virus infection whereas an impairment of NPs release contributes to the virus deleterious effects. In this review article we explore the potential involvement of NPs in the COVID-19 disease. To this aim, we will first focus on the interactions between NPs and the Ang II/ATIR arm of the renin-angiotensin-aldosterone system (RAAS) as well as with the protective ACE2/Ang (1-7) arm of the RAAS. Subsequently, we will review evidence that strongly supports the role of increased NT-proBNP level as a marker of cardiac damage and of worse prognosis in the COVID-19 affected patients. Finally, we will discuss the potential therapeutic benefits of these protective hormones toward the viral infection through their endothelial protective function, anti-inflammatory and anti-thrombotic effects. In conclusion, the potential implications of NPs in the SARS-CoV-2 infection, as discussed in our article, represent an important issue that deserves to be fully investigated.
Substantial and Reproducible Individual Variability in Skeletal Muscle Outcomes in the Cross-Over Designed Planica Bed Rest Program
Authors: Fernandez-Gonzalo Rodrigo , McDonnell Adam C. , Simpson Elizabeth J. , Macdonald Ian A. , Rullman Eric , Mekjavic Igor B.
Published: July 2021

To evaluate the individual responses in skeletal muscle outcomes following bed rest, data from three studies (21-day PlanHab; 10-day FemHab and LunHab) were combined. Subjects (n = 35) participated in three cross-over campaigns within each study: normoxic (NBR) and hypoxic bed rest (HBR), and hypoxic ambulation (HAMB; used as control). Individual variability (SDIR) was investigated as √(SDExp2–SDCon2), where SDExp and SDCon are the standard deviations of the change score (i.e., post – pre) in the experimental (NBR and HBR) and the control (HAMB) groups, respectively. Repeatability and moderators of the individual variability were explored. Significant SDIR was detected for knee extension torque, and thigh and calf muscle area, which translated into an individual response ranging from 3 to −17% for knee extension torque, −2 to −12% for calf muscle area, and −1 to −8% for thigh muscle area. Strong correlations were found for changes in NBR vs. HBR (i.e., repeatability) in thigh and calf muscle area (r = 0.65–0.75, P < 0.0001). Change-scores in knee extension torque, and thigh and calf muscle area strongly correlated with baseline values (P < 0.001; r between −0.5 and −0.9). Orthogonal partial least squares regression analysis explored if changes in the investigated variables could predict calf muscle area alterations. This analysis indicated that 43% of the variance in calf muscle area could be attributed to changes in all of the other variables. This is the first study using a validated methodology to report clinically relevant individual variability after bed rest in knee extension torque, calf muscle area, and (to a lower extent) thigh muscle area. Baseline values emerged as a moderator of the individual response, and a global bed rest signature served as a moderately strong predictor of the individual variation in calf muscle area alterations.
Bayesian Physics-Based Modeling of Tau Propagation in Alzheimer's Disease
Authors: Schäfer Amelie , Peirlinck Mathias , Linka Kevin , Kuhl Ellen ,   The Alzheimer's Disease Neuroimaging Initiative (ADNI)
Published: July 2021

Amyloid-β and hyperphosphorylated tau protein are known drivers of neuropathology in Alzheimer's disease. Tau in particular spreads in the brains of patients following a spatiotemporal pattern that is highly sterotypical and correlated with subsequent neurodegeneration. Novel medical imaging techniques can now visualize the distribution of tau in the brain in vivo, allowing for new insights to the dynamics of this biomarker. Here we personalize a network diffusion model with global spreading and local production terms to longitudinal tau positron emission tomography data of 76 subjects from the Alzheimer's Disease Neuroimaging Initiative. We use Bayesian inference with a hierarchical prior structure to infer means and credible intervals for our model parameters on group and subject levels. Our results show that the group average protein production rate for amyloid positive subjects is significantly higher with 0.019±0.27/yr, than that for amyloid negative subjects with −0.143±0.21/yr (p = 0.0075). These results support the hypothesis that amyloid pathology drives tau pathology. The calibrated model could serve as a valuable clinical tool to identify optimal time points for follow-up scans and predict the timeline of disease progression.
The Impact of Phloem Feeding Insects on Leaf Ecophysiology Varies With Leaf Age
Authors: Pincebourde Sylvain , Ngao Jérôme
Published: July 2021

Herbivore insects have strong impacts on leaf gas exchange when feeding on the plant. Leaf age also drives leaf gas exchanges but the interaction of leaf age and phloem herbivory has been largely underexplored. We investigated the amplitude and direction of herbivore impact on leaf gas exchange across a wide range of leaf age in the apple tree–apple green aphid (Aphis pomi) system. We measured the gas exchange (assimilation and transpiration rates, stomatal conductance and internal CO2 concentration) of leaves infested versus non-infested by the aphid across leaf age. For very young leaves up to 15 days-old, the gas exchange rates of infested leaves were similar to those of non-infested leaves. After few days, photosynthesis, stomatal conductance and transpiration rate increased in infested leaves up to about the age of 30 days, and gradually decreased after that age. By contrast, gas exchanges in non-infested leaves gradually decreased across leaf age such that they were always lower than in infested leaves. Aphids were observed on relatively young leaves up to 25 days and despite the positive effect on leaf photosynthesis and leaf performance, their presence negatively affected the growth rate of apple seedlings. Indeed, aphids decreased leaf dry mass, leaf surface, and leaf carbon content except in old leaves. By contrast, aphids induced an increase in leaf nitrogen content and the deviation relative to non-infested leaves increased with leaf age. Overall, the impacts of aphids at multiple levels of plant performance depend on leaf age. While aphids cause an increase in some leaf traits (gas exchanges and nitrogen content), they also depress others (plant growth rate and carbon content). The balance between those effects, as modulated by leaf age, may be the key for herbivory mitigation in plants.