bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developmental regulation of Dirofilaria immitis microfilariae and evaluation of ecdysone signaling pathway transcript level using droplet digital polymerase chain reaction
Authors: Kuan Tsai-Chi Shang , Prichard Roger K 
Published: October 2020

Abstract
BackgroundCurrent Dirofilaria immitis prevention relies on macrocyclic lactones but evidence of drug-resistant isolates has called for alternative approaches to disease intervention. As microfilariae are known to be in a state of developmental arrest in their mammalian host and then undergo two molts once inside the arthropod, this study aimed to look at the developmental regulation of D. immitis microfilariae that occurs in their arthropod host using in vitro approaches and to investigate the role of the ecdysone signaling system in this development. MethodsD. immitis microfilariae extracted from dog blood were incubated in various media conditions to identify suitable conditions for in vitro culture and development, and to determine the effects of FBS, mosquito cells, and ecdysteroid on the development of the microfilariae. Transcript level of the ecdysone signaling pathway components were measured with droplet digital PCR. ResultsIn vitro conditions that best promote early development of D. immitis microfilariae to the “late sausage stage” have been identified, although shedding of the cuticle was not observed. FBS showed inhibitory effects on the development and motility of the microfilariae, but media conditioned with Anopheles gambiae cells was favorable to microfilarial growth. Transcript level study using droplet digital PCR also showed that developing microfilariae displayed upregulation of the ecdysone signaling system components, and 20‑hydroxyecdysone increased the proportion of larvae developing to the sausage and late sausage stages in vitro.ConclusionsThe arthropod host environment provides cues required for the rapid development of the D. immitis microfilariae and the ecdysone signaling system may play an important role in filarial nematode developmental transitions. This study contributes to a better understanding the developmental process of D. immitis microfilariae.
HBP1-mediated transcriptional regulation of AFP and its impact on hepatoma
Authors: Cao Zhengyi , Cheng Yuning , Wang Jiyin , Liu Yujuan , Yang Ruixiang , Jiang Wei , Li Hui , Zhang Xiaowei 
Published: October 2020

Abstract
Background: Hepatoma is a common malignancy of the liver. The abnormal high expression of alpha-fetoprotein (AFP) is intimately associated with hepatoma progress, but the mechanism of transcriptional regulation and singularly activation of AFP gene in hepatoma is not clear. Methods: The expression of transcription factor HBP1 and AFP and clinical significance were father analyzed in hepatoma tissues from the patients who received surgery or TACE and then monitored for relapse for up 10 years. HBP1-mediated transcriptional regulation of AFP was analyzed by Western blotting, luciferase assay, Realtime-PCR, ChIP and EMSA. After verified the axis of HBP-AFP, its impact on hepatoma was measured by MTT, Transwell and FACS in hepatoma cells and by tumorigenesis in HBP1-/- mice.Results: This study demonstrated that the relative expressions of HBP1 and AFP correlated with decreased survival and prognosis in hepatoma patients. HBP1 represses the expression of AFP gene by directly binding to the AFP gene promoter. Hepatitis B Virus (HBV)-encoded protein HBx promotes malignancy in hepatoma cells through binding to HBP1 directly. Icaritin, an active ingredient of Chinese herb epimedium, inhibits malignancy in hepatoma cells through enhancing HBP1 transrepression of AFP. The repression of AFP by HBP1 attenuates AFP effect on PTEN, MMP9 and caspase-3, thus inhibits proliferation and migration, and induces apoptosis in hepatoma cells. The deregulation of AFP by HBP1 contributes to hepatoma progression in mice. Conclusion: Our data clarify the mechanism of HBP1 in inhibiting the expression of AFP and its suppression in malignancy of hepatoma cells, providing a more comprehensive theoretical basis and potential solutions for the early diagnosis and treatment of hepatoma.
Markers of endothelial and epithelial pulmonary injury in mechanically ventilated COVID-19 ICU patients
Authors: Spadaro Savino , Fogagnolo Alberto , Campo Gianluca , Zucchetti Ottavio , Verri Marco , Ottaviani Irene , Tanushree Tunstall , Grasso Salvatore , Scaramuzzo Valentina , Murgolo Francesco , Marangoni Elisabetta , Sega Francesco Vieceli Dalla , Fortini Francesca , Pavasini Rita , Rizzo Paola , Ferrari Roberto , Papi Alberto , Volta Carlo Alberto , Contoli Marco 
Published: October 2020

Abstract
BackgroundEvaluation of biomarkers in the context of ARDS is used to detect the presence of endothelial and/or alveolar epithelial injuries. Angiopoietin-2 (Ang-2), soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion protein-1 (VCAM-1), P-selectin and E-selectin are biomarkers of endothelial injury, whereas the receptor for advanced glycation end-products (RAGE) reflects alveolar epithelial injury. The aim of this study was to evaluate whether the trends in plasma concentration of the biomarkers mentioned above were different in survivors and non-survivors of COVID-19-related ARDS. Furthermore, we compared the expression of biomarkers of vascular and endothelial injury in patients with COVID-19-related ARDS and classical ARDS. MethodsThis prospective study was performed in two COVID-19 dedicated Intensive Care Units (ICU) and one non-COVID-19 ICU at Ferrara University Hospital. A cohort of 31 mechanically ventilated patients with COVID-19 ARDS and a cohort of 10 patients with classical ARDS were enrolled. Ang-2, ICAM-1, VCAM-1, P-selectin, E-selectin and RAGE were determined with a bead-based multiplex immunoassay at three time points: inclusion in the study (T1), after 7±2 days (T2) and 14±2 days (T3). The primary outcome was to evaluate the plasma trend of the biomarker levels in survivors and non survivors. The secondary outcome was to evaluate the differences in respiratory mechanics variables and gas exchanges between survivors and non survivors. Furthermore, we compared the plasma levels of the biomarkers at T1 in patients with COVID-19-related ARDS and classical ARDS.ResultsIn COVID-19-related ARDS, the plasma levels of Ang-2 and ICAM-1 at T1 were statistically higher in non-survivors than survivors, (p=0.04 and p=0.03, respectively) whereas those of P-selectin, E-selectin and RAGE did not differ. Ang-2 and ICAM-1 at T1 were predictors of mortality (AUROC 0.650 and 0.717, respectively). At T1, RAGE and P-selectin levels were higher in classical ARDS, than in COVID-19-related ARDS. Ang-2, ICAM-1 and E-selectin were lower in classical ARDS than in COVID-19 related ARDS (all p<0.001).ConclusionsCOVID-19 ARDS is characterized by an early pulmonary endothelial injury, as detected by Ang-2 and ICAM-1. COVID-19 ARDS and classical ARDS exhibited a different expression of biomarkers, suggesting different pathological pathways.Trial registration: NCT04343053 Date of registration: April 13, 2020
Verification of the Efficacy of New Diagnostic Criteria for Retropharyngeal Nodes in a Cohort of Nasopharyngeal Carcinoma Patients
Authors: Tu Dom-Gene , Chen Hsuan-Yu , Yao Wei-Jen , Hung Yu-Sheng , Chang Yu-Kang , Chang Chih-Han , Wang Yu Wen 
Published: October 2020

Abstract
Background: A multistage approach to diagnose lateral retropharyngeal nodes (LRPNs) of nasopharyngeal carcinoma (NPC) had been proposed and warranted for validation. Methods: From 2012 to 2017, we collected NPC cases with LRPNs before radiotherapy-based treatments. The responsive nodes or those that progressed during follow-up were positive. The proposed criteria for the multistage approach delimited LRPNs with a minimal axial diameter (MIAD) ≥ 6.1 mm were positive and if the mean standard uptake value ≥ 2.6, or if the maximal coronal diameter ≥ 25 mm and maximal axial diameter ≥ 8 mm with nodes MIAD < 6.1 mm were also positive. The outcomes were compared with the MIAD cutoff value ≥ 6 mm (traditional method). Chi-squared test was used to compare two areas under the curve (AUC) of receiver operating characteristic curves. Results: A total of 67 eligible NPC cases and 155 LRPNs (72 positive and 83 negative) were analyzed. The accuracy, specificity, and sensitivity of the traditional method were 0.91, 0.93, and 0.89, respectively. The values for the multistage approach all reached 0.94. The AUC was significantly greater for the multistage approach compared with that for the traditional method (p = 0.023). Conclusion: The results of LRPN data in this cohort of patients support the advantage of the multistage approach.
Stopping-power ratio of mouthpiece materials for charged-particle therapy in head and neck cancer
Authors: Ikawa Hiroaki , Inaniwa Taku , Koto Masashi , Bhattacharyya Tapesh , Kaneko Takashi , Takiyama Hirotoshi , Shinoto Makoto , Yamada Shigeru , Tsuji Hiroshi 
Published: October 2020

Abstract
Background: In charged-particle therapy treatment planning, CT numbers of a patient’s body are converted into stopping power ratios (SPRs) using a CT-number-to-SPR conversion table constructed for standard human tissues. Since artificial devices used in treatments of head and neck cancer, such as mouthpieces, do not fit into the CT-number-to-SPR conversion table, they may deteriorate treatment accuracy. In this study, the SPRs of five mouthpiece materials were measured, and the error in predicted SPRs based on the conversion table was investigated.Methods: SPRs of five mouthpiece materials were predicted from their CT numbers using a calibrated conversion table. Independently, the SPRs of the materials were measured by the Bragg-peak shift of a carbon-ion beam passing through the materials. The errors in SPR of the materials were determined as the difference between the predicted and measured SPRs.Results: The SPRs (error) of the ethylene-vinyl acetate copolymers (EVAs), Nipoflex 710TM and BioplastTM, were 0.997 (0.023) and 0.982 (0.007), respectively. The SPRs (error) of the vinyl silicon impression material (Exafine putty typeTM), the light curable resin (Clear Photoreactive Resin for Formlabs 3D printersTM), and the bis-acrylic resin (TempsmartTM) were 1.517 (0.134), 1.161 (0.068), and 1.26 (0.101), respectively. Conclusions: The EVA BioplastTM had the minimum SPR error among the five tested materials, indicating the highest human-tissue equivalency. If other artificial materials such as Exafine putty typeTM are used as mouthpieces, it is recommended that their SPRs be overwritten by the correct values in treatment planning processes.
Heat Killed Salmonella typhimurium protects intestine against radiation injury through Wnt signaling pathway
Authors: Chen Yuanyuan , Cao Kun , Hu Xuguang , Liu Tingting , Li Bailong , Cui Jianguo , Cai Jian ming , Gao Fu , Yang Yanyong 
Published: October 2020

Abstract
Purpose: Gastrointestinal (GI) toxicity caused by ionizing radiation (IR) appears to be a limited factor in radiotherapy and a great threat for soldiers on nuclear-related military missions. However, there are currently no approved medical strategies to effectively prevent or mitigate the damage on intestine induced by IR. The present study aimed to elucidate the protective activity of Heat Killed Salmonella typhimurium (HKST) on intestine against ionizing radiation exposure. Materials and Methods: Mouse intestinal crypts and intestinal organoids were isolated from C57BL/6J mice. Mice and HIEC cells were exposed to 60Co γ‐radiation. The dosage was set as following: whole body radiation of 8 Gy; mouse intestinal organoids were irradiated with 0 Gy, 4 Gy, and 6 Gy of γ-rays at dose rate of 1 Gy/min. Cells or mice were pretreated with Heat Killed Salmonella typhimurium (HKST) (107 cells/mice) at 12 hours prior to irradiation.Results: By culturing mouse intestinal organoids and employing whole body irradiation of mice, we found that the radiation-induced damage on intestine was dramatically mitigated by pretreating with HSKT in vitro and in vivo, in which the structure of intestinal organoids and small intestine of the HKST-treated group was more integrated than of the radiation damage group, and HKST pretreatment remarkably promoted the proliferation of intestinal cells post IR exposure (Figure 1 and 2). Further study showed that the radio-protective effects of HKST was involved in DNA damage response (DDR) signaling. Moreover, the stimulation of DDR signaling by HKST upon radiation damage was mediated by Wnt signaling, in which the inhibition of Wnt signaling diminished the radio-protective effects of HKST. Conclusion: Our study demonstrated that Heat Killed Salmonella typhimurium (HKST) could significantly alleviate the damage on intestine induced by IR, and the radio-protective effect of HKST was depended on DDR mediated by Wnt signaling pathway. These findings demonstrated that HKST is a potential bacterium using for the prevention of IR-induced GI toxicity in clinical practice.
Protocol for Systematic Review on Inequity in Child Health Care Service Utilization in Low and Middle-income Countries
Authors: Demessie Hailu Fekadu , Hailemariam Damen Hailemariam , Kloos Helmut Kloos , Adugna Aynalem Adugna , Mekonnen Wubegzier Mekonnen 
Published: October 2020

Abstract
Background: One challenge to achieving Millennium Development Goals was inequitable access to quality health services. In order to achieve the Sustainable Development Goals, interventions need to reach underserved populations, it appears that the maternal, newborn and child health goals (MDG 4 and 5) will not be universally achieved. There was early recognition that it could be possible to achieve the health goals while decreasing health inequity, because most of the gains might go to the better-off rather than to the very poor.Methodology/Design: The current protocol adopts a strategy informed by the guidelines of The Cochrane Handbook for Systematic Reviews. Our systematic review will identify studies in English, provided inclusion of an English abstract - from 2010 onwards till 2020, by searching MEDLINE (PubMed interface), EMBASE (OVID interface), Cochrane Central (OVID interface) and the gray literature. Study selection criteria include research setting, study design, reported outcomes and determinants of interest. Our primary outcome is inequity in utilization of child health care services, and determinants of concern are: 1) socioeconomic status (for example, income, education); 2) geographic determinants (for example, distance to a health center, rural versus urban residence); and 3) demographic determinants (for example, age, ethnicity, religion, and marital status). Screening, data abstraction, and scientific quality assessment will be conducted independently by two reviewers using standardized forms. Where feasible, study results will be combined through meta-analyses to obtain a pooled measure of association between utilization of child health care services and key determinants. Results will be stratified by income levels (World Bank classification) geographical residence and demographical determinants.Discussion: Our review will inform policy-making with the aim of decreasing inequities in utilization of child health care services. This research will provide evidence on unmet needs for child health care services in LMICs, knowledge gaps and recommendations to health policy planners. Our research will help promote universal coverage of quality child health care services as an integral part of the continuum of maternal and child health care. This protocol will be registered with the Prospero database.
Antimicrobial-associated Organ Injury Among Older Adults: A Systematic Review and Meta-analyses Protocol
Authors: Chinzowu Tichawona , Roy Sandipan , Nishtala Prasad S 
Published: October 2020

Abstract
Background: Older adults (aged 65 years and above) constitute the fastest growing population cohort in the western world. There is increasing evidence that the burden of infections disproportionately affects older adults, and hence this vulnerable population is frequently exposed to antimicrobials. There is currently no systematic review summarising the evidence for risk of organ injury following antimicrobial exposure among older adults. This protocol will outline how we will conduct a systematic review and meta-analyses to examine the relationship between antimicrobial exposure and organ injury in older adults. Methodology: We will search for Psych INFO, PubMed, and EMBASE databases for relevant articles using MeSH terms where applicable. After removing duplicates, articles will be screened for inclusion into or exclusion from the study by two reviewers. Title and abstract screening will be done first, followed by full-text screening. The Newcastle-Ottawa scale will be used to assess the risk of bias for cohort and case-control studies, and the Cochrane collaboration's tool will be used to assess the risk of bias for randomised control trials. We will explore the potential sources of heterogeneity and bias using funnel and forest plots of the included studies. Discussion and registration: In this protocol, systematic review methods to identify relevant literature on antimicrobial exposure and associated organ injury have been described. The findings from the review are intended to increase our understanding of the different types of antimicrobials associated with organ injury among older adults, therefore has the potential for improving the prescribing practice for this vulnerable population. This protocol is registered in the PROSPERO database (registration number CRD42020152621).
Guidelines on the Diagnosis, Clinical Assessments, Treatment and Management for CLN2 Disease Patients
Authors: Mole Sara , Schulz Angela , Badoe Eben , Berkovic Samuel , Reyes Emily de Los , Dulz Simon , Gissen Paul , Gilbert Norberto , Lourenco Charles , Mink Jonathan , Murphy Noreen , Nickel Miriam , Olaya Joffre , Scarpa Maurizio , Scheffer Ingrid , Simonati Alessandro , Specchio Nicola , Von Lobbecke Ina , Wang Raymond , Williams Ruth 
Published: October 2020

Abstract
Background: CLN2 disease (Neuronal Ceroid Lipofuscinosis Type 2), or Late-Infantile Neuronal Ceroid Lipofuscinosis (LINCL), is an ultra-rare, neurodegenerative lysosomal storage disease, caused by an enzyme deficiency of tripeptidyl peptidase 1 (TPP1). Lack of disease awareness and the non-specificity of presenting symptoms often leads to delayed diagnosis. These guidelines provide robust evidence-based, expert-agreed recommendations on the risks/benefits of disease-modifying treatments and the medical interventions used to manage this condition. Methods: An expert mapping tool process was developed ranking multidisciplinary professionals, with knowledge of CLN2 disease, diagnostic or management experience of CLN2 disease, or family support professionals. Individuals were sequentially approached to identify two chairs, ensuring that the process was transparent and unbiased. A systematic literature review of published evidence using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidance was independently and simultaneously conducted to develop key statements based upon the strength of the publications. Clinical care statements formed the basis of an international modified Delphi consensus determination process using the virtual meeting (Within3) online platform which requested experts to agree or disagree with any changes. Statements reaching the consensus mark became the guiding statements within this manuscript, which were subsequently assessed against the Appraisal of Guidelines for Research and Evaluation (AGREEII) criteria.Results: Twenty-one international experts from 7 different specialities, including a patient advocate, were identified. Fifty-three guideline statements were developed covering 13 domains: General Description and Statements, Diagnostics, Clinical Recommendations and Management, Assessments, Interventions and Treatment, Additional Care Considerations, Social Care Considerations, Pain Management, Epilepsy / Seizures, Nutritional Care Interventions, Respiratory Health, Sleep and Rest, and End of Life Care. Consensus was reached after a single round of voting, with one exception which was revised, and agreed by 100% of the SC and achieved 80% consensus in the second voting round. The overall AGREE II assessment score obtained for the development of the guidelines was 5.7 (where 1 represents the lowest quality, and 7 represents the highest quality). Conclusion: This program provides robust evidence- and consensus-driven guidelines that can be used by all healthcare professionals involved in the management of patients with CLN2 disease. This addresses the clinical need to complement other information available.
Identification of novel salivary candidate protein biomarkers for tuberculosis diagnosis
Authors: Mutavhatsindi Hygon , Calder Bridget , McAnda Shirley , Malherbe Stephanus T. , Stanley Kim , Kidd Martin , Walzl Gerhard , Chegou Novel N 
Published: October 2020

Abstract
Background: The diagnosis of TB remains one of the major challenges in the control of the disease, due to limitations in the currently available diagnostic tests. There is an urgent need for new, accurate, rapid, and affordable diagnostic tests. The aim of the present study was to use mass spectrometry to identify new candidate TB diagnostic protein biomarkers in saliva obtained from individuals with TB, and patients with other respiratory diseases (ORD).Methods: Saliva samples were collected from 22 individuals who self-presented with symptoms requiring investigation for TB as part of a larger TB biomarker project. Eleven of the participants were finally diagnosed with TB using routine clinical, radiological and laboratory tests and 11 with ORD. Salivary proteins were concentrated and purified, followed by tryptic digestion. Peptides were analyzed using a QExactive Orbitrap MS coupled to a Dionex liquid chromatography system. Raw files were processed using MaxQuant software against the database of human proteins. Identified proteins were subjected to gene ontology and ingenuity pathway analysis for functional enrichment analysis.Results: We identified 1176 protein groups across all samples, of which 46 (3.91%) were contaminants, 12 (1.02%) were reverse hits and 170 (14.46%) were single-peptide protein groups. After removal of the contaminants, reverse hits and protein groups represented by single peptides, 26 of the remaining 948 proteins significantly discriminated individuals with TB from those with ORD after Benjamini Hochberg correction, with five of these proteins diagnosing TB with AUC ³ 0.80. A 5-protein biosignature comprising of P01011, Q8NCW5, P28072, A0A2Q2TTZ9 and Q99574 diagnosed TB with an AUC of 1.00 (95% CI, 1.00-1.00), sensitivity of 100% (95% CI, 76.2-100%) and specificity of 90.9% (95% CI, 58.7-99.8%) after leave-one-out cross validation. Conclusions: We identified novel salivary protein biomarkers and biosignatures with strong potential as TB diagnostic candidates. Our results are preliminary and require validation in larger studies.